The cationic region of Rhes mediates its interactions with specific Gβ subunits

Ras homologue enriched in striatum (Rhes) is a small monomeric G protein which functions in a variety of cellular processes, including attenuation of G protein-coupled receptor (GPCR)signalling. There have been many studies into the effects of Rhes, but there is no molecular information about how Rhes might bring about these effects. Rhes shares striking sequence homology to AGS1 (activator of G protein signalling 1) and we considered whether the two proteins function in similar ways. AGS1 binds to the Gβ1 subunit of heterotrimeric G proteins and we have used yeast two-hybrid studies to show that Rhes binds selectively to Gβ1, Gβ2 and Gβ3 subunits. Binding to the Gβ subunits involves the cationic regions of AGS1 and Rhes, and we used Rhes-AGS1 chimeras to show that their different cationic regions determine the Gβ-specificity of the interactions. Possible implications of this interaction for the activity of Rhes are discussed

Predictions of structural elements for the binding of Hin recombinase with the hix site of DNA

Molecular dynamics simulations were coupled with experimental data from biochemistry and genetics to generate a theoretical structure for the binding domain of Hin recombinase complexed with the hix site of DNA. The theoretical model explains the observed sequence specificity of Hin recombinase and leads to a number of testable predictions concerning altered sequence selectivity for various mutants of protein and DNA. Combining molecular dynamics simulations with constraints based on current knowledge of protein structure leads to a theoretical structure of the binding domain of Hin recombinase with the hix site of DNA. The model offers a mechanistic explanation of the presently known characteristics of Hin and predicts the effects of specific mutations of both protein and DNA. The predictions can be tested by currently feasible experiments that should lead to refinements in and improvements on the current theoretical model. Because current experimental and theoretical methods are all limited to providing only partial information about protein-DNA interactions, we believe that this approach of basing molecular simulations on experimental knowledge and using the results of these simulations to design new, more precise experimental tests will be of general utility. These results provide additional evidence for the generality of the helix-turn-helix motif in DNA recognition and stabilization of proteins on DNA

Exploring the antecedents to the online customer engagement behaviours; sharing, learning & endorsing

The aim of this research is to add to the growing empirical research around customer engagement and examine if motivational drivers mediate the relationship between personality traits and the online customer engagement behaviours (OCEB); sharing, learning and endorsing. The research was undertaken using an online survey with 401 respondents who interacted with brands online using social media sites; Facebook, Twitter and Instagram. The study provides evidence that the antecedents to online customer engagement behaviour not only interact but that together personality traits and motivational drivers impact specific types of OCEB. These findings help to deepen the understanding of what influences customers to take part in specific OCEBs, and can be used by managers who are seeking to develop programs to strategically influence online customer engagement, to better understand these customers.

Note and Comment

The Permanent International Court of Justice - For the first time in history leading powers both great and small have been able to agree upon a plan for an international court of justice. The plan was formulated last summer by an advisory committee of jurists sitting at The Hague. Since then it has been submitted to the Council and the Assembly of the League of Nations and has been approved. It will come into operation as soon as the project has been ratified by a majority of the nations belonging to the Leagu

Molecular evolution of the Bovini tribe (Bovidae, Bovinae): Is there evidence of rapid evolution or reduced selective constraint in Domestic cattle?

BACKGROUND: If mutation within the coding region of the genome is largely not adaptive, the ratio of nonsynonymous (dN) to synonymous substitutions (dS) per site (dN/dS) should be approximately equal among closely related species. Furthermore, dN/dS in divergence between species should be equivalent to dN/dS in polymorphisms. This hypothesis is of particular interest in closely related members of the Bovini tribe, because domestication has promoted rapid phenotypic divergence through strong artificial selection of some species while others remain undomesticated. We examined a number of genes that may be involved in milk production in Domestic cattle and a number of their wild relatives for evidence that domestication had affected molecular evolution. Elevated rates of dN/dS were further queried to determine if they were the result of positive selection, low effective population size (N(e)) or reduced selective constraint. RESULTS: We have found that the domestication process has contributed to higher dN/dS ratios in cattle, especially in the lineages leading to the Domestic cow (Bos taurus) and Mithan (Bos frontalis) and within some breeds of Domestic cow. However, the high rates of dN/dS polymorphism within B. taurus when compared to species divergence suggest that positive selection has not elevated evolutionary rates in these genes. Likewise, the low rate of dN/dS in Bison, which has undergone a recent population bottleneck, indicates a reduction in population size alone is not responsible for these observations. CONCLUSION: The effect of selection depends on effective population size and the selection coefficient (N(e)s). Typically under domestication both selection pressure for traits important in fitness in the wild and Ne are reduced. Therefore, reduced selective constraint could be responsible for the observed elevated evolutionary ratios in domesticated species, especially in B. taurus and B. frontalis, which have the highest dN/dS in the Bovini. This may have important implications for tests of selection such as the McDonald-Kreitman test. Surprisingly we have also detected a significant difference in the supposed neutral substitution rate between synonymous and noncoding sites in the Bovine genome, with a 30% higher rate of substitution at synonymous sites. This is due, at least in part, to an excess of the highly mutable CpG dinucleotides at synonymous sites, which will have implications for time of divergence estimates from molecular data

Testing the neutral theory of molecular evolution using genomic data: a comparison of the human and bovine transcriptome

Despite growing evidence of rapid evolution in protein coding genes, the contribution of positive selection to intra- and interspecific differences in protein coding regions of the genome is unclear. We attempted to see if genes coding for secreted proteins and genes with narrow expression, specifically those preferentially expressed in the mammary gland, have diverged at a faster rate between domestic cattle (Bos taurus) and humans (Homo sapiens) than other genes and whether positive selection is responsible. Using a large data set, we identified groups of genes based on secretion and expression patterns and compared them for the rate of nonsynonymous (dN) and synonymous (dS) substitutions per site and the number of radical (Dr) and conservative (Dc) amino acid substitutions. We found evidence of rapid evolution in genes with narrow expression, especially for those expressed in the liver and mammary gland and for genes coding for secreted proteins. We compared common human polymorphism data with human-cattle divergence and found that genes with high evolutionary rates in human-cattle divergence also had a large number of common human polymorphisms. This argues against positive selection causing rapid divergence in these groups of genes. In most cases dN/dS ratios were lower in human-cattle divergence than in common human polymorphism presumably due to differences in the effectiveness of purifying selection between long-term divergence and short-term polymorphism

Note and Comment

James H. Brewster - Thousands of alumni and former students of the Law School will learn with deep regret of the sudden death of Professor Brewster in Denver, Colorado, on October 7, 1920

METHYL PARATHION RESIDUES IN PROTECTIVE APPAREL FABRIC: EFFECT OF RESIDUAL SOILS ON DECONTAMINATION

This study evaluated the contribution of oily and particulate soil residue to pesticide residue removal. 100% cotton and 65% polyester/35% cotton, were artificially soiled with a standard soil. The fabrics were laundered with the same substrate fabric without soil. Initial methyl parathion contamination was not dependent on the soil level or fiber content of the fabric. Residues remaining after laundering were affected by soiling level. Pesticide residues were greater when the fabric had a heavy soil build-up even though the initial contamination had been lower. Based on these findings, protective apparel should be kept as clean as possible, with daily laundering, for the presence of soil residue affected decontamination of the fabrics