PIAS1 regulates CP2c localization and active promoter complex formation in erythroid cell-specific α-globin expression

Data presented here extends our previous observations on α-globin transcriptional regulation by the CP2 and PIAS1 proteins. Using RNAi knockdown, we have now shown that CP2b, CP2c and PIAS1 are each necessary for synergistic activation of endogenous α-globin gene expression in differentiating MEL cells. In this system, truncated PIAS1 mutants lacking the ring finger domain recruited CP2c to the nucleus, as did wild-type PIAS1, demonstrating that this is a sumoylation-independent process. In vitro, recombinant CP2c, CP2b and PIAS1 bound DNA as a stable CBP (CP2c/CP2b/PIAS1) complex. Following PIAS1 knockdown in MEL cells, however, the association of endogenous CP2c and CP2b with the α-globin promoter simultaneously decreased. By mapping the CP2b- and CP2c-binding domains on PIAS1, and the PIAS1-binding domains on CP2b and CP2c, we found that two regions of PIAS1 that interact with CP2c/CP2b are required for its co-activator function. We propose that CP2c, CP2b, and PIAS1 form a hexametric complex with two units each of CP2c, CP2b, and PIAS1, in which PIAS1 serves as a clamp between two CP2 proteins, while CP2c binds directly to the target DNA and CP2b mediates strong transactivation

Key mechanisms governing resolution of lung inflammation

Innate immunity normally provides excellent defence against invading microorganisms. Acute inflammation is a form of innate immune defence and represents one of the primary responses to injury, infection and irritation, largely mediated by granulocyte effector cells such as neutrophils and eosinophils. Failure to remove an inflammatory stimulus (often resulting in failed resolution of inflammation) can lead to chronic inflammation resulting in tissue injury caused by high numbers of infiltrating activated granulocytes. Successful resolution of inflammation is dependent upon the removal of these cells. Under normal physiological conditions, apoptosis (programmed cell death) precedes phagocytic recognition and clearance of these cells by, for example, macrophages, dendritic and epithelial cells (a process known as efferocytosis). Inflammation contributes to immune defence within the respiratory mucosa (responsible for gas exchange) because lung epithelia are continuously exposed to a multiplicity of airborne pathogens, allergens and foreign particles. Failure to resolve inflammation within the respiratory mucosa is a major contributor of numerous lung diseases. This review will summarise the major mechanisms regulating lung inflammation, including key cellular interplays such as apoptotic cell clearance by alveolar macrophages and macrophage/neutrophil/epithelial cell interactions. The different acute and chronic inflammatory disease states caused by dysregulated/impaired resolution of lung inflammation will be discussed. Furthermore, the resolution of lung inflammation during neutrophil/eosinophil-dominant lung injury or enhanced resolution driven via pharmacological manipulation will also be considered

Fatores associados à capacidade para o trabalho de trabalhadores do Setor Elétrico Factors associated with labor capacity in electric industry workers

O Setor Elétrico passou por recente processo de reestruturação produtiva com reflexos nas condições e organização do trabalho, podendo comprometer a capacidade para o trabalho. Este estudo objetivou avaliar fatores associados à capacidade para o trabalho junto a 475 trabalhadores de uma empresa do Setor Elétrico no Estado de São Paulo, Brasil. Neste estudo transversal foi realizada análise descritiva e análise de regressão linear múltipla. A média do Índice de Capacidade para o Trabalho (ICT) foi de 41,8 pontos (escala de 7,0 a 49,0 pontos). A análise múltipla mostrou que os fatores que melhor explicaram a variabilidade do ICT foram estresse no trabalho (p < 0,001) e saúde física (p < 0,001 em todas as dimensões). Em outra análise, excluídas as dimensões da saúde, as variáveis associadas ao ICT foram estresse no trabalho (p < 0,001), local de trabalho (p = 0,022), prática de atividade física (p = 0,001), consumo de álcool (p = 0,012) e índice de massa corporal (p < 0,001). Os resultados identificaram aspectos a serem considerados no desenvolvimento de medidas visando a preservação da capacidade para o trabalho, com ênfase no controle do estresse no trabalho e na promoção da saúde.<br>The Brazilian electric utility sector has recently undergone major industrial restructuring, with impacts on working conditions and work organization that could jeopardize the capacity for work. This study aimed to evaluate factors associated with labor capacity in a sample of 475 workers from an electric utility company in the State of São Paulo, Brazil. This cross-sectional study included descriptive and multiple linear regression analyses. The mean labor capacity index (LCI) was 41.8 points (on a scale from 7.0 to 49.0). Multiple regression showed that the factors that best explained LCI variability were work stress (p < 0.001) and physical health (p < 0.001 in all the dimensions). In a separate analysis, excluding all the health dimensions, the variables associated with LCI were work stress (p < 0.001), workplace (p = 0.022), physical activity (p = 0.001), alcohol consumption (p = 0.012), and body mass index (p < 0.001). The results highlighted aspects to be considered when developing measures to protect labor capacity, with an emphasis on stress prevention and health promotion

Diversität : Führung von Menschen mit unterschiedlichem Hintergrund

Mit der zunehmenden Mobilität und Vielfalt von Arbeits- und Lebensformen wächst auch die Vielfalt von Menschen, die mit unterschiedlichen Erfahrungshintergründen und kulturellen Wissensbeständen aufeinandertreffen und zusammenarbeiten. Damit diese Zusammenarbeit gelingen kann, steht besonders die Führung vor der Aufgabe, die Unterschiedlichkeiten zu verstehen und als Ressourcen zu nutzen, aber auch die daraus entstehenden Konfliktpotenziale wahrzunehmen. Unterschiedliche Perspektiven erweitern den kollektiven Denk- und Handlungsraum. Die Rolle der Führung ist es, diesen Raum im Hinblick auf die Ziele der Organisation gemeinsam mit den Mitarbeitenden zu nutzen und sinnhaft zu gestalten