142 resultados para Epigenetic inheritance


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

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Due to the exclusively maternal inheritance of mitochondria, mitochondrial genotypes can be coupled to a particular nuclear genotype by continuous mating of founder females and their female offspring to males of the desired nuclear genotype. However, backcrossing is a gradual procedure that, apart from being lengthy, cannot ascertain that genetic and epigenetic changes will modify the original nuclear genotype. Animal cloning by nuclear transfer using host ooplasm carrying polymorphic mitochondrial genomes allows, among other biotechnology applications, the coupling of nuclear and mitochondrial genotypes of diverse origin within a single generation. Previous attempts to use Bos taurus oocytes as hosts to transfer nuclei from unrelated species led to the development to the blastocyst stage but none supported gestation to term. Our aim in this study was to determine whether B. taurus oocytes support development of nuclei from the closely related B. indicus cattle and to examine the fate of their mitochondrial genotypes throughout development. We show that indicus:taurus reconstructed oocytes develop to the blastocyst stage and produce live offspring after transfer to surrogate cows. We also demonstrate that, in reconstructed embryos, donor cell-derived mitochondria undergo a stringent genetic drift during early development leading, in most cases, to a reduction or complete elimination of B. indicus mtDNA. These results demonstrate that cross-subspecies animal cloning is a viable approach both for matching diverse nuclear and cytoplasmic genes to create novel breeds of cattle and for rescuing closely related endangered cattle.

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Penile carcinoma (PeCa) represents an important public health problem in poor and developing countries. Despite its unpredictable behavior and aggressive treatment, there have only been a few reports regarding its molecular data, especially epigenetic mechanisms. The functional diversity in different cell types is acquired by chromatin modifications, which are established by epigenetic regulatory mechanisms involving DNA methylation, histone acetylation, and miRNAs. Recent evidence indicates that the dysregulation in these processes can result in the development of several diseases, including cancer. Epigenetic alterations, such as the methylation of CpGs islands, may reveal candidates for the development of specific markers for cancer detection, diagnosis and prognosis. There are a few reports on the epigenetic alterations in PeCa, and most of these studies have only focused on alterations in specific genes in a limited number of cases. This review aims to provide an overview of the current knowledge of the epigenetic alterations in PeCa and the promising results in this field. The identification of epigenetically altered genes in PeCa is an important step in understanding the mechanisms involved in this unexplored disease. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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Transmissibility of dental and jaw characteristics is strongly influenced by environmental factors during the years of extra uterine life when odontogenesis occurs. Through biochemical factors, such as enzymes, proteins, hormones and other mediators, genes are activated or silenced to suit the cell or organism to its environment. These changes are not transmitted to our descendants, because of that, these factors are called epigenetic. Among the most cited epigenetic factors are food, pollution, drugs and exercise. The objective of this study was to assess the transmissibility of dental characteristics in two pairs of twins. In one case, 13-year-old boys had the same basic dental and jaw characteristics with prolonged retention of the second upper deciduous molars and the presence of permanent successors. In the other case, 14-year-old boys had prolonged retention of lower deciduous second molars and absence of permanent successors, but only one of them had the germs of third lower molars. The phenotypic difference in the dentition of twins from clinical case 2 could be due to epigenetic factors, showing the absence of genetic determinism in the transmissibility of dental characteristics.

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Regulation of chromosome inheritance is essential to ensure proper transmission of genetic information. To accomplish accurate genome segregation, cells organize their chromosomes and actively separate them prior to cytokinesis. In Bacillus subtilis the Spo0J protein is required for accurate chromosome segregation and it regulates the developmental switch from vegetative growth to sporulation. Spo0J is a DNA-binding protein that recognizes at least eight identified parS sites located near the origin of replication. As judged by fluorescence microscopy, Spo0J forms discrete foci associated with the oriC region of the chromosome throughout the cell cycle. In an attempt to determine the mechanisms utilized by Spo0J to facilitate productive chromosome segregation, we have investigated the DNA binding activity of Spo0J. In vivo we find Spo0J associates with several kilobases of DNA flanking its specific binding sites (parS) through a parS-dependent nucleation event that promotes lateral spreading of Spo0J along the chromosome. Using purified components we find that Spo0J has the ability to coat non-specific DNA substrates. These 'Spo0J domains' provide large structures near oriC that could potentially demark, organize or localize the origin region of the chromosome.

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A concepção filosófica do mundo se inicia com os gregos sintetizados por Platão e Aristóteles. Para o primeiro o mundo físico é aparente e para se chegar à verdade é preciso se lembrar das idéias originais que determinam seu significado. Para o segundo as coisas físicas são dirigidas pelas idéias e para entendê-las é preciso a lógica. Durante o helenismo a escola de Alexandria elabora o neoplatonismo, a base da Patrística. Após a queda de Roma, os filósofos bizantinos guardam a herança clássica. A Igreja constrói uma visão neoplatônica da cristandade, a Escolástica. No oriente os persas também sofreram a influência grega. Entre os árabes do Oriente o pensamento neoplatônico orienta filósofos e religiosos de forma que para eles a razão e a fé não se separam. Aí a ciências se desenvolvem na física, na alquimia, na botânica, na medicina, na matemática e na lógica, até serem subjugadas pela doutrina conservadora dos otomanos. Na Espanha mulçumana sem as restrições da teologia, a filosofia de Aristóteles é mais bem compreendida do que no resto do Islã. Também aí todas as ciências se desenvolvem rápido. Mas a Espanha sucumbe aos cristãos. Os árabes e judeus apresentam Aristóteles à Europa Ocidental que elabora um Aristóteles cristão. A matemática, a física experimental, a alquimia e a medicina dos árabes influenciam intensamente o Ocidente. Os artesãos constroem instrumentos cada vez mais precisos, os navegadores constroem navios e mapas mais eficientes e minuciosos, os armeiros calculam melhor a forma de lançamento e pontaria de suas armas e os agrimensores melhor elaboram a medida de sua área de mapeamento. Os artistas principalmente italianos, a partir dos clássicos gregos e árabes, criam a perspectiva no desenho, possibilitando a matematização do espaço. Os portugueses, junto com cientistas árabes, judeus e italianos, concluem um projeto de expansão naval e ampliam os horizontes do mundo. Os pensadores italianos, como uma reação à Escolástica, constroem um pensamento humanista influenciado pelo pensamento grego clássico original e pelos últimos filósofos bizantinos. Por todas essas mudanças se inicia a construção de um novo universo e de um novo método, que viria décadas mais tarde.

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Os objetivos deste trabalho foram determinar a herança da resistência ao complexo de enfezamento em milho e determinar as melhores fontes de resistência entre as linhagens estudadas. Foram realizadas as análises dialélica e médias de gerações em linhagens de milho. Para a análise dialélica, foram cruzadas 12 linhagens de milho, em dialélico parcial. Para análises de médias de gerações, foram cruzadas três linhagens resistentes e quatro suscetíveis, para a obtenção das gerações F1, F2, RCP R e RCP S. Os trabalhos foram conduzidos em Jaboticabal, SP. A incidência de enfezamento foi avaliada no estádio fenológico R3. Efeitos significativos quanto à capacidade geral de combinação e capacidade específica de combinação foram obtidos, o que indicou que, no controle do caráter enfezamentos, estão envolvidos tanto os efeitos aditivos quanto os de dominância. Análises de médias de gerações mostraram a presença de poucos genes envolvidos com o controle da resistência, com predominância de efeitos aditivos, o que permite a seleção de genótipos resistentes. As linhagens L02, L03 e L05 poderão ser utilizadas como fontes de resistência, em futuras combinações híbridas.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Mitochondria are endosymbiotic organelles responsible for energy production in practically every eukaryotic cell. Their uniparental fashion of inheritance, maternally inherited in mammals, and the homogeneity of mitochondrial DNA (mtDNA) within individuals and matrilineages, are biological phenomena that remain unexplained. This paper reviews some of the recent findings on mitochondrial influences on the manner in which embryos develop and how their genotypes are inherited in mammals, with particular emphasis on the genetic bottleneck effect. Animal models carrying a mix of mtDNAs (heteroplasmic) have been produced by karyoplast and cytoplast transplantation to analyze the segregation patterns at different stages during embryogenesis, in fetuses and offspring. Comparisons performed between murine and bovine reveal interesting changes in segregation and replication of transplanted mtDNAs. We have recently obtained Bos indicus and Bos taurus fetuses and calves from embryos reconstructed using enucleated polymorphic oocytes of Bos taurus origin. These and other findings on mitochondrial biology will have important implications in determining the cytoplasmic genotype of clones and in the preservation of endangered breeds and species. (C) 1999 by Elsevier B.V.

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Background: Embryonic stem cells are cells derived from early-stage embryos that are characterized by pluripotency and self-renewal capacity. The in vitro cultured murine embryonic stem cells can indefinitely propagate in an undifferentiated state in the presence of leukemia inhibitory factor (LIF). However, when stimulated, these cells can differentiate into cell lines derived from all three embryonic germ layers. The trichostatin A (TSA) is an epigenetic modifier agent and several studies have used the TSA to stimulate cellular differentiation. However, most of these studies only assessed one TSA concentration. Therefore, this study aimed to evaluate the effects of different TSA concentrations on histone hyperacetylation during in vitro cell differentiation of murine pluripotent embryonic stem cells, cultured with or without LIF, in the quest of to standardize their application on early cultures of embryonic stem cells.Materials, Methods & Results: Undifferentiated murine embryonic stem cells were plated in the presence of different TSA concentrations (0 nM, 15 nm, 50 nM and 100 nM) in the presence or absence of LIF. Thus, the treatments were evaluated in undifferentiated embryonic stem cells cultured in the presence of LIF (Control group: 0 nM LIF(+); Group 15 nM LIF+; Group 50 nM LIF+ and Group 100 nM LIF+), and in embryonic stem cells cultured in the absence of LIF (Control group: 0 nM LIF; Group 15 nM LIF(-); Group 50 nM LIF(-) and Group 100 nM LIF-). Treatment with TSA was performed for 24 h. After that the medium was replaced with fresh medium without TSA. Samples were collected at 0, 12, 24, 36 and 48 h after the beginning of the experiment. Three replicates were performed in each experimental group. The relative amount of Histone H3 lysine 9 acetylation was analyzed in all groups, as well as the cell proliferation in the embryonic stem cells cultured in the presence of LIF. In the control group (0 nM), the absence of LIF resulted in higher levels (P < 0.05) of H3lys9ac compared to the cultures supplemented with LIF. In the embryonic stem cells cultured in the presence of LIF, the 50 nM and 100 nM treatments resulted in higher levels (P < 0.05) of H3lys9ac when compared with 0 nM and 15 nM treatments. Evaluating the Hoechst area in the 0 nM group, it was observed that the number of cells increased (P < 0.05) according to the time of culture. Treatment with 15 nM also reflected a similar distribution, but the Hoechst area in 15 nM group was lower (P < 0.05) at 24 and 48h when compared to the observed in the control group. In the 100 nM treatment, was observed that the area of Hoechst was lower (P < 0.05) to that obtained in the control group at 12, 24 and 48h. In addition, it was observed that treatment with TSA induces greater cellular differentiation when compared to control groups in stem cells cultured in the presence of LIF as well as in the absence of LIF.Discussion: In the present study it was observed that TSA treatment increased the levels of histone acetylation in murine embryonic stem cells at a 50 nM concentration, making it possible to reduce the concentration recommended in the literature (100 nM). In addtion, it was concluded that the lower TSA concentrations utilized (15 nm and 50 nM) was less harmful to cellular proliferation than the 100 nM TSA concentration.