Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits

This work is licensed under a Creative Commons Attribution 4.0 International License.It has been hypothesized that individually-rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. Here we identified more than 20,000 euchromatic SVs from 14 Drosophila melanogaster genome assemblies, of which ~40% are invisible to high specificity short-read genotyping approaches. SVs are common, with 31.5% of diploid individuals harboring a SV in genes larger than 5kb, and 24% harboring multiple SVs in genes larger than 10kb. SV minor allele frequencies are rarer than amino acid polymorphisms, suggesting that SVs are more deleterious. We show that a number of functionally important genes harbor previously hidden structural variants likely to affect complex phenotypes. Furthermore, SVs are overrepresented in candidate genes associated with quantitative trait loci mapped using the Drosophila Synthetic Population Resource. We conclude that SVs are ubiquitous, frequently constitute a heterogeneous allelic series, and can act as rare alleles of large effect

Fluid Intelligence and Psychosocial Outcome: From Logical Problem Solving to Social Adaptation

While fluid intelligence has proved to be central to executive functioning, logical reasoning and other frontal functions, the role of this ability in psychosocial adaptation has not been well characterized.Lower fluid intelligence scores were associated with physical violence, both in the role of victim and victimizer. Drug intake, especially cannabis, cocaine and inhalants and lower self-esteem were also associated with lower fluid intelligence. Finally, scores on the perceived mental health assessment were better when fluid intelligence scores were higher.Our results show evidence of a strong association between psychosocial adaptation and fluid intelligence, suggesting that the latter is not only central to executive functioning but also forms part of a more general capacity for adaptation to social contexts

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term ‘prebiotic’ by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation

Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes

Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ(10)), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 μM H(2)O(2))-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ(10) can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ(10) not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ(10) prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ(10) preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important pathophysiological mechanism in the dysfunction of ONH astrocytes. CoQ(10) may provide new therapeutic potentials and strategies for protecting ONH astrocytes against oxidative stress-mediated mitochondrial dysfunction or alteration in glaucoma and other optic neuropathies

The atacama cosmology telescope: A catalog of >4000 Sunyaev–Zel’dovich galaxy clusters

We present a catalog of 4195 optically confirmed Sunyaev-Zel'dovich (SZ) selected galaxy clusters detected with signal-to-noise > 4 in 13,211 deg$^2$ of sky surveyed by the Atacama Cosmology Telescope (ACT). Cluster candidates were selected by applying a multi-frequency matched filter to 98 and 150 GHz maps constructed from ACT observations obtained from 2008-2018, and confirmed using deep, wide-area optical surveys. The clusters span the redshift range 0.04 < z 1 clusters, and a total of 868 systems are new discoveries. Assuming an SZ-signal vs. mass scaling relation calibrated from X-ray observations, the sample has a 90% completeness mass limit of M500c > 3.8 x 10$^{14}$ MSun, evaluated at z = 0.5, for clusters detected at signal-to-noise ratio > 5 in maps filtered at an angular scale of 2.4'. The survey has a large overlap with deep optical weak-lensing surveys that are being used to calibrate the SZ-signal mass-scaling relation, such as the Dark Energy Survey (4566 deg$^2$), the Hyper Suprime-Cam Subaru Strategic Program (469 deg$^2$), and the Kilo Degree Survey (825 deg$^2$). We highlight some noteworthy objects in the sample, including potentially projected systems; clusters with strong lensing features; clusters with active central galaxies or star formation; and systems of multiple clusters that may be physically associated. The cluster catalog will be a useful resource for future cosmological analyses, and studying the evolution of the intracluster medium and galaxies in massive clusters over the past 10 Gyr