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Jae Min Cho SeulKi Park Rajeshwary Ghosh Kellsey Ly Caroline Ramous Lauren Thompson Michele Hansen Maria Sara de Lima Coutinho Mattera Karla Maria Pires Maroua Ferhat Sohom Mookherjee Kevin J. Whitehead Kandis Carter Mrcio Buffolo Sihem Boudina J. David Symons 《Aging cell》2021,20(10)
Protein quality control mechanisms decline during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age‐associated cardiac dysfunction. Macroautophagy is the process by which post‐mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late‐in‐life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs. adult mice. As expected, 24‐month‐old male C57BL/6J mice (old) exhibited repressed autophagosome formation and protein aggregate accumulation in the heart, systolic and diastolic dysfunction, and reduced exercise capacity vs. 8‐month‐old (adult) mice (all p < 0.05). To investigate the influence of late‐in‐life exercise training, additional cohorts of 21‐month‐old mice did (old‐ETR) or did not (old‐SED) complete a 3‐month progressive resistance treadmill running program. Body composition, exercise capacity, and soleus muscle citrate synthase activity improved in old‐ETR vs. old‐SED mice at 24 months (all p < 0.05). Importantly, protein expression of autophagy markers indicate trafficking of the autophagosome to the lysosome increased, protein aggregate clearance improved, and overall function was enhanced (all p < 0.05) in hearts from old‐ETR vs. old‐SED mice. These data provide the first evidence that a physiological intervention initiated late‐in‐life improves autophagic flux, protein aggregate clearance, and contractile performance in mouse hearts. 相似文献
13.
Altered patterns of fractionation and exon deletions in Brassica rapa support a two-step model of paleohexaploidy 总被引:2,自引:0,他引:2
Tang H Woodhouse MR Cheng F Schnable JC Pedersen BS Conant G Wang X Freeling M Pires JC 《Genetics》2012,190(4):1563-1574
The genome sequence of the paleohexaploid Brassica rapa shows that fractionation is biased among the three subgenomes and that the least fractionated subgenome has approximately twice as many orthologs as its close (and relatively unduplicated) relative Arabidopsis than had either of the other two subgenomes. One evolutionary scenario is that the two subgenomes with heavy gene losses (I and II) were in the same nucleus for a longer period of time than the third subgenome (III) with the fewest gene losses. This "two-step" hypothesis is essentially the same as that proposed previously for the eudicot paleohexaploidy; however, the more recent nature of the B. rapa paleohexaploidy makes this model more testable. We found that subgenome II suffered recent small deletions within exons more frequently than subgenome I, as would be expected if the genes in subgenome I had already been near maximally fractionated before subgenome III was introduced. We observed that some sequences, before these deletions, were flanked by short direct repeats, a unique signature of intrachromosomal illegitimate recombination. We also found, through simulations, that short--single or two-gene--deletions appear to dominate the fractionation patterns in B. rapa. We conclude that the observed patterns of the triplicated regions in the Brassica genome are best explained by a two-step fractionation model. The triplication and subsequent mode of fractionation could influence the potential to generate morphological diversity--a hallmark of the Brassica genus. 相似文献
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Tiago I Mendes V Pires C Morais PV Veríssimo A 《Systematic and applied microbiology》2006,29(2):100-108
A Gram-negative bacterium designated AC-74(T) was isolated from a highly alkaline groundwater environment (pH 11.4). This organism formed rod-shaped cells, is strictly aerobic, catalase and oxidase positive, tolerates up to 3.0% NaCl, has an optimum growth temperature of 30 degrees C, but no growth occurs at 10 or 40 degrees C, and an optimum pH value of 8.0, but no growth occurs at pH 7.0 or 11.3. The predominant fatty acids are iso-15:0, iso-17:1 omega9c and 16:1 omega7c and or iso-15:2OH. The G+C content of DNA was 43.5mol%. The phylogenetic analyses of the sequences of the 16s RNA genes indicated that strain AC-74(T) belongs to the family "Flexibacteriaceae" and is phylogenetically equidistant ( approximately 94.5%) from the majority of the species of the genus Algoriphagus and from the genus Hongiella. Based on the phylogenetic analyses and distinct phenotypic characteristics, we are of the opinion that strain AC-74(T), represents a new species of the novel genus for which we propose the name Chimaereicella alkaliphila gen. nov., sp. nov. 相似文献
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Pires MJ Martel P Baptista A Petersen SB Willson RC Cabral JM 《Biotechnology and bioengineering》1994,44(7):773-780
The mechanism of extraction of rat cytochrome b(5) from water into a sodium dioctylsulfosuccinate (AOT) micellar organic phase was studied using protein engineering of surface charged residues. The extraction behavior of native cytochrome b(5) and modified proteins with substitutions of the type glutamic acid --> lysine at positions 44 (E44K), 56 (E56K), and 92 (E92K), was studied as a function of pH. The results indicate that an important mechanism of extraction is an electrostatic interaction of this protein with the negatively charged surfactant. We demonstrate that it is possible to improve extraction by engineering the protein surface charge, increasing the driving force responsible for the protein transfer to the micellar phase. (c) 1994 John Wiley & Sons, Inc. 相似文献
18.
Adeliane Castro da Costa Abadio de Oliveira Costa-Júnior Fábio Muniz de Oliveira Sarah Veloso Nogueira Joseane Damaceno Rosa Danilo Pires Resende André Kipnis Ana Paula Junqueira-Kipnis 《PloS one》2014,9(11)
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials. 相似文献
19.
Bárbara Santos Pires da Silva Eloísa Bonfá Júlio César Bertacini de Moraes Carla Gonçalves Schain Saad Ana Cristina de Medeiros Ribeiro Célio Roberto Gonçalves Jozélio Freire de Carvalho 《Biologicals》2010,38(5):567-569
The objective of this study was to evaluate the influence of anti-tumor necrosis factor (anti-TNF) in juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Sixty-two patients were investigated: 7 JIA; 37 AS; and 18 PsA. Caucasian race accounted for 79% and 29% were female. Mean age was 40.4 ± 12.6years. None of the patients had a history of diabetes, and none had used oral hypoglycemic agents or insulin. Treatment was with adalimumab, infliximab and etanercept. Glucose, inflammatory markers and prednisone dose were assessed at baseline, as well as after three and six months of treatment. The mean erythrocyte sedimentation rate was significantly lower at three months and six months than at baseline (13.7 ± 18.0 and 18 ± 22.5 vs. 27.9 ± 23.4 mm; p = 0.001). At baseline, three months and six months, we found the following: mean C-reactive protein levels were comparable (22.1 ± 22.7, 14.5 ± 30.7 and 16.0 ± 23.8 mg/L, respectively; p = 0.26); mean glucose levels remained unchanged (90.8 ± 22.2 mg/dl, 89.5 ± 14.6 mg/dl and 89.8 ± 13.6 mg/dl, respectively; p = 0.91); and mean prednisone doses were low and stable (3.9 ± 4.9 mg/day, 3.7 ± 4.8 mg/day and 2.6 ± 4.0 mg/day, respectively; p = 0.23). During the first six months of treatment, anti-TNF therapy does not seem to influence glucose metabolism in JIA, AS or PsA. 相似文献
20.
Zuccolo A Bowers JE Estill JC Xiong Z Luo M Sebastian A Goicoechea JL Collura K Yu Y Jiao Y Duarte J Tang H Ayyampalayam S Rounsley S Kudrna D Paterson AH Pires JC Chanderbali A Soltis DE Chamala S Barbazuk B Soltis PS Albert VA Ma H Mandoli D Banks J Carlson JE Tomkins J dePamphilis CW Wing RA Leebens-Mack J 《Genome biology》2011,12(5):R48-14