Lack of association of CD36 SNPs with early onset obesity: a meta-analysis in 9,973 European subjects

A recent study suggested that four CD36 polymorphisms (namely rs3211867, rs3211883, rs3211908, and rs1527483) were associated with an increased risk of obesity, an increased BMI and percentage of body fat in European adolescents. We first attempted to confirm these results in three independent case-control genome-wide association studies (GWAS) data totaling 3,509 subjects of French and German origin, but we were unable to find any association of these variants with early onset obesity risk. We then genotyped the four CD36 single-nucleotide polymorphisms (SNPs) in a large population-based study of 4,667 Finnish subjects and we did not replicate any of the recently reported associations with BMI. By combining all available data in a meta-analysis (N = 9,973), we found no evidence for an association of the reported four variants in CD36 with increased obesity risk or increased BMI (0.07 ≤ P values ≤ 0.93). Finally, we assessed the contribution of the full CD36 locus gene variation to obesity risk in 3,509 subjects and we did not detect any significant association with obesity after correction for multiple testing. In summary, we were unable to confirm the recently reported association of variants in CD36 with early onset obesity in populations of European ancestry.     

p38α‐MAPK‐deficient myeloid cells ameliorate symptoms and pathology of APP‐transgenic Alzheimer's disease mice

Alzheimer''s disease (AD), the most common cause of dementia in the elderly, is pathologically characterized by extracellular deposition of amyloid‐β peptides (Aβ) and microglia‐dominated inflammatory activation in the brain. p38α‐MAPK is activated in both neurons and microglia. How p38α‐MAPK in microglia contributes to AD pathogenesis remains unclear. In this study, we conditionally knocked out p38α‐MAPK in all myeloid cells or specifically in microglia of APP‐transgenic mice, and examined animals for AD‐associated pathologies (i.e., cognitive deficits, Aβ pathology, and neuroinflammation) and individual microglia for their inflammatory activation and Aβ internalization at different disease stages (e.g., at 4 and 9 months of age). Our experiments showed that p38α‐MAPK‐deficient myeloid cells were more effective than p38α‐MAPK‐deficient microglia in reducing cerebral Aβ and neuronal impairment in APP‐transgenic mice. Deficiency of p38α‐MAPK in myeloid cells inhibited inflammatory activation of individual microglia at 4 months but enhanced it at 9 months. Inflammatory activation promoted microglial internalization of Aβ. Interestingly, p38α‐MAPK‐deficient myeloid cells reduced IL‐17a‐expressing CD4‐positive lymphocytes in 9 but not 4‐month‐old APP‐transgenic mice. By cross‐breeding APP‐transgenic mice with Il‐17a‐knockout mice, we observed that IL‐17a deficiency potentially activated microglia and reduced Aβ deposition in the brain as shown in 9‐month‐old myeloid p38α‐MAPK‐deficient AD mice. Thus, p38α‐MAPK deficiency in all myeloid cells, but not only in microglia, prevents AD progression. IL‐17a‐expressing lymphocytes may partially mediate the pathogenic role of p38α‐MAPK in peripheral myeloid cells. Our study supports p38α‐MAPK as a therapeutic target for AD patients.     

Can Yeast (S. cerevisiae) Metabolic Volatiles Provide Polymorphic Signaling?

Chemical signaling between organisms is a ubiquitous and evolutionarily dynamic process that helps to ensure mate recognition, location of nutrients, avoidance of toxins, and social cooperation. Evolutionary changes in chemical communication systems progress through natural variation within the organism generating the signal as well as the responding individuals. A promising yet poorly understood system with which to probe the importance of this variation exists between D. melanogaster and S. cerevisiae. D. melanogaster relies on yeast for nutrients, while also serving as a vector for yeast cell dispersal. Both are outstanding genetic and genomic models, with Drosophila also serving as a preeminent model for sensory neurobiology. To help develop these two genetic models as an ecological model, we have tested if - and to what extent - S. cerevisiae is capable of producing polymorphic signaling through variation in metabolic volatiles. We have carried out a chemical phenotyping experiment for 14 diverse accessions within a common garden random block design. Leveraging genomic sequences for 11 of the accessions, we ensured a genetically broad sample and tested for phylogenetic signal arising from phenotypic dataset. Our results demonstrate that significant quantitative differences for volatile blends do exist among S. cerevisiae accessions. Of particular ecological relevance, the compounds driving the blend differences (acetoin, 2-phenyl ethanol and 3-methyl-1-butanol) are known ligands for D. melanogasters chemosensory receptors, and are related to sensory behaviors. Though unable to correlate the genetic and volatile measurements, our data point clear ways forward for behavioral assays aimed at understanding the implications of this variation.     

Ungulates increase forest plant species richness to the benefit of non‐forest specialists

Large wild ungulates are a major biotic factor shaping plant communities. They influence species abundance and occurrence directly by herbivory and plant dispersal, or indirectly by modifying plant‐plant interactions and through soil disturbance. In forest ecosystems, researchers’ attention has been mainly focused on deer overabundance. Far less is known about the effects on understory plant dynamics and diversity of wild ungulates where their abundance is maintained at lower levels to mitigate impacts on tree regeneration. We used vegetation data collected over 10 years on 82 pairs of exclosure (excluding ungulates) and control plots located in a nation‐wide forest monitoring network (Renecofor). We report the effects of ungulate exclusion on (i) plant species richness and ecological characteristics, (ii) and cover percentage of herbaceous and shrub layers. We also analyzed the response of these variables along gradients of ungulate abundance, based on hunting statistics, for wild boar (Sus scrofa), red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Outside the exclosures, forest ungulates maintained higher species richness in the herbaceous layer (+15%), while the shrub layer was 17% less rich, and the plant communities became more light‐demanding. Inside the exclosures, shrub cover increased, often to the benefit of bramble (Rubus fruticosus agg.). Ungulates tend to favour ruderal, hemerobic, epizoochorous and non‐forest species. Among plots, the magnitude of vegetation changes was proportional to deer abundance. We conclude that ungulates, through the control of the shrub layer, indirectly increase herbaceous plant species richness by increasing light reaching the ground. However, this increase is detrimental to the peculiarity of forest plant communities and contributes to a landscape‐level biotic homogenization. Even at population density levels considered to be harmless for overall plant species richness, ungulates remain a conservation issue for plant community composition.     

Increased heat requirement for leaf flushing in temperate woody species over 1980–2012: effects of chilling,precipitation and insolation

Recent studies have revealed large unexplained variation in heat requirement‐based phenology models, resulting in large uncertainty when predicting ecosystem carbon and water balance responses to climate variability. Improving our understanding of the heat requirement for spring phenology is thus urgently needed. In this study, we estimated the species‐specific heat requirement for leaf flushing of 13 temperate woody species using long‐term phenological observations from Europe and North America. The species were defined as early and late flushing species according to the mean date of leaf flushing across all sites. Partial correlation analyses were applied to determine the temporal correlations between heat requirement and chilling accumulation, precipitation and insolation sum during dormancy. We found that the heat requirement for leaf flushing increased by almost 50% over the study period 1980–2012, with an average of 30 heat units per decade. This temporal increase in heat requirement was observed in all species, but was much larger for late than for early flushing species. Consistent with previous studies, we found that the heat requirement negatively correlates with chilling accumulation. Interestingly, after removing the variation induced by chilling accumulation, a predominantly positive partial correlation exists between heat requirement and precipitation sum, and a predominantly negative correlation between heat requirement and insolation sum. This suggests that besides the well‐known effect of chilling, the heat requirement for leaf flushing is also influenced by precipitation and insolation sum during dormancy. However, we hypothesize that the observed precipitation and insolation effects might be artefacts attributable to the inappropriate use of air temperature in the heat requirement quantification. Rather than air temperature, meristem temperature is probably the prominent driver of the leaf flushing process, but these data are not available. Further experimental research is thus needed to verify whether insolation and precipitation sums directly affect the heat requirement for leaf flushing.     

Freezing tolerance of the European water frogs: the good, the bad, and the ugly

Survival and some physiological responses to freezing were investigated in three European water frogs (Rana lessonae, Rana ridibunda, and their hybridogen Rana esculenta). The three species exhibited different survival times during freezing (from 10 h for R. lessonae to 20 h for R. ridibunda). The time courses of percent water frozen were similar; however, because of the huge differences in body mass among species (from 10 g for Rana lessonae to nearly 100 g for Rana ridibunda), the ice mass accumulation rate varied markedly (from 0.75 +/- 0.12 to 1.43 +/- 0.11 g ice/h, respectively) and was lowest in the terrestrial hibernator Rana lessonae. The hybrid Rana esculenta exhibited an intermediate response between the two parental species; furthermore, within-species correlation existed between body mass and ice mass accumulation rates, suggesting the occurrence of subpopulations in this species (0.84 +/- 0.08 g ice/h for small R. esculenta and 1.78 +/- 0.09 g ice/h for large ones). Biochemical analyses showed accumulation of blood glucose and lactate, liver glucose (originating from glycogen), and liver alanine in Rana lessonae and Rana esculenta but not in Rana ridibunda in response to freezing. The variation of freeze tolerance between these three closely related species could bring understanding to the physiological processes involved in the evolution of freeze tolerance in vertebrates.     

Disruption of the langerin/CD207 gene abolishes Birbeck granules without a marked loss of Langerhans cell function

Langerin is a C-type lectin expressed by a subset of dendritic leukocytes, the Langerhans cells (LC). Langerin is a cell surface receptor that induces the formation of an LC-specific organelle, the Birbeck granule (BG). We generated a langerin(-/-) mouse on a C57BL/6 background which did not display any macroscopic aberrant development. In the absence of langerin, LC were detected in normal numbers in the epidermis but the cells lacked BG. LC of langerin(-/-) mice did not present other phenotypic alterations compared to wild-type littermates. Functionally, the langerin(-/-) LC were able to capture antigen, to migrate towards skin draining lymph nodes, and to undergo phenotypic maturation. In addition, langerin(-/-) mice were not impaired in their capacity to process native OVA protein for I-A(b)-restricted presentation to CD4(+) T lymphocytes or for H-2K(b)-restricted cross-presentation to CD8(+) T lymphocytes. langerin(-/-) mice inoculated with mannosylated or skin-tropic microorganisms did not display an altered pathogen susceptibility. Finally, chemical mutagenesis resulted in a similar rate of skin tumor development in langerin(-/-) and wild-type mice. Overall, our data indicate that langerin and BG are dispensable for a number of LC functions. The langerin(-/-) C57BL/6 mouse should be a valuable model for further functional exploration of langerin and the role of BG.