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981.
982.
Waltemath D Adams R Beard DA Bergmann FT Bhalla US Britten R Chelliah V Cooling MT Cooper J Crampin EJ Garny A Hoops S Hucka M Hunter P Klipp E Laibe C Miller AK Moraru I Nickerson D Nielsen P Nikolski M Sahle S Sauro HM Schmidt H Snoep JL Tolle D Wolkenhauer O Le Novère N 《PLoS computational biology》2011,7(4):e1001122
983.
Plague GR Dougherty KM Boodram KS Boustani SE Cao H Manning SR McNally CC 《Genetica》2011,139(7):895-902
Insertion sequences (ISs) are transposable genetic elements in bacterial genomes. IS elements are common among bacteria but
are generally rare within free-living species, probably because of the negative fitness effects they have on their hosts.
Conversely, ISs frequently proliferate in intracellular symbionts and pathogens that recently transitioned from a free-living
lifestyle. IS elements can profoundly influence the genomic evolution of their bacterial hosts, although it is unknown why
they often expand in intracellular bacteria. We designed a laboratory evolution experiment with Escherichia coli K-12 to test the hypotheses that IS elements often expand in intracellular bacteria because of relaxed natural selection
due to (1) their generally small effective population sizes (N
e) and thus enhanced genetic drift, and (2) their nutrient rich environment, which makes many biosynthetic genes unnecessary
and thus selectively neutral territory for IS insertion. We propagated 12 populations under four experimental conditions:
large N
e versus small N
e, and nutrient rich medium versus minimal medium. We found that relaxed selection over 4,000 generations was not sufficient
to permit IS element expansion in any experimental population, thus leading us to hypothesize that IS expansion in intracellular
symbionts may often be spurred by enhanced transposition rates, possibly due to environmental stress, coupled with relaxed
natural selection. 相似文献
984.
985.
De Felice C Signorini C Durand T Oger C Guy A Bultel-Poncé V Galano JM Ciccoli L Leoncini S D'Esposito M Filosa S Pecorelli A Valacchi G Hayek J 《Journal of lipid research》2011,52(12):2287-2297
Oxidative damage has been reported in Rett syndrome (RTT), a pervasive developmental disorder caused in up to 95% of cases by mutations in the X-linked methyl-CpG binding protein 2 gene. Herein, we have synthesized F(2)-dihomo-isoprostanes (F(2)-dihomo-IsoPs), peroxidation products from adrenic acid (22:4 n-6), a known component of myelin, and tested the potential value of F(2)-dihomo-IsoPs as a novel disease marker and its relationship with clinical presentation and disease progression. F(2)-dihomo-IsoPs were determined by gas chromatography/negative-ion chemical ionization tandem mass spectrometry. Newly synthesized F(2)-dihomo-IsoP isomers [ent-7(RS)-F(2t)-dihomo-IsoP and 17-F(2t)-dihomo-IsoP] were used as reference standards. The measured ions were the product ions at m/z 327 derived from the [M-181](-) precursor ions (m/z 597) produced from both the derivatized ent-7(RS)-F(2t)-dihomo-IsoP and 17-F(2t)-dihomo-IsoP. Average plasma F(2)-dihomo-IsoP levels in RTT were about one order of magnitude higher than those in healthy controls, being higher in typical RTT as compared with RTT variants, with a remarkable increase of about two orders of magnitude in patients at the earliest stage of the disease followed by a steady decrease during the natural clinical progression. hese data indicate for the first time that quantification of F(2)-dihomo-IsoPs in plasma represents an early marker of the disease and may provide a better understanding of the pathogenic mechanisms behind the neurological regression in patients with RTT. 相似文献
986.
987.
988.
Schuh RA Jackson KC Khairallah RJ Ward CW Spangenburg EE 《American journal of physiology. Regulatory, integrative and comparative physiology》2012,302(6):R712-R719
Measurement of mitochondrial function in skeletal muscle is a vital tool for understanding regulation of cellular bioenergetics. Currently, a number of different experimental approaches are employed to quantify mitochondrial function, with each involving either mechanically or chemically induced disruption of cellular membranes. Here, we describe a novel approach that allows for the quantification of substrate-induced mitochondria-driven oxygen consumption in intact single skeletal muscle fibers isolated from adult mice. Specifically, we isolated intact muscle fibers from the flexor digitorum brevis muscle and placed the fibers in culture conditions overnight. We then quantified oxygen consumption rates using a highly sensitive microplate format. Peak oxygen consumption rates were significantly increased by 3.4-fold and 2.9-fold by simultaneous stimulation with the uncoupling agent, carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), and/or pyruvate or palmitate exposure, respectively. However, when calculating the total oxygen consumed over the entire treatment, palmitate exposure resulted in significantly more oxygen consumption compared with pyruvate. Further, as proof of principle for the procedure, we isolated fibers from the mdx mouse model, which has known mitochondrial deficits. We found significant reductions in initial and peak oxygen consumption of 51% and 61% compared with fibers isolated from the wild-type (WT) animals, respectively. In addition, we determined that fibers isolated from mdx mice exhibited less total oxygen consumption in response to the FCCP + pyruvate stimulation compared with the WT mice. This novel approach allows the user to make mitochondria-specific measures in a nondisrupted muscle fiber that has been isolated from a whole muscle. 相似文献
989.
Meinzer U Barreau F Esmiol-Welterlin S Jung C Villard C Léger T Ben-Mkaddem S Berrebi D Dussaillant M Alnabhani Z Roy M Bonacorsi S Wolf-Watz H Perroy J Ollendorff V Hugot JP 《Cell host & microbe》2012,11(4):337-351
Yersinia pseudotuberculosis is an enteropathogenic bacteria that disrupts the intestinal barrier and invades its host through gut-associated lymphoid tissue and Peyer's patches (PP). We show that the Y.?pseudotuberculosis effector YopJ induces intestinal barrier dysfunction by subverting signaling of the innate immune receptor Nod2, a phenotype that can be reversed by pretreating with the Nod2 ligand muramyl-dipeptide. YopJ, but not the catalytically inactive mutant YopJ(C172A), acetylates critical sites in the activation loops of the RICK and TAK1 kinases, which are central mediators of Nod2 signaling, and decreases the affinity of Nod2 for RICK. Concomitantly, Nod2 interacts with and activates caspase-1, resulting in increased levels of IL-1β. Finally, IL-1β within PP plays an essential role in inducing intestinal barrier dysfunction. Thus, YopJ alters intestinal permeability and promotes the dissemination of Yersinia as well as commensal bacteria by exploiting the mucosal inflammatory response. 相似文献
990.