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951.
MJ Claesson IB Jeffery S Conde SE Power EM O'Connor S Cusack HM Harris M Coakley B Lakshminarayanan O O'Sullivan GF Fitzgerald J Deane M O'Connor N Harnedy K O'Connor D O'Mahony D van Sinderen M Wallace L Brennan C Stanton JR Marchesi AP Fitzgerald F Shanahan C Hill RP Ross PW O'Toole 《Nature》2012,488(7410):178-184
Alterations in intestinal microbiota composition are associated with several chronic conditions, including obesity and inflammatory diseases. The microbiota of older people displays greater inter-individual variation than that of younger adults. Here we show that the faecal microbiota composition from 178 elderly subjects formed groups, correlating with residence location in the community, day-hospital, rehabilitation or in long-term residential care. However, clustering of subjects by diet separated them by the same residence location and microbiota groupings. The separation of microbiota composition significantly correlated with measures of frailty, co-morbidity, nutritional status, markers of inflammation and with metabolites in faecal water. The individual microbiota of people in long-stay care was significantly less diverse than that of community dwellers. Loss of community-associated microbiota correlated with increased frailty. Collectively, the data support a relationship between diet, microbiota and health status, and indicate a role for diet-driven microbiota alterations in varying rates of health decline upon ageing. 相似文献
952.
A mutation in APP protects against Alzheimer's disease and age-related cognitive decline 总被引:1,自引:0,他引:1
T Jonsson JK Atwal S Steinberg J Snaedal PV Jonsson S Bjornsson H Stefansson P Sulem D Gudbjartsson J Maloney K Hoyte A Gustafson Y Liu Y Lu T Bhangale RR Graham J Huttenlocher G Bjornsdottir OA Andreassen EG Jönsson A Palotie TW Behrens OT Magnusson A Kong U Thorsteinsdottir RJ Watts K Stefansson 《Nature》2012,488(7409):96-99
The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms. 相似文献
953.
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955.
The dynamics of a single impurity in an environment is a fundamental problem in many-body physics. In the solid state, a well known case is an impurity coupled to a bosonic bath (such as lattice vibrations); the impurity and its accompanying lattice distortion form a new entity, a polaron. This quasiparticle plays an important role in the spectral function of high-transition-temperature superconductors, as well as in colossal magnetoresistance in manganites. For impurities in a fermionic bath, studies have considered heavy or immobile impurities which exhibit Anderson's orthogonality catastrophe and the Kondo effect. More recently, mobile impurities have moved into the focus of research, and they have been found to form new quasiparticles known as Fermi polarons. The Fermi polaron problem constitutes the extreme, but conceptually simple, limit of two important quantum many-body problems: the crossover between a molecular Bose-Einstein condensate and a superfluid with BCS (Bardeen-Cooper-Schrieffer) pairing with spin-imbalance for attractive interactions, and Stoner's itinerant ferromagnetism for repulsive interactions. It has been proposed that such quantum phases (and other elusive exotic states) might become realizable in Fermi gases confined to two dimensions. Their stability and observability are intimately related to the theoretically debated properties of the Fermi polaron in a two-dimensional Fermi gas. Here we create and investigate Fermi polarons in a two-dimensional, spin-imbalanced Fermi gas, measuring their spectral function using momentum-resolved photoemission spectroscopy. For attractive interactions, we find evidence for a disputed pairing transition between polarons and tightly bound dimers, which provides insight into the elementary pairing mechanism of imbalanced, strongly coupled two-dimensional Fermi gases. Additionally, for repulsive interactions, we study novel quasiparticles--repulsive polarons--the lifetime of which determines the possibility of stabilizing repulsively interacting Fermi systems. 相似文献
956.
A. Ramírez-López R. Aguilar-López M. Palomar-Pardavé M. A. Romero-Romo D. Mu?oz-Negrón 《矿物冶金与材料学报》2010,17(4):403-416
This work is focused on the development of computational algorithms to create a simulator for solving the heat transfer during the continuous casting process of steel. The temperatures and the solid shell thickness profiles were calculated and displayed on the screen for a billet through a defined continuous casting plant (CCP). The algorithms developed to calculate billet temperatures, involve the solutions of the corresponding equations for the heat removal conditions such as radiation, forced convection, and conduction according to the billet position through the CCP. This is done by a simultaneous comparison with the kinematics model previously developed. A finite difference method known as Crank-Nicholson is applied to solve the two-dimensional computational array (2D model). Enthalpy (HI,J) and temperature (TI,J) in every node are updated at each step time. The routines to display the results have been developed using a graphical user interface (GUI) in the programming language C++. Finally, the results obtained are compared with those of industrial trials for the surface temperature of three steel casters with different plant configurations in different casting conditions. 相似文献
957.
独立分量分析(ICA)可用于分离多通道脑磁图信号(MEG)中的信号源。基于约束ICA的思想,通过在ICA模型中加入能够反映事件相关皮层神经活动特征的功能约束条件,实现了一种脑磁逆问题的解决方法,即功能源提取(FSS)方法。文中利用该方法对一例手指按键诱发MEG信号进行功能源提取,结果表明功能源位置位于对侧中央前回皮质运动区,且通过验证功能源提取所得到的分离向量与SAM法计算得到的空间滤波器系数间的相关性,验证了所提取的功能源有效。同时,功能源提取方法所提供的神经活动源的时域与频域信息,为在大量样本中探索大脑对手指运动控制的时间演化机制奠定了基础。 相似文献
958.
Ratje AH Loerke J Mikolajka A Brünner M Hildebrand PW Starosta AL Dönhöfer A Connell SR Fucini P Mielke T Whitford PC Onuchic JN Yu Y Sanbonmatsu KY Hartmann RK Penczek PA Wilson DN Spahn CM 《Nature》2010,468(7324):713-716
The elongation cycle of protein synthesis involves the delivery of aminoacyl-transfer RNAs to the aminoacyl-tRNA-binding site (A?site) of the ribosome, followed by peptide-bond formation and translocation of the tRNAs through the ribosome to reopen the A?site. The translocation reaction is catalysed by elongation factor G (EF-G) in a GTP-dependent manner. Despite the availability of structures of various EF-G-ribosome complexes, the precise mechanism by which tRNAs move through the ribosome still remains unclear. Here we use multiparticle cryoelectron microscopy analysis to resolve two previously unseen subpopulations within Thermus thermophilus EF-G-ribosome complexes at subnanometre resolution, one of them with a partly translocated tRNA. Comparison of these substates reveals that translocation of tRNA on the 30S subunit parallels the swivelling of the 30S head and is coupled to unratcheting of the 30S body. Because the tRNA maintains contact with the peptidyl-tRNA-binding site (P?site) on the 30S head and simultaneously establishes interaction with the exit site (E?site) on the 30S platform, a novel intra-subunit 'pe/E' hybrid state is formed. This state is stabilized by domain?IV of EF-G, which interacts with the swivelled 30S-head conformation. These findings provide direct structural and mechanistic insight into the 'missing link' in terms of tRNA intermediates involved in the universally conserved translocation process. 相似文献
959.
Garneau JE Dupuis MÈ Villion M Romero DA Barrangou R Boyaval P Fremaux C Horvath P Magadán AH Moineau S 《Nature》2010,468(7320):67-71
Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains. 相似文献
960.
Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment 总被引:2,自引:0,他引:2
Scherber C Eisenhauer N Weisser WW Schmid B Voigt W Fischer M Schulze ED Roscher C Weigelt A Allan E Bessler H Bonkowski M Buchmann N Buscot F Clement LW Ebeling A Engels C Halle S Kertscher I Klein AM Koller R König S Kowalski E Kummer V Kuu A Lange M Lauterbach D Middelhoff C Migunova VD Milcu A Müller R Partsch S Petermann JS Renker C Rottstock T Sabais A Scheu S Schumacher J Temperton VM Tscharntke T 《Nature》2010,468(7323):553-556
Biodiversity is rapidly declining, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades. 相似文献