Notch-effector CSL promotes squamous cell carcinoma by repressing histone demethylase KDM6B.

Notch 1/2 genes play tumor-suppressing functions in squamous cell carcinoma (SCC), a very common malignancy in skin and internal organs. In contrast with Notch, we show that the transcription factor CSL (also known as RBP-Jκ), a key effector of canonical Notch signaling endowed with intrinsic transcription-repressive functions, plays a tumor-promoting function in SCC development. Expression of this gene decreased in upper epidermal layers and human keratinocytes (HKCs) undergoing differentiation, while it increased in premalignant and malignant SCC lesions from skin, head/neck, and lung. Increased CSL levels enhanced the proliferative potential of HKCs and SCC cells, while silencing of CSL induced growth arrest and apoptosis. In vivo, SCC cells with increased CSL levels gave rise to rapidly expanding tumors, while cells with silenced CSL formed smaller and more differentiated tumors with enhanced inflammatory infiltrate. Global transcriptomic analysis of HKCs and SCC cells with silenced CSL revealed major modulation of apoptotic, cell-cycle, and proinflammatory genes. We also show that the histone demethylase KDM6B is a direct CSL-negative target, with inverse roles of CSL in HKC and SCC proliferative capacity, tumorigenesis, and tumor-associated inflammatory reaction. CSL/KDM6B protein expression could be used as a biomarker of SCC development and indicator of cancer treatment

Genetic and environmental influences on sleep quality in middle‐aged men: a twin study

Poor sleep quality is a risk factor for a number of cognitive and physiological age-related disorders. Identifying factors underlying sleep quality are important in understanding the etiology of these age-related health disorders. We investigated the extent to which genes and the environment contribute to subjective sleep quality in middle-aged male twins using the classical twin design. We used the Pittsburgh Sleep Quality Index to measure sleep quality in 1218 middle-aged twin men from the Vietnam Era Twin Study of Aging (mean age = 55.4 years; range 51-60; 339 monozygotic twin pairs, 257 dizygotic twin pairs, 26 unpaired twins). The mean PSQI global score was 5.6 [SD = 3.6; range 0-20]. Based on univariate twin models, 34% of variability in the global PSQI score was due to additive genetic effects (heritability) and 66% was attributed to individual-specific environmental factors. Common environment did not contribute to the variability. Similarly, the heritability of poor sleep-a dichotomous measure based on the cut-off of global PSQI>5-was 31%, with no contribution of the common environment. Heritability of six of the seven PSQI component scores (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, and daytime dysfunction) ranged from 0.15 to 0.31, whereas no genetic influences contributed to the use of sleeping medication. Additive genetic influences contribute to approximately one-third of the variability of global subjective sleep quality. Our results in middle-aged men constitute a first step towards examination of the genetic relationship between sleep and other facets of aging.Accepted manuscrip

Pathways towards Legal Migration into the EU: Reappraising concepts, trajectories and policies. CEPS Paperback, September 2017

On 27 January 2017, the Justice and Home Affairs Section of CEPS and the Directorate-General for Migration and Home Affairs (DG HOME) of the European Commission co-organised a policy workshop in Brussels entitled “Reappraising the EU legal migration acquis: Legal pathways for a new model of economic migration, and the role of social science research”. The event brought together leading academics, practitioners and European Commission representatives to assess and discuss the state of play in the (internal and external) EU legal migration acquis, and its role in developing legal pathways towards economic migration. Held under the Chatham House Rule, the policy workshop’s roundtable discussions allowed participants to identify and address some of the key challenges, inconsistencies and gaps in the standing EU policies and legislation in the area of legal and economic migration. Scholars involved in EU and nationally funded, collaborative research projects on social science and humanities (SSH) had the opportunity to exchange interdisciplinary knowledge with European Commission officials representing the different services working on legal migration policies. The role and potential of independent academic research in the framework of EU migration policymaking were also discussed. The full programme of the policy workshop is reproduced in the annex of this book

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging

Synaptic and transcriptionally downregulated genes are associated with cortical thickness differences in autism.

Differences in cortical morphology-in particular, cortical volume, thickness and surface area-have been reported in individuals with autism. However, it is unclear what aspects of genetic and transcriptomic variation are associated with these differences. Here we investigate the genetic correlates of global cortical thickness differences (ΔCT) in children with autism. We used Partial Least Squares Regression (PLSR) on structural MRI data from 548 children (166 with autism, 295 neurotypical children and 87 children with ADHD) and cortical gene expression data from the Allen Institute for Brain Science to identify genetic correlates of ΔCT in autism. We identify that these genes are enriched for synaptic transmission pathways and explain significant variation in ΔCT. These genes are also significantly enriched for genes dysregulated in the autism post-mortem cortex (Odd Ratio (OR) = 1.11, Pcorrected  10-14), driven entirely by downregulated genes (OR = 1.87, Pcorrected  10-15). We validated the enrichment for downregulated genes in two independent data sets: Validation 1 (OR = 1.44, Pcorrected = 0.004) and Validation 2 (OR = 1.30; Pcorrected = 0.001). We conclude that transcriptionally downregulated genes implicated in autism are robustly associated with global changes in cortical thickness variability in children with autism

France and Migration Between Logistification and Ethical Minimalism

The article analizes French migration policies in historical perspective, arguing that the country progressively adopted a discursive and legal framework that implements a managerial dimension of migration policies which can be described as logistification and resonates with developments in other European countries and the European Unio

Adiposity is Associated with Regional Cortical Thinning

BACKGROUND: Although obesity is associated with structural changes in brain grey matter, findings have been inconsistent and the precise nature of these changes is unclear. Inconsistencies may partly be due to the use of different volumetric morphometry methods, and the inclusion of participants with comorbidities that exert independent effects on brain structure. The latter concern is particularly critical when sample sizes are modest. The purpose of the current study was to examine the relationship between cortical grey matter and body mass index (BMI), in healthy participants, excluding confounding comorbidities and using a large sample size. SUBJECTS: A total of 202 self-reported healthy volunteers were studied using surface-based morphometry, which permits the measurement of cortical thickness, surface area and cortical folding, independent of each other. RESULTS: Although increasing BMI was not associated with global cortical changes, a more precise, region-based analysis revealed significant thinning of the cortex in two areas: left lateral occipital cortex (LOC) and right ventromedial prefrontal cortex (vmPFC). An analogous region-based analysis failed to find an association between BMI and regional surface area or folding. Participants' age was also found to be negatively associated with cortical thickness of several brain regions; however, there was no overlap between the age- and BMI-related effects on cortical thinning. CONCLUSIONS: Our data suggest that the key effect of increasing BMI on cortical grey matter is a focal thinning in the left LOC and right vmPFC. Consistent implications of the latter region in reward valuation, and goal control of decision and action suggest a possible shift in these processes with increasing BMI.We thank all the participants and the staff of the Wolfson Brain Imaging Centre. This work was supported by the Bernard Wolfe Health Neuroscience Fund (NM, HZ, ISF, PCF), the Wellcome Trust (RGAG/144 to N.M, RGAG/188 to ISF, RNAG/259 to PCF) and the Medical Research Council (G0701497 to KDE).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ijo.2016.42

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function : a report from the COGENT consortium

CORRIGENDUM Molecular Psychiatry (2017) 22, 1651–1652 http://www.nature.com/articles/mp2017197.pdfThe complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (similar to 8M single-nucleotide polymorphisms (SNP) with minor allele frequency >= 1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (PPeer reviewe

Development of a UV/Vis spectrophotometric method for analysis of total polyphenols from Caesalpinia peltophoroides Benth

Caesalpinia peltophoroides is a domesticated tree found in Brazil. It was necessary to develop an analytical method to determine the content of total polyphenols (TP) in this herbal drug. The pre-analytical method was standardized for analysis time, wavelength, and the best standard to use. The optimum conditions were: pyrogallol, 760 nm, and 30 min respectively. Under these conditions, validation by UV/Vis spectrophotometry proved to be reliable for TP of the crude extract and semipurified fractions from C. peltophoroides. Standardization is required for every herbal drug, and this method proved to be linear, precise, accurate, reproducible, robust, and easy to perform