Genes,psychological traits and civic engagement

Civic engagement is a classic example of a collective action problem: while civic participation improves life in the community as a whole, it is individually costly and thus there is an incentive to free ride on the actions of others. Yet, we observe significant inter-individual variation in the degree to which people are in fact civically engaged. Early accounts reconciling the theoretical prediction with empirical reality focused either on variation in individuals’ material resources or their attitudes, but recent work has turned to genetic differences between individuals. We show an underlying genetic contribution to an index of civic engagement (0.41), as well as for the individual acts of engagement of volunteering for community or public service activities (0.33), regularly contributing to charitable causes (0.28) and voting in elections (0.27). There are closer genetic relationships between donating and the other two activities; volunteering and voting are not genetically correlated. Further, we show that most of the correlation between civic engagement and both positive emotionality and verbal IQ can be attributed to genes that affect both traits. These results enrich our understanding of the way in which genetic variation may influence the wide range of collective action problems that individuals face in modern community life.     

A novel series of IKKβ inhibitors part II: description of a potent and pharmacologically active series of analogs

A novel series of (E)-1-((2-(1-methyl-1H-imidazol-5-yl) quinolin-4-yl) methylene) thiosemicarbazides was discovered as potent inhibitors of IKKβ. In this Letter we document our efforts at further optimization of this series, culminating in 2 with submicromolar potency in a HWB assay and efficacy in a CIA mouse model.     

Proteolysis of the matricellular protein hevin by matrix metalloproteinase-3 produces a SPARC-like fragment (SLF) associated with neovasculature in a murine glioma model

The matricellular SPARC-family member hevin (Sparc-like 1/SPARCL-1/SC1/Mast9) contributes to neural development and alters tumor progression in a range of mammalian models. Based on sequence similarity, we hypothesized that proteolytic digestion of hevin would result in SPARC-like fragments (SLF) that affect the activity and/or location of these proteins. Incubation of hevin with matrix metalloproteinase-3 (MMP-3), a protease known to cleave SPARC, produced a limited number of peptides. Sequencing revealed the major proteolytic products to be SPARC-like in primary structure. In gliomas implanted into murine brain, a SLF was associated with SPARC in the neovasculature but not with hevin, the latter prominent in the astrocytes encompassed by infiltrating tumor. In this model of invasive glioma that involves MMP-3 activity, host-derived SLF was not observed in the extracellular matrix adjacent to tumor cells. In contrast, it occurred with its homolog SPARC in the angiogenic response to the tumor. We conclude that MMP-3-derived SLF is a marker of neovessels in glioma, where it could influence the activity of SPARC.     

OTUbase: an R infrastructure package for operational taxonomic unit data

SUMMARY: OTUbase is an R package designed to facilitate the analysis of operational taxonomic unit (OTU) data and sequence classification (taxonomic) data. Currently there are programs that will cluster sequence data into OTUs and/or classify sequence data into known taxonomies. However, there is a need for software that can take the summarized output of these programs and organize it into easily accessed and manipulated formats. OTUbase provides this structure and organization within R, to allow researchers to easily manipulate the data with the rich library of R packages currently available for additional analysis. AVAILABILITY: OTUbase is an R package available through Bioconductor. It can be found at http://www.bioconductor.org/packages/release/bioc/html/OTUbase.html.     

Covalent surface chemistry gradients for presenting bioactive peptides

The activation of surfaces by covalent attachment of bioactive moieties is an important strategy for improving the performance of biomedical materials. Such techniques have also been used as tools to study cellular responses to particular chemistries of interest. The creation of gradients of covalently bound chemistries is a logical extension of this technique. Gradient surfaces may permit the rapid screening of a large range of concentrations in a single experiment. In addition, the biological response to the gradient itself may provide new information on receptor requirements and cell signaling. The current work describes a rapid and flexible technique for the covalent addition of bioactive peptide gradients to a surface or gel and a simple fluorescence technique for assaying the gradient. In this technique, bioactive peptides with a terminal cysteine are bound via a heterobifunctional coupling agent to primary amine-containing surfaces and gels. A gradient in the coupling agent is created on the surfaces or gels by varying the residence time of the coupling agent across the surface or gel, thereby controlling the extent of reaction. We demonstrate this technique using poly(l-lysine)-coated glass surfaces and fibrin gels. Once the surface or gel has been activated by the addition of the coupling agent gradient, the bioactive peptide is added. Quantitation of the gradient is achieved by measuring the reaction kinetics of the coupling agent with the surface or gel of interest. This can be done either by fluorescently labeling the coupling agent (in the case of surfaces) or by spectrophotometrically detecting the release of pyridine-2-thione, which is produced when the thiol-reactive portion of the coupling agent reacts. By these methods, we can obtain reasonably precise estimates for the peptide gradients without using expensive spectroscopic or radiolabeling techniques. Validation with changes in fibroblast cell migration behavior across a bioactive peptide gradient illustrates preservation of peptide function as well as the usefulness of this technique.     

Inferring protein interactions from phylogenetic distance matrices

Finding the interacting pairs of proteins between two different protein families whose members are known to interact is an important problem in molecular biology. We developed and tested an algorithm that finds optimal matches between two families of proteins by comparing their distance matrices. A distance matrix provides a measure of the sequence similarity of proteins within a family. Since the protein sets of interest may have dozens of proteins each, the use of an efficient approximate solution is necessary. Therefore the approach we have developed consists of a Metropolis Monte Carlo optimization algorithm which explores the search space of possible matches between two distance matrices. We demonstrate that by using this algorithm we are able to accurately match chemokines and chemokine-receptors as well as the tgfbeta family of ligands and their receptors.     

Comparative Genomic Analysis of 60 Mycobacteriophage Genomes: Genome Clustering, Gene Acquisition, and Gene Size

Mycobacteriophages are viruses that infect mycobacterial hosts. Expansion of a collection of sequenced phage genomes to a total of 60—all infecting a common bacterial host—provides further insight into their diversity and evolution. Of the 60 phage genomes, 55 can be grouped into nine clusters according to their nucleotide sequence similarities, 5 of which can be further divided into subclusters; 5 genomes do not cluster with other phages. The sequence diversity between genomes within a cluster varies greatly; for example, the 6 genomes in Cluster D share more than 97.5% average nucleotide similarity with one another. In contrast, similarity between the 2 genomes in Cluster I is barely detectable by diagonal plot analysis. In total, 6858 predicted open-reading frames have been grouped into 1523 phamilies (phams) of related sequences, 46% of which possess only a single member. Only 18.8% of the phams have sequence similarity to non-mycobacteriophage database entries, and fewer than 10% of all phams can be assigned functions based on database searching or synteny. Genome clustering facilitates the identification of genes that are in greatest genetic flux and are more likely to have been exchanged horizontally in relatively recent evolutionary time. Although mycobacteriophage genes exhibit a smaller average size than genes of their host (205 residues compared with 315), phage genes in higher flux average only 100 amino acids, suggesting that the primary units of genetic exchange correspond to single protein domains.     

Do Lions Panthera leo Actively Select Prey or Do Prey Preferences Simply Reflect Chance Responses via Evolutionary Adaptations to Optimal Foraging?

Research on coursing predators has revealed that actions throughout the predatory behavioral sequence (using encounter rate, hunting rate, and kill rate as proxy measures of decisions) drive observed prey preferences. We tested whether similar actions drive the observed prey preferences of a stalking predator, the African lion Panthera leo. We conducted two 96 hour, continuous follows of lions in Addo Elephant National Park seasonally from December 2003 until November 2005 (16 follows), and compared prey encounter rate with prey abundance, hunt rate with prey encounter rate, and kill rate with prey hunt rate for the major prey species in Addo using Jacobs' electivity index. We found that lions encountered preferred prey species far more frequently than expected based on their abundance, and they hunted these species more frequently than expected based on this higher encounter rate. Lions responded variably to non-preferred and avoided prey species throughout the predatory sequence, although they hunted avoided prey far less frequently than expected based on the number of encounters of them. We conclude that actions of lions throughout the predatory behavioural sequence, but particularly early on, drive the prey preferences that have been documented for this species. Once a hunt is initiated, evolutionary adaptations to the predator-prey interactions drive hunting success.     

Complete genome sequence of Mahella australiensis type strain (50-1 BON)

Mahella australiensis Bonilla Salinas et al. 2004 is the type species of the genus Mahella, which belongs to the family Thermoanaerobacteraceae. The species is of interest because it differs from other known anaerobic spore-forming bacteria in its G+C content, and in certain phenotypic traits, such as carbon source utilization and relationship to temperature. Moreover, it has been discussed that this species might be an indigenous member of petroleum and oil reservoirs. This is the first completed genome sequence of a member of the genus Mahella and the ninth completed type strain genome sequence from the family Thermoanaerobacteraceae. The 3,135,972 bp long genome with its 2,974 protein-coding and 59 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.