Structural transitions in full-length human prion protein detected by xenon as probe and spin labeling of the N-terminal domain

Fatal neurodegenerative disorders termed transmissible spongiform encephalopathies (TSEs) are associated with the accumulation of fibrils of misfolded prion protein PrP. The noble gas xenon accommodates into four transiently enlarged hydrophobic cavities located in the well-folded core of human PrP(23-230) as detected by [H-1, N-15]-HSQC spectroscopy. In thermal equilibrium a fifth xenon binding site is formed transiently by amino acids A120 to L125 of the presumably disordered N-terminal domain and by amino acids K185 to T193 of the well-folded domain. Xenon bound PrP was modelled by restraint molecular dynamics. The individual microscopic and macroscopic dissociation constants could be derived by fitting the data to a model including a dynamic opening and closing of the cavities. As observed earlier by high pressure NMR spectroscopy xenon binding influences also other amino acids all over the N-terminal domain including residues of the AGAAAAGA motif indicating a structural coupling between the N-terminal domain and the core domain. This is in agreement with spin labelling experiments at positions 93 or 107 that show a transient interaction between the N-terminus and the start of helix 2 and the end of helix 3 of the core domain similar to that observed earlier by Zn2+-binding to the octarepeat motif

Correlation between Moberg Pick-Up test and sensation threshold test after median nerve reconstruction

Functional assessment of sensitivity is essential to analyzing the status, recovery, and effectiveness of the treatment program for patients who have suffered losses due to physical and/or sensory disability after peripheral nerve injuries. Such losses of sensation lead to a significant loss of hand function. Objective: The purpose of the present study was to establish a correlation between functional and sensory threshold tests after a peripheral nerve lesion in the hand. Method: Fourteen men aged 18 to 40 years, who had bruises and cut injuries at the volar region of the wrist resulting in median nerve lesion, were selected for study. All the subjects were at least 1-year post-surgery. An esthesiometer SORRI® and a modified Moberg pick-up test were used. The test was divided into two phases, one with eyes open and the other with eyes closed. Also, the same test was performed by two different examiners. It was a “blinded” test that was performed three times, being repeated by the examiners according to a random sequence kept during the entire evaluation. Mean age and standard deviation were obtained during analysis in which Pearson’s coefficient was calculated and the non-parametric Mann-Whitney test was applied at 5% significance. Results: The mean age was 27.14 years with a standard deviation of 6.43 years, with the lesions being more frequently seen in men aged 21 to 30 years. Also, 64% of the cases involved lesion of the dominant hand. Pearson’s coefficient (r) regarding the correlation between sensory threshold test and Moberg pick-up test ranged from 0.5 to 0.7, which was statistically significant. Confidence intervals and p-values obtained from the Mann-Whitney test showed no statistically significant differences. Conclusion: One can conclude, therefore, that despite lacking standardized measures, the Moberg pick-up test correlated with the functional test. However, further studies are needed to support validation and reliability of the two methods.A avaliação funcional da sensibilidade é essencial para analisar o estado, recuperação, e efetividade do programa de tratamento em pacientes que sofreram perdas decorrentes de deficiência motora e/ou sensitiva, após lesões nervosas periféricas. Estas lesões geram a interrupção das sensações ocasionando a perda da sensibilidade e uma significante perda funcional da mão. Objetivo: O objetivo deste estudo foi correlacionar o teste funcional Pick-Up de Moberg com o teste de limiar sensitivo Estesiômetro SORRI® na reconstrução do nervo mediano. Método: Foram analisados 14 homens com idade entre 18 e 40 anos que sofreram ferimento corto-contuso na região volar do punho e tratamento cirúrgico há pelo menos um ano de pós-operatório. Foram utilizados para a avaliação da sensibilidade cutânea o Estesiômetro SORRI® e o teste Pick-Up de Moberg modificado, no qual a avaliação foi dividida em duas fases, olhos abertos e fechados, ambas realizadas com a mão dominante e não dominante, e em duas etapas com diferentes avaliadores, sendo repetidas três vezes em cada mão. A sequência dos avaliadores foi sorteada e mantida durante toda a avaliação. Na análise dos dados foi utilizado o coeficiente de Pearson e aplicado o teste não-paramétrico de Mann-Whitney com o nível de significância α = 0,05. Resultados: A média da idade foi de 27,14 anos (± 6,43), com maior frequência entre 21 a 30 anos sendo que 64% apresentaram lesão na mão dominante. O coeficiente de Pearson (r) entre o Estesiômetro e o Pick-Up foi entre 0,5 e 0,7, com p-valor < 0,05. Os intervalos de confiança e p-valores dos testes de Mann-Whitney não indicaram diferenças estatisticamente significantes. Conclusão: Apesar do teste Pick-Up de Moberg não possuir medidas padronizadas, na amostra estudada pode-se concluir que existe correlação entre o teste funcional e o teste de limiar sensitivo. Novos estudos são necessários para a validação e confiabilidade de ambos os métodos

The complete genome sequence of Chromobacterium violaceum reveals remarkable and exploitable bacterial adaptability

Chromobacterium violaceum is one of millions of species of free-living microorganisms that populate the soil and water in the extant areas of tropical biodiversity around the world. Its complete genome sequence reveals (i) extensive alternative pathways for energy generation, (ii) ≈500 ORFs for transport-related proteins, (iii) complex and extensive systems for stress adaptation and motility, and (iv) wide-spread utilization of quorum sensing for control of inducible systems, all of which underpin the versatility and adaptability of the organism. The genome also contains extensive but incomplete arrays of ORFs coding for proteins associated with mammalian pathogenicity, possibly involved in the occasional but often fatal cases of human C. violaceum infection. There is, in addition, a series of previously unknown but important enzymes and secondary metabolites including paraquat-inducible proteins, drug and heavy-metal-resistance proteins, multiple chitinases, and proteins for the detoxification of xenobiotics that may have biotechnological applications

Estudo estrutural por RMN do peptídeo policatiônico polybine I de veneno da vespa social Polybia paulista

Os venenos de vespas socias são ricos em peptídeos biologicamente ativos que causam alguns males ao ser humano como: dores prolongadas, edema, eritema, reações alérgicas e sistêmicas. Possuem em sua composição vários tipos de aminas biogênicas, peptídeos e proteínas. Dentre eles, o que chama mais atenção na atividade farmacológica do veneno são os peptídeos policatiônicos. São diversas as atividades desses peptídeos como: neurotoxicidade, hemólise, liberação de histamina de mastócitos e antibatericida. Neste trabalho, foram estudados peptídeos catiônicos da família Polybine, sintetizados pelo Departamento de Biologia, Unesp, Rio Claro-SP. Os peptídeos Polybine I e II foram sintetizados na forma acetilada e não-acetilada para o estudo detalhado da sua estrutura. Com este objetivo, utilizamos as técnicas de Dicroísmo Circular (CD), para uma análise da estrutura secundária da amostra e espectroscopia de Ressonância Magnética Nuclear (RMN) para o estudo da estrutura tridimensional do peptídeo em solução.Social wasp venoms are rich of biologically active peptides that may cause some malady to human such as prolonged pains, edema, erythema, allergies and systemic reactions. They have, in its composition, many kinds of biogenic amines, series of polycationics peptides and proteins. Among them, the most interesting thing in pharmacological activity are the polycationics peptides. These peptides show several activities like neurotoxicity, hemolytic activity, histamine releasing activity and antimicrobial activity. In this project, cationic peptides of the Polybine family synthesized by the Department of Biology, CEIS/IBRC, UNESP, Rio Claro, SP were studied. The cationic peptides Polybine I and II were synthesized in acetylad and non-acetylad forms to the detailed study of the structure. This way, CD spectroscopy were performed to analyze secondary structure of the sample and, to analyze treedimension structure, NMR spectroscopy were used.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Viabilidade do retalho cutâneo randômico dorsal em camundongos submetidos à fotobiomodulação e ultrassom terapêutico

Introdução: O retalho cutâneo é uma técnica cirúrgica amplamente empregada na prática clínica e comumente apresenta complicações pós-operatórias, portanto, elucidar intervenções que auxiliem na conservação do tecido são fundamentais. A fotobiomodulação (PBM) e o ultrassom terapêutico (UST) são alternativas não invasivas que auxiliam no reparo tecidual, contudo, ainda não há consenso sobre os parâmetros a serem utilizados. Objetivo: Descrever a efetividade dos diferentes parâmetros da PBM e do UST na viabilidade do retalho cutâneo randômico dorsal em camundongos. Métodos: Utilizou-se 55 camundongos Swiss, distribuídos em onze grupos. Os animais foram submetidos à técnica cirúrgica com a revascularização da área limitada através de uma barreira plástica (poliéster/polietileno) da mesma dimensão do retalho. Aplicou-se a PBM ou UST durante cinco dias consecutivos. O registro fotográfico e termográfico foi realizado com as câmeras Cyber-Shot DSC-P72 e FlirC2, sendo posteriormente analisados nos softwares ImageJ® e FLIR Tools, respectivamente. Na análise estatística, os dados foram submetidos ao software GraphPad Prism® 8.0 e ao teste Shapiro-Wilk para a análise da normalidade. Realizou-se a análise de variância (ANOVA TWO-WAY) e pós-teste de Tukey, com nível de significância de 5%. Resultados: Os grupos-5 (PBM 830nm; 10J/cm²) e 6 (UST 3MHz; 0,4W/cm²) apresentaram as maiores porcentagens de tecido viável no terceiro e quinto dia do experimento, sendo estatisticamente significativas quando comparados aos outros grupos. A temperatura reduziu significativamente no grupo-1 quando comparado aos demais no pós-operatório. Conclusão: O UST contínuo à 3MHz e PBM 830nm, foram mais eficazes em melhorar a viabilidade do retalho cutâneo randômico dorsal em camundongos

Síndrome de Aicardi e papiloma do plexo coróide: uma associação rara. Relato de caso Aicardi syndrome and choroid plexus papilloma: a rare association. Case report

Relata-se o caso clínico de uma criança de 5 meses de idade, do sexo feminino, com achados característicos da síndrome de Aicardi: agenesia do corpo caloso, espasmos infantis, anormalidades oculares ("chorioretinal lacunae" e microftalmia), atraso do desenvolvimento neuropsicomotor e malformações vertebrais com cifoescoliose. Os exames complementares confirmaram o diagnóstico e as imagens neurorradiológicas evidenciaram, além da agenesia do corpo caloso, massa localizada em região atrioventricular esquerda (papiloma do plexo coróide). A síndrome de Aicardi associada a papiloma do plexo coróide é rara, sendo este o sétimo caso relatado na literatura. Os autores sugerem que o papiloma do plexo coróide seja considerado tumor característico da síndrome de Aicardi, pois a sua freqüência é mais do que coincidental.<br>The authors report a case of a 5 months old female child with clinical features of Aicardi syndrome: agenesis of the corpus callosum, occular abnormalities ("chorioretinal lacunae" and microphthalmus), infantile spasms, mental retardation, vertebral malformations and thoracic deformity. The pacient was submitted to complementary examinations that confirmed the diagnosis. The neuroradiologic images (MRI) showed besides corpus callosum agenesis a tumor located at the left ventricular atrium (choroid plexus papilloma). This association is a rare occurrence and the present case is the seventh described in literature. Furthermore, we suggest that the choroid plexus pappilloma could be a characteristic tumor of the Aicardi syndrome

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: an individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts ConsortiumResearch in context

Summary: Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%. Funding: National Council for Scientific and Technological Development - Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq); Wellcome Trust and the United Kingdom's Department for International Development; European Union's Horizon 2020 research and innovation program; Medical Research Council on behalf of the Newton Fund and Wellcome Trust; National Institutes of Health/National Institute of Allergy and Infectious Diseases; Foundation Christophe et Rodolphe Mérieux; Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes); Ministry of Health of Brazil; Brazilian Department of Science and Technology; Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP); Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ); Foundation of Support for Research and Scientific and Technological Development of Maranhão; Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Ministério da Saúde); Foundation of Research Support of the State of Goiás (Fundação de Amparo à Pesquisa do Estado de Goiás – FAPEG); Foundation of Research Support of the State of Rio Grande do Sul (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS); Foundation to Support Teaching, Research and Assistance at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto); São Paulo State Department of Health (Secretaria de Saúde do Estado de São Paulo); Support Foundation of Pernambuco Science and Technology (Fundação de Amparo à Ciência e Tecnologia de Pernambuco – FACEPE)

Resumos concluídos - Saúde Coletiva

Resumos concluídos - Saúde Coletiv