Institution
University of California, Irvine
Education•Irvine, California, United States•
About: University of California, Irvine is a education organization based out in Irvine, California, United States. It is known for research contribution in the topics: Population & Galaxy. The organization has 47031 authors who have published 113602 publications receiving 5521832 citations. The organization is also known as: UC Irvine & UCI.
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TL;DR: This study strongly implicates intraneuronal Abeta in the onset of cognitive dysfunction in the 3xTg-AD mice, and rescues the early cognitive deficits on a hippocampal-dependent task.
1,210 citations
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University of Pennsylvania1, Colorado State University2, Mayo Clinic3, Harvard University4, National Institutes of Health5, King's College London6, University of Freiburg7, Washington University in St. Louis8, Stanford University9, University of Miami10, Boston Biomedical Research Institute11, University of California, Irvine12
TL;DR: Dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease and related proteins with PrLDs should be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
Abstract: Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.
1,209 citations
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TL;DR: DNA studies revealed point mutations in the FGFR3 gene in ACH heterozygotes and homozygotes, which result in the substitution of an arginine residue for a glycine at position 380 of the mature protein, which is in the transmembrane domain ofFGFR3.
1,207 citations
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TL;DR: Coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation of nuclear receptors through its association with p160 coactivators.
Abstract: The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when GRIP1 or SRC-1a was coexpressed. Thus, CARM1 functions as a secondary coactivator through its association with p160 coactivators. CARM1 can methylate histone H3 in vitro, and a mutation in the putative S-adenosylmethionine binding domain of CARM1 substantially reduced both methyltransferase and coactivator activities. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation.
1,206 citations
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TL;DR: In this paper, the authors found that participants often used the Internet, especially social networking sites, to connect and reconnect with friends and family members, and there was overlap between participants' online and offline networks.
1,205 citations
Authors
Showing all 47751 results
Name | H-index | Papers | Citations |
---|---|---|---|
Daniel Levy | 212 | 933 | 194778 |
Rob Knight | 201 | 1061 | 253207 |
Lewis C. Cantley | 196 | 748 | 169037 |
Dennis W. Dickson | 191 | 1243 | 148488 |
Terrie E. Moffitt | 182 | 594 | 150609 |
Joseph Biederman | 179 | 1012 | 117440 |
John R. Yates | 177 | 1036 | 129029 |
John A. Rogers | 177 | 1341 | 127390 |
Avshalom Caspi | 170 | 524 | 113583 |
Yang Gao | 168 | 2047 | 146301 |
Carl W. Cotman | 165 | 809 | 105323 |
John H. Seinfeld | 165 | 921 | 114911 |
Gregg C. Fonarow | 161 | 1676 | 126516 |
Jerome I. Rotter | 156 | 1071 | 116296 |
David Cella | 156 | 1258 | 106402 |