DNA double-strand breaks induce H2Ax phosphorylation domains in a contact-dependent manner

Formation of γH2Ax serves as a checkpoint for double-strand break (DSB) repair pathways. Here the authors reveal via integrated chromatin analysis that γH2Ax domains are established by chromosomal contacts with the DSB site

The development and initial evaluation of the Diarrhoea Management Diary (DMD) in patients with metastatic breast cancer

Purpose Chemotherapy-induced diarrhoea (CID) is a common, but often underreported problem in patients with breast cancer that has a profound effect on quality of life. It is best measured from a patient’s perspective, but tools are limited. The aim of this study was to develop and evaluate the Diarrhoea Management Diary (DMD), a self-report measure to assess CID, use of self-management strategies and treatment adherence. Methods The DMD was constructed using an iterative process of instrument development: concept elicitation (literature review), item generation and reduction (cognitive debriefing), and pilot testing in the target population. After translation into eight languages, the DMD was used in an international randomised trial for women receiving lapatinib and capecitabine for metastatic breast cancer with or without prophylactic octreotide. Patterns of missing data and sensitivity to change were examined. Results The understandability and completeness of the 8-item DMD was confirmed in cognitive interviews and pilot testing. Practicability of the DMD was evaluated in 62 women with metastatic breast cancer (median age 57). Up to 68% reported CID at any given time-point, and 19% had diarrhoea at each time-point. Patients also described efficacy of different strategies for diarrhoea management. Missing data were associated with study discontinuation. DMD missing item response was 0.9%. Sensitivity to change was good at most assessment points. Conclusions Although further psychometric testing is recommended, initial evaluation of the DMD showed good content validity and practicability in international research with cancer patients

Exploring Web-Based University Policy Statements on Plagiarism by Research-Intensive Higher Education Institutions

Plagiarism may distress universities in the US, but there is little agreement as to exactly what constitutes plagiarism. While there is ample research on plagiarism, there is scant literature on the content of university policies regarding it. Using a systematic sample, we qualitatively analyzed 20 Carnegie-classified universities that are “Very High in Research.” This included 15 public state universities and five high-profile private universities. We uncovered highly varied and even contradictory policies at these institutions. Notable policy variations existed for verbatim plagiarism, intentional plagiarism and unauthorized student collaboration at the studied institutions. We conclude by advising that the American Association of University Professors (AAUP), the American Association of Colleges and Universities (AACU) and others confer and come to accord on the disposition of these issues

Functioning of Coastal River-Dominated Ecosystems and Implications for Oil Spill Response: From Observations to Mechanisms and Models

Coastal river-dominated oceans are physically complex, biologically productive, and intimately connected to human socioeconomic activity. The Deepwater Horizon blowout and subsequent advection of oil into coastal waters of the northern Gulf of Mexico (nGOM) highlighted the complex linkages among oceanographic processes within this river-dominated system and knowledge gaps about it that resulted in imprecise information on both oil transport and ecosystem consequences. The interdisciplinary research program implemented through the CONsortium for oil exposure pathways in COastal River-Dominated Ecosystems (CONCORDE) is designed to identify and quantitatively assess key physical, biological, and geochemical processes acting in the nGOM, in order to provide the foundation for implementation of a synthesis model (coupled circulation and biogeochemistry) of the nGOM shelf system that can ultimately aid in prediction of oil spill transport and impacts. CONCORDE field and modeling efforts in 2015–2016 focused on defining the influence of freshwater input from river plumes in the nGOM. In situ observations, combined with field-deployed and simulated drifters, show considerable variability in the spatial extent of freshwater influence that is related to wind direction and strength. Increased primary production and particle abundance (a proxy for secondary production) was observed during the spring when nGOM shelf waters were becoming stratified. Zooplankton and marine snow displayed intense vertical and horizontal patchiness during all seasons, often aggregating near the halocline. Simulations of a neutrally buoyant tracer released offshore of the Mississippi Bight showed surface advection of low tracer concentrations onto the inner shelf under high river discharge, high stratification, and variable wind conditions compared to almost no advection onto the inner shelf under low discharge, negligible stratification, and generally northeasterly winds. The interconnectedness of environmental variables and biological activity indicate that multiple factors can affect the transport of oil and the resulting ecological impacts. The process-oriented understanding provided by CONCORDE is necessary to predict ecosystem-level impacts of oil spills, and these results are applicable to other river-dominated coastal systems worldwide that often support oil extraction activities

Characterizing Anxiety Subtypes And The Relationship To Behavioral Phenotyping In Major Depression: Results From The Embarc Study

The current study aimed to characterize the multifaceted nature of anxiety in patients with major depression by evaluating distinct anxiety factors. We then related these derived anxiety factors to performance on a Flanker Task of cognitive control, in order to further validate these factors. Data were collected from 195 patients with nonpsychotic chronic or recurrent major depression or dysthymic disorder. At baseline, participants completed self-report measures of anxiety, depression, and other related symptoms (mania, suicidality) and clinicians administered a structured diagnostic interview and the Hamilton Rating Scale for Depression, including anxiety/ somatization items. Four discrete factors (State Anxiety, Panic, Neuroticism/Worry, and Restlessness/Agitation) emerged, with high degrees of internal consistency. Discriminant and convergent validity analyses also yielded findings in the expected direction. Furthermore, the neuroticism/worry factor was associated with Flanker Task interference, such that individuals higher on neuroticism/worry responded more incorrectly (yet faster) to incongruent vs. congruent trials whereas individuals higher on the fear/panic factor responded more slowly, with no accuracy effect, to the Flanker Task stimuli. These results parse anxiety into four distinct factors that encompass physiological, psychological, and cognitive components of anxiety. While state anxiety, panic and neuroticism/worry are related to existing measures of anxiety, the Restlessness/Agitation factor appears to be a unique measure of general anxious arousal. Furthermore, two factors were independently validated through the Flanker Task. These results suggest that these anxiety domains have distinct behavioral profiles and could have differential responses to distinct treatments

Comparing genotyping algorithms for Illumina's Infinium whole-genome SNP BeadChips

The Brassica napus 60K Illumina Infinium™ SNP array has had huge international uptake in the rapeseed community due to the revolutionary speed of acquisition and ease of analysis of this high-throughput genotyping data, particularly when coupled with the newly available reference genome sequence. However, further utilization of this valuable resource can be optimized by better understanding the promises and pitfalls of SNP arrays. We outline how best to analyze Brassica SNP marker array data for diverse applications, including linkage and association mapping, genetic diversity and genomic introgression studies. We present data on which SNPs are locus-specific in winter, semi-winter and spring B. napus germplasm pools, rather than amplifying both an A-genome and a C-genome locus or multiple loci. Common issues that arise when analyzing array data will be discussed, particularly those unique to SNP markers and how to deal with these for practical applications in Brassica breeding applications

A Glial Variant of the Vesicular Monoamine Transporter Is Required To Store Histamine in the Drosophila Visual System

Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest