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991.
992.
Matheu A Maraver A Klatt P Flores I Garcia-Cao I Borras C Flores JM Viña J Blasco MA Serrano M 《Nature》2007,448(7151):375-379
The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity. 相似文献
993.
994.
Projected increase in continental runoff due to plant responses to increasing carbon dioxide 总被引:13,自引:0,他引:13
Betts RA Boucher O Collins M Cox PM Falloon PD Gedney N Hemming DL Huntingford C Jones CD Sexton DM Webb MJ 《Nature》2007,448(7157):1037-1041
In addition to influencing climatic conditions directly through radiative forcing, increasing carbon dioxide concentration influences the climate system through its effects on plant physiology. Plant stomata generally open less widely under increased carbon dioxide concentration, which reduces transpiration and thus leaves more water at the land surface. This driver of change in the climate system, which we term 'physiological forcing', has been detected in observational records of increasing average continental runoff over the twentieth century. Here we use an ensemble of experiments with a global climate model that includes a vegetation component to assess the contribution of physiological forcing to future changes in continental runoff, in the context of uncertainties in future precipitation. We find that the physiological effect of doubled carbon dioxide concentrations on plant transpiration increases simulated global mean runoff by 6 per cent relative to pre-industrial levels; an increase that is comparable to that simulated in response to radiatively forced climate change (11 +/- 6 per cent). Assessments of the effect of increasing carbon dioxide concentrations on the hydrological cycle that only consider radiative forcing will therefore tend to underestimate future increases in runoff and overestimate decreases. This suggests that freshwater resources may be less limited than previously assumed under scenarios of future global warming, although there is still an increased risk of drought. Moreover, our results highlight that the practice of assessing the climate-forcing potential of all greenhouse gases in terms of their radiative forcing potential relative to carbon dioxide does not accurately reflect the relative effects of different greenhouse gases on freshwater resources. 相似文献
995.
The human microbiome project 总被引:3,自引:0,他引:3
A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease. 相似文献
996.
Ambra1 regulates autophagy and development of the nervous system 总被引:1,自引:0,他引:1
Fimia GM Stoykova A Romagnoli A Giunta L Di Bartolomeo S Nardacci R Corazzari M Fuoco C Ucar A Schwartz P Gruss P Piacentini M Chowdhury K Cecconi F 《Nature》2007,447(7148):1121-1125
Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals. 相似文献
997.
D'Angelo G Polishchuk E Di Tullio G Santoro M Di Campli A Godi A West G Bielawski J Chuang CC van der Spoel AC Platt FM Hannun YA Polishchuk R Mattjus P De Matteis MA 《Nature》2007,449(7158):62-67
The molecular machinery responsible for the generation of transport carriers moving from the Golgi complex to the plasma membrane relies on a tight interplay between proteins and lipids. Among the lipid-binding proteins of this machinery, we previously identified the four-phosphate adaptor protein FAPP2, the pleckstrin homology domain of which binds phosphatidylinositol 4-phosphate and the small GTPase ARF1. FAPP2 also possesses a glycolipid-transfer-protein homology domain. Here we show that human FAPP2 is a glucosylceramide-transfer protein that has a pivotal role in the synthesis of complex glycosphingolipids, key structural and signalling components of the plasma membrane. The requirement for FAPP2 makes the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. Thus, by coupling the synthesis of glycosphingolipids with their export to the cell surface, FAPP2 emerges as crucial in determining the lipid identity and composition of the plasma membrane. 相似文献
998.
Trench-parallel flow and seismic anisotropy in the Mariana and Andean subduction systems 总被引:2,自引:0,他引:2
Shear-wave splitting measurements above the mantle wedge of the Mariana and southern Andean subduction zones show trench-parallel seismically fast directions close to the trench and abrupt rotations to trench-perpendicular anisotropy in the back arc. These patterns of seismic anisotropy may be caused by three-dimensional flow associated with along-strike variations in slab geometry. The Mariana and Andean subduction systems are associated with the largest along-strike variations of slab geometry observed on Earth and are ideal for testing the link between slab geometry and solid-state creep processes in the mantle. Here we show, with fully three-dimensional non-newtonian subduction zone models, that the strong curvature of the Mariana slab and the transition to shallow slab dip in the Southern Andes give rise to strong trench-parallel stretching in the warm-arc and warm-back-arc mantle and to abrupt rotations in stretching directions that are accompanied by strong trench-parallel stretching. These models show that the patterns of shear-wave splitting observed in the Mariana and southern Andean systems may be caused by significant three-dimensional flow induced by along-strike variations in slab geometry. 相似文献
999.
1000.
Ruban AV Berera R Ilioaia C van Stokkum IH Kennis JT Pascal AA van Amerongen H Robert B Horton P van Grondelle R 《Nature》2007,450(7169):575-578
Under conditions of excess sunlight the efficient light-harvesting antenna found in the chloroplast membranes of plants is rapidly and reversibly switched into a photoprotected quenched state in which potentially harmful absorbed energy is dissipated as heat, a process measured as the non-photochemical quenching of chlorophyll fluorescence or qE. Although the biological significance of qE is established, the molecular mechanisms involved are not. LHCII, the main light-harvesting complex, has an inbuilt capability to undergo transformation into a dissipative state by conformational change and it was suggested that this provides a molecular basis for qE, but it is not known if such events occur in vivo or how energy is dissipated in this state. The transition into the dissipative state is associated with a twist in the configuration of the LHCII-bound carotenoid neoxanthin, identified using resonance Raman spectroscopy. Applying this technique to study isolated chloroplasts and whole leaves, we show here that the same change in neoxanthin configuration occurs in vivo, to an extent consistent with the magnitude of energy dissipation. Femtosecond transient absorption spectroscopy, performed on purified LHCII in the dissipative state, shows that energy is transferred from chlorophyll a to a low-lying carotenoid excited state, identified as one of the two luteins (lutein 1) in LHCII. Hence, it is experimentally demonstrated that a change in conformation of LHCII occurs in vivo, which opens a channel for energy dissipation by transfer to a bound carotenoid. We suggest that this is the principal mechanism of photoprotection. 相似文献