Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets

Low water quality in tropical fishponds in southeastern Brazil

Expansion of aquaculture around the world has heavily impacted the environment. Because fertilizers are needed to raise fish, one of the main impacts is eutrophication, which lowers water quality and increases the frequency of algal blooms, mostly cyanobacteria. To evaluate whether the water quality in 30 fishponds in southeastern Brazilian met the requirements of Brazilian legislation, we analyzed biotic and abiotic water conditions. We expected that the high nutrient levels due to fertilization would cause low water quality. We also analyzed cyanotoxins in seston and fish muscle in some systems where cyanobacteria were dominant. The fishponds ranged from eutrophic and hypereutrophic with high phytoplankton biomass. Although cyanobacteria were dominant in most of the systems, cyanotoxins occurred in low concentrations, possibly because only two of the 12 dominant species were potential producers of microcystins. The high phosphorus concentrations caused the low water quality by increasing cyanobacteria, chlorophyll-a, turbidity, and thermotolerant coliforms, and by depleting dissolved oxygen. We found that all the 30 systems were inappropriate for fish culture, according to Brazilian legislation, based on at least one of the parameters measured. Furthermore, there was not any single system in the water-quality thresholds, according to the Brazilian legislation, to grow fish. Our findings indicate the need for better management to minimize the impacts of eutrophication in fishponds, in addition to a rigorous control to guarantee good food

Lesional accumulation of CD163-expressing cells in the gut of patients with inflammatory bowel disease.

Monocytes/macrophages displaying different markers of activation/differentiation infiltrate the inflamed gut of patients with inflammatory bowel diseases (IBD), but the role that each monocyte/macrophage subpopulation plays in the pathogenesis of IBD is not fully understood. The hemoglobin scavenger receptor CD163, a specific marker of monocytes/macrophages, has been associated with either anti-inflammatory or inflammatory functions of macrophages in several pathologies. In this study we examined the tissue distribution and function of CD163-expressing monocytes/macrophages in IBD. CD163 RNA and protein expression was more pronounced in IBD in comparison to normal controls, with no significant difference between Crohn's disease and Ulcerative colitis. In IBD, over-expression of CD163 was restricted to areas with active inflammation and not influenced by current therapy. Immunohistochemical analysis confirmed the accumulation of CD163-expressing cells in IBD, mostly around and inside blood vessels, thus suggesting that these cells are partly recruited from the systemic circulation. Indeed, FACS analysis of circulating mononuclear cells showed that the fractions of CD163-positive monocytes were increased in IBD patients as compared to controls. Functionally, interleukin-6 up-regulated CD163 expression in lamina propria mononuclear cells and mucosal explants of normal subjects. In IBD blood and mucosal cell cultures, cross-linking of CD163 with a specific monoclonal anti-CD163 antibody enhanced tumor necrosis factor-α synthesis. These findings indicate that IBD mucosa is abundantly infiltrated with CD163-positive cells, which could contribute to amplify the inflammatory cytokine response