33 research outputs found

    Arsenic in Water Resources of the Southern Pampa Plains, Argentina

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    Confronted with the need for accessible sources of good quality water and in view of the fact that the threat to public health posed by arsenic occurs mainly through the ingestion of contaminated drinking water, the presence and distribution of arsenic was evaluated in the southern Pampa Plains of Bahía Blanca district in Argentina. The findings show variable concentrations of arsenic in a complex distribution pattern. Complementary information is provided on the behavior of the groundwater resource and its salinity in terms of dissolved ions. Groundwater is the most severely affected, 97% of the samples exceeding the guideline value for arsenic in drinking water as recommended by the WHO (Guidelines for Drinking Water Quality, 2004). and showing maximum concentrations of up to 0.30 mg/L. Informing those responsible for preventive medicine and alerting the community at large will facilitate measures to mitigate exposure and ensure the safety of drinking water

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

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    The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

    Mapping genomic loci implicates genes and synaptic biology in schizophrenia

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    Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

    SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

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    Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

    Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

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    Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

    A first update on mapping the human genetic architecture of COVID-19

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    Lámina, intervalo y umbral hídrico del cultivo de la cebolla en suelos del valle bonaerense del río Colorado (provincia de Buenos Aires)

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    El presente trabajo de investigación relativo al riego del cultivo de la Cebolla en suelos representativos del Valle Bonaerense del río Colorado en territorio de la Pcia. de Buenos Aires, ha permitido experimentar en un lapso de tres años sobre la técnica del riego en este cultivo, su comportamiento y metodología más conveniente. Trabajando sobre tres series de suelo del área de Hilario Ascasubi y Mayor Buratovich, se establecieron y/o calcularon los requerimientos hídricos de la Cebolla en exportación comercial, primero en forma teórica por procedimientos "Blaney-Criddle-FAO" y "Cropwat Comp" y luego mediante ensayos de aplicación e intervalo con avance de lámina. En el primer caso se estableció una Necesidad neta: "Nan" de 620,6 mm. período y un Requerimiento bruto de riego: "Rbr" fr 1.154,8 mm. en igual lapso siendo la cantidad de aplicaciones de 2 2 riegos. En los ensayos llevados a cabo por el sistema de gravedad en superficie con avance de lámina, se establecieron consumos por período de 1.092 a 1.260 mm. lográndose una medida de 20 a 23 aplicaciones o riegos. Se analizó el "patrón de infiltración" en función del "Tiempo de oportunidad" de riego, extrayendo conclusiones en cuanto a la eficiencia. Dentro de las conclusiones básicas logradas, se consigna la ventaja de trabajar con bajos caudales unitarios por surco (menores de 1 lt/srg., con media de 0,6 lt/seg.); se lograron elementos hidráulicos de diseño, etc. y finalmente, se realizó un primer ensayo de la aplicación del riego por Goteo en cebolla, con resultado sumamente auspicioso. Lógicamente, el rendimiento de cebolla comercial obtenida en cada ensayo intervino como parámetro de comparación.Academia Nacional de Agronomía y Veterinaria (ANAV

    Lámina, intervalo y umbral hídrico del cultivo de la cebolla en suelos del valle bonaerense del río Colorado (provincia de Buenos Aires)

    No full text
    El presente trabajo de investigación relativo al riego del cultivo de la Cebolla en suelos representativos del Valle Bonaerense del río Colorado en territorio de la Pcia. de Buenos Aires, ha permitido experimentar en un lapso de tres años sobre la técnica del riego en este cultivo, su comportamiento y metodología más conveniente. Trabajando sobre tres series de suelo del área de Hilario Ascasubi y Mayor Buratovich, se establecieron y/o calcularon los requerimientos hídricos de la Cebolla en exportación comercial, primero en forma teórica por procedimientos "Blaney-Criddle-FAO" y "Cropwat Comp" y luego mediante ensayos de aplicación e intervalo con avance de lámina. En el primer caso se estableció una Necesidad neta: "Nan" de 620,6 mm. período y un Requerimiento bruto de riego: "Rbr" fr 1.154,8 mm. en igual lapso siendo la cantidad de aplicaciones de 2 2 riegos. En los ensayos llevados a cabo por el sistema de gravedad en superficie con avance de lámina, se establecieron consumos por período de 1.092 a 1.260 mm. lográndose una medida de 20 a 23 aplicaciones o riegos. Se analizó el "patrón de infiltración" en función del "Tiempo de oportunidad" de riego, extrayendo conclusiones en cuanto a la eficiencia. Dentro de las conclusiones básicas logradas, se consigna la ventaja de trabajar con bajos caudales unitarios por surco (menores de 1 lt/srg., con media de 0,6 lt/seg.); se lograron elementos hidráulicos de diseño, etc. y finalmente, se realizó un primer ensayo de la aplicación del riego por Goteo en cebolla, con resultado sumamente auspicioso. Lógicamente, el rendimiento de cebolla comercial obtenida en cada ensayo intervino como parámetro de comparación.Academia Nacional de Agronomía y Veterinaria (ANAV

    Spatial Variability and Concentration of Arsenic in the Groundwater of a Region in Southwest Buenos Aires Province, Argentina

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    Arsenic is widely found in the natural environment mainly as an outcome of processes related to vulcanicity but also as a consequence of anthropogenic use of inorganic forms such as arsenate and arsenite (Varillas et al. 1997). Material of volcanic origin is transported in suspension in the atmosphere and deposited as lenticular layers in the sediment on plains (Bolzicco et al. 1997). These layers undergo a washing process and the resulting fragments are subsequently mobilized by means of various infiltration and straining mechanisms, ending up in surface and groundwater (Bhumbla and Keefer 1994). Chronic endemic hydro-arsenism is caused by the consumption, over prolonged periods, of water containing higher than normal concentrations of arsenic (Biagini et al. 1995). It is estimated that some 30 μg of arsenic per kilo of body weight is incorporated into the human organism daily, solely on the basis of the average arsenic content in food (Formigli et al. 1997). The World Health Organization (WHO) (1995) estimated that the average daily intake of inorganic arsenic from water reaches similar levels to that ingested via foodstuffs. This serious public health hazard is known to exist in Argentina (Salvador 1987) and was already recognized early this century (Ayerza 1978).Fil: Paoloni, Juan Dario. Universidad Nacional del Sur. Departamento de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fiorentino, Carmen E.. Universidad Nacional del Sur. Departamento de Agronomía; ArgentinaFil: Sequeira, Mario Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida. Universidad Nacional del Sur. Centro de Recursos Naturales Renovables de la Zona Semiárida; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería; ArgentinaFil: Echeverría, Nora Elena. Universidad Nacional del Sur. Departamento de Agronomía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin
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