The sensitivity of the tropical circulation and Maritime Continent precipitation to climate model resolution

The dependence of the annual mean tropical precipitation on horizontal resolution is investigated in the atmospheric version of the Hadley Centre General Environment Model (HadGEM1). Reducing the grid spacing from about 350 km to 110 km improves the precipitation distribution in most of the tropics. In particular, characteristic dry biases over South and Southeast Asia including the Maritime Continent as well as wet biases over the western tropical oceans are reduced. The annual-mean precipitation bias is reduced by about one third over the Maritime Continent and the neighbouring ocean basins associated with it via the Walker circulation. Sensitivity experiments show that much of the improvement with resolution in the Maritime Continent region is due to the specification of better resolved surface boundary conditions (land fraction, soil and vegetation parameters) at the higher resolution. It is shown that in particular the formulation of the coastal tiling scheme may cause resolution sensitivity of the mean simulated climate. The improvement in the tropical mean precipitation in this region is not primarily associated with the better representation of orography at the higher resolution, nor with changes in the eddy transport of moisture. Sizeable sensitivity to changes in the surface fields may be one of the reasons for the large variation of the mean tropical precipitation distribution seen across climate models

Norepinephrine Controls Both Torpor Initiation and Emergence via Distinct Mechanisms in the Mouse

Some mammals, including laboratory mice, enter torpor in response to food deprivation, and leptin can attenuate these bouts of torpor. We previously showed that dopamine β-hydroxylase knockout (Dbh −/−) mice, which lack norepinephrine (NE), do not reduce circulating leptin upon fasting nor do they enter torpor. To test whether the onset of torpor in mice during a fast requires a NE-mediated reduction in circulating leptin, double mutant mice deficient in both leptin (ob/ob) and DBH (DBL MUT) were generated. Upon fasting, control and ob/ob mice entered torpor as assessed by telemetric core Tb acquisition. While fasting failed to induce torpor in Dbh −/− mice, leptin deficiency bypassed the requirement for NE, as DBL MUT mice readily entered torpor upon fasting. These data indicate that sympathetic activation of white fat and suppression of leptin is required for the onset of torpor in the mouse. Emergence from torpor was severely retarded in DBL MUT mice, revealing a novel, leptin-independent role for NE in torpor recovery. This phenotype was mimicked by administration of a β3 adrenergic receptor antagonist to control mice during a torpor bout. Hence, NE signaling via β3 adrenergic receptors presumably in brown fat is the first neurotransmitter-receptor system identified that is required for normal recovery from torpor

The PLIN4 Variant rs8887 Modulates Obesity Related Phenotypes in Humans through Creation of a Novel miR-522 Seed Site

PLIN4 is a member of the PAT family of lipid storage droplet (LSD) proteins. Associations between seven single nucleotide polymorphisms (SNPs) at human PLIN4 with obesity related phenotypes were investigated using meta-analysis followed by a determination if these phenotypes are modulated by interactions between PLIN4 SNPs and dietary PUFA. Samples consisted of subjects from two populations of European ancestry. We demonstrated association of rs8887 with anthropometrics. Meta-analysis demonstrated significant interactions between the rs8887 minor allele with PUFA n3 modulating anthropometrics. rs884164 showed interaction with both n3 and n6 PUFA modulating anthropometric and lipid phenotypes. In silico analysis of the PLIN4 3′UTR sequence surrounding the rs8887 minor A allele predicted a seed site for the human microRNA-522 (miR-522), suggesting a functional mechanism. Our data showed that a PLIN4 3′UTR luciferase reporter carrying the A allele of rs8887 was reduced in response to miR-522 mimics compared to the G allele. These results suggest variation at the PLIN4 locus, and its interaction with PUFA as a modulator of obesity related phenotypes, acts in part through creation of a miR-522 regulatory site

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN