Anti-Group A Streptococcal Vaccine Epitope STRUCTURE, STABILITY, AND ITS ABILITY TO INTERACT WITH HLA CLASS II MOLECULES

Streptococcus pyogenes infections remain a health problem in several countries due to poststreptococcal sequelae. We developed a vaccine epitope (StreptInCor) composed of 55 amino acids residues of the C-terminal portion of the M protein that encompasses both T and B cell protective epitopes. The nuclear magnetic resonance (NMR) structure of the StreptInCor peptide showed that the structure was composed of two microdomains linked by an 18-residue alpha-helix. A chemical stability study of the StreptInCor folding/unfolding process using far-UV circular dichroism showed that the structure was chemically stable with respect to pH and the concentration of urea. The T cell epitope is located in the first microdomain and encompasses 11 out of the 18 alpha-helix residues, whereas the B cell epitope is in the second microdomain and showed no alpha-helical structure. The prediction of StreptInCor epitope binding to different HLA class II molecules was evaluated based on an analysis of the 55 residues and the theoretical possibilities for the processed peptides to fit into the P1, P4, P6, and P9 pockets in the groove of several HLA class II molecules. We observed 7 potential sites along the amino acid sequence of StreptInCor that were capable of recognizing HLA class II molecules (DRB1*, DRB3*, DRB4*, and DRB5*). StreptInCoroverlapping peptides induced cellular and humoral immune responses of individuals bearing different HLA class II molecules and could be considered as a universal vaccine epitope.

Germination of the seeds of Castanospermum australe (black bean) as studied by the high-field NMR microimaging

The germination of the seeds from the Chesnut tree (Castanospermum australe) has been investigated by the NMR Microimaging at 190 MHz. Conventional H-1 spin-echo and T-1 images reveals some details of black bean seeds vascular structure: a system of small spherical holes and curvelinear pathways.

Distribution of HDL-cholesterol and non-HDL-cholesterol in Brazilian children and adolescents - The Floripa study

Background and aims: HDL-cholesterol (HDL-C) and non-HDL-cholesterol (nHDL-C) are involved in atherosclerosis. The aim of this study was to determine the distribution of HDL-C and nHDL-C and its association with cardiovascular and socio-cultural variables in a pediatric Brazilian sample. Methods and results: Children and adolescents from Florianopolis were randomly selected and a structured questionnaire was administered, a physical examination was performed and a blood sample was collected. Enzymatic and Direct methods in vitro were used to determine the total cholesterol and HDL-cholesterol levels. The associations among HDL-C and nHDL-C and the described variables were tested by odds ratio and logistic regression. A total of 1009 individuals were examined. Based on the Brazilian criteria, 23% were classified with low levels of HDL-C and 25% with high levels of non-HDL-C. After multivariate analysis there were significant associations among low HDL-C and high C-reactive protein (OR, 3.3; 95% CI, 2.1-5.2), paternal tobacco use (OR, 1.5; 95% CI, 1.1-2.1), and high triceps-to-subscapular index (OR, 1.5; 95% CI, 1.1-2.2). There were also significant associations among high nHDL-C and high waist circumference (OR, 1.95; 95% CI, 1.16-3.29), black skin color (OR, 1.78; 95% CI, 1.06-3.06), and high income (OR, 1.48; 95% CI, 1.09-2.02). Conclusions: In this sample, low levels of HDL-C were associated with other clinical variables such as a centripetal fat pattern and C-reactive protein, and n-HDL-C was associated with abdominal obesity, skin color and economic class. (C) 2009 Elsevier B. V. All rights reserved.

Correlation between CD34(+) and exercise capacity, functional class, quality of life and norepinephrine in heart failure patients

Background: A previous study associated CD34(+) levels with NYHA functional class in heart failure patients. The aim of this study was to correlate CD34(+) levels to exercise capacity, functional class, quality of life and norepinephrine in heart failure patients. Methods: Twenty three sedentary patients (52 +/- 7 years, 78% male) answered the Minnesota Living with Heart Failure Questionnaire and rested for 20 minutes before an investigator collect a blood sample. After this, patients performed a cardiopulmonary exercise test to determine the heart rate at anaerobic and ventilatory threshold and oxygen consumption at peak effort, at anaerobic and ventilatory threshold. One other blood sample was collected during the peak effort to investigate the norepinephrine and CD34(+) levels. Results: Rest percentage of CD34(+) did not show correlation with: left ventricle ejection fraction (r = 0.03, p = 0.888), peakVO(2) (r = 0.32, p = 0.13), VO(2) at anaerobic threshold (VO(2)AT) (r = 0.03, p = 0.86), VO(2) at ventilatory threshold (VO(2)VT) (r = 0.36, p = 0.08), NYHA functional class (r = -0.2, p = 0.35), quality of life (Minnesota) (r = -0.17, p = 0.42). CD34(+) did not show correlation, either, with: peak VO(2) (r = 0.38, p = 0.06), VO(2)AT (r = 0.09, p = 0.65), VO(2)VT (r = 0.43, p = 0.4), NYHA functional class (r = -0.13, p = 0.54), quality of life (r = 0.00, p = 0.99). Conclusions: CD34(+) levels did not correlate with exercise capacity, functional class, quality of life and norepinephrine. Percentage of CD34(+) levels did not increase during the cardiopulmonary exercise test in heart failure patients. (Cardiol J 2009; 16, 5: 426-431)

Metabolic syndrome determinants in an urban population from Brazil: Social class and gender-specific interaction

Introduction: The metabolic syndrome (MS) is characterized by multiple cardiovascular risk factors such as central obesity, arterial hypertension, dislipidemia and hyperinsulinemia and is associated with a higher incidence of cardiovascular events and mortality. The aim of the present work is to describe the prevalence of MS in an urban population from a highly admixed developing country and to characterize the different correlations between this diagnosis, cardiovascular risk factors and demographic variables distributed in this population. Materials and methods: A cross-sectional study of risk factors for cardiovascular diseases was performed in the urban population of Vitoria, Brazil (n= 1507). Major cardiovascular risk factors such as smoking habits, alcohol intake, amount of physical activity, diabetes and hypertension were inquired. Blood biochemical assays were performed by standard techniques in 12 h fasting blood sample and Metabolic Syndrome (MS) was characterizes following the ATP III criteria. Results: The analysis of 1507 individuals showed a 25.43% general prevalence of MS without any significant difference between sexes, but a clear relation of the prevalence with progressing age (p=<0.0001). Even though both sexes showed similar prevalence rates, distribution of risk factors that defined MS was different between men and women, with the prevalence of hypertension, fasting hyperglycemia and hypertriglyceridemia being higher in men. Race was not an important risk factor for MS in this population as opposed to social economic class that was highly associated with the risk of MS in women as their social class was lower, but not in men. Conclusion: This cross-sectional study from a large urban population in Brazil showed a high general prevalence of MS (25.4%), which is increased as the population becomes older (especially in women) and poorer. Although prevalence was very similar in both genders, the frequency of components defining the syndrome varied greatly amongst them. In particular, a significant interaction between gender and social class was observed and may shed light in our understanding of the complex interplay between demographic and biological risk factors for metabolic syndrome. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

An fMRI Normative Database for Connectivity Networks Using One-Class Support Vector Machines

The application of functional magnetic resonance imaging (fMRI) in neuroscience studies has increased enormously in the last decade. Although primarily used to map brain regions activated by specific stimuli, many studies have shown that fMRI can also be useful in identifying interactions between brain regions (functional and effective connectivity). Despite the widespread use of fMRI as a research tool, clinical applications of brain connectivity as studied by fMRI are not well established. One possible explanation is the lack of normal pattern, and intersubject variability-two variables that are still largely uncharacterized in most patient populations of interest. In the current study, we combine the identification of functional connectivity networks extracted by using Spearman partial correlation with the use of a one-class support vector machine in order construct a normative database. An application of this approach is illustrated using an fMRI dataset of 43 healthy Subjects performing a visual working memory task. In addition, the relationships between the results obtained and behavioral data are explored. Hum Brain Mapp 30:1068-1076, 2009. (C) 2008 Wiley-Liss. Inc.

An Insight into the Sialotranscriptome of Simulium nigrimanum, a Black Fly Associated with Fogo Selvagem in South America

Pemphigus foliaceus is a life threatening skin disease that is associated with autoimmunity to desmoglein, a skin protein involved in the adhesion of keratinocytes. This disease is endemic in certain areas of South America, suggesting the mediation of environmental factors triggering autoimmunity. Among the possible environmental factors, exposure to bites of black flies, in particular Simulittm nigrimanum has been suggested. In this work, we describe the sialotranscriptome of adult female S. nigrimanum flies. It reveals the complexity of the salivary potion of this insect, comprised by over 70 distinct genes within over 30 protein families, including several novel families, even when compared with the previously described sialotranscriptome of the autogenous black fly, S. vitiation. The uncovering of this sialotranscriptome provides a platform for testing pemphigus patient sera against recombinant salivary proteins from S. nigrimanum and for the discovery of novel pharmacologically active compounds.

Investigating the influence of achievement on self-concept using an intra-class design and a comparison of the PASS and SDQ-1 self-concept tests

Background. The formation and measurement of self-concept were the foci of this research. Aims. The study aimed to investigate the influence of achievement on academic self-concept and to compare the Perception of Ability Scale for Students (PASS, Boersma & Chapman, 1992) with the Self-Description Questionnaire-1 (SDQ-1, Marsh, 1988). Sample. The participants were 479 grade 5 (mean age 126.6 months) coeducational Australian students, located in 18 schools. Method. An intra-class research design was used to investigate the influence of frame-of-reference on self-concept development. Results. As students' academic scores rose above their class mean their self-concepts increased and as students' academic scores fell below their class mean their self-concepts decreased. Students' difference from class mean predicted their self-concept scores. This finding was consistently shown across the reading, spelling, and mathematics domains using test and teaching rating data. A comparison between the PASS and the SDQ-1 demonstrated concurrent validity across self-concept domains. Conclusion. The findings support the notions that the social environment is a significant agent that influences self-concept, and that teacher ratings and standardised tests of achievement and the PASS and the SDQ-1 are valid measures for self-concept research.

Hepatitis B virus and hepatitis delta virus genotypes in outbreaks of fulminant hepatitis (Labrea black fever) in the western Brazilian Amazon region

The genotypes of hepatitis B (HBV) and delta (HDV) viruses circulating among fulminant hepatitis cases from the western Amazon Basin of Brazil were characterized in this study. HBV and HDV isolates were obtained from liver samples from 14 patients who developed fulminant hepatitis and died during 1978-1989. HBV DNA and HDV RNA were detected in all samples. Phylogenetic analyses of HDV sequences showed that they all clustered with previously characterized sequences of HDV genotype 3 (HDV-3). HBV genotypes F, A and D were found in 50.0, 28.6 and 21.4% of cases, respectively. These results confirm the predominance of HDV-3 in South America and its association with the severe form of hepatitis, and the finding of the co-infection of HDV-3 with different genotypes of HBV suggests that the association between HDV-3 and HBV-F is not necessarily causally related to a more severe clinical course of infection.

Major histocompatibility complex (MHC) class II-positive dendritic cells in the rat iris - In situ development from MHC class II-negative precursors

Purpose. To examine the postnatal development of major histocompatibility complex (MHC) class II-positive dendritic cells (DC) in the iris of the normal rat eye. Methods. Single-and double-color immunomorphologic studies were performed on whole mounts prepared from rat iris taken at selected postnatal ages (2 to 3 days to 78 weeks). Immunopositive cells were enumerated, using a quantitative light microscope, and MHC class II expression on individual cells was assessed by microdensitometric analysis. Results. Major histocompatibility class II-positive DCs in the iris developed in an age-dependent manner and reached adult-equivalent density and structure at approximately 10 weeks of age, considerably later than previously described in other DC populations in the rat. In contrast, the anti-rat DC monoclonal antibody OX62 revealed a population of cells present at adult-equivalent levels as early as 3 weeks after birth. Dual-color immunostaining and microdensitometric analysis demonstrated that during postnatal growth, development of the network of MHC class II-positive DCs was a consequence of the progressive increase in expression of MHC class II antigen by OX62-positive cells. Conclusions. During postnatal growth, the DC population of the iris develops initially as an OX62-positive-MHC class II-negative population, which then develops increasing MHC class II expression in situ and finally resembles classic DC populations in other tissue sites. Maturation of the iris DC population is temporally delayed compared with time to maturation in other tissue sites in the rat.

MHC class I and II expression in juvenile dermatomyositis skeletal muscle

Objective To assess MHC I and II expressions in muscle fibres of juvenile dermatomyositis (JDM) and compare with the expression in polymyositis (PM), dermatomyositis (DM) and dystrophy. Patients and methods Forty-eight JDM patients and 17 controls (8 PM, 5 DM and 4 dystrophy) were studied. The mean age at disease onset was 7.1 +/- 3.0 years and the mean duration of weakness before biopsy was 9.4 +/- 12.9 months. Routine histochemistry and immunohistochemistry (StreptABComplex/HRP) for MHC I and II (Dakopatts) were performed on serial frozen muscle sections in all patients. Mann-Whitney, Kruskal Wallis, chi-square and Fisher`s exact statistical methods were used. Results MHC I expression was positive in 47 (97.9%) JDM cases. This expression was observed independent of time of disease corticotherapy previous to muscle biopsy and to the grading of inflammation observed in clinical, laboratorial and histological parameters. The expression of MHC I was similar on JDM, PM and DM, and lower in dystrophy. On the other hand, MHC II expression was positive in just 28.2% of JDM cases was correlated to histological features as inflammatory infiltrate, increased connective tissue and VAS for global degree of abnormality (p < 0.05). MCH II expression was similar in DM/PM and lower in JDM and dystrophy, and it was based on the frequency of positive staining rather than to the degree of the MCH II expression. Conclusions MHC I expression in muscle fibres is a premature and late marker of JDM patient independent to corticotherapy, and MHC II expression was lower in JDM than in PM and DM.

A hypothesis for explaining single outbreaks (like the Black Death in European cities) of vector-borne infections

We propose a mechanism by which single outbreaks of vector-borne infections can happen even when the value of the basic reproduction number, R(o), of the infection is below one. With this hypothesis we have shown that dynamical models simulations demonstrate that the arrival of a relatively small (with respect to the host population) number of infected vectors can trigger a short-lived epidemic but with a huge number of cases. These episodes are characterized by a sudden outbreak in a previously virgin area that last from weeks to a few months, and then disappear without leaving vestiges. The hypothesis proposed in this paper to explain those single outbreaks of vector-borne infections, even when total basic reproduction number, Ro, is less than one (which explain the fact that those infections fail to establish themselves at endemic levels), is that the vector-to-host component of Ro is greater than one and that a sufficient amount of infected vectors are imported to the vulnerable area, triggering the outbreak. We tested the hypothesis by performing numerical simulations that reproduce the observed outbreaks of chikungunya in Italy in 2007 and the plague in Florence in 1348. The theory proposed provides an explanation for isolated outbreaks of vector-borne infections, ways to calculate the size of those outbreaks from the number of infected vectors arriving in the affected areas. Given the ever-increasing worldwide transportation network, providing a high degree of mobility from endemic to virgin areas, the proposed mechanism may have important implications for public health planning. (C) 2009 Elsevier Ltd. All rights reserved.