Ubiquitin Proteasome System Activity is Suppressed by Curcumin Following Exercise-Induced Muscle Damage in Human Skeletal Muscle

PURPOSE: Curcumin is a natural polyphenolic compound with antioxidant and anti-inflammatory properties. In vitro and in vivo animal studies have demonstrated that exposure to curcumin leads to dysregulation of the ubiquitin-proteasome system (UPS). However, to date, no study has investigated curcumin’s ability to influence UPS activity in a human model. Therefore, the purpose of this study was to investigate the effects of curcumin supplementation on markers of UPS activity in the presence of elevations in UPS activity due to exercise-induced muscle damage. METHODS: Twenty-three recreationally active male and female participants between the ages of 18-30 were randomized into a curcumin (CUR; n=11) or placebo (PLA; n=12) group. Both groups were instructed to consume 2 g of their respective supplement and 20 mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45 minute eccentrically-biased muscle damaging treadmill protocol at 60% VO2max. Muscle biopsies and delayed onset muscle soreness (DOMS) analyses were performed 30 minutes prior and 3, 24, 48, and 72 hours following exercise-induced muscle damage. Skeletal muscle ubiquitin, MAFbx/Atrogin-1, ubiquitin specific peptidase 19 (USP19), and chymotrypsin-like protease concentrations were measured using ELISA. A 3-way repeated measures ANOVA with pairwise comparisons was conducted with significance set at p≤0.05. RESULTS: Both groups had a significant time effect for DOMS (p \u3c .001). Pairwise comparisons indicated DOMS was significantly greater from baseline at all time points except 72 hours following muscle damage. No significant differences were found for USP19 between groups. Regardless of time, a significant main effect for condition was observed for ubiquitin (p=.016) and MAFbx/Atrogin-1 (p=.006) where CUR was significantly lower than PLA. Additionally, a significant main effect for gender was observed for MAFbx/Atrogin-1 (p=.013) where females were greater than males. A significant group x gender interaction was found for chymotrypsin-like protease (p = .049) where males had lower values with curcumin supplementation while females had slightly higher. CONCLUSION: Curcumin supplementation in humans does appear to dysregulate UPS activity in the presence of exercise-induced muscle damage. Specifically, curcumin’s ability to suppress protein ubiquination provides preliminary evidence of curcumin supplementation’s potential therapeutic role in decreasing protein degradation associated with skeletal muscle damage and perhaps other atrophic scenarios

Wnt/β-Catenin and Androgen Receptor Signaling Increase Following High Load Resistance Exercise Without Elevations in Serum/Muscle Testosterone or Androgen Receptor Content

PURPOSE: The purpose of this study was 1) to determine the effect of single bouts of volume- and intensity-equated low (LL) and high load (HL) full-body resistance exercise (RE) on AR-DNA binding, serum/muscle testosterone and dihydrotestosterone, muscle androgen receptor (AR), and AR-DNA binding and 2) to determine the effect of RE on sarcoplasmic and nucleoplasmic β-catenin concentrations in order to determine their impact on mediating AR-DNA binding in the absence/presence of serum/muscle androgen and AR protein. METHODS: In a cross-over design, ten resistance-trained males completed volume- and intensity-equated LL and HL full-body RE. Blood and muscle samples were collected at pre-, 3h-, and 24h post-exercise. Separate 2x3 factorial ANOVAs with repeated measures and pairwise comparisons with a Bonferroni adjustment were used to analyze main effects. RESULTS: No significant differences were observed in muscle AR, testosterone, dihydrotestosterone, or serum total testosterone in either condition (p \u3e.05). Serum free testosterone was significantly decreased 3h post-exercise and remained significantly less than baseline 24h post-exercise in both conditions (p.05). Moreover, sarcoplasmic β-catenin was significantly greater in HL (p.05). CONCLUSION: Increases in AR-DNA binding in response to HL indicates AR signaling may be load-dependent. Furthermore, despite the lack of increase in serum and muscle androgens or AR content following HL RE, elevations in AR-DNA binding with elevated sarcoplasmic β-catenin suggests β-catenin may be facilitating this response

The Impacts of Wrist Wrap Type and Sex on Bench Press Muscular Strength and Power

While wrist wraps have become increasingly prevalent in both competitive and recreational demographics, their posited ability to augment bench press performance by enhanced wrist stability still remains unclear. PURPOSE: To determine the effect of varying wrap styles on bench-specific muscular strength and associated power, as well as quantitative and subjective differences between sexes. METHODS: Eighteen resistance trained males and females (9M/9F; 24±4y; 176±33cm; 80±15kg) visited the laboratory on three separate occasions in randomized, crossover, and counterbalanced design to sport either a flexible wrist wrap (FW), stiff wrap (SW), or a no wrap control (NW) condition. All participants underwent a bench press one-repetition maximum (1RM) test and linear position transducer-derived peak power and velocity assessments. Furthermore, subjective stability (SS) and discomfort (SD) were determined promptly following 1RM attempts. Bench press performance and sex-collapsed subjective variables were analyzed using a two-way (condition x sex) mixed model ANOVA with repeated measures and a nonparametric Friedman’s ANOVA, respectively. Both analyses were performed at a p\u3c.05 significance level. RESULTS: Analyses failed to detect any main condition or interaction effects for bench press 1RM, however, a statistically significant main sex effect was observed (p\u3c.001; ηp2=.597) favoring males relative to females (p\u3c.001; 114±22kg vs 68±16kg). Both peak power and velocity failed to reveal any significant main condition or sex effects, nor any interactions. Nonparametric assessments further revealed significant wrist wrap condition effects for both SS (p\u3c.001; Kendall’s W=.628) and SD (p\u3c.001; Kendall’s W=.935), whereby NW was statistically more comfortable (p\u3c.001) than either wrap condition, without any difference between DW and SW (p\u3e.05). CONCLUSION: Although wrist wraps did not significantly alter bench press-specific strength and power, participants nonetheless perceived wrist wraps as subjectively more stable irrespective of increased discomfort. ACKNOWLEDGEMENTS: The authors of this abstract would like to thank Peter Spence and SBD Apparel for generously donating the wrist wraps utilized in the present investigation

The Prevalence of Wrist Wrap Use in Actively Competing Powerlifters

Wrist wraps are often ergogenically employed by competitive powerlifters to improve bench press performance, but several product-specific variations may impact any potential benefits. Moreover, the prevalence of athletic wrist wrap use is hitherto undescribed. PURPOSE: to characterize the pervasiveness of wrist wrap use amongst competitive powerlifters with regards to style (flexible [F] or stiff [S]), length, and tightness amongst competitive powerlifters. METHODS: Powerlifters (n = 70; 27±6y) who competed in the last two years were randomly recruited at sanctioned meets across the USA. After providing consent and following a 5-minute seated rest, participant wrist wrap use descriptive data (wrap style [F or S], wrap length, and events used) were collected. Additionally, wrap tightness was assessed via pulse oximeter-detected oxygen saturation (SpO2). Post-meet bench press one repetition maximum (1RM) was also recorded from the Openpowerlifting.com open database. Wrist wrap use prevalence data (wrap style [F or S], wrap length, and events used) were assessed across Central, West Coast, and East Coast regions via separate Pearson’s Chi-squared tests. Furthermore, the relationships between both region-collapsed wrapped SpO2 and bench press 1RM were assessed using Pearson’s product-moment correlations and all statistical analyses were set at a significance level of pRESULTS: Analyses failed to detect any significant regional differences in wrap style, length, or events used (p\u3e0.05). Furthermore, there was a weak, negative correlation between wrapped SpO2 and bench press 1RM (r = -0.393, p = 0.086). CONCLUSIONS: Although we failed to detect any significant relationships between performance and wrap tightness, actively competing powerlifters nonetheless prominently utilize wraps similarly across the US regions assessed. Therefore, the potential for wrist wraps to augment bench press performance warrants further elucidation in a controlled, standardized investigation

LGD-4033 and MK-677 Use Impacts Body Composition, Circulating Biomarkers, and Skeletal Muscle Androgenic Hormone and Receptor Content: A Case Report

LGD-4033, a selective androgen receptor modulator, and MK-677, a growth hormone secretagogue, are being used increasingly amongst recreationally active demographics. However, limited data exist describing their effects on health- and androgen-related biomarkers. The purpose of this case study was to determine changes in body composition and biomarkers during and after continued co-administration of LGD-4033 and MK-677. We also aimed to examine muscular strength and intramuscular androgen-associated biomarkers relative to non-users. A 25-year-old male ingested LGD-4033 (10 mg) and MK-677 (15 mg) daily for 5 weeks. Blood and body composition metrics were obtained pre-, on- and post-cycle. One-repetition maximum leg and bench press, in addition to intramuscular androgens and androgen receptor content, were analysed on-cycle. We observed pre- to on-cycle changes in body composition (body mass, +6.0%; total lean body mass, +3.1%; trunk lean body mass, +6.6%; appendicular lean body mass, +4.3%; total fat mass, +15.4%; trunk fat mass, +2.8%; and appendicular fat mass, +14.8%), bone (bone mineral content, −3.60%; area, −1.1%; and bone mineral density, −2.1%), serum lipid-associated biomarkers (cholesterol, +14.8%; triglycerides, +39.2%; low-density lipoprotein–cholesterol, +40.0%; and high-density lipoprotein–cholesterol, −36.4%), liver-associated biomarkers (aspartate aminotransferase, +95.8%; and alanine aminotransferase, +205.0%) and androgen-associated biomarkers (free testosterone, −85.7%; total testosterone, −62.3%; and sex hormone-binding globulin, −79.6%); however, all variables returned to pre-cycle values post-cycle, apart from total fat mass, appendicular fat mass, bone area, total cholesterol and low-density lipoprotein–cholesterol. Follicle-stimulating hormone was below clinical reference values on- (1.2 IU/L) and post-cycle (1.3 IU/L). Intramuscular androgen receptor (−44.6%), testosterone (+47.8%) and dihydrotestosterone (+34.4%), in addition to one-repetition maximum leg press and bench press (+39.2 and +32.0%, respectively), were different in the case subject compared with non-users. These data demonstrate that LGD-4033 and MK-677 increase several body composition parameters, whilst negatively impacting bone and several serum biomarkers. Given the sparsity of data in recreationally using demographics, further research is warranted to elucidate the acute and chronic physiological effects of these anabolic agents

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Search for anomalous t t-bar production in the highly-boosted all-hadronic final state

A search is presented for a massive particle, generically referred to as a Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are sufficiently massive to produce highly Lorentz-boosted top quarks, which yield collimated decay products that are partially or fully merged into single jets. The analysis uses new methods to analyze jet substructure, providing suppression of the non-top multijet backgrounds. The analysis is based on a data sample of proton-proton collisions at a center-of-mass energy of 7 TeV, corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits in the range of 1 pb are set on the product of the production cross section and branching fraction for a topcolor Z' modeled for several widths, as well as for a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any enhancement in t t-bar production beyond expectations of the standard model for t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version includes a minor typo correction that will be submitted as an erratu