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191.
Direct observations over the past four centuries show that the number of sunspots observed on the Sun's surface varies periodically, going through successive maxima and minima. Following sunspot cycle 23, the Sun went into a prolonged minimum characterized by a very weak polar magnetic field and an unusually large number of days without sunspots. Sunspots are strongly magnetized regions generated by a dynamo mechanism that recreates the solar polar field mediated through plasma flows. Here we report results from kinematic dynamo simulations which demonstrate that a fast meridional flow in the first half of a cycle, followed by a slower flow in the second half, reproduces both characteristics of the minimum of sunspot cycle 23. Our model predicts that, in general, very deep minima are associated with weak polar fields. Sunspots govern the solar radiative energy and radio flux, and, in conjunction with the polar field, modulate the solar wind, the heliospheric open flux and, consequently, the cosmic ray flux at Earth. 相似文献
192.
Structural insight into brassinosteroid perception by BRI1 总被引:1,自引:0,他引:1
She J Han Z Kim TW Wang J Cheng W Chang J Shi S Wang J Yang M Wang ZY Chai J 《Nature》2011,474(7352):472-476
Brassinosteroids are essential phytohormones that have crucial roles in plant growth and development. Perception of brassinosteroids requires an active complex of BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED KINASE 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, brassinosteroids induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1(LRR) in free and brassinolide-bound forms. BRI1(LRR) exists as a monomer in crystals and solution independent of brassinolide. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, brassinolide binds to a hydrophobicity-dominating surface groove on BRI1(LRR). Brassinolide recognition by BRI1(LRR) is through an induced-fit mechanism involving stabilization of two interdomain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes brassinosteroids and provide insight into brassinosteroid-induced BRI1 activation. 相似文献
193.
Haematopoietic stem cells (HSCs) are a self-renewing population of cells that continuously replenish all blood and immune cells during the lifetime of an individual. HSCs are used clinically to treat a wide array of diseases, including acute leukaemias and congenital blood disorders, but obtaining suitable numbers of cells and finding immune-compatible donors remain serious problems. These difficulties have led to an interest in the conversion of embryonic stem cells or induced pluripotent stem cells into HSCs, which is not possible using current methodologies. To accomplish this goal, it is critical to understand the native mechanisms involved in the specification of HSCs during embryonic development. Here we demonstrate in zebrafish that Wnt16 controls a novel genetic regulatory network required for HSC specification. Non-canonical signalling by Wnt16 is required for somitic expression of the Notch ligands deltaC (dlc) and deltaD (dld), and these ligands are, in turn, required for the establishment of definitive haematopoiesis. Notch signalling downstream of Dlc and Dld is earlier than, and distinct from, known cell-autonomous requirements for Notch, strongly suggesting that novel Notch-dependent relay signal(s) induce the first HSCs in parallel to other established pathways. Our results demonstrate that somite-specific gene expression is required for the production of haemogenic endothelium. 相似文献
194.
195.
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
196.
197.
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
198.
199.
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
200.
Programming the magnitude and persistence of antibody responses with innate immunity 总被引:1,自引:0,他引:1
Kasturi SP Skountzou I Albrecht RA Koutsonanos D Hua T Nakaya HI Ravindran R Stewart S Alam M Kwissa M Villinger F Murthy N Steel J Jacob J Hogan RJ García-Sastre A Compans R Pulendran B 《Nature》2011,470(7335):543-547
Many successful vaccines induce persistent antibody responses that can last a lifetime. The mechanisms by which they do so remain unclear, but emerging evidence indicates that they activate dendritic cells via Toll-like receptors (TLRs). For example, the yellow fever vaccine YF-17D, one of the most successful empiric vaccines ever developed, activates dendritic cells via multiple TLRs to stimulate proinflammatory cytokines. Triggering specific combinations of TLRs in dendritic cells can induce synergistic production of cytokines, which results in enhanced T-cell responses, but its impact on antibody responses remain unknown. Learning the critical parameters of innate immunity that program such antibody responses remains a major challenge in vaccinology. Here we demonstrate that immunization of mice with synthetic nanoparticles containing antigens plus ligands that signal through TLR4 and TLR7 induces synergistic increases in antigen-specific, neutralizing antibodies compared to immunization with nanoparticles containing antigens plus a single TLR ligand. Consistent with this there was enhanced persistence of germinal centres and of plasma-cell responses, which persisted in the lymph nodes for >1.5 years. Surprisingly, there was no enhancement of the early short-lived plasma-cell response relative to that observed with single TLR ligands. Molecular profiling of activated B cells, isolated 7 days after immunization, indicated that there was early programming towards B-cell memory. Antibody responses were dependent on direct triggering of both TLRs on B cells and dendritic cells, as well as on T-cell help. Immunization protected completely against lethal avian and swine influenza virus strains in mice, and induced robust immunity against pandemic H1N1 influenza in rhesus macaques. 相似文献