小胶质细胞在脑中的生理功能

小胶质细胞是脑中的巨噬细胞,也是脑实质中唯一的一种免疫细胞,因而被看作是中枢神经系统抵御病原入侵的第一道防线。在其他非感染病理状态下,如脑损伤及神经退行性疾病等,小胶质细胞也发挥着保护和毒性损伤的双重作用。相比较其病理功能,人们对小胶质细胞的生理功能长期以来很少关注。然而,近几年关于小胶质细胞生理功能的研究在多个方面都有突破。这些研究结果揭示,小胶质细胞在发育的神经系统中起着调控神经元存活和修饰突触的作用,并且在成熟的健康脑中具有探测和调控神经元活动的功能。将着重对近几年关于小胶质细胞生理功能的相关研究做一综述。     

北京半城子水库水体营养物质表观沉降速率

表观沉降速率是流域非点源污染模型中反映水体营养物质通过不同过程,输移进入水库沉积物净效果的参数。选择位于密云水库上游的半城子水库进行水体营养物质监测,计算营养物质表观沉降速率,分析其影响因素,主要得出以下结论:半城子水库TN表观沉降速率平均为55.5mm/d,TP表观沉降速率平均为25.2mm/d,相对于世界其它地区的湖泊水库而言,TP表观沉降速率较慢。水体营养物质表观沉降速率受表层水温和水流条件共同影响。TN表观沉降速率均随表层水温的升高而递增。上游来水后,水体中P元素则经历了内源磷快速释放,之后快速沉降的变化过程。研究成果可为水污染防治和流域环境综合治理提供理论依据。     

Evolutionary Phylodynamics of Korean Noroviruses Reveals a Novel GII.2/GII.10 Recombination Event

Viral gastroenteritis is the most common causal agent of public health problems worldwide. Noroviruses cause nonbacterial acute gastroenteritis in humans of all ages. In this study, we investigated the occurrence of norovirus infection in children with acute gastroenteritis admitted to university hospitals in South Korea. We also analyzed the genetic diversity of the viruses and identified novel recombination events among the identified viral strains. Of 502 children with acute gastroenteritis admitted to our three hospitals between January 2011 and March 2012, genotyping of human noroviruses was performed in 171 (34%) norovirus-positive samples. Of these samples, 170 (99.5%) were in genogroup II (GII), while only one (0.5%) was in genogroup I (GI). The most common GII strain was the GII.4-2006b variant (n = 96, 56.5%), followed by GII.6 (n = 23, 13.5%), GII.12 (n = 22, 12.9%), GII.3 (n = 20, 11.8%), GII.2 (n = 6, 3.5%), GII.b (n = 2, 1.2%), and GII.10 (n = 1, 0.6%). Potential recombination events (polymerase/capsid) were detected in 39 GII strains (22.9%), and the most frequent genotypes were GII.4/GII.12 (n = 12, 30.8%), GII.4/GII.6 (n = 12, 30.8%), GII.4/GII.3 (n = 8, 20.5%), GII.b/GII.3 (n = 3, 7.7%), GII.16/GII.2 (n = 2, 5.1%), GII.4/GII.2 (n = 1, 2.6%), and GII.2/GII.10 (n = 1, 2.6%). For the first time, a novel GII.2/GII.10 recombination was detected; we also identified the GII.16/GII.2 strain for the first time in South Korea. Our data provided important insights into new recombination events, which may prove valuable for predicting the emergence of circulating norovirus strains with global epidemic potential.     

Genome Wide Association Study Identifies 20 Novel Promising Genes Associated with Milk Fatty Acid Traits in Chinese Holstein

Detecting genes associated with milk fat composition could provide valuable insights into the complex genetic networks of genes underling variation in fatty acids synthesis and point towards opportunities for changing milk fat composition via selective breeding. In this study, we conducted a genome-wide association study (GWAS) for 22 milk fatty acids in 784 Chinese Holstein cows with the PLINK software. Genotypes were obtained with the Illumina BovineSNP50 Bead chip and a total of 40,604 informative, high-quality single nucleotide polymorphisms (SNPs) were used. Totally, 83 genome-wide significant SNPs and 314 suggestive significant SNPs associated with 18 milk fatty acid traits were detected. Chromosome regions that affect milk fatty acid traits were mainly observed on BTA1, 2, 5, 6, 7, 9, 13, 14, 18, 19, 20, 21, 23, 26 and 27. Of these, 146 SNPs were associated with more than one milk fatty acid trait; most of studied fatty acid traits were significant associated with multiple SNPs, especially C18:0 (105 SNPs), C18 index (93 SNPs), and C14 index (84 SNPs); Several SNPs are close to or within the DGAT1, SCD1 and FASN genes which are well-known to affect milk composition traits of dairy cattle. Combined with the previously reported QTL regions and the biological functions of the genes, 20 novel promising candidates for C10:0, C12:0, C14:0, C14:1, C14 index, C18:0, C18:1n9c, C18 index, SFA, UFA and SFA/UFA were found, which composed of HTR1B, CPM, PRKG1, MINPP1, LIPJ, LIPK, EHHADH, MOGAT1, ECHS1, STAT1, SORBS1, NFKB2, AGPAT3, CHUK, OSBPL8, PRLR, IGF1R, ACSL3, GHR and OXCT1. Our findings provide a groundwork for unraveling the key genes and causal mutations affecting milk fatty acid traits in dairy cattle.     

Variants Identified by Hepatocellular Carcinoma and Chronic Hepatitis B Virus Infection Susceptibility GWAS Associated with Survival in HBV-Related Hepatocellular Carcinoma

Recent genome-wide association studies (GWAS) have identified several common susceptibility loci associated with the risk of hepatocellular carcinoma (HCC) or chronic hepatitis B infection (CHB). However, the relationship between these genetic variants and survival of patients with hepatitis B virus (HBV)-related HCC is still unknown. In this study, 22 single nucleotide polymorphisms (SNPs) were genotyped among 330 HBV-related HCC patients using the MassARRAY system from Sequenom. Cox proportional hazards regression was used to examine the effects of genotype on survival time under an additive model with age, sex, smoking status and clinical stage as covariates. We identified four SNPs on 6p21 (rs1419881 T>C, rs7453920 G>A,rs3997872 G>A and rs7768538 T>C), and two SNPs on 8p12 (rs2275959 C>T and rs7821974 C>T) significantly associated with survival time of HBV-related HCC patients. Our results suggest that HCC or CHB susceptibility loci might also affect the prognosis of patients with HBV-related HCC.     

Toxocara Seroprevalence among Clinically Healthy Individuals,Pregnant Women and Psychiatric Patients and Associated Risk Factors in Shandong Province,Eastern China

Background

Toxocarosis is a widespread zoonosis caused by the ascarid nematodes Toxocara canis and Toxocara cati, which primarily infect dogs and cats, respectively. Most human infections with Toxocara are asymptomatic; however, some infected individuals may develop a serious illness and even death. Nevertheless, epidemiological knowledge regarding the prevalence and risks associated with Toxocara infection is limited in China. Therefore, we performed a cross-sectional pilot study and estimated the seroprevalence of Toxocara infection in humans in Shandong Province, eastern China for the first time, from June 2011 to July 2013, involving clinically healthy individuals, pregnant women and psychiatric patients, aiming to attract public attention to Toxocara infection.

Methodology/Principle Findings

Seroprevalence of Toxocara was determined using an enzyme-linked immunosorbent assay based on a cross-sectional study conducted in Qingdao and Weihai, Shandong Province, eastern China. Factors potentially associated with Toxocara infection were identified by logistic regression analysis. The overall Toxocara seroprevalence among the study population (n = 2866) was 12.25%, and a significantly higher seroprevalence in psychiatric patients (16.40%, 73/445) than that in clinically healthy individuals (13.07%, 187/1431) and pregnant women (9.19%, 91/990) was revealed. Univariate analyses suggested that keeping dogs at home (OR = 0.06, 95% CI 0.05–0.08, P<0.001), contact with cats and dogs (OR = 0.42, 95% CI 0.33–0.53, P<0.001) and exposure with soil (OR = 0.37, 95% CI 0.28–0.49, P<0.001) were risk factors associated with Toxocara infection.

Conclusions/Significance

The present study revealed, for the first time, that human infection with Toxocara is common in eastern China, posing a significant public health concern. Increasing human and dog populations, population movements and climate change all will serve to increase the importance of this zoonosis. Further studies under controlled conditions are necessary to define potential morbidity associated with Toxocara infection.     

Systematic comparison of a two-dimensional ion trap and a three-dimensional ion trap mass spectrometer in proteomics

The utility and advantages of the recently introduced two-dimensional quadrupole ion trap mass spectrometer in proteomics over the traditional three-dimensional ion trap mass spectrometer have not been systematically characterized. Here we rigorously compared the performance of these two platforms by using over 100,000 tandem mass spectra acquired with identical complex peptide mixtures and acquisition parameters. Specifically we compared four factors that are critical for a successful proteomic study: 1) the number of proteins identified, 2) sequence coverage or the number of peptides identified for every protein, 3) the data base matching SEQUEST X(corr) and S(p) score, and 4) the quality of the fragment ion series of peptides. We found a 4-6-fold increase in the number of peptides and proteins identified on the two-dimensional ion trap mass spectrometer as a direct result of improvement in all the other parameters examined. Interestingly more than 70% of the doubly and triply charged peptides, but not the singly charged peptides, showed better quality of fragmentation spectra on the two-dimensional ion trap. These results highlight specific advantages of the two-dimensional ion trap over the conventional three-dimensional ion traps for protein identification in proteomic experiments.     

Evaluation of caffeic acid amide analogues as anti-platelet aggregation and anti-oxidative agents

A series of amides of caffeic acid were synthesized and evaluated for their anti-platelet and anti-oxidative activities. N-(2-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (12) and N-(3-Bromo-phenyl)-3-(3,4-dihydroxy-phenyl)-acrylamide (13) exhibited potent inhibitory activity (IC(50)=5.8 and 6.7 microM, respectively) against arachidonic acid-induced (AA) platelet aggregation, comparable with invalid caffeic acid. Most of the synthesized caffeic acid anilides exhibited the promising anti-platelet aggregation in AA-induced assay and anti-oxidative activities. This study also exhibited that caffeic anilides displayed more potent anti-oxidative activity in the radical scavenging activity assay than trolox and vitamin E.     

Retrieving backbone string neighbors provides insights into structural modeling of membrane proteins

Identification of protein structural neighbors to a query is fundamental in structure and function prediction. Here we present BS-align, a systematic method to retrieve backbone string neighbors from primary sequences as templates for protein modeling. The backbone conformation of a protein is represented by the backbone string, as defined in Ramachandran space. The backbone string of a query can be accurately predicted by two innovative technologies: a knowledge-driven sequence alignment and encoding of a backbone string element profile. Then, the predicted backbone string is employed to align against a backbone string database and retrieve a set of backbone string neighbors. The backbone string neighbors were shown to be close to native structures of query proteins. BS-align was successfully employed to predict models of 10 membrane proteins with lengths ranging between 229 and 595 residues, and whose high-resolution structural determinations were difficult to elucidate both by experiment and prediction. The obtained TM-scores and root mean square deviations of the models confirmed that the models based on the backbone string neighbors retrieved by the BS-align were very close to the native membrane structures although the query and the neighbor shared a very low sequence identity. The backbone string system represents a new road for the prediction of protein structure from sequence, and suggests that the similarity of the backbone string would be more informative than describing a protein as belonging to a fold.