Normal Ribosomal Biogenesis but Shortened Protein Synthetic Response to Acute Eccentric Resistance Exercise in Old Skeletal Muscle.

Anabolic resistance to feeding in aged muscle is well-characterized; however, whether old skeletal muscle is intrinsically resistant to acute mechanical loading is less clear. The aim of this study was to determine the impact of aging on muscle protein synthesis (MPS), ribosome biogenesis, and protein breakdown in skeletal muscle following a single bout of resistance exercise. Adult male F344/BN rats aged 10 (Adult) and 30 (Old) months underwent unilateral maximal eccentric contractions of the hindlimb. Precursor rRNA increased early post-exercise (6-18 h), preceding elevations in ribosomal mass at 48 h in Adult and Old; there were no age-related differences in these responses. MPS increased early post-exercise in both Adult and Old; however, at 48 h of recovery, MPS returned to baseline in Old but not Adult. This abbreviated protein synthesis response in Old was associated with decreased levels of IRS1 protein and increased BiP, CHOP and eIF2α levels. Other than these responses, anabolic signaling was similar in Adult and Old muscle in the acute recovery phase. Basal proteasome activity was lower in Old, and resistance exercise did not increase the activity of either the ATP-dependent or independent proteasome, or autophagy (Cathepsin L activity) in either Adult or Old muscle. We conclude that MPS and ribosome biogenesis in response to maximal resistance exercise in old skeletal muscle are initially intact; however, the MPS response is abbreviated in Old, which may be the result of ER stress and/or blunted exercise-induced potentiation of the MPS response to feeding

Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis.

Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength

Effects of No-Tillage Production Practices on Crop Yields as Influenced by Crop and Growing Environment Factors

This paper evaluated differences between yields of no-tillage compared to conventional or reduced tillage and their associated downside risk. Six crops were evaluated along with how those yields and risks differed by various environmental factors such geographic location, precipitation, soil type and how long the practice had been used.no-tillage, conservation, conventional tillage, downside-risk, yield, Agribusiness, Environmental Economics and Policy, Farm Management, Land Economics/Use, Production Economics, Risk and Uncertainty,

Cardiovascular and neuropsychiatric risks of varenicline and bupropion in smokers with chronic obstructive pulmonary disease

BACKGROUND: Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD. OBJECTIVE: To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD. METHODS: In a retrospective cohort study, we used data from 14 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6 months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders. RESULTS: Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely. CONCLUSION: In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT

The Formation of Kiloparsec-scale HI Holes in Dwarf Galaxies

The origin of kpc-scale holes in the atomic hydrogen (H i) distributions of some nearby dwarf irregular galaxies presents an intriguing problem. Star formation histories (SFHs) derived from resolved stars give us the unique opportunity to study past star-forming events that may have helped shape the currently visible Hi distribution. Our sample of five nearby dwarf irregular galaxies spans over an order of magnitude in both total Hi mass and absolute B-band magnitude and is at the low-mass end of previously studied systems. We use Very Large Array Hi line data to estimate the energy required to create the centrally dominant hole in each galaxy. We compare this energy estimate to the past energy released by the underlying stellar populations computed from SFHs derived from data taken with the Hubble Space Telescope. The inferred integrated stellar energy released within the characteristic ages exceeds our energy estimates for creating the holes in all cases, assuming expected efficiencies. Therefore, it appears that stellar feedback provides sufficient energy to produce the observed holes. However, we find no obvious signature of single star-forming events responsible for the observed structures when comparing the global SFHs of each galaxy in our sample to each other or to those of dwarf irregular galaxies reported in the literature. We also fail to find evidence of a central star cluster in FUV or Hα imaging. We conclude that large Hi holes are likely formed from multiple generations of star formation and only under suitable interstellar medium conditions

Results of ASERTAA, a randomized prospective crossover pharmacogenetic study of immediate-release versus extended-release tacrolimus in African American kidney transplant recipients

BACKGROUND: Differences in tacrolimus dosing across ancestries is partly attributable to polymorphisms in CYP3A5 genes that encode tacrolimus-metabolizing cytochrome P450 3A5 enzymes. The CYP3A5*1 allele, preponderant in African Americans, is associated with rapid metabolism, subtherapeutic concentrations, and higher dose requirements for tacrolimus, all contributing to worse outcomes. Little is known about the relationship between CYP3A5 genotype and the tacrolimus pharmacokinetic area under the curve (AUC) profile in African Americans or whether pharmacogenetic differences exist between conventional twice-daily, rapidly absorbed, immediate-release tacrolimus (IR-Tac) and once-daily extended-release tacrolimus (LifeCycle Pharma Tac [LCPT]) with a delayed absorption profile. STUDY DESIGN: Randomized prospective crossover study. SETTING & PARTICIPANTS: 50 African American maintenance kidney recipients on stable IR-Tac dosing. INTERVENTION: Recipients were randomly assigned to continue IR-Tac on days 1 to 7 and then switch to LCPT on day 8 or receive LCPT on days 1 to 7 and then switch to IR-Tac on day 8. The LCPT dose was 85% of the IR-Tac total daily dose. OUTCOMES: Tacrolimus 24-hour AUC (AUC MEASUREMENTS: CYP3A5 genotype, 24-hour tacrolimus pharmacokinetic profiles. RESULTS: ∼80% of participants carried the CYP3A5*1 allele (CYP3A5 expressers). There were no significant differences in AUC LIMITATIONS: This was primarily a pharmacogenetic study rather than an efficacy study; the follow-up period was too short to capture clinical outcomes. CONCLUSIONS: Achieving therapeutic tacrolimus trough concentrations with IR-Tac in most African Americans results in significantly higher peak concentrations, potentially magnifying the risk for toxicity and adverse outcomes. This pharmacogenetic effect is attenuated by delayed tacrolimus absorption with LCPT. TRIAL REGISTRATION: Registered at ClinicalTrials.gov, with study number NCT01962922

Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI).

Purpose: The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. Methods: Nineteen adolescents (mean age 14.7 years) who experienced mTBI 3–12 months previously (mean 7.5 months) and 19 matched healthy controls (mean age 14.0 years) completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. Results: No between-group differences were found for cognition, behavior, or N-back task performance, though the expected decreased accuracy and increased reaction time as task difficulty increased were apparent. However, the mTBI group showed significantly greater brain activation than controls during the most difficult working memory task condition. Conclusion: Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of natural recovery, which could have important clinical implications

The XMM Cluster Survey: a massive galaxy cluster at z = 1.45

We report the discovery of XMMXCS J2215.9-1738, a massive galaxy cluster at z=1.45, which was found in the XMM Cluster Survey. The cluster candidate was initially identified as an extended X-ray source in archival XMM data. Optical spectroscopy shows that six galaxies within a ~60" diameter region lie at z=1.45+/-0.01. Model fits to the X-ray spectra of the extended emission yield kT=7.4+2.7-1.8 keV (90% confidence); if there is an undetected central X-ray point source, then kT=6.5+2.6-1.8 keV. The bolometric X-ray luminosity is LX=4.4+0.8-0.6C 1044 ergs s-1 over a 2 Mpc radial region. The measured TX, which is the highest for any known cluster at z>1, suggests that this cluster is relatively massive for such a high redshift. The redshift of XMMXCS J2215.9-1738 is the highest currently known for a spectroscopically confirmed cluster of galaxies

Development of a Low-Resource Combined Gamma-Ray and Neutron Spectrometer for Planetary Science

Planetary neutron and gamma-ray spectroscopy (NGRS) has become a standard technique to measure distinctive geochemical composition and volatile abundance signatures for key elements relevant to planetary structure and evolution. Previous NGRS measurements have led to the discovery of the concentration of many elements including hydrogen on the Moon, Mars, Mercury, and the asteroids Eros, Vesta, and Ceres, but by utilizing separate NGRS. We have developed the Elpasolite Planetary Ice and Composition Spectrometer (EPICS) instrument, an innovative and combined NGRS with low resource requirements. EPICS incorporates elpasolite scintillator read out by silicon photomultipliers (SiPMs) to provide significant reduction in size, weight, and power, while achieving excellent neutron detection sensitivity and gamma-ray energy resolution as good as 2.9% full-width half-maximum at 662 keV. EPICS is ideally suited to resource constrained missions and is applicable to numerous targets such as the Moon, Mars, and small planetary bodies. An overview of the EPICS instrument and its simulated performance on a few notional missions is presented. We have integrated and done performance testing of a prototype of the EPICS instrument, including optimization of an amplification and summing circuit for a 64-element SiPM array that preserves pulse shape discrimination capability, which will be summarized