The Council of Fisheries and Ocean Librarians/Conseil des Bibliotheques de Peches et Oceans--twenty five years and still going strong

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PON1 status does not influence cholinesterase activity in Egyptian agricultural workers exposed to chlorpyrifos.

Animal studies have shown that paraoxonase 1 (PON1) genotype can influence susceptibility to the organophosphorus pesticide chlorpyrifos (CPF). However, Monte Carlo analysis suggests that PON1 genotype may not affect CPF-related toxicity at low exposure conditions in humans. The current study sought to determine the influence of PON1 genotype on the activity of blood cholinesterase as well as the effect of CPF exposure on serum PON1 in workers occupationally exposed to CPF. Saliva, blood and urine were collected from agricultural workers (n=120) from Egypt's Menoufia Governorate to determine PON1 genotype, blood cholinesterase activity, serum PON1 activity towards chlorpyrifos-oxon (CPOase) and paraoxon (POase), and urinary levels of the CPF metabolite 3,5,6-trichloro-2-pyridinol (TCPy). The PON1 55 (P≤0.05) but not the PON1 192 genotype had a significant effect on CPOase activity. However, both the PON1 55 (P≤0.05) and PON1 192 (P≤0.001) genotypes had a significant effect on POase activity. Workers had significantly inhibited AChE and BuChE after CPF application; however, neither CPOase activity nor POase activity was associated with ChE depression when adjusted for CPF exposure (as determined by urinary TCPy levels) and stratified by PON1 genotype. CPOase and POase activity were also generally unaffected by CPF exposure although there were alterations in activity within specific genotype groups. Together, these results suggest that workers retained the capacity to detoxify chlorpyrifos-oxon under the exposure conditions experienced by this study population regardless of PON1 genotype and activity and that effects of CPF exposure on PON1 activity are minimal

Independent Living Oldest-Old and Their Primary Health Provider: A Mixed Method Examination of the Influence of Patient Personality Characteristics

This convergent mixed methods study examined 35 healthy, independent living individuals\u27 (over 85 years) perceptions of their relationship with their primary health provider (PHP) and health practices. The relationship between PHP relationship perceptions and locus of control (LOC), resilience, and self-efficacy was explored through surveys and interviews. The majority indicated they visited their PHP just for preventative care; the number of PHP visits per year was significantly lower than reported for individuals over 85 by the CDC, possible reasons for this finding are provided. A positive relationship between LOC, resiliency, and self-efficacy for the oldest-old was found. Few participants indicated their PHP had discussed normal changes with aging. This study has deepened understanding of the complexity inherent to the healthy oldest-olds\u27 relationship with their PHP. The findings suggest this relationship relates to the PHP\u27s personal characteristics, the elderly patients\u27 personality, and the influence of the accompanying patient escort

Independent Living Oldest-Old and Their Primary Health Provider: A Mixed Method Examination of the Influence of Patient Personality Characteristics

This convergent mixed methods study examined 35 healthy, independent living individuals\u27 (over 85 years) perceptions of their relationship with their primary health provider (PHP) and health practices. The relationship between PHP relationship perceptions and locus of control (LOC), resilience, and self-efficacy was explored through surveys and interviews. The majority indicated they visited their PHP just for preventative care; the number of PHP visits per year was significantly lower than reported for individuals over 85 by the CDC, possible reasons for this finding are provided. A positive relationship between LOC, resiliency, and self-efficacy for the oldest-old was found. Few participants indicated their PHP had discussed normal changes with aging. This study has deepened understanding of the complexity inherent to the healthy oldest-olds\u27 relationship with their PHP. The findings suggest this relationship relates to the PHP\u27s personal characteristics, the elderly patients\u27 personality, and the influence of the accompanying patient escort

Computing and applying atomic regulons to understand gene expression and regulation

The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fmicb.2016.01819/full#supplementary-materialUnderstanding gene function and regulation is essential for the interpretation prediction and ultimate design of cell responses to changes in the environment. An important step toward meeting the challenge of understanding gene function and regulation is the identification of sets of genes that are always co-expressed. These gene sets Atomic Regulons ARs represent fundamental units of function within a cell and could be used to associate genes of unknown function with cellular processes and to enable rational genetic engineering of cellular systems. Here we describe an approach for inferring ARs that leverages large-scale expression data sets gene context and functional relationships among genes. We computed ARs for Escherichia coli based on 907 gene expression experiments and compared our results with gene clusters produced by two prevalent data-driven methods: hierarchical clustering and k-means clustering. We compared ARs and purely data-driven gene clusters to the curated set of regulatory interactions for E. coli found in RegulonDB showing that ARs are more consistent with gold standard regulons than are data-driven gene clusters. We further examined the consistency of ARs and data-driven gene clusters in the context of gene interactions predicted by Context Likelihood of Relatedness CLR analysis finding that the ARs show better agreement with CLR predicted interactions. We determined the impact of increasing amounts of expression data on AR construction and find that while more data improve ARs it is not necessary to use the full set of gene expression experiments available for E. coli to produce high quality ARs. In order to explore the conservation of co-regulated gene sets across different organisms we computed ARs for Shewanella oneidensis Pseudomonas aeruginosa Thermus thermophilus and Staphylococcus aureus each of which represents increasing degrees of phylogenetic distance from E. coli. Comparison of the organism-specific ARs showed that the consistency of AR gene membership correlates with phylogenetic distance but there is clear variability in the regulatory networks of closely related organisms. As large scale expression data sets become increasingly common for model and non-model organisms comparative analyses of atomic regulons will provide valuable insights into fundamental regulatory modules used across the bacterial domain.JF acknowledges funding from [SFRH/BD/70824/2010] of the FCT (Portuguese Foundation for Science and Technology) PhD program. CH and PW were supported by the National Science Foundation under grant number EFRI-MIKS-1137089. RT was supported by the Genomic Science Program (GSP), Office of Biological and Environmental Research (OBER), U.S. Department of Energy(DOE),and his work is a contribution of the Pacific North west National Laboratory (PNNL) Foundational Scientific Focus Area. This work was partially supported by an award from the National Science Foundation to MD, AB, NT, and RO (NSFABI-0850546). This work was also supported by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Service [Contract No. HHSN272201400027C]

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations