MF2102

Gerald Stokka et al., Dairy "preventive herd health program" (PHHP), Kansas State University, October 1996

EP51

Gerald L. Stokka et al., Bovine Leukosis, Kansas State University, November 1998

The yeast high mobility group protein HMO2, a subunit of the chromatin-remodeling complex INO80, binds DNA ends

DNA damage is a common hazard that all cells have to combat. Saccharomyces cerevisiae HMO2 is a high mobility group protein (HMGB) that is a component of the chromatin-remodeling complex INO80, which is involved in double strand break (DSB) repair. We show here using DNA end-joining and exonuclease protection assays that HMO2 binds preferentially to DNA ends. While HMO2 binds DNA with both blunt and cohesive ends, the sequence of a single stranded overhang significantly affects binding, supporting the conclusion that HMO2 recognizes features at DNA ends. Analysis of the effect of duplex length on the ability of HMO2 to protect DNA from exonucleolytic cleavage suggests that more than one HMO2 must assemble at each DNA end. HMO2 binds supercoiled DNA with higher affinity than linear DNA and has a preference for DNA with lesions such as pairs of tandem mismatches; however, comparison of DNA constructs of increasing length suggests that HMO2 may not bind stably as a monomer to distorted DNA. The remarkable ability of HMO2 to protect DNA from exonucleolytic cleavage, combined with reports that HMO2 arrives early at DNA DSBs, suggests that HMO2 may play a role in DSB repair beyond INO80 recruitment

A Science-Based Policy for Managing Free-Roaming Cats

Free-roaming domestic cats (i.e., cats that are owned or unowned and are considered ‘at large’) are globally distributed non-native species that have marked impacts on biodiversity and human health. Despite clear scientific evidence of these impacts, free-roaming cats are either unmanaged or managed using scientifically unsupported and ineffective approaches (e.g., trap-neuter-release [TNR]) in many jurisdictions around the world. A critical first initiative for effective, science-driven management of cats must be broader political and legislative recognition of free-roaming cats as a non-native, invasive species. Designating cats as invasive is important for developing and implementing science-based management plans, which should include efforts to prevent cats from becoming free-roaming, policies focused on responsible pet ownership and banning outdoor cat feeding, and better enforcement of existing laws. Using a science-based approach is necessary for responding effectively to the politically charged and increasingly urgent issue of managing free-roaming cat populations

Setting priorities for humanitarian water, sanitation and hygiene research: a meeting report

Recent systematic reviews have highlighted a paucity of rigorous evidence to guide water, sanitation and hygiene (WASH) interventions in humanitarian crises. In June 2017, the Research for Health in Humanitarian Crises (R2HC) programme of Elhra, convened a meeting of representatives from international response agencies, research institutions and donor organisations active in the field of humanitarian WASH to identify research priorities, discuss challenges conducting research and to establish next steps. Topics including cholera transmission, menstrual hygiene management, and acute undernutrition were identified as research priorities. Several international response agencies have existing research programmes; however, a more cohesive and coordinated effort in the WASH sector would likely advance this field of research. This report shares the conclusions of that meeting and proposes a research agenda with the aim of strengthening humanitarian WASH policy and practice

Reproductive factors and risk of hormone receptor positive and negative breast cancer: a cohort study

Background: The association of reproductive factors with hormone receptor (HR)-negative breast tumors remains uncertain. Methods: Within the EPIC cohort, Cox proportional hazards models were used to describe the relationships of reproductive factors (menarcheal age, time between menarche and first pregnancy, parity, number of children, age at first and last pregnancies, time since last full-term childbirth, breastfeeding, age at menopause, ever having an abortion and use of oral contraceptives [OC]) with risk of ER-PR-(n = 998) and ER+PR+ (n = 3,567) breast tumors. Results: A later first full-term childbirth was associated with increased risk of ER+PR+ tumors but not with risk of ER-PR-tumors (= 35 vs. = 19 years HR: 1.47 [95% CI 1.15-1.88] p(trend) < 0.001 for ER+PR+ tumors; = 35 vs. = 19 years HR: 0.93 [95% CI 0.53-1.65] p(trend) = 0.96 for ER-PR-tumors; P-het = 0.03). The risk associations of menarcheal age, and time period between menarche and first full-term childbirth with ER-PR-tumors were in the similar direction with risk of ER+PR+ tumors (p(het) = 0.50), although weaker in magnitude and statistically only borderline significant. Other parity related factors such as ever a full-term birth, number of births, age-and time since last birth were associated only with ER+PR+ malignancies, however no statistical heterogeneity between breast cancer subtypes was observed. Breastfeeding and OC use were generally not associated with breast cancer subtype risk. Conclusion: Our study provides possible evidence that age at menarche, and time between menarche and first full-term childbirth may be associated with the etiology of both HR-negative and HR-positive malignancies, although the associations with HR-negative breast cancer were only borderline significant

A Mendelian randomization study of circulating uric acid and type 2 diabetes

We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid associated loci. We used data of the EPIC-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident type 2 diabetes cases were ascertained. Higher uric acid associated with higher diabetes risk following adjustment for confounders, with a HR of 1.20 (95%CI: 1.11,1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95%CI: 15,18) per SD increase, and explained 4% of uric acid variation. Using the genetic score to estimate the unconfounded effect found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01, 95%CI: 0.87,1.16). Including data from DIAGRAM consortium, increasing our dataset to 41,508 diabetes cases, the summary OR estimate was 0.99 (95%CI: 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid lowering therapies may therefore not be beneficial in reducing diabetes risk

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort.

Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit). Data were randomly divided into discovery (2/3) and replication (1/3) sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05) were further tested in the replication set (Bonferroni-corrected p-value < 0.05). Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions

Sources of Pre-Analytical Variations in Yield of DNA Extracted from Blood Samples: Analysis of 50,000 DNA Samples in EPIC

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies