Institution
University of Texas Southwestern Medical Center
Healthcare•Dallas, Texas, United States•
About: University of Texas Southwestern Medical Center is a healthcare organization based out in Dallas, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 39107 authors who have published 75242 publications receiving 4497256 citations. The organization is also known as: UT Southwestern & UT Southwestern Medical School.
Topics: Population, Cancer, Signal transduction, Receptor, Transplantation
Papers published on a yearly basis
Papers
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TL;DR: It is demonstrated that PCSK9 regulates the amount of LDLR protein in liver and suggested that inhibitors of PCSK 9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol.
Abstract: PCSK9 encodes proprotein convertase subtilisin/kexin type 9a (PCSK9), a member of the proteinase K subfamily of subtilases. Missense mutations in PCSK9 cause an autosomal dominant form of hypercholesterolemia in humans, likely due to a gain-of-function mechanism because overexpression of either WT or mutant PCSK9 reduces hepatic LDL receptor protein (LDLR) in mice. Here, we show that livers of knockout mice lacking PCSK9 manifest increased LDLR protein but not mRNA. Increased LDLR protein led to increased clearance of circulating lipoproteins and decreased plasma cholesterol levels (46 mg/dl in Pcsk9(-/-) mice versus 96 mg/dl in WT mice). Statins, a class of drugs that inhibit cholesterol synthesis, increase expression of sterol regulatory element-binding protein-2 (SREBP-2), a transcription factor that activates both the Ldlr and Pcsk9 genes. Statin administration to Pcsk9(-/-) mice produced an exaggerated increase in LDLRs in liver and enhanced LDL clearance from plasma. These data demonstrate that PCSK9 regulates the amount of LDLR protein in liver and suggest that inhibitors of PCSK9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol.
782 citations
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TL;DR: The crystal structure of STING bound to 2'3'-cGAMP revealed the structural basis of this high-affinity binding and a ligand-induced conformational change in STING that may underlie its activation, and showed that endogenous cGAMP in mammalian cells contains two distinct phosphodiester linkages.
782 citations
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TL;DR: It is shown that deletion mutant mice lacking neuroligin expression die shortly after birth due to respiratory failure, and that neuroligins are required for proper synapse maturation and brain function, but not for the initial formation of synaptic contacts.
781 citations
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TL;DR: Transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.
Abstract: Overexpression of the nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c/ADD1) in cultured 3T3-L1 preadipocytes was shown previously to promote adipocyte differentiation. Here, we produced transgenic mice that overexpress nSREBP-1c in adipose tissue under the control of the adipocyte-specific aP2 enhancer/promoter. A syndrome with the following features was observed: (1) Disordered differentiation of adipose tissue. White fat failed to differentiate fully, and the size of white fat depots was markedly decreased. Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C/EBPalpha, PPARgamma, adipsin, leptin, UCP1) were reduced, but levels of Pref-1 and TNFalpha were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (>300 mg/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.
779 citations
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TL;DR: It is indicated that R2D2 bridges the initiation and effector steps of the Drosophila RNAi pathway by facilitating siRNA passage from Dicer to RISC.
Abstract: The RNA interference (RNAi) pathway is initiated by processing long double-stranded RNA into small interfering RNA (siRNA). The siRNA-generating enzyme was purified from Drosophila S2cells and consists of two stoichiometric subunits: Dicer-2(DCR-2) and a previously unknown protein that we named R2D2. R2D2 is homologous to the Caenorhabditis elegans RNAi protein RDE-4. Association with R2D2 does not affect the enzymatic activity of DCR-2. Rather, the DCR-2/R2D2 complex, but not DCR-2 alone, binds to siRNA and enhances sequence-specific messenger RNA degradation mediated by the RNA-initiated silencing complex (RISC). These results indicate that R2D2 bridges the initiation and effector steps of the Drosophila RNAi pathway by facilitating siRNA passage from Dicer to RISC.
779 citations
Authors
Showing all 39410 results
Name | H-index | Papers | Citations |
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Eugene Braunwald | 230 | 1711 | 264576 |
Joseph L. Goldstein | 207 | 556 | 149527 |
Eric N. Olson | 206 | 814 | 144586 |
Craig B. Thompson | 195 | 557 | 173172 |
Thomas C. Südhof | 191 | 653 | 118007 |
Scott M. Grundy | 187 | 841 | 231821 |
Michael S. Brown | 185 | 422 | 123723 |
Eric Boerwinkle | 183 | 1321 | 170971 |
Jiaguo Yu | 178 | 730 | 113300 |
John J.V. McMurray | 178 | 1389 | 184502 |
Eric J. Nestler | 178 | 748 | 116947 |
John D. Minna | 169 | 951 | 106363 |
Yuh Nung Jan | 162 | 460 | 74818 |
Andrew P. McMahon | 162 | 415 | 90650 |
Elliott M. Antman | 161 | 716 | 179462 |