Selective C-Rel Activation via Malt1 Controls Anti-Fungal TH-17 Immunity by Dectin-1 and Dectin-2

C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of TH1 and TH-17 cellular responses. Fungal recognition by dectin-1 on human dendritic cells engages the CARD9-Bcl10-Malt1 module to activate NF-κB. Here we demonstrate that Malt1 recruitment is pivotal to TH-17 immunity by selective activation of NF-κB subunit c-Rel, which induces expression of TH-17-polarizing cytokines IL-1β and IL-23p19. Malt1 inhibition abrogates c-Rel activation and TH-17 immunity to Candida species. We found that Malt1-mediated activation of c-Rel is similarly essential to induction of TH-17-polarizing cytokines by dectin-2. Whereas dectin-1 activates all NF-κB subunits, dectin-2 selectively activates c-Rel, signifying a specialized TH-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. Thus, dectin-1 and dectin-2 control adaptive TH-17 immunity to fungi via Malt1-dependent activation of c-Rel

A Combination of Independent Transcriptional Regulators Shapes Bacterial Virulence Gene Expression during Infection

Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS) suggested that the transcriptional regulator catabolite control protein A (CcpA) influences many of the same genes as the control of virulence (CovRS) two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both ΔccpA and ΔcovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, ΔccpA and ΔcovRΔccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the ΔccpA and ΔcovRΔccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection

SOCIAL NETWORK DYNAMICS OF QUALITY ENHANCEMENT INITIATIVES IN THE COMMUNITY COLLEGE SETTING : STRATEGIC CHOICE AND EMERGENT CHANGE

This study used social network analysis to examine the strategic and emergent dynamics of externally mandated quality enhancement initiatives in the community college setting. The theoretical context for this study relies on complex adaptive systems theory to anticipate that when institutions confront new demands from their external environment, they will employ emergent and/or strategic approaches to adaptation. Three community colleges in the Southeast were selected as research sites. Each of these colleges was at a different point in implementing a quality enhancement initiative as part of the decennial reaffirmation of accreditation cycle with their regional accrediting agency. Social network analysis was conducted using an own-tie survey instrument. An own-tie survey was generated for each research site based on a roster of individuals who had formal involvement with their college’s quality enhancement initiative in the previous year. Data collected from the own-tie surveys were analyzed using the UCINET program (Borgatti, Everett, & Freeman, 2002) for three complete network measures (network density, core-periphery, and external-internal index) and three individual network measures (total connections, eigenvector centrality, and boundary spanner). These measures were then used to identify three informants representing diverse network positions from each research site for semi-structured interviews (Daly & Finnigan, 2010). These interviews asked informants to describe the network dynamics they perceived for their quality enhancement initiatives as well as the extent to which these dynamics were strategic or emergent in nature. This study’s findings suggest that quality enhancement initiatives are characterized by primarily strategic dynamics. A likely explanation for this is the data collection and assessment emphasis typical of externally mandated quality enhancement initiatives. Theoretical, methodological, and practical implications of this study’s findings are also discussed

Riscos biomecânicos posturais em trabalhadores de uma serraria Biomechanical risks in sawmill worker postures

Os trabalhadores em serrarias estão sujeitos a riscos biomecânicos advindos das posturas adotadas durante suas atividades laborais. Este trabalho visou avaliar as posturas adotadas por esses trabalhadores por meio do método de avaliação rápida do corpo inteiro (REBA, rapid entire body assessment), buscando detectar e classificar os riscos biomecânicos. Participaram 15 trabalhadores do setor de produção de uma serraria em João Pessoa, PB, do sexo masculino, com idade média de 44±10,9), avaliando-se quatro posturas: flexão anterior do tronco com levantamento de carga, agachamento profundo, flexão ântero-lateral do tronco e corpo estendido para mover uma prensa. Sintomas musculoesqueléticos foram identificados no mapa corporal de Corlett. Um questionário semi-estruturado levantou os dados demográficos, ambientais e as funções executadas. Pelo REBA, a flexão anterior de tronco apresentou nível de risco muito alto e as posturas de agachamento profundo, flexão ântero-lateral do tronco e movimento do corpo em extensão, nível de risco alto. Uma alta proporção (73,3%) deles queixaram-se de dor ou desconforto na coluna e 26,8% na região dos ombros. Considerando os níveis de riscos apresentados, requerem-se intervenções ergonômicas preventivas no posto de trabalho para adoção de posturas que melhor propiciem a execução das atividades com menor risco à saúde do trabalhador.<br>Workers in sawmills are exposed to biomechanical risks due to the postures adopted during their activities. The purpose here was to assess postures adopted by these workers by using the rapid entire body assessment (REBA), in order to detect and classify possible biomechanical risks. Fifteen male workers from the production section of a sawmill in João Pessoa, PB (mean age 44±10.9 years old) were assessed as to the postures adopted at work. A semi-structured questionnaire collected demographic and environmental data as well as functions in the workplace. Musculoskeletal symptoms were identified using Corlett's body map. Four postures were evaluated: anterior trunk flexion with weight lifting, deep crouching, anterior trunk flexion with lateral inclination and extended body to move a press. The REBA method showed a very high risk level for the anterior trunk flexion; the other postures - deep crouching, anterior trunk flexion with lateral inclination, and extended body to move a press - were shown to bear a high risk level. Accordingly, 73.3% of the workers complained of back pain or discomfort and 26.8% of pain in the shoulder area. Considering the risk levels assessed, there is a need for ergonomic and preventive interventions in the workplace so that workers adopt postures that best suit their work activities with lesser risk to their health