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901.
Riedel CG Katis VL Katou Y Mori S Itoh T Helmhart W Gálová M Petronczki M Gregan J Cetin B Mudrak I Ogris E Mechtler K Pelletier L Buchholz F Shirahige K Nasmyth K 《Nature》2006,441(7089):53-61
Segregation of homologous maternal and paternal centromeres to opposite poles during meiosis I depends on post-replicative crossing over between homologous non-sister chromatids, which creates chiasmata and therefore bivalent chromosomes. Destruction of sister chromatid cohesion along chromosome arms due to proteolytic cleavage of cohesin's Rec8 subunit by separase resolves chiasmata and thereby triggers the first meiotic division. This produces univalent chromosomes, the chromatids of which are held together by centromeric cohesin that has been protected from separase by shugoshin (Sgo1/MEI-S332) proteins. Here we show in both fission and budding yeast that Sgo1 recruits to centromeres a specific form of protein phosphatase 2A (PP2A). Its inactivation causes loss of centromeric cohesin at anaphase I and random segregation of sister centromeres at the second meiotic division. Artificial recruitment of PP2A to chromosome arms prevents Rec8 phosphorylation and hinders resolution of chiasmata. Our data are consistent with the notion that efficient cleavage of Rec8 requires phosphorylation of cohesin and that this is blocked by PP2A at meiosis I centromeres. 相似文献
902.
The magnetic field in the central few hundred parsecs of the Milky Way has a dipolar geometry and is substantially stronger than elsewhere in the Galaxy, with estimates ranging up to a milligauss (refs 1-6). Characterization of the magnetic field at the Galactic Centre is important because it can affect the orbits of molecular clouds by exerting a drag on them, inhibit star formation, and could guide a wind of hot gas or cosmic rays away from the central region. Here we report observations of an infrared nebula having the morphology of an intertwined double helix about 100 parsecs from the Galaxy's dynamical centre, with its axis oriented perpendicular to the Galactic plane. The observed segment is about 25 parsecs in length, and contains about 1.25 full turns of each of the two continuous, helically wound strands. We interpret this feature as a torsional Alfvén wave propagating vertically away from the Galactic disk, driven by rotation of the magnetized circumnuclear gas disk. The direct connection between the circumnuclear disk and the double helix is ambiguous, but the images show a possible meandering channel that warrants further investigation. 相似文献
903.
In the visual cortex of higher mammals, neurons are arranged across the cortical surface in an orderly map of preferred stimulus orientations. This map contains 'orientation pinwheels', structures that are arranged like the spokes of a wheel such that orientation changes continuously around a centre. Conventional optical imaging first demonstrated these pinwheels, but the technique lacked the spatial resolution to determine the response properties and arrangement of cells near pinwheel centres. Electrophysiological recordings later demonstrated sharply selective neurons near pinwheel centres, but it remained unclear whether they were arranged randomly or in an orderly fashion. Here we use two-photon calcium imaging in vivo to determine the microstructure of pinwheel centres in cat visual cortex with single-cell resolution. We find that pinwheel centres are highly ordered: neurons selective to different orientations are clearly segregated even in the very centre. Thus, pinwheel centres truly represent singularities in the cortical map. This highly ordered arrangement at the level of single cells suggests great precision in the development of cortical circuits underlying orientation selectivity. 相似文献
904.
Kleinman ME Yamada K Takeda A Chandrasekaran V Nozaki M Baffi JZ Albuquerque RJ Yamasaki S Itaya M Pan Y Appukuttan B Gibbs D Yang Z Karikó K Ambati BK Wilgus TA DiPietro LA Sakurai E Zhang K Smith JR Taylor EW Ambati J 《Nature》2008,452(7187):591-597
Clinical trials of small interfering RNA (siRNA) targeting vascular endothelial growth factor-A (VEGFA) or its receptor VEGFR1 (also called FLT1), in patients with blinding choroidal neovascularization (CNV) from age-related macular degeneration, are premised on gene silencing by means of intracellular RNA interference (RNAi). We show instead that CNV inhibition is a siRNA-class effect: 21-nucleotide or longer siRNAs targeting non-mammalian genes, non-expressed genes, non-genomic sequences, pro- and anti-angiogenic genes, and RNAi-incompetent siRNAs all suppressed CNV in mice comparably to siRNAs targeting Vegfa or Vegfr1 without off-target RNAi or interferon-alpha/beta activation. Non-targeted (against non-mammalian genes) and targeted (against Vegfa or Vegfr1) siRNA suppressed CNV via cell-surface toll-like receptor 3 (TLR3), its adaptor TRIF, and induction of interferon-gamma and interleukin-12. Non-targeted siRNA suppressed dermal neovascularization in mice as effectively as Vegfa siRNA. siRNA-induced inhibition of neovascularization required a minimum length of 21 nucleotides, a bridging necessity in a modelled 2:1 TLR3-RNA complex. Choroidal endothelial cells from people expressing the TLR3 coding variant 412FF were refractory to extracellular siRNA-induced cytotoxicity, facilitating individualized pharmacogenetic therapy. Multiple human endothelial cell types expressed surface TLR3, indicating that generic siRNAs might treat angiogenic disorders that affect 8% of the world's population, and that siRNAs might induce unanticipated vascular or immune effects. 相似文献
905.
Images returned by the spacecraft Clementine have been used to produce a quantitative illumination map of the north pole of the Moon, revealing the percentage of time that points on the surface are illuminated during the lunar day. We have used this map to identify areas that are constantly illuminated during a lunar day in summer and which may therefore be in permanent sunlight. All are located on the northern rim of Peary crater, close to the north pole. Permanently sunlit areas represent prime locations for lunar outpost sites as they have abundant solar energy, are relatively benign thermally (when compared with equatorial regions), and are close to permanently shadowed regions that may contain water ice. 相似文献