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Xinzhu Deng David Michaelson Jason Tchieu Jin Cheng Diana Rothenstein Regina Feldman Sang-gyu Lee John Fuller Adriana Haimovitz-Friedman Lorenz Studer Simon Powell Zvi Fuks E. Jane Albert Hubbard Richard Kolesnick 《PloS one》2015,10(6)
Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models. 相似文献
63.
Household‐level correlates of children's physical activity levels in and across 12 countries 下载免费PDF全文
Deirdre M. Harrington Fiona Gillison Stephanie T. Broyles Jean‐Philippe Chaput Mikael Fogelholm Gang Hu Rebecca Kuriyan Anura Kurpad Allana G. LeBlanc Carol Maher Jose Maia Victor Matsudo Timothy Olds Vincent Onywera Olga L. Sarmiento Martyn Standage Mark S. Tremblay Catrine Tudor‐Locke Pei Zhao Peter T. Katzmarzyk for the ISCOLE Research Group 《Obesity (Silver Spring, Md.)》2016,24(10):2150-2157
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Chen Chen Raymond Dagnino Jr. Charles Q. Huang James R. McCarthy Dimitri E. Grigoriadis 《Bioorganic & medicinal chemistry letters》2001,11(24):3165-3168
Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF1 receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF1 receptor (Ki=9 nM). 相似文献
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Jos C. García‐Borrn Berta L. Snchez‐Laorden Celia Jimnez‐Cervantes 《Pigment cell & melanoma research》2005,18(6):393-410
The melanogenic actions of the melanocortins are mediated by the melanocortin‐1 receptor (MC1R). MC1R is a member of the G‐protein‐coupled receptors (GPCR) superfamily expressed in cutaneous and hair follicle melanocytes. Activation of MC1R by adrenocorticotrophin or α‐melanocyte stimulating hormone is positively coupled to the cAMP signaling pathway and leads to a stimulation of melanogenesis and a switch from the synthesis of pheomelanins to the production of eumelanic pigments. The functional behavior of the MC1R agrees with emerging concepts in GPCR signaling including dimerization, coupling to more than one signaling pathway and a high agonist‐independent constitutive activity accounting for inverse agonism phenomena. In addition, MC1R displays unique properties such as an unusually high number of natural variants often associated with clearly visible phenotypes and the occurrence of endogenous peptide antagonists. Therefore MC1R is an ideal model to study GPCR function. Here we review our current knowledge of MC1R structure and function, with emphasis on information gathered from the analysis of natural variants. We also discuss recent data on the regulation of MC1R function by paracrine and endocrine factors and by external stimuli such as ultraviolet light. 相似文献
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Jun‐juan Wang Qi‐min Zhang Wei‐wei Ni Xin Zhang Ying Li Ai‐li Li Peng Du Chun Li Su‐su Yu 《Microbiology and immunology》2019,63(8):303-315
We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with β‐lactoglobulin (β‐Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short‐chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G‐protein–coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor‐β and IFN‐γ (p < .05), but negatively with the serum concentrations of IL‐17, IL‐4, and IL‐6 in the L. acidophilus–treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43. 相似文献
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Elio R.D. Castillo Dardo A. Martí Maximiliano M. Maronna María C. Scattolini Diogo C. Cabral‐de‐Mello María M. Cigliano 《Systematic Entomology》2019,44(1):61-74
In an attempt to unveil the origin of neo‐sex chromosomes in Ronderosia Cigliano grasshoppers, we performed a combined phylogenetic analysis based on morphological (external morphology and male genitalia) and molecular data (COI, COII, 16S and ITS2) to explore the chromosome evolution within the genus. We also analysed the distributional patterns of the various Ronderosia species and considered the possible role of chromosome rearrangements (CRs) in speciation processes within the genus in the light of ‘suppressed‐recombination’ models. We mapped the states of three chromosomal characters on the combined tree topology. The combined evidence supported Ronderosia as a monophyletic group. The cytogenetic analyses of the genus demonstrated the importance of rearranged karyotypes with single, complex and multiples neo‐sex chromosome determination systems in all species. The chromosome character optimisation suggests X‐autosome centric fusion as the mechanism responsible for neo‐sex chromosome formation in most Ronderosia species, except in R. dubia and R. bergii. Similar autosomes were involved in fusions with the ancestral X chromosome in Ronderosia, supporting previous hypotheses on the unique origin of X‐autosome fusion for the sex chromosome in the genus. As a source of chromosome variation, autosome‐autosome centric fusion played a secondary role in Ronderosia compared with other Dichroplini. Given the homogeneity in the morphological features, the sympatric distribution of closely related species and the intrinsic property of centric fusion as suppressors of the crossing over, we suggest that CRs may have played a key role during the speciation process within Ronderosia. 相似文献
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