444 research outputs found

    The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by zika virus

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    The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water sup-plies of NE compared to other regions of Brazil. Experimentally, we described that STX dou-bled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.Fil: Pedrosa, Carolina da S. G.. D’Or Institute for Research and Education; BrasilFil: Souza, Leticia R. Q.. D’Or Institute for Research and Education; BrasilFil: Gomes, Tiago A.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Oswaldo Cruz; BrasilFil: de Lima, Caroline V. F.. D’Or Institute for Research and Education; BrasilFil: Ledur, Pitia F.. D’Or Institute for Research and Education; BrasilFil: Karmirian, Karina. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Barbeito AndrĂ©s, Jimena. Universidade Federal do Rio de Janeiro; Brasil. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. NĂ©stor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones CientĂ­ficas y TĂ©cnicas. Centro CientĂ­fico TecnolĂłgico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Costa, Marcelo do N.. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, Luiza M.. Universidade Federal do Rio de Janeiro; BrasilFil: Rossi, Átila D.. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, Amilcar. Universidade Federal do Rio de Janeiro; BrasilFil: Prata Barbosa, Arnaldo. D’Or Institute for Research and Education; BrasilFil: Tovar Moll, Fernanda. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Garcez, Patricia P.. Universidade Federal do Rio de Janeiro; BrasilFil: Lara, Flavio A.. Instituto Oswaldo Cruz; BrasilFil: Molica, Renato J. R.. Universidad Federal Rural Pernambuco; BrasilFil: Rehen, Stevens K.. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; Brasi

    Global sourcing of low-inorganic arsenic rice grain

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    Arsenic in rice grain is dominated by two species: the carcinogen inorganic arsenic (the sum of arsenate and arsenite) and dimethylarsinic acid (DMA). Rice is the dominant source of inorganic arsenic into the human diet. As such, there is a need to identify sources of low-inorganic arsenic rice globally. Here we surveyed polished (white) rice across representative regions of rice production globally for arsenic speciation. In total 1180 samples were analysed from 29 distinct sampling zones, across 6 continents. For inorganic arsenic the global x ~ x~ was 66 ÎŒg/kg, and for DMA this figure was 21 ÎŒg/kg. DMA was more variable, ranging from < 2 to 690 ÎŒg/kg, while inorganic arsenic ranged from < 2 to 399 ÎŒg/kg. It was found that inorganic arsenic dominated when grain sum of species was < 100 ÎŒg/kg, with DMA dominating at higher concentrations. There was considerable regional variance in grain arsenic speciation, particularly in DMA where temperate production regions had higher concentrations. Inorganic arsenic concentrations were relatively consistent across temperate, subtropical and northern hemisphere tropical regions. It was only in southern hemisphere tropical regions, in the eastern hemisphere that low-grain inorganic arsenic is found, namely East Africa (x ~ x~  < 10 ÎŒg/kg) and the Southern Indonesian islands (x ~ x~  < 20 ÎŒg/kg). Southern hemisphere South American rice was universally high in inorganic arsenic, the reason for which needs further exploration

    Rice grain cadmium concentrations in the global supply-chain

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    One of cadmium’s major exposure routes to humans is through rice consumption. The concentrations of cadmium in the global polished (white), market rice supply-chain were assessed in 2270 samples, purchased from retailers across 32 countries, encompassing 6 continents. It was found on a global basis that East Africa had the lowest cadmium with a median for both Malawi and Tanzania at 4.9 ÎŒg/kg, an order of magnitude lower than the highest country, China with a median at 69.3 ÎŒg/kg. The Americas were typically low in cadmium, but the Indian sub-continent was universally elevated. In particular certain regions of Bangladesh had high cadmium, that when combined with the high daily consumption rate of rice of that country, leads to high cadmium exposures. Concentrations of cadmium were compared to the European Standard for polished rice of 200 ÎŒg/kg and 5% of the global supply-chain exceeded this threshold. For the stricter standard of 40 ÎŒg/kg for processed infant foods, for which rice can comprise up to 100% by composition (such as rice porridges, puffed rice cereal and cakes), 25% of rice would not be suitable for making pure rice baby foods. Given that rice is also elevated in inorganic arsenic, the only region of the world where both inorganic arsenic and cadmium were low in grain was East Africa

    Finding Diagnostically Useful Patterns in Quantitative Phenotypic Data.

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    Trio-based whole-exome sequence (WES) data have established confident genetic diagnoses in ∌40% of previously undiagnosed individuals recruited to the Deciphering Developmental Disorders (DDD) study. Here we aim to use the breadth of phenotypic information recorded in DDD to augment diagnosis and disease variant discovery in probands. Median Euclidean distances (mEuD) were employed as a simple measure of similarity of quantitative phenotypic data within sets of ≄10 individuals with plausibly causative de novo mutations (DNM) in 28 different developmental disorder genes. 13/28 (46.4%) showed significant similarity for growth or developmental milestone metrics, 10/28 (35.7%) showed similarity in HPO term usage, and 12/28 (43%) showed no phenotypic similarity. Pairwise comparisons of individuals with high-impact inherited variants to the 32 individuals with causative DNM in ANKRD11 using only growth z-scores highlighted 5 likely causative inherited variants and two unrecognized DNM resulting in an 18% diagnostic uplift for this gene. Using an independent approach, naive Bayes classification of growth and developmental data produced reasonably discriminative models for the 24 DNM genes with sufficiently complete data. An unsupervised naive Bayes classification of 6,993 probands with WES data and sufficient phenotypic information defined 23 in silico syndromes (ISSs) and was used to test a "phenotype first" approach to the discovery of causative genotypes using WES variants strictly filtered on allele frequency, mutation consequence, and evidence of constraint in humans. This highlighted heterozygous de novo nonsynonymous variants in SPTBN2 as causative in three DDD probands

    Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations

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    Background: Raine syndrome (RS) is a rare autosomal recessive bone dysplasia typified by osteosclerosis and dysmorphic facies due to FAM20C mutations. Initially reported as lethal in infancy, survival is possible into adulthood. We describe the molecular analysis and clinical phenotypes of five individuals from two consanguineous Brazilian families with attenuated Raine Syndrome with previously unreported features. Methods: The medical and dental clinical records were reviewed. Extracted deciduous and permanent teeth as well as oral soft tissues were analysed. Whole exome sequencing was undertaken and FAM20C cDNA sequenced in family 1. Results: Family 1 included 3 siblings with hypoplastic Amelogenesis Imperfecta (AI) (inherited abnormal dental enamel formation). Mild facial dysmorphism was noted in the absence of other obvious skeletal or growth abnormalities. A mild hypophosphataemia and soft tissue ectopic mineralization were present. A homozygous FAM20C donor splice site mutation (c.784 + 5 g > c) was identified which led to abnormal cDNA sequence. Family 2 included 2 siblings with hypoplastic AI and tooth dentine abnormalities as part of a more obvious syndrome with facial dysmorphism. There was hypophosphataemia, soft tissue ectopic mineralization, but no osteosclerosis. A homozygous missense mutation in FAM20C (c.1487C > T; p.P496L) was identified. Conclusions: The clinical phenotype of non-lethal Raine Syndrome is more variable, including between affected siblings, than previously described and an adverse impact on bone growth and health may not be a prominent feature. By contrast, a profound failure of dental enamel formation leading to a distinctive hypoplastic AI in all teeth should alert clinicians to the possibility of FAM20C mutations
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