Oxysterols direct immune cell migration via EBI2

Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) is a G-protein-coupled receptor that is required for humoral immune responses; polymorphisms in the receptor have been associated with inflammatory autoimmune diseases. The natural ligand for EBI2 has been unknown. Here we describe the identification of 7α,25-dihydroxycholesterol (also called 7α,25-OHC or 5-cholesten-3β,7α,25-triol) as a potent and selective agonist of EBI2. Functional activation of human EBI2 by 7α,25-OHC and closely related oxysterols was verified by monitoring second messenger readouts and saturable, high-affinity radioligand binding. Furthermore, we find that 7α,25-OHC and closely related oxysterols act as chemoattractants for immune cells expressing EBI2 by directing cell migration in vitro and in vivo. A critical enzyme required for the generation of 7α,25-OHC is cholesterol 25-hydroxylase (CH25H). Similar to EBI2 receptor knockout mice, mice deficient in CH25H fail to position activated B cells within the spleen to the outer follicle and mount a reduced plasma cell response after an immune challenge. This demonstrates that CH25H generates EBI2 biological activity in vivo and indicates that the EBI2-oxysterol signalling pathway has an important role in the adaptive immune response.     

Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is a common, heritable neuropsychiatric disorder of unknown etiology. We performed a whole-genome copy number variation (CNV) study on 1,013 cases with ADHD and 4,105 healthy children of European ancestry using 550,000 SNPs. We evaluated statistically significant findings in multiple independent cohorts, with a total of 2,493 cases with ADHD and 9,222 controls of European ancestry, using matched platforms. CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts (P = 2.1 × 10(-9)). We saw GRM5 (encoding glutamate receptor, metabotropic 5) deletions in ten cases and one control (P = 1.36 × 10(-6)). We saw GRM7 deletions in six cases, and we saw GRM8 deletions in eight cases and no controls. GRM1 was duplicated in eight cases. We experimentally validated the observed variants using quantitative RT-PCR. A gene network analysis showed that genes interacting with the genes in the GRM family are enriched for CNVs in ～10% of the cases (P = 4.38 × 10(-10)) after correction for occurrence in the controls. We identified rare recurrent CNVs affecting glutamatergic neurotransmission genes that were overrepresented in multiple ADHD cohorts.     

Exome sequencing of liver fluke-associated cholangiocarcinoma

Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.     

Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.     

A renormalization group approach to crowd psychology and inter-group coupling in social many-body systems

By adopting majority rule within a renormalization group approach, we can show that the strength of inter-group interaction in a social system either grows or shrinks monotonically with increasing group size, depending on the initial coupling strength of individuals in the group. This contrasts with the findings of previous studies in which the strength of the interaction grows with group size regardless of the initial strength. Our approach clearly demonstrates that the phenomena of crowd psychology, such as an extreme anti-reaction between different ethnic or ideological groups, could be a consequence of the many-particle nature of social systems when the initial strength of the interaction is larger than a critical value. The effect of neutral opinion holders is critically examined using the spin-one Ising model. The critical size of the population of neutral opinion holders, that can prevent crowd polarization, depends on the block spin rule.     

利用杀菌剂防治松萎蔫病

松萎蔫病是一种非常复杂的病害。据报道,松材线虫(Bursaphelenchus xylophilus)及其携带的细菌诱导了该病,但是对于细菌的的作用尚存争议。笔者筛选出杀细菌剂进行了温室和林间防治松萎蔫病的实验。利用每株3年生赤松(Pinus densiflora)注射3 mg的恶喹酸,松萎蔫病防效达到71 %。利用恶喹酸或阿维菌素及两者混合物对大约20年生赤松的试验表明,3种处理均显示了很高的防效。以上结果证明伴生细菌是诱导松萎蔫病的必要因素,对松萎蔫病可利用杀细菌剂或杀细菌剂与杀线剂混合物进行防控。     

长白山区次生林恢复过程中天然更新的动态

以长白山区天然次生林为研究对象,采用空间代替时间的方法,分别对不同年度进行择代后形成的天然次生林进行群落学调查,分析择伐后28年恢复期间高度小于3m的幼苗幼树的天然更新过程及特点。结果表明,恢复初期更新幼苗幼树的树种出现比率较低,随着次生林恢复时间的增加,更新幼苗幼树的树种出现比率超过75％,且15年后变化相对较小;次生林内更新幼苗幼树的分布密度随着恢复时间的增加呈增加的趋势,恢复15年时分布密度达7500株／hm^2,此后分布密度的变化相对较小;在次生林内幼苗幼树主要是集中分布在距最近立木1．5～3．5m的范围内,随着次生林恢复时间的增加,幼树的分布范围相对靠近立木,幼苗的分布范围则相对远离立木。     

《奉使图》与《东游集》及郑玙等问题的考辨

《奉使图》是从《东游集》而来的。《东游集》中的诗都是阿克敦从前三次出使朝鲜的诗稿中选出来的,本来只是供蒋衡书法,但后来它的影响进一步扩大,于是阿克敦在第四次出使朝鲜时充分准备了作画的素材,并于雍正三年请当时在京城很活跃的海宁画家郑玙作了20幅画。