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排序方式: 共有316条查询结果,搜索用时 31 毫秒
101.
Nahzli Dilek Nicolas Poirier Philippe Hulin Flora Coulon Caroline Mary Simon Ville Henri Vie Béatrice Clémenceau Gilles Blancho Bernard Vanhove 《PloS one》2013,8(12)
CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs). What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff) but inhibition of suppression by regulatory T cells (Tregs), while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted. 相似文献
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In the present work the hydrogenesis in the anaerobic alkalithermophilic bacterium Thermobrachium celere was studied. The impact of several factors on hydrogen production during glucose fermentation was investigated in batch conditions. The optimal hydrogen production occurred at pH67 °C 8.2 with phosphate buffer concentration of 50 mM. Hydrogen yield reached the highest value of 3.36 mol H2/mol glucose when the partial pressure in the gas headspace was reduced. Supplementation of nitrogen sources and iron affected hydrogen production. Under optimized conditions, the maximum H2 accumulation and H2 production rate were estimated to be respectively 124.3 mmol H2/l culture and 20.7 mmol H2/l/h. Considering the efficient and rapid hydrogen evolution, and the ability to grow in extreme environments, T. celere might be a good candidate for biohydrogen production in open (non-sterile) bioprocess system. 相似文献
104.
Ville Vasko Toni Laaksonen Jari Valkama Erkki Korpimäki 《Journal of avian biology》2011,42(6):552-563
Costs and benefits of dispersal can vary in space and time, depending on environmental factors and individual state. Plastic, condition‐dependent dispersal strategies, in which individuals rely on external cues such as food abundance to adjust their dispersal distances, are therefore expected to evolve in temporally fluctuating environments. We examined factors affecting breeding dispersal distances in Eurasian kestrels Falco tinnunculus subsisting on multi‐annually and cyclically fluctuating voles as their main food. We attempted to avoid traditional bias in dispersal studies by having large study areas and by taking detection probabilities into account. We observed 320 dispersal events of male and 215 events of female kestrels from our study areas in western Finland during 24 yr. After correcting for distance‐specific detection probability, the estimates of mean dispersal distances increased two‐fold being still clearly higher for females than males. Vole abundance in the spring of settlement was more important in determining average dispersal distances than vole abundance in the previous autumn. At the population level (cross‐sectional model), both males and females dispersed longer distances when the spring abundance of their main food (voles) was low compared to when it was abundant, as predicted by the food depletion hypothesis. At the individual level (longitudinal model), only females responded to the food situation by dispersing more when food abundance was low in the spring of settlement. Females also dispersed longer when vole abundance in the previous autumn had been high. Individual males did not respond to vole abundance, which implies that the population level response in males might have been caused by long‐distance dispersers, which breed in the study area only in good vole years. Our results show that the dispersal distances of kestrels at northern latitudes depend both on individual properties (gender, age, and possibly individual tendency to disperse) and environmental conditions (temporal variation in main food abundance). 相似文献
105.
HannaKaarina Juppi Sarianna Sipil Vasco Fachada Matti Hyvrinen Neil Cronin Pauliina Aukee Jari E. Karppinen Harri Selnne Urho M. Kujala Vuokko Kovanen Sira Karvinen Eija K. Laakkonen 《Aging cell》2022,21(6)
For women, menopausal transition is a time of significant hormonal changes, which may contribute to altered body composition and regional adipose tissue accumulation. Excess adiposity, and especially adipose tissue accumulation in the central body region, increases women''s risk of cardiovascular and metabolic conditions and affects physical functioning. We investigated the associations between menopausal progression and total and regional body adiposity measured with dual‐energy X‐ray absorptiometry and computed tomography in two longitudinal cohort studies of women aged 47–55 (n = 230 and 148, mean follow‐up times 1.3 ± 0.7 and 3.9 ± 0.2 years, mean baseline BMI 25.5 kg/m2). We also examined associations between menopausal progression and skeletal muscle fiber characteristics, as well as adipose tissue‐derived adipokines. Relative increases of 2%–14% were observed in regional and total body adiposity measures, with a pronounced fat mass increase in the android area (4% and 14% during short‐ and long‐term follow‐ups). Muscle fiber oxidative and glycolytic capacities and intracellular adiposity were not affected by menopause, but were differentially correlated with total and regional body adiposity at different menopausal stages. Menopausal progression and regional adipose tissue masses were positively associated with serum adiponectin and leptin, and negatively associated with resistin levels. Higher diet quality and physical activity level were also inversely associated with several body adiposity measures. Therefore, healthy lifestyle habits before and during menopause might delay the onset of severe metabolic conditions in women. 相似文献
106.
Missing-in-metastasis and IRSp53 deform PI(4,5)P2-rich membranes by an inverse BAR domain-like mechanism
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Mattila PK Pykäläinen A Saarikangas J Paavilainen VO Vihinen H Jokitalo E Lappalainen P 《The Journal of cell biology》2007,176(7):953-964
The actin cytoskeleton plays a fundamental role in various motile and morphogenetic processes involving membrane dynamics. We show that actin-binding proteins MIM (missing-in-metastasis) and IRSp53 directly bind PI(4,5)P(2)-rich membranes and deform them into tubular structures. This activity resides in the N-terminal IRSp53/MIM domain (IMD) of these proteins, which is structurally related to membrane-tubulating BAR (Bin/amphiphysin/Rvs) domains. We found that because of a difference in the geometry of the PI(4,5)P(2)-binding site, IMDs induce a membrane curvature opposite that of BAR domains and deform membranes by binding to the interior of the tubule. This explains why IMD proteins induce plasma membrane protrusions rather than invaginations. We also provide evidence that the membrane-deforming activity of IMDs, instead of the previously proposed F-actin-bundling or GTPase-binding activities, is critical for the induction of the filopodia/microspikes in cultured mammalian cells. Together, these data reveal that interplay between actin dynamics and a novel membrane-deformation activity promotes cell motility and morphogenesis. 相似文献
107.
NDH-1 is a gigantic redox-driven proton pump linked with respiration and cyclic electron flow in cyanobacterial cells. Based on experimentally resolved X-ray and cryo-EM structures of the respiratory complex I, we derive here molecular models of two isoforms of the cyanobacterial NDH-1 complex involved in redox-driven proton pumping (NDH-1L) and CO2-fixation (NDH-1MS). Our models show distinct structural and dynamic similarities to the core architecture of the bacterial and mammalian respiratory complex I. We identify putative plastoquinone-binding sites that are coupled by an electrostatic wire to the proton pumping elements in the membrane domain of the enzyme. Molecular simulations suggest that the NDH-1L isoform undergoes large-scale hydration changes that support proton-pumping within antiporter-like subunits, whereas the terminal subunit of the NDH-1MS isoform lacks such structural motifs. Our work provides a putative molecular blueprint for the complex I-analogue in the photosynthetic energy transduction machinery and demonstrates that general mechanistic features of the long-range proton-pumping machinery are evolutionary conserved in the complex I-superfamily. 相似文献
108.
Ville T. M?nnist? Marko Simonen Pasi Soininen Mika Tiainen Antti J. Kangas Dorota Kaminska Sari Venesmaa Pirjo K?kel? Vesa K?rj? Helena Gylling Mika Ala-Korpela Jussi Pihlajam?ki 《Journal of lipid research》2014,55(12):2676-2684
Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m2, 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH. 相似文献
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