Sterility and Gene Expression in Hybrid Males of Xenopus laevis and X. muelleri

BACKGROUND: Reproductive isolation is a defining characteristic of populations that represent unique biological species, yet we know very little about the gene expression basis for reproductive isolation. The advent of powerful molecular biology tools provides the ability to identify genes involved in reproductive isolation and focuses attention on the molecular mechanisms that separate biological species. Herein we quantify the sterility pattern of hybrid males in African Clawed Frogs (Xenopus) and apply microarray analysis of the expression pattern found in testes to identify genes that are misexpressed in hybrid males relative to their two parental species (Xenopus laevis and X. muelleri). METHODOLOGY/PRINCIPAL FINDINGS: Phenotypic characteristics of spermatogenesis in sterile male hybrids (X. laevis x X. muelleri) were examined using a novel sperm assay that allowed quantification of live, dead, and undifferentiated sperm cells, the number of motile vs. immotile sperm, and sperm morphology. Hybrids exhibited a dramatically lower abundance of mature sperm relative to the parental species. Hybrid spermatozoa were larger in size and accompanied by numerous undifferentiated sperm cells. Microarray analysis of gene expression in testes was combined with a correction for sequence divergence derived from genomic hybridizations to identify candidate genes involved in the sterility phenotype. Analysis of the transcriptome revealed a striking asymmetric pattern of misexpression. There were only about 140 genes misexpressed in hybrids compared to X. laevis but nearly 4,000 genes misexpressed in hybrids compared to X. muelleri. CONCLUSIONS/SIGNIFICANCE: Our results provide an important correlation between phenotypic characteristics of sperm and gene expression in sterile hybrid males. The broad pattern of gene misexpression suggests intriguing mechanisms creating the dominance pattern of the X. laevis genome in hybrids. These findings significantly contribute to growing evidence for allelic dominance in hybrids and have implications for the mechanism of species differentiation at the transcriptome level

The Obama administration: what can social science offer?

This paper reports on the 2009 Academy of Social Sciences annual debate about prospects for the new United States administration. Just half way into the 'first hundred days' of President Barack Obama's term, a panel of social scientists, convened by Philip Davies, Director of the British Library's Eccles Centre for American Studies, addressed the question of what social science could offer the new president in various areas of policy and government action. Each of the panellists was offered the opportunity to revisit their presentations in the light of the discussion that took place, and this paper brings these thoughts together. Dilys Hill introduces the contributions with an overview commentary on the debate contributions. Andrew Rudalevige's analysis of the scholarship on managing the presidency leads him to state that 'Presidential leadership lies … in garnering the benefits of centralising without losing the wider expertise brought to bear by a decentralised process. Herein—somewhere!—lies the holy grail of Cabinet Government, American-style.' George C. Edwards examines presidential strategies for government with the conclusion that 'Rather than creating the conditions for important shifts in public policy, such as moving public opinion in their direction, effective leaders are the less heroic facilitators who work at the margins of coalition building to recognise and exploit opportunities in their environments.' Jenel Virden points out that in 2008 the percentage and numerical turnout of women was higher than that for men; women voted more for Obama than did men; and they were strongly hopeful that under the new administration prospects would improve. Having engaged so successfully with this sector of the population, the Obama Administration is under pressure to recognise and address its needs. Robert Singh points out that there are necessary reservations about the utility of social science in informing an Obama foreign policy, but nonetheless elaborates three propositions and seven principles that could usefully frame the administration's approach

Risk Factor Management to Prevent First Stroke

This article provides an overview on the management of risk factors to prevent primary strokes, the gaps in successful management, and future directions for the research and management of stroke risk factors. The major focus is given to the management of modifiable risk factors for stroke, including hypertension, diabetes, dyslipidemia, atrial fibrillation and other cardiac conditions, carotid artery stenosis, smoking, poor diet, physical inactivity, and obesity. A brief discussion on the management of potentially modifiable risk factors, such as alcohol and drug abuse, sleep apnea, and hyperhomocysteinemia, is included, as is the use of antiplatelet therapy in primary stroke prevention. Finally, prognostic scores to assess an individual risk for a first stroke are reviewed

Biolink Model: A universal schema for knowledge graphs in clinical, biomedical, and translational science

<h2>What's Changed</h2> <ul> <li>Documentation and repo hierarchy refactoring by @sierra-moxon in https://github.com/biolink/biolink-model/pull/1418</li> </ul> <p>Summary: 4.0.0 is a major release that includes many changes to the documentation for Biolink Model as well as the reorganization of the repository to support the new documentation structure and comply with LinkML best practices. The model itself has not changed significantly, but the documentation has been updated to reflect the current state of the model, and includes new visualizations of the model, additional text-based documentation, and a new gh-pages documentation layout.</p> <p><strong>Full Changelog</strong>: https://github.com/biolink/biolink-model/compare/v3.6.0...v4.0.0</p>Please cite the following works when using this software

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy

Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)–associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings