Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever.

UnlabelledCoccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region.ImportanceCoccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii

Augmentation of post-swelling surgical sealant potential of adhesive hydrogels

National Institutes of Health (U.S.) (Grant GM 49039)National Institutes of Health (U.S.) (Grant GM 1S10RR13886-01)Philip Morris InternationalDuPont (Firm)National Defense Science and Engineering Graduate Fellowshi

FELIX: an algorithm for indexing multiple crystallites in X-ray free-electron laser snapshot diffraction images

A novel algorithm for indexing multiple crystals in snapshot X-ray diffraction images, especially suited for serial crystallography data, is presented. The algorithm, FELIX, utilizes a generalized parametrization of the Rodrigues–Frank space, in which all crystal systems can be represented without singularities. The new algorithm is shown to be capable of indexing more than ten crystals per image in simulations of cubic, tetragonal and monoclinic crystal diffraction patterns. It is also used to index an experimental serial crystallography dataset from lysozyme microcrystals. The increased number of indexed crystals is shown to result in a better signal-to-noise ratio, and fewer images are needed to achieve the same data quality as when indexing one crystal per image. The relative orientations between the multiple crystals indexed in an image show a slight tendency of the lysozme microcrystals to adhere on $(\overline {1}10)$ facets

Lifetime measurement of the 2₁⁺ state in ⁷⁴Rb and isospin properties of quadrupole transition strengths at N = Z

Self-conjugate nuclei in the A ≈ 70–80 region have attracted a great deal of attention due to phenomena such as shape coexistence and increasing collectivity along the N=Zline. We investigate the structure of nuclei in this region through lifetime measurements using the GRETINA array. The first implementation of the Differential Recoil Distance Doppler Shift technique with fast radioactive beams is demonstrated and verified through a measurement of the well-known B(E2; 2₁⁺→ 0₁⁺)transition strength in ⁷⁴Kr. The method is then applied to determine the B(E2; 2₁⁺→ 0₁⁺) transition strength in ⁷⁴Rb, the heaviest odd–odd N=Z nucleus for which this quantity has been determined. This result and extended systematics along N=Z suggest the dominance of the isoscalar part of the quadrupole transition strengths in self-conjugate nuclei, as well as the possible presence of shape coexistence in ⁷⁴Rb

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer 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