Far away from the lamppost

[No abstract available

Severe feed restriction increases permeability of mammary gland cell tight junctions and reduces ethanol stability of milk.

201

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

Unexplored therapeutic opportunities in the human genome

A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved

Erratum: Unexplored therapeutic opportunities in the human genome (Nature reviews. Drug discovery (2018) 17 5 (317-332))

This corrects the article DOI: 10.1038/nrd.2018.14

Influência da estação do ano sobre a estrutura testicular em ovinos explorados no sul do Estado do Piauí

RESUMO: Objetivou-se avaliar a influência da estação do ano sobre a estrutura testicular de ovinos SRD. Foram utilizados 10 animais com idade entre dois e três anos. Os testículos foram seccionados e fixados em solução de Bouin por 24h. Os fragmentos foram submetidos ao processamento histológico, emblocados em parafina e corados com hematoxilina eosina. Foram avaliadas a proporção volumétrica dos compartimentos testiculares, o diâmetro dos túbulos seminíferos, altura do epitélio seminífero e frequências dos estágios do ciclo do epitélio seminíferos. Os dados foram submetidos à análise de variância a 5% de probabilidade, do programa estatístico SAS 9.0. Os resultados revelaram todos os valores pesquisados sofreram influência da estação do ano. O valor do diâmetro tubular foi de 143,98±17,83 e 170,37±26,64μm, a altura do epitélio seminífero foi de 44,92±9,23 e 50,06±13,61μm e a proporção volumétrica foi de 78,32±13,68 e 80,13±15,14% nos períodos seco e chuvoso, respectivamente. A quantificação das células germinativas e de Sertoli mostrou todos os valores foram maiores no período chuvoso quando comparados com o seco. Concluiu-se que a estação do ano interferiu na estrutura testicular, tendo em vista que todos os valores da proporção volumétrica dos componentes testiculares mostraram diferença significativa entre as estações do ano, pois os valores foram mais acentuados no período chuvoso

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available