Identification of spatial genetic boundaries using a multifractal model in human population genetics

There are two purposes in displaying spatial genetic structure. One is that a visual representation of the variation of the genetic variable should be provided in the contour map. The other is that spatial genetic structure should be reflected by the patterns or the gradients with genetic boundaries in the map. Nevertheless, most conventional interpolation methods, such as Cavalli-Sforza's method in genography, inverse distance-weighted methods, and the Kriging technique, focus only on the first primary purpose because of their arbitrary thresholds marked on the maps. In this paper we present an application of the contour area multifractal model (CAMM) to human population genetics. The method enables the analysis of the geographic distribution of a genetic marker and provides an insight into the spatial and geometric properties of obtained patterns. Furthermore, the CAMM may overcome some of the limitations of other interpolation techniques because no arbitrary thresholds are necessary in the computation of genetic boundaries. The CAMM is built by establishing power law relationships between the area A (> or =rho) in the contour map and the value p itself after plotting these values on a log-log graph. A series of straight-line segments can be fitted to the points on the log-log graph, each representing a power law relationship between the area A (> or =rho) and the cutoff genetic variable value for rho in a particular range. These straight-line segments can yield a group of cutoff values, which can be identified as the genetic boundaries that can classify the map of genetic variable into discrete genetic zones. These genetic zones usually correspond to spatial genetic structure on the landscape. To provide a better understanding of the interest in the CAMM approach, we analyze the spatial genetic structures of three loci (ABO, HLA-A, and TPOX) in China using the CAMM. Each synthetic principal component (SPC) contour map of the three loci is created by using both Han and minority groups data together. These contour maps all present an obvious geographic diversity, which gradually increases from north to south, and show that the genetic differences among populations in different districts of the same nationality are greater than those among different nationalities of the same district. It is surprising to find that both the value of p and the fractal dimension alpha have a clear north to south gradient for each locus, and the same clear boundary between southern and northern Asians in each contour map is still seen in the zone of the Yangtze River, although substantial population migrations have occurred because of war or famine in the last 2,000 or 3,000 years. A clear genetic boundary between Europeans and Asians in each contour map is still seen in northwestern China with a small value of alpha, although the genetic gradient caused by gene flow between Europeans and Asians has tended to show expansion from northwestern China. From the three contour maps another interesting result can be found: The values of alpha north of the Yangtze River are generally less than those south of the Yangtze River. This indicates that the genetic differences among the populations north of the Yangtze River are generally smaller than those in populations south of the Yangtze River.     

Mapping-by-Sequencing Identifies HvPHYTOCHROME C as a Candidate Gene for the early maturity 5 Locus Modulating the Circadian Clock and Photoperiodic Flowering in Barley

Phytochromes play an important role in light signaling and photoperiodic control of flowering time in plants. Here we propose that the red/far-red light photoreceptor HvPHYTOCHROME C (HvPHYC), carrying a mutation in a conserved region of the GAF domain, is a candidate underlying the early maturity 5 locus in barley (Hordeum vulgare L.). We fine mapped the gene using a mapping-by-sequencing approach applied on the whole-exome capture data from bulked early flowering segregants derived from a backcross of the Bowman(eam5) introgression line. We demonstrate that eam5 disrupts circadian expression of clock genes. Moreover, it interacts with the major photoperiod response gene Ppd-H1 to accelerate flowering under noninductive short days. Our results suggest that HvPHYC participates in transmission of light signals to the circadian clock and thus modulates light-dependent processes such as photoperiodic regulation of flowering.     

Determining the Precise Cerebral Response to Acupuncture: An Improved fMRI Study

Background

In acupuncture brain imaging trials, there are many non-acupuncture factors confounding the neuronal mapping. The modality of the placebo, subjects’ psychological attitude to acupuncture and their physical state are the three most confounding factors.

Objective

To obtain more precise and accurate cerebral fMRI mapping of acupuncture.

Design and Setting

A 2×2 randomized, controlled, participant-blinded cross-over factorial acupuncture trial was conducted at Xuanwu Hospital in Beijing, China.

Participants

Forty-one college students with myopia were recruited to participate in our study and were allocated randomly to four groups, Group A, Group B, Group C and Group D.

Interventions

Group A received real acupuncture (RA) and treatment instruction (TI); Group B received RA and non-treatment instruction (NI); Group C received sham acupuncture (SA) and TI; Group D received SA and NI.

Results

Stimulation at LR3 activated some areas of the visual cortex, and the cerebral response to non-acupuncture factors was complex and occurred in multiple areas.

Conclusions

The results provide more evidence regarding the credibility of acupuncture therapy and suggest that more precise experimental designs are needed to eliminate sources of bias in acupuncture controlled trials and to obtain sound results.     

Analysis of DYS19 and DYS287 polymorphisms in the Han population and three other ethnic groups of northeast China

The allelic distribution of the Y-chromosome specific microsatellite DYS19 in the Han population and in the Daur, Oroqen and Ewenki ethnic groups (Northeast China) was analyzed by PCR and denatured polyacrylamide gel electrophoresis. The allelic distribution in the Han population group is as follows: A = 2.90%, B = 26.09%, C = 26.09%, D = 29.98%, E = 15.94%. This allelic distribution differs statistically significant from that observed in the three other ethnic groups (p < 0.05). Furthermore the polymorphism of the Y-chromosome specific Alu insert sequence DYS287 was tested in these four groups. However, no Alu sequence insert was found.     

The role of dendritic cells regulated by HMGB1/TLR4 signalling pathway in myocardial ischaemia reperfusion injury

Inflammatory response plays an important role in ischaemia reperfusion injury (IRI) through a variety of inflammatory cells. Apart from neutrophils, macrophages and lymphocytes, the role of dendritic cells (DCs) in IRI has been noticed. The study was aimed at investigating whether the high‐mobility group protein box‐1/toll like receptor 4 (HMGB1/TLR4) signalling pathway regulate the migration, adhesion and aggregation of DCs to the myocardium, induce DCs activation and maturation, stimulate the expression of surface costimulatory molecules and participate in myocardial IRI. In vivo, migration, adhesion, and aggregation of DCs was enhanced; the expression of peripheral blood DCs CD80 and CD86, myocardial adhesion molecules were increased; and the infarct size was increased during myocardial ischaemia reperfusion injury myocardial ischemic/reperfusion injury (MI/RI). These responses induced by MI/RI were significantly inhibited by HMGB1 specific neutralizing antibody treatment. Cellular experiments confirmed that HMGB1 promoted the release of inflammatory cytokines through TLR4/MyD88/NF‐κB, upregulated CD80 and CD86 expression, mediated the damage of cardiomyocytes and accelerated the apoptosis. Our results indicate that DCs activation and maturation, stimulate the expression of surface costimulatory molecules by promoting the release of inflammatory factors through NF‐κB pathway and participate in myocardial IRI.     

中国产桫椤类配子体在不同基质胁迫下的形态畸变多样性研究

为了明确土壤污染对中国产桫椤科植物的生殖影响,以探讨中国桫椤类乃至其他濒危蕨类濒危的内在原因。该研究以中国产9种桫椤植物为材料,采用各植物原产地地表土壤培养孢子至配子体成熟,全程比较观察配子体畸变类型,统计畸变率;并分别取3个属的代表种笔筒树、大叶黑桫椤和中华桫椤的孢子,以MS培养基为对照,分别用5mg·kg^-1Pb^2+和1mg·kg^-1Cd^2+单因素胁迫培养配子体,比较观察各组的配子体形态畸变类型,统计畸变率。结果表明:(1)中国产桫椤类9种植物配子体培养过程中共出现17种形态畸变类型,其中4种为分化畸变,7种为假根畸变,4种为细胞畸变,2种为性器畸变。(2)不同培养基——对照组(MS培养基)、原产地土壤、Cd^2+胁迫、Pb^2+胁迫对中国产桫椤科9种植物配子体的平均畸变比例分别是2.28%、12.61%、31.58%和33.58%。(3)9种桫椤的配子体畸变类型及其畸变率均与培养基的胁迫程度呈正相关关系,其配子体发育都受到了产地土壤污染的严重伤害。(4)3种桫椤属植物配子体对土壤环境胁迫的耐受力强弱为黑桫椤属>白桫椤属>桫椤属。(5)桫椤科配子体的形态畸变多样性与胁迫条件之间具有稳定的对应关系。     

云南48种木兰科野生植物资源遗传多样性研究

为了解云南省木兰科（Magnoliaceae）野生植物资源的遗传多样性,利用ISSR分子标记技术对48种木兰科野生植物资源进行研究。结果表明,10对引物共扩增出151条带,均为多态性条带,多态性条带百分率为100%。总的观测等位基因数（N_a）为2.000 0,有效等位基因数（N_e）为1.564 5,Nei’s基因多样性指数（H）0.337 9,Shannon’s信息指数（I）为0.510 1。总的基因多样性指数（H_t）为0.368 0,属间基因多样性指数（D_st）为0.251 9,占68.4%,基因分化系数（G_st）为0.684 0,基因流（N_m）为0.231 0。UPGMA聚类分析将48种木兰科植物划分为7个类群,各类群并非按照属聚在一起,而是不同属植物相间分布,长喙厚朴（Magnolia rostrata）、素黄含笑（Michelia flaviflora）和球花含笑（M.sphaerantha）可能为云南省木兰科植物中的原始种。48种木兰科野生植物总体具有较高的遗传多样性,但属间遗传变异较高,基因流较小,存在遗传漂变的风险,聚类结果与刘玉壶的分类系统存在分歧,这从分子水平为木兰科植物间的起源、进化与分类提供了重要依据。     

Coexpression of EGFR and CXCR4 Predicts Poor Prognosis in Resected Pancreatic Ductal Adenocarcinoma

BackgroundEpidermal growth factor receptor (EGFR) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in tumorigenesis and development. However, EGFR expression alone has limited clinical and prognostic significance. Recently, the cross-talk between EGFR and G-protein-coupled chemokine receptor CXCR4 has become increasingly recognized.MethodsIn the present study, immunohistochemical staining of EGFR and CXCR4 was performed on paraffin-embedded specimens from 131 patients with surgically resected PDAC. Subsequently, the associations between EGFR expression, CXCR4 expression, EGFR/CXCR4 coexpression and clinicopathologic factors were assessed, and survival analyses were performed.ResultsIn total, 64 (48.9%) patients expressed EGFR, 68 (51.9%) expressed CXCR4, and 33 (25.2%) coexpressed EGFR and CXCR4. No significant association between EGFR and CXCR4 expression was observed (P = 0.938). EGFR expression significantly correlated with tumor differentiation (P = 0.031), whereas CXCR4 expression significantly correlated with lymph node metastasis (P = 0.001). EGFR/CXCR4 coexpression was significantly associated with lymph node metastasis (P = 0.026), TNM stage (P = 0.048), and poor tumor differentiation (P = 0.004). By univariate survival analysis, both CXCR4 expression and EGFR/CXCR4 coexpression were significant prognostic factors for poor disease-free survival (DFS) and overall survival (OS). Moreover, EGFR/CXCR4 coexpression significantly increased the hazard ratio for both recurrence and death compared with EGFR or CXCR4 protein expression alone. Multivariate survival analysis demonstrated that EGFR/CXCR4 coexpression was an independent prognostic factor for DFS (HR = 2.33, P<0.001) and OS (HR = 2.48, P = 0.001).ConclusionsIn conclusion, our data indicate that although EGFR expression alone has limited clinical and prognostic significance, EGFR/CXCR4 coexpression identified a subset of PDAC patients with more aggressive tumor characteristics and a significantly worse prognosis. Our results suggest a potentially important "cross-talk" between CXCR4 and EGFR intracellular pathways and indicate that the simultaneous inhibition of these pathways might be an attractive therapeutic strategy for PDAC.     

CRISPR Primer Designer:Design primers for knockout and chromosome imaging CRISPR-Cas system

The clustered regularly interspaced short palin-dromic repeats (CRISPR)-associated system enables biologists to edit genomes precisely and provides a powerful tool for perturbing endogenous gene regula...