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排序方式: 共有328条查询结果,搜索用时 15 毫秒
71.
Thomas Obadia Romain Silhol Lulla Opatowski Laura Temime Judith Legrand Anne C. M. Thiébaut Jean-Louis Herrmann éric Fleury Didier Guillemot Pierre-Yves Bo?lle 《PLoS computational biology》2015,11(3)
Close proximity interactions (CPIs) measured by wireless electronic devices are increasingly used in epidemiological models. However, no evidence supports that electronically collected CPIs inform on the contacts leading to transmission. Here, we analyzed Staphylococcus aureus carriage and CPIs recorded simultaneously in a long-term care facility for 4 months in 329 patients and 261 healthcare workers to test this hypothesis. In the broad diversity of isolated S. aureus strains, 173 transmission events were observed between participants. The joint analysis of carriage and CPIs showed that CPI paths linking incident cases to other individuals carrying the same strain (i.e. possible infectors) had fewer intermediaries than predicted by chance (P < 0.001), a feature that simulations showed to be the signature of transmission along CPIs. Additional analyses revealed a higher dissemination risk between patients via healthcare workers than via other patients. In conclusion, S. aureus transmission was consistent with contacts defined by electronically collected CPIs, illustrating their potential as a tool to control hospital-acquired infections and help direct surveillance. 相似文献
72.
Victor Certal Frank Halley Angela Virone-Oddos Fabienne Thompson Bruno Filoche-Rommé Youssef El-Ahmad Jean-Christophe Carry Cécile Delorme Andreas Karlsson Pierre-Yves Abecassis Loic Vincent Hélène Bonnevaux Jean-Paul Nicolas Renaud Morales Nadine Michot Isabelle Vade Audrey Louboutin Sébastien Perron Gilles Doerflinger Bernadette Tric Laurent Schio 《Bioorganic & medicinal chemistry letters》2012,22(20):6381-6384
From a HTS campaign, a new series of pyrimidone anilides exemplified by compound 1 has been identified with good inhibitory activity for the PI3Kβ isoform. The structure of compound 1 in PI3Kγ was solved revealing a binding mode in agreement with the SAR observed on PI3Kβ. These compounds displayed inhibition in the nanomolar range in the biochemical assay and were also potent p-Akt inhibitors in a PTEN-deficient PC3 prostate cancer cell line. Optimization of in vitro pharmocokinetic properties led to compound 25 exhibiting 52% bioavailability in mice and target engagement in an acute PK/PD study. 相似文献
73.
Molecular mechanisms underlying FOXP3 induction in human T cells 总被引:15,自引:0,他引:15
74.
Vandromme L Piguel S Lozach O Meijer L Legraverend M Grierson DS 《Bioorganic & medicinal chemistry letters》2006,16(12):3144-3146
A new series of 2-aryl-substituted purine derivatives has been synthesized by Suzuki Pd(0) coupling reactions. Moderate in vitro inhibitory activity against Cdk1 and Cdk5 was observed. These compounds are inactive against GSK3. 相似文献
75.
Testard A Logé C Léger B Robert JM Lozach O Blairvacq M Meijer L Thiéry V Besson T 《Bioorganic & medicinal chemistry letters》2006,16(13):3419-3423
In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the micromolar range. Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme. 相似文献
76.
Fabrice Teletchea Alexis Fostier Ewa Kamler Jean-Noël Gardeur Pierre-Yves Le Bail Bernard Jalabert Pascal Fontaine 《Reviews in Fish Biology and Fisheries》2009,19(4):403-430
Based on an extensive literature search (1,000 references), the objectives of the present study were to establish a numerical
clustering of temperate freshwater fish based on their reproductive traits and to evaluate whether it was possible to extrapolate
zootechnical knowledge among species belonging to the same cluster. About 65 species were classified into ten homogeneous
clusters from the analysis of 29 reproductive traits, among which the most important were temperature during spawning, egg
incubation and larval rearing, degree-days for incubation, larval size upon hatching, spawning season, and parental care.
From this typology, a rather regular continuum of reproductive clusters emerges with two obvious endpoints. Between these
two extremes, species could be ordered chiefly according to temperature requirement, spawning season and parental care. In
conclusion, this new typology, differing significantly from all others proposed earlier, may now serve as a possible framework
to help enhancing the domestication of new species by comparison to species belonging to the same cluster. 相似文献
77.
Tian L Cai T Pfeffer MA Piankov N Cremieux PY Wei LJ 《Biostatistics (Oxford, England)》2009,10(2):275-281
Recently, meta-analysis has been widely utilized to combine information across comparative clinical studies for evaluating drug efficacy or safety profile. When dealing with rather rare events, a substantial proportion of studies may not have any events of interest. Conventional methods either exclude such studies or add an arbitrary positive value to each cell of the corresponding 2 x 2 tables in the analysis. In this article, we present a simple, effective procedure to make valid inferences about the parameter of interest with all available data without artificial continuity corrections. We then use the procedure to analyze the data from 48 comparative trials involving rosiglitazone with respect to its possible cardiovascular toxicity. 相似文献
78.
79.
Jean-Philippe Coppé Christopher K. Patil Francis Rodier Ana Krtolica Christian M. Beauséjour Simona Parrinello J. Graeme Hodgson Koei Chin Pierre-Yves Desprez Judith Campisi 《PloS one》2010,5(2)
Cellular senescence irreversibly arrests cell proliferation in response to oncogenic stimuli. Human cells develop a senescence-associated secretory phenotype (SASP), which increases the secretion of cytokines and other factors that alter the behavior of neighboring cells. We show here that “senescent” mouse fibroblasts, which arrested growth after repeated passage under standard culture conditions (20% oxygen), do not express a human-like SASP, and differ from similarly cultured human cells in other respects. However, when cultured in physiological (3%) oxygen and induced to senesce by radiation, mouse cells more closely resemble human cells, including expression of a robust SASP. We describe two new aspects of the human and mouse SASPs. First, cells from both species upregulated the expression and secretion of several matrix metalloproteinases, which comprise a conserved genomic cluster. Second, for both species, the ability to promote the growth of premalignant epithelial cells was due primarily to the conserved SASP factor CXCL-1/KC/GRO-α. Further, mouse fibroblasts made senescent in 3%, but not 20%, oxygen promoted epithelial tumorigenesis in mouse xenographs. Our findings underscore critical mouse-human differences in oxygen sensitivity, identify conditions to use mouse cells to model human cellular senescence, and reveal novel conserved features of the SASP. 相似文献
80.
Dron M Bailly Y Beringue V Haeberlé AM Griffond B Risold PY Tovey MG Laude H Dandoy-Dron F 《Autophagy》2006,2(1):58-60
The Scrg1 gene was initially discovered as one of the genes upregulated in transmissible spongiform encephalopathies (TSE). Scrg1 encodes a highly conserved, cysteine-rich protein expressed principally in the central nervous system. The protein is targeted to the Golgi apparatus and large dense-core vesicles/secretory granules in neurons. We have recently shown that the Scrg1 protein is widely induced in neurons of scrapie-infected mice, suggesting that Scrg1 is involved in the host response to stress and/or the death of neurons. At the ultrastructural level, Scrg1 is associated with dictyosomes of the Golgi apparatus and autophagic vacuoles of degenerative neurons. It is well known that apoptosis plays a major role in the events leading to neuronal cell death in TSE. However, autophagy was identified in experimentally induced scrapie a long time ago and was recently reevaluated as a possible cell death program in prion diseases. The consistent association of Scrg1 with autophagic structures typical of scrapie is in agreement with the recruitment of Golgi-specific proteins in this degradation process and we suggest that Scrg1 might be used as a specific probe to identify neuronal autophagy in TSE. 相似文献