Capillarity-like growth of protein folding nuclei

We analyzed folding routes predicted by a variational model in terms of a generalized formalism of the capillarity scaling theory for 28 two-state proteins. The scaling exponent ranged from 0.2 to 0.45 with an average of 0.33. This average value corresponds to packing of rigid objects.That is, on average the folded core of the nucleus is found to be relatively diffuse. We also studied the growth of the folding nucleus and interface along the folding route in terms of the density or packing fraction. The evolution of the folded core and interface regions can be classified into three patterns of growth depending on how the growth of the folded core is balanced by changes in density of the interface. Finally, we quantified the diffuse versus polarized structure of the critical nucleus through direct calculation of the packing fraction of the folded core and interface regions. Our results support the general picture of describing protein folding as the capillarity-like growth of folding nuclei.Comment: 16 pages,6 figures. Submitted to Proc.Natl.Acad.Sc

Phi-values in protein folding kinetics have energetic and structural components

Phi-values are experimental measures of how the kinetics of protein folding is changed by single-site mutations. Phi-values measure energetic quantities, but are often interpreted in terms of the structures of the transition state ensemble. Here we describe a simple analytical model of the folding kinetics in terms of the formation of protein substructures. The model shows that Phi-values have both structural and energetic components. In addition, it provides a natural and general interpretation of "nonclassical" Phi-values (i.e., less than zero, or greater than one). The model reproduces the Phi-values for 20 single-residue mutations in the alpha-helix of the protein CI2, including several nonclassical Phi-values, in good agreement with experiments.Comment: 15 pages, 3 figures, 1 tabl

Transition states in protein folding kinetics: Modeling Phi-values of small beta-sheet proteins

Small single-domain proteins often exhibit only a single free-energy barrier, or transition state, between the denatured and the native state. The folding kinetics of these proteins is usually explored via mutational analysis. A central question is which structural information on the transition state can be derived from the mutational data. In this article, we model and structurally interpret mutational Phi-values for two small beta-sheet proteins, the PIN and the FBP WW domain. The native structure of these WW domains comprises two beta-hairpins that form a three-stranded beta-sheet. In our model, we assume that the transition state consists of two conformations in which either one of the hairpins is formed. Such a transition state has been recently observed in Molecular Dynamics folding-unfolding simulations of a small designed three-stranded beta-sheet protein. We obtain good agreement with the experimental data (i) by splitting up the mutation-induced free-energy changes into terms for the two hairpins and for the small hydrophobic core of the proteins, and (ii) by fitting a single parameter, the relative degree to which hairpin 1 and 2 are formed in the transition state. The model helps to understand how mutations affect the folding kinetics of WW domains, and captures also negative Phi-values that have been difficult to interpret.Comment: 27 pages, 6 pages, 3 tables; to appear in Biophys.

Folding Pathways of Prion and Doppel

The relevance of various residue positions for the stability and the folding characteristics of the prion protein are investigated by using molecular dynamics simulations of models exploiting the topology of the native state. Highly significant correlations are found between the most relevant sites in our analysis and the single point mutations known to be associated with the arousal of the genetic forms of prion disease (caused by the conformational change from the cellular to the scrapie isoform). Considerable insight into the conformational change is provided by comparing the folding process of prion and doppel (a newly discovered protein) sharing very similar native state topology: the folding pathways of the former can be grouped in two main classes according to which tertiary structure contacts are formed first enroute to the native state. For the latter a single class of pathways leads to the native state. Our results are consistent and supportive of the recent experimental findings that doppel lacks the scrapie isoform and that such remarkably different behavior results from differences in the region containing the two $\beta-$strands and the intervening helix.Comment: 16 pages, 2 tables, 5 figure

Naturally light right-handed neutrinos in a 3-3-1 Model

In this work we show that light right-handed neutrinos, with mass in the sub-eV scale, is a natural outcome in a 3-3-1 model. By considering effective dimension five operators, the model predicts three light right-handed neutrinos, weakly mixed with the left-handed ones. We show also that the model is able to explain the LSND experiment and still be in agreement with solar and atmospheric data for neutrino oscillation.Comment: About 5 pages, no-figure

Taxing the Informal Economy: The Current State of Knowledge and Agendas for Future Research

This paper reviews the literature on taxation of the informal economy, taking stock of key debates and drawing attention to recent innovations. Conventionally, the debate on whether to tax has frequently focused on the limited revenue potential, high cost of collection, and potentially adverse impact on small firms. Recent arguments have increasingly emphasised the more indirect benefits of informal taxation in relation to economic growth, broader tax compliance, and governance. More research is needed, we argue, into the relevant costs and benefits for all, including quasi-voluntary compliance, political and administrative incentives for reform, and citizen-state bargaining over taxation

Conhecimento sobre hipertensão arterial e fatores associados à não adesão à farmacoterapia

OBJECTIVES: to identify the degree of knowledge of people with hypertension concerning the disease and to verify the factors associated with the non-adherence to anti-hypertensive drug therapy. METHOD: Cross sectional study, involving 422 people. Data collection took place at their homes, between December 2011 and March 2012, through interviews using the following instruments: Medication Adherence Questionnaire (MAQ-Q), Medication Regimen Complexity Index (MRCI) and a guide with questions related to sociodemographic profile, satisfaction with healthcare service and knowledge about the disease. RESULTS: 42.6% did not adhere to the drug therapy and 17.7% had poor knowledge about the disease. Factors associated with the non-adherence were: complex drug therapy, poor knowledge about the disease and dissatisfaction with the healthcare service. CONCLUSION: The findings reinforce that the complex drug therapy prescriptions, little knowledge about the disease and dissatisfaction with the healthcare service have influence on the process of non-adherence to anti-hypertensive drug therapy.OBJETIVOS: identificar el nivel de conocimiento de personas con hipertensión arterial acerca de la enfermedad y verificar los factores asociados a la no adhesión a la farmacoterapia antihipertensiva. MÉTODO: estudio transversal realizado en 422 individuos. Los datos fueron recolectados en los domicilios, entre diciembre de 2011 y marzo de 2012, por medio de entrevistas utilizando los instrumentos: Cuestionario de Adhesión a Medicamentos (CAM-Q), Índice de Complejidad de la Farmacoterapia y un guión con preguntas relativas al perfil sociodemográfico, satisfacción con el servicio de salud y conocimiento sobre la enfermedad. RESULTADOS: 42,6% no adherían a la farmacoterapia y 17,7% poseían conocimiento insatisfactorio sobre la enfermedad. Los factores asociados a la no adhesión fueron: farmacoterapia compleja, conocimiento insatisfactorio sobre la enfermedad e insatisfacción con el servicio de salud. CONCLUSIÓN: Los hallazgos refuerzan que prescripciones farmacológicas complejas, poco conocimiento sobre la enfermedad e insatisfacción con el servicio de salud influyen en el proceso de la no adhesión al tratamiento medicamentoso antihipertensivo.OBJETIVOS: identificar o nível de conhecimento de pessoas com hipertensão arterial acerca da doença e verificar os fatores associados à não adesão à farmacoterapia anti-hipertensiva. MÉTODO: estudo transversal, realizado com 422 indivíduos. Os dados foram coletados nos domicílios, entre dezembro de 2011 e março de 2012, por meio de entrevistas, utilizando os instrumentos: Questionário de Adesão a Medicamentos, Índice de Complexidade da Farmacoterapia e um roteiro com questões relativas ao perfil sociodemográfico, satisfação com o serviço de saúde e conhecimento sobre a doença. RESULTADOS: 42,6% não aderiram à farmacoterapia e 17,7% possuíam conhecimento insatisfatório sobre a doença. Os fatores associados à não adesão foram: farmacoterapia complexa, conhecimento insatisfatório sobre a doença e insatisfação com o serviço de saúde. CONCLUSÃO: os achados reforçam que prescrições farmacológicas complexas, pouco conhecimento sobre a doença e insatisfação com o serviço de saúde influenciam no processo de não adesão ao tratamento medicamentoso anti-hipertensivo

Body mass index and dental caries in children and adolescents : a systematic review of literature published 2004 to 2011

The objectiveThe authors undertook an updated systematic review of the relationship between body mass index and dental caries in children and adolescents.MethodThe authors searched Medline, ISI, Cochrane, Scopus, Global Health and CINAHL databases and conducted lateral searches from reference lists for papers published from 2004 to 2011, inclusive. All empirical papers that tested associations between body mass index and dental caries in child and adolescent populations (aged 0 to 18 years) were included.ResultsDental caries is associated with both high and low body mass index.ConclusionA non-linear association between body mass index and dental caries may account for inconsistent findings in previous research. We recommend future research investigate the nature of the association between body mass index and dental caries in samples that include a full range of body mass index scores, and explore how factors such as socioeconomic status mediate the association between body mass index and dental caries.<br /