Circuit Specific Functions of Cannabinoid CB1 Receptor in the Balance of Investigatory Drive and Exploration

Well balanced novelty seeking and exploration are fundamental behaviours for survival and are found to be dysfunctional in several psychiatric disorders. Recent studies suggest that the endocannabinoid (eCB) system is an important control system for investigatory drive. Pharmacological treatment of rodents with cannabinergic drugs results in altered social and object investigation. Interestingly, contradictory results have been obtained, depending on the treatment, drug concentration and experimental conditions. The cannabinoid type 1 (CB1) receptor, a central component of the eCB system, is predominantly found at the synapses of two opposing neuronal populations, i.e. on inhibitory GABAergic and excitatory glutamatergic neurons. In the present study, using different transgenic mouse lines, we aimed at investigating the impact of CB1 receptor inactivation in glutamatergic or GABAergic neurons on investigatory behaviour. We evaluated animate (interaction partner) and inanimate (object) exploratory behaviour in three different paradigms. We show that exploration was increased when CB1 receptor was deleted from cortical and striatal GABAergic neurons. No effect was observed when CB1 receptor was deleted specifically from dopamine receptor D1-expressing striatal GABAergic medium spiny neurons. In contrast, deletion of CB1 receptor from cortical glutamatergic neurons resulted in a decreased exploration. Thus, our results indicate that exploratory behaviour is accurately balanced in both, the social and non-social context, by the eCB system via CB1 receptor activation on cortical glutamatergic and GABAergic neurons. In addition, the results could explain the contradictory findings of previous pharmacological studies and could further suggest a possibility to readjust an imbalance in exploratory behaviour observed in psychiatric disorders

Cloud and Precipitation Observed with Radar

Meteorological radar is an essential tool for research, diagnosis, and nowcasting of clouds and precipitation. Cloud radars use short wavelengths to enable detection of small ice particles or cloud droplets. The cloud radar at UFS Schneefernerhaus is operated since end of 2011. It has been used for a number of studies related to clouds and precipitation. In a synergistic combination with additional remote sensing instruments, a large variety of cloud and precipitation properties can be retrieved. The measurements at UFS Schneefernerhaus can be used for the evaluation of numerical weather prediction models and satellite measurements. The long-term observations allow assessing the seasonal and long-term evolution of cloud properties above the UFS in a warming climate

The Myocyte Expression of Adiponectin Receptors and PPARδ Is Highly Coordinated and Reflects Lipid Metabolism of the Human Donors

Muscle lipid oxidation is stimulated by peroxisome proliferator-activated receptor (PPAR) δ or adiponectin receptor signalling. We studied human myocyte expression of the PPARδ and adiponectin receptor genes and their relationship to lipid parameters of the donors. The mRNA levels of the three adiponectin receptors, AdipoR1, AdipoR2, and T-cadherin, were highly interrelated (r ≥ 0.91). However, they were not associated with GPBAR1, an unrelated membrane receptor. In addition, the adiponectin receptors were positively associated with PPARδ expression (r ≥ 0.75). However, they were not associated with PPARα. Using stepwise multiple linear regression analysis, PPARδ was a significant determinant of T-cadherin (P = .0002). However, pharmacological PPARδ activation did not increase T-cadherin expression. The myocyte expression levels of AdipoR1 and T-cadherin were inversely associated with the donors' fasting plasma triglycerides (P < .03). In conclusion, myocyte expression of PPARδ and the adiponectin receptors are highly coordinated, and this might be of relevance for human lipid metabolism in vivo

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion

<p>Abstract</p> <p>Background</p> <p>Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene <it>PCSK1</it>, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity. We studied whether these SNPs influence the prediabetic traits insulin resistance, β-cell dysfunction, or glucose intolerance.</p> <p>Methods</p> <p>We genotyped 1498 German subjects for SNPs rs6232 and rs6235 within <it>PCSK1</it>. The subjects were metabolically characterized by oral glucose tolerance test with glucose, insulin, proinsulin, and C-peptide measurements. A subgroup of 512 subjects underwent a hyperinsulinemic-euglycemic clamp.</p> <p>Results</p> <p>The minor allele frequencies were 25.8% for SNP rs6235 and 6.0% for rs6232. After adjustment for sex and age, we found no association of SNPs rs6235 and rs6232 with BMI or other weight-related traits (all p ≥ 0.07). Both minor alleles, adjusted for sex, age, BMI and insulin sensitivity were associated with elevated AUC_proinsulinand AUC_proinsulin/AUC_insulin(rs6235: p_{additive model}≤ 0.009, effect sizes 8/8%, rs6232: p_{dominant model}≤ 0.01, effect sizes 10/21%). Insulin secretion was not affected by the variants (different secretion parameters, all p ≥ 0.08). The minor allele of SNP rs6232 was additionally associated with 15% higher OGTT-derived and 19% higher clamp-derived insulin sensitivity (p_dom≤ 0.0047), 4.5% lower HOMA_IR(p_dom= 0.02) and 3.5% lower 120-min glucose (p_dom= 0.0003) independently of BMI and proinsulin conversion. SNP rs6235 was not associated with parameters of glucose metabolism.</p> <p>Conclusions</p> <p>Like rare mutations in <it>PCSK1</it>, the more common variants tested determine glucose-stimulated proinsulin conversion, but not insulin secretion. In addition, rs6232, encoding the amino acid exchange N221D, influences insulin sensitivity and glucose homeostasis.</p

Common Genetic Variation in the SERPINF1 Locus Determines Overall Adiposity, Obesity-Related Insulin Resistance, and Circulating Leptin Levels

OBJECTIVE: Pigment epithelium-derived factor (PEDF) belongs to the serpin family of peptidase inhibitors (serpin F1) and is among the most abundant glycoproteins secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a candidate mediator of obesity-induced insulin resistance. Therefore, we assessed whether common genetic variation within the SERPINF1 locus contributes to adipose tissue-related prediabetic phenotypes in humans. SUBJECTS/METHODS: A population of 1,974 White European individuals at increased risk for type 2 diabetes was characterized by an oral glucose tolerance test with glucose and insulin measurements (1,409 leptin measurements) and genotyped for five tagging SNPs covering 100% of common genetic variation (minor allele frequency ≥ 0.05) in the SERPINF1 locus. In addition, a subgroup of 486 subjects underwent a hyperinsulinaemic-euglycaemic clamp and a subgroup of 340 magnetic resonance imaging (MRI) and spectroscopy (MRS). RESULTS: After adjustment for gender and age and Bonferroni correction for the number of SNPs tested, SNP rs12603825 revealed significant association with MRI-derived total adipose tissue mass (p = 0.0094) and fasting leptin concentrations (p = 0.0035) as well as nominal associations with bioelectrical impedance-derived percentage of body fat (p = 0.0182) and clamp-derived insulin sensitivity (p = 0.0251). The association with insulin sensitivity was completely abolished by additional adjustment for body fat (p = 0.8). Moreover, the fat mass-increasing allele of SNP rs12603825 was significantly associated with elevated fasting PEDF concentrations (p = 0.0436), and the PEDF levels were robustly and positively associated with all body fat parameters measured and with fasting leptin concentrations (p<0.0001, all). CONCLUSION: In humans at increased risk for type 2 diabetes, a functional common genetic variant in the gene locus encoding PEDF contributes to overall body adiposity, obesity-related insulin resistance, and circulating leptin levels

Decomposition numbers for the cyclotomic Brauer algebras in characteristic zero

We study the representation theory of the cyclotomic Brauer algebra via truncation to idempotent subalgebras which are isomorphic to a product of walled and classical Brauer algebras. In particular, we determine the block structure and decomposition numbers in characteristic zero.Comment: 20 pages, 12 figure

The UV properties of E+A galaxies: constraints on feedback-driven quenching of star formation

We present the first large-scale study of E+A (post-starburst) galaxies that incorporates photometry in the ultraviolet (UV) wavelengths. We find that the starburst that creates the E+A galaxy typically takes place within the last Gyr and creates a high fraction (20-60 percent) of the stellar mass in the remnant over a short timescale (< 0.1 Gyrs). We find a tight correlation between the luminosity of our E+A galaxies and the implied star formation rate (SFR) during the starburst. While low-luminosity E+As (M(z) > -20) exhibit implied SFRs of less than 50 solar masses per year, their luminous counterparts (M(z) < -22) shows SFRs greater than 300 and as high as 2000 solar masses per year, suggesting that luminous and ultra-luminous infrared galaxies in the low-redshift Universe could be the progenitors of massive nearby E+A galaxies. We perform a comprehensive study of the characteristics of the quenching that truncates the starburst in E+A systems.We find that, for galaxies less massive than 10^10 MSun, the quenching efficiency decreases as the galaxy mass increases. However, for galaxies more massive than 10^10 MSun, this trend is reversed and the quenching efficiency increases with galaxy mass. Noting that the mass threshold at which this reversal occurs is in excellent agreement with the mass above which AGN become significantly more abundant in nearby galaxies, we use simple energetic arguments to show that the bimodal behaviour of the quenching efficiency is consistent with AGN and supernovae (SN) being the principal sources of negative feedback above and below M ~ 10^10 MSun respectively. (abridged)Comment: MNRAS in press (accepted September 2007

SDSS 0956+5128: A Broad-line Quasar with Extreme Velocity Offsets

We report on the discovery of a Type 1 quasar, SDSS 0956+5128, with a surprising combination of extreme velocity offsets. SDSS 0956+5128 is a broad-lined quasar exhibiting emission lines at three substantially different redshifts: a systemic redshift of z ~ 0.714 based on narrow emission lines, a broad MgII emission line centered 1200 km/s bluer than the systemic velocity, at z ~ 0.707, and broad H\alpha and H\beta emission lines centered at z ~ 0.690. The Balmer line peaks are 4100 km/s bluer than the systemic redshift. There are no previously known objects with such an extreme difference between broad MgII and broad Balmer emission. The two most promising explanations are either an extreme disk emitter or a high-velocity black hole recoil. However, neither explanation appears able to explain all of the observed features of SDSS 0956+5128, so the object may provide a challenge to our general understanding of quasar physics.Comment: ApJ, accepte