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Kharchenko PV Alekseyenko AA Schwartz YB Minoda A Riddle NC Ernst J Sabo PJ Larschan E Gorchakov AA Gu T Linder-Basso D Plachetka A Shanower G Tolstorukov MY Luquette LJ Xi R Jung YL Park RW Bishop EP Canfield TK Sandstrom R Thurman RE MacAlpine DM Stamatoyannopoulos JA Kellis M Elgin SC Kuroda MI Pirrotta V Karpen GH Park PJ 《Nature》2011,471(7339):480-485
Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function. 相似文献
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The myosin motor in muscle generates a smaller and slower working stroke at higher load 总被引:1,自引:0,他引:1
Reconditi M Linari M Lucii L Stewart A Sun YB Boesecke P Narayanan T Fischetti RF Irving T Piazzesi G Irving M Lombardi V 《Nature》2004,428(6982):578-581
Muscle contraction is driven by the motor protein myosin II, which binds transiently to an actin filament, generates a unitary filament displacement or 'working stroke', then detaches and repeats the cycle. The stroke size has been measured previously using isolated myosin II molecules at low load, with rather variable results, but not at the higher loads that the motor works against during muscle contraction. Here we used a novel X-ray-interference technique to measure the working stroke of myosin II at constant load in an intact muscle cell, preserving the native structure and function of the motor. We show that the stroke is smaller and slower at higher load. The stroke size at low load is likely to be set by a structural limit; at higher loads, the motor detaches from actin before reaching this limit. The load dependence of the myosin II stroke is the primary molecular determinant of the mechanical performance and efficiency of skeletal muscle. 相似文献
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Synaptic defects in ataxia mice result from a mutation in Usp14, encoding a ubiquitin-specific protease 总被引:7,自引:0,他引:7
Wilson SM Bhattacharyya B Rachel RA Coppola V Tessarollo L Householder DB Fletcher CF Miller RJ Copeland NG Jenkins NA 《Nature genetics》2002,32(3):420-425
Mice that are homozygous with respect to a mutation (ax(J)) in the ataxia (ax) gene develop severe tremors by 2-3 weeks of age followed by hindlimb paralysis and death by 6-10 weeks of age. Here we show that ax encodes ubiquitin-specific protease 14 (Usp14). Ubiquitin proteases are a large family of cysteine proteases that specifically cleave ubiquitin conjugates. Although Usp14 can cleave a ubiquitin-tagged protein in vitro, it is unable to process polyubiquitin, which is believed to be associated with the protein aggregates seen in Parkinson disease, spinocerebellar ataxia type 1 (SCA1; ref. 4) and gracile axonal dystrophy (GAD). The physiological substrate of Usp14 may therefore contain a mono-ubiquitin side chain, the removal of which would regulate processes such as protein localization and protein activity. Expression of Usp14 is significantly altered in ax(J)/ax(J) mice as a result of the insertion of an intracisternal-A particle (IAP) into intron 5 of Usp14. In contrast to other neurodegenerative disorders such as Parkinson disease and SCA1 in humans and GAD in mice, neither ubiquitin-positive protein aggregates nor neuronal cell loss is detectable in the central nervous system (CNS) of ax(J) mice. Instead, ax(J) mice have defects in synaptic transmission in both the central and peripheral nervous systems. These results suggest that ubiquitin proteases are important in regulating synaptic activity in mammals. 相似文献
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Vincenzo Luca Annarita Stringaro Marisa Colone Alessandro Pini Maria Luisa Mangoni 《Cellular and molecular life sciences : CMLS》2013,70(15):2773-2786
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that forms sessile communities, named biofilms. The non-motile forms are very difficult to eradicate and are often associated with the establishment of persistent infections, especially in patients with cystic fibrosis. The resistance of P. aeruginosa to conventional antibiotics has become a growing health concern worldwide and has prompted the search for new anti-infective agents with new modes of action. Naturally occurring antimicrobial peptides (AMPs) represent promising future template candidates. Here we report on the potent activity and membrane-perturbing effects of the amphibian AMP esculentin(1-21), on both the free-living and sessile forms of P. aeruginosa, as a possible mechanism for biofilm disruption. Furthermore, the findings that esculentin(1-21) is able to prolong survival of animals in models of sepsis and pulmonary infection indicate that this peptide can be a promising template for the generation of new antibiotic formulations to advance care of infections caused by P. aeruginosa. 相似文献
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CH Wu C Fallini N Ticozzi PJ Keagle PC Sapp K Piotrowska P Lowe M Koppers D McKenna-Yasek DM Baron JE Kost P Gonzalez-Perez AD Fox J Adams F Taroni C Tiloca AL Leclerc SC Chafe D Mangroo MJ Moore JA Zitzewitz ZS Xu LH van den Berg JD Glass G Siciliano ET Cirulli DB Goldstein F Salachas V Meininger W Rossoll A Ratti C Gellera DA Bosco GJ Bassell V Silani VE Drory RH Brown JE Landers 《Nature》2012,488(7412):499-503
Amyotrophic lateral sclerosis (ALS) is a late-onset neurodegenerative disorder resulting from motor neuron death. Approximately 10% of cases are familial (FALS), typically with a dominant inheritance mode. Despite numerous advances in recent years, nearly 50% of FALS cases have unknown genetic aetiology. Here we show that mutations within the profilin 1 (PFN1) gene can cause FALS. PFN1 is crucial for the conversion of monomeric (G)-actin to filamentous (F)-actin. Exome sequencing of two large ALS families showed different mutations within the PFN1 gene. Further sequence analysis identified 4 mutations in 7 out of 274 FALS cases. Cells expressing PFN1 mutants contain ubiquitinated, insoluble aggregates that in many cases contain the ALS-associated protein TDP-43. PFN1 mutants also display decreased bound actin levels and can inhibit axon outgrowth. Furthermore, primary motor neurons expressing mutant PFN1 display smaller growth cones with a reduced F/G-actin ratio. These observations further document that cytoskeletal pathway alterations contribute to ALS pathogenesis. 相似文献
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Vincenzo Vita 《Archive for History of Exact Sciences》1982,27(2):101-114
Summary In this note we claim that the two words
and
, which were used in Greece to indicate the geometrical point, had both been introduced in the scientific language in the first half of the IVth century B.C., and that they became popular independently of each other in two different cultural circles, those of philosophy and of mathematics, respectively.We propose therefore, in contrast to a conjecture by Heiberg, a new explanation for the predominance of
during the golden age of Greek mathematics and for the resurgence of
during the period of decadence.
Memoria presentata da A. Seidenberg 相似文献
Memoria presentata da A. Seidenberg 相似文献
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We discuss Manchak (2009a)'s result that there are locally (but not globally) isometric universes observationally indistinguishable from our own. This theorem makes the epistemic predicament of modern cosmology particularly problematic and the prospects of ever gaining knowledge of the global structure of the universe rather unlikely in the context of general relativity. We argue however that this conclusion is too quick; indeed, Manchak's theorem deploys spacetimes which are not physically reasonable, since they have features which are not the product of any physical process. This ultimately rests on the fact that local isometry between two spacetimes is not sufficient to guarantee that they are both physically reasonable. We propose an additional condition to properly define when a spacetime is physically reasonable, and we show that Manchak's spacetimes do not satisfy this further demand. 相似文献