Extracting Functional Modules from Biological Pathways

It has been proposed that functional modules are the fundamental units of cellular function. Methods to identify these modules have thus far relied on gene expression data or protein-protein interaction (PPI) data, but have a few limitations. We propose a new method, using biological pathway data to identify functional modules, that can potentially overcome these limitations. We also construct a network of these modules using functionally relevant PPI data. This network displays the flow and integration of information between modules and can be used to map cellular function

Effect of Mg/B ratio on the superconductivity of MgB2 bulk with SiC addition

To improve the self-field critical current density (Jc) and critical temperature (Tc) in SiC-doped MgB2, optimization of the nominal Mg/B mixing ratio has been performed. The effects of the nominal Mg/B mixing ratio (x:2) on the superconductivity, Raman spectra, current transport properties, and flux pinning mechanisms in MgB2 with 10 wt.% SiC doping were investigated systematically, with x varied from 1 to 1.2. It has been found that the sample with the Mg/B ratio of 1.15:2 exhibited the best Jc performance for all fields (0–8.5 T), and its Tc was also enhanced. The optimized Mg/B ratio diminished the interband scattering caused by Mg or B vacancies, and in turn, increased Tc. The connectivity and disorder were increased in the Mg1.15B2 sample. Both of these were responsible for the improved Jc under all the fields examined

Alterations of neural activity in the prefrontal cortex associated with deficits in working memory performance

Working memory (WM), a core cognitive function, enables the temporary holding and manipulation of information in mind to support ongoing behavior. Neurophysiological recordings conducted in nonhuman primates have revealed neural correlates of this process in a network of higher-order cortical regions, particularly the prefrontal cortex (PFC). Here, we review the circuit mechanisms and functional importance of WM-related activity in these areas. Recent neurophysiological data indicates that the absence of these neural correlates at different stages of WM is accompanied by distinct behavioral deficits, which are characteristic of various disease states/normal aging and which we review here. Finally, we discuss emerging evidence of electrical stimulation ameliorating these WM deficits in both humans and non-human primates. These results are important for a basic understanding of the neural mechanisms supporting WM, as well as for translational efforts to developing therapies capable of enhancing healthy WM ability or restoring WM from dysfunction

Genome-wide investigation reveals high evolutionary rates in annual model plants

<p>Abstract</p> <p>Background</p> <p>Rates of molecular evolution vary widely among species. While significant deviations from molecular clock have been found in many taxa, effects of life histories on molecular evolution are not fully understood. In plants, annual/perennial life history traits have long been suspected to influence the evolutionary rates at the molecular level. To date, however, the number of genes investigated on this subject is limited and the conclusions are mixed. To evaluate the possible heterogeneity in evolutionary rates between annual and perennial plants at the genomic level, we investigated 85 nuclear housekeeping genes, 10 non-housekeeping families, and 34 chloroplast genes using the genomic data from model plants including <it>Arabidopsis thaliana </it>and <it>Medicago truncatula </it>for annuals and grape (<it>Vitis vinifera</it>) and popular (<it>Populus trichocarpa</it>) for perennials.</p> <p>Results</p> <p>According to the cross-comparisons among the four species, 74-82% of the nuclear genes and 71-97% of the chloroplast genes suggested higher rates of molecular evolution in the two annuals than those in the two perennials. The significant heterogeneity in evolutionary rate between annuals and perennials was consistently found both in nonsynonymous sites and synonymous sites. While a linear correlation of evolutionary rates in orthologous genes between species was observed in nonsynonymous sites, the correlation was weak or invisible in synonymous sites. This tendency was clearer in nuclear genes than in chloroplast genes, in which the overall evolutionary rate was small. The slope of the regression line was consistently lower than unity, further confirming the higher evolutionary rate in annuals at the genomic level.</p> <p>Conclusions</p> <p>The higher evolutionary rate in annuals than in perennials appears to be a universal phenomenon both in nuclear and chloroplast genomes in the four dicot model plants we investigated. Therefore, such heterogeneity in evolutionary rate should result from factors that have genome-wide influence, most likely those associated with annual/perennial life history. Although we acknowledge current limitations of this kind of study, mainly due to a small sample size available and a distant taxonomic relationship of the model organisms, our results indicate that the genome-wide survey is a promising approach toward further understanding of the mechanism determining the molecular evolutionary rate at the genomic level.</p

Rapidly Evolving R Genes in Diverse Grass Species Confer Resistance to Rice Blast Disease

We show that the genomes of maize, sorghum, and brachypodium contain genes that, when transformed into rice, confer resistance to rice blast disease. The genes are resistance genes (R genes) that encode proteins with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains (NBS–LRR proteins). By using criteria associated with rapid molecular evolution, we identified three rapidly evolving R-gene families in these species as well as in rice, and transformed a randomly chosen subset of these genes into rice strains known to be sensitive to rice blast disease caused by the fungus Magnaporthe oryzae. The transformed strains were then tested for sensitivity or resistance to 12 diverse strains of M. oryzae. A total of 15 functional blast R genes were identified among 60 NBS–LRR genes cloned from maize, sorghum, and brachypodium; and 13 blast R genes were obtained from 20 NBS–LRR paralogs in rice. These results show that abundant blast R genes occur not only within species but also among species, and that the R genes in the same rapidly evolving gene family can exhibit an effector response that confers resistance to rapidly evolving fungal pathogens. Neither conventional evolutionary conservation nor conventional evolutionary convergence supplies a satisfactory explanation of our findings. We suggest a unique mechanism termed “constrained divergence,” in which R genes and pathogen effectors can follow only limited evolutionary pathways to increase fitness. Our results open avenues for R-gene identification that will help to elucidate R-gene vs. effector mechanisms and may yield new sources of durable pathogen resistance.Organismic and Evolutionary Biolog