915 resultados para Non-insulin-dependent diabetes - Genetic aspects


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Background and aim: given that obesity is an independent risk factor for the development of cardiovascular diseases we decided to investigate the mechanisms involved in microvascular dysfunction using a monosodium glutamate (MSG)-induced model of obesity, which allows us to work on both normotensive and normoglycemic conditions. Methods and results: Male offspring of Wistar rats received MSG from the second to the sixth day after birth. Sixteen-week-old MSG rats displayed higher Lee index, fat accumulation, dyslipidemia and insulin resistance, with no alteration in glycemia and blood pressure. The effect of norepinephrine (NE), which was increased in MSG rats, was potentiated by L-nitro arginine methyl ester (L-NAME) or tetraethylammonium (TEA) and was reversed by indomethacin and NS-398. Sensitivity to acetylcholine (ACh), which was reduced in MSG rats, was further impaired by L-NAME or TEA, and was corrected by indomethacin, NS-398 and tetrahydrobiopterin (BH4). MSG rats displayed increased endothelium-independent relaxation to sodium nitroprusside. A reduced prostacyclin/tromboxane ratio was found in the mesenteric beds of MSG rats. Mesenteric arterioles of MSG rats also displayed reduced nitric oxide (NO) production along with increased reactive oxygen species (ROS) generation; these were corrected by BH4 and either L-NAME or superoxide dismutase, respectively. The protein expression of eNOS and cyclooxygenase (COX)-2 was increased in mesenteric arterioles from MSG rats. Conclusion: Obesity/insulin resistance has a detrimental impact on vascular function. Reduced NO bioavailability and increased ROS generation from uncoupled eNOS and imbalanced release of COX products from COX-2 play a critical role in the development of these vascular alterations (C) 2010 Elsevier B.V. All rights reserved.

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We hypothesize that, in kidney of diabetic rats, hepatocyte nuclear factors (HNF-1 alpha. and HNF-3 beta) play a critical role in the overexpression of solute carrier 2A2 (SLC2A2) gene. Diabetic rats submitted or not to rapid (up to 12 h) and short-term (1, 4 and 6 days) insulin treatment were investigated. Twofold increase in GLUT2 mRNA was observed in diabetic, accompanied by significant increases in HNF-1 alpha and HNF-3 beta expression and binding activity. Additional 2-fold increase in GLUT2 mRNA and HNF-3 beta expression/activity was observed in 12-h insulin-treated rats. Six-day insulin treatment decreased GLUT2 mRNA and HNF-1 alpha expression and activity to levels of non-diabetic rats, whereas HNF-3 beta decreased to levels of non-insulin-treated diabetic rats. Our results provide evidence for a link between the overexpression of SLC2A2 gene and the transcriptional activity of HNF-1 alpha and HNF-3 beta in kidney of diabetic rats. Furthermore, recovery of SLC2A2 gene after 6-day insulin treatment also involves HNF-1 alpha and HNF-3 beta activity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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In this study zebrafish were used to identify, characterize and study leukemic "cancer"-genes as well as to investigate their role in normal development, particularly blood cell development. The experiments demonstrated that zebrafish represent an excellent tool for studying leukemogenesis, the genes involved in this process and for testing anti-cancer therapeutics.

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Menkes disease is a copper deficiency caused by mutations in the Menkes gene, which encodes a copper-transporting protein. This study identified the causative mutations in several Menkes patients, which provided a diagnostic test for relatives and identified critical regions of the Menkes protein. Further regions were identified through functional analysis of mutations introduced by in vitro mutagenesis.

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The characterisation of novel bovine RNA polymerase III promoters for the expression of short hairpin RNAs for gene silencing resulted in the identification of a highly efficient promoter sequence. The replication of bovine viral diarrhea virus was them suppressed using short hairpin RNAs expressed form this promoter in vitro.

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Menkes disease is a fatal genetic copper deficiency. The Menkes protein (ATP7A) was found to remove copper from tissues in mice that expressed the human ATP7A. Promising results were obtained with the use of a new copper complex for treatment of Menkes disease using a mouse model.

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Short term exposure to low levels of arsenic in human cells increased the cells' capacity to repair its DNA. In turn, cells became resistant to the toxic effects of UV radiation. However prolonged increases in principal repair proteins may actually lead to cancerous effects by destabilizing DNA repair.

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The effect of DNA damaging agents and age on expression of damage-processing genes was examined in plants and mice. Treatment with these agents increased expression of some genes. The effect of gene expression in the absence of treatment decreased with age, suggesting links between ageing and genetic instability.

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Ikaros-related transcription factors are essential for adaptive immunity. Evolutionary analysis suggested derivation from a precursor similar to the 'atypical' Pegasus protein, and possibly related to invertebrate Hunchback. Pegasus was shown to regulate neural, gut and blood cell development in zebrafish, with Ikaros identified as one of several potential gene targets.

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‘The good editor,’ suggests Thomas McCormack in his Fiction Editor, the Novel and the Novelist, ‘reads, and … responds aptly’ to the writer’s work, ‘where “aptly” means “as the ideal appropriate reader would”.’ McCormack develops an argument that encompasses the dual ideas of sensibility and craft as essential characteristics of the fiction editor. But at an historical juncture that has seen increasing interest in the publication of Indigenous writing, and when Indigenous writers themselves may envisage a multiplicity of readers (writing, for instance, for family and community, and to educate a wider white audience), who is the ‘ideal appropriate reader’ for the literary works of the current generation of Australian Indigenous writers? And what should the work of this ‘good editor’ be when engaging with the text of an Indigenous writer? This paper examines such questions using the work of Margaret McDonell and Jennifer Jones, among others, to explore ways in which non-Indigenous editors may apply aspects of McCormack’s ‘apt response’ to the editing of Indigenous texts.

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Perciformes are dominant in the marine environment, characterized as the largest and most diverse fish group. Some families, as Gerreidae, popularly known as silver jennies, carapebas, or mojarras have a high economic potential to marine fish farming, natural explotation and game fishing. Genetic information of these species are of fundamental importance for their management and production. Despite exist over 13,000 marine fish species described, only 2% were cytogenetically analyzed and less than 1% have some reproductive characteristics known. Induced breeding, cytogenetic characterization and cryopreservation of gametes, represent important areas in applied fish studies. In this project cytogenetic analyzes were performed to acess genetic aspects of Gerreidae species, distributed in coastal and estuarine regions of Northeast Brazil. Different methods for identifying chromosomal regions were employed using conventional techniques (Ag-NORs, C-banding), staining with base-specific fluorochromes (DAPI-CMA3), and physical mapping of ribosomal genes 18S and 5S rDNA, through hybridization in situ with fluorescent probes (FISH). The six species analyzed showed remarkable chromosome conservatism. The 18S and 5S ribosomal genes when analyzed in phylogenetic perspective demonstrate varied evolutionary dynamics, suggesting ocurrence of stasis process in some groups and greater dynamism in others. Double FISH with 18S and 5S probes showed both how efficient cytotaxonomic markers in the homogeneous karyotypes of this group of species. The karyotypic pattern identified in addition to the evolutionary aspects of karyotype, are suggestive of existence of low potential of post-zygotic barrier, prompting further research to prospect for artificial interspecific hybridization of these species of commercial importance

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The present work aimed the elaboration of an environmental study focused on the hotel sector in order to present an analysis of the environmental aspects of Ponta Negra Beach, in Natal, RN, Brazil and also the aspects of the small and medium hotels existing in this area. By means of this work, it is possible to elaborate a model of a simplified System of Environmental Management which can attend to the exigencies required by NBR ISO 14001: 2004, as well as to present economical viability and possibility to be implemented in a way that hotels may converge to the sustainable environmental development of the tourism in Ponta Negra Beach. The research methodology presents itself divided into three items: execution of the environmental characterization of Ponta Negra Beach, by way of technical visits and interpretation of satellite images and cartograms of the main environmental characteristics of the region; execution of the work already made concerning the development, application and interpretation of the evaluation of the environmental aspects of each hotel, considering the hotels and the period of data collection, these used in evaluation, research instrument and a description of the procedure utilized for the analysis of the collected data and the utilized methodology for the elaboration of a model of a simplified System of Environmental Management. In a general way, it has been concluded that the practices executed by hotels in Ponta Negra Beach are impact-like and harmful to the environment. The simple implementation of analysis procedures and control of the environmental aspects could suggestively contribute to the reduction of environmental impacts promoted by the hotel section at this beach and in the nearby areas. It had been noticed that the study contributed to the sensitization of managers concerning the environmental problems since, in many other times, the detected problem was, in fact, the non-acquaintance about the environmental aspects and impacts from those hotels administrators, because of the lack of surveys and studies about the theme. It had also been noticed the arousing of a possible environmental attitude from some managers

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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In this report, we present a boy with lower lip pits, distinct craniofacial dysmorphism with cleft lip and palate, central nervous system malformation, and severe mental retardation. Similar but less pronounced facial findings were present in his mentally normal mother and maternal grandfather, both presenting with lower lip pits. Cleft lip was present in patient's father. Analysis of the VWS1 and VWS2 regions were performed to elucidate the molecular basis of the phenotype of the propositus. Screening or mutations at the IRF6 gene detected a pathogenic mutation (c.960G > C) in the propositus and in his mother; and a single nucleotide polymorphism (c.175-5C > G) in the propositus and in his father. Clinical and genetic aspects of this case are discussed.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)