排序方式: 共有24条查询结果,搜索用时 31 毫秒
11.
Crow YJ Hayward BE Parmar R Robins P Leitch A Ali M Black DN van Bokhoven H Brunner HG Hamel BC Corry PC Cowan FM Frints SG Klepper J Livingston JH Lynch SA Massey RF Meritet JF Michaud JL Ponsot G Voit T Lebon P Bonthron DT Jackson AP Barnes DE Lindahl T 《Nature genetics》2006,38(8):917-920
Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. 相似文献
12.
Zhou X Gomez-Smith M Qin Z Duquette PM Cardenas-Blanco A Rai PS Harper ME Tsai EC Anisman H Chen HH 《Cellular and molecular life sciences : CMLS》2012,69(5):819-828
The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its function there is not known. Using mice with
LMO4 ablated in postnatal glutamatergic neurons, including most neurons of the paraventricular (PVN) and ventromedial (VMH)
hypothalamic nuclei where LMO4 is expressed, we asked whether LMO4 is required for metabolic homeostasis. LMO4 mutant mice
exhibited early onset adiposity. These mice had reduced energy expenditure and impaired thermogenesis together with reduced
sympathetic outflow to adipose tissues. The peptide hormone leptin, produced from adipocytes, activates Jak/Stat3 signaling
at the hypothalamus to control food intake, energy expenditure, and fat metabolism. Intracerebroventricular infusion of leptin
suppressed feeding similarly in LMO4 mutant and control mice. However, leptin-induced fat loss was impaired and activation
of Stat3 in the VMH was blunted in these mice. Thus, our study identifies LMO4 as a novel modulator of leptin function in
selective hypothalamic nuclei to regulate fat metabolism. 相似文献
13.
14.
Asma Ali Mohd.Shadab Khan Rekha Rani 《吉林大学学报(理学版)》2003,41(3):279-280
得到了满足下列任何一个条件时拟环的分解定理:
(1) xy=ym(xy)pyn;
(2) xy=ym(yx)pyn, 这里m=m(x,y)≥0, n=n(x,y)≥0, 且p=p(x,y)>1是整数. 相似文献
15.
Na?Li Marcus?Parrish Tze?Khee?Chan Lu?Yin Prashant?Rai Yamada?Yoshiyuki Nona?Abolhassani Kong?Bing?Tan Orsolya?Kiraly Vincent?T.?K.?Chow Bevin?P.?EngelwardEmail author 《Cellular and molecular life sciences : CMLS》2015,72(15):2973-2988
Influenza viruses account for significant morbidity worldwide. Inflammatory responses, including excessive generation of reactive oxygen and nitrogen species (RONS), mediate lung injury in severe influenza infections. However, the molecular basis of inflammation-induced lung damage is not fully understood. Here, we studied influenza H1N1 infected cells in vitro, as well as H1N1 infected mice, and we monitored molecular and cellular responses over the course of 2 weeks in vivo. We show that influenza induces DNA damage to both, when cells are directly exposed to virus in vitro (measured using the comet assay) and also when cells are exposed to virus in vivo (estimated via γH2AX foci). We show that DNA damage, as well as responses to DNA damage persist in vivo until long after virus has been cleared, at times when there are inflammation associated RONS (measured by xanthine oxidase activity and oxidative products). The frequency of lung epithelial and immune cells with increased γH2AX foci is elevated in vivo, especially for dividing cells (Ki-67-positive) exposed to oxidative stress during tissue regeneration. Additionally, we observed a significant increase in apoptotic cells as well as increased levels of DNA double strand break (DSB) repair proteins Ku70, Ku86 and Rad51 during the regenerative phase. In conclusion, results show that influenza induces DNA damage both in vitro and in vivo, and that DNA damage responses are activated, raising the possibility that DNA repair capacity may be a determining factor for tissue recovery and disease outcome. 相似文献
16.
Crow YJ Leitch A Hayward BE Garner A Parmar R Griffith E Ali M Semple C Aicardi J Babul-Hirji R Baumann C Baxter P Bertini E Chandler KE Chitayat D Cau D Déry C Fazzi E Goizet C King MD Klepper J Lacombe D Lanzi G Lyall H Martínez-Frías ML Mathieu M McKeown C Monier A Oade Y Quarrell OW Rittey CD Rogers RC Sanchis A Stephenson JB Tacke U Till M Tolmie JL Tomlin P Voit T Weschke B Woods CG Lebon P Bonthron DT Ponting CP Jackson AP 《Nature genetics》2006,38(8):910-916
Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation. 相似文献
17.
Srdja Drakulic Jay Rai Steen Vang Petersen Monika M. Golas Bjoern Sander 《Cellular and molecular life sciences : CMLS》2018,75(16):3009-3026
The pyruvate dehydrogenase complex (PDC) bridges glycolysis and the citric acid cycle. In human, PDC deficiency leads to severe neurodevelopmental delay and progressive neurodegeneration. The majority of cases are caused by variants in the gene encoding the PDC subunit E1α. The molecular effects of the variants, however, remain poorly understood. Using yeast as a eukaryotic model system, we have studied the substitutions A189V, M230V, and R322C in yeast E1α (corresponding to the pathogenic variants A169V, M210V, and R302C in human E1α) and evaluated how substitutions of single amino acid residues within different functional E1α regions affect PDC structure and activity. The E1α A189V substitution located in the heterodimer interface showed a more compact conformation with significant underrepresentation of E1 in PDC and impaired overall PDC activity. The E1α M230V substitution located in the tetramer and heterodimer interface showed a relatively more open conformation and was particularly affected by low thiamin pyrophosphate concentrations. The E1α R322C substitution located in the phosphorylation loop of E1α resulted in PDC lacking E3 subunits and abolished overall functional activity. Furthermore, we show for the E1α variant A189V that variant E1α accumulates in the Hsp60 chaperonin, but can be released upon ATP supplementation. Our studies suggest that pathogenic E1α variants may be associated with structural changes of PDC and impaired folding of E1α. 相似文献
18.
Flynn RL Centore RC O'Sullivan RJ Rai R Tse A Songyang Z Chang S Karlseder J Zou L 《Nature》2011,471(7339):532-536
Maintenance of telomeres requires both DNA replication and telomere 'capping' by shelterin. These two processes use two single-stranded DNA (ssDNA)-binding proteins, replication protein A (RPA) and protection of telomeres 1 (POT1). Although RPA and POT1 each have a critical role at telomeres, how they function in concert is not clear. POT1 ablation leads to activation of the ataxia telangiectasia and Rad3-related (ATR) checkpoint kinase at telomeres, suggesting that POT1 antagonizes RPA binding to telomeric ssDNA. Unexpectedly, we found that purified POT1 and its functional partner TPP1 are unable to prevent RPA binding to telomeric ssDNA efficiently. In cell extracts, we identified a novel activity that specifically displaces RPA, but not POT1, from telomeric ssDNA. Using purified protein, here we show that the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) recapitulates the RPA displacing activity. The RPA displacing activity is inhibited by the telomeric repeat-containing RNA (TERRA) in early S phase, but is then unleashed in late S phase when TERRA levels decline at telomeres. Interestingly, TERRA also promotes POT1 binding to telomeric ssDNA by removing hnRNPA1, suggesting that the re-accumulation of TERRA after S phase helps to complete the RPA-to-POT1 switch on telomeric ssDNA. Together, our data suggest that hnRNPA1, TERRA and POT1 act in concert to displace RPA from telomeric ssDNA after DNA replication, and promote telomere capping to preserve genomic integrity. 相似文献
19.
A. K. Rai 《Cellular and molecular life sciences : CMLS》1977,33(5):595-595
Summary Phycoerythrin was not present in Anabaena ambigua Rao, and in its strains, Lh- and Ha-forms under normal culture conditions, but it developed in parent and Lh-form when treated with green light and nitrate. However, Ha-form appeared to be unable to form phycoerythrin.My thanks are due to Atomic Energy Commission, India, for the financial assistance. 相似文献
20.
Summary Drought resistant cv. C-214 ofCicer arietinum L. showed higher accumulation of alanine, threonine, glutamine, -alanine, arginine, amino butyric acid, valine, leucine, phenylalanine than the susceptible cv. G130 under water stress. 相似文献