Role of exercise intensity on GLUT4 content,aerobic fitness and fasting plasma glucose in type 2 diabetic mice

Type 2 diabetes mellitus (T2D) results in several metabolic and cardiovascular dysfunctions, clinically characterized by hyperglycaemia due to lower glucose uptake and oxidation. Physical exercise is an effective intervention for glycaemic control. However, the effects of exercising at different intensities have not yet been addressed. The present study analysed the effects of 8 weeks of training performed at different exercise intensities on type 4 glucose transporters (GLUT4) content and glycaemic control of T2D (ob/ob) and non‐diabetic mice (ob/OB). The animals were divided into six groups, with four groups being subjected either to low‐intensity (ob/obL and ob/OBL: 3% body weight, three times/week/40 min) or high‐intensity (ob/obH and ob/OBH: 6% body weight, three times per week per 20 min) swimming training. An incremental swimming test was performed to measure aerobic fitness. After the training intervention period, glycaemia and the content of GLUT4 were quantified. Although both training intensities were beneficial, the high‐intensity regimen induced a more significant improvement in GLUT4 levels and glycaemic profile compared with sedentary controls (p < 0·05). Only animals in the high‐intensity exercise group improved aerobic fitness. Thus, our study shows that high‐intensity training was more effective for increasing GLUT4 content and glycaemia reduction in insulin‐resistant mice, perhaps because of a higher metabolic demand imposed by this form of exercise. Copyright © 2015 John Wiley & Sons, Ltd.     

Freshwater mussel conservation: A global horizon scan of emerging threats and opportunities

We identified 14 emerging and poorly understood threats and opportunities for addressing the global conservation of freshwater mussels over the next decade. A panel of 17 researchers and stakeholders from six continents submitted a total of 56 topics that were ranked and prioritized using a consensus-building Delphi technique. Our 14 priority topics fell into five broad themes (autecology, population dynamics, global stressors, global diversity, and ecosystem services) and included understanding diets throughout mussel life history; identifying the drivers of population declines; defining metrics for quantifying mussel health; assessing the role of predators, parasites, and disease; informed guidance on the risks and opportunities for captive breeding and translocations; the loss of mussel–fish co-evolutionary relationships; assessing the effects of increasing surface water changes; understanding the effects of sand and aggregate mining; understanding the effects of drug pollution and other emerging contaminants such as nanomaterials; appreciating the threats and opportunities arising from river restoration; conserving understudied hotspots by building local capacity through the principles of decolonization; identifying appropriate taxonomic units for conservation; improved quantification of the ecosystem services provided by mussels; and understanding how many mussels are enough to provide these services. Solutions for addressing the topics ranged from ecological studies to technological advances and socio-political engagement. Prioritization of our topics can help to drive a proactive approach to the conservation of this declining group which provides a multitude of important ecosystem services.     

Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome

Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn’s genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10⁻⁵). The IL12RB2 gene (p-value: 2.18x10^-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.     

Effect of an acute moderate‐exercise session on metabolic and inflammatory profile of PPAR‐α knockout mice

Peroxisome proliferator‐activated receptors (PPARs) play a major role in metabolism and inflammatory control. Exercise can modulate PPAR expression in skeletal muscle, adipose tissue, and macrophages. Little is known about the effects of PPAR‐α in metabolic profile and cytokine secretion after acute exercise in macrophages. In this context, the aim of this study was to understand the influence of PPAR‐α on exercise‐mediated immune metabolic parameters in peritoneal macrophages. Mice C57BL/6 (WT) and PPAR‐α knockout (KO) were examined in non‐exercising control (n = 4) or 24 hours after acute moderate exercise (n = 8). Metabolic parameters (glucose, non‐esterified fatty acids, total cholesterol [TC], and triacylglycerol [TG]) were assessed in serum. Cytokine concentrations (IL‐1β, IL‐6, IL‐10, TNF‐α, and MCP‐1) were measured from peritoneal macrophages cultured or not with LPS (2.5 μg/mL) and Rosiglitazone (1 μM). Exercised KO mice exhibited low glucose concentration and higher TC and TG in serum. At baseline, no difference in cytokine production between the genotypes was observed. However, IL‐1β was significantly higher in KO mice after LPS stimulus. IL‐6 and IL‐1β had increased concentrations in KO compared with WT, even after exercise. MCP‐1 was not restored in exercised KO LPS group. Rosiglitazone was not able to reduce proinflammatory cytokine production in KO mice at baseline level or associated with exercise. Acute exercise did not alter mRNA expression in WT mice. Conclusion: PPAR‐α seems to be needed for metabolic glucose homeostasis and anti‐inflammatory effect of acute exercise. Its absence may induce over‐expression of pro‐inflammatory cytokines in LPS stimulus. Moreover, moderate exercise or PPAR‐γ agonist did not reverse this response.     

How are local fish communities structured in Brazilian semiarid headwater streams?

The spread of antibiotic-resistant bacteria is a threatening risk for human health at a global scale. Improved knowledge on the cycle of antibiotic resistance spread between human and the environment is a major requirement for the management of the current crisis. Compared to the well-studied cycle in clinical settings much less is known about the factor allowing their persistence in the environment. In fact, lakes and rivers exposed to high anthropogenic impact seem to become long-term reservoirs for resistance genes. The presence of antibiotic resistance genes (ARGs) within the resident microbiome of large subalpine lakes (i.e. Lake Geneva, Lake Maggiore) has recently been investigated in both the water column and the sediment. These studies suggest a correlation between the abundance of some ARGs and the anthropogenic impact. Within the system, however, abiotic factors and the food-web structure determine the survival of specific bacterial genotypes and thus the resistance genes they harbour. Thus, a growing body of work suggests an important role of ecological interactions in the persistence or elimination of such genes from the environment. This article reviews the current literature regarding the presence of ARGs in subalpine lakes, the impact of anthropogenic pollution on their appearance and the potential role of various ecological interactions on their persistence in the system.     

Local environmental risk assessment of anticancer drugs in a developing country

Abstract

Anticancer drugs used in cancer treatment are excreted unchanged or as metabolites by feces and urine in hospitals and households. These drugs enter the municipal sewage system but wastewater treatment plants are not capable of removing all of these micro pollutants. In many countries such as Brazil, sanitation departments do not provide service, nor have access to all of the population, therefore most sewage is still released into untreated receiving bodies. This study analyzes the consumption of anticancer drugs in a Brazilian hospital located in one of the 10 municipalities with the best sanitation index in the country. It estimates its environmental risk in aquatic matrixes by the European Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use. Among the 20 drugs analyzed, the three most consumed (cyclophosphamide, 5-fluoruracil, and cytarabine) show a predicted environmental concentration value greater than the action limit of 0.01?µg/L recommended by the guideline. The risk assessment was performed on all pharmaceuticals consumed to get a greater awareness of risk. Results do not indicate local environmental risk but, considering that the study was performed under the best sanitation scenario, it cannot be extrapolated in the other municipalities. The study highlights that development of suitable methodologies should be considered to perform environmental risk assessment of pharmaceuticals in developing countries sanitation conditions.