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Selenium (Se) has been known for many years to have played a role in boosting the immune function, but the manner in which this element acts at the molecular level in host defence and inflammatory diseases is poorly understood. To elucidate the role of Se-containing proteins in the immune function, we knocked out the expression of this protein class in T-cells or macrophages of mice by targeting the removal of the selenocysteine tRNA gene using loxP-Cre technology. Mice with selenoprotein-less T-cells manifested reduced pools of mature and functional T-cells in lymphoid tissues and an impairment in T-cell-dependent antibody responses. Furthermore, selenoprotein deficiency in T-cells led to an inability of these cells to suppress reactive oxygen species production, which in turn affected their ability to proliferate in response to T-cell receptor stimulation. Selenoprotein-less macrophages, on the other hand, manifested mostly normal inflammatory responses, but this deficiency resulted in an altered regulation in extracellular matrix-related gene expression and a diminished migration of macrophages in a protein gel matrix. These observations provided novel insights into the role of selenoproteins in the immune function and tissue homeostasis. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to examine the influence of upper-body static stretching and dynamic stretching on upper-body muscular performance. Eleven healthy men, who were National Collegiate Athletic Association Division I track and field athletes (age, 19.6 +/- 1.7 years; body mass, 93.7 +/- 13.8 kg; height, 183.6 +/- 4.6 cm; bench press 1 repetition maximum [1RM], 106.2 +/- 23.0 kg), participated in this study. Over 4 sessions, subjects participated in 4 different stretching protocols (i.e., no stretching, static stretching, dynamic stretching, and combined static and dynamic stretching) in a balanced randomized order followed by 4 tests: 30% of 1 RM bench throw, isometric bench press, overhead medicine ball throw, and lateral medicine ball throw. Depending on the exercise, test peak power (Pmax), peak force (Fmax), peak acceleration (Amax), peak velocity (Vmax), and peak displacement (Dmax) were measured. There were no differences among stretch trials for Pmax, Fmax, Amax, Vmax, or Dmax for the bench throw or for Fmax for the isometric bench press. For the overhead medicine ball throw, there were no differences among stretch trials for Vmax or Dmax. For the lateral medicine ball throw, there was no difference in Vmax among stretch trials; however, Dmax was significantly larger (p

Previous research has shown that L-carnitine L-tartrate (LCLT) supplementation beneficially affects markers of hypoxic stress following resistance exercise. However, the mechanism of this response is unclear. Therefore, the primary purpose of this study was to determine the effects of LCLT supplementation on muscle tissue oxygenation during and after multiple sets of squat exercise. Nine healthy, previously resistance-trained men (25.2 +/- 6.years, 91.2 +/- 10.2 kg, 180.2 +/- 6.3 cm) ingested 2 g.d of LCLT or an identical placebo for 23 days in a randomized, balanced, crossover, double-blind, placebo-controlled, repeated-measures study design. On day 21, forearm muscle oxygenation was measured during and after an upper arm occlusion protocol using near infrared spectroscopy (NIRS), which measures the balance of oxygen delivery in relation to oxygen consumption. On day 22, subjects performed 5 sets of 15 to 20 repetitions of squat exercise with corresponding measures of thigh muscle oxygenation, via NIRS, and serial blood draws. Compared to the placebo trial, muscle oxygenation was reduced in the LCLT trial during upper arm occlusion and following each set of resistance exercise. Despite reduced oxygenation, plasma malondealdehyde, a marker of membrane damage, was attenuated during the LCLT trial. There were no differences between trials in the vasoactive substance prostacyclin. In conclusion, because oxygen delivery was occluded during the forearm protocol, it is proposed that enhanced oxygen consumption mediated the reduced muscle oxygenation during the LCLT trial. Enhanced oxygen consumption would explain why hypoxic stress was attenuated with LCLT supplementation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Severe physical and environmental stress seems to have a suppressive effect on the hypothalamic-pituitary-gonadal (HPG) axis in men. Examining hormonal responses to an extreme 160-km competition across frozen Alaska provides a unique opportunity to study this intense stress. OBJECTIVE: To examine hormonal responses to an ultra-endurance race. METHODS: Blood samples were obtained from 16 men before and after racing and analyzed for testosterone, interleukin-6 (IL-6), growth hormone (GH) and cortisol. Six subjects (mean (SD) age 42 (7) years; body mass 78.9 (7.1) kg; height 1.78 (0.05) m raced by bicycle (cyclists) and 10 subjects (age 35 (9) years; body mass 77.9 (10.6) kg; height, 1.82 (0.05) m) raced by foot (runners). Mean (SD) finish times were 21.83 (6.27) and 33.98 (6.12) h, respectively. RESULTS: In cyclists there were significant (p< or =0.05) mean (SD) pre-race to post-race increases in cortisol (254.83 (135.26) to 535.99 (232.22) nmol/l), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.36 (0.42) to 10.15 (3.28) pg/ml), and a significant decrease in testosterone (13.81 (3.19) to 5.59 (3.74) nmol/l). Similarly, in runners there were significant pre-race to post-race increases in cortisol (142.09 (50.74) to 452.21 (163.40) ng/ml), GH (0.12 (0.23) to 3.21 (3.33) microg/ml) and IL-6 (2.42 (0.68) to 12.25 (1.78) pg/ml), and a significant decrease in testosterone (12.32 (4.47) to 6.96 (3.19) nmol/l). There were no significant differences in the hormonal levels between cyclists and runners (p>0.05). CONCLUSIONS: These data suggest a suppression of the hypopituitary-gonadal axis potentially mediated by amplification of adrenal stress responses to such an ultra-endurance race in environmentally stressful conditions. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether kinetic chain pattern during knee extensor strength training influences quadriceps femoris center of mass and moment of inertia about the hip in a predictable manner as such changes can affect running economy. Methods: Twelve participants completed 8 weeks of both unilateral open (OKC) and closed (CKC) kinetic chain resistance training on opposing legs. Changes in quadriceps femoris muscle volume (VOL QF ), center of mass location (CoM QF ), and moment of inertia ( I QF ) about the hip were determined from magnetic resonance images scans. Regional hemodynamics of the vastus lateralis taken at 30% and 70% of muscle length during OKC and CKC bouts early in the training program were measured using near-infrared spectroscopy (NIRS) and used post hoc to predict changes in CoM QF . Results: While increases in VOL QF were similar between OKC (Δ79.5 ± 87.9 cm 3 ) and CKC (Δ60.2 ± 110.5 cm 3 , p = 0.29), the patterns of hypertrophy differed; a distal shift in CoM QF (Δ2.4 ± 0.4 cm, p < 0.001) and increase in I QF (Δ0.017 ± 0.014 kg m 2 , p < 0.001) occurred in OKC but not in CKC (CoM QF : Δ-2.2 ± 2.0 cm, I QF : Δ-0.022 ± 0.020 kg m 2 , p > 0.05). Regional hemodynamics assessed by NIRS during a single training session displayed similar exercise and regional differences and predicted 39.6% of observed changes in CoM QF . Conclusions: Exercise selection influences muscle shape sufficiently to affect CoM QF and I QF , and these changes may be predicted in part from NIRS measurements during a single workout. Given I QF is inversely related to running economy and since CKC exercise provides a more proximal pattern of hypertrophy than OKC, it may be more preferential for running. The results from the present study also highlight the potential of NIRS as a tool for predicting patterns of hypertrophy between different exercises and exercise conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Earp, Angelino, Hatfield, Colantuono, Jackson, Morgan, Adami, Melanson and Blazevich.)

Background: Exercise-associated muscle damage (EAMD) temporally impairs muscle function and intramuscular glycogen storage. Contrast with compression (CwC) therapy provides localized EAMD treatment with minimal changes in core/tissue temperature that can impair glycogen resynthesis., Hypothesis: CwC will enhance the recovery of strength, power, and joint mobility, reduce markers of EAMD, and attenuate the disruption of glycogen storage observed after damaging exercise., Study Design: Randomized controlled trial with crossover design., Level of Evidence: Level 2., Methods: Ten men completed 2 bouts of eccentric elbow flexor exercise, separated by 1 week, using contralateral arms. After each bout, participants received either CwC therapy (at 0, 24, and 48 h postexercise) or no therapy with intervention order and limb randomly assigned. Prior to (pre-exercise) and 1, 24, 48, and 72 h after each exercise bout, muscular strength, muscular power, intramuscular glycogen, creatine kinase, muscle thickness, muscle soreness, pressure pain threshold, active elbow flexion, passive elbow extension, and dietary intake were assessed. Comparisons were made between conditions over time (interaction effects) using separate repeated-measures analyses of variance/multivariate analyses of variance and effect sizes (Cohen d ) to describe treatment effect at each time point., Results: Significant interaction effects were observed for muscular strength ( d = 0.67-1.12), muscular power ( d = 0.20-0.65), intramuscular glycogen ( d = 0.29-0.81), creatine kinase ( d = 0.01-0.96), muscle thickness ( d = 0.35-0.70), muscle soreness ( d = 0.18-0.85), and active elbow flexion ( d = 0.65-1.17) indicating a beneficial effect of CwC over time ( P ≤ 0.05). In contrast, no significant interaction effect was observed for pressure pain threshold or passive elbow extension ( P > 0.05)., Conclusion: These results support the use of CwC for the recovery of muscle function after damaging exercise in male patients and indicate that CwC attenuates, but does not remove, the disruption of intramuscular glycogen stores observed after intense eccentric exercise., Clinical Relevance: Glycolysis-dependent athletes may benefit from CwC therapy after training/competition that causes EAMD.

Selenophosphate synthetase (SEPHS) was originally discovered in prokaryotes as an enzyme that catalyzes selenophosphate synthesis using inorganic selenium and ATP as substrates. However, in contrast to prokaryotes, two paralogs, SEPHS1 and SEPHS2, occur in many eukaryotes. Prokaryotic SEPHS, also known as SelD, contains either cysteine (Cys) or selenocysteine (Sec) in the catalytic domain. In eukaryotes, only SEPHS2 carries out selenophosphate synthesis and contains Sec at the active site. However, SEPHS1 contains amino acids other than Sec or Cys at the catalytic position. Phylogenetic analysis of SEPHSs reveals that the ancestral SEPHS contains both selenophosphate synthesis and another unknown activity, and that SEPHS1 lost the selenophosphate synthesis activity. The three-dimensional structure of SEPHS1 suggests that its homodimer is unable to form selenophosphate, but retains ATPase activity to produce ADP and inorganic phosphate. The most prominent function of SEPHS1 is that it is implicated in the regulation of cellular redox homeostasis. Deficiency of SEPHS1 leads to the disturbance in the expression of genes involved in redox homeostasis. Different types of reactive oxygen species (ROS) are accumulated in response to SEPHS deficiency depending on cell or tissue types. The accumulation of ROS causes pleiotropic effects such as growth retardation, apoptosis, DNA damage, and embryonic lethality. SEPHS1 deficiency in mouse embryos affects retinoic signaling and other related signaling pathways depending on the embryonal stage until the embryo dies at E11.5. Dysregulated SEPHS1 is associated with the pathogenesis of various diseases including cancer, Crohn's disease, and osteoarthritis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aging and mechanical overload are prominent risk factors for osteoarthritis (OA), which lead to an imbalance in redox homeostasis. The resulting state of oxidative stress drives the pathological transition of chondrocytes during OA development. However, the specific molecular pathways involved in disrupting chondrocyte redox homeostasis remain unclear. Here, we show that selenophosphate synthetase 1 (SEPHS1) expression is downregulated in human and mouse OA cartilage. SEPHS1 downregulation impairs the cellular capacity to synthesize a class of selenoproteins with oxidoreductase functions in chondrocytes, thereby elevating the level of reactive oxygen species (ROS) and facilitating chondrocyte senescence. Cartilage-specific Sephs1 knockout in adult mice causes aging-associated OA, and augments post-traumatic OA, which is rescued by supplementation of N-acetylcysteine (NAC). Selenium-deficient feeding and Sephs1 knockout have synergistic effects in exacerbating OA pathogenesis in mice. Therefore, we propose that SEPHS1 is an essential regulator of selenium metabolism and redox homeostasis, and its dysregulation governs the progression of OA., (© 2022. The Author(s).)

The selenium field expanded at a rapid rate for about 45 years, from the mid-1970's until about 2015 (see [...].

Selenium is a fascinating element that has a long history, most of which documents it as a deleterious element to health. In more recent years, selenium has been found to be an essential element in the diet of humans, all other mammals, and many other life forms. It has many health benefits that include, for example, roles in preventing heart disease and certain forms of cancer, slowing AIDS progression in HIV patients, supporting male reproduction, inhibiting viral expression, and boosting the immune system, and it also plays essential roles in mammalian development. Elucidating the molecular biology of selenium over the past 40 years generated an entirely new field of science which encompassed the many novel features of selenium. These features were (1) how this element makes its way into protein as the 21st amino acid in the genetic code, selenocysteine (Sec); (2) the vast amount of machinery dedicated to synthesizing Sec uniquely on its tRNA; (3) the incorporation of Sec into protein; and (4) the roles of the resulting Sec-containing proteins (selenoproteins) in health and development. One of the research areas receiving the most attention regarding selenium in health has been its role in cancer prevention, but further research has also exposed the role of this element as a facilitator of various maladies, including cancer.

Abstract: Hatfield, DL, Stranieri, AM, Vincent, LM, and Earp, JE. Effect of a neoprene knee sleeve on performance and muscle activity in men and women during high-intensity, high-volume resistance training. J Strength Cond Res 35(12): 3300-3307, 2021-The purpose of this study was to assess the effects of a commercially available neoprene knee sleeve (KS) on exercise performance and muscle activity during an exhaustive leg press exercise. Twenty resistance-trained individuals, 11 men {21.0 ± 2.2 years; 77.7 ± 8.7 kg; 1 repetition maximum (1RM/body mass [BM]): 0.30 ± 0.04} and 9 women (22.0 ± 3.5 years; 66.1 ± 9.1 kg; 1RM/BM: 0.30 ± 0.04), all subjects (21.5 ± 2.8 years; 72.5 ± 10.5 kg; 1RM/BM: 0.30 ± 0.04), participated in 3 testing sessions. The second and third sessions were performed using a counterbalanced and randomized design in which subjects exercised with (WS) or without (NS) KSs and performed 6 sets of leg press exercise at 80% of 1RM until failure with a 3-minute rest between sets. Number of repetitions, blood lactate (BL), heart rate (HR), rating of perceived exertion (RPE), and peak and average power were recorded after each set. Surface electromyography (EMG) of the right and left vastus lateralis muscles was also recorded to compare muscle activity between conditions. Significance was set at p ≤ 0.05, and values are presented as mean ± SD. No significant differences were observed in the total number of repetitions for all sets (p = 0.3; WS 75.3 ± 33.7, NS 79.8 ± 34.3) and the number of repetitions per set between conditions (p ≤ 0.05) or between men and women. Similarly, no significance differences (p ≤ 0.05) were observed for BL, HR, RPE, or EMG per set between conditions or between men and women. These results suggest that wearing compressive neoprene KSs has no effect on improving performance and associated variables during high-load, high-volume lower-body resistance training., (Copyright © 2021 National Strength and Conditioning Association.)

The primary function of selenophosphate synthetase (SEPHS) is to catalyze the synthesis of selenophosphate that serves as a selenium donor during selenocysteine synthesis. In eukaryotes, there are two isoforms of SEPHS (SEPHS1 and SEPHS2). Between these two isoforms, only SEPHS2 is known to contain selenophosphate synthesis activity. To examine the function of SEPHS1 in endothelial cells, we introduced targeted null mutations to the gene for SEPHS1, Sephs1, in cultured mouse 2H11 endothelial cells. SEPHS1 deficiency in 2H11 cells resulted in the accumulation of superoxide and lipid peroxide, and reduction in nitric oxide. Superoxide accumulation in Sephs1 -knockout 2H11 cells is due to the induction of xanthine oxidase and NADPH oxidase activity, and due to the decrease in superoxide dismutase 1 (SOD1) and 3 (SOD3). Superoxide accumulation in 2H11 cells also led to the inhibition of cell proliferation and angiogenic tube formation. Sephs1 -knockout cells were arrested at G2/M phase and showed increased gamma H2AX foci. Angiogenic dysfunction in Sephs1 -knockout cells is mediated by a reduction in nitric oxide and an increase in ROS. This study shows for the first time that superoxide was accumulated by SEPHS1 deficiency, leading to cell dysfunction through DNA damage and inhibition of cell proliferation.

Selenophosphate synthetase 1 (SEPHS1) plays an essential role in cell growth and survival. However, the underlying molecular mechanisms remain unclear. In the present study, the pathways regulated by SEPHS1 during gastrulation were determined by bioinformatical analyses and experimental verification using systemic knockout mice targeting Sephs1 . We found that the coagulation system and retinoic acid signaling were most highly affected by SEPHS1 deficiency throughout gastrulation. Gene expression patterns of altered embryo morphogenesis and inhibition of Wnt signaling were predicted with high probability at E6.5. These predictions were verified by structural abnormalities in the dermal layer of Sephs1 -/- embryos. At E7.5, organogenesis and activation of prolactin signaling were predicted to be affected by Sephs1 knockout. Delay of head fold formation was observed in the Sephs1 -/- embryos. At E8.5, gene expression associated with organ development and insulin-like growth hormone signaling that regulates organ growth during development was altered. Consistent with these observations, various morphological abnormalities of organs and axial rotation failure were observed. We also found that the gene sets related to redox homeostasis and apoptosis were gradually enriched in a time-dependent manner until E8.5. However, DNA damage and apoptosis markers were detected only when the Sephs1 -/- embryos aged to E9.5. Our results suggest that SEPHS1 deficiency causes a gradual increase of oxidative stress which changes signaling pathways during gastrulation, and afterwards leads to apoptosis.

The role of the essential trace element selenium in hypothalamic physiology has begun to come to light over recent years. Selenium is used to synthesize a family of proteins participating in redox reactions called selenoproteins, which contain a selenocysteine residue in place of a cysteine. Past studies have shown that disrupted selenoprotein expression in the hypothalamus can adversely impact energy homeostasis. There is also evidence that selenium supports leptin signaling in the hypothalamus by maintaining proper redox balance. In this study, we generated mice with conditional knockout of the selenocysteine tRNA [Ser]Sec gene ( Trsp ) in an orexigenic cell population called agouti-related peptide (Agrp)-positive neurons. We found that female Trsp Agrp KO mice gain less weight while on a high-fat diet, which occurs due to changes in adipose tissue activity. Female Trsp Agrp KO mice also retained hypothalamic sensitivity to leptin administration. Male mice were unaffected, however, highlighting the sexually dimorphic influence of selenium on neurobiology and energy homeostasis. These findings provide novel insight into the role of selenoproteins within a small yet heavily influential population of hypothalamic neurons.

Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein ( Selenof ) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof 's potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.

The purpose of this study was to examine the responses of growth hormone (GH) and insulin-like growth factor-I (IGFI) to intense heavy resistance exercise in highly trained men and women to determine what sex-dependent responses may exist. Subjects were highly resistance trained men (N = 8, Mean ± SD; age, yrs., 21 ± 1, height, cm, 175.3 ± 6.7, body mass, kg, 87.0 ± 18.5, % body fat, 15.2 ± 5.4, squat X body mass, 2.1 ± 0.4; and women (N = 7; Mean ± SD, age, yrs. 24 ± 5, height, cm 164.6 ± 6.7, body mass, kg 76.4 ± 8.8, % body fat, 26.9 ± 5.3, squat X body mass, 1.7 ± 0.6). An acute resistance exercise test protocol (ARET) consisted of 6 sets of 10 repetitions at 80% of the 1 RM with 2 min rest between sets was used as the stressor. Blood samples were obtained pre-exercise, after 3 sets, and then immediately after exercise (IP), 5, 15, 30, and 70 min post-exercise for determination of blood lactate (HLa), and plasma glucose, insulin, cortisol, and GH. Determination of plasma concentrations of IGFI, IGF binding proteins 1, 2, and 3 along with molecular weight isoform factions were determined at pre, IP and 70 min. GH significantly (P ≤ 0.05) increased at all time points with resting concentrations significantly higher in women. Significant increases were observed for HLa, glucose, insulin, and cortisol with exercise and into recovery with no sex-dependent observations. Women showed IGF-I values that were higher than men at all times points with both seeing exercise increases. IGFBP-1 and 2 showed increase with exercise with no sex-dependent differences. IGFBP-3 concentrations were higher in women at all-time points with no exercise induced changes. Both women and men saw an exercise induced increase with significantly higher values in GH in only the mid-range (30-60 kD) isoform.  Only women saw an exercise induced increase with significantly higher values for IGF fractions only in the mid-range (30-60 kD) isoform, which were significantly greater than the men at the IP and 70 min post-exercise time points. In conclusion, the salient findings of this investigation were that in highly resistance trained men and women, sexual dimorphisms exist but appear different from our prior work in untrained men and women and appear to support a sexual dimorphism related to compensatory aspects in women for anabolic mediating mechanisms in cellular interactions., (Copyright © 2021. Published by Elsevier Ltd.)

This consensus statement is an update of the 1987 American College of Sports Medicine (ACSM) position stand on the use of anabolic-androgenic steroids (AAS). Substantial data have been collected since the previous position stand, and AAS use patterns have changed significantly. The ACSM acknowledges that lawful and ethical therapeutic use of AAS is now an accepted mainstream treatment for several clinical disorders; however, there is increased recognition that AAS are commonly used illicitly to enhance performance and appearance in several segments of the population, including competitive athletes. The illicit use of AAS by competitive athletes is contrary to the rules and ethics of many sport governing bodies. Thus, the ACSM deplores the illicit use of AAS for athletic and recreational purposes. This consensus statement provides a brief history of AAS use, an update on the science of how we now understand AAS to be working metabolically/biochemically, potential side effects, the prevalence of use among athletes, and the use of AAS in clinical scenarios., (Copyright © 2021 by the American College of Sports Medicine.)

Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific cis and trans factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA [Ser]Sec , encoded in mice by the gene Trsp . Whole-body deletion of Trsp in mouse is embryonically lethal, while targeted deletion of Trsp in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues. We developed a mouse model with the targeted deletion of Trsp in brown adipocytes ( Trsp f/f -Ucp1-Cre +/- ), a cell type predominant in brown adipose tissue (BAT) controlling energy expenditure via activation of adaptive thermogenesis, mostly using uncoupling protein 1 (Ucp1). At room temperature, Trsp f/f -Ucp1-Cre +/- mice maintain oxygen consumption and Ucp1 expression, with male Trsp f/f -Ucp1-Cre +/- mice accumulating more triglycerides in BAT than both female Trsp f/f -Ucp1-Cre +/- mice or Trsp f/f controls. Acute cold exposure neither reduced core body temperature nor changed the expression of selenoprotein iodothyronine deiodinase type II (Dio2), a marker of adaptive thermogenesis, in Trsp f/f -Ucp1-Cre +/- mice. Microarray analysis of BAT from Trsp f/f -Ucp1-Cre +/- mice revealed glutathione S-transferase alpha 3 ( Gsta3 ) and ELMO domain containing 2 ( Elmod2 ) as the transcripts most affected by the loss of Trsp . Male Trsp f/f -Ucp1-Cre +/- mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes Thrsp and Tshr in their BATs. In summary, modest changes in the BAT of Trsp f/f -Ucp1-Cre +/- mice implicate a mild thyroid hormone dysfunction in brown adipocytes.

Purpose: Post-operative changes in moderate-to-vigorous physical activity (MVPA) may contribute to improved weight loss and long-term weight maintenance of individuals after bariatric surgery. Patients experience minimal changes in MVPA > 6 months after surgery, but no studies have investigated early changes in physical activity after surgery. This study aims to assess MVPA changes during the rapid weight loss phase through self-reporting and objective measures., Methods: Physical activity patterns were assessed as minutes per day spent doing MVPA. A walking cadence of ≥ 100 steps per minute defined MVPA. Individuals completing gastric bypass (N = 7) and sleeve gastrectomy (N = 17) procedures (21 females, 3 males, age 42.2 ± 12.6 years, body mass 121.8 ± 24.8 kg, BMI 44.0 ± 6.5) completed office visits at 12 ± 6 days pre- and 35 ± 10 days post-operative. Each wore an ActiGraph GT3X tri-axial accelerometer at the hip for 7 days before and again for 7 days 30.6 ± 10 days after surgery. Assessments also included a subjective question about their anticipated and perceived post-operative MVPA (scale of - 3 to 3 with 3 being much more physically active and - 3 being much less)., Results: Participants did not change their minutes per day of MVPA significantly (pre-operative 1.5 ± 2.1; post-operative 2.6 ± 5.6, NS). Participants predicted their post-operative physical activity level would increase (2.8 ± 0.4). The self-reported activity level on the same scale after surgery was significantly less than predicted (1.9 ± 1.0, p < 0.05) but still suggested that participants thought they were more physically active., Conclusion: Consistent with reports > 6 months after surgery, MVPA did not increase in the early post-operative period, despite patient expectations. The early post-operative period may be a time for behavioral intervention.

There are well-known disparities in the prevalence of obesity across racial-ethnic groups, although the behavioral and psychological factors driving these disparities are less well understood. Therefore, the objectives of this study were: (1) to examine differences in dietary quality by race/ethnicity and weight-related variables [body mass index (BMI), weight loss attempt, and weight dissatisfaction] and physical activity (PA) using the Health Eating Index-2015 (HEI-2015); and (2) to investigate the interactions and independent associations of race/ethnicity, weight-related variables and PA on dietary quality. Data for adolescents aged 12-19 years ( n = 3373) were abstracted from the 2007-2014 National Health and Nutrition and Examination Survey and analyzed using multiple PROC SURVEYREG, adjusting for demographics and accounting for complex sampling. Analyses determined that Hispanic males had better overall HEI-2015 scores than non-Hispanic whites (48.4 ± 0.5 vs. 45.7 ± 0.6, p = 0.003) or blacks (48.4 ± 0.5 vs. 45.5 ± 0.5, p < 0.001). Hispanic females also had better dietary quality than non-Hispanic whites (50.2 ± 0.4 vs. 47.5 ± 0.5, p < 0.001) and blacks (50.2 ± 0.4 vs. 47.1 ± 0.5, p < 0.001). Meeting the PA recommendation modified racial/ethnic differences in dietary quality for females ( p = 0.011) and this was primarily driven by the associations among non-Hispanic white females (ΔR 2 = 2.6%, p = 0.0004). The study identified racial/ethnic and gender differences among adolescents in factors that may promote obesity. Results may be useful for obesity prevention efforts designed to reduce health disparities in adolescents.

Introduction: Cold-water immersion (CWI) is often used to promote recovery by reducing exercise-induced muscle damage, soreness, and inflammation. However, recent reports have cautioned that CWI may attenuate the adaptive response to resistance training., Purpose: To determine the effect of post resistance-exercise CWI on circulating free testosterone (T) and cytokine (IL-6 and TNF-α) response., Methods: Using a randomized and counterbalanced repeated-measures design, 11 resistance-trained men completed two workouts (6 sets of 10 repetitions of back squats at 80% of maximum load) a week apart after which they took part in either 15 min of CWI (15 °C) or passive recovery. T, IL-6, and TNFα were measured in blood samples taken before (PRE) and 5 (5POST), 15 (15POST), 30 (30POST), and 60 (60POST) min post-exercise and compared between treatments and over time., Results: For T, a significant interaction effect of condition over time (p = 0.030) as well as greater relative concentrations of T in CON (Δ9.2%) than CWI (Δ-0.5%, p = 0.049) at 30POST were observed. In addition, at 60POST, T dropped below PRE values in CWI (Δ-10.4%, p = 0.028) but not in CON (Δ-1.6%, p = 0.850). A suppressed cytokine response was observed after CWI in IL-6 at 30POST (CWI: Δ4.9%, CON: Δ47.5%, p = 0.041) and TNFα at 15POST (CWI: Δ5.3%, CON: Δ17.0%, p = 0.022)., Conclusions: CWI blunted the T and cytokine response after a bout of resistance exercise. These results indicate that CWI results in an altered anabolic response and may help to explain the previous observation of attenuated hypertrophy when CWI is used after resistance exercise.

Hatfield, DL, Murphy, KM, Nicoll, JX, Sullivan, WM, and Henderson, J. Effects of different athletic playing surfaces on jump height, force, and power. J Strength Cond Res 33(4): 965-973, 2019-Artificial turfs (ATs) have become more commonplace. Some aspects of performance such as speed seem to be better on ATs, but there are few published studies on the effects of playing surfaces on performance. Furthermore, there is no research that compares performance on ATs, hard surfaces (HSs), and different composite natural surfaces. Forty-three subjects, 21 men (age: 20 ± 1.82 years; height: 177.53 ± 5.87 cm; body mass: 78.44 ± 11.59 kg; and body fat: 11.17 ± 4.45%) and 22 women (age: 25 ± 1.32 years; height: 161.37 ± 6.47 cm; body mass: 60.94 ± 10.24 kg; and body fat: 27.16 ± 7.08%) performed a single countermovement jump (SCMJ), repeated CMJs (RCMJs), and single depth jump (SDJ) on 4 different playing surfaces (peat soil composition turf [NT1], sandy loam composition turf [NT2], 1 AT, and 1 HS. Repeated-measures analysis of variance with Bonferroni post hoc was used to calculate differences in performance across playing surfaces. Statistical significance was set at p ≤ 0.05. Force and jump height were not different across different surfaces. Men had significantly higher force, power, and jump height on all surfaces. Only SCMJ power was lower on NT1 compared with all other surfaces. The difference in power between surfaces was not reproduced when RCMJ and SDJ were performed, and may be due to the increased reactiveness of the stretch-shortening cycle during those jumps. Because of marginal differences between athletic performance and playing surface type, future research comparing playing surface type and other aspects of athletic success such as rate of injury should be considered.

Vincent, LM, Blissmer, BJ, and Hatfield, DL. National Scouting Combine scores as performance predictors in the National Football League. J Strength Cond Res 33(1): 104-111, 2019-The National Football League (NFL) hosts an annual scouting combine to evaluate the approximately 300 elite college football players who are most likely to be selected in the upcoming NFL draft. Given the public interest, player obligations, coaching staff commitments, and business aspects of the combine, several questions have arose in recent years concerning the applicability of combine scores to eventual draft NFL performance. The primary purpose of this study is to investigate the relationship between specified National Scouting Combine (NSC) scores and measures of performance by player position. A secondary aim was to determine whether correlated variables could predict player performance at the quarterback (QB), running back (RB), wide receiver (WR), defensive end (DE), defensive tackle (DT), and linebacker (LB) positions. Subjects in this study were combine participants between the years 2005-2010 who subsequently played in the NFL. The positional groups investigated were QBs (N = 44), RBs (N = 82), WRs (N = 116), LBs (N = 139), DEs (N = 59), and DTs (N = 72). Combine raw scores for 40-yd dash time, countermovement vertical jump (CMVJ) height, standing long jump (SLJ) distance, and pro-agility time were recorded. Measures of horizontal and vertical power were calculated for the 40-yd dash and CMVJ. Combine scores and on-field positional statistics for the first 4 years for QBs and 3 years of all other players' careers were analyzed to investigate relationships. Significant correlations were shown between at least one combine measure and on-field success at every position. Hierarchal regression showed combine measures could predict between 4% and 62% of the variance for individual on-field variables. Quarterback rushing yards were significantly correlated with 40T, CMVJ, vertical jump power (VJP), vertical jump relative power (VJRP), and horizontal power (HP), and those factors accounted for 62.2% of the total variance. Horizontal power and VJP were predictive of QB rushing attempts (r = 0.370). At RB, 40T and SLJ combined were predictive of total rushing yards (r = 0.200), rushing attempts (r = 0.195), and yards per game (r = 0.197). Power variables were predictive of total tackles for DEs' 40HP (r = 0.096) and VJP (r = 0.018), accounting for a total of 21% of the variance. The current study suggests that combine tests are modest predictors of future performance. Should the NFL change the current NSC testing battery, the addition of horizontal and vertical power measurements, as well as position-specific skill tests are recommended.

Selenophosphate synthetase (SEPHS) synthesizes selenophosphate, the active selenium donor, using ATP and selenide as substrates. SEPHS was initially identified and isolated from bacteria and has been characterized in many eukaryotes and archaea. Two SEPHS paralogues, SEPHS1 and SEPHS2, occur in various eukaryotes, while prokaryotes and archaea have only one form of SEPHS. Between the two isoforms in eukaryotes, only SEPHS2 shows catalytic activity during selenophosphate synthesis. Although SEPHS1 does not contain any significant selenophosphate synthesis activity, it has been reported to play an essential role in regulating cellular physiology. Prokaryotic SEPHS contains a cysteine or selenocysteine (Sec) at the catalytic domain. However, in eukaryotes, SEPHS1 contains other amino acids such as Thr, Arg, Gly, or Leu at the catalytic domain, and SEPHS2 contains only a Sec. Sequence comparisons, crystal structure analyses, and ATP hydrolysis assays suggest that selenophosphate synthesis occurs in two steps. In the first step, ATP is hydrolyzed to produce ADP and gamma-phosphate. In the second step, ADP is further hydrolyzed and selenophosphate is produced using gamma-phosphate and selenide. Both SEPHS1 and SEPHS2 have ATP hydrolyzing activities, but Cys or Sec is required in the catalytic domain for the second step of reaction. The gene encoding SEPHS1 is divided by introns, and five different splice variants are produced by alternative splicing in humans. SEPHS1 mRNA is abundant in rapidly proliferating cells such as embryonic and cancer cells and its expression is induced by various stresses including oxidative stress and salinity stress. The disruption of the SEPHS1 gene in mice or Drosophila leads to the inhibition of cell proliferation, embryonic lethality, and morphological changes in the embryos. Targeted removal of SEPHS1 mRNA in insect, mouse, and human cells also leads to common phenotypic changes similar to those observed by in vivo gene knockout: the inhibition of cell growth/proliferation, the accumulation of hydrogen peroxide in mammals and an unidentified reactive oxygen species (ROS) in Drosophila, and the activation of a defense system. Hydrogen peroxide accumulation in SEPHS1-deficient cells is mainly caused by the down-regulation of genes involved in ROS scavenging, and leads to the inhibition of cell proliferation and survival. However, the mechanisms underlying SEPHS1 regulation of redox homeostasis are still not understood., (Copyright © 2018. Published by Elsevier Inc.)

Selenof (15-kDa selenoprotein; Sep15) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase that occurs in a complex with UDP-glucose:glycoprotein glucosyltransferase. We found that Selenof deficiency in mice leads to elevated levels of non-functional circulating plasma immunoglobulins and increased secretion of IgM during in vitro splenic B cell differentiation. However, Selenof knockout animals show neither enhanced bacterial killing capacity nor antigen-induced systemic IgM activity, suggesting that excess immunoglobulins are not functional. In addition, ER-to-Golgi transport of a target glycoprotein was delayed in Selenof knockout embryonic fibroblasts, and proteomic analyses revealed that Selenof deficiency is primarily associated with antigen presentation and ER-to-Golgi transport. Together, the data suggest that Selenof functions as a gatekeeper of immunoglobulins and, likely, other client proteins that exit the ER, thereby supporting redox quality control of these proteins., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The selenocysteine (Sec) tRNA [Ser]Sec population consists of two isoforms that differ from each other by a single 2'-O-methylribosyl moiety at position 34 (Um34). These two isoforms, which are encoded in a single gene, Trsp, and modified posttranscriptionally, are involved individually in the synthesis of two subclasses of selenoproteins, designated housekeeping and stress-related selenoproteins. Techniques used in obtaining these isoforms for their characterization include extraction of RNA from mammalian cells and tissues, purifying the tRNA [Ser]Sec population by one or more procedures, and finally resolving the two isoforms from each other. Since some of the older techniques for isolating tRNA [Ser]Sec and resolving the isoforms are used in only a few laboratories, these procedures will be discussed briefly and references provided for more detailed information, while the more recently developed procedures are discussed in detail. In addition, a novel technique that was developed in sequencing tRNA [Ser]Sec for identifying their occurrence in other organisms is also presented.

Purpose: Overtraining syndrome (OTS) is reported in endurance sports. Thyroid hormones (TH) regulate metabolism, mood, and energy production, and may play a role in OTS of endurance athletes. The purpose of this study was to investigate relationships in TH and symptoms of OTS in track and field endurance runners (ER)., Methods: Sixteen female track and field middle distance (MD; n = 9; age: 20.2 ± 1.5 years; ht: 167.86 ± 5.04 cm; body-mass: 57.97 ± 5.05 kg; VO 2MAX : 53.62 ± 6.04 ml/kg/min) and long distance (LD; n = 7; age: 20.5 ± 1.5 years; ht: 162.48 ± 6.11 cm; body-mass: 56.15 ± 5.99 kg; VO 2MAX : 61.94 ± 3.29 ml/kg/min) ER participated in this descriptive study (15-weeks). Thyroid-stimulating hormone (TSH), triiodothyronine (T 3 ), and thyroxine (T 4 ), were collected at pre-(PRE) and post-season (POST). A fatigue scale was administered weekly, and percent change (PΔ) in race time (season best vs. championship performance) was calculated. Wilcoxon-sign ranked tests and Spearman's rho correlations were used to determine changes and relationships between TH and performance., Results: TSH, T 3 and T 4 did not change from PRE to POST. The percent change (PΔ) in T 3 from PRE to POST was correlated with running performance at the end of the season (ρ = - 0.70, p = 0.036). Fatigue at week 12 correlated with running performance at the end of the season (ρ = - 0.74, p = 0.004)., Conclusion: TH may be valuable in assessing the overall training state of ER. TH concentrations change too slowly to be a frequent marker of monitoring OTS, but are related to markers of decreased performance. Monitoring dietary intake, and fatigue may be predictive markers to assess OTS and training status of female ER.

Due to the important interactions of proenkephalin fragments (e.g., proenkephalin [107-140] Peptide F) to enhance activation of immune cells and potentially combat pain associated with exercise-induced muscle tissue damage, we examined the differential plasma responses of Peptide F to different exercise training programs. Participants were tested pre-training (T1), and after 8 weeks (T2) of training. Fifty-nine healthy women were matched and then randomly assigned to one of four groups: heavy resistance strength training (STR, n=18), high intensity endurance training (END, n=14), combined strength and endurance training (CMB, n=17), or control (CON, n=10). Blood was collected using a cannula inserted into a superficial vein in the antecubital fossa with samples collected at rest and immediately after an acute bout of 6 X 10 RM in a squat resistance exercise before training and after training. Prior to any training, no significant differences were observed for any of the groups before or after acute exercise. With training, significant (P≤0.95) elevations were observed with acute exercise in each of the exercise training groups and this effect was significantly greater in the CMB group. These data indicate that in untrained women exercise training will not change resting of plasma Peptide F concentrations unless both forms of exercise are performed but will result in significant increases in the immediate post-exercise responses. Such findings appear to indicate adrenal medullary adaptations opioid production significantly altered with exercise training., (Copyright © 2017. Published by Elsevier Inc.)

Dual-assignment of codons as termination and elongation codons is used to expand the genetic code. In mammals, UGA can be reassigned to selenocysteine during translation of selenoproteins by a mechanism involving a 3΄ untranslated region (UTR) selenocysteine insertion sequence (SECIS) and the SECIS-binding protein Secisbp2. Here, we present data from ribosome profiling, RNA-Seq and mRNA half-life measurements that support distinct roles for Secisbp2 in UGA-redefinition and mRNA stability. Conditional deletions of the Secisbp2 and Trsp (tRNASec) genes in mouse liver were compared to determine if the effects of Secisbp2 loss on selenoprotein synthesis could be attributed entirely to the inability to incorporate Sec. As expected, tRNASec depletion resulted in loss of ribosome density downstream of all UGA-Sec codons. In contrast, the absence of Secisbp2 resulted in variable effects on ribosome density downstream of UGA-Sec codons that demonstrate gene-specific differences in Sec incorporation. For several selenoproteins in which loss of Secisbp2 resulted in greatly diminished mRNA levels, translational activity and Sec incorporation efficiency were shown to be unaffected on the remaining RNA. Collectively, these results demonstrate that Secisbp2 is not strictly required for Sec incorporation and has a distinct role in stabilizing mRNAs that can be separated from its effects on UGA-redefinition., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The tRNA for the 21st proteinogenic amino acid, selenocysteine, exists in mammalian cells as 2 isoforms differing by a single 2'-O-methylribosyl moiety at position 34 (Um34). These isoforms contain either 5-methoxycarbonylmethyluridine (mcm 5 U) or 5-methoxycarbonylmethyl-2'-O-methyluridine (mcm 5 Um) at position 34. The accumulation of the mcm 5 Um isoform is tightly correlated with the expression of nonessential "stress response" selenoproteins such as glutathione peroxidase 1 (GPX1). The expression of essential selenoproteins, such as thioredoxin reductase 1 (TXNRD1), is not affected by changes in Sec-tRNA [Ser]Sec isoform accumulation. In this work we used purified mcm 5 U and mcm 5 Um Sec-tRNA [Ser]Sec isoforms to analyze possible differences in binding to the selenocysteine-specific elongation factor, EEFSEC, and the translation of GPX1 and TXNRD1 in vitro . Our results indicate that no major distinction between mcm 5 U and mcm 5 Um isoforms is made by the translation machinery, but a small consistent increase in GPX1 translation is associated with the mcm 5 Um isoform. These results implicate fundamental differences in translation efficiency in playing a role in regulating selenoprotein expression as a function of isoform accumulation.

The ribosome can change its reading frame during translation in a process known as programmed ribosomal frameshifting. These rare events are supported by complex mRNA signals. However, we found that the ciliates Euplotes crassus and Euplotes focardii exhibit widespread frameshifting at stop codons. 47 different codons preceding stop signals resulted in either +1 or +2 frameshifts, and +1 frameshifting at AAA was the most frequent. The frameshifts showed unusual plasticity and rapid evolution, and had little influence on translation rates. The proximity of a stop codon to the 3' mRNA end, rather than its occurrence or sequence context, appeared to designate termination. Thus, a 'stop codon' is not a sufficient signal for translation termination, and the default function of stop codons in Euplotes is frameshifting, whereas termination is specific to certain mRNA positions and probably requires additional factors.

Ouellette, KA, Brusseau, TA, Davidson, LE, Ford, CN, Hatfield, DL, Shaw, JM, and Eisenman, PA. Comparison of the effects of seated, supine, and walking interset rest strategies on work rate. J Strength Cond Res 30(12): 3396-3404, 2016-The idea that an upright posture should be maintained during the interset rest periods of training sessions is pervasive. The primary aim of this study was to determine differences in work rate associated with 3 interset rest strategies. Male and female members of the CrossFit community (male n = 5, female n = 10) were recruited to perform a strenuous training session designed to enhance work capacity that involved both cardiovascular and muscular endurance exercises. The training session was repeated on 3 separate occasions to evaluate 3 interset rest strategies, which included lying supine on the floor, sitting on a flat bench, and walking on a treadmill (0.67 m·s). Work rate was calculated for each training session by summing session joules of work and dividing by the time to complete the training session (joules of work per second). Data were also collected during the interset rest periods (heart rate [HR], respiratory rate [RR], and volume of oxygen consumed) and were used to explain why one rest strategy may positively impact work rate compared with another. Statistical analyses revealed significant differences (p ≤ 0.05) between the passive and active rest strategies, with the passive strategies allowing for improved work rate (supine = 62.77 ± 7.32, seated = 63.66 ± 8.37, and walking = 60.61 ± 6.42 average joules of work per second). Results also suggest that the passive strategies resulted in superior HR, RR, and oxygen consumption recovery. In conclusion, work rate and physiological recovery were enhanced when supine and seated interset rest strategies were used compared with walking interset rest.

The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15-kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV), and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing, and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian glutathione peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance of Gpx4 and of another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion of Gpx4 in hepatocytes were studied, along with those lacking Txnrd1 and selenocysteine (Sec) tRNA (Trsp) in hepatocytes. Unlike Txnrd1- and Trsp-deficient mice, Gpx4 -/- mice died shortly after birth and presented extensive hepatocyte degeneration. Similar to Txnrd1-deficient livers, Gpx4 -/- livers manifested upregulation of nuclear factor (erythroid-derived)-like 2 (Nrf2) response genes. Remarkably, Gpx4 -/- pups born from mothers fed a vitamin E-enriched diet survived, yet this protection was reversible as subsequent vitamin E deprivation caused death of Gpx4-deficient mice ~4 weeks thereafter. Abrogation of selenoprotein expression in Gpx4 -/- mice did not result in viable mice, indicating that the combined deficiency aggravated the loss of Gpx4 in liver. By contrast, combined Trsp/Txnrd1-deficient mice were born, but had significantly shorter lifespans than either single knockout, suggesting that Txnrd1 plays an important role in supporting liver function of mice lacking Trsp. In sum our study demonstrates that the ferroptosis regulator Gpx4 is critical for hepatocyte survival and proper liver function, and that vitamin E can compensate for its loss by protecting cells against deleterious lipid peroxidation., (Published by Elsevier B.V.)

Selenophosphate synthetase (SPS) was initially detected in bacteria and was shown to synthesize selenophosphate, the active selenium donor. However, mammals have two SPS paralogues, which are designated SPS1 and SPS2. Although it is known that SPS2 catalyses the synthesis of selenophosphate, the function of SPS1 remains largely unclear. To examine the role of SPS1 in mammals, we generated a Sps1-knockout mouse and found that systemic SPS1 deficiency led to embryos that were clearly underdeveloped by embryonic day (E)8.5 and virtually resorbed by E14.5. The knockout of Sps1 in the liver preserved viability, but significantly affected the expression of a large number of mRNAs involved in cancer, embryonic development and the glutathione system. Particularly notable was the extreme deficiency of glutaredoxin 1 (GLRX1) and glutathione transferase Omega 1 (GSTO1). To assess these phenotypes at the cellular level, we targeted the removal of SPS1 in F9 cells, a mouse embryonal carcinoma (EC) cell line, which affected the glutathione system proteins and accordingly led to the accumulation of hydrogen peroxide in the cell. Furthermore, we found that several malignant characteristics of SPS1-deficient F9 cells were reversed, suggesting that SPS1 played a role in supporting and/or sustaining cancer. In addition, the overexpression of mouse or human GLRX1 led to a reversal of observed increases in reactive oxygen species (ROS) in the F9 SPS1/GLRX1-deficient cells and resulted in levels that were similar to those in F9 SPS1-sufficient cells. The results suggested that SPS1 is an essential mammalian enzyme with roles in regulating redox homoeostasis and controlling cell growth., (© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.)

Professor Vadim N. Gladyshev is recognized here as a Redox Pioneer, because he has published an article on antioxidant/redox biology that has been cited more than 1000 times and 29 articles that have been cited more than 100 times. Gladyshev is world renowned for his characterization of the human selenoproteome encoded by 25 genes, identification of the majority of known selenoprotein genes in the three domains of life, and discoveries related to thiol oxidoreductases and mechanisms of redox control. Gladyshev's first faculty position was in the Department of Biochemistry, the University of Nebraska. There, he was a Charles Bessey Professor and Director of the Redox Biology Center. He then moved to the Department of Medicine at Brigham and Women's Hospital, Harvard Medical School, where he is Professor of Medicine and Director of the Center for Redox Medicine. His discoveries in redox biology relate to selenoenzymes, such as methionine sulfoxide reductases and thioredoxin reductases, and various thiol oxidoreductases. He is responsible for the genome-wide identification of catalytic redox-active cysteines and for advancing our understanding of the general use of cysteines by proteins. In addition, Gladyshev has characterized hydrogen peroxide metabolism and signaling and regulation of protein function by methionine-R-sulfoxidation. He has also made important contributions in the areas of aging and lifespan control and pioneered applications of comparative genomics in redox biology, selenium biology, and aging. Gladyshev's discoveries have had a profound impact on redox biology and the role of redox control in health and disease. He is a true Redox Pioneer. Antioxid. Redox Signal. 25, 1-9.

Circadian rhythms (CRs) persist in many physiological systems related to performance. The effects of circadian patterns on dynamic muscular power are minimal and conflicting. Furthermore, no study to date has investigated the effect of CR on bench press throws (BPTs) despite its popularity as a modality to increase muscular power. The purpose of this study was to examine the effects of circadian variations on muscular power output and hormonal changes in men. College aged men (n = 7, age: 23.6 ± 1.3 years, height: 179.9 ± 5.4 cm, and body mass: 81.5 ± 19.7 kg.) were recruited for this repeated measures study. Testing occurred at 4 different times of day (04:00, 10:00, 16:00, and 22:00 hours). Testosterone (T) and cortisol (C) hand dynamometer strength (GS), heart rate (HR), mental readiness (MR), BPT and squat jumps (SJs), power (P), and force (F) were measured at each time point. Statistical significance was set at (p ≤ 0.05). There were no significant differences in HR, MR, and GS among all time points. There were no decrements in P or F in BPT or SJ among any time point (p ≥ 0.05). Testosterone and C decreased significantly throughout the day (p ≤ 0.05). Although P and F output differed at various percentages of 1 repetition maximum, they were not affected by circadian pattern, such that muscular performance was not impaired at any time point. Practical implications of these data indicate that high force and power exercises using BPT or SJ may be performed any time of day without detrimental decreases in acute performance.

A common characteristic of many cancer cells is that they suffer from oxidative stress. They, therefore, require effective redox regulatory systems to combat the higher levels of reactive oxygen species that accompany accelerated growth compared to the normal cells of origin. An elevated dependence on these systems in cancers suggests that targeting these systems may provide an avenue for retarding the malignancy process. Herein, we examined the redox regulatory systems in human liver and lung cancers by comparing human lung adenocarcinoma and liver carcinoma to their respective surrounding normal tissues. Significant differences were found in the two major redox systems, the thioredoxin and glutathione systems. Thioredoxin reductase 1 levels were elevated in both malignancies, but thioredoxin was highly upregulated in lung tumor and only slightly upregulated in liver tumor, while peroxiredoxin 1 was highly elevated in lung tumor, but downregulated in liver tumor. There were also major differences within the glutathione system between the malignancies and their normal tissues. The data suggest a greater dependence of liver on either the thioredoxin or glutathione system to drive the malignancy, while lung cancer appeared to depend primarily on the thioredoxin system.

Selenoproteins are a unique group of proteins that contain selenium in the form of selenocysteine (Sec) co-translationally inserted in response to a UGA codon with the help of cis- and trans-acting factors. Mammalian selenoproteins contain single Sec residues, with the exception of selenoprotein P (SelP) that has 7-15 Sec residues depending on species. Assessing an individual's selenium status is important under various pathological conditions, which requires a reliable selenium biomarker. Due to a key role in organismal selenium homeostasis, high Sec content, regulation by dietary selenium, and availability of robust assays in human plasma, SelP has emerged as a major biomarker of selenium status. Here, we found that Cys is present in various Sec positions in human SelP. Treatment of cells expressing SelP with thiophosphate, an analog of the selenium donor for Sec synthesis, led to a nearly complete replacement of Sec with Cys, whereas supplementation of cells with selenium supported Sec insertion. SelP isolated directly from human plasma had up to 8% Cys inserted in place of Sec, depending on the Sec position. These findings suggest that a change in selenium status may be reflected in both SelP concentration and its Sec content, and that availability of the SelP-derived selenium for selenoprotein synthesis may be overestimated under conditions of low selenium status due to replacement of Sec with Cys.

Selenium is an essential element that is required to support a number of cellular functions and biochemical pathways. The objective of this study was to examine the effects of reduced dietary selenium levels on gene expression to assess changes in expression of non-selenoprotein genes that may contribute to the physiological consequences of selenium deficiency. Mice were fed diets that were either deficient in selenium or supplemented with selenium in the form of sodium selenite for six weeks. Differences in liver mRNA expression and translation were measured using a combination of ribosome profiling, RNA-Seq, microarrays, and qPCR. Expression levels and translation of mRNAs encoding stress-related selenoproteins were shown to be up-regulated by increased selenium status, as were genes involved in inflammation and response to interferon-γ. Changes in serum cytokine levels were measured which confirmed that interferon-γ, as well as IL-6, were increased in selenium adequate mice. Finally, microarray and qPCR analysis of lung tissue demonstrated that the selenium effects on immune function are not limited to liver. These data are consistent with previous reports indicating that adequate selenium levels can support beneficial immune responses, and further identify the IL-6 and interferon-γ pathways as being responsive to dietary selenium intake.

Selenocysteine tRNA 1 associated protein (Trnau1ap) has been characterized as a tRNA[Ser]Sec-binding protein of 43 kDa, hence initially named SECp43. Previous studies reported its presence in complexes containing tRNA[Ser]Sec implying a role of SECp43 as a co-factor in selenoprotein expression. We generated two conditionally mutant mouse models targeting exons 3+4 and exons 7+8 eliminating parts of the first RNA recognition motif or of the tyrosine-rich domain, respectively. Constitutive inactivation of exons 3+4 of SECp43 apparently did not affect the mice or selenoprotein expression in several organs. Constitutive deletion of exons 7+8 was embryonic lethal. We therefore generated hepatocyte-specific Secp43 knockout mice and characterized selenoprotein expression in livers of mutant mice. We found no significant changes in the levels of 75Se-labelled hepatic proteins, selenoprotein levels as determined by Western blot analysis, enzymatic activity or selenoprotein mRNA abundance. The methylation pattern of tRNA[Ser]Sec remained unchanged. Truncated Secp43 Δ7,8mRNA increased in Secp43-mutant livers suggesting auto-regulation of Secp43 mRNA abundance. We found no signs of liver damage in Secp433-mutant mice, but neuron-specific deletion of exons 7+8 impaired motor performance, while not affecting cerebral selenoprotein expression or cerebellar development. These findings suggest that the targeted domains in the SECp43 protein are not essential for selenoprotein biosynthesis in hepatocytes and neurons. Whether the remaining second RNA recognition motif plays a role in selenoprotein biosynthesis and which other cellular process depends on SECp43 remains to be determined.

The concept of developing talent and athleticism in youth is the goal of many coaches and sports systems. Consequently, an increasing number of sporting organizations have adopted long-term athletic development models in an attempt to provide a structured approach to the training of youth. It is clear that maximizing sporting talent is an important goal of long-term athletic development models. However, ensuring that youth of all ages and abilities are provided with a strategic plan for the development of their health and physical fitness is also important to maximize physical activity participation rates, reduce the risk of sport- and activity-related injury, and to ensure long-term health and well-being. Critical reviews of independent models of long-term athletic development are already present within the literature; however, to the best of our knowledge, a comprehensive examination and review of the most prominent models does not exist. Additionally, considerations of modern day issues that may impact on the success of any long-term athletic development model are lacking, as are proposed solutions to address such issues. Therefore, within this 2-part commentary, Part 1 provides a critical review of existing models of practice for long-term athletic development and introduces a composite youth development model that includes the integration of talent, psychosocial and physical development across maturation. Part 2 identifies limiting factors that may restrict the success of such models and offers potential solutions.

The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.

The first installment of this two-part commentary reviewed existing models of long-term athletic development. However, irrespective of the model that is adopted by practitioners, existing structures within competitive youth sports in addition to the prevalence of physical inactivity in a growing number of modern-day youth may serve as potential barriers to the success of any developmental pathway. The second part of this commentary will initially highlight common issues that are likely to impede the success of long-term athletic development programs and then propose solutions that will address the negative impact of such issues.

Selenoproteins mediate much of the cancer-preventive properties of the essential nutrient selenium, but some of these proteins have been shown to also have cancer-promoting effects. We examined the contributions of the 15kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and formation of experimental metastases of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially interferon-γ-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient, but not in TR1-deficient cells. Interestingly, components of the Wnt/β-catenin signaling pathway were up-regulated in cells lacking both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, our results provide insights into new roles of selenoproteins in cancer.

The 15-kDa selenoprotein (Sep15) has been implicated in etiology of some types of cancer. Herein, inducible RNAi cell lines were established and cell morphology and motility were analyzed. The majority of Sep15-deficient cells (>95%) formed membrane blebs in a dynamic manner. Blebbing cells transformed cell morphology from a normal flat spindle shape to a spherical morphology. In blebbing cells, actin fibers moved to the cell periphery, covering and obscuring visualization of α-tubulin. Bleb formation was suppressed by the inhibitors of Rho-associated protein kinase (ROCK), RhoA or myosin light chain (MLC), restoring blebbing cells to wild-type morphology. RhoA activation and phosphorylation of myosin phosphatase target subunit 1 was induced by Sep15 knockdown. Sep15-deficient cells were non-apoptotic, and displayed a distinct relative localization of F-actin and α-tubulin from typical apoptotic blebbing cells. Our data suggest that Sep15 in Chang liver cells regulates the pathway that antagonizes RhoA/ROCK/MLC-dependent non-apoptotic bleb formation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

To better understand how developmental differences impact performance on a broad selection of common physical fitness measures, we examined changes in boys and girls from fourth to fifth grade. Subjects included 273 boys (age, 9.5 ± 0.6 years; height, 139.86 ± 7.52 cm; mass, 38.00 ± 9.55 kg) and 295 girls (age, 9.6 ± 0.5 years; height, 139.30 ± 7.19 cm; weight, 37.44 ± 9.35 kg). We compared anthropometrics, cardiorespiratory and local muscular endurance, flexibility, power, and strength. A mixed-method analysis of variance was used to compare boys and girls at the 2 time points. Pearson correlation coefficients were used to examine relationships between anthropometric and fitness measurements. Significance was set at p ≤ 0.05. Weight increased significantly (>10%) in both sexes, and girls became significantly taller than boys after growing 4.9% by fifth grade (vs. 3.5%). Both groups improved cardiorespiratory endurance and power, although boys performed better than girls at both time points. Boys were stronger in fourth grade, but girls improved more, leading to similar fifth-grade values. Girls were more flexible in fourth grade, but their significant decreases (∼32.4%) coupled with large improvements in boys (∼105%) resulted in similar fifth-grade scores. Body mass index (BMI) was positively correlated with run time regardless of grade or sex. Power was negatively correlated with BMI and run time in fourth grade. In conclusion, sex-specific differences in physical fitness are apparent before pubescence. Furthermore, this selection of measures reveals sexually dimorphic changes, which likely reflect the onset of puberty in girls. Coaches and teachers should account these developmental differences and their effects on anthropometrics and fitness in boys and girls.