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A microRNA component of the p53 tumour suppressor network 总被引:5,自引:0,他引:5
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Lederman L 《Nature》2007,448(7151):310-312
The territory of the Large Hadron Collider might be populated not just by the Higgs particle but also by all manner of other exotic apparitions. 相似文献
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Epithelial-cell-intrinsic IKK-beta expression regulates intestinal immune homeostasis 总被引:1,自引:0,他引:1
Zaph C Troy AE Taylor BC Berman-Booty LD Guild KJ Du Y Yost EA Gruber AD May MJ Greten FR Eckmann L Karin M Artis D 《Nature》2007,446(7135):552-556
Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown. Here we show that IEC-intrinsic IkappaB kinase (IKK)-beta-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-beta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (T(H)2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-alpha, increased levels of CD4+ T-cell-derived interferon-gamma and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-beta in IECs to promote CD4+ T(H)2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation. 相似文献
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LI YingTao LONG ShiBing LIU Qi Lü HangBing LIU Su & LIU Ming * School of Physical Science Technology Lanzhou University Lanzhou China Laboratory of Nano-Fabrication Novel Device Integration Institute of Microelectronics Chinese Academy of Sciences Beijing 《科学通报(英文版)》2011,(Z2):3072-3078
With recent progress in material science, resistive random access memory (RRAM) devices have attracted interest for nonvolatile, low-power, nondestructive readout, and high-density memories. Relevant performance parameters of RRAM devices include operating voltage, operation speed, resistance ratio, endurance, retention time, device yield, and multilevel storage. Numerous resistive-switching mechanisms, such as conductive filament, space-charge-limited conduction, trap charging and discharging, Schottky Emission, and Pool-Frenkel emission, have been proposed to explain the resistive switching of RRAM devices. In addition to a discussion of these mechanisms, the effects of electrode materials, doped oxide materials, and different configuration devices on the resistive-switching characteristics in nonvolatile memory applications, are reviewed. Finally, suggestions for future research, as well as the challenges awaiting RRAM devices, are given. 相似文献
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MicroRNA-mediated conversion of human fibroblasts to neurons 总被引:2,自引:0,他引:2
Yoo AS Sun AX Li L Shcheglovitov A Portmann T Li Y Lee-Messer C Dolmetsch RE Tsien RW Crabtree GR 《Nature》2011,476(7359):228-231
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The ribosome translates the genetic information encoded in messenger RNA into protein. Folded structures in the coding region of an mRNA represent a kinetic barrier that lowers the peptide elongation rate, as the ribosome must disrupt structures it encounters in the mRNA at its entry site to allow translocation to the next codon. Such structures are exploited by the cell to create diverse strategies for translation regulation, such as programmed frameshifting, the modulation of protein expression levels, ribosome localization and co-translational protein folding. Although strand separation activity is inherent to the ribosome, requiring no exogenous helicases, its mechanism is still unknown. Here, using a single-molecule optical tweezers assay on mRNA hairpins, we find that the translation rate of identical codons at the decoding centre is greatly influenced by the GC content of folded structures at the mRNA entry site. Furthermore, force applied to the ends of the hairpin to favour its unfolding significantly speeds translation. Quantitative analysis of the force dependence of its helicase activity reveals that the ribosome, unlike previously studied helicases, uses two distinct active mechanisms to unwind mRNA structure: it destabilizes the helical junction at the mRNA entry site by biasing its thermal fluctuations towards the open state, increasing the probability of the ribosome translocating unhindered; and it mechanically pulls apart the mRNA single strands of the closed junction during the conformational changes that accompany ribosome translocation. The second of these mechanisms ensures a minimal basal rate of translation in the cell; specialized, mechanically stable structures are required to stall the ribosome temporarily. Our results establish a quantitative mechanical basis for understanding the mechanism of regulation of the elongation rate of translation by structured mRNAs. 相似文献