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Lissauer JJ Fabrycky DC Ford EB Borucki WJ Fressin F Marcy GW Orosz JA Rowe JF Torres G Welsh WF Batalha NM Bryson ST Buchhave LA Caldwell DA Carter JA Charbonneau D Christiansen JL Cochran WD Desert JM Dunham EW Fanelli MN Fortney JJ Gautier TN Geary JC Gilliland RL Haas MR Hall JR Holman MJ Koch DG Latham DW Lopez E McCauliff S Miller N Morehead RC Quintana EV Ragozzine D Sasselov D Short DR Steffen JH 《Nature》2011,470(7332):53-58
When an extrasolar planet passes in front of (transits) its star, its radius can be measured from the decrease in starlight and its orbital period from the time between transits. Multiple planets transiting the same star reveal much more: period ratios determine stability and dynamics, mutual gravitational interactions reflect planet masses and orbital shapes, and the fraction of transiting planets observed as multiples has implications for the planarity of planetary systems. But few stars have more than one known transiting planet, and none has more than three. Here we report Kepler spacecraft observations of a single Sun-like star, which we call Kepler-11, that reveal six transiting planets, five with orbital periods between 10 and 47?days and a sixth planet with a longer period. The five inner planets are among the smallest for which mass and size have both been measured, and these measurements imply substantial envelopes of light gases. The degree of coplanarity and proximity of the planetary orbits imply energy dissipation near the end of planet formation. 相似文献
234.
Peça J Feliciano C Ting JT Wang W Wells MF Venkatraman TN Lascola CD Fu Z Feng G 《Nature》2011,472(7344):437-442
Autism spectrum disorders (ASDs) comprise a range of disorders that share a core of neurobehavioural deficits characterized by widespread abnormalities in social interactions, deficits in communication as well as restricted interests and repetitive behaviours. The neurological basis and circuitry mechanisms underlying these abnormal behaviours are poorly understood. SHANK3 is a postsynaptic protein, whose disruption at the genetic level is thought to be responsible for the development of 22q13 deletion syndrome (Phelan-McDermid syndrome) and other non-syndromic ASDs. Here we show that mice with Shank3 gene deletions exhibit self-injurious repetitive grooming and deficits in social interaction. Cellular, electrophysiological and biochemical analyses uncovered defects at striatal synapses and cortico-striatal circuits in Shank3 mutant mice. Our findings demonstrate a critical role for SHANK3 in the normal development of neuronal connectivity and establish causality between a disruption in the Shank3 gene and the genesis of autistic-like behaviours in mice. 相似文献
235.
Suhre K Shin SY Petersen AK Mohney RP Meredith D Wägele B Altmaier E;CARDIoGRAM Deloukas P Erdmann J Grundberg E Hammond CJ de Angelis MH Kastenmüller G Köttgen A Kronenberg F Mangino M Meisinger C Meitinger T Mewes HW Milburn MV Prehn C Raffler J Ried JS Römisch-Margl W Samani NJ Small KS Wichmann HE Zhai G Illig T Spector TD Adamski J Soranzo N Gieger C 《Nature》2011,477(7362):54-60
Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research. 相似文献
236.
Extended megadroughts in the southwestern United States during Pleistocene interglacials 总被引:1,自引:0,他引:1
Fawcett PJ Werne JP Anderson RS Heikoop JM Brown ET Berke MA Smith SJ Goff F Donohoo-Hurley L Cisneros-Dozal LM Schouten S Sinninghe Damsté JS Huang Y Toney J Fessenden J WoldeGabriel G Atudorei V Geissman JW Allen CD 《Nature》2011,470(7335):518-521
The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ~2?°C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6?°C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase. 相似文献
237.
Sicardy B Ortiz JL Assafin M Jehin E Maury A Lellouch E Hutton RG Braga-Ribas F Colas F Hestroffer D Lecacheux J Roques F Santos-Sanz P Widemann T Morales N Duffard R Thirouin A Castro-Tirado AJ Jelínek M Kubánek P Sota A Sánchez-Ramírez R Andrei AH Camargo JI da Silva Neto DN Gomes AR Martins RV Gillon M Manfroid J Tozzi GP Harlingten C Saravia S Behrend R Mottola S Melendo EG Peris V Fabregat J Madiedo JM Cuesta L Eibe MT Ullán A Organero F Pastor S de Los Reyes JA Pedraz S Castro A 《Nature》2011,478(7370):493-496
The dwarf planet Eris is a trans-Neptunian object with an orbital eccentricity of 0.44, an inclination of 44 degrees and a surface composition very similar to that of Pluto. It resides at present at 95.7 astronomical units (1?AU is the Earth-Sun distance) from Earth, near its aphelion and more than three times farther than Pluto. Owing to this great distance, measuring its size or detecting a putative atmosphere is difficult. Here we report the observation of a multi-chord stellar occultation by Eris on 6 November 2010 UT. The event is consistent with a spherical shape for Eris, with radius 1,163?±?6?kilometres, density 2.52?±?0.05 grams per cm(3) and a high visible geometric albedo, Pv = 0.96(+0.09)(-0.04). No nitrogen, argon or methane atmospheres are detected with surface pressure larger than ~1?nanobar, about 10,000 times more tenuous than Pluto's present atmosphere. As Pluto's radius is estimated to be between 1,150 and 1,200 kilometres, Eris appears as a Pluto twin, with a bright surface possibly caused by a collapsed atmosphere, owing to its cold environment. We anticipate that this atmosphere may periodically sublimate as Eris approaches its perihelion, at 37.8 astronomical units from the Sun. 相似文献
238.
J. Kim D. C. Han J. M. Kim S. Y. Lee S. J. Kim J. R. Woo J. W. Lee S.-K. Jung K. S. Yoon H. G. Cheon S. S. Kim S. H. Hong B.-M. Kwon 《Cellular and molecular life sciences : CMLS》2009,66(10):1766-1781
Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals
that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis
showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte
cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2
in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated
by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte
cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte
cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological
responses of the ligands.
Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009 相似文献
239.
Ruth Seelige Stephen Searles Jack D. Bui 《Cellular and molecular life sciences : CMLS》2018,75(2):225-240
The purpose of this review is to explore immune-mediated mechanisms of stress surveillance in cancer, with particular emphasis on the idea that all cancers have classical hallmarks (Hanahan and Weinberg in Cell 100:57–70, 67; Cell 144:646–674, 68) that could be interrelated. We postulate that hallmarks of cancer associated with cellular stress pathways (Luo et al. in Cell 136:823–837, 101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage, and metabolic stress could define and modulate the inflammatory component of cancer. As such, the overarching goal of this review is to define the types of cellular stress that cancer cells undergo, and then to explore mechanisms by which immune cells recognize, respond to, and are affected by each stress response. 相似文献
240.
Antonietta Pietrangelo Neale D. Ridgway 《Cellular and molecular life sciences : CMLS》2018,75(17):3079-3098
Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large eukaryotic gene family that transports and regulates the metabolism of sterols and phospholipids. The original classification of the family based on oxysterol-binding activity belies the complex dual lipid-binding specificity of the conserved OSBP homology domain (OHD). Additional protein- and membrane-interacting modules mediate the targeting of select OSBP/ORPs to membrane contact sites between organelles, thus positioning the OHD between opposing membranes for lipid transfer and metabolic regulation. This unique subcellular location, coupled with diverse ligand preferences and tissue distribution, has identified OSBP/ORPs as key arbiters of membrane composition and function. Here, we will review how molecular models of OSBP/ORP-mediated intracellular lipid transport and regulation at membrane contact sites relate to their emerging roles in cellular and organismal functions. 相似文献