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601.
Jyoti Chhibber-Goel Caroline Coleman-Vaughan Vishal Agrawal Neha Sawhney Emer Hickey James C. Powell Justin V. McCarthy 《The Journal of biological chemistry》2016,291(11):5971-5985
The γ-secretase protease and associated regulated intramembrane proteolysis play an important role in controlling receptor-mediated intracellular signaling events, which have a central role in Alzheimer disease, cancer progression, and immune surveillance. An increasing number of γ-secretase substrates have a role in cytokine signaling, including the IL-6 receptor, IL-1 receptor type I, and IL-1 receptor type II. In this study, we show that following TNF-converting enzyme-mediated ectodomain shedding of TNF type I receptor (TNFR1), the membrane-bound TNFR1 C-terminal fragment is subsequently cleaved by γ-secretase to generate a cytosolic TNFR1 intracellular domain. We also show that clathrin-mediated internalization of TNFR1 C-terminal fragment is a prerequisite for efficient γ-secretase cleavage of TNFR1. Furthermore, using in vitro and in vivo model systems, we show that in the absence of presenilin expression and γ-secretase activity, TNF-mediated JNK activation was prevented, assembly of the TNFR1 pro-apoptotic complex II was reduced, and TNF-induced apoptosis was inhibited. These observations demonstrate that TNFR1 is a γ-secretase substrate and suggest that γ-secretase cleavage of TNFR1 represents a new layer of regulation that links the presenilins and the γ-secretase protease to pro-inflammatory cytokine signaling. 相似文献
602.
603.
Gold nanorods are known to exhibit two distinct surface plasmon oscillations namely, transverse and longitudinal bands corresponding
to oscillations of conduction electrons along width and length of gold nanorods. Considerable changes in these surface plasmon
resonance peak positions occurred when KOH was added to the nanorod solution. Nanorods with initial longitudinal plasmon band
at 739, 796, and 895 nm are studied with variation in KOH concentration. While the longitudinal plasmon resonance peak showed
blue shift, transverse plasmon resonance peak exhibited only intensity variations. Changes could be attributed to the shape
transition of gold nanorods on variation of pH in the solution. Shape transition of gold nanorods is confirmed by transmission
electron microscopy images. 相似文献
604.
Neha Potnis José Pablo Soto-Arias Kimberly N. Cowles Ariena H. C. van Bruggen Jeffrey B. Jones Jeri D. Barak 《Applied and environmental microbiology》2014,80(10):3173-3180
Salmonella enterica rarely grows on healthy, undamaged plants, but its persistence is influenced by bacterial plant pathogens. The interactions between S. enterica, Xanthomonas perforans (a tomato bacterial spot pathogen), and tomato were characterized. We observed that virulent X. perforans, which establishes disease by suppressing pathogen-associated molecular pattern (PAMP)-triggered immunity that leads to effector-triggered susceptibility, created a conducive environment for persistence of S. enterica in the tomato phyllosphere, while activation of effector-triggered immunity by avirulent X. perforans resulted in a dramatic reduction in S. enterica populations. S. enterica populations persisted at ∼10 times higher levels in leaves coinoculated with virulent X. perforans than in those where S. enterica was applied alone. In contrast, S. enterica populations were ∼5 times smaller in leaves coinoculated with avirulent X. perforans than in leaves inoculated with S. enterica alone. Coinoculation with virulent X. perforans increased S. enterica aggregate formation; however, S. enterica was not found in mixed aggregates with X. perforans. Increased aggregate formation by S. enterica may serve as the mechanism of persistence on leaves cocolonized by virulent X. perforans. S. enterica association with stomata was altered by X. perforans; however, it did not result in appreciable populations of S. enterica in the apoplast even in the presence of large virulent X. perforans populations. Gene-for-gene resistance against X. perforans successively restricted S. enterica populations. Given the effect of this interaction, breeding for disease-resistant cultivars may be an effective strategy to limit both plant disease and S. enterica populations and, consequently, human illness. 相似文献
605.
606.
Sleep and Biological Rhythms - Up to date, it is found that the presence of obstructive sleep apnea (OSA) contributes to the development of structural, ultra-structural, functional, and proteomics... 相似文献
607.
Khaja Shameem Mohammed Abdul Jayachandra Rayadurgam Neha Faiz Aleksandar Jovanovi Wen Tan 《Journal of cellular and molecular medicine》2020,24(18):10924-10934
In the present study, we have investigated potential cardioprotective properties of Isosteviol analogue we recently synthesized and named JC105. Treatment of heart embryonic H9c2 cells with JC105 (10 μM) significantly increased survival of cells exposed to hypoxia‐reoxygenation. JC105 (10 μM) activated ERK1/2, DRP1 and increased levels of cardioprotective SUR2A in hypoxia‐reoxygenation, but did not have any effects on ERK1/2, DRP1 and/or SUR2A in normoxia. U0126 (10 μM) inhibited JC105‐mediated phosphorylation of ERK1/2 and DRP1 without affecting AKT or AMPK, which were also not regulated by JC105. Seahorse bioenergetic analysis demonstrated that JC105 (10 μM) did not affect mitochondria at rest, but it counteracted all mitochondrial effects of hypoxia‐reoxygenation. Cytoprotection afforded by JC105 was inhibited by U0126 (10 μM). Taken all together, these demonstrate that (a) JC105 protects H9c2 cells against hypoxia‐reoxygenation and that (b) this effect is mediated via ERK1/2. The unique property of JC105 is that selectively activates ERK1/2 in cells exposed to stress, but not in cells under non‐stress conditions. 相似文献
608.
Seckin Akin Neha Arora Shaik M. Zakeeruddin Michael Grtzel Richard H. Friend M. Ibrahim Dar 《Liver Transplantation》2020,10(13)
Lead halide perovskite solar cells now show excellent efficiencies and encouraging levels of stability. Further improvements in performance require better control of the trap states which are considered to be associated with vacancies and defects at crystallite surfaces. Herein, a reflection on the ways in which these traps can be mitigated is presented by improving the quality of the perovskite layer and interfaces in fully assembled device configurations. In this review, the most recent design strategies reported in the literature, which have been explored to tune grain orientation, to passivate defects, and to improve charge‐carrier lifetimes, are presented. Specifically, the advances made with single‐cation, mixed‐cation and/or mixed‐halide, and 3D/2D bilayer‐based light absorbers are discussed. The interfacial, compositional, and band alignment engineering along with their consequent effects on the open‐circuit voltage, power conversion efficiency, and stability are a particular focus. 相似文献
609.
A paradigm shift toward fusion proteins to render multiple functionalities and applications on a single platform has been incurred in enzyme based diagnosis. Herein, we report development and systematic characterizations of glutathione-S-transferase (GST) and human lactate dehydrogenase A (hLDHA) in a fusion protein (GST–hLDHA) to achieve functional activities of GST and hLDHA simultaneously. The GST-pGEX-4T-2 vector system was used for cloning and purification of hLDHA, utilizing the affinity based interaction between GST and GSH in column chromatography. Bacterially purified protein was subjected to the Western blot analysis and structural analysis by circular dichroism spectroscopy, which revealed intact structural framework of the fusion construct. Kinetic characterization of the fusion GST–hLDHA protein toward GSH and NADH, suggested retention of functional activities of GST and hLDHA in fused protein as indicated by the kinetic parameters km and kcat/km. Further analysis of effect of temperature and pH on GST–hLDHA activity revealed maximum activity around human physiological conditions (37°C and pH 8). Preservation of the structural and functional characteristics of the fusion enzyme paves the way for potential application for the detection of NADH and GSH in conjunction as biomarkers for cancer diagnosis. 相似文献
610.
EDC3 phosphorylation regulates growth and invasion through controlling P‐body formation and dynamics
Jeremiah J Bearss Sathish KR Padi Neha Singh Marina CardoVila Jin H Song Ghassan Mouneimne Nikita Fernandes Yang Li Matthew R Harter Jaime MC Gard Anne E Cress Wolfgang Peti Andrew DL Nelson J Ross Buchan Andrew S Kraft Koichi Okumura 《EMBO reports》2021,22(4)
Regulation of mRNA stability and translation plays a critical role in determining protein abundance within cells. Processing bodies (P‐bodies) are critical regulators of these processes. Here, we report that the Pim1 and 3 protein kinases bind to the P‐body protein enhancer of mRNA decapping 3 (EDC3) and phosphorylate EDC3 on serine (S)161, thereby modifying P‐body assembly. EDC3 phosphorylation is highly elevated in many tumor types, is reduced upon treatment of cells with kinase inhibitors, and blocks the localization of EDC3 to P‐bodies. Prostate cancer cells harboring an EDC3 S161A mutation show markedly decreased growth, migration, and invasion in tissue culture and in xenograft models. Consistent with these phenotypic changes, the expression of integrin β1 and α6 mRNA and protein is reduced in these mutated cells. These results demonstrate that EDC3 phosphorylation regulates multiple cancer‐relevant functions and suggest that modulation of P‐body activity may represent a new paradigm for cancer treatment. 相似文献