917 research outputs found

    THE ROLES AND MECHANISMS OF LINEAR AND ANGULAR IMPULSE GENERATION FOR BOTH LEGS IN BASEBALL PITCHING: A WHOLE-BODY PERSPECTIVE

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    This study compared the role of each leg in generating linear and angular impulse during fastball pitches performed by professional pitchers (n=4). Participants were asked to pitch from an instrumented mound and 6-11 successful fastball pitches were used for the analysis. The results indicate that back leg generated forward linear impulse and the front leg generated backward linear impulse for all pitchers. Back leg ground reaction forces generated significantly larger angular impulse about a horizontal axis passing through the body center of mass from the mound to first base than the front leg in three of four pitchers. Additionally, the mechanisms of moment generation about the axis by each leg differed

    A 3D APPROACH TO BASEBALL PITCHING KINEMATIC SEQUENCE

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    A proximal-to-distal sequence (PDS) in baseball pitching is theorized to be more efficient and can reduce upper limb joint loads. However, studies investigating PDS using timing of peak segment angular velocity magnitude did not identify the use of “full” PDS from pelvis to hand. This study investigated PDS by comparing the timings of peak angular velocities about each global axis for the pelvis, trunk, upper arm, forearm, and hand during fastballs thrown by professional pitchers (n=4). We found that pitchers demonstrated full PDS about the global left axis (from pitching mound to first base) in 67-100% of their trials, depending on the pitcher. No pitcher demonstrated full PDS about the other two global axes. Similar to prior studies, we also did not observe full PDS when using angular velocity magnitude. This could be explained by differences in body segment rotation sequences between global axes. We also preliminarily uncovered impacts of filtering on the kinematic sequence detected. Analyzing 3D angular velocities with carefully selected filters may advance our understanding of the dynamics of pitching

    Hydroxamate production as a high affinity iron acquisition mechanism in Paracoccidioides Spp.

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    Iron is a micronutrient required by almost all living organisms, including fungi. Although this metal is abundant, its bioavailability is low either in aerobic environments or within mammalian hosts. As a consequence, pathogenic microorganisms evolved high affinity iron acquisition mechanisms which include the production and uptake of siderophores. Here we investigated the utilization of these molecules by species of the Paracoccidioides genus, the causative agents of a systemic mycosis. It was demonstrated that iron starvation induces the expression of Paracoccidioides ortholog genes for siderophore biosynthesis and transport. Reversed-phase HPLC analysis revealed that the fungus produces and secretes coprogen B, which generates dimerumic acid as a breakdown product. Ferricrocin and ferrichrome C were detected in Paracoccidioides as the intracellular produced siderophores. Moreover, the fungus is also able to grow in presence of siderophores as the only iron sources, demonstrating that beyond producing, Paracoccidioides is also able to utilize siderophores for growth, including the xenosiderophore ferrioxamine. Exposure to exogenous ferrioxamine and dimerumic acid increased fungus survival during co-cultivation with macrophages indicating that these molecules play a role during host-pathogen interaction. Furthermore, cross-feeding experiments revealed that Paracoccidioides siderophores promotes growth of Aspergillus nidulans strain unable to produce these iron chelators. Together, these data denote that synthesis and utilization of siderophores is a mechanism used by Paracoccidioides to surpass iron limitation. As iron paucity is found within the host, siderophore production may be related to fungus pathogenicity

    Sleep, emotional and behavioral difficulties in children and adolescents.

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    Links between sleep and psychopathology are complex and likely bidirectional. Sleep problems and alteration of normal sleep patterns have been identified in major forms of child psychopathology including anxiety, depression and attention disorders as well as symptoms of difficulties in the full range. This review summarizes some key findings with regard to the links between sleep and associated difficulties in childhood and adolescence. It then proposes a selection of possible mechanisms underlying some of these associations. Suggestions for future research include the need to 1) use multi-methods to assess sleep; 2) measure sleep in large-scale studies; 3) conduct controlled experiments to further establish the effects of sleep variations on emotional and behavioral difficulties; 4) take an interdisciplinary approach to further understand the links between sleep and associated difficulties

    Reconstructing Single Field Inflationary Actions From CMBR Data

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    This paper describes a general program for deriving the action of single field inflation models with nonstandard kinetic energy terms using CMBR power spectrum data. This method assumes that an action depends on a set of undetermined functions, each of which is a function of either the inflaton wave function or its time derivative. The scalar, tensor and non-gaussianity of the curvature perturbation spectrum are used to derive a set of reconstruction equations whose solution set can specify up to three of the undetermined functions. The method is then used to find the undetermined functions in various types of actions assuming power law type scalar and tensor spectra. In actions that contain only two unknown functions, the third reconstruction equation implies a consistency relation between the non-gaussianty, sound speed and slow roll parameters. In particular we focus on reconstructing a generalized DBI action with an unknown potential and warp factor. We find that for realistic scalar and tensor spectra, the reconstructed warp factor and potential are very similar to the theoretically derived result. Furthermore, physical consistency of the reconstructed warp factor and potential imposes strict constraints on the scalar and tensor spectral indices.Comment: 33 pages, 3 figures: v3 - References adde

    An siRNA Screen in Pancreatic Beta Cells Reveals a Role for Gpr27 in Insulin Production

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    The prevalence of type 2 diabetes in the United States is projected to double or triple by 2050. We reasoned that the genes that modulate insulin production might be new targets for diabetes therapeutics. Therefore, we developed an siRNA screening system to identify genes important for the activity of the insulin promoter in beta cells. We created a subclone of the MIN6 mouse pancreatic beta cell line that expresses destabilized GFP under the control of a 362 base pair fragment of the human insulin promoter and the mCherry red fluorescent protein under the control of the constitutively active rous sarcoma virus promoter. The ratio of the GFP to mCherry fluorescence of a cell indicates its insulin promoter activity. As G protein coupled receptors (GPCRs) have emerged as novel targets for diabetes therapies, we used this cell line to screen an siRNA library targeting all known mouse GPCRs. We identified several known GPCR regulators of insulin secretion as regulators of the insulin promoter. One of the top positive regulators was Gpr27, an orphan GPCR with no known role in beta cell function. We show that knockdown of Gpr27 reduces endogenous mouse insulin promoter activity and glucose stimulated insulin secretion. Furthermore, we show that Pdx1 is important for Gpr27's effect on the insulin promoter and insulin secretion. Finally, the over-expression of Gpr27 in 293T cells increases inositol phosphate levels, while knockdown of Gpr27 in MIN6 cells reduces inositol phosphate levels, suggesting this orphan GPCR might couple to Gq/11. In summary, we demonstrate a MIN6-based siRNA screening system that allows rapid identification of novel positive and negative regulators of the insulin promoter. Using this system, we identify Gpr27 as a positive regulator of insulin production

    Comparison of Pittsburgh compound B and florbetapir in cross-sectional and longitudinal studies.

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    IntroductionQuantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B-based and florbetapir-based amyloid imaging in the same participants from two independent cohorts using a crossover design.MethodsPittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter-individual variability of the two tracers were compared using multivariate linear models both cross-sectionally and longitudinally.ResultsGlobal amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers.DiscussionAlthough the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers

    SREB, a GATA Transcription Factor That Directs Disparate Fates in Blastomyces dermatitidis Including Morphogenesis and Siderophore Biosynthesis

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    Blastomyces dermatitidis belongs to a group of human pathogenic fungi that exhibit thermal dimorphism. At 22°C, these fungi grow as mold that produce conidia or infectious particles, whereas at 37°C they convert to budding yeast. The ability to switch between these forms is essential for virulence in mammals and may enable these organisms to survive in the soil. To identify genes that regulate this phase transition, we used Agrobacterium tumefaciens to mutagenize B. dermatitidis conidia and screened transformants for defects in morphogenesis. We found that the GATA transcription factor SREB governs multiple fates in B. dermatitidis: phase transition from yeast to mold, cell growth at 22°C, and biosynthesis of siderophores under iron-replete conditions. Insertional and null mutants fail to convert to mold, do not accumulate significant biomass at 22°C, and are unable to suppress siderophore biosynthesis under iron-replete conditions. The defect in morphogenesis in the SREB mutant was independent of exogenous iron concentration, suggesting that SREB promotes the phase transition by altering the expression of genes that are unrelated to siderophore biosynthesis. Using bioinformatic and gene expression analyses, we identified candidate genes with upstream GATA sites whose expression is altered in the null mutant that may be direct or indirect targets of SREB and promote the phase transition. We conclude that SREB functions as a transcription factor that promotes morphogenesis and regulates siderophore biosynthesis. To our knowledge, this is the first gene identified that promotes the conversion from yeast to mold in the dimorphic fungi, and may shed light on environmental persistence of these pathogens

    Predictive Markers of Honey Bee Colony Collapse

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    Across the Northern hemisphere, managed honey bee colonies, Apis mellifera, are currently affected by abrupt depopulation during winter and many factors are suspected to be involved, either alone or in combination. Parasites and pathogens are considered as principal actors, in particular the ectoparasitic mite Varroa destructor, associated viruses and the microsporidian Nosema ceranae. Here we used long term monitoring of colonies and screening for eleven disease agents and genes involved in bee immunity and physiology to identify predictive markers of honeybee colony losses during winter. The data show that DWV, Nosema ceranae, Varroa destructor and Vitellogenin can be predictive markers for winter colony losses, but their predictive power strongly depends on the season. In particular, the data support that V. destructor is a key player for losses, arguably in line with its specific impact on the health of individual bees and colonies
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