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

Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation

The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. m

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

The Duodenum harbors a Broad Untapped Therapeutic Potential

The gastroenterologist, when performing an esophagogastroduodenoscopy, is the only medical care provider with easy access to the duodenum (Figure 1A). This simple fact is pivotal in this article that discusses why the duodenum has become such an important anatomic region of interest. Recent insights have revealed the critical physiologic and pathophysiologic role of the small bowel in metabolic homeostasis and its potential role as a driver of obesity, insulin resistance, and subsequent type 2 diabetes mellitus (T2DM). Although the other parts of the small bowel cannot be ignored when describing the potential mechanisms involved in the development of metabolic diseases and T2DM, the excellent endoscopic accessibility of the duodenum makes it a prime target for disease-modifying intervention

Development of a real-time algorithm for detection of the divertor detachment radiation front using multi-spectral imaging

In this paper we present a novel algorithm to extract the optical plasma boundary and radiation front for detached divertor plasmas. We show that reliable detection of the divertor leg and radiation front is possible using lightweight image processing tools. Using a non-tomographic approach, the detected divertor leg and radiation front can be mapped to the poloidal plane. This approach is fast and accurate enough for real-time control purposes, allowing in particular real-time plasma shape and detachment control, and post-shot detachment physics and dynamics analysis.</p

A Possible Detection of Occultation by a Proto-planetary Clump in GM Cephei

GM Cep in the young (~4 Myr) open cluster Trumpler 37 has been known to be an abrupt variable and to have a circumstellar disk with very active accretion. Our monitoring observations in 2009-2011 revealed the star to show sporadic flare events, each with brightening of < 0.5 mag lasting for days. These brightening events, associated with a color change toward the blue, should originate from an increased accretion activity. Moreover, the star also underwent a brightness drop of ~1 mag lasting for about a month, during which the star became bluer when fainter. Such brightness drops seem to have a recurrence time scale of a year, as evidenced in our data and the photometric behavior of GM Cep over a century. Between consecutive drops, the star brightened gradually by about 1 mag and became blue at peak luminosity. We propose that the drop is caused by obscuration of the central star by an orbiting dust concentration. The UX Orionis type of activity in GM Cep therefore exemplifies the disk inhomogeneity process in transition between grain coagulation and planetesimal formation in a young circumstellar disk.Comment: In submission to the Astrophysical Journal, 4 figure