A Biological Signature of Stress Resilience: Immunization with Either Mycobacterium vaccae NCTC 11659 or M. vaccae ATCC 15483 Prevents Stress-induced Changes to Proteomic, Metabolomic, Lipidomic, and Immunological Profiles in Adult Male Rodent Models

A novel deployable radiator system has been designed to reject kilowatt-scale power at afraction of the mass compared to existing technology. The architecture involves a mechanically pumped fluid loop (MPFL) system, inspired by Mars Rover missions, to scale up for the high heat-rejection capabilities that will be necessary as spacecraft become more powerful. The system consists of layered and tapered radiator panels that undergo a similar deployment to rigid solar panels: stowed in a zigzag configuration before flattening straight out. Thin tubes are proposed as structural connectors between panels, acting as deployable hinges as well as thermal-fluid transport tubes. Experiments have characterized the tubes&rsquo; bending moment vs angle relationship, and a prototype successfully demonstrated the deployment process using only static pressure from an accumulator which would be sufficient to deploy the tubes in space. A release mechanism for initiating the deployment, using a scrolling sheet released through a burn wire, enables deployment after experiencing launching loads. The single-phase fluid loop system was designed based on existing similar technology, and simplified in order to reduce mass and complexity. The performance of traditional radiator panels is improved by combining advances in materials science with optimal thermal geometry. Instead of aluminum sandwich panels, pyrolytic graphite sheets are used in a tapered configuration to reject 61 W for each 126 g panel when at the layer base temperature of 300 K. Finite element analysis and numerical models are used to determine the effects of layer anisotropy of the design, as well as compute the thermal performance. A single radiator panel was prototyped with the same process and materials as proposed, and the design appears capable of good thermal contact without the need for fasteners. A dynamic analysis was conducted for the 28-panel system for the expected critical modes of vibration resulting in an insufficient natural frequency of 0.02 iii Hz. Through the addition of lightweight hinges and lengthened panels, the system is expected to perform with a fundamental frequency over 0.4 Hz, which is similar to existing deployed panel arrays. Finally, a thermal resistance network was created and solved numerically to determine the heat rejection from a 28-panel pumped-fluid-loop system for a 50 ◦ C spacecraft. Areal density was found to be 1.9 kg/m 2 , or 3.9 kg/m 2 if considering planform area, both considering the total system mass. Heat flux, or rejection per unit radiating area is 205 W/m 2 , or 409 W/m 2 for the planform area. With a weight of 13.3 kg, the system is projected to reject 1400 W of heat, 106 W/kg, a threefold improvement in specific power over similar existing architectures. By incorporating features, developing, and scaling aspects of this design, the next generation of high-power space missions can be realized.</p

Rare coding variants in ten genes confer substantial risk for schizophrenia

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, PPeer reviewe

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead