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: The data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.
898 citations
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TL;DR: The results suggest that AECs undergo EMT when chronically exposed to TGF-beta1, raising the possibility that epithelial cells may serve as a novel source of myofibroblasts in IPF.
Abstract: The hallmark of idiopathic pulmonary fibrosis (IPF) is the myofibroblast, the cellular origin of which in the lung is unknown. We hypothesized that alveolar epithelial cells (AECs) may serve as a source of myofibroblasts through epithelial-mesenchymal transition (EMT). Effects of chronic exposure to transforming growth factor (TGF)-β1 on the phenotype of isolated rat AECs in primary culture and a rat type II cell line (RLE-6TN) were evaluated. Additionally, tissue samples from patients with IPF were evaluated for cells co-expressing epithelial (thyroid transcription factor (TTF)-1 and pro-surfactant protein-B (pro-SP-B), and mesenchymal (α-smooth muscle actin (α-SMA)) markers. RLE-6TN cells exposed to TGF-β1 for 6 days demonstrated increased expression of mesenchymal cell markers and a fibroblast-like morphology, an effect augmented by tumor necrosis factor-α (TNF-α). Exposure of rat AECs to TGF-β1 (100 pmol/L) resulted in increased expression of α-SMA, type I collagen, vimentin, and desmin, with concurrent transition to a fibroblast-like morphology and decreased expression of TTF-1, aquaporin-5 (AQP5), zonula occludens-1 (ZO-1), and cytokeratins. Cells co-expressing epithelial markers and α-SMA were abundant in lung tissue from IPF patients. These results suggest that AECs undergo EMT when chronically exposed to TGF-β1, raising the possibility that epithelial cells may serve as a novel source of myofibroblasts in IPF.
896 citations
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TL;DR: It is demonstrated that ligand binding facilitates cleavage at a novel site (S2), within the extracellular juxtamembrane region, which serves to release ectodomain repression of NICD production.
895 citations
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TL;DR: Data from the OPTIMIZE-HF registry reveal a high prevalence of HF with PSF, and these patients have a similar post-discharge mortality risk and equally high rates of rehospitalization as patients with HF and LVSD.
892 citations
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TL;DR: It is reported that several cloned inward rectifier K+ channels directly bind PIP2, and that this binding correlates with channel activity and coexpression of Gβγ with GIRK channels slows the inhibition of K+ currents by PIP1 antibodies.
Abstract: Inward rectifier K+ channels, which modulate electrical activity in many cell types, are regulated by protein kinases, guanine-nucleotide-binding proteins (G proteins) and probably actin cytoskeleton. Generation of phosphatidylinositol 4,5-bisphosphate (PIP2) by ATP-dependent lipid kinases is known to activate inward rectifier K+ channels in cardiac membrane patches. Here we report that several cloned inward rectifier K+ channels directly bind PIP2, and that this binding correlates with channel activity. Application of ATP or PIP2 liposomes activates the cloned channels. Stabilized by lipid phosphatase inhibitors, PIP2 antibodies potently inhibit each channel with a unique rate (GIRK1/4 approximately GIRK2 >> IRK1 approximately ROMK. Consistent with the faster dissociation of PIP2 from the GIRK channels, the carboxy terminus of GIRK1 binds 3H-PIP2 liposomes more weakly than does that of IRK1 or ROMK1. Mutation of a conserved arginine to glutamine at position 188 reduces the ability of ROMK1 to bind PIP2 and increases its sensitivity to inhibition by PIP2 antibodies. Interactions between GIRK channels and PIP2 are modulated by the betagamma subunits of the G protein (Gbetagamma). When GIRK1/4 channels are allowed to run down completely, they are not activated by addition of Gbetagamma alone, but application of PIP2 activates them in minutes without Gbetagamma and in just seconds with Gbetagamma. Finally, coexpression of Gbetagamma with GIRK channels slows the inhibition of K+ currents by PIP2 antibodies by more than 10-fold. Thus Gbetagamma activates GIRK channels by stabilizing interactions between PIP2 and the K+ channel.
892 citations
Authors
Showing all 39410 results
Name | H-index | Papers | Citations |
---|---|---|---|
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 |