Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

The Relationship Between Rating of Perceived Exertion and Muscle Activity During Exhaustive Constant-Load Cycling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The aims of this study were to verify the relationship between rating of perceived exertion (RPE) and electromyography (EMG) increases during exhaustive constant-load cycling bouts and, to compare and to correlate the power outputs corresponding to perceived exertion threshold (PET) and neuromuscular fatigue threshold (NFT). 11 men completed 3-4 different exhaustive constant-load cycling bouts on a cycle ergometer, being RPE and EMG measured throughout the bouts. The linear regression of the RPE(slope) and EMG(slope) against the power output identified the PET and NFT intensity, respectively. There was a significant relationship between RPE slope and EMG(slope) (R(2) = 0.69; P < 0.01). However, the linearity of RPE(slope) (R(2) = 0.93 +/- 0.07) was significantly higher (P < 0.001) than EMG(slope) (R(2) = 0.63 +/- 0.25). In addition, the RPE(slope) and EMG(slope) were related to time to exhaustion (r = -0.59 and r = -0.60; P < 0.001). There was no significant difference (P = 0.42) between PET (201.5 +/- 27.9W) and NFT (210.3 +/- 22.6W) and they were significantly correlated (r = 0.78; P = 0.005). Therefore, the RPE and EMG increases during exhaustive constant-load cycling bouts are related and, PET and NFT intensities are similar and closely associated.3110683688Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [04/12589-0

The Genomic Ancestry of Individuals from Different Geographical Regions of Brazil Is More Uniform Than Expected

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a “total ancestry” estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries - a phenomenon described and intended as the “whitening of Brazil” - is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Postnatal depression in Southern Brazil: prevalence and its demographic and socioeconomic determinants

<p>Abstract</p> <p>Background</p> <p>Studies investigating the prevalence of postnatal depression (PND) show rates ranging from 5% to 36.7%. The investigation of age, race, educational levels, religion and income as risk factors for PND has yielded conflicting results. The aim of this study is to investigate the prevalence of PND in women residing in Southern Brazil and the associated risk factors.</p> <p>Methods</p> <p>This is population-based cross-sectional study of women residing in Porto Alegre who delivered in June 2001. A sample of 271 participants were selected from the Record of Living Newborn Infants of the State Health Department (the official Brazilian database and stores the name and address of all women who give birth to living newborn infants) using a process based on pseudo-random numbers which choose a random sample from 2.000 records. Once the addresses were identified, the women were visited at their place of residence (home, hotel, boarding house and prison), with the interviews taking place between the 6^thand the 8^thweek after delivery.</p> <p>The association between the risk factors and PND was investigated through bivariate analysis using Pearson's chi-square test. Student's t-test was used to analyze the continuous variables. To identify independent risk factors, multivariate analysis was performed using hierarchical levels with a predefined model that took into account the time relationship between PND and the risk factors. Cox's regression was used to calculate the prevalence ratios.</p> <p>Results</p> <p>The PND prevalence rate found was 20.7% (CI 95% 15.7 – 25.7). After adjusting for confounding variables, per capita income was found to have a significant association with PND.</p> <p>Conclusion</p> <p>The prevalence of PND is higher than the figures found in most developed countries and similar to the figures found in developing countries. Differences in PND by regions or countries can be partially explained by the effect of income on the mediation of risk factors. In low income populations, women should be routinely evaluated for postnatal depression, and those with no partner or spouse are likely to require further care from health services and should be given the benefit of mental health prevention programs.</p