Novel Bayesian Networks for Genomic Prediction of Developmental Traits in Biomass Sorghum.

The ability to connect genetic information between traits over time allow Bayesian networks to offer a powerful probabilistic framework to construct genomic prediction models. In this study, we phenotyped a diversity panel of 869 biomass sorghum (Sorghum bicolor (L.) Moench) lines, which had been genotyped with 100,435 SNP markers, for plant height (PH) with biweekly measurements from 30 to 120 days after planting (DAP) and for end-of-season dry biomass yield (DBY) in four environments. We evaluated five genomic prediction models: Bayesian network (BN), Pleiotropic Bayesian network (PBN), Dynamic Bayesian network (DBN), multi-trait GBLUP (MTr-GBLUP), and multi-time GBLUP (MTi-GBLUP) models. In fivefold cross-validation, prediction accuracies ranged from 0.46 (PBN) to 0.49 (MTr-GBLUP) for DBY and from 0.47 (DBN, DAP120) to 0.75 (MTi-GBLUP, DAP60) for PH. Forward-chaining cross-validation further improved prediction accuracies of the DBN, MTi-GBLUP and MTr-GBLUP models for PH (training slice: 30-45 DAP) by 36.4-52.4% relative to the BN and PBN models. Coincidence indices (target: biomass, secondary: PH) and a coincidence index based on lines (PH time series) showed that the ranking of lines by PH changed minimally after 45 DAP. These results suggest a two-level indirect selection method for PH at harvest (first-level target trait) and DBY (second-level target trait) could be conducted earlier in the season based on ranking of lines by PH at 45 DAP (secondary trait). With the advance of high-throughput phenotyping technologies, our proposed two-level indirect selection framework could be valuable for enhancing genetic gain per unit of time when selecting on developmental traits

Impacts of elevated atmospheric CO₂ on nutrient content of important food crops.

One of the many ways that climate change may affect human health is by altering the nutrient content of food crops. However, previous attempts to study the effects of increased atmospheric CO2 on crop nutrition have been limited by small sample sizes and/or artificial growing conditions. Here we present data from a meta-analysis of the nutritional contents of the edible portions of 41 cultivars of six major crop species grown using free-air CO2 enrichment (FACE) technology to expose crops to ambient and elevated CO2 concentrations in otherwise normal field cultivation conditions. This data, collected across three continents, represents over ten times more data on the nutrient content of crops grown in FACE experiments than was previously available. We expect it to be deeply useful to future studies, such as efforts to understand the impacts of elevated atmospheric CO2 on crop macro- and micronutrient concentrations, or attempts to alleviate harmful effects of these changes for the billions of people who depend on these crops for essential nutrients

Flavor in Minimal Conformal Technicolor

We construct a complete, realistic, and natural UV completion of minimal conformal technicolor that explains the origin of quark and lepton masses and mixing angles. As in "bosonic technicolor", we embed conformal technicolor in a supersymmetric theory, with supersymmetry broken at a high scale. The exchange of heavy scalar doublets generates higher-dimension interactions between technifermions and quarks and leptons that give rise to quark and lepton masses at the TeV scale. Obtaining a sufficiently large top quark mass requires strong dynamics at the supersymmetry breaking scale in both the top and technicolor sectors. This is natural if the theory above the supersymmetry breaking also has strong conformal dynamics. We present two models in which the strong top dynamics is realized in different ways. In both models, constraints from flavor-changing effects can be easily satisfied. The effective theory below the supersymmetry breaking scale is minimal conformal technicolor with an additional light technicolor gaugino. We argue that this light gaugino is a general consequence of conformal technicolor embedded into a supersymmetric theory. If the gaugino has mass below the TeV scale it will give rise to an additional pseudo Nambu-Goldstone boson that is observable at the LHC.Comment: 37 pages; references adde

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab

Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab.Agência financiadora Merck Sharp and Dohme, Lda, Portugal MK8259-22info:eu-repo/semantics/publishedVersio

Minimal Conformal Technicolor and Precision Electroweak Tests

We study the minimal model of conformal technicolor, an SU(2) gauge theory near a strongly coupled conformal fixed point, with conformal symmetry softly broken by technifermion mass terms. Conformal symmetry breaking triggers chiral symmetry breaking in the pattern SU(4) -> Sp(4), which gives rise to a pseudo-Nambu-Goldstone boson that can act as a composite Higgs boson. The top quark is elementary, and the top and electroweak gauge loop contributions to the Higgs mass are cut off entirely by Higgs compositeness. In particular, the model requires no top partners and no "little Higgs" mechanism. A nontrivial vacuum alignment results from the interplay of the top loop and technifermion mass terms. The composite Higgs mass is completely determined by the top loop, in the sense that m_h/m_t is independent of the vacuum alignment and is computable by a strong-coupling calculation. There is an additional composite pseudoscalar A with mass larger than m_h and suppressed direct production at LHC. We discuss the electroweak fit in this model in detail. Corrections to Z -> bb and the T parameter from the top sector are suppressed by the enhanced Sp(4) custodial symmetry. Even assuming that the strong contribution to the S parameter is positive and usuppressed, a good electroweak fit can be obtained for v/f ~ 0.25, where v and f are the electroweak and chiral symmetry breaking scales respectively. This requires fine tuning at the 10% level.Comment: 34 pages, 4 figures; v2: updated precision electroweak fi

Social entrepreneurs in challenging places: A Delphi study of experiences and perspectives

Social Enterprises have grown in number and scope in response to reductions in state-provided welfare and increasing ambition to improve social conditions. While a range of issues have been identified in the literature as affecting the ability of Social Enterprises to successfully conduct their activities, there is currently a dearth of research into the relative influence of these factors. This study explores and ranks the challenges faced by social entrepreneurs in South Wales. Based on a Delphi study with 21 social entrepreneurs, government policy-developers and scholars, it presents a hierarchy of 14 factors, useful instruments for informing social entrepreneurs and policy-makers about the way social enterprises are managed, and how national and local policy should be developed. As part of this, the study also identifies four novel factors that affect the sustainability of social enterprises: ‘Professionalisation of Marketing’, ‘Perception of Validity’, ‘Leadership’ and ‘Situatedness’

Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

Testing for hepatitis C virus (HCV) infection may reduce the risk of liver-related morbidity, by facilitating earlier access to treatment and care. This review investigated the effectiveness of targeted testing interventions on HCV case detection, treatment uptake, and prevention of liver-related morbidity. A literature search identified studies published up to 2013 that compared a targeted HCV testing intervention (targeting individuals or groups at increased risk of HCV) with no targeted intervention, and results were synthesised using meta-analysis. Exposure to a targeted testing intervention, compared to no targeted intervention, was associated with increased cases detected [number of studies (n) = 14; pooled relative risk (RR) 1.7, 95 % CI 1.3, 2.2] and patients commencing therapy (n = 4; RR 3.3, 95 % CI 1.1, 10.0). Practitioner-based interventions increased test uptake and cases detected (n = 12; RR 3.5, 95 % CI 2.5, 4.8; and n = 10; RR 2.2, 95 % CI 1.4, 3.5, respectively), whereas media/information-based interventions were less effective (n = 4; RR 1.5, 95 % CI 0.7, 3.0; and n = 4; RR 1.3, 95 % CI 1.0, 1.6, respectively). This meta-analysis provides for the first time a quantitative assessment of targeted HCV testing interventions, demonstrating that these strategies were effective in diagnosing cases and increasing treatment uptake. Strategies involving practitioner-based interventions yielded the most favourable outcomes. It is recommended that testing should be targeted at and offered to individuals who are part of a population with high HCV prevalence, or who have a history of HCV risk behaviour

A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila

Development of effective malaria vaccines is hampered by the problem of producing correctly folded Plasmodium proteins for use as vaccine components. We have investigated the use of a novel ciliate expression system, Tetrahymena thermophila, as a P. falciparum vaccine antigen platform. A synthetic vaccine antigen composed of N-terminal and C-terminal regions of merozoite surface protein-1 (MSP-1) was expressed in Tetrahymena thermophila. The recombinant antigen was secreted into the culture medium and purified by monoclonal antibody (mAb) affinity chromatography. The vaccine was immunogenic in MF1 mice, eliciting high antibody titers against both N- and C-terminal components. Sera from immunized animals reacted strongly with P. falciparum parasites from three antigenically different strains by immunofluorescence assays, confirming that the antibodies produced are able to recognize parasite antigens in their native form. Epitope mapping of serum reactivity with a peptide library derived from all three MSP-1 Block 2 serotypes confirmed that the MSP-1 Block 2 hybrid component of the vaccine had effectively targeted all three serotypes of this polymorphic region of MSP-1. This study has successfully demonstrated the use of Tetrahymena thermophila as a recombinant protein expression platform for the production of malaria vaccine antigens

The individual and combined effects of obesity- and ageing-induced systemic inflammation on human skeletal muscle properties.

BACKGROUND/OBJECTIVES: The purpose of this study was to determine whether circulating pro-inflammatory cytokines, elevated with increased fat mass and ageing, were associated with muscle properties in young and older people with variable adiposity. SUBJECTS/METHODS: Seventy-five young (18-49 yrs) and 67 older (50-80 yrs) healthy, untrained men and women (BMI: 17-49 kg/m(2)) performed isometric and isokinetic plantar flexor maximum voluntary contractions (MVCs). Volume (Vm), fascicle pennation angle (FPA), and physiological cross-sectional area (PCSA) of the gastrocnemius medialis (GM) muscle were measured using ultrasonography. Voluntary muscle activation (VA) was assessed using electrical stimulation. GM specific force was calculated as GM fascicle force/PCSA. Percentage body fat (BF%), body fat mass (BFM), and lean mass (BLM) were assessed using dual-energy X-ray absorptiometry. Serum concentration of 12 cytokines was measured using multiplex luminometry. RESULTS: Despite greater Vm, FPA, and PCSA (P0.05), while IL-8 correlated with VA in older but not young adults (r⩾0.378, P⩽0.027). TNF-alpha correlated with MVC, lean mass, GM FPA and maximum force in older adults (r⩾0.458; P⩽0.048). CONCLUSIONS: The age- and adiposity-dependent relationships found here provide evidence that circulating pro-inflammatory cytokines may play different roles in muscle remodelling according to the age and adiposity of the individual.International Journal of Obesity accepted article preview online, 29 August 2016. doi:10.1038/ijo.2016.151