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排序方式: 共有166条查询结果,搜索用时 31 毫秒
81.
Early consolidation in human primary motor cortex. 总被引:26,自引:0,他引:26
Wolf Muellbacher Ulf Ziemann Joerg Wissel Nguyet Dang Markus Kofler Stefano Facchini Babak Boroojerdi Werner Poewe Mark Hallett 《Nature》2002,415(6872):640-644
Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation. 相似文献
82.
Walker LM Huber M Doores KJ Falkowska E Pejchal R Julien JP Wang SK Ramos A Chan-Hui PY Moyle M Mitcham JL Hammond PW Olsen OA Phung P Fling S Wong CH Phogat S Wrin T Simek MD;Protocol G Principal Investigators Koff WC Wilson IA Burton DR Poignard P 《Nature》2011,477(7365):466-470
Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine. 相似文献
83.
Yoshida K Sanada M Shiraishi Y Nowak D Nagata Y Yamamoto R Sato Y Sato-Otsubo A Kon A Nagasaki M Chalkidis G Suzuki Y Shiosaka M Kawahata R Yamaguchi T Otsu M Obara N Sakata-Yanagimoto M Ishiyama K Mori H Nolte F Hofmann WK Miyawaki S Sugano S Haferlach C Koeffler HP Shih LY Haferlach T Chiba S Nakauchi H Miyano S Ogawa S 《Nature》2011,478(7367):64-69
Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent (~45 to ~85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3'-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia. 相似文献
84.
MicroRNAs can generate thresholds in target gene expression 总被引:2,自引:0,他引:2
Mukherji S Ebert MS Zheng GX Tsang JS Sharp PA van Oudenaarden A 《Nature genetics》2011,43(9):854-859
MicroRNAs (miRNAs) are short, highly conserved noncoding RNA molecules that repress gene expression in a sequence-dependent manner. We performed single-cell measurements using quantitative fluorescence microscopy and flow cytometry to monitor a target gene's protein expression in the presence and absence of regulation by miRNA. We find that although the average level of repression is modest, in agreement with previous population-based measurements, the repression among individual cells varies dramatically. In particular, we show that regulation by miRNAs establishes a threshold level of target mRNA below which protein production is highly repressed. Near this threshold, protein expression responds sensitively to target mRNA input, consistent with a mathematical model of molecular titration. These results show that miRNAs can act both as a switch and as a fine-tuner of gene expression. 相似文献
85.
86.
Werner Schuhmann 《Systemic Practice and Action Research》1990,3(3):265-287
This paper describes a framework for information systems development, based on the Viable System Model, currently used within the Film Division of Hoechst AG. 相似文献
87.
88.
89.
G. de Stevens L. H. Werner W. E. Barrett J. J. Chart A. H. Renzi 《Cellular and molecular life sciences : CMLS》1960,16(3):113-114
Zusammenfassung In der Reihe der Dihydro-benzothiadiazine wurde mit Hydrotrichlorthiazid (III) ein neues, ausserordentlich stark wirksames Diuretikum gefunden. Herstellung und pharmakologische Evaluation werden kurz beschrieben. Im Vergleich zu Hydrochlorthiazid (I) ist III beim Hundper os bis zu 20mal stärker diuretisch wirksam. 相似文献
90.
Transport and membrane integration of polypeptides is carried out by specific protein complexes in the membranes of all living cells. The Sec transport path provides an essential and ubiquitous route for protein translocation. In the bacterial cytoplasmic membrane, the channel is formed by oligomers of a heterotrimeric membrane protein complex consisting of subunits SecY, SecE and SecG. In the endoplasmic reticulum membrane, the channel is formed from the related Sec61 complex. Here we report the structure of the Escherichia coli SecYEG assembly at an in-plane resolution of 8 A. The three-dimensional map, calculated from two-dimensional SecYEG crystals, reveals a sandwich of two membranes interacting through the extensive cytoplasmic domains. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices. In the centre of the dimer we observe a 16 x 25 A cavity closed on the periplasmic side by two highly tilted transmembrane helices. This may represent the closed state of the protein-conducting channel. 相似文献