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41.
Predicting the structural effects of insertions in proteins by homology modeling remains a challenge. To investigate the molecular basis for conformational adaptations to insertions, ten mutants of ubiquitin were generated by introducing five different inserts, varying from five to 11 residues in size, at two different sites. Most insertion sequences were derived from homologous positions in structurally homologous ubiquitin-like proteins; to test sequence specificity, insertions were made into both homologous and non-homologous sites in ubiquitin. Structural inferences from NMR data suggest that each insertion site shows a reflex response to insertions: the sequence of the insertion has much less impact on structural adaptations than does the site of the insertion. Further, each site responds to insertions in a unique but consistent manner. For a given insertion site, different inserted sequences give rise to different stabilities, but the relationship between stability and sequence is not yet clear. However, the change in stability is similar for all insertions in a given site. 相似文献
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Ferraro P Pontarin G Crocco L Fabris S Reichard P Bianchi V 《The Journal of biological chemistry》2005,280(26):24472-24480
Mitochondrial (mt) DNA depletion syndromes can arise from genetic deficiencies for enzymes of dNTP metabolism, operating either inside or outside mitochondria. MNGIE is caused by the deficiency of cytosolic thymidine phosphorylase that degrades thymidine and deoxyuridine. The extracellular fluid of the patients contains 10-20 microM deoxynucleosides leading to changes in dTTP that may disturb mtDNA replication. In earlier work, we suggested that mt dTTP originates from two distinct pathways: (i) the reduction of ribonucleotides in the cytosol (in cycling cells) and (ii) intra-mt salvage of thymidine (in quiescent cells). In MNGIE and most other mtDNA depletion syndromes, quiescent cells are affected. Here, we demonstrate in quiescent fibroblasts (i) the existence of small mt dNTP pools, each usually 3-4% of the corresponding cytosolic pool; (ii) the rapid metabolic equilibrium between mt and cytosolic pools; and (iii) the intra-mt synthesis and rapid turnover of dTTP in the absence of DNA replication. Between 0.1 and 10 microM extracellular thymidine, intracellular thymidine rapidly approaches the extracellular concentration. We mimic the conditions of MNGIE by maintaining quiescent fibroblasts in 10-40 microM thymidine and/or deoxyuridine. Despite a large increase in intracellular thymidine concentration, cytosolic and mt dTTP increase at most 4-fold, maintaining their concentration for 41 days. Other dNTPs are marginally affected. Deoxyuridine does not increase the normal dNTP pools but gives rise to a small dUTP and a large dUMP pool, both turning over rapidly. We discuss these results in relation to MNGIE. 相似文献
44.
de Melo LD Nepomuceno-Silva JL Sant'Anna C Eisele N Ferraro RB Meyer-Fernandes JR de Souza W Cunha-e-Silva NL Lopes UG 《Biochemical and biophysical research communications》2004,323(3):1009-1016
Here we have investigated the function of TcRho1, a Rho family orthologue from the parasite Trypanosoma cruzi. We have selected parasites overexpressing wild-type TcRho1 and a truncated form of TcRho1 (TcRho1-DeltaCaaX) which is unable to undergo farnesylation and supposed to interfere with recruitment of Rho effectors to membranes. TcRho1 protein was localized at the anterior region of wild-type and TcRho1 overexpressing epimastigotes, suggesting association with the Golgi apparatus. Accordingly, parasites overexpressing TcRho1-DeltaCaaX presented cytoplasmic fluorescence. To address the function of TcRho1 during differentiation, from epimastigotes to trypomastigotes, we submitted parasites overexpressing the above-cited lineages to metacyclogenesis assays. Parasites overexpressing TcRho1-DeltaCaaX generated a discrete number of metacyclic trypomastigotes when compared with other lineages. Strikingly, TcRho1-DeltaCaaX cells died synchronously during the process of metacyclogenesis. 相似文献
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Free radicals are associated with the appearance of disorders such as tumours, CNS alterations and inflammatory pathologies. Their levels are known to be increased in inflammatory diseases due to the activity of prostaglandins, which are related to protein secretion including enzymes. Peroxidase is an oral enzyme that is implicated in the defence of the oral cavity. In this paper, investigations of the effect and mechanism of the activity of prostaglandin E2 (PGE2) on peroxidase secretion of female rat submandibular glands are reported. Results showed that PGE2 significantly increased the secretion of submandibular peroxidase and that this effect was mediated by an increase of intracellular cAMP and nitric oxide synthase activation. This could imply that prostaglandins play a modulatory role in diseases where free radicals are involved. 相似文献
47.
Integrating economic costs into conservation planning 总被引:3,自引:0,他引:3
Naidoo R Balmford A Ferraro PJ Polasky S Ricketts TH Rouget M 《Trends in ecology & evolution》2006,21(12):681-687
Recent studies that incorporate the spatial distributions of biological benefits and economic costs in conservation planning have shown that limited budgets can achieve substantially larger biological gains than when planning ignores costs. Despite concern from donors about the effectiveness of conservation interventions, these increases in efficiency from incorporating costs into planning have not yet been widely recognized. Here, we focus on what these costs are, why they are important to consider, how they can be quantified and the benefits of their inclusion in priority setting. The most recent work in the field has examined the degree to which dynamics and threat affect the outcomes of conservation planning. We assess how costs fit into this new framework and consider prospects for integrating them into conservation planning. 相似文献
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Profita M Bonanno A Montalbano AM Albano GD Riccobono L Siena L Ferraro M Casarosa P Pieper MP Gjomarkaj M 《Biochimica et biophysica acta》2012,1822(7):1079-1089
We quantified TGF-β1 and acetylcholine (ACh) concentrations in induced sputum supernatants (ISSs) from 18 healthy controls (HC), 22 healthy smokers (HS) and 21 COPDs. ISSs from HC, HS and COPD as well as rhTGF-β1 were also tested in neutrophil adhesion and in mAChR2, mAChR3 and ChAT expression experiments in human bronchial epithelial cells (16-HBE). Finally, we evaluated the effects of Olodaterol (a novel inhaled β(2)-adrenoceptor agonist) and Tiotropium Spiriva?, alone or in combination, on neutrophil adhesion and mAChRs and ChAT expression in stimulated 16-HBE. The results showed that 1) TGF-β1 and ACh concentrations are increased in ISSs from COPD in comparison to HC and HS, and TGF-β1 in HS is higher than in HC; 2) ISSs from COPD and HS caused increased neutrophil adhesion to 16-HBE when compared to ISSs from HC. The effect of ISSs from COPD was significantly reduced by TGF-β1 depletion or by the pretreatment with Olodaterol or Tiotropium alone or in combination, while the effect of ISSs from HS was significantly reduced by the pretreatment with Olodaterol alone; 3) mAChR2, mAChR3 and ChAT expression was increased in 16-HBE stimulated with ISSs from COPD and TGF-β1 depletion significantly reduced this effect on mAChR3 and ChAT expression; 4) rhTGF-β1 increased mAChR2, mAChR3 and ChAT expression in 16-HBE; 5) Olodaterol did not affect the expression of mAChRs and ChAT in 16-HBE. Our findings support the use of β? long-acting and anticholinergic drugs to control the bronchoconstriction and TGF-β1-mediated neutrophilic inflammation in COPD. 相似文献
50.
Elisabetta Pace Caterina Di Sano Stefania La Grutta Maria Ferraro Giuseppe Albeggiani Giuseppe Liotta Serena Di Vincenzo Carina Gabriela Uasuf Jean Bousquet Mark Gjomarkaj 《PloS one》2012,7(12)