Evidence for the intracellular accumulation of anandamide in adiposomes

Anandamide is a lipid messenger that carries out a wide variety of biological functions. It has been suggested that anandamide accumulation involves binding to a saturable cellular component. To identify the structure(s) involved in this process, we analyzed the intracellular distribution of both biotinylated and radiolabeled anandamide, providing direct evidence that lipid droplets, also known as adiposomes, constitute a dynamic reservoir for the sequestration of anandamide. In addition, confocal microscopy and biochemical studies revealed that the anandamide-hydrolase is also spatially associated with lipid droplets, and that cells with a larger adiposome compartment have an enhanced catabolism of anandamide. Overall, these findings suggest that adiposomes may have a critical role in accumulating anandamide, possibly by connecting plasma membrane to internal organelles along the metabolic route of this endocannabinoid. S. Oddi, F. Fezza: These authors contributed equally to the study.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.     

Heterogeneous Forecast Adjustment

There is ample empirical evidence that expert‐adjusted model forecasts can be improved. One way to potential improvement concerns providing various forms of feedback to the sales forecasters. It is also often recognized that the experts (forecasters) might not constitute a homogeneous group. This paper provides a data‐based methodology to discern latent clusters of forecasters, and applies it to a fully new large database with data on expert‐adjusted forecasts, model forecasts and realizations. For the data at hand, two clusters can clearly be identified. Next, the consequences of having clusters are discussed. Copyright © 2016 John Wiley & Sons, Ltd.     

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.     

职住变迁与通勤自平衡

采用2011年和2014年各两周的上海移动手机信令数据,通过跟踪分析识别出居住地、就业地发生变迁的居民作为研究对象,数据可视化、描述性统计、定量对比分析等方法对同一批变迁居民的通勤行为进行跟踪研究,以此对其中存在的“自平衡”特征进行分析,并进一步研究该变化特征与城市空间之间所存在的联系。研究表明：总体层面,从平均通勤距离变化以及过剩通勤率变化方面来看,居民在进行居住地、就业地变迁时均存在通勤“自平衡”的特征与趋势;个体层面,原通勤距离越远,通过居住地、就业地变迁以改善自身通勤关系追求通勤“自平衡”的效果越明显;就业地变迁居民的通勤“自平衡”特征相较于居住地变迁来说更加显著;空间集合层面,职住关系较差的居住区、就业区,存在总体的“自平衡”现象。     

矿区植物--环境恢复的重要资源

综述了矿区植物的研究现状矿区植物的生态学、遗传学、植物分类学特性,矿区植物对重金属的耐性与吸收性,矿区植物在矿山及污染环境修复中的功能与作用;最后,探讨了矿区植物资源研究的未来发展方向。