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These findings corroborate the relevance of sympathetic activation in PCOS and suggest that renal denervation exerts beneficial effects not only on blood pressure control but also on insulin sensitivity, renal, and endocrine abnormalities characteristic of PCOS.

in women, in two cohorts of older normal individuals. These risk alleles have previously been associated with schizophrenia, bipolar disorder, and social and physical anhedonia, mainly in females. 1,7 Reports suggest that heritability of neuroticism, anxiety and depression is higher in females than in males, and that the genes involved differ between men and women. [8][9][10] We tested SNPs and models specifically chosen on the basis of earlier evidence, and hence do not believe that stringent multiple testing corrections are appropriate, but these results need to be replicated in other suitable cohorts before variation in DISC1 is fully accepted as contributing to normal variation in neuroticism and mood. Conflict of interestThe authors declare no conflict of interest. In the central nervous system (CNS), the oxidative deamination of monoamine neurotransmitters is accomplished by two membrane-bound enzymes: monoamine oxidase (of which there are two isoforms, MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase (SSAO). The combined activities of these proteins are crucial for the regulation of neurotransmitter disposition and, consequently, normal brain function. It is therefore not surprising that MAO-A and B gene polymorphisms and altered expression are implicated in a variety of neurological disorders. [1][2][3][4][5] Moreover, the demonstration that MAO inhibitors, such as iproniazid, were effective antidepressant agents was pivotal in Schildkraut's 6 formulation of the catecholamine hypothesis of affective disorders. Here, we report for the first time the identification of a novel flavin adenine dinucleotide (FAD)-dependent protein, renalase, in various regions of the CNS. We show that the renalase gene is expressed in the hypothalamus and peripheral nerves. Furthermore, we reveal the existence of several splice variants of the renalase gene, which potentially serve to further regulate levels of monoamine neurotransmitters in the brain. Together, our findings provide further insight into the pathways regulating monoamine neurotransmitter disposition in the brain. Until recently, it was thought that MAO and SSAO were the only monoamine oxidases expressed in humans. The discovery of a novel FAD-dependent protein, renalase, was reported in 2005. 7 Renalase was identified using an in silico approach that aimed to discover novel proteins secreted by the kidney. The renalase protein sequence contains a highly conserved N-terminal FAD-binding domain and an amine oxidoreductase domain. Renalase shares low sequence identity with MAO-A and MAO-B (17 and 20 %, respectively) but, nonetheless, its predicted secondary and tertiary structures closely resemble those of Recombinant renalase was shown to generate hydrogen peroxide in the presence of monoamines (including catecholamines), suggesting that it may share the catecholamine-degrading activity of This activity was greatest in the presence of dopamine (followed by adrenaline and noradrenaline), 7 but it was not inhibited by MAO inhibitors, indicating differen...

Transthyretin (TTR) is a tetrameric protein involved in the distribution of thyroid hormones in vertebrates. The amino acid sequence of TTR is highly conserved across vertebrates. Hypothetical TTR-like proteins (TLPs) were inferred from the identification of genes in nonvertebrate species. Here, we identified five motifs defining TLPs and three motifs defining both TTRs and TLPs. These motifs were mapped onto structurally conserved and functionally important regions of TTRs. These motifs were used to build hidden Markov models for accurate identification of TLPs in other organisms. TLPs were divided into three main groups based on their N-terminal regions. Most TLPs are cytosolic, but in plants and slime mold, we predict they are peroxisomal. We verified that the TLPs from enterobacteria were periplasmic. We demonstrated that TLP genes are expressed in a bacterium (E. coli), an invertebrate animal (C. elegans), and a plant (A. thaliana). These TLPs have similar subunit molecular weights to TTRs, are tetramers, and are predicted to have similar three-dimensional (3D) structures to TTRs, but do not bind thyroid hormones or similar ligands. We suggest that like TTRs, the N-terminal and C-terminal regions of TLPs are integral in defining the function of TLPs in nonvertebrate species and that the TLP gene duplicated in primitive vertebrates to produce the TTR gene. TLP/TTR has retained its overall structure, but changed function and localization during evolution in bacteria, invertebrates, plants, and vertebrates.

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