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排序方式: 共有142条查询结果,搜索用时 31 毫秒
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Nader Morshed William T Ralvenius Alexi Nott L Ashley Watson Felicia H Rodriguez Leyla A Akay Brian A Joughin PingChieh Pao Jay Penney Lauren LaRocque Diego Mastroeni LiHuei Tsai Forest M White 《Molecular systems biology》2020,16(12)
Alzheimer’s disease (AD) is characterized by the appearance of amyloid‐β plaques, neurofibrillary tangles, and inflammation in brain regions involved in memory. Using mass spectrometry, we have quantified the phosphoproteome of the CK‐p25, 5XFAD, and Tau P301S mouse models of neurodegeneration. We identified a shared response involving Siglec‐F which was upregulated on a subset of reactive microglia. The human paralog Siglec‐8 was also upregulated on microglia in AD. Siglec‐F and Siglec‐8 were upregulated following microglial activation with interferon gamma (IFNγ) in BV‐2 cell line and human stem cell‐derived microglia models. Siglec‐F overexpression activates an endocytic and pyroptotic inflammatory response in BV‐2 cells, dependent on its sialic acid substrates and immunoreceptor tyrosine‐based inhibition motif (ITIM) phosphorylation sites. Related human Siglecs induced a similar response in BV‐2 cells. Collectively, our results point to an important role for mouse Siglec‐F and human Siglec‐8 in regulating microglial activation during neurodegeneration. 相似文献
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Larson Boundenga Boris Makanga Benjamin Ollomo Aude Gilabert Virginie Rougeron Bertrand Mve-Ondo Céline Arnathau Patrick Durand Nancy Diamella Moukodoum Alain-Prince Okouga Lucresse Delicat-Loembet Lauriane Yacka-Mouele Nil Rahola Eric Leroy Cheikh Tidiane BA Francois Renaud Franck Prugnolle Christophe Paupy 《PloS one》2016,11(2)
Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes. 相似文献
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Claire E Naylor Claire Bagnéris Paul G DeCaen Altin Sula Antonella Scaglione David E Clapham BA Wallace 《The EMBO journal》2016,35(8):820-830
Voltage‐gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na+ ≈ Li+ ≫ K+, Ca2+, Mg2+) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones. 相似文献
6.
Proteomic identification of 14-3-3zeta as a mitogen-activated protein kinase-activated protein kinase 2 substrate: role in dimer formation and ligand binding 总被引:1,自引:0,他引:1
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Powell DW Rane MJ Joughin BA Kalmukova R Hong JH Tidor B Dean WL Pierce WM Klein JB Yaffe MB McLeish KR 《Molecular and cellular biology》2003,23(15):5376-5387
Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MAPKAPK2) mediates multiple p38 MAPK-dependent inflammatory responses. To define the signal transduction pathways activated by MAPKAPK2, we identified potential MAPKAPK2 substrates by using a functional proteomic approach consisting of in vitro phosphorylation of neutrophil lysate by active recombinant MAPKAPK2, protein separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and phosphoprotein identification by peptide mass fingerprinting with matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and protein database analysis. One of the eight candidate MAPKAPK2 substrates identified was the adaptor protein, 14-3-3zeta. We confirmed that MAPKAPK2 interacted with and phosphorylated 14-3-3zeta in vitro and in HEK293 cells. The chemoattractant formyl-methionyl-leucyl-phenylalanine (fMLP) stimulated p38-MAPK-dependent phosphorylation of 14-3-3 proteins in human neutrophils. Mutation analysis showed that MAPKAPK2 phosphorylated 14-3-3zeta at Ser-58. Computational modeling and calculation of theoretical binding energies predicted that both phosphorylation at Ser-58 and mutation of Ser-58 to Asp (S58D) compromised the ability of 14-3-3zeta to dimerize. Experimentally, S58D mutation significantly impaired both 14-3-3zeta dimerization and binding to Raf-1. These data suggest that MAPKAPK2-mediated phosphorylation regulates 14-3-3zeta functions, and this MAPKAPK2 activity may represent a novel pathway mediating p38 MAPK-dependent inflammation. 相似文献
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van der Veen BA Uitdehaag JC Dijkstra BW Dijkhuizen L 《Biochimica et biophysica acta》2000,1543(2):336-360
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Claudia G Petersen Fabiana C Massaro Ana L Mauri Joao BA Oliveira Ricardo LR Baruffi Jose G FrancoJr 《Reproductive biology and endocrinology : RB&E》2010,8(1):149
Background
The present study aimed to evaluate the efficacy of the hyaluronic acid (HA) binding assay in the selection of motile spermatozoa with normal morphology at high magnification (8400x). 相似文献9.
辽宁是东北林蛙Rana dybowskii主要分布地之一,种群数量巨大,其群体遗传多样性有待评估.本研究应用ISSR标记技术对东北林蛙4个种群105个样本进行研究,5个引物共获得44条清晰谱带,4个种群的多态位点率均大于75%,Nei's基因多样性为0.2851,Shannon信息指数为0.4476,显示了较高的遗传多样性.对遗传分化系数、Nei's遗传距离、AMOVA分子变异巢式方差分析和F-统计量等遗传参数的统计结果表明,辽宁东北林蛙种群间已经出现一定程度的遗传分化,分析认为,自然屏障(高山和平原等)以及栖息地片段化是其遗传分化形成的主要因素. 相似文献
10.
Joughin BA Green DF Tidor B 《Protein science : a publication of the Protein Society》2005,14(5):1363-1369
The identification of protein mutations that enhance binding affinity may be achieved by computational or experimental means, or by a combination of the two. Sources of affinity enhancement may include improvements to the net balance of binding interactions of residues forming intermolecular contacts at the binding interface, such as packing and hydrogen-bonding interactions. Here we identify noncontacting residues that make substantial contributions to binding affinity and that also provide opportunities for mutations that increase binding affinity of the TEM1 beta-lactamase (TEM1) to the beta-lactamase inhibitor protein (BLIP). A region of BLIP not on the direct TEM1-binding surface was identified for which changes in net charge result in particularly large increases in computed binding affinity. Some mutations to the region have previously been characterized, and our results are in good correspondence with this results of that study. In addition, we propose novel mutations to BLIP that were computed to improve binding significantly without contacting TEM1 directly. This class of noncontacting electrostatic interactions could have general utility in the design and tuning of binding interactions. 相似文献