Quantitative trait loci associated with different polar metabolites in perennial ryegrass - providing scope for breeding towards increasing certain polar metabolites

peer-reviewedBackground Recent advances in the mapping of biochemical traits have been reported in Lolium perenne. Although the mapped traits, including individual sugars and fatty acids, contribute greatly towards ruminant productivity, organic acids and amino acids have been largely understudied despite their influence on the ruminal microbiome. Results In this study, we used a targeted gas-chromatography mass spectrometry (GC-MS) approach to profile the levels of 25 polar metabolites from different classes (sugars, amino acids, phenolic acids, organic acids and other nitrogen-containing compounds) present in a L. perenne F2 population consisting of 325 individuals. A quantitative trait (QTL) mapping approach was applied and successfully identified QTLs regulating seven of those polar metabolites (L-serine, L-leucine, glucose, fructose, myo-inositol, citric acid and 2, 3-hydroxypropanoic acid).Two QTL mapping approaches were carried out using SNP markers on about half of the population only and an imputation approach using SNP and DArT markers on the entire population. The imputation approach confirmed the four QTLs found in the SNP-only analysis and identified a further seven QTLs. Conclusions These results highlight the potential of utilising molecular assisted breeding in perennial ryegrass to modulate a range of biochemical quality traits with downstream effects in livestock productivity and ruminal digestion.This study was financed through a Research Stimulus Fund Grant by the Irish Department of Agriculture, Fisheries and Marine (RSF 06–346). AF, CH and DS acknowledge support from The Scottish Government’s Rural and Environment Science and Analytical Services Division

STAT2 deficiency and susceptibility to viral illness in humans

Severe infectious disease in children may be a manifestation of primary immunodeficiency. These genetic disorders represent important experiments of nature with the capacity to elucidate nonredundant mechanisms of human immunity. We hypothesized that a primary defect of innate antiviral immunity was responsible for unusually severe viral illness in two siblings; the proband developed disseminated vaccine strain measles following routine immunization, whereas an infant brother died after a 2-d febrile illness from an unknown viral infection. Patient fibroblasts were indeed abnormally permissive for viral replication in vitro, associated with profound failure of type I IFN signaling and absence of STAT2 protein. Sequencing of genomic DNA and RNA revealed a homozygous mutation in intron 4 of STAT2 that prevented correct splicing in patient cells. Subsequently, other family members were identified with the same genetic lesion. Despite documented infection by known viral pathogens, some of which have been more severe than normal, surviving STAT2-deficient individuals have remained generally healthy, with no obvious defects in their adaptive immunity or developmental abnormalities. These findings imply that type I IFN signaling [through interferon-stimulated gene factor 3 (ISGF3)] is surprisingly not essential for host defense against the majority of common childhood viral infections

5-SPICE: the application of an original framework for community health worker program design, quality improvement and research agenda setting

Introduction: Despite decades of experience with community health workers (CHWs) in a wide variety of global health projects, there is no established conceptual framework that structures how implementers and researchers can understand, study and improve their respective programs based on lessons learned by other CHW programs. Objective: To apply an original, non-linear framework and case study method, 5-SPICE, to multiple sister projects of a large, international non-governmental organization (NGO), and other CHW projects. Design: Engaging a large group of implementers, researchers and the best available literature, the 5-SPICE framework was refined and then applied to a selection of CHW programs. Insights gleaned from the case study method were summarized in a tabular format named the ‘5×5-SPICE chart’. This format graphically lists the ways in which essential CHW program elements interact, both positively and negatively, in the implementation field. Results: The 5×5-SPICE charts reveal a variety of insights that come from a more complex understanding of how essential CHW projects interact and influence each other in their unique context. Some have been well described in the literature previously, while others are exclusive to this article. An analysis of how best to compensate CHWs is also offered as an example of the type of insights that this method may yield. Conclusions: The 5-SPICE framework is a novel instrument that can be used to guide discussions about CHW projects. Insights from this process can help guide quality improvement efforts, or be used as hypothesis that will form the basis of a program's research agenda. Recent experience with research protocols embedded into successfully implemented projects demonstrates how such hypothesis can be rigorously tested

Prospectus, April 26, 1977

VOTE TODAY-TOMORROW: FOUR VIE FOR PRES. IN STU-GO ELECTION; Remus, Mayeda run for V.P.; Albert Dodson unopposed; Activities Day May 3; Letters to the editor: Pres. Praises carnival, Mayeda warns of lies, Cartoon good…but, Stu-Go made many contributions: Onley; Editorial: Trouble for athletics; Hackett vs. Slack for convo., Cox opposes Stoeber for IOC; Unopposed: Propeck runs alone for secretary; Thursday set for wheel chair awareness; State provides funding for food sanitation course; Law Enforcement Club sponsors Mk\u27t Place fair; Markland: bigger not better for Twin City police force; Energy saving tips: Ripple effect causes waste; Police Chief Dye: \u27Recruitment-lifeline of police dep\u27t.\u27; Bike race today; Blooming Idiots come out of woodwork for IOC Carnival; Workshop set for Saturday: Puppetmaster Schmidt displays at PC; Afro American Theatre Workshop starts at PC; \u27Alcohol, sophisticated, sexy?\u27; Bike tour Sunday, May 1; Classifieds; Bat girls provide needed help for baseball team; Cobras expand record with 3rd no-hitter; Lincolnland doubleheader tomorrow: Women\u27s softball season nears end; June 7-10: Mudrock headed to JC golf nationalshttps://spark.parkland.edu/prospectus_1977/1018/thumbnail.jp

Data Science and Machine Learning in Education

The growing role of data science (DS) and machine learning (ML) in high-energy physics (HEP) is well established and pertinent given the complex detectors, large data, sets and sophisticated analyses at the heart of HEP research. Moreover, exploiting symmetries inherent in physics data have inspired physics-informed ML as a vibrant sub-field of computer science research. HEP researchers benefit greatly from materials widely available materials for use in education, training and workforce development. They are also contributing to these materials and providing software to DS/ML-related fields. Increasingly, physics departments are offering courses at the intersection of DS, ML and physics, often using curricula developed by HEP researchers and involving open software and data used in HEP. In this white paper, we explore synergies between HEP research and DS/ML education, discuss opportunities and challenges at this intersection, and propose community activities that will be mutually beneficial.Comment: Contribution to Snowmass 202

Affordances, constraints and information flows as ‘leverage points’ in design for sustainable behaviour

Copyright @ 2012 Social Science Electronic PublishingTwo of Donella Meadows' 'leverage points' for intervening in systems (1999) seem particularly pertinent to design for sustainable behaviour, in the sense that designers may have the scope to implement them in (re-)designing everyday products and services. The 'rules of the system' -- interpreted here to refer to affordances and constraints -- and the structure of information flows both offer a range of opportunities for design interventions to in fluence behaviour change, and in this paper, some of the implications and possibilities are discussed with reference to parallel concepts from within design, HCI and relevant areas of psychology

The Development of Three Long Universal Nuclear Protein-Coding Locus Markers and Their Application to Osteichthyan Phylogenetics with Nested PCR

BACKGROUND: Universal nuclear protein-coding locus (NPCL) markers that are applicable across diverse taxa and show good phylogenetic discrimination have broad applications in molecular phylogenetic studies. For example, RAG1, a representative NPCL marker, has been successfully used to make phylogenetic inferences within all major osteichthyan groups. However, such markers with broad working range and high phylogenetic performance are still scarce. It is necessary to develop more universal NPCL markers comparable to RAG1 for osteichthyan phylogenetics. METHODOLOGY/PRINCIPAL FINDINGS: We developed three long universal NPCL markers (>1.6 kb each) based on single-copy nuclear genes (KIAA1239, SACS and TTN) that possess large exons and exhibit the appropriate evolutionary rates. We then compared their phylogenetic utilities with that of the reference marker RAG1 in 47 jawed vertebrate species. In comparison with RAG1, each of the three long universal markers yielded similar topologies and branch supports, all in congruence with the currently accepted osteichthyan phylogeny. To compare their phylogenetic performance visually, we also estimated the phylogenetic informativeness (PI) profile for each of the four long universal NPCL markers. The PI curves indicated that SACS performed best over the whole timescale, while RAG1, KIAA1239 and TTN exhibited similar phylogenetic performances. In addition, we compared the success of nested PCR and standard PCR when amplifying NPCL marker fragments. The amplification success rate and efficiency of the nested PCR were overwhelmingly higher than those of standard PCR. CONCLUSIONS/SIGNIFICANCE: Our work clearly demonstrates the superiority of nested PCR over the conventional PCR in phylogenetic studies and develops three long universal NPCL markers (KIAA1239, SACS and TTN) with the nested PCR strategy. The three markers exhibit high phylogenetic utilities in osteichthyan phylogenetics and can be widely used as pilot genes for phylogenetic questions of osteichthyans at different taxonomic levels

Erythroid-Specific Expression of β-globin from Sleeping Beauty-Transduced Human Hematopoietic Progenitor Cells

Gene therapy for sickle cell disease will require efficient delivery of a tightly regulated and stably expressed gene product to provide an effective therapy. In this study we utilized the non-viral Sleeping Beauty (SB) transposon system using the SB100X hyperactive transposase to transduce human cord blood CD34+ cells with DsRed and a hybrid IHK–β-globin transgene. IHK transduced cells were successfully differentiated into multiple lineages which all showed transgene integration. The mature erythroid cells had an increased β-globin to γ-globin ratio from 0.66±0.08 to 1.05±0.12 (p = 0.05), indicating expression of β-globin from the integrated SB transgene. IHK–β-globin mRNA was found in non-erythroid cell types, similar to native β-globin mRNA that was also expressed at low levels. Additional studies in the hematopoietic K562 cell line confirmed the ability of cHS4 insulator elements to protect DsRed and IHK–β-globin transgenes from silencing in long-term culture studies. Insulated transgenes had statistically significant improvement in the maintenance of long term expression, while preserving transgene regulation. These results support the use of Sleeping Beauty vectors in carrying an insulated IHK–β-globin transgene for gene therapy of sickle cell disease