28 research outputs found

    Retirement from elite sport and self-esteem: a longitudinal study over 12 years

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    This study examined the complex associations between athletic retirement and self-esteem among former elite athletes. With reference to theoretical and empirical work on the quality of the transition out of sport, information was collected from 290 (junior) elite athletes in a retrospective-prospective design: at the first measurement, active athletes assessed satisfaction with their sporting career, athletic identity, and self-esteem. At the second measurement (12  years later), the now former athletes rated transition characteristics of their career ending, sporting career success, emotional reactions to career termination, extent of necessary adjustment required following athletic retirement, duration and quality of adjustment, and self-esteem. Structural equation modelling revealed that neither sporting career success nor sporting career satisfaction had a direct effect on adjustment. However, athletic identity and retirement planning predicted the extent of adjustment, which in turn predicted the duration and quality of adjustment, and ultimately self-esteem. Voluntariness, timeliness, and perceptions of gain predicted emotional reactions towards career termination, which also predicted the duration of adjustment. Extent of adjustment and emotional reactions mediated between preconditions of career termination and transition characteristics and self-esteem. While self-esteem after career termination was predominantly predicted by self-esteem 12  years earlier, perceived quality of adjustment to career termination had a significant effect on self-esteem in the post-athletic career. These results complement existing literature illustrating that athletic retirement is a complex and dynamic process and the quality of this transition has a small, but still noteworthy effect on self-esteem, a central construct for well-being

    Nucleotide sugar biosynthesis occurs in the glycosomes of procyclic and bloodstream form <i>Trypanosoma brucei</i>

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    In Trypanosoma brucei, there are fourteen enzymatic biotransformations that collectively convert glucose into five essential nucleotide sugars: UDP-Glc, UDP-Gal, UDP-GlcNAc, GDP-Man and GDP-Fuc. These biotransformations are catalyzed by thirteen discrete enzymes, five of which possess putative peroxisome targeting sequences. Published experimental analyses using immunofluorescence microscopy and/or digitonin latency and/or subcellular fractionation and/or organelle proteomics have localized eight and six of these enzymes to the glycosomes of bloodstream form and procyclic form T. brucei, respectively. Here we increase these glycosome localizations to eleven in both lifecycle stages while noting that one, phospho-N-acetylglucosamine mutase, also localizes to the cytoplasm. In the course of these studies, the heterogeneity of glycosome contents was also noted. These data suggest that, unlike other eukaryotes, all of nucleotide sugar biosynthesis in T. brucei is compartmentalized to the glycosomes in both lifecycle stages. The implications are discussed

    Late toxicity and biochemical recurrence after external-beam radiotherapy combined with permanent-source prostate brachytherapy

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    BACKGROUND The combination of external-beam radiotherapy and brachytherapy is used commonly to treat men with prostate cancer. In this analysis, the authors examined the rate of biochemical recurrence (BR) and late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity after treatment with external-beam radiotherapy and brachytherapy in a multiinstitutional, cooperative group setting. METHODS All eligible patients received external-beam radiotherapy (45 Gray [Gy] in 25 fractions) followed 2 to 6 weeks later by an interstitial implant using iodine-125 to deliver an additional 108 Gy. BR was defined in 2 ways: according to the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Definition (ACD) and according to the Phoenix definition (PD) (prostate-specific antigen nadir +2 ng/mL). The Radiation Therapy Oncology Group(RTOG)/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used to grade all toxicity. RESULTS One hundred thirty-eight patients were enrolled, and 130 were eligible for the current analysis. The median follow-up for surviving patients was 49 months (range, 20–60 months). The 48-month estimate of late grade ≥3 GU/GI toxicity was 15% (95% confidence interval [95% CI], 8–21%), and the 48-month estimate of BR was 19% (95% CI, 12–26%) and 14% (95% CI, 8–20%) according to the ACD and PD, respectively. CONCLUSIONS The morbidity observed in this multiinstitutional, cooperative group study was slightly higher than that reported in recent RTOG studies using brachytherapy alone or high-dose external-beam radiotherapy. The BR rate observed in this report was similar to that observed with high-dose external-beam radiotherapy alone in similar patients. Cancer 2007. © 2007 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55987/1/22560_ftp.pd

    Metabolomics guides rational development of a simplified cell culture medium for drug screening against <i>Trypanosoma brucei</i>

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    n vitro culture methods underpin many experimental approaches to biology and drug discovery. The modification of established cell culture methods to make them more biologically relevant or to optimize growth is traditionally a laborious task. Emerging metabolomic technology enables the rapid evaluation of intra- and extracellular metabolites and can be applied to the rational development of cell culture media. In this study, untargeted semiquantitative and targeted quantitative metabolomic analyses of fresh and spent media revealed the major nutritional requirements for the growth of bloodstream form &lt;i&gt;Trypanosoma brucei&lt;/i&gt;. The standard culture medium (HMI11) contained unnecessarily high concentrations of 32 nutrients that were subsequently removed to make the concentrations more closely resemble those normally found in blood. Our new medium, Creek's minimal medium (CMM), supports in vitro growth equivalent to that in HMI11 and causes no significant perturbation of metabolite levels for 94% of the detected metabolome (&#60;3-fold change; α = 0.05). Importantly, improved sensitivity was observed for drug activity studies in whole-cell phenotypic screenings and in the metabolomic mode of action assays. Four-hundred-fold 50% inhibitory concentration decreases were observed for pentamidine and methotrexate, suggesting inhibition of activity by nutrients present in HMI11. CMM is suitable for routine cell culture and offers important advantages for metabolomic studies and drug activity screening

    Bridge to the stars: A mission concept to an interstellar object

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    Exoplanet discoveries since the mid-1990’s have revealed an astounding diversity of planetary systems. Studying these systems is essential to understanding planetary formation processes, as well as the development of life in the universe. Unfortunately, humanity can only observe limited aspects of exoplanetary systems by telescope, and the significant distances between stars presents a barrier to in situ exploration. In this study, we propose an alternative path to gain insight into exoplanetary systems: Bridge, a mission concept design to fly by an interstellar object as it passes through our solar system. Designed as a New Frontiers-class mission during the National Aeronautics and Space Administration (NASA) Planetary Science Summer School, Bridge would provide a unique opportunity to gain insight into potential physical, chemical, and biological differences between solar systems as well as the possible exchange of planetary materials between them. Bridge employs ultraviolet/visible, near-infrared, and mid-infrared point spectrometers, a visible camera, and a guided impactor. We also provide a quantitative Monte Carlo analysis that estimates wait times for a suitable target, and examines key trades between ground storage and a parking orbit, power sources, inner versus outer solar system encounters, and launch criteria. Due to the fleeting nature of interstellar objects, reaching an interstellar object may require an extended ground storage phase for the spacecraft until a suitable ISO is discovered, followed by a rapid response launch strategy. To enable rapid response missions designed to intercept such unique targets, language would need to be added to future NASA announcements of opportunity such that ground storage and rapid response would be allowable components of a proposed mission

    Joint Inference in Weakly-Annotated Image Datasets via Dense Correspondence

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    We present a principled framework for inferring pixel labels in weakly-annotated image datasets. Most previous, example-based approaches to computer vision rely on a large corpus of densely labeled images. However, for large, modern image datasets, such labels are expensive to obtain and are often unavailable. We establish a large-scale graphical model spanning all labeled and unlabeled images, then solve it to infer pixel labels jointly for all images in the dataset while enforcing consistent annotations over similar visual patterns. This model requires significantly less labeled data and assists in resolving ambiguities by propagating inferred annotations from images with stronger local visual evidences to images with weaker local evidences. We apply our proposed framework to two computer vision problems, namely image annotation with semantic segmentation, and object discovery and co-segmentation (segmenting multiple images containing a common object). Extensive numerical evaluations and comparisons show that our method consistently outperforms the state-of-the-art in automatic annotation and semantic labeling, while requiring significantly less labeled data. In contrast to previous co-segmentation techniques, our method manages to discover and segment objects well even in the presence of substantial amounts of noise images (images not containing the common object), as typical for datasets collected from Internet search

    Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

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    SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long-term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug clas

    High-confidence glycosome proteome for procyclic form <em>Trypanosoma brucei</em> by epitope-tag organelle enrichment and SILAC proteomics

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    The glycosome of the pathogenic African trypanosome Trypanosoma brucei is a specialized peroxisome that contains most of the enzymes of glycolysis and several other metabolic and catabolic pathways. The contents and transporters of this membrane-bounded organelle are of considerable interest as potential drug targets. Here we use epitope tagging, magnetic bead enrichment, and SILAC quantitative proteomics to determine a high-confidence glycosome proteome for the procyclic life cycle stage of the parasite using isotope ratios to discriminate glycosomal from mitochondrial and other contaminating proteins. The data confirm the presence of several previously demonstrated and suggested pathways in the organelle and identify previously unanticipated activities, such as protein phosphatases. The implications of the findings are discussed
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