32 research outputs found
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<i>Shigella</i> Effector OspB Activates mTORC1 in a Manner That Depends on IQGAP1 and Promotes Cell Proliferation
<div><p>The intracellular bacterial pathogen <i>Shigella</i> infects and spreads through the human intestinal epithelium. Effector proteins delivered by <i>Shigella</i> into cells promote infection by modulating diverse host functions. We demonstrate that the effector protein OspB interacts directly with the scaffolding protein IQGAP1, and that the absence of either OspB or IQGAP1 during infection leads to larger areas of <i>S</i>. <i>flexneri</i> spread through cell monolayers. We show that the effect on the area of bacterial spread is due to OspB triggering increased cell proliferation at the periphery of infected foci, thereby replacing some of the cells that die within infected foci and restricting the area of bacterial spread. We demonstrate that OspB enhancement of cell proliferation results from activation of mTORC1, a master regulator of cell growth, and is blocked by the mTORC1-specific inhibitor rapamycin. OspB activation of mTORC1, and its effects on cell proliferation and bacterial spread, depends on IQGAP1. Our results identify OspB as a regulator of mTORC1 and mTORC1-dependent cell proliferation early during <i>S</i>. <i>flexneri</i> infection and establish a role for IQGAP1 in mTORC1 signaling. They also raise the possibility that IQGAP1 serves as a scaffold for the assembly of an OspB-mTORC1 signaling complex.</p></div
Delayed effect of funding rates in solicited HE applications.
[A] Chart showing changes in zing rates in solicited HE applications up to one year after publication of the guidance and starting one year after publication of the guidance. [B] Table summarizing the coefficients from the time series analysis.</p
Vocabulary of health economics terms.
Compiled from several authoritative sources and used to build machine learning algorithm. (PDF)</p
Funding rates in solicited HE applications.
[A] Chart showing changes in funding rates in solicited HE applications prior to and following publication of the guidance in 2015. [B] Table summarizing the coefficients from the time series analysis.</p
HE and non-HE applications and awards by activity code from FY2010- FY 2020.
Competing applications and awards for HE and non-HE research were determined for FY2010- FY2020 and then broken out by activity code. [A] HE applications from FY2010- FY2020. [B] Non-HE applications from FY2010- FY2020. [C] HE awards from FY2010- FY2020. [D] Non-HE awards from FY2010- FY2020.</p
Delayed effect of funding rates in HE applications.
[A] Chart showing changes in funding rates in HE applications up to one year after publication of the guidance and starting one year after publication of the guidance. [B] Table summarizing the coefficients from the time series analysis.</p
Delayed effect of application rates in unsolicited HE applications.
[A] Chart showing changes in application rates in unsolicited HE applications up to one year after publication of the guidance and starting one year after publication of the guidance. [B] Table summarizing the coefficients from the time series analysis.</p
Analysis of competing applications that were solicited for HE and non-HE research from FY2010 to FY2020.
Application counts were divided by the total number of applications for HE and non-HE research for each Fiscal Year. (TIF)</p