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排序方式: 共有498条查询结果,搜索用时 15 毫秒
241.
David N. Lerner Steven F. ThorntonDepartment of Civil Structural Engineering University of Sheffield Mappin Street. Sheffield S JD UK 《清华大学学报》2000,5(3)
IntroductionThere is increasing interest in naturalattenuation (NA) as a remedial option in the risk-based management of groundwater resources.NAis the net effect of all the processes thatreduce theconcentration of a pollutant to an acceptable levelbefore the water reaches a receptor,such as adrinking- water supply or a river.These processesinclude dispersion and dilution,volatilisation,sorption and other chemical reactions,andbiodegradation. For many pollutants,biodegradation is the most im… 相似文献
242.
Nègre N Brown CD Ma L Bristow CA Miller SW Wagner U Kheradpour P Eaton ML Loriaux P Sealfon R Li Z Ishii H Spokony RF Chen J Hwang L Cheng C Auburn RP Davis MB Domanus M Shah PK Morrison CA Zieba J Suchy S Senderowicz L Victorsen A Bild NA Grundstad AJ Hanley D MacAlpine DM Mannervik M Venken K Bellen H White R Gerstein M Russell S Grossman RL Ren B Posakony JW Kellis M White KP 《Nature》2011,471(7339):527-531
243.
Fu S Yang L Li P Hofmann O Dicker L Hide W Lin X Watkins SM Ivanov AR Hotamisligil GS 《Nature》2011,473(7348):528-531
The endoplasmic reticulum (ER) is the main site of protein and lipid synthesis, membrane biogenesis, xenobiotic detoxification and cellular calcium storage, and perturbation of ER homeostasis leads to stress and the activation of the unfolded protein response. Chronic activation of ER stress has been shown to have an important role in the development of insulin resistance and diabetes in obesity. However, the mechanisms that lead to chronic ER stress in a metabolic context in general, and in obesity in particular, are not understood. Here we comparatively examined the proteomic and lipidomic landscape of hepatic ER purified from lean and obese mice to explore the mechanisms of chronic ER stress in obesity. We found suppression of protein but stimulation of lipid synthesis in the obese ER without significant alterations in chaperone content. Alterations in ER fatty acid and lipid composition result in the inhibition of sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and ER stress. Correcting the obesity-induced alteration of ER phospholipid composition or hepatic Serca overexpression in vivo both reduced chronic ER stress and improved glucose homeostasis. Hence, we established that abnormal lipid and calcium metabolism are important contributors to hepatic ER stress in obesity. 相似文献
244.
Xiao B Sanders MJ Underwood E Heath R Mayer FV Carmena D Jing C Walker PA Eccleston JF Haire LF Saiu P Howell SA Aasland R Martin SR Carling D Gamblin SJ 《Nature》2011,472(7342):230-233
The heterotrimeric AMP-activated protein kinase (AMPK) has a key role in regulating cellular energy metabolism; in response to a fall in intracellular ATP levels it activates energy-producing pathways and inhibits energy-consuming processes. AMPK has been implicated in a number of diseases related to energy metabolism including type 2 diabetes, obesity and, most recently, cancer. AMPK is converted from an inactive form to a catalytically competent form by phosphorylation of the activation loop within the kinase domain: AMP binding to the γ-regulatory domain promotes phosphorylation by the upstream kinase, protects the enzyme against dephosphorylation, as well as causing allosteric activation. Here we show that ADP binding to just one of the two exchangeable AXP (AMP/ADP/ATP) binding sites on the regulatory domain protects the enzyme from dephosphorylation, although it does not lead to allosteric activation. Our studies show that active mammalian AMPK displays significantly tighter binding to ADP than to Mg-ATP, explaining how the enzyme is regulated under physiological conditions where the concentration of Mg-ATP is higher than that of ADP and much higher than that of AMP. We have determined the crystal structure of an active AMPK complex. The structure shows how the activation loop of the kinase domain is stabilized by the regulatory domain and how the kinase linker region interacts with the regulatory nucleotide-binding site that mediates protection against dephosphorylation. From our biochemical and structural data we develop a model for how the energy status of a cell regulates AMPK activity. 相似文献
245.
Collins PY Patel V Joestl SS March D Insel TR Daar AS;Scientific Advisory Board the Executive Committee of the Grand Challenges on Global Mental Health Anderson W Dhansay MA Phillips A Shurin S Walport M Ewart W Savill SJ Bordin IA Costello EJ Durkin M Fairburn C Glass RI Hall W Huang Y Hyman SE Jamison K Kaaya S Kapur S Kleinman A Ogunniyi A Otero-Ojeda A Poo MM Ravindranath V Sahakian BJ Saxena S Singer PA Stein DJ 《Nature》2011,475(7354):27-30
246.
Jirawatnotai S Hu Y Michowski W Elias JE Becks L Bienvenu F Zagozdzon A Goswami T Wang YE Clark AB Kunkel TA van Harn T Xia B Correll M Quackenbush J Livingston DM Gygi SP Sicinski P 《Nature》2011,474(7350):230-234
Cyclin D1 is a component of the core cell cycle machinery. Abnormally high levels of cyclin D1 are detected in many human cancer types. To elucidate the molecular functions of cyclin D1 in human cancers, we performed a proteomic screen for cyclin D1 protein partners in several types of human tumours. Analyses of cyclin D1 interactors revealed a network of DNA repair proteins, including RAD51, a recombinase that drives the homologous recombination process. We found that cyclin D1 directly binds RAD51, and that cyclin D1-RAD51 interaction is induced by radiation. Like RAD51, cyclin D1 is recruited to DNA damage sites in a BRCA2-dependent fashion. Reduction of cyclin D1 levels in human cancer cells impaired recruitment of RAD51 to damaged DNA, impeded the homologous recombination-mediated DNA repair, and increased sensitivity of cells to radiation in vitro and in vivo. This effect was seen in cancer cells lacking the retinoblastoma protein, which do not require D-cyclins for proliferation. These findings reveal an unexpected function of a core cell cycle protein in DNA repair and suggest that targeting cyclin D1 may be beneficial also in retinoblastoma-negative cancers which are currently thought to be unaffected by cyclin D1 inhibition. 相似文献
247.
Chatterjee A Abeydeera ND Bale S Pai PJ Dorrestein PC Russell DH Ealick SE Begley TP 《Nature》2011,478(7370):542-546
Thiamine pyrophosphate 1 is an essential cofactor in all living systems. Its biosynthesis involves the separate syntheses of the pyrimidine 2 and thiazole 3 precursors, which are then coupled. Two biosynthetic routes to the thiamine thiazole have been identified. In prokaryotes, five enzymes act on three substrates to produce the thiazole via a complex oxidative condensation reaction, the mechanistic details of which are now well established. In contrast, only one gene product is involved in thiazole biosynthesis in eukaryotes (THI4p in Saccharomyces cerevisiae). Here we report the preparation of fully active recombinant wild-type THI4p, the identification of an iron-dependent sulphide transfer reaction from a conserved cysteine residue of the protein to a reaction intermediate and the demonstration that THI4p is a suicide enzyme undergoing only a single turnover. 相似文献
248.
Alföldi J Di Palma F Grabherr M Williams C Kong L Mauceli E Russell P Lowe CB Glor RE Jaffe JD Ray DA Boissinot S Shedlock AM Botka C Castoe TA Colbourne JK Fujita MK Moreno RG ten Hallers BF Haussler D Heger A Heiman D Janes DE Johnson J de Jong PJ Koriabine MY Lara M Novick PA Organ CL Peach SE Poe S Pollock DD de Queiroz K Sanger T Searle S Smith JD Smith Z Swofford R Turner-Maier J Wade J Young S Zadissa A Edwards SV Glenn TC Schneider CJ Losos JB Lander ES Breen M Ponting CP Lindblad-Toh K 《Nature》2011,477(7366):587-591
The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations. 相似文献
249.
250.