SNA--a toolbox for the stoichiometric analysis of metabolic networks

BACKGROUND: Despite recent algorithmic and conceptual progress, the stoichiometric network analysis of large metabolic models remains a computationally challenging problem. RESULTS: SNA is a interactive, high performance toolbox for analysing the possible steady state behaviour of metabolic networks by computing the generating and elementary vectors of their flux and conversions cones. It also supports analysing the steady states by linear programming. The toolbox is implemented mainly in Mathematica and returns numerically exact results. It is available under an open source license from: http://bioinformatics.org/project/?group_id=546. CONCLUSION: Thanks to its performance and modular design, SNA is demonstrably useful in analysing genome scale metabolic networks. Further, the integration into Mathematica provides a very flexible environment for the subsequent analysis and interpretation of the results.

Transport model of the human Na+-coupled L-ascorbic acid (vitamin C) transporter SVCT1

Vitamin C (L-ascorbic acid) is an essential micronutrient that serves as an antioxidant and as a cofactor in many enzymatic reactions. Intestinal absorption and renal reabsorption of the vitamin is mediated by the epithelial apical L-ascorbic acid cotransporter SVCT1 (SLC23A1). We explored the molecular mechanisms of SVCT1-mediated L-ascorbic acid transport using radiotracer and voltage-clamp techniques in RNA-injected Xenopus oocytes. L-ascorbic acid transport was saturable (K(0.5) approximately 70 microM), temperature dependent (Q(10) approximately 5), and energized by the Na(+) electrochemical potential gradient. We obtained a Na(+)-L-ascorbic acid coupling ratio of 2:1 from simultaneous measurement of currents and fluxes. L-ascorbic acid and Na(+) saturation kinetics as a function of cosubstrate concentrations revealed a simultaneous transport mechanism in which binding is ordered Na(+), L-ascorbic acid, Na(+). In the absence of L-ascorbic acid, SVCT1 mediated pre-steady-state currents that decayed with time constants 3-15 ms. Transients were described by single Boltzmann distributions. At 100 mM Na(+), maximal charge translocation (Q(max)) was approximately 25 nC, around a midpoint (V(0.5)) at -9 mV, and with apparent valence approximately -1. Q(max) was conserved upon progressive removal of Na(+), whereas V(0.5) shifted to more hyperpolarized potentials. Model simulation predicted that the pre-steady-state current predominantly results from an ion-well effect on binding of the first Na(+) partway within the membrane electric field. We present a transport model for SVCT1 that will provide a framework for investigating the impact of specific mutations and polymorphisms in SLC23A1 and help us better understand the contribution of SVCT1 to vitamin C metabolism in health and disease.

Equality and Diversity in the Dutch Welfare State

Under the Constitution, the equality principle is very important in the Netherlands. This article argues that there is little evidence for equal citizenship in the Netherlands. There is anti-discrimination legislation in the Netherlands, but it is not very robust. The core argument in this article is that the equality principle must be supplemented by the diversity principle. Diversity is multi-dimensional and can refer to religion, philosophy of life, political persuasion, race (ethnicity), gender, nationality, sexual orientation, age, disability and chronic illness. In this paper multi-culturalism and disability are taken into account and we make a comparison of the social position of disabled people and people from ethnic minorities. Policies on diversity are needed to arrive at diverse citizenship in a varied society. This implies that a distinction has to be made between political citizenship and cultural citizenship. The former has to do with equality, and the latter with diversity.