Gaining insight into electron capture dissociation mass spectrometry of peptides and proteins

The study of protein structure is crucial to the understanding of protein function as the two are inter dependent. Protein structure analysis is especially important as misfolded proteins often result in fatal diseases. Gas phase protein structure analysis provides a way to study the forces the effects of solvent and involved in the determination of protein structure. Mass spectrometry (MS) is a rapid and sensitive technique that can be used for the analysis of gas phase protein structure. Electron capture dissociation (ECD) tandem mass spectrometry (MS/MS) has been used in the analysis of primary, secondary, and tertiary gas phase protein structure. ECD MS/MS has proved to be exceptionally applicable in the study of protein structure due to the ability to cleave protein backbone bonds with the retention of noncovalent interactions and small molecule post translational modifications. The work described in this dissertation expands the use ECD and other electron capture techniques for protein structure analysis. All of the experiments were performed using a unique and versatile hybrid linear ion trap / time of flight (LIT/TOF) mass spectrometer capable of multiple ion activation techniques, such as collision induced dissociation (CID), infrared multiphoton dissociation (IRMPD), ECD, hot ECD (HECD), and activated ion ECD (AI ECD). IR activation in conjunction with ECD (AI ECD) to disrupt noncovalent interactions was used to enhance primary structure analysis and monitor changes in tertiary structure via gas phase protein unfolding. The structure of the z type product ions was probed using ion molecule reactions, and the formation different structures was found to depend on the electron capture technique used to dissociate the parent ion. The work described in this dissertation demonstrates the use of AI ECD for analysis of gas phase protein structure. Also, the first analysis of z ion structure from various electron capture techniques is presented. This work highlights the versatility and utility of the LIT TOF for ECD MS/MS as an alternative to the commercial Fourier transform ion cyclotron resonance (FTICR) mass spectrometers

Beyond Marine Reserves: Exploring the Approach of Selecting Areas where Fishing Is Permitted, Rather than Prohibited

Background:\ud Marine populations have been declining at a worrying rate, due in large part to fishing pressures. The challenge is to secure a future for marine life while minimizing impacts on fishers and fishing communities.\ud \ud Methods and Principal Findings:\ud Rather than selecting areas where fishing is banned – as is usually the case with spatial management – we assess the concept of designating areas where fishing is permitted. We use spatial catch statistics for thirteen commercial fisheries on Canada’s west coast to determine the minimum area that would be needed to maintain a pre-ascribed target percentage of current catches. We found that small reductions in fisheries yields, if strategically allocated, could result in large unfished areas that are representative of biophysical regions and habitat types, and have the potential to achieve remarkable conservation gains.\ud \ud Conclusions:\ud Our approach of selecting fishing areas instead of reserves could help redirect debate about the relative values that society places on conservation and extraction, in a framework that could gain much by losing little. Our ideas are intended to promote discussions about the current status quo in fisheries management, rather than providing a definitive solution

Interpersonal trauma and its relation to childhood psychopathic traits : what does ADHD and ODD add to the equation?

Acknowledgements Thank you to the parents and young people who participated in the CATSS-9 studies.Peer reviewedPublisher PD

Measuring Transit Signal Recovery in the Kepler Pipeline II: Detection Efficiency as Calculated in One Year of Data

The Kepler planet sample can only be used to reconstruct the underlying planet occurrence rate if the detection efficiency of the Kepler pipeline is known, here we present the results of a second experiment aimed at characterising this detection efficiency. We inject simulated transiting planet signals into the pixel data of ~10,000 targets, spanning one year of observations, and process the pixels as normal. We compare the set of detections made by the pipeline with the expectation from the set of simulated planets, and construct a sensitivity curve of signal recovery as a function of the signal-to-noise of the simulated transit signal train. The sensitivity curve does not meet the hypothetical maximum detection efficiency, however it is not as pessimistic as some of the published estimates of the detection efficiency. For the FGK stars in our sample, the sensitivity curve is well fit by a gamma function with the coefficients a = 4.35 and b = 1.05. We also find that the pipeline algorithms recover the depths and periods of the injected signals with very high fidelity, especially for periods longer than 10 days. We perform a simplified occurrence rate calculation using the measured detection efficiency compared to previous assumptions of the detection efficiency found in the literature to demonstrate the systematic error introduced into the resulting occurrence rates. The discrepancies in the calculated occurrence rates may go some way towards reconciling some of the inconsistencies found in the literature.Comment: 13 pages, 7 figures, 1 electronic table, accepted by Ap

Development of the Aboriginal Communication Assessment After Brain Injury (ACAABI): A screening tool for identifying acquired communication disorders in Aboriginal Australians

Purpose: Acquired communication disorders (ACD), following stroke and traumatic brain injury, may not be correctly identified in Aboriginal Australians due to a lack of linguistically and culturally appropriate assessment tools. Within this paper we explore key issues that were considered in the development of the Aboriginal Communication Assessment After Brain Injury (ACAABI) – a screening tool designed to assess the presence of ACD in Aboriginal populations. Method: A literature review and consultation with key stakeholders were undertaken to explore directions needed to develop a new tool, based on existing tools and recommendations for future developments. Result: The literature searches revealed no existing screening tool for ACD in these populations, but identified tools in the areas of cognition and social-emotional wellbeing. Articles retrieved described details of the content and style of these tools, with recommendations for the development and administration of a new tool. The findings from the interview and focus group views were consistent with the approach recommended in the literature. Conclusions: There is a need for a screening tool for ACD to be developed but any tool must be informed by knowledge of Aboriginal language, culture and community input in order to be acceptable and valid

Does habitat stability structure intraspecific genetic diversity? It’s complicated...

Regional phylogeographic studies have long been conducted in the southeastern United States for a variety of species. With some exceptions, many of these studies focus on single species or single clades of organisms, and those considering multiple species tend to focus on deep historical breaks causing differentiation. However, in many species more recent factors may be influencing genetic diversity. To understand the roles of historic and contemporary processes in structuring genetic diversity, we reanalyzed existing genetic data from Southeast of North America using approaches gleaned from phylogeographic and landscape genetic literature that were implemented across species including AMOVAs, PCoAs, Species Distribution Modelling, and tests of isolation by distance, environment, and habitat instability. Genetic variance was significantly partitioned by ecoregions, watersheds, and across phylogeographic breaks in the majority of species. Similarly, genetic variation was significantly associated with some combination of geographic or environmental distance or habitat instability in most species. Patterns of genetic variation were largely idiosyncratic across species. While habitat instability over time is significantly correlated with genetic diversity in some species, it appears generally less important than isolation by geographic or environmental distance. Our results suggest that many factors, both historical and contemporary, impact genetic diversity within a species, and more so, that these patterns aren’t always similar in closely related species. This supports the importance of species- specific factors and cautions against assumptions that closely related species will respond to historical and contemporary forces in similar ways

Influence of depression and interpersonal support on adherence to antiretroviral therapy among people living with HIV

BackgroundPoor adherence and under-utilization of antiretroviral therapy (ART) services have been major setbacks to achieving 95-95-95 policy goals in Sub-Saharan Africa. Social support and mental health challenges may serve as barriers to accessing and adhering to ART but are under-studied in low-income countries. The purpose of this study was to examine the association of interpersonal support and depression scores with adherence to ART among persons living with HIV (PLWH) in the Volta region of Ghana.MethodsWe conducted a cross-sectional survey among 181 PLWH 18 years or older who receive care at an ART clinic between November 2021 and March 2022. The questionnaire included a 6-item simplified ART adherence scale, the 20-item Center for Epidemiologic Studies Depression Scale (CES-D), and the 12-item Interpersonal Support Evaluation List-12 (ISEL-12). We first used a chi-squared or Fisher’s exact test to assess the association between these and additional demographic variables with ART adherence status. We then built a stepwise multivariable logistic regression model to explain ART adherence.ResultsART adherence was 34%. The threshold for depression was met by 23% of participants, but it was not significantly associated with adherence in multivariate analysis(p = 0.25). High social support was reported by 48.1%, and associated with adherence (p = 0.033, aOR = 3.45, 95% CI = 1.09–5.88). Other factors associated with adherence included in the multivariable model included not disclosing HIV status (p = 0.044, aOR = 2.17, 95% CI = 1.03–4.54) and not living in an urban area (p = 0.00037, aOR = 0.24, 95% CI = 0.11–0.52).ConclusionInterpersonal support, rural residence, and not disclosing HIV status were independent predictors of adherence to ART in the study area

Measuring Transit Signal Recovery in the Kepler Pipeline. III. Completeness of the Q1-Q17 DR24 Planet Candidate Catalogue, with Important Caveats for Occurrence Rate Calculations

With each new version of the Kepler pipeline and resulting planet candidate catalogue, an updated measurement of the underlying planet population can only be recovered with an corresponding measurement of the Kepler pipeline detection efficiency. Here, we present measurements of the sensitivity of the pipeline (version 9.2) used to generate the Q1-Q17 DR24 planet candidate catalog (Coughlin et al. 2016). We measure this by injecting simulated transiting planets into the pixel-level data of 159,013 targets across the entire Kepler focal plane, and examining the recovery rate. Unlike previous versions of the Kepler pipeline, we find a strong period dependence in the measured detection efficiency, with longer (>40 day) periods having a significantly lower detectability than shorter periods, introduced in part by an incorrectly implemented veto. Consequently, the sensitivity of the 9.2 pipeline cannot be cast as a simple one-dimensional function of the signal strength of the candidate planet signal as was possible for previous versions of the pipeline. We report on the implications for occurrence rate calculations based on the Q1-Q17 DR24 planet candidate catalog and offer important caveats and recommendations for performing such calculations. As before, we make available the entire table of injected planet parameters and whether they were recovered by the pipeline, enabling readers to derive the pipeline detection sensitivity in the planet and/or stellar parameter space of their choice.Comment: 8 pages, 5 figures, full electronic version of Table 1 available at the NASA Exoplanet Archive; accepted by ApJ May 2nd, 201

The impact of physical inactivity on glucose homeostasis when diet is adjusted to maintain energy balance in healthy, young males

Background & aims: It is unclear if dietary adjustments to maintain energy balance during reduced physical activity can offset inactivity-induced reductions in insulin sensitivity and glucose disposal to produce normal daily glucose concentrations and meal responses. Therefore, the aim of the present study was to examine the impact of long-term physical inactivity (60 days of bed rest) on daily glycemia when in energy balance.Methods: Interstitial glucose concentrations were measured using Continuous Glucose Monitoring Systems (CGMS) for 5 days before and towards the end of bed rest in 20 healthy, young males (Age: 34 ± 8 years; BMI: 23.5 ± 1.8 kg/m2). Energy intake was reduced during bed rest to match energy expenditure, but the types of foods and timing of meals was maintained. Fasting venous glucose and insulin concentrations were determined, as well as the change in whole-body glucose disposal using a hyperinsulinemic-euglycemic clamp (HIEC).Results: Following long-term bed rest, fasting plasma insulin concentration increased 40% (p = 0.004) and glucose disposal during the HIEC decreased 24% (p < 0.001). Interstitial daily glucose total area under the curve (tAUC) from pre-to post-bed rest increased on average by 6% (p = 0.041), despite a 20 and 25% reduction in total caloric and carbohydrate intake, respectively. The nocturnal period (00:00–06:00) showed the greatest change to glycemia with glucose tAUC for this period increasing by 9% (p = 0.005). CGMS measures of daily glycemic variability (SD, J-Index, M-value and MAG) were not changed during bed rest.Conclusions: Reduced physical activity (bed rest) increases glycemia even when daily energy intake is reduced to maintain energy balance. However, the disturbance to daily glucose homeostasis was much more modest than the reduced capacity to dispose of glucose, and glycemic variability was not negatively affected by bed rest, likely due to positive mitigating effects from the contemporaneous reduction in dietary energy and carbohydrate intake.Clinical trials record: NCT03594799 (registered July 20, 2018) (https://clinicaltrials.gov/ct2/show/NCT03594799)

Terrestrial Planet Occurrence Rates for the Kepler GK Dwarf Sample

We measure planet occurrence rates using the planet candidates discovered by the Q1-Q16 Kepler pipeline search. This study examines planet occurrence rates for the Kepler GK dwarf target sample for planet radii, 0.75<Rp<2.5 Rearth, and orbital periods, 50<Porb<300 days, with an emphasis on a thorough exploration and identification of the most important sources of systematic uncertainties. Integrating over this parameter space, we measure an occurrence rate of F=0.77 planets per star, with an allowed range of 0.3<F<1.9. The allowed range takes into account both statistical and systematic uncertainties, and values of F beyond the allowed range are significantly in disagreement with our analysis. We generally find higher planet occurrence rates and a steeper increase in planet occurrence rates towards small planets than previous studies of the Kepler GK dwarf sample. Through extrapolation, we find that the one year orbital period terrestrial planet occurrence rate, zeta_1=0.1, with an allowed range of 0.01<zeta_1<2, where zeta_1 is defined as the number of planets per star within 20% of the Rp and Porb of Earth. For G dwarf hosts, the zeta_1 parameter space is a subset of the larger eta_earth parameter space, thus zeta_1 places a lower limit on eta_earth for G dwarf hosts. From our analysis, we identify the leading sources of systematics impacting Kepler occurrence rate determinations as: reliability of the planet candidate sample, planet radii, pipeline completeness, and stellar parameters.Comment: 19 Pages, 17 Figures, Submitted ApJ. Python source to support Kepler pipeline completeness estimates available at http://github.com/christopherburke/KeplerPORTs