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201.
Recent theoretical studies of selection in finite structured populations have worked with one of two measures of selective advantage of an allele: fixation probability and inclusive fitness. Each approach has its own analytical strengths, but given certain assumptions they provide equivalent results. In most instances the structure of the population can be specified by a network of nodes connected by edges (that is, a graph), and much of the work here has focused on a continuous-time model of evolution, first described by ref. 11. Working in this context, we provide an inclusive fitness analysis to derive a surprisingly simple analytical condition for the selective advantage of a cooperative allele in any graph for which the structure satisfies a general symmetry condition ('bi-transitivity'). Our results hold for a broad class of population structures, including most of those analysed previously, as well as some for which a direct calculation of fixation probability has appeared intractable. Notably, under some forms of population regulation, the ability of a cooperative allele to invade is seen to be independent of the nature of population structure (and in particular of how game partnerships are specified) and is identical to that for an unstructured population. For other types of population regulation our results reveal that cooperation can invade if players choose partners along relatively 'high-weight' edges. 相似文献
202.
Among the many surprises to arise from studies of prion biology, perhaps the most unexpected is the strain phenomenon whereby a single protein can misfold into structurally distinct, infectious states that cause distinguishable phenotypes. Similarly, proteins can adopt a spectrum of conformations in non-infectious diseases of protein folding; some are toxic and others are well tolerated. However, our understanding of the structural differences underlying prion strains and how these differences alter their physiological impact remains limited. Here we use a combination of solution NMR, amide hydrogen/deuterium (H/D) exchange and mutagenesis to study the structural differences between two strain conformations, termed Sc4 and Sc37 (ref. 5), of the yeast Sup35 prion. We find that these two strains have an overlapping amyloid core spanning most of the Gln/Asn-rich first 40 amino acids that is highly protected from H/D exchange and very sensitive to mutation. These features indicate that the cores are composed of tightly packed beta-sheets possibly resembling 'steric zipper' structures revealed by X-ray crystallography of Sup35-derived peptides. The stable structure is greatly expanded in the Sc37 conformation to encompass the first 70 amino acids, revealing why this strain shows increased fibre stability and decreased ability to undergo chaperone-mediated replication. Our findings establish that prion strains involve large-scale conformational differences and provide a structural basis for understanding a broad range of functional studies, including how conformational changes alter the physiological impact of prion strains. 相似文献
203.
Chan CS Guzman JN Ilijic E Mercer JN Rick C Tkatch T Meredith GE Surmeier DJ 《Nature》2007,447(7148):1081-1086
Why dopamine-containing neurons of the brain's substantia nigra pars compacta die in Parkinson's disease has been an enduring mystery. Our studies suggest that the unusual reliance of these neurons on L-type Ca(v)1.3 Ca2+ channels to drive their maintained, rhythmic pacemaking renders them vulnerable to stressors thought to contribute to disease progression. The reliance on these channels increases with age, as juvenile dopamine-containing neurons in the substantia nigra pars compacta use pacemaking mechanisms common to neurons not affected in Parkinson's disease. These mechanisms remain latent in adulthood, and blocking Ca(v)1.3 Ca2+ channels in adult neurons induces a reversion to the juvenile form of pacemaking. Such blocking ('rejuvenation') protects these neurons in both in vitro and in vivo models of Parkinson's disease, pointing to a new strategy that could slow or stop the progression of the disease. 相似文献
204.
Although Earth's continental crust is thought to have been derived from the mantle, the timing and mode of crust formation have proven to be elusive issues. The area of preserved crust diminishes markedly with age, and this can be interpreted as being the result of either the progressive accumulation of new crust or the tectonic recycling of old crust. However, there is a disproportionate amount of crust of certain ages, with the main peaks being 1.2, 1.9, 2.7 and 3.3 billion years old; this has led to a third model in which the crust has grown through time in pulses, although peaks in continental crust ages could also record preferential preservation. The 187Re-187Os decay system is unique in its ability to track melt depletion events within the mantle and could therefore potentially link the crust and mantle differentiation records. Here we employ a laser ablation technique to analyse large numbers of osmium alloy grains to quantify the distribution of depletion ages in the Earth's upper mantle. Statistical analysis of these data, combined with other samples of the upper mantle, show that depletion ages are not evenly distributed but cluster in distinct periods, around 1.2, 1.9 and 2.7 billion years. These mantle depletion events coincide with peaks in the generation of continental crust and so provide evidence of coupled, global and pulsed mantle-crust differentiation, lending strong support to pulsed models of continental growth by means of large-scale mantle melting events. 相似文献
205.
Mackereth CD Madl T Bonnal S Simon B Zanier K Gasch A Rybin V Valcárcel J Sattler M 《Nature》2011,475(7356):408-411
Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins. 相似文献
206.
Young DA Wright AP Roberts JL Warner RC Young NW Greenbaum JS Schroeder DM Holt JW Sugden DE Blankenship DD van Ommen TD Siegert MJ 《Nature》2011,474(7349):72-75
The first Cenozoic ice sheets initiated in Antarctica from the Gamburtsev Subglacial Mountains and other highlands as a result of rapid global cooling ~34 million years ago. In the subsequent 20 million years, at a time of declining atmospheric carbon dioxide concentrations and an evolving Antarctic circumpolar current, sedimentary sequence interpretation and numerical modelling suggest that cyclical periods of ice-sheet expansion to the continental margin, followed by retreat to the subglacial highlands, occurred up to thirty times. These fluctuations were paced by orbital changes and were a major influence on global sea levels. Ice-sheet models show that the nature of such oscillations is critically dependent on the pattern and extent of Antarctic topographic lowlands. Here we show that the basal topography of the Aurora Subglacial Basin of East Antarctica, at present overlain by 2-4.5?km of ice, is characterized by a series of well-defined topographic channels within a mountain block landscape. The identification of this fjord landscape, based on new data from ice-penetrating radar, provides an improved understanding of the topography of the Aurora Subglacial Basin and its surroundings, and reveals a complex surface sculpted by a succession of ice-sheet configurations substantially different from today's. At different stages during its fluctuations, the edge of the East Antarctic Ice Sheet lay pinned along the margins of the Aurora Subglacial Basin, the upland boundaries of which are currently above sea level and the deepest parts of which are more than 1?km below sea level. Although the timing of the channel incision remains uncertain, our results suggest that the fjord landscape was carved by at least two iceflow regimes of different scales and directions, each of which would have over-deepened existing topographic depressions, reversing valley floor slopes. 相似文献
207.
Lee X Goulden ML Hollinger DY Barr A Black TA Bohrer G Bracho R Drake B Goldstein A Gu L Katul G Kolb T Law BE Margolis H Meyers T Monson R Munger W Oren R Paw U KT Richardson AD Schmid HP Staebler R Wofsy S Zhao L 《Nature》2011,479(7373):384-387
Deforestation in mid- to high latitudes is hypothesized to have the potential to cool the Earth's surface by altering biophysical processes. In climate models of continental-scale land clearing, the cooling is triggered by increases in surface albedo and is reinforced by a land albedo-sea ice feedback. This feedback is crucial in the model predictions; without it other biophysical processes may overwhelm the albedo effect to generate warming instead. Ongoing land-use activities, such as land management for climate mitigation, are occurring at local scales (hectares) presumably too small to generate the feedback, and it is not known whether the intrinsic biophysical mechanism on its own can change the surface temperature in a consistent manner. Nor has the effect of deforestation on climate been demonstrated over large areas from direct observations. Here we show that surface air temperature is lower in open land than in nearby forested land. The effect is 0.85 ± 0.44 K (mean ± one standard deviation) northwards of 45° N and 0.21 ± 0.53 K southwards. Below 35° N there is weak evidence that deforestation leads to warming. Results are based on comparisons of temperature at forested eddy covariance towers in the USA and Canada and, as a proxy for small areas of cleared land, nearby surface weather stations. Night-time temperature changes unrelated to changes in surface albedo are an important contributor to the overall cooling effect. The observed latitudinal dependence is consistent with theoretical expectation of changes in energy loss from convection and radiation across latitudes in both the daytime and night-time phase of the diurnal cycle, the latter of which remains uncertain in climate models. 相似文献
208.
International Consortium for Blood Pressure Genome-Wide Association Studies Ehret GB Munroe PB Rice KM Bochud M Johnson AD Chasman DI Smith AV Tobin MD Verwoert GC Hwang SJ Pihur V Vollenweider P O'Reilly PF Amin N Bragg-Gresham JL Teumer A Glazer NL Launer L Zhao JH Aulchenko Y Heath S Sõber S Parsa A Luan J Arora P Dehghan A Zhang F Lucas G Hicks AA Jackson AU Peden JF Tanaka T Wild SH Rudan I Igl W Milaneschi Y Parker AN Fava C Chambers JC Fox ER Kumari M Go MJ van der Harst P Kao WH 《Nature》2011,478(7367):103-109
Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. 相似文献
209.
Cederwall B Moradi FG Bäck T Johnson A Blomqvist J Clément E de France G Wadsworth R Andgren K Lagergren K Dijon A Jaworski G Liotta R Qi C Nyakó BM Nyberg J Palacz M Al-Azri H Algora A de Angelis G Ataç A Bhattacharyya S Brock T Brown JR Davies P Di Nitto A Dombrádi Z Gadea A Gál J Hadinia B Johnston-Theasby F Joshi P Juhász K Julin R Jungclaus A Kalinka G Kara SO Khaplanov A Kownacki J La Rana G Lenzi SM Molnár J Moro R Napoli DR Singh BS Persson A Recchia F Sandzelius M Scheurer JN Sletten G 《Nature》2011,469(7328):68-71
Shell structure and magic numbers in atomic nuclei were generally explained by pioneering work that introduced a strong spin-orbit interaction to the nuclear shell model potential. However, knowledge of nuclear forces and the mechanisms governing the structure of nuclei, in particular far from stability, is still incomplete. In nuclei with equal neutron and proton numbers (N = Z), enhanced correlations arise between neutrons and protons (two distinct types of fermions) that occupy orbitals with the same quantum numbers. Such correlations have been predicted to favour an unusual type of nuclear superfluidity, termed isoscalar neutron-proton pairing, in addition to normal isovector pairing. Despite many experimental efforts, these predictions have not been confirmed. Here we report the experimental observation of excited states in the N = Z = 46 nucleus (92)Pd. Gamma rays emitted following the (58)Ni((36)Ar,2n)(92)Pd fusion-evaporation reaction were identified using a combination of state-of-the-art high-resolution γ-ray, charged-particle and neutron detector systems. Our results reveal evidence for a spin-aligned, isoscalar neutron-proton coupling scheme, different from the previous prediction. We suggest that this coupling scheme replaces normal superfluidity (characterized by seniority coupling) in the ground and low-lying excited states of the heaviest N = Z nuclei. Such strong, isoscalar neutron-proton correlations would have a considerable impact on the nuclear level structure and possibly influence the dynamics of rapid proton capture in stellar nucleosynthesis. 相似文献
210.
Ospelkaus C Warring U Colombe Y Brown KR Amini JM Leibfried D Wineland DJ 《Nature》2011,476(7359):181-184
Control over physical systems at the quantum level is important in fields as diverse as metrology, information processing, simulation and chemistry. For trapped atomic ions, the quantized motional and internal degrees of freedom can be coherently manipulated with laser light. Similar control is difficult to achieve with radio-frequency or microwave radiation: the essential coupling between internal degrees of freedom and motion requires significant field changes over the extent of the atoms' motion, but such changes are negligible at these frequencies for freely propagating fields. An exception is in the near field of microwave currents in structures smaller than the free-space wavelength, where stronger gradients can be generated. Here we first manipulate coherently (on timescales of 20 nanoseconds) the internal quantum states of ions held in a microfabricated trap. The controlling magnetic fields are generated by microwave currents in electrodes that are integrated into the trap structure. We also generate entanglement between the internal degrees of freedom of two atoms with a gate operation suitable for general quantum computation; the entangled state has a fidelity of 0.76(3), where the uncertainty denotes standard error of the mean. Our approach, which involves integrating the quantum control mechanism into the trapping device in a scalable manner, could be applied to quantum information processing, simulation and spectroscopy. 相似文献