Multi-Scaled Explorations of Binding-Induced Folding of Intrinsically Disordered Protein Inhibitor IA3 to its Target Enzyme

Biomolecular function is realized by recognition, and increasing evidence shows that recognition is determined not only by structure but also by flexibility and dynamics. We explored a biomolecular recognition process that involves a major conformational change – protein folding. In particular, we explore the binding-induced folding of IA3, an intrinsically disordered protein that blocks the active site cleft of the yeast aspartic proteinase saccharopepsin (YPrA) by folding its own N-terminal residues into an amphipathic alpha helix. We developed a multi-scaled approach that explores the underlying mechanism by combining structure-based molecular dynamics simulations at the residue level with a stochastic path method at the atomic level. Both the free energy profile and the associated kinetic paths reveal a common scheme whereby IA3 binds to its target enzyme prior to folding itself into a helix. This theoretical result is consistent with recent time-resolved experiments. Furthermore, exploration of the detailed trajectories reveals the important roles of non-native interactions in the initial binding that occurs prior to IA3 folding. In contrast to the common view that non-native interactions contribute only to the roughness of landscapes and impede binding, the non-native interactions here facilitate binding by reducing significantly the entropic search space in the landscape. The information gained from multi-scaled simulations of the folding of this intrinsically disordered protein in the presence of its binding target may prove useful in the design of novel inhibitors of aspartic proteinases

Cardiovascular disease prevention in Ghana: feasibility of a faith-based organizational approach

Objective To examine the feasibility of using community health workers (CHWs) to implement cardiovascular disease (CVD) prevention programmes within faith-based organizations in Accra, Ghana. Methods Faith-based organization capacity, human resources, health programme sustainability/barriers and community members’ knowledge were evaluated. Data on these aspects were gathered through a mixed method design consisting of in-depth interviews and focus groups with 25 church leaders and health committee members from five churches, and of a survey of 167 adult congregants from two churches. Findings The delivery of a CVD prevention programme in faith-based organizations by CHWs is feasible. Many faith-based organizations already provide health programmes for congregants and involve non-health professionals in their health-care activities, and most congregants have a basic knowledge of CVD. Yet despite the feasibility of the proposed approach to CVD prevention through faith-based organizations, sociocultural and health-care barriers such as poverty, limited human and economic resources and limited access to health care could hinder programme implementation. Conclusion The barriers to implementation identified in this study need to be considered when defining CVD prevention programme policy and planning

Fatores de risco associados à obesidade e sobrepeso em crianças em idade escolar Factores de riesgo asociados a la obesidad y sobrepeso de niños en edad escolar Risk factors associated with obesity and overweight in school children

OBJETIVO: Analisar os fatores de risco associados à obesidade e sobrepeso em crianças de ambos os sexos em idade escolar. MÉTODO: Pesquisa do tipo survey realizada com 162 crianças matriculadas no ensino fundamental I de uma escola pública da cidade de São Paulo. A coleta de dados foi obtida por meio de um formulário contendo dados antropométricos e sobre os hábitos alimentares. Os dados foram analisados por meio de estatística inferencial. RESULTADOS: As crianças com sobrepeso e obesidade representaram 38,2% da amostra. Os fatores de risco associados relevantes foram o consumo de refrigerantes e a prática de atividade física. CONCLUSÃO: O estudo evidencia a presença de sobrepeso e obesidade entre as crianças estudadas, confirmando a tendência mundial de mudança no perfil nutricional da população em geral.<br>OBJETIVO: Analizar los factores de riesgo asociados a la obesidad y sobrepeso en niños en edad escolar de ambos los sexos. MÉTODO: Estudio do tipo survey realizado con 162 niños de una escuela pública en la cuidad de São Paulo, SP, Brasil. La regida de datos fue obtenida por medio de un formulario con datos antropométricos y sobre las costumbres alimentarias. Los datos fueran analizados por el uso de estadística de inferencia. RESULTADOS: Los niños con obesidad y sobrepeso representaron 38,2% de la amuestra. Los factores de riesgo asociado fueran el consumo de refrigerantes del tipo soda y la práctica de ejercicios físicos. CONCLUSIÓN: El estudio evidenció la presencia de obesidad y sobrepeso en la muestra bajo estudio, confirmando la tendencia mundial de cambio en el perfil nutricional da la población en general.<br>PURPOSE: To analyze the risk factors associated with obesity and overweight in school children of both sex. METHOD: Survey study carried out with 162 children students from a public school in the city of São Paulo, SP, Brazil. Data collection was obtained by means of a form with anthropometric data and about dietary habits. Data were analyzed using inferential statistics. RESULTS: Obese and over weighted children represent 38.2% of the sample. Relevant associated risk factor was the use of soda beverages and the practice of physical exercises. CONCLUSION: The study highlighted the presence of obesity and overweight in the sample under study, confirming the global trend of change in the nutritional profile of the population in general