Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility

Reph, a Regulator of Eph Receptor Expression in the Drosophila melanogaster Optic Lobe

Receptors of the Eph family of tyrosine kinases and their Ephrin ligands are involved in developmental processes as diverse as angiogenesis, axon guidance and cell migration. However, our understanding of the Eph signaling pathway is incomplete, and could benefit from an analysis by genetic methods. To this end, we performed a genetic modifier screen for mutations that affect Eph signaling in Drosophila melanogaster. Several dozen loci were identified on the basis of their suppression or enhancement of an eye defect induced by the ectopic expression of Ephrin during development; many of these mutant loci were found to disrupt visual system development. One modifier locus, reph (regulator of eph expression), was characterized in molecular detail and found to encode a putative nuclear protein that interacts genetically with Eph signaling pathway mutations. Reph is an autonomous regulator of Eph receptor expression, required for the graded expression of Eph protein and the establishment of an optic lobe axonal topographic map. These results reveal a novel component of the regulatory pathway controlling expression of eph and identify reph as a novel factor in the developing visual system

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Psychosocial and Behavioral Factors in Awake Bruxism—Self-Report versus Ecological Momentary Assessment

The issue of psychosocial factors and concurrent conditions associated with AB is a relatively new approach in the study of Awake Bruxism (AB). In the present study a population of 84 dental students were assessed for probable AB with two modes of AB assessment: Single point self-report (SR) and ecological momentary assessment through a designated smartphone application (BA). The two assessment modes were compared with regard to their ability to phenotype subjects as far as the following psychosocial and behavioral variables are concerned: Gender; depression; somatization; oral behaviors; chronic pain and associated pain symptoms in the head, neck and scapula. Two-way ANOVA showed main effect of SR for the following variables: Chronic Pain Intensity score (F(1,49) = 6.441, p < 0.02), migraine/headache (F(1,81) = 7.396, p < 0.01), pain in neck (F(1,81) = 6.726, p < 0.05), pain in scapula (F(1,81) = 8.546, p < 0.005) and the oral behaviors of pushing the tongue forcefully against the teeth (F(1,81) = 5.222, p < 0.05) and inserting the tongue between the upper and lower teeth (F(1,81) = 5.344, p < 0.03). The effect of SR on the habit of chewing gum was borderline (F(1,81) = 3.369, p = 0.07). Main effect of BA was found for depression (F(1,81) = 6.049, p < 0.05), while the effect of BA on somatization was borderline (F(1,81) = 3.657, p = 0.059). An interaction between SR and BA groups could be observed for the behavior of biting, chewing or playing with the tongue, cheeks or lips (F(1,81) = 4.117, p < 0.05). The results suggest that a combination of a single-point self-report referring to the past 30 days, and an ecological momentary assessment supplying information about the actual timing of the report, can help us to better assess AB, as well as increase our ability to define the phenotype of subjects with AB as far as psychosocial and behavioral factors are concerned

Experiment on biogeochemical changes following Rhopilema nomadica decomposition

This study estimated the short-term decomposition effects of the invasive jellyfish Rhopilema nomadica on nutrient dynamics at the sediment-water interface in the Eastern Mediterranean Sea using core incubations. The degradation of R. nomadica has led to increased oxygen demand and acidification of overlying water as well as high rates of dissolved organic nitrogen and phosphate production