PCB-containing wood floor finish is a likely source of elevated PCBs in residents' blood, household air and dust: a case study of exposure

© 2008 Rudel et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Characterization of Sulfolobus islandicus rod-shaped virus 2 gp19, a single-strand specific endonuclease

The hyperthermophilic Sulfolobus islandicus rod-shaped virus 2 (SIRV2) encodes a 25-kDa protein (SIRV2gp19) annotated as a hypothetical protein with sequence homology to the RecB nuclease superfamily. Even though SIRV2gp19 homologs are conserved throughout the rudivirus family and presumably play a role in the viral life cycle, SIRV2gp19 has not been functionally characterized. To define the minimal requirements for activity, SIRV2gp19 was purified and tested under varying conditions. SIRV2gp19 is a single-strand specific endonuclease that requires Mg2+ for activity and is inactive on double-stranded DNA. A conserved aspartic acid in RecB nuclease superfamily Motif II (D89) is also essential for SIRV2gp19 activity and mutation to alanine (D89A) abolishes activity. Therefore, the SIRV2gp19 cleavage mechanism is similar to previously described RecB nucleases. Finally, SIRV2gp19 single-stranded DNA endonuclease activity could play a role in host chromosome degradation during SIRV2 lytic infection

Knowledge, attitude and skills before and after a module on pharmaceutical promotion in a Nepalese medical school

<p>Abstract</p> <p>Background</p> <p>Pharmaceutical promotion is widespread and can impact prescribing by health professionals. Little research has been conducted on interactions between medical students and the pharmaceutical industry. Teaching about pharmaceutical promotion is inadequate. A survey showed that many schools spend only about two hours teaching this important topic while others spend around six hours. Recently a manual on understanding and responding to promotion has been published by Health Action International (HAI) and the World Health Organization (WHO). From April to August 2011 the department of Clinical Pharmacology at KIST Medical College, Lalitpur, Nepal conducted a module on pharmaceutical promotion for second year students based on the manual. The module used active learning strategies such as brainstorming sessions, role plays and group activities. The study worked on the hypothesis that a module on pharmaceutical promotion will be effective in improving the knowledge, attitude and skills of medical students regarding pharmaceutical promotion. The impact of the module on knowledge, attitude and skills was tested using a retrospective-pre questionnaire. The scores according to gender and method of financing of medical education before and after the module were compared using appropriate non-parametric tests.</p> <p>Results</p> <p>Eighty-seven of the 100 second year students (87%) participated in the study. 47 were females (54%) and 39 (44.83%) were males and one did not state the gender. Seventy-seven students (88.5%) were self-financing while 9 were scholarship students. The median knowledge, attitude and skills score before the module were 9, 13 and 6 respectively while the overall score was 28. The scores increased significantly to 16, 15 and 14 respectively after the module while the overall score increased to 45. The median attitude scores and total scores were significantly higher among females both before and after the module. The scores did not vary with method of financing of medical education. All scores increased significantly at the end of the module.</p> <p>Conclusions</p> <p>The nine hour module held over a period of four months was effective in improving respondents' knowledge, attitudes and skills about pharmaceutical promotion. The module was not resource intensive and used resources already available in the institution. Similar modules can be considered in other medical and health profession schools in Nepal, South Asia and other developing countries.</p

Breast cancer risk and drinking water contaminated by wastewater: a case control study

BACKGROUND: Drinking water contaminated by wastewater is a potential source of exposure to mammary carcinogens and endocrine disrupting compounds from commercial products and excreted natural and pharmaceutical hormones. These contaminants are hypothesized to increase breast cancer risk. Cape Cod, Massachusetts, has a history of wastewater contamination in many, but not all, of its public water supplies; and the region has a history of higher breast cancer incidence that is unexplained by the population's age, in-migration, mammography use, or established breast cancer risk factors. We conducted a case-control study to investigate whether exposure to drinking water contaminated by wastewater increases the risk of breast cancer. METHODS: Participants were 824 Cape Cod women diagnosed with breast cancer in 1988–1995 and 745 controls who lived in homes served by public drinking water supplies and never lived in a home served by a Cape Cod private well. We assessed each woman's exposure yearly since 1972 at each of her Cape Cod addresses, using nitrate nitrogen (nitrate-N) levels measured in public wells and pumping volumes for the wells. Nitrate-N is an established wastewater indicator in the region. As an alternative drinking water quality indicator, we calculated the fraction of recharge zones in residential, commercial, and pesticide land use areas. RESULTS: After controlling for established breast cancer risk factors, mammography, and length of residence on Cape Cod, results showed no consistent association between breast cancer and average annual nitrate-N (OR = 1.8; 95% CI 0.6 – 5.0 for ≥ 1.2 vs. < .3 mg/L), the sum of annual nitrate-N concentrations (OR = 0.9; 95% CI 0.6 – 1.5 for ≥ 10 vs. 1 to < 10 mg/L), or the number of years exposed to nitrate-N over 1 mg/L (OR = 0.9; 95% CI 0.5 – 1.5 for ≥ 8 vs. 0 years). Variation in exposure levels was limited, with 99% of women receiving some of their water from supplies with nitrate-N levels in excess of background. The total fraction of residential, commercial, and pesticide use land in recharge zones of public supply wells was associated with a small statistically unstable higher breast cancer incidence (OR = 1.4; 95% CI 0.8–2.4 for highest compared with lowest land use), but risk did not increase for increasing land use fractions. CONCLUSION: Results did not provide evidence of an association between breast cancer and drinking water contaminated by wastewater. The computer mapping methods used in this study to link routine measurements required by the Safe Drinking Water Act with interview data can enhance individual-level epidemiologic studies of multiple health outcomes, including diseases with substantial latency

Yes, I Am Ready Now: Differential Effects of Paced versus Unpaced Mating on Anxiety and Central Oxytocin Release in Female Rats

Sexual activity and partner intimacy results in several positive consequences in the context of stress-coping, both in males and females, such as reduced state anxiety in male rats after successful mating. However, in female rats, mating is a rewarding experience only when the estrous female is able to control sexual interactions, i.e., under paced-mating conditions. Here, we demonstrate that sex-steroid priming required for female mating is anxiolytic; subsequent sexual activity under paced mating conditions did not disrupt this anxiolytic priming effect, whereas mating under unpaced conditions increased anxiety-related behavior. In primed females, the release of the neuropeptide oxytocin (OT) within the hypothalamic paraventricular nucleus was found to be elevated and to further increase during paced, but not unpaced mating. Central administration of an OT receptor antagonist partly prevented priming/mating-induced anxiolysis indicating the involvement of brain OT in the anxiolysis triggered by priming and/or sexual activity

Lactic Acid Induces Aberrant Amyloid Precursor Protein Processing by Promoting Its Interaction with Endoplasmic Reticulum Chaperone Proteins

Lactic acid, a natural by-product of glycolysis, is produced at excess levels in response to impaired mitochondrial function, high-energy demand, and low oxygen availability. The enzyme involved in the production of β-amyloid peptide (Aβ) of Alzheimer's disease, BACE1, functions optimally at lower pH, which led us to investigate a potential role of lactic acid in the processing of amyloid precursor protein (APP).Lactic acid increased levels of Aβ40 and 42, as measured by ELISA, in culture medium of human neuroblastoma cells (SH-SY5Y), whereas it decreased APP metabolites, such as sAPPα. In cell lysates, APP levels were increased and APP was found to interact with ER-chaperones in a perinuclear region, as determined by co-immunoprecipitation and fluorescence microscopy studies. Lactic acid had only a very modest effect on cellular pH, did increase the levels of ER chaperones Grp78 and Grp94 and led to APP aggregate formation reminiscent of aggresomes.These findings suggest that sustained elevations in lactic acid levels could be a risk factor in amyloidogenesis related to Alzheimer's disease through enhanced APP interaction with ER chaperone proteins and aberrant APP processing leading to increased generation of amyloid peptides and APP aggregates

A Neural Correlate of the Processing of Multi-Second Time Intervals in Primate Prefrontal Cortex

Several areas of the brain are known to participate in temporal processing. Neurons in the prefrontal cortex (PFC) are thought to contribute to perception of time intervals. However, it remains unclear whether the PFC itself can generate time intervals independently of external stimuli. Here we describe a group of PFC neurons in area 9 that became active when monkeys recognized a particular elapsed time within the range of 1–7 seconds. Another group of area 9 neurons became active only when subjects reproduced a specific interval without external cues. Both types of neurons were individually tuned to recognize or reproduce particular intervals. Moreover, the injection of muscimol, a GABA agonist, into this area bilaterally resulted in an increase in the error rate during time interval reproduction. These results suggest that area 9 may process multi-second intervals not only in perceptual recognition, but also in internal generation of time intervals

Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes

One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are ∼22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA “master regulators” (miR-22 and miR-125) and one candidate pair of “master co-regulators” (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18–28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p  =  0.045), total homocysteine levels (tHcy) (p  =  0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM

Exploring the pastiche hegemony of men

In this article I explore the continued hegemony of certain men. I use interview extracts to help think through the notion of pastiche hegemony as a means of understanding how men, and narratives about them, have changed, but unequal power relations persist. In particular, I explore this process within men’s understandings of how they were able to gain and maintain influence and power at work. Through their reflexive reading of the changing shape of late modern Western society, these men believed they were able to craft selves and employ social scripts to produce social influence and power in situational and contingent forms. I argue that it is within this interactional process that the increasingly undermined ideological and material legacy of patriarchy might still be reified. As such, while there is clear evidence highlighting the undermining of men’s ability to assume power, within this article I theoretically unpack how certain men might be able to produce a localized, pastiche hegemony. This article is published as part of a thematic collection on gender studies