排序方式: 共有49条查询结果,搜索用时 31 毫秒
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The frequency-dependent dielectric dispersion of ZnO-Na2O-AI2O3-B2O3 (in mol%)glass prepared by the melt quenching technique is investigated in the temperature ranges from room temperature to 420 K.Die... 相似文献
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Rosy El Ramy Najat Magroun Nadia Messadecq Laurent R. Gauthier François D. Boussin Ullas Kolthur-Seetharam Valérie Schreiber Michael W. McBurney Paolo Sassone-Corsi Françoise Dantzer 《Cellular and molecular life sciences : CMLS》2009,66(19):3219-3234
Poly(ADP-ribose) polymerase-1 (Parp-1) and the protein deacetylase SirT1 are two of the most effective NAD+-consuming enzymes in the cell with key functions in genome integrity and chromatin-based pathways. Here, we examined the
in vivo crosstalk between both proteins. We observed that the double disruption of both genes in mice tends to increase late
post-natal lethality before weaning consistent with important roles of both proteins in genome integrity during mouse development.
We identified increased spontaneous telomeric abnormalities associated with decreased cell growth in the absence of either
SirT1 or SirT1 and Parp-1 in mouse cells. In contrast, the additional disruption of Parp-1 rescued the abnormal pericentric
heterochromatin, the nucleolar disorganization and the mitotic defects observed in SirT1-deficient cells. Together, these
findings are in favor of key functions of both proteins in cellular response to DNA damage and in the modulation of histone
modifications associated with constitutive heterochromatin integrity. 相似文献
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Karhadkar SS Bova GS Abdallah N Dhara S Gardner D Maitra A Isaacs JT Berman DM Beachy PA 《Nature》2004,431(7009):707-712
Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs, such as the ability to proliferate and alter tissue organization. We find here that activity of the Hedgehog (Hh) signalling pathway, which has essential roles in developmental patterning, is required for regeneration of prostate epithelium, and that continuous pathway activation transforms prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation can modulate invasiveness and metastasis. Pathway activity is triggered in response to endogenous expression of Hh ligands, and is dependent upon the expression of Smoothened, an essential Hh response component that is not expressed in benign prostate epithelial cells. Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential. 相似文献
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Vogt G Chapgier A Yang K Chuzhanova N Feinberg J Fieschi C Boisson-Dupuis S Alcais A Filipe-Santos O Bustamante J de Beaucoudrey L Al-Mohsen I Al-Hajjar S Al-Ghonaium A Adimi P Mirsaeidi M Khalilzadeh S Rosenzweig S de la Calle Martin O Bauer TR Puck JM Ochs HD Furthner D Engelhorn C Belohradsky B Mansouri D Holland SM Schreiber RD Abel L Cooper DN Soudais C Casanova JL 《Nature genetics》2005,37(7):692-700
Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N-glycosylation site in the IFNgammaR2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFNgamma. We then searched the Human Gene Mutation Database for potential gain-of-N-glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( approximately 1.4%) in 77 genes ( approximately 13.3%). Six mutant proteins bore new N-linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N-glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N-linked carbohydrate. 相似文献
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Paciorek T Zazímalová E Ruthardt N Petrásek J Stierhof YD Kleine-Vehn J Morris DA Emans N Jürgens G Geldner N Friml J 《Nature》2005,435(7046):1251-1256
One of the mechanisms by which signalling molecules regulate cellular behaviour is modulating subcellular protein translocation. This mode of regulation is often based on specialized vesicle trafficking, termed constitutive cycling, which consists of repeated internalization and recycling of proteins to and from the plasma membrane. No such mechanism of hormone action has been shown in plants although several proteins, including the PIN auxin efflux facilitators, exhibit constitutive cycling. Here we show that a major regulator of plant development, auxin, inhibits endocytosis. This effect is specific to biologically active auxins and requires activity of the Calossin-like protein BIG. By inhibiting the internalization step of PIN constitutive cycling, auxin increases levels of PINs at the plasma membrane. Concomitantly, auxin promotes its own efflux from cells by a vesicle-trafficking-dependent mechanism. Furthermore, asymmetric auxin translocation during gravitropism is correlated with decreased PIN internalization. Our data imply a previously undescribed mode of plant hormone action: by modulating PIN protein trafficking, auxin regulates PIN abundance and activity at the cell surface, providing a mechanism for the feedback regulation of auxin transport. 相似文献
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The world's soils store more carbon than is present in biomass and in the atmosphere. Little is known, however, about the factors controlling the stability of soil organic carbon stocks and the response of the soil carbon pool to climate change remains uncertain. We investigated the stability of carbon in deep soil layers in one soil profile by combining physical and chemical characterization of organic carbon, soil incubations and radiocarbon dating. Here we show that the supply of fresh plant-derived carbon to the subsoil (0.6-0.8 m depth) stimulated the microbial mineralization of 2,567 +/- 226-year-old carbon. Our results support the previously suggested idea that in the absence of fresh organic carbon, an essential source of energy for soil microbes, the stability of organic carbon in deep soil layers is maintained. We propose that a lack of supply of fresh carbon may prevent the decomposition of the organic carbon pool in deep soil layers in response to future changes in temperature. Any change in land use and agricultural practice that increases the distribution of fresh carbon along the soil profile could however stimulate the loss of ancient buried carbon. 相似文献
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Laurie CC Laurie CA Rice K Doheny KF Zelnick LR McHugh CP Ling H Hetrick KN Pugh EW Amos C Wei Q Wang LE Lee JE Barnes KC Hansel NN Mathias R Daley D Beaty TH Scott AF Ruczinski I Scharpf RB Bierut LJ Hartz SM Landi MT Freedman ND Goldin LR Ginsburg D Li J Desch KC Strom SS Blot WJ Signorello LB Ingles SA Chanock SJ Berndt SI Le Marchand L Henderson BE Monroe KR Heit JA de Andrade M Armasu SM Regnier C Lowe WL Hayes MG Marazita ML Feingold E Murray JC Melbye M Feenstra B Kang JH Wiggs JL 《Nature genetics》2012,44(6):642-650
We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18). 相似文献