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101.
Edery P Marcaillou C Sahbatou M Labalme A Chastang J Touraine R Tubacher E Senni F Bober MB Nampoothiri S Jouk PS Steichen E Berland S Toutain A Wise CA Sanlaville D Rousseau F Clerget-Darpoux F Leutenegger AL 《Science (New York, N.Y.)》2011,332(6026):240-243
The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for protein translation. We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no. 210710]. Expression of a subgroup of genes, possibly linked to the disease phenotype, and minor intron splicing were affected in cell lines derived from TALS patients. Our findings demonstrate a crucial role of the minor spliceosome component U4atac snRNA in early human development and postnatal survival. 相似文献
102.
Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity 总被引:2,自引:0,他引:2
Lamming DW Ye L Katajisto P Goncalves MD Saitoh M Stevens DM Davis JG Salmon AB Richardson A Ahima RS Guertin DA Sabatini DM Baur JA 《Science (New York, N.Y.)》2012,335(6076):1638-1643
Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis. Further, decreased mTORC1 signaling was sufficient to extend life span independently from changes in glucose homeostasis, as female mice heterozygous for both mTOR and mLST8 exhibited decreased mTORC1 activity and extended life span but had normal glucose tolerance and insulin sensitivity. Thus, mTORC2 disruption is an important mediator of the effects of rapamycin in vivo. 相似文献
103.
Côté AP Benin AI Ockwig NW O'Keeffe M Matzger AJ Yaghi OM 《Science (New York, N.Y.)》2005,310(5751):1166-1170
Covalent organic frameworks (COFs) have been designed and successfully synthesized by condensation reactions of phenyl diboronic acid {C6H4[B(OH)2]2} and hexahydroxytriphenylene [C18H6(OH)6]. Powder x-ray diffraction studies of the highly crystalline products (C3H2BO)6.(C9H12)1 (COF-1) and C9H4BO2 (COF-5) revealed expanded porous graphitic layers that are either staggered (COF-1, P6(3)/mmc) or eclipsed (COF-5, P6/mmm). Their crystal structures are entirely held by strong bonds between B, C, and O atoms to form rigid porous architectures with pore sizes ranging from 7 to 27 angstroms. COF-1 and COF-5 exhibit high thermal stability (to temperatures up to 500 degrees to 600 degrees C), permanent porosity, and high surface areas (711 and 1590 square meters per gram, respectively). 相似文献
104.
Seshadri R Adrian L Fouts DE Eisen JA Phillippy AM Methe BA Ward NL Nelson WC Deboy RT Khouri HM Kolonay JF Dodson RJ Daugherty SC Brinkac LM Sullivan SA Madupu R Nelson KE Kang KH Impraim M Tran K Robinson JM Forberger HA Fraser CM Zinder SH Heidelberg JF 《Science (New York, N.Y.)》2005,307(5706):105-108
105.
Sonnenberg GF Monticelli LA Alenghat T Fung TC Hutnick NA Kunisawa J Shibata N Grunberg S Sinha R Zahm AM Tardif MR Sathaliyawala T Kubota M Farber DL Collman RG Shaked A Fouser LA Weiner DB Tessier PA Friedman JR Kiyono H Bushman FD Chang KM Artis D 《Science (New York, N.Y.)》2012,336(6086):1321-1325
The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases. 相似文献
106.
Weller GR Kysela B Roy R Tonkin LM Scanlan E Della M Devine SK Day JP Wilkinson A d'Adda di Fagagna F Devine KM Bowater RP Jeggo PA Jackson SP Doherty AJ 《Science (New York, N.Y.)》2002,297(5587):1686-1689
In eukaryotic cells, double-strand breaks (DSBs) in DNA are generally repaired by the pathway of homologous recombination or by DNA nonhomologous end joining (NHEJ). Both pathways have been highly conserved throughout eukaryotic evolution, but no equivalent NHEJ system has been identified in prokaryotes. The NHEJ pathway requires a DNA end-binding component called Ku. We have identified bacterial Ku homologs and show that these proteins retain the biochemical characteristics of the eukaryotic Ku heterodimer. Furthermore, we show that bacterial Ku specifically recruits DNA ligase to DNA ends and stimulates DNA ligation. Loss of these proteins leads to hypersensitivity to ionizing radiation in Bacillus subtilis. These data provide evidence that many bacteria possess a DNA DSB repair apparatus that shares many features with the NHEJ system of eukarya and suggest that this DNA repair pathway arose before the prokaryotic and eukaryotic lineages diverged. 相似文献
107.
Periodic signaling controlled by an oscillatory circuit that includes protein kinases ERK2 and PKA 总被引:1,自引:0,他引:1
Maeda M Lu S Shaulsky G Miyazaki Y Kuwayama H Tanaka Y Kuspa A Loomis WF 《Science (New York, N.Y.)》2004,304(5672):875-878
Self-regulating systems often use robust oscillatory circuits. One such system controls the chemotactic signaling mechanism of Dictyostelium, where pulses of adenosine 3',5'-monophosphate (cAMP) are generated with a periodicity of 7 minutes. We have observed spontaneous oscillations in activation of the mitogen-activated protein (MAP) kinase ERK2 that occur in phase with peaks of cAMP, and we show that ERK2 modulates cAMP levels through the phosphodiesterase RegA. Computer modeling and simulations of the underlying circuit faithfully account for the ability of the cells to spontaneously generate periodic pulses during specific stages of development. Similar oscillatory processes may occur in cells of many different species. 相似文献
108.
Feinberg AW Feigel A Shevkoplyas SS Sheehy S Whitesides GM Parker KK 《Science (New York, N.Y.)》2007,317(5843):1366-1370
We demonstrate the assembly of biohybrid materials from engineered tissues and synthetic polymer thin films. The constructs were built by culturing neonatal rat ventricular cardiomyocytes on polydimethylsiloxane thin films micropatterned with extracellular matrix proteins to promote spatially ordered, two-dimensional myogenesis. The constructs, termed muscular thin films, adopted functional, three-dimensional conformations when released from a thermally sensitive polymer substrate and were designed to perform biomimetic tasks by varying tissue architecture, thin-film shape, and electrical-pacing protocol. These centimeter-scale constructs perform functions as diverse as gripping, pumping, walking, and swimming with fine spatial and temporal control and generating specific forces as high as 4 millinewtons per square millimeter. 相似文献
109.
Stevens J Corper AL Basler CF Taubenberger JK Palese P Wilson IA 《Science (New York, N.Y.)》2004,303(5665):1866-1870
The 1918 "Spanish" influenza pandemic represents the largest recorded outbreak of any infectious disease. The crystal structure of the uncleaved precursor of the major surface antigen of the extinct 1918 virus was determined at 3.0 angstrom resolution after reassembly of the hemagglutinin gene from viral RNA fragments preserved in 1918 formalin-fixed lung tissues. A narrow avian-like receptor-binding site, two previously unobserved histidine patches, and a less exposed surface loop at the cleavage site that activates viral membrane fusion reveal structural features primarily found in avian viruses, which may have contributed to the extraordinarily high infectivity and mortality rates observed during 1918. 相似文献
110.
Ramachandran GK Hopson TJ Rawlett AM Nagahara LA Primak A Lindsay SM 《Science (New York, N.Y.)》2003,300(5624):1413-1416
Stochastic on-off conductivity switching observed in phenylene-ethynylene oligomers has been explained in terms of changes in ring conformations, or electron localization, or both. We report the observation of stochastic on-off switching in the simplest of wired molecules: octanedithiol, decanedithiol, and dodecanedithiol bonded on an Au(111) surface. Stochastic switching was observed even when a top gold contact was pressed on by a conducting atomic force microscope tip at constant force. The rate of switching increased substantially at 60 degrees C, a temperature at which these films are commonly annealed. Because such switching in alkanethiols is unlikely to be caused by internal molecular electronic changes and cannot be fully accounted for by breaking of the top contact, we argue that the cause is the well-known mobility of molecules tethered to gold via a thiol linkage. 相似文献