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

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

THE ECONOMICS OF CARCASS BEEF PRODUCTION: AN APPRAISAL OF FLORIDA'S FEEDLOT POTENTIAL

Livestock Production/Industries,

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

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

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

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

Verifying the Japanese version of the Preschool Confusion Assessment Method for the ICU (psCAM‐ICU)

AimPediatric delirium has been well investigated and its prevalence is reported to be from 20% to 44%. For pediatric intensive care settings, several validated assessment tools for diagnosing delirium, including the Preschool Confusion Assessment Method for the Intensive Care Unit (psCAM‐ICU), are available in English. However, validated assessment tools for identifying pediatric delirium are unavailable in Japanese. Therefore, the aim of this study is to verify the Japanese translation of the psCAM‐ICU.MethodsWe enrolled patients at the Pediatric ICU at University of Tsukuba Hospital (Tsukuba, Japan) from May 2017 to February 2019. Enrollment criteria included patients aged 6 months to 5 years, and we excluded coma patients scoring under −4 on the Richmond Agitation–Sedation Scale or suffering from stroke. Pediatric patient delirium was simultaneously evaluated by three medical workers (pediatric intensivist and researchers). Psychiatrists then verified these findings against criteria of the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition. We evaluated criterion validity (sensitivity and specificity) and reliability using Cohen\u27s κ coefficient.ResultsWe made a total of 56 independent assessments of 19 patients (42% female) with an average age of 18 (±15) weeks. Mechanical ventilation was used at least once in 73% of patients and the positive rate of delirium was 54% in total observation. Overall, the psCAM‐ICU showed high sensitivity, specificity (sensitivity, 0.90 [95% confidence interval [CI], 0.80–0.94]; specificity, 0.93 [95% CI, 0.83–0.97]), and high reliability within the researcher assessments (κ = 0.92; 95% CI, 0.82–1.0).ConclusionWe verified the psCAM‐ICU and it shows high validity and reliability

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Galaxy formation in pre-processed dark halos

Recent N-body simulations show that the formation of a present-day, galaxy sized dark matter halo in the CDM cosmogony in general consists of an early fast collapse phase, during which the potential associated with a halo is established, followed by a slow accretion phase, during which mass is added rather gently in the outer region. Here we outline a scenario in which the fast collapse phase is accompanied with rapid formation of cold clouds and with starbursts that can eject a large amount of gas from the halo center.The loss of orbital energy of the cold clouds to the dark matter and the ejection of gas from halo center by starburst can significantly reduce the halo concentration. The outflow from the starburst can also heat the gas in the protogalaxy region. Subsequent formation of galaxies in the slow accretion regime is therefore in halos that have been pre-processed by these processes and may have properties different from that given by N-body simulations. This scenario can help to solve several outstanding problems in the standard Lambda CDM model of galaxy formation without compromising its success in allowing structure formation at high redshift. The predicted rotation curves are quite flat,alleviating the discrepancy of the Tully-Fisher relation predicted in the Lambda CDM model with observations. The flattened galaxy halos allow accreted minihalos to survive in their central regions longer, which may be helpful in producing the flux anomalies observed in some gravitational lensing systems. The preheating by the early starbursts effectively reduces the amount of gas that can be accreted into galaxy halos, which may explain why the baryon fraction in a spiral galaxy is in general much lower than the universal baryon fraction, f_B~0.16, in the standard Lambda CDM model.Comment: 12 pages, 6 figures, version accepted by MNRA

Towards Cosmological Concordance on Galactic Scales

We use the observed abundance and clustering of galaxies from the 2dFGRS to determine the matter density Omega_m and the linear amplitude of mass fluctuations sigma_8. We use a method based on the conditional luminosity function, which allows straightforward computation of the luminosity dependent bias of galaxies. In addition, it allows the inclusion of constraints on the redshift space distortion parameter beta=Omega_m^{0.6}/b, and yields average mass-to-light ratios as function of halo mass. Using only the luminosity function and the correlation lengths as function of luminosity we obtain constraints on Omega_m and sigma_8 that are in good agreement with COBE. Using additional constraints on the mass-to-light ratios of clusters and on the value of beta as determined from the 2dFGRS yields Omega_m = (0.27 +/- 0.06) and sigma_8 = (0.77 +/- 0.06). Adding further constraints from current CMB data, we obtain Omega_m = (0.25 +/- 0.04) and sigma_8 = (0.78 +/- 0.06). Thus, we find strong indications that both Omega_m and sigma_8 are significantly lower than their ``standard'' concordance values of 0.3 and 0.9, respectively. Finally, we show that the cosmologies favored here predict dark matter haloes that are significantly less centrally concentrated than for the standard LCDM concordance model. This may solve both the problem with the rotation curves of dwarf and LSB galaxies, as well as the problem of simultaneously matching the galaxy luminosity function and the Tully-Fisher zero-point. (Abridged)Comment: Due to a normalization error in the luminosity function provided to us, and used to constrain the models, the normalization of our models was wrong by about 15 percent. In this new version of the paper we use the properly normalized data, which results in small changes to most figures and to the actual constraints on the cosmological parameters. This version supersedes the version published in MNRA

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder