Loss of Regulator of G Protein Signaling 5 Exacerbates Obesity, Hepatic Steatosis, Inflammation and Insulin Resistance

BACKGROUND: The effect of regulator of G protein signaling 5 (RGS5) on cardiac hypertrophy, atherosclerosis and angiogenesis has been well demonstrated, but the role in the development of obesity and insulin resistance remains completely unknown. We determined the effect of RGS5 deficiency on obesity, hepatic steatosis, inflammation and insulin resistance in mice fed either a normal-chow diet (NC) or a high-fat diet (HF). METHODOLOGY/PRINCIPAL FINDINGS: Male, 8-week-old RGS5 knockout (KO) and littermate control mice were fed an NC or an HF for 24 weeks and were phenotyped accordingly. RGS5 KO mice exhibited increased obesity, fat mass and ectopic lipid deposition in the liver compared with littermate control mice, regardless of diet. When fed an HF, RGS5 KO mice had a markedly exacerbated metabolic dysfunction and inflammatory state in the blood serum. Meanwhile, macrophage recruitment and inflammation were increased and these increases were associated with the significant activation of JNK, IκBα and NF-κBp65 in the adipose tissue, liver and skeletal muscle of RGS5 KO mice fed an HF relative to control mice. These exacerbated metabolic dysfunction and inflammation are accompanied with decreased systemic insulin sensitivity in the adipose tissue, liver and skeletal muscle of RGS5 KO mice, reflected by weakened Akt/GSK3β phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that loss of RGS5 exacerbates HF-induced obesity, hepatic steatosis, inflammation and insulin resistance

The Influence of Social Comparison on Visual Representation of One's Face

Can the effects of social comparison extend beyond explicit evaluation to visual self-representation—a perceptual stimulus that is objectively verifiable, unambiguous, and frequently updated? We morphed images of participants' faces with attractive and unattractive references. With access to a mirror, participants selected the morphed image they perceived as depicting their face. Participants who engaged in upward comparison with relevant attractive targets selected a less attractive morph compared to participants exposed to control images (Study 1). After downward comparison with relevant unattractive targets compared to control images, participants selected a more attractive morph (Study 2). Biased representations were not the products of cognitive accessibility of beauty constructs; comparisons did not influence representations of strangers' faces (Study 3). We discuss implications for vision, social comparison, and body image

Cell Walls of Saccharomyces cerevisiae Differentially Modulated Innate Immunity and Glucose Metabolism during Late Systemic Inflammation

BACKGROUND: Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS) from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. METHODS AND PRINCIPAL FINDINGS: Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic) on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK) and liver glycolysis (ENO2), and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS) down-regulation and ATP citrate lyase (ACLY) and malic enzyme (ME) up-regulations. However, MOS host's lower energy demands were sufficiently met through TCA citrate-derived energy, as indicated by CS up-regulation. CONCLUSIONS: MOS terminated inflammation earlier than VIRG and reduced glucose mobilization, thus representing a novel biological strategy to alleviate Salmonella-induced systemic inflammation in human and animal hosts

Food additives and children's behaviour: evidence‐based policy at the margins of certainty

The possible effects of food additives (specifically artificial colours) have been debated for over 30 years. The evidence accumulated suggests that for some children with attention deficit hyperactivity disorder (ADHD) food colours exacerbate their condition. Two studies undertaken by a research group at the University of Southampton have extended these findings to the effects on hyperactivity in children from the general population who do not show ADHD. This article reviews the response from policy-makers to these findings and concludes that the failure to impose a mandatory ban on the six food colours in the Southampton study is inadequate and that such a ban would be an appropriate application of the precautionary principle when the evidence is considered to be at the margins of certaint

A validated agent-based model to study the spatial and temporal heterogeneities of malaria incidence in the rainforest environment

BACKGROUND: The Amazon environment has been exposed in the last decades to radical changes that have been accompanied by a remarkable rise of both Plasmodium falciparum and Plasmodium vivax malaria. The malaria transmission process is highly influenced by factors such as spatial and temporal heterogeneities of the environment and individual-based characteristics of mosquitoes and humans populations. All these determinant factors can be simulated effectively trough agent-based models. METHODS: This paper presents a validated agent-based model of local-scale malaria transmission. The model reproduces the environment of a typical riverine village in the northern Peruvian Amazon, where the malaria transmission is highly seasonal and apparently associated with flooding of large areas caused by the neighbouring river. Agents representing humans, mosquitoes and the two species of Plasmodium (P.falciparum and P. vivax) are simulated in a spatially explicit representation of the environment around the village. The model environment includes: climate, people houses positions and elevation. A representation of changes in the mosquito breeding areas extension caused by the river flooding is also included in the simulation environment. RESULTS: A calibration process was carried out to reproduce the variations of the malaria monthly incidence over a period of 3 years. The calibrated model is also able to reproduce the spatial heterogeneities of local scale malaria transmission. A “what if” eradication strategy scenario is proposed: if the mosquito breeding sites are eliminated through mosquito larva habitat management in a buffer area extended at least 200 m around the village, the malaria transmission is eradicated from the village. CONCLUSIONS: The use of agent-based models can reproduce effectively the spatiotemporal variations of the malaria transmission in a low endemicity environment dominated by river floodings like in the Amazon

WSES Guidelines for the management of acute left sided colonic diverticulitis in the emergency setting

Acute left sided colonic diverticulitis is one of the most common clinical conditions encountered by surgeons in acute setting. A World Society of Emergency Surgery (WSES) Consensus Conference on acute diverticulitis was held during the 3rd World Congress of the WSES in Jerusalem, Israel, on July 7th, 2015. During this consensus conference the guidelines for the management of acute left sided colonic diverticulitis in the emergency setting were presented and discussed. This document represents the executive summary of the final guidelines approved by the consensus conference.Peer reviewe

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning