An improved structural characterisation of reduced French bean plastocyanin based on NMR data and local-elevation molecular dynamics simulation

Deriving structural information about a protein from NMR experimental data is still a non-trivial challenge to computational biochemistry. This is because of the low ratio of the number of independent observables to the number of molecular degrees of freedom, the approximations involved in the different relationships between particular observable quantities and molecular conformation, and the averaged character of the experimental data. For example, protein 3 J-coupling data are seldom used for structure refinement because of the multiple-valuedness and limited accuracy of the Karplus relationship linking a 3 J-coupling to a torsional angle. Moreover, sampling of the large conformational space is still problematic. Using the 99-residue protein plastocyanin as an example we investigated whether use of a thermodynamically calibrated force field, inclusion of solvent degrees of freedom, and application of adaptive local-elevation sampling that accounts for conformational averaging produces a more realistic representation of the ensemble of protein conformations than standard single-structure refinement in a non-explicit solvent using restraints that do not account for averaging and are partly based on non-observed data. Yielding better agreement with observed experimental data, the protein conformational ensemble is less restricted than when using standard single-structure refinement techniques, which are likely to yield a picture of the protein which is too rigi

Vitiligo

Vitiligo is a skin disease of unknown etiology that affects 1% of the population. It affects both sexes equally and the mean age at onset is between 10 and 30 years. Some of the factors involved are: emotional or physical stress, mechanical trauma, chemicals such as phenol and certain diseases. Autoimmune diseases, especially of thyroid origin, may be linked to vitiligo. New and emerging therapies have been proposed such as topical immunomodulators, allied to traditional therapies with psoralen and steroids. The most important factor in the therapeutic success depends on the doctor and patient relationship.O vitiligo é doença de pele de causa desconhecida que acomete cerca de 1% da população, comprometendo de modo semelhante homens e mulheres, preferencialmente entre 10 e 30 anos de idade. Alguns fatores precipitantes para essa doença são: estresse físico e emocional, traumas mecânicos e substâncias químicas, como derivados do fenol. Doenças auto-imunes, principalmente as tireoidianas, podem estar associadas ao vitiligo. Novas terapias têm sido propostas, como o uso de imunomoduladores tópicos, aliadas àquelas já consolidadas, como os psoralenos e os corticosteróides; o sucesso terapêutico, entretanto, está estritamente relacionado à qualidade da relação médico/paciente.33535

Vitiligo

Vitiligo is a skin disease of unknown etiology that affects 1% of the population. It affects both sexes equally and the mean age at onset is between 10 and 30 years. Some of the factors involved are: emotional or physical stress, mechanical trauma, chemicals such as phenol and certain diseases. Autoimmune diseases, especially of thyroid origin, may be linked to vitiligo. New and emerging therapies have been proposed such as topical immunomodulators, allied to traditional therapies with psoralen and steroids. The most important factor in the therapeutic success depends on the doctor and patient relationship.O vitiligo é doença de pele de causa desconhecida que acomete cerca de 1% da população, comprometendo de modo semelhante homens e mulheres, preferencialmente entre 10 e 30 anos de idade. Alguns fatores precipitantes para essa doença são: estresse físico e emocional, traumas mecânicos e substâncias químicas, como derivados do fenol. Doenças auto-imunes, principalmente as tireoidianas, podem estar associadas ao vitiligo. Novas terapias têm sido propostas, como o uso de imunomoduladores tópicos, aliadas àquelas já consolidadas, como os psoralenos e os corticosteróides; o sucesso terapêutico, entretanto, está estritamente relacionado à qualidade da relação médico/paciente.Faculdade de Medicina de Jundiaí Serviço de DermatologiaUniversidade Estadual de CampinasClínica StöckliEscola Paulista de Medicina Serviço de DermatologiaFundação ABC Faculdade de MedicinaUNIFESP, EPM, Serviço de DermatologiaSciEL

On the calculation of 3 J αβ-coupling constants for side chains in proteins

Structural knowledge about proteins is mainly derived from values of observables, measurable in NMR spectroscopic or X-ray diffraction experiments, i.e. absorbed or scattered intensities, through theoretically derived relationships between structural quantities such as atom positions or torsional angles on the one hand and observable quantities such as squared structure factor amplitudes, NOE intensities or 3 J-coupling constants on the other. The standardly used relation connecting 3 J-couplings to torsional angles is the Karplus relation, which is used in protein structure refinement as well as in the evaluation of simulated properties of proteins. The accuracy of the simple and generalised Karplus relations is investigated using side-chain structural and 3 J αβ-coupling data for three different proteins, Plastocyanin, Lysozyme, and FKBP, for which such data are available. The results show that the widely used Karplus relations are only a rough estimate for the relation between 3 J αβ-couplings and the corresponding χ1-angle in protein

Acne vulgaris: prevalence and clinical forms in adolescents from São Paulo, Brazil

BACKGROUND: Acne is a common disease in adolescents, but there are no epidemiological data for acne in Brazil. OBJECTIVES: To estimate the prevalence and degree of acne in adolescents from São Paulo and study socio-demographic factors, family history and lifestyle, associated with the disease. METHODS: Cross-sectional study with 452 adolescents aged between 10 and 17 (mean=13.3 years), students from elementary and high school, examined by 3 independent evaluators. RESULTS: 62.4% were female, 85.8% white and 6.4% were aged 14. The prevalence was 96.0% and increased with age - all students over 14 had acne. The most prevalent form of acne was comedonal (61.1%), followed by mild (30.6%) and moderate (7.6%) papular-pustular, which affected mostly the face (97.5%). About half of the adolescents reported family history for acne in mother or father, and 20.6% reported previous treatment for acne. There was a higher chance of presenting non-comedonal acne with increased age (p<0.001). DISCUSSION: The prevalence of acne in adolescents varies widely due to the clinical features and diagnostic methods used. Adolescents whose brothers/sisters had acne (OR=1.7-p=0.027) and those over 13 (OR=8.3-p<0.001), were more likely to have non-comedonal acne. CONCLUSION: This study showed high prevalence of acne in adolescents from São Paulo, predominantly the comedonal form on the face, with a higher chance of presenting non-comedonal acne with increased age.Universidade Federal de São Paulo (UNIFESP)Universidade de Mogi das CruzesFaculdade de Medicina do ABCaff04UNIFESPSciEL

Evaluation of the Dawson College shooting psychological intervention: moving toward a multimodal extensive plan

In 2006, following the shooting at Dawson College, the authorities implemented an intervention plan. This provided an opportunity to analyze the responses to services offered, and afforded a learning opportunity, which led to the proposal of an extensive multimodal short- and long-term psychological plan for future needs. Both quantitative and qualitative data were gathered 18 months after the event, involving the participation of 948 students and staff. Mental health problems and the perception of services offered after the shooting were investigated, using standardized measures. Second, focus groups and individual interviews were conducted among a subgroup of participants (support team members; teachers and employees; students and parents) and permitted to gather data on services received and services required. Individual report of events, the extent of psychological impact and services offered and received were analyzed in terms of the following dimensions: intervention philosophy, training, ongoing offer of services and finally, detection and outreach. A significant incidence of disorders and a high rate of exacerbation of preexisting mental disorders were observed within the 18 months following the shooting. Postimmediate and short-term intervention appeared adequate, but the long-term collective vision toward community support and availability of mental health services were lacking. Lessons learned from this evaluation and other school shootings suggest that preparedness and long-term community responses are often overlooked. A multimodal extensive plan is proposed based on a theoretical model from which interventions strategies could be drawn

Intestinal S100/Calgranulin Expression in Cats with Chronic Inflammatory Enteropathy and Intestinal Lymphoma.

Diagnosing chronic inflammatory enteropathies (CIE) in cats and differentiation from intestinal lymphoma (IL) using currently available diagnostics is challenging. Intestinally expressed S100/calgranulins, measured in fecal samples, appear to be useful non-invasive biomarkers for canine CIE but have not been evaluated in cats. We hypothesized S100/calgranulins to play a role in the pathogenesis of feline chronic enteropathies (FCE) and to correlate with clinical and/or histologic disease severity. This retrospective case-control study included patient data and gastrointestinal (GI) tissues from 16 cats with CIE, 8 cats with IL, and 16 controls with no clinical signs of GI disease. GI tissue biopsies were immunohistochemically stained using polyclonal α-S100A8/A9 and α-S100A12 antibodies. S100A8/A9+ and S100A12+ cells were detected in all GI segments, with few significant differences between CIE, IL, and controls and no difference between diseased groups. Segmental inflammatory lesions were moderately to strongly correlated with increased S100/calgranulin-positive cell counts. Clinical disease severity correlated with S100A12+ cell counts in cats with IL (ρ = 0.69, p = 0.042) and more severe diarrhea with colonic lamina propria S100A12+ cells with CIE (ρ = 0.78, p = 0.021) and duodenal S100A8/A9+ cells with IL (ρ = 0.71, p = 0.032). These findings suggest a role of the S100/calgranulins in the pathogenesis of the spectrum of FCE, including CIE and IL