Patterns of genic intolerance of rare copy number variation in 59,898 human exomes.

Copy number variation (CNV) affecting protein-coding genes contributes substantially to human diversity and disease. Here we characterized the rates and properties of rare genic CNVs (<0.5% frequency) in exome sequencing data from nearly 60,000 individuals in the Exome Aggregation Consortium (ExAC) database. On average, individuals possessed 0.81 deleted and 1.75 duplicated genes, and most (70%) carried at least one rare genic CNV. For every gene, we empirically estimated an index of relative intolerance to CNVs that demonstrated moderate correlation with measures of genic constraint based on single-nucleotide variation (SNV) and was independently correlated with measures of evolutionary conservation. For individuals with schizophrenia, genes affected by CNVs were more intolerant than in controls. The ExAC CNV data constitute a critical component of an integrated database spanning the spectrum of human genetic variation, aiding in the interpretation of personal genomes as well as population-based disease studies. These data are freely available for download and visualization online

Mitochondrial and nuclear genes suggest that stony corals are monophyletic but most families of stony corals are not (Order Scleractinia, Class Anthozoa, Phylum Cnidaria)

Modern hard corals (Class Hexacorallia; Order Scleractinia) are widely studied because of their fundamental role in reef building and their superb fossil record extending back to the Triassic. Nevertheless, interpretations of their evolutionary relationships have been in flux for over a decade. Recent analyses undermine the legitimacy of traditional suborders, families and genera, and suggest that a non-skeletal sister clade (Order Corallimorpharia) might be imbedded within the stony corals. However, these studies either sampled a relatively limited array of taxa or assembled trees from heterogeneous data sets. Here we provide a more comprehensive analysis of Scleractinia (127 species, 75 genera, 17 families) and various outgroups, based on two mitochondrial genes (cytochrome oxidase I, cytochrome b), with analyses of nuclear genes (ßtubulin, ribosomal DNA) of a subset of taxa to test unexpected relationships. Eleven of 16 families were found to be polyphyletic. Strikingly, over one third of all families as conventionally defined contain representatives from the highly divergent "robust" and "complex" clades. However, the recent suggestion that corallimorpharians are true corals that have lost their skeletons was not upheld. Relationships were supported not only by mitochondrial and nuclear genes, but also often by morphological characters which had been ignored or never noted previously. The concordance of molecular characters and more carefully examined morphological characters suggests a future of greater taxonomic stability, as well as the potential to trace the evolutionary history of this ecologically important group using fossils

Host-Associated Bacteriophage Isolation and Preparation for Viral Metagenomics.

Prokaryotic viruses, or bacteriophages, are viruses that infect bacteria and archaea. These viruses have been known to associate with host systems for decades, yet only recently have their influence on the regulation of host-associated bacteria been appreciated. These studies have been conducted in many host systems, from the base of animal life in the Cnidarian phylum to mammals. These prokaryotic viruses are useful for regulating the number of bacteria in a host ecosystem and for regulating the strains of bacteria useful for the microbiome. These viruses are likely selected by the host to maintain bacterial populations. Viral metagenomics allows researchers to profile the communities of viruses associating with animal hosts, and importantly helps to determine the functional role these viruses play. Further, viral metagenomics show the sphere of viral involvement in gene flow and gene shuffling in an ever-changing host environment. The influence of prokaryotic viruses could, therefore, have a clear impact on host health

Процесс анализа угроз, влияющих на экономическую устойчивость предприятия

На основании проведенного исследования были выявлены факторы возникновения угроз, их группировка по степени воздействию на экономическую устойчивость предприятий и рассмотрена формализация процесса анализа угроз экономической устойчивости предприятий. В условиях рыночной экономики невозможно управлять предприятием без учета влияния угроз, а для эффективного управления важно не только знать об их присутствии, а и правильно идентифицировать конкретную угрозу.На підставі проведеного дослідження були виявлені чинники виникнення загроз, їх угруповання по степені впливу на економічну стійкість підприємств і розглянута формалізація процесу аналізу загроз економічної стійкості підприємств. В умовах ринкової економіки неможливо керувати підприємством без вивчення впливу загроз, а для ефективного керування важливо не тільки знати про їх присутність, а і правильно ідентифікувати конкретну загрозу.On the basis of the conducted research the factors of origin of threats were exposed, their gourmet on a degree to influence on economic stability of enterprises and formalization of process of analysis of threats of economic stability of enterprises is considered. In the conditions of market economy it is impossible to manage an enterprise without taking into account influencing of threats, and for the effective management it is important not only to know about their presence, and to identify the concrete threat correctly

Key features of palliative care service delivery to Indigenous peoples in Australia, New Zealand, Canada and the United States: A comprehensive review

Background: Indigenous peoples in developed countries have reduced life expectancies, particularly from chronic diseases. The lack of access to and take up of palliative care services of Indigenous peoples is an ongoing concern. Objectives: To examine and learn from published studies on provision of culturally safe palliative care service delivery to Indigenous people in Australia, New Zealand (NZ), Canada and the United States of America (USA); and to compare Indigenous peoples’ preferences, needs, opportunities and barriers to palliative care. Methods: A comprehensive search of multiple databases was undertaken. Articles were included if they were published in English from 2000 onwards and related to palliative care service delivery for Indigenous populations; papers could use quantitative or qualitative approaches. Common themes were identified using thematic synthesis. Studies were evaluated using Daly’s hierarchy of evidence-for-practice in qualitative research. Results: Of 522 articles screened, 39 were eligible for inclusion. Despite diversity in Indigenous peoples’ experiences across countries, some commonalities were noted in the preferences for palliative care of Indigenous people: to die close to or at home; involvement of family; and the integration of cultural practices. Barriers identified included inaccessibility, affordability, lack of awareness of services, perceptions of palliative care, and inappropriate services. Identified models attempted to address these gaps by adopting the following strategies: community engagement and ownership; flexibility in approach; continuing education and training; a whole-of-service approach; and local partnerships among multiple agencies. Better engagement with Indigenous clients, an increase in number of palliative care patients, improved outcomes, and understanding about palliative care by patients and their families were identified as positive achievements. Conclusions: The results provide a comprehensive overview of identified effective practices with regards to palliative care delivered to Indigenous populations to guide future program developments in this field. Further research is required to explore the palliative care needs and experiences of Indigenous people living in urban areas

Management Approach : The Virtuous Corporation as a Moral Agent for Sustainable Development

This chapter examines the corporation as a moral agent for sustainable development. While sustainable development in business organizations can be argued from utility-and duty-based ethical theories, it is suggested that virtue-based ethics is needed to develop a moral agency for sustainable development, as it focuses on the organizational character. In addition, it is proposed that the biosphere (the global sum of all ecosystems) is accepted as the ultimate principal for all planetary agents to avoid an anthropocentric and only inward-looking position typical for ethical theories. Thus, a business organization can work as a nexus for virtue and develop a moral agency that contributes to the well-being of the biosphere and all of its members.Peer reviewe

Cryptic speciation in gentoo penguins is driven by geographic isolation and regional marine conditions: Unforeseen vulnerabilities to global change

The conservation of biodiversity is hampered by data deficiencies, with many new species and subspecies awaiting description or reclassification. Population genomics and ecological niche modelling offer complementary new tools for un-covering functional units of phylogenetic diversity. We hypothesize that phyloge-netically delineated lineages of gentoo penguins (Pygoscelis papua) distributed across Antarctica and sub-Antarctic Islands are subject to spatially explicit ecological con-ditions that have limited gene flow, facilitating genetic differentiation, and thereby speciation processes

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized controlled trial

Background - While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss. Methods/Design - Using a two-arm randomized controlled trial, this 6-month study builds upon the community-based progressive resistance training (PRT) programme Lift for Life® to evaluate whether ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, body composition and cardiometabolic health in older adults with type 2 diabetes. Approximately 200 adults aged 50 to 75 years with type 2 diabetes, treated with either diet alone or oral hypoglycaemic agents (not insulin), will be recruited. All participants will be asked to participate in a structured, supervised PRT programme based on the Lift for Life® programme structure, and randomly allocated to receive a whey-protein drink (20 g daily of whey-protein plus 20 g after each PRT session) plus vitamin D supplements (2000 IU/day), or no additional powder and supplements. The primary outcome measures to be collected at baseline, 3 and 6 months will be glycated haemoglobin (HbA1c) and insulin sensitivity (homeostatic model assessment). Secondary outcomes will include changes in: muscle mass, size and intramuscular fat; fat mass; muscle strength and function; blood pressure; levels of lipids, adipokines and inflammatory markers, serum insulin-like growth factor-1 and 25-hydroxyvitamin D; renal function; diabetes medication; health-related quality of life, and cognitive function. Discussion - The findings from this study will provide new evidence on whether increased dietary protein achieved through the ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, muscle mass and size, and cardiometabolic risk factors in older adults with type 2 diabetes

Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders

Background Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs. Methods Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 controls were statistically evaluated for de novo variant burden in gene families. Results We demonstrate that disease-associated missense variants are enriched at paralog-conserved sites across all disease groups and inheritance models tested. We developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in NDD patients of which 28 represent novel candidate genes for NDD which are brain expressed and under evolutionary constraint. Conclusion This study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes