Short wheat challenge is a reproducible in-vivo assay to detect immune response to gluten.

It has been reported that interferon (IFN)-γ-secreting T cells reactive to gluten can be detected in the peripheral blood of individuals with treated coeliac disease (CD) after a short consumption of wheat-containing food. By contrast, very little is known about the reproducibility of this in-vivo procedure in the same patient cohort which underwent two, or more, gluten consumptions. Fourteen coeliac patients in remission consumed wheat bread for 3 days; 13 underwent a second gluten challenge after a wash-out of 3-10 months on a strict gluten-free diet. Immune reactivity to gluten was analysed in peripheral blood by detecting IFN-γ before and 6 days after commencing a gluten diet. Gliadin-specific IFN-γ-secreting CD4(+) T cells increased significantly on day 6 of the first challenge. These cells resulted as prevalently human leucocyte antigen (HLA)-DQ restricted and with a phenotype of gut homing, as suggested by the expression of β7-integrin. Similarly, reactiveness to gliadin was observed after the second wheat consumption, although with an individual variability of responses at each challenge. Our findings confirmed that the short wheat challenge is a non-invasive approach to investigate the gluten-related immune response in peripheral blood of subjects intolerant to gluten. Furthermore, we demonstrated that the in-vivo procedure can be reproduced in the same subject cohort after a gluten wash-out of at least 3 months. Our study has important implications for the application of this procedure to clinical practice

Predicting cell types and genetic variations contributing to disease by combining GWAS and epigenetic data

Genome-wide association studies (GWASs) identify single nucleotide polymorphisms (SNPs) that are enriched in individuals suffering from a given disease. Most disease-associated SNPs fall into non-coding regions, so that it is not straightforward to infer phenotype or function; moreover, many SNPs are in tight genetic linkage, so that a SNP identified as associated with a particular disease may not itself be causal, but rather signify the presence of a linked SNP that is functionally relevant to disease pathogenesis. Here, we present an analysis method that takes advantage of the recent rapid accumulation of epigenomics data to address these problems for some SNPs. Using asthma as a prototypic example; we show that non-coding disease-associated SNPs are enriched in genomic regions that function as regulators of transcription, such as enhancers and promoters. Identifying enhancers based on the presence of the histone modification marks such as H3K4me1 in different cell types, we show that the location of enhancers is highly cell-type specific. We use these findings to predict which SNPs are likely to be directly contributing to disease based on their presence in regulatory regions, and in which cell types their effect is expected to be detectable. Moreover, we can also predict which cell types contribute to a disease based on overlap of the disease-associated SNPs with the locations of enhancers present in a given cell type. Finally, we suggest that it will be possible to re-analyze GWAS studies with much higher power by limiting the SNPs considered to those in coding or regulatory regions of cell types relevant to a given disease

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

Land-use and land-cover mapping of the Brazilian cerrado based mainly on Landsat-8 satellite images.

The Brazilian Cerrado is one of the world´s biodiversity hotspot and hosts some of the most intensive agricultural activities for food production in the world. The objective of this study was to produce a land-use and land-cover (LULC) map of the Cerrado based on Landsat-8 Operational Land Imager (OLI) images. A set of 121 scenes from 2013 was processed using the image segmentation technique. The segments were exported in the shapefile format and interpreted visually in a geographical information system software using RGB/564 color composites. The following LULC classes were considered: annual croplands, perennial croplands, cultivated pasturelands, reforestation, mosaic of occupation, urban areas, mining areas, bare soil, forestlands, non-forestlands, water bodies, and non-identified (clouds and burned areas). The overall accuracy was estimated by an independent scientist with large experience in Cerrado´s image interpretation. The results showed that 43.4% of the study area (88.5 million hectares) were already converted into agricultural, urban and mining areas, 54.6% (111 million hectares) were still natural areas, and 1.9% (3.9 million hectares) was classified as non-identified. Cultivated pasturelands were the most representative land-use type (29.5%), followed by annual croplands (8.5%) and perennial croplands (3.1%). The overall accuracy of the final map was 80.2%.Título em português: Mapeamento de uso e cobertura de terras do cerrado com base principalmente em imagens do satélite Landsat-8

Land-use and land-cover mapping of the Brazilian cerrado based mainly on Landsat-8 satellite images.

The Brazilian Cerrado is one of the world´s biodiversity hotspot and hosts some of the most intensive agricultural activities for food production in the world. The objective of this study was to produce a land-use and land-cover (LULC) map of the Cerrado based on Landsat-8 Operational Land Imager (OLI) images. A set of 121 scenes from 2013 was processed using the image segmentation technique. The segments were exported in the shapefile format and interpreted visually in a geographical information system software using RGB/564 color composites. The following LULC classes were considered: annual croplands, perennial croplands, cultivated pasturelands, reforestation, mosaic of occupation, urban areas, mining areas, bare soil, forestlands, non-forestlands, water bodies, and non-identified (clouds and burned areas). The overall accuracy was estimated by an independent scientist with large experience in Cerrado´s image interpretation. The results showed that 43.4% of the study area (88.5 million hectares) were already converted into agricultural, urban and mining areas, 54.6% (111 million hectares) were still natural areas, and 1.9% (3.9 million hectares) was classified as non-identified. Cultivated pasturelands were the most representative land-use type (29.5%), followed by annual croplands (8.5%) and perennial croplands (3.1%). The overall accuracy of the final map was 80.2%.Título em português: Mapeamento de uso e cobertura de terras do cerrado com base principalmente em imagens do satélite Landsat-8

Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% for TBLH-BMD, and 39% for TB-LM, with a shared genetic component of 43%. We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: _WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5_. Variants in the _TOM1L2/SREBF1_ locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that _SREBF1_ is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass

Desafios do cumprimento da NDC brasileira no bioma Amazônia.

Resumo: A Contribuição Nacionalmente Determinada (NDC) brasileira estabeleceu metas ambiciosas de redução de emissões de gases de efeito estufa. Este artigo avalia os desafios para cumprimento da NDC na redução do desmatamento e restauração florestal no bioma Amazônia. O diagnóstico inédito considera a extensão do desmatamento ilegal e os déficits e excedentes de reserva legal por tamanho de propriedade e tipo de uso da terra

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted-in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects