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Sir2 (silent information regulator 2) is a nicotinamide adenine dinucleotide-dependent deacetylase required for longevity due to calorie restriction in yeast and Drosophila. In mammals, calorie restriction induces a complex pattern of physiological and behavioral changes. Here we report that the mammalian Sir2 ortholog, Sirt1, is required for the induction of a phenotype by calorie restriction in mice. 相似文献
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Scherer SW Cheung J MacDonald JR Osborne LR Nakabayashi K Herbrick JA Carson AR Parker-Katiraee L Skaug J Khaja R Zhang J Hudek AK Li M Haddad M Duggan GE Fernandez BA Kanematsu E Gentles S Christopoulos CC Choufani S Kwasnicka D Zheng XH Lai Z Nusskern D Zhang Q Gu Z Lu F Zeesman S Nowaczyk MJ Teshima I Chitayat D Shuman C Weksberg R Zackai EH Grebe TA Cox SR Kirkpatrick SJ Rahman N Friedman JM Heng HH Pelicci PG Lo-Coco F Belloni E Shaffer LG Pober B Morton CC Gusella JF Bruns GA Korf BR 《Science (New York, N.Y.)》2003,300(5620):767-772
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Walmsley MJ Ooi SK Reynolds LF Smith SH Ruf S Mathiot A Vanes L Williams DA Cancro MP Tybulewicz VL 《Science (New York, N.Y.)》2003,302(5644):459-462
The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance. 相似文献
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The Maternal-Effect Sterile (MES) proteins are essential for germline viability in Caenorhabditis elegans. Here, we report that MES-4, a SET-domain protein, binds to the autosomes but not to the X chromosomes. MES-2, MES-3, and MES-6 are required to exclude MES-4 and markers of active chromatin from the X chromosomes. These findings strengthen the emerging view that in the C. elegans germ line, the X chromosomes differ in chromatin state from the autosomes and are generally silenced. We propose that all four MES proteins participate in X-chromosome silencing, and that the role of MES-4 is to exclude repressors from the autosomes, thus enabling efficient repression of the Xs. 相似文献
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Ray RS Corcoran AE Brust RD Kim JC Richerson GB Nattie E Dymecki SM 《Science (New York, N.Y.)》2011,333(6042):637-642
Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function. 相似文献