42 research outputs found

    R-Smad Competition Controls Activin Receptor Output in Drosophila

    Get PDF
    Animals use TGF-β superfamily signal transduction pathways during development and tissue maintenance. The superfamily has traditionally been divided into TGF-β/Activin and BMP branches based on relationships between ligands, receptors, and R-Smads. Several previous reports have shown that, in cell culture systems, “BMP-specific” Smads can be phosphorylated in response to TGF-β/Activin pathway activation. Using Drosophila cell culture as well as in vivo assays, we find that Baboon, the Drosophila TGF-β/Activin-specific Type I receptor, can phosphorylate Mad, the BMP-specific R-Smad, in addition to its normal substrate, dSmad2. The Baboon-Mad activation appears direct because it occurs in the absence of canonical BMP Type I receptors. Wing phenotypes generated by Baboon gain-of-function require Mad, and are partially suppressed by over-expression of dSmad2. In the larval wing disc, activated Baboon cell-autonomously causes C-terminal Mad phosphorylation, but only when endogenous dSmad2 protein is depleted. The Baboon-Mad relationship is thus controlled by dSmad2 levels. Elevated P-Mad is seen in several tissues of dSmad2 protein-null mutant larvae, and these levels are normalized in dSmad2; baboon double mutants, indicating that the cross-talk reaction and Smad competition occur with endogenous levels of signaling components in vivo. In addition, we find that high levels of Activin signaling cause substantial turnover in dSmad2 protein, providing a potential cross-pathway signal-switching mechanism. We propose that the dual activity of TGF-β/Activin receptors is an ancient feature, and we discuss several ways this activity can modulate TGF-β signaling output

    California Men's Health Study (CMHS): a multiethnic cohort in a managed care setting

    Get PDF
    BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002 – 2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men's Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men's health

    Menstruation and the cycle of poverty: a cluster quasi-randomised control trial of sanitary pad and puberty education provision in Uganda

    Get PDF
    BACKGROUND: Poor menstrual knowledge and access to sanitary products have been proposed as barriers to menstrual health and school attendance. In response, interventions targeting these needs have seen increasing implementation in public and private sectors. However, there has been limited assessment of their effectiveness. // OBJECTIVES: Assess the impact of providing reusable sanitary pads and puberty education on girls’ school attendance and psychosocial wellbeing outcomes. // METHODS: A cluster quasi-randomised controlled trial was conducted across 8 schools, including 1124 girls, in rural Uganda. Schools were allocated to one of four conditions: the provision of puberty education alone; reusable sanitary pads alone; puberty education and reusable sanitary pads; and a control (no intervention). The primary outcome was school attendance. Secondary outcomes reflected psychosocial wellbeing. // RESULTS: At follow-up, school attendance had worsened for girls across all conditions. Per-protocol analysis revealed that this decline was significantly greater for those in the control condition d = 0.52 (95%CI 0.26–0.77), with those in control schools having a 17.1% (95%CI: 8.7–25.5) greater drop in attendance than those in any intervention school. There were no differences between the intervention conditions. High rates of school drop-out and transfer meant the trial suffered from substantial participant drop-out. Intention-to-treat analyses using two different imputation strategies were consistent with the main results, with mean differences of 5.2% attendance in best-case and 24.5% in worst-case imputations. Results were robust to adjustments for clustering. There was no impact of the interventions on girls’ self-reported shame or insecurity during menstruation. // CONCLUSION: Results of the trial support the hypothesised positive impact of providing sanitary pads or puberty education for girls’ school attendance in a developing country context. Findings must be interpreted with caution in light of poor participant retention, intervention fidelity, and the attendance measures used

    Divergent Roles of Clock Genes in Retinal and Suprachiasmatic Nucleus Circadian Oscillators

    Get PDF
    The retina is both a sensory organ and a self-sustained circadian clock. Gene targeting studies have revealed that mammalian circadian clocks generate molecular circadian rhythms through coupled transcription/translation feedback loops which involve 6 core clock genes, namely Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1 and that the roles of individual clock genes in rhythms generation are tissue-specific. However, the mechanisms of molecular circadian rhythms in the mammalian retina are incompletely understood and the extent to which retinal neural clocks share mechanisms with the suprachiasmatic nucleus (SCN), the central neural clock, is unclear. In the present study, we examined the rhythmic amplitude and period of real-time bioluminescence rhythms in explants of retina from Per1-, Per2-, Per3-, Cry1-, Cry2-, and Clock-deficient mice that carried transgenic PERIOD2::LUCIFERASE (PER2::LUC) or Period1::luciferase (Per1::luc) circadian reporters. Per1-, Cry1- and Clock-deficient retinal and SCN explants showed weakened or disrupted rhythms, with stronger effects in retina compared to SCN. Per2, Per3, and Cry2 were individually dispensable for sustained rhythms in both tissues. Retinal and SCN explants from double knockouts of Cry1 and Cry2 were arrhythmic. Gene effects on period were divergent with reduction in the number of Per1 alleles shortening circadian period in retina, but lengthening it in SCN, and knockout of Per3 substantially shortening retinal clock period, but leaving SCN unaffected. Thus, the retinal neural clock has a unique pattern of clock gene dependence at the tissue level that it is similar in pattern, but more severe in degree, than the SCN neural clock, with divergent clock gene regulation of rhythmic period

    Effects of the Distribution of Female Primates on the Number of Males

    Get PDF
    The spatiotemporal distribution of females is thought to drive variation in mating systems, and hence plays a central role in understanding animal behavior, ecology and evolution. Previous research has focused on investigating the links between female spatiotemporal distribution and the number of males in haplorhine primates. However, important questions remain concerning the importance of spatial cohesion, the generality of the pattern across haplorhine and strepsirrhine primates, and the consistency of previous findings given phylogenetic uncertainty. To address these issues, we examined how the spatiotemporal distribution of females influences the number of males in primate groups using an expanded comparative dataset and recent advances in Bayesian phylogenetic and statistical methods. Specifically, we investigated the effect of female distributional factors (female number, spatial cohesion, estrous synchrony, breeding season duration and breeding seasonality) on the number of males in primate groups. Using Bayesian approaches to control for uncertainty in phylogeny and the model of trait evolution, we found that the number of females exerted a strong influence on the number of males in primate groups. In a multiple regression model that controlled for female number, we found support for temporal effects, particularly involving female estrous synchrony: the number of males increases when females are more synchronously receptive. Similarly, the number of males increases in species with shorter birth seasons, suggesting that greater breeding seasonality makes defense of females more difficult for male primates. When comparing primate suborders, we found only weak evidence for differences in traits between haplorhines and strepsirrhines, and including suborder in the statistical models did not affect our conclusions or give compelling evidence for different effects in haplorhines and strepsirrhines. Collectively, these results demonstrate that male monopolization is driven primarily by the number of females in groups, and secondarily by synchrony of female reproduction within groups

    O impacto odontológico no desempenho diário dos trabalhadores do departamento municipal de limpeza urbana de Porto Alegre, Rio Grande do Sul, Brasil The impact of oral health on daily performance of municipal waste disposal workers in Porto Alegre, Rio Grande do Sul State, Brazil

    No full text
    O objetivo deste estudo foi investigar a prevalência do impacto bucal no desempenho diário em adultos brasileiros. Uma amostra representativa, composta por 276 funcionários do Departamento Municipal de Limpeza Urbana de Porto Alegre, Rio Grande do Sul, Brasil, entre 35 e 44 anos, responderam a entrevista e permitiram a realização do exame clínico. O Oral Impacts on Daily Performances (OIDP) foi utilizado para avaliar o impacto bucal no desempenho diário. Do total de participantes, 73,6% tiveram pelo menos um desempenho diário afetado por problemas odontológicos nos últimos seis meses. O mais afetado foi comer e apreciar a comida (48,6%). O desconforto (40,6%) e a insatisfação com a aparência (31,5%) foram os sintomas mais prevalentes. A falta de dentes (21,7%) e a dor de dente (20,7%) foram as principais causas percebidas de impacto no desempenho diário. O OIDP mostrou-se útil para avaliar os impactos odontológicos nas dimensões físicas, psicológicas e sociais do desempenho diário.<br>This study aimed to investigate the prevalence of oral health impact on daily performance in Brazilian adults. 276 civil servants 35 to 44 years of age from the Public Works and Waste Disposal Department of Porto Alegre, in southern Brazil, were interviewed and clinically examined. Oral Impacts on Daily Performance (OIDP) was used to evaluate the impact of oral health status on daily performance. 73.6% of all subjects had at least one daily performance affected by an oral impact in the previous six months. The most commonly affected performance was eating (48.6%), while the most common symptoms were discomfort (40.6%) and dissatisfaction with one's appearance (31.5%). Missing teeth (21.7%) and toothache (20.7%) were recognized as the main causes of oral impacts on daily performance. OIDP was useful for measuring (physically, psychologically, and socially) the oral impacts on daily performance

    Riscos e agravos à saúde e à vida dos trabalhadores das indústrias madeireiras de Mato Grosso Risks and injuries to the health and life of the workers of the lumber industries of Mato Grosso

    No full text
    Na atual fase de ocupação antrópica da Amazônia, ou desenvolvimento agroindustrial-florestal, o setor da indústria madeireira, um dos pólos da economia do Estado de Mato Grosso, provoca grande impacto negativo no ambiente e na saúde. No estudo foram analisadas as situações de risco de 1.381 indústrias e avaliados 4.381 trabalhadores dos 21.607 que laboravam durante o ano de 2000. Foi observada a precarização do trabalho em todos os locais, em graus variados, demonstrando-se que, quanto mais as indústrias se afastam das sedes dos municípios, pioram as condições de trabalho/salário/saúde. Os resultados apontaram que 11% dos trabalhadores estavam mutilados, outros 25% apresentavam outras seqüelas de acidentes de trabalho e 28% estavam com deformidades de coluna vertebral, dentre outros agravos diagnosticados. A pesquisa apontou para a máxima exploração da força de trabalho, desresponsabilização patronal com as situações de riscos e ainda a insuficiente organização dos trabalhadores e precária regulação e fiscalização do Estado, acarretando desproteção social dos trabalhadores das indústrias madeireiras nessa região, expressando a violência social estrutural dessa ocupação/destruição da Amazônia.<br>In the current phase of anthropoid occupation of the Amazonia, called agro-industrial-forest development, the sector of the lumber industry, one of polar regions of the economy of the state of Mato Grosso provokes great negative impact in the environment and the health. In the study were analyzed the conditions of risk of 1.389 industries and evaluated 4.381 workers of the total of 21.607 that worked during the year of 2000. The precaution of work was observed in all places, in varied degrees, demonstrating that yet, the more the industry is moved away from the headquarters of the cities, the conditions of work, salary and healthy becomes worse. The results had shown that 11% of the workers in active were mutilated to others 25% presented other sequels of industrial accidents and 28% were with column deformities of the vertebral column, amongst other injuries diagnosed. The research pointed with respected to the maximum exploration of the force of the work, irresponsible patron with the situation risks and still the insufficient organization of the workers from the lumber industries of this region, who express the structural social violence of this occupation and destruction of the Amazonia
    corecore