465 research outputs found

    Biotransformation of a tetrahydrofuran lignan by the endophytic fungus Phomopsis Sp.

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    The biotrasformation of the tetrahydrofuran lignan, (-)-grandisin, by the endophitic fungus Phomopsis sp, obtained from Viguiera arenaria, led to the formation of a new compound determined as 3,4-dimethyl-2-(4'-hydroxy-3',5'-dimethoxyphenyl)-5-methoxy-tetrahydrofuran. The metabolite was evaluated against the parasite Trypanosoma cruzi, the causative agent of Chagas's disease, and showed a trypanocidal activity (IC50 9.8 μmol L-1) similar to the natural precursor (IC50 3.7 μmol L-1).A biotransformação da lignana tetraidrofurânica, (-)-grandisina, pelo fungo endofítico Phomopsis sp, obtido de Viguiera arenaria, conduziu à formação de um novo metabólito caracterizado como 3,4-dimetil-2-(4'-hidróxi-3',5'-dimetóxifenil)-5-metóxi-tetraidrofurano. O metabólito foi analisado contra o parasita Trypanosoma cruzi, o agente causador da doença de Chagas, e mostrou uma atividade tripanocida (IC50 9,8 μmol L-1) similar ao precursor natural (IC50 3,7 μmol L-1).Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

    Normative spatiotemporal fetal brain maturation with satisfactory development at 2 years

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    Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2 , selected using World Health Organization recommendations for growth standards3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5 . The atlas was produced using 1,059 optimal quality, three dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8 . The atlas corresponds structurally to published magnetic resonance images9 , but with finer anatomical details in deep grey matter. The between study site variability represented less than 8.0% of the total variance of all brain measures, supporting pooling data from the eight study sites to produce patterns of normative maturation. We have thereby generated an average representation of each cerebral hemisphere between 14 and 31 weeks’ gestation with quantification of intracranial volume variability and growth patterns. Emergent asymmetries were detectable from as early as 14 weeks, with peak asymmetries in regions associated with language development and functional lateralization between 20 and 26 weeks’ gestation. These patterns were validated in 1,487 three-dimensional brain volumes from 1,295 different fetuses in the same cohort. We provide a unique spatiotemporal benchmark of fetal brain maturation from a large cohort with normative postnatal growth and neurodevelopment

    Women Are More Susceptible to Caries but Individuals Born with Clefts Are Not

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    The identification of individuals at a higher risk of developing caries is of great interest. Isolated forms of cleft lip and palate are among the most common craniofacial congenital anomalies in humans. Historically, several reports suggest that individuals born with clefts have a higher risk for caries. Caries continues to be the most common infectious noncontagious disease worldwide and a great burden to any health system. The identification of individuals of higher susceptibility to caries is of great interest. In this paper, we assessed caries experience of 1,593 individuals from three distinct populations. The study included individuals born with clefts, their unaffected relatives, and unrelated unaffected controls that were recruited from areas with similar cultural pressures and limited access to dental care. DMFT/dmft scores were obtained, and caries experience rates were compared among the three groups in each geographic area. Individuals born with clefts did not present higher caries experience in comparison to their unaffected relatives or unrelated unaffected controls. Women tend to present higher caries rates in comparison to men. Our work provides strong evidence that individuals born with clefts are not at higher risk to caries; however, women tend to have more severe caries experience

    Translation and validation of the Brazilian version of the Cerebral Palsy Quality of Life Questionnaire for Children – child report

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    AbstractObjectiveTo verify the psychometric properties of the Cerebral Palsy: Quality of Life Questionnaire Children – child report (CPQol-Child) questionnaire, after it was translated and culturally adapted into Brazilian Portuguese.MethodsAfter the translation and cultural adaptation of the tool into Brazilian Portuguese, the questionnaire was answered by 65 children with cerebral palsy, aged 9–12 years. The intraclass correlation coefficient and Cronbach's alpha were used to assess the reliability and internal consistency of the tool and its validity was analyzed through the association between CPQol-Child: self-report tool and Kidscreen-10 using Pearson's correlation coefficient.ResultsInternal consistency ranged from 0.6579 to 0.8861, the intraobserver reliability from 0.405 to 0.894, and the interobserver from 0.537 to 0.937. There was a weak correlation between the participation domain and physical health of CPQol-Child: self-report tool and Kidscreen-10.ConclusionThe analysis suggests that the tool has psychometric acceptability for the Brazilian population

    The chromatin and single-cell transcriptional landscapes of CD4 T cells in inflammatory bowel disease link risk loci with a proinflammatory Th17 cell population

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    IntroductionThe imbalance between Th17 and regulatory T cells in inflammatory bowel diseases (IBD) promotes intestinal epithelial cell damage. In this scenario, T helper cell lineage commitment is accompanied by dynamic changes to the chromatin that facilitate or repress gene expression. MethodsHere, we characterized the chromatin landscape and heterogeneity of intestinal and peripheral CD4 T cellsfrom IBD patients using in house ATAC-Seq and single cell RNA-Seq libraries. ResultsWe show that chromatin accessibility profiles of CD4 T cells from inflamed intestinal biopsies relate to genes associated with a network of inflammatory processes. After integrating the chromatin profiles of tissue-derived CD4 T cells and in-vitro polarized CD4 T cell subpopulations, we found that the chromatin accessibility changes of CD4 T cells were associated with a higher predominance of pathogenic Th17 cells (pTh17 cells) in inflamed biopsies. In addition, IBD risk loci in CD4 T cells were colocalized with accessible chromatin changes near pTh17-related genes, as shown in intronic STAT3 and IL23R regions enriched in areas of active intestinal inflammation. Moreover, single cell RNA-Seq analysis revealed a population of pTh17 cells that co-expresses Th1 and cytotoxic transcriptional programs associated with IBD severity. DiscussionAltogether, we show that cytotoxic pTh17 cells were specifically associated with IBD genetic variants and linked to intestinal inflammation of IBD patients
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