
<?xml version="1.0" encoding="UTF-8" ?><xml>
	<records>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>626</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Jacobson, G. A.</style></author>
										<author><style face="normal" font="default" size="100%">Chong, F. V.</style></author>
										<author><style face="normal" font="default" size="100%">Wood-Baker, R.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">School of Pharmacy, University of Tasmania, GPO BOX 252-26, Hobart, Tasmania 7001, Australia. glenn.jacobson@utas.edu.au</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">(R,S)-salbutamol plasma concentrations in severe asthma</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">235-8</style></pages>
			<volume><style face="normal" font="default" size="100%">28</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Administration, Inhalation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Albuterol/*blood/chemistry/therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Asthma/blood/*drug therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Bronchodilator Agents/*blood/chemistry/therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Linear Models</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Pilot Projects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Status Asthmaticus/*blood</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Stereoisomerism</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2003</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">6</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">OBJECTIVE: Salbutamol is commonly delivered as a racemic mixture of pharmacologically active (R)-salbutamol and inactive (S)-salbutamol. This study investigated inactive (S)- and active (R)-salbutamol plasma levels and their relationship to dose in patients with severe asthma. METHODS: Basic demographics, racemic-salbutamol dose in the preceding 24 h, lung function tests at baseline and 1 h, and a 10 mL plasma sample were obtained from subjects presenting to the Department of Emergency Medicine with acute asthma. Plasma determinations were carried out using an LC-MS assay with solid phase extraction. RESULTS: All patients (n = 5) had detectable levels of drug in plasma with range of 0.9-7.7 and 4.7-27.4 ng/mL for (R)-salbutamol and (S)-salbutamol respectively. These were correlated to total racemic salbutamol dose. The range of the (S) : (R) ratio was 2.0-5.2, with (R)-salbutamol representing 16-33% of the total plasma concentration, which did not correlate with total salbutamol dose. CONCLUSION: Only a small fraction of total plasma salbutamol concentration was found to consist of active enantiomer in patients with an acute severe exacerbation of asthma actively undergoing treatment with racemic-salbutamol. As a result of the possible contribution of (S)-salbutamol to poor asthma control further enantioselective investigations are warranted in severe asthma.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12795782 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>4</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Bertini, E.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A.</style></author>
										<author><style face="normal" font="default" size="100%">Bushby, K.</style></author>
										<author><style face="normal" font="default" size="100%">Estournet-Mathiaud, B.</style></author>
										<author><style face="normal" font="default" size="100%">Finkel, R. S.</style></author>
										<author><style face="normal" font="default" size="100%">Hughes, R. A.</style></author>
										<author><style face="normal" font="default" size="100%">Iannaccone, S. T.</style></author>
										<author><style face="normal" font="default" size="100%">Melki, J.</style></author>
										<author><style face="normal" font="default" size="100%">Mercuri, E.</style></author>
										<author><style face="normal" font="default" size="100%">Muntoni, F.</style></author>
										<author><style face="normal" font="default" size="100%">Voit, T.</style></author>
										<author><style face="normal" font="default" size="100%">Reitter, B.</style></author>
										<author><style face="normal" font="default" size="100%">Swoboda, K. J.</style></author>
										<author><style face="normal" font="default" size="100%">Tiziano, D.</style></author>
										<author><style face="normal" font="default" size="100%">Tizzano, E.</style></author>
										<author><style face="normal" font="default" size="100%">Topaloglu, H.</style></author>
										<author><style face="normal" font="default" size="100%">Wirth, B.</style></author>
										<author><style face="normal" font="default" size="100%">Zerres, K.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Laboratories, Unit of Molecular Medicine, Bambino Gesu' Children's Research Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy. ebertini@tin.it</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">134th ENMC International Workshop: Outcome Measures and Treatment of Spinal Muscular Atrophy, 11-13 February 2005, Naarden, The Netherlands</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">802-16</style></pages>
			<volume><style face="normal" font="default" size="100%">15</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/classification/*diagnosis/*therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Netherlands</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Treatment Outcome</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16202598 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1071</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Sarkozy, A.</style></author>
										<author><style face="normal" font="default" size="100%">Bushby, K.</style></author>
										<author><style face="normal" font="default" size="100%">Beroud, C.</style></author>
										<author><style face="normal" font="default" size="100%">Lochmuller, H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute of Human Genetics, University of Newcastle, TREAT-NMD Office, Newcastle upon Tyne NE1 3BZ, UK.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">157th ENMC International Workshop: patient registries for rare, inherited muscular disorders 25-27 January 2008 Naarden, The Netherlands</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">997-1001</style></pages>
			<volume><style face="normal" font="default" size="100%">18</style></volume>
			<number><style face="normal" font="default" size="100%">12</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Data Collection/methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genetic Screening/methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/diagnosis/genetics/therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Diseases/classification/congenital/*diagnosis</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Dystrophy, Duchenne/diagnosis/genetics/therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Registries/*statistics & numerical data</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">12</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18948006 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>439</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Waza, M.</style></author>
										<author><style face="normal" font="default" size="100%">Adachi, H.</style></author>
										<author><style face="normal" font="default" size="100%">Katsuno, M.</style></author>
										<author><style face="normal" font="default" size="100%">Minamiyama, M.</style></author>
										<author><style face="normal" font="default" size="100%">Sang, C.</style></author>
										<author><style face="normal" font="default" size="100%">Tanaka, F.</style></author>
										<author><style face="normal" font="default" size="100%">Inukai, A.</style></author>
										<author><style face="normal" font="default" size="100%">Doyu, M.</style></author>
										<author><style face="normal" font="default" size="100%">Sobue, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1088-95</style></pages>
			<volume><style face="normal" font="default" size="100%">11</style></volume>
			<number><style face="normal" font="default" size="100%">10</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression Regulation/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">HSP90 Heat-Shock Proteins/*antagonists & inhibitors/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Transgenic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/*drug effects/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/drug therapy/*genetics/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Peptides/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Phenotype</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Receptors, Androgen/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rifabutin/*analogs & derivatives/pharmacology/therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Trinucleotide Repeat Expansion/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">10</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Heat-shock protein 90 (Hsp90) functions as part of a multichaperone complex that folds, activates and assembles its client proteins. Androgen receptor (AR), a pathogenic gene product in spinal and bulbar muscular atrophy (SBMA), is one of the Hsp90 client proteins. We examined the therapeutic effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent Hsp90 inhibitor, and its ability to degrade polyglutamine-expanded mutant AR. Administration of 17-AAG markedly ameliorated motor impairments in the SBMA transgenic mouse model without detectable toxicity, by reducing amounts of monomeric and aggregated mutant AR. The mutant AR showed a higher affinity for Hsp90-p23 and preferentially formed an Hsp90 chaperone complex as compared to wild-type AR; mutant AR was preferentially degraded in the presence of 17-AAG in both cells and transgenic mice as compared to wild-type AR. 17-AAG also mildly induced Hsp70 and Hsp40. 17-AAG would thus provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16155577 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>997</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Tokui, K.</style></author>
										<author><style face="normal" font="default" size="100%">Adachi, H.</style></author>
										<author><style face="normal" font="default" size="100%">Waza, M.</style></author>
										<author><style face="normal" font="default" size="100%">Katsuno, M.</style></author>
										<author><style face="normal" font="default" size="100%">Minamiyama, M.</style></author>
										<author><style face="normal" font="default" size="100%">Doi, H.</style></author>
										<author><style face="normal" font="default" size="100%">Tanaka, K.</style></author>
										<author><style face="normal" font="default" size="100%">Hamazaki, J.</style></author>
										<author><style face="normal" font="default" size="100%">Murata, S.</style></author>
										<author><style face="normal" font="default" size="100%">Tanaka, F.</style></author>
										<author><style face="normal" font="default" size="100%">Sobue, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">898-910</style></pages>
			<volume><style face="normal" font="default" size="100%">18</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The ubiquitin-proteasome system (UPS) is the principal protein degradation system that tags and targets short-lived proteins, as well as damaged or misfolded proteins, for destruction. In spinal and bulbar muscular atrophy (SBMA), the androgen receptor (AR), an Hsp90 client protein, is such a misfolded protein that tends to aggregate in neurons. Hsp90 inhibitors promote the degradation of Hsp90 client proteins via the UPS. In a transgenic mouse model of SBMA, we examined whether a functioning UPS is preserved, if it was capable of degrading polyglutamine-expanded mutant AR, and what might be the therapeutic effects of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), an oral Hsp90 inhibitor. Ubiquitin-proteasomal function was well preserved in SBMA mice and was even increased during advanced stages when the mice developed severe phenotypes. Administration of 17-DMAG markedly ameliorated motor impairments in SBMA mice without detectable toxicity and reduced amounts of monomeric and nuclear-accumulated mutant AR. Mutant AR was preferentially degraded in the presence of 17-DMAG in both SBMA cell and mouse models when compared with wild-type AR. 17-DMAG also significantly induced Hsp70 and Hsp40. Thus, 17-DMAG would exert a therapeutic effect on SBMA via preserved proteasome function.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19066230 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>250</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Koessler, W.</style></author>
										<author><style face="normal" font="default" size="100%">Wanke, T.</style></author>
										<author><style face="normal" font="default" size="100%">Winkler, G.</style></author>
										<author><style face="normal" font="default" size="100%">Nader, A.</style></author>
										<author><style face="normal" font="default" size="100%">Toifl, K.</style></author>
										<author><style face="normal" font="default" size="100%">Kurz, H.</style></author>
										<author><style face="normal" font="default" size="100%">Zwick, H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Ludwig Boltzmann-Institute for Environmental Pulmonology and Pulmonary Department, City Hospital Lainz, Vienna, Austria. Kow@khl.pul.magwien.gv.at</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">2 Years' experience with inspiratory muscle training in patients with neuromuscular disorders</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">765-9</style></pages>
			<volume><style face="normal" font="default" size="100%">120</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adolescent</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Breathing Exercises</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Forced Expiratory Volume</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*complications/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Dystrophy, Duchenne/*complications/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Respiratory Insufficiency/etiology/*rehabilitation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Respiratory Muscles/*physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Vital Capacity</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2001</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">9</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">PURPOSE: The aim of our study was to assess the long-term effects of specific inspiratory muscle training (IMT) in patients with neuromuscular disorders (NMDs) who have various degrees of respiratory impairment. Patients and methods: Twenty-seven patients with NMDs (Duchenne's muscular dystrophy, 18 patients; spinal muscular atrophy, 9 patients) underwent 24 months of IMT. Patients were divided into three groups according to their vital capacity (VC) values. VC was measured as the parameter for the respiratory system involvement of the disease. Maximal inspiratory pressure (PImax) was assessed as the parameter for respiratory muscle strength, and the results of the 12-s maximum voluntary ventilation test (12sMVV) were assessed as the parameter for respiratory muscle endurance. Pulmonary and inspiratory muscle function parameters were assessed 6 months before training, at the beginning of training, and then every 3 months. RESULTS: The PImax values improved in group A (VC, 27 to 50% predicted) from 51.45 to 87.00 cm H(2)O, in group B (VC, 51 to 70% predicted) from 59.38 to 94.4 cm H(2)O, and in group C (VC, 71 to 96% predicted) from 71.25 to 99.00 cm H(2)O. The 12sMVV values improved in group A from 52.69 to 69.50 L/min, in group B from 53.18 to 62.40 L/min, and in group C from 59.48 to 70.5 L/min. For all three groups, there was a significant improvement of PImax (p < 0.007) and 12sMVV (p < 0.015) until the 10th month when a plateau phase was reached with no decline in the following month until the end of training. CONCLUSION: With IMT, respiratory muscle function can be improved in the long term of up to 2 years.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11555507 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>554</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Garriga-Canut, M.</style></author>
										<author><style face="normal" font="default" size="100%">Schoenike, B.</style></author>
										<author><style face="normal" font="default" size="100%">Qazi, R.</style></author>
										<author><style face="normal" font="default" size="100%">Bergendahl, K.</style></author>
										<author><style face="normal" font="default" size="100%">Daley, T. J.</style></author>
										<author><style face="normal" font="default" size="100%">Pfender, R. M.</style></author>
										<author><style face="normal" font="default" size="100%">Morrison, J. F.</style></author>
										<author><style face="normal" font="default" size="100%">Ockuly, J.</style></author>
										<author><style face="normal" font="default" size="100%">Stafstrom, C.</style></author>
										<author><style face="normal" font="default" size="100%">Sutula, T.</style></author>
										<author><style face="normal" font="default" size="100%">Roopra, A.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">[1] Department of Neurology, Medical Science Center, Room 1715, University of Wisconsin-Madison, 1300 University Avenue, Madison, Wisconsin 53706, USA. [2] These authors contributed equally to this work.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1382-7</style></pages>
			<volume><style face="normal" font="default" size="100%">9</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Temporal lobe epilepsy is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in the rat kindling model of temporal lobe epilepsy. We show that 2DG potently reduces the progression of kindling and blocks seizure-induced increases in the expression of brain-derived neurotrophic factor and its receptor, TrkB. This reduced expression is mediated by the transcription factor NRSF, which recruits the NADH-binding co-repressor CtBP to generate a repressive chromatin environment around the BDNF promoter. Our results show that 2DG has anticonvulsant and antiepileptic properties, suggesting that anti-glycolytic compounds may represent a new class of drugs for treating epilepsy. The metabolic regulation of neuronal genes by CtBP will open avenues of therapy for neurological disorders and cancer.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17041593 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>807</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Parkinson, N. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Physiology, Anatomy and Genetics, University of Oxford, Henry Wellcome Centre for Gene Function, South Parks Road, Oxford OX1 3QX, United Kingdom.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">4th UK spinal muscular atrophy (SMA) researchers network meeting</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">349-53</style></pages>
			<volume><style face="normal" font="default" size="100%">18</style></volume>
			<number><style face="normal" font="default" size="100%">4</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">4</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18396402 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>76</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Zerres, K.</style></author>
										<author><style face="normal" font="default" size="100%">Davies, K. E.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute for Human Genetics, Technical University, Aachen Germany.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">59th ENMC International Workshop: Spinal Muscular Atrophies: recent progress and revised diagnostic criteria 17-19 April 1998, Soestduinen, The Netherlands</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">272-8</style></pages>
			<volume><style face="normal" font="default" size="100%">9</style></volume>
			<number><style face="normal" font="default" size="100%">4</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Muscular Atrophy, Spinal/diagnosis/genetics/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1999</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">6</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10399757 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>415</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Delhalle, S.</style></author>
										<author><style face="normal" font="default" size="100%">Blasius, R.</style></author>
										<author><style face="normal" font="default" size="100%">Dicato, M.</style></author>
										<author><style face="normal" font="default" size="100%">Diederich, M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Laboratoire de Biologie Moleculaire et Cellulaire du Cancer, Hopital Kirchberg, L-2540 Luxembourg, Luxembourg.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A beginner's guide to NF-kappaB signaling pathways</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1-13</style></pages>
			<volume><style face="normal" font="default" size="100%">1030</style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">NF-kappa B/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Signal Transduction</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2004</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">12</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Nuclear factor kappaB (NF-kappaB) belongs to a family of heterodimeric transcription factors that play a key role in inflammatory and stress responses as well as in tumor cell resistance to apoptosis. These effects are due to the NF-kappaB-dependent transcription of many proinflammatory and antiapoptotic genes, whose products ensure various cell responses to environmental conditions. The signal transduction pathways leading to NF-kappaB activation are well characterized, and the different steps implicated in these pathways involve proteins that could constitute targets for NF-kappaB inhibition. Several inhibitors aiming to prevent NF-kappaB activity and thus the transcription of target genes are studied, and a few compounds seem particularly promising. We try here to summarize the advantages that can issue from various studies on NF-kappaB.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15659775 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>349</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Pugh, P. L.</style></author>
										<author><style face="normal" font="default" size="100%">Ahmed, S. F.</style></author>
										<author><style face="normal" font="default" size="100%">Smith, M. I.</style></author>
										<author><style face="normal" font="default" size="100%">Upton, N.</style></author>
										<author><style face="normal" font="default" size="100%">Hunter, A. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Neurology and GI CEDD, GlaxoSmithKline, Third Avenue, Harlow, Essex CM19 5AW, UK. Pippa_L_Pugh@gsk.com</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A behavioural characterisation of the FVB/N mouse strain</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">283-9</style></pages>
			<volume><style face="normal" font="default" size="100%">155</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Aggression/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Behavior, Animal/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Behavioral Research/instrumentation/*methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Circadian Rhythm/genetics/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cognition/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Comparative Study</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Genetics, Behavioral</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genotype</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Learning/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Transgenic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Activity/genetics/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Retina/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Species Specificity</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Visual Perception/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2004</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The use of transgenic models in scientific research has made an enormous contribution to our understanding of the causes and symptoms of many diseases, including neurodegenerative conditions such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). In the creation of transgenic models of neurodegenerative disease, effects of the background strain of the animal on the resulting genotype must be taken into consideration. This is particularly true for behavioural studies in which the background strain of the mouse may mask the phenotype of the genetic manipulation. Here, the behaviour of two mouse strains used in transgenic models, FVB/N and C57BL6/J, were compared. Studies of circadian wheel activity, cognition and aggression revealed considerable phenotypic differences between strains. These data also indicate that the FVB/N strain is not appropriate as a background strain in the behavioural assessment of transgenic mouse models.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15364488 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>319</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Wang, J.</style></author>
										<author><style face="normal" font="default" size="100%">Dreyfuss, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A cell system with targeted disruption of the SMN gene: functional conservation of the SMN protein and dependence of Gemin2 on SMN</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">9599-605</style></pages>
			<volume><style face="normal" font="default" size="100%">276</style></volume>
			<number><style face="normal" font="default" size="100%">13</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Southern</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Western</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Death</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Survival</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chickens</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Conserved Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DNA, Complementary/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Electrophoresis, Polyacrylamide Gel</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Flow Cytometry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Library</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Mutagenesis, Site-Directed</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/chemistry/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Plasmids</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Promoter Regions (Genetics)</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Recombination, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tetracycline/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Time Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transfection</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2001</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The motor neuron degenerative disease spinal muscular atrophy is caused by reduced expression of the survival motor neuron (SMN) protein. Here we report a genetic system developed in the chicken pre-B cell line DT40, in which the endogenous SMN gene is disrupted by homologous recombination, and SMN protein is expressed from a chicken SMN cDNA under control of a tetracycline (tet)-repressible promoter. Addition of tet results in depletion of SMN protein and consequent cell death, which directly demonstrates that SMN is required for cell viability. The tet-induced lethality can be rescued by expression of human SMN, indicating that the function of SMN is highly conserved between the two species. Cells expressing low levels of SMN display slow growth proportional to the amount of SMN they contain. Interestingly, the level of the SMN-interacting protein Gemin2 decreases significantly following depletion of SMN, supporting the conclusion that SMN and Gemin2 form a stable complex in vivo. This system provides a powerful setting for studying the function of SMN in vivo and for screening for potential therapeutics for spinal muscular atrophy.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11121410 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>365</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Zerres, K.</style></author>
										<author><style face="normal" font="default" size="100%">Rudnik-Schoneborn, S.</style></author>
										<author><style face="normal" font="default" size="100%">Forrest, E.</style></author>
										<author><style face="normal" font="default" size="100%">Lusakowska, A.</style></author>
										<author><style face="normal" font="default" size="100%">Borkowska, J.</style></author>
										<author><style face="normal" font="default" size="100%">Hausmanowa-Petrusewicz, I.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute for Human Genetics, University of Bonn, Germany. zerres@snphysio2.wilhelm.uni-bonn.de</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">67-72</style></pages>
			<volume><style face="normal" font="default" size="100%">146</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adolescent</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Age of Onset</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child, Preschool</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Databases, Factual</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Progression</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Germany</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant, Newborn</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/pathology/*physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Poland</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Probability</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal Muscular Atrophies of Childhood/pathology/*physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Walking/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1997</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">We analyzed clinical data of 569 patients in two combined series with childhood and juvenile proximal SMA. This cohort included only patients who had achieved the ability to sit unaided (type II and III SMA). The survival rate among 240 type II patients (who sat but never walked) was 98.5% at 5 years and 68.5% at 25 years. SMA III (n = 329) (those who walked and had symptoms before age 30 years) was subdivided into those with an onset before and after age 3 years (type IIIa, n = 195; SMA IIIb, n = 134). In patients with SMA III, life expectancy is not significantly less than a normal population. The probabilities of being able to walk at 10 years after onset was 70.3%, and at 40 years, 22.0% in SMA IIa. For SMA IIIb, 96.7% were walking 10 years after onset and 58.7% at 40 years. The subdivision of type III SMA was justified by the probability of being ambulatory depending on age at onset; the prognosis differed for those with onset before or after age 3 years. The data provide a reliable basis of the natural history of proximal SMA and support a classification system that is based primarily on age at onset and the achievement of motor milestones.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9077498 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>587</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Otter, S.</style></author>
										<author><style face="normal" font="default" size="100%">Grimmler, M.</style></author>
										<author><style face="normal" font="default" size="100%">Neuenkirchen, N.</style></author>
										<author><style face="normal" font="default" size="100%">Chari, A.</style></author>
										<author><style face="normal" font="default" size="100%">Sickmann, A.</style></author>
										<author><style face="normal" font="default" size="100%">Fischer, U.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Biochemistry, Theodor Boveri Institute, University of Wuerzburg, Wuerzburg D-97074.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A comprehensive interaction map of the human SMN-complex</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Assembly of the Sm-class of U-rich small nuclear ribonucleoprotein particles (U snRNPs) is a process facilitated by the macromolecular SMN-complex. This entity promotes the binding of a set of factors, termed LSm/Sm proteins, onto snRNA to form the core structure of these particles. Nine factors, including the survival motor neuron (SMN) protein, the product of the spinal muscular atrophy (SMA) disease gene, Gemins 2-8 and unrip have been identified as the major components of the SMN-complex. So far however, only little is known about the architecture of this complex and the contribution of individual components to its function. Here, we present a comprehensive interaction map of all core components of the SMN-complex based upon in vivo and in vitro methods. Our studies reveal a modular composition of the SMN-complex with the three proteins SMN, Gemin8 and Gemin7 in its center. Onto this central building block the other components are bound via multiple interactions. Furthermore, by employing a novel assay, we were able to reconstitute the SMN-complex from individual components and confirm the interaction map. Interestingly, SMN protein carrying an SMA-causing mutation was severely impaired in formation of the SMN-complex. Finally, we show that the peripheral component Gemin5 contributes an essential activity to the SMN-complex, most likely the transfer of Sm proteins onto the U snRNA. Collectively, the data presented here provide a basis for the detailed mechanistic and structural analysis of the assembly machinery of U snRNPs.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17178713 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1005</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Mitchell, R. M.</style></author>
										<author><style face="normal" font="default" size="100%">Freeman, W. M.</style></author>
										<author><style face="normal" font="default" size="100%">Randazzo, W. T.</style></author>
										<author><style face="normal" font="default" size="100%">Stephens, H. E.</style></author>
										<author><style face="normal" font="default" size="100%">Beard, J. L.</style></author>
										<author><style face="normal" font="default" size="100%">Simmons, Z.</style></author>
										<author><style face="normal" font="default" size="100%">Connor, J. R.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurosurgery, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA 17033-0850, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">14-9</style></pages>
			<volume><style face="normal" font="default" size="100%">72</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges with respect to diagnosis and monitoring of disease progression. OBJECTIVES: To identify a biomarker panel that elucidates ALS disease pathogenesis, distinguishes patients with ALS from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile. METHODS: We obtained CSF samples by lumbar puncture from 41 patients with ALS and 33 neurologic disease controls. All patients were genotyped for HFE polymorphisms. We performed a multiplex cytokine and growth factor analysis and immunoassays for iron-related analytes. Classification statistics were generated using a support vector machine algorithm. RESULTS: The groups of patients with ALS and neurologic disease controls were each associated with distinct profiles of biomarkers. Fourteen biomarkers differed between patients with ALS and the control group. The five proteins with the lowest p values differentiated patients with ALS from controls with 89.2% accuracy, 87.5% sensitivity, and 91.2% specificity. Expression of IL-8 was higher in those patients with lower levels of physical function. Expression of beta2-microglobulin was higher in subjects carrying an H63D HFE allele, while expression of several markers was higher in subjects carrying a C282Y HFE allele. CONCLUSIONS: A CSF inflammatory profile associated with amyotrophic lateral sclerosis (ALS) pathogenesis may distinguish patients with ALS from neurologic disease controls, and may serve as a biomarker panel to aid in the diagnosis of ALS pending further validation. Some of these biomarkers differ by HFE genotype.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18987350 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1407</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Das, M.</style></author>
										<author><style face="normal" font="default" size="100%">Rumsey, J. W.</style></author>
										<author><style face="normal" font="default" size="100%">Bhargava, N.</style></author>
										<author><style face="normal" font="default" size="100%">Stancescu, M.</style></author>
										<author><style face="normal" font="default" size="100%">Hickman, J. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Hybrid Systems Lab, NanoScience Technology Center, Suite 402, 12424 Research Parkway, University of Central Florida, Orlando, FL 32826, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A defined long-term in vitro tissue engineered model of neuromuscular junctions</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Neuromuscular junction (NMJ) formation, occurring between motoneurons and skeletal muscle, is a complex multistep process involving a variety of signaling molecules and pathways. In vitro motoneuron-muscle co-cultures are powerful tools to study the role of different growth factors, hormones and cellular structures involved in NMJ formation. In this study, a serum-free culture system utilizing defined temporal growth factor application and a non-biological substrate resulted in the formation of robust NMJs. The system resulted in long-term survival of the co-culture and selective expression of neonatal myosin heavy chain, a marker of myotube maturation. NMJ formation was verified by colocalization of dense clusters of acetylcholine receptors visualized using alpha-bungarotoxin and synaptophysin containing vesicles present in motoneuron axonal terminals. This model will find applications in basic NMJ research and tissue engineering applications such as bio-hybrid device development for limb prosthesis and regenerative medicine as well as for high-throughput drug and toxin screening applications.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20346499 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1392</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Cho, S.</style></author>
										<author><style face="normal" font="default" size="100%">Dreyfuss, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A degron created by SMN2 exon 7 skipping is a principal contributor to spinal muscular atrophy severity</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">438-42</style></pages>
			<volume><style face="normal" font="default" size="100%">24</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/genetics/metabolism/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Stability</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Alignment</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Severity of Illness Index</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Signal Transduction/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Survival of Motor Neuron 2 Protein/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is caused by homozygous survival of motor neurons 1 (SMN1) gene deletions, leaving a duplicate gene, SMN2, as the sole source of SMN protein. However, most of the mRNA produced from SMN2 pre-mRNA is exon 7-skipped ( approximately 80%), resulting in a highly unstable and almost undetectable protein (SMNDelta7). We show that this splicing defect creates a potent degradation signal (degron; SMNDelta7-DEG) at SMNDelta7's C-terminal 15 amino acids. The S270A mutation inactivates SMNDelta7-DEG, generating a stable SMNDelta7 that rescues viability of SMN-deleted cells. These findings explain a key aspect of the SMA disease mechanism, and suggest new treatment approaches based on interference with SMNDelta7-DEG activity.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20194437 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>292</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Young, P. J.</style></author>
										<author><style face="normal" font="default" size="100%">Day, P. M.</style></author>
										<author><style face="normal" font="default" size="100%">Zhou, J.</style></author>
										<author><style face="normal" font="default" size="100%">Androphy, E. J.</style></author>
										<author><style face="normal" font="default" size="100%">Morris, G. E.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C. L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Biology, Arizona State University, Tempe, Arizona 85287, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A direct interaction between the survival motor neuron protein and p53 and its relationship to spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">2852-9</style></pages>
			<volume><style face="normal" font="default" size="100%">277</style></volume>
			<number><style face="normal" font="default" size="100%">4</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Apoptosis</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Biosensing Techniques</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dimerization</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fibroblasts/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Glutathione Transferase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microscopy, Fluorescence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation, Missense</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Precipitin Tests</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Binding</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Structure, Tertiary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Recombinant Proteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Time Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transfection</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tumor Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tumor Suppressor Protein p53/*metabolism/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2002</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Mutations in the SMN1 (survival motor neuron 1) gene cause spinal muscular atrophy (SMA). We now show that SMN protein, the SMN1 gene product, interacts directly with the tumor suppressor protein, p53. Pathogenic missense mutations in SMN reduce both self-association and p53 binding by SMN, and the extent of the reductions correlate with disease severity. The inactive, truncated form of SMN produced by the SMN2 gene in SMA patients fails to bind p53 efficiently. SMN and p53 co-localize in nuclear Cajal bodies, but p53 redistributes to the nucleolus in fibroblasts from SMA patients. These results suggest a functional interaction between SMN and p53, and the potential for apoptosis when this interaction is impaired may explain motor neuron death in SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11704667 </style></url>
										<url><style face="normal" font="default" size="100%">file:///S:/Clinical%20Research%20Papers/Young,%20A%20direct%20interaction%20between%20the%20survival%20motor%20neuron%20protein%20and%20p53%20and%20its%20relationship%20to%20spinal%20muscular%20atrophy,%20J%20Bio%20Chem%202002.pdf</style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>866</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Dictenberg, J. B.</style></author>
										<author><style face="normal" font="default" size="100%">Swanger, S. A.</style></author>
										<author><style face="normal" font="default" size="100%">Antar, L. N.</style></author>
										<author><style face="normal" font="default" size="100%">Singer, R. H.</style></author>
										<author><style face="normal" font="default" size="100%">Bassell, G. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Dictenberg@genectr.hunter.cuny.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">926-39</style></pages>
			<volume><style face="normal" font="default" size="100%">14</style></volume>
			<number><style face="normal" font="default" size="100%">6</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dendrites/drug effects/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Models, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fragile X Mental Retardation Protein/chemistry/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fragile X Syndrome/*genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Green Fluorescent Proteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hippocampus/cytology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">In Situ Hybridization, Fluorescence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Kinesin/antagonists & inhibitors</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Knockout</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microscopy, Video</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Biological</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Structure, Tertiary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Pseudopodia/*metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*RNA Transport</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA, Messenger/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sulfuric Acid Esters/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">6</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The function of local protein synthesis in synaptic plasticity and its dysregulation in fragile X syndrome (FXS) is well studied, however the contribution of regulated mRNA transport to this function remains unclear. We report a function for the fragile X mental retardation protein (FMRP) in the rapid, activity-regulated transport of mRNAs important for synaptogenesis and plasticity. mRNAs were deficient in glutamatergic signaling-induced dendritic localization in neurons from Fmr1 KO mice, and single mRNA particle dynamics in live neurons revealed diminished kinesis. Motor-dependent translocation of FMRP and cognate mRNAs involved the C terminus of FMRP and kinesin light chain, and KO brain showed reduced kinesin-associated mRNAs. Acute suppression of FMRP and target mRNA transport in WT neurons resulted in altered filopodia-spine morphology that mimicked the FXS phenotype. These findings highlight a mechanism for stimulus-induced dendritic mRNA transport and link its impairment in a mouse model of FXS to altered developmental morphologic plasticity.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18539120 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>600</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Rajendra, T. K.</style></author>
										<author><style face="normal" font="default" size="100%">Gonsalvez, G. B.</style></author>
										<author><style face="normal" font="default" size="100%">Walker, M. P.</style></author>
										<author><style face="normal" font="default" size="100%">Shpargel, K. B.</style></author>
										<author><style face="normal" font="default" size="100%">Salz, H. K.</style></author>
										<author><style face="normal" font="default" size="100%">Matera, A. G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Genetics, Case Western Reserve University School of Medicine, Cleveland, OH 44106.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">831-41</style></pages>
			<volume><style face="normal" font="default" size="100%">176</style></volume>
			<number><style face="normal" font="default" size="100%">6</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2007</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Mutations in human survival motor neurons 1 (SMN1) cause spinal muscular atrophy (SMA) and are associated with defects in assembly of small nuclear ribonucleoproteins (snRNPs) in vitro. However, the etiological link between snRNPs and SMA is unclear. We have developed a Drosophila melanogaster system to model SMA in vivo. Larval-lethal Smn-null mutations show no detectable snRNP reduction, making it unlikely that these animals die from global snRNP deprivation. Hypomorphic mutations in Smn reduce dSMN protein levels in the adult thorax, causing flightlessness and acute muscular atrophy. Mutant flight muscle motoneurons display pronounced axon routing and arborization defects. Moreover, Smn mutant myofibers fail to form thin filaments and phenocopy null mutations in Act88F, which is the flight muscle-specific actin isoform. In wild-type muscles, dSMN colocalizes with sarcomeric actin and forms a complex with alpha-actinin, the thin filament crosslinker. The sarcomeric localization of Smn is conserved in mouse myofibrils. These observations suggest a muscle-specific function for SMN and underline the importance of this tissue in modulating SMA severity.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17353360 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>937</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Mullender, M.</style></author>
										<author><style face="normal" font="default" size="100%">Blom, N.</style></author>
										<author><style face="normal" font="default" size="100%">De Kleuver, M.</style></author>
										<author><style face="normal" font="default" size="100%">Fock, J.</style></author>
										<author><style face="normal" font="default" size="100%">Hitters, W.</style></author>
										<author><style face="normal" font="default" size="100%">Horemans, A.</style></author>
										<author><style face="normal" font="default" size="100%">Kalkman, C.</style></author>
										<author><style face="normal" font="default" size="100%">Pruijs, J.</style></author>
										<author><style face="normal" font="default" size="100%">Timmer, R.</style></author>
										<author><style face="normal" font="default" size="100%">Titarsolej, P.</style></author>
										<author><style face="normal" font="default" size="100%">Van Haasteren, N.</style></author>
										<author><style face="normal" font="default" size="100%">Jager, M. V.</style></author>
										<author><style face="normal" font="default" size="100%">Van Vught, A.</style></author>
										<author><style face="normal" font="default" size="100%">Van Royen, B.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Dept, Orthopaedic Surgery, Vrije Universiteit Medical Center (VUmc), Research Institute MOVE, Amsterdam, The Netherlands. m.mullender@vumc.nl.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A Dutch guideline for the treatment of scoliosis in neuromuscular disorders</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">14</style></pages>
			<volume><style face="normal" font="default" size="100%">3</style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">ABSTRACT: BACKGROUND: Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care. METHODS: The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence. RESULTS: For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands. CONCLUSION: In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18822133 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>510</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Pyatt, R. E.</style></author>
										<author><style face="normal" font="default" size="100%">Prior, T. W.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pathology, Ohio State University, Columbus, Ohio 43210, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A feasibility study for the newborn screening of spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">428-37</style></pages>
			<volume><style face="normal" font="default" size="100%">8</style></volume>
			<number><style face="normal" font="default" size="100%">7</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">7</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">PURPOSE: The natural history of spinal muscular atrophy suggests that for maximum effect, therapeutics will need to be administered in the earliest phases of the disease. This will require the adoption of techniques for the genetic analysis of affected individuals at the newborn stage. Our objective was to examine the feasibility surrounding the newborn screening for spinal muscular atrophy. METHODS: We investigated the application of real-time polymerase chain reaction technology for newborn screening. A multiplex assay was designed to identify homozygous deletions in SMN1 exon 7 and validated using 266 samples with defined SMN1 and SMN2 copy numbers. Sensitivity and specificity were then evaluated as part of a newborn screening strategy using DNA from 153 blood spots. RESULTS: Real-time technology validation demonstrated correct exclusion of all normal and carrier samples, and identified the homozygous SMN1 exon 7 deletions in all 32 affected samples. In the series of blood spots, all 59 affected samples were correctly identified yielding an analytic sensitivity of 100%; 56 normal and 39 carrier samples were correctly excluded yielding an analytic specificity of 100% for this blood spot series. CONCLUSION: We demonstrate that effective molecular technology exists and that ethics may soon warrant the newborn screening of spinal muscular atrophy.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16845275 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1422</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Hirano, M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Columbia University Medical Center, 630 West 168th Street, P&S 4-423, New York, NY 10032, USA. mh29@columbia.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A first step in viral gene therapy for muscular dystrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">71-2</style></pages>
			<volume><style face="normal" font="default" size="100%">10</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">3</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20425230 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>247</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Kelley, B. P.</style></author>
										<author><style face="normal" font="default" size="100%">Lunn, M. R.</style></author>
										<author><style face="normal" font="default" size="100%">Root, D. E.</style></author>
										<author><style face="normal" font="default" size="100%">Flaherty, S. P.</style></author>
										<author><style face="normal" font="default" size="100%">Martino, A. M.</style></author>
										<author><style face="normal" font="default" size="100%">Stockwell, B. R.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Biological Sciences, Columbia University, Fairchild Center, MC 2406, 1212 Amsterdam Avenue, New York, NY 10027 USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A flexible data analysis tool for chemical genetic screens</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1495-503</style></pages>
			<volume><style face="normal" font="default" size="100%">11</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Databases, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Drug Evaluation, Preclinical</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Flavonoids/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genes, Reporter</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Software</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2004</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">High-throughput assays generate immense quantities of data that require sophisticated data analysis tools. We have created a freely available software tool, SLIMS (Small Laboratory Information Management System), for chemical genetics which facilitates the collection and analysis of large-scale chemical screening data. Compound structures, physical locations, and raw data can be loaded into SLIMS. Raw data from high-throughput assays are normalized using flexible analysis protocols, and systematic spatial errors are automatically identified and corrected. Various computational analyses are performed on tested compounds, and dilution-series data are processed using standard or user-defined algorithms. Finally, published literature associated with active compounds is automatically retrieved from Medline and processed to yield potential mechanisms of actions. SLIMS provides a framework for analyzing high-throughput assay data both as a laboratory information management system and as a platform for experimental analysis.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15556000 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>968</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Ogunnika, O. T.</style></author>
										<author><style face="normal" font="default" size="100%">Scharfstein, M.</style></author>
										<author><style face="normal" font="default" size="100%">Cooper, R. C.</style></author>
										<author><style face="normal" font="default" size="100%">Ma, H.</style></author>
										<author><style face="normal" font="default" size="100%">Dawson, J. L.</style></author>
										<author><style face="normal" font="default" size="100%">Rutkove, S. B.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Microsystems Technology Laboratory, Massachusetts Institute of Technology, Cambridge, 02139 USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A Handheld Electrical Impedance Myography probe for the assessment of neuromuscular disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">3566-9</style></pages>
			<volume><style face="normal" font="default" size="100%">1</style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Electrical Impedance Myography (EIM) is a non-invasive, painless clinical technique for the diagnosis and monitoring of a variety of neuromuscular diseases including amyotrophic lateral sclerosis and focal nerve injuries. It involves the application of a low-intensity alternating current to a muscle group and the measurement of the consequent surface voltage patterns. This paper presents a system for the rapid and accurate acquisition of data employing an interrogating signal composed of multiple tones with frequencies between 10 kHz and 4 MHz. The use of this composite signal makes possible measurement of impedance at multiple frequencies simultaneously. In addition, this system takes impedance measurements at multiple orientations with respect to the muscle fibers by means of an electronically reconfigurable electrode array and utilizes the linearity of muscle tissue to reduce the required measurement time. Testing of the EIM system on beef has established the capability of this system to rapidly detect the anisotropic conductive properties of muscle tissue at multiple frequencies.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19163479 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>503</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Bandyopadhyay, S.</style></author>
										<author><style face="normal" font="default" size="100%">Ni, J.</style></author>
										<author><style face="normal" font="default" size="100%">Ruggiero, A.</style></author>
										<author><style face="normal" font="default" size="100%">Walshe, K.</style></author>
										<author><style face="normal" font="default" size="100%">Rogers, M. S.</style></author>
										<author><style face="normal" font="default" size="100%">Chattopadhyay, N.</style></author>
										<author><style face="normal" font="default" size="100%">Glicksman, M. A.</style></author>
										<author><style face="normal" font="default" size="100%">Rogers, J. T.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Neurochemistry Laboratory, Genetics and Aging Research Unit, Psychiatry Department, Massachusetts General Hospital, Boston, MA, USA, and School of Biological and Environmental Science, University College Dublin, Belfield, Ireland.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A high-throughput drug screen targeted to the 5'untranslated region of Alzheimer amyloid precursor protein mRNA</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">469-80</style></pages>
			<volume><style face="normal" font="default" size="100%">11</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">8</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The authors employed a novel approach to identify therapeutics effective in Alzheimer disease (AD). The 5'untranslated region (5'UTR) of the mRNA of AD amyloid precursor protein (APP) is a significant regulator of the levels of the APP holoprotein and amyloid beta (Abeta) peptide in the central nervous system. The authors generated stable neuroblastoma SH-SY5Y transfectants that express luciferase under the translational control of the 146-nucleotide APP mRNA 5'UTR and green fluorescent protein (GFP) driven by a viral internal ribosomal entry site. Using a high-throughput screen (HTS), they screened for the effect of 110,000 compounds obtained from the library of the Laboratory for Drug Discovery on Neurodegeneration (LDDN) on the APP mRNA 5'UTR-controlled translation of the luciferase reporter. This screening yielded several nontoxic specific inhibitors of APP mRNA 5'UTR-driven luciferase that had no effect on the GFP expression in the stable SH-SY5Y transfectants. Moreover, these compounds either did not inhibit or inhibited to a much lower extent the expression of the luciferase reporter regulated by a prion protein (PrP) mRNA 5'UTR, used as an alternative mRNA structure to counterscreen APP mRNA 5'UTR in stably transfected SH-SY5Y cell lines. The hits obtained from this robust, specific, and highly quantitative HTS will be characterized to identify agents that may be developed into useful future therapeutic agents to limit APP translation and Abeta production for AD.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16928984 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1319</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Pronicki, M.</style></author>
										<author><style face="normal" font="default" size="100%">Kowalski, P.</style></author>
										<author><style face="normal" font="default" size="100%">Piekutowska-Abramczuk, D.</style></author>
										<author><style face="normal" font="default" size="100%">Taybert, J.</style></author>
										<author><style face="normal" font="default" size="100%">Karkucinska-Wieckowska, A.</style></author>
										<author><style face="normal" font="default" size="100%">Szymanska-Debinska, T.</style></author>
										<author><style face="normal" font="default" size="100%">Karczmarewicz, E.</style></author>
										<author><style face="normal" font="default" size="100%">Pajdowska, M.</style></author>
										<author><style face="normal" font="default" size="100%">Migdal, M.</style></author>
										<author><style face="normal" font="default" size="100%">Milewska-Bobula, B.</style></author>
										<author><style face="normal" font="default" size="100%">Sykut-Cegielska, J.</style></author>
										<author><style face="normal" font="default" size="100%">Popowska, E.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pathology, Children's Memorial Health Institute, 04-730 Warsaw, Poland.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A homozygous mutation in the SCO2 gene causes a spinal muscular atrophy like presentation with stridor and respiratory insufficiency</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Infants with deficiency of cytochrome c oxidase (COX) due to SCO2 mutations observed so far usually demonstrated early cardiomyopathy, encephalopathy and lactic acidosis. Milder spinal muscular atrophy-like (SMA-like) phenotype was also rarely reported. The aim is to present 18 Polish patients with SCO2 mutations. Molecular study revealed p.E140K mutation in all cases (on 32 alleles); p.Q53X mutation and novel p.M177T change were identified in single patients. In three families no second mutation was found. Thirteen p.E140K homozygotes presented in infancy with floppiness and remarkable stridor. Survival motor neuron (SMN) gene deletion was excluded. Mild to moderate lactic academia was found. Neurological involvement manifested as spasticity and psychomotor retardation. In some patients strabismus, ptosis and episodes of seizures were seen. During second half of the year chronic respiratory failure with artificial respiration dependency appeared in all homozygotes. Heart involvement was never present at the beginning. Rapidly progressive hypertrophic cardiomyopathy developed in several patients at the terminal stage. The stridor was constant and striking feature. Skeletal muscle biopsy was performed in 16 patients including 11 homozygotes. Four pathological patterns were discerned - from neurogenic muscle changes, including spinal muscular atrophy (SMA) to unspecific findings. Histochemical cytochrome c oxidase (COX) deficit was not a constant feature. Significant decrease in respiratory chain complex IV activity was detected in muscle homogenate by spectrophotometric method only in 7 out of 12 examined cases. CONCLUSIONS: 1/Mutations of SCO2 gene should be considered as a possible cause of neurogenic skeletal muscle features (including SMA-like) in infants with encephalomyopathy even in the absence of heart involvement and COX deficit; 2/Inspiratory stridor may be symptomatic of SCO2 gene mutation(s).</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19879173 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>417</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Fehlbaum, P.</style></author>
										<author><style face="normal" font="default" size="100%">Guihal, C.</style></author>
										<author><style face="normal" font="default" size="100%">Bracco, L.</style></author>
										<author><style face="normal" font="default" size="100%">Cochet, O.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">ExonHit Therapeutics, 63/65 boulevard Massena, 75013 Paris, France.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A microarray configuration to quantify expression levels and relative abundance of splice variants</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">e47</style></pages>
			<volume><style face="normal" font="default" size="100%">33</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">*Alternative Splicing</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression Profiling/*methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Introns</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Oligonucleotide Array Sequence Analysis/*methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Oligonucleotide Probes/chemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Isoforms/analysis/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Over the past decade, alternative RNA splicing has raised a great interest appearing to be of high importance in the generation of expression diversity. This regulatory process plays a critical role in the normal development and its impact on the initiation and development of human disorders as well as on the pharmacological properties of drugs is increasingly being recognized. Only few studies describe specific alternative splicing expression profiling. Microarray strategies have been conceived to address alternative splicing events but with very few experimental data related to their abilities to provide true quantification values. We have developed a specific microarray configuration relying on a few, well optimized probes per splice event. Basically, five probes of 24mer are used to fully characterize a splice event. These probes are of two types, exon probes and junction probes, and are either specific to a splice event or not. The performances of such a 'splice array' were validated on synthetic model systems and on complex biological materials. The results indicate that DNA chips based on this design combining exon and junction derived probes enable the detection and, absolute and relative quantification of splice variants. In addition, this strategy is compatible with all the microarrays that use oligonucleotide probes.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15760843 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>487</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Krosschell, K. J.</style></author>
										<author><style face="normal" font="default" size="100%">Maczulski, J. A.</style></author>
										<author><style face="normal" font="default" size="100%">Crawford, T. O.</style></author>
										<author><style face="normal" font="default" size="100%">Scott, C.</style></author>
										<author><style face="normal" font="default" size="100%">Swoboda, K. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Suite 1100, 645 North Michigan Avenue, Chicago, IL 60611, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A modified Hammersmith functional motor scale for use in multi-center research on spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The Hammersmith functional motor scale for children with spinal muscular atrophy was modified to establish a standard measure of functional ability in children with non-ambulant spinal muscular atrophy types 2 and 3 in a longitudinal multi-center clinical trial. This study assessed the intra- and interrater reliability and the test-retest stability of a modified version of the scale. Both intra- and interrater reliability were established. Results indicate that the scale is reliable and stable over a 6 month period. Reliability was maintained when patient sample criteria were expanded to include children younger than 30 months and children with popliteal angles greater than 20 degrees . These data establish the modified Hammersmith functional motor scale for children with spinal muscular atrophy as a reliable instrument for use in multi-center treatment trials in non-ambulant spinal muscular atrophy children. Our data provides additional support for the use of original scale items in terms of ease of administration, usefulness and reliability, while incorporating modifications to optimize its use in a multi-center clinical research setting.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16750368 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1002</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Cauchi, R. J.</style></author>
										<author><style face="normal" font="default" size="100%">Davies, K. E.</style></author>
										<author><style face="normal" font="default" size="100%">Liu, J. L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Physiology, Medical Research Council Functional Genomics Unit, University of Oxford, Oxford, United Kingdom.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A motor function for the DEAD-box RNA helicase, Gemin3, in Drosophila</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">e1000265</style></pages>
			<volume><style face="normal" font="default" size="100%">4</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DEAD Box Protein 20/genetics/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DEAD-box RNA Helicases/genetics/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Drosophila melanogaster/embryology/*enzymology/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Larva/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/*enzymology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Survival of Motor Neuron 1 Protein/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transgenes</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The survival motor neuron (SMN) protein, the determining factor for spinal muscular atrophy (SMA), is complexed with a group of proteins in human cells. Gemin3 is the only RNA helicase in the SMN complex. Here, we report the identification of Drosophila melanogaster Gemin3 and investigate its function in vivo. Like in vertebrates, Gemin3 physically interacts with SMN in Drosophila. Loss of function of gemin3 results in lethality at larval and/or prepupal stages. Before they die, gemin3 mutant larvae exhibit declined mobility and expanded neuromuscular junctions. Expression of a dominant-negative transgene and knockdown of Gemin3 in mesoderm cause lethality. A less severe Gemin3 disruption in developing muscles leads to flightless adults and flight muscle degeneration. Our findings suggest that Drosophila Gemin3 is required for larval development and motor function.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19023405 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1301</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Berard, C.</style></author>
										<author><style face="normal" font="default" size="100%">Payan, C.</style></author>
										<author><style face="normal" font="default" size="100%">Hodgkinson, I.</style></author>
										<author><style face="normal" font="default" size="100%">Fermanian, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Paediatric Rehabilitation, l'Escale, Centre Hospitalier Lyon-Sud, France. carole.berard@chu-lyon.fr</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A motor function measure for neuromuscular diseases. Construction and validation study</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">463-70</style></pages>
			<volume><style face="normal" font="default" size="100%">15</style></volume>
			<number><style face="normal" font="default" size="100%">7</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adolescent</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Disability Evaluation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Extremities/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Factor Analysis, Statistical</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Activity/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neuromuscular Diseases/classification/*physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Pain Measurement</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Predictive Value of Tests</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Reproducibility of Results</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Severity of Illness Index</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Time Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">7</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">A new scale for motor function measurement has been developed for neuromuscular diseases. The validation study included 303 patients, aged 6-62 years. Seventy-two patients had Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30 limb-girdle muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic dystrophy, 21 congenital myopathy, 10 congenital muscular dystrophy, 35 spinal muscular atrophy and 35 hereditary neuropathy. The scale comprised 32 items, in three dimensions: standing position and transfers, axial and proximal motor function, distal motor function. Agreement coefficients for inter-rater reliability were excellent (kappa=0.81-0.94) for nine items, good (kappa=0.61-0.80) for 20 items and moderate (kappa=0.51-0.60) for three items. High correlations were found between the total score and other scores: Vignos (r=0.91) and Brooke (r=0.85) grades, Functional Independence Measure (r=0.91), the global severity of disability evaluated with visual analog scales by physicians (r=0.88) and physiotherapists (r=0.91). This scale is reliable, does not require any special equipment and is well-accepted by patients. Its sensitivity to change is being assessed to permit its use in clinical trials of neuromuscular diseases.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16106528 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>241</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Hsieh-Li, H. M.</style></author>
										<author><style face="normal" font="default" size="100%">Chang, J. G.</style></author>
										<author><style face="normal" font="default" size="100%">Jong, Y. J.</style></author>
										<author><style face="normal" font="default" size="100%">Wu, M. H.</style></author>
										<author><style face="normal" font="default" size="100%">Wang, N. M.</style></author>
										<author><style face="normal" font="default" size="100%">Tsai, C. H.</style></author>
										<author><style face="normal" font="default" size="100%">Li, H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A mouse model for spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">66-70</style></pages>
			<volume><style face="normal" font="default" size="100%">24</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Base Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DNA Primers</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Models, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Transgenic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Reverse Transcriptase Polymerase Chain Reaction</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transgenes</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2000</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10615130 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>578</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">McManamny, P.</style></author>
										<author><style face="normal" font="default" size="100%">Chy, H.S.</style></author>
										<author><style face="normal" font="default" size="100%">Finkelstein, D.I.</style></author>
										<author><style face="normal" font="default" size="100%">Craythorn, R.G.</style></author>
										<author><style face="normal" font="default" size="100%">Crack, P.J.</style></author>
										<author><style face="normal" font="default" size="100%">Kola, I.</style></author>
										<author><style face="normal" font="default" size="100%">Cheema, S.S.</style></author>
										<author><style face="normal" font="default" size="100%">Horne, M.K.</style></author>
										<author><style face="normal" font="default" size="100%">Wreford, N.G.</style></author>
										<author><style face="normal" font="default" size="100%">O'Bryan, M.K.</style></author>
										<author><style face="normal" font="default" size="100%">De Kretser, D.M.</style></author>
										<author><style face="normal" font="default" size="100%">Morrison, J.R.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%"></style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A mouse model of spinal and bulbar muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">2103-2011</style></pages>
			<volume><style face="normal" font="default" size="100%">11</style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2002</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1306</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Freeman, W. M.</style></author>
										<author><style face="normal" font="default" size="100%">Bixler, G. V.</style></author>
										<author><style face="normal" font="default" size="100%">Brucklacher, R. M.</style></author>
										<author><style face="normal" font="default" size="100%">Lin, C. M.</style></author>
										<author><style face="normal" font="default" size="100%">Patel, K. M.</style></author>
										<author><style face="normal" font="default" size="100%">Vanguilder, H. D.</style></author>
										<author><style face="normal" font="default" size="100%">Lanoue, K. F.</style></author>
										<author><style face="normal" font="default" size="100%">Kimball, S. R.</style></author>
										<author><style face="normal" font="default" size="100%">Barber, A. J.</style></author>
										<author><style face="normal" font="default" size="100%">Antonetti, D. A.</style></author>
										<author><style face="normal" font="default" size="100%">Gardner, T. W.</style></author>
										<author><style face="normal" font="default" size="100%">Bronson, S. K.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">[1] Functional Genomics Core Facility, Penn State College of Medicine, Hershey, PA, USA [2] Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A multistep validation process of biomarkers for preclinical drug development</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Biomarkers that can be measured in preclinical models in a high-throughput, reproducible manner offer the potential to increase the speed and efficacy of drug development. Development of therapeutic agents for many conditions is hampered by the limited number of validated preclinical biomarkers available to gauge pharmacoefficacy and disease progression, but the validation process for preclinical biomarkers has received limited attention. This report defines a five-step preclinical biomarker validation process and applies the process to a case study of diabetic retinopathy. By showing that a gene expression panel is highly reproducible, coincides with disease manifestation, accurately classifies individual animals and identifies animals treated with a known therapeutic agent, a biomarker panel can be considered validated. This particular biomarker panel consisting of 14 genes (C1inh, C1s, Carhsp1, Chi3l1, Gat3, Gbp2, Hspb1, Icam1, Jak3, Kcne2, Lama5, Lgals3, Nppa, Timp1) can be used in diabetic retinopathy pharmacotherapeutic research, and the biomarker development process outlined here is applicable to drug development efforts for other diseases.The Pharmacogenomics Journal advance online publication, 8 December 2009; doi:10.1038/tpj.2009.60.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19997081 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>401</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Ackerley, S.</style></author>
										<author><style face="normal" font="default" size="100%">James, P. A.</style></author>
										<author><style face="normal" font="default" size="100%">Kalli, A.</style></author>
										<author><style face="normal" font="default" size="100%">French, S.</style></author>
										<author><style face="normal" font="default" size="100%">Davies, K. E.</style></author>
										<author><style face="normal" font="default" size="100%">Talbot, K.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Human Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A mutation in the small heat-shock protein HSPB1 leading to distal hereditary motor neuronopathy disrupts neurofilament assembly and the axonal transport of specific cellular cargoes</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">347-54</style></pages>
			<volume><style face="normal" font="default" size="100%">15</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Distal hereditary motor neuronopathies (dHMNs) are a clinically and genetically heterogeneous group of disorders in which motor neurons selectively undergo age-dependant degeneration. Mutations in the small heat-shock protein HSPB1 (HSP27) are responsible for one form of dHMN. In this study, we have analysed the effect of expressing a form of mutant HSPB1 in primary neuronal cells in culture. Mutant (P182L) but not wild-type HSPB1 led to the formation of insoluble intracellular aggregates and to the sequestration in the cytoplasm of selective cellular components, including neurofilament middle chain subunit (NF-M) and p150 dynactin. These findings suggest a possible pathogenic mechanism for HSPB1 whereby the mutation may lead to preferential motor neuron loss by disrupting selective components essential for axonal structure and transport.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16368711 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>116</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Nishimura, A. L.</style></author>
										<author><style face="normal" font="default" size="100%">Mitne-Neto, M.</style></author>
										<author><style face="normal" font="default" size="100%">Silva, H. C.</style></author>
										<author><style face="normal" font="default" size="100%">Richieri-Costa, A.</style></author>
										<author><style face="normal" font="default" size="100%">Middleton, S.</style></author>
										<author><style face="normal" font="default" size="100%">Cascio, D.</style></author>
										<author><style face="normal" font="default" size="100%">Kok, F.</style></author>
										<author><style face="normal" font="default" size="100%">Oliveira, J. R.</style></author>
										<author><style face="normal" font="default" size="100%">Gillingwater, T.</style></author>
										<author><style face="normal" font="default" size="100%">Webb, J.</style></author>
										<author><style face="normal" font="default" size="100%">Skehel, P.</style></author>
										<author><style face="normal" font="default" size="100%">Zatz, M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Human Genome Research Center, Department of Biology, Biosciences Institute, Sao Paulo University, Sao Paulo, Brazil.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">822-31</style></pages>
			<volume><style face="normal" font="default" size="100%">75</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amyotrophic Lateral Sclerosis/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Brazil</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Calcium-Binding Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromosome Mapping</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromosomes, Human, Pair 20/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DNA Primers</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Founder Effect</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Gene Expression</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Green Fluorescent Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Kv Channel-Interacting Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Molecular</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation, Missense/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Pedigree</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Structure, Tertiary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Alignment</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Analysis, DNA</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Vesicular Transport Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2004</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Motor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis. Recently, we have mapped a new locus for an atypical form of ALS/MND (atypical amyotrophic lateral sclerosis [ALS8]) at 20q13.3 in a large white Brazilian family. Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family. Subsequently, the same mutation was identified in patients from six additional kindreds but with different clinical courses, such as ALS8, late-onset SMA, and typical severe ALS with rapid progression. Although it was not possible to link all these families, haplotype analysis suggests a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have been shown to have a function in membrane transport. These data suggest that clinically variable MNDs may be caused by a dysfunction in intracellular membrane trafficking.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15372378 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1037</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Piepers, S.</style></author>
										<author><style face="normal" font="default" size="100%">van den Berg, L. H.</style></author>
										<author><style face="normal" font="default" size="100%">Brugman, F.</style></author>
										<author><style face="normal" font="default" size="100%">Scheffer, H.</style></author>
										<author><style face="normal" font="default" size="100%">Ruiterkamp-Versteeg, M.</style></author>
										<author><style face="normal" font="default" size="100%">van Engelen, B. G.</style></author>
										<author><style face="normal" font="default" size="100%">Faber, C. G.</style></author>
										<author><style face="normal" font="default" size="100%">de Visser, M.</style></author>
										<author><style face="normal" font="default" size="100%">van der Pol, W. L.</style></author>
										<author><style face="normal" font="default" size="100%">Wokke, J. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Dept. of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, HP G 02.320, 85500, 3508, GA Utrecht, The Netherlands. s.piepers-2@umcutrecht.nl</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A natural history study of late onset spinal muscular atrophy types 3b and 4</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1400-4</style></pages>
			<volume><style face="normal" font="default" size="100%">255</style></volume>
			<number><style face="normal" font="default" size="100%">9</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adolescent</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Age of Onset</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Progression</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fatigue/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Follow-Up Studies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Dosage</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Genetic Predisposition to Disease</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle Weakness/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/classification/epidemiology/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Netherlands/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Prospective Studies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Quality of Life</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Respiratory Insufficiency/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">SMN Complex Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Survival of Motor Neuron 1 Protein/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Time Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">9</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: Spinal muscular atrophy (SMA) is caused by a homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene plays a disease modifying role. SMA is classified into four different subtypes based on age of onset and clinical course (SMA types 1-4). The natural history of early onset SMA types 1-3a has been studied extensively. Late onset SMA is rare and disease course has not been studied in detail. OBJECTIVE: To perform a prospective study on the clinical course and the correlation with SMN2 copy numbers of late onset SMA. METHODS: Patients fulfilling the diagnostic criteria for late onset SMA (types 3b and 4) were included in the study. At inclusion and follow-up, muscle strength, respiratory function, functional status and quality of life were assessed. SMN2 copy number was determined in all patients. RESULTS: Twelve patients were identified and included. Six patients were siblings from one family, two patients were brothers from a second family and four patients were sporadic cases. All patients carried four copies of the SMN2 gene. Median age of disease onset was 22.2 years (10-37). Age of disease onset in patients from family one was lower as compared to the other patients. None of the outcome measures changed after a follow-up of 2.5 years. Five patients reported an increase in fatigue and muscle weakness. None of the patients showed symptoms of respiratory insufficiency. CONCLUSIONS: This study indicates that late onset SMA is not characterized by disease progression and that alternative or surrogate disease markers are required for the design of future trials. This study confirms the finding that SMN2 copy number is a SMA disease course modifier.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18575920 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>104</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Kashima, T.</style></author>
										<author><style face="normal" font="default" size="100%">Manley, J. L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Biological Sciences, Columbia University, New York, New York 10027, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A negative element in SMN2 exon 7 inhibits splicing in spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">460-3</style></pages>
			<volume><style face="normal" font="default" size="100%">34</style></volume>
			<number><style face="normal" font="default" size="100%">4</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Base Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Enhancer Elements (Genetics)</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hela Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA Interference</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA Splicing/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Silencer Elements, Transcriptional</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transfection</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2003</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">8</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a relatively common neurodegenerative disease caused by homozygous loss of the survival motor neuron 1 (SMN1) gene. Humans possess a linked, nearly identical gene, SMN2, which produces a functional SMN protein but at levels insufficient to compensate for loss of SMN1 (refs. 1,2). A C/T transition at position +6 in exon 7 is all that differentiates the two genes, but this is sufficient to prevent efficient exon 7 splicing in SMN2 (refs. 2,3). Here we show that the C/T transition functions not to disrupt an exonic splicing enhancer (ESE) in SMN1 (ref. 4), as previously suggested, but rather to create an exonic splicing silencer (ESS) in SMN2. We show that this ESS functions as a binding site for a known repressor protein, hnRNP A1, which binds to SMN2 but not SMN1 exon 7 RNA. We establish the physiological importance of these results by using small interfering RNAs to reduce hnRNP A protein levels in living cells and show that this results in efficient SMN2 exon 7 splicing. Our findings not only define a new mechanism underlying the inefficient splicing of SMN2 exon 7 but also illustrate more generally the remarkable sensitivity and precision that characterizes control of mRNA splicing.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12833158 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>914</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Dickson, A.</style></author>
										<author><style face="normal" font="default" size="100%">Osman, E.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">University of Missouri, Molecular Microbiology and Immunology, COLUMBIA, Missouri, United States; amtpn7@missouri.edu.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A Negatively-Acting Bifunctional RNA Increases Survival Motor Neuron in vitro and in vivo</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder and is the leading genetic cause of infant mortality. SMA is caused by the loss of survival motor neuron-1 (SMN1). In humans, a nearly identical copy gene is present called SMN2, but this gene cannot compensate for the loss of SMN1 due to a single silent nucleotide difference in SMN2 exon 7. This single nucleotide difference attenuates an exonic splice enhancer, resulting in the production of an alternatively spliced isoform lacking exon 7, which is essential for protein function. SMN2, however, is a critical disease modifier and is an outstanding target for therapeutic intervention since all SMA patients retain SMN2 and SMN2 maintains the same coding sequence as SMN1. Therefore, compounds or molecules that increase SMN2 exon 7 inclusion hold great promise for SMA therapeutics. Bifunctional RNAs have been previously utilized to increase SMN protein levels and derive their name from the presence of two domains: an antisense RNA sequence specific to the target RNA and an untethered RNA segment that serves as a binding platform for splicing factors. This study was designed to develop negatively-acting bifunctional RNAs that recruit hnRNPA1 to exon 8 and block the general splicing machinery from the exon 8. By blocking the downstream splice site, this could competitively favor the inclusion of SMN exon 7 and therefore increase full-length SMN production. Here we identify a bifunctional RNA that stimulated full-length SMN expression in a variety of cell-based assays including SMA patient fibroblasts. Importantly, this molecule was also able to induce SMN expression in a previously described mouse model of SMA and demonstrates a novel therapeutic approach for SMA as well as a variety of diseases caused by a defect in splicing.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18724800 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>716</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Eggermann, T.</style></author>
										<author><style face="normal" font="default" size="100%">Eggermann, K.</style></author>
										<author><style face="normal" font="default" size="100%">Elbracht, M.</style></author>
										<author><style face="normal" font="default" size="100%">Zerres, K.</style></author>
										<author><style face="normal" font="default" size="100%">Rudnik-Schoneborn, S.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute of Human Genetics, Technical University of Aachen, Pauwelsstr. 30, D-52074 Aachen, Germany.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A new splice site mutation in the SMN1 gene causes discrepant results in SMN1 deletion screening approaches</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2007</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">In most patients with infantile spinal muscular atrophy (SMA) both exons 7 and 8 of the SMN1 gene are deleted, but the deletion may also be restricted to exon 7. We report on an SMA type I patient who was initially diagnosed to be homozygous for an exon 7 deletion only. However, multiplex ligation-dependent probe amplification (MLPA) analyses revealed a heterozygous deletion of exons 7 and 8 of the SMN1 gene. By sequencing a new subtle splice site mutation (IVS6-2A>G) was identified. This variant affects the target sequence of oligonucleotides of all applied tests in a way that it has contrary effects on the efficiencies of the different assays. The results have major impacts on genetic counselling and carrier detection of the patient's paternal relatives.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18155522 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>299</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Wolstencroft, E. C.</style></author>
										<author><style face="normal" font="default" size="100%">Mattis, V.</style></author>
										<author><style face="normal" font="default" size="100%">Bajer, A. A.</style></author>
										<author><style face="normal" font="default" size="100%">Young, P. J.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C. L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211-7310, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1199-210</style></pages>
			<volume><style face="normal" font="default" size="100%">14</style></volume>
			<number><style face="normal" font="default" size="100%">9</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Alanine/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amikacin/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Aminoglycosides/*metabolism/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Anti-Bacterial Agents/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Antibodies, Monoclonal/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Western</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Codon, Terminator</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Epithelial Cells/drug effects/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fibroblasts/drug effects/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fluorescein-5-isothiocyanate</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fluorescent Antibody Technique</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fluorescent Dyes</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Deletion</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hela Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Homozygote</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Indoles</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Kinetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/deficiency/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, N.I.H., Extramural</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tissue Distribution</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tobramycin/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transcription, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is caused by homozygous loss of the survival motor neuron (SMN1) gene. In virtually all SMA patients, a nearly identical copy gene is present, SMN2. SMN2 cannot fully compensate for the loss of SMN1 because the majority of transcripts derived from SMN2 lack a critical exon (exon 7), resulting in a dysfunctional SMN protein. Therefore, the critical distinction between a functional and a dysfunctional SMN protein is the inclusion or the exclusion of the exon 7 encoded peptide. To determine the role of the 16 amino acids encoded by SMN exon 7, a panel of synthetic mutations were transiently expressed in SMA patient fibroblasts and HeLa cells. Consistent with previous reports, the protein encoded by SMN exons 1-6 was primarily restricted to the nucleus. However, a variety of heterologous sequences fused to the C-terminus of SMN exons 1-6 allowed mutant SMN proteins to properly distribute to the cytoplasm and to the nuclear gems. These data demonstrate that the SMN exon 7 sequence is not specifically required, rather this region functions as a non-specific 'tail' that facilitates proper localization. Therefore, a possible means to restore additional activity to the SMNDelta7 protein could be to induce a longer C-terminus by suppressing recognition of the native stop codon. To address this possibility, aminoglycosides were examined for their ability to restore detectable levels of SMN protein in SMA patient fibroblasts. Aminoglycosides can suppress the accurate identification of translation termination codons in eukaryotic cells. Consistent with this, treatment of SMA patient fibroblasts with tobramycin and amikacin resulted in a quantitative increase in SMN-positive gems and an overall increase in detectable SMN protein. Taken together, this work describes the role of the critical exon 7 region and identifies a possible alternative approach for therapeutic intervention.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15790598 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>158</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Lefebvre, S.</style></author>
										<author><style face="normal" font="default" size="100%">Burlet, P.</style></author>
										<author><style face="normal" font="default" size="100%">Viollet, L.</style></author>
										<author><style face="normal" font="default" size="100%">Bertrandy, S.</style></author>
										<author><style face="normal" font="default" size="100%">Huber, C.</style></author>
										<author><style face="normal" font="default" size="100%">Belser, C.</style></author>
										<author><style face="normal" font="default" size="100%">Munnich, A.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">INSERM U393, IRNEM Institute, Hopital Necker-Enfants Malades, 149 Rue de Sevres, 75743 Paris Cedex 15, France. lefebvre@necker.fr</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel association of the SMN protein with two major non-ribosomal nucleolar proteins and its implication in spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1017-27</style></pages>
			<volume><style face="normal" font="default" size="100%">11</style></volume>
			<number><style face="normal" font="default" size="100%">9</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Antineoplastic Agents/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">COS Cells/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Nucleolus/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fibroblasts/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fluorescent Antibody Technique, Indirect</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Frameshift Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunoblotting</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microscopy, Confocal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mimosine/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nocodazole/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nuclear Proteins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nucleolus Organizer Region/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Phosphoproteins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Precipitin Tests</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Recombinant Fusion Proteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transfection</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2002</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is caused by the loss of functional survival motor neuron 1 (SMN1) protein. This ubiquitously expressed protein is a component of a novel complex immunodetected in both the cytoplasm and the nucleus, which is associated with complexes involved in mRNA splicing, ribosome biogenesis and transcription. Here, we study a mutant protein corresponding to the N-terminal half of the protein that is encoded by the SMA frameshift mutation SMN 472del5. We show by confocal microscopy that the resulting mutant protein exhibits various distribution patterns in different transiently transfected COS cells. The mutant distributes into the nucleoplasm and/or the nucleolus, whereas the normal SMN protein accumulates at discrete nucleocytoplasmic dot-like structures previously named gems/Cajal bodies. The cell population with the nucleolar distribution is enriched upon treatment with mimosine, a synchronizing drug in late G(1) phase. Co-immunoprecipitation studies carried out on nuclear extracts reveal that both the endogenous SMN and mutant proteins are associated with complexes containing two major non-ribosomal nucleolar proteins, namely nucleolin and protein B23, and that the association is mediated, by among other things, RNA moieties. Both the association of the SMN protein with nucleolin-containing complexes and the nucleolin/B23 complex are disrupted in fibroblasts derived from a type I SMA patient harboring a homozygous SMN1 gene deletion. These findings suggest that altered assembly and/or stability of ribonucleoprotein complexes may contribute to the pathophysiological processes in SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11978761 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>339</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Kolb, S. J.</style></author>
										<author><style face="normal" font="default" size="100%">Gubitz, A. K.</style></author>
										<author><style face="normal" font="default" size="100%">Olszewski, R. F., Jr.</style></author>
										<author><style face="normal" font="default" size="100%">Ottinger, E.</style></author>
										<author><style face="normal" font="default" size="100%">Sumner, C. J.</style></author>
										<author><style face="normal" font="default" size="100%">Fischbeck, K. H.</style></author>
										<author><style face="normal" font="default" size="100%">Dreyfuss, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Howard Hughes Medical Institute And Department of Biochemistry & Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA. skolb@mail.med.upenn.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel cell immunoassay to measure survival of motor neurons protein in blood cells</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">6</style></pages>
			<volume><style face="normal" font="default" size="100%">6</style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: The motor neuron degenerative disease spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality and is caused by mutations in the survival of motor neurons (SMN) gene that reduce the expression levels of the SMN protein. A major goal of current therapeutic approaches is to increase SMN levels in SMA patients. The purpose of this study was to develop a reliable assay to measure SMN protein levels from peripheral blood samples. METHODS: We developed a novel cell immunoassay to quantitatively measure SMN levels from peripheral blood mononuclear cells (PBMCs) using a single anti-SMN antibody. RESULTS: SMN levels determined by the cell immunoassay are comparable to levels determined by Western blot, but in contrast, the immunoassay does not involve cell lysis, requires a small amount of patient material, and can be done on a large number of samples simultaneously. SMN levels from PBMCs are not influenced by cell type heterogeneity. CONCLUSION: SMN levels measured from total PBMCs provide an important snapshot of SMN protein expression, which should be a useful aid in SMA diagnosis, and a surrogate marker of efficacy of treatment in SMA clinical trials.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16451734 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>174</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Pellizzoni, L.</style></author>
										<author><style face="normal" font="default" size="100%">Kataoka, N.</style></author>
										<author><style face="normal" font="default" size="100%">Charroux, B.</style></author>
										<author><style face="normal" font="default" size="100%">Dreyfuss, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">615-24</style></pages>
			<volume><style face="normal" font="default" size="100%">95</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Autoantigens/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hela Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microscopy, Fluorescence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nuclear Proteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Open Reading Frames</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Organelles/metabolism/ultrastructure</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Phosphoproteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA Precursors/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*RNA Splicing</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ribonucleoproteins, Small Nuclear/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spliceosomes/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1998</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a common motor neuron degenerative disease that results from reduced levels of, or mutations in, the Survival of Motor Neurons (SMN) protein. SMN is found in the cytoplasm and the nucleus where it is concentrated in gems. SMN interacts with spliceosomal snRNP proteins and is critical for snRNP assembly in the cytoplasm. We show that a dominant-negative mutant SMN (SMNdeltaN27) causes a dramatic reorganization of snRNPs in the nucleus. Furthermore, SMNdeltaN27 inhibits pre-mRNA splicing in vitro, while wild-type SMN stimulates splicing. SMN mutants found in SMA patients cannot stimulate splicing. These findings demonstrate that SMN plays a crucial role in the generation of the pre-mRNA splicing machinery and thus in mRNA biogenesis, and they link the function of SMN in this pathway to SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9845364 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>582</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Butchbach, M. E.</style></author>
										<author><style face="normal" font="default" size="100%">Edwards, J. D.</style></author>
										<author><style face="normal" font="default" size="100%">Schussler, K. R.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Molecular and Cellular Biochemistry, College of Medicine, Ohio State University, 363 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel method for oral delivery of drug compounds to the neonatal SMNDelta7 mouse model of spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a devastating motor neuron disease that is one of the leading genetic causes of infant mortality. Currently, there is no cure for SMA. Mouse models that genetically and phenotypically resemble SMA have been generated and have the potential to be used for the discovery of novel therapeutics. Oral administration is a commonly used mode of drug delivery in humans as well as in rodents. Unfortunately, there is no method of drug delivery that can accurately and reliably deliver drug compounds orally to neonatal mice. In this report, we describe a novel method to orally administer compounds to neonatal SMA mice. Oral delivery to neonatal mice, usually starting at postnatal day 4 (PND04), is both rapid and safe to the pup. Oral delivery of two different commonly used vehicle formulations, distilled water and 2-hydroxypropyl-beta-cyclodextrin, does not affect the survival of SMA mice. After oral delivery for 3 days, 5-bromo-2'-deoxyuridine could be detected in the kidneys, brains and spinal cords of treated non-SMA as well as SMA neonatal pups. In conclusion, we have developed a method by which drugs can be safely and reliably administered orally to neural targets of neonatal mice. This approach offers a simple and rapid means by which potential therapeutics for SMA can be identified.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17161463 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>165</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Liu, Q.</style></author>
										<author><style face="normal" font="default" size="100%">Dreyfuss, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel nuclear structure containing the survival of motor neurons protein</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">3555-65</style></pages>
			<volume><style face="normal" font="default" size="100%">15</style></volume>
			<number><style face="normal" font="default" size="100%">14</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">3T3 Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Antibodies, Monoclonal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Antibody Specificity</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Nucleus/metabolism/*ultrastructure</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromosomal Proteins, Non-Histone/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fluorescent Antibody Technique, Indirect</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hela Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Heterogeneous-Nuclear Ribonucleoprotein U</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Heterogeneous-Nuclear Ribonucleoproteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Inbred A</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA Processing, Post-Transcriptional</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ribonucleoproteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ribonucleoproteins, Small Nuclear/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spliceosomes/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Xenopus</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1996</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a common, often fatal, autosomal recessive disease leading to progressive muscle wasting and paralysis as a result of degeneration of anterior horn cells of the spinal cord. A gene termed survival of motor neurons (SMN), at 5q13, has been identified as the determining gene of SMA (Lefebvre et al., 1995). The SMN gene is deleted in > 98% of SMA patients, but the function of the SMN protein is unknown. In searching for hnRNP-interacting proteins we found that SMN interacts with the RGG box region of hnRNP U, with itself, with fibrillarin and with several novel proteins. We have produced monoclonal antibodies to the SMN protein, and we report here on its striking cellular localization pattern. Immunolocalization studies using SMN monoclonal antibodies show several intense dots in HeLa cell nuclei. These structures are similar in number (2-6) and size (0.1-1.0 micron) to coiled bodies, and frequently are found near or associated with coiled bodies. We term these prominent nuclear structures gems, for Gemini of coiled bodies.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8670859 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>631</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Yotsumoto, T.</style></author>
										<author><style face="normal" font="default" size="100%">Naitoh, T.</style></author>
										<author><style face="normal" font="default" size="100%">Kanaki, T.</style></author>
										<author><style face="normal" font="default" size="100%">Matsuda, M.</style></author>
										<author><style face="normal" font="default" size="100%">Tsuruzoe, N.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Biological Research Laboratories, Nissan Chemical Industries Ltd, Minamisaitama, Saitama, Japan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel peroxisome proliferator-activated receptor (PPAR)gamma agonist, NIP-222, reduces urinary albumin excretion in streptozotocin-diabetic mice independent of PPARgamma activation</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1633-7</style></pages>
			<volume><style face="normal" font="default" size="100%">52</style></volume>
			<number><style face="normal" font="default" size="100%">12</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Albuminuria/complications/*drug therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Angiotensin-Converting Enzyme Inhibitors/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blood Glucose/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blood Pressure/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Body Weight/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Captopril/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromans/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Diabetes Mellitus, Experimental/*complications/urine</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Diabetes Mellitus, Type 2/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Diabetic Nephropathies/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genes, Reporter/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hypoglycemic Agents/*pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Kidney/drug effects/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Luciferases/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Organ Size/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Plasmids/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Receptors, Cytoplasmic and Nuclear/*agonists/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Thiazolidinediones/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transcription Factors/*agonists/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Urodynamics/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2003</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">12</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">NIP-222 is a novel peroxisome proliferator-activated receptor (PPAR)gamma agonist. This study provides evidence that NIP-222 decreases urinary albumin excretion (UAE) in diabetic mice independent of its PPARgamma activation. We compared the effect of NIP-222 and another PPARgamma agonist, troglitazone, on UAE, plasma glucose level, blood pressure, and creatinine clearance (C(cr)) in streptozotocin (STZ)-induced diabetic mice. Treatment for 3 weeks with NIP-222 (30 mg/kg) was associated with a significant decrease in UAE without any change in blood pressure, creatinine clearance, or plasma glucose level. In contrast, UAE did not decrease in mice treated with troglitazone (300 mg/kg). These results indicate that NIP-222 has PPARgamma independent effects on UAE in diabetic mice and suggest that this agent may have potential to minimize the development and progression of diabetic nephropathy.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14669169 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>915</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Gordon, P. H.</style></author>
										<author><style face="normal" font="default" size="100%">Cheung, Y. K.</style></author>
										<author><style face="normal" font="default" size="100%">Levin, B.</style></author>
										<author><style face="normal" font="default" size="100%">Andrews, H.</style></author>
										<author><style face="normal" font="default" size="100%">Doorish, C.</style></author>
										<author><style face="normal" font="default" size="100%">Macarthur, R. B.</style></author>
										<author><style face="normal" font="default" size="100%">Montes, J.</style></author>
										<author><style face="normal" font="default" size="100%">Bednarz, K.</style></author>
										<author><style face="normal" font="default" size="100%">Florence, J.</style></author>
										<author><style face="normal" font="default" size="100%">Rowin, J.</style></author>
										<author><style face="normal" font="default" size="100%">Boylan, K.</style></author>
										<author><style face="normal" font="default" size="100%">Mozaffar, T.</style></author>
										<author><style face="normal" font="default" size="100%">Tandan, R.</style></author>
										<author><style face="normal" font="default" size="100%">Mitsumoto, H.</style></author>
										<author><style face="normal" font="default" size="100%">Kelvin, E. A.</style></author>
										<author><style face="normal" font="default" size="100%">Chapin, J.</style></author>
										<author><style face="normal" font="default" size="100%">Bedlack, R.</style></author>
										<author><style face="normal" font="default" size="100%">Rivner, M.</style></author>
										<author><style face="normal" font="default" size="100%">McCluskey, L. F.</style></author>
										<author><style face="normal" font="default" size="100%">Pestronk, A.</style></author>
										<author><style face="normal" font="default" size="100%">Graves, M.</style></author>
										<author><style face="normal" font="default" size="100%">Sorenson, E. J.</style></author>
										<author><style face="normal" font="default" size="100%">Barohn, R. J.</style></author>
										<author><style face="normal" font="default" size="100%">Belsh, J. M.</style></author>
										<author><style face="normal" font="default" size="100%">Lou, J. S.</style></author>
										<author><style face="normal" font="default" size="100%">Levine, T.</style></author>
										<author><style face="normal" font="default" size="100%">Saperstein, D.</style></author>
										<author><style face="normal" font="default" size="100%">Miller, R. G.</style></author>
										<author><style face="normal" font="default" size="100%">Scelsa, S. N.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, Columbia University, New York, USA. PHG8@columbia.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A novel, efficient, randomized selection trial comparing combinations of drug therapy for ALS</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">212-22</style></pages>
			<volume><style face="normal" font="default" size="100%">9</style></volume>
			<number><style face="normal" font="default" size="100%">4</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Aged, 80 and over</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amyotrophic Lateral Sclerosis/*drug therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Creatine/administration & dosage/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Double-Blind Method</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Drug Eruptions</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Drug Therapy, Combination</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Minocycline/administration & dosage/adverse effects/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neuroprotective Agents/administration & dosage/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Patient Selection</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Pyrazoles/administration & dosage/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sulfonamides/administration & dosage/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Treatment Outcome</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">8</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Combining agents with different mechanisms of action may be necessary for meaningful results in treating ALS. The combinations of minocycline-creatine and celecoxib-creatine have additive effects in the murine model. New trial designs are needed to efficiently screen the growing number of potential neuroprotective agents. Our objective was to assess two drug combinations in ALS using a novel phase II trial design. We conducted a randomized, double-blind selection trial in sequential pools of 60 patients. Participants received minocycline (100 mg)-creatine (10 g) twice daily or celecoxib (400 mg)-creatine (10 g) twice daily for six months. The primary objective was treatment selection based on which combination best slowed deterioration in the ALS Functional Rating Scale-Revised (ALSFRS-R); the trial could be stopped after one pool if the difference between the two arms was adequately large. At trial conclusion, each arm was compared to a historical control group in a futility analysis. Safety measures were also examined. After the first patient pool, the mean six-month decline in ALSFRS-R was 5.27 (SD=5.54) in the celecoxib-creatine group and 6.47 (SD=9.14) in the minocycline-creatine group. The corresponding decline was 5.82 (SD=6.77) in the historical controls. The difference between the two sample means exceeded the stopping criterion. The null hypothesis of superiority was not rejected in the futility analysis. Skin rash occurred more frequently in the celecoxib-creatine group. In conclusion, the celecoxib-creatine combination was selected as preferable to the minocycline-creatine combination for further evaluation. This phase II design was efficient, leading to treatment selection after just 60 patients, and can be used in other phase II trials to assess different agents.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18608093 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>282</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Russman, B. S.</style></author>
										<author><style face="normal" font="default" size="100%">Iannaccone, S. T.</style></author>
										<author><style face="normal" font="default" size="100%">Samaha, F. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Oregon Health Sciences University and Shriners Hospital for Children, Portland, OR 97201, USA. brussman@shrinenet.org</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A phase 1 trial of riluzole in spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1601-3</style></pages>
			<volume><style face="normal" font="default" size="100%">60</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Age of Onset</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child, Preschool</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Excitatory Amino Acid Antagonists/adverse effects/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant, Newborn</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*drug therapy/mortality</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Riluzole/adverse effects/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2003</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: Severe spinal muscular atrophy (SMA) (Werdnig-Hoffmann disease, acute SMA, and SMA I) is a disease of the motor neuron characterized by onset before 6 months of age, failure ever to achieve sitting without support, and a life expectancy of 2 years or less. There is no known treatment for SMA, and, until recently, no therapeutic trials have been attempted. There is reason to believe that glutamate, an excitatory neurotransmitter, enhances programmed cell death of anterior horn cells. Riluzole, a glutamate inhibitor, has been shown to slow the rate of decline in patients with amyotrophic lateral sclerosis, another form of motor neuron disease. OBJECTIVES: To determine whether a glutamate inhibitor might be tolerated by infants with SMA and, furthermore, whether this medication could have a positive effect on life expectancy. DESIGN: Subjects with homozygous deletions of the survival motor neuron gene were recruited from pediatric neuromuscular clinics and randomized in a 2:1 ratio, 2 riluzole to 1 placebo. Neurologic examination was performed at the first visit by one of the investigators. Complete blood count, hepatic and renal screens, and urinalysis were performed at baseline, 2 weeks, 1 month, 2 months, 3 months, 6 months, and 9 months after drug or placebo was started. An electrocardiogram was done at baseline, 3 months, 6 months, and 12 months. Treatment was stopped after 9 months, and blood work was repeated at 12 months. Treatment was reinstituted at 1 year if requested by the parents. The enrollment goal was 30 patients; however, support from the pharmaceutical company was withdrawn when Rhone-Poulenc Rorer was taken over by Aventis. The investigational review boards of the participating centers approved the protocol and consent forms. RESULTS: Seven patients received riluzole and 3 received placebo medication. All 3 patients in the placebo group died (mean age, 9 months). Three of 7 who received active drug are still living at ages 513 years, 4 years, and 30 months. None of the 10 subjects experienced adverse effects or changes in laboratory test results. None showed any change in motor abilities. CONCLUSIONS: Riluzole appears to be safe in young children. This was a limited study with insufficient power to show a difference between the 2 groups. Because there is a suggestion of possible benefit in treated subjects, we recommend further study of riluzole in pediatric patients with SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14623733 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>263</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Miller, R. G.</style></author>
										<author><style face="normal" font="default" size="100%">Moore, D. H.</style></author>
										<author><style face="normal" font="default" size="100%">Dronsky, V.</style></author>
										<author><style face="normal" font="default" size="100%">Bradley, W.</style></author>
										<author><style face="normal" font="default" size="100%">Barohn, R.</style></author>
										<author><style face="normal" font="default" size="100%">Bryan, W.</style></author>
										<author><style face="normal" font="default" size="100%">Prior, T. W.</style></author>
										<author><style face="normal" font="default" size="100%">Gelinas, D. F.</style></author>
										<author><style face="normal" font="default" size="100%">Iannaccone, S.</style></author>
										<author><style face="normal" font="default" size="100%">Kissel, J.</style></author>
										<author><style face="normal" font="default" size="100%">Leshner, R.</style></author>
										<author><style face="normal" font="default" size="100%">Mendell, J.</style></author>
										<author><style face="normal" font="default" size="100%">Mendoza, M.</style></author>
										<author><style face="normal" font="default" size="100%">Russman, B.</style></author>
										<author><style face="normal" font="default" size="100%">Samaha, F.</style></author>
										<author><style face="normal" font="default" size="100%">Smith, S.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, California Pacific Medical Center, Forbes Norris MSDA/ALS Center, 2324 Sacramento Street, #150, San Francisco, CA 94115, USA. rmiller@cooper.cpmc.org</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A placebo-controlled trial of gabapentin in spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">127-31</style></pages>
			<volume><style face="normal" font="default" size="100%">191</style></volume>
			<number><style face="normal" font="default" size="100%">1-2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Acetic Acids/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Amines</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Arm/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Cyclohexanecarboxylic Acids</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Double-Blind Method</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Excitatory Amino Acid Antagonists/*therapeutic use</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Feasibility Studies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hand Strength</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle Contraction/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Severity of Illness Index</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sickness Impact Profile</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal Muscular Atrophies of Childhood/*drug therapy/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Treatment Outcome</style></keyword>
								<keyword><style face="normal" font="default" size="100%">United States</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Vital Capacity/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*gamma-Aminobutyric Acid</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2001</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">OBJECTIVE: To evaluate the efficacy of gabapentin in increasing muscle strength of patients with spinal muscular atrophy (SMA). BACKGROUND: Preclinical data in experimental models of motor neuron disease suggest a neuroprotective effect of gabapentin. METHODS: Gabapentin (1200 mg), or placebo, was administered three times daily in a randomized, double-blind trial for 12 months. The primary outcome measure was the average percent change from baseline, based on the measurement of strength in four muscles (elbow flexion and hand grip bilaterally) for each patient. Drug efficacy was examined by comparing the percent change in strength for patients on drug vs. placebo. Secondary efficacy variables included: forced vital capacity (FVC), SMA functional rating scale (SMAFRS), and mini-Sickness Impact Profile (SIP). RESULTS: Eighty-four patients, with type II or III SMA, were enrolled at eight sites across the United States. There were no differences in baseline features. There was no difference between the placebo and drug groups in any outcome measure. CONCLUSIONS: This study demonstrates the feasibility of this trial design and provides data for the design of future clinical trials in SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11677003 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>976</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Arkblad, E.</style></author>
										<author><style face="normal" font="default" size="100%">Tulinius, M.</style></author>
										<author><style face="normal" font="default" size="100%">Kroksmark, A. K.</style></author>
										<author><style face="normal" font="default" size="100%">Henricsson, M.</style></author>
										<author><style face="normal" font="default" size="100%">Darin, N.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Clinical Genetics, Sahlgrenska University Hospital, Goteborg, Sweden.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Aims: To describe the occurrence of spinal muscular atrophy (SMA) in childhood; to evaluate if any of the genes in the SMA region on chromosome 5q13 correlates with disease severity; to make genotype-phenotype correlations; to evaluate the variability of different disease alleles in carriers and the sensitivity of multiplex ligation-dependent probe amplification (MLPA) for detecting carriers. Methods: In a population-based study from Western Sweden MLPA was used to determine the copy-numbers of several genes in the SMA region (SMN1, SMN2, BIRC1, GTF2H2 and SERF1A) in SMA-patients and their parents. Results: We estimated the incidence of SMN1-related SMA in childhood at 1 in 11 800 live births and confirmed the relationship between the number of SMN2 copies and the severity of disease. No other direct relationships were found. All but one of the analysed parents were confirmed as carriers by MLPA analysis. A total of at least 30 different disease alleles were identified and no specific disease allele represented more than 15% of the total. Conclusion: The childhood incidence of SMA in the Swedish population is around 1 in 12 000 live births and it is unlikely that there is any founder effect involved in SMA in western Sweden.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19154529 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>233</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Gu, W.</style></author>
										<author><style face="normal" font="default" size="100%">Pan, F.</style></author>
										<author><style face="normal" font="default" size="100%">Zhang, H.</style></author>
										<author><style face="normal" font="default" size="100%">Bassell, G. J.</style></author>
										<author><style face="normal" font="default" size="100%">Singer, R. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A predominantly nuclear protein affecting cytoplasmic localization of beta-actin mRNA in fibroblasts and neurons</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">41-51</style></pages>
			<volume><style face="normal" font="default" size="100%">156</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Actins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Western</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Brain/cytology/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chick Embryo</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chickens/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromatography, Affinity</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cloning, Molecular</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cytoplasm/*genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DNA, Complementary/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Electrophoretic Mobility Shift Assay</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fibroblasts/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression Regulation, Developmental</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">In Situ Hybridization</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurons/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nuclear Proteins/chemistry/genetics/isolation & purification/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Binding</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Structure, Tertiary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA, Messenger/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins/chemistry/genetics/isolation &</style></keyword>
								<keyword><style face="normal" font="default" size="100%">purification/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Trans-Activators</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2002</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The localization of beta-actin mRNA to the leading lamellae of chicken fibroblasts and neurite growth cones of developing neurons requires a 54-nt localization signal (the zipcode) within the 3' untranslated region. In this study we have identified and isolated five proteins binding to the zipcode. One of these we previously identified as zipcode binding protein (ZBP)1, a 4-KH domain protein. A second is now investigated in detail: a 92-kD protein, ZBP2, that is especially abundant in extracts from embryonic brain. We show that ZBP2 is a homologue of the human hnRNP protein, KSRP, that appears to mediate pre-mRNA splicing. However, ZBP2 has a 47-amino acid (aa) sequence not present in KSRP. Various portions of ZBP2 fused to GFP indicate that the protein most likely shuttles between the nucleus and the cytoplasm, and that the 47-aa insert promotes the nuclear localization. Expression of a truncated ZBP2 inhibits the localization of beta-actin mRNA in both fibroblast and neurons. These data suggest that ZBP2, although predominantly a nuclear protein, has a role in the cytoplasmic localization of beta-actin mRNA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11781334 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>794</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Dayangac-Erden, D.</style></author>
										<author><style face="normal" font="default" size="100%">Topaloglu, H.</style></author>
										<author><style face="normal" font="default" size="100%">Erdem-Yurter, H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Medical Biology, Hacettepe University, Faculty of Medicine, Ankara, Turkey, didayan@hacettepe.edu.tr.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A preliminary report on spinal muscular atrophy lymphoblastoid cell lines: Are they an appropriate tool for drug screening?</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">INTRODUCTION: Spinal muscular atrophy (SMA) is a neurodegenerative disease of the motor neurons that results in progressive muscle weakness. It is also the leading hereditary cause of infant mortality. Homozygous loss of the survival motor neuron (SMN1) gene causes SMA, and the number of copies of the SMN2 gene modulates the severity of the disease. Increasing the expression of the SMN2 gene by pharmacological agents is one of the therapeutic approaches currently being implemented. METHODS: In this preliminary study, we investigated the effect of phenylbutyrate, a histone deacetylase (HDAC) inhibitor, on SMN2 expression in two SMA type III Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines to understand the suitability of lymphoblastoid cell lines in drug screening. These cell lines are regarded as a good source as they can easily be established from the peripheral leucocytes of patients. Quantitative analysis of SMN2 mRNA was performed on established cell lines treated with various concentrations of phenylbutyrate and for a range of incubation periods using real-time polymerase chain reaction. Western blot analysis was used to determine SMN protein levels. RESULTS: Real-time polymerase chain reaction and Western blot analysis demonstrated that the levels of SMN2 full-length (fl-SMN2) transcripts and protein were not increased in phenylbutyrate-treated cell lines compared to non-treated controls. CONCLUSION: These results suggest that EBV-transformed lymphoblastoid cell lines are not suitable for studying the effect of certain HDAC inhibitors on SMN2 gene expression.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18345520 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>848</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Pielage, J.</style></author>
										<author><style face="normal" font="default" size="100%">Cheng, L.</style></author>
										<author><style face="normal" font="default" size="100%">Fetter, R. D.</style></author>
										<author><style face="normal" font="default" size="100%">Carlton, P. M.</style></author>
										<author><style face="normal" font="default" size="100%">Sedat, J. W.</style></author>
										<author><style face="normal" font="default" size="100%">Davis, G. W.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2822, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A presynaptic giant ankyrin stabilizes the NMJ through regulation of presynaptic microtubules and transsynaptic cell adhesion</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">195-209</style></pages>
			<volume><style face="normal" font="default" size="100%">58</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Motifs/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals, Genetically Modified</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ankyrins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Adhesion Molecules, Neuronal/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Drosophila</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Drosophila Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression Regulation/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Horseradish Peroxidase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Larva</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Luminescent Proteins/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microscopy, Electron, Transmission/methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microtubules/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neuromuscular Junction/*physiology/ultrastructure</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Presynaptic Terminals/*metabolism/ultrastructure</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Synapsins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Synaptic Transmission/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">In a forward genetic screen for mutations that destabilize the neuromuscular junction, we identified a novel long isoform of Drosophila ankyrin2 (ank2-L). We demonstrate that loss of presynaptic Ank2-L not only causes synapse disassembly and retraction but also disrupts neuronal excitability and NMJ morphology. We provide genetic evidence that ank2-L is necessary to generate the membrane constrictions that normally separate individual synaptic boutons and is necessary to achieve the normal spacing of subsynaptic protein domains, including the normal organization of synaptic cell adhesion molecules. Mechanistically, synapse organization is correlated with a lattice-like organization of Ank2-L, visualized using extended high-resolution structured-illumination microscopy. The stabilizing functions of Ank2-L can be mapped to the extended C-terminal domain that we demonstrate can directly bind and organize synaptic microtubules. We propose that a presynaptic Ank2-L lattice links synaptic membrane proteins and spectrin to the underlying microtubule cytoskeleton to organize and stabilize the presynaptic terminal.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18439405 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1414</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">van der Ploeg, A. T.</style></author>
										<author><style face="normal" font="default" size="100%">Clemens, P. R.</style></author>
										<author><style face="normal" font="default" size="100%">Corzo, D.</style></author>
										<author><style face="normal" font="default" size="100%">Escolar, D. M.</style></author>
										<author><style face="normal" font="default" size="100%">Florence, J.</style></author>
										<author><style face="normal" font="default" size="100%">Groeneveld, G. J.</style></author>
										<author><style face="normal" font="default" size="100%">Herson, S.</style></author>
										<author><style face="normal" font="default" size="100%">Kishnani, P. S.</style></author>
										<author><style face="normal" font="default" size="100%">Laforet, P.</style></author>
										<author><style face="normal" font="default" size="100%">Lake, S. L.</style></author>
										<author><style face="normal" font="default" size="100%">Lange, D. J.</style></author>
										<author><style face="normal" font="default" size="100%">Leshner, R. T.</style></author>
										<author><style face="normal" font="default" size="100%">Mayhew, J. E.</style></author>
										<author><style face="normal" font="default" size="100%">Morgan, C.</style></author>
										<author><style face="normal" font="default" size="100%">Nozaki, K.</style></author>
										<author><style face="normal" font="default" size="100%">Park, D. J.</style></author>
										<author><style face="normal" font="default" size="100%">Pestronk, A.</style></author>
										<author><style face="normal" font="default" size="100%">Rosenbloom, B.</style></author>
										<author><style face="normal" font="default" size="100%">Skrinar, A.</style></author>
										<author><style face="normal" font="default" size="100%">van Capelle, C. I.</style></author>
										<author><style face="normal" font="default" size="100%">van der Beek, N. A.</style></author>
										<author><style face="normal" font="default" size="100%">Wasserstein, M.</style></author>
										<author><style face="normal" font="default" size="100%">Zivkovic, S. A.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A randomized study of alglucosidase alfa in late-onset Pompe's disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1396-406</style></pages>
			<volume><style face="normal" font="default" size="100%">362</style></volume>
			<number><style face="normal" font="default" size="100%">15</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: Pompe's disease is a metabolic myopathy caused by a deficiency of acid alpha glucosidase (GAA), an enzyme that degrades lysosomal glycogen. Late-onset Pompe's disease is characterized by progressive muscle weakness and loss of respiratory function, leading to early death. We conducted a randomized, placebo-controlled trial of alglucosidase alfa, a recombinant human GAA, for the treatment of late-onset Pompe's disease. METHODS: Ninety patients who were 8 years of age or older, ambulatory, and free of invasive ventilation were randomly assigned to receive biweekly intravenous alglucosidase alfa (20 mg per kilogram of body weight) or placebo for 78 weeks at eight centers in the United States and Europe. The two primary end points were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC). RESULTS: At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa (an increase of 28.1+/-13.1 m on the 6-minute walk test and an absolute increase of 3.4+/-1.2 percentage points in FVC; P=0.03 and P=0.006, respectively). Similar proportions of patients in the two groups had adverse events, serious adverse events, and infusion-associated reactions; events that occurred only in patients who received the active study drug included anaphylactic reactions and infusion-associated reactions of urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure (each of which occurred in 5 to 8% of the patients). CONCLUSIONS: In this study population, treatment with alglucosidase alfa was associated with improved walking distance and stabilization of pulmonary function over an 18-month period. (ClinicalTrials.gov number, NCT00158600.)</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20393176 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>361</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%"></style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">664-71</style></pages>
			<volume><style face="normal" font="default" size="100%">66</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: Creatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson disease (PD). OBJECTIVE: To test whether creatine and minocycline alter the course of early PD relative to a predetermined futility threshold for progression of PD in a randomized, double-blind, Phase II futility clinical trial. Agents that do not perform better than the futility threshold are rejected as futile and are not considered for further study. METHODS: Participants had a diagnosis of PD within 5 years, but did not require medications for the management of symptoms. The primary outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline to either the time when there was sufficient disability to warrant symptomatic therapy for PD or 12 months, whichever came first. Subjects were randomized 1:1:1 to receive creatine 10 g/day, minocycline 200 mg/day, or matching placebo. The futility threshold was set as a 30% reduction in UPDRS progression based on the placebo/tocopherol arm of the Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism (DATATOP) trial. p values < or = 0.1 indicate futility. RESULTS: Two hundred subjects were randomized to the three groups. Neither creatine (p = 0.96) nor minocycline (p = 0.66) could be rejected as futile based on the DATATOP futility threshold. The rate of progression for the calibration placebo group fell outside the 95% CI for the DATATOP historical control. In a sensitivity analysis, based on the threshold derived from the calibration placebo group, again neither drug could be rejected as futile. Tolerability was 91% in the creatine group and 77% in the minocycline group. Common adverse events included upper respiratory symptoms (26%), joint pain (19%), and nausea (17%). CONCLUSIONS: Both creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson disease (PD). Additional factors must be weighed before selecting agents for Phase III trials, including safety, tolerability, activity, cost, and availability of these two agents in comparison with other agents currently in development for PD.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16481597 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1294</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Vezain, M.</style></author>
										<author><style face="normal" font="default" size="100%">Saugier-Veber, P.</style></author>
										<author><style face="normal" font="default" size="100%">Goina, E.</style></author>
										<author><style face="normal" font="default" size="100%">Touraine, R.</style></author>
										<author><style face="normal" font="default" size="100%">Manel, V.</style></author>
										<author><style face="normal" font="default" size="100%">Toutain, A.</style></author>
										<author><style face="normal" font="default" size="100%">Fehrenbach, S.</style></author>
										<author><style face="normal" font="default" size="100%">Frebourg, T.</style></author>
										<author><style face="normal" font="default" size="100%">Pagani, F.</style></author>
										<author><style face="normal" font="default" size="100%">Tosi, M.</style></author>
										<author><style face="normal" font="default" size="100%">Martins, A.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Inserm U614, IFRMP, Institute for Biomedical Research, Faculty of Medicine, University of Rouen, 76183 Rouen, France.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A rare SMN2 variant in a previously unrecognized composite splicing regulatory element induces exon 7 inclusion and reduces the clinical severity of spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by homozygous inactivation of the SMN1 (Survival Motor Neuron 1) gene. The disease severity is mainly influenced by the copy number of SMN2, a nearly identical gene from which only low amounts of full-length mRNA are produced. This correlation is not absolute, suggesting the existence of yet unknown factors modulating disease progression. We identified and characterized the rare variant c.859G>C (p.Gly287Arg) in exon 7 in both SMN2 copies of a male patient affected with type III SMA, a milder form of the disease rarely associated with only two SMN2 copies. We demonstrated in vivo, in this patient and in a second unrelated patient, and ex vivo, using SMN splicing assays, that the variant induces inclusion of exon 7 into SMN2 mRNA. Moreover, we show that the c.859G>C variation is located in a composite splicing regulatory element in the centre of exon 7. The variation does not affect binding of HTra2a nor creates a novel SF2/ASF enhancer, but disrupts an hnRNP A1 binding site. The natural occurrence of enhanced inclusion of SMN2 exon 7 in milder SMA cases supports the current therapeutic strategies based on splicing modulation in SMA patients. (c) 2009 Wiley-Liss, Inc.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19953646 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1225</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Kishnani, P. S.</style></author>
										<author><style face="normal" font="default" size="100%">Hwu, W. L.</style></author>
										<author><style face="normal" font="default" size="100%">Mandel, H.</style></author>
										<author><style face="normal" font="default" size="100%">Nicolino, M.</style></author>
										<author><style face="normal" font="default" size="100%">Yong, F.</style></author>
										<author><style face="normal" font="default" size="100%">Corzo, D.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. kishn001@mc.duke.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">671-676</style></pages>
			<volume><style face="normal" font="default" size="100%">148</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Cohort Studies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Progression</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Europe/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Glycogen Storage Disease Type II/*complications/*epidemiology/therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant, Newborn</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Israel/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">North America/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Respiration, Artificial</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Retrospective Studies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Survival Rate</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Taiwan/epidemiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">5</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">OBJECTIVE: To characterize the natural progression of infantile-onset Pompe disease. STUDY DESIGN: Retrospective chart reviews of 168 patients with documented acid alpha-glucosidase deficiency and symptom onset by 12 months of age; Kaplan-Meier analysis of total and ventilator-free survival time; Cox proportional hazards regression modeling of mortality risk factors. RESULTS: The median age at symptom onset was 2.0 months (range 0 to 12 months), 4.7 months at diagnosis (range: prenatal to 4.2 months), 5.9 months at first ventilator support (range 0.1 to 31.1 months), and 8.7 months at death (range 0.3 to 73.4 months). Survival rates at 12 months of age were 25.7% overall and 16.9% ventilator-free; at 18 months 12.3% and 6.7%. Cardiomegaly (92%), hypotonia (88%), cardiomyopathy (88%), respiratory distress (78%), muscle weakness (63%), feeding difficulties (57%), and failure to thrive (53%) appeared after a median age of approximately 4.0 months. Multiple covariate analysis confirmed that early symptom onset increased risk of early death. CONCLUSION: Despite frequent therapeutic interventions, infantile-onset Pompe disease remains lethal.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16737883 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>192</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Culetto, E.</style></author>
										<author><style face="normal" font="default" size="100%">Sattelle, D. B.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">MRC Functional Genetics Unit, Department of Human Anatomy and Genetics, University of Oxford, UK.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">869-77</style></pages>
			<volume><style face="normal" font="default" size="100%">9</style></volume>
			<number><style face="normal" font="default" size="100%">6</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Caenorhabditis elegans/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Models, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Ligases</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Dystrophies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Polycystic Kidney Diseases/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Proteins/chemistry/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Homology, Amino Acid</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Ubiquitin-Protein Ligases</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2000</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">A growing number of medical research teams have begun to explore the experimental advantages of using a genetic animal model, the nematode worm Caenorhabditis elegans, with a view to enhancing our understanding of genes underlying human congenital disorders. In this study, we have compared sequences of positionally cloned human disease genes with the C.elegans database of predicted genes. Drawing on examples from spinal muscular atrophy, polycystic kidney disease, muscular dystrophy and Alzheimer's disease, we illustrate how data from C.elegans can yield new insights into the function and interactions of human disease genes.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10767309 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>24</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Sharma, A.</style></author>
										<author><style face="normal" font="default" size="100%">Lambrechts, A.</style></author>
										<author><style face="normal" font="default" size="100%">Hao le, T.</style></author>
										<author><style face="normal" font="default" size="100%">Le, T. T.</style></author>
										<author><style face="normal" font="default" size="100%">Sewry, C. A.</style></author>
										<author><style face="normal" font="default" size="100%">Ampe, C.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%">Morris, G. E.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Biochemistry Group, N. E. Wales Institute, Mold Road, Wrexham LL11 2AW, UK.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A role for complexes of survival of motor neurons (SMN) protein with gemins and profilin in neurite-like cytoplasmic extensions of cultured nerve cells</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">185-97</style></pages>
			<volume><style face="normal" font="default" size="100%">309</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Inbred BALB C</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/*metabolism/pathology/ultrastructure</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neoplasm Proteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurites/*metabolism/ultrastructure</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nuclear Proteins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">PC12 Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Profilins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rabbits</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, N.I.H., Extramural</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is caused by reduced levels of SMN (survival of motor neurons protein) and consequent loss of motor neurons. SMN is involved in snRNP transport and nuclear RNA splicing, but axonal transport of SMN has also been shown to occur in motor neurons. SMN also binds to the small actin-binding protein, profilin. We now show that SMN and profilin II co-localise in the cytoplasm of differentiating rat PC12 cells and in neurite-like extensions, especially at their growth cones. Many components of known SMN complexes were also found in these extensions, including gemin2 (SIP-1), gemin6, gemin7 and unrip (unr-interacting protein). Coilin p80 and Sm core protein immunoreactivity, however, were seen only in the nucleus. SMN is known to associate with beta-actin mRNA and specific hnRNPs in axons and in neurite extensions of cultured nerve cells, and SMN also stimulates neurite outgrowth in cultures. Our results are therefore consistent with SMN complexes, rather than SMN alone, being involved in the transport of actin mRNPs along the axon as in the transport of snRNPs into the nucleus by similar SMN complexes. Antisense knockdown of profilin I and II isoforms inhibited neurite outgrowth of PC12 cells and caused accumulation of SMN and its associated proteins in cytoplasmic aggregates. BIAcore studies demonstrated a high affinity interaction of SMN with profilin IIa, the isoform present in developing neurons. Pathogenic missense mutations in SMN, or deletion of exons 5 and 7, prevented this interaction. The interaction is functional in that SMN can modulate actin polymerisation in vitro by reducing the inhibitory effect of profilin IIa. This suggests that reduced SMN in SMA might cause axonal pathfinding defects by disturbing the normal regulation of microfilament growth by profilins.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15975577 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>674</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Vezain, M.</style></author>
										<author><style face="normal" font="default" size="100%">Saugier-Veber, P.</style></author>
										<author><style face="normal" font="default" size="100%">Melki, J.</style></author>
										<author><style face="normal" font="default" size="100%">Toutain, A.</style></author>
										<author><style face="normal" font="default" size="100%">Bieth, E.</style></author>
										<author><style face="normal" font="default" size="100%">Husson, M.</style></author>
										<author><style face="normal" font="default" size="100%">Pedespan, J. M.</style></author>
										<author><style face="normal" font="default" size="100%">Viollet, L.</style></author>
										<author><style face="normal" font="default" size="100%">Penisson-Besnier, I.</style></author>
										<author><style face="normal" font="default" size="100%">Fehrenbach, S.</style></author>
										<author><style face="normal" font="default" size="100%">Bou, J.</style></author>
										<author><style face="normal" font="default" size="100%">Frebourg, T.</style></author>
										<author><style face="normal" font="default" size="100%">Tosi, M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">1Department of Genetics, Rouen University Hospital and INSERM U614, Institute for Biomedical Research, University of Rouen, Rouen, France.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A sensitive assay for measuring SMN mRNA levels in peripheral blood and in muscle samples of patients affected with spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2007</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Different therapeutic strategies are currently evaluated in spinal muscular atrophy (SMA) that are aimed at increasing full-length (FL) mRNA levels produced from the SMN2 gene. Assays measuring SMN mRNA levels are needed. We have developed a sensitive, comparative assay based on multiplex fluorescent reverse-transcription polymerase chain reaction (RT-PCR) that can measure, in the same reaction, the levels of SMN mRNA with and without exon 7 sequences as well as those of total SMN mRNA. This assay allows to calculate directly the ratios of FL SMN mRNA to SMN mRNA without exon 7 (Delta7). We have used this assay to compare the levels of SMN transcripts in the blood of 75 unrelated normal subjects and of 48 SMA patients, and in muscle samples of 8 SMA patients. The SMN1 and the SMN2 genes produced very similar levels of total mRNA. Levels of transcripts lacking exon 7 were linearly dependent on the number of SMN2 copies, both in SMA patients and in controls. In patients, FL mRNA levels correlated with SMN2 copy number. A significant but weaker inverse correlation was also observed between FL or Delta7 mRNA levels and disease severity, but patients with three SMN2 copies and different SMA types displayed similar mRNA levels. A significantly higher FL to Delta7 ratio was measured in blood cells than in skeletal muscle (0.80+/-0.18 versus 0.47+/-0.11). This assay can be used as a sensitive biomarker for monitoring the effects of various drugs in forthcoming clinical trials of SMA.European Journal of Human Genetics advance online publication, 4 July 2007; doi:10.1038/sj.ejhg.5201885.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17609673 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1124</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Singh, N. N.</style></author>
										<author><style face="normal" font="default" size="100%">Shishimorova, M.</style></author>
										<author><style face="normal" font="default" size="100%">Cao, L. C.</style></author>
										<author><style face="normal" font="default" size="100%">Gangwani, L.</style></author>
										<author><style face="normal" font="default" size="100%">Singh, R. N.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Biomedical Sciences, Iowa State University, Ames, IA, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%">6</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Most SMA cases are associated with the low levels of SMN owing to deletion of Survival Motor Neuron 1 (SMN1). SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Hence, correction of aberrant splicing of SMN2 exon 7 holds the potential for cure of SMA. Here we report an 8-mer antisense oligonucleotide (ASO) to have a profound stimulatory response on correction of aberrant splicing of SMN2 exon 7 by binding to a unique GC-rich sequence located within intron 7 of SMN2. We confirm that the splicing-switching ability of this short ASO comes with a high degree of specificity and reduced off-target effect compared to larger ASOs targeting the same sequence. We further demonstrate that a single low nanomolar dose of this 8-mer ASO substantially increases the levels of SMN and a host of factors including Gemin 2, Gemin 8, ZPR1, hnRNP Q and Tra2-beta1 known to be down-regulated in SMA. Our findings underscore the advantages and unmatched potential of very short ASOs in splicing modulation in vivo.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19430205 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1066</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Passon, N.</style></author>
										<author><style face="normal" font="default" size="100%">Pozzo, F.</style></author>
										<author><style face="normal" font="default" size="100%">Molinis, C.</style></author>
										<author><style face="normal" font="default" size="100%">Bregant, E.</style></author>
										<author><style face="normal" font="default" size="100%">Gellera, C.</style></author>
										<author><style face="normal" font="default" size="100%">Damante, G.</style></author>
										<author><style face="normal" font="default" size="100%">Lonigro, R. I.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Dipartimento di Scienze e Tecnologie Biomediche, Universita degli Studi, Udine, Italy.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A simple multiplex real-time PCR methodology for the SMN1 gene copy number quantification</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">37-42</style></pages>
			<volume><style face="normal" font="default" size="100%">13</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">2</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is an autosomal recessive disease caused, in about 95% of SMA cases, by homozygous deletion of the survival motor neuron 1 (SMN1) gene or its conversion to the highly homologous SMN2 gene. The molecular diagnosis of SMA is usually carried out by a PCR-Restriction fragment length polymorphism (RFLP) approach. However, this approach is not useful for identification of healthy deletion carriers. TaqMan technology is one of the most reliable and widely adopted techniques for the SMN1 copy number evaluation. However, several limitations of this technique have been described. Particularly, DNA extraction methods and accurate template quantification have been shown to be critical for reliable results. In this work, we set up a reliable, highly reproducible, and easy-to-perform TaqMan technology-based protocol to obtain the SMN1 gene copy number assessment. We demonstrate that PCR amplification of both target gene and reference gene in the same reaction mix, instead of separated mixes, greatly reduces reported criticisms of simplex TaqMan technology. The multiplex real-time PCR we describe allows interlaboratory samples and data exchange, without the need to equalize the DNA isolation technique. Further, the protocol described below requires fewer replica tests than the simplex methodology does, leading to reduced overall cost for the diagnostic assay.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19309272 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>437</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Zhang, J. H.</style></author>
										<author><style face="normal" font="default" size="100%">Chung, T. D.</style></author>
										<author><style face="normal" font="default" size="100%">Oldenburg, K. R.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">DuPont Pharmaceuticals Research Laboratories, Leads Discovery, DuPont Pharmaceuticals Company, Wilmington, Delaware.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">67-73</style></pages>
			<volume><style face="normal" font="default" size="100%">4</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1999</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The ability to identify active compounds ((3)hits(2)) from large chemical libraries accurately and rapidly has been the ultimate goal in developing high-throughput screening (HTS) assays. The ability to identify hits from a particular HTS assay depends largely on the suitability or quality of the assay used in the screening. The criteria or parameters for evaluating the (3)suitability(2) of an HTS assay for hit identification are not well defined and hence it still remains difficult to compare the quality of assays directly. In this report, a screening window coefficient, called (3)Z-factor,(2) is defined. This coefficient is reflective of both the assay signal dynamic range and the data variation associated with the signal measurements, and therefore is suitable for assay quality assessment. The Z-factor is a dimensionless, simple statistical characteristic for each HTS assay. The Z-factor provides a useful tool for comparison and evaluation of the quality of assays, and can be utilized in assay optimization and validation.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10838414 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>18</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Monani, U. R.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C. L.</style></author>
										<author><style face="normal" font="default" size="100%">Parsons, D. W.</style></author>
										<author><style face="normal" font="default" size="100%">Prior, T. W.</style></author>
										<author><style face="normal" font="default" size="100%">Androphy, E. J.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%">McPherson, J. D.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, The Ohio State University, Columbus 43210, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1177-83</style></pages>
			<volume><style face="normal" font="default" size="100%">8</style></volume>
			<number><style face="normal" font="default" size="100%">7</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">*Alternative Splicing</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genotype</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Point Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Analysis, DNA</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1999</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">7</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a recessive disorder characterized by loss of motor neurons in the spinal cord. It is caused by mutations in the telomeric survival motor neuron 1 ( SMN1 ) gene. Alterations within an almost identical copy gene, the centromeric survival motor neuron 2 ( SMN2 ) gene produce no known phenotypic effect. The exons of the two genes differ by just two nucleotides, neither of which alters the encoded amino acids. At the genomic level, only five nucleotides that differentiate the two genes from one another have been reported. The entire genomic sequence of the two genes has not been determined. Thus, differences which might explain why SMN1 is the SMA gene are not readily apparent. In this study, we have completely sequenced and compared genomic clones containing the SMN genes. The two genes show striking similarity, with the homology being unprecedented between two different yet functional genes. The only critical difference in an approximately 32 kb region between the two SMN genes is the C->T base change 6 bp inside exon 7. This alteration but not other variations in the SMN genes affects the splicing pattern of the genes. The majority of the transcript from the SMN1 locus is full length, whereas the majority of the transcript produced by the SMN2 locus lacks exon 7. We suggest that the exon 7 nucleotide change affects the activity of an exon splice enhancer. In SMA patients, the loss of SMN1 but the presence of SMN2 results in low levels of full-length SMN transcript and therefore low SMN protein levels which causes SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10369862 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1083</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Workman, E.</style></author>
										<author><style face="normal" font="default" size="100%">Saieva, L.</style></author>
										<author><style face="normal" font="default" size="100%">Carrel, T. L.</style></author>
										<author><style face="normal" font="default" size="100%">Crawford, T. O.</style></author>
										<author><style face="normal" font="default" size="100%">Liu, D.</style></author>
										<author><style face="normal" font="default" size="100%">Lutz, C.</style></author>
										<author><style face="normal" font="default" size="100%">Beattie, C. E.</style></author>
										<author><style face="normal" font="default" size="100%">Pellizzoni, L.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH, 43210 USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease. Loss of the survival motor neuron (SMN1) gene, in the presence of the SMN2 gene causes SMA. SMN functions in snRNP assembly in all cell types, however, it is unclear how this function results in specifically motor neuron cell death. Lack of endogenous mouse SMN (Smn) in mice results in embryonic lethality. Introduction of 2 copies of human SMN2 results in a mouse with severe SMA, while 1 copy of SMN2 is insufficient to overcome embryonic lethality. We show that SMN(A111G), an allele capable of snRNP assembly, can rescue mice that lack Smn and contain either one or two copies of SMN2 (SMA mice). The correction of SMA in these animals was directly correlated with snRNP assembly activity in spinal cord, as was correction of snRNA levels. These data support snRNP assembly as being the critical function affected in SMA and suggests that the levels of snRNPs are critical to motor neurons. Furthermore, SMN(A111G) cannot rescue Smn-/- mice without SMN2 suggesting that both SMN(A111G) and SMN from SMN2 undergo intragenic complementation in vivo to function in heteromeric complexes that have greater function than either allele alone. The oligomer composed of limiting full-length SMN and SMN(A111G) has substantial snRNP assembly activity. Also, the SMN(A2G) and SMN(A111G) alleles in vivo did not complement each other leading to the possibility that these mutations could affect the same function.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19329542 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>872</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Mattis, V. B.</style></author>
										<author><style face="normal" font="default" size="100%">Bowerman, M.</style></author>
										<author><style face="normal" font="default" size="100%">Kothary, R.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C. L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Veterinary Pathobiology, Life Sciences Center, Room 404, University of Missouri, Columbia, MO 65211, United States.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A SMNDelta7 read-through product confers functionality to the SMNDelta7 protein</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) affects about 1 in every 6000 children born and is the leading genetic cause of infant death. SMA is a recessive disorder caused by the mutation or deletion of Survival Motor Neuron-1 (SMN1). SMN2, a nearly identical copy gene, has the potential to encode the same protein as SMN1 and is retained in all SMA patients. The majority of SMN2-derived transcripts are alternatively spliced and therefore encode a truncated isoform lacking exon 7 (SMNDelta7), which is a defective protein because it is unstable, has a reduced ability to self-associate and is unable to efficiently function in SMN cellular activities. However, we have shown that the SMN C-terminus functions non-specifically, since heterologous sequences can compensate for the exon 7 sequence. Several classes of compounds identified in SMN-inducing high throughput screens have been proposed to function through a read-through mechanism; however, a functional analysis of the SMNDelta7 read-through product has not been performed. In this report, the SMNDelta7 read-through product is characterized and compared to the SMNDelta7 protein. In a series of in vitro and cell based assays, SMNDelta7 read-through product is shown to increase protein stability, promote neurite outgrowths in SMN deficient neurons, and significantly elevate SMN-dependent UsnRNP assembly in extracts from SMA patient fibroblasts. Collectively, these results demonstrate that SMNDelta7 read-through product is more active than the SMNDelta7 protein and suggest that SMA therapeutics that specifically induce SMNDelta7 read-through may provide an alternative platform for drug discovery.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18601974 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1418</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Eggers, R.</style></author>
										<author><style face="normal" font="default" size="100%">Tannemaat, M. R.</style></author>
										<author><style face="normal" font="default" size="100%">Ehlert, E. M.</style></author>
										<author><style face="normal" font="default" size="100%">Verhaagen, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, An Institute of the Royal Academy of Arts and Sciences, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. r.eggers@nin.knaw.nl</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">207-20</style></pages>
			<volume><style face="normal" font="default" size="100%">223</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Survival/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Choline O-Acetyltransferase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Models, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Enzyme-Linked Immunosorbent Assay/methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression Regulation/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hindlimb/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Lumbosacral Plexus/pathology/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Growth Factors/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Regeneration/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Radiculopathy/pathology/physiopathology/surgery</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats, Wistar</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Replantation/*methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sciatic Nerve/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Time Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">5</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Reimplantation of avulsed rat lumbar spinal ventral roots results in poor recovery of function of the denervated hind limb muscles. In contrast, reimplantation of cervical or sacral ventral roots is a successful repair strategy that results in a significant degree of regeneration. A possible explanation for this difference could be that following lumbar root avulsion, axons have to travel longer distances towards their target muscles, resulting in prolonged denervation of the distal nerve and a diminished capacity to support regeneration. Here we present a detailed spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression following unilateral avulsion and implantation of lumbar ventral roots L3, L4, and L5. Reimplantation prolongs the survival of motoneurons up to one month post-lesion. The first regenerating motor axons entered the reimplanted ventral roots during the first week and large numbers of fibers gradually enter the lumbar plexus between 2 and 4 weeks, indicating that axons enter the reimplanted roots and plexus over an extended period of time. However, motor axon counts show that relatively few axons reach the distal sciatic nerve in the 16 week post-lesion period. The observed initial increase and subsequent decline in expression of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor correlate with the apparent spatio-temporal decline in the regenerative capacity of motor axons, indicating that the distal nerve is losing its capacity to support regenerating motor axons following prolonged denervation. These findings have important implications for future strategies to promote long-distance regeneration through distal, chronically denervated peripheral nerves.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19646436 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1054</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Roca, X.</style></author>
										<author><style face="normal" font="default" size="100%">Krainer, A. R.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%"></style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A splicing component adapted to gene silencing</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">250-1</style></pages>
			<volume><style face="normal" font="default" size="100%">27</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">3</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19270672 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>216</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Francis, J. W.</style></author>
										<author><style face="normal" font="default" size="100%">Figueiredo, D.</style></author>
										<author><style face="normal" font="default" size="100%">vanderSpek, J. C.</style></author>
										<author><style face="normal" font="default" size="100%">Ayala, L. M.</style></author>
										<author><style face="normal" font="default" size="100%">Kim, Y. S.</style></author>
										<author><style face="normal" font="default" size="100%">Remington, M. P.</style></author>
										<author><style face="normal" font="default" size="100%">Young, P. J.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C. L.</style></author>
										<author><style face="normal" font="default" size="100%">Ikebe, S.</style></author>
										<author><style face="normal" font="default" size="100%">Fishman, P. S.</style></author>
										<author><style face="normal" font="default" size="100%">Brown, R. H., Jr.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Cecil B. Day Laboratory for Neuromuscular Research, Massachusetts General Hospital, Building 114, 16th Street, Room 3003, Charlestown, MA 02129, USA. jwfrancis@partners.org</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A survival motor neuron:tetanus toxin fragment C fusion protein for the targeted delivery of SMN protein to neurons</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">84-96</style></pages>
			<volume><style face="normal" font="default" size="100%">995</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals, Newborn</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Antibodies/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Membrane/drug effects/immunology/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cytotoxins/genetics/immunology/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Diphtheria Toxin/genetics/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Endocytosis/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*drug therapy/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurons/drug effects/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Peptide Fragments/*genetics/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Binding/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Structure, Tertiary/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Transport/drug effects/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Recombinant Fusion Proteins/genetics/immunology/*pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, Non-P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tetanus Toxin/*genetics/immunology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2004</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a degenerative disorder of spinal motor neurons caused by homozygous mutations in the survival motor neuron (SMN1) gene. Because increased tissue levels of human SMN protein (hSMN) in transgenic mice reduce the motor neuron loss caused by murine SMN knockout, we engineered a recombinant SMN fusion protein to deliver exogenous hSMN to the cytosolic compartment of motor neurons. The fusion protein, SDT, is comprised of hSMN linked to the catalytic and transmembrane domains of diphtheria toxin (DTx) followed by fragment C of tetanus toxin (TTC). Following overexpression in Escherichia coli, SDT possessed a subunit molecular weight of approximately 130 kDa as revealed by both SDS-PAGE and immunoblot analyses with anti-SMN, anti-DTx, and anti-TTC antibodies. Like wild-type SMN, purified SDT showed specific binding in vitro to an RG peptide derived from Ewing's sarcoma protein. The fusion protein also bound to cultured primary neurons in amounts similar to those achieved by TTC. Unlike the case with TTC, however, immunolabeling of SDT-treated neurons with anti-TTC and anti-SMN antibodies showed staining restricted to the cell surface. Results from cytotoxicity studies in which the DTx catalytic domain of SDT was used as a reporter protein for internalization and membrane translocation activity suggest that the SMN moiety of the fusion protein is interfering with one or both of these processes. While these studies indicate that SDT may not be useful for SMA therapy, the use of the TTC:DTx fusion construct to deliver other passenger proteins to the neuronal cytosol should not be ruled out.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14644474 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>20</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Monani, U. R.</style></author>
										<author><style face="normal" font="default" size="100%">Pastore, M. T.</style></author>
										<author><style face="normal" font="default" size="100%">Gavrilina, T. O.</style></author>
										<author><style face="normal" font="default" size="100%">Jablonka, S.</style></author>
										<author><style face="normal" font="default" size="100%">Le, T. T.</style></author>
										<author><style face="normal" font="default" size="100%">Andreassi, C.</style></author>
										<author><style face="normal" font="default" size="100%">DiCocco, J. M.</style></author>
										<author><style face="normal" font="default" size="100%">Lorson, C.</style></author>
										<author><style face="normal" font="default" size="100%">Androphy, E. J.</style></author>
										<author><style face="normal" font="default" size="100%">Sendtner, M.</style></author>
										<author><style face="normal" font="default" size="100%">Podell, M.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, Ohio State University, Columbus, OH 43210, USA. monani.2@osu.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A transgene carrying an A2G missense mutation in the SMN gene modulates phenotypic severity in mice with severe (type I) spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">41-52</style></pages>
			<volume><style face="normal" font="default" size="100%">160</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Axons/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Southern</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Western</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DNA, Complementary/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Electromyography</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Electrophysiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genotype</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Glutathione Transferase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Homozygote</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Knockout</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Transgenic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Biological</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscles/cytology/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Mutation, Missense</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Phenotype</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Binding</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Reverse Transcriptase Polymerase Chain Reaction</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Time Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Tissue Distribution</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Transgenes</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2003</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">5q spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and the leading genetic cause of infantile death. Patients lack a functional survival of motor neurons (SMN1) gene, but carry one or more copies of the highly homologous SMN2 gene. A homozygous knockout of the single murine Smn gene is embryonic lethal. Here we report that in the absence of the SMN2 gene, a mutant SMN A2G transgene is unable to rescue the embryonic lethality. In its presence, the A2G transgene delays the onset of motor neuron loss, resulting in mice with mild SMA. We suggest that only in the presence of low levels of full-length SMN is the A2G transgene able to form partially functional higher order SMN complexes essential for its functions. Mild SMA mice exhibit motor neuron degeneration, muscle atrophy, and abnormal EMGs. Animals homozygous for the mutant transgene are less severely affected than heterozygotes. This demonstrates the importance of SMN levels in SMA even if the protein is expressed from a mutant allele. Our mild SMA mice will be useful in (a) determining the effect of missense mutations in vivo and in motor neurons and (b) testing potential therapies in SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12515823 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>881</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Thi Man, N.</style></author>
										<author><style face="normal" font="default" size="100%">Humphrey, E.</style></author>
										<author><style face="normal" font="default" size="100%">Lam, L. T.</style></author>
										<author><style face="normal" font="default" size="100%">Fuller, H. R.</style></author>
										<author><style face="normal" font="default" size="100%">Lynch, T. A.</style></author>
										<author><style face="normal" font="default" size="100%">Sewry, C. A.</style></author>
										<author><style face="normal" font="default" size="100%">Goodwin, P. R.</style></author>
										<author><style face="normal" font="default" size="100%">Mackenzie, A. E.</style></author>
										<author><style face="normal" font="default" size="100%">Morris, G. E.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">From the Wolfson Centre for Inherited Neuromuscular Disease (N.t.M., E.H., L.T.L., H.R.F., T.A.L., C.A.S., G.E.M.), Oswestry, UK; Hallmark Analytical Ventures (P.R.G.), Saltney, Flintshire, UK; Children's Hospital of Eastern Ontario Research Institute (A.E.M.), Ottawa, Canada; and Institute for Science and Technology in Medicine (G.E.M.), Keele University, UK.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A two-site ELISA can quantify upregulation of SMN protein by drugs for spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">OBJECTIVES: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons during early or postnatal development. Severity is variable and is inversely related to the levels of survival of motor neurons (SMN) protein. The aim of this study was to produce a two-site ELISA capable of measuring both the low, basal levels of SMN protein in cell cultures from patients with severe SMA and small increases in these levels after treatment of cells with drugs. METHODS: A monoclonal antibody against recombinant SMN, MANSMA1, was selected for capture of SMN onto microtiter plates. A selected rabbit antiserum against refolded recombinant SMN was used for detection of the captured SMN. RESULTS: The ratio of SMN levels in control fibroblasts to levels in SMA fibroblasts was greater than 3.0, consistent with Western blot data. The limit of detection was 0.13 ng/mL and SMN could be measured in human NT-2 neuronal precursor cells grown in 96-well culture plates (3 x 10(4) cells per well). Increases in SMN levels of 50% were demonstrable by ELISA after 24 hours treatment of 10(5) SMA fibroblasts with valproate or phenylbutyrate. CONCLUSION: A rapid and specific two-site, 96-well ELISA assay, available in kit format, can now quantify the effects of drugs on survival of motor neurons protein levels in cell cultures.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18633133 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>357</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Levy, G.</style></author>
										<author><style face="normal" font="default" size="100%">Kaufmann, P.</style></author>
										<author><style face="normal" font="default" size="100%">Buchsbaum, R.</style></author>
										<author><style face="normal" font="default" size="100%">Montes, J.</style></author>
										<author><style face="normal" font="default" size="100%">Barsdorf, A.</style></author>
										<author><style face="normal" font="default" size="100%">Arbing, R.</style></author>
										<author><style face="normal" font="default" size="100%">Battista, V.</style></author>
										<author><style face="normal" font="default" size="100%">Zhou, X.</style></author>
										<author><style face="normal" font="default" size="100%">Mitsumoto, H.</style></author>
										<author><style face="normal" font="default" size="100%">Levin, B.</style></author>
										<author><style face="normal" font="default" size="100%">Thompson, J. L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY 10032, USA. GL227@columbia.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">A two-stage design for a phase II clinical trial of coenzyme Q10 in ALS</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">660-3</style></pages>
			<volume><style face="normal" font="default" size="100%">66</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">BACKGROUND: The combination of a small pool of patients at any given time with the availability of many potential neuroprotective agents to be tested in ALS requires efficient phase II trial designs. OBJECTIVE: To describe the design of the Clinical Trial of High Dose Coenzyme Q10 (CoQ10) in ALS (QALS study)--a phase II, randomized, placebo-controlled, double-blind, multicenter clinical trial. METHODS: The study design features two stages. The first stage (dose selection) identifies which of two doses of CoQ10 (1800 mg or 2700 mg) is preferred using a selection procedure rather than a formal hypothesis test. The second stage (early efficacy test) compares the preferred dose of CoQ10 against placebo using a non-superiority or futility design. Data from patients assigned to the preferred dose of CoQ10 in the first stage are also used in the second stage. The primary outcome measure is the decline in Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRSr) score from baseline to 9 months. RESULTS: The total sample size required is 185 patients, as compared to a much larger sample size estimated to be necessary using a conventional superiority design (total: 852 patients). The authors report a bias correction made necessary by the inclusion of patient data from the first stage in the second stage. CONCLUSIONS: Several features of the Clinical Trial of High Dose Coenzyme Q10 in ALS study design promote efficiency. These features may be beneficial in phase II trials in amyotrophic lateral sclerosis and other fields.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16534103 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1058</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Suzuki, E.</style></author>
										<author><style face="normal" font="default" size="100%">Zhao, Y.</style></author>
										<author><style face="normal" font="default" size="100%">Ito, S.</style></author>
										<author><style face="normal" font="default" size="100%">Sawatsubashi, S.</style></author>
										<author><style face="normal" font="default" size="100%">Murata, T.</style></author>
										<author><style face="normal" font="default" size="100%">Furutani, T.</style></author>
										<author><style face="normal" font="default" size="100%">Shirode, Y.</style></author>
										<author><style face="normal" font="default" size="100%">Yamagata, K.</style></author>
										<author><style face="normal" font="default" size="100%">Tanabe, M.</style></author>
										<author><style face="normal" font="default" size="100%">Kimura, S.</style></author>
										<author><style face="normal" font="default" size="100%">Ueda, T.</style></author>
										<author><style face="normal" font="default" size="100%">Fujiyama, S.</style></author>
										<author><style face="normal" font="default" size="100%">Lim, J.</style></author>
										<author><style face="normal" font="default" size="100%">Matsukawa, H.</style></author>
										<author><style face="normal" font="default" size="100%">Kouzmenko, A. P.</style></author>
										<author><style face="normal" font="default" size="100%">Aigaki, T.</style></author>
										<author><style face="normal" font="default" size="100%">Tabata, T.</style></author>
										<author><style face="normal" font="default" size="100%">Takeyama, K.</style></author>
										<author><style face="normal" font="default" size="100%">Kato, S.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">3818-22</style></pages>
			<volume><style face="normal" font="default" size="100%">106</style></volume>
			<number><style face="normal" font="default" size="100%">10</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat (polyQ) expansion within the human androgen receptor (AR). Unlike other neurodegenerative diseases caused by abnormal polyQ expansion, the onset of SBMA depends on androgen binding to mutant human polyQ-AR proteins. This is also observed in Drosophila eyes ectopically expressing the polyQ-AR mutants. We have genetically screened mediators of androgen-induced neurodegeneration caused by polyQ-AR mutants in Drosophila eyes. We identified Rbf (Retinoblastoma-family protein), the Drosophila homologue of human Rb (Retinoblastoma protein), as a neuroprotective factor. Androgen-dependent association of Rbf or Rb with AR was remarkably potentiated by aberrant polyQ expansion. Such potentiated Rb association appeared to attenuate recruitment of histone deacetyltransferase 1 (HDAC1), a corepressor of E2F function. Either overexpression of Rbf or E2F deficiency in fly eyes reduced the neurotoxicity of the polyQ-AR mutants. Induction of E2F function by polyQ-AR-bound androgen was suppressed by Rb in human neuroblastoma cells. We conclude that abnormal expansion of polyQ may potentiate innate androgen-dependent association of AR with Rb. This appears to lead to androgen-dependent onset of SBMA through aberrant E2F transactivation caused by suppressed histone deacetylation.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19237573 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1375</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Anthony, K.</style></author>
										<author><style face="normal" font="default" size="100%">Gallo, J. M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">MRC Centre for Neurodegeneration Research, King's College London, Institute of Psychiatry, Department of Clinical Neuroscience, PO37, De Crespigny Park, London, SE5 8AF, United Kingdom.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aberrant RNA processing events in neurological disorders</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The importance of aberrant RNA processing in neurodegeneration is becoming increasingly clear; a recent example being the identification of the splicing factor TDP-43 as the major component of inclusions characteristic of a number of neurodegenerative conditions including amyotrophic lateral sclerosis (ALS). Due to the enormous diversity generated by alternative splicing and its importance in the nervous system, it is no surprise that defective alternative splicing in disease has been particularly well documented. However, in addition to splicing, other RNA processing events such as RNA editing, polyadenylation and mRNA stability are also disrupted in some neurological disorders. For instance: the editing efficiency of specific ionotropic receptors is reduced in ALS affecting ion permeability and the function of RNA-processing proteins is affected by their sequestration to trinucleotide repeat expanded mRNAs in several disorders. Due to the extensive coupling between RNA processing events and the multifunctionality of the RNA processing factors that regulate them it is important to consider RNA processing as a whole. Here we review RNA processing events, their extensive coupling to one another and detail the associations of RNA processing including, but not exclusively, alternative splicing with neurodegeneration.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20226177 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>545</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Crawford, T. O.</style></author>
										<author><style face="normal" font="default" size="100%">Sladky, J. T.</style></author>
										<author><style face="normal" font="default" size="100%">Hurko, O.</style></author>
										<author><style face="normal" font="default" size="100%">Besner-Johnston, A.</style></author>
										<author><style face="normal" font="default" size="100%">Kelley, R. I.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abnormal fatty acid metabolism in childhood spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">337-43</style></pages>
			<volume><style face="normal" font="default" size="100%">45</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Age Distribution</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Child, Preschool</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fatty Acids/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Infant</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Lauric Acids/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1999</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">3</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Our previous experience with abnormal fatty acid metabolism in several children with spinal muscular atrophy (SMA) prompted evaluation of fatty acid metabolism in a larger cohort. Thirty-three infants with severe infantile SMA were shown to have a significantly increased ratio of dodecanoic to tetradecanoic acid in plasma compared with normal infants and 6 infants affected with equally debilitating, non-SMA denervating disorders. Seventeen children with milder forms of SMA had normal fatty acid profiles. In addition, all 5 infants with severe SMA evaluated in a fasting state developed a distinctive and marked dicarboxylic aciduria, including saturated, unsaturated, and 3-hydroxy forms, comparable in severity with the dicarboxylic aciduria of children with primary defects of mitochondrial fatty acid beta-oxidation. Nine children with chronic SMA and 23 control patients did not develop an abnormal dicarboxylic aciduria during fasting. No known disorder of fatty acid metabolism explains all of the abnormalities we find in SMA. Our data suggest, however, that the abnormalities are not a consequence of SMA-related immobility, systemic illness, muscle denervation, or muscle atrophy. These abnormalities in fatty acid metabolism may be caused by changes in cellular physiology related to the molecular defects of the SMA-pathogenic survival motor neuron gene or neighboring genes.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10072048 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1264</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Su, B.</style></author>
										<author><style face="normal" font="default" size="100%">Wang, X.</style></author>
										<author><style face="normal" font="default" size="100%">Zheng, L.</style></author>
										<author><style face="normal" font="default" size="100%">Perry, G.</style></author>
										<author><style face="normal" font="default" size="100%">Smith, M. A.</style></author>
										<author><style face="normal" font="default" size="100%">Zhu, X.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abnormal Mitochondrial Dynamics and Neurodegenerative Diseases</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Mitochondrial dysfunction is a prominent feature of various neurodegenerative diseases. A deeper understanding of the remarkably dynamic nature of mitochondria, characterized by a delicate balance of fission and fusion, has helped to fertilize a recent wave of new studies demonstrating abnormal mitochondrial dynamics in neurodegenerative diseases. This review highlights mitochondrial dysfunction and abnormal mitochondrial dynamics in Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease and discusses how these abnormal mitochondrial dynamics may contribute to mitochondrial and neuronal dysfunction. We propose that abnormal mitochondrial dynamics represents a key common pathway that mediates or amplifies mitochondrial dysfunction and neuronal dysfunction during the course of neurodegeneration.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19799998 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>871</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Simic, G.</style></author>
										<author><style face="normal" font="default" size="100%">Mladinov, M.</style></author>
										<author><style face="normal" font="default" size="100%">Seso Simic, D.</style></author>
										<author><style face="normal" font="default" size="100%">Jovanov Milosevic, N.</style></author>
										<author><style face="normal" font="default" size="100%">Islam, A.</style></author>
										<author><style face="normal" font="default" size="100%">Pajtak, A.</style></author>
										<author><style face="normal" font="default" size="100%">Barisic, N.</style></author>
										<author><style face="normal" font="default" size="100%">Sertic, J.</style></author>
										<author><style face="normal" font="default" size="100%">Lucassen, P. J.</style></author>
										<author><style face="normal" font="default" size="100%">Hof, P. R.</style></author>
										<author><style face="normal" font="default" size="100%">Kruslin, B.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neuroscience, School of Medicine, Croatian Institute for Brain Research, Medical School Zagreb, Zagreb University, Salata 12, 10000 Zagreb, Croatia. gsimic@hiim.hr</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">313-26</style></pages>
			<volume><style face="normal" font="default" size="100%">115</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Axons/metabolism/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Brain/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Differentiation/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Movement/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">In Situ Nick-End Labeling</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/metabolism/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal Cord/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal Muscular Atrophies of Childhood/metabolism/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">3</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying a homozygous deletion of exon 7 in the SMN1 gene. Unlike controls, virtually free from HMN, all SMA subjects showed a significant number of HMN at all levels of the spinal cord. Heterotopic neurons were hyperchromatic, located mostly in the ventral white matter and had no axon or dendrites. More than half of the HMN were very undifferentiated, as judged from their lack of immunoreactivity for NeuN and MAP2 proteins. Small numbers of more differentiated heterotopic neurons were also found in the dorsal and lateral white matter region. As confirmed by ultrastructural analysis, in situ end labeling (ISEL) and CD68 immunoreactivity, HMN in the ventral outflow were found to have no synapses, to activate microglial cells, and to eventually die by necrosis. An unbiased quantitative analysis showed a significant negative correlation between age of SMA subjects (a reflection of the clinical severity) and the number of HMN. Subjects who died at older ages had increased number of GFAP-positive astrocytes. Complementing our previous report on motoneuron apoptosis within the ventral horns in SMA, we now propose that abnormal migration, differentiation, and lack of axonal outgrowth may induce motoneuron apoptosis predominantly during early stages, whereas a slower necrosis-like cell death of displaced motoneurons which "escaped" apoptosis characterizes later stages of SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18075747 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>664</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Butchbach, M. E.</style></author>
										<author><style face="normal" font="default" size="100%">Edwards, J. D.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Molecular and Cellular Biochemistry, College of Medicine, The Ohio State University, Columbus, OH, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abnormal motor phenotype in the SMNDelta7 mouse model of spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2007</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a recessive motor neuron disease that affects motor neurons in the anterior horn of the spinal cord. SMA results from the reduction of SMN (survival motor neuron) protein. Even though SMN is ubiquitously expressed, motor neurons are more sensitive to the reduction in SMN than other cell types. We have previously generated mouse models of SMA with varying degrees of clinical severity. So as to more clearly understand the pathogenesis of motor neuron degeneration in SMA, we have characterized the phenotype of the SMNDelta7 SMA mouse which normally lives for 13.6+/-0.7 days. These mice are smaller than their non-SMA littermates and begin to lose body mass at 10.4+/-0.4 days. SMNDelta7 SMA mice exhibit impaired responses to surface righting, negative geotaxis and cliff aversion but not to tactile stimulation. Spontaneous motor activity and grip strength are also significantly impaired in SMNDelta7 SMA mice. In summary, we have demonstrated an impairment of neonatal motor responses in SMNDelta7 SMA mice. This phenotype characterization could be used to assess the effectiveness of potential therapies for SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17561409 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1238</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Goldknopf, I. L.</style></author>
										<author><style face="normal" font="default" size="100%">Bryson, J. K.</style></author>
										<author><style face="normal" font="default" size="100%">Strelets, I.</style></author>
										<author><style face="normal" font="default" size="100%">Quintero, S.</style></author>
										<author><style face="normal" font="default" size="100%">Sheta, E. A.</style></author>
										<author><style face="normal" font="default" size="100%">Mosqueda, M.</style></author>
										<author><style face="normal" font="default" size="100%">Park, H. R.</style></author>
										<author><style face="normal" font="default" size="100%">Appel, S. H.</style></author>
										<author><style face="normal" font="default" size="100%">Shill, H.</style></author>
										<author><style face="normal" font="default" size="100%">Sabbagh, M.</style></author>
										<author><style face="normal" font="default" size="100%">Chase, B.</style></author>
										<author><style face="normal" font="default" size="100%">Kaldjian, E.</style></author>
										<author><style face="normal" font="default" size="100%">Markopoulou, K.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Power3 Medical Products, Inc., The Woodlands, TX 77381, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abnormal serum concentrations of proteins in Parkinson's disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Blood serum was used to identify protein biomarkers for diagnosis of Parkinson's disease (PD) using analytically validated quantitative 2D-gel electrophoresis, and single variable and multivariate statistics. Using banked samples from a first medical center, we identified 57 specific protein spot biomarkers with disease-specific abnormal levels in serum of patients with PD, Alzheimer's disease, amyotrophic lateral sclerosis and similar neurodegenerative conditions (337 samples), when compared to age-matched normal controls (132 samples). To further assess their clinical usefulness in Parkinson's disease, we obtained prospective newly drawn blood serum samples from a second (56 PD, 30 controls) and third (6 PD, 48 controls) medical center. The protein concentrations of the 57 biomarkers were assessed by 2D-gel electrophoresis. Stepwise linear discriminant analysis selected a combination of 21 of the 57 as optimal to distinguish PD patients from controls. When applied to the samples from the second site, the 21 proteins had sensitivity of 93.3% (52 of 56 PD correctly classified), specificity of 92.9% (28 of 30 controls correctly classified); 15 of 15 patients with mild, 28 of 30 with moderate to severe symptoms, and all of the 6 PD patients from the third site were correctly classified. Eleven of the 21 proteins showed statistically significant abnormal concentrations in patients with mild symptoms, and 14 in patients with moderate-severe symptoms. The protein identities reflect the heterogeneity of Parkinson's disease, and thus may provide the capability of monitoring the blood for a diverse range of PD pathophysiological mechanisms: cellular degeneration, oxidative stress, inflammation, and transport.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19723509 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>952</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Corcia, P.</style></author>
										<author><style face="normal" font="default" size="100%">Mayeux-Portas, V.</style></author>
										<author><style face="normal" font="default" size="100%">Khoris, J.</style></author>
										<author><style face="normal" font="default" size="100%">de Toffol, B.</style></author>
										<author><style face="normal" font="default" size="100%">Autret, A.</style></author>
										<author><style face="normal" font="default" size="100%">Muh, J. P.</style></author>
										<author><style face="normal" font="default" size="100%">Camu, W.</style></author>
										<author><style face="normal" font="default" size="100%">Andres, C.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">INSERM U316, Tours, France.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abnormal SMN1 gene copy number is a susceptibility factor for amyotrophic lateral sclerosis</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">243-6</style></pages>
			<volume><style face="normal" font="default" size="100%">51</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amyotrophic Lateral Sclerosis/epidemiology/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Dosage</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Risk Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2002</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">2</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The etiology of amyotrophic lateral sclerosis remains unknown in the majority of cases. Homozygous SMN1 (survival motor neuron) gene deletion causes spinal muscular atrophy, and SMN2 gene deletions are possible risk factors in lower motor neuron disease. We studied SMN1 and SMN2 genes copy numbers in 167 amyotrophic lateral sclerosis patients and in 167 matched controls. We noted that 16% of amyotrophic lateral sclerosis patients had an abnormal copy number of the SMN1 gene (1 or 3 copies), compared with 4% of controls. An abnormal SMN1 gene locus may be a susceptibility factor for amyotrophic lateral sclerosis.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11835381 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>321</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Tsai, M. S.</style></author>
										<author><style face="normal" font="default" size="100%">Chiu, Y. T.</style></author>
										<author><style face="normal" font="default" size="100%">Wang, S. H.</style></author>
										<author><style face="normal" font="default" size="100%">Hsieh-Li, H. M.</style></author>
										<author><style face="normal" font="default" size="100%">Lian, W. C.</style></author>
										<author><style face="normal" font="default" size="100%">Li, H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abolishing Bax-Dependent Apoptosis Shows Beneficial Effects on Spinal Muscular Atrophy Model Mice</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron degeneration is unclear. We previously generated SMA model mice, which genotypically and phenotypically mimicked human SMA patients, by a combination of knockout and transgenic techniques. Here, we used these SMA model mice to decipher the apoptotic mechanism(s) involved in SMA motoneuron degeneration. We found a significant increase in proapoptotic Bax expression in the spinal cords of SMA mice in comparison with their wild-type littermates. After crossing SMA mice with Bax knockout mice, we produced in vivo evidence indicating that Bax protein plays an important role in the degeneration of SMA spinal motoneurons. Progeny Bax-deficient SMA mice showed milder disease severity, longer life spans, and significant increases in spinal motoneuron densities compared to SMA littermates with wild-type Bax genes. Our results strongly suggest that suppression of Bax-involved apoptosis has the potential for amelioration of SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16564230 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>133</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Tsai, M. S.</style></author>
										<author><style face="normal" font="default" size="100%">Chiu, Y. T.</style></author>
										<author><style face="normal" font="default" size="100%">Wang, S. H.</style></author>
										<author><style face="normal" font="default" size="100%">Hsieh-Li, H. M.</style></author>
										<author><style face="normal" font="default" size="100%">Li, H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">[1] 1Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan [2] 2Department of Bioindustry Technology, Da-Yeh University, Da-Tsuen, Chang-Hua, Taiwan.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Abolishing Trp53-dependent apoptosis does not benefit spinal muscular atrophy model mice</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">372-5</style></pages>
			<volume><style face="normal" font="default" size="100%">14</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">3</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron death is unclear. Previously, a direct interaction between tumor-suppressive TP53 protein and the SMA determinant gene product, survival motor neuron protein, was identified and therefore it has been suggested that a mechanism of TP53-dependent apoptosis plays an important role in motoneuron degeneration in SMA. We used our SMA model mice, generated by a combination of knockout and transgenic techniques, to decipher the role of TP53 protein in the motoneuron degeneration in SMA. We detected a significant increase of Trp53 expression in the spinal cord of SMA-like mice compared to their normal littermates. After crossing SMA-like mice with Trp53 knockout mice, the progeny Trp53-deficient SMA-like mice did not show milder disease severity or longer lifespan compared to SMA littermates with wild-type Trp53 genes. Our studies provide in vivo evidence indicating that Trp53-dependent apoptosis does not play a crucial role in motoneuron degeneration in SMA-like mice.European Journal of Human Genetics (2006) 14, 372-375. doi:10.1038/sj.ejhg.5201556; published online 4 January 2006.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16391561 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>811</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Yampolsky, P.</style></author>
										<author><style face="normal" font="default" size="100%">Gensler, S.</style></author>
										<author><style face="normal" font="default" size="100%">McArdle, J.</style></author>
										<author><style face="normal" font="default" size="100%">Witzemann, V.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Max-Planck-Institute for Medical Research, Department of Cell Physiology, Jahnstrasse 29, D-69120 Heidelberg, Germany.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">AChR channel conversion and AChR-adjusted neuronal survival during embryonic development</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">634-45</style></pages>
			<volume><style face="normal" font="default" size="100%">37</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Acetylcholinesterase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals, Newborn</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Autoradiography</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Bungarotoxins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Survival</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Embryo, Mammalian</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Embryonic Development</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression Regulation, Developmental/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Luminescent Proteins/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Transgenic</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/cytology/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Smooth/embryology/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Neuromuscular Junction/embryology/growth & development/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Binding/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Transport/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Receptors, Cholinergic/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Receptors, Nicotinic/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">3</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">We generated knock-in mice that express GFP-labeled embryonic-type acetylcholine receptors (AChR) to follow postsynaptic differentiation and innervation during embryonic development and to visualize the postnatally occurring channel conversion from embryonic- to adult-type AChR. The dynamics of AChRgamma/AChRepsilon conversion at the neuromuscular junction indicates that muscle-specific programs of receptor subunit gene transcription control AChR replacement. While conversion proceeds from peripheral to central regions for individual endplates, it does not occur simultaneously for all endplates. Although GFP-labeled receptors were expressed at reduced levels, the localization of postsynaptic sites and synapse formation was not noticeably altered. However, these alterations correlated with a striking reduction of motoneuron programmed cell death, transient increase of neurite growth and axon branching. This animal model refines the view on reciprocal neuromuscular signaling and suggests that motoneuron survival and axon branching are directly regulated by AChR function to enable optimal innervation and timing of neurally evoked muscle contraction.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18226545 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Andreassi, C.</style></author>
										<author><style face="normal" font="default" size="100%">Jarecki, J.</style></author>
										<author><style face="normal" font="default" size="100%">Zhou, J.</style></author>
										<author><style face="normal" font="default" size="100%">Coovert, D. D.</style></author>
										<author><style face="normal" font="default" size="100%">Monani, U. R.</style></author>
										<author><style face="normal" font="default" size="100%">Chen, X.</style></author>
										<author><style face="normal" font="default" size="100%">Whitney, M.</style></author>
										<author><style face="normal" font="default" size="100%">Pollok, B.</style></author>
										<author><style face="normal" font="default" size="100%">Zhang, M.</style></author>
										<author><style face="normal" font="default" size="100%">Androphy, E.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, OH 43210, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">2841-9</style></pages>
			<volume><style face="normal" font="default" size="100%">10</style></volume>
			<number><style face="normal" font="default" size="100%">24</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Aclarubicin/*pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Alternative Splicing/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Blotting, Western</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Line</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dose-Response Relationship, Drug</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Drug Evaluation, Preclinical</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Feasibility Studies</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fibroblasts</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/drug effects/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA, Messenger/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Reverse Transcriptase Polymerase Chain Reaction</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal Muscular Atrophies of Childhood/*drug therapy/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transcription, Genetic/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transfection</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2001</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Proximal spinal muscular atrophy (SMA) is a common motor neuron disorder caused by mutation of the telomeric survival of motor neuron gene SMN1. The centromeric survival of motor neuron SMN2 gene is retained in all SMA patients but does not produce sufficient SMN protein to prevent the development of clinical symptoms. The SMN1 and SMN2 genes differ functionally by a single nucleotide change. This change affects the efficiency with which exon 7 is incorporated into the mRNA transcript. Thus, SMN2 produces less full-length mRNA and protein than SMN1. We have screened a library of compounds in order to identify ones that can alter the splicing pattern of the SMN2 gene. Here, we report that the compound aclarubicin increases the retention of exon 7 into the SMN2 transcript. We show that aclarubicin effectively induces incorporation of exon 7 into SMN2 transcripts from the endogenous gene in type I SMA fibroblasts as well as into transcripts from a SMN2 minigene in the motor neuron cell line NSC34. In type I fibroblasts, treatment resulted in an increase in SMN protein and gems to normal levels. Our results suggest that alteration of splicing pattern represents a new approach to modification of gene expression in disease treatment and demonstrate the feasibility of high throughput screens to detect compounds that affect the splicing pattern of a gene.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11734549 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1106</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%"></style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">ACOG Committee Opinion No. 432: Spinal Muscular Atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1194-6</style></pages>
			<volume><style face="normal" font="default" size="100%">113</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">5</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%"></style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19384151 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>189</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Olaso, R.</style></author>
										<author><style face="normal" font="default" size="100%">Joshi, V.</style></author>
										<author><style face="normal" font="default" size="100%">Fernandez, J.</style></author>
										<author><style face="normal" font="default" size="100%">Roblot, N.</style></author>
										<author><style face="normal" font="default" size="100%">Courageot, S.</style></author>
										<author><style face="normal" font="default" size="100%">Bonnefont, J. P.</style></author>
										<author><style face="normal" font="default" size="100%">Melki, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Molecular Neurogenetics Laboratory, Institut National de la Sante et de la Recherche Medicale (INSERM), E-223, University of Evry, Genopole, Evry, France.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Activation of RNA metabolism-related genes in mouse but not human tissues deficient in SMN</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">97-104</style></pages>
			<volume><style face="normal" font="default" size="100%">24</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Mutations of the survival of motor neuron gene (SMN1) are responsible for spinal muscular atrophies (SMA), a frequent recessive autosomal motor neuron disease. SMN is involved in various processes including RNA metabolism. However, the molecular pathway linking marked deficiency of SMN to SMA phenotype remains unclear. Homozygous deletion of murine Smn exon 7 directed to neurons or skeletal muscle causes severe motor axonal or myofiber degeneration, respectively. With the use of cDNA microarrays, expression profiles of 8,400 genes were analyzed in skeletal muscle and spinal cord of muscular and neuronal mutants, respectively, and compared with age-matched controls. A high proportion of genes (20 of 429, 5%) was involved in pre-mRNA splicing, ribosomal RNA processing, or RNA decay, and 18 of them were upregulated in mutant tissues. By analyzing other neuromuscular disorders, we showed that most of them (14 of 18) were specific to the SMN defect. Quantitative PCR analysis of these transcripts showed that gene activation was an early adaptive response to the lack but not reduced amount of full-length SMN in mouse mutant tissues. In human SMA tissues, activation of this program was not observed, which could be ascribed to the reduction but not the absence of full-length SMN.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16118268 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>293</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Zhang, H. L.</style></author>
										<author><style face="normal" font="default" size="100%">Pan, F.</style></author>
										<author><style face="normal" font="default" size="100%">Hong, D.</style></author>
										<author><style face="normal" font="default" size="100%">Shenoy, S. M.</style></author>
										<author><style face="normal" font="default" size="100%">Singer, R. H.</style></author>
										<author><style face="normal" font="default" size="100%">Bassell, G. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neuroscience, Rose F. Kennedy Center for Mental Retardation, Albert Einstein College of Medicine, Bronx, New York 10461, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Active transport of the survival motor neuron protein and the role of exon-7 in cytoplasmic localization</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">6627-37</style></pages>
			<volume><style face="normal" font="default" size="100%">23</style></volume>
			<number><style face="normal" font="default" size="100%">16</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Nucleus/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cells, Cultured</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chick Embryo</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cytoplasm/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cytoplasmic Granules/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fibroblasts/cytology/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genes, Reporter</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Growth Cones/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microfilaments/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Microtubules/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurites/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurons/cytology/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Transport/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Deletion</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2003</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by deletion and/or mutation of the survival motor neuron protein Gene (SMN1) that results in the expression of a truncated protein lacking the C terminal exon-7. Whereas SMN has been shown to be an important component of diverse ribonucleoprotein (RNP) complexes, its function in neurons is unknown. We hypothesize that the active transport of SMN may be important for neurite outgrowth and that disruption of exon-7 could impair its normal intracellular trafficking. SMN was localized in granules that were associated with cytoskeletal filament systems and distributed throughout neurites and growth cones. Live cell imaging of enhanced green fluorescent protein (EGFP)-SMN granules revealed rapid, bidirectional and cytoskeletal-dependent movements. Exon-7 was necessary for localization of SMN into the cytoplasm but was not sufficient for granule formation and transport. A cytoplasmic targeting signal within exon-7 was identified that could completely redistribute the nuclear protein D-box binding factor 1 into the cytoplasm. Neurons transfected with SMN lacking exon-7 had significantly shorter neurites, a defect that could be rescued by redirecting the exon-7 deletion mutant into neurites by a targeting sequence from growth-associated protein-43. These findings provide the first demonstration of cytoskeletal-based active transport of SMN in neuronal processes and the function of exon-7 in cytoplasmic localization. Such observations provide motivation to investigate possible transport defects or inefficiency of SMN associated RNPs in motor neuron axons in SMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12878704 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>395</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Bruno, M. A.</style></author>
										<author><style face="normal" font="default" size="100%">Cuello, A. C.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Departments of Pharmacology and Therapeutics, Anatomy and Cell Biology, and Neurology and Neurosurgery, McGill University, Montreal, QC, Canada H3G 1Y6.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%"></style></pages>
			<volume><style face="normal" font="default" size="100%"></style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">In this report, we provide direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF) and that it is in this compartment that its maturation and degradation takes place because of the coordinated release and the action of proenzymes and enzyme regulators. This converting protease cascade and its endogenous regulators (including tissue plasminogen activator, plasminogen, neuroserpin, precursor matrix metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in neurons of the cerebral cortex and released upon neuronal stimulation. We also provide evidence that this mechanism operates in in vivo conditions, as the CNS application of inhibitors of converting and degrading enzymes lead to dramatic alterations in the tissue levels of either precursor NGF or mature NGF. Pathological alterations of this cascade in the CNS might cause or contribute to a lack of proper neuronal trophic support in conditions such as cerebral ischemia, seizure and Alzheimer's disease or, conversely, to excessive local production of neurotrophins as reported in inflammatory arthritis pain.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16618925 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1214</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Ciobanu, C.</style></author>
										<author><style face="normal" font="default" size="100%">Reid, G.</style></author>
										<author><style face="normal" font="default" size="100%">Babes, A.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, Romania.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Acute and chronic effects of neurotrophic factors BDNF and GDNF on responses mediated by thermo-sensitive TRP channels in cultured rat dorsal root ganglion neurons</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">54-67</style></pages>
			<volume><style face="normal" font="default" size="100%">1284</style></volume>
			<number><style face="normal" font="default" size="100%"></style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Neurotrophic factors (NTFs), beside regulating neuronal survival in the central and peripheral nervous system, are also involved in the modulation of neuronal function in the adult animal. Both brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) levels are altered in pathological pain states, and exogenous BDNF and GDNF have multiple effects on pain behavior, depending on the animal model (i.e. inflammatory vs. neuropathic). Thermally gated TRP channels TRPM8, TRPA1 and TRPV1 play a significant role in pain signaling and their pattern and level of expression as well as their biophysical properties are altered in chronic pain states. Our aim was to investigate the effect of long-term and acute exposure to BDNF and GDNF on the functional expression of these thermoTRP channels in cultured rat dorsal root ganglion (DRG) neurons. We found that while BDNF treatment primarily increased the fraction of capsaicin-sensitive (TRPV1-expressing) neurons, GDNF exposure led to an increase in the allyl isothiocyanate (AITC)-responding (TRPA1-expressing) population. Moreover, BDNF treatment increased the amplitude of the response to both AITC and capsaicin. Acute treatment with both NTFs leads to a reduction in the magnitude of tachyphylaxis to noxious stimuli (heat and AITC). Overall, our data provides evidence for a role of BDNF and GDNF in regulating the pattern of expression and level of activity of the transducer channels TRPA1 and TRPV1, leading to enhanced neuronal sensitivity to painful stimuli and increased co-expression of thermoTRP channels.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19524560 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>708</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Wiese, S.</style></author>
										<author><style face="normal" font="default" size="100%">Jablonka, S.</style></author>
										<author><style face="normal" font="default" size="100%">Holtmann, B.</style></author>
										<author><style face="normal" font="default" size="100%">Orel, N.</style></author>
										<author><style face="normal" font="default" size="100%">Rajagopal, R.</style></author>
										<author><style face="normal" font="default" size="100%">Chao, M. V.</style></author>
										<author><style face="normal" font="default" size="100%">Sendtner, M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute for Clinical Neurobiology, University of Wurzburg, Josef Schneider Strasse 11, D-97080 Wurzburg, Germany.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Adenosine receptor A2A-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">17210-5</style></pages>
			<volume><style face="normal" font="default" size="100%">104</style></volume>
			<number><style face="normal" font="default" size="100%">43</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2007</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Neurotrophins are potent survival factors for developing and injured neurons. However, they are not being used to treat neurodegenerative diseases because of difficulties in administration and numerous side effects that have been encountered in previous clinical trials. Their biological activities use Trk (tropomyosin-related kinase) transmembrane tyrosine kinases. Therefore, one alternative approach is to use transactivation pathways such as adenosine 2A receptor agonists, which can activate Trk receptor signaling independent of neurotrophin binding. However, the relevance in vivo and applicability of these transactivation events during neurodegenerative and injury conditions have never been extensively studied. Here we demonstrate that motoneuron survival after facial nerve lesioning is significantly enhanced by transactivation of Trk receptor tyrosine kinases by adenosine agonists. Moreover, survival of motoneurons directly required the activation of the BDNF receptor TrkB and an increase in Akt (AKT8 virus oncogene cellular homolog) activity. The ability of small molecules to activate a trophic response by using Trk signaling provides a unique mechanism to promote survival signals in motoneurons and suggests new strategies for using transactivation in neurodegenerative diseases.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17940030 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1040</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Mannes, A. J.</style></author>
										<author><style face="normal" font="default" size="100%">Caudle, R. M.</style></author>
										<author><style face="normal" font="default" size="100%">O'Connell, B. C.</style></author>
										<author><style face="normal" font="default" size="100%">Iadarola, M. J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">NAB/NIDR/NIH, Bethesda, MD 20892, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Adenoviral gene transfer to spinal-cord neurons: intrathecal vs. intraparenchymal administration</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1-6</style></pages>
			<volume><style face="normal" font="default" size="100%">793</style></volume>
			<number><style face="normal" font="default" size="100%">1-2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adenoviridae/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cytomegalovirus/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Expression/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Gene Transfer Techniques</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Injections, Spinal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurons/drug effects/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Promoter Regions, Genetic/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats, Sprague-Dawley</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal Cord/*cytology/drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">beta-Galactosidase/diagnostic use/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1998</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The spinal cord is the site of many chronic, debilitating, neurological disorders that may be amenable to gene therapy. The present study, using quantitative and anatomical methods, examines the ability of replication deficient adenovirus to transfer a transcription cassette composed of the cytomegalovirus promoter driving the expression of the LacZ reporter gene (AdCMVbetagal) to spinal-cord neurons. Rats were microinjected with AdCMVbetagal into the spinal-cord parenchyma or subarachnoid space and sacrificed between 1 and 60 days post-infusion. The spinal cord was assayed for beta-galactosidase (beta-gal) activity fluorometrically (MUG). Intraparenchymal injection resulted in significant beta-gal activity at day 1, which peaked at day 7, and decreased at day 14 (21-, 57- and 9.8-fold of control respectively). The spatial distribution of beta-gal activity on day 7 was confined to the 1-cm section containing the injection site but was detected 2 cm caudal to this section by day 14. Histochemical staining and immunocytochemistry revealed a prominent reaction product in neurons, particularly motor neurons, and glia within the ventral grey matter bilaterally. Intrathecal viral injections showed comparatively modest, yet significant increases in beta-gal activity throughout the spinal cord with the greatest activity (170% control) closest to the catheter tip. This study demonstrates that AdCMVbetagal injected into the ventral spinal cord results in extensive in vivo neuronal gene transfer with beta-gal activity reaching a peak by day 7 and remaining detectable at 60 days. Intrathecal viral injections result in greater spatial distribution but a comparatively lower level of expression.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9630472 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>667</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Stoick-Cooper, C. L.</style></author>
										<author><style face="normal" font="default" size="100%">Moon, R. T.</style></author>
										<author><style face="normal" font="default" size="100%">Weidinger, G.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pharmacology, Howard Hughes Medical Institute, and Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1292-315</style></pages>
			<volume><style face="normal" font="default" size="100%">21</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Regeneration/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Regenerative Medicine</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Signal Transduction</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Vertebrates/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2007</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">While all animals have evolved strategies to respond to injury and disease, their ability to functionally recover from loss of or damage to organs or appendages varies widely damage to skeletal muscle, but, unlike amphibians and fish, they fail to regenerate heart, lens, retina, or appendages. The relatively young field of regenerative medicine strives to develop therapies aimed at improving regenerative processes in humans and is predicated on >40 years of success with bone marrow transplants. Further progress will be accelerated by implementing knowledge about the molecular mechanisms that regulate regenerative processes in model organisms that naturally possess the ability to regenerate organs and/or appendages. In this review we summarize the current knowledge about the signaling pathways that regulate regeneration of amphibian and fish appendages, fish heart, and mammalian liver and skeletal muscle. While the cellular mechanisms and the cell types involved in regeneration of these systems vary widely, it is evident that shared signals are involved in tissue regeneration. Signals provided by the immune system appear to act as triggers of many regenerative processes. Subsequently, pathways that are best known for their importance in regulating embryonic development, in particular fibroblast growth factor (FGF) and Wnt/beta-catenin signaling (as well as others), are required for progenitor cell formation or activation and for cell proliferation and specification leading to tissue regrowth. Experimental activation of these pathways or interference with signals that inhibit regenerative processes can augment or even trigger regeneration in certain contexts.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17545465 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>488</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Morrison, K. E.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Clinical Neurology, University of Oxford, UK.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Advances in SMA research: review of gene deletions</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">397-408</style></pages>
			<volume><style face="normal" font="default" size="100%">6</style></volume>
			<number><style face="normal" font="default" size="100%">6</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Chromosome Aberrations/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromosome Disorders</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cloning, Molecular</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Gene Deletion</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Genetic Diseases, Inborn/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Motor Neurons/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neuronal Apoptosis-Inhibitory Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, Non-U.S. Gov't</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">1996</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">12</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The term spinal muscular atrophy (SMA) is used to encompass a group of inherited disorders in which the striking pathological feature is loss of the cell bodies of alpha motor neurons in the anterior horn cell of the spinal cord and, in some cases, of the bulbar motor nuclei. Although the pathological features of these disorders have been well characterized, the nature of the primary underlying biochemical abnormality remains to be determined. In the 1990s genetic linkage was established for the childhood onset recessive forms of SMA (types I, II and III) to markers mapping to the chromosomal region 5q11.2-13.3. Physical maps of the region were then constructed, several candidate genes isolated and in 1995 deletions in two genes, the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene, were identified in significant numbers of patients. Already the impact of the characterization of these deletions is being seen in clinical practice in terms of aiding diagnosis in symptomatic cases and in prenatal diagnosis. As discussed in this review however, several questions remain unresolved. It is unclear whether deletions in one or both of these genes, or indeed in other, as yet unidentified, genes are important in generating the SMA phenotype. The function of the protein product of the SMN gene is unknown. The NAIP gene encodes a protein which inhibits apoptosis in a mammalian cell line: is it disruption of this function which is relevant in SMA? What underlies the variation in disease severity evident both between and within families? Resolution of such issues is of crucial importance if the identification of these deleted gene sequences is to lead to the development of rational therapies for motor neuron diseases.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9027847 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>328</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Salehi, A. H.</style></author>
										<author><style face="normal" font="default" size="100%">Morris, S. J.</style></author>
										<author><style face="normal" font="default" size="100%">Ho, W. C.</style></author>
										<author><style face="normal" font="default" size="100%">Dickson, K. M.</style></author>
										<author><style face="normal" font="default" size="100%">Doucet, G.</style></author>
										<author><style face="normal" font="default" size="100%">Milutinovic, S.</style></author>
										<author><style face="normal" font="default" size="100%">Durkin, J.</style></author>
										<author><style face="normal" font="default" size="100%">Gillard, J. W.</style></author>
										<author><style face="normal" font="default" size="100%">Barker, P. A.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Quebec, Canada.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">AEG3482 is an antiapoptotic compound that inhibits Jun kinase activity and cell death through induced expression of heat shock protein 70</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">213-23</style></pages>
			<volume><style face="normal" font="default" size="100%">13</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">2</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">We describe a group of small-molecule inhibitors of Jun kinase (JNK)-dependent apoptosis. AEG3482, the parental compound, was identified in a screening effort designed to detect compounds that reduce apoptosis of neonatal sympathetic neurons after NGF withdrawal. We show that AEG3482 blocks apoptosis induced by the p75 neurotrophin receptor (p75NTR) or its cytosolic interactor, NRAGE, and demonstrate that AEG3482 blocks proapoptotic JNK activity. We show that AEG3482 induces production of heat shock protein 70 (HSP70), an endogenous inhibitor of JNK, and establish that HSP70 accumulation is required for the AEG3482-induced JNK blockade. We show that AEG3482 binds HSP90 and induces HSF1-dependent HSP70 mRNA expression and find that AEG3482 facilitates HSP70 production while retaining HSP90 chaperone activity. These studies establish that AEG3482 inhibits JNK activation and apoptosis by a mechanism involving induced expression of HSP proteins.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16492569 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1280</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Haller, R. G.</style></author>
										<author><style face="normal" font="default" size="100%">Wyrick, P.</style></author>
										<author><style face="normal" font="default" size="100%">Taivassalo, T.</style></author>
										<author><style face="normal" font="default" size="100%">Vissing, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Neuromuscular Center, Institute for Exercise and Environmental Medicine of Presbyterian Hospital, Dallas, TX 75231, USA. ronald.haller@utsouthwestern.edu</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aerobic conditioning: an effective therapy in McArdle's disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">922-8</style></pages>
			<volume><style face="normal" font="default" size="100%">59</style></volume>
			<number><style face="normal" font="default" size="100%">6</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">3-Hydroxyacyl CoA Dehydrogenases/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cardiac Output/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Citrate (si)-Synthase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Creatine Kinase/blood</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Exercise Therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Glucose/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Glycogen Storage Disease Type V/*therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Oxygen Consumption/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Physical Fitness/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Quadriceps Muscle/enzymology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">6</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">OBJECTIVE: Susceptibility to exertional cramps and rhabdomyolysis in myophosphorylase deficiency (McArdle's disease [MD]) may lead patients to shun exercise. However, physical inactivity may worsen exercise intolerance by further reducing the limited oxidative capacity caused by blocked glycogenolysis. We investigated whether aerobic conditioning can safely improve exercise capacity in MD. METHODS: Eight MD patients (4 men and 4 women; age range, 33-61 years) pedalled a cycle ergometer for 30 to 40 minutes a day, 4 days a week, for 14 weeks, at an intensity corresponding to 60 to 70% of maximal heart rate. We monitored serum creatine kinase levels; changes in peak cycle work, oxygen uptake, and cardiac output; presence and magnitude of a spontaneous and glucose-induced second wind; and citrate synthase and beta-hydroxyacyl coenzyme A dehydrogenase enzyme activities in quadriceps muscle. RESULTS: The prescribed exercise program increased average work capacity (36%), oxygen uptake (14%), cardiac output (15%), and citrate synthase and beta-hydroxyacyl coenzyme A dehydrogenase enzyme levels (80 and 62%, respectively) without causing pain or cramping or increasing serum creatine kinase. A spontaneous and glucose-induced second wind was present and was of similar magnitude in each patient before and after training. INTERPRETATION: Moderate aerobic exercise is an effective means of improving exercise capacity in MD by increasing circulatory delivery and mitochondrial metabolism of bloodborne fuels.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16718692 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1282</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Olsen, D. B.</style></author>
										<author><style face="normal" font="default" size="100%">Orngreen, M. C.</style></author>
										<author><style face="normal" font="default" size="100%">Vissing, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology and the Copenhagen Muscle Research Center, National University Hospital Rigshospitalet, Copenhagen, Denmark. d.benee@mfi.ku.dk</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aerobic training improves exercise performance in facioscapulohumeral muscular dystrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1064-6</style></pages>
			<volume><style face="normal" font="default" size="100%">64</style></volume>
			<number><style face="normal" font="default" size="100%">6</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adolescent</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Age Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Creatine Kinase/blood</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Energy Metabolism/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exercise/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exercise Therapy/*methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exercise Tolerance/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle Fibers, Skeletal/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/blood supply/*physiology/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Dystrophy, Facioscapulohumeral/*therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Oxygen Consumption/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Physical Fitness/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Questionnaires</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Regional Blood Flow/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sex Factors</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Treatment Outcome</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Exercise programs have been shown to increase strength and endurance in patients with myopathic disorders. The authors investigated the effect of aerobic training in patients with facioscapulohumeral dystrophy (FSHD). Twelve weeks of low-intense aerobic exercise improved maximal oxygen uptake and workload with no signs of muscle damage. The authors conclude that aerobic training is a safe method to increase exercise performance in patients with FSHD.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15781829 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1281</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Orngreen, M. C.</style></author>
										<author><style face="normal" font="default" size="100%">Olsen, D. B.</style></author>
										<author><style face="normal" font="default" size="100%">Vissing, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Copenhagen Muscle Research Center and the Department of Neurology, National University Hospital, Rigshospitalet, Copenhagen, Denmark. rh10679@rh.dk</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aerobic training in patients with myotonic dystrophy type 1</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">754-7</style></pages>
			<volume><style face="normal" font="default" size="100%">57</style></volume>
			<number><style face="normal" font="default" size="100%">5</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Activities of Daily Living</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Anaerobic Threshold/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cell Size</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Creatine Kinase/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Exercise</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exercise Test</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Exercise Therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle Fibers, Skeletal/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/pathology/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Myotonic Dystrophy/pathology/physiopathology/*therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Oxygen Consumption/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">5</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12 patients with myotonic dystrophy. Efficacy was evaluated by cycle testing and muscle morphology before and after training. Patients increased their maximal oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter increased significantly, and creatine kinase did not increase with training. The study indicates that aerobic training is safe and can improve fitness effectively in patients with myotonic dystrophy.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15852373 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1278</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Jeppesen, T. D.</style></author>
										<author><style face="normal" font="default" size="100%">Schwartz, M.</style></author>
										<author><style face="normal" font="default" size="100%">Olsen, D. B.</style></author>
										<author><style face="normal" font="default" size="100%">Wibrand, F.</style></author>
										<author><style face="normal" font="default" size="100%">Krag, T.</style></author>
										<author><style face="normal" font="default" size="100%">Duno, M.</style></author>
										<author><style face="normal" font="default" size="100%">Hauerslev, S.</style></author>
										<author><style face="normal" font="default" size="100%">Vissing, J.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neurology, Neuromuscular Research Unit, The Copenhagen Muscle Research Centre, Rigshospitalet, Copenhagen, Denmark. dysgaard@rh.dk</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Aerobic training is safe and improves exercise capacity in patients with mitochondrial myopathy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">3402-12</style></pages>
			<volume><style face="normal" font="default" size="100%">129</style></volume>
			<number><style face="normal" font="default" size="100%">Pt 12</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Adult</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Aerobiosis/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Creatine Kinase/blood</style></keyword>
								<keyword><style face="normal" font="default" size="100%">DNA, Mitochondrial/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exercise Therapy/*methods</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Gene Deletion</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Heart Rate/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Lactates/blood</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Middle Aged</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mitochondria/enzymology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mitochondrial Myopathies/genetics/physiopathology/*therapy</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/enzymology/pathology/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Oxygen Consumption/physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Point Mutation/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Quality of Life</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Treatment Outcome</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2006</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">12</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Exercise intolerance is a prominent symptom in patients with mitochondrial myopathy (MM), but it is still unsettled whether exercise training is safe and beneficial for patients with MM. To address this, we studied the effect of 12 weeks cycle training on exercise capacity, quality of life and underlying molecular and cellular events in five patients with single large-scale deletions, one with a microdeletion and 14 with point mutations of mitochondrial DNA (mtDNA), and 13 healthy subjects. Each training session lasted 30 min, and was performed at an intensity of 70% of VO2max (maximal oxygen uptake). Each subject performed 50 training sessions in 12 weeks. All subjects were evaluated before and after training, and 13 MM patients were studied after 8 weeks of deconditioning. Evaluation included VO2max and mutation load and mtDNA quantity, mitochondrial enzymatic activity, and number of centrally nucleated, apoptotic, ragged red and cytochrome oxidase (COX)-negative fibres in muscle biopsies from the quadriceps muscle. After 12 weeks of training, VO2max and muscle citrate synthase increased in MM (26 and 67%) and healthy (17 and 65%) subjects, while mtDNA quantity in muscle only increased in the MM patients (81%). In the MM patients, training did not change mtDNA mutation load in muscle, mitochondrial enzyme complex activities, muscle morphology and plasma creatine kinase. After deconditioning, VO2max and citrate synthase activity returned to values before training, while muscle mtDNA mutation load decreased. These findings show that aerobic training efficiently improves oxidative capacity in MM patients. Based on unchanged levels of mutant load in muscle, morphological findings on muscle biopsy and plasma creatine kinase levels during training, the treatment appears to be safe. Regular, supervised aerobic exercise is therefore recommended in MM patients with the studied mutations.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16815877 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>408</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Bodine, S. C.</style></author>
										<author><style face="normal" font="default" size="100%">Stitt, T. N.</style></author>
										<author><style face="normal" font="default" size="100%">Gonzalez, M.</style></author>
										<author><style face="normal" font="default" size="100%">Kline, W. O.</style></author>
										<author><style face="normal" font="default" size="100%">Stover, G. L.</style></author>
										<author><style face="normal" font="default" size="100%">Bauerlein, R.</style></author>
										<author><style face="normal" font="default" size="100%">Zlotchenko, E.</style></author>
										<author><style face="normal" font="default" size="100%">Scrimgeour, A.</style></author>
										<author><style face="normal" font="default" size="100%">Lawrence, J. C.</style></author>
										<author><style face="normal" font="default" size="100%">Glass, D. J.</style></author>
										<author><style face="normal" font="default" size="100%">Yancopoulos, G. D.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707, USA. sue.bodine@regeneron.com</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1014-9</style></pages>
			<volume><style face="normal" font="default" size="100%">3</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Calcineurin/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cardiomegaly/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclosporine/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Enzyme Inhibitors/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Kinases/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Protein-Serine-Threonine Kinases</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Proto-Oncogene Proteins/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Proto-Oncogene Proteins c-akt</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Rats, Sprague-Dawley</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ribosomal Protein S6 Kinases/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Signal Transduction</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2001</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">11</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Skeletal muscles adapt to changes in their workload by regulating fibre size by unknown mechanisms. The roles of two signalling pathways implicated in muscle hypertrophy on the basis of findings in vitro, Akt/mTOR (mammalian target of rapamycin) and calcineurin/NFAT (nuclear factor of activated T cells), were investigated in several models of skeletal muscle hypertrophy and atrophy in vivo. The Akt/mTOR pathway was upregulated during hypertrophy and downregulated during muscle atrophy. Furthermore, rapamycin, a selective blocker of mTOR, blocked hypertrophy in all models tested, without causing atrophy in control muscles. In contrast, the calcineurin pathway was not activated during hypertrophy in vivo, and inhibitors of calcineurin, cyclosporin A and FK506 did not blunt hypertrophy. Finally, genetic activation of the Akt/mTOR pathway was sufficient to cause hypertrophy and prevent atrophy in vivo, whereas genetic blockade of this pathway blocked hypertrophy in vivo. We conclude that the activation of the Akt/mTOR pathway and its downstream targets, p70S6K and PHAS-1/4E-BP1, is requisitely involved in regulating skeletal muscle fibre size, and that activation of the Akt/mTOR pathway can oppose muscle atrophy induced by disuse.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11715023 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>227</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Green, S. L.</style></author>
										<author><style face="normal" font="default" size="100%">Westendorf, J. M.</style></author>
										<author><style face="normal" font="default" size="100%">Jaffe, H.</style></author>
										<author><style face="normal" font="default" size="100%">Pant, H. C.</style></author>
										<author><style face="normal" font="default" size="100%">Cork, L. C.</style></author>
										<author><style face="normal" font="default" size="100%">Ostrander, E. A.</style></author>
										<author><style face="normal" font="default" size="100%">Vignaux, F.</style></author>
										<author><style face="normal" font="default" size="100%">Ferrell, J. E., Jr.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Comparative Medicine, Stanford University, Stanford, CA 94305, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Allelic variants of the canine heavy neurofilament (NFH) subunit and extensive phosphorylation in dogs with motor neuron disease</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">33-50</style></pages>
			<volume><style face="normal" font="default" size="100%">132</style></volume>
			<number><style face="normal" font="default" size="100%">1</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">*Alleles</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Base Sequence</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromatography, High Pressure Liquid/veterinary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chromosome Mapping/veterinary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cloning, Molecular</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dog Diseases/*genetics/metabolism/pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Dogs</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy, Spinal/genetics/metabolism/pathology/*veterinary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neurofilament Proteins/chemistry/*genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Phosphorylation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Polymorphism, Restriction Fragment Length</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Research Support, U.S. Gov't, P.H.S.</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Sequence Analysis, DNA/veterinary</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spectrometry, Mass, Electrospray Ionization/veterinary</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2005</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">1</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Aberrant accumulation of extensively phosphorylated heavy (high molecular weight) neurofilament (NFH) and neurodegeneration are features of hereditary canine spinal muscular atrophy (HCSMA), an animal model of human motor neuron disease. In this study, the canine NFH gene was mapped, cloned, and sequenced, and electrospray/mass spectrometry was used to evaluate the phosphorylation state of NFH protein from normal dogs and dogs with HCSMA. The canine NFH gene was localized to a region on canine chromosome 26 that corresponds to human NFH on chromosome 22q. The predicted length of the canine NFH protein is 1135 amino acids, and it shares an 80.3% identity with human NFH and >74.6% with murine NFH proteins. Direct sequencing of NFH cDNA from HCSMA dogs revealed no mutations, although cDNA sequence and restriction fragment length polymorphism (RFLP) analysis indicates that there are at least three canine NFH alleles, differing in the position and number (61 or 62) of Lys-Ser-Proline (KSP) motifs. The two longest alleles (L1 and L2), each with 62 KSP repeats, contain an additional 24-base insert and were observed in both normal and HCSMA dogs. However, the shorter allele (the C allele), with 61 KSP sites and lacking the 24-base insertion, was absent in dogs with HCSMA. Mass spectrometry data indicated that almost all of the NFH KSP phosphorylation sites were occupied. No new or extra sites were identified in native NFH purified from the HCSMA dogs. The predominance of the two longest NFH alleles and the additional KSP phosphorylation sites they confer probably account for the presence of extensively phosphorylated NFs detected immunohistochemically in dogs with HCSMA.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15629478 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1356</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Auer-Grumbach, M.</style></author>
										<author><style face="normal" font="default" size="100%">Olschewski, A.</style></author>
										<author><style face="normal" font="default" size="100%">Papic, L.</style></author>
										<author><style face="normal" font="default" size="100%">Kremer, H.</style></author>
										<author><style face="normal" font="default" size="100%">McEntagart, M. E.</style></author>
										<author><style face="normal" font="default" size="100%">Uhrig, S.</style></author>
										<author><style face="normal" font="default" size="100%">Fischer, C.</style></author>
										<author><style face="normal" font="default" size="100%">Frohlich, E.</style></author>
										<author><style face="normal" font="default" size="100%">Balint, Z.</style></author>
										<author><style face="normal" font="default" size="100%">Tang, B.</style></author>
										<author><style face="normal" font="default" size="100%">Strohmaier, H.</style></author>
										<author><style face="normal" font="default" size="100%">Lochmuller, H.</style></author>
										<author><style face="normal" font="default" size="100%">Schlotter-Weigel, B.</style></author>
										<author><style face="normal" font="default" size="100%">Senderek, J.</style></author>
										<author><style face="normal" font="default" size="100%">Krebs, A.</style></author>
										<author><style face="normal" font="default" size="100%">Dick, K. J.</style></author>
										<author><style face="normal" font="default" size="100%">Petty, R.</style></author>
										<author><style face="normal" font="default" size="100%">Longman, C.</style></author>
										<author><style face="normal" font="default" size="100%">Anderson, N. E.</style></author>
										<author><style face="normal" font="default" size="100%">Padberg, G. W.</style></author>
										<author><style face="normal" font="default" size="100%">Schelhaas, H. J.</style></author>
										<author><style face="normal" font="default" size="100%">van Ravenswaaij-Arts, C. M.</style></author>
										<author><style face="normal" font="default" size="100%">Pieber, T. R.</style></author>
										<author><style face="normal" font="default" size="100%">Crosby, A. H.</style></author>
										<author><style face="normal" font="default" size="100%">Guelly, C.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Institute of Human Genetics, Medical University of Graz, Austria. michaela.auergrumbach@medunigraz.at</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Alterations in the ankyrin domain of TRPV4 cause congenital distal SMA, scapuloperoneal SMA and HMSN2C</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">160-4</style></pages>
			<volume><style face="normal" font="default" size="100%">42</style></volume>
			<number><style face="normal" font="default" size="100%">2</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Amino Acid Substitution/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Ankyrin Repeat</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Calcium/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hela Cells</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Hereditary Sensory and Motor</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neuropathy/complications/*genetics/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Immunohistochemistry</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Intracellular Space/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ion Channel Gating</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Molecular</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Molecular Sequence Data</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscular Atrophy,</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Spinal/complications/*congenital/*genetics/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutant Proteins/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Osmosis</style></keyword>
								<keyword><style face="normal" font="default" size="100%">TRPV Cation Channels/*chemistry/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transfection</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">2</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophies (SMA, also known as hereditary motor neuropathies) and hereditary motor and sensory neuropathies (HMSN) are clinically and genetically heterogeneous disorders of the peripheral nervous system. Here we report that mutations in the TRPV4 gene cause congenital distal SMA, scapuloperoneal SMA, HMSN 2C. We identified three missense substitutions (R269H, R315W and R316C) affecting the intracellular N-terminal ankyrin domain of the TRPV4 ion channel in five families. Expression of mutant TRPV4 constructs in cells from the HeLa line revealed diminished surface localization of mutant proteins. In addition, TRPV4-regulated Ca(2+) influx was substantially reduced even after stimulation with 4alphaPDD, a TRPV4 channel-specific agonist, and with hypo-osmotic solution. In summary, we describe a new hereditary channelopathy caused by mutations in TRPV4 and present evidence that the resulting substitutions in the N-terminal ankyrin domain affect channel maturation, leading to reduced surface expression of functional TRPV4 channels.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20037588 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1340</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Ruiz, R.</style></author>
										<author><style face="normal" font="default" size="100%">Casanas, J. J.</style></author>
										<author><style face="normal" font="default" size="100%">Torres-Benito, L.</style></author>
										<author><style face="normal" font="default" size="100%">Cano, R.</style></author>
										<author><style face="normal" font="default" size="100%">Tabares, L.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Medical Physiology and Biophysics, School of Medicine, University of Seville, 41009 Seville, Spain.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Altered intracellular Ca2+ homeostasis in nerve terminals of severe spinal muscular atrophy mice</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">849-57</style></pages>
			<volume><style face="normal" font="default" size="100%">30</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%"></style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Low levels of survival motor neuron (SMN) protein result in spinal muscular atrophy (SMA), a severe genetic disease characterized by motor impairment and premature lethality. Although SMN is a ubiquitous protein, motor neurons are much more vulnerable to low levels of SMN than other cells. To gain insight into the pathogenesis of SMA, we have compared synaptic function of motor terminals in wild-type and severe SMA mice at different ages and in two proximal muscles. Our results show that mutant muscle fibers fire normal action potentials and that multi-innervated terminals are functional. By studying the characteristics of the three main components of synaptic transmission in nerve terminals (spontaneous, evoked, and asynchronous release), we found that the kinetics of the postsynaptic potentials are slowed and evoked neurotransmitter release is decreased by approximately 55%. In addition, asynchronous release is increased approximately 300%, indicating an anomalous augmentation of intraterminal bulk Ca(2+) during repetitive stimulation. Together, these results show that the reduction of SMN affects synaptic maturation, evoked release, and regulation of intraterminal Ca(2+) levels.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20089893 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1382</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Yu, Z.</style></author>
										<author><style face="normal" font="default" size="100%">Wang, A. M.</style></author>
										<author><style face="normal" font="default" size="100%">Robins, D. M.</style></author>
										<author><style face="normal" font="default" size="100%">Lieberman, A. P.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pathology, The University of Michigan Medical School, Ann Arbor, MI 48109, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Altered RNA splicing contributes to skeletal muscle pathology in Kennedy disease knock-in mice</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">500-7</style></pages>
			<volume><style face="normal" font="default" size="100%">2</style></volume>
			<number><style face="normal" font="default" size="100%">9-10</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Bulbo-Spinal Atrophy, X-Linked/*genetics/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Chloride Channels/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*Gene Knock-In Techniques</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Glutamine/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ligands</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Mutant Strains</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle Denervation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/innervation/*pathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA Splicing/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA, Messenger/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA-Binding Proteins/genetics/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Receptors, Androgen/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Trinucleotide Repeat Expansion/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Troponin T/metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Here, we used a mouse model of Kennedy disease, a degenerative disorder caused by an expanded CAG repeat in the androgen receptor (AR) gene, to explore pathways leading to cellular dysfunction. We demonstrate that male mice containing a targeted Ar allele with 113 CAG repeats (AR113Q mice) exhibit hormone- and glutamine length-dependent missplicing of Clcn1 RNA in skeletal muscle. Changes in RNA splicing are associated with increased expression of the RNA-binding protein CUGBP1. Furthermore, we show that skeletal muscle denervation in the absence of a repeat expansion leads to increased CUGBP1 expression. However, this induction of CUGBP1 is not sufficient to alter Clcn1 RNA splicing, indicating that changes mediated by both denervation and AR113Q toxicity contribute to altered RNA processing. To test this notion directly, we exogenously expressed the AR in vitro and observed hormone-dependent changes in the splicing of pre-mRNAs from a human cardiac troponin T minigene. These effects were notably similar to changes mediated by RNA with expanded CUG tracts, but not CAG tracts, highlighting unanticipated similarities between CAG and CUG repeat diseases. The expanded glutamine AR also altered hormone-dependent splicing of a calcitonin/calcitonin gene-related peptide minigene, suggesting that toxicity of the mutant protein additionally affects RNA processing pathways that are distinct from those regulated by CUGBP1. Our studies demonstrate the occurrence of hormone-dependent alterations in RNA splicing in Kennedy disease models, and they indicate that these changes are mediated by both the cell-autonomous effects of the expanded glutamine AR protein and by alterations in skeletal muscle that are secondary to denervation.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19692580 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>762</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Huber, K. M.</style></author>
										<author><style face="normal" font="default" size="100%">Gallagher, S. M.</style></author>
										<author><style face="normal" font="default" size="100%">Warren, S. T.</style></author>
										<author><style face="normal" font="default" size="100%">Bear, M. F.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Neuroscience, Howard Hughes Medical Institute, Brown University, Providence, RI 02912, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Altered synaptic plasticity in a mouse model of fragile X mental retardation</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">7746-50</style></pages>
			<volume><style face="normal" font="default" size="100%">99</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Disease Models, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fragile X Mental Retardation Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Fragile X Syndrome/genetics/*physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Humans</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mental Retardation/genetics/physiopathology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Knockout</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Models, Neurological</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mutation</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Nerve Tissue Proteins/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Neuronal Plasticity/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein Biosynthesis</style></keyword>
								<keyword><style face="normal" font="default" size="100%">RNA, Messenger/genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">*RNA-Binding Proteins</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Synapses/*physiology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Transcription, Genetic</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2002</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Fragile X syndrome, the most common inherited form of human mental retardation, is caused by mutations of the Fmr1 gene that encodes the fragile X mental retardation protein (FMRP). Biochemical evidence indicates that FMRP binds a subset of mRNAs and acts as a regulator of translation. However, the consequences of FMRP loss on neuronal function in mammals remain unknown. Here we show that a form of protein synthesis-dependent synaptic plasticity, long-term depression triggered by activation of metabotropic glutamate receptors, is selectively enhanced in the hippocampus of mutant mice lacking FMRP. This finding indicates that FMRP plays an important functional role in regulating activity-dependent synaptic plasticity in the brain and suggests new therapeutic approaches for fragile X syndrome.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12032354 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1304</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Baumer, D.</style></author>
										<author><style face="normal" font="default" size="100%">Lee, S.</style></author>
										<author><style face="normal" font="default" size="100%">Nicholson, G.</style></author>
										<author><style face="normal" font="default" size="100%">Davies, J. L.</style></author>
										<author><style face="normal" font="default" size="100%">Parkinson, N. J.</style></author>
										<author><style face="normal" font="default" size="100%">Murray, L. M.</style></author>
										<author><style face="normal" font="default" size="100%">Gillingwater, T. H.</style></author>
										<author><style face="normal" font="default" size="100%">Ansorge, O.</style></author>
										<author><style face="normal" font="default" size="100%">Davies, K. E.</style></author>
										<author><style face="normal" font="default" size="100%">Talbot, K.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">Alternative splicing events are a late feature of pathology in a mouse model of spinal muscular atrophy</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">e1000773</style></pages>
			<volume><style face="normal" font="default" size="100%">5</style></volume>
			<number><style face="normal" font="default" size="100%">12</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">No keywords found</style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2009</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%">12</style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">Spinal muscular atrophy is a severe motor neuron disease caused by inactivating mutations in the SMN1 gene leading to reduced levels of full-length functional SMN protein. SMN is a critical mediator of spliceosomal protein assembly, and complete loss or drastic reduction in protein leads to loss of cell viability. However, the reason for selective motor neuron degeneration when SMN is reduced to levels which are tolerated by all other cell types is not currently understood. Widespread splicing abnormalities have recently been reported at end-stage in a mouse model of SMA, leading to the proposition that disruption of efficient splicing is the primary mechanism of motor neuron death. However, it remains unclear whether splicing abnormalities are present during early stages of the disease, which would be a requirement for a direct role in disease pathogenesis. We performed exon-array analysis of RNA from SMN deficient mouse spinal cord at 3 time points, pre-symptomatic (P1), early symptomatic (P7), and late-symptomatic (P13). Compared to littermate control mice, SMA mice showed a time-dependent increase in the number of exons showing differential expression, with minimal differences between genotypes at P1 and P7, but substantial variation in late-symptomatic (P13) mice. Gene ontology analysis revealed differences in pathways associated with neuronal development as well as cellular injury. Validation of selected targets by RT-PCR confirmed the array findings and was in keeping with a shift between physiologically occurring mRNA isoforms. We conclude that the majority of splicing changes occur late in SMA and may represent a secondary effect of cell injury, though we cannot rule out significant early changes in a small number of transcripts crucial to motor neuron survival.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20019802 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>1108</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Narkar, V. A.</style></author>
										<author><style face="normal" font="default" size="100%">Downes, M.</style></author>
										<author><style face="normal" font="default" size="100%">Yu, R. T.</style></author>
										<author><style face="normal" font="default" size="100%">Embler, E.</style></author>
										<author><style face="normal" font="default" size="100%">Wang, Y. X.</style></author>
										<author><style face="normal" font="default" size="100%">Banayo, E.</style></author>
										<author><style face="normal" font="default" size="100%">Mihaylova, M. M.</style></author>
										<author><style face="normal" font="default" size="100%">Nelson, M. C.</style></author>
										<author><style face="normal" font="default" size="100%">Zou, Y.</style></author>
										<author><style face="normal" font="default" size="100%">Juguilon, H.</style></author>
										<author><style face="normal" font="default" size="100%">Kang, H.</style></author>
										<author><style face="normal" font="default" size="100%">Shaw, R. J.</style></author>
										<author><style face="normal" font="default" size="100%">Evans, R. M.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">AMPK and PPARdelta agonists are exercise mimetics</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">405-15</style></pages>
			<volume><style face="normal" font="default" size="100%">134</style></volume>
			<number><style face="normal" font="default" size="100%">3</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">AMP-Activated Protein Kinases</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Administration, Oral</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Aminoimidazole Carboxamide/administration & dosage/*analogs &</style></keyword>
								<keyword><style face="normal" font="default" size="100%">derivatives/pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Animals</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Biomimetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Male</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Mice, Inbred C57BL</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Multienzyme Complexes/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Muscle, Skeletal/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">PPAR delta/*agonists</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Physical Conditioning, Animal</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Physical Endurance/*drug effects</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Protein-Serine-Threonine Kinases/*metabolism</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Ribonucleotides/administration & dosage/*pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Thiazoles/*pharmacology</style></keyword>
								<keyword><style face="normal" font="default" size="100%"></style></keyword>
							</keywords>
			<dates>
				<year><style face="normal" font="default" size="100%">2008</style></year>
				<pub-dates>
					<date><style face="normal" font="default" size="100%"></style></date>
				</pub-dates>
			</dates>
			<accession-num><style face="normal" font="default" size="100%"></style></accession-num>
			<abstract><style face="normal" font="default" size="100%">The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test. We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.</style></abstract>
			<urls>
				<related-urls>
										<url><style face="normal" font="default" size="100%">http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18674809 </style></url>
										<url><style face="normal" font="default" size="100%"></style></url>
									</related-urls>
			</urls>
		</record>
			<record>
			<database name="smatrial.enl" path="">smatrial.enl</database>
			<source-app name="EndNote" version="8.0">EndNote</source-app>
			<rec-number>23</rec-number>
			<ref-type name="Journal Article">17</ref-type>
			<contributors>
				<authors>
										<author><style face="normal" font="default" size="100%">Parsons, D. W.</style></author>
										<author><style face="normal" font="default" size="100%">McAndrew, P. E.</style></author>
										<author><style face="normal" font="default" size="100%">Monani, U. R.</style></author>
										<author><style face="normal" font="default" size="100%">Mendell, J. R.</style></author>
										<author><style face="normal" font="default" size="100%">Burghes, A. H.</style></author>
										<author><style face="normal" font="default" size="100%">Prior, T. W.</style></author>
										<author><style face="normal" font="default" size="100%"></style></author>
									</authors>
			</contributors>
			<auth-address><style face="normal" font="default" size="100%">Department of Pathology, College of Biological Sciences, Ohio State University College of Medicine, Columbus 43210, USA.</style></auth-address>
			<titles>
				<title><style face="normal" font="default" size="100%">An 11 base pair duplication in exon 6 of the SMN gene produces a type I spinal muscular atrophy (SMA) phenotype: further evidence for SMN as the primary SMA-determining gene</style></title>
				<secondary-title><style face="normal" font="default" size="100%"></style></secondary-title>
			</titles>
			<pages><style face="normal" font="default" size="100%">1727-32</style></pages>
			<volume><style face="normal" font="default" size="100%">5</style></volume>
			<number><style face="normal" font="default" size="100%">11</style></number>
			<keywords>
								<keyword><style face="normal" font="default" size="100%">Alleles</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Cyclic AMP Response Element-Binding Protein</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Exons/*genetics</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Female</style></keyword>
								<keyword><style face="normal" font="default" size="100%">Frameshift Mu