43 research outputs found

    Selenoprotein W promotes cell cycle recovery from G2 arrest through the activation of CDC25B

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    AbstractSelenoprotein W (SelW) contains a highly reactive selenocysteine (Sec; U) in the CXXU motif corresponding to the CXXC motif in thioredoxin (Trx) and thus it appears to be involved in regulating the cellular redox state. Recent reports on the interaction between SelW and 14-3-3 suggest that SelW may be redox dependently involved in the cell cycle. However, the precise function of SelW has not yet been elucidated. Here, we show that SelW is involved in the G2–M transition, especially in the recovery from G2 arrest after deoxyribonucleic acid (DNA) damage. Knockdown of SelW significantly accumulated phosphorylated cyclin‐dependent kinase (Cdk1), which eventually led to a delay in recovery from G2 arrest. We also found that inactive Cdk1 is caused by the sustained inactivation of CDC25B, which removes the inhibitory phosphate from Cdk1. Our observation from this study reveals that SelW activated CDC25B by promoting the dissociation of 14-3-3 from CDC25B through the reduction of the intramolecular disulfide bond during recovery. We suggest that SelW plays an important role in the recovery from G2 arrest by determining the dissociation of 14-3-3 from CDC25B in a redox-dependent manner

    Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein

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    AbstractSelenoprotein W (SelW) is expressed in various tissues, particularly in skeletal muscle. We have previously reported that SelW is up-regulated during C2C12 skeletal muscle differentiation and inhibits binding of 14-3-3 to its target proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear translocation of transcriptional co-activator with PDZ-binding motif (TAZ). Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells. Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually resulted in decreasing translocation of TAZ to the nucleus. However, phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear translocation of TAZ was increased by ectopic expression of SelW. This result was due to decreased binding of TAZ to 14-3-3. We also found that the interaction between TAZ and MyoD was increased by ectopic expression of SelW. Taken together, these findings strongly demonstrate that SelW enhances C2C12 cell differentiation by inhibiting TAZ binding to 14-3-3

    Comparative Analysis Of Energy Expenditure Assessments From The Graded Exercise Test Vs. Galaxy Watch And Apple Watch In Korean College Students During A 30-minute Workout: A Pilot Study

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    OBJECTIVES In the modern era, there is heightened interest in understanding energy expenditure during exercise. Consequently, wearable devices such as the Galaxy Watch and Apple Watch have emerged as pivotal tools for daily health monitoring, given their convenience and increasing popularity. This study aimed to compare the calculated energy expenditure derived from the graded exercise test with readings from Galaxy and Apple Watches during a 30-min exercise session among Korean university students. Through this, we anticipate offering both motivation and clear insights into energy expenditure, thereby potentially aiding in weight management strategies for contemporary individuals. METHODS This study involved 27 college students from Korea National University of Transportation in Chungcheongbuk-do, Korea. We utilized COSMED's exercise load respiratory gas analysis system (Quark-CPET, COSMED, Rome, Italy), along with the Galaxy Watch (Galaxy Watch 5, Samsung, Seoul, Korea) and the Apple Watch (Apple watch series 5, Apple, Cupertino, USA) for measurements. Energy expenditure was monitored in real-time every 5 min throughout the 30-min exercise session. For statistical evaluations, we employed a one-way analysis of variance. Subsequent post-tests utilized the Tukey post-hoc test and Pearson correlation, with a significance level set at p0.05). Conversely, a notable difference was observed when comparing energy expenditure data from the graded exercise test to that of the Apple Watch for time intervals of 10, 15, 20, 25, and 30 min (p>0.05), although the 5-min interval did not exhibit a significant difference (p>0.05). Furthermore, a robust positive correlation was evident between the energy expenditure values derived from the graded exercise test and those from both the Galaxy Watch (r=0.952, p<0.001) and the Apple Watch (r=0.917, p<0.001). CONCLUSIONS Both devices demonstrated high reliability in calculating energy expenditure. Notably, the Galaxy Watch exhibited a more precise calculation compared to the Apple Watch, with a relative reliability margin of 3.5% higher. For individuals, especially those struggling with obesity, precise wearable devices that accurately reflect energy consumption can significantly boost motivation for exercise. Consequently, this study lays a foundation for future advancements in energy expenditure measurement tools, emphasizing enhanced convenience, reliability, and mobility

    Rapid access to polycyclic N-heteroarenes from unactivated, simple azines via a base-promoted Minisci-type annulation

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    Conventional synthetic methods to yield polycyclic heteroarenes have largely relied on metal-mediated arylation reactions requiring pre-functionalised substrates. However, the functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Herein, we report a transition-metal-free, radical relay pi-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts. Mechanistic and electron paramagnetic resonance studies provide evidence for the in situ generation of organic electron donors, while chemical trapping and electrochemical experiments implicate an iodanyl radical intermediate serving as a formal biaryl radical equivalent. This intermediate, formed by one-electron reduction of the cyclic iodonium salt, acts as the key intermediate driving the Minisci-type arylation reaction. The synthetic utility of this radical-based annulative pi-extension method is highlighted by the preparation of an N-doped heptacyclic nanographene fragment through fourfold C-H arylation. The functionalisation of unactivated azines has been restricted because of their intrinsic low reactivity. Here the authors show a transition-metal-free, radical relay pi-extension approach to produce N-doped polycyclic aromatic compounds directly from simple azines and cyclic iodonium salts

    Elevated IFNA1 and suppressed IL12p40 associated with persistent hyperinflammation in COVID-19 pneumonia

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    IntroductionDespite of massive endeavors to characterize inflammation in COVID-19 patients, the core network of inflammatory mediators responsible for severe pneumonia stillremain remains elusive. MethodsHere, we performed quantitative and kinetic analysis of 191 inflammatory factors in 955 plasma samples from 80 normal controls (sample n = 80) and 347 confirmed COVID-19 pneumonia patients (sample n = 875), including 8 deceased patients. ResultsDifferential expression analysis showed that 76% of plasmaproteins (145 factors) were upregulated in severe COVID-19 patients comparedwith moderate patients, confirming overt inflammatory responses in severe COVID-19 pneumonia patients. Global correlation analysis of the plasma factorsrevealed two core inflammatory modules, core I and II, comprising mainly myeloid cell and lymphoid cell compartments, respectively, with enhanced impact in a severity-dependent manner. We observed elevated IFNA1 and suppressed IL12p40, presenting a robust inverse correlation in severe patients, which was strongly associated with persistent hyperinflammation in 8.3% of moderate pneumonia patients and 59.4% of severe patients. DiscussionAberrant persistence of pulmonary and systemic inflammation might be associated with long COVID-19 sequelae. Our comprehensive analysis of inflammatory mediators in plasmarevealed the complexity of pneumonic inflammation in COVID-19 patients anddefined critical modules responsible for severe pneumonic progression

    Analysis of high burnup pressurized water reactor fuel using uranium, plutonium, neodymium, and cesium isotope correlations with burnup

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    The correlation of the isotopic composition of uranium, plutonium, neodymium, and cesium with the burnup for high burnup pressurized water reactor fuels irradiated in nuclear power reactors has been experimentally investigated. The total burnup was determined by Nd-148 and the fractional 235U burnup was determined by U and Pu mass spectrometric methods. The isotopic compositions of U, Pu, Nd, and Cs after their separation from the irradiated fuel samples were measured using thermal ionization mass spectrometry. The contents of these elements in the irradiated fuel were determined through an isotope dilution mass spectrometric method using 233U, 242Pu, 150Nd, and 133Cs as spikes. The activity ratios of Cs isotopes in the fuel samples were determined using gamma-ray spectrometry. The content of each element and its isotopic compositions in the irradiated fuel were expressed by their correlation with the total and fractional burnup, burnup parameters, and the isotopic compositions of different elements. The results obtained from the experimental methods were compared with those calculated using the ORIGEN-S code

    Elucidating the Correlation between Bone Mineral Density and Multifidus Muscle Characteristics: A Cross-Modal Study with Dual-Energy X-ray Absorptiometry and Spinal Computed Tomography Texture Analysis

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    Background: Recent research underscores the clinical relevance of muscle conditions such as sarcopenia and their links to bone mineral density (BMD), yet notable gaps persist in the understanding of their interconnections. Our study addresses this by introducing a novel approach to decipher the correlation between BMD and the texture of the multifidus muscle, utilizing spinal computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) to evaluate muscle texture, BMD, and bone mineral content (BMC) at the total lumbar vertebra and total hip. Methods: Our single-institution study examined 395 cases collected from 6 May 2012 to 30 November 2021. Each patient underwent a spinal CT scan and a DXA scan within a one-month interval. BMD and BMC at the total lumbar vertebra and total hip were measured. The texture features of the multifidus muscle from the axial cuts of T12 to S1 vertebrae were assessed via gray-level co-occurrence matrices. CT texture analysis values at angles of 45 + 45 and 90 degrees were calculated and correlated with BMD and BMC. A regression model was then constructed to predict BMD values, and the precision of these correlations was evaluated using mean square error (MSE) analysis. Results: Total lumbar BMC showed a correlation of 0.583–0.721 (MSE 1.568–1.842) and lumbar BMD of 0.632–0.756 (MSE 0.068–0.097). Total hip BMC had a correlation of 0.556–0.690 (MSE 0.448–0.495), while hip BMD ranged from 0.585 to 0.746 (MSE 0.072–0.092). Conclusions: The analysis of spinal CT texture alongside BMD and BMC measures provides a new approach to understanding the relationship between bone and muscle health. The strong correlations expected from our research affirm the importance of integrating bone and muscle measures in the prevention, diagnosis, and management of conditions such as sarcopenia and osteoporosis
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