173 research outputs found

    Transcriptional And Post-Transcriptional Regulation Of NRF2 In The Heart By The Deubiquitinase CYLD

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    The cylindromatosis (CYLD) is a K63-linked deubiquitinase (DUB) that has been linked to the regulation of multiple physiological or pathological processes, such as neural development, inflammation and fibrosis. However, a novel paradigm for CYLD has been recently postulated; namely that of CYLD as a mediator of cardiac disease. Nuclear factor, erythroid-2 related factor 2 (Nrf2), a master antioxidant transcription factor, has been shown to suppress cardiac pathological remodeling and dysfunction via downregulation of reactive oxygen species formation (ROS). It is normally regulated by Kelch-like ECH associated protein 1 (Keap1). However, the regulatory link between CYLD and Nrf2 in the diseased heart has heretofore been unclear. In this study, a potential role of CYLD in the control of Nrf2 signaling in the heart is proposed. I found that, in a mouse model of pressure overload-induced cardiac remodeling and dysfunction via transverse aortic constriction (TAC), knockout of CYLD attenuates cardiac oxidative stress, pathological remodeling and dysfunction associated with upregulation of Nrf2- mediated antioxidant signaling. At the molecular level, CYLD inactivates MAPK/AP-1 and c-Myc pathways which are required to activate Nrf2-operated antioxidant defense in cardiomyocytes. Moreover, CYLD is capable of suppressing autophagy-dependent posttranscriptional upregulation of Nrf2 expression via activation of mammalian target of rapamycin complex 1 (mTORC1), contributing to cardiomyocyte necrosis. Taken together, these results reveal that CYLD functions as a mediator of cardiac pathological remodeling and dysfunction via facilitating cardiomyocyte death by suppressing Nrf2-driven antioxidant defense. CYLD may serve as an important target for future therapies

    Risk of female athlete triad development in Japanese collegiate athletes is related to sport type and competitive level

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    Introduction: Menstrual dysfunction, musculoskeletal injury, and poor nutrition combine to form the female athlete triad (FAT), which results in serious health consequences for affected athletes. To this point, the risk factors of this phenomenon have not been fully explored in Japanese female college athletes. Additionally, the effect of competitive level on FAT risk factors has also not been reported. Therefore, we aimed to examine FAT risk factors in Japanese female athletes of various sports as well as examine the impact of competitive level on FAT.Methods: A Japanese-language survey was completed by 531 athletes and 20 nonathletes at two Japanese universities and answers with regard to menstrual status, musculoskeletal injury, nutrition, and other variables were analyzed based on classification of the sports into nine distinct groups based on activity type. Sport intensity, training volume, and competitive levels were used to further classify each sport. One-way ANOVA and the Bonferroni post hoc test using SPSS were carried out to analyze significance for relationships between sport intensity and FAT risk factors. Additionally, the relationship between competitive level and FAT risk factors was analyzed by ANOVA and Bonferroni post hoc tests.Results: Sport intensity was positively correlated with a delay in menarche as well as dysmenorrhea and poor nutrition while musculoskeletal injury was correlated with repetitive, high-training volume sports. Lower competitive levels increased dysmenorrhea but did not impact injury status or nutrition.Conclusion: Sport intensity and training volume, but not competitive level, are the critical factors affecting FAT risk in Japanese female college athletes

    Predictors of Pericardial Effusion in Patients Undergoing Pulmonary Artery Banding

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    Background:Although pulmonary artery banding (PAB) is a common palliative procedure for pediatric heart malformation, there are concerns of pressure overload and concomitant immune reactions in the right ventricle causing postsurgical complications such as pericardial effusion. At this time, no clear guidelines as to potential risk factors or procedural contraindications have been widely disseminated. Therefore, a study was undertaken to examine wide-ranging factors to find potential biomarkers for postsurgical pericardial effusion formation risk.Methods:A retrospective study was conducted on all cardiac surgeries performed over an eight-year period, and the main inclusion criterion was pericardial effusion development after PAB that required surgical drainage. Nine cases were then analyzed against a control group of 45 cases with respect to body measurements, concomitant surgeries, genetic screens, laboratory tests results, and cardiac function parameters.Results:Trisomy 21 was strongly associated with the development of severe pericardial effusion after PAB, and postoperative serum albumin levels in patients with trisomy 21 were associated with pericardial effusion development. Other parameters showed no significant correlation with pericardial effusion development.Conclusions:Our data indicate a strong association between trisomy 21 and pericardial effusion requiring drainage after PAB, which is in line with translational research findings. Pressure overload from PAB may play a role in the formation of severe pericardial effusion that is exacerbated by cardiac structural defects commonly associated with trisomy 21. Surgical teams should therefore use caution and plan to implement drainage in PAB cases, and postoperative serum albumin may serve as a useful biomarker for pericardial effusion formation

    Radiobiological response of U251MG, CHO-K1 and V79 cell lines to accelerator-based boron neutron capture therapy

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    In the current article, we provide in vitro efficacy evaluation of a unique accelerator-based neutron source, constructed at the Budker Institute of Nuclear Physics (Novosibirsk, Russian Federation), for boron neutron capture therapy (BNCT), which is particularly effective in the case of invasive cancers. U251MG, CHO-K1 and V79 cells were incubated and irradiated in various concentrations of boric acid with epithermal neutrons for 2–3 h in a plexiglass phantom, using 2.0 MeV proton energy and 1.5–3.0 mA proton current, resulting in a neutron fluence of 2.16 × 1012 cm−2. The survival curves of cells loaded with boron were normalized to those irradiated without boron (to exclude the influence of the fast neutron and gamma dose components) and fit to the linear–quadratic (LQ) model. Colony formation assays showed the following cell survival rates (means ± SDs): CHO-K1: 0.348 ± 0.069 (10 ppm), 0.058 ± 0.017 (20 ppm), 0.018 ± 0.005 (40 ppm); V79: 0.476 ± 0.160 (10 ppm), 0.346 ± 0.053 (20 ppm), 0.078 ± 0.015 (40 ppm); and U251MG: 0.311 ± 0.061 (10 ppm), 0.131 ± 0.022 (20 ppm), 0.020 ± 0.010 (40 ppm). The difference between treated cells and controls was significant in all cases (P < 0.01) and confirmed that the neutron source and irradiation regimen were sufficient for control over cell colony formation. We believe our study will serve as a model for ongoing in vitro experiments on neutron capture therapy to advance in this area for further development of accelerator-based BNCT into the clinical phase

    Modeling Integrated Properties and the Polarization of the Sunyaev-Zeldovich Effect

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    Two little explored aspects of Compton scattering of the CMB in clusters are discussed: The statistical properties of the Sunyaev-Zeldovich (S-Z) effect in the context of a non-Gaussian density fluctuation field, and the polarization patterns in a hydrodynamcially-simulated cluster. We have calculated and compared the power spectrum and cluster number counts predicted within the framework of two density fields that yield different cluster mass functions at high redshifts. This is done for the usual Press & Schechter mass function, which is based on a Gaussian density fluctuation field, and for a mass function based on a chi^2-distributed density field. We quantify the significant differences in the respective integrated S-Z observables in these two models. S-Z polarization levels and patterns strongly depend on the non-uniform distributions of intracluster gas and on peculiar and internal velocities. We have therefore calculated the patterns of two polarization components that are produced when the CMB is doubly scattered in a simulated cluster. These are found to be very different than the patterns calculated based on spherical clusters with uniform structure and simplified gas distribution.Comment: 22 pages, 25 figures, Proceedings of the Francesco Melchiorri memorial conference, New Astronomy Reviews, in pres

    MRI reveals menstrually-related muscle edema that negatively affects athletic agility in young women

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    ContextAbout 10% of Japanese female athletes are afflicted by menstrually-related edema, mainly in the lower limbs, and, with few studies on this problem, the effect on performance remains unclear.ObjectiveTo quantitatively evaluate fluid retention in the calf in female students over their menstrual cycle using magnetic resonance imaging (MRI) and to determine the relationship of MRI changes and athletic performance.DesignThe menstrual cycle was divided into 5 phases: menstrual, follicular, ovulatory, early luteal, and late luteal with sampling done in either morning (AM) or afternoon (PM) sessions. At each phase, MRI of the calf (7:00–8:00, 14:00–16:00), body composition and hormones (7:00–8:00), and athletic performance (14:00–16:00) were evaluated

    Large Einstein Radii: A Problem for LambdaCDM

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    The Einstein radius of a cluster provides a relatively model-independent measure of the mass density of a cluster within a projected radius of ~ 150 kpc, large enough to be relatively unaffected by gas physics. We show that the observed Einstein radii of four well-studied massive clusters, for which reliable virial masses are measured, lie well beyond the predicted distribution of Einstein radii in the standard LambdaCDM model. Based on large samples of numerically simulated cluster-sized objects with virial masses ~ 1e15 solar, the predicted Einstein radii are only 15-25'', a factor of two below the observed Einstein radii of these four clusters. This is because the predicted mass profile is too shallow to exceed the critical surface density for lensing at a sizable projected radius. After carefully accounting for measurement errors as well as the biases inherent in the selection of clusters and the projection of mass measured by lensing, we find that the theoretical predictions are excluded at a 4-sigma significance. Since most of the free parameters of the LambdaCDM model now rest on firm empirical ground, this discrepancy may point to an additional mechanism that promotes the collapse of clusters at an earlier time thereby enhancing their central mass density.Comment: 9 pages, 5 figures, accepted by MNRA

    A compact dust shell in the symbiotic system HM Sge

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    We present high spatial resolution observations of the mid-infrared core of the dusty symbiotic system HM Sge. The MIDI interferometer was used with the VLT UTs and ATs providing baselines oriented from PA=42&deg; to 105&deg;. The MIDI visibilities are compared with the ones predicted in the frame of various spherical dust shells published in the literature involving single or double dusty shells. The mid-IR environment is unresolved by a 8m telescope and the MIDI spectrum exhibits a level similar to the ISO spectra recorded 10 yr ago. The estimated Gaussian HWHM of the shell of 12AU in the 8-9μ\mum range, and 18AU in the 11-12μ\mum range, are much smaller than the angular separation between the Mira and the White Dwarf of 60AU. The discrepancies between the HWHM at different angle orientations suggest an increasing level of asymmetry from 13 to 8μ\mum. The observations are well fitted by the densest and smallest model published in the literature based on the ISO data, although such a model does not account for the variations of near-IR photometry due to the Mira pulsation cycle suggesting a much smaller optical thickness. These observations also discard the two shells models, developed to take into account the effect of the WD illumination onto the dusty wind of the Mira. These observations show that a high rate of dust formation is occurring in the vicinity of the Mira which seems to be not highly perturbed by the hot companion

    Isolating signatures of major cloud-cloud collisions using position-velocity diagrams

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    This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.Collisions between giant molecular clouds are a potential mechanism for triggering the formation of massive stars, or even super star clusters. The trouble is identifying this process observationally and distinguishing it from other mechanisms. We produce synthetic position–velocity diagrams from models of cloud–cloud collisions, non-interacting clouds along the line of sight, clouds with internal radiative feedback and a more complex cloud evolving in a galactic disc, to try and identify unique signatures of collision. We find that a broad bridge feature connecting two intensity peaks, spatially correlated but separated in velocity, is a signature of a high-velocity cloud–cloud collision. We show that the broad bridge feature is resilient to the effects of radiative feedback, at least to around 2.5 Myr after the formation of the first massive (ionizing) star. However for a head-on 10 km s−1 collision, we find that this will only be observable from 20 to 30 per cent of viewing angles. Such broad–bridge features have been identified towards M20, a very young region of massive star formation that was concluded to be a site of cloud–cloud collision by Torii et al., and also towards star formation in the outer Milky Way by Izumi et al.Peer reviewe
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