排序方式: 共有151条查询结果,搜索用时 15 毫秒
81.
Logan CV Lucke B Pottinger C Abdelhamed ZA Parry DA Szymanska K Diggle CP van Riesen A Morgan JE Markham G Ellis I Manzur AY Markham AF Shires M Helliwell T Scoto M Hübner C Bonthron DT Taylor GR Sheridan E Muntoni F Carr IM Schuelke M Johnson CA 《Nature genetics》2011,43(12):1189-1192
Infantile myopathies with diaphragmatic paralysis are genetically heterogeneous, and clinical symptoms do not assist in differentiating between them. We used phased haplotype analysis with subsequent targeted exome sequencing to identify MEGF10 mutations in a previously unidentified type of infantile myopathy with diaphragmatic weakness, areflexia, respiratory distress and dysphagia. MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia. 相似文献
82.
Challen GA Sun D Jeong M Luo M Jelinek J Berg JS Bock C Vasanthakumar A Gu H Xi Y Liang S Lu Y Darlington GJ Meissner A Issa JP Godley LA Li W Goodell MA 《Nature genetics》2012,44(1):23-31
Loss of the de novo DNA methyltransferases Dnmt3a and Dnmt3b in embryonic stem cells obstructs differentiation; however, the role of these enzymes in somatic stem cells is largely unknown. Using conditional ablation, we show that Dnmt3a loss progressively impairs hematopoietic stem cell (HSC) differentiation over serial transplantation, while simultaneously expanding HSC numbers in the bone marrow. Dnmt3a-null HSCs show both increased and decreased methylation at distinct loci, including substantial CpG island hypermethylation. Dnmt3a-null HSCs upregulate HSC multipotency genes and downregulate differentiation factors, and their progeny exhibit global hypomethylation and incomplete repression of HSC-specific genes. These data establish Dnmt3a as a critical participant in the epigenetic silencing of HSC regulatory genes, thereby enabling efficient differentiation. 相似文献
83.
KU Ludwig E Mangold S Herms S Nowak H Reutter A Paul J Becker R Herberz T Alchawa E Nasser AC Böhmer M Mattheisen MA Alblas S Barth N Kluck C Lauster B Braumann RH Reich A Hemprich S Pötzsch B Blaumeiser N Daratsianos T Kreusch JC Murray ML Marazita I Ruczinski AF Scott TH Beaty FJ Kramer TF Wienker RP Steegers-Theunissen M Rubini PA Mossey P Hoffmann C Lange S Cichon P Propping M Knapp MM Nöthen 《Nature genetics》2012,44(9):968-971
We have conducted the first meta-analyses for nonsyndromic cleft lip with or without cleft palate (NSCL/P) using data from the two largest genome-wide association studies published to date. We confirmed associations with all previously identified loci and identified six additional susceptibility regions (1p36, 2p21, 3p11.1, 8q21.3, 13q31.1 and 15q22). Analysis of phenotypic variability identified the first specific genetic risk factor for NSCLP (nonsyndromic cleft lip plus palate) (rs8001641; P(NSCLP) = 6.51 × 10(-11); homozygote relative risk = 2.41, 95% confidence interval (CI) 1.84-3.16). 相似文献
84.
Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus 总被引:1,自引:0,他引:1
Neural stem cells in various regions of the vertebrate brain continuously generate neurons throughout life. In the mammalian hippocampus, a region important for spatial and episodic memory, thousands of new granule cells are produced per day, with the exact number depending on environmental conditions and physical exercise. The survival of these neurons is improved by learning and conversely learning may be promoted by neurogenesis. Although it has been suggested that newly generated neurons may have specific properties to facilitate learning, the cellular and synaptic mechanisms of plasticity in these neurons are largely unknown. Here we show that young granule cells in the adult hippocampus differ substantially from mature granule cells in both active and passive membrane properties. In young neurons, T-type Ca2+ channels can generate isolated Ca2+ spikes and boost fast Na+ action potentials, contributing to the induction of synaptic plasticity. Associative long-term potentiation can be induced more easily in young neurons than in mature neurons under identical conditions. Thus, newly generated neurons express unique mechanisms to facilitate synaptic plasticity, which may be important for the formation of new memories. 相似文献
85.
Seibert MM Ekeberg T Maia FR Svenda M Andreasson J Jönsson O Odić D Iwan B Rocker A Westphal D Hantke M DePonte DP Barty A Schulz J Gumprecht L Coppola N Aquila A Liang M White TA Martin A Caleman C Stern S Abergel C Seltzer V Claverie JM Bostedt C Bozek JD Boutet S Miahnahri AA Messerschmidt M Krzywinski J Williams G Hodgson KO Bogan MJ Hampton CY Sierra RG Starodub D Andersson I Bajt S Barthelmess M Spence JC Fromme P Weierstall U Kirian R Hunter M Doak RB Marchesini S Hau-Riege SP Frank M 《Nature》2011,470(7332):78-81
X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000?K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies. 相似文献
86.
Wnt and Hedgehog family proteins are secreted signalling molecules (morphogens) that act at both long and short range to control growth and patterning during development. Both proteins are covalently modified by lipid, and the mechanism by which such hydrophobic molecules might spread over long distances is unknown. Here we show that Wingless, Hedgehog and glycophosphatidylinositol-linked proteins copurify with lipoprotein particles, and co-localize with them in the developing wing epithelium of Drosophila. In larvae with reduced lipoprotein levels, Hedgehog accumulates near its site of production, and fails to signal over its normal range. Similarly, the range of Wingless signalling is narrowed. We propose a novel function for lipoprotein particles, in which they act as vehicles for the movement of lipid-linked morphogens and glycophosphatidylinositol-linked proteins. 相似文献
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88.
A fundamental aspect of all biological systems is cooperation. Cooperative interactions are required for many levels of biological organization ranging from single cells to groups of animals. Human society is based to a large extent on mechanisms that promote cooperation. It is well known that in unstructured populations, natural selection favours defectors over cooperators. There is much current interest, however, in studying evolutionary games in structured populations and on graphs. These efforts recognize the fact that who-meets-whom is not random, but determined by spatial relationships or social networks. Here we describe a surprisingly simple rule that is a good approximation for all graphs that we have analysed, including cycles, spatial lattices, random regular graphs, random graphs and scale-free networks: natural selection favours cooperation, if the benefit of the altruistic act, b, divided by the cost, c, exceeds the average number of neighbours, k, which means b/c > k. In this case, cooperation can evolve as a consequence of 'social viscosity' even in the absence of reputation effects or strategic complexity. 相似文献
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90.
Realization of the Cirac-Zoller controlled-NOT quantum gate 总被引:4,自引:0,他引:4
Schmidt-Kaler F Häffner H Riebe M Gulde S Lancaster GP Deuschle T Becher C Roos CF Eschner J Blatt R 《Nature》2003,422(6930):408-411
Quantum computers have the potential to perform certain computational tasks more efficiently than their classical counterparts. The Cirac-Zoller proposal for a scalable quantum computer is based on a string of trapped ions whose electronic states represent the quantum bits of information (or qubits). In this scheme, quantum logical gates involving any subset of ions are realized by coupling the ions through their collective quantized motion. The main experimental step towards realizing the scheme is to implement the controlled-NOT (CNOT) gate operation between two individual ions. The CNOT quantum logical gate corresponds to the XOR gate operation of classical logic that flips the state of a target bit conditioned on the state of a control bit. Here we implement a CNOT quantum gate according to the Cirac-Zoller proposal. In our experiment, two 40Ca+ ions are held in a linear Paul trap and are individually addressed using focused laser beams; the qubits are represented by superpositions of two long-lived electronic states. Our work relies on recently developed precise control of atomic phases and the application of composite pulse sequences adapted from nuclear magnetic resonance techniques. 相似文献