Genome sequencing analysis of Streptomyces coelicolor mutants that overcome the phosphate-depending vancomycin lethal effect

Abstract Background Glycopeptide antibiotics inhibit bacterial cell-wall synthesis, and are important for the treatment of infections caused by multi drug-resistant strains of enterococci, streptococci and staphylococci. The main mechanism by which bacteria resist the action of glycopeptides is by producing a modified cell-wall in which the dipeptide D-Alanine-D-Alanine is substituted by D-Alanine-D-Lactate or D-Alanine-D-Serine. Recently, it has been shown that inorganic phosphate (Pi) induces hypersensitivity to vancomycin in Streptomyces coelicolor (which is highly resistant to the antibiotic in low-Pi media). This finding was surprising because the bacterium possesses the entire set of genes responsible for vancomycin resistance (VR); including those coding for the histidine kinase/response regulator pair VanS/VanR that activates the system. Results This work shows that high Pi amounts in the medium hamper the activation of the van promoters and consequently inhibit VR in S. coelicolor; i.e. the repression effect being stronger when basic or acidic forms of the nutrient are used. In addition, this work shows that lysozyme resistance is also highly regulated by the Pi concentration in the medium. At least five different mutations contribute to the overcoming of this repression effect over VR (but not over lysozyme resistance). Therefore, the interconnection of VR and lysozyme resistance mechanisms might be inexistent or complex. In particular, two kinds of mutant in which Pi control of VR has been lost (one class expresses the van genes in a constitutive manner; the other retains inducibility by vancomycin) have been isolated and further characterized in this study. Sequencing revealed that the first class of mutation conferred a single amino acid substitution in the second transmembrane helix of the VanS protein; whereas the other class hampered the expression or activity of a putative homolog (SCO1213) to the staphylococcal GatD protein. Complementation, phenotypic and bioinformatics analyses identified SCO1213, and its upstream gene (i.e. murT), as relevant genetic determinants involved with VR in S. coelicolor. Conclusion The genomic approach of this study together with other genetic and phenotypic analyses has allowed the identification of the uncharacterized murT-gatD Streptomyces genes and the characterization of their involvement with the Pi control of VR in S. coelicolor

The morality of political liberalism

The paper discusses two ways to understand political liberalism. On the one hand, political liberalism may rely on the existence of an overlapping consensus among all reasonable comprehensive views present in our society. On the other hand, we may ground political liberalism on the moral value of equal respect for everyone. The dilemma between a factual identification of an overlapping consensus and a normative appeal to moral values arises at two levels. First, when we fill the content of our political conception of justice. And second, when we require impartiality to fill that content. In the former case, we may argue for a particular conception of justice through normative argument with moral premises, or our political conception of justice might be the area where all reasona-ble comprehensive views overlap. Similarly, we require that citizens offer impartial public reasons because this is what people holding different comprehensive views do think ap-propriate, or because they should consider it so. The author argues that we should define our political conception of justice through impartial normative argument, and that we should ground the demand of impartiality on the moral value of equal respect

Combustível "hidrogénio"

A partir da primeira crise petrolífera, na década de 70, passou-se a considerar o hidrogénio como uma possível fonte de energia, através da conversão electroquímica, usando células de combustível, que até então tinham como grande aplicação prática a utilização em missões espaciais. O hidrogénio pode ser considerado como uma fonte de energia intermédia, sendo necessário produzi-lo, transportá-lo e armazená-lo antes de o usar. É ainda preciso encontrar soluções tecnologicamente eficientes, económicas e seguras para o seu manuseamento. O hidrogénio é um combustível leve, mas com baixa densidade de massa por m 3 No entanto, sendo o . combustível de utilização mais eficiente, na prática, a relação de volume entre o hidrogénio e os combustíveis convencionais não lhe é assim tão desfavorável

Using torsion to manipulate spin currents

We address the problem of quantum particles moving on a manifold characterised by the presence of torsion along a preferential axis. In fact, such a torsion may be taylored by the presence of a single screw dislocation, whose Burgers vector measures the torsion amplitude. The problem, first treated in the relativistic limit describing fermions that couple minimally to torsion, is then analysed in the Pauli limit We show that torsion induces a geometric potential and also that it couples generically to the phase of the wave function, giving rise to the possibility of using torsion to manipulate spin currents in the case of spinor wave functions. These results emerge as an alternative strategy for using screw dislocations in the design of spintronic-based devices

Investment Rates and the Aggregate Production Function

In this paper we consider a simple version of the neoclassical growth model, and carry out an empirical analysis of the main determinants of aggregate investment across countries. More specifically, we study the effects on aggregate investment of income growth, capital income shares, the relative price of capital, and various market distortions. This exercise also sheds light into the shape of the neoclassical production function. We check these investment patterns for both OECD and non-OECD countries. We also decompose investment data into equipment and structures, and explore major factors affecting their relative pricesInvestment rates; Aggregate production function; Relative price of investment