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991.
Mitochondria are organelles of elaborate structure that in addition to supplying cellular energy, have significant roles in calcium homeostasis and apoptosis. Failure to maintain mitochondrial dynamics results in neurodegenerative diseases and neuromuscular pathologies. The Miro GTPases, which constitute a unique subgroup of the Ras superfamily, have emerged as essential regulators of mitochondrial morphogenesis and trafficking along microtubules. Miro GTPases function as calcium-dependent sensors in the control of mitochondrial motility. Increased awareness of the biological function of Miro GTPases can contribute to elucidate the molecular mechanisms underlying diseases caused by deregulated mitochondrial dynamics. 相似文献
992.
Cardoso AM Trabulo S Cardoso AL Lorents A Morais CM Gomes P Nunes C Lúcio M Reis S Padari K Pooga M Pedroso de Lima MC Jurado AS 《Biochimica et biophysica acta》2012,1818(3):877-888
The present work aims to gain insights into the role of peptide-lipid interactions in the mechanisms of cellular internalization and endosomal escape of the S4(13)-PV cell-penetrating peptide, which has been successfully used in our laboratory as a nucleic acid delivery system. A S4(13)-PV analogue, S4(13)-PVscr, displaying a scrambled amino acid sequence, deficient cell internalization and drug delivery inability, was used in this study for comparative purposes. Differential scanning calorimetry, fluorescence polarization and X-ray diffraction at small and wide angles techniques showed that both peptides interacted with anionic membranes composed of phosphatidylglycerol or a mixture of this lipid with phosphatidylethanolamine, increasing the lipid order, shifting the phase transition to higher temperatures and raising the correlation length between the bilayers. However, S4(13)-PVscr, in contrast to the wild-type peptide, did not promote lipid domain segregation and induced the formation of an inverted hexagonal lipid phase instead of a cubic phase in the lipid systems assayed. Electron microscopy showed that, as opposed to S4(13)-PVscr, the wild-type peptide induced the formation of a non-lamellar organization in membranes of HeLa cells. We concluded that lateral phase separation and destabilization of membrane lamellar structure without compromising membrane integrity are on the basis of the lipid-driven and receptor-independent mechanism of cell entry of S4(13)-PV peptide. Overall, our results can contribute to a better understanding of the role of peptide-lipid interactions in the mechanisms of cell-penetrating peptide membrane translocation, helping in the future design of more efficient cell-penetrating peptide-based drug delivery systems. 相似文献
993.
Barros LA de Aguiar HJ Andrade-Souza V Mariano Cdos S Delabie JH Pompolo SD 《Hereditas》2012,149(1):50-54
The ant Mycocepurus goeldii (Forel) is known for having a relict karyotype with low chromosome number and the present study help the understanding of this ant cytogenetics by describing the occurrence of pre-nucleolar bodies in their chromosomes using impregnation with silver nitrate (Ag-NOR) and the location of 45S rDNA sites by means of the FISH (fluorescent in situ hybridization) technique. Several spots were observed surrounding all chromosomes when submitted to the Ag-NOR technique. These unusual markings were observed in both chromatids of metaphase and early anaphase chromosomes, and are associated to the presence of pre-nucleolar bodies, allowing the observation of the phenomenon of nucleologenesis. Although recent studies have shown that all chromosomes of M. goeldii exhibit centromeric or pericentromeric markings for the CMA(3) fluorochrome, the FISH technique indicated the presence of 45S rDNA in only one pair of chromosomes that differed in the number of CMA(3) markings observed for this species, pointing that the other markings observed with this fluorochrome do not match the sequences in ribosomal genes. 相似文献
994.
FE Pethick AF Lainson R Yaga A Flockhart DG Smith W Donachie LT Cerdeira A Silva E Bol TS Lopes MS Barbosa AC Pinto AR Dos Santos SC Soares SS Almeida LC Guimaraes FF Aburjaile VA Abreu D Ribeiro KK Fiaux CA Diniz EG Barbosa UP Pereira SS Hassan A Ali SM Bakhtiar FA Dorella AR Carneiro RT Ramos FS Rocha MP Schneider A Miyoshi V Azevedo MC Fontaine 《Journal of bacteriology》2012,194(17):4736-4737
Here, we report the whole-genome sequences of two ovine-pathogenic Corynebacterium pseudotuberculosis isolates: strain 3/99-5, which represents the first C. pseudotuberculosis genome originating from the United Kingdom, and 42/02-A, the second from Australia. These genome sequences will contribute to the objective of determining the global pan-genome of this bacterium. 相似文献
995.
Functional Analysis of Bacillus subtilis Genes Involved in the Biosynthesis of 4-Thiouridine in tRNA
ThiI has been identified as an essential enzyme involved in the biosynthesis of thiamine and the tRNA thionucleoside modification, 4-thiouridine. In Escherichia coli and Salmonella enterica, ThiI acts as a sulfurtransferase, receiving the sulfur donated from the cysteine desulfurase IscS and transferring it to the target molecule or additional sulfur carrier proteins. However, in Bacillus subtilis and most species from the Firmicutes phylum, ThiI lacks the rhodanese domain that contains the site responsible for the sulfurtransferase activity. The lack of the gene encoding for a canonical IscS cysteine desulfurase and the presence of a short sequence of ThiI in these bacteria pointed to mechanistic differences involving sulfur trafficking reactions in both biosynthetic pathways. Here, we have carried out functional analysis of B. subtilis thiI and the adjacent gene, nifZ, encoding for a cysteine desulfurase. Gene inactivation experiments in B. subtilis indicate the requirement of ThiI and NifZ for the biosynthesis of 4-thiouridine, but not thiamine. In vitro synthesis of 4-thiouridine by ThiI and NifZ, along with labeling experiments, suggests the occurrence of an alternate transient site for sulfur transfer, thus obviating the need for a rhodanese domain. In vivo complementation studies in E. coli IscS- or ThiI-deficient strains provide further support for specific interactions between NifZ and ThiI. These results are compatible with the proposal that B. subtilis NifZ and ThiI utilize mechanistically distinct and mutually specific sulfur transfer reactions. 相似文献
996.
997.
Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet. 相似文献
998.
999.
Correa-Costa M Semedo P Monteiro AP Silva RC Pereira RL Gonçalves GM Marques GD Cenedeze MA Faleiros AC Keller AC Shimizu MH Seguro AC Reis MA Pacheco-Silva A Câmara NO 《PloS one》2010,5(12):e14298
Background
The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed.Aim
We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease.Methods
Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed.Results
Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-β protein production was significantly lower in Hemin-treated animals.Conclusion
Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection. 相似文献1000.
Lúcio F. C. Ferraz Leandro C. L. Verde Fernanda C. Reis Fabiana Alexandrino Ana P. Felício Maria T. M. Novo Oswaldo Garcia Jr Laura M. M. Ottoboni 《Archives of microbiology》2010,192(7):531-540
Acidithiobacillus ferrooxidans is a mesophilic, acidophilic, chemolithoautotrophic bacterium that obtains energy from the oxidation of ferrous iron (Fe2+), elemental sulfur and reduced sulfur compounds. The industrial interest in A. ferrooxidans resides in its capacity to oxidize insoluble metal sulfides into soluble metal sulfates, thus allowing the recovery of the
desired metals from low-grade sulfide ores. In the present work, RNA arbitrarily primed PCR (RAP-PCR) was performed to identify
cDNAs differentially expressed in A. ferrooxidans cells grown in the presence of Fe2+ and cells maintained for 24 h in the presence of the copper sulfides bornite and chalcopyrite. Eighteen cDNAs corresponding
to genes with known function were identified, and their relative expression was further characterized by real-time quantitative
PCR. Bornite had a mild effect on the expression of the 18 genes analyzed. None of these genes was down-regulated and among
the few genes up-regulated, it is worth mentioning lepA and def-2 that are involved in protein synthesis. Chalcopyrite presented the most significant changes. Five genes related to protein
processing were down-regulated, and another 5 genes related to the transport system were up-regulated. The up- and down-regulation
of these genes in the presence of bornite and chalcopyrite could be due to alterations in the ideal pH, presence of copper
ions in solution and nutrient limitation. The results suggest that gene expression modulation might be important for the A. ferrooxidans early response to copper sulfides. 相似文献