61 research outputs found

    DET1-mediated degradation of a SAGA-like deubiquitination module controls H2Bub homeostasis

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    DE-ETIOLATED 1 (DET1) is an evolutionarily conserved component of the ubiquitination machinery that mediates the destabilization of key regulators of cell differentiation and proliferation in multicellular organisms. In this study, we provide evidence from Arabidopsis that DET1 is essential for the regulation of histone H2B monoubiquitination (H2Bub) over most genes by controlling the stability of a deubiquitination module (DUBm). In contrast with yeast and metazoan DUB modules that are associated with the large SAGA complex, the Arabidopsis DUBm only comprises three proteins (hereafter named SGF11, ENY2 and UBP22) and appears to act independently as a major H2Bub deubiquitinase activity. Our study further unveils that DET1-DDB1-Associated-1 (DDA1) protein interacts with SGF11 in vivo, linking the DET1 complex to light-dependent ubiquitin-mediated proteolytic degradation of the DUBm. Collectively, these findings uncover a signaling path controlling DUBm availability, potentially adjusting H2Bub turnover capacity to the cell transcriptional status

    Sobrevida em pacientes com câncer de cólo de útero: acesso e oportunidades de tratamento no serviço público

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    -Introdução: o câncer de colo de útero é o segundo tipo mais comum de câncer entre as mulheres, responsável por aproximadamente 234.000 óbitosem países em desenvolvimento, sendo a maioria dos casos diagnosticados com doença localmente avançada ou metastática. Os principais fatoresde risco para o desenvolvimento do câncer de colo de útero as infecções ginecológicas, principalmente pelo Papiloma Vírus Humano (HPV), aprecocidade no início da vida sexual, múltiplos parceiros, o uso de contraceptivos orais, tabagismo e a ausência de regularidade do examepreventivo. Entre as principais estratégias utilizadas em Saúde Coletiva para o controle da doença na população, destacam-se as medidas deprevenção primária como a educação em saúde e o uso de preservativos, e a prevenção secundária realizada por meio da detecção precoce docâncer cervical através da realização regular do exame de Papanicolaou (exame preventivo). As opções de tratamento para mulheres diagnosticadascom câncer de colo de útero serão definidas de acordo com o tamanho do tumor, estadiamento, histologia e risco de envolvimento de linfonodos. Aabordagem terapêutica do câncer de colo uterino pode envolver cirurgia, radioterapia, quimioterapia ou uma associação destas modalidades detratamento.Métodos: Para a coleta dos dados foi utilizada uma ficha padronizada, que foi aplicada aos prontuários dos hospitais e das clínicas de Juiz de Foraque oferecem tratamento oncológico. As variáveis de interesse foram: idade (em anos); escolaridade; variáveis sócio-econômicas; tipo histológico;estadiamento, de acordo com a classificação TNM (National Cancer Institute, 2004) e o esquema de tratamento realizado. O estudo envolveupacientes portadoras de câncer de colo de útero, diagnosticadas entre janeiro de 2000 e dezembro de 2002, e assistidas em todos os serviços deoncologia (hospitais e clínicas) da rede pública e privada do município de Juiz de Fora.Resultados: Foram analisados 35 prontuários dos quais a maior parte das pacientes, 22,7% tinha entre 56 e 60 anos ao diagnóstico. 30,5% daspacientes eram analfabetas. Dos sintomas que levaram a paciente a procurar atendimento os principais apurados foram: secreção transvaginal(34,8%), seguido de sangramento (30,4) e dor pélvica (26,1%). Quanto às modalidades terapêuticas, 21,7% das pacientes receberam radioterapiaisolada, 8,7% receberam quimioterapia isolada. As demais pacientes receberam terapias combinadas. Conclusão: O câncer de colo de útero é um problema de saúde pública em países em desenvolvimento, o que inclui o Brasil, e deve receber grandeatenção dos programas de saúde publica para o seu diagnóstico precoce e erradicação dos fatores de risco

    Sexual health (excluding reproductive health, intimate partner violence and gender-based violence) and COVID-19: a scoping review

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    OBJECTIVES: The COVID-19 pandemic has exposed and exacerbated existing socioeconomic and health disparities, including disparities in sexual health and well-being. While there have been several reviews published on COVID-19 and population health disparities generally-including some with attention to HIV-none has focused on sexual health (ie, STI care, female sexual health, sexual behaviour). We have conducted a scoping review focused on sexual health (excluding reproductive health (RH), intimate partner violence (IPV) and gender-based violence (GBV)) in the COVID-19 era, examining sexual behaviours and sexual health outcomes. METHODS: A scoping review, compiling both peer-reviewed and grey literature, focused on sexual health (excluding RH, IPV and GBV) and COVID-19 was conducted on 15 September 2020. Multiple bibliographical databases were searched. Study selection conformed to Joanna Briggs Institute (JBI) Reviewers' Manual 2015 Methodology for JBI Scoping Reviews. We only included English-language original studies. RESULTS: We found that men who have sex with men may be moving back toward pre-pandemic levels of sexual activity, and that STI and HIV testing rates seem to have decreased. There was minimal focus on outcomes such as the economic impact on sexual health (excluding RH, IPV and GBV) and STI care, especially STI care of marginalised populations. In terms of population groups, there was limited focus on sex workers or on women, especially women's sexual behaviour and mental health. We noticed limited use of qualitative techniques. Very few studies were in low/middle-income countries (LMICs). CONCLUSIONS: Sexual health research is critical during a global infectious disease pandemic and our review of studies suggested notable research gaps. Researchers can focus efforts on LMICs and under-researched topics within sexual health and explore the use of qualitative techniques and interventions where appropriate

    Arabidopsis S2Lb links AtCOMPASS-like and SDG2 activity in H3K4me3 independently from histone H2B monoubiquitination.

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    The functional determinants of H3K4me3, their potential dependency on histone H2B monoubiquitination, and their contribution to defining transcriptional regimes are poorly defined in plant systems. Unlike in Saccharomyces cerevisiae, where a single SET1 protein catalyzes H3K4me3 as part of COMPlex of proteins ASsociated with Set1 (COMPASS), in Arabidopsis thaliana, this activity involves multiple histone methyltransferases. Among these, the plant-specific SET DOMAIN GROUP 2 (SDG2) has a prominent role. We report that SDG2 co-regulates hundreds of genes with SWD2-like b (S2Lb), a plant ortholog of the Swd2 axillary subunit of yeast COMPASS. We show that S2Lb co-purifies with the AtCOMPASS core subunit WDR5, and both S2Lb and SDG2 directly influence H3K4me3 enrichment over highly transcribed genes. S2Lb knockout triggers pleiotropic developmental phenotypes at the vegetative and reproductive stages, including reduced fertility and seed dormancy. However, s2lb seedlings display little transcriptomic defects as compared to the large repertoire of genes targeted by S2Lb, SDG2, or H3K4me3, suggesting that H3K4me3 enrichment is important for optimal gene induction during cellular transitions rather than for determining on/off transcriptional status. Moreover, unlike in budding yeast, most of the S2Lb and H3K4me3 genomic distribution does not rely on a trans-histone crosstalk with histone H2B monoubiquitination. Collectively, this study unveils that the evolutionarily conserved COMPASS-like complex has been co-opted by the plant-specific SDG2 histone methyltransferase and mediates H3K4me3 deposition through an H2B monoubiquitination-independent pathway in Arabidopsis

    Künstliche Riesenzellengranulome

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    Ein Beitrag zur Histogenese der Mäusetumoren

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    Complex patterns in phytoplankton and microeukaryote diversity along the estuarine continuum

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    International audienceEstuaries and coastal lagoons are included within the transitional waters category, according to the Water Framework Directive. However, criteria for their differentiation and characterisation are still under discussion and require more research. In particular, detailed observations of biodiversity in more complex transitional and coastal waters are lacking. Microscopic and molecular analyses were therefore used to investigate phytoplankton diversity and spatial community structure, in early spring, along the freshwater-to-marine continuum of the Segura River (Spain), an intensively regulated semiarid basin discharging into the Mediterranean Sea. In addition to the salinity gradient as the major factor determining taxa distribution, influence of multiple anthropogenic and climatic impacting factors (drought, confined waters, irrigation canal) leads to a significant spatial heterogeneity of the aquatic habitat types associated with variations in community composition. Several shifts within the phytoplankton distribution pattern along the continuum are revealed using multivariate analyses. An impressive bloom of the cryptophyte Plagioselmis prolonga occurred in the mixing zone, associated with a typical euryhaline community indicative of eutrophication. The 18S rDNA diversity revealed a microeukaryotic richness including several little-known groups, heterotrophic representatives, and potential parasites. By combining morphological and molecular approaches we revealed the presence of a ‘hidden’ diversity often neglected in traditional surveys
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