Institution
Howard Hughes Medical Institute
Nonprofit•Chevy Chase, Maryland, United States•
About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.
Topics: Gene, RNA, Population, Receptor, Cellular differentiation
Papers published on a yearly basis
Papers
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TL;DR: This work explores the use of 3D structural information to guide sequence alignments constructed by the MSA program PROMALS, and outperforms a number of existing methods for constructing multiple sequence or structural alignments using both reference-dependent and reference-independent evaluation methods.
Abstract: Although multiple sequence alignments (MSAs) are essential for a wide range of applications from structure modeling to prediction of functional sites, construction of accurate MSAs for distantly related proteins remains a largely unsolved problem. The rapidly increasing database of spatial structures is a valuable source to improve alignment quality. We explore the use of 3D structural information to guide sequence alignments constructed by our MSA program PROMALS. The resulting tool, PROMALS3D, automatically identifies homologs with known 3D structures for the input sequences, derives structural constraints through structure-based alignments and combines them with sequence constraints to construct consistency-based multiple sequence alignments. The output is a consensus alignment that brings together sequence and structural information about input proteins and their homologs. PROMALS3D can also align sequences of multiple input structures, with the output representing a multiple structure-based alignment refined in combination with sequence constraints. The advantage of PROMALS3D is that it gives researchers an easy way to produce high-quality alignments consistent with both sequences and structures of proteins. PROMALS3D outperforms a number of existing methods for constructing multiple sequence or structural alignments using both reference-dependent and reference-independent evaluation methods.
1,204 citations
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TL;DR: Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA.
Abstract: An understanding of the differences and similarities of the retinoid X receptor (RXR) and retinoic acid receptor (RAR) systems requires knowledge of the diversity of their family members, their patterns of expression, and their pharmacological response to ligands. In this paper we report the isolation of a family of mouse RXR genes encoding three distinct receptors (RXRa, p, and y). They are closely related to each other in their DNAand ligand-binding domains but are quite divergent from the RAR subfamily in both structure and ligand specificity. Recently, we demonstrated that all-trans retinoic acid (RA) serves as a "pro-hormone" to the isomer 9-cis RA, which is a high-affinity ligand for the human RXRa. We extend those findings to show that 9-cis RA is also "retinoid X" for mouse RXRa, p, and y. Trans-activation analyses show that although all three RXRs respond to a variety of endogenous retinoids, 9-cis RA is their most potent ligand and is up to 40-fold more active than all-trans RA. Northern blot and in situ hybridization analyses define a broad spectrum of expression for the RXRs, which display unique patterns and only partially overlap themselves and the RARs. This study suggests that the RXR family plays critical roles in diverse aspects of development, from embryo implantation to organogenesis and central nervous system differentiation, as well as in adult physiology.
1,203 citations
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TL;DR: K, a hematopoietic growth factor obtained from conditioned medium of BALB/c 3T3 fibroblasts that stimulates the proliferation of mast cells and early erythroid progenitors, specifically binds to the c-kit receptor.
1,201 citations
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TL;DR: It is proposed that PPARγ coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.
1,201 citations
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TL;DR: Activation of PKA may be a component of the mechanism that generates L-LTP, and analogs of cAMP induced a potentiation that blocked naturally induced L- LTP, which was blocked by inhibitors of protein synthesis.
Abstract: Hippocampal long-term potentiation (LTP) is thought to serve as an elementary mechanism for the establishment of certain forms of explicit memory in the mammalian brain. As is the case with behavioral memory, LTP in the CA1 region has stages: a short-term early potentiation lasting 1 to 3 hours, which is independent of protein synthesis, precedes a later, longer lasting stage (L-LTP), which requires protein synthesis. Inhibitors of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) blocked L-LTP, and analogs of cAMP induced a potentiation that blocked naturally induced L-LTP. The action of the cAMP analog was blocked by inhibitors of protein synthesis. Thus, activation of PKA may be a component of the mechanism that generates L-LTP.
1,200 citations
Authors
Showing all 20486 results
Name | H-index | Papers | Citations |
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Bert Vogelstein | 247 | 757 | 332094 |
Richard A. Flavell | 231 | 1328 | 205119 |
Steven A. Rosenberg | 218 | 1204 | 199262 |
Kenneth W. Kinzler | 215 | 640 | 243944 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Rob Knight | 201 | 1061 | 253207 |
Irving L. Weissman | 201 | 1141 | 172504 |
Ronald M. Evans | 199 | 708 | 166722 |
Francis S. Collins | 196 | 743 | 250787 |
Craig B. Thompson | 195 | 557 | 173172 |
Thomas C. Südhof | 191 | 653 | 118007 |
Joan Massagué | 189 | 408 | 149951 |
Stuart H. Orkin | 186 | 715 | 112182 |
John P. A. Ioannidis | 185 | 1311 | 193612 |
Eric R. Kandel | 184 | 603 | 113560 |