Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer.

Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of Polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Sex Differences in General Knowledge: Meta-Analysis and New Data on the Contribution of School-Related Moderators among High-School Students

<div><p>Research from various countries consistently reported an advantage of boys over girls in general knowledge and was also suggestive of some overall trends regarding specific domains of general knowledge that were speculated to stem from biologically differentiated interests. However, results were heterogeneous and, as of yet, had not been evaluated meta-analytically. Moreover, previous research drew on overly homogeneous high-school or undergraduate samples whose representativeness appears problematic; mostly, likely moderators, such as school type, student age or parental education, were also not directly investigated or controlled for. We provide a meta-analytical aggregation of available results regarding sex differences in general knowledge and present new data, investigating the psychometric properties of the General Knowledge Test (GKT), on which previous research primarily relied, and explored sex differences in a large and heterogeneous Austrian high-school student sample (<i>N</i> = 1088). The aggregated sex effect in general knowledge was of medium size in previous research, but differences in specific domains were heterogeneous across countries and only modest at best. Large sex differences in our data could be explained to a large part by school-related moderators (school type, school, student age, parental education) and selection processes. Boys had a remaining advantage over girls that was only small in size and that was consistent with the magnitude of sex differences in general intelligence. Analysis of the GKT yielded no evidence of biologically differentiated interests, but of a specific interest in the humanities among girls. In conclusion, previous research likely overestimated sex differences in general knowledge.</p></div

Fit Statistics of Unidimensional Models in Domains.

<p>Fit Statistics of Unidimensional Models in Domains.</p

Scale Reliabilities, Sum Score Means and Standard Deviations, and Sex Differences in Factor Scores, Unadjusted and Adjusted for Moderators.

<p>Scale Reliabilities, Sum Score Means and Standard Deviations, and Sex Differences in Factor Scores, Unadjusted and Adjusted for Moderators.</p

Fit Statistics of the Higher-Order Factor Models.

<p>Fit Statistics of the Higher-Order Factor Models.</p

Effect Tests in the GLMs.

<p>Effect Tests in the GLMs.</p

Sex Differences in General Knowledge and its Domains in Previous Studies and Aggregated Effect Estimates.

<p>Sex Differences in General Knowledge and its Domains in Previous Studies and Aggregated Effect Estimates.</p