Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G.C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G.C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response toa nutritional interventionwithMD.An intervention study ina high cardiovascular riskMediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplementedwith virgin olive oil ornuts.Measureswereobtained at baseline and after a 3-mointervention period.At baseline, the COX-2 -765G.C polymorphismwas associated with lower serum IL-6 (5.85 6 4.82 in GG vs. 4.74 6 4.14 ng/L in C-allele carriers; P ¼ 0.002) and ICAM-1 (265.8 6 114.8 in GG vs. 243.0 6 107.1 mg/L in C-carriers; P ¼ 0.018) concentrations. These differences remained significant aftermultivariate adjustment. The IL-6 -174G.C polymorphism was associatedwith higher (CC vs. G-carriers) serumICAM-1concentrations in bothmenandwomenandwithhigherserumIL-6 concentrations inmen.Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G.C and IL-6 -174G.C polymorphismswere associatedwith inflammation, consuming aMD(either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.

Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages

Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices) with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas), and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves) and low-mobility (e.g. Gastropoda) groups had the strongest responses to fire (higher R scores of the ANOSIM); however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental changes caused by fire.

Circadian variation of salivary immunoglobin A, alpha-amylase activity and mood in response to repeated double-poling sprints in hypoxia.

PURPOSE: To assess the circadian variations in salivary immunoglobin A (sIgA) and alpha-amylase activity (sAA), biomarkers of mucosal immune function, together with mood during 2 weeks of repeated sprint training in hypoxia (RSH) and normoxia (RSN). METHODS: Over a 2-week period, 17 competitive cross-country skiers performed six training sessions, each consisting of four sets of five 10-s bouts of all-out double-poling under either normobaric hypoxia (FiO2: 13.8 %, 3000 m) or normoxia. The levels of sIgA and sAA activity and mood were determined five times during each of the first (T1) and sixth (T6) days of training, as well as during days preceding (baseline) and after the training intervention (follow-up). RESULTS: With RSH, sIgA was higher on T6 than T1 (P = 0.049), and sAA was increased on days T1, T6, and during the follow-up (P < 0.01). With RSN, sIgA remained unchanged and sAA was elevated on day T1 only (P = 0.04). Similarly, the RSH group demonstrated reduced mood on days T1, T6, and during the follow-up, while mood was lowered only on T1 with RSN (P < 0.01). CONCLUSIONS: The circadian variation of sIgA and sAA activity, biomarkers of mucosal immune function, as well as mood were similar on the first day of training when repeated double-poling sprints were performed with or without hypoxia. Only with RSH did the levels of sIgA and sAA activity rise with time, becoming maximal after six training sessions, when mood was still lowered. Therefore, six sessions of RSH reduced mood, but did not impair mucosal immune function.

Sex- and melanism-specific variations in the oxidative status of adult tawny owls in response to manipulated reproductive effort.

Oxidative stress, determined by the balance between the production of damaging reactive oxygen species (ROS) and antioxidant defences, is hypothesized to play an important role in shaping the cost of reproduction and life history trade-offs. To test this hypothesis, we manipulated reproductive effort in 94 breeding pairs of tawny owls (Strix aluco) to investigate the sex- and melanism-specific effects on markers of oxidative stress in red blood cells (RBCs). This colour polymorphic bird species shows sex-specific division of labour and melanism-specific history strategies. Brood sizes at hatching were experimentally enlarged or reduced to increase or decrease reproductive effort, respectively. We obtained an integrative measure of the oxidative balance by measuring ROS production by RBCs, intracellular antioxidant glutathione levels and membrane resistance to ROS. We found that light melanic males (the sex undertaking offspring food provisioning) produced more ROS than darker conspecifics, but only when rearing an enlarged brood. In both sexes, light melanic individuals had also a larger pool of intracellular antioxidant glutathione than darker owls under relaxed reproductive conditions (i.e. reduced brood), but not when investing substantial effort in current reproduction (enlarged brood). Finally, resistance to oxidative stress was differently affected by the brood size manipulation experiment in males and females independently of their plumage coloration. Altogether, our results support the hypothesis that reproductive effort can alter the oxidative balance in a sex- and colour-specific way. This further emphasizes the close link between melanin-based coloration and life history strategies.

Biological Characterization of Gene Response to Insulin-Induced Hypoglycemia in Mouse Retina.

Glucose is the most important metabolic substrate of the retina and maintenance of normoglycemia is an essential challenge for diabetic patients. Chronic, exaggerated, glycemic excursions could lead to cardiovascular diseases, nephropathy, neuropathy and retinopathy. We recently showed that hypoglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression was modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we identify by gene set enrichment analysis, three important pathways, including lysosomal function, GSH metabolism and apoptotic pathways. Then we tested the effect of recurrent hypoglycemia (three successive 4h periods of hypoglycemia spaced by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevented GSH decrease and retinal cell death, or adapted the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining "normal" GSH level, as well as a strict glycemic control, represents a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy.

Host Genetics of Response to Hepatitis B Vaccine: A Systematic Review

Background. Hepatitis B virus (HBV) is an important cause of chronic viral disease worldwide and can be life threatening. While a safe and effective vaccine is widely available, 5 to 10% of healthy vaccinees fail to achieve a protective anti-hepatitis B surface antigen antibody (anti-HBs) titer (>10mIU/ml). A limited number of studies investigated host genetics of the response to HBV vaccine. To our knowledge, no comprehensive overview of genetic polymorphisms both within and outside the HLA system has been done so far. Aim. The aim of this study was to perform a systematic review of the literature of human genetics influencing immune response after hepatitis B vaccination. Methods. Literature searches using keywords were conducted in the electronic databases Medline, Embase and ISI Web of Science the cut-off date being March 2014. After selection of papers according to stringent inclusion criteria, relevant information was systematically collected from the remaining articles, including demographic data, number of patients, schedule and type of vaccine, phenotypes, genes and single nucleotide polymorphisms (SNPs) genotyping results and their association with immune response to hepatitis B vaccine. Results. The literature search produced a total of 1968 articles from which 46 studies were kept for further analyses. From these studies, data was extracted for 19 alleles from the human leukocyte antigen (HLA) region that were reported as significant at least twice. Among those alleles, 9 were firmly associated with vaccine response outcome (DQ2 [DQB1*02 and DQB1*0201], DR3 [DRB1*03 and DRB1*0301], DR7 [DRB1*07 and DRB1*0701], C4AQ0, DPB1*0401, DQ3, DQB1*06, DRB1*01 and DRB1*13 [DRB1*1301]). In addition, data was extracted for 55 different genes from which 13 extra-HLA genes had polymorphisms that were studied by different group of investigators or by the same group with a replication study. Among the 13 genes allowing comparison, 4 genes (IL-1B, IL-2, IL-4R and IL- 6) revealed no significant data, 6 genes (IL-4, IL-10, IL-12B, IL-13, TNFA, IFNG and TLR2) were explored with inconsistent results and 2 genes (CD3Z and ITGAL) yielded promising results as their association with vaccine response was confirmed by a replication approach. Furthermore, this review produced a list of 46 SNPs from 26 genes that were associated with immune response to vaccine only once, providing novel candidates to be tested in datasets from existing genome-wide association studies (GWAS). Conclusion. To the best of our knowledge, this is the first systematic review of immunogenetic studies of response to hepatitis B vaccine. While this work reassesses the role of several HLA alleles on vaccine response outcome, the associations with polymorphisms in genes outside the HLA region were rather inconsistent. Moreover, this work produced a list of 46 significant SNPs that were reported by a single group of investigators, opening up some interesting possibilities for further research.

Compensatory embryonic response to allele-specific inactivation of the murine X-linked gene Hcfc1.

Early in female mammalian embryonic development, cells randomly inactivate one of the two X chromosomes to achieve overall equal inactivation of parental X-linked alleles. Hcfc1 is a highly conserved X-linked mouse gene that encodes HCF-1 - a transcriptional co-regulator implicated in cell proliferation in tissue culture cells. By generating a Cre-recombinase inducible Hcfc1 knock-out (Hcfc1(lox)) allele in mice, we have probed the role of HCF-1 in actively proliferating embryonic cells and in cell-cycle re-entry of resting differentiated adult cells using a liver regeneration model. HCF-1 function is required for both extraembryonic and embryonic development. In heterozygous Hcfc1(lox/+) female embryos, however, embryonic epiblast-specific Cre-induced Hcfc1 deletion (creating an Hcfc1(epiKO) allele) around E5.5 is well tolerated; it leads to a mixture of HCF-1-positive and -negative epiblast cells owing to random X-chromosome inactivation of the wild-type or Hcfc1(epiKO) mutant allele. At E6.5 and E7.5, both HCF-1-positive and -negative epiblast cells proliferate, but gradually by E8.5, HCF-1-negative cells disappear owing to cell-cycle exit and apoptosis. Although generating a temporary developmental retardation, the loss of HCF-1-negative cells is tolerated, leading to viable heterozygous offspring with 100% skewed inactivation of the X-linked Hcfc1(epiKO) allele. In resting adult liver cells, the requirement for HCF-1 in cell proliferation was more evident as hepatocytes lacking HCF-1 fail to re-enter the cell cycle and thus to proliferate during liver regeneration. The survival of the heterozygous Hcfc1(epiKO/+) female embryos, even with half the cells genetically compromised, illustrates the developmental plasticity of the post-implantation mouse embryo - in this instance, permitting survival of females heterozygous for an X-linked embryonic lethal allele.

Predicted decrease in global climate suitability masks regional complexity of invasive fruit fly species response to climate change

Climate change affects the rate of insect invasions as well as the abundance, distribution and impacts of such invasions on a global scale. Among the principal analytical approaches to predicting and understanding future impacts of biological invasions are Species Distribution Models (SDMs), typically in the form of correlative Ecological Niche Models (ENMs). An underlying assumption of ENMs is that species-environment relationships remain preserved during extrapolations in space and time, although this is widely criticised. The semi-mechanistic modelling platform, CLIMEX, employs a top-down approach using species ecophysiological traits and is able to avoid some of the issues of extrapolation, making it highly applicable to investigating biological invasions in the context of climate change. The tephritid fruit flies (Diptera: Tephritidae) comprise some of the most successful invasive species and serious economic pests around the world. Here we project 12 tephritid species CLIMEX models into future climate scenarios to examine overall patterns of climate suitability and forecast potential distributional changes for this group. We further compare the aggregate response of the group against species-specific responses. We then consider additional drivers of biological invasions to examine how invasion potential is influenced by climate, fruit production and trade indices. Considering the group of tephritid species examined here, climate change is predicted to decrease global climate suitability and to shift the cumulative distribution poleward. However, when examining species-level patterns, the predominant directionality of range shifts for 11 of the 12 species is eastward. Most notably, management will need to consider regional changes in fruit fly species invasion potential where high fruit production, trade indices and predicted distributions of these flies overlap.

The state's response to the Catalan question : an emerging ethnic component in contemporary Spanish nationalism?

Peer-reviewed

The state's response to the Catalan question : an emerging ethnic component in contemporary Spanish nationalism?

Peer-reviewed