Diacylglycerol-containing oleic acid induces increases in [Ca]i via TRPC3/6 channels in human T-cells

Though most of the studies have focused on the effects of free fatty acids on T-cell activation, fatty acids incorporated into plasma membrane phospholipids may also affect cell signaling via diacylglycerol (DAG), generally produced by phospholipid hydrolysis. In the present study, we have synthesized a DAG-containing oleic acid and studied its implication in the modulation of calcium signaling in human Jurkat T-cells. 1-palmitoyl-2-oleoyl-sn-glycerol (POG) induced a dose-dependent increase in [Ca²⁺]_i. This effect was due to the presence of oleic acid at the sn-2 position as no differences were observed between POG and 1-stearoly-2-oleoyl-sn-glycerol (SOG). However, the substitution of oleic acid with arachidonic acid at the sn-2 position of the DAG moiety exerted a different response on the increases in [Ca²⁺]_i in these cells. POG-evoked increases in [Ca²⁺]_i were not due to its metabolites. Furthermore, POG-induced increases in [Ca²⁺]_i were due to the opening of TRPC3/TRPC6 channels as silencing of TRPC3 and TRPC6 genes by shRNA abolished calcium entry. Moreover, disruption of lipid rafts with methyl-β-cyclodextrin completely abolished POG-evoked increases in [Ca²⁺]_i. In conclusion, our results demonstrate that oleic acid can influence T-lymphocyte functions, in the conjugated form of DAG, via opening TRPC3/6 channels.     

Altered Mitochondrial Function and Oxidative Stress in Leukocytes of Anorexia Nervosa Patients

Context

Anorexia nervosa is a common illness among adolescents and is characterised by oxidative stress.

Objective

The effects of anorexia on mitochondrial function and redox state in leukocytes from anorexic subjects were evaluated.

Design and setting

A multi-centre, cross-sectional case-control study was performed.

Patients

Our study population consisted of 20 anorexic patients and 20 age-matched controls, all of which were Caucasian women.

Main outcome measures

Anthropometric and metabolic parameters were evaluated in the study population. To assess whether anorexia nervosa affects mitochondrial function and redox state in leukocytes of anorexic patients, we measured mitochondrial oxygen consumption, membrane potential, reactive oxygen species production, glutathione levels, mitochondrial mass, and complex I and III activity in polymorphonuclear cells.

Results

Mitochondrial function was impaired in the leukocytes of the anorexic patients. This was evident in a decrease in mitochondrial O₂ consumption (P<0.05), mitochondrial membrane potential (P<0.01) and GSH levels (P<0.05), and an increase in ROS production (P<0.05) with respect to control subjects. Furthermore, a reduction of mitochondrial mass was detected in leukocytes of the anorexic patients (P<0.05), while the activity of mitochondrial complex I (P<0.001), but not that of complex III, was found to be inhibited in the same population.

Conclusions

Oxidative stress is produced in the leukocytes of anorexic patients and is closely related to mitochondrial dysfunction. Our results lead us to propose that the oxidative stress that occurs in anorexia takes place at mitochondrial complex I. Future research concerning mitochondrial dysfunction and oxidative stress should aim to determine the physiological mechanism involved in this effect and the physiological impact of anorexia.     

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10⁻⁸–1.2×10⁻⁴³). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10⁻⁴). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10⁻³, n = 22,044), increased triglycerides (p = 2.6×10⁻¹⁴, n = 93,440), increased waist-to-hip ratio (p = 1.8×10⁻⁵, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10⁻³, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10⁻¹³, n = 96,748) and decreased BMI (p = 1.4×10⁻⁴, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.     

Association of functional variants of <Emphasis Type="Italic">PTPN22</Emphasis> and <Emphasis Type="Italic">tp53</Emphasis>in psoriatic arthritis: a case-control study

Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis. Because autoimmune diseases may share similar susceptibility loci, investigation of these genes in psoriatic arthritis (PsA) is of potential relevance. As a result we investigated known coding polymorphisms in PTPN22 and tp53 in a homogenous Caucasian PsA cohort from Newfoundland, Canada and an admixed Caucasian PsA cohort from Toronto, Canada. We observed a moderate association of the R620W variant of PTPN22 with PsA in the Toronto population only. Because of the conflicting findings reported regarding the association of PTPN22 with PsA, further studies in other PsA populations are warranted.     

Ecological zoogeography of the bats of Paraguay

Aim To relate the composition of bat assemblages in Paraguay to environmental factors (vegetation) and to test the hypothesis that the observed patterns of distribution of Paraguayan mammals is ultimately due to soils and geological features. Location Paraguay. Methods Museum specimens were used to create a data base of 3762 individuals of forty-eight species collected in twenty-six 50 × 50 km sites distributed throughout the country. Proportion of each of sixteen vegetation types per site was estimated from vegetation maps. Vegetation and bat data were related using canonical correspondence analysis (CCA) and Mantel tests. The same analyses were performed with the bat data grouped in terms of trophic strategies. Results A significant relationship was found between composition of vegetation and composition of bat assemblages. CCA ordination arranged plant associations and bat assemblages into three distinct groups: Dry Chaco, Floodable Lands and Eastern Paraguay, which correspond to the major characteristics of the Paraguayan vegetation, geology and soils. Frugivorous bats were restricted to Eastern Paraguay and Floodable Lands, whereas most insectivore and omnivore species occur across the entire country. However, the maximum abundance of insectivorous and omnivorous species within each genus indicates that there is at least a partial segregation of species to one of the three regions, and in those cases where the maximum abundance of congeneric species coincide, those species differ considerably in size. Main conclusions The Paraguayan bat fauna is a composite of species from various South American biomes, with no endemic species. However, species are not randomly distributed across the country despite the lack of geographical barriers and the high dispersal capabilities of bats. Instead, species presence at any given site is strongly associated with vegetation patterns that are ultimately the result of the geological history of the area. This correlation can be explained partially in terms of habitat suitability and resource availability. Additionally, results suggest that interspecific interactions are also an important component in determining the composition of a given bat assemblage.     

Functional microbiome deficits associated with ageing: Chronological age threshold

Composition of the gut microbiota changes during ageing, but questions remain about whether age is also associated with deficits in microbiome function and whether these changes occur sharply or progressively. The ability to define these deficits in populations of different ages may help determine a chronological age threshold at which deficits occur and subsequently identify innovative dietary strategies for active and healthy ageing. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics in three well‐defined age groups consisting of 30 healthy volunteers, namely, ten infants, ten adults and ten elderly individuals. Samples from each volunteer at intervals of up to 6 months (n = 83 samples) were used for validation. Ageing gradually increases the diversity of gut bacteria that actively synthesize proteins, that is by 1.4‐fold from infants to elderly individuals. An analysis of functional deficits consistently identifies a relationship between tryptophan and indole metabolism and ageing (p < 2.8e^?8). Indeed, the synthesis of proteins involved in tryptophan and indole production and the faecal concentrations of these metabolites are directly correlated (r² > .987) and progressively decrease with age (r² > .948). An age threshold for a 50% decrease is observed ca. 11–31 years old, and a greater than 90% reduction is observed from the ages of 34–54 years. Based on recent investigations linking tryptophan with abundance of indole and other “healthy” longevity molecules and on the results from this small cohort study, dietary interventions aimed at manipulating tryptophan deficits since a relatively “young” age of 34 and, particularly, in the elderly are recommended.     

Prospects for tropical forest biodiversity in a human-modified world

The future of tropical forest biodiversity depends more than ever on the effective management of human-modified landscapes, presenting a daunting challenge to conservation practitioners and land use managers. We provide a critical synthesis of the scientific insights that guide our understanding of patterns and processes underpinning forest biodiversity in the human-modified tropics, and present a conceptual framework that integrates a broad range of social and ecological factors that define and contextualize the possible future of tropical forest species. A growing body of research demonstrates that spatial and temporal patterns of biodiversity are the dynamic product of interacting historical and contemporary human and ecological processes. These processes vary radically in their relative importance within and among regions, and have effects that may take years to become fully manifest. Interpreting biodiversity research findings is frequently made difficult by constrained study designs, low congruence in species responses to disturbance, shifting baselines and an over-dependence on comparative inferences from a small number of well studied localities. Spatial and temporal heterogeneity in the potential prospects for biodiversity conservation can be explained by regional differences in biotic vulnerability and anthropogenic legacies, an ever-tighter coupling of human-ecological systems and the influence of global environmental change. These differences provide both challenges and opportunities for biodiversity conservation. Building upon our synthesis we outline a simple adaptive-landscape planning framework that can help guide a new research agenda to enhance biodiversity conservation prospects in the human-modified tropics.