Androgênios e o trato reprodutor masculino: ações clássicas e perspectivas atuais

Androgens are steroid hormones that play key roles in the development and maintenance of male phenotype and reproductive function. These hormones also affect the function of several non-reproductive organs, such as bone and skeletal muscle. Endogenous androgens exert most of their effects by genomic mechanisms, which involve hormone binding to the androgen receptor (AR), a ligand-activated transcription factor, resulting in the modulation of gene expression. AR-induced non-genomic mechanisms have also been reported. A large number of steroidal and non-steroidal AR-ligands have been developed for therapeutic use, including the treatment of male hypogonadism (AR agonists) and prostate diseases (AR antagonists), among other pathological conditions. Here, the AR gene and protein structure, mechanism of action and AR gene homologous regulation were reviewed. The AR expression pattern, its in vivo regulation and physiological relevance in the developing and adult testis and epididymis, which are sites of sperm production and maturation, respectively, were also presented.Os androgênios são hormônios esteroides com papel fundamental no desenvolvimento e na manutenção do fenótipo masculino e da função reprodutiva. Esses hormônios também afetam a função de diversos tecidos não reprodutivos, como, por exemplo, o ósseo e musculoesquelético. Os androgênios endógenos exercem a maioria de suas funções por mecanismo genômico, que envolve a ligação do hormônio ao receptor de androgênio (RA), um fator de transcrição ativado por ligante, o que resulta no controle da expressão gênica. Mecanismos não genômicos também têm sido associados aos efeitos induzidos pelo RA. Um grande número de ligantes do RA, esteroidais e não esteroidais, tem sido desenvolvido para o uso terapêutico, incluindo o tratamento do hipogonadismo masculino (agonistas do RA) e de doenças da próstata (antagonistas do RA), entre outras condições patológicas. Neste trabalho, foram discutidas as características estruturais básicas do RA (gene e proteína), os mecanismos de ação desse receptor, bem como aspectos relacionados à sua regulação homóloga. O padrão de expressão do RA, sua regulação in vivo e relevância fisiológica durante o desenvolvimento e a vida adulta na função do testículo e epidídimo, tecidos responsáveis pela produção e maturação de espermatozoides, respectivamente, também foram discutidos.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de FarmacologiaUNIFESP, EPM, Depto. de FarmacologiaSciEL

Disparate dispersal limitation in Geomalacus slugs unveiled by the shape and slope of the genetic–spatial distance relationship

Long‐term dispersal ability is a key species’ trait constraining species ranges and thus large‐scale biodiversity patterns. Here we infer the long‐term dispersal abilities of three Geomalacus (Gastropoda, Pulmonata) species from their range‐wide genetic–spatial distance relationships. This approach follows recent advances in statistical modelling of the analogous pattern at the community level: the distance decay in assemblage similarity. While linear relationships are expected for species with high long‐term dispersal abilities, asymptotic relationships are expected for those with more restricted mobility. We evaluated three functional forms (linear, negative exponential and power‐law) for the relationship between genetic distance (computed from mitochondrial cox1 sequences, n = 701) and spatial distance. Range fragmentation at present time and at the Last Glacial Maximum was also estimated based on the projection of climatic niches. The power‐law function best fit the relationship between genetic and spatial distances, suggesting strong dispersal limitation and long‐term population isolation in all three species. However, the differences in slope and explained variance pointed to disparities in dispersal ability among these weak dispersers. Phylogeographic patterns of Geomalacus species are thus largely driven by the same major process (i.e. dispersal limitation), operating at different strengths. This strong dispersal limitation results in geographic clustering of genetic diversity that makes these species highly vulnerable to genetic erosion due to climate changThe authors were supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF) through grant CGL2016‐76637‐P and fellowship IJCI‐2014‐20881 to CG‐RS

A feature selection approach for identification of signature genes from SAGE data

<p>Abstract</p> <p>Background</p> <p>One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements.</p> <p>Results</p> <p>A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology.</p> <p>Conclusion</p> <p>The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers.</p

Healthy lifestyle behaviors and the periodicity of mammography screening in brazilian women

INTRODUCTION: Certain behaviors have been associated with health promotion, including mammography screening, in women worldwide. OBJECTIVE: The objective of this study was to determine whether there is an association between the periodicity of mammography screening and healthy lifestyle behaviors in Brazilian women employed at a public university in Bahia, Brazil. METHODS: A total of 635 women of 50–69 years of age at the time of the interview, from the Brazilian Longitudinal Study of Adult Health cohort who were resident in Bahia, participated in the study. Data were collected using a multidimensional questionnaire that included questions on participants’ sociodemographic characteristics and health-related behaviors (smoking, alcohol consumption, leisure-time physical activity and diet) and another questionnaire that dealt with risk factors and breast cancer screening. Measures of association were calculated using simple and multivariate logistic regression. RESULTS: The practice of physical activity, not smoking, moderate alcohol consumption and a healthy diet were the health behaviors most adopted by the women who had last had a mammogram ⩽2 years previously (which is in line with the interval recommended by the Brazilian Ministry of Health). A statistically significant association was found between a lapse of ⩾3 years since last undergoing mammography screening and excessive alcohol consumption, while a borderline association was found between the same screening interval and leisure-time physical inactivity. CONCLUSION: There was an association between lifestyle risk behaviors and a longer time interval between mammography screenings. The present results contribute to the debate on the use of mammography, lifestyle behaviors and health promotion among women

Isometries, submetries and distance coordinates on Finsler manifolds

This paper considers fundamental issues related to Finslerian iso- metries, submetries, distance and geodesics. It is shown that at each point of a Finsler manifold there is a distance coordinate system. Us- ing distance coordinates, a simple proof is given for the Finslerian version of the Myers-Steenrod theorem and for the differentiability of Finslerian submetries

Working from home, work-time control and mental health: results from the brazilian longitudinal study of adult health (ELSA-Brasil)

This cross-sectional study investigated the association between work-time control (WTC), independently and in combination with hours worked (HW), and four mental health outcomes among 2,318 participants of the Longitudinal Study of Adult Health (ELSA-Brasil) who worked from home during the COVID-19 pandemic. WTC was assessed by the WTC Scale, and mental health outcomes included depression, anxiety, stress (measured by the Depression, Anxiety and Stress Scale, DASS-21), and self-rated mental health. Logistic regression models were used to determine odds ratios (ORs) and 95% confidence intervals (CIs). Among women, long HW were associated with stress (OR = 1.56; 95% CI = 1.11–2.20) and poor self-rated mental health (OR = 1.64; 95% CI = 1.13–2.38), whereas they were protective against anxiety among men (OR = 0.59; 95% CI = 0.37–0.93). In both sexes, weak WTC was associated with all mental health outcomes. Among women, the long HW/weak WTC combination was associated with all mental health outcomes, and short HW/weak WTC was associated with anxiety and stress. Among men, long HW/strong WTC was protective against depression and stress, while short HW/strong WTC and short HW/weak WTC was associated with all mental health outcomes. In both sexes, weak WTC, independently and in combination with HW, was associated with all mental health outcomes. WTC can improve working conditions, protect against mental distress, and fosterwork-life balance for those who work from home

Different diversity-dependent declines in speciation rate unbalances species richness in terrestrial slugs

Two genera of terrestrial slugs (Arion and Geomalacus) display a striking disproportion in species richness in the Iberian Peninsula. While there are 17 Iberian endemic species in Arion, morphological criteria only recognize four species within Geomalacus. Sequence data were used to test whether these differences could result from: (1) cryptic diversity within Geomalacus; (2) an earlier origin for Arion (older clades are expected to accumulate more species); (3) distinct patterns of diversification rates (higher initial speciation rates in Arion), and (4) some combination of the above factors (e.g., an older clade with higher speciation rates). Species delimitation tests based on mitochondrial and nuclear data revealed eight cryptic lineages within Geomalacus that lessened the asymmetry; nevertheless, the disparity required further investigation. No meaningful differences in crown group ages of each recovered clade were found. Regardless the different premises of the two equally plausible diversification models (similar initial speciation rates vs. higher initial speciation rates in Geomalacus), both coincide on diversity-dependent diversification for the two groups but weaker rate declines in Arion best explains the observed asymmetry in species richness. Also, the broader environmental tolerance combined with a faster dispersal and wider distribution may have represented an evolutionary advantage for Arion.FCT (Fundacao para a Ciencia e Tecnologia, Portugal) [SFRH/BPD/109685/2015]; FSE (Fundo Social Europeu). [SFRH/BD/30024/2006]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Review on computational methods for Lyapunov functions

Lyapunov functions are an essential tool in the stability analysis of dynamical systems, both in theory and applications. They provide sufficient conditions for the stability of equilibria or more general invariant sets, as well as for their basin of attraction. The necessity, i.e. the existence of Lyapunov functions, has been studied in converse theorems, however, they do not provide a general method to compute them. Because of their importance in stability analysis, numerous computational construction methods have been developed within the Engineering, Informatics, and Mathematics community. They cover different types of systems such as ordinary differential equations, switched systems, non-smooth systems, discrete-time systems etc., and employ di_erent methods such as series expansion, linear programming, linear matrix inequalities, collocation methods, algebraic methods, set-theoretic methods, and many others. This review brings these different methods together. First, the different types of systems, where Lyapunov functions are used, are briefly discussed. In the main part, the computational methods are presented, ordered by the type of method used to construct a Lyapunov function