A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures

MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA-pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA-pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA-pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes ("hubs"), most nodes in the miRNA-pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA-pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available.     

Treatment of fresh leachate with high-strength organics and calcium from municipal solid waste incineration plant using UASB reactor

Treatment of a fresh leachate with high-strength organics and calcium from municipal solid waste (MSW) incineration plant by an up-flow anaerobic sludge blanket (UASB) reactor was investigated under mesophilic conditions, emphasizing the influence of organic loading rate (OLR). When the reactor was fed with the raw leachate (COD as high as 70,390-75,480 mg/L) at an OLR of 12.5 kg COD/(m³ d), up to ∼82.4% of COD was removed suggesting the feasibility of UASB process for treating fresh leachates from incineration plants. The ratio of volatile solids/total solids (VS/TS) of the anaerobic sludge in the UASB decreased significantly after a long-term operation due to the precipitation of calcium carbonate in the granules. Scanning electron microscopy (SEM) observation shows that Methanosaeta-like species were in abundance, accompanied by a variety of other species. The result was further confirmed by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and sequencing.     

Green microwave-assisted synthesis of cellulose/calcium silicate nanocomposites in ionic liquids and recycled ionic liquids

Fabrication of biomass materials by a microwave-assisted method in ionic liquids allows the high value-added applications of biomass by combining three major green chemistry principles: using environmentally preferable solvents, using an environmentally friendly method, and making use of renewable biomass materials. Herein, we report a rapid and green microwave-assisted method for the synthesis of the cellulose/calcium silicate nanocomposites in ionic liquids and recycled ionic liquids. These calcium silicate nanoparticles or nanosheets as prepared were homogeneously dispersed in the cellulose matrix. The experimental results confirm that the ionic liquids can be used repeatedly. Of course, the slight differences were also observed using ionic liquids and recycled ionic liquids. Compared with other conventional methods, the rapid, green, and environmentally friendly microwave-assisted method in ionic liquids opens a new window to the high value-added applications of biomass.     

基于RAPD技术探讨黄精属部分药用植物系统位置

目的：从分子水平探讨黄精属部分药用植物间的系统位置。方法：采用RAPD分子标记方法,以同科万寿竹属植物宝铎草（Disporum sessile D．Don）为外类群,对百合科黄精属19批（6种）药用植物进行基因组DNA的多态性分析,通过聚类分析探讨黄精种属间亲缘关系。结果：筛选出7条随机引物,聚类结果表明,黄精属植物在属级分类上特征明显,但属内分类有交叉。结论：RAPD技术可以为黄精属的分类和种的鉴别提供一定的理论依据。     

Extent of height variability explained by known height-associated genetic variants in an isolated population of the Adriatic coast of Croatia

Background

Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2∼10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia.

Methodology/Principal Findings

In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20∼50 SNPs reported by the remaining individual GWA studies explained 3∼5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent.

Conclusions/Significance

We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.     

Towards online multiresolution community detection in large-scale networks

The investigation of community structure in networks has aroused great interest in multiple disciplines. One of the challenges is to find local communities from a starting vertex in a network without global information about the entire network. Many existing methods tend to be accurate depending on a priori assumptions of network properties and predefined parameters. In this paper, we introduce a new quality function of local community and present a fast local expansion algorithm for uncovering communities in large-scale networks. The proposed algorithm can detect multiresolution community from a source vertex or communities covering the whole network. Experimental results show that the proposed algorithm is efficient and well-behaved in both real-world and synthetic networks.     

The Hsp70 and Hsp40 chaperones influence microtubule stability in Chlamydomonas

Mutations at the APM1 and APM2 loci in the green alga Chlamydomonas reinhardtii confer resistance to phosphorothioamidate and dinitroaniline herbicides. Genetic interactions between apm1 and apm2 mutations suggest an interaction between the gene products. We identified the APM1 and APM2 genes using a map-based cloning strategy. Genomic DNA fragments containing only the DNJ1 gene encoding a type I Hsp40 protein rescue apm1 mutant phenotypes, conferring sensitivity to the herbicides and rescuing a temperature-sensitive growth defect. Lesions at five apm1 alleles include missense mutations and nucleotide insertions and deletions that result in altered proteins or very low levels of gene expression. The HSP70A gene, encoding a cytosolic Hsp70 protein known to interact with Hsp40 proteins, maps near the APM2 locus. Missense mutations found in three apm2 alleles predict altered Hsp70 proteins. Genomic fragments containing the HSP70A gene rescue apm2 mutant phenotypes. The results suggest that a client of the Hsp70-Hsp40 chaperone complex may function to increase microtubule dynamics in Chlamydomonas cells. Failure of the chaperone system to recognize or fold the client protein(s) results in increased microtubule stability and resistance to the microtubule-destabilizing effect of the herbicides. The lack of redundancy of genes encoding cytosolic Hsp70 and Hsp40 type I proteins in Chlamydomonas makes it a uniquely valuable system for genetic analysis of the function of the Hsp70 chaperone complex.