Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.

Glucocorticoids promote lipolysis in white adipose tissue (WAT) to adapt to energy demands under stress, whereas superfluous lipolysis causes metabolic disorders, including dyslipidemia and hepatic steatosis. Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone-sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). We previously identified Pik3r1 (also called p85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specific Pik3r1-null (AKO) mice. Furthermore, in lipid droplets, the phosphorylation of HSL and Plin1 and the levels of catalytic and regulatory subunits of PKA were increased by glucocorticoids in wild-type mice. However, these effects were attenuated in AKO mice. In agreement with reduced WAT lipolysis, glucocorticoid- initiated hepatic steatosis and hypertriglyceridemia were improved in AKO mice. Our data demonstrated a novel role of Pik3r1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids. Thus, the inhibition of Pik3r1 in adipocytes could alleviate lipid disorders caused by excess glucocorticoid exposure

The Abelian Manna model on two fractal lattices

We analyze the avalanche size distribution of the Abelian Manna model on two different fractal lattices with the same dimension d_g=ln(3)/ln(2), with the aim to probe for scaling behavior and to study the systematic dependence of the critical exponents on the dimension and structure of the lattices. We show that the scaling law D(2-tau)=d_w generalizes the corresponding scaling law on regular lattices, in particular hypercubes, where d_w=2. Furthermore, we observe that the lattice dimension d_g, the fractal dimension of the random walk on the lattice d_w, and the critical exponent D, form a plane in 3D parameter space, i.e. they obey the linear relationship D=0.632(3) d_g + 0.98(1) d_w - 0.49(3).Comment: 4 pages, 3 figures, 3 tables, submitted to PRE as a Brief Repor

Damage assessment of concrete gravity dams using vibration characteristics

Vibration-based Structural Health Monitoring (VBSHM) has emerged as a feasible technique in long-term monitoring, structural performance evaluation and damage assessment of civil structures. As an important as-pect of the complete VBSHM system, over the last three decades, many vibration-based damage detection methods have been developed for buildings and bridges. However, the application of these techniques to con-crete gravity (CG) dams has been limited. In the present study, damage indices based on changes in modal flexibility and modal strain energy are suitably enhanced to be applicable for plane-strain structures. They are then used to investigate the feasibility of detecting and locating damage in a finite element CG dam model without noise effects. Results show that the enhanced damage indices can be promising for locating damage in the upstream part of CG dams by using only the first lateral mode of vibration. In addition, it is necessary to monitor both horizontal and vertical mode shape components and use these for structural damage diagnoses in CG dams

Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti.

The insect bacterium Wolbachia pipientis is being introgressed into Aedes aegypti populations as an intervention against the transmission of medically important arboviruses. Here we compare Ae. aegypti mosquitoes infected with wMelCS or wAlbB to the widely used wMel Wolbachia strain on an Australian nuclear genetic background for their susceptibility to infection by dengue virus (DENV) genotypes spanning all four serotypes. All Wolbachia-infected mosquitoes were more resistant to intrathoracic DENV challenge than their wildtype counterparts. Blocking of DENV replication was greatest by wMelCS. Conversely, wAlbB-infected mosquitoes were more susceptible to whole body infection than wMel and wMelCS. We extended these findings via mosquito oral feeding experiments, using viremic blood from 36 acute, hospitalised dengue cases in Vietnam, additionally including wMel and wildtype mosquitoes on a Vietnamese nuclear genetic background. As above, wAlbB was less effective at blocking DENV replication in the abdomen compared to wMel and wMelCS. The transmission potential of all Wolbachia-infected mosquito lines (measured by the presence/absence of infectious DENV in mosquito saliva) after 14 days, was significantly reduced compared to their wildtype counterparts, and lowest for wMelCS and wAlbB. These data support the use of wAlbB and wMelCS strains for introgression field trials and the biocontrol of DENV transmission. Furthermore, despite observing significant differences in transmission potential between wildtype mosquitoes from Australia and Vietnam, no difference was observed between wMel-infected mosquitoes from each background suggesting that Wolbachia may override any underlying variation in DENV transmission potential

Diagnostic Performances of an Occupational Burnout Detection Method Designed for Healthcare Professionals.

We aimed to assess the validity (criterion and cross-cultural validity) and reliability of the first occupational burnout (OB) detection tool designed for healthcare professionals in Belgium in the context of Swiss medical practice. First, we assessed the sensitivity and specificity of the Tool. We developed this tool based on the consultation reports of 42 patients and compared its detection to the results of the Oldenburg Burnout Inventory (OLBI), filled-in by patients before a consultation. Second, we performed an inter-rater reliability (IRR) assessment on the OB symptoms and detection reached by the Tool between a psychiatrist, two psychologists, and an occupational physician. The Tool correctly identified over 80% of patients with OB, regardless of the cutoff value used for OLBI scores, reflecting its high sensitivity. Conversely, its specificity strongly varied depending on the OLBI cutoff. There was a slight to fair overall agreement between the four raters on the detection of OB and the number of OB symptoms. Around 41% of symptoms showed a substantial to an almost perfect agreement, and 36% showed a slight to a moderate agreement. The Tool seems useful for identifying OB of moderate and strong severity in both the Belgian and Swiss contexts

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were assessed in ∼456,000 individuals from the UK Biobank. Of the 53 lipid-loci that showed evidence of association (P \u3c 1 × 10−3), 43 loci were associated with at least one lipid endophenotype. These findings illustrate the value of integrative biology to investigate the aetiology of atherosclerosis and CAD, with implications for other complex diseases

Novel biogenic silver and gold nanoparticles for multifunctional applications: Green synthesis, catalytic and antibacterial activity, and colorimetric detection of Fe(III) ions

In this study, novel biogenic silver (AgNPs) and gold nanoparticles (AuNPs) were developed using a green approach with Ganoderma lucidum (GL) extract. The optimization of synthesis conditions for the best outcomes was conducted. The prepared materials were characterized and their applicability in catalysis, antibacterial and chemical sensing was comprehensively evaluated. The GL-AgNPs crystals were formed in a spherical shape with an average diameter of 50 nm, while GL-AuNPs exhibited multi-shaped structures with sizes ranging from 15 to 40 n

Causes and consequences of tipping points in river delta social-ecological systems

The sustainability of social-ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative” or “positive” tipping points depending on actors’ perspectives, e.g., regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological and land use management of the world’s river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social-ecological systems on a pathway towards sustainable development

A Two-Step Certified Reduced Basis Method

In this paper we introduce a two-step Certified Reduced Basis (RB) method. In the first step we construct from an expensive finite element “truth” discretization of dimension N an intermediate RB model of dimension N≪N . In the second step we construct from this intermediate RB model a derived RB (DRB) model of dimension M≤N. The construction of the DRB model is effected at cost O(N) and in particular at cost independent of N ; subsequent evaluation of the DRB model may then be effected at cost O(M) . The DRB model comprises both the DRB output and a rigorous a posteriori error bound for the error in the DRB output with respect to the truth discretization. The new approach is of particular interest in two contexts: focus calculations and hp-RB approximations. In the former the new approach serves to reduce online cost, M≪N: the DRB model is restricted to a slice or subregion of a larger parameter domain associated with the intermediate RB model. In the latter the new approach enlarges the class of problems amenable to hp-RB treatment by a significant reduction in offline (precomputation) cost: in the development of the hp parameter domain partition and associated “local” (now derived) RB models the finite element truth is replaced by the intermediate RB model. We present numerical results to illustrate the new approach.United States. Air Force Office of Scientific Research (AFOSR Grant number FA9550-07-1-0425)United States. Department of Defense. Office of the Secretary of Defense (OSD/AFOSR Grant number FA9550-09-1-0613)Norwegian University of Science and Technolog

Quantifying mangrove leaf area index from Sentinel-2 imagery using hybrid models and active learning

Environmental Biolog