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Bloom M.S.,University at Albany | Kannan K.,University at Albany | Kannan K.,New York State Department of Health | Spliethoff H.M.,New York State Department of Health | And 6 more authors.
Physiology and Behavior | Year: 2010

Thyroid hormones play critical roles in human neurodevelopment and adult neurocognitive function. Persistent organohalogen pollutants, such as perfluorinated compounds (PFCs), may interfere with thyroid homeostasis and thus exposures to these compounds might represent risk factors for neurologic and cognitive abnormalities. In this study, serum specimens collected from thirty-one licensed anglers in New York State were analyzed for levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), perfluoroheptanoic acid (PFHpA), perfluorohexanesulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), perfluorooctanesulfonamide (PFOSA), and perfluoroundecanoic acid (PFUnDA). PFOS and PFOA occurred in the highest concentrations with geometric means of 19.6 ng/mL (95% CI 16.3-23.5) and 1.3 ng/mL (95% CI 1.2-1.5), respectively. In a cross-sectional analysis, no statistically significant associations were detected for PFCs, or their sum, with TSH or FT4 at α = 0.05. However, post hoc power analyses, though limited, suggested that moderate increases in sample size, to 86 and 129 subjects, might facilitate 80% power to detect statistically significant associations for FT4 and PFDA (β = 0.09) and PFUnDA (β = 0.08), respectively. The consumption of sportfish may have contributed to PFDA (r = 0.52, P = 0.003) and PFUnDA (r = 0.40, P = 0.025) levels. This preliminary study does not indicate associations between non-occupational PFCs exposures and thyroid function. However, the possibility for weak associations for FT4 with PFDA and PFUnDA, PFCs measured in low concentrations, is raised. Given the ubiquity of PFCs in the environment and the importance of thyroid function to neurodevelopmental and neurocognitive endpoints, a confirmatory study is warranted. © 2009 Elsevier Inc. All rights reserved. Source

Bechard M.,Paul verdell Center For Biomedical And Health Science | Bechard M.,University of Georgia | Bechard M.,Vanderbilt University | Trost R.,Paul verdell Center For Biomedical And Health Science | And 5 more authors.
Molecular and Cellular Biology | Year: 2012

Suppressing the activity of Gsk3β is critical for maintenance of murine pluripotent stem cells. In murine embryonic stem cells (mESCs), Gsk3β is inhibited by multiple mechanisms, including its inhibitory phosphorylation on serine 9 by protein kinase B (Akt), a major effector of the canonical phosphatidylinositol 3-kinase (PI3K) pathway. A second PI3K/Akt-regulated mechanism promotes the nuclear export of Gsk3β, thereby restricting its access to nuclear substrates such as c-myc andβ-catenin. Although Gsk3β shuttles between the nucleus and cytoplasm under self-renewing conditions, its localization is primarily cytoplasmic because its rate of nuclear export exceeds its rate of nuclear import. In this report, we show that Gsk3β is exported from the nucleus in a complex with Frat. Loss of PI3K/Akt activity results in dissociation of this complex and retention of Gsk3β in the nucleus. Frat continues to shuttle between the nucleus and cytoplasm under these conditions and remains predominantly in the cytoplasm. These results indicate that Frat carries Gsk3β out of the nucleus under self-renewing conditions and that PI3K regulates this by promoting its association with Frat. These findings provide new links between PI3K/Akt signaling and regulation of Gsk3β activity by Frat, an oncogene previously shown to cooperate with Myc in tumorigenesis. © 2012, American Society for Microbiology. Source

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