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Background The concept and assessment of resilience have attracted considerable attention in recent years, but none of the instruments developed to measure resilience in adolescents have been adapted to the Spanish context. The Adolescent Resilience Questionnaire (ARQ) provides a comprehensive and multidimensional assessment of the resources associated with resilience in adolescents. Methods This study analyzes the psychometric properties of the ARQ. Participants included a community sample of 1101 Spanish adolescents (53.5 % boys) aged 12–17 years ( M  = 14.51; SD  = 1.755). Results Results confirm the factor structure based on 12 scales. Internal consistency was generally adequate (between .60 and .84), although the unacceptable coefficient for the Empathy/Tolerance scale (α = .38) means that this scale needs to be revised for the Spanish context. Relationships between ARQ scales and psychopathology were in the expected direction and magnitude. Some gender differences were observed, with higher scores for boys on Confidence and Negative cognition . Conclusions The Spanish version of the ARQ can help to identify personal characteristics associated with resilience and signs of positive engagement with family, peers, school, and the community. It can identify those adolescents most likely to show resilience in response to adversity, as well as those who may be vulnerable under situations of stress.

Universities are increasingly paying more attention to developing academic entrepreneurship. This paper analyses the existing relationships between the relevant factors that contribute to the development of the entrepreneurial university. A previously validated questionnaire was administered to a sample of 84 deans of a number of faculties in Spain. The aim was to assess the universities’ development in terms of 13 influencing factors in encouraging entrepreneurship. The findings show that universities’ contextual factors had only minor influence on internal factors. Internal resources were found to be moderately or highly correlated with the processes put in place by universities to promote entrepreneurship. In particular, reference to entrepreneurship in a university’s mission, strategy, policies and procedures had a correlation with all the entrepreneurship factors analysed. Support from the management team and organisational design were not among the most important factors; however, they were positively associated with training and research processes, which, in turn, seemed to be strongly related to all factors in the development of the entrepreneurial university, especially with university mission and strategy. The findings show the relationships between the factors involved in the development of the entrepreneurial university. This will help universities to adopt measures that are better suited to promoting entrepreneurship.

The pancreas is a central organ for human diseases. Most alleles uncovered by genome-wide association studies of pancreatic dysfunction traits overlap with non-coding sequences of DNA. Many contain epigenetic marks of cis-regulatory elements active in pancreatic cells, suggesting that alterations in these sequences contribute to pancreatic diseases. Animal models greatly help to understand the role of non-coding alterations in disease. However, interspecies identification of equivalent cis-regulatory elements faces fundamental challenges, including lack of sequence conservation. Here we combine epigenetic assays with reporter assays in zebrafish and human pancreatic cells to identify interspecies functionally equivalent cis-regulatory elements, regardless of sequence conservation. Among other potential disease-relevant enhancers, we identify a zebrafish ptf1a distal-enhancer whose deletion causes pancreatic agenesis, a phenotype previously found to be induced by mutations in a distal-enhancer of PTF1A in humans, further supporting the causality of this condition in vivo. This approach helps to uncover interspecies functionally equivalent cis-regulatory elements and their potential role in human disease. Alterations in cis-regulatory elements (CREs) can contribute to pancreatic diseases. Here the authors combine chromatin profiling and interaction points with in vivo reporter assays in zebrafish to uncover functionally equivalent human CREs, helping to predict disease-relevant enhancers.

The evolution of winged insects revolutionized terrestrial ecosystems and led to the largest animal radiation on Earth. However, we still have an incomplete picture of the genomic changes that underlay this diversification. Mayflies, as one of the sister groups of all other winged insects, are key to understanding this radiation. Here, we describe the genome of the mayfly Cloeon dipterum and its gene expression throughout its aquatic and aerial life cycle and specific organs. We discover an expansion of odorant-binding-protein genes, some expressed specifically in breathing gills of aquatic nymphs, suggesting a novel sensory role for this organ. In contrast, flying adults use an enlarged opsin set in a sexually dimorphic manner, with some expressed only in males. Finally, we identify a set of wing-associated genes deeply conserved in the pterygote insects and find transcriptomic similarities between gills and wings, suggesting a common genetic program. Globally, this comprehensive genomic and transcriptomic study uncovers the genetic basis of key evolutionary adaptations in mayflies and winged insects. Genomic studies of paleopteran insects, such as mayflies, are needed to reconstruct early insect evolution. Here, Almudi and colleagues present the genome of the mayfly Cloeon dipterum and use transcriptomics to characterize its adaptations to distinct habitats and the origin of insect wings.

Nrf2 is a master transcriptional regulator of antioxidant and cytoprotective pathways. Currently in its third decade, research on Nrf2 has expanded to encompass not only basic but also clinical studies. In the present bibliometric review, we employed the VOSviewer tool to describe the existing Nrf2 literature landscape. As of July 2019, 11,931 papers on Nrf2 were listed in the “Web of Science” database, with more than 1000 new papers published each year. As expected, terms related to oxidative stress and antioxidant molecules occur very often in the Nrf2 literature throughout the years. Interestingly, there is also a gradual increase in the occurrence of terms related to diseases or to natural compounds, the most prominent being sulforaphane, curcumin, and resveratrol that modulate the Nrf2 pathway. Going beyond molecular biology/biochemistry and related fields, Nrf2 research has begun to spread into more clinical areas like endocrinology/metabolism, cardiology, and nephrology, likely reflecting an increased interest in clinical applications of Nrf2 pathway activators. China has become the most prolific producer of Nrf2 papers the last five years followed by the USA and Japan, a reverse pattern compared to the past. In conclusion, Nrf2 is the subject of a globally active research field that keeps growing and extends from bench to bedside.

Age-related changes in DNA methylation have been implicated in cellular senescence and longevity, yet the causes and functional consequences of these variants remain unclear. To elucidate the role of age-related epigenetic changes in healthy ageing and potential longevity, we tested for association between whole-blood DNA methylation patterns in 172 female twins aged 32 to 80 with age and age-related phenotypes. Twin-based DNA methylation levels at 26,690 CpG-sites showed evidence for mean genome-wide heritability of 18%, which was supported by the identification of 1,537 CpG-sites with methylation QTLs in cis at FDR 5%. We performed genome-wide analyses to discover differentially methylated regions (DMRs) for sixteen age-related phenotypes (ap-DMRs) and chronological age (a-DMRs). Epigenome-wide association scans (EWAS) identified age-related phenotype DMRs (ap-DMRs) associated with LDL (STAT5A), lung function (WT1), and maternal longevity (ARL4A, TBX20). In contrast, EWAS for chronological age identified hundreds of predominantly hyper-methylated age DMRs (490 a-DMRs at FDR 5%), of which only one (TBX20) was also associated with an age-related phenotype. Therefore, the majority of age-related changes in DNA methylation are not associated with phenotypic measures of healthy ageing in later life. We replicated a large proportion of a-DMRs in a sample of 44 younger adult MZ twins aged 20 to 61, suggesting that a-DMRs may initiate at an earlier age. We next explored potential genetic and environmental mechanisms underlying a-DMRs and ap-DMRs. Genome-wide overlap across cis-meQTLs, genotype-phenotype associations, and EWAS ap-DMRs identified CpG-sites that had cis-meQTLs with evidence for genotype-phenotype association, where the CpG-site was also an ap-DMR for the same phenotype. Monozygotic twin methylation difference analyses identified one potential environmentally-mediated ap-DMR associated with total cholesterol and LDL (CSMD1). Our results suggest that in a small set of genes DNA methylation may be a candidate mechanism of mediating not only environmental, but also genetic effects on age-related phenotypes.

A strong association between the HLA-B*1502 allele and SJS and TEN induced by carbamazepine has been shown. This study involving Europeans implicates a different HLA allele, HLA-A*3101, in conferring susceptibility to a broad range of carbamazepine-induced reactions. Carbamazepine is one of the most commonly prescribed drugs for the treatment of epilepsy, as well as trigeminal neuralgia and bipolar disorder. A minority of treated persons have hypersensitivity reactions that vary in prevalence and severity, 1 with some forms associated with substantial morbidity and mortality. The mildest form, maculopapular exanthema, occurs in 5 to 10% of treated persons of European ancestry and resolves spontaneously after drug discontinuation. More severe reactions, such as the hypersensitivity syndrome, are associated with mortality of up to 10% 2 and include symptoms such as rash, fever, eosinophilia, hepatitis, and nephritis. The most severe reactions, such as . . .

Cornelis Albers, Cedric Ghevaert and colleagues report that a majority of thrombocytopenia with absent radii (TAR) syndrome cases are caused by compound heterzygosity of a null allele and a low-frequency SNP in the regulatory regions of the RBM8A gene, which encodes the Y14 subunit of the exon-junction complex (EJC). TAR syndrome is the first reported human disorder caused by a defect in an EJC component. The exon-junction complex (EJC) performs essential RNA processing tasks 1 , 2 , 3 , 4 , 5 . Here, we describe the first human disorder, thrombocytopenia with absent radii (TAR) 6 , caused by deficiency in one of the four EJC subunits. Compound inheritance of a rare null allele and one of two low-frequency SNPs in the regulatory regions of RBM8A , encoding the Y14 subunit of EJC, causes TAR. We found that this inheritance mechanism explained 53 of 55 cases ( P < 5 × 10 −228 ) of the rare congenital malformation syndrome. Of the 53 cases with this inheritance pattern, 51 carried a submicroscopic deletion of 1q21.1 that has previously been associated with TAR 7 , and two carried a truncation or frameshift null mutation in RBM8A . We show that the two regulatory SNPs result in diminished RBM8A transcription in vitro and that Y14 expression is reduced in platelets from individuals with TAR. Our data implicate Y14 insufficiency and, presumably, an EJC defect as the cause of TAR syndrome.

Background Tobacco smoking is a risk factor for multiple diseases, including cardiovascular disease and diabetes. Many smoking-associated signals have been detected in the blood methylome, but the extent to which these changes are widespread to metabolically relevant tissues, and impact gene expression or metabolic health, remains unclear. Methods We investigated smoking-associated DNA methylation and gene expression variation in adipose tissue biopsies from 542 healthy female twins. Replication, tissue specificity, and longitudinal stability of the smoking-associated effects were explored in additional adipose, blood, skin, and lung samples. We characterized the impact of adipose tissue smoking methylation and expression signals on metabolic disease risk phenotypes, including visceral fat. Results We identified 42 smoking-methylation and 42 smoking-expression signals, where five genes ( AHRR , CYP1A1 , CYP1B1 , CYTL1 , F2RL3 ) were both hypo-methylated and upregulated in current smokers. CYP1A1 gene expression achieved 95% prediction performance of current smoking status. We validated and replicated a proportion of the signals in additional primary tissue samples, identifying tissue-shared effects. Smoking leaves systemic imprints on DNA methylation after smoking cessation, with stronger but shorter-lived effects on gene expression. Metabolic disease risk traits such as visceral fat and android-to-gynoid ratio showed association with methylation at smoking markers with functional impacts on expression, such as CYP1A1 , and at tissue-shared smoking signals, such as NOTCH1 . At smoking-signals, BHLHE40 and AHRR DNA methylation and gene expression levels in current smokers were predictive of future gain in visceral fat upon smoking cessation. Conclusions Our results provide the first comprehensive characterization of coordinated DNA methylation and gene expression markers of smoking in adipose tissue. The findings relate to human metabolic health and give insights into understanding the widespread health consequence of smoking outside of the lung.

DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls. The strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways, and related to taurocholate levels in blood. Integrating the DNA methylome findings with T2D GWAS meta-analysis results reveals a strong enrichment for DMRs in T2D-susceptibility loci. We also detect signals specific to T2D-discordant twins in the GPR61 and PRKCB genes. These replicated T2D associations reflect both likely causal and consequential pathways of the disease. The analysis indicates how an integrated genomics and epigenomics approach, utilizing an MZ twin design, can provide pathogenic insights as well as potential drug targets and biomarkers for T2D and other complex traits. Type 2 diabetes (T2D) is a highly heterogeneous disease with a strong genetic component. Here the authors examine genome-wide methylation patterns in T2D-discordant, T2D-concordant and healthy concordant monozygotic twin pairs, and identify DNA methylation signals that may represent new biomarkers or drug targets for T2D.