排序方式: 共有103条查询结果,搜索用时 15 毫秒
51.
Annette S. Flozak Anna P. Lam Susan Russell Manu Jain Ofra N. Peled Kerry A. Sheppard Rohinee Beri G?khan M. Mutlu G. R. Scott Budinger Cara J. Gottardi 《The Journal of biological chemistry》2010,285(5):3157-3167
The Wnt/β-catenin signaling cascade activates genes that allow cells to adopt particular identities throughout development. In adult self-renewing tissues like intestine and blood, activation of the Wnt pathway maintains a progenitor phenotype, whereas forced inhibition of this pathway promotes differentiation. In the lung alveolus, type 2 epithelial cells (AT2) have been described as progenitors for the type 1 cell (AT1), but whether AT2 progenitors use the same signaling mechanisms to control differentiation as rapidly renewing tissues is not known. We show that adult AT2 cells do not exhibit constitutive β-catenin signaling in vivo, using the AXIN2+/LacZ reporter mouse, or after fresh isolation of an enriched population of AT2 cells. Rather, this pathway is activated in lungs subjected to bleomycin-induced injury, as well as upon placement of AT2 cells in culture. Forced inhibition of β-catenin/T-cell factor signaling in AT2 cultures leads to increased cell death. Cells that survive show reduced migration after wounding and reduced expression of AT1 cell markers (T1α and RAGE). These results suggest that AT2 cells may function as facultative progenitors, where activation of Wnt/β-catenin signaling during lung injury promotes alveolar epithelial survival, migration, and differentiation toward an AT1-like phenotype. 相似文献
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Novikov I Kalter-Leibovici O Chetrit A Stav N Epstein Y 《International journal of biometeorology》2012,56(1):121-127
Global climate changes affect health and present new challenges to healthcare systems. The aim of the present study was to analyze the pattern of visits to the medical wing of emergency rooms (ERs) in public hospitals during warm seasons, and to develop a predictive model that will forecast the number of visits to ERs 2 days ahead. Data on daily visits to the ERs of the four largest medical centers in the Tel-Aviv metropolitan area during the warm months of the year (April–October, 2001–2004), the corresponding daily meteorological data, daily electrical power consumption (a surrogate marker for air-conditioning), air-pollution parameters, and calendar information were obtained and used in the analyses. The predictive model employed a time series analysis with transitional Poisson regression. The concise multivariable model was highly accurate (r 2 = 0.819). The contribution of mean daily temperature was small but significant: an increase of 1°C in ambient temperature was associated with a 1.47% increase in the number of ER visits (P < 0.001). An increase in electrical power consumption significantly attenuated the effect of weather conditions on ER visits by 4% per 1,000 MWh (P < 0.001). Higher daily mean SO2 concentrations were associated with a greater number of ER visits (1% per 1 ppb increment; P = 0.017). Calendar data were the main predictors of ER visits (r 2 = 0.794). The predictive model was highly accurate in forecasting the number of visits to ERs 2 days ahead. The marginal effect of temperature on the number of ER visits can be attributed to behavioral adaptations, including the use of air-conditioning. 相似文献
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Chiara Gabbiani Angela Casini Guido Mastrobuoni Noam Kirshenbaum Ofra Moshel Giuseppe Pieraccini Gloriano Moneti Luigi Messori Dan Gibson 《Journal of biological inorganic chemistry》2008,13(5):755-764
Carboplatin (CPT), today the most important platinum(II) anticancer drug, manifests an extreme kinetic inertness, in vitro, at physiological pH; the actual mechanisms for its activation inside cells are still poorly understood. We show here that horse heart cytochrome c reacts with CPT, leading to the formation of stable platinum/protein adducts. The two major CPT-cytochrome c species resulting from the aforementioned reaction were characterised by electrospray ionisation mass spectrometry (ESI-MS). Notably, both these adducts have the ability to react with guanosine 5'-monophosphate (5'-GMP), giving rise to the respective cytochrome c-CPT-5'-GMP ternary complexes. Additional ESI-MS measurements on enzymatically cleaved cytochrome c adducts suggest that protein platination probably occurs at Met65. The mechanistic implications of these findings are discussed. 相似文献
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Semaphorin-3A and semaphorin-3F work together to repel endothelial cells and to inhibit their survival by induction of apoptosis 总被引:1,自引:0,他引:1
Guttmann-Raviv N Shraga-Heled N Varshavsky A Guimaraes-Sternberg C Kessler O Neufeld G 《The Journal of biological chemistry》2007,282(36):26294-26305
Semaphorin-3A (sema3A) is a neuropilin-1 (np1) agonist. It inhibits the binding of the 165-amino acid form of VEGF (VEGF(165)) to np1 and was reported to inhibit angiogenesis as a result. However, we find that sema3A concentrations that inhibit the mitogenic effects of VEGF(165) do not inhibit VEGF(165)-induced phosphorylation of VEGF receptor-2 (VEGFR-2). Furthermore, sema3A inhibits the biological effects of VEGF(121), a VEGF form that does not bind to neuropilins and basic fibroblast growth factor, a growth factor whose activity, unlike that of VEGF, is not inhibited by small interfering RNA directed against np1. Therefore, the mechanism by which sema3A inhibits VEGF(165) activity does not depend on competition with VEGF(165) for binding to np1. Sema3A induced rapid disappearance of focal contacts followed by collapse of the actin cytoskeleton in human umbilical vein-derived endothelial cells. HEK293 cells expressing sema3A repel human endothelial cells and at high concentrations induce their death by apoptosis. Furthermore, sema3A inhibited the formation of tubes from endothelial cells in an in vitro angiogenesis assay. Similar effects are induced by the neuropilin-2 (np2) agonist sema3F. These inhibitory effects are abrogated by small interfering RNAs directed against np1 or np2, respectively. The anti-proliferative effects of sema3A and sema3F are additive when the semaphorins are added as pure proteins. However, when sema3A and sema3F were co-expressed in HEK293 cells their pro-apoptotic and cell repellant activities appeared to be synergistic. These observations suggest that combinations of sema3A and sema3F may be able to inhibit tumor angiogenesis more effectively than single semaphorins. 相似文献
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Glantz Y Sabag O Lichtenstein M Grodzovski I Lorberboum-Galski H 《Biotechnology progress》2012,28(2):573-580
Designing a chimeric protein and developing a procedure for its stable production as a biologically active protein, are key steps in its potential application to clinical trails. IL2-Caspase3 chimeric protein designed to target activated T lymphocytes was found to be a promising molecule for targeted treatment, however was found to be difficult to produce as a biological active molecule. Thus, we designed a new version of the molecule, IL2-Caspase3s, in which six amino acids (aa 29-34) from the N-terminus of the large subunit of caspase 3 were excluded. Repeated expressions, productions, and partial purifications of the IL2-Caspase3s yielded reproducible batches with consistent results. We found that IL2-Caspase3s causes cell death in a specific, dose-, and time-dependent manner. Cell death due to IL2-Caspase3s is caused by apoptosis. This improved and biologically stable IL2-Caspase3s chimeric protein may be developed in the future for clinical trails as a promising therapy for several pathologies involving activated T-cells. Moreover, this truncated caspase 3 sequence, lacking the N-terminal six amino acids of its large subunit, may be used in other caspase 3-based chimeric proteins targeted against various human diseases, using the appropriate targeting moiety. 相似文献
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Economic games on the internet: the effect of $1 stakes 总被引:1,自引:0,他引:1
Online labor markets such as Amazon Mechanical Turk (MTurk) offer an unprecedented opportunity to run economic game experiments quickly and inexpensively. Using Mturk, we recruited 756 subjects and examined their behavior in four canonical economic games, with two payoff conditions each: a stakes condition, in which subjects' earnings were based on the outcome of the game (maximum earnings of $1); and a no-stakes condition, in which subjects' earnings are unaffected by the outcome of the game. Our results demonstrate that economic game experiments run on MTurk are comparable to those run in laboratory settings, even when using very low stakes. 相似文献
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Ofra Goldstein-Gidoni 《Ethnos》2013,78(1):33-55
In this article I examine the production of culture in the contemporary commercial Japanese wedding. This is analyzed in relation to the theoretical discourse of ‘the invention of tradition’. However, while this ‘invention’ is usually related to political motivations, I discuss the invention of tradition and of culture for economic motivations. I offer a broader perspective of tradition and culture and show how flexible these two may be as they are manufactured, played with or imagined. The contemporary wedding consists of both ‘traditional-Japanese’ and ‘Western’ inventions. These are regarded here as cultural constructs which both play a significant role in the construction of contemporary Japanese cultural identity. 相似文献
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Zahava Vadasz Tharwat Haj Katalin Halasz Itzhak Rosner Gleb Slobodin Dina Attias Aharon Kessel Ofra Kessler Gera Neufeld Elias Toubi 《Arthritis research & therapy》2012,14(3):1-8