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

Prognostic value of early magnetic resonance imaging in dogs after traumatic brain injury: 50 cases

Retrospective study of dogs with TBI that underwent 1.5T MRI within 14 days after head trauma. MRI evaluators were blinded to the clinical presentation, and all images were scored based on an MRI grading system (Grade I [normal brain parenchyma] to Grade VI [bilateral lesions affecting the brainstem with or without any lesions of lesser grade]). Skull fractures, percentage of intraparenchymal lesions, degree of midline shift, and type of brain herniation were evaluated. MGCS was assessed at presentation. The presence of seizures was recorded. Outcome was assessed at 48 h (alive or dead) and at 3, 6, 12, and 24 months after TBI

Is it pleasure or health from leisure that we benefit from most?:An analysis of well-being alternatives and implications for policy

International policy now constantly advocates a need for populations to engage in more physical activity to promote health and to reduce society’s health care costs. Such policy has developed guidelines on recommended levels and intensity of physical activity and implicitly equates health with well-being. It is assumed that individual, and hence social welfare will be enhanced if the activity guidelines are met. This paper challenges that claim and raises questions for public policy priorities. Using an instrumental variable analysis to value the well-being from active leisure, it is shown that the well-being experienced from active leisure that is not of a recommended intensity to generate health benefits, perhaps due to its social, recreational or fun purpose, has a higher value of well-being than active leisure that does meet the guidelines. This suggests rethinking the motivation and foundation of existing policy and perhaps a realignment of priorities towards activity that has a greater contribution to social welfare through its intrinsic fun and possibly social interaction

Visual search in the real world:Color vision deficiency affects peripheral guidance, but leaves foveal verification largely unaffected

Background: People with color vision deficiencies report numerous limitations in daily life. However, they use basic color terms systematically and in a similar manner as people with people with normal color vision. We hypothesize that a possible explanation for this discrepancy between color perception and behavioral consequences might be found in the gaze behavior of people with color vision deficiency.Methods: A group of participants with color vision deficiencies and a control group performed several search tasks in a naturalistic setting on a lawn.Results: Search performance was similar in both groups in a color-unrelated search task as well as in a search for yellow targets. While searching for red targets, color vision deficient participants exhibited a strongly degraded performance. This was closely matched by the number of fixations on red objects shown by the two groups. Importantly, once they fixated a target, participants with color vision deficiencies exhibited only few identification errors. Conclusions: Participants with color vision deficiencies are not able to enhance their search for red targets on a (green) lawn by an efficient guiding mechanism. The data indicate that the impaired guiding is the main influence on search performance, while foveal identification (verification) largely unaffected

Proceedings of International Science Foundation Brainpower Forum, 1958

Held August 6-8, 1958, U.S. Naval Postgraduate School, Monterey, California[A]t the invitation of Rear Admiral Earl E. Stone, USN, then Superintendent of the U. S. Naval Postgraduate Scrnol, approximately sixty leaders in industry, government, and education met in Monterey, California, October 24-25, 1956, for the first conference of the !SF Brainpower Forum. This conference served to highlight the fact that we had not effectively utilized all sources of scientific manpower which were presently available. At the recommendations of the Forum partici- pants, the International Science Foundation initiated a continuing pro- gram in the area of scientific manpower and suggested that several of its members set up projects which would provide answers to some of the problems considered at the 1956 conference. As a matter of first priority, it was decided to give consideration to the gains that might be realized by giving recognition to and seeking better utilization of retired or senior professional manpower. The 1958 conference was held to give Forum participants an opportunity to report on projects in the area of senior scientific manpower that were conducted as a result of suggestions made at the 1956 conference. Among the NPS participants: Roy S. Glasgow, Dean; Captain H. M. Heming, USN, Director, Engineering School; Frank E. LaCauza, Academic Chairman, General Line and Naval Science School; Captain Paul Foley, Jr., USN, Chief of Staff; Dr. Austin R. Frey, Chairman, Department of Physics; Mitchell L. Cotton, Assistant Professor of Engineering ElectronicsThe following members of the International Science Foundation have served as the sponsors of this 1958 Conference of the Brainpower Forum: Stauffer Chemical Company, General Electric Company, U. S. Army Ordnance Missile Command. U. S. Naval Postgraduate School, Cooperative Research Institute, The Firestone Tire & Rubber Company, Federal Pacific Electric Company, Rheem Manufacturing Company, Northrop Aircraft, Inc., Standard Oil Company of California, Varian Associates, Ford Motor Company, Tidewater Oil Compan

Public Good Provision Mechanisms and Reciprocity

This paper determines optimal public good provision mechanisms in an environment where agents are motivated by reciprocity. In a two-agent economy, we show that the standard pivot mechanism is not strategy-proof if at least one agent cares strongly enough about reciprocity. Truthful reporting maximises a player's own payoff and hence is viewed as selfish by his opponent, who retaliates by understating demand for the public good. Incentive compatibility is restored if the mechanism is implemented sequentially. When agents are asked to report their demands in turn, a high report by the first mover (he) may result in him paying an unfairly large share of the provision cost, should the second mover (she) understate her demand. Hence, truthful reporting is not judged as selfish by the second mover, who reciprocates by stating her true demand. Our results alert the institutional designer to the importance of game dynamics when agents are non-selfish