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211.
Reza Sadjadpour Olivia K. Donau Masashi Shingai Alicia Buckler-White Sandra Kao Klaus Strebel Yoshiaki Nishimura Malcolm A. Martin 《Journal of virology》2013,87(15):8798-8804
Neutralization-resistant simian-human immunodeficiency virus AD8 (SHIVAD8) variants that emerged in an infected macaque elite neutralizer targeting the human immunodeficiency virus type 1 (HIV-1) gp120 N332 glycan acquired substitutions of critical amino acids in the V3 region rather than losing the N332 glycosylation site. One of these resistant variants, carrying the full complement of gp120 V3 changes, was also resistant to the potent anti-HIV-1 monoclonal neutralizing antibodies PGT121 and 10-1074, both of which are also dependent on the presence of the gp120 N332 glycan. 相似文献
212.
Using the National Longitudinal Survey of Freshmen (NLSF), we examine both between- and within-group differences in the odds of feeling intraracially harassed. Specifically, we investigate the effects of colleges’ and universities’ racial composition as well as the nature of students’ associations with non-group members, including involvement in racially homogeneous campus organizations, ethnoracial diversity of friendship networks, and interracial dating. Our findings suggest that although college racial composition appears to have little effect on experiencing intraracial harassment, the nature of students’ involvement with other-race students matters a great deal. For all groups, interracial dating increased odds of harassment. Among black and white students, more diverse friendship networks did as well. And among Asian and Latino students, involvement in any racially homogeneous campus organization was associated with increases in reports of intraracial harassment. Thus, we propose a baseline theoretical model of intraracial harassment that highlights the nature of students’ associations with outgroups. 相似文献
213.
Bhaskar Ponugoti Fanxing Xu Chenying Zhang Chen Tian Sandra Pacios Dana T. Graves 《The Journal of cell biology》2013,203(2):327-343
Keratinocyte mobilization is a critical aspect of wound re-epithelialization, but the mechanisms that control its precise regulation remain poorly understood. We set out to test the hypothesis that forkhead box O1 (FOXO1) has a negative effect on healing because of its capacity to inhibit proliferation and promote apoptosis. Contrary to expectations, FOXO1 is required for keratinocyte transition to a wound-healing phenotype that involves increased migration and up-regulation of transforming growth factor β1 (TGF-β1) and its downstream targets, integrin-α3 and -β6 and MMP-3 and -9. Furthermore, we show that FOXO1 functions in keratinocytes to reduce oxidative stress, which is necessary to maintain cell migration and prevent cell death in a TGF-β1–independent manner. Thus, our studies identify a novel function for FOXO1 in coordinating the response of keratinocytes to wounding through up-regulation of TGF-β1 and other factors needed for keratinocyte migration and protection against oxidative stress, which together promote migration and decrease apoptosis. 相似文献
214.
Shantanu Karkare Terence T. H. Chung Frederic Collin Lesley A. Mitchenall Adam R. McKay Sandra J. Greive Jacobus J. M. Meyer Namrita Lall Anthony Maxwell 《The Journal of biological chemistry》2013,288(7):5149-5156
Tuberculosis and other bacterial diseases represent a significant threat to human health. The DNA topoisomerases are excellent targets for chemotherapy, and DNA gyrase in particular is a well-validated target for antibacterial agents. Naphthoquinones (e.g. diospyrin and 7-methyljuglone) have been shown to have therapeutic potential, particularly against Mycobacterium tuberculosis. We have found that these compounds are inhibitors of the supercoiling reaction catalyzed by M. tuberculosis gyrase and other gyrases. Our evidence strongly suggests that the compounds bind to the N-terminal domain of GyrB, which contains the ATPase active site, but are not competitive inhibitors of the ATPase reaction. We propose that naphthoquinones bind to GyrB at a novel site close to the ATPase site. This novel mode of action could be exploited to develop new antibacterial agents. 相似文献
215.
216.
Aliaksei Shymanets Prajwal Kirsten Bucher Sandra Beer-Hammer Christian Harteneck Bernd Nürnberg 《The Journal of biological chemistry》2013,288(43):31059-31068
Class IB phosphoinositide 3-kinase γ (PI3Kγ) comprises a single catalytic p110γ subunit, which binds to two non-catalytic subunits, p87 or p101, and controls a plethora of fundamental cellular responses. The non-catalytic subunits are assumed to be redundant adaptors for Gβγ enabling G-protein-coupled receptor-mediated regulation of PI3Kγ. Growing experimental data provide contradictory evidence. To elucidate the roles of the non-catalytic subunits in determining the specificity of PI3Kγ, we tested the impact of p87 and p101 in heterodimeric p87-p110γ and p101-p110γ complexes on the modulation of PI3Kγ activity in vitro and in living cells. RT-PCR, biochemical, and imaging data provide four lines of evidence: (i) specific expression patterns of p87 and p101, (ii) up-regulation of p101, providing the basis to consider p87 as a protein forming a constitutively and p101 as a protein forming an inducibly expressed PI3Kγ, (iii) differences in basal and stimulated enzymatic activities, and (iv) differences in complex stability, all indicating apparent diversity within class IB PI3Kγ. In conclusion, expression and activities of PI3Kγ are modified differently by p87 and p101 in vitro and in living cells, arguing for specific regulatory roles of the non-catalytic subunits in the differentiation of PI3Kγ signaling pathways. 相似文献
217.
Haiyan Chen Giorgia Valle Sandra Furlan Alma Nani Sandor Gyorke Michael Fill Pompeo Volpe 《The Journal of general physiology》2013,142(2):127-136
Release of Ca2+ from the sarcoplasmic reticulum (SR) drives contractile function of cardiac myocytes. Luminal Ca2+ regulation of SR Ca2+ release is fundamental not only in physiology but also in physiopathology because abnormal luminal Ca2+ regulation is known to lead to arrhythmias, catecholaminergic polymorphic ventricular tachycardia (CPVT), and/or sudden cardiac arrest, as inferred from animal model studies. Luminal Ca2+ regulates ryanodine receptor (RyR)2-mediated SR Ca2+ release through mechanisms localized inside the SR; one of these involves luminal Ca2+ interacting with calsequestrin (CASQ), triadin, and/or junctin to regulate RyR2 function.CASQ2-RyR2 regulation was examined at the single RyR2 channel level. Single RyR2s were incorporated into planar lipid bilayers by the fusion of native SR vesicles isolated from either wild-type (WT), CASQ2 knockout (KO), or R33Q-CASQ2 knock-in (KI) mice. KO and KI mice have CPVT-like phenotypes. We show that CASQ2(WT) action on RyR2 function (either activation or inhibition) was strongly influenced by the presence of cytosolic MgATP. Function of the reconstituted CASQ2(WT)–RyR2 complex was unaffected by changes in luminal free [Ca2+] (from 0.1 to 1 mM). The inhibition exerted by CASQ2(WT) association with the RyR2 determined a reduction in cytosolic Ca2+ activation sensitivity. RyR2s from KO mice were significantly more sensitive to cytosolic Ca2+ activation and had significantly longer mean open times than RyR2s from WT mice. Sensitivity of RyR2s from KI mice was in between that of RyR2 channels from KO and WT mice. Enhanced cytosolic RyR2 Ca2+ sensitivity and longer RyR2 open times likely explain the CPVT-like phenotype of both KO and KI mice. 相似文献
218.
We consider the Moran model in continuous time with two types, mutation, and selection. We concentrate on the ancestral line and its stationary type distribution. Building on work by Fearnhead (J. Appl. Probab. 39 (2002), 38–54) and Taylor (Electron. J. Probab. 12 (2007), 808–847), we characterise this distribution via the fixation probability of the offspring of all individuals of favourable type (regardless of the offspring’s types). We concentrate on a finite population and stay with the resulting discrete setting all the way through. This way, we extend previous results and gain new insight into the underlying particle picture. 相似文献
219.
220.
Rosane Dias Costa Vanessa Amaral Mendon?a Frederico Marianetti Soriani Sandra Lyon Rachel Adriana Penido Ana Maria Duarte Dias Costa Marina Dias Costa Fabio de Souza Terra Mauro Martins Teixeira Carlos Mauricio de Figueiredo Antunes Antonio Lúcio Teixeira 《Memórias do Instituto Oswaldo Cruz》2013,108(8):1051-1056
Leprosy is an infectious and contagious spectral disease accompanied by a series of
immunological events triggered by the host response to the aetiologic agent,
Mycobacterium leprae . The induction and maintenance of the
immune/inflammatory response in leprosy are linked to multiple cell interactions and
soluble factors, primarily through the action of cytokines. The purpose of the
present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and
its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages
of multidrug treatment (MDT) in comparison with non-infected individuals and to
determine their role as putative biomarkers of the severity of leprosy or the
treatment response. ELISA was used to measure the levels of these molecules in 30
healthy controls and 37 leprosy patients at the time of diagnosis and during and
after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in
infected individuals in comparison with controls. The levels of TNF-α, but not
sTNF-R2, decreased with treatment. The current results corroborate previous reports
of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the
control of this cytokine during MDT. 相似文献