Molecular Targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the Zebrafish Ovary: Insights into TCDD-induced Endocrine Disruption and Reproductive Toxicity

TCDD is a reproductive toxicant and endocrine disruptor, yet the mechanisms by which it causes these reproductive alterations are not fully understood. In order to provide additional insight into the molecular mechanisms that underlie TCDD\u27s reproductive toxicity, we assessed TCDD-induced transcriptional changes in the ovary as they relate to previously described impacts on serum estradiol concentrations and altered follicular development in zebrafish. In silico computational approaches were used to correlate candidate regulatory motifs with observed changes in gene expression. Our data suggest that TCDD inhibits follicle maturation via attenuated gonadotropin responsiveness and/or depressed estradiol biosynthesis, and that interference of estrogen-regulated signal transduction may also contribute to TCDD\u27s impacts on follicular development. TCDD may also alter ovarian function by disrupting various signaling pathways such as glucose and lipid metabolism, and regulation of transcription. Furthermore, events downstream from initial TCDD molecular-targets likely contribute to ovarian toxicity following chronic exposure to TCDD. Data presented here provide further insight into the mechanisms by which TCDD disrupts follicular development and reproduction in fish, and can be used to formulate new hypotheses regarding previously documented ovarian toxicity

Burnout Assessment Tool (BAT): Validity Evidence from Brazil and Portugal

The Burnout Assessment Tool (BAT) has been gaining increased attention as a sound and innovative instrument in its conceptualization of burnout. BAT has been adapted for several countries, revealing promising validity evidence. This paper aims to present the psychometric properties of the Brazilian and Portuguese versions of the BAT in both the 23-item and 12-item versions. BAT’s validity evidence based on the internal structure (dimensionality, reliability, and measurement invariance) and validity evidence based on the relations to other variables are the focus of research. A cross-sectional study was conducted with two non-probabilistic convenience samples from two countries (N = 3103) one from Brazil (nBrazil = 2217) and one from Portugal (nPortugal = 886). BAT’s original structure was confirmed, and it achieved measurement invariance across countries. Using both classic test theory and item response theory as frameworks, the BAT presented good validity evidence based on the internal structure. Furthermore, the BAT showed good convergent evidence (i.e., work engagement, co-worker support, role clarity, work overload, and negative change). In conclusion, the psychometric properties of the BAT make this freely available instrument a promising way to measure and compare burnout levels of Portuguese and Brazilian workers.info:eu-repo/semantics/publishedVersio

Burnout Assessment Tool (BAT): Validity evidence from Brazil and Portugal

The Burnout Assessment Tool (BAT) is gaining increased attention as a sound and innovative instrument in its conceptualization of burnout. BAT has been adapted by several countries, revealing promising validity evidence. This paper aims to present the psychometric properties of the Brazilian and Portuguese versions of the BAT in both the 23-item and 12-item versions. BAT’s validity evidence based on the internal structure (dimensionality, reliability, and measurement invariance) and validity evidence based on the relations to other variables are the focus of research. A cross-sectional study was conducted with two non-probabilistic convenience samples from two countries (N = 3103) one from Brazil (nBrazil = 2217) and one from Portugal (nPortugal = 886). BAT’s original structure was confirmed, and it achieved measurement invariance across countries. Using both classic test theory and item response theory as frameworks, the BAT presented good validity evidence based on the internal structure. Furthermore, the BAT showed good convergent evidence (i.e., work engagement, co-worker support, role clarity, work overload, and negative change). In conclusion, the psychometric properties of the BAT make this freely available instrument a promising way to measure and compare burnout levels of Portuguese and Brazilian workers.info:eu-repo/semantics/publishedVersio

Histopathologic Alterations Associated with Global Gene Expression Due to Chronic Dietary TCDD Exposure in Juvenile Zebrafish

The goal of this project was to investigate the effects and possible developmental disease implication of chronic dietary TCDD exposure on global gene expression anchored to histopathologic analysis in juvenile zebrafish by functional genomic, histopathologic and analytic chemistry methods. Specifically, juvenile zebrafish were fed Biodiet starter with TCDD added at 0, 0.1, 1, 10 and 100 ppb, and fish were sampled following 0, 7, 14, 28 and 42 d after initiation of the exposure. TCDD accumulated in a dose- and time-dependent manner and 100 ppb TCDD caused TCDD accumulation in female (15.49 ppb) and male (18.04 ppb) fish at 28 d post exposure. Dietary TCDD caused multiple lesions in liver, kidney, intestine and ovary of zebrafish and functional dysregulation such as depletion of glycogen in liver, retrobulbar edema, degeneration of nasal neurosensory epithelium, underdevelopment of intestine, and diminution in the fraction of ovarian follicles containing vitellogenic oocytes. Importantly, lesions in nasal epithelium and evidence of endocrine disruption based on alternatively spliced vasa transcripts are two novel and significant results of this study. Microarray gene expression analysis comparing vehicle control to dietary TCDD revealed dysregulated genes involved in pathways associated with cardiac necrosis/cell death, cardiac fibrosis, renal necrosis/cell death and liver necrosis/cell death. These baseline toxicological effects provide evidence for the potential mechanisms of developmental dysfunctions induced by TCDD and vasa as a biomarker for ovarian developmental disruption

PINTA: a web server for network-based gene prioritization from expression data

PINTA (available at http://www.esat.kuleuven.be/pinta/; this web site is free and open to all users and there is no login requirement) is a web resource for the prioritization of candidate genes based on the differential expression of their neighborhood in a genome-wide protein–protein interaction network. Our strategy is meant for biological and medical researchers aiming at identifying novel disease genes using disease specific expression data. PINTA supports both candidate gene prioritization (starting from a user defined set of candidate genes) as well as genome-wide gene prioritization and is available for five species (human, mouse, rat, worm and yeast). As input data, PINTA only requires disease specific expression data, whereas various platforms (e.g. Affymetrix) are supported. As a result, PINTA computes a gene ranking and presents the results as a table that can easily be browsed and downloaded by the user

Transthyretin: No association between serum levels or gene variants and schizophrenia

It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer's disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia.http://www.sciencedirect.com/science/article/B6T8T-4K12CM6-2/1/78223a224d1392e250f7562405e6796

Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes

Objective  ACTH resistance is a feature of several human syndromes with known genetic causes, including familial glucocorticoid deficiency (types 1 and 2) and triple A syndrome. However, many patients with ACTH resistance lack an identifiable genetic aetiology. The human homolog of the Acd gene, mutated in a mouse model of adrenal insufficiency, was sequenced in 25 patients with a clinical diagnosis of familial glucocorticoid deficiency or triple A syndrome. Design  A 3·4 kilobase genomic fragment containing the entire ACD gene was analysed for mutations in all 25 patients. Setting  Samples were obtained by three investigators from different institutions. Patients  The primary cohort consisted of 25 unrelated patients, primarily of European or Middle Eastern descent, with a clinical diagnosis of either familial glucocorticoid deficiency (FGD) or triple A syndrome. Patients lacked mutations in other genes known to cause ACTH resistance, including AAAS for patients diagnosed with triple A syndrome and MC2R and MRAP for patients diagnosed with familial glucocorticoid deficiency. Thirty-five additional patients with adrenal disease phenotypes were added to form an expanded cohort of 60 patients. Measurements  Identification of DNA sequence changes in the ACD gene in the primary cohort and analysis of putative ACD haplotypes in the expanded cohort. Results  No disease-causing mutations were found, but several novel single nucleotide polymorphisms (SNPs) and two putative haplotypes were identified. The overall frequency of SNPs in ACD is low compared to other gene families. Conclusions  No mutations were identified in ACD in this collection of patients with ACTH resistance phenotypes. However, the newly identified SNPs in ACD should be more closely examined for possible links to disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73948/1/j.1365-2265.2007.02855.x.pd

Apolipoprotein B signal peptide polymorphism distribution among South Amerindian populations

This is the published version, also available here: http://www.jstor.org/stable/41465798