Institution
Protein Sciences
About: Protein Sciences is a based out in . It is known for research contribution in the topics: Proteome & Proteomics. The organization has 2429 authors who have published 1932 publications receiving 74811 citations.
Topics: Proteome, Proteomics, Signal transduction, Gene, Immune system
Papers published on a yearly basis
Papers
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TL;DR: The Reactome Knowledgebase provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations—an extended version of a classic metabolic map, in a single consistent data model.
Abstract: The Reactome Knowledgebase (www.reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations-an extended version of a classic metabolic map, in a single consistent data model. Reactome functions both as an archive of biological processes and as a tool for discovering unexpected functional relationships in data such as gene expression pattern surveys or somatic mutation catalogues from tumour cells. Over the last two years we redeveloped major components of the Reactome web interface to improve usability, responsiveness and data visualization. A new pathway diagram viewer provides a faster, clearer interface and smooth zooming from the entire reaction network to the details of individual reactions. Tool performance for analysis of user datasets has been substantially improved, now generating detailed results for genome-wide expression datasets within seconds. The analysis module can now be accessed through a RESTFul interface, facilitating its inclusion in third party applications. A new overview module allows the visualization of analysis results on a genome-wide Reactome pathway hierarchy using a single screen page. The search interface now provides auto-completion as well as a faceted search to narrow result lists efficiently.
5,065 citations
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TL;DR: A new role for circRNAs in regulating gene expression in the nucleus is revealed, in which EIciRNAs enhance the expression of their parental genes in cis, and a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EICIRNAs is highlighted.
Abstract: Noncoding RNAs (ncRNAs) have numerous roles in development and disease, and one of the prominent roles is to regulate gene expression A vast number of circular RNAs (circRNAs) have been identified, and some have been shown to function as microRNA sponges in animal cells Here, we report a class of circRNAs associated with RNA polymerase II in human cells In these circRNAs, exons are circularized with introns 'retained' between exons; we term them exon-intron circRNAs or EIciRNAs EIciRNAs predominantly localize in the nucleus, interact with U1 snRNP and promote transcription of their parental genes Our findings reveal a new role for circRNAs in regulating gene expression in the nucleus, in which EIciRNAs enhance the expression of their parental genes in cis, and highlight a regulatory strategy for transcriptional control via specific RNA-RNA interaction between U1 snRNA and EIciRNAs
2,077 citations
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TL;DR: Asp2 is a new protein target for drugs that are designed to block the production of amyloid β-peptide peptide and the consequent formation ofAmyloid plaque in Alzheimer's disease.
Abstract: Mutations in the gene encoding the amyloid protein precursor (APP) cause autosomal dominant Alzheimer's disease1,2,3. Cleavage of APP by unidentified proteases, referred to as β- and γ-secretases4,5,6,7, generates the amyloid β-peptide, the main component of the amyloid plaques found in Alzheimer's disease patients8. The disease-causing mutations flank the protease cleavage sites in APP and facilitate its cleavage. Here we identify a new membrane-bound aspartyl protease (Asp2) with β-secretase activity. The Asp2 gene is expressed widely in brain and other tissues. Decreasing the expression of Asp2 in cells reduces amyloid β-peptide production and blocks the accumulation of the carboxy-terminal APP fragment that is created by β-secretase cleavage. Solubilized Asp2 protein cleaves a synthetic APP peptide substrate at the β-secretase site, and the rate of cleavage is increased tenfold by a mutation associated with early-onset Alzheimer's disease in Sweden3. Thus, Asp2 is a new protein target for drugs that are designed to block the production of amyloid β-peptide peptide and the consequent formation of amyloid plaque in Alzheimer's disease.
1,569 citations
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TL;DR: It is shown in vivo and in vitro that the cGAS-catalysed reaction product is distinct from previously characterized cyclic dinucleotides, and it is found that the presence of this 2′-5′ linkage was required to exert potent activation of human STING.
Abstract: Detection of cytoplasmic DNA represents one of the most fundamental mechanisms of the innate immune system to sense the presence of microbial pathogens. Moreover, erroneous detection of endogenous DNA by the same sensing mechanisms has an important pathophysiological role in certain sterile inflammatory conditions. The endoplasmic-reticulum-resident protein STING is critically required for the initiation of type I interferon signalling upon detection of cytosolic DNA of both exogenous and endogenous origin. Next to its pivotal role in DNA sensing, STING also serves as a direct receptor for the detection of cyclic dinucleotides, which function as second messenger molecules in bacteria. DNA recognition, however, is triggered in an indirect fashion that depends on a recently characterized cytoplasmic nucleotidyl transferase, termed cGAMP synthase (cGAS), which upon interaction with DNA synthesizes a dinucleotide molecule that in turn binds to and activates STING. We here show in vivo and in vitro that the cGAS-catalysed reaction product is distinct from previously characterized cyclic dinucleotides. Using a combinatorial approach based on mass spectrometry, enzymatic digestion, NMR analysis and chemical synthesis we demonstrate that cGAS produces a cyclic GMP-AMP dinucleotide, which comprises a 2'-5' and a 3'-5' phosphodiester linkage >Gp(2'-5')Ap(3'-5')>. We found that the presence of this 2'-5' linkage was required to exert potent activation of human STING. Moreover, we show that cGAS first catalyses the synthesis of a linear 2'-5'-linked dinucleotide, which is then subject to cGAS-dependent cyclization in a second step through a 3'-5' phosphodiester linkage. This 13-membered ring structure defines a novel class of second messenger molecules, extending the family of 2'-5'-linked antiviral biomolecules.
1,126 citations
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TL;DR: It is suggested that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.
Abstract: The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two-photon Ca2+ imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca2+ transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.
880 citations
Authors
Showing all 2429 results
Name | H-index | Papers | Citations |
---|---|---|---|
Yang Liu | 129 | 2506 | 122380 |
Christian Haass | 119 | 445 | 58107 |
Franz Hofmann | 113 | 471 | 49938 |
Yigong Shi | 106 | 248 | 48257 |
Horst Kessler | 101 | 878 | 44392 |
Johannes Buchner | 99 | 360 | 34381 |
Amos Marc Bairoch | 96 | 222 | 74599 |
Magdalena Götz | 92 | 237 | 28760 |
Thomas Cremer | 88 | 289 | 29486 |
David E. Shaw | 88 | 298 | 42616 |
Charles O. Rock | 87 | 275 | 22236 |
Arthur Konnerth | 86 | 206 | 26952 |
F. Ulrich Hartl | 85 | 196 | 35238 |
Stefan Endres | 83 | 298 | 31542 |
Gaurav Sharma | 82 | 1244 | 31482 |