Activity

05). In men, in addition to these two pollutants, PM10 exposure was positively associated with TSH level (p = 0.03). Age-stratified analysis showed stronger effects of NO2 and CO exposure in older than in younger adults. Exposure to these air pollutants was related to serum TSH and FT4 concentrations in people with overweight or obesity but not in those of normal weight. Conclusions This study provides the first evidence that air pollution exposure is linked to thyroid function in the general population and that this association may be stronger in older or overweight or obese adults.To support rapid chemical toxicity assessment and mechanistic hypothesis generation, here we present an intuitive webtool allowing a user to identify target organs in the human body where a substance is estimated to be more likely to produce effects. This tool, called Tox21BodyMap, incorporates results of 9,270 chemicals tested in the United States federal Tox21 research consortium in 971 high-throughput screening (HTS) assays whose targets were mapped onto human organs using organ-specific gene expression data. Via Tox21BodyMap’s interactive tools, users can visualize chemical target specificity by organ system, and implement different filtering criteria by changing gene expression thresholds and activity concentration parameters. Dynamic network representations, data tables, and plots with comprehensive activity summaries across all Tox21 HTS assay targets provide an overall picture of chemical bioactivity. Tox21BodyMap webserver is available at https//sandbox.ntp.niehs.nih.gov/bodymap/.Adenylate/uridylate-rich elements (AREs) are the most common cis-regulatory elements in the 3′-untranslated region (UTR) of mRNAs, where they fine-tune turnover by mediating mRNA decay. They increase plasticity and efficacy of mRNA regulation and are recognized by several ARE-specific RNA-binding proteins (RBPs). Typically, AREs are short linear motifs with a high content of complementary A and U nucleotides and often occur in multiple copies. Although thermodynamically rather unstable, the high AU-content might enable transient secondary structure formation and modify mRNA regulation by RBPs. We have recently suggested that the immunoregulatory RBP Roquin recognizes folded AREs as constitutive decay elements (CDEs), resulting in shape-specific ARE-mediated mRNA degradation. However, the structural evidence for a CDE-like recognition of AREs by Roquin is still lacking. M6620 cost We here present structures of CDE-like folded AREs, both in their free and protein-bound form. Moreover, the AREs in the UCP3 3′-UTR are additionally bound by the canonical ARE-binding protein AUF1 in their linear form, adopting an alternative binding-interface compared to the recognition of their CDE structure by Roquin. Strikingly, our findings thus suggest that AREs can be recognized in multiple ways, allowing control over mRNA regulation by adapting distinct conformational states, thus providing differential accessibility to regulatory RBPs.Based on decades of research, there is strong evidence that supports ongoing dietary recommendations to decrease intakes of SFAs and, more recently, to replace SFAs with unsaturated fat, including PUFAs and MUFAs. Epidemiologic research has shown that replacement of SFAs with unsaturated fat, but not refined carbohydrate and added sugars, is associated with a reduction in coronary heart disease events and death. There is much evidence from controlled clinical studies demonstrating that SFAs increase LDL cholesterol, a major causal factor in the development of cardiovascular disease. When each (nonprotein) dietary macronutrient isocalorically replaces SFA, the greatest LDL-cholesterol-lowering effect is seen with PUFA, followed by MUFA, and then total carbohydrate. New research on full-fat dairy products high in saturated fat, particularly fermented dairy foods, demonstrates some benefits for cardiometabolic diseases. However, compared with food sources of unsaturated fats, full-fat dairy products increase LDL cholesterol. Thus, current dietary recommendations to decrease SFA and replace it with unsaturated fat should continue to the basis for healthy food-based dietary patterns.There is ongoing debate as to whether public health guidelines should advocate reducing SFA consumption as much as possible to reduce the risk of chronic diseases, especially cardiovascular disease (CVD). In considering both sides of this question, we identified a number of points of agreement, most notably that the overall dietary patterns in which SFAs are consumed are of greater significance for cardiometabolic and general health than SFA intake alone. Nevertheless, there remained significant disagreements, centered largely on the interpretation of evidence bearing on 4 major questions 1) does reducing dietary SFAs lower the incidence of CVD, 2) is the LDL-cholesterol reduction with lower SFA intake predictive of reduced CVD risk, 3) do dietary SFAs affect factors other than LDL cholesterol that may impact CVD risk, and 4) is there a sufficient rationale for setting a target for maximally reducing dietary SFAs? Finally, we identified specific research needs for addressing knowledge gaps that have contributed to the controversies.The long-term fidelity of pinniped hosts to their natal rookery site suggests the genetic architecture of their Uncinaria spp. hookworms should be strongly structured by host breeding biology. However, historical events affecting host populations may also shape parasite genetic structure. Sequences of the mitochondrial cytochrome c oxidase 1 (COI) gene of 86 Uncinaria lucasi individuals were obtained to assess genetic variation and structure of nematodes from 2 host species (68 hookworms from northern fur seals; 18 hookworms from Steller sea lions) and rookeries from 3 widely separated geographic regions the western Bering Sea and Sea of Okhotsk, eastern Bering Sea, and the eastern Pacific Ocean. High COI haplotype (h = 0.96-0.98) and nucleotide (π = 0.014) diversity was found. The haplotype network showed a star-shaped pattern with a large number of haplotypes separated by few substitutions. The network did not show separation of U. lucasi by geographic region or host species. Fst values between U. lucasi individuals representing geographic regions showed no differentiation, consistent with the absence of genetic structure.