Metabolic reconstructions identify plant 3‐methylglutaconyl‐CoA hydratase that is crucial for branched‐chain amino acid catabolism in mitochondria

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144600/1/tpj13955_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144600/2/tpj13955.pd

A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in \u3ci\u3eArabidopsis\u3c/i\u3e

Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylatebridged di-iron domain, At1g24340 is homologous to FADdependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone’s ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of ho

Conduite d’essais relatifs aux politiques qui soutiennent le modèle d’intervention accordant la priorité au logement : l’histoire de deux pays

L’article décrit les contextes entourant les politiques qui soutiennent l’application du modèle d’intervention qui accorde la priorité au logement (Housing First) pour les personnes itinérantes présentant des troubles mentaux au Canada et en France. Le modèle consiste en une modalité d’intervention complexe qui élargit le concept de traitement en santé mentale pour y inclure la notion de logement. La démarche, axée sur le rétablissement, place le choix de l’usager quant au logement et aux services de soutien au centre de la philosophie de la prestation de soins. L’article décrit deux essais multicentriques liés à l’intervention qui se déroulent dans deux pays et précise en quoi ils se ressemblent ou diffèrent, compte tenu des particularités culturelles et sociales. Les essais pragmatiques portant sur des modalités d’intervention complexes représentent des défis et ont un pouvoir d’influence unique. C’est ce dont tiennent compte les deux études.This paper describes the policy environments supporting housing first as an intervention for those who are homeless and mentally ill in Canada and in France. Housing first is a complex intervention that expands mental health treatment to include a focus upon housing.  A recovery orientation places the consumer’s choice of housing and supports at the center of the philosophy of care. The design of two, large multi-site intervention trials underway in both countries are described, noting similarities and differences related to the cultural and social context. Pragmatic trials of complex interventions have unique challenges and potential for influence, which both studies are addressing