1,412 research outputs found

    Hawk on Wire: Ecopoems by Scott T. Starbuck

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    Review of Scott T. Starbuck’s Hawk on Wire: Ecopoem

    Winter Wren by Theresa Kishkan

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    Review of Theresa Kishkan\u27s Winter Wren

    Niche by Basma Kavanagh

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    Review of Basma Kavanagh\u27s Niche

    From the Tundra to the Trenches by Eddy Weetaltuk

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    Review of Eddy Weetaltuk\u27s From the Tundra to the Trenches

    Yardwork: A Biography of an Urban Place by Daniel Coleman

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    Review of Daniel Coleman\u27s Yardwork: A Biography of an Urban Place

    The Lost Letters by Catherine Greenwood

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    Review of Catherine Greenwood\u27s The Lost Letters

    Linking Metabolic QTLs with Network and cis-eQTLs Controlling Biosynthetic Pathways

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    Phenotypic variation between individuals of a species is often under quantitative genetic control. Genomic analysis of gene expression polymorphisms between individuals is rapidly gaining popularity as a way to query the underlying mechanistic causes of variation between individuals. However, there is little direct evidence of a linkage between global gene expression polymorphisms and phenotypic consequences. In this report, we have mapped quantitative trait loci (QTLs)‚Äďcontrolling glucosinolate content in a population of 403 Arabidopsis Bay √ó Sha recombinant inbred lines, 211 of which were previously used to identify expression QTLs controlling the transcript levels of biosynthetic genes. In a comparative study, we have directly tested two plant biosynthetic pathways for association between polymorphisms controlling biosynthetic gene transcripts and the resulting metabolites within the Arabidopsis Bay √ó Sha recombinant inbred line population. In this analysis, all loci controlling expression variation also affected the accumulation of the resulting metabolites. In addition, epistasis was detected more frequently for metabolic traits compared to transcript traits, even when both traits showed similar distributions. An analysis of candidate genes for QTL-controlling networks of transcripts and metabolites suggested that the controlling factors are a mix of enzymes and regulatory factors. This analysis showed that regulatory connections can feedback from metabolism to transcripts. Surprisingly, the most likely major regulator of both transcript level for nearly the entire pathway and aliphatic glucosinolate accumulation is variation in the last enzyme in the biosynthetic pathway, AOP2. This suggests that natural variation in transcripts may significantly impact phenotypic variation, but that natural variation in metabolites or their enzymatic loci can feed back to affect the transcripts

    Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach

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    Accepted manuscript version. Published version available at https://doi.org/10.1016/j.envint.2015.01.007. Accepted manuscript version, licensed CC BY-NC-ND 4.0.The mechanisms involved in thyroid homeostasis are complex, and perfluoroalkyl substances (PFASs) have been indicated to interfere at several levels in this endocrine system. Disruption of the maternal thyroid homeostasis during early pregnancy is of particular concern, where subclinical changes in maternal thyroid hormones (THs) may affect embryonic and foetal development. The present study investigated associations between THs, thyroid binding proteins (TH-BPs) and PFAS concentrations in pregnant women from Northern Norway. Women participating in The Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood sample at three visits related to their pregnancy and postpartum period (during the second trimester, 3 days and 6 weeks after delivery) in the period 2007‚Äď2009. Participants were assigned to quartiles according to PFAS concentrations during the second trimester and mixed effects linear models were used to investigate potential associations between PFASs and repeated measurements of THs, TH-BPs, thyroxin binding capacity and thyroid peroxidase antibodies (anti-TPOs). Women within the highest perfluorooctane sulfonate (PFOS) quartile had 24% higher mean concentrations of thyroid stimulating hormone (TSH) compared to the first quartile at all sampling points. Women within the highest quartiles of perfluorodecanoate (PFDA) had 4% lower mean concentrations of triiodothyronine (T3) and women within the highest quartile of perfluoroundecanoate (PFUnDA) had 3% lower mean concentrations of free triiodothyronine (FT3). Further, the difference in concentrations and the changes between three time points were the same for the PFAS quartiles. Thyroxin binding capacity was associated with all the THs and TH-BPs, and was selected as a holistic adjustment for individual changes in TH homeostasis during pregnancy. Finally, adjusting for maternal iodine status did not influence the model predictions. Findings in the present study suggest modifications of TH homeostasis by PFASs in a background exposed maternal population. The variation in levels of THs between PFAS quartiles was within normal reference ranges and may not be of clinical significance in the pregnant woman. However, subtle individual changes in maternal THs may have significant consequences for foetal health

    Genetic variation in insulin‚Äźinduced kinase signaling

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    Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20‚Äźfold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis‚Äźacting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance.SynopsisGenetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.Extensive individual variation is observed in insulin‚Äźinduced activation of signal transduction.The variation in signaling response is propagated downstream to influence gene expression and cell growth.There is a genetic component to the individual differences in signaling and gene expression response to insulin.Genetic variants contribute to individual variation in insulin response, including kinase activation, changes in gene expression and cell growth, suggesting kinase modulators as promising therapeutics for diseases characterized by insulin resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/1/msb156250-sup-0001-EVFigs.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/2/msb156250.reviewer_comments.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/112224/3/msb156250.pd

    Persistent Organic Pollutants and the Association with Maternal and Infant Thyroid Homeostasis: A Multipollutant Assessment

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    Source: doi: 10.1289/EHP152.Reproduced with permission from Environmental Health Perspectives.Background:Disruption of thyroid homeostasis has been indicated in human studies targeting effects of persistent organic pollutants (POPs). Influence on the maternal thyroid system by POPs is of special interest during pregnancy because such effects could impair infant thyroid homeostasis. Objectives:We investigated the association between POPs and thyroid-stimulating hormone (TSH) and thyroid hormones (THs) in mother and child pairs from the Northern Norway Motherand- Child Contaminant Cohort Study (MISA). Methods:Nineteen POPs and 10 thyroid parameters were analyzed in serum from 391 pregnant women in their second trimester. In addition, TSH concentrations in heel-prick samples from the infants were analyzed by the Norwegian Newborn Screening program. Association studies with a multipollutant approach were performed using multivariate analyses; partial least squares (PLS) regression, hierarchical clustering, and principal component analysis (PCA). Results:Several POPs were significantly associated with TSH and THs: a) PFOS was positively associated with TSH; b) PCBs, HCB, and nonachlors were inversely associated with T3, T4, and FT4; and, c) PFDA and PFUnDA were inversely associated with T3 and FT3. After mutual adjustments for the other contaminants, only PFDA and PFUnDA remained significantly associated with T3 and FT3, respectively. Infants born to mothers within the highest TSH quartile had 10% higher mean concentrations of TSH compared with children born to mothers in the lowest TSH quartile. Conclusion:The present results suggest that background exposures to POPs can alter maternal thyroid homeostasis. This research contributes to the understanding of multipollutant exposures using multivariate statistical approaches and highlights the complexity of investigating environmental concentrations and mixtures in regard to maternal and infant thyroid function
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