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

The Perceived Advantage of Agile Development Methodologies By Software Professionals: Testing an Innovation-Theoretic Model

Proponents of agile processes claim that agile practices result in higher quality software while allowing the flexibility to respond to evolving user requirements. Yet, to the best of our knowledge, no empirical study has really confirmed that benefits accrue to those who use agile processes. Grounded in the agility and diffusion of innovations literature, this research introduces a measure of process agility within the software development domain and relates it to constructs previously employed in the innovation literature. For agile methods, our study has provided empirical support for the proposal that agile development methods lead to developers’ beliefs that they are less complex, more compatible and provide increased benefits. Since developers believe that agility leads to increased benefits, they will be more likely to accept agile methods. For practitioners, this study provides valuable insights into the underlying factors that influence a developer’s beliefs about agile methods

Emerging Roles of Glycogen Synthase Kinase 3 in the Treatment of Brain Tumors

The constitutively active protein glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, acts paradoxically as a tumor suppressor in some cancers while potentiates growth in others. Deciphering what governs its actions is vital for understanding many pathological conditions, including brain cancer. What are seemingly disparate roles of GSK3 stems from the complex regulation of many cellular functions by GSK3. This review focuses on the regulation of GSK3, its role in survival, apoptosis and DNA damage, and finally its potential therapeutic impact in brain cancer. A thorough understanding of this versatile protein is critical for improving the outcome of various diseases, especially cancer

Histone H2AX Is Phosphorylated at Sites of Retroviral DNA Integration but Is Dispensable for Postintegration Repair

The histone variant H2AX is rapidly phosphorylated (denoted {gamma}H2AX) in large chromatin domains (foci) flanking double strand DNA (dsDNA) breaks that are produced by ionizing radiation or genotoxic agents and during V(D)J recombination. H2AX-deficient cells and mice demonstrate increased sensitivity to dsDNA break damage, indicating an active role for {gamma}H2AX in DNA repair; however, {gamma}H2AX formation is not required for V(D)J recombination. The latter finding has suggested a greater dependence on {gamma}H2AX for anchoring free broken ends versus ends that are held together during programmed breakage-joining reactions. Retroviral DNA integration produces a unique intermediate in which a dsDNA break in host DNA is held together by the intervening viral DNA, and such a reaction provides a useful model to distinguish {gamma}H2AX functions. We found that integration promotes transient formation of {gamma}H2AX at retroviral integration sites as detected by both immunocytological and chromatin immunoprecipitation methods. These results provide the first direct evidence for the association of newly integrated viral DNA with a protein species that is an established marker for the onset of a DNA damage response. We also show that H2AX is not required for repair of the retroviral integration intermediate as determined by stable transduction. These observations provide independent support for an anchoring model for the function of {gamma}H2AX in chromatin repair

Single-Walled Carbon Nanotube (SWCNT)-induced interstitial fibrosis in the lungs of rats is associated with increased levels of PDGF mRNA and the formation of unique intercellular carbon structures that bridge alveolar macrophages In Situ

BACKGROUND: Nanotechnology is a rapidly advancing industry with many new products already available to the public. Therefore, it is essential to gain an understanding of the possible health risks associated with exposure to nanomaterials and to identify biomarkers of exposure. In this study, we investigated the fibrogenic potential of SWCNT synthesized by chemical vapor deposition using cobalt (Co) and molybdenum (Mo) as catalysts. Following a single oropharyngeal aspiration of SWCNT in rats, we evaluated lung histopathology, cell proliferation, and growth factor mRNAs at 1 and 21 days post-exposure. Comparisons were made to vehicle alone (saline containing a biocompatible nonionic surfactant), inert carbon black (CB) nanoparticles, or vanadium pentoxide (V(2)O(5)) as a known inducer of fibrosis. RESULTS: SWCNT or CB caused no overt inflammatory response at 1 or 21 days post-exposure as determined by histopathology and evaluation of cells (>95% macrophages) in bronchoalveolar lavage (BAL) fluid. However, SWCNT induced the formation of small, focal interstitial fibrotic lesions within the alveolar region of the lung at 21 days. A small fraction of alveolar macrophages harvested by BAL from the lungs of SWCNT-exposed rats at 21 days were bridged by unique intercellular carbon structures that extended into the cytoplasm of each macrophage. These "carbon bridge" structures between macrophages were also observed in situ in the lungs of SWCNT-exposed rats. No carbon bridges were observed in CB-exposed rats. SWCNT caused cell proliferation only at sites of fibrotic lesion formation as measured by bromodeoxyuridine uptake into alveolar cells. SWCNT increased platelet-derived growth factor (PDGF)-A, PDGF-B, and PDGF-C mRNA levels significantly at 1 day as measured by Taqman quantitative real-time RT-PCR. At 21 days, SWCNT did not increase any mRNAs evaluated, while V(2)O(5 )significantly increased mRNAs encoding PDGF-A, -B, and -C chains, PDGF-Rα, osteopontin (OPN), connective tissue growth factor (CTGF), and transforming growth factor (TGF)-β1. CONCLUSION: Our findings indicate that SWCNT do not cause lung inflammation and yet induce the formation of small, focal interstital fibrotic lesioins in the alveolar region of the lungs of rats. Of greatest interest was the discovery of unique intercellular carbon structures composed of SWCNT that bridged lung macrophages. These "carbon bridges" offer a novel and easily identifiable biomarker of exposure

Respiratory syncytial virus infection reduces lung inflammation and fibrosis in mice exposed to vanadium pentoxide

<p>Abstract</p> <p>Background</p> <p>Vanadium pentoxide (V₂O₅) exposure is a cause of occupational bronchitis and airway fibrosis. Respiratory syncytial virus (RSV) is a ubiquitous pathogen that causes airway inflammation. It is unknown whether individuals with pre-existing respiratory viral infection are susceptible to V₂O₅-induced bronchitis. We hypothesized that respiratory viral infection will exacerbate vanadium-induced lung fibrosis.</p> <p>Methods</p> <p>In this study we investigated the effect of RSV pre- or post-exposure to V₂O₅in male AKR mice. Mice were pre-exposed by intranasal aspiration to RSV or media vehicle prior to intranasal aspiration of V₂O₅or saline vehicle at day 1 or day 7. A parallel group of mice were treated first with V₂O₅or saline vehicle at day 1 and day 7 then post-exposed to RSV or media vehicle at day 8.</p> <p>Results</p> <p>V₂O₅-induced airway inflammation and fibrosis were decreased by RSV pre- or post-exposure. Real time quantitative RT-PCR showed that V₂O₅significantly increased lung mRNAs encoding pro-fibrogenic growth factors (TGF-β1, CTGF, PDGF-C) and collagen (Col1A2), but also increased mRNAs encoding anti-fibrogenic type I interferons (IFN-α, -β) and IFN-inducible chemokines (CXCL9 and CXCL10). RSV pre- or post-exposure caused a significantly reduced mRNAs of pro-fibrogenic growth factors and collagen, yet reduced RNA levels of anti-fibrogenic interferons and CXC chemokines.</p> <p>Conclusions</p> <p>Collectively these data suggest that RSV infection reduces the severity of V₂O₅-induced fibrosis by suppressing growth factors and collagen genes. However, RSV suppression of V₂O₅-induced IFNs and IFN-inducible chemokines suggests that viral infection also suppresses the innate immune response that normally serves to resolve V₂O₅-induced fibrosis.</p

Drivers of Flight Performance of California Condors (\u3cem\u3eGymnogyps californianus\u3c/em\u3e)

Flight behavior of soaring birds depends on a complex array of physiological, social, demographic, and environmental factors. California Condors (Gymnogyps californianus) rely on thermal and orographic updrafts to subsidize extended bouts of soaring flight, and their soaring flight performance is expected to vary in response to environmental variation and, potentially, with experience. We collected 6298 flight tracks described by high-frequency GPS telemetry data from five birds ranging in age from 1 to 19 yr old and followed over 32 d in summer 2016. Using these data, we tested the hypothesis that climb rate, an indicator of flight performance, would be related to the topographic and meteorological variables the bird experienced, and also to its age. Climb rate was greater when condors were flying in faster winds and during environmental conditions that were conducive to updraft development. However, we found no effect of age on climb rate. Although many of these relationships were expected based on flight theory, the lack of an effect of age was unexpected. Our work expands understanding of the relationship condors have with the environment, and it also suggests the potential for as-yet unexplored complexity to this relationship. As such, this study provides insight into avian flight behavior and, because flight performance influences bird behavior and exposure to anthropogenic risk, it has potential consequences for development of conservation management plans