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

A Numerical Model for Brownian Particles Fluctuating in Incompressible Fluids

We present a numerical method that consistently implements thermal fluctuations and hydrodynamic interactions to the motion of Brownian particles dispersed in incompressible host fluids. In this method, the thermal fluctuations are introduced as random forces acting on the Brownian particles. The hydrodynamic interactions are introduced by directly resolving the fluid motions with the particle motion as a boundary condition to be satisfied. The validity of the method has been examined carefully by comparing the present numerical results with the fluctuation-dissipation theorem whose analytical form is known for dispersions of a single spherical particle. Simulations are then performed for more complicated systems, such as a dispersion composed of many spherical particles and a single polymeric chain in a solvent.Comment: 6 pages, 8 figure

On the Equipollence of Lx ̳and Lxr̳̳

In this paper the deductive systems Lx and Lxr from [Tarski, Givant (1987)] are shown to be equipollent. Following [Tarski, Givant (1987)], a third deductive system, Lxs , is defined. It is then noted that Lxs is an extension of both Lx and Lxr , thus showing that Lx and Lxr are no stronger than Lxs . Finally two Translation Mappings from G : Lxs → Lx and H : Lxs → Lxr are defined. These mappings show that Lxs is no stronger than either Lx or Lxr . Therefore we conclude that, as they are both equipollent to a relative extension, Lx and Lxr are equipollent

Simulating (electro)hydrodynamic effects in colloidal dispersions: smoothed profile method

Previously, we have proposed a direct simulation scheme for colloidal dispersions in a Newtonian solvent [Phys.Rev.E 71,036707 (2005)]. An improved formulation called the ``Smoothed Profile (SP) method'' is presented here in which simultaneous time-marching is used for the host fluid and colloids. The SP method is a direct numerical simulation of particulate flows and provides a coupling scheme between the continuum fluid dynamics and rigid-body dynamics through utilization of a smoothed profile for the colloidal particles. Moreover, the improved formulation includes an extension to incorporate multi-component fluids, allowing systems such as charged colloids in electrolyte solutions to be studied. The dynamics of the colloidal dispersions are solved with the same computational cost as required for solving non-particulate flows. Numerical results which assess the hydrodynamic interactions of colloidal dispersions are presented to validate the SP method. The SP method is not restricted to particular constitutive models of the host fluids and can hence be applied to colloidal dispersions in complex fluids

The MOSDEF Survey: The Metallicity Dependence of X-Ray Binary Populations at z ∼ 2

Population synthesis models predict that high-mass X-ray binary (HMXB) populations produced in low-metallicity environments should be more X-ray luminous, a trend supported by studies of nearby galaxies. This trend may be responsible for the observed increase of the X-ray luminosity (L X) per star formation rate (SFR) with redshift due to the decrease of metallicity (Z) at fixed stellar mass as a function of redshift. To test this hypothesis, we use a sample of 79 z ∼ 2 star-forming galaxies with oxygen abundance measurements from the MOSDEF survey, which obtained rest-frame optical spectra for ∼1500 galaxies in the CANDELS fields at 1.37 < z < 3.80. Using Chandra data from the Chandra AEGIS-X Deep, Chandra Deep Field North, and Chandra Deep Field South surveys, we stack the X-ray data at the galaxy locations in bins of redshift and Z because the galaxies are too faint to be individually detected. In agreement with previous studies, the average L X/SFR of our z ∼ 2 galaxy sample is enhanced by ≈0.4-0.8 dex relative to local HMXB L X-SFR scaling relations. Splitting our sample by Z, we find that L X/SFR and Z are anticorrelated with 97% confidence. This observed Z dependence for HMXB-dominated galaxies is consistent with both the local L X-SFR-Z relation and a subset of population synthesis models. Although the statistical significance of the observed trends is weak owing to the low X-ray statistics, these results constitute the first direct evidence connecting the redshift evolution of L X/SFR and the Z dependence of HMXBs

Religious Styles Predict Interreligious Prejudice: A Study of German Adolescents with the Religious Schema Scale

Streib H, Klein C. Religious Styles Predict Interreligious Prejudice: A Study of German Adolescents with the Religious Schema Scale. International Journal for the Psychology of Religion. 2014;24(2):151-163.Based on a sample of 340 German adolescents age 12 to 25, this article presents an analysis of the effects of religion on two instances of interreligious prejudice: anti-Islamic and anti-Semitic prejudice. Reflecting the emergent interest in implementing a perspective of religious maturity and religious development into research on religion and prejudice, the present study has included the Religious Schema Scale (RSS) which, with its three subscales, Truth of Texts & Teachings (ttt), Fairness, Tolerance & Rational Choice (ftr), and Xenosophia/Interreligious Dialog (xenos), differentiates religious styles. Regression analyses indicate the superior explanatory power of the RSS in comparison to other measures of religiosity. The RSS subscale ttt relates to and predicts anti-Islamic and anti-Semitic prejudice, whereas ftr and xenos relate to and predict disagreement with interreligious prejudice. Results of an analysis of variance using high agreement on ttt, ftr, and xenos for group construction indicate a decrease in interreligious prejudice in relation to religious development

Non-Optic Glioma-like Lesions in Adult Neurofibromatosis Type 1 Patients

Background/Objectives: Physicians face clinical dilemmas in the diagnosis of non-optic intraparenchymal lesions on MRI brain scans of patients with neurofibromatosis type 1. As the incidence and evolution of these lesions into adulthood remain unclear, we conducted a retrospective study on this topic. Methods: All adult neurofibromatosis type 1 patients who had at least one MRI brain scan in our center were selected for this study. Brain lesions with contrast enhancement after gadolinium administration and/or mass effect were named “glioma-like lesions”. Results: In our cohort of 396 adult neurofibromatosis type 1 patients, 182 had at least one MRI scan of the brain. A total of 48 glioma-like lesions were found in 38/182 patients. The majority of glioma-like lesions remained stable, decreased in size or even disappeared during a median follow-up time of 8.5 years. Twelve glioma-like lesions in 11/182 patients were resected or biopsied, and histology showed gliomas of astrocytic origin (WHO grade 1–4).Conclusions: It was concluded from these data that asymptomatic glioma-like lesions on MRI brain scans in neurofibromatosis type 1 patients, either with contrast enhancement and/or mass effect, had an indolent nature. Mildly symptomatic or asymptomatic patients can therefore be followed without invasive diagnostic and therapeutic procedures.</p

Social disparities in food preparation behaviours: a DEDIPAC study

BACKGROUND: The specific role of major socio-economic indicators in influencing food preparation behaviours could reveal distinct socio-economic patterns, thus enabling mechanisms to be understood that contribute to social inequalities in health. This study investigated whether there was an independent association of each socio-economic indicator (education, occupation, income) with food preparation behaviours. METHODS: A total of 62,373 adults participating in the web-based NutriNet-Santé cohort study were included in our cross-sectional analyses. Cooking skills, preparation from scratch and kitchen equipment were assessed using a 0-10-point score; frequency of meal preparation, enjoyment of cooking and willingness to cook better/more frequently were categorical variables. Independent associations between socio-economic factors (education, income and occupation) and food preparation behaviours were assessed using analysis of covariance and logistic regression models stratified by sex. The models simultaneously included the three socio-economic indicators, adjusting for age, household composition and whether or not they were the main cook in the household. RESULTS: Participants with the lowest education, the lowest income group and female manual and office workers spent more time preparing food daily than participants with the highest education, those with the highest income and managerial staff (P < 0.0001). The lowest educated individuals were more likely to be non-cooks than those with the highest education level (Women: OR = 3.36 (1.69;6.69); Men: OR = 1.83 (1.07;3.16)) while female manual and office workers and the never-employed were less likely to be non-cooks (OR = 0.52 (0.28;0.97); OR = 0.30 (0.11;0.77)). Female manual and office workers had lower scores of preparation from scratch and were less likely to want to cook more frequently than managerial staff (P < 0.001 and P < 0.001). Women belonging to the lowest income group had a lower score of kitchen equipment (P < 0.0001) and were less likely to enjoy cooking meal daily (OR = 0.68 (0.45;0.86)) than those with the highest income. CONCLUSION: Lowest socio-economic groups, particularly women, spend more time preparing food than high socioeconomic groups. However, female manual and office workers used less raw or fresh ingredients to prepare meals than managerial staff. In the unfavourable context in France with reduced time spent preparing meals over last decades, our findings showed socioeconomic disparities in food preparation behaviours in women, whereas few differences were observed in men

Use of Flash Glucose-Sensing Technology for 12 months as a Replacement for Blood Glucose Monitoring in Insulin-treated Type 2 Diabetes

Introduction: Published evaluations of sensor glucose monitoring use in insulin treated type 2 diabetes are limited. The aim of this study was to assess the impact of flash glucose-sensing technology as a replacement for self-monitoring of blood glucose (SMBG) over a 12-month period in participants with type 2 diabetes who were on intensive insulin therapy. Methods: An open-label, randomized, controlled study in adults with type 2 diabetes on intensive insulin therapy from 26 European diabetes centers aimed at assessing flash glucose sensing technology was conducted. Participants (N = 224) were randomized (1:2 respectively) to a control group (n = 75) that used SMBG (FreeStyle Lite™) or to an intervention group (n = 149) which used sensor glucose data (FreeStyle Libre™ Flash Glucose Monitoring System) for self-management over 6 months. All intervention group participants who completed the 6-month treatment phase continued into an additional 6-month open-access phase. Results: A total of 139 intervention participants completed the 6-month treatment phase and continued into the open-access phase. At 12 months (end of open-access period), time in hypoglycemia [sensor glucose <3.9 mmol/L (70 mg/dL)] was reduced by 50% compared to baseline [−0.70 ± 1.85/24 h (mean ± standard deviation); p = 0.0002]. Nocturnal hypoglycemia [2300 to 0600 hours, <3.9 mmol/L (70 mg/dL)] was reduced by 52%; p = 0.0002. There was no change in time in range [sensor glucose 3.9–10.0 mmol/L (70–180 mg/dL)]. SMBG testing fell from a mean of 3.9 (median 3.9) times/day at baseline to 0.2 (0.0), with an average frequency of sensor scanning of 7.1 (5.7) times/day at 12 months, and mean sensor utilization was 83.6 ± 13.8% (median 88.3%) during the open-access phase. During this 6-month extension period no device-related serious adverse events were reported. Nine participants reported 16 instances of device-related adverse events (e.g. infection, allergy) and 28 participants (20.1%) experienced 134 occurrences of anticipated skin symptoms/sensor-insertion events expected with device use (e.g. erythema, itching and rash). Conclusion: The use of flash glucose-sensing technology for glycemic management in individuals with type 2 diabetes treated by intensive insulin therapy over 12 months was associated with a sustained reduction in hypoglycemia and safely and effectively replaced SMBG. Trial Registration: ClinicalTrials.gov identifier, NCT02082184

Sec17 Can Trigger Fusion of Trans-SNARE Paired Membranes without Sec18

Sec17 [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein; α-SNAP] and Sec18 (NSF) perform ATP-dependent disassembly of cis-SNARE complexes, liberating SNAREs for subsequent assembly of trans-complexes for fusion. A mutant of Sec17, with limited ability to stimulate Sec18, still strongly enhanced fusion when ample Sec18 was supplied, suggesting that Sec17 has additional functions. We used fusion reactions where the four SNAREs were initially separate, thus requiring no disassembly by Sec18. With proteoliposomes bearing asymmetrically disposed SNAREs, tethering and trans-SNARE pairing allowed slow fusion. Addition of Sec17 did not affect the levels of trans-SNARE complex but triggered sudden fusion of trans-SNARE paired proteoliposomes. Sec18 did not substitute for Sec17 in triggering fusion, but ADP- or ATPγS-bound Sec18 enhanced this Sec17 function. The extent of the Sec17 effect varied with the lipid headgroup and fatty acyl composition of the proteoliposomes. Two mutants further distinguished the two Sec17 functions: Sec17(L291A,L292A) did not stimulate Sec18 to disassemble cis-SNARE complex but triggered the fusion of trans-SNARE paired membranes. Sec17(F21S,M22S), with diminished apolar character to its hydrophobic loop, fully supported Sec18-mediated SNARE complex disassembly but had lost the capacity to stimulate the fusion of trans-SNARE paired membranes. To model the interactions of SNARE-bound Sec17 with membranes, we show that Sec17, but not Sec17(F21S,M22S), interacted synergistically with the soluble SNARE domains to enable their stable association with liposomes. We propose a model in which Sec17 binds to trans-SNARE complexes, oligomerizes, and inserts apolar loops into the apposed membranes, locally disturbing the lipid bilayer and thereby lowering the energy barrier for fusion