Widening the Adaptation of White Clover by Incorporation of Valuable New Traits from Wild Clover Species

Although white clover (Trifolium repens) is the most widely used legume in grazed pastures of temperate and sub-tropical regions, it is severely restricted in genetic diversity for adaptive traits to low soil fertility and other stress environments, including drought. The objective of this research was to transfer traits for wider adaptation from other clover species by hybridisation. Eight Trifolium species with contrasting adaptations were shown by DNA sequence phylogenetics to be closely related to white clover. Interspecific hybridisation was undertaken among these species using embryo rescue, and an array of partially fertile F1 hybrids was obtained. Population development from these F1 hybrids showed that hybrids involving six taxa could be selected for high sexual fertility. Most showed strong inter-species chromosome pairing and the potential for introgression of exotic genomes into white clover. Several of the new genomic combinations, which do not occur in nature, will improve prospects for extending the adaptive range of white clover

Volunteer satisfaction in sports clubs: A multilevel analysis in 10 European countries

Regular voluntary engagement is a basic resource for sports clubs that may also promote social cohesion and active citizenship. The satisfaction of volunteers is an imperative factor in this engagement, and the purpose of this article is to explore individual and organizational determinants of volunteer satisfaction in sports clubs. Theoretically, our study builds on the actor-theory concepts where volunteer satisfaction depends on subjective evaluations of expectations and experiences in a sports club (‘logic of situation’), so that positive evaluations lead to higher satisfaction and, hopefully, retention of volunteers. This research uses a sample of 8131 volunteers from 642 sports clubs in 10 European countries, and is the first analysis to combine determinants at the level of the club and the volunteer (multilevel). Results show that the most important determinants of satisfaction are the conditions of volunteering (recognition, support, leadership and material incentives) and the workload of volunteers. Surprisingly, club characteristics, size or having paid staff are not significant determinants of volunteer satisfaction. The results of this analysis can assist more effective volunteer management in sports clubs that are facing challenges of individualization and professionalization

A Novel and Critical Role for Oct4 as a Regulator of the Maternal-Embryonic Transition

Compared to the emerging embryonic stem cell (ESC) gene network, little is known about the dynamic gene network that directs reprogramming in the early embryo. We hypothesized that Oct4, an ESC pluripotency regulator that is also highly expressed at the 1- to 2-cell stages in embryos, may be a critical regulator of the earliest gene network in the embryo.Using antisense morpholino oligonucleotide (MO)-mediated gene knockdown, we show that Oct4 is required for development prior to the blastocyst stage. Specifically, Oct4 has a novel and critical role in regulating genes that encode transcriptional and post-transcriptional regulators as early as the 2-cell stage. Our data suggest that the key function of Oct4 may be to switch the developmental program from one that is predominantly regulated by post-transcriptional control to one that depends on the transcriptional network. Further, we propose to rank candidate genes quantitatively based on the inter-embryo variation in their differential expression in response to Oct4 knockdown. Of over 30 genes analyzed according to this proposed paradigm, Rest and Mta2, both of which have established pluripotency functions in ESCs, were found to be the most tightly regulated by Oct4 at the 2-cell stage.We show that the Oct4-regulated gene set at the 1- to 2-cell stages of early embryo development is large and distinct from its established network in ESCs. Further, our experimental approach can be applied to dissect the gene regulatory network of Oct4 and other pluripotency regulators to deconstruct the dynamic developmental program in the early embryo

A novel platform to enable the high-throughput derivation and characterization of feeder-free human iPSCs

Human induced pluripotent stem cells (hiPSCs) hold enormous potential, however several obstacles impede their translation to industrial and clinical applications. Here we describe a platform to efficiently generate, characterize and maintain single cell and feeder-free (FF) cultured hiPSCs by means of a small molecule cocktail media additive. Using this strategy we have developed an effective multiplex sorting and high-throughput selection platform where individual clonal hiPSC lines are readily obtained from a pool of candidate clones, expanded and thoroughly characterized. By promoting survival and self-renewal, the selected hiPSC clones can be rapidly expanded over multiple FF, single-cell passages while maintaining their pluripotency and genomic stability as demonstrated by trilineage differentiation, karyotype and copy number variation analysis. This study provides a robust platform that increases efficiency, throughput, scale and quality of hiPSC generation and facilitates the industrial and clinical use of iPSC technology

Predicting the impact of Lynch syndrome-causing missense mutations from structural calculations

Accurate methods to assess the pathogenicity of mutations are needed to fully leverage the possibilities of genome sequencing in diagnosis. Current data-driven and bioinformatics approaches are, however, limited by the large number of new variations found in each newly sequenced genome, and often do not provide direct mechanistic insight. Here we demonstrate, for the first time, that saturation mutagenesis, biophysical modeling and co-variation analysis, performed in silico, can predict the abundance, metabolic stability, and function of proteins inside living cells. As a model system, we selected the human mismatch repair protein, MSH2, where missense variants are known to cause the hereditary cancer predisposition disease, known as Lynch syndrome. We show that the majority of disease-causing MSH2 mutations give rise to folding defects and proteasome-dependent degradation rather than inherent loss of function, and accordingly our in silico modeling data accurately identifies disease-causing mutations and outperforms the traditionally used genetic disease predictors. Thus, in conclusion, in silico biophysical modeling should be considered for making genotype-phenotype predictions and for diagnosis of Lynch syndrome, and perhaps other hereditary diseases

The ATLAS SCT Optoelectronics and the Associated Electrical Services

The requirements for the optical links of the ATLAS SCT are described. From the individual detector modules to the first patch panel, the electrical services are integrated with the optical links to aid in mechanical design, construction and integration. The system architecture and critical elements of the system are described. The optical links for the ATLAS SCT have been assembled and mounted onto the carbon fibre support structures. The performance of the system as measured during QA is summarised and compared to the final performance obtained after mounting modules onto the support structures

The optical links of the ATLAS SemiConductor tracker

Optical links are used for the readout of the 4088 silicon microstrip modules that make up the SemiConductor Tracker of the ATLAS experiment at the CERN Large Hadron Collider (LHC). The optical link requirements are reviewed, with particular emphasis on the very demanding environment at the LHC. The on-detector components have to operate in high radiation levels for 10 years, with no maintenance, and there are very strict requirements on power consumption, material and space. A novel concept for the packaging of the on-detector optoelectronics has been developed to meet these requirements. The system architecture, including its redundancy features, is explained and the critical on-detector components are described. The results of the extensive Quality Assurance performed during all steps of the assembly are discussed

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders. Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach. Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable). Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies. Funding: Bill & Melinda Gates Foundation