排序方式: 共有51条查询结果,搜索用时 15 毫秒
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Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration 总被引:23,自引:0,他引:23
Lin SJ Kaeberlein M Andalis AA Sturtz LA Defossez PA Culotta VC Fink GR Guarente L 《Nature》2002,418(6895):344-348
Calorie restriction (CR) extends lifespan in a wide spectrum of organisms and is the only regimen known to lengthen the lifespan of mammals. We established a model of CR in budding yeast Saccharomyces cerevisiae. In this system, lifespan can be extended by limiting glucose or by reducing the activity of the glucose-sensing cyclic-AMP-dependent kinase (PKA). Lifespan extension in a mutant with reduced PKA activity requires Sir2 and NAD (nicotinamide adenine dinucleotide). In this study we explore how CR activates Sir2 to extend lifespan. Here we show that the shunting of carbon metabolism toward the mitochondrial tricarboxylic acid cycle and the concomitant increase in respiration play a central part in this process. We discuss how this metabolic strategy may apply to CR in animals. 相似文献
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Lucas Matt Stylianos Michalakis Franz Hofmann Verena Hammelmann Andreas Ludwig Martin Biel Thomas Kleppisch 《Cellular and molecular life sciences : CMLS》2011,68(1):125-137
Neuronal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to modulate spontaneous activity, resting
membrane potential, input resistance, afterpotential, rebound activity, and dendritic integration. To evaluate the role of
HCN2 for hippocampal synaptic plasticity, we recorded long-term potentiation (LTP) in the direct perforant path (PP) to CA1
pyramidal cells. LTP was enhanced in mice carrying a global deletion of the channel (HCN2−/−) but not in a pyramidal neuron-restricted knockout. This precludes an influence of HCN2 located in postsynaptic pyramidal
neurons. Additionally, the selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons
in wild-type but not HCN2−/− mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells. Finally, we found
amplified LTP in the PP of mice carrying an interneuron-specific deletion of HCN2. We conclude that HCN2 channels in inhibitory
interneurons modulate synaptic plasticity in the PP by facilitating the GABAergic output onto pyramidal neurons. 相似文献
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Hillier LW Graves TA Fulton RS Fulton LA Pepin KH Minx P Wagner-McPherson C Layman D Wylie K Sekhon M Becker MC Fewell GA Delehaunty KD Miner TL Nash WE Kremitzki C Oddy L Du H Sun H Bradshaw-Cordum H Ali J Carter J Cordes M Harris A Isak A van Brunt A Nguyen C Du F Courtney L Kalicki J Ozersky P Abbott S Armstrong J Belter EA Caruso L Cedroni M Cotton M Davidson T Desai A Elliott G Erb T Fronick C Gaige T Haakenson W Haglund K Holmes A Harkins R Kim K Kruchowski SS Strong CM Grewal N Goyea E 《Nature》2005,434(7034):724-731
Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions. 相似文献
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Martínez-Sansigre A Rawlings S Lacy M Fadda D Marleau FR Simpson C Willott CJ Jarvis MJ 《Nature》2005,436(7051):666-669
Supermassive black holes underwent periods of exponential growth during which we see them as quasars in the distant Universe. The summed emission from these quasars generates the cosmic X-ray background, the spectrum of which has been used to argue that most black-hole growth is obscured. There are clear examples of obscured black-hole growth in the form of 'type-2' quasars, but their numbers are fewer than expected from modelling of the X-ray background. Here we report the direct detection of a population of distant type-2 quasars, which is at least comparable in size to the well-known unobscured type-1 population. We selected objects that have mid-infrared and radio emissions characteristic of quasars, but which are faint at near-infrared and optical wavelengths. We conclude that this population is responsible for most of the black-hole growth in the young Universe and that, throughout cosmic history, black-hole growth occurs in the dusty, gas-rich centres of active galaxies. 相似文献
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Changing Arctic Ocean freshwater pathways 总被引:7,自引:0,他引:7
Freshening in the Canada basin of the Arctic Ocean began in the 1990s and continued to at least the end of 2008. By then, the Arctic Ocean might have gained four times as much fresh water as comprised the Great Salinity Anomaly of the 1970s, raising the spectre of slowing global ocean circulation. Freshening has been attributed to increased sea ice melting and contributions from runoff, but a leading explanation has been a strengthening of the Beaufort High--a characteristic peak in sea level atmospheric pressure--which tends to accelerate an anticyclonic (clockwise) wind pattern causing convergence of fresh surface water. Limited observations have made this explanation difficult to verify, and observations of increasing freshwater content under a weakened Beaufort High suggest that other factors must be affecting freshwater content. Here we use observations to show that during a time of record reductions in ice extent from 2005 to 2008, the dominant freshwater content changes were an increase in the Canada basin balanced by a decrease in the Eurasian basin. Observations are drawn from satellite data (sea surface height and ocean-bottom pressure) and in situ data. The freshwater changes were due to a cyclonic (anticlockwise) shift in the ocean pathway of Eurasian runoff forced by strengthening of the west-to-east Northern Hemisphere atmospheric circulation characterized by an increased Arctic Oscillation index. Our results confirm that runoff is an important influence on the Arctic Ocean and establish that the spatial and temporal manifestations of the runoff pathways are modulated by the Arctic Oscillation, rather than the strength of the wind-driven Beaufort Gyre circulation. 相似文献