The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties

There are two common forms of NRH-quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2-F47) and the other leucine (NQO2-L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2-L47 has a slightly lower specificity constant. NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. Both forms are inhibited by resveratrol, but NQO2-F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings. © 2014 Federation of European Biochemical Societies.

The Map of Watchful Architecture 2.0:Defensive forms along Ireland's border

For The Map of Watchful Architecture I only concerned myself with defensive architecture along the Border. As the map followed a border it came out as a wavy line of points. This was largely artificial, I only charted architecture within the Border corridor, but was not entirely artificial. That linear landscape has long been staked-out by the regularity of certain kinds of architecture. The 1st/2nd century Black Pig’s Dyke and Dorsey correspond with today’s Border. The concentration of souterrains in north Louth indicate that it may have been a volatile interface zone in later centuries. In 1618 Londonderry and its walls were built. Further north and two centuries later, Martello Towers were constructed to watch over Lough Foyle. During the Second World War pillboxes and observation posts were manned along the Border, close to what was now an international frontier. Then came the Operation Banner installations built during The Troubles. All this adds up to be one of the longest unbroken traditions of defensive architecture anywhere in Western Europe, a tradition some thought finally broken as the last of the Operation Banner towers were de-installed in 2007. But, take a bus south across the Border and you will often be pulled over by the Garda Síochána. They ID check the passengers in an attempt to stop illegal immigration via the UK. What about illegal immigrants who walk through the fields or along quiet lanes? They will have understood the Border is not really how it seems on most maps. It is not a solid line, it is a row of points.

Wahrnehmungs- und Betätigungsformen des Vertrauens im deutsch-französischen Vergleich:Representations, Forms and practice of Trust in French and German comparison

Thomas Würtenberger, Dieter K. Tscheulin, Jean-Claude Usunier, Dominique Jeannerod, Eric Davoine (Hrsg.):
Wahrnehmungs- und Betätigungsformen des Vertrauens im deutsch-französischen Vergleich
Berlin, Berlin GmbH, 2002

Relationships between Religion and Two Forms of Homonegativity in Europe—A Multilevel Analysis of Effects of Believing, Belonging and Religious Practice

This paper examines relationships between religion and two forms of homonegativity
across 43 European countries using a bivariate response binary logistic multilevel model. The model analyzes effects of religious believing, belonging and practice on two response variables: a) a moral rejection of homosexuality as a practice and b) intolerance toward homosexuals as a group. The findings indicate that both forms of homonegativity are prevalent in Europe. Traditional doctrinal religious believing (belief in a personal God) is positively related to a moral rejection of homosexuality but to a much lesser extent associated with intolerance toward homosexuals as a group. Members of religious denominations are more likely than non-members to reject homosexuality as morally wrong and to reject homosexuals as neighbors. The analysis found significant differences between denominations that are likely context-dependent. Attendance at religious services is positively related to homonegativity in a majority of countries. The findings vary considerably across countries: Religion is more strongly related to homonegativity in Western than in Eastern Europe. In the post-soviet countries homonegativity appears to be largely a secular phenomenon. National contexts of high religiosity, high perceived government corruption, high income inequality and shortcomings in the implementation of gay rights in the countries’ legislations are statistically related to higher levels of both moralistic homonegativity and intolerance toward homosexuals as a group.

Genome wide interactions of wild-type and activator bypass forms of σ54

Enhancer-dependent transcription involving the promoter specificity factor σ54 is widely distributed amongst bacteria and commonly associated with cell envelope function. For transcription initiation, σ54-RNA polymerase yields open promoter complexes through its remodelling by cognate AAA+ ATPase activators. Since activators can be bypassed in vitro, bypass transcription in vivo could be a source of emergent gene expression along evolutionary pathways yielding new control networks and transcription patterns. At a single test promoter in vivo bypass transcription was not observed. We now use genome-wide transcription profiling, genome-wide mutagenesis and gene over-expression strategies in Escherichia coli, to (i) scope the range of bypass transcription in vivo and (ii) identify genes which might alter bypass transcription in vivo. We find little evidence for pervasive bypass transcription in vivo with only a small subset of σ54 promoters functioning without activators. Results also suggest no one gene limits bypass transcription in vivo, arguing bypass transcription is strongly kept in check. Promoter sequences subject to repression by σ54 were evident, indicating loss of rpoN (encoding σ54) rather than creating rpoN bypass alleles would be one evolutionary route for new gene expression patterns. Finally, cold-shock promoters showed unusual σ54-dependence in vivo not readily correlated with conventional σ54 binding-sites.

AURKA overexpression accompanies dysregulation of DNA-damage response genes in invasive urothelial cell carcinoma

Invasive urothelial cell carcinoma (UCC) is characterized by increased chromosomal instability and follows an aggressive clinical course in contrast to non-invasive disease. To identify molecular processes that confer and maintain an aggressive malignant phenotype, we used a high-throughput genome-wide approach to interrogate a cohort of high and low clinical risk UCC tumors. Differential expression analyses highlighted cohesive dysregulation of critical genes involved in the G(2)/M checkpoint in aggressive UCC. Hierarchical clustering based on DNA Damage Response (DDR) genes separated tumors according to a pre-defined clinical risk phenotype. Using array-comparative genomic hybridization, we confirmed that the DDR was disrupted in tumors displaying high genomic instability. We identified DNA copy number gains at 20q13.2-q13.3 (AURKA locus) and determined that overexpression of AURKA accompanied dysregulation of DDR genes in high risk tumors. We postulated that DDR-deficient UCC tumors are advantaged by a selective pressure for AURKA associated override of M phase barriers and confirmed this in an independent tissue microarray series. This mechanism that enables cancer cells to maintain an aggressive phenotype forms a rationale for targeting AURKA as a therapeutic strategy in advanced stage UCC.