WorldWideScience

Sample records for biologically relevant exposures

  1. Genotoxic exposure and biological effects in the rubber manufacturing industry. Relevance of the dermal route

    NARCIS (Netherlands)

    Vermeulen, R.

    2001-01-01

    This thesis describes an industry wide survey on genotoxic exposure and biological effects in the rubber manifacturing industry. Chapters are devoted to long-term trends in inhalable and dermal contamination levels, identification of dermal exposure pathways and the assessment of mutagenic

  2. Biological effect markers for exposure to carcinogenic compound and their relevance for risk assessment

    NARCIS (Netherlands)

    Delft, J.H.M. van; Baan, R.A.; Roza, L.

    1998-01-01

    In this review data are summarized on biomarkers that are used for biological effect monitoring of human populations exposed to genotoxic carcinogens. The biomarkers are DNA and protein adducts and cytogenetic effects. Most of these biomarkers are relevant for the process of carcinogenesis. Emphasis

  3. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    Science.gov (United States)

    Schultz, M.M.; Painter, M.M.; Bartell, S.E.; Logue, A.; Furlong, E.T.; Werner, S.L.; Schoenfuss, H.L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimephales promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305. ng/L and 1104. ng/L) and SER (5.2. ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28. ng/L induced vitellogenin in male fish-a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies. ?? 2011 Elsevier B.V.

  4. Selective uptake and biological consequences of environmentally relevant antidepressant pharmaceutical exposures on male fathead minnows

    Science.gov (United States)

    Schultz, Melissa M.; Painter, Meghan M.; Bartell, Stephen E.; Logue, Amanda; Furlong, Edward T.; Werner, Stephen L.; Schoenfuss, Heiko L.

    2011-01-01

    Antidepressant pharmaceuticals have been reported in wastewater effluent at the nanogram to low microgram-per-liter range, and include bupropion (BUP), fluoxetine (FLX), sertraline (SER), and venlafaxine (VEN). To assess the effects of antidepressants on reproductive anatomy, physiology, and behavior, adult male fathead minnows (Pimeplwles promelas) were exposed for 21 days either to a single concentration of the antidepressants FLX, SER, VEN, or BUP, or to an antidepressant mixture. The data demonstrated that exposure to VEN (305 ng/L and 1104 ng/L) and SER (5.2 ng/L) resulted in mortality. Anatomical alterations were noted within the testes of fish exposed to SER and FLX, both modulators of the neurotransmitter serotonin. Additionally, FLX at 28 ng/L induced vitellogenin in male fish—a common endpoint for estrogenic endocrine disruption. Significant alterations in male secondary sex characteristics were noted with single exposures. Effects of single compound exposures neither carried over, nor became additive in the antidepressant mixtures, and reproductive behavior was not affected. Analysis of brain tissues from the exposed fish suggested increased uptake of FLX, SER and BUP and minimal uptake of VEN when compared to exposure water concentrations. Furthermore, the only metabolite detected consistently in the brain tissues was norfluoxetine. Similar trends of uptake by brain tissue were observed when fish were exposed to antidepressant mixtures. The present study demonstrates that anatomy and physiology, but not reproductive behavior, can be disrupted by exposure to environmental concentrations of some antidepressants. The observation that antidepressant uptake into fish tissues is selective may have consequences on assessing the mode-of-action and effects of these compounds in future studies.

  5. Achieving Relevance Through Biology

    Science.gov (United States)

    Buikema, Arthur L., Jr.

    1972-01-01

    Describes a one-semester biology course for nonmajors which explores the interdisciplinary potential of psychology, anthropology, history, literature, philosophy, and religion. Satisfactory results in the 1970 tryout with 126 college students are identified. (CC)

  6. Biology relevant to space radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M. [Oak Ridge National Lab., TN (United States)

    1997-04-30

    There are only very limited data on the health effects to humans from the two major components of the radiations in space, namely protons and heavy ions. As a result, predictions of the accompanying effects must be based either on (1) data generated through studies of experimental systems exposed on earth at rates and fluences higher than those in space, or (2) extrapolations from studies of gamma and x rays. Better information is needed about the doses, dose rates, and the energy and LET spectra of the radiations at the organ level that are anticipated to be encountered during extended space missions. In particular, there is a need for better estimates of the relationship between radiation quality and biological effects. In the case of deterministic effects, it is the threshold that is important. The possibility of the occurrence of a large solar particle event (SPE) requires that such effects be considered during extended space missions. Analyses suggest, however, that it is feasible to provide sufficient shielding so as to reduce such effects to acceptable levels, particularly if the dose rates can be limited. If these analyses prove correct, the primary biological risks will be the stochastic effects (latent cancer induction). The contribution of one large SPE to the risk of stochastic effects while undesirable will not be large in comparison to the potential total dose on a mission of long duration.

  7. Gregory Bateson's relevance to current molecular biology

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2008-01-01

    not come as a surprise today to realize how the general ideas that he was postulating for the study of communication systems in biology fit so well with the astonishing findings of current molecular biology, for example in the field of cellular signal transduction networks. I guess this is the case due......-dependent information, hierarchical contexts and analog/digital communication, which I think molecular biologists could find of great inspiration. In particular I highlight ten “Batesonean ideas” that may prove to be of great relevance to the field of cellular signal transduction....

  8. Gregory Bateson's relevance to current molecular biology

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio

    2008-01-01

    not come as a surprise today to realize how the general ideas that he was postulating for the study of communication systems in biology fit so well with the astonishing findings of current molecular biology, for example in the field of cellular signal transduction networks. I guess this is the case due......-dependent information, hierarchical contexts and analog/digital communication, which I think molecular biologists could find of great inspiration. In particular I highlight ten “Batesonean ideas” that may prove to be of great relevance to the field of cellular signal transduction....

  9. Measurement of biological relevant UV exposure. Investigations in a dental practice; Messung der biologisch relevanten UV-Strahlenbelastung. Untersuchungen in einer Zahnarztpraxis

    Energy Technology Data Exchange (ETDEWEB)

    Braches, J.M.H.

    2001-07-01

    Light sources used in a dental treatment room were examined in order to determine their spectral output in the UV region. Using an UVX-radiometer, the polymerization curing unit and the dental operating light were identified as the sole UV sources and thus they were examined spectroradiometrically. The curing unit exhibits a moderate fraction of UV-A radiation in the wavelength region of 350-400 nm, the operating light emitted UV-A as well as UV-B radiation (280-400 nm). Both light sources were used to determine the biological effective radiation employing the DLR biofilm technology. Results show an effect on the biofilm for the polymerization curing unit only at a distance of 0.2 cm and an unrealistic long exposure period (up to 30 min), pointing to underlying mechanisms of thermal nature. Using the operating light, a dose-dependent inactivation of the DLR biofilm could be documented. A reduction of the effect could be obtained using different shielding materials (mylar foil, medical gloves). From these experiments, the mean UV radiation exposure was calculated to be 3.163 Jm{sup -2} Biofilm/h (0.045 MED/h) for the patient's oral mucosa region and 0.145 Jm{sup -2} Biofilm/h (0.002 MED/h) for the dentist's wrist region. The results point out that there is an only marginal UV radiation risk for the dentist and the patient from the light sources of a dental practice. (orig.) [German] Die in einem Behandlungsraum einer Zahnarztpraxis vorhandenen Lichtquellen wurden in Hinblick auf deren Strahlungsabgabe im UV-Bereich des elektromagnetischen Spektrums untersucht. Mittels eines UVX-Radiometers wurden zunaechst die Polymerisationsleuchte und die Behandlungsleuchte als alleinige UV-Strahlenquellen identifiziert und daraufhin spektroradiometrisch untersucht. Die Polymerisationsleuchte zeigte dabei einen moderaten Anteil an UV-A-Strahlung im Wellenlaengenbereich von 350-400 nm, die Behandlungsleuchte emittierte UV-Strahlung sowohl im UV-A- als auch im UV

  10. Comparing the ecological relevance of four wave exposure models

    Science.gov (United States)

    Sundblad, G.; Bekkby, T.; Isæus, M.; Nikolopoulos, A.; Norderhaug, K. M.; Rinde, E.

    2014-03-01

    Wave exposure is one of the main structuring forces in the marine environment. Methods that enable large scale quantification of environmental variables have become increasingly important for predicting marine communities in the context of spatial planning and coastal zone management. Existing methods range from cartographic solutions to numerical hydrodynamic simulations, and differ in the scale and spatial coverage of their outputs. Using a biological exposure index we compared the performance of four wave exposure models ranging from simple to more advanced techniques. All models were found to be related to the biological exposure index and their performance, measured as bootstrapped R2 distributions, overlapped. Qualitatively, there were differences in the spatial patterns indicating higher complexity with more advanced techniques. In order to create complex spatial patterns wave exposure models should include diffraction, especially in coastal areas rich in islands. The inclusion of wind strength and frequency, in addition to wind direction and bathymetry, further tended to increase the amount of explained variation. The large potential of high-resolution numerical models to explain the observed patterns of species distribution in complex coastal areas provide exciting opportunities for future research. Easy access to relevant wave exposure models will aid large scale habitat classification systems and the continuously growing field of marine species distribution modelling, ultimately serving marine spatial management and planning.

  11. Plasmonic optical trapping in biologically relevant media.

    Directory of Open Access Journals (Sweden)

    Brian J Roxworthy

    Full Text Available We present plasmonic optical trapping of micron-sized particles in biologically relevant buffer media with varying ionic strength. The media consist of 3 cell-growth solutions and 2 buffers and are specifically chosen due to their widespread use and applicability to breast-cancer and angiogenesis studies. High-precision rheological measurements on the buffer media reveal that, in all cases excluding the 8.0 pH Stain medium, the fluids exhibit Newtonian behavior, thereby enabling straightforward measurements of optical trap stiffness from power-spectral particle displacement data. Using stiffness as a trapping performance metric, we find that for all media under consideration the plasmonic nanotweezers generate optical forces 3-4x a conventional optical trap. Further, plasmonic trap stiffness values are comparable to those of an identical water-only system, indicating that the performance of a plasmonic nanotweezer is not degraded by the biological media. These results pave the way for future biological applications utilizing plasmonic optical traps.

  12. Biologically Relevant Glycopeptides: Synthesis and Applications

    Science.gov (United States)

    Bennett, Clay S.; Payne, Richard J.; Koeller, Kathryn M.; Wong, Chi-Huey

    Over the past two decades interest in glycopeptides and glycoproteins has intensified, due in part to the development of new and efficient methods for the synthesis of these compounds. This includes a number of chemical and enzymatic techniques for incorporating glycosylation onto the peptide backbone as well as the introduction of powerful peptide ligation methods for the construction of glycoproteins. This review discusses these methods with a special emphasis on biologically relevant glycopeptides and glycoproteins. This includes the development of a number of antigens which hold promise as potential vaccines for HIV, cancer, or a host of other clinically important diseases. In addition the development of new antibiotics aimed at overcoming the problem of resistance will be discussed. Finally, chemical and enzymatic methods for the construction of glycopeptide mimetics will be described.

  13. Human biological monitoring of occupational genotoxic exposures

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Sorsa, M

    1993-01-01

    ) occupational exposure limit value of styrene in ambient air. The consideration of ethical issues in human genetic monitoring is an important but often overlooked aspect. This includes the scientific and preventional relevance of performing a test on individuals, pre- and post study information of donors......Human biological monitoring is a valuable tool for exposure assessment in groups of persons occupationally exposed to genotoxic agents. If the monitoring activity covers genetic material the term genetic monitoring is used. The methods used for genetic monitoring are either substance specific, e...... for and the biomonitoring results should preferentially be linked with accurate ambient air monitoring. In persons occupationally exposed to styrene the endpoints of DNA-damage and DNA-repair in genetic monitoring are methods of choice in exposure situations above the current Danish (25 ppm) or Finnish (20 ppm...

  14. Biological effects from electromagnetic field exposure and public exposure standards.

    Science.gov (United States)

    Hardell, Lennart; Sage, Cindy

    2008-02-01

    During recent years there has been increasing public concern on potential health risks from power-frequency fields (extremely low frequency electromagnetic fields; ELF) and from radiofrequency/microwave radiation emissions (RF) from wireless communications. Non-thermal (low-intensity) biological effects have not been considered for regulation of microwave exposure, although numerous scientific reports indicate such effects. The BioInitiative Report is based on an international research and public policy initiative to give an overview of what is known of biological effects that occur at low-intensity electromagnetic fields (EMFs) exposure. Health endpoints reported to be associated with ELF and/or RF include childhood leukaemia, brain tumours, genotoxic effects, neurological effects and neurodegenerative diseases, immune system deregulation, allergic and inflammatory responses, breast cancer, miscarriage and some cardiovascular effects. The BioInitiative Report concluded that a reasonable suspicion of risk exists based on clear evidence of bioeffects at environmentally relevant levels, which, with prolonged exposures may reasonably be presumed to result in health impacts. Regarding ELF a new lower public safety limit for habitable space adjacent to all new or upgraded power lines and for all other new constructions should be applied. A new lower limit should also be used for existing habitable space for children and/or women who are pregnant. A precautionary limit should be adopted for outdoor, cumulative RF exposure and for cumulative indoor RF fields with considerably lower limits than existing guidelines, see the BioInitiative Report. The current guidelines for the US and European microwave exposure from mobile phones, for the brain are 1.6 W/Kg and 2 W/Kg, respectively. Since use of mobile phones is associated with an increased risk for brain tumour after 10 years, a new biologically based guideline is warranted. Other health impacts associated with exposure to

  15. Biological monitoring of acrylonitrile exposure

    Energy Technology Data Exchange (ETDEWEB)

    Houthuijs, D.; Remijn, B.; Willems, H.; Boleij, J.; Biersteker, K.

    1982-01-01

    A study was made of the excretion pattern of acrylonitrile (AN) in urine of 15 AN-exposed workers. During a 7-day working period with the following 2 days off, the workers delivered all their urines separately. Exposure data, collected by personal monitoring, showed a mean 8-hour TWA value of 0.13 ppm. The excretion of AN in urine (AN(U) ) showed a typical pattern; concentrations peaked at the end or shortly after the end of the workday and decreased rapidly until the beginning of the next workday. A control group of 41 nonexposed workers of the same company showed a significant increase of AN(U) with increasing number of cigarettes smoked. The AN(U) concentrations of the exposed workers however were, despite the low exposure, much higher than those of the controls, both during the workdays and during the days off. Biological monitoring of AN-exposed workers by assessing AN(U) therefore seems a very sensitive exposure evaluation method, especially because it accounts for inhalation as well as skin penetration as routes for entering the body.

  16. Relevance of Dynamic Clustering to Biological Networks

    CERN Document Server

    Kaneko, K

    1993-01-01

    Abstract Network of nonlinear dynamical elements often show clustering of synchronization by chaotic instability. Relevance of the clustering to ecological, immune, neural, and cellular networks is discussed, with the emphasis of partially ordered states with chaotic itinerancy. First, clustering with bit structures in a hypercubic lattice is studied. Spontaneous formation and destruction of relevant bits are found, which give self-organizing, and chaotic genetic algorithms. When spontaneous changes of effective couplings are introduced, chaotic itinerancy of clusterings is widely seen through a feedback mechanism, which supports dynamic stability allowing for complexity and diversity, known as homeochaos. Second, synaptic dynamics of couplings is studied in relation with neural dynamics. The clustering structure is formed with a balance between external inputs and internal dynamics. Last, an extension allowing for the growth of the number of elements is given, in connection with cell differentiation. Effecti...

  17. Linking exposure to environmental pollutants with biological effects

    DEFF Research Database (Denmark)

    Sørensen, Mette; Autrup, Herman; Møller, Peter

    2003-01-01

    Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene......, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual....... With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM(2.5) exposure. Several types of DNA damage showed seasonal...

  18. Biological relevance and synthesis of C-substituted morpholine derivatives

    NARCIS (Netherlands)

    Wijtmans, R.; Vink, M.K.S.; Schoemaker, H.E.; Delft, F.L. van; Blaauw, R.H.; Rutjes, F.P.J.T.

    2004-01-01

    C-Functionalized morpholines are found in a variety of natural products and biologically active compounds, but have also for other reasons been applied in organic synthesis. This review deals with the biological relevance of C-substituted morpholines, their synthesis and important applications in ot

  19. The Biological Relevance of Artificial Life: Lessons from Artificial Intelligence

    Science.gov (United States)

    Colombano, Silvano

    2000-01-01

    There is no fundamental reason why A-life couldn't simply be a branch of computer science that deals with algorithms that are inspired by, or emulate biological phenomena. However, if these are the limits we place on this field, we miss the opportunity to help advance Theoretical Biology and to contribute to a deeper understanding of the nature of life. The history of Artificial Intelligence provides a good example, in that early interest in the nature of cognition quickly was lost to the process of building tools, such as "expert systems" that, were certainly useful, but provided little insight in the nature of cognition. Based on this lesson, I will discuss criteria for increasing the biological relevance of A-life and the probability that this field may provide a theoretical foundation for Biology.

  20. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  1. Hands-on-Entropy, Energy Balance with Biological Relevance

    Science.gov (United States)

    Reeves, Mark

    2015-03-01

    Entropy changes underlie the physics that dominates biological interactions. Indeed, introductory biology courses often begin with an exploration of the qualities of water that are important to living systems. However, one idea that is not explicitly addressed in most introductory physics or biology textbooks is important contribution of the entropy in driving fundamental biological processes towards equilibrium. From diffusion to cell-membrane formation, to electrostatic binding in protein folding, to the functioning of nerve cells, entropic effects often act to counterbalance deterministic forces such as electrostatic attraction and in so doing, allow for effective molecular signaling. A small group of biology, biophysics and computer science faculty have worked together for the past five years to develop curricular modules (based on SCALEUP pedagogy). This has enabled students to create models of stochastic and deterministic processes. Our students are first-year engineering and science students in the calculus-based physics course and they are not expected to know biology beyond the high-school level. In our class, they learn to reduce complex biological processes and structures in order model them mathematically to account for both deterministic and probabilistic processes. The students test these models in simulations and in laboratory experiments that are biologically relevant such as diffusion, ionic transport, and ligand-receptor binding. Moreover, the students confront random forces and traditional forces in problems, simulations, and in laboratory exploration throughout the year-long course as they move from traditional kinematics through thermodynamics to electrostatic interactions. This talk will present a number of these exercises, with particular focus on the hands-on experiments done by the students, and will give examples of the tangible material that our students work with throughout the two-semester sequence of their course on introductory

  2. Linking exposure to environmental pollutants with biological effects

    DEFF Research Database (Denmark)

    Sørensen, Mette; Autrup, Herman; Møller, Peter

    2003-01-01

    Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene......, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual...... breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1). With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion...

  3. Measuring Biological Parameters in Rivers: Relevance of the Spatial Scale

    Energy Technology Data Exchange (ETDEWEB)

    Romani, A. M.

    2009-07-01

    The analyses of biological parameters in river ecosystems have been traditionally used as indicative of water quality with the advantage over chemical or physical analyses that they integrate the effects of punctual as well as long term effects. However, analyses of biological parameters (such as biomass and metabolism) performed at different spatial scales (from the microbial communities to the whole river) inform about different key processes. At the finer scale, microbial interactions and the structure of the microbial community (biofilm microbial biomass, three dimensional structure, and relevance of polysaccharide matrix) can be detected. At the reach scale, the different stream bed substrate (sediment, rocks, and particulate organic matter accumulation) are shown to play differential and specific roles on the processing of organic and inorganic materials in the flowing water. (Author)

  4. Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures.

    Science.gov (United States)

    Bach, Jordi; Sampayo-Reyes, Adriana; Marcos, Ricard; Hernández, Alba

    2014-03-01

    Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.

  5. Linking exposure to environmental pollutants with biological effects.

    Science.gov (United States)

    Sørensen, Mette; Autrup, Herman; Møller, Peter; Hertel, Ole; Jensen, Steen Solvang; Vinzents, Peter; Knudsen, Lisbeth E; Loft, Steffen

    2003-11-01

    Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual exposure to PM(2.5), nitrogen dioxide (NO(2)) and benzene has been measured in groups of 40-50 subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1). With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion. With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM(2.5) exposure. Several types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand breaks and 8-oxodG in lymphocytes increased significantly in the summer period, requiring control of confounders. Similar seasonal effects on strand breaks and expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported. In the present setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time

  6. Review: Biological relevance of disseminated tumor cells in cancer patients.

    Science.gov (United States)

    Riethdorf, Sabine; Wikman, Harriet; Pantel, Klaus

    2008-11-01

    The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

  7. Exposure-Relevant Ozone Chemistry in Occupied Spaces

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, Beverly Kaye [Univ. of California, Berkeley, CA (United States)

    2009-04-01

    Ozone, an ambient pollutant, is transformed into other airborne pollutants in the indoor environment. In this dissertation, the type and amount of byproducts that result from ozone reactions with common indoor surfaces, surface residues, and vapors were determined, pollutant concentrations were related to occupant exposure, and frameworks were developed to predict byproduct concentrations under various indoor conditions. In Chapter 2, an analysis is presented of secondary organic aerosol formation from the reaction of ozone with gas-phase, terpene-containing consumer products in small chamber experiments under conditions relevant for residential and commercial buildings. The full particle size distribution was continuously monitored, and ultrafine and fine particle concentrations were in the range of 10 to>300 mu g m-3. Particle nucleation and growth dynamics were characterized.Chapter 3 presents an investigation of ozone reactions with aircraft cabin surfaces including carpet, seat fabric, plastics, and laundered and worn clothing fabric. Small chamber experiments were used to determine ozone deposition velocities, ozone reaction probabilities, byproduct emission rates, and byproduct yields for each surface category. The most commonly detected byproducts included C1?C10 saturated aldehydes and skin oil oxidation products. For all materials, emission rates were higher with ozone than without. Experimental results were used to predict byproduct exposure in the cabin and compare to other environments. Byproduct levels are predicted to be similar to ozone levels in the cabin, which have been found to be tens to low hundreds of ppb in the absence of an ozone converter. In Chapter 4, a model is presented that predicts ozone uptake by and byproduct emission from residual chemicals on surfaces. The effects of input parameters (residue surface concentration, ozone concentration, reactivity of the residue and the surface, near-surface airflow conditions, and

  8. Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions

    Science.gov (United States)

    Semenov, Sergey N.; Kraft, Lewis J.; Ainla, Alar; Zhao, Mengxia; Baghbanzadeh, Mostafa; Campbell, Victoria E.; Kang, Kyungtae; Fox, Jerome M.; Whitesides, George M.

    2016-09-01

    Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate-thioester exchange, thiolate-disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov-Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving

  9. Behavioural biology: an effective and relevant conservation tool.

    Science.gov (United States)

    Buchholz, Richard

    2007-08-01

    'Conservation behaviour' is a young discipline that investigates how proximate and ultimate aspects of the behaviour of an animal can be of value in preventing the loss of biodiversity. Rumours of its demise are unfounded. Conservation behaviour is quickly building a capacity to positively influence environmental decision making. The theoretical framework used by animal behaviourists is uniquely valuable to elucidating integrative solutions to human-wildlife conflicts, efforts to reintroduce endangered species and reducing the deleterious effects of ecotourism. Conservation behaviourists must join with other scientists under the multidisciplinary umbrella of conservation biology without giving up on their focus: the mechanisms, development, function and evolutionary history of individual differences in behaviour. Conservation behaviour is an increasingly relevant tool in the preservation of nature.

  10. Biclustering methods: biological relevance and application in gene expression analysis.

    Directory of Open Access Journals (Sweden)

    Ali Oghabian

    Full Text Available DNA microarray technologies are used extensively to profile the expression levels of thousands of genes under various conditions, yielding extremely large data-matrices. Thus, analyzing this information and extracting biologically relevant knowledge becomes a considerable challenge. A classical approach for tackling this challenge is to use clustering (also known as one-way clustering methods where genes (or respectively samples are grouped together based on the similarity of their expression profiles across the set of all samples (or respectively genes. An alternative approach is to develop biclustering methods to identify local patterns in the data. These methods extract subgroups of genes that are co-expressed across only a subset of samples and may feature important biological or medical implications. In this study we evaluate 13 biclustering and 2 clustering (k-means and hierarchical methods. We use several approaches to compare their performance on two real gene expression data sets. For this purpose we apply four evaluation measures in our analysis: (1 we examine how well the considered (biclustering methods differentiate various sample types; (2 we evaluate how well the groups of genes discovered by the (biclustering methods are annotated with similar Gene Ontology categories; (3 we evaluate the capability of the methods to differentiate genes that are known to be specific to the particular sample types we study and (4 we compare the running time of the algorithms. In the end, we conclude that as long as the samples are well defined and annotated, the contamination of the samples is limited, and the samples are well replicated, biclustering methods such as Plaid and SAMBA are useful for discovering relevant subsets of genes and samples.

  11. Dilution thermodynamics of the biologically relevant cation mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Kaczyński, Marek, E-mail: marek.kaczynski@pwr.wroc.pl; Borowik, Tomasz, E-mail: office@novel-id.pl; Przybyło, Magda, E-mail: magdalena.przybylo@pwr.wroc.pl; Langner, Marek, E-mail: marek.langner@pwr.wroc.pl

    2014-01-10

    Graphical abstract: - Highlights: • Dilution energetics of Ca{sup 2+} can be altered by the aqueous phase ionic composition. • Dissipated heat upon Ca{sup 2+} dilution is drastically reduced in the K{sup +} presence. • Reduction of the enthalpy change upon Ca{sup 2+} dilution is K{sup +} concentration dependent. • The cooperativity of Ca{sup 2+} hydration might be of great biological relevance providing a thermodynamic argument for the specific ionic composition of the intracellular environment. - Abstract: The ionic composition of intracellular space is rigorously controlled by a variety of processes consuming large quantities of energy. Since the energetic efficiency is an important evolutional criterion, therefore the ion fluxes within the cell should be optimized with respect to the accompanying energy consumption. In the paper we present the experimental evidence that the dilution enthalpies of the biologically relevant ions; i.e. calcium and magnesium depend on the presence of monovalent cations; i.e. sodium and potassium. The heat flow generated during the dilution of ionic mixtures was measured with the isothermal titration calorimetry. When calcium was diluted together with potassium the dilution enthalpy was drastically reduced as the function of the potassium concentration present in the solution. No such effect was observed when the potassium ions were substituted with sodium ones. When the dilution of magnesium was investigated the dependence of the dilution enthalpy on the accompanying monovalent cation was much weaker. In order to interpret experimental evidences the ionic cluster formation is postulated. The specific organization of such cluster should depend on ions charges, sizes and organization of the hydration layers.

  12. Identification of biologically relevant enhancers in human erythroid cells.

    Science.gov (United States)

    Su, Mack Y; Steiner, Laurie A; Bogardus, Hannah; Mishra, Tejaswini; Schulz, Vincent P; Hardison, Ross C; Gallagher, Patrick G

    2013-03-22

    Identification of cell type-specific enhancers is important for understanding the regulation of programs controlling cellular development and differentiation. Enhancers are typically marked by the co-transcriptional activator protein p300 or by groups of cell-expressed transcription factors. We hypothesized that a unique set of enhancers regulates gene expression in human erythroid cells, a highly specialized cell type evolved to provide adequate amounts of oxygen throughout the body. Using chromatin immunoprecipitation followed by massively parallel sequencing, genome-wide maps of candidate enhancers were constructed for p300 and four transcription factors, GATA1, NF-E2, KLF1, and SCL, using primary human erythroid cells. These data were combined with gene expression analyses, and candidate enhancers were identified. Consistent with their predicted function as candidate enhancers, there was statistically significant enrichment of p300 and combinations of co-localizing erythroid transcription factors within 1-50 kb of the transcriptional start site (TSS) of genes highly expressed in erythroid cells. Candidate enhancers were also enriched near genes with known erythroid cell function or phenotype. Candidate enhancers exhibited moderate conservation with mouse and minimal conservation with nonplacental vertebrates. Candidate enhancers were mapped to a set of erythroid-associated, biologically relevant, SNPs from the genome-wide association studies (GWAS) catalogue of NHGRI, National Institutes of Health. Fourteen candidate enhancers, representing 10 genetic loci, mapped to sites associated with biologically relevant erythroid traits. Fragments from these loci directed statistically significant expression in reporter gene assays. Identification of enhancers in human erythroid cells will allow a better understanding of erythroid cell development, differentiation, structure, and function and provide insights into inherited and acquired hematologic disease.

  13. Biological Relevance and Therapeutic Potential of the Hypusine Modification System.

    Science.gov (United States)

    Pällmann, Nora; Braig, Melanie; Sievert, Henning; Preukschas, Michael; Hermans-Borgmeyer, Irm; Schweizer, Michaela; Nagel, Claus Henning; Neumann, Melanie; Wild, Peter; Haralambieva, Eugenia; Hagel, Christian; Bokemeyer, Carsten; Hauber, Joachim; Balabanov, Stefan

    2015-07-24

    Hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is emerging as a crucial regulator in cancer, infections, and inflammation. Although its contribution in translational regulation of proline repeat-rich proteins has been sufficiently demonstrated, its biological role in higher eukaryotes remains poorly understood. To establish the hypusine modification system as a novel platform for therapeutic strategies, we aimed to investigate its functional relevance in mammals by generating and using a range of new knock-out mouse models for the hypusine-modifying enzymes deoxyhypusine synthase and deoxyhypusine hydroxylase as well as for the cancer-related isoform eIF-5A2. We discovered that homozygous depletion of deoxyhypusine synthase and/or deoxyhypusine hydroxylase causes lethality in adult mice with different penetrance compared with haploinsufficiency. Network-based bioinformatic analysis of proline repeat-rich proteins, which are putative eIF-5A targets, revealed that these proteins are organized in highly connected protein-protein interaction networks. Hypusine-dependent translational control of essential proteins (hubs) and protein complexes inside these networks might explain the lethal phenotype observed after deletion of hypusine-modifying enzymes. Remarkably, our results also demonstrate that the cancer-associated isoform eIF-5A2 is dispensable for normal development and viability. Together, our results provide the first genetic evidence that the hypusine modification in eIF-5A is crucial for homeostasis in mammals. Moreover, these findings highlight functional diversity of the hypusine system compared with lower eukaryotes and indicate eIF-5A2 as a valuable and safe target for therapeutic intervention in cancer. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Classifying transcription factor targets and discovering relevant biological features

    Directory of Open Access Journals (Sweden)

    DeLisi Charles

    2008-05-01

    Full Text Available Abstract Background An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties. Principal Findings (1 Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4, Ino2(2.6, Yaf1(2.4, and Yap6(2.4. (2 Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression. (3 A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties. (4 An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and

  15. Characterization of Nanoparticle Aggregation in Biologically Relevant Fluids

    Science.gov (United States)

    McEnnis, Kathleen; Lahann, Joerg

    Nanoparticles (NPs) are often studied as drug delivery vehicles, but little is known about their behavior in blood once injected into animal models. If the NPs aggregate in blood, they will be shunted to the liver or spleen instead of reaching the intended target. The use of animals for these experiments is costly and raises ethical questions. Typically dynamic light scattering (DLS) is used to analyze aggregation behavior, but DLS cannot be used because the components of blood also scatter light. As an alternative, a method of analyzing NPs in biologically relevant fluids such as blood plasma has been developed using nanoparticle tracking analysis (NTA) with fluorescent filters. In this work, NTA was used to analyze the aggregation behavior of fluorescent polystyrene NPs with different surface modifications in blood plasma. It was expected that different surface chemistries on the particles will change the aggregation behavior. The effect of the surface modifications was investigated by quantifying the percentage of NPs in aggregates after addition to blood plasma. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems, specifically aggregation, can be addressed before investing in in vivo studies.

  16. Status-Relevant Experiences and Conspicuous Consumption - the Moderating Role of Prenatal Androgen Exposure.

    Science.gov (United States)

    Cornelissen, Gert; Palacios-Fenech, Javier

    2016-09-20

    In this paper we study consumers' interest in acquiring and displaying expensive luxury products. Based on recent insights in consumer psychology, which build on developments in evolutionary biology, we consider luxury products as "costly signals": wasteful and costly goods, whose purpose is to communicate one's biological fitness, and social status, to others. In line with previous research, we show that experiences that trigger mate attraction goals (Study 1: Exposure to others in bathing outfit) or status display goals (Study 2: Experiencing a vicarious victory of one's favorite sports team) can increase people's interest in luxury products. However, we demonstrate that some individuals are predictably more responsive to those experiences than others. We used a physiological measure (the proportion of the length of the index finger and ring finger of the right hand, 2D:4D) as a proxy for individual differences in exposure to prenatal androgens (i.e., testosterone). This measure has been related to dominant and competitive behavior later in life. We predict and find that individuals with a low 2D:4D (i.e., high exposure to prenatal androgens) were more responsive to the status-relevant experiences: they became more interested in luxury goods after these experiences. This was not the case for high 2D:4D individuals.

  17. Fingernails as biological indices of metal exposure

    Indian Academy of Sciences (India)

    Rita Mehra; Meenu Juneja

    2005-03-01

    Metal determination in human tissues is the most common application of biological monitoring for screening, diagnosis and assessment of metal exposures and their risks. Various biopsy-materials may be used. This paper deals with the quantitative determination of Cd, Pb, Cr, Mn, Fe, Ni, Cu, and Zn concentrations in nails of male subjects exposed to these metals alongwith their respective controls, while working in locomotive, carriage and roadways workshops, and lead battery factories. The levels of Cd, Pb, Cr, Mn, Fe, Ni, Cu and Zn in fingernails, assayed by atomic absorption spectrophotometry, were compared with their respective controls by student ‘’ test. All the obtained values were correlated to the personal and medical history of the subjects under study. Significantly high levels of Cd, Pb, Cr, Fe, Ni, Cu and Zn were present in smokers, compared to nonsmokers. The concentrations of Cd, Pb, Cr, Mn and Fe were not significantly high in vegetarian subjects. It was also observed that there is no contribution of liquor towards nail-metal concentration. Significant correlations were observed between skin disease and Cr, Mn, Fe, Cu; hypertension and Cd, Mn, Cu; mental stress and Cd, Pb, Mn, Ni, Cu, Zn; diabetes and Cr, Mn, Ni; chest pain and Pb; respiratory trouble and Cr, Mn, Fe, Ni, Zn; tuberculosis and Zn; acidity and Cd; and ophthalmic problems and Mn, Fe, Ni, and Zn.

  18. Biological Relevance and Therapeutic Potential of the Hypusine Modification System*

    Science.gov (United States)

    Pällmann, Nora; Braig, Melanie; Sievert, Henning; Preukschas, Michael; Hermans-Borgmeyer, Irm; Schweizer, Michaela; Nagel, Claus Henning; Neumann, Melanie; Wild, Peter; Haralambieva, Eugenia; Hagel, Christian; Bokemeyer, Carsten; Hauber, Joachim; Balabanov, Stefan

    2015-01-01

    Hypusine modification of the eukaryotic initiation factor 5A (eIF-5A) is emerging as a crucial regulator in cancer, infections, and inflammation. Although its contribution in translational regulation of proline repeat-rich proteins has been sufficiently demonstrated, its biological role in higher eukaryotes remains poorly understood. To establish the hypusine modification system as a novel platform for therapeutic strategies, we aimed to investigate its functional relevance in mammals by generating and using a range of new knock-out mouse models for the hypusine-modifying enzymes deoxyhypusine synthase and deoxyhypusine hydroxylase as well as for the cancer-related isoform eIF-5A2. We discovered that homozygous depletion of deoxyhypusine synthase and/or deoxyhypusine hydroxylase causes lethality in adult mice with different penetrance compared with haploinsufficiency. Network-based bioinformatic analysis of proline repeat-rich proteins, which are putative eIF-5A targets, revealed that these proteins are organized in highly connected protein-protein interaction networks. Hypusine-dependent translational control of essential proteins (hubs) and protein complexes inside these networks might explain the lethal phenotype observed after deletion of hypusine-modifying enzymes. Remarkably, our results also demonstrate that the cancer-associated isoform eIF-5A2 is dispensable for normal development and viability. Together, our results provide the first genetic evidence that the hypusine modification in eIF-5A is crucial for homeostasis in mammals. Moreover, these findings highlight functional diversity of the hypusine system compared with lower eukaryotes and indicate eIF-5A2 as a valuable and safe target for therapeutic intervention in cancer. PMID:26037925

  19. Natural killer cells: Biology, functions and clinical relevance

    Directory of Open Access Journals (Sweden)

    Vojvodić Svetlana

    2010-01-01

    Full Text Available Introduction. Natural Killer cells (NK cells represent the subset of peripheral lymphocytes that play critical role in the innate immune response to virus-infected and tumor transformed cells. Lysis of NK sensitive target cells could be mediated independently of antigen stimulation and without requirement of peptide presentation by the major histocompatibility complex (MHC molecules. NK cell activity and functions are controlled by a considerable number of cell surface receptors, which exist in both inhibitory and activating isoforms. There are several groups of NK cell surface receptors: 1 killer immunoglobulin like receptors-KIR, 2 C-type lectin receptors,3natural citotoxicity receptors-NCR and 4 Toll-like receptors-TLR. Functions of NK receptors. Defining the biology of NK cell surface receptors has contributed to the concept of the manner how NK cells selectively recognize and lyse tumor and virally infected cells while sparing normal cells. Further, identification of NK receptor ligands and their expression on the normal and transformed cells has led to the development of clinical approaches to manipulating receptor/ligand interactions that showed clinical benefit. NK cells are the first lymphocyte subset that reconstitute the peripheral blood following allogeneic HSCT and multiple roles for alloreactive donor NK cells have been demonstrated, in diminishing Graft vs. Host Disease (GvHD through selective killing recipient dendritic cells, prevention of graft rejection by killing recipient T cells and participation in Graft vs. Leukaemia (GvL effect through destruction of residual host tumor cells. Conclusion. Besides their role in HSCT, NK cell receptors have an important clinical relevance that reflects from the fact that they play a crucial role in the development of some diseases as well as in possibilities of managing all NK receptors through selective expansion and usage of NK cells in cancer immunotherapy.

  20. Diamond coatings exposure to fusion-relevant plasma conditions

    NARCIS (Netherlands)

    Porro, S.; De Temmerman, G.; Lisgo, S.; Rudakov, D. L.; Litnovsky, A.; Petersson, P.; John, P.; Wilson, J. I. B.

    2011-01-01

    Several types of diamond layers have been deposited on molybdenum tiles by chemical vapour deposition techniques, and exposed under erosion-dominated conditions in the SOL of TEXTOR in order to assess them as a suitable candidate for plasma-facing material. Post-exposure characterisation of physical

  1. Exposure to endocrine disrupting compounds via the food chain: Is packaging a relevant source?

    Science.gov (United States)

    Muncke, Jane

    2009-08-01

    Contamination of foodstuffs by environmental pollutants (e.g. dioxins, metals) receives much attention. Until recently, food packaging as a source of xenobiotics, especially those with endocrine disrupting properties, has received little awareness despite its ubiquitous use. This article reviews the regulations and use of endocrine disrupting compounds (EDCs) in food packaging and discusses their presence within the context of new toxicology paradigms. I focused on substances known to be legally used in food packaging that have been shown to exhibit endocrine disruptive effects in biological systems. I compiled a list of 50 known or potential EDCs used in food contact materials and examined data of EDCs leaching from packaging into food, with a focus on nonylphenol. I included recent advances in toxicology: mixture effects, the developmental origins of adult disease hypothesis, low-dose effects, and epigenetics. I especially considered the case of bisphenol A. The core hypothesis of this review is that chemicals leaching from packaging into food contribute to human EDCs exposure and might lead to chronic disease in light of the current knowledge. Food contact materials are a major source of food contaminants. Many migrating compounds, possibly with endocrine disruptive properties, remain unidentified. There is a need for information on identity/quantity of chemicals leaching into food, human exposure, and long-term impact on health. Especially EDCs in food packaging are of concern. Even at low concentrations, chronic exposure to EDCs is toxicologically relevant. Concerns increase when humans are exposed to mixtures of similar acting EDCs and/or during sensitive windows of development. In particular, non-intentionally added substances (NIAS) migrating from food contact materials need toxicological characterization; the overall migrate of the finished packaging could be evaluated for biological effects using bioassays. The widespread legal use of EDCs in food

  2. PubChem3D: Biologically relevant 3-D similarity

    Directory of Open Access Journals (Sweden)

    Kim Sunghwan

    2011-07-01

    Full Text Available Abstract Background The use of 3-D similarity techniques in the analysis of biological data and virtual screening is pervasive, but what is a biologically meaningful 3-D similarity value? Can one find statistically significant separation between "active/active" and "active/inactive" spaces? These questions are explored using 734,486 biologically tested chemical structures, 1,389 biological assay data sets, and six different 3-D similarity types utilized by PubChem analysis tools. Results The similarity value distributions of 269.7 billion unique conformer pairs from 734,486 biologically tested compounds (all-against-all from PubChem were utilized to help work towards an answer to the question: what is a biologically meaningful 3-D similarity score? The average and standard deviation for the six similarity measures STST-opt, CTST-opt, ComboTST-opt, STCT-opt, CTCT-opt, and ComboTCT-opt were 0.54 ± 0.10, 0.07 ± 0.05, 0.62 ± 0.13, 0.41 ± 0.11, 0.18 ± 0.06, and 0.59 ± 0.14, respectively. Considering that this random distribution of biologically tested compounds was constructed using a single theoretical conformer per compound (the "default" conformer provided by PubChem, further study may be necessary using multiple diverse conformers per compound; however, given the breadth of the compound set, the single conformer per compound results may still apply to the case of multi-conformer per compound 3-D similarity value distributions. As such, this work is a critical step, covering a very wide corpus of chemical structures and biological assays, creating a statistical framework to build upon. The second part of this study explored the question of whether it was possible to realize a statistically meaningful 3-D similarity value separation between reputed biological assay "inactives" and "actives". Using the terminology of noninactive-noninactive (NN pairs and the noninactive-inactive (NI pairs to represent comparison of the "active/active" and

  3. Biomedically relevant circuit-design strategies in mammalian synthetic biology.

    Science.gov (United States)

    Bacchus, William; Aubel, Dominique; Fussenegger, Martin

    2013-01-01

    The development and progress in synthetic biology has been remarkable. Although still in its infancy, synthetic biology has achieved much during the past decade. Improvements in genetic circuit design have increased the potential for clinical applicability of synthetic biology research. What began as simple transcriptional gene switches has rapidly developed into a variety of complex regulatory circuits based on the transcriptional, translational and post-translational regulation. Instead of compounds with potential pharmacologic side effects, the inducer molecules now used are metabolites of the human body and even members of native cell signaling pathways. In this review, we address recent progress in mammalian synthetic biology circuit design and focus on how novel designs push synthetic biology toward clinical implementation. Groundbreaking research on the implementation of optogenetics and intercellular communications is addressed, as particularly optogenetics provides unprecedented opportunities for clinical application. Along with an increase in synthetic network complexity, multicellular systems are now being used to provide a platform for next-generation circuit design.

  4. Hormesis [Biological Effects of Low Level Exposures (Belle)] and Dermatology

    OpenAIRE

    Thong, Haw-Yueh; Maibach, Howard I.

    2008-01-01

    Hormesis, or biological effects of low level exposures (BELLE), is characterized by nonmonotonic dose response which is biphasic, displaying opposite effects at low and high dose. Its occurrence has been documented across a broad range of biological models and diverse type of exposure. Since hormesis appears to be a relatively common phenomenon in many areas, the objective of this review is to explore its occurrence related to dermatology and its public health and risk assessment implication....

  5. Daily animal exposure and children's biological concepts.

    Science.gov (United States)

    Geerdts, Megan S; Van de Walle, Gretchen A; LoBue, Vanessa

    2015-02-01

    A large body of research has focused on the developmental trajectory of children's acquisition of a theoretically coherent naive biology. However, considerably less work has focused on how specific daily experiences shape the development of children's knowledge about living things. In the current research, we investigated one common experience that might contribute to biological knowledge development during early childhood-pet ownership. In Study 1, we investigated how children interact with pets by observing 24 preschool-aged children with their pet cats or dogs and asking parents about their children's daily involvement with the pets. We found that most of young children's observed and reported interactions with their pets are reciprocal social interactions. In Study 2, we tested whether children who have daily social experiences with animals are more likely to attribute biological properties to animals than children without pets. Both 3- and 5-year-olds with pets were more likely to attribute biological properties to animals than those without pets. Similarly, both older and younger children with pets showed less anthropocentric patterns of extension of novel biological information. The results suggest that having pets may facilitate the development of a more sophisticated, human-inclusive representation of animals.

  6. Iron decreases biological effects of ozone exposure

    Science.gov (United States)

    CONTEXT: Ozone (0(3)) exposure is associated with a disruption of iron homeostasis and increased availability of this metal which potentially contributes to an oxidative stress and biologicaleffects. OBJECTIVE: We tested the postulate that increased concentrations of iron in c...

  7. Streptococcus pyogenes biofilms – formation, biology,and clinical relevance

    Directory of Open Access Journals (Sweden)

    Tomas eFiedler

    2015-02-01

    Full Text Available Streptococcus pyogenes (group A streptococci, GAS is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  8. Streptococcus pyogenes biofilms-formation, biology, and clinical relevance.

    Science.gov (United States)

    Fiedler, Tomas; Köller, Thomas; Kreikemeyer, Bernd

    2015-01-01

    Streptococcus pyogenes (group A streptococci, GAS) is an exclusive human bacterial pathogen. The virulence potential of this species is tremendous. Interactions with humans range from asymptomatic carriage over mild and superficial infections of skin and mucosal membranes up to systemic purulent toxic-invasive disease manifestations. Particularly the latter are a severe threat for predisposed patients and lead to significant death tolls worldwide. This places GAS among the most important Gram-positive bacterial pathogens. Many recent reviews have highlighted the GAS repertoire of virulence factors, regulators and regulatory circuits/networks that enable GAS to colonize the host and to deal with all levels of the host immune defense. This covers in vitro and in vivo studies, including animal infection studies based on mice and more relevant, macaque monkeys. It is now appreciated that GAS, like many other bacterial species, do not necessarily exclusively live in a planktonic lifestyle. GAS is capable of microcolony and biofilm formation on host cells and tissues. We are now beginning to understand that this feature significantly contributes to GAS pathogenesis. In this review we will discuss the current knowledge on GAS biofilm formation, the biofilm-phenotype associated virulence factors, regulatory aspects of biofilm formation, the clinical relevance, and finally contemporary treatment regimens and future treatment options.

  9. Exposure to environmentally-relevant levels of ozone negatively influence pollen and fruit development.

    Science.gov (United States)

    Gillespie, Colin; Stabler, Daniel; Tallentire, Eva; Goumenaki, Eleni; Barnes, Jeremy

    2015-11-01

    A combination of in vitro and in vivo studies on tomato (Lycopersicon esculentum Mill. cv. Triton) revealed that environmentally-relevant levels of ozone (O3) pollution adversely affected pollen germination, germ tube growth and pollen-stigma interactions - pollen originating from plants raised in charcoal-Purafil(®) filtered air (CFA) exhibited reduced germ tube development on the stigma of plants exposed to environmentally-relevant levels of O3. The O3-induced decline in in vivo pollen viability was reflected in increased numbers of non-fertilized and fertilized non-viable ovules in immature fruit. Negative effects of O3 on fertilization occurred regardless of the timing of exposure, with reductions in ovule viability evident in O3 × CFA and CFA × O3 crossed plants. This suggests O3-induced reductions in fertilization were associated with reduced pollen viability and/or ovule development. Fruit born on trusses independently exposed to 100 nmol mol(-1) O3 (10 h d(-1)) from flowering exhibited a decline in seed number and this was reflected in a marked decline in the weight and size of individual fruit - a clear demonstration of the direct consequence of the effects of the pollutant on reproductive processes. Ozone exposure also resulted in shifts in the starch and ascorbic acid (Vitamin C) content of fruit that were consistent with accelerated ripening. The findings of this study draw attention to the need for greater consideration of, and possibly the adoption of weightings for the direct impacts of O3, and potentially other gaseous pollutants, on reproductive biology during 'risk assessment' exercises.

  10. Biologically relevant neural network architectures for support vector machines.

    Science.gov (United States)

    Jändel, Magnus

    2014-01-01

    Neural network architectures that implement support vector machines (SVM) are investigated for the purpose of modeling perceptual one-shot learning in biological organisms. A family of SVM algorithms including variants of maximum margin, 1-norm, 2-norm and ν-SVM is considered. SVM training rules adapted for neural computation are derived. It is found that competitive queuing memory (CQM) is ideal for storing and retrieving support vectors. Several different CQM-based neural architectures are examined for each SVM algorithm. Although most of the sixty-four scanned architectures are unconvincing for biological modeling four feasible candidates are found. The seemingly complex learning rule of a full ν-SVM implementation finds a particularly simple and natural implementation in bisymmetric architectures. Since CQM-like neural structures are thought to encode skilled action sequences and bisymmetry is ubiquitous in motor systems it is speculated that trainable pattern recognition in low-level perception has evolved as an internalized motor programme. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Biological exposure limit for occupational exposure to coal tar pitch volatiles at cokeovens.

    Science.gov (United States)

    Jongeneelen, F J

    1992-01-01

    Biological monitoring is an efficient tool in the evaluation of exposure to chemical agents. However, the dose-response of adverse health effects using biological exposure indices and biological limit values are rarely available. This paper presents an estimation of the occupational exposure limit value of 1-hydroxypyrene in urine, a biological exposure indicator of polycyclic aromatic hydrocarbons (PAH). A large-scale study of the exposure of cokeoven workers to PAH, in which both air sampling (benzene soluble matter and individual PAH including benzo(a)pyrene) and biological monitoring (1-hydroxypyrene in urine) were applied, made it possible to establish an empirical mathematical relationship between the air sampling data and biological monitoring data. It was calculated that cokeoven workers with a urinary concentration of 1-hydroxypyrene of 2.3 mumol/mol creatinine after a 3-day working period equals the airborne threshold limit value (TLV) of coal tar pitch volatiles (CTPV). Epidemiological studies have quantified the relative risk of lung cancer for topside and non-topside cokeoven workers. The published environmental exposure data of topside and non-topside cokeoven workers were used to determine the time-average exposure. The data of 1-hydroxypyrene in the urine of cokeoven workers and data of epidemiological studies from different coke plants were combined according to the concentrations of PAH in the air. Thus, it was possible to establish an indirect relationship between lung cancer mortality risk and the biological exposure indicator for cokeoven workers. Exposure at the level of the suggested tentative biological exposure limit (BEL) of 2.3 mumol/mol creatinine is estimated to be equal to a relative risk of lung cancer of approximately 1.3.

  12. Neighboring amide participation in thioether oxidation: relevance to biological oxidation.

    Science.gov (United States)

    Glass, Richard S; Hug, Gordon L; Schöneich, Christian; Wilson, George S; Kuznetsova, Larisa; Lee, Tang-man; Ammam, Malika; Lorance, Edward; Nauser, Thomas; Nichol, Gary S; Yamamoto, Takuhei

    2009-09-30

    To investigate neighboring amide participation in thioether oxidation, which may be relevant to brain oxidative stress accompanying beta-amyloid peptide aggregation, conformationally constrained methylthionorbornyl derivatives with amido moieties were synthesized and characterized, including an X-ray crystallographic study of one of them. Electrochemical oxidation of these compounds, studied by cyclic voltammetry, revealed that their oxidation peak potentials were less positive for those compounds in which neighboring group participation was geometrically possible. Pulse radiolysis studies provided evidence for bond formation between the amide moiety and sulfur on one-electron oxidation in cases where the moieties are juxtaposed. Furthermore, molecular constraints in spiro analogues revealed that S-O bonds are formed on one-electron oxidation. DFT calculations suggest that isomeric sigma*(SO) radicals are formed in these systems.

  13. Student perception of relevance of biology content to everyday life: A study in higher education biology courses

    Science.gov (United States)

    Himschoot, Agnes Rose

    The purpose of this mixed method case study was to examine the effects of methods of instruction on students' perception of relevance in higher education non-biology majors' courses. Nearly ninety percent of all students in a liberal arts college are required to take a general biology course. It is proposed that for many of those students, this is the last science course they will take for life. General biology courses are suspected of discouraging student interest in biology with large enrollment, didactic instruction, covering a huge amount of content in one semester, and are charged with promoting student disengagement with biology by the end of the course. Previous research has been aimed at increasing student motivation and interest in biology as measured by surveys and test results. Various methods of instruction have been tested and show evidence of improved learning gains. This study focused on students' perception of relevance of biology content to everyday life and the methods of instruction that increase it. A quantitative survey was administered to assess perception of relevance pre and post instruction over three topics typically taught in a general biology course. A second quantitative survey of student experiences during instruction was administered to identify methods of instruction used in the course lecture and lab. While perception of relevance dropped in the study, qualitative focus groups provided insight into the surprising results by identifying topics that are more relevant than the ones chosen for the study, conveying the affects of the instructor's personal and instructional skills on student engagement, explanation of how active engagement during instruction promotes understanding of relevance, the roll of laboratory in promoting students' understanding of relevance as well as identifying external factors that affect student engagement. The study also investigated the extent to which gender affected changes in students' perception of

  14. Biological Functional Relevance of Asymmetric Dimethylarginine (ADMA in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sara Franceschelli

    2013-12-01

    Full Text Available There is growing evidence that increased levels of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA may contribute to endothelial dysfunction. Studies in animal models as well as in humans have suggested that the increase in ADMA occurs at a time when vascular disease has not yet become clinically evident. ADMA competitively inhibits NO elaboration by displacing L-arginine from NO synthase. In a concentration-dependent manner, it thereby interferes not only with endothelium-dependent, NO-mediated vasodilation, but also with other biological functions exerted by NO. The upshot may be a pro-atherogenic state. Recently, several studies have investigated the effect of various therapeutical interventions on ADMA plasma concentrations.

  15. Biology and relevance of human acute myeloid leukemia stem cells.

    Science.gov (United States)

    Thomas, Daniel; Majeti, Ravindra

    2017-03-23

    Evidence of human acute myeloid leukemia stem cells (AML LSCs) was first reported nearly 2 decades ago through the identification of rare subpopulations of engrafting cells in xenotransplantation assays. These AML LSCs were shown to reside at the apex of a cellular hierarchy that initiates and maintains the disease, exhibiting properties of self-renewal, cell cycle quiescence, and chemoresistance. This cancer stem cell model offers an explanation for chemotherapy resistance and disease relapse and implies that approaches to treatment must eradicate LSCs for cure. More recently, a number of studies have both refined and expanded our understanding of LSCs and intrapatient heterogeneity in AML using improved xenotransplant models, genome-scale analyses, and experimental manipulation of primary patient cells. Here, we review these studies with a focus on the immunophenotype, biological properties, epigenetics, genetics, and clinical associations of human AML LSCs and discuss critical questions that need to be addressed in future research. © 2017 by The American Society of Hematology.

  16. Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

    NARCIS (Netherlands)

    Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

    2003-01-01

    Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

  17. Chiral alkynylcarbinols from marine sponges: asymmetric synthesis and biological relevance.

    Science.gov (United States)

    Listunov, Dymytrii; Maraval, Valérie; Chauvin, Remi; Génisson, Yves

    2015-01-01

    Covering: up to March 2014. Previous review on the topic: B. W. Gung, C. R. Chim., 2009, 12, 489-505. Chiral α-functional lipidic propargylic alcohols extracted from marine sponges, in particular of the pacific genus Petrosia, constitute a class of acetylenic natural products exhibiting remarkable in vitro biological activities, especially anti-tumoral cytotoxicity. These properties, associated to functionalities that are uncommon among natural products, have prompted recent projects on asymmetric total synthesis. On the basis of a three-sector structural typology, three main sub-types of secondary alkynylcarbinols (with either alkyl, alkenyl, or alkynyl as the second substituent) can be identified as the minimal pharmacophoric units. Selected natural products containing these functionalities have been targeted using previously known or on purpose-designed procedures, where the stereo-determining step can be: (i) a C-C bond forming reaction (e.g. the Zn-mediated addition of alkynyl nucleophiles to aldehydes in the presence of chiral aminoalcohols), (ii) a functional layout (e.g. the asymmetric organo- or metallo-catalytic reduction of ynones), or (iii) an enantiomeric resolution (e.g. a lipase-mediated kinetic resolution via acetylation). The promising medicinal importance of these targets is finally surveyed, and future investigation prospects are proposed, such as: (i) further total synthesis of known or future extraction products; (ii) the synthesis of non-natural analogues, with simpler lipophilic environments of the alkynylcarbinol-based pharmacophoric units; (iii) the variation and optimization of both the pharmacophoric units and their lipophilic environment; and (iv) investigations into the biological mode of action of these unique structures.

  18. Biological exposure models for oil spill impact analysis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The oil spill impact analysis (OSIA) software system has been developed to supply a tool for comprehensive, quantitative environmental impact assessments resulting from oil spills. In the system, a biological component evaluates potential effects on exposed organisms based on results from a physico-chemieal fates component, including the extent and characteristics of the surface slick, and dissolved and total concentrations of hydrocarbons in the water column. The component includes a particle-based exposure model for migratory adult fish populations, a particle-based exposure model for spawning planktonic organisms (eggs and larvae), and an exposure model for wildlife species (sea birds or marine mammals). The exposure model for migratory adult fish populations simulates the migration behaviors of fish populations migrating to or staying in their feeding areas, over-wintering areas or spawning areas, and determines the acute effects (mortality) and chronic accumulation (body burdens) from the dissolved contaminant. The exposure model for spawning planktonic organisms simulates the release of eggs and larvae, also as particles, from specific spawning areas during the spawning period, and determines their potential exposure to contaminants in the water or sediment. The exposure model for wild species calculates the exposure to surrace oil of wildlife (bird and marine mammal ) categories inhabiting the contaminated area. Compared with the earlier models in which all kinds of organisms are assumed evenly and randomly distributed, the updated biological exposure models can more realistically estimate potential effects on marine ecological system from oil spill pollution events.

  19. MRI probes for sensing biologically relevant metal ions.

    Science.gov (United States)

    Bonnet, Célia S; Tóth, Eva

    2010-03-01

    Given the important role of metal ions in fundamental biological processes, the visualization of their concentration in living animals by repeatable, noninvasive imaging techniques, such as MRI, would be highly desirable. A large number of metal-responsive MRI contrast agents, the majority based on Gd(3+) complexes, have been reported in recent years. The contrast-enhancing properties (relaxivity) of a Gd(3+) complex can be most conveniently modulated by interaction with the sensed metal cation via changes in the number of water molecules bound directly to Gd(3+) or changes in the size of the complex, which represent the two major strategies to develop metal sensitive MRI probes. Here, we survey paramagnetic lanthanide complexes involving Gd(3+) agents and paramagnetic chemical exchange saturation transfer probes designed to detect the most important endogenous metal ions: calcium, zinc, iron and copper. Future work will likely focus on extending applications of these agents to living animals, as well as on exploring new ways of creating molecular MRI probes in order to meet requirements such as higher specificity or lower detection limits.

  20. Radon exposure of the skin: I. Biological effects

    Energy Technology Data Exchange (ETDEWEB)

    Charles, M W [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2007-09-15

    Radon progeny can plate out on skin and give rise to exposure of the superficial epidermis from alpha emitters Po-218 (7.7 MeV, range {approx}66 {mu}m) and Po-214 (6 MeV, range {approx}44 {mu}m). Dose rates from beta/gamma emitters Pb-214 and Bi-214 are low and only predominate at depths in excess of the alpha range. This paper reviews the evidence for a causal link between exposure from radon and its progeny, and deterministic and stochastic biological effects in human skin. Radiation induced skin effects such as ulceration and dermal atrophy, which require irradiation of the dermis, are ruled out for alpha irradiation from radon progeny because the target cells are considerably deeper than the range of alpha particles. They have not been observed in man or animals. Effects such as erythema and acute epidermal necrosis have been observed in a few cases of very high dose alpha particle exposures in man and after acute high dose exposure in animals from low energy beta radiations with similar depth doses to radon progeny. The required skin surface absorbed doses are in excess of 100 Gy. Such effects would require extremely high levels of radon progeny. They would involve quite exceptional circumstances, way outside the normal range of radon exposures in man. There is no definitive identification of the target cells for skin cancer induction in animals or man. The stem cells in the basal layer which maintain the epidermis are the most plausible contenders for target cells. The majority of these cells are near the end of the range of radon progeny alpha particles, even on the thinnest body sites. The nominal depth of these cells, as recommended by the International Commission on Radiological Protection (ICRP), is 70 {mu}m. There is evidence however that some irradiation of the hair follicles and/or the deeper dermis, as well as the inter-follicular epidermis, is also necessary for skin cancer induction. Alpha irradiation of rodent skin that is restricted to the

  1. "Evo in the News:" Understanding Evolution and Students' Attitudes toward the Relevance of Evolutionary Biology

    Science.gov (United States)

    Infanti, Lynn M.; Wiles, Jason R.

    2014-01-01

    This investigation evaluated the effects of exposure to the "Evo in the News" section of the "Understanding Evolution" website on students' attitudes toward biological evolution in undergraduates in a mixed-majors introductory biology course at Syracuse University. Students' attitudes toward evolution and changes therein were…

  2. Occupational accidents with exposure to biological material: Description of cases in Bahia

    Directory of Open Access Journals (Sweden)

    Técia Maria Santos Carneiro e Cordeiro

    2016-04-01

    Full Text Available Background and Objective: This study is included in the field of public health in Brazil, in particular occupational health, by the occupational accidents with exposure to biological material consists of a preventable injury. Thus, the objective was to describe risk factors the of occupational accidents with exposure to biological material and the conduct postexposure adopted notified of cases in Notifiable Diseases Information System (SINAN in the State of Bahia in 2012. Methods: This is a descriptive epidemiological study realized with data from the injuries of notifications SINAN in February 2013, the analysis was realized using descriptive statistics in absolute frequencies and relative. Results: The results indicate a higher occurrence of occupational accidents involving exposure to biological materials in Bahia in the female population (78.1% and aged between 30-49 years (51.5%; the blood was fluid larger contact in accidents 75.2% by percutaneous (71.5%; post-exposure procedures were adopted in accordance recommended by the Ministry of Health; divers information were not fulfilled in the notifications and only 23.8% of Occupational Accidents Comunication (CAT were issued. Conclusion: It is considered necessary to draw up strategies on occupational health and safety, consciousness of workers about the relevance of the measures adopted after occupational accidents with exposure to biological material and the training of professionals for case notification and research to fill all the fields of the notification form and also the issuance of CAT.

  3. Air and biological monitoring of solvent exposure during graffiti removal.

    Science.gov (United States)

    Anundi, H; Langworth, S; Johanson, G; Lind, M L; Akesson, B; Friis, L; Itkes, N; Söderman, E; Jönsson, B A; Edling, C

    2000-11-01

    The principal aim of the study was to estimate the level of exposure to organic solvents of graffiti removers, and to identify the chemicals used in different cleaning agents. A secondary objective was to inform about the toxicity of various products and to optimise working procedures. Exposure to organic solvents was determined by active air sampling and biological monitoring among 38 graffiti removers during an 8-h work shift in the Stockholm underground system. The air samples and biological samples were analysed by gas chromatography. Exposure to organic solvents was also assessed by a questionnaire and interviews. Solvents identified were N-methylpyrrolidone (NMP), dipropylene glycol monomethyl ether (DPGME), propylene glycol monomethyl ether (PGME), diethylene glycol monoethyl ether (DEGEE), toluene, xylene, pseudocumene, hemimellitine, mesitylene, ethylbenzene, limonene, nonane, decane, undecane, hexandecane and gamma-butyrolactone. The 8-h average exposures [time-weighted average (TWA)] were below 20% of the Swedish permissible exposure limit value (PEL) for all solvents identified. In poorly ventilated spaces, e.g. in elevators etc., the short-term exposures exceeded occasionally the Swedish short-term exposure limit values (STEL). The blood and urine concentrations of NMP and its metabolites were low. Glycol ethers and their metabolites (2-methoxypropionic acid (MPA), ethoxy acetic acid (EAA), butoxy acetic acid (BAA), and 2-(2-methoxyethoxy) acetic acid (MEAA)) were found in low concentrations in urine. There were significant correlation between the concentrations of NMP in air and levels of NMP and its metabolites in blood and urine. The use of personal protective equipment, i.e. gloves and respirators, was generally high. Many different cleaning agents were used. The average exposure to solvents was low, but some working tasks included relatively high short-term exposure. To prevent adverse health effects, it is important to inform workers about the

  4. Dermal echogenicity: a biological indicator of individual cumulative UVR exposure?

    Science.gov (United States)

    Sandby-Møller, Jane; Thieden, Elisabeth; Philipsen, Peter Alshede; Schmidt, Grethe; Wulf, Hans Christian

    2004-04-01

    Dermal alterations due to chronic UVR exposure may influence dermal ultrasound echogenicity, and a subepidermal low-echogenic band has been proposed as a marker of photoaging. The aim of this study was to determine whether dermal echogenicity could be used as a biological UVR dosimeter. We included 201 subjects (138 healthy volunteers, 31 patients with basal cell carcinoma, and 32 patients with cutaneous malignant melanoma). The number of low-echogenic pixels in the upper dermis relative to the lower dermis (LEP(u/l)) was determined in sun-exposed and sun-protected skin. Individual UVR exposure data were collected retrospectively and prospectively using a questionnaire and electronic personal UVR dosimeters. Age, but not sex, skin type, constitutive pigmentation or smoking, correlated significantly with LEP(u/l) at all body sites. Different measures of individual UVR exposure were significantly positively correlated with LEP(u/l) (together r(2)=0.39, dorsal forearm), but separately the correlations were poor ( r(2)=0.04-0.19). LEP(u/l) was higher in the dorsal forearm in a group with high UVR exposure compared to a low-exposure group ( P=0.007). Skin cancer patients in general had a lower LEP(u/l) than healthy subjects. The results indicate that the age-related increase in LEP(u/l) might be attributed mainly to UVR exposure, and that the methods used to obtain the UVR exposure data might not be sufficiently sensitive or specific. Genetic factors might also influence LEP(u/l). We consider LEP(u/l) to be a sensitive and specific marker for UVR exposure at the dorsal aspect of the forearm in healthy subjects.

  5. Methodology and biological monitoring of exposure to chemical warfare agents

    Energy Technology Data Exchange (ETDEWEB)

    Shih, M.L.; Smith, J.R.; McMonagle, J.D. [Army Medical Research Inst. of Chemical Defense, Aberdeen Proving Ground, MD (United States)

    1995-06-01

    In the past few years, our institute has developed several GC/MS methods for the detection of the breakdown products of toxic organophosphonates (soman, sarin, GF) and vesicant sulfur mustard in biological samples. Recently we developed a modified GC/MS method for VX and are continually working on the methodology for lewisite and tabun. The purpose is to have an analytical tool to verify the exposure of chemical warfare agents in humans. Analytical procedures for quantitating the hydrolyzed phosphonic acids from nerve agents in environmental samples have been reported by many analysts. For more complex matrices such as biological samples, there is not yet a method reported. To make these polar acids amenable to gas chromatographic analysis a prior derivatization is needed. We found the pentafluorobenzyl ester derivatives of the phosphonates are suitable for verification and pharmacokinetic studies in biological samples. This method may also serve as an alternative method for confirmation purposes in environmental samples.

  6. Estimation of relevant variables on high-dimensional biological patterns using iterated weighted kernel functions.

    Directory of Open Access Journals (Sweden)

    Sergio Rojas-Galeano

    Full Text Available BACKGROUND: The analysis of complex proteomic and genomic profiles involves the identification of significant markers within a set of hundreds or even thousands of variables that represent a high-dimensional problem space. The occurrence of noise, redundancy or combinatorial interactions in the profile makes the selection of relevant variables harder. METHODOLOGY/PRINCIPAL FINDINGS: Here we propose a method to select variables based on estimated relevance to hidden patterns. Our method combines a weighted-kernel discriminant with an iterative stochastic probability estimation algorithm to discover the relevance distribution over the set of variables. We verified the ability of our method to select predefined relevant variables in synthetic proteome-like data and then assessed its performance on biological high-dimensional problems. Experiments were run on serum proteomic datasets of infectious diseases. The resulting variable subsets achieved classification accuracies of 99% on Human African Trypanosomiasis, 91% on Tuberculosis, and 91% on Malaria serum proteomic profiles with fewer than 20% of variables selected. Our method scaled-up to dimensionalities of much higher orders of magnitude as shown with gene expression microarray datasets in which we obtained classification accuracies close to 90% with fewer than 1% of the total number of variables. CONCLUSIONS: Our method consistently found relevant variables attaining high classification accuracies across synthetic and biological datasets. Notably, it yielded very compact subsets compared to the original number of variables, which should simplify downstream biological experimentation.

  7. Biological monitoring of exposure to tebuconazole in winegrowers.

    Science.gov (United States)

    Fustinoni, Silvia; Mercadante, Rosa; Polledri, Elisa; Rubino, Federico Maria; Mandic-Rajcevic, Stefan; Vianello, Giorgio; Colosio, Claudio; Moretto, Angelo

    2014-11-01

    Tebuconazole (TEB) is a fungicide widely used in vineyards and is a suspected teratogen for humans. The aim of this research was to identify urinary biomarkers and the best sampling time for the biological monitoring of exposure to TEB in agricultural workers. Seven vineyard workers of the Monferrato region, Piedemont, Italy, were investigated for a total of 12 workdays. They treated the vineyards with TEB for 1-2 consecutive days, one of them for 3 days. During each application coveralls, underwears, hand washing liquids and head coverings were used to estimate dermal exposure. For biomonitoring, spot samples of urine from each individual were collected starting from 24 h before the first application, continuing during the application, and again after the application for about 48 h. TEB and its metabolites TEB-OH and TEB-COOH were measured by liquid chromatography/triple quadrupole mass spectrometry. TEB contamination of coveralls and total dermal exposure showed median levels of 6180 and 1020 μg. Urinary TEB-OH was the most abundant metabolite; its excretion rate peaked within 24 h after product application (post 24 h). In this time frame, median levels of TEB-OH and TEB-COOH ranged from 8.0 to 387.8 μg/l and from 5.7 to 102.9 μg/l, respectively, with a ratio between the two metabolites of about 3.5. The total amount of urinary metabolites (U-TEBeq) post 24 h was significantly correlated with both TEB on coveralls and total dermal exposure (Pearson's r=0.756 and 0.577). The amount of metabolites excreted in urine represented about 17% of total dermal TEB exposure. Our results suggest that TEB-OH and TEB-COOH in post-exposure urine samples are promising candidates for biomonitoring TEB exposure in agricultural workers.

  8. Biological effects of low level exposures to chemicals and radiation

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, E.J. (ed.)

    1992-01-01

    In May 1990 a group of scientists representing several federal agencies, the International Society of Regulatory Toxicology and Pharmacology, the private sector, and academia met to develop a strategy to encourage the study of the biological effects of low level exposures (BELLE) to chemical agents and radioactivity. A workshop was held in 1991 with seven invited speakers focusing on the toxicological implications of biological adaptations. The selection of topics and speakers was designed to consider critically the concept of hormesis, not only in a broad, conceptual manner, but also at the molecular and biochemical levels. These presentations offered a complementary perspective on the diverse range of molecular mechanisms that can become activated at low levels of toxicant exposure. In addition to chemical toxicology research, an overview of current research on Effects of low-dose radiation on the immune response' was presented as well as Cellular adaptation as an important response during chemical carcinogenesis'. The final presentation was devoted to biostatistical considerations when designing studies that address issues associated with the biological responses to low doses of chemicals and radiation, as well as issues in interpretation of the findings from such studies.

  9. Predictive modeling of nanomaterial exposure effects in biological systems

    Directory of Open Access Journals (Sweden)

    Liu X

    2013-09-01

    Full Text Available Xiong Liu,1 Kaizhi Tang,1 Stacey Harper,2 Bryan Harper,2 Jeffery A Steevens,3 Roger Xu1 1Intelligent Automation, Inc., Rockville, MD, USA; 2Department of Environmental and Molecular Toxicology, School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR, USA; 3ERDC Environmental Laboratory, Vicksburg, MS, USA Background: Predictive modeling of the biological effects of nanomaterials is critical for industry and policymakers to assess the potential hazards resulting from the application of engineered nanomaterials. Methods: We generated an experimental dataset on the toxic effects experienced by embryonic zebrafish due to exposure to nanomaterials. Several nanomaterials were studied, such as metal nanoparticles, dendrimer, metal oxide, and polymeric materials. The embryonic zebrafish metric (EZ Metric was used as a screening-level measurement representative of adverse effects. Using the dataset, we developed a data mining approach to model the toxic endpoints and the overall biological impact of nanomaterials. Data mining techniques, such as numerical prediction, can assist analysts in developing risk assessment models for nanomaterials. Results: We found several important attributes that contribute to the 24 hours post-fertilization (hpf mortality, such as dosage concentration, shell composition, and surface charge. These findings concur with previous studies on nanomaterial toxicity using embryonic zebrafish. We conducted case studies on modeling the overall effect/impact of nanomaterials and the specific toxic endpoints such as mortality, delayed development, and morphological malformations. The results show that we can achieve high prediction accuracy for certain biological effects, such as 24 hpf mortality, 120 hpf mortality, and 120 hpf heart malformation. The results also show that the weighting scheme for individual biological effects has a significant influence on modeling the overall impact of

  10. Impairment of the reproductive potential of male fathead minnows by environmentally relevant exposures to 4-nonylphenolf

    Science.gov (United States)

    Schoenfuss, H.L.; Bartell, S.E.; Bistodeau, T.B.; Cediel, R.A.; Grove, K.J.; Zintek, L.; Lee, K.E.; Barber, L.B.

    2008-01-01

    The synthetic organic compound 4-nonylphenol (NP) has been detected in many human-impacted surface waters in North America. In this study, we examined the ability of NP to alter reproductive competence in male fathead minnows after a 28 day flow-through exposure in a range of environmentally relevant concentrations bracketing the U.S. Environmental Protection Agency toxicity-based NP chronic exposure criterion of 6.1 ??g NP/L. Exposure to NP at and above the EPA chronic exposure criterion resulted in an induction of plasma vitellogenin (VTG) within 14 days. However, 7 days after the cessation of exposure, VTG concentrations had dropped more than 50% and few males expressed VTG above the detection threshold. All of the morphological endpoints, including gonadosomatic index, hepatosomatic index, secondary sexual characters, and histopathology, were unaltered by all NP treatments. However, when NP-exposed male fish were allowed to compete with control males for access to nest sites and females, most treatments altered the reproductive competence of exposed males. At lower NP concentrations, exposed males out-competed control males, possibly by being primed through the estrogenic NP exposure in a fashion similar to priming by pheromones released from female fathead minnows. At higher NP exposure concentrations, this priming effect was negated by the adverse effects of the exposure and control males out-competed treated males. Results of this study indicate the complexity of endocrine disrupting effects and the need for multiple analysis levels to assess the effects of these compounds on aquatic organisms. ?? 2007 Elsevier B.V. All rights reserved.

  11. Industry 5.0—The Relevance and Implications of Bionics and Synthetic Biology

    OpenAIRE

    Peter Sachsenmeier

    2016-01-01

    Bionics (the imitation or abstraction of the “inventions of nature) and, to an even greater extent, synthetic biology, will be as relevant to engineering development and industry as the silicon chip was over the last 50 years. Chemical industries already use so-called “white biotechnology” for new processes, new raw materials, and more sustainable use of resources. Synthetic biology is also used for the development of second-generation biofuels and for harvesting the sun's energy with the hel...

  12. Relevant uses of surface proteins – display on self‐organized biological structures

    OpenAIRE

    Jahns, Anika C.; Rehm, Bernd H. A.

    2012-01-01

    Summary Proteins are often found attached to surfaces of self‐assembling biological units such as whole microbial cells or subcellular structures, e.g. intracellular inclusions. In the last two decades surface proteins were identified that could serve as anchors for the display of foreign protein functions. Extensive protein engineering based on structure–function data enabled efficient display of technically and/or medically relevant protein functions. Small size, diversity of the anchor pro...

  13. Making developmental biology relevant to undergraduates in an era of economic rationalism in Australia.

    Science.gov (United States)

    Key, Brian; Nurcombe, Victor

    2003-01-01

    This report describes the road map we followed at our university to accommodate three main factors: financial pressure within the university system; desire to enhance the learning experience of undergraduates; and motivation to increase the prominence of the discipline of developmental biology in our university. We engineered a novel, multi-year undergraduate developmental biology program which was "student-oriented," ensuring that students were continually exposed to the underlying principles and philosophy of this discipline throughout their undergraduate career. Among its key features are introductory lectures in core courses in the first year, which emphasize the relevance of developmental biology to tissue engineering, reproductive medicine, therapeutic approaches in medicine, agriculture and aquaculture. State-of-the-art animated computer graphics and images of high visual impact are also used. In addition, students are streamed into the developmental biology track in the second year, using courses like human embryology and courses shared with cell biology, which include practicals based on modern experimental approaches. Finally, fully dedicated third-year courses in developmental biology are undertaken in conjunction with stand-alone practical courses where students experiencefirst-hand work in a research laboratory. Our philosophy is a "cradle-to-grave" approach to the education of undergraduates so as to prepare highly motivated, enthusiastic and well-educated developmental biologists for entry into graduate programs and ultimately post-doctoral research.

  14. A Critical Review of Naphthalene Sources and Exposures Relevant to Indoor and Outdoor Air

    Directory of Open Access Journals (Sweden)

    Chunrong Jia

    2010-07-01

    Full Text Available Both the recent classification of naphthalene as a possible human carcinogen and its ubiquitous presence motivate this critical review of naphthalene’s sources and exposures. We evaluate the environmental literature on naphthalene published since 1990, drawing on nearly 150 studies that report emissions and concentrations in indoor, outdoor and personal air. While naphthalene is both a volatile organic compound and a polycyclic aromatic hydrocarbon, concentrations and exposures are poorly characterized relative to many other pollutants. Most airborne emissions result from combustion, and key sources include industry, open burning, tailpipe emissions, and cigarettes. The second largest source is off-gassing, specifically from naphthalene’s use as a deodorizer, repellent and fumigant. In the U.S., naphthalene’s use as a moth repellant has been reduced in favor of para-dichlorobenzene, but extensive use continues in mothballs, which appears responsible for some of the highest indoor exposures, along with off-label uses. Among the studies judged to be representative, average concentrations ranged from 0.18 to 1.7 μg m-3 in non-smoker’s homes, and from 0.02 to 0.31 μg m-3 outdoors in urban areas. Personal exposures have been reported in only three European studies. Indoor sources are the major contributor to (non-occupational exposure. While its central tendencies fall well below guideline levels relevant to acute health impacts, several studies have reported maximum concentrations exceeding 100 μg m-3, far above guideline levels. Using current but draft estimates of cancer risks, naphthalene is a major environmental risk driver, with typical individual risk levels in the 10-4 range, which is high and notable given that millions of individuals are exposed. Several factors influence indoor and outdoor concentrations, but the literature is inconsistent on their effects. Further investigation is needed to better characterize naphthalene

  15. Consumer exposure to biocides - identification of relevant sources and evaluation of possible health effects

    Directory of Open Access Journals (Sweden)

    Heger Wolfgang

    2010-02-01

    Full Text Available Abstract Background Products containing biocides are used for a variety of purposes in the home environment. To assess potential health risks, data on products containing biocides were gathered by means of a market survey, exposures were estimated using a worst case scenario approach (screening, the hazard of the active components were evaluated, and a preliminary risk assessment was conducted. Methods Information on biocide-containing products was collected by on-site research, by an internet inquiry as well as research into databases and lists of active substances. Twenty active substances were selected for detailed investigation. The products containing these substances were subsequently classified by range of application; typical concentrations were derived. Potential exposures were then estimated using a worst case scenario approach according to the European Commission's Technical Guidance Document on Risk Assessment. Relevant combinations of scenarios and active substances were identified. The toxicological data for these substances were compiled in substance dossiers. For estimating risks, the margins of exposure (MOEs were determined. Results Numerous consumer products were found to contain biocides. However, it appeared that only a limited number of biocidal active substances or groups of biocidal active substances were being used. The lowest MOEs for dermal exposure or exposure by inhalation were obtained for the following scenarios and biocides: indoor pest control using sprays, stickers or evaporators (chlorpyrifos, dichlorvos and spraying of disinfectants as well as cleaning of surfaces with concentrates (hydrogen peroxide, formaldehyde, glutardialdehyde. The risk from aggregate exposure to individual biocides via different exposure scenarios was higher than the highest single exposure on average by a factor of three. From the 20 biocides assessed 10 had skin-sensitizing properties. The biocides isothiazolinone (mixture of 5-chloro

  16. Bisphenol A exposure at an environmentally relevant dose induces meiotic abnormalities in adult male rats.

    Science.gov (United States)

    Liu, Chuan; Duan, Weixia; Zhang, Lei; Xu, Shangcheng; Li, Renyan; Chen, Chunhai; He, Mindi; Lu, Yonghui; Wu, Hongjuan; Yu, Zhengping; Zhou, Zhou

    2014-01-01

    Whether environmental exposure to bisphenol A (BPA) may induce reproductive disorders is still controversial but certain studies have reported that BPA may cause meiotic abnormalities in C. elegans and female mice. However, little is known about the effect of BPA on meiosis in adult males. To determine whether BPA exposure at an environmentally relevant dose could induce meiotic abnormalities in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 20 μg/kg body weight (bw)/day for 60 consecutive days. We found that BPA significantly increased the proportion of stage VII seminiferous epithelium and decreased the proportion of stage VIII. Consequently, spermiation was inhibited and spermatogenesis was disrupted. Further investigation revealed that BPA exposure delayed meiosis initiation in the early meiotic stage and induced the accumulation of chromosomal abnormalities and meiotic DNA double-strand breaks (DSBs) in the late meiotic stage. The latter event subsequently activated the phosphatidylinositol 3-kinase-related protein kinase (ATM). Our results suggest that long-term exposure to BPA may lead to continuous meiotic abnormalities and ultimately put mammalian reproductive health at risk.

  17. Biological effects of exposure to magnetic resonance imaging: an overview

    Directory of Open Access Journals (Sweden)

    Formica Domenico

    2004-04-01

    Full Text Available Abstract The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to allow the integration of the specific literature on the bio-effects produced by magnetic resonance systems with the vast literature concerning the bio-effects produced by electromagnetic fields. This work gives an overview of the findings about the safety concerns of exposure to static magnetic fields, radio-frequency fields, and time varying magnetic field gradients, focusing primarily on the physics of the interactions between these electromagnetic fields and biological matter. The scientific literature is summarized, integrated, and critically analyzed with the help of authoritative reviews by recognized experts, international safety guidelines are also cited.

  18. Human urinary biomarkers of dioxin exposure: analysis by metabolomics and biologically driven data dimensionality reduction.

    Science.gov (United States)

    Jeanneret, Fabienne; Boccard, Julien; Badoud, Flavia; Sorg, Olivier; Tonoli, David; Pelclova, Daniela; Vlckova, Stepanka; Rutledge, Douglas N; Samer, Caroline F; Hochstrasser, Denis; Saurat, Jean-Hilaire; Rudaz, Serge

    2014-10-15

    Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers submitted to severe dioxin occupational exposure in a herbicide production plant in the late 1960s. Experiments were carried out with ultra-high pressure liquid chromatography (UHPLC) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry. A chemistry-driven feature selection was applied to focus on steroid-related metabolites. Supervised multivariate data analysis allowed biomarkers, mainly related to bile acids, to be highlighted. These results supported the hypothesis of liver damage and oxidative stress for long-term dioxin toxicity. As a second step of data analysis, the information gained from the urine analysis of Victor Yushchenko after his poisoning was examined. A subset of relevant urinary markers of acute dioxin toxicity from this extreme phenotype, including glucuro- and sulfo-conjugated endogenous steroid metabolites and bile acids, was assessed for its ability to detect long-term effects of exposure. The metabolomic strategy presented in this work allowed the determination of metabolic patterns related to dioxin effects in human and the discovery of highly predictive subsets of biologically meaningful and clinically relevant compounds. These results are expected to provide valuable information for a deeper understanding of the molecular events related to dioxin toxicity. Furthermore, it presents an original methodology of data dimensionality reduction by using extreme phenotype as a guide to select relevant features prior to data modeling (biologically driven data reduction).

  19. Nanogold – Biological effects and occupational exposure levels

    Directory of Open Access Journals (Sweden)

    Anna Maria Świdwińska-Gajewska

    2017-08-01

    Full Text Available Nanogold has different properties and biological activity compared to metallic gold. It can be applied in many fields, such as medicine, laboratory diagnostics and electronics. Studies on laboratory animals show that nanogold can be absorbed by inhalation and ingestion. It can penetrate deep into the epidermis and dermis, but there is no evidence that it is absorbed through the skin. Gold nanoobjects accumulate mainly in the liver and spleen, but they can also reach other internal organs. Nanogold can cross the blood–brain and blood–placenta barriers. Toxicokinetics of nanogold depends on the particle size, shape and surface charge. In animals exposure to gold nanoparticles via inhalation induces slight changes in the lungs. Exposure to nanogold by the oral route does not cause adverse health effects in rodents. In animals after injection of gold nanoobjects changes in the liver and lungs were observed. Nanogold induced genotoxic effects in cells, but not in animals. No adverse effects on the fetus or reproduction were found. There are no carcinogenicity studies on gold nanoparticles. The mechanism of toxicity may be related to the interaction of gold nanoobjects with proteins and DNA, and it leads to the induction of oxidative stress and genetic material damage. The impact of nanostructures on human health has not yet been fully understood. The person, who works with nanomaterials should exercise extreme caution and apply existing recommendations on the evaluation of nanoobjects exposure. The risk assessment should be the basis for taking appropriate measures to limit potential exposure to nanometals, including nanogold. Med Pr 2017;68(4:545–556

  20. Population distribution models: species distributions are better modeled using biologically relevant data partitions.

    Science.gov (United States)

    Gonzalez, Sergio C; Soto-Centeno, J Angel; Reed, David L

    2011-09-19

    Predicting the geographic distribution of widespread species through modeling is problematic for several reasons including high rates of omission errors. One potential source of error for modeling widespread species is that subspecies and/or races of species are frequently pooled for analyses, which may mask biologically relevant spatial variation within the distribution of a single widespread species. We contrast a presence-only maximum entropy model for the widely distributed oldfield mouse (Peromyscus polionotus) that includes all available presence locations for this species, with two composite maximum entropy models. The composite models either subdivided the total species distribution into four geographic quadrants or by fifteen subspecies to capture spatially relevant variation in P. polionotus distributions. Despite high Area Under the ROC Curve (AUC) values for all models, the composite species distribution model of P. polionotus generated from individual subspecies models represented the known distribution of the species much better than did the models produced by partitioning data into geographic quadrants or modeling the whole species as a single unit. Because the AUC values failed to describe the differences in the predictability of the three modeling strategies, we suggest using omission curves in addition to AUC values to assess model performance. Dividing the data of a widespread species into biologically relevant partitions greatly increased the performance of our distribution model; therefore, this approach may prove to be quite practical and informative for a wide range of modeling applications.

  1. Recent developments on ultrasound-assisted one-pot multicomponent synthesis of biologically relevant heterocycles.

    Science.gov (United States)

    Banerjee, Bubun

    2017-03-01

    Heterocycles are the backbone of organic compounds. Specially, N- &O-containing heterocycles represent privileged structural subunits well distributed in naturally occurring compounds with immense biological activities. Multicomponent reactions (MCRs) are becoming valuable tool for synthesizing structurally diverse molecular entities. On the other hand, the last decade has seen a tremendous outburst in modifying chemical processes to make them sustainable for the betterment of our environment. The application of ultrasound in organic synthesis is fulfilling some of the goals of 'green and sustainable chemistry' as it has some advantages over the traditional thermal methods in terms of reaction rates, yields, purity of the products, product selectivity, etc. Therefore the synthesis of biologically relevant heterocycles using one-pot multi-component technique coupled with the application of ultrasound is one of the thrusting areas in the 21st Century among the organic chemists. The present review deals with the "up to date" developments on ultrasound assisted one-pot multi-component synthesis of biologically relevant heterocycles reported so far.

  2. [Microbiological and biological methods of the European Pharmacopoeia. Relevant for each medicinal product].

    Science.gov (United States)

    Norwig, J

    2014-10-01

    According to the EU Directive 2001/83 the European Pharmacopoeia is the official Pharmacopoeia of the European Union. Therefore the European Pharmacopoeia is one of the legal pharmacopoeial compendia in Germany. Any licensed medicinal product on the German market complies with the requirements of the compendial monographs, if applicable. Because the general monographs of the European Pharmacopoeia on Dosage Forms, Substances for Pharmaceutical Use and Pharmaceutical Preparations refer to the microbiological and biological methods of the Pharmacopoeia, the methods are relevant for medicinal products, too. This article presents a rough summary of the microbiological and biological methods of the European Pharmacopoeia and is intended to be a stimulus for the reader to better understand the original compendia. The short description of the methods mentioned, here, is a summary from the Pharmacopoeia and the non-official collection of comments on the texts of the European Pharmacopoeia.

  3. Ideas and perspectives: climate-relevant marine biologically driven mechanisms in Earth system models

    Science.gov (United States)

    Hense, Inga; Stemmler, Irene; Sonntag, Sebastian

    2017-01-01

    The current generation of marine biogeochemical modules in Earth system models (ESMs) considers mainly the effect of marine biota on the carbon cycle. We propose to also implement other biologically driven mechanisms in ESMs so that more climate-relevant feedbacks are captured. We classify these mechanisms in three categories according to their functional role in the Earth system: (1) biogeochemical pumps, which affect the carbon cycling; (2) biological gas and particle shuttles, which affect the atmospheric composition; and (3) biogeophysical mechanisms, which affect the thermal, optical, and mechanical properties of the ocean. To resolve mechanisms from all three classes, we find it sufficient to include five functional groups: bulk phyto- and zooplankton, calcifiers, and coastal gas and surface mat producers. We strongly suggest to account for a larger mechanism diversity in ESMs in the future to improve the quality of climate projections.

  4. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles

    Energy Technology Data Exchange (ETDEWEB)

    Roedel, Erik Q., E-mail: Erik.Roedel@amedd.army.mil [Department of General Surgery, Tripler Army Medical Center, Honolulu, HI 96859 (United States); Cafasso, Danielle E., E-mail: Danielle.Cafasso@amedd.army.mil [Department of General Surgery, Tripler Army Medical Center, Honolulu, HI 96859 (United States); Lee, Karen W.M., E-mail: Karen.W.Lee@amedd.army.mil [Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, HI 96859 (United States); Pierce, Lisa M., E-mail: Lisa.Pierce@amedd.army.mil [Department of Clinical Investigation, Tripler Army Medical Center, Honolulu, HI 96859 (United States)

    2012-02-15

    Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24 h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals. -- Highlights: ► Intratracheal instillation of W–Ni–Co and W–Ni–Fe induces lung inflammation in rats. ► W–Ni–Co and W–Ni–Fe alter expression of oxidative stress and toxicity genes. ► W

  5. Environmentally relevant exposure to 17{alpha}-ethinylestradiol affects the telencephalic proteome of male fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Martyniuk, Christopher J., E-mail: cmartyn@unb.ca [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611 (United States); Kroll, Kevin J.; Doperalski, Nicholas J.; Barber, David S.; Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611 (United States)

    2010-07-15

    Estrogens are key mediators of neuronal processes in vertebrates. As such, xenoestrogens present in the environment have the potential to alter normal central nervous system (CNS) function. The objectives of the present study were (1) to identify proteins with altered abundance in the male fathead minnow telencephalon as a result of low-level exposure to17{alpha}-ethinylestradiol (EE{sub 2}), and (2) to better understand the underlying mechanisms of 17{beta}-estradiol (E{sub 2}) feedback in this important neuroendocrine tissue. Male fathead minnows exposed to a measured concentration of 5.4 ng EE{sub 2}/L for 48 h showed decreased plasma E{sub 2} levels of approximately 2-fold. Of 77 proteins that were quantified statistically, 14 proteins were down-regulated after EE{sub 2} exposure, including four histone proteins, ATP synthase, H+ transporting subunits, and metabolic proteins (lactate dehydrogenase B4, malate dehydrogenase 1b). Twelve proteins were significantly induced by EE{sub 2} including microtubule-associated protein tau (Mapt), astrocytic phosphoprotein, ependymin precursor, and calmodulin. Mapt showed an increase in protein abundance but a decrease in mRNA expression after EE{sub 2} exposure{sub ,} suggesting there may be a negative feedback response in the telencephalon to decreased mRNA transcription with increasing Mapt protein abundance. These results demonstrate that a low, environmentally relevant exposure to EE{sub 2} can rapidly alter the abundance of proteins involved in cell differentiation and proliferation, neuron network morphology, and long-term synaptic potentiation. Together, these findings provide a better understanding of the molecular responses underlying E{sub 2} feedback in the brain and demonstrate that quantitative proteomics can be successfully used in ecotoxicology to characterize affected cellular pathways and endocrine physiology.

  6. Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles.

    Science.gov (United States)

    Roedel, Erik Q; Cafasso, Danielle E; Lee, Karen W M; Pierce, Lisa M

    2012-02-15

    Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals.

  7. The development of Army relevant peptide-based surface enhanced Raman scattering (SERS) sensors for biological threat detection

    Science.gov (United States)

    Farrell, Mikella E.; Strobbia, Pietro; Sarkes, Deborah A.; Stratis-Cullum, Dimitra N.; Cullum, Brian M.; Pellegrino, Paul M.

    2016-05-01

    The utility of peptide-based molecular sensing for the development of novel biosensors has resulted in a significant increase in their development and usage for sensing targets like chemical, biological, energetic and toxic materials. Using peptides as a molecular recognition element is particularly advantageous because there are several mature peptide synthesis protocols that already exist, peptide structures can be tailored, selected and manipulated to be highly discerning towards desired targets, peptides can be modified to be very stable in a host of environments and stable under many different conditions, and through the development of bifunctionalized peptides can be synthesized to also bind onto desired sensing platforms (various metal materials, glass, etc.). Two examples of the several Army relevant biological targets for peptide-based sensing platforms include Ricin and Abrin. Ricin and Abrin are alarming threats because both can be weaponized and there is no antidote for exposure. Combining the sensitivity of SERS with the selectivity of a bifunctional peptide allows for the emergence of dynamic hazard sensor for Army application.

  8. Inactivation of the antibacterial and cytotoxic properties of silver ions by biologically relevant compounds.

    Directory of Open Access Journals (Sweden)

    Geraldine Mulley

    Full Text Available There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells. We demonstrate that biologically relevant compounds such as glutathione, cysteine and human blood components significantly reduce the toxicity of silver ions to clinically relevant pathogenic bacteria and primary human dermal fibroblasts (skin cells. Bacteria are able to grow normally in the presence of silver nitrate at >20-fold the minimum inhibitory concentration (MIC if Ag+ and thiols are added in a 1:1 ratio because the reaction of Ag+ with extracellular thiols prevents silver ions from interacting with cells. Extracellular thiols and human serum also significantly reduce the antimicrobial activity of silver wound dressings Aquacel-Ag (Convatec and Acticoat (Smith & Nephew to Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have important implications for the deployment of silver as an antimicrobial agent in environments exposed to biological tissue or secretions. Significant amounts of money and effort have been directed at the development of silver-coated medical devices (e.g. dressings, catheters, implants. We believe our findings are essential for the effective design and testing of antimicrobial silver coatings.

  9. Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting.

    Science.gov (United States)

    DeBord, D Gayle; Burgoon, Lyle; Edwards, Stephen W; Haber, Lynne T; Kanitz, M Helen; Kuempel, Eileen; Thomas, Russell S; Yucesoy, Berran

    2015-01-01

    In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments. This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identification of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely.

  10. Late biological effects from internal and external exposure

    Energy Technology Data Exchange (ETDEWEB)

    Adams, W.H.

    1985-01-01

    Information on late biological effects of radiation was obtained from the long-term medical followup of a small population of Marshallese accidentally exposed to radioactive fallout from a thermonuclear test in 1954. Endocrine data are compatible with a sequence of nonstochastic radiation effects. The ingestion of radioisotopes of iodine produced clinical thyroid hypofunction in children, biochemical evidence of thyroid dysfunction in some adults, thyroid adenomatous module formation, and, as a possible indirect effect of thyroid damage, at least two cases of pituitary adenoma. In contrast, the only evidence of a stochastic effect has been a real increase in thyroid cancers among the more highly exposed people of Rongelap, none of whom have evidence of residual disease. While three nonthyroidal cancers which are known to be inducible in humans by external irradiation have been documented in the exposed population, three similar cancers have occurred in an unexposed comparison population of Marshallese. Nonstochastic effects of radiation exposure may be common but subtle. In the Marshallese experience the morbidity of delayed nonstochastic effects far exceeds that of the stochastic. 20 refs., 5 figs., 1 tab.

  11. Industry 5.0—The Relevance and Implications of Bionics and Synthetic Biology

    Directory of Open Access Journals (Sweden)

    Peter Sachsenmeier

    2016-06-01

    Full Text Available Bionics (the imitation or abstraction of the “inventions of nature and, to an even greater extent, synthetic biology, will be as relevant to engineering development and industry as the silicon chip was over the last 50 years. Chemical industries already use so-called “white biotechnology” for new processes, new raw materials, and more sustainable use of resources. Synthetic biology is also used for the development of second-generation biofuels and for harvesting the sun's energy with the help of tailor-made microorganisms or biometrically designed catalysts. The market potential for bionics in medicine, engineering processes, and DNA storage is huge. “Moonshot” projects are already aggressively focusing on diseases and new materials, and a US-led competition is currently underway with the aim of creating a thousand new molecules. This article describes a timeline that starts with current projects and then moves on to code engineering projects and their implications, artificial DNA, signaling molecules, and biological circuitry. Beyond these projects, one of the next frontiers in bionics is the design of synthetic metabolisms that include artificial food chains and foods, and the bioengineering of raw materials; all of which will lead to new insights into biological principles. Bioengineering will be an innovation motor just as digitalization is today. This article discusses pertinent examples of bioengineering, particularly the use of alternative carbon-based biofuels and the techniques and perils of cell modification. Big data, analytics, and massive storage are important factors in this next frontier. Although synthetic biology will be as pervasive and transformative in the next 50 years as digitization and the Internet are today, its applications and impacts are still in nascent stages. This article provides a general taxonomy in which the development of bioengineering is classified in five stages (DNA analysis, bio

  12. Ion-binding of glycine zwitterion with inorganic ions in biologically relevant aqueous electrolyte solutions.

    Science.gov (United States)

    Fedotova, Marina V; Kruchinin, Sergey E

    2014-06-01

    The ion-binding between inorganic ions and charged functional groups of glycine zwitter-ion in NaCl(aq), KCl(aq), MgCl2(aq), and CaCl2(aq) has been investigated over a wide salt concentration range by using integral equation theory in the 3D-RISM approach. These systems mimic biological systems where binding of ions to charged residues at protein surfaces is relevant. It has been found that the stability of ion pairs formed by the carboxylate group and added inorganic cations decreases in the sequence Mg(2+)>Ca(2+)>Na(+)>K(+). However, all formed ion pairs are weak and decrease in stability with increasing salt concentration. On the other hand, at a given salt concentration the stability of (-NH3(+):Cl(-))aq ion pairs is similar in all studied systems. The features of ion-binding and the salt concentration effect on this process are discussed.

  13. Biologically relevant photoacoustic imaging phantoms with tunable optical and acoustic properties

    Science.gov (United States)

    Vogt, William C.; Jia, Congxian; Wear, Keith A.; Garra, Brian S.; Joshua Pfefer, T.

    2016-10-01

    Established medical imaging technologies such as magnetic resonance imaging and computed tomography rely on well-validated tissue-simulating phantoms for standardized testing of device image quality. The availability of high-quality phantoms for optical-acoustic diagnostics such as photoacoustic tomography (PAT) will facilitate standardization and clinical translation of these emerging approaches. Materials used in prior PAT phantoms do not provide a suitable combination of long-term stability and realistic acoustic and optical properties. Therefore, we have investigated the use of custom polyvinyl chloride plastisol (PVCP) formulations for imaging phantoms and identified a dual-plasticizer approach that provides biologically relevant ranges of relevant properties. Speed of sound and acoustic attenuation were determined over a frequency range of 4 to 9 MHz and optical absorption and scattering over a wavelength range of 400 to 1100 nm. We present characterization of several PVCP formulations, including one designed to mimic breast tissue. This material is used to construct a phantom comprised of an array of cylindrical, hemoglobin-filled inclusions for evaluation of penetration depth. Measurements with a custom near-infrared PAT imager provide quantitative and qualitative comparisons of phantom and tissue images. Results indicate that our PVCP material is uniquely suitable for PAT system image quality evaluation and may provide a practical tool for device validation and intercomparison.

  14. The ChEBI reference database and ontology for biologically relevant chemistry: enhancements for 2013.

    Science.gov (United States)

    Hastings, Janna; de Matos, Paula; Dekker, Adriano; Ennis, Marcus; Harsha, Bhavana; Kale, Namrata; Muthukrishnan, Venkatesh; Owen, Gareth; Turner, Steve; Williams, Mark; Steinbeck, Christoph

    2013-01-01

    ChEBI (http://www.ebi.ac.uk/chebi) is a database and ontology of chemical entities of biological interest. Over the past few years, ChEBI has continued to grow steadily in content, and has added several new features. In addition to incorporating all user-requested compounds, our annotation efforts have emphasized immunology, natural products and metabolites in many species. All database entries are now 'is_a' classified within the ontology, meaning that all of the chemicals are available to semantic reasoning tools that harness the classification hierarchy. We have completely aligned the ontology with the Open Biomedical Ontologies (OBO) Foundry-recommended upper level Basic Formal Ontology. Furthermore, we have aligned our chemical classification with the classification of chemical-involving processes in the Gene Ontology (GO), and as a result of this effort, the majority of chemical-involving processes in GO are now defined in terms of the ChEBI entities that participate in them. This effort necessitated incorporating many additional biologically relevant compounds. We have incorporated additional data types including reference citations, and the species and component for metabolites. Finally, our website and web services have had several enhancements, most notably the provision of a dynamic new interactive graph-based ontology visualization.

  15. Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks

    Science.gov (United States)

    Wiencko, Heather L.; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J.

    2016-01-01

    Highly connected nodes (hubs) in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT), which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed) than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest. Availability: CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store ( http://apps.cytoscape.org/apps/chat). PMID:27853512

  16. Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks.

    Science.gov (United States)

    Muetze, Tanja; Goenawan, Ivan H; Wiencko, Heather L; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J

    2016-01-01

    Highly connected nodes (hubs) in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT), which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed) than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest.

  17. Fungal Contaminants in Drinking Water Regulation? A Tale of Ecology, Exposure, Purification and Clinical Relevance

    Science.gov (United States)

    Novak Babič, Monika; Gunde-Cimerman, Nina; Vargha, Márta; Tischner, Zsófia; Magyar, Donát; Veríssimo, Cristina; Sabino, Raquel; Viegas, Carla; Meyer, Wieland; Brandão, João

    2017-01-01

    Microbiological drinking water safety is traditionally monitored mainly by bacterial parameters that indicate faecal contamination. These parameters correlate with gastro-intestinal illness, despite the fact that viral agents, resulting from faecal contamination, are usually the cause. This leaves behind microbes that can cause illness other than gastro-intestinal and several emerging pathogens, disregarding non-endemic microbial contaminants and those with recent pathogenic activity reported. This white paper focuses on one group of contaminants known to cause allergies, opportunistic infections and intoxications: Fungi. It presents a review on their occurrence, ecology and physiology. Additionally, factors contributing to their presence in water distribution systems, as well as their effect on water quality are discussed. Presence of opportunistic and pathogenic fungi in drinking water can pose a health risk to consumers due to daily contact with water, via several exposure points, such as drinking and showering. The clinical relevance and influence on human health of the most common fungal contaminants in drinking water is discussed. Our goal with this paper is to place fungal contaminants on the roadmap of evidence based and emerging threats for drinking water quality safety regulations.

  18. Relevant shellfish consumption data for dietary exposure assessment among high shellfish consumers, Western Brittany, France.

    Science.gov (United States)

    Picot, Cyndie; Nguyen, Thuan Anh; Carpentier, François-Gilles; Roudot, Alain-Claude; Parent-Massin, Dominique

    2011-04-01

    Shellfish consumption can be a major pathway of exposure to pollutants for humans. It is fundamental to know if people eat enough shellfish to cause health problems, firstly in high consumers as recreational shellfish harvesters. The objectives of this study were to investigate the types of shellfish eaten, number of meals, portion size, sources of shellfish and shellfish consumption rates among French recreational shellfish harvesters; to determine factors affecting consumption patterns and to examine the reliability of the two methods used: a Food Frequency Questionnaire and a one-month food diary. The mean consumption rates were 11.63 and 26.21 g/person/day for shellfish derived from a self-harvested source only and from all sources, respectively. Harvester consumption rates were between 6- and 15-fold higher than the general French population. The comparison between the FFQ and the food diary showed that results were reliable. Thereby, our results are relevant to assess risk due to shellfish consumption.

  19. MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic.

    Science.gov (United States)

    Stanton, Bruce A; Caldwell, Kathleen; Congdon, Clare Bates; Disney, Jane; Donahue, Maria; Ferguson, Elizabeth; Flemings, Elsie; Golden, Meredith; Guerinot, Mary Lou; Highman, Jay; James, Karen; Kim, Carol; Lantz, R Clark; Marvinney, Robert G; Mayer, Greg; Miller, David; Navas-Acien, Ana; Nordstrom, D Kirk; Postema, Sonia; Rardin, Laurie; Rosen, Barry; SenGupta, Arup; Shaw, Joseph; Stanton, Elizabeth; Susca, Paul

    2015-09-01

    This report is the outcome of the meeting "Environmental and Human Health Consequences of Arsenic" held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13-15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food, and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the US Environmental Protection Agency (EPA) has set a limit of 10 μg/L in public water supplies and the WHO has recommended an upper limit of 10 μg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry, and educators at the local, state, national, and international levels to (1) establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry, and others; (3) develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods; and (5) develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies.

  20. Stability of silver nanoparticles: agglomeration and oxidation in biological relevant conditions

    Science.gov (United States)

    Valenti, Laura E.; Giacomelli, Carla E.

    2017-05-01

    Silver nanoparticles (Ag-NP) are the most used nanomaterial in consumer products due to the intrinsic antimicrobial capacity of silver. However, Ag-NP may be also harmful to algae, aquatic species, mammalian cells, and higher plants because both Ag+ and nanoparticles are responsible of cell damages. The oxidative dissolution of Ag-NP would proceed to completion under oxic conditions, but the rate and extent of the dissolution depend on several factors. This work correlates the effect of the capping agent (albumin and citrate) with the stability of Ag-NP towards agglomeration in simulated body fluid (SBF) and oxidation in the presence of ROS species (H2O2). Capping provides colloidal stability only through electrostatic means, whereas albumin acts as bulky ligands giving steric and electrostatic repulsion, inhibiting the agglomeration in SBF. However, citrate capping protects Ag-NP from dissolution to a major extent than albumin does because of its reducing power. Moreover, citrate in solution minimizes the oxidation of albumin-coated Ag-NP even after long incubation times. H2O2-induced dissolution proceeds to completion with Ag-NP incubated in SBF, while incubation in citrate leads to an incomplete oxidation. In short, albumin is an excellent capping agent to minimize Ag-NP agglomeration whereas citrate provides a mild-reductive medium that prevents dissolution in biological relevant media as well as in the presence of ROS species. These results provide insight into how the surface properties and media composition affect the release of Ag+ from Ag-NP, related to the cell toxicity and relevant to the storage and lifetime of silver-containing nanomaterials.

  1. A Comparison of Biological and Adoptive Mothers and Fathers: The Relevance of Biological Kinship and Gendered Constructs of Parenthood.

    Science.gov (United States)

    Miall, Charlene E.; March, Karen

    2003-01-01

    Used qualitative interviews to examine beliefs and values about biological and adoptive parents. Considered how biological kinship, gender, and actual parenting behavior affect the assessments respondents made of the emotional bonding between parents and children. Found that biological and adoptive parents viewed motherhood as instinctive and…

  2. Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramnayam [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); Marcos, Ricard, E-mail: ricard.marcos@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); CIBER Epidemiología y Salud Pública, ISCIII, Madrid (Spain); Hernández, Alba, E-mail: alba.hernandez@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona (Spain); CIBER Epidemiología y Salud Pública, ISCIII, Madrid (Spain)

    2015-09-15

    Highlights: • Repair ability under long-term exposure to arsenic was tested using the comet assay. • Effects were measured under Ogg1 wild-type and deficient backgrounds. • Exposed cells repair less efficiency the DNA damage induced by SA, KBrO{sub 3}, MMA{sup III} or UVC radiation. • Oxidative damage and Ogg1 deficient background exacerbate repair deficiencies. • Overexpression of the arsenic metabolizing enzyme As3mt acts as adaptive mechanism. - Abstract: Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1{sup +/+} and Ogg1{sup −/−} genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1{sup +/+} and Ogg1{sup −/−} cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1{sup −/−} cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1{sup −/−} cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage—and Ogg1 deficiency

  3. Messina: a novel analysis tool to identify biologically relevant molecules in disease.

    Directory of Open Access Journals (Sweden)

    Mark Pinese

    Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

  4. Extracellular membrane vesicles in blood products-biology and clinical relevance

    Directory of Open Access Journals (Sweden)

    Emilija Krstova Krajnc

    2016-01-01

    Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

  5. Relevant uses of surface proteins--display on self-organized biological structures.

    Science.gov (United States)

    Jahns, Anika C; Rehm, Bernd H A

    2012-03-01

    Proteins are often found attached to surfaces of self-assembling biological units such as whole microbial cells or subcellular structures, e.g. intracellular inclusions. In the last two decades surface proteins were identified that could serve as anchors for the display of foreign protein functions. Extensive protein engineering based on structure-function data enabled efficient display of technically and/or medically relevant protein functions. Small size, diversity of the anchor protein as well as support structure, genetic manipulability and controlled cultivation of phages, bacterial cells and yeasts contributed to the establishment of designed and specifically functionalized tools for applications as sensors, catalysis, biomedicine, vaccine development and library-based screening technologies. Traditionally, phage display is employed for library screening but applications in biomedicine and vaccine development are also perceived. For some diagnostic purposes phages are even too small in size so other carrier materials where needed and gave way for cell and yeast display. Only recently, intracellular inclusions such as magnetosomes, polyhydroxyalkanoate granules and lipid bodies were conceived as stable subcellular structures enabling the display of foreign protein functions and showing potential as specific and tailor-made devices for medical and biotechnological applications.

  6. Discrimination between biologically relevant calcium phosphate phases by surface-analytical techniques

    Energy Technology Data Exchange (ETDEWEB)

    Kleine-Boymann, Matthias, E-mail: matthias.kleine-boymann@phys.chemie.uni-giessen.de; Rohnke, Marcus, E-mail: marcus.rohnke@phys.chemie.uni-giessen.de; Henss, Anja, E-mail: anja.henss@phys.chemie.uni-giessen.de; Peppler, Klaus, E-mail: klaus.peppler@phys.chemie.uni-giessen.de; Sann, Joachim, E-mail: joachim.sann@phys.chemie.uni-giessen.de; Janek, Juergen, E-mail: juergen.janek@phys.chemie.uni-giessen.de

    2014-08-01

    The spatially resolved phase identification of biologically relevant calcium phosphate phases (CPPs) in bone tissue is essential for the elucidation of bone remodeling mechanisms and for the diagnosis of bone diseases. Analytical methods with high spatial resolution for the discrimination between chemically quite close phases are rare. Therefore the applicability of state-of-the-art ToF-SIMS, XPS and EDX as chemically specific techniques was investigated. The eight CPPs hydroxyapatite (HAP), β-tricalcium phosphate (β-TCP), α-tricalcium phosphate (α-TCP), octacalcium phosphate (OCP), dicalcium phosphate dihydrate (DCPD), dicalcium phosphate (DCP), monocalcium phosphate (MCP) and amorphous calcium phosphate (ACP) were either commercial materials in high purity or synthesized by ourselves. The phase purity was proven by XRD analysis. All of the eight CPPs show different mass spectra and the phases can be discriminated by applying the principal component analysis method to the mass spectrometric data. The Ca/P ratios of all phosphates were determined by XPS and EDX. With both methods some CPPs can be distinguished, but the obtained Ca/P ratios deviate systematically from their theoretical values. It is necessary in any case to determine a calibration curve, respectively the ZAF values, from appropriate standards. In XPS also the O(1s)-satellite signals are correlated to the CPPs composition. Angle resolved and long-term XPS measurements of HAP clearly prove that there is no phosphate excess at the surface. Decomposition due to X-ray irradiation has not been observed.

  7. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

    Science.gov (United States)

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H; Johnson, Andrew D; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B; Nolte, Ilja M; van der Most, Peter J; Wright, Alan F; Shuldiner, Alan R; Morrison, Alanna C; Hofman, Albert; Smith, Albert V; Dreisbach, Albert W; Franke, Andre; Uitterlinden, Andre G; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I; Ponte, Belen; Oostra, Ben A; Paulweber, Bernhard; Krämer, Bernhard K; Mitchell, Braxton D; Buckley, Brendan M; Peralta, Carmen A; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N; Shaffer, Christian M; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J; Holliday, Elizabeth G; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B; Navis, Gerjan J; Curhan, Gary C; Ehret, George B; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K; Kramer, Holly; Lin, Honghuang; Leach, I Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M; Kolcic, Ivana; Persico, Ivana; Jukema, J Wouter; Wilson, James F; Felix, Janine F; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M; Gaspoz, Jean-Michel; Smith, Jennifer A; Faul, Jessica D; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N; Attia, John; Whitfield, John B; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C; Karjalainen, Juha; Fernandes, Jyotika K; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L; Lohman, Kurt; Portas, Laura; Launer, Lenore J; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K; Sale, Michele M; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B; Ridker, Paul M; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H; Kovacs, Peter; Wild, Philipp S; Froguel, Philippe; Rettig, Rainer; Mägi, Reedik; Biffar, Reiner; Schmidt, Reinhold; Middelberg, Rita P S; Carroll, Robert J; Penninx, Brenda W; Scott, Rodney J; Katz, Ronit; Sedaghat, Sanaz; Wild, Sarah H; Kardia, Sharon L R; Ulivi, Sheila; Hwang, Shih-Jen; Enroth, Stefan; Kloiber, Stefan; Trompet, Stella; Stengel, Benedicte; Hancock, Stephen J; Turner, Stephen T; Rosas, Sylvia E; Stracke, Sylvia; Harris, Tamara B; Zeller, Tanja; Zemunik, Tatijana; Lehtimäki, Terho; Illig, Thomas; Aspelund, Thor; Nikopensius, Tiit; Esko, Tonu; Tanaka, Toshiko; Gyllensten, Ulf; Völker, Uwe; Emilsson, Valur; Vitart, Veronique; Aalto, Ville; Gudnason, Vilmundur; Chouraki, Vincent; Chen, Wei-Min; Igl, Wilmar; März, Winfried; Koenig, Wolfgang; Lieb, Wolfgang; Loos, Ruth J F; Liu, Yongmei; Snieder, Harold; Pramstaller, Peter P; Parsa, Afshin; O'Connell, Jeffrey R; Susztak, Katalin; Hamet, Pavel; Tremblay, Johanne; de Boer, Ian H; Böger, Carsten A; Goessling, Wolfram; Chasman, Daniel I; Köttgen, Anna; Kao, W H Linda; Fox, Caroline S

    2016-01-21

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

  8. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

    Science.gov (United States)

    Pattaro, Cristian; Teumer, Alexander; Gorski, Mathias; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Garnaas, Maija; Tin, Adrienne; Sorice, Rossella; Li, Yong; Taliun, Daniel; Olden, Matthias; Foster, Meredith; Yang, Qiong; Chen, Ming-Huei; Pers, Tune H.; Johnson, Andrew D.; Ko, Yi-An; Fuchsberger, Christian; Tayo, Bamidele; Nalls, Michael; Feitosa, Mary F.; Isaacs, Aaron; Dehghan, Abbas; d'Adamo, Pio; Adeyemo, Adebowale; Dieffenbach, Aida Karina; Zonderman, Alan B.; Nolte, Ilja M.; van der Most, Peter J.; Wright, Alan F.; Shuldiner, Alan R.; Morrison, Alanna C.; Hofman, Albert; Smith, Albert V.; Dreisbach, Albert W.; Franke, Andre; Uitterlinden, Andre G.; Metspalu, Andres; Tonjes, Anke; Lupo, Antonio; Robino, Antonietta; Johansson, Åsa; Demirkan, Ayse; Kollerits, Barbara; Freedman, Barry I.; Ponte, Belen; Oostra, Ben A.; Paulweber, Bernhard; Krämer, Bernhard K.; Mitchell, Braxton D.; Buckley, Brendan M.; Peralta, Carmen A.; Hayward, Caroline; Helmer, Catherine; Rotimi, Charles N.; Shaffer, Christian M.; Müller, Christian; Sala, Cinzia; van Duijn, Cornelia M.; Saint-Pierre, Aude; Ackermann, Daniel; Shriner, Daniel; Ruggiero, Daniela; Toniolo, Daniela; Lu, Yingchang; Cusi, Daniele; Czamara, Darina; Ellinghaus, David; Siscovick, David S.; Ruderfer, Douglas; Gieger, Christian; Grallert, Harald; Rochtchina, Elena; Atkinson, Elizabeth J.; Holliday, Elizabeth G.; Boerwinkle, Eric; Salvi, Erika; Bottinger, Erwin P.; Murgia, Federico; Rivadeneira, Fernando; Ernst, Florian; Kronenberg, Florian; Hu, Frank B.; Navis, Gerjan J.; Curhan, Gary C.; Ehret, George B.; Homuth, Georg; Coassin, Stefan; Thun, Gian-Andri; Pistis, Giorgio; Gambaro, Giovanni; Malerba, Giovanni; Montgomery, Grant W.; Eiriksdottir, Gudny; Jacobs, Gunnar; Li, Guo; Wichmann, H-Erich; Campbell, Harry; Schmidt, Helena; Wallaschofski, Henri; Völzke, Henry; Brenner, Hermann; Kroemer, Heyo K.; Kramer, Holly; Lin, Honghuang; Leach, I. Mateo; Ford, Ian; Guessous, Idris; Rudan, Igor; Prokopenko, Inga; Borecki, Ingrid; Heid, Iris M.; Kolcic, Ivana; Persico, Ivana; Jukema, J. Wouter; Wilson, James F.; Felix, Janine F.; Divers, Jasmin; Lambert, Jean-Charles; Stafford, Jeanette M.; Gaspoz, Jean-Michel; Smith, Jennifer A.; Faul, Jessica D.; Wang, Jie Jin; Ding, Jingzhong; Hirschhorn, Joel N.; Attia, John; Whitfield, John B.; Chalmers, John; Viikari, Jorma; Coresh, Josef; Denny, Joshua C.; Karjalainen, Juha; Fernandes, Jyotika K.; Endlich, Karlhans; Butterbach, Katja; Keene, Keith L.; Lohman, Kurt; Portas, Laura; Launer, Lenore J.; Lyytikäinen, Leo-Pekka; Yengo, Loic; Franke, Lude; Ferrucci, Luigi; Rose, Lynda M.; Kedenko, Lyudmyla; Rao, Madhumathi; Struchalin, Maksim; Kleber, Marcus E.; Cavalieri, Margherita; Haun, Margot; Cornelis, Marilyn C.; Ciullo, Marina; Pirastu, Mario; de Andrade, Mariza; McEvoy, Mark A.; Woodward, Mark; Adam, Martin; Cocca, Massimiliano; Nauck, Matthias; Imboden, Medea; Waldenberger, Melanie; Pruijm, Menno; Metzger, Marie; Stumvoll, Michael; Evans, Michele K.; Sale, Michele M.; Kähönen, Mika; Boban, Mladen; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Bouatia-Naji, Nabila; Martin, Nicholas G.; Hastie, Nick; Probst-Hensch, Nicole; Soranzo, Nicole; Devuyst, Olivier; Raitakari, Olli; Gottesman, Omri; Franco, Oscar H.; Polasek, Ozren; Gasparini, Paolo; Munroe, Patricia B.; Ridker, Paul M.; Mitchell, Paul; Muntner, Paul; Meisinger, Christa; Smit, Johannes H.; Abecasis, Goncalo R.; Adair, Linda S.; Alexander, Myriam; Altshuler, David; Amin, Najaf; Arking, Dan E.; Arora, Pankaj; Aulchenko, Yurii; Bakker, Stephan J. L.; Bandinelli, Stefania; Barroso, Ines; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Bis, Joshua C.; Boehnke, Michael; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bots, Michiel L.; Bragg-Gresham, Jennifer L.; Brand, Stefan-Martin; Brand, Eva; Braund, Peter S.; Brown, Morris J.; Burton, Paul R.; Casas, Juan P.; Caulfield, Mark J.; Chakravarti, Aravinda; Chambers, John C.; Chandak, Giriraj R.; Chang, Yen-Pei C.; Charchar, Fadi J.; Chaturvedi, Nish; Shin Cho, Yoon; Clarke, Robert; Collins, Francis S.; Collins, Rory; Connell, John M.; Cooper, Jackie A.; Cooper, Matthew N.; Cooper, Richard S.; Corsi, Anna Maria; Dörr, Marcus; Dahgam, Santosh; Danesh, John; Smith, George Davey; Day, Ian N. M.; Deloukas, Panos; Denniff, Matthew; Dominiczak, Anna F.; Dong, Yanbin; Doumatey, Ayo; Elliott, Paul; Elosua, Roberto; Erdmann, Jeanette; Eyheramendy, Susana; Farrall, Martin; Fava, Cristiano; Forrester, Terrence; Fowkes, F. Gerald R.; Fox, Ervin R.; Frayling, Timothy M.; Galan, Pilar

    2016-01-01

    Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. PMID:26831199

  9. [Biological monitoring of PAH exposure among asphalt workers].

    Science.gov (United States)

    Campo, Laura; Calisti, Roberto; Polledri, Elisa; Barretta, Francesco; Stopponi, Roberta; Massacesi, Stefania; Bertazzi, Pieralberto; Fustinoni, Silvia

    2011-01-01

    Aim of this work was the assessment of exposure to polycyclic aromatic hydrocarbons (PAHs) by urinary 1-hydroxypyrene (1-OHPyr) in asphalt workers. Median levels of 1-OHPyr resulted higher in asphalt workers than in controls (184 vs. < 20 ng/L, p < 0.001). The determinants of exposure of 1-OHPyr resulted smoking habit, the number of consecutive days at work and the job task; 1-OHPyr was also associated to urinary creatinine. End of work week 1-OHPyr is suggested as an useful indicator of occupational exposure to PAHs in bitumen fumes.

  10. Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

    Science.gov (United States)

    Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

    2013-07-01

    The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship.

  11. Reduced cellular DNA repair capacity after environmentally relevant arsenic exposure. Influence of Ogg1 deficiency.

    Science.gov (United States)

    Bach, Jordi; Peremartí, Jana; Annangi, Balasubramnayam; Marcos, Ricard; Hernández, Alba

    2015-09-01

    Inorganic arsenic (i-As) is a genotoxic and carcinogenic environmental contaminant known to affect millions of people worldwide. Our previous work demonstrated that chronic sub-toxic i-As concentrations were able to induce biologically significant levels of genotoxic and oxidative DNA damage that were strongly influenced by the Ogg1 genotype. In order to study the nature of the observed levels of damage and the observed differences between MEF Ogg1(+/+) and Ogg1(-/-) genetic backgrounds, the genotoxic and oxidative DNA repair kinetics of 18-weeks exposed MEF cells were evaluated by the comet assay. Results indicate that MEF Ogg1(+/+) and Ogg1(-/-) cells chronically exposed to i-As repair the DNA damage induced by arsenite, potassium bromide and UVC radiation less efficiently than control cells, being that observation clearly more pronounced in MEF Ogg1(-/-) cells. Consequently, exposed cells accumulate a higher percentage of unrepaired DNA damage at the end of the repair period. As an attempt to eliminate i-As associated toxicity, chronically exposed MEF Ogg1(-/-) cells overexpress the arsenic metabolizing enzyme As3mt. This adaptive response confers cells a significant resistance to i-As-induced cell death, but at expenses of accumulating high levels of DNA damage due to their repair impairment. Overall, the work presented here evidences that i-As chronic exposure disrupts the normal cellular repair function, and that oxidative DNA damage-and Ogg1 deficiency-exacerbates this phenomenon. The observed cell death resistance under a chronic scenario of genotoxic and oxidative stress may in turn contribute to the carcinogenic effects of i-As.

  12. Isopropanol exposure : environmental and biological monitoring in a printing works

    OpenAIRE

    Brugnone, F; Perbellini, L; Apostoli, P.; Bellomi, M; Caretta, D.

    1983-01-01

    Occupational exposure to isopropanol was studied in 12 workers by testing environmental air, alveolar air, venous blood, and urine during their work shift. Isopropanol, which ranged in environmental air between 7 and 645 mg/m3, was detected in alveolar air, where it ranged between 4 and 437 mg/m3, but not in blood or in urine. Alveolar isopropanol concentration (Ca) was significantly correlated with environmental isopropanol concentration (Ci) at any time of exposure. The value of the arithme...

  13. Organizational influence on the occurrence of work accidents involving exposure to biological material

    National Research Council Canada - National Science Library

    Marziale, Maria Helena Palucci; Rocha, Fernanda Ludmilla Rossi; Robazzi, Maria Lúcia do Carmo Cruz; Cenzi, Camila Maria; Santos, Heloisa Ehmke Cardoso dos; Trovó, Marli Elisa Mendes

    2013-01-01

    OBJECTIVES: to analyze work accidents involving exposure to biological materials which took place among personnel working in nursing and to evaluate the influence of the organizational culture on the occurrence of these accidents. METHOD...

  14. A SIMPLE COLORIMETRIC METHOD TO DETECT BIOLOGICAL EVIDENCE OF HUMAN EXPOSURE TO MICROCYSTINS

    Science.gov (United States)

    Toxic cyanobacteria are contaminants of surface waters worldwide. Microcystins are some of the most commonly detected toxins. Biological evidence of human exposure may be difficult to obtain due to limitations associated with cost, laboratory capacity, analytic support, and exp...

  15. Biological effects of exposure to magnetic resonance imaging: an overview

    OpenAIRE

    Formica Domenico; Silvestri Sergio

    2004-01-01

    Abstract The literature on biological effects of magnetic and electromagnetic fields commonly utilized in magnetic resonance imaging systems is surveyed here. After an introduction on the basic principles of magnetic resonance imaging and the electric and magnetic properties of biological tissues, the basic phenomena to understand the bio-effects are described in classical terms. Values of field strengths and frequencies commonly utilized in these diagnostic systems are reported in order to a...

  16. Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

    Directory of Open Access Journals (Sweden)

    Kuei-Fang Lee

    2014-01-01

    Full Text Available Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.

  17. Dietary exposure of Daphnia to microcystins: no in vivo relevance of biotransformation.

    Science.gov (United States)

    Sadler, Thomas; von Elert, Eric

    2014-05-01

    Anthropogenic nutrient input into lakes has contributed to the increased frequency of toxic cyanobacterial blooms. Daphnia populations have been shown to be locally adapted to toxic cyanobacteria and are able to suppress bloom formation; little is known about the physiology behind this phenomenon. Microcystin-LR (MCLR) is the most widespread cyanobacterial toxin, and, based on in vitro experiments, it is assumed that the enzyme glutathione-S-transferase (GST) might act as the first step of detoxification in Daphnia by conjugating MCLR with glutathione. In the present study Daphnia magna was fed a diet of 100% Microcystis aeruginosa PCC7806, a cyanobacterial strain that contains MCLR in high amounts (4.8-5.6 fg cell(-1)), in order to test for a possible conjugation of MCLR with GST in Daphnia in vivo. We used high-resolution LCMS to analyze incubation water, cyanobacterial cells and Daphnia tissue for the presence of MCLR conjugation products as well as unconjugated MCLR. Newly formed conjugation products were detected neither in Daphnia tissue nor in the incubation water. Moreover, the presence of Daphnia led to a decrease in unconjugated MCLR in the cyanobacterial cell fraction due to grazing, in comparison to a control without daphnids, which was well reflected by a similar increase of MCLR in the respective incubation water. As a consequence, the MCLR content did not change due to Daphnia presence within the entire experimental setup. In summary, MCLR ingestion by Daphnia led neither to the formation of conjugation products, nor to a decrease of unconjugated MCLR. GST-mediated conjugation thus seems to be of minor relevance for microcystin (MC) tolerance in Daphnia in vivo. This finding is supported by the fact that GST activity in Daphnia feeding on the MC-containing wildtype or a MC-free mutant of M. aeruginosa PCC7806 revealed an identical increase of specific activity in comparison to a cyanobacteria-free diet. Therefore, the frequently observed induction of

  18. Biological processes and optical measurements near the sea surface: Some issues relevant to remote sensing

    Science.gov (United States)

    Cullen, John J.; Lewis, Marlon R.

    1995-01-01

    The advent of remote sensing, the develpmemt of new optical instrumentation, and the associated advances in hydrological optics have transformed oceanography; it is now feasible to describe ocean-scale biogeochemical dynamcis from satellite observations, verified and complemented by measurements from optical sensors on profilers, moorings, and drifters. Only near-surface observations are common to both remote sensing and in situ observation, so it is critical to understand processes in the upper euphotic zone. Unfortunately, the biological principles that must be used to interpret optical variability near the sea surface are weaker than we would like, because relatively few experiments and analyses have examined bio-optical relationships under high irradiance characteristic of the upper optical depth. Special consideration of this stratum is justified, because there is good evidence that bio-optical relationships are altered near the surface; (1) the fluorescence yield from chlorophyll declines, leading to bias in the estimation of pigment from fluorometry; (2) the modeled relationship between solar-stimulated fluorecence and photosynthesis seems to deviate significantly from that presented for the lower euphotic zone; and (3) carbon-specific and cellular attenuation cross sections of phytoplankton change substantially during exposures to bright light. Even the measurement of primary productivity is problematic near the sea surface, because vertical mixing is not simulated and artifactual inhibition of photosynthesis can result. These problems can be addressed by focusing more sampling effort, experimental simulation, and analytical consideration on the upper optical depth, and by shortening timescales for the measurement of marine photosynthesis. Special efforts to study near-surface processes are justified, because new bio-optical algorithms will require quantitaitve descriptions of the responses of phytoplankton to bright light.

  19. Identifying genes relevant to specific biological conditions in time course microarray experiments.

    Science.gov (United States)

    Singh, Nitesh Kumar; Repsilber, Dirk; Liebscher, Volkmar; Taher, Leila; Fuellen, Georg

    2013-01-01

    Microarrays have been useful in understanding various biological processes by allowing the simultaneous study of the expression of thousands of genes. However, the analysis of microarray data is a challenging task. One of the key problems in microarray analysis is the classification of unknown expression profiles. Specifically, the often large number of non-informative genes on the microarray adversely affects the performance and efficiency of classification algorithms. Furthermore, the skewed ratio of sample to variable poses a risk of overfitting. Thus, in this context, feature selection methods become crucial to select relevant genes and, hence, improve classification accuracy. In this study, we investigated feature selection methods based on gene expression profiles and protein interactions. We found that in our setup, the addition of protein interaction information did not contribute to any significant improvement of the classification results. Furthermore, we developed a novel feature selection method that relies exclusively on observed gene expression changes in microarray experiments, which we call "relative Signal-to-Noise ratio" (rSNR). More precisely, the rSNR ranks genes based on their specificity to an experimental condition, by comparing intrinsic variation, i.e. variation in gene expression within an experimental condition, with extrinsic variation, i.e. variation in gene expression across experimental conditions. Genes with low variation within an experimental condition of interest and high variation across experimental conditions are ranked higher, and help in improving classification accuracy. We compared different feature selection methods on two time-series microarray datasets and one static microarray dataset. We found that the rSNR performed generally better than the other methods.

  20. Biological markers in animals can provide information on exposure and bioavailability of environmental contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L.R.; Adams, S.M.; Jimenez, B.D.; Talmage, S.S.; McCarthy, J.F.

    1987-01-01

    Epidemiologic studies of agents present in the environment seek to identify the extent to which they contribute to the causation of a specific toxic, clinical, or pathological endpoint. The multifactorial nature of disease etiology, long latency periods and the complexity of exposure, all contribute to the difficulty of establishing associations and casual relationships between a specific exposure and an adverse outcome. These barriers to studies of exposures and subsequent risk assessment cannot generally be changed. However, the appropriate use of biological markers in animal species living in a contaminated habitat can provide a measure of potential damage from that exposure and, in some instances, act as a surrogate for human environmental exposures. Quantitative predictivity of the effect of exposure to environmental pollutants is being approached by employing an appropriate array of biological end points. 34 refs., 1 fig., 6 tabs.

  1. Study about the relevance and the disclosure of biological assets of listed companies in BM&FBOVESPA

    Directory of Open Access Journals (Sweden)

    Luciana Holtz

    2013-08-01

    Full Text Available The main objective this article is to verify that the information content of biological assets disclosed in the financial statements are relevant and, the secondary objective perform content analysis of the notes verifying the compliance of information supplied by entities with CPC 29. The study sample was composed of publicly traded stock companies listed on the BM & FBOVESPA with data for the year 2010 and 2011. The empirical tests were conducted applying relevance models, using observations of 347 active companies characterizing a study model pooled ordinary least squares – POLS, including companies that have reported biological assets into account specific .The companies that had values of biological assets posted have had analyzed explanatory notes referring to this account. The results provide empirical evidence that the information content of biological assets disclosed by companies is not relevant to the sample. In relation the content analysis of the notes was checked a partial compliance of the standard, there is a disparity in the information disclosure practices by the companies analyzed, as well as an omission of items required by the standard. Can be inferred that loss of the relevance has occurred, in part, by the poor quality of the notes, which may make it difficult for outside users in interpreting the information disclosed.

  2. Exposure-Relevant Consumer Product Usage Information Derived from Longitudinal Purchasing Data

    Science.gov (United States)

    Consumer products that are used in and around the home are a dominant source for anthropogenic chemical exposure. Prediction of the population distribution of chemical exposures encountered due to the residential use of consumer products (such as personal care products, cleaning ...

  3. Lung tumors in mice induced by "whole-life" inorganic arsenic exposure at human-relevant doses.

    Science.gov (United States)

    Waalkes, Michael P; Qu, Wei; Tokar, Erik J; Kissling, Grace E; Dixon, Darlene

    2014-08-01

    In mice, inorganic arsenic in the drinking water in the parts per million range via the dam during in utero life or with whole-life exposure is a multi-site carcinogen in the offspring. However, human arsenic exposure is typically in the parts per billion (ppb) range. Thus, we studied "whole-life" inorganic arsenic carcinogenesis in mice at levels more relevant to humans. Breeder male and female CD1 mice were exposed to 0, 50, 500 or 5,000 ppb arsenic (as sodium arsenite) in the drinking water for 3 weeks prior to breeding, during pregnancy and lactation, and after weaning (at week 3) groups of male and female offspring (initial n = 40) were exposed for up to 2 years. Tumors were assessed in these offspring. Arsenic exposure had no effect on pregnant dam weights or water consumption, litter size, offspring birthweight or weight at weaning compared to control. In male offspring mice, arsenic exposure increased (p ppb group (51 %) and 500-ppb group (54 %), but not at 5,000-ppb group (28 %) compared to control (22 %). These arsenic-induced bronchiolo-alveolar tumors included increased (p ppb group (27 %) compared to controls (8 %). An increase (p ppb group compared to control (11 %) occurred in female offspring. Thus, in CD1 mice whole-life arsenic exposure induced lung tumors at human-relevant doses (i.e., 50 and 500 ppb).

  4. Lung Tumors in Mice Induced by “Whole Life” Inorganic Arsenic Exposure at Human Relevant Doses

    Science.gov (United States)

    Qu, Wei; Tokar, Erik J.; Kissling, Grace E.; Dixon, Darlene

    2014-01-01

    In mice, inorganic arsenic in the drinking water in the parts per million (ppm) range via the dam during in utero life or with whole life exposure is a multi-site carcinogen in the offspring. However, human arsenic exposure is typically in the parts per billion (ppb) range. Thus, we studied “whole life” inorganic arsenic carcinogenesis in mice at levels more relevant to humans. Breeder male and female CD1 mice were exposed to 0, 50, 500 or 5000 ppb arsenic (as sodium arsenite) in the drinking water for three weeks prior to breeding, during pregnancy and lactation, and after weaning (at week 3) groups of male and female offspring (initial n = 40) were exposed for up to 2 years. Tumors were assessed in these offspring. Arsenic exposure had no effect on pregnant dam weights or water consumption, litter size, offspring birth weight, or weight at weaning compared to control. In male offspring mice, arsenic exposure increased (p ppb (51%) and 500 ppb (54%), but not at 5000 ppb (28%) compared to control (22%). These arsenic-induced bronchiolo-alveolar tumors included increased (p ppb (27%) compared to controls (8%). An increase (p ppb group compared to control (11%) occurred in female offspring. Thus, in CD1 mice whole life arsenic exposure induced lung tumors at human relevant doses (i.e. 50 and 500 ppb). PMID:25005685

  5. Sensitivity of the sea snail Gibbula umbilicalis to mercury exposure--linking endpoints from different biological organization levels.

    Science.gov (United States)

    Cabecinhas, Adriana S; Novais, Sara C; Santos, Sílvia C; Rodrigues, Andreia C M; Pestana, João L T; Soares, Amadeu M V M; Lemos, Marco F L

    2015-01-01

    Mercury contamination is a common phenomenon in the marine environment and for this reason it is important to develop cost-effective and relevant tools to assess its toxic effects on a number of different species. To evaluate the possible effects of Hg in the sea snail Gibbula umbilicalis, animals were exposed to increasing concentrations of the contaminant in the ionic form for 96 h. After this exposure period, mortality, feeding and flipping behavior, the activity of the biomarkers glutathione S-transferase, superoxide dismutase, catalase, lactate dehydrogenase and cholinesterase, the levels of lipid peroxidation and cellular energy allocation were measured. After 96 h of exposure to the highest Hg concentration (≈LC20), there was a significant inhibition of the cholinesterase activity as well as impairment in the flipping behavior and post-exposure feeding of the snails. Cholinesterase inhibition was correlated with the impairment of behavioral responses also caused by exposure to Hg. These endpoints, including the novel flipping test, revealed sensitivity to Hg and might be used as relevant early warning indicators of prospective effects at higher biological organization levels, making these parameters potential tools for environmental risk assessment. The proposed test species showed sensitivity to Hg and proved to be a suitable and resourceful species to be used in ecotoxicological testing to assess effects of other contaminants in marine ecosystems.

  6. Biological exposure metrics of beryllium-exposed dental technicians.

    Science.gov (United States)

    Stark, Moshe; Lerman, Yehuda; Kapel, Arik; Pardo, Asher; Schwarz, Yehuda; Newman, Lee; Maier, Lisa; Fireman, Elizabeth

    2014-01-01

    Beryllium is commonly used in the dental industry. This study investigates the association between particle size and shape in induced sputum (IS) with beryllium exposure and oxidative stress in 83 dental technicians. Particle size and shape were defined by laser and video, whereas beryllium exposure data came from self-reports and beryllium lymphocyte proliferation test (BeLPT) results. Heme oxygenase-1 (HO1) gene expression in IS was evaluated by quantitative polymerase chain reaction. A high content of particles (92%) in IS >5 μ in size is correlated to a positive BeLPT risk (odds ratio [OR] = 3.4, 95% confidence interval [CI]: 0.9-13). Use of masks, hoods, and type of exposure yielded differences in the transparency of IS particles (gray level) and modulate HO1 levels. These results indicate that parameters of size and shape of particles in IS are sensitive to workplace hygiene, affect the level of oxidative stress, and may be potential markers for monitoring hazardous dust exposures.

  7. A Study to Interpret the Biological Significance of Behavior Associated with 3S Experimental Sonar Exposures

    Science.gov (United States)

    2014-09-30

    Behavior Associated with 3S Experimental Sonar Exposures Patrick Miller Sea Mammal Research Unit Scottish Oceans Institute School of Biology...to investigate behavioral reactions of cetaceans to naval sonar and various control sounds, and the sound exposures required to elicit responses, in...order to establish safety limits for sonar operations. 3S project efforts have been focused upon informing the ‘exposure-effect assessment

  8. FDTD Simulation of Exposure of Biological Material to Electromagnetic Nanopulses

    CERN Document Server

    Simicevic, N; Simicevic, Neven; Haynie, Donald T

    2004-01-01

    Ultra-wideband (UWB) electromagnetic pulses of nanosecond duration, or nanopulses, are of considerable interest to the communications industry and are being explored for various applications in biotechnology and medicine. The propagation of a nanopulse through biological matter has been computed in the time domain using the finite difference-time domain method (FDTD). The approach required existing Cole-Cole model-based descriptions of dielectric properties of biological matter to be re-parametrized using the Debye model, but without loss of accuracy. The approach has been applied to several tissue types. Results show that the electromagnetic field inside a biological tissue depends on incident pulse rise time and width. Rise time dominates pulse behavior inside a tissue as conductivity increases. It has also been found that the amount of energy deposited by 20 $kV/m$ nanopulses is insufficient to change the temperature of the exposed material for the pulse repetition rates of 1 $MHz$ or less.

  9. Lung Tumors in Mice Induced by “Whole Life” Inorganic Arsenic Exposure at Human Relevant Doses

    OpenAIRE

    Waalkes, Michael P.; Qu, Wei; Tokar, Erik J.; Kissling, Grace E.; Dixon, Darlene

    2014-01-01

    In mice, inorganic arsenic in the drinking water in the parts per million (ppm) range via the dam during in utero life or with whole life exposure is a multi-site carcinogen in the offspring. However, human arsenic exposure is typically in the parts per billion (ppb) range. Thus, we studied “whole life” inorganic arsenic carcinogenesis in mice at levels more relevant to humans. Breeder male and female CD1 mice were exposed to 0, 50, 500 or 5000 ppb arsenic (as sodium arsenite) in the drinking...

  10. Behaviour of biological indicators of cadmium in relation to occupational exposure

    Energy Technology Data Exchange (ETDEWEB)

    Ghezzi, I.; Toffoletto, F.; Sesana, G.; Fagioli, M.G.; Micheli, A.; Di Silvestro, P.; Zocchetti, C.; Alessio, L.

    1985-01-01

    Cadmium in blood (CdB), cadmium in urine (CdU) and beta 2-microglobulins (beta 2MU) were determined in 83 male workers exposed to cadmium fumes. The behaviour of the biological indicators of cadmium was assessed in relation to degree of current exposure, length of exposure and cumulative exposure (computed as concentration of cadmium at the workplace multiplied by duration of exposure). CdB values were significantly higher in the subgroups of subjects with higher current cadmium exposure and in the subgroups of subjects with greater cumulative exposure, but the test levels were not influenced by duration of exposure. CdU levels were significantly higher in the subgroup of subjects with greater cumulative exposure, but were less influenced by current exposure or duration of exposure. Considering the entire population, a rather close correlation was observed between CdB and CdU. When the population was divided according to level of current exposure, a close relationship was observed between the two indicators in all subgroups; nevertheless, for identical CdU values, the CdB values were higher in the subjects with heavier current exposure. The data confirm that CdU is prevalently influenced by the body burden of metal, but they also suggest that the CdB levels are not influenced solely by the intensity of current exposure but also depend to a considerable degree on the body burden.

  11. Urinary metallothionein as a biological indicator of occupational cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tohyama, C.; Shaikh, Z.A.; Ellis, K.J.; Cohn, S.H.

    1981-01-01

    Radioimmunoassay and neutron activation data indicate that the urinary metallothionein concentration is related to the liver Cd concentration in occupational Cd exposure. It is also related to the kidney Cd content - but only before the onset of renal dysfunction. Further epidemiological studies are needed to establish a dose-response relationship, which may be useful in minimizing the hazard of Cd-induced renal dysfunction.

  12. Enhanced stability and local structure in biologically relevant amorphous materials containing pyrophosphate

    Energy Technology Data Exchange (ETDEWEB)

    Slater, Colin; Laurencin, Danielle; Burnell, Victoria; Smith, Mark E.; Grover, Liam M.; Hriljac, Joseph A.; Wright, Adrian J. (CNRS-UMR); (Birmingham UK)

    2012-10-25

    There is increasing evidence that amorphous inorganic materials play a key role in biomineralisation in many organisms, however the inherent instability of synthetic analogues in the absence of the complex in vivo matrix limits their study and clinical exploitation. To address this, we report here an approach that enhances long-term stability to >1 year of biologically relevant amorphous metal phosphates, in the absence of any complex stabilizers, by utilizing pyrophosphates (P{sub 2}O{sub 7}{sup 4-}); species themselves ubiquitous in vivo. Ambient temperature precipitation reactions were employed to synthesise amorphous Ca{sub 2}P{sub 2}O{sub 7}.nH{sub 2}O and Sr{sub 2}P{sub 2}O{sub 7}.nH{sub 2}O (3.8 < n < 4.2) and their stability and structure were investigated. Pair distribution functions (PDF) derived from synchrotron X-ray data indicated a lack of structural order beyond 8 {angstrom} in both phases, with this local order found to resemble crystalline analogues. Further studies, including {sup 1}H and {sup 31}P solid state NMR, suggest the unusually high stability of these purely inorganic amorphous phases is partly due to disorder in the P-O-P bond angles within the P{sub 2}O{sub 7} units, which impede crystallization, and to water molecules, which are involved in H-bonds of various strengths within the structures and hamper the formation of an ordered network. In situ high temperature powder X-ray diffraction data indicated that the amorphous nature of both phases surprisingly persisted to 450 C. Further NMR and TGA studies found that above ambient temperature some water molecules reacted with P{sub 2}O{sub 7} anions, leading to the hydrolysis of some P-O-P linkages and the formation of HPO{sub 4}{sup 2-} anions within the amorphous matrix. The latter anions then recombined into P{sub 2}O{sub 7} ions at higher temperatures prior to crystallization. Together, these findings provide important new materials with unexplored potential for enzyme

  13. Biological effects of low-dose ionizing radiation exposure; Biologische Wirkungen niedriger Dosen ionisierender Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst (comps.)

    2009-07-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  14. Current research on biological effects of low-level exposures

    Energy Technology Data Exchange (ETDEWEB)

    Sagan, L.A.

    1994-12-31

    Rather substantial numbers of industrial chemicals, pharmaceuticals, and radiation display U-shaped or seemingly paradoxical dose-response relationships. A limited listing of studies providing examples of data fitting the U-shaped curve has been published. This array suggests that the U-shaped response is broadly generalizable and therefore potentially of considerable significance in the toxicological and public health domains. In fact, in 1992 and 1993, three conferences (Japan, United States, and China) were held exclusively on the topic of the biological effects of low doses of chemicals and radioactivity with articular emphasis on U-shaped curves. Substantial efforts have been made at understanding this observation.

  15. Isotopically modified silver nanoparticles to assess nanosilver bioavailability and toxicity at environmentally relevant exposures

    Science.gov (United States)

    Croteau, Marie-Noële; Dybowska, Agnieszka D.; Luoma, Samuel N.; Misra, Superb K.; Valsami-Jones, Eugenia

    2014-01-01

    A major challenge in understanding the environmental implications of nanotechnology lies in studying nanoparticle uptake in organisms at environmentally realistic exposure concentrations. Typically, high exposure concentrations are needed to trigger measurable effects and to detect accumulation above background. But application of tracer techniques can overcome these limitations. Here we synthesised, for the first time, citrate-coated Ag nanoparticles using Ag that was 99.7 % 109Ag. In addition to conducting reactivity and dissolution studies, we assessed the bioavailability and toxicity of these isotopically modified Ag nanoparticles (109Ag NPs) to a freshwater snail under conditions typical of nature. We showed that accumulation of 109Ag from 109Ag NPs is detectable in the tissues of Lymnaea stagnalis after 24-h exposure to aqueous concentrations as low as 6 ng L–1 as well as after 3 h of dietary exposure to concentrations as low as 0.07 μg g–1. Silver uptake from unlabelled Ag NPs would not have been detected under similar exposure conditions. Uptake rates of 109Ag from 109Ag NPs mixed with food or dispersed in water were largely linear over a wide range of concentrations. Particle dissolution was most important at low waterborne concentrations. We estimated that 70 % of the bioaccumulated 109Ag concentration in L. stagnalis at exposures –1 originated from the newly solubilised Ag. Above this concentration, we predicted that 80 % of the bioaccumulated 109Ag concentration originated from the 109Ag NPs. It was not clear if agglomeration had a major influence on uptake rates.

  16. Chronic ZnO-NPs exposure at environmentally relevant concentrations results in metabolic and locomotive toxicities in Caenorhabditis elegans.

    Science.gov (United States)

    Huang, Chi-Wei; Li, Shang-Wei; Hsiu-Chuan Liao, Vivian

    2017-01-01

    ZnO nanoparticles (ZnO-NPs) are emerging contaminants that raise the concerns of potential risk in the aquatic environment. It has been estimated that the environmental ZnO-NPs concentration is 76 μg/l in the aquatic environment. Our aim was to determine the aquatic toxicity of ZnO-NPs with chronic exposure at environmentally relevant concentrations using the nematode Caenorhabditis elegans. Two simulated environmentally relevant mediums-moderately hard reconstituted water (EPA water) and simulated soil pore water (SSPW)-were used to represent surface water and pore water in sediment, respectively. The results showed that the ZnO-NPs in EPA water has a much smaller hydrodynamic diameter than that in SSPW. Although the ionic release of Zn ions increased time-dependently in both mediums, the Zn ions concentrations in EPA water increased two-fold more than that in SSPW at 48 h and 72 h. The ZnO-NPs did not induce growth defects or decrease head thrashes in C. elegans in either media. However, chronic exposure to ZnO-NPs caused a significant reduction in C. elegans body bends in EPA water even with a relatively low concentration (0.05 μg/l); similar results were not observed in SSPW. Moreover, at the same concentrations (50 and 500 μg/l), body bends in C. elegans were reduced more severely in ZnO-NPs than in ZnCl2 in EPA water. The ATP levels were consistently and significantly decreased, and ROS was induced after ZnO-NPs exposure (50 and 500 μg/l) in EPA water. Our results provide evidences that chronic exposure to ZnO-NPs under environmentally relevant concentrations causes metabolic and locomotive toxicities implicating the potential ecotoxicity of ZnO-NPs at low concentrations in aquatic environments.

  17. The Fortymile caribou herd: novel proposed management and relevant biology, 1992-1997

    Directory of Open Access Journals (Sweden)

    Rodney D. Boertje

    2000-04-01

    Full Text Available A diverse, international Fortymile Planning Team wrote a novel Fortymile caribou herd {Rangifer tarandus granti Management Plan in 1995 (Boertje & Gardner, 1996: 56-77. The primary goal of this plan is to begin restoring the Fortymile herd to its former range; >70% of the herd's former range was abandoned as herd size declined. Specific objectives call for increasing the Fortymile herd by at least 5-10% annually from 1998-2002. We describe demographics of the herd, factors limiting the herd, and condition of the herd and range during 1992-1997. These data were useful in proposing management actions for the herd and should be instrumental in future evaluations of the plan's actions. The following points summarize herd biology relevant to management proposed by the Fortymile Planning Team: 1. Herd numbers remained relatively stable during 1990-1995 (about 22 000-23 000 caribou. On 21 June 1996 we counted about 900 additional caribou in the herd, probably a result of increased pregnancy rates in 1996. On 26 June 1997 we counted about 2500 additional caribou in the herd, probably a result of recruitment of the abundant 1996 calves and excellent early survival of the 1997 calves. The Team deemed that implementing management actions during a period of natural growth would be opportune. 2. Wolf (Canis lupus and grizzly bear (Ursus arctos predation were the most important sources of mortality, despite over a decade of the most liberal regulations in the state for harvesting of wolves and grizzly bears. Wolves were the most important predator. Wolves killed between 2000 and 3000 caribou calves annually during this study and between 1000 and 2300 older caribou; 1200-1900 calves were killed from May through September. No significant differences in annual wolf predation rates on calves or adults were observed between 1994 and early winter 1997. Reducing wolf predation was judged by the Team to be the most manageable way to help hasten or stimulate

  18. Serological evidence of exposure to globally relevant zoonotic parasites in the Estonian population

    DEFF Research Database (Denmark)

    Lassen, Brian; Janson, Marilin; Viltrop, Arvo;

    2016-01-01

    .0%, Toxocara spp. seroprevalence was 14.5%, and Trichinella spp. seroprevalence was 2.7%. WB-confirmed Toxocara spp. seroprevalence was higher in animal caretakers than in the general population. We found serological evidence of exposure to zoonotic parasites in all tested groups. This calls for higher...... awareness of zoonotic parasitic infections in Estonia....

  19. Relevancy of human exposure via house dust to the contaminants lead and asbestos

    NARCIS (Netherlands)

    Oomen AG; Lijzen JPA; SIR; LER

    2004-01-01

    The present report addresses the issues whether house dust is likely to contribute substantially to the exposure of humans, in particular for the contaminants lead and asbestos. House dust consists for 30-70% of soil material, indicating that contaminated soil can lead to contaminated house dust. It

  20. Investigation of Occupational Asthma: Do Clinicians Fail to Identify rRelevant Occupational Exposures?

    Directory of Open Access Journals (Sweden)

    Carlo de Olim

    2015-01-01

    Full Text Available BACKGROUND: Specific inhalation challenges (SIC enable the identification of the agent responsible of occupational asthma (OA. A clinician may fail to identify a specific agent in the workplace, which may potentially lead to a misdiagnosis. The expert assessment method performed by an occupational hygienist has been used to evaluate occupational exposures in epidemiological studies.

  1. Relevancy of human exposure via house dust to the contaminants lead and asbestos

    NARCIS (Netherlands)

    Oomen AG; Lijzen JPA; SIR; LER

    2004-01-01

    The present report addresses the issues whether house dust is likely to contribute substantially to the exposure of humans, in particular for the contaminants lead and asbestos. House dust consists for 30-70% of soil material, indicating that contaminated soil can lead to contaminated house dust. It

  2. Application of biological dosimetry in accidental radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Nosal, M.; Batora, I.; Kolesar, D.; Stojkovic, J. (Komenskeho Univ., Bratislava (Czechoslovakia). Lekarska Fakulta); Gaal, P.; Sklovsky, A. (Krajska Hygienicka Stanica, Bratislava (Czechoslovakia)); Cizova, O. (Sexuologicka Ambulancia KUNZ, Bratislava (Czechoslovakia))

    1982-03-01

    The case is described of accidental irradiation of a male person with /sup 137/Cs of an activity of 24.71 GBq. The first estimate induced a reasonable suspicion that the absorbed dose could be very high and life-threatening. On the other hand the clinical picture, usual laboratory examinations, findings in the fluorescent blood count, the analysis of chromosomal count of lymphocytes in the peripheral blood, the spermiogram, and the negative post-irradiation porphyrinuria suggested that the absorbed dose could be much lower than the original estimate. The results of dosimetry obtained after the reconstruction of the accident by measuring on a phantom revealed that the actual dose was very close to that presumed from the results of biological dosimetry during the first days of examination of the patient.

  3. Larval exposure to environmentally relevant mixtures of alkylphenolethoxylates reduces reproductive competence in male fathead minnows

    Science.gov (United States)

    Bistodeau, T.J.; Barber, L.B.; Bartell, S.E.; Cediel, R.A.; Grove, K.J.; Klaustermeier, J.; Woodard, J.C.; Lee, K.E.; Schoenfuss, H.L.

    2006-01-01

    The ubiquitous presence of nonylphenolethoxylate/octylphenolethoxylate (NPE/OPE) compounds in aquatic environments adjacent to wastewater treatment plants (WWTP) warrants an assessment of the endocrine disrupting potential of these complex mixtures on aquatic vertebrates. In this study, fathead minnow larvae were exposed for 64 days to a mixture of NPE/OPE, which closely models the NPE/OPE composition of a major metropolitan WWTP effluent. Target exposure concentrations included a total NPE/OPE mixture load of 200% of the WWTP effluent concentration (148 ??g/L), 100% of the WWTP effluent concentration (74 ??g/L) and 50% of the WWTP effluent concentration (38 ??g/L). The NPE/OPE mixture contained 0.2% 4-t-octylphenol, 2.8% 4-nonylphenol, 5.1% 4-nonylphenolmonoethoxylate, 9.3% 4-nonylphenoldiethoxylate, 0.9% 4-t-octylphenolmonoethoxylate, 3.1% 4-t-octylphenoldiethoxylate, 33.8% 4-nonylphenolmonoethoxycarboxylate, and 44.8% 4-nonylphenoldiethoxycarboxylate. An additional exposure of 5 ??g/L 4-nonylphenol (nominal) was conducted. The exposure utilized a flow-through system supplied by ground water and designed to deliver consistent concentrations of applied chemicals. Following exposure, larvae were raised to maturity. Upon sexual maturation, exposed male fish were allowed to compete with control males in a competitive spawning assay. Nest holding ability of control and exposed fish was carefully monitored for 7 days. All male fish were then sacrificed and analyzed for plasma vitellogenin, developmental changes in gonadal tissues, alterations in the development of secondary sexual characters, morphometric changes, and changes to reproductive behavior. When exposed to the 200% NPE/OPE treatment most larvae died within the first 4 weeks of exposure. Both the 100% and 50% NPE/OPE exposures caused a significant decrease in reproductive behavior, as indicated by an inability of many of the previously exposed males to acquire and hold a nest site required for reproduction

  4. Biological effects of exposure to intermediate neutron and repair mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Utsumi, Hiroshi; Sasaki, Masao [Kyoto Univ. (Japan); Onishi, Takeo; Onizuka, Masahiko

    2000-01-01

    An investigation was made on cytotoxic effects of neutron capture using chicken B-cell line mutants, DT40, KURO{sup -/-}, RAD54 {sup -/-} and KU70{sup -/-} / RAD54{sup -/-}. Suspensions of these cells were exposed to two times X-radiation at various doses and the cell surviving was evaluated. The sensitivity to radiation was highest in the double defective mutant, KU70{sup -/-} / RAD54{sup -/-} and followed by that of RAD54 {sup -/-}, a homologous recombination mutant, whereas KURO {sup -/-} cell, a non-homologous end-joining mutant showed a peculiar surviving curve composed of two phases and the cell was highly sensitive to a low-dose radiation. This indicates that there are two different DNA repair systems for double-strand breaks and the system for non-homologous end-joining repair can be involved in all phases of cell cycle, but the system for the homologous one is involved only in S-phase. Therefore, it was thought that variation of sensitivity to radiation exposure depending to the phase of cell cycle might explain the alternation of repair system depending to the phase progressing of cell cycle. It was thus likely that the recovery from radiation injury, which is still a black box might be explained with the double strand breaks of DNA. (M.N.)

  5. Perceptions of Workplace Heat Exposure and Controls among Occupational Hygienists and Relevant Specialists in Australia.

    Science.gov (United States)

    Xiang, Jianjun; Hansen, Alana; Pisaniello, Dino; Bi, Peng

    2015-01-01

    With warmer weather projections, workplace heat exposure is presenting a growing challenge to workers' health and safety. Occupational hygienists are the specialist group conducting measurements and providing advice on heat stress management to industry. In order to provide insights into hygienists perceptions on workplace heat exposure, current and future preparedness for extreme heat, and barriers to possible heat adaptation strategies, a self-administered questionnaire survey was conducted during a national conference of the Australian Institute of Occupational Hygienists. Nearly 90% of the 180 respondents were at least moderately concerned about extreme heat and 19% were dissatisfied with current heat stress prevention measures. Barriers recognized by the participants were lack of awareness (68%), insufficient training (56%), unsatisfactory management commitment (52%), and low compliance with prevention policies (40%). The findings suggest a need to refine occupational heat management and prevention strategies.

  6. Perceptions of Workplace Heat Exposure and Controls among Occupational Hygienists and Relevant Specialists in Australia.

    Directory of Open Access Journals (Sweden)

    Jianjun Xiang

    Full Text Available With warmer weather projections, workplace heat exposure is presenting a growing challenge to workers' health and safety. Occupational hygienists are the specialist group conducting measurements and providing advice on heat stress management to industry. In order to provide insights into hygienists perceptions on workplace heat exposure, current and future preparedness for extreme heat, and barriers to possible heat adaptation strategies, a self-administered questionnaire survey was conducted during a national conference of the Australian Institute of Occupational Hygienists. Nearly 90% of the 180 respondents were at least moderately concerned about extreme heat and 19% were dissatisfied with current heat stress prevention measures. Barriers recognized by the participants were lack of awareness (68%, insufficient training (56%, unsatisfactory management commitment (52%, and low compliance with prevention policies (40%. The findings suggest a need to refine occupational heat management and prevention strategies.

  7. Susceptibility Factors Relevant for the Association Between Long-Term Air Pollution Exposure and Incident Asthma.

    Science.gov (United States)

    Burte, Emilie; Nadif, Rachel; Jacquemin, Bénédicte

    2016-03-01

    In this review, we identified 15 studies in children and 10 studies in adults that assessed the association between long-term exposure to air pollution and incident asthma and that conducted stratified analyses to explore potential susceptibility factors. Overall, adult never-/former smokers seem to be at higher risk of incident asthma due to air pollution. Children without atopy and children from low socioeconomic status families also seem to be at higher risk of incident asthma due to air pollution. While interaction between air pollution and genes involved in the response to oxidative stress pathways have been explored, results are somewhat inconsistent and in need of replication. To evaluate interactions, large sample sizes are necessary, and much more research, including data pooling from existing studies, is needed to further explore susceptibility factors for asthma incidence due to long-term air pollution exposure.

  8. Glyphosate accumulation, translocation, and biological effects in Coffea arabica after single and multiple exposures

    DEFF Research Database (Denmark)

    Schrübbers, Lars Christoph; Valverde, Bernal E.; Strobel, Bjarne W.

    2016-01-01

    In perennial crops like coffee, glyphosate drift exposure can occur multiple times during its commercial life span. Due to limited glyphosate degradation in higher plants, a potential accumulation of glyphosate could lead to increased biological effects with increased exposure frequency....... In this study, we investigated glyphosate translocation over time, and its concentration and biological effects after single and multiple simulated spray-drift exposures. Additionally, shikimic acid/glyphosate ratios were used as biomarkers for glyphosate binding to its target enzyme.Four weeks after...... the exposure, glyphosate was continuously translocated. Shikimic acid levels were lin-ear correlated with glyphosate levels. After two months, however, glyphosate appeared to have reduced activity. In the greenhouse, multiple applications resulted in higher internal glyphosate concentrations.The time...

  9. Dermal Exposure to Cumene Hydroperoxide: Assessing Its Toxic Relevance and Oxidant Potential.

    Science.gov (United States)

    Rider, Cynthia V; Chan, Po; Herbert, Ron A; Kissling, Grace E; Fomby, Laurene M; Hejtmancik, Milton R; Witt, Kristine L; Waidyanatha, Suramya; Travlos, Greg S; Kadiiska, Maria B

    2016-07-01

    Cumene hydroperoxide (CHP) is a high production volume chemical that is used to generate phenol and acetone. Dermal exposure to CHP was hypothesized to result in systemic tissue toxicity, production of free radicals, and consequent decrease in plasma antioxidant levels. To evaluate the hypothesis and characterize the toxicity of CHP, male and female B6C3F1/N mice and F344/N rats were exposed to varying doses of CHP applied topically for 14 or 90 days. No significant changes in survival or body weight of mice and rats were observed following 14 days of exposure. However, 90 days of CHP exposure at the high dose (12 mg/kg) triggered a significant decrease (-15%) in the body weight of the male rat group only. Irritation of the skin was observed at the site of application and was characterized by inflammation and epidermal hyperplasia. In treated animals, histology of liver tissue, free radical generation, and antioxidant levels in blood plasma were not significantly changed as compared to the corresponding controls. Consistent with the lack of systemic damage, no increase in micronucleated erythrocytes was seen in peripheral blood. In conclusion, topical CHP application caused skin damage only at the application site and did not cause systemic tissue impairment.

  10. Prevalence of lead disease among secondary lead smelter workers and biological indicators of lead exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lilis, R. (City Univ. of New York); Fischbein, A.; Eisinger, J.

    1977-10-01

    The report concerns itself primarily with the assessment of medical and biochemical effects of chronic lead exposure and comparing the usefulness of various biological screening parameters. In addition it appraises the effects of chelation therapy to control blood lead levels in lead workers, which have recently attracted critical attention. It is of considerable importance to ascertain whether such a therapeutic approach may, under some circumstances, in fact contribute to the deleterious effects of undue lead exposure.

  11. Biological dosimetry following exposure to neutrons in a criticality accident

    Energy Technology Data Exchange (ETDEWEB)

    Lindholm, C. (Radiation and Nuclear Safety Authority, STUK (Finland)); Wojcik, A. (Stockholm Univ. (SU), Stockholm (Sweden)); Jaworska, A. (Norwegian Radiation Protection Authority (NRPA) (Norway))

    2011-01-15

    The aim of the BIONCA project was to implement cytogenetic techniques for biodosimetry purposes in the Nordic countries. The previous NKS-funded biodosimetry activities (BIODOS and BIOPEX) concentrated on experiments using gamma-irradiation and on developing the PCC ring assay for biodosimetry. Experiments conducted during the present BIONCA project has broadened the biodosimetry capacity of the Nordic countries to include dose estimation of exposure to neutrons for both PCC ring and dicentric chromosome techniques. In 2009, experiments were conducted for establishing both PCC ring and dicentric dose calibration curves. Neutron irradiation of human whole blood obtained from two volunteers was conducted in the Netherlands at the Petten reactor. Cell cultures and analysis of whole blood exposed to eight doses between 0 and 10 Gy were performed for both techniques. For the dicentric assay, excellent uniformity in dose calibration for data from both SU and STUK was observed. For PCC rings, the SU and STUK curves were not equally congruent, probably due to the less uniform scoring criteria. However, both curves displayed strong linearity throughout the dose range. In 2010, an exercise was conducted to simulate a criticality accident and to test the validity of the established dose calibration curves. For accident simulation, 16 blood samples were irradiated in Norway at the Kjeller reactor and analysed for dose estimation with both assays. The results showed that, despite a different com-position of the radiation beams in Petten and Kjeller, good dose estimates were obtained. The activity has provided good experience on collaboration required in radiation emergency situations where the biodosimetry capacity and resources of one laboratory may be inadequate. In this respect, the project has strengthened the informal network between the Nordic countries: STUK, the Finnish Radiation and Nuclear Safety Authority, NRPA, the Norwegian Radiation Protection Authority and SU

  12. System approaches of Weiss and Bertalanffy and their relevance for systems biology today.

    Science.gov (United States)

    Drack, Manfred; Wolkenhauer, Olaf

    2011-06-01

    System approaches in biology have a long history. We focus here on the thinking of Paul A. Weiss and Ludwig von Bertalanffy, who contributed a great deal towards making the system concept operable in biology in the early 20th century. To them, considering whole living systems, which includes their organisation or order, is equally important as the dynamics within systems and the interplay between different levels from molecules over cells to organisms. They also called for taking the intrinsic activity of living systems and the conservation of system states into account. We compare these notions with today's systems biology, which is often a bottom-up approach from molecular dynamics to cellular behaviour. We conclude that bringing together the early heuristics with recent formalisms and novel experimental set-ups can lead to fruitful results and understanding. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.

    2005-01-01

    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and dru

  14. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.

    2005-01-01

    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and

  15. Genomics and systems biology - How relevant are the developments to veterinary pharmacology, toxicology and therapeutics?

    NARCIS (Netherlands)

    Witkamp, R.F.

    2005-01-01

    This review discusses some of the recent developments in genomics and its current and future relevance for veterinary pharmacology and toxicology. With the rapid progress made in this field several new approaches in pharmacological and toxicological research have developed and drug discovery and dru

  16. The interaction of platinum-based drugs with native biologically relevant proteins

    NARCIS (Netherlands)

    Brauckmann, Christine; Wehe, Christoph A.; Kieshauer, Michael; Lanvers-Kaminsky, Claudia; Sperling, Michael; Karst, Uwe

    2013-01-01

    This study focuses on the identification of the products that are formed upon binding of therapeutically relevant platinum complexes to proteins like beta-lactoglobulin A (LGA), human serum albumin (HSA), or human hemoglobin (HB). The respective proteins were incubated with the platinum-based antica

  17. Susceptibility to urinary bladder cancer: relevance of rs9642880[T], GSTM1 0/0 and occupational exposure.

    Science.gov (United States)

    Golka, Klaus; Hermes, Matthias; Selinski, Silvia; Blaszkewicz, Meinolf; Bolt, Hermann M; Roth, Gerhard; Dietrich, Holger; Prager, Hans-Martin; Ickstadt, Katja; Hengstler, Jan G

    2009-11-01

    Recently, a genome-wide single nucleotide polymorphism association study has identified a sequence variant 30 kb upstream of the c-Myc gene (allele T of rs9642880) that confers susceptibility to bladder cancer. However, the role of exposure to bladder carcinogens has not been considered. This prompted us to analyse the relevance of this polymorphism in 515 bladder cancer cases and 893 controls where the quality and quantity of occupational exposure to bladder carcinogens has been documented. When we analysed a hospital-based case-control series not selected for occupational exposure, rs9642880[T] was influential, in contrast to GSTM1 0/0. However, in a case-control series of patients that have been occupationally exposed to aromatic amines and polycyclic aromatic hydrocarbons, rs9642880[T] was not influential but GSTM1 0/0 was significantly associated with bladder cancer risk. Therefore, the degree to which rs9642880[T] and GSTM1 0/0 confer susceptibility to urinary bladder cancer seems to depend on the extent of exposure to urinary bladder carcinogens.

  18. Physical interactions among plant MADS-box transcription factors and their biological relevance

    NARCIS (Netherlands)

    Nougalli Tonaco, I.A.

    2008-01-01

    The biological interpretation of the genome starts from transcription, and many different signaling pathways are integrated at this level. Transcription factors play a central role in the transcription process, because they select the down-stream genes and determine their spatial and temporal

  19. Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport

    DEFF Research Database (Denmark)

    Bonne, Thomas Christian; Lundby, Carsten; Lundby, Anne Kristine

    2015-01-01

    The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international-level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n = 10)...

  20. Physical interactions among plant MADS-box transcription factors and their biological relevance

    NARCIS (Netherlands)

    Nougalli Tonaco, I.A.

    2008-01-01

    The biological interpretation of the genome starts from transcription, and many different signaling pathways are integrated at this level. Transcription factors play a central role in the transcription process, because they select the down-stream genes and determine their spatial and temporal expres

  1. Relevance of aerosol dynamics and dustiness for personal exposure to manufactured nanoparticles

    Science.gov (United States)

    Schneider, Thomas; Jensen, Keld A.

    2009-10-01

    Production and handling of manufactured nanoparticles (MNP) may result in unwanted worker exposure. The size distribution and structure of MNP in the breathing zone of workers will differ from the primary MNP produced. Homogeneous coagulation, scavenging by background aerosols, and surface deposition losses are determinants of this change during transport from source to the breathing zone, and to a degree depending on the relative time scale of these processes. Modeling and experimental studies suggest that in MNP production scenarios, workers are most likely exposed to MNP agglomerates or MNP attached to other particles. Surfaces can become contaminated by MNP, which constitute potential secondary sources of airborne MNP-containing particles. Dustiness testing can provide insight into the state of agglomeration of particles released during handling of bulk MNP powder. Test results, supported by field data, suggest that the particles released from powder handling occur in distinct size modes and that the smallest mode can be expected to have a geometric mean diameter >100 nm. The dominating presence of MNP agglomerates or MNP attached to background particles in the air during production and use of MNP implies that size alone cannot, in general, be used to demonstrate presence or absence of MNP in the breathing zone of workers. The entire respirable size fraction should be assessed for risk from inhalation exposure to MNP.

  2. Genomic and proteomic responses to environmentally relevant exposures to dieldrin: indicators of neurodegeneration?

    Science.gov (United States)

    Martyniuk, Christopher J; Kroll, Kevin J; Doperalski, Nicholas J; Barber, David S; Denslow, Nancy D

    2010-09-01

    Dieldrin is a persistent organochlorine pesticide that induces neurotoxicity in the vertebrate central nervous system and impairs reproductive processes in fish. This study examined the molecular events produced by subchronic dietary exposures to 2.95 mg dieldrin/kg feed in the neuroendocrine brain of largemouth bass, an apex predator. Microarrays, proteomics, and pathway analysis were performed to identify genes, proteins, and cell processes altered in the male hypothalamus. Fifty-four genes were induced, and 220 genes were reduced in steady-state levels (p dieldrin. Using isobaric tagging for relative and absolute quantitation, 90 proteins in the male hypothalamus were statistically evaluated for changes in protein abundance. Several proteins altered by dieldrin are known to be associated with human neurodegenerative diseases, including apolipoprotein E, microtubule-associated tau protein, enolase 1, stathmin 1a, myelin basic protein, and parvalbumin. Proteins altered by dieldrin were involved in oxidative phosphorylation, differentiation, proliferation, and cell survival. This study demonstrates that a subchronic exposure to dieldrin alters the abundance of messenger RNAs and proteins in the hypothalamus that are associated with cell metabolism, cell stability and integrity, stress, and DNA repair.

  3. Serological evidence of exposure to globally relevant zoonotic parasites in the Estonian population

    DEFF Research Database (Denmark)

    Lassen, Brian; Janson, Marilin; Viltrop, Arvo

    2016-01-01

    We investigated Estonian population and its selected subgroups for serological evidence of exposure to Ascaris lumbricoides, Echinococcus spp., Taenia solium, Toxocara canis, Toxoplasma gondii, and Trichinella spiralis. Serum samples from 999 adults representing general population, 248 children...... aged 14–18, 158 veterinarians, 375 animal caretakers, and 144 hunters were tested for specific immunoglobulin G antibodies against the selected parasites using commercial enzyme immunoassays (ELISA). Sera yielding positive or twice grey zone Echinococcus spp, T. solium, T. canis, and T. spiralis...... results were subjected to western blot (WB) analysis. In the general population, based on the ELISA results, the A. lumbricoides seroprevalence was 12.7%, Echinococcus spp. seroprevalence was 3.3%, T. solium seroprevalence was 0.7%, T. canis seroprevalence was 12.1%, T. gondii seroprevalence was 55...

  4. RELEVANCE OF CROP BIOLOGY FOR ENVIRONMENTAL RISK ASSESSMENT OF GENETICALLY MODIFIED CROPS IN AFRICA

    Directory of Open Access Journals (Sweden)

    Olalekan eAkinbo

    2015-10-01

    Full Text Available Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERA. This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for environmental risk assessment (ERA include: growth habit, centre of origin, centre of genetic diversity, proximity of wild relatives, inter-fertility, mode of pollen dispersal, length of pollen viability, mating system, invasiveness, weediness, mode of propagation, mode of seed dispersal and length of seed dormancy. In this paper, we discuss the crops being genetic engineered in Africa and describe the crop biology of those with native relatives.

  5. Serological Evidence of Exposure to Globally Relevant Zoonotic Parasites in the Estonian Population

    Science.gov (United States)

    Viltrop, Arvo; Neare, Kädi; Hütt, Pirje; Golovljova, Irina; Tummeleht, Lea; Jokelainen, Pikka

    2016-01-01

    We investigated Estonian population and its selected subgroups for serological evidence of exposure to Ascaris lumbricoides, Echinococcus spp., Taenia solium, Toxocara canis, Toxoplasma gondii, and Trichinella spiralis. Serum samples from 999 adults representing general population, 248 children aged 14–18, 158 veterinarians, 375 animal caretakers, and 144 hunters were tested for specific immunoglobulin G antibodies against the selected parasites using commercial enzyme immunoassays (ELISA). Sera yielding positive or twice grey zone Echinococcus spp, T. solium, T. canis, and T. spiralis results were subjected to western blot (WB) analysis. In the general population, based on the ELISA results, the A. lumbricoides seroprevalence was 12.7%, Echinococcus spp. seroprevalence was 3.3%, T. solium seroprevalence was 0.7%, T. canis seroprevalence was 12.1%, T. gondii seroprevalence was 55.8%, and T. spiralis seroprevalence was 3.1%. Ascaris lumbricoides seroprevalences were higher in children and in animal caretakers than in the general population, and T. canis seroprevalence was higher in animal caretakers than in the general population. Compared with the general population, Echinococcus spp. seroprevalence was higher in children. By contrast, T. gondii seroprevalence was higher in animal caretakers, and lower in children, than in the general population. In the general population, the WB-confirmed Echinococcus spp. seroprevalence was 0.5%, T. solium cysticercosis seroprevalence was 0.0%, Toxocara spp. seroprevalence was 14.5%, and Trichinella spp. seroprevalence was 2.7%. WB-confirmed Toxocara spp. seroprevalence was higher in animal caretakers than in the general population. We found serological evidence of exposure to zoonotic parasites in all tested groups. This calls for higher awareness of zoonotic parasitic infections in Estonia. PMID:27723790

  6. Serological Evidence of Exposure to Globally Relevant Zoonotic Parasites in the Estonian Population.

    Science.gov (United States)

    Lassen, Brian; Janson, Marilin; Viltrop, Arvo; Neare, Kädi; Hütt, Pirje; Golovljova, Irina; Tummeleht, Lea; Jokelainen, Pikka

    2016-01-01

    We investigated Estonian population and its selected subgroups for serological evidence of exposure to Ascaris lumbricoides, Echinococcus spp., Taenia solium, Toxocara canis, Toxoplasma gondii, and Trichinella spiralis. Serum samples from 999 adults representing general population, 248 children aged 14-18, 158 veterinarians, 375 animal caretakers, and 144 hunters were tested for specific immunoglobulin G antibodies against the selected parasites using commercial enzyme immunoassays (ELISA). Sera yielding positive or twice grey zone Echinococcus spp, T. solium, T. canis, and T. spiralis results were subjected to western blot (WB) analysis. In the general population, based on the ELISA results, the A. lumbricoides seroprevalence was 12.7%, Echinococcus spp. seroprevalence was 3.3%, T. solium seroprevalence was 0.7%, T. canis seroprevalence was 12.1%, T. gondii seroprevalence was 55.8%, and T. spiralis seroprevalence was 3.1%. Ascaris lumbricoides seroprevalences were higher in children and in animal caretakers than in the general population, and T. canis seroprevalence was higher in animal caretakers than in the general population. Compared with the general population, Echinococcus spp. seroprevalence was higher in children. By contrast, T. gondii seroprevalence was higher in animal caretakers, and lower in children, than in the general population. In the general population, the WB-confirmed Echinococcus spp. seroprevalence was 0.5%, T. solium cysticercosis seroprevalence was 0.0%, Toxocara spp. seroprevalence was 14.5%, and Trichinella spp. seroprevalence was 2.7%. WB-confirmed Toxocara spp. seroprevalence was higher in animal caretakers than in the general population. We found serological evidence of exposure to zoonotic parasites in all tested groups. This calls for higher awareness of zoonotic parasitic infections in Estonia.

  7. Relevance of Crop Biology for Environmental Risk Assessment of Genetically Modified Crops in Africa

    OpenAIRE

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERAs). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for ERA include growth habit, ce...

  8. RELEVANCE OF CROP BIOLOGY FOR ENVIRONMENTAL RISK ASSESSMENT OF GENETICALLY MODIFIED CROPS IN AFRICA

    OpenAIRE

    2015-01-01

    Knowledge about the crop biology of economic crops in Africa is needed for regulators to accurately review dossiers and conduct comprehensive environmental risk assessments (ERA). This information allows regulators to decide whether biotech crops present a risk to biodiversity, since crossing between domesticated crops and their wild relatives could affect the adaptations of the wild species. The criteria that should be used in the evaluation of African crops for environmental risk assessmen...

  9. Model fit versus biological relevance: Evaluating photosynthesis-temperature models for three tropical seagrass species

    Science.gov (United States)

    Adams, Matthew P.; Collier, Catherine J.; Uthicke, Sven; Ow, Yan X.; Langlois, Lucas; O’Brien, Katherine R.

    2017-01-01

    When several models can describe a biological process, the equation that best fits the data is typically considered the best. However, models are most useful when they also possess biologically-meaningful parameters. In particular, model parameters should be stable, physically interpretable, and transferable to other contexts, e.g. for direct indication of system state, or usage in other model types. As an example of implementing these recommended requirements for model parameters, we evaluated twelve published empirical models for temperature-dependent tropical seagrass photosynthesis, based on two criteria: (1) goodness of fit, and (2) how easily biologically-meaningful parameters can be obtained. All models were formulated in terms of parameters characterising the thermal optimum (Topt) for maximum photosynthetic rate (Pmax). These parameters indicate the upper thermal limits of seagrass photosynthetic capacity, and hence can be used to assess the vulnerability of seagrass to temperature change. Our study exemplifies an approach to model selection which optimises the usefulness of empirical models for both modellers and ecologists alike.

  10. BILIARY PAH METABOLITES AS A BIOLOGICAL INDICATOR OF FISH EXPOSURE IN TRIBUTARIES OF LAKE ERIE

    Science.gov (United States)

    Biliary polynuclear aromatic hydrocarbons (PAH) metabolites have been studied as a biological indicator of fish exposure to PAHs since the mid 1980's. Brown bullheads were collected from the following Lake Erie tributaries: Buffalo River (BUF), Niagara River at Love Canal (NIA)...

  11. Demodulation in tissue, the relevant parameters and the implications for limiting exposure.

    Science.gov (United States)

    Silny, Jiri

    2007-06-01

    In the biomedical literature there are a number of reports that speculate about possible effects in the body due to the demodulation of electromagnetic fields. However, only few interactions in amplitude-modulated or even pulse-modulated electromagnetic waves are fundamentally plausible and have been demonstrated to occur in humans. The following observations fall into this specific category: thermal effects of amplitude- or pulse-modulated microwaves; demodulation of amplitude- or pulse-modulated electromagnetic waves in cell membranes; and demodulation of amplitude- or pulse-modulated electromagnetic fields in the electronics of implants such as cardiac pacemakers or cardioverter defibrillators. The possible consequences of these effects for the organism, their probability of occurrence in everyday life field conditions, and, consequently, the implications for limiting exposure are very different. Microwave hearing is a harmless effect which is perceived by humans only in strong fields with high peak power densities of more than 100 mW cm(-2). In normal residential or occupational environments the peak power density of even the strongest microwave sources is only around 1 mW cm(-2). Demodulation of pulse-modulated electromagnetic fields in the cell membranes decreases the stimulation threshold of nerves and muscles and can introduce numerous adverse effects ranging from perception of pain to dangerous cardiac fibrillations. The stimulation and demodulation effects are restricted to carrier frequencies up to several MHz. In experiments with 900 and 1,800 MHz packets with lengths of up to 100 ms and applied powers of up to 100 W, neither a direct stimulation of superficial nerves and muscles nor the conditioning of an electrical current stimulus could be confirmed. Pulse-modulated electromagnetic waves are demodulated in the electronic circuits of implants and can inhibit cardiac pacemakers and introduce cardiac arrest in this way. The highest sensitivity results

  12. Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

    Science.gov (United States)

    Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

    2017-05-18

    Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Concise Review: Quiescence in Adult Stem Cells: Biological Significance and Relevance to Tissue Regeneration.

    Science.gov (United States)

    Rumman, Mohammad; Dhawan, Jyotsna; Kassem, Moustapha

    2015-10-01

    Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim of this review is to provide an update regarding the biological mechanisms of ASC quiescence and their role in tissue regeneration.

  14. Occupational exposure to potentially infectious biological material in a dental teaching environment.

    Science.gov (United States)

    Machado-Carvalhais, Helenaura P; Ramos-Jorge, Maria L; Auad, Sheyla M; Martins, Laura H P M; Paiva, Saul M; Pordeus, Isabela A

    2008-10-01

    The aims of this cross-sectional study were to determine the prevalence of occupational accidents with exposure to biological material among undergraduate students of dentistry and to estimate potential risk factors associated with exposure to blood. Data were collected through a self-administered questionnaire (86.4 percent return rate), which was completed by a sample of 286 undergraduate dental students (mean age 22.4 +/-2.4 years). The students were enrolled in the clinical component of the curriculum, which corresponds to the final six semesters of study. Descriptive, bivariate, simple logistic regression and multiple logistic regression (Forward Stepwise Procedure) analyses were performed. The level of statistical significance was set at 5 percent. Percutaneous and mucous exposures to potentially infectious biological material were reported by 102 individuals (35.6 percent); 26.8 percent reported the occurrence of multiple episodes of exposure. The logistic regression analyses revealed that the incomplete use of individual protection equipment (OR=3.7; 95 percent CI 1.5-9.3), disciplines where surgical procedures are carried out (OR=16.3; 95 percent CI 7.1-37.2), and handling sharp instruments (OR=4.4; 95 percent CI 2.1-9.1), more specifically, hollow-bore needles (OR=6.8; 95 percent CI 2.1-19.0), were independently associated with exposure to blood. Policies of reviewing the procedures during clinical practice are recommended in order to reduce occupational exposure.

  15. Exposure of Female Rats to an Environmentally Relevant Mixture of Brominated Flame Retardants Targets the Ovary, Affecting Folliculogenesis and Steroidogenesis.

    Science.gov (United States)

    Lefèvre, Pavine L C; Berger, Robert G; Ernest, Sheila R; Gaertner, Dean W; Rawn, Dorothea F K; Wade, Michael G; Robaire, Bernard; Hales, Barbara F

    2016-01-01

    Brominated flame retardants (BFRs) are incorporated into various consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure and contamination. Pregnancy failure is associated with high levels of BFRs in human follicular fluid, raising serious questions regarding their impact on female reproductive health. The goal of this study is to elucidate the effects of an environmentally relevant BFR mixture on female rat ovarian functions (i.e., folliculogenesis and steroidogenesis). A BFR dietary mixture formulated to mimic the relative BFR congener levels in North American house dust was administered to adult female Sprague-Dawley rats from 2 to 3 wk before mating until Gestational Day 20; these diets were designed to deliver nominal doses of 0, 0.06, 20, or 60 mg/kg/day of the BFR mixture. Exposure to BFRs triggered an approximately 50% increase in the numbers of preantral and antral follicles and an enlargement of the antral follicles in the ovaries of the dams. A significant reduction in the expression of catalase, an antioxidant enzyme, and downregulation of the expression of insulin-like factor 3 (Insl3) and 17alpha-hydroxylase (Cyp17a1) were observed in the ovary. In addition, BFR exposure affected steroidogenesis; we observed a significant decrease in circulating 17-hydroxypregnenolone and an increase in testosterone concentrations in BFR-exposed dams. Thus, BFRs target ovarian function in the rat, adversely affecting both folliculogenesis and steroidogenesis.

  16. Collisions between low-energy electrons and small polyatomic targets of biological relevance

    Science.gov (United States)

    Hargreaves, Leigh

    2016-05-01

    Over the last decade, cross section measurements and calculations for DNA prototype molecules have received significant attention from the collisions community, due to the potential applications of this data in modelling electron transport through biological matter with a view to improving radiation dosimetry. Such data are additionally interesting from a fundamental aspect, as small carbon-based molecules are ideal targets for considering effects including target conformation, long-range dynamical interactions and coupling effects between the various degrees of freedom on the scattering properties of the target. At the California State University Fullerton, we have made a series of measurements of the elastic, vibrationally inelastic and electronically inelastic cross sections for a variety of small polyatomic targets, including water and the basic alcohols, ethylene, toluene and several fluorinated alkanes. These processes are important in a range of applications, primarily for modelling electron transport and thermalization, and energy deposition to a biological media. The data were obtained using a high resolution electron energy-loss spectrometer, operating in a crossed beam configuration with a moveable aperture gas source. The gas source design facilitates both an expedient and highly accurate method of removing background signal, and removes uncertainties from the data due to uncertainties in the beam profile. We have also performed scattering calculations employing the Schwinger Multichannel method, in collaboration with the California institute of technology, to compare with our measurements. In this talk, I will present an overview of our recent data and future research plans.

  17. BIOLOGICAL THERAPY AND INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS: RELEVANCE AND PROSPECTS

    Directory of Open Access Journals (Sweden)

    B. S. Belov

    2014-01-01

    Full Text Available The past decades are marked by the obvious progress in rheumatology, which is related to the practical introduction of biological agents. At the same time the use of these drugs is associated with the increasing risk of infections of different nature and locations, including opportunistic ones (invasive mycoses, Pneumocystis pneumonia, etc., and with the greater risk of reactivation of latent infection, primary with that of tuberculosis. Beyond that point, there are cases of severe infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissue lesions, etc., including those with a fatal outcome. This review analyzes mainly the past 3-year literature data on the rate and location of infections treated with biologics, which have been obtained in the placebo-controlled and direct comparative studies of patients with rheuma- toid arthritis. It characterizes the importance of different infections (tuberculosis, pneumonia, chronic viral hepati- tides, herpesvirus infections, etc. for treatment policy in the above patients. This underlines the need for wider immu- nization with different vaccines (chiefly against pneumococcus and influenza in patients with autoimmune inflam- matory rheumatic diseases. 

  18. What is stochastic resonance? Definitions, misconceptions, debates, and its relevance to biology.

    Directory of Open Access Journals (Sweden)

    Mark D McDonnell

    2009-05-01

    Full Text Available Stochastic resonance is said to be observed when increases in levels of unpredictable fluctuations--e.g., random noise--cause an increase in a metric of the quality of signal transmission or detection performance, rather than a decrease. This counterintuitive effect relies on system nonlinearities and on some parameter ranges being "suboptimal". Stochastic resonance has been observed, quantified, and described in a plethora of physical and biological systems, including neurons. Being a topic of widespread multidisciplinary interest, the definition of stochastic resonance has evolved significantly over the last decade or so, leading to a number of debates, misunderstandings, and controversies. Perhaps the most important debate is whether the brain has evolved to utilize random noise in vivo, as part of the "neural code". Surprisingly, this debate has been for the most part ignored by neuroscientists, despite much indirect evidence of a positive role for noise in the brain. We explore some of the reasons for this and argue why it would be more surprising if the brain did not exploit randomness provided by noise--via stochastic resonance or otherwise--than if it did. We also challenge neuroscientists and biologists, both computational and experimental, to embrace a very broad definition of stochastic resonance in terms of signal-processing "noise benefits", and to devise experiments aimed at verifying that random variability can play a functional role in the brain, nervous system, or other areas of biology.

  19. Features of Microglia and Neuroinflammation Relevant to Environmental Exposure and Neurotoxicity

    Directory of Open Access Journals (Sweden)

    G. Jean Harry

    2011-07-01

    Full Text Available Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They belong to the monocytic-macrophage lineage and serve as brain immune cells to orchestrate innate immune responses; however, they are distinct from other tissue macrophages due to their relatively quiescent phenotype and tight regulation by the CNS microenvironment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. In culture, microglia have been shown to be capable of releasing several potentially cytotoxic substances, such as reactive oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives, excitatory amino acids, and cytokines; however, they also produce various neurotrophic factors and quench damage from free radicals and excitotoxins. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Neuroinflammation should be considered as a balanced network of processes whereby subtle modifications can shift the cells toward disparate outcomes. For any evaluation of neuroinflammation and microglial responses, within the framework of neurotoxicity or degeneration, one key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. As examples of environmental exposure-related neuroinflammation in the literature, we provide an evaluation of data on manganese

  20. Computer controlled chamber measurements for clay adherence relevant for potential dioxin exposure through skin.

    Science.gov (United States)

    Ferguson, Alesia; Bursac, Zoran; Johnson, Wayne; Davis, Jasmine

    2012-01-01

    A computer-controlled mechanical chamber was used to control the contact between aluminum sheet samples laden with clay, and cotton sheet samples for the measurement of mass transfer. The contact parameters of pressure (20 to 60 kPa) and time (10 to 70 sec) were varied for 160 multiple experiments of mass soil transfer. Before log transformation the average transfer for 'First Transfer' of clay particles was 34.4 ± 6.3 mg/8.97 cm(2) while that for 'Total Transfer' was 36.1 ± 6.8 mg/8.97 cm(2). Second contact, therefore, resulted in an average transfer of 1.70 ± 0.76 mg/8.97 cm(2). These values are well above adherence values measured for potting soil and sand as reported for previous experiments using the same methodologies. Based on the univariate analysis and the multiple regression analysis we were able to see some effect of parameters on the clay adherence values. The effect of pressure increases was significant for the higher levels of 50 and 60 kPa. In addition, we observed that increases in temperature were significant for 'First Transfer,' and less so for 'Total Transfer'. Past experiments using potting soil and play sand show high adherence values to human cadaver skin over cotton sample; the same scenario would be expected for clay. This data set can be used to improve estimates of dermal exposure to dioxins found in ball clays often used by artisans in the making of pottery.

  1. Environmental exposure to allergens of different dog breeds and relevance in allergological diagnostics.

    Science.gov (United States)

    Heutelbeck, Astrid R R; Schulz, Thomas; Bergmann, Karl-Christian; Hallier, Ernst

    2008-01-01

    In our environment, dogs are a relevant source of allergens, but diagnosing dog-related allergies may present difficulties, as in diagnostic tests with commercial dog allergens, some patients show only slight positive or negative results, even though they suffer from dog-related symptoms. Occasionally, allergy tests with extracts of dog hair belonging to patients' dogs or from dogs of the same breed were found to yield more reliable results, possibly due to breed-specific allergen components. The purpose of this study was to determine breed-specific differences or possibly hypo- or hyperallergenic dog breeds. The dog allergen content and protein patterns of different commercial and self-prepared dog allergen extracts were compared. Protein extracts were separated using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and stained with silver. The major allergen Can f 1 was quantified using the commercially available enzyme-linked immunosorbent assay (ELISA) technique. The majority of the bands in the self-prepared extracts of different breeds had a molecular mass lower than 30 kD. Notably, the self-prepared extracts of hair of common breeds showed distinct protein bands with a molecular mass lower than 14 kD, which the commercial extracts did not. With regard to Can f 1 content, a marked variability occurred. Factors related to individual dogs seem to influence the allergenicity more than breed or gender. This is the first report to describe allergens with low molecular mass that are absent in extracts of commercial test kits. Consequently, skin tests with self-prepared dog allergen extracts need to be performed in case of inconsistent test results with commercial extracts.

  2. Biological effects on human health due to radiofrequency/microwave exposure

    DEFF Research Database (Denmark)

    Breckenkamp, Jürgen; Berg, Gabriele; Blettner, Maria

    2003-01-01

    electromagnetic pulses similar to those after a nuclear explosion. In all studies (except one that used a qualitative job-exposure-matrix) either the duration of occupational work as an approximation to actual exposure was determined or a simple yes/no differentiation was used based on a definition of high......We evaluated the methods and results of nine cohort studies dealing with the biological effects on human health from exposure to radiofrequencies/microwaves, published between 1980 and 2002. The size of the cohorts varied between 304 (3,362 person years) and nearly 200,000 persons (2.7 million...... person years). As exposures were defined: dielectric heaters in a plastic manufacturing plant, working with radio devices (professional and amateur), production of wireless communication technologies, radar devices of the Canadian police, radar units used by the military as well as artificially produced...

  3. Paul Ehrlich's mastzellen: a historical perspective of relevant developments in mast cell biology.

    Science.gov (United States)

    Ghably, Jack; Saleh, Hana; Vyas, Harsha; Peiris, Emma; Misra, Niva; Krishnaswamy, Guha

    2015-01-01

    Following the discovery of mast cells (or mastzellen) by the prolific physician researcher, Paul Ehrlich, many advances have improved our understanding of these cells and their fascinating biology. The discovery of immunoglobulin E and receptors for IgE and IgG on mast cells heralded further in vivo and in vitro studies, using molecular technologies and gene knockout models. Mast cells express an array of inflammatory mediators including tryptase, histamine, cytokines, chemokines, and growth factors. They play a role in many varying disease states, from atopic diseases, parasitic infections, hematological malignancies, and arthritis to osteoporosis. This review will attempt to summarize salient evolving areas in mast cell research over the last few centuries that have led to our current understanding of this pivotal multifunctional cell.

  4. A review of air quality, biological indicators and health effects of second-hand waterpipe smoke exposure.

    Science.gov (United States)

    Kumar, Sumit R; Davies, Shelby; Weitzman, Michael; Sherman, Scott

    2015-03-01

    There has been a rapid increase in the use of waterpipe tobacco and non-tobacco based shisha in many countries. Understanding the impact and effects of second-hand smoke (SHS) from cigarette was a crucial factor in reducing cigarette use, leading to clean indoor air laws and smoking bans. This article reviews what is known about the effects of SHS exposure from waterpipes. We used PubMed and EMBASE to review the literature. Articles were grouped into quantitative measures of air quality and biological markers, health effects, exposure across different settings, different types of shisha and use in different countries. Criteria for study selection were based on the key words related to SHS: waterpipe, hookah, shisha and third-hand smoke. Independent extraction with two reviewers was performed with inclusion criteria applied to articles on SHS and waterpipe/hookah/shisha. We excluded articles related to pregnancy or prenatal exposure to SHS, animal studies, and non-specific source of exposure as well as articles not written in English. A primary literature search yielded 54 articles, of which only 11 were included based on relevance to SHS from a waterpipe/hookah/shisha. The negative health consequences of second-hand waterpipe exposure have major implications for clean indoor air laws and for occupational safety. There exists an urgent need for public health campaigns about the effects on children and household members from smoking waterpipe at home, and for further development and implementation of regulations to protect the health of the public from this rapidly emerging threat. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Childhood exposure to violence and lifelong health: Clinical intervention science and stress biology research join forces

    Science.gov (United States)

    Moffitt, Terrie E.

    2013-01-01

    Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child’s body, alterations which may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people. PMID:24342859

  6. State-of-the-art exposure chamber for highly controlled and reproducible THz biological effects studies

    Science.gov (United States)

    Cerna, Cesario Z.; Elam, David P.; Echchgadda, Ibtissam; Sloan, Mark A.; Wilmink, Gerald J.

    2014-03-01

    Terahertz (THz) imaging and sensing technologies are increasingly being used at international airports for security screening purposes and at major medical centers for cancer and burn diagnosis. The emergence of new THz applications has directly resulted in an increased interest regarding the biological effects associated with this frequency range. Knowledge of THz biological effects is also desired for the safe use of THz systems, identification of health hazards, and development of empirically-based safety standards. In this study, we developed a state-of-the-art exposure chamber that allowed for highly controlled and reproducible studies of THz biological effects. This innovative system incorporated an industry grade cell incubator system that permitted a highly controlled exposure environment, where temperatures could be maintained at 37 °C +/- 0.1 °C, carbon dioxide (CO2) levels at 5% +/- 0.1%, and relative humidity (RH) levels at 95% +/- 1%. To maximize the THz power transmitted to the cell culture region inside the humid incubator, a secondary custom micro-chamber was fabricated and incorporated into the system. This micro-chamber shields the THz beam from the incubator environment and could be nitrogen-purged to eliminate water absorption effects. Additionally, a microscope that allowed for real-time visualization of the live cells before, during, and after THz exposure was integrated into the exposure system.

  7. Rapid release of tissue enzymes into blood after blast exposure: potential use as biological dosimeters.

    Directory of Open Access Journals (Sweden)

    Peethambaran Arun

    Full Text Available Explosive blast results in multiple organ injury and polytrauma, the intensity of which varies with the nature of the exposure, orientation, environment and individual resilience. Blast overpressure alone may not precisely indicate the level of body or brain injury after blast exposure. Assessment of the extent of body injury after blast exposure is important, since polytrauma and systemic factors significantly contribute to blast-induced traumatic brain injury. We evaluated the activity of plasma enzymes including aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH and creatine kinase (CK at different time points after blast exposure using a mouse model of single and repeated blast exposures to assess the severity of injury. Our data show that activities of all the enzymes in the plasma were significantly increased as early as 1 h after blast exposure. The elevated enzyme activity remained up to 6 h in an overpressure dose-dependent manner and returned close to normal levels at 24 h. Head-only blast exposure with body protection showed no increase in the enzyme activities suggesting that brain injury alone does not contribute to the systemic increase. In contrast to plasma increase, AST, ALT and LDH activity in the liver and CK in the skeletal muscle showed drastic decrease at 6 h after blast exposures. Histopathology showed mild necrosis at 6 h and severe necrosis at 24 h after blast exposures in liver and no changes in the skeletal muscle suggesting that the enzyme release from the tissue to plasma is probably triggered by transient cell membrane disruption from shockwave and not due to necrosis. Overpressure dependent transient release of tissue enzymes and elevation in the plasma after blast exposure suggest that elevated enzyme activities in the blood can be potentially used as a biological dosimeter to assess the severity of blast injury.

  8. Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction.

    Science.gov (United States)

    Pocar, P; Fischer, B; Klonisch, T; Hombach-Klonisch, S

    2005-04-01

    The dioxin/aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsive to both natural and man-made environmental compounds. AhR and its nuclear partner ARNT are expressed in the female reproductive tract in a variety of species and several indications suggest that the AhR might play a pivotal role in the physiology of reproduction. Furthermore, it appears to be the mediator of most, if not all, the adverse effects on reproduction of a group of highly potent environmental pollutants collectively called aryl hydrocarbons (AHs), including the highly toxic compound 2,3,7,8-tetrachlor-odibenzo-p-dioxin (TCDD). Although a large body of recent literature has implicated AhR in multiple signal transduction pathways, the mechanisms of action resulting in a wide spectrum of effects on female reproduction are largely unknown. Here we summarize the major types of molecular cross-talks that have been identified for the AhR and linked cell signaling pathways and that are relevant for the understanding of the role of this transcription factor in female reproduction.

  9. Reactivity of the one-electron reduction product from nifedipine with relevant biological targets.

    Science.gov (United States)

    Núñez-Vergara, L J; Navarrete-Encina, P A; Ortiz, M E; Bollo, S; Squella, J A

    1996-08-14

    The reactivity of the electrochemically generated nitro radical anion from nifedipine, a nitro aryl 1,4-dihydropyridine derivative, with relevant endobiotics and thiol-containing xenobiotics, was quantitatively assessed by cyclic voltammetry. The method was based on the decrease in the return-to-forward peak current ratio after the addition of compounds. A quantitative procedure to calculate the respective interaction constants between the radicals and the xeno/endobiotics is also provided. In the optimal selected conditions, i.e. mixed media (0.015 M aqueous citrate/DMF: 40/60, 0.3 M KCl, 0.1 TBAI) at pH 9.0 the following order of reactivity was obtained: glutathione > uracil > adenine and cysteamine > N-acetylcysteine > captopril > penicillamine. In all cases, the interaction rate constants for these derivatives were greater than the natural decay constant of the radical. Studies on the reactivity at pH 7.4 were also conducted. Results from these experiments indicate a significant reactivity between the radical and the endo/xenobiotics. The increase in the stability of the radical anion by increasing the pH of the mixed media resulted in a decreased reaction with the endo/xenobiotics tested. Computerized simulation with DIGISIM 2.0 of the proposed mechanisms fitted very well with the experimental results for both the natural decay of the radical and its reaction with the tested compounds.

  10. Biological Production of a Hydrocarbon Fuel Intermediate Polyhydroxybutyrate (Phb) from a Process Relevant Lignocellulosic Derived Sugar

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Wei; Mohagheghi, Ali; Mittal, Ashutosh; Pilath, Heidi; Johnson, David K.

    2015-03-22

    PHAs are synthesized by many microorganisms to serve as intracellular carbon storage molecules. In some bacterial strains, PHB can account for up to 80% of cell mass. In addition to its application in the packaging sector, PHB also has great potential as an intermediate in the production of hydrocarbon fuels. PHB can be thermally depolymerized and decarboxylated to propene which can be upgraded to hydrocarbon fuels via commercial oligomerization technologies. In recent years a great effort has been made in bacterial production of PHB, yet the production cost of the polymer is still much higher than conventional petrochemical plastics. The high cost of PHB is because the cost of the substrates can account for as much as half of the total product cost in large scale fermentation. Thus searching for cheaper and better substrates is very necessary for PHB production. In this study, we demonstrate production of PHB by Cupriavidus necator from a process relevant lignocellulosic derived sugar stream, i.e., saccharified hydrolysate slurry from pretreated corn stover. Good cell growth was observed on slurry saccharified with advanced enzymes and 40~60% of PHB was accumulated in the cells. The mechanism of inhibition in the toxic hydrolysate generated by pretreatment and saccharification of biomass, will be discussed.

  11. TaBoo SeArch Algorithm with a Modified Inverse Histogram for Reproducing Biologically Relevant Rare Events of Proteins.

    Science.gov (United States)

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2016-05-10

    The TaBoo SeArch (TBSA) algorithm [ Harada et al. J. Comput. Chem. 2015 , 36 , 763 - 772 and Harada et al. Chem. Phys. Lett. 2015 , 630 , 68 - 75 ] was recently proposed as an enhanced conformational sampling method for reproducing biologically relevant rare events of a given protein. In TBSA, an inverse histogram of the original distribution, mapped onto a set of reaction coordinates, is constructed from trajectories obtained by multiple short-time molecular dynamics (MD) simulations. Rarely occurring states of a given protein are statistically selected as new initial states based on the inverse histogram, and resampling is performed by restarting the MD simulations from the new initial states to promote the conformational transition. In this process, the definition of the inverse histogram, which characterizes the rarely occurring states, is crucial for the efficiency of TBSA. In this study, we propose a simple modification of the inverse histogram to further accelerate the convergence of TBSA. As demonstrations of the modified TBSA, we applied it to (a) hydrogen bonding rearrangements of Met-enkephalin, (b) large-amplitude domain motions of Glutamine-Binding Protein, and (c) folding processes of the B domain of Staphylococcus aureus Protein A. All demonstrations numerically proved that the modified TBSA reproduced these biologically relevant rare events with nanosecond-order simulation times, although a set of microsecond-order, canonical MD simulations failed to reproduce the rare events, indicating the high efficiency of the modified TBSA.

  12. Biological exposure assessment to tetrachloroethylene for workers in the dry cleaning industry

    Directory of Open Access Journals (Sweden)

    Ashley David L

    2008-04-01

    Full Text Available Abstract Background The purpose of this study was to assess the feasibility of conducting biological tetrachloroethylene (perchloroethylene, PCE exposure assessments of dry cleaning employees in conjunction with evaluation of possible PCE health effects. Methods Eighteen women from four dry cleaning facilities in southwestern Ohio were monitored in a pilot study of workers with PCE exposure. Personal breathing zone samples were collected from each employee on two consecutive work days. Biological monitoring included a single measurement of PCE in blood and multiple measurements of pre- and post-shift PCE in exhaled breath and trichloroacetic acid (TCA in urine. Results Post-shift PCE in exhaled breath gradually increased throughout the work week. Statistically significant correlations were observed among the exposure indices. Decreases in PCE in exhaled breath and TCA in urine were observed after two days without exposure to PCE. A mixed-effects model identified statistically significant associations between PCE in exhaled breath and airborne PCE time weighted average (TWA after adjusting for a random participant effect and fixed effects of time and body mass index. Conclusion Although comprehensive, our sampling strategy was challenging to implement due to fluctuating work schedules and the number (pre- and post-shift on three consecutive days and multiplicity (air, blood, exhaled breath, and urine of samples collected. PCE in blood is the preferred biological index to monitor exposures, but may make recruitment difficult. PCE TWA sampling is an appropriate surrogate, although more field intensive. Repeated measures of exposure and mixed-effects modeling may be required for future studies due to high within-subject variability. Workers should be monitored over a long enough period of time to allow the use of a lag term.

  13. Biological exposure assessment to tetrachloroethylene for workers in the dry cleaning industry.

    Science.gov (United States)

    McKernan, Lauralynn T; Ruder, Avima M; Petersen, Martin R; Hein, Misty J; Forrester, Christy L; Sanderson, Wayne T; Ashley, David L; Butler, Mary A

    2008-04-15

    The purpose of this study was to assess the feasibility of conducting biological tetrachloroethylene (perchloroethylene, PCE) exposure assessments of dry cleaning employees in conjunction with evaluation of possible PCE health effects. Eighteen women from four dry cleaning facilities in southwestern Ohio were monitored in a pilot study of workers with PCE exposure. Personal breathing zone samples were collected from each employee on two consecutive work days. Biological monitoring included a single measurement of PCE in blood and multiple measurements of pre- and post-shift PCE in exhaled breath and trichloroacetic acid (TCA) in urine. Post-shift PCE in exhaled breath gradually increased throughout the work week. Statistically significant correlations were observed among the exposure indices. Decreases in PCE in exhaled breath and TCA in urine were observed after two days without exposure to PCE. A mixed-effects model identified statistically significant associations between PCE in exhaled breath and airborne PCE time weighted average (TWA) after adjusting for a random participant effect and fixed effects of time and body mass index. Although comprehensive, our sampling strategy was challenging to implement due to fluctuating work schedules and the number (pre- and post-shift on three consecutive days) and multiplicity (air, blood, exhaled breath, and urine) of samples collected. PCE in blood is the preferred biological index to monitor exposures, but may make recruitment difficult. PCE TWA sampling is an appropriate surrogate, although more field intensive. Repeated measures of exposure and mixed-effects modeling may be required for future studies due to high within-subject variability. Workers should be monitored over a long enough period of time to allow the use of a lag term.

  14. Application of Benchmark Dose (BMD) in Estimating Biological Exposure Limit (BEL) to Cadmium

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology. Methods Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary β2-microgloburin (B2M), N-acetyl-β-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD. Results The cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG, and ALB) and exposure biomarker (UCd). BEL value was 5 μg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 μg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected. Conclusion BMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

  15. The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

    Directory of Open Access Journals (Sweden)

    Proutski Vitali

    2010-12-01

    Full Text Available Abstract Background To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome. Methods DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information. Results The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance. Conclusions Analysis from our in vitro and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including IGF2BP2, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear

  16. Recent excitements in protein NMR: Large proteins and biologically relevant dynamics

    Indian Academy of Sciences (India)

    SAI CHAITANYA CHILIVERI; MANDAR V DESHMUKH

    2016-12-01

    The advent of Transverse Relaxation Optimized SpectroscopY (TROSY) and perdeuteration allowed biomolecularNMR spectroscopists to overcome the size limitation barrier (~20 kDa) in de novo structure determination of proteins.The utility of these techniques was immediately demonstrated on large proteins and protein complexes (e.g. GroELGroES,ClpP protease, Hsp90-p53, 20S proteasome, etc.). Further, recent methodological developments such asResidual Dipolar Couplings and Paramagnetic Relaxation Enhancement allowed accurate measurement of long-rangestructural restraints. Additionally, Carr-Purcell-Meiboom-Gill (CPMG), rotating frame relaxation experiments (R1ρ)and saturation transfer experiments (CEST and DEST) created never-before accessibility to the μs–ms timescaledynamic parameters that led to the deeper understanding of biological processes. Meanwhile, the excitement in thefield continued with a series of developments in the fast data acquisition methods allowing rapid structural studies onless stable proteins. This review aims to discuss important developments in the field of biomolecular NMRspectroscopy in the recent past, i.e., in the post TROSY era. These developments not only gave access to the structuralstudies of large protein assemblies, but also revolutionized tools in the arsenal of today’s biomolecular NMR and pointto a bright future of biomolecular NMR spectroscopy.

  17. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Directory of Open Access Journals (Sweden)

    Dimitrios Mougiakakos

    2011-03-01

    Full Text Available Regulatory T cells (Tregs were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  18. Next generation techniques in the high resolution spectroscopy of biologically relevant molecules.

    Science.gov (United States)

    Neill, Justin L; Douglass, Kevin O; Pate, Brooks H; Pratt, David W

    2011-04-28

    Recent advances in the technology of test and measurement equipment driven by the computer and telecommunications industries have made possible the development of a new broadband, Fourier-transform microwave spectrometer that operates on principles similar to FTNMR. This technique uses a high sample-rate arbitrary waveform generator to construct a phase-locked chirped microwave pulse that gives a linear frequency sweep over a wide frequency range in 1 μs. The chirped pulse efficiently polarizes the molecular sample at all frequencies lying within this band. The subsequent free induction decay of this polarization is measured with a high-speed digitizer and then fast Fourier-transformed to yield a broadband, frequency-resolved rotational spectrum, spanning up to 11.5 GHz and containing lines that are as narrow as 100 kHz. This new technique is called chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. The technique offers the potential to determine the structural and dynamical properties of very large molecules solely from fully resolved pure rotational spectra. FTMW double resonance techniques employing a low-resolution UV laser facilitate an easy assignment of overlapping spectra produced by different conformers in the sample. Of particular interest are the energy landscapes of conformationally flexible molecules of biological importance, including studies of their interaction with solvent and/or other weakly bound molecules. An example is provided from the authors' work on p-methoxyphenethylamine, a neurotransmitter, and its complexes with water.

  19. G Quadruplex in Plants: A Ubiquitous Regulatory Element and Its Biological Relevance

    Directory of Open Access Journals (Sweden)

    Vikas Yadav

    2017-07-01

    Full Text Available G quadruplexes (G4 are higher-order DNA and RNA secondary structures formed by G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential G4 quadruplex sequences have been identified in G-rich eukaryotic non-telomeric and telomeric genomic regions. Upon function, G4 formation is known to involve in chromatin remodeling, gene regulation and has been associated with genomic instability, genetic diseases and cancer progression. The natural role and biological validation of G4 structures is starting to be explored, and is of particular interest for the therapeutic interventions for human diseases. However, the existence and physiological role of G4 DNA and G4 RNA in plants species have not been much investigated yet and therefore, is of great interest for the development of improved crop varieties for sustainable agriculture. In this context, several recent studies suggests that these highly diverse G4 structures in plants can be employed to regulate expression of genes involved in several pathophysiological conditions including stress response to biotic and abiotic stresses as well as DNA damage. In the current review, we summarize the recent findings regarding the emerging functional significance of G4 structures in plants and discuss their potential value in the development of improved crop varieties.

  20. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Energy Technology Data Exchange (ETDEWEB)

    Mougiakakos, Dimitrios [Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm (Sweden)

    2011-03-29

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  1. Direct observation and characterization of DMPC/DHPC aggregates under conditions relevant for biological solution NMR.

    Science.gov (United States)

    van Dam, Lorens; Karlsson, Göran; Edwards, Katarina

    2004-08-30

    We have used cryo-transmission electron microscopy (cryo-TEM) for inspection of aggregates formed by dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in aqueous solution at total phospholipid concentrations cL DHPC ratios q < or = 4.0. In combination with ocular inspections, we are able to sketch out this part of phase-diagram at T = 14-80 degrees C. The temperature and the ratio q are the dominating variables for changing sample morphology, while cL to a lesser extent affects the aggregate structure. At q = 0.5, small, possibly disc-shaped, aggregates with a diameter of approximately 6 nm are formed. At higher q-values, distorted discoidal micelles that tend to short cylindrical micelles are observed. The more well-shaped discs have a diameter of around 20 nm. Upon increasing q or the temperature, long slightly flattened cylindrical micelles that eventually branch are formed. A holey lamellar phase finally appears upon further elevation of q or temperature. The implications for biological NMR work are two. First, discs prepared as membrane mimics are frequently much smaller than predicted by current "ideal bicelle" models. Second, the q approximately 3 preparations used for aligning water-soluble biomolecules in magnetic fields consist of perforated lamellar sheets. Furthermore, the discovered sequence of morphological transitions may have important implications for the development of bicelle-based membrane protein crystallization methods.

  2. Characterization of the electronic states of the biological relevant SSNO molecule

    Science.gov (United States)

    Ayari, Tarek; Hochlaf, Majdi; Mogren Al-Mogren, Muneerah; Francisco, Joseph S.

    2017-02-01

    Using configuration interaction ab initio methods, we investigate the lowest electronic states of doublet and quartet spin multiplicities of SSNO where the one-dimensional cuts of the six-dimensional potential energy surfaces of these electronic states along the stretching and bending coordinates are computed. Mainly, these electronic states are found to be repulsive along the central SN distance. A high density of electronic states is computed even at low excitation energies that may favor their couplings. Therefore, the dynamics of the SSNO electronic states is expected to be very complex. We also characterized the bound electronic states spectroscopically where we derived their equilibrium structures and vibrational frequencies. Our calculations show the importance of taking into account of dynamical correlation, in addition to static correlation, for the accurate description of SSNO electronic excited states and more generally for those of R-NO molecular species. Finally, we highlighted the potential role of SSNO in light-induced NO delivery from SSNO related species in biological media.

  3. Analysis of six relevant toxaphene congeners in biological samples using ion trap MS/MS.

    Science.gov (United States)

    Gouteux, Bruno; Lebeuf, Michel; Trottier, Steve; Gagné, Jean-Pierre

    2002-10-01

    The quantification of six polychlorinated bornanes (CHBs) was studied using ion trap MS/MS. The significance of the selection of parent ions (Ip) and daughter ions (Id) on the detection of these toxaphene congeners was assessed in standard solution and biological samples. Our results indicate that different Ip and Id, selected at either low or high mass-to-charge (m/z) ratios, influence drastically the response factor of the CHBs and the chemical noise observed. For the octachlorinated toxaphene congeners (Parlar-26 (P-26), Parlar-40/41 (P-40/41), Parlar-44 (P-44)), the detection performance of the ion trap MS/MS is similar whether Ip and Id were chosen at low or high m/z ratios. However, the selection of Ip and Id at high m/z ratios clearly enhances the detection of the nonachlorinated toxaphene congeners (Parlar-50 (P-50), Parlar-62 (P-62)). The improved method, which selects Ip and Id at low m/z ratios for P-26, P-40/41 and P-44 and at high m/z ratios for P-50 and P-62, permitted to obtain low detection limits as well as repeatable and accurate results.

  4. Biological, Clinical, and Population Relevance of 95 Loci for Blood Lipids

    Science.gov (United States)

    Teslovich, Tanya M.; Musunuru, Kiran; Smith, Albert V.; Edmondson, Andrew C.; Stylianou, Ioannis M.; Koseki, Masahiro; Pirruccello, James P.; Ripatti, Samuli; Chasman, Daniel I.; Willer, Cristen J.; Johansen, Christopher T.; Fouchier, Sigrid W.; Isaacs, Aaron; Peloso, Gina M.; Barbalic, Maja; Ricketts, Sally L.; Bis, Joshua C.; Aulchenko, Yurii S.; Thorleifsson, Gudmar; Feitosa, Mary F.; Chambers, John; Orho-Melander, Marju; Melander, Olle; Johnson, Toby; Li, Xiaohui; Guo, Xiuqing; Li, Mingyao; Cho, Yoon Shin; Go, Min Jin; Kim, Young Jin; Lee, Jong-Young; Park, Taesung; Kim, Kyunga; Sim, Xueling; Ong, Rick Twee-Hee; Croteau-Chonka, Damien C.; Lange, Leslie A.; Smith, Joshua D.; Song, Kijoung; Zhao, Jing Hua; Yuan, Xin; Luan, Jian'an; Lamina, Claudia; Ziegler, Andreas; Zhang, Weihua; Zee, Robert Y.L.; Wright, Alan F.; Witteman, Jacqueline C.M.; Wilson, James F.; Willemsen, Gonneke; Wichmann, H-Erich; Whitfield, John B.; Waterworth, Dawn M.; Wareham, Nicholas J.; Waeber, Gérard; Vollenweider, Peter; Voight, Benjamin F.; Vitart, Veronique; Uitterlinden, Andre G.; Uda, Manuela; Tuomilehto, Jaakko; Thompson, John R.; Tanaka, Toshiko; Surakka, Ida; Stringham, Heather M.; Spector, Tim D.; Soranzo, Nicole; Smit, Johannes H.; Sinisalo, Juha; Silander, Kaisa; Sijbrands, Eric J.G.; Scuteri, Angelo; Scott, James; Schlessinger, David; Sanna, Serena; Salomaa, Veikko; Saharinen, Juha; Sabatti, Chiara; Ruokonen, Aimo; Rudan, Igor; Rose, Lynda M.; Roberts, Robert; Rieder, Mark; Psaty, Bruce M.; Pramstaller, Peter P.; Pichler, Irene; Perola, Markus; Penninx, Brenda W.J.H.; Pedersen, Nancy L.; Pattaro, Cristian; Parker, Alex N.; Pare, Guillaume; Oostra, Ben A.; O'Donnell, Christopher J.; Nieminen, Markku S.; Nickerson, Deborah A.; Montgomery, Grant W.; Meitinger, Thomas; McPherson, Ruth; McCarthy, Mark I.; McArdle, Wendy; Masson, David; Martin, Nicholas G.; Marroni, Fabio; Mangino, Massimo; Magnusson, Patrik K.E.; Lucas, Gavin; Luben, Robert; Loos, Ruth J. F.; Lokki, Maisa; Lettre, Guillaume; Langenberg, Claudia; Launer, Lenore J.; Lakatta, Edward G.; Laaksonen, Reijo; Kyvik, Kirsten O.; Kronenberg, Florian; König, Inke R.; Khaw, Kay-Tee; Kaprio, Jaakko; Kaplan, Lee M.; Johansson, Åsa; Jarvelin, Marjo-Riitta; Janssens, A. Cecile J.W.; Ingelsson, Erik; Igl, Wilmar; Hovingh, G. Kees; Hottenga, Jouke-Jan; Hofman, Albert; Hicks, Andrew A.; Hengstenberg, Christian; Heid, Iris M.; Hayward, Caroline; Havulinna, Aki S.; Hastie, Nicholas D.; Harris, Tamara B.; Haritunians, Talin; Hall, Alistair S.; Gyllensten, Ulf; Guiducci, Candace; Groop, Leif C.; Gonzalez, Elena; Gieger, Christian; Freimer, Nelson B.; Ferrucci, Luigi; Erdmann, Jeanette; Elliott, Paul; Ejebe, Kenechi G.; Döring, Angela; Dominiczak, Anna F.; Demissie, Serkalem; Deloukas, Panagiotis; de Geus, Eco J.C.; de Faire, Ulf; Crawford, Gabriel; Collins, Francis S.; Chen, Yii-der I.; Caulfield, Mark J.; Campbell, Harry; Burtt, Noel P.; Bonnycastle, Lori L.; Boomsma, Dorret I.; Boekholdt, S. Matthijs; Bergman, Richard N.; Barroso, Inês; Bandinelli, Stefania; Ballantyne, Christie M.; Assimes, Themistocles L.; Quertermous, Thomas; Altshuler, David; Seielstad, Mark; Wong, Tien Y.; Tai, E-Shyong; Feranil, Alan B.; Kuzawa, Christopher W.; Adair, Linda S.; Taylor, Herman A.; Borecki, Ingrid B.; Gabriel, Stacey B.; Wilson, James G.; Stefansson, Kari; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Krauss, Ronald M.; Mohlke, Karen L.; Ordovas, Jose M.; Munroe, Patricia B.; Kooner, Jaspal S.; Tall, Alan R.; Hegele, Robert A.; Kastelein, John J.P.; Schadt, Eric E.; Rotter, Jerome I.; Boerwinkle, Eric; Strachan, David P.; Mooser, Vincent; Holm, Hilma; Reilly, Muredach P.; Samani, Nilesh J; Schunkert, Heribert; Cupples, L. Adrienne; Sandhu, Manjinder S.; Ridker, Paul M; Rader, Daniel J.; van Duijn, Cornelia M.; Peltonen, Leena; Abecasis, Gonçalo R.; Boehnke, Michael; Kathiresan, Sekar

    2010-01-01

    Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with serum lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 × 10-8), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (e.g., CYP7A1, NPC1L1, and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and impact lipid traits in three non-European populations (East Asians, South Asians, and African Americans). Our results identify several novel loci associated with serum lipids that are also associated with CAD. Finally, we validated three of the novel genes—GALNT2, PPP1R3B, and TTC39B—with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD. PMID:20686565

  5. Copper isotope fractionation between aqueous compounds relevant to low temperature geochemistry and biology

    Science.gov (United States)

    Fujii, Toshiyuki; Moynier, Frédéric; Abe, Minori; Nemoto, Keisuke; Albarède, Francis

    2013-06-01

    Isotope fractionation between the common Cu species present in solution (Cu+, Cu2+, hydroxide, chloride, sulfide, carbonate, oxalate, and ascorbate) has been investigated using both ab initio methods and experimental solvent extraction techniques. In order to establish unambiguously the existence of equilibrium isotope fractionation (as opposed to kinetic isotope fractionation), we first performed laboratory-scale liquid-liquid distribution experiments. Upon exchange between HCl medium and a macrocyclic complex, the 65Cu/63Cu ratio fractionated by -1.06‰ to -0.39‰. The acidity dependence of the fractionation was appropriately explained by ligand exchange reactions between hydrated H2O and Cl- via intramolecular vibrations. The magnitude of the Cu isotope fractionation among important Cu ligands was also estimated by ab initio methods. The magnitude of the nuclear field shift effect to the Cu isotope fractionation represents only ˜3% of the mass-dependent fractionation. The theoretical estimation was expanded to chlorides, hydroxides, sulfides, sulfates, and carbonates under different conditions of pH. Copper isotope fractionation of up to 2‰ is expected for different forms of Cu present in seawater and for different sediments (carbonates, hydroxides, and sulfides). We found that Cu in dissolved carbonates and sulfates is isotopically much heavier (+0.6‰) than free Cu. Isotope fractionation of Cu in hydroxide is minimal. The relevance of these new results to the understanding of metabolic processes was also discussed. Copper is an essential element used by a large number of proteins for electron transfer. Further theoretical estimates of δ65Cu in hydrated Cu(I) and Cu(II) ions, Cu(II) ascorbates, and Cu(II) oxalate predict Cu isotope fractionation during the breakdown of ascorbate into oxalate and account for the isotopically heavy Cu found in animal kidneys.

  6. Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.

    Science.gov (United States)

    Willenberg, Ina; Meschede, Anna K; Gueler, Faikah; Jang, Mi-Sun; Shushakova, Nelli; Schebb, Nils Helge

    2015-01-01

    Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX-2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX-2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX-2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.

  7. Meta-analysis of muscle transcriptome data using the MADMuscle database reveals biologically relevant gene patterns

    Directory of Open Access Journals (Sweden)

    Teusan Raluca

    2011-02-01

    Full Text Available Abstract Background DNA microarray technology has had a great impact on muscle research and microarray gene expression data has been widely used to identify gene signatures characteristic of the studied conditions. With the rapid accumulation of muscle microarray data, it is of great interest to understand how to compare and combine data across multiple studies. Meta-analysis of transcriptome data is a valuable method to achieve it. It enables to highlight conserved gene signatures between multiple independent studies. However, using it is made difficult by the diversity of the available data: different microarray platforms, different gene nomenclature, different species studied, etc. Description We have developed a system tool dedicated to muscle transcriptome data. This system comprises a collection of microarray data as well as a query tool. This latter allows the user to extract similar clusters of co-expressed genes from the database, using an input gene list. Common and relevant gene signatures can thus be searched more easily. The dedicated database consists in a large compendium of public data (more than 500 data sets related to muscle (skeletal and heart. These studies included seven different animal species from invertebrates (Drosophila melanogaster, Caenorhabditis elegans and vertebrates (Homo sapiens, Mus musculus, Rattus norvegicus, Canis familiaris, Gallus gallus. After a renormalization step, clusters of co-expressed genes were identified in each dataset. The lists of co-expressed genes were annotated using a unified re-annotation procedure. These gene lists were compared to find significant overlaps between studies. Conclusions Applied to this large compendium of data sets, meta-analyses demonstrated that conserved patterns between species could be identified. Focusing on a specific pathology (Duchenne Muscular Dystrophy we validated results across independent studies and revealed robust biomarkers and new pathways of interest

  8. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?

    Science.gov (United States)

    Strolin, Silvia; Bossi, Gianluca; Strigari, Lidia

    2017-01-01

    Background Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR). In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence. In this work we introduce a new dose-response relationship based on relevant publications concerning preclinical models with regard to delivered dose, fractionation schedule and occurrence of biological effects on non-irradiated tissue, abscopal effects. Methods We reviewed relevant publications on murine models and the abscopal effect in radiation cancer research following PRISMA methodology. In particular, through a log-likelihood method, we evaluated whether the occurrence of abscopal effects may be related to the biologically effective dose (BED). To this aim, studies accomplished with different tumor histotypes were considered in our analysis including breast, colon, lung, fibrosarcoma, pancreas, melanoma and head and neck cancer. For all the tumors, the α / β ratio was assumed to be 10 Gy, as generally adopted for neoplastic cells. Results Our results support the hypothesis that the occurrence rate of abscopal effects in preclinical models increases with BED. In particular, the probability of revealing abscopal effects is 50% when a BED of 60 Gy is generated. Conclusion Our study provides evidence that SABR treatments associated with high BEDs could be considered an effective strategy in triggering the abscopal effect, thus shedding light on the promising outcomes revealed in clinical practice. PMID:28222111

  9. Type-2 diabetes-associated variants with cross-trait relevance: Post-GWAs strategies for biological function interpretation.

    Science.gov (United States)

    Frau, Francesca; Crowther, Daniel; Ruetten, Hartmut; Allebrandt, Karla V

    2017-05-01

    Genome-wide association studies (GWAs) for type 2 diabetes (T2D) have been successful in identifying many loci with robust association signals. Nevertheless, there is a clear need for post-GWAs strategies to understand mechanism of action and clinical relevance of these variants. The association of several comorbidities with T2D suggests a common etiology for these phenotypes and complicates the management of the disease. In this study, we focused on the genetics underlying these relationships, using systems genomics to identify genetic variation associated with T2D and 12 other traits. GWAs studies summary statistics for pairwise comparisons were obtained for glycemic traits, obesity, coronary artery disease, and lipids from large consortia GWAs meta-analyses. We used a network medicine approach to leverage experimental information about the identified genes and variants with cross traits effects for biological function interpretation. We identified a set of 38 genetic variants with cross traits effects that point to a main network of genes that should be relevant for T2D and its comorbidities. We prioritized the T2D associated genes based on the number of traits they showed association with and the experimental evidence showing their relation to the disease etiology. In this study, we demonstrated how systems genomics and network medicine approaches can shed light into GWAs discoveries, translating findings into a more therapeutically relevant context. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Relevance of the neuropeptide Y system in the biology of cancer progression.

    Science.gov (United States)

    Ruscica, M; Dozio, E; Motta, M; Magni, P

    2007-01-01

    The peptides pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) share a similar structure, known as PP-fold. Within this family of peptides, NPY, a highly conserved 36-aminoacid residue peptide, is involved in the regulation of a wide range of physiological functions, such as food intake and energy metabolism, as well as in the promotion of some remarkable aspects of tumor progression, including cell proliferation, matrix invasion, metastatization, and angiogenesis. NPY exerts its biological effects through five G-protein coupled receptors, named Y1-, Y2-, Y4-, Y5-, and y6-R, which appear associated with different aspects of oncogenesis. Y1-R seems involved in the modulation of cancer cell proliferation, whereas Y2-R activation appears to promote angiogenesis. The development of NPY receptor subtype selective analogs has helped to elucidate the physiological and pathophysiological role and localization of each receptor and may contribute to a better understanding of the receptor-ligand interaction. The NPY system appears to be variously associated with specific tumors, including neural crest-derived tumors, breast and prostate cancers. In addition to NPY, PYY is also able to affect cancer cell growth in a dose-dependent manner and through Y-Rs. In conclusion, peptides of the NPY family and the related receptors play an important role in the progression of different cancer types, with some molecular specificity according to each step of this process. On this basis, future studies may be directed to the implementation of novel diagnostic and therapeutic approaches targeting this system.

  11. Behavior toxicity to Caenorhabditis elegans transferred to the progeny after exposure to sulfamethoxazole at environmentally relevant concentrations

    Institute of Scientific and Technical Information of China (English)

    Zhenyang Yu; Lei Jiang; Daqiang Yin

    2011-01-01

    Sulfamethoxazole (SMX) is one of the most common detected antibiotics in the environment. In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny, Caenorhabditis elegans was exposed at environmentally relevant concentrations for 24, 48, 72 and 96 hr, respectively. After exposure, the exposed parent generation (Po) was measured for behavior and growth indicators, which were presented as percentage of controls (POC). Then their corresponding unexposed progeny (F1) was separated and measured for the same indicators. The lowest POC for Po after 96 hr-exposure at 100 mg/L were 37.8%, 12.7%, 45.8% and 70.1% for body bending frequency (BBF), reversal movement (RM), Omega turns (OT) and body length (BL), respectively. And F1 suffered defects with the lowest POC as 55.8%, 24.1%, 48.5% and 60.7% for BBF, RM, OT and BL, respectively. Defects in both Po and F1 showed a time- and concentration-dependent fashion and behavior indicators showed better sensitivity than growth indicator. The observed effects on F1 demonstrated the transferable properties of SMX. Defects of SMX at environmental concentrations suggested that it is necessary to perform further systematical studies on its ecological risk in actual conditions.

  12. In vitro exposure of Leydig cells to an environmentally relevant mixture of organochlorines represses early steps of steroidogenesis.

    Science.gov (United States)

    Enangue Njembele, Annick N; Bailey, Janice L; Tremblay, Jacques J

    2014-06-01

    Leydig cell steroidogenesis is mainly regulated by LH via increased cAMP production leading to STAR protein activation. STAR is essential for cholesterol shuttling inside mitochondria where steroidogenesis is initiated. Accumulating evidence suggest that persistent organochlorine compounds disrupt testicular function, but the mechanism of action remains poorly characterized. Here we report that in vitro exposure of MA-10 and MLTC-1 Leydig cells to an environmentally relevant mixture of 15 organochlorines impairs steroidogenesis. While having no effect on cell viability and basal steroid production, the organochlorine mixture caused a 50% decrease in cAMP-induced progesterone production. The mixture also reduced cAMP-induced 30 kDa STAR protein by 50% while having no effect on basal STAR protein. Basal or cAMP-induced Star mRNA levels and promoter activity were unaffected by the mixture, indicating that the organochlorine mixture acted at the translational/posttranslational level. Further supporting this is the fact that in COS-7 cells overexpressing STAR, the organochlorine mixture caused a decrease in the 30 kDa form of STAR and an accumulation of the 37 kDa forms. In addition to STAR, we found that the organochlorine mixture also decreases the levels of CYP11A1 and ADXR, two proteins essential for the conversion of cholesterol into pregnenolone. In conclusion, our data show that organochlorine exposure disrupts Leydig cell function by targeting different components of the steroidogenic pathway.

  13. Mapping biological soil crusts for understanding their functional relevance in dryland ecosystems

    Science.gov (United States)

    Rodriguez-Caballero, E.; Escribano, P.; Chamizo, S.; Canton, Y.

    2012-04-01

    Biological soil crusts (BSCs) are considered a key element in the functioning of arid and semiarid ecosystems as they modify numerous soil surface properties involved in primary ecosystem processes such as hydrological and erosion processes, and nutrient cycling.. It is known that arid and semiarid ecosystems are conformed by a complex matrix of vegetated and open ground patches usually covered by BSCs. Geomorphic evolution of drylands depends on the individual response of patches and also on the interactions and feedback-processes among patches. These interactions are controlled by patch spatial distribution. On this account, to understand the role of BSCs in the system, it is necessary to introduce their effect at coarser scales, and to have accurate and spatially continuous information of BSC distribution. The inherent complexity and the spatial heterogeneity of drylands make field survey methods very limited for BSC mapping. Images reported by remote sensors are presented as a powerful tool for mapping BSC spatial distribution. Remote sensors provide synoptic and spatially continuous information of the territory. Different indices for mapping BSCs have been published. These indices are based on distinctive spectral characteristic of BSCs and differ in nature and objectives. The aim of this work was to analyze the feasibility of some of these indices in a semiarid area characterized by sparse vegetation cover usually mixed at subpixel level with elements characterized by very similar spectral response (bare soil, BSCs and dry vegetation). These indices were: i) CRCIA, index applied for mapping BSCs from hyperspectral images. ii) CI, index developed for mapping of cyanobacteria-dominated BSCs and iii) BSCI, index for mapping of lichen-dominated BSCs. The multispectral indices (CI and BSCI) classified as BSCs 50% of the pixels dominated by BSCs. The CRCIA hyperspectral index, showed better results than those obtained with multispectral indices. This index

  14. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    Science.gov (United States)

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  15. In utero exposure to environmentally relevant concentrations of PCB 153 and PCB 118 disrupts fetal testis development in sheep.

    Science.gov (United States)

    Krogenæs, Anette K; Ropstad, Erik; Gutleb, Arno C; Hårdnes, Nina; Berg, Vidar; Dahl, Ellen; Fowler, Paul A

    2014-01-01

    Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.

  16. Gene expression profiling to identify potentially relevant disease outcomes and support human health risk assessment for carbon black nanoparticle exposure.

    Science.gov (United States)

    Bourdon, Julie A; Williams, Andrew; Kuo, Byron; Moffat, Ivy; White, Paul A; Halappanavar, Sabina; Vogel, Ulla; Wallin, Håkan; Yauk, Carole L

    2013-01-07

    New approaches are urgently needed to evaluate potential hazards posed by exposure to nanomaterials. Gene expression profiling provides information on potential modes of action and human relevance, and tools have recently become available for pathway-based quantitative risk assessment. The objective of this study was to use toxicogenomics in the context of human health risk assessment. We explore the utility of toxicogenomics in risk assessment, using published gene expression data from C57BL/6 mice exposed to 18, 54 and 162 μg Printex 90 carbon black nanoparticles (CBNP). Analysis of CBNP-perturbed pathways, networks and transcription factors revealed concomitant changes in predicted phenotypes (e.g., pulmonary inflammation and genotoxicity), that correlated with dose and time. Benchmark doses (BMDs) for apical endpoints were comparable to minimum BMDs for relevant pathway-specific expression changes. Comparison to inflammatory lung disease models (i.e., allergic airway inflammation, bacterial infection and tissue injury and fibrosis) and human disease profiles revealed that induced gene expression changes in Printex 90 exposed mice were similar to those typical for pulmonary injury and fibrosis. Very similar fibrotic pathways were perturbed in CBNP-exposed mice and human fibrosis disease models. Our synthesis demonstrates how toxicogenomic profiles may be used in human health risk assessment of nanoparticles and constitutes an important step forward in the ultimate recognition of toxicogenomic endpoints in human health risk. As our knowledge of molecular pathways, dose-response characteristics and relevance to human disease continues to grow, we anticipate that toxicogenomics will become increasingly useful in assessing chemical toxicities and in human health risk assessment. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  17. New applications of biological monitoring for environmental exposure and susceptibility monitoring. Report of the 7th International Symposium on Biological Monitoring in Occupational and Environmental Health.

    NARCIS (Netherlands)

    Scheepers, P.T.J.; Heussen, G.A.

    2008-01-01

    Validated biological monitoring methods are used in large-scale monitoring programmes involving determination of ubiquitous environmental pollutants such as metals and pesticides. Some programmes focus on children's exposure, and policies to prevent adverse health effects. Most of these initiatives

  18. New applications of biological monitoring for environmental exposure and susceptibility monitoring. Report of the 7th International Symposium on Biological Monitoring in Occupational and Environmental Health.

    NARCIS (Netherlands)

    Scheepers, P.T.J.; Heussen, G.A.

    2008-01-01

    Validated biological monitoring methods are used in large-scale monitoring programmes involving determination of ubiquitous environmental pollutants such as metals and pesticides. Some programmes focus on children's exposure, and policies to prevent adverse health effects. Most of these initiatives

  19. The scaling law of climate change and its relevance to assessing (palaeo)biological responses

    Science.gov (United States)

    Kiessling, Wolfgang; Eichenseer, Kilian

    2014-05-01

    interglacials, are not monotonic, but punctuated by short-term cooling intervals. The fossil record tells us that biodiversity responded dramatically to ancient intervals of climate warming. We can now see that the apparently slower rates of change in some mass extinctions (Permian-Triassic, Triassic-Jurassic) were greater than today when the scaling law is considered. This reassures us that studying deep time patterns of organismic response to climate change is a worthwhile endeavor that is relevant for predicting the future. References Burrows, M. T., Schoeman, D. S., Buckley, L. B., Moore, P., Poloczanska, E. S., Brander, K. M., Brown, C., Bruno, J. F., Duarte, C. M., Halpern, B. S., Holding, J., Kappel, C. V., Kiessling, W., O'Connor, M. I., Pandolfi, J. M., Parmesan, C., Schwing, F. B., Sydeman, W. J., and Richardson, A. J.: The pace of shifting climate in marine and terrestrial ecosystems, Science, 334, 652-655, 2011. Gingerich, P. D.: Quantification and comparison of evolutionary rates, American Journal of Science, 293A, 453-478, 1993. Sadler, P. M.: Sediment accumulation rates and the completeness of stratigraphic sections, Journal of Geology, 89, 569-584, 1981. Sun, Y., Joachimski, M. M., Wignall, P. B., Yan, C., Chen, Y., Jiang, H., Wang, L., and Lai, X.: Lethally hot temperatures during the Early Triassic greenhouse, Science, 338, 366-370, 2012.

  20. [Indoor fungal exposure: What impact on clinical and biological status regarding Aspergillus during cystic fibrosis].

    Science.gov (United States)

    Pricope, D; Deneuville, E; Frain, S; Chevrier, S; Belaz, S; Roussey, M; Gangneux, J-P

    2015-06-01

    The sources of exposure during diseases due to Aspergillus fungi in cystic fibrosis patients are still poorly explored. We assessed home fungal exposure in patients suffering from cystic fibrosis and analysed its impact on the presence of Aspergillus biological markers, the colonisation of airways, as well as the sensitization and Aspergillus serology. Between March 2012 and August 2012, 34 patients benefited from a visit performed by a home environment medical adviser including sampling for mycological analysis. The number of colonies of Aspergillus was not significantly different in the various sampling sites (P=0.251), but the number of non-Aspergillus colonies was much higher in the kitchen (P=0.0045). Subsequently, home fungal exposure was compared between the groups "absence of Aspergillus-related markers" and "presence of Aspergillus-related markers". Home exposure to Aspergillus (P=0.453) and non-Aspergillus (P=0.972) flora was not significant between the 2 groups. Within this series of 34 patients that should be expanded, we note an absence of clear relationship between home exposure and the Aspergillus-linked markers in patients suffering from cystic fibrosis. This result should be taken into account regarding too restrictive hygiene advices provided to families, given the fact that fungal exposure can also results from activities performed away from home. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Biological effects of low-level exposures: a perspective from U.S. EPA scientists.

    OpenAIRE

    Davis, J M; Farland, W H

    1998-01-01

    Biological effects of low-level exposures (BELLE) may be very important in characterizing the potential health risks of environmental pollutants. Before some features of BELLE, such as effects that may be modulated by adaptive or defense mechanisms, can be taken into greater consideration in U.S. Environmental Protection Agency risk assessments, however adequate information on a toxicant's mode of action and answers to other questions are needed.

  2. Biological Effects of Short, High-Level Exposure to Gases: Nitrogen Oxides.

    Science.gov (United States)

    1980-07-01

    SUPPLEMENTARY NOT ES3 This project was one of four under the same contract; the others covered ammonia , carbon monoxide, and sulfur dioxide. 3 IS. KEY wOROS...characterize the biological responses to short, high-level exposures to four gases associated with certain Army weapons systems ( ammonia , carbon monoxide...20- i --- 7 (2) Biochemical and Other Effects Buckley and BalchumlO found biochemical changes, principally in enzyme activity of the liver, spleen

  3. The Role of Molecular Biology in the Biomonitoring of Human Exposure to Chemicals

    OpenAIRE

    Balam Muñoz; Arnulfo Albores

    2010-01-01

    Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring ...

  4. Organizational influence on the occurrence of work accidents involving exposure to biological material.

    Science.gov (United States)

    Marziale, Maria Helena Palucci; Rocha, Fernanda Ludmilla Rossi; Robazzi, Maria Lúcia do Carmo Cruz; Cenzi, Camila Maria; dos Santos, Heloisa Ehmke Cardoso; Trovó, Marli Elisa Mendes

    2013-01-01

    to analyze work accidents involving exposure to biological materials which took place among personnel working in nursing and to evaluate the influence of the organizational culture on the occurrence of these accidents. a retrospective, analytical study, carried out in two stages in a hospital that was part of the Network for the Prevention of Work Accidents. The first stage involved the analysis of the characteristics of the work accidents involving exposure to biological materials as recorded over a seven-year period by the nursing staff in the hospital studied, and registered in the Network databank. The second stage involved the analysis of 122 nursing staff members' perception of the institutional culture, who were allocated to the control group (workers who had not had an accident) and the case group (workers who had had an accident). 386 accidents had been recorded: percutaneous lesions occurred in 79% of the cases, needles were the materials involved in 69.7% of the accidents, and in 81.9% of the accident there was contact with blood. Regarding the influence of the organizational culture on the occurrence of accidents, the results obtained through the analysis of the two groups did not demonstrate significant differences between the average scores attributed by the workers in each organizational value or practice category. It is concluded that accidents involving exposure to biological material need to be avoided, however, it was not possible to confirm the influence of organizational values or practices on workers' behavior concerning the occurrence of these accidents.

  5. Evaluation of Occupational Exposure and Biological Monitoring of Sand Washing Workers Exposed to Silica Dusts

    Directory of Open Access Journals (Sweden)

    Gholamreza Parsaseresht

    2017-01-01

    Full Text Available Background and Objectives:The health of sand washing workers could be threatened by the crystalline silica dust exposure. The aim of this study was the evaluation of occupational and biological monitoring with crystalline silica dusts in the sand washing workers. Materials and Methods: This was an analytical and cross-sectional study of 44 sand washing workers exposed to crystalline silica and also 63 municipality gardeners as a control group in the city of Dorood. Occupational exposure monitoring to respirable total dust and silica dust was performed according to the National Institute for Occupational Safety and Health (NIOSH methods 0600 and 7602-respectively. Biological monitoring of workers' was carried out according to the Karatas method for the analysis of Malondialdehyde in the blood serum of exposed and control subjects. The informed consents were taken for obtaining blood samples of workers, according to the Helsinki Declaration. Statistical analysis of data was done using SPSS version 16. The statistical test of Pearson, t-tests and linear regression was applied. Results: The occupational exposure of 54.55% was exceeded the occupational exposure limit of Iran at the level of 3 mg/m3. The mean exposure of sand miners and control group to respirable silica dust was evaluated at 0.219 ± 0.177 and 0.010 ± 0.002 as mg/m3respectively. Occupational exposure of all sand washing workers was higher than the occupational exposure limit of Iran at the level of 0.025 mg/m3.The concentration of serum Malondialdehyde (MDA exposed group and the control group were 36.64 ± 10.75 and 19.40 ± 4.68 as µM respectively. Conclusion: Due to the positive correlation between exposure of sand washing workers to silica dust sand serum MDA among exposed group(P-value<0.0001, r=0.881, periodical biological monitoring along with effective control measures of workers are recommended for the health promotion of these workers.

  6. HExpoChem: a systems biology resource to explore human exposure to chemicals

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Jacobsen, Ulrik Plesner; Kalhauge, Christian Gram

    2013-01-01

    of computational biology approaches are needed to assess the health risks of chemical exposure. Here we present HExpoChem, a tool based on environmental chemicals and their bioactivities on human proteins with the objective of aiding the qualitative exploration of human exposure to chemicals. The chemical......Summary: Humans are exposed to diverse hazardous chemicals daily. Although an exposure to these chemicals is suspected to have adverse effects on human health, mechanistic insights into how they interact with the human body are still limited. Therefore, acquisition of curated data and development......–protein interactions have been enriched with a quality-scored human protein–protein interaction network, a protein–protein association network and a chemical–chemical interaction network, thus allowing the study of environmental chemicals through formation of protein complexes and phenotypic outcomes enrichment...

  7. Biomonitoring of benzene and 1,3-butadiene exposure and early biological effects in traffic policemen.

    Science.gov (United States)

    Arayasiri, Manaswee; Mahidol, Chulabhorn; Navasumrit, Panida; Autrup, Herman; Ruchirawat, Mathuros

    2010-09-15

    The objective of this study was to determine benzene and 1,3-butadiene exposure through ambient air and personal air monitoring, as well as through biomarkers of exposure, and to evaluate the potential health risk of exposure through the use of biomarkers of early biological effects in central Bangkok traffic policemen. Ambient air concentrations of benzene and 1,3-butadiene at the roadsides were significantly higher than in police offices used as control sites (pbutadiene (median 3.08 microg/m(3)) than office policemen (median 6.17 microg/m(3) for benzene and 0.37 microg/m(3) for 1,3-butadiene) (pbutadiene metabolite, monohydroxy-butenyl mercapturic acid. Biomarkers of early biological effects, 8-hydroxy-2'-deoxyguanosine in leukocytes (8-OHdG), DNA-strand breaks, and DNA-repair capacity, measured as an increase in gamma ray-induced chromosome aberrations were significantly higher in traffic policemen than controls (pbutadiene exposure were significantly associated with 8-OHdG and olive tail moment at pbutadiene on DNA damage. These results indicated that traffic policemen, who are exposed to benzene and 1,3-butadiene at the roadside in central Bangkok, are potentially at a higher risk for development of diseases such as cancer than office policemen.

  8. Uranium bioaccumulation and biological disorders induced in zebrafish (Danio rerio) after a depleted uranium waterborne exposure

    Energy Technology Data Exchange (ETDEWEB)

    Barillet, Sabrina, E-mail: sabrina.barillet@free.f [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Adam-Guillermin, Christelle, E-mail: christelle.adam-guillermin@irsn.f [Laboratory of Radioecology and Ecotoxicology, IRSN (Institute for Radiological protection and Nuclear Safety), DEI/SECRE/LRE, Cadarache, Bat 186, BP 3, 13115 St-Paul-Lez-Durance cedex (France); Palluel, Olivier, E-mail: olivier.palluel@ineris.f [Ecotoxicological Risk Assessment Unit, INERIS (National Institute for Industrial Environment and Risks), Parc technologique ALATA, 60 550 Verneuil-en-Halatte (France); Porcher, Jean-Marc, E-mail: jean-marc.porcher@ineris.f [Ecotoxicological Risk Assessment Unit, INERIS (National Institute for Industrial Environment and Risks), Parc technologique ALATA, 60 550 Verneuil-en-Halatte (France); Devaux, Alain, E-mail: alain.devaux@entpe.f [Universite de Lyon, INRA, EFPA-SA, Environmental Science Laboratory (LSE), ENTPE, 69518 Vaulx en Velin cedex (France)

    2011-02-15

    Because of its toxicity and its ubiquity within aquatic compartments, uranium (U) represents a significant hazard to aquatic species such as fish. In a previous study, we investigated some biological responses in zebrafish either exposed to depleted or to enriched U (i.e., to different radiological activities). However, results required further experiments to better understand biological responses. Moreover, we failed to clearly demonstrate a significant relationship between biological effects and U radiological activity. We therefore chose to herein examine U bioaccumulation and induced effects in zebrafish according to a chemical dose-response approach. Results showed that U is highly bioconcentrated in fish, according to a time- and concentration-dependent model. Additionally, hepatic antioxidant defenses, red blood cells DNA integrity and brain acetylcholinesterase activity were found to be significantly altered. Generally, the higher the U concentration, the sooner and/or the greater the effect, suggesting a close relationship between accumulation and effect. - Research highlights: Depleted U bioconcentration factor is of about 1000 in zebrafish exposed to 20 {mu}g/L. Hepatic antioxidant disorders are noticed as soon as the first hours of exposure. DNA damage is induced in red blood cells after 20 d of exposure to 500 {mu}g DU/L. The brain cholinergic system (AChE activity) is impacted. - This study demonstrates that U is highly bioaccumulated in fish, resulting in biological disorders such as hepatic oxidative stress as well as genotoxic and neurotoxic events.

  9. Biological monitoring in occupational exposure to low levels of 1,3-butadiene.

    Science.gov (United States)

    Fustinoni, S; Perbellini, L; Soleo, L; Manno, M; Foà, V

    2004-04-01

    Exposure to 1,3-butadiene (BD), a probable carcinogen to humans, was investigated in two groups of subjects working in a petrochemical plant where BD is produced and used to prepare polymers: 42 occupationally exposed workers and 43 internal non-occupationally exposed controls. BD personal exposure was very low but significantly different in the two groups (median airborne BD 1.5 and 0.4 microg/m(3) in exposed and controls, respectively). Similarly, BD in blood and urine, but not in exhaled air, was higher in the exposed workers than in controls (blood BD 3.7 ng/l versus <1.8 ng/l, urinary BD 2.4 ng/l versus <1.0 ng/l). These three biomarkers correlated significantly with personal exposure ( 0.283 < or = Pearson's r < or = 0.383) and between them (0.780 < or = r < or = 0.896). Excretion of urinary mercapturic acids N-acetyl-S-(3,4-hydroxybutyl)-l-cysteine (MI), N-acetyl-S-(1-hydroxymethyl-2-propenyl)-l-cysteine and N-acetyl-S-(2-hydroxy-3-butenyl)-l-cysteine (MII), chromosomal aberrations (CA), and sister chromatid exchanges (SCE) in peripheral blood lymphocytes were not influenced by occupational exposure. Our results show that unmetabolised BD in biological fluids, and particularly urinary BD, represents the biomarker of choice for assessing occupational exposure to low airborne concentrations of BD.

  10. The practicalities and pitfalls of establishing a policy-relevant and cost-effective soil biological monitoring scheme.

    Science.gov (United States)

    Faber, Jack H; Creamer, Rachel E; Mulder, Christian; Römbke, Jörg; Rutgers, Michiel; Sousa, J Paulo; Stone, Dorothy; Griffiths, Bryan S

    2013-04-01

    A large number of biological indicators have been proposed over the years for assessing soil quality. Although many of those have been applied in monitoring schemes across Europe, no consensus exists on the extent to which these indicators might perform best and how monitoring schemes can be further optimized in terms of scientific and policy relevance. Over the past decade, developments in environmental monitoring and risk assessment converged toward the use of indicators and endpoints that are related to soil functioning and ecosystem services. In view of the proposed European Union (EU) Soil Framework Directive, there is an urgent need to identify and evaluate indicators for soil biodiversity and ecosystem services. The recently started integrated project, Ecological Function and Biodiversity Indicators in European Soils (EcoFINDERS), aims to address this specific issue within the EU Framework Program FP7. Here, we 1) discuss how to use the concept of ecosystem services in soil monitoring, 2) review former and ongoing monitoring schemes, and 3) present an analysis of metadata on biological indicators in some EU member states. Finally, we discuss our experiences in establishing a logical sieve approach to devise a monitoring scheme for a standardized and harmonized application at European scale.

  11. Culturally relevant inquiry-based laboratory module implementations in upper-division genetics and cell biology teaching laboratories.

    Science.gov (United States)

    Siritunga, Dimuth; Montero-Rojas, María; Carrero, Katherine; Toro, Gladys; Vélez, Ana; Carrero-Martínez, Franklin A

    2011-01-01

    Today, more minority students are entering undergraduate programs than ever before, but they earn only 6% of all science or engineering PhDs awarded in the United States. Many studies suggest that hands-on research activities enhance students' interest in pursuing a research career. In this paper, we present a model for the implementation of laboratory research in the undergraduate teaching laboratory using a culturally relevant approach to engage students. Laboratory modules were implemented in upper-division genetics and cell biology courses using cassava as the central theme. Students were asked to bring cassava samples from their respective towns, which allowed them to compare their field-collected samples against known lineages from agricultural stations at the end of the implementation. Assessment of content and learning perceptions revealed that our novel approach allowed students to learn while engaged in characterizing Puerto Rican cassava. In two semesters, based on the percentage of students who answered correctly in the premodule assessment for content knowledge, there was an overall improvement of 66% and 55% at the end in the genetics course and 24% and 15% in the cell biology course. Our proposed pedagogical model enhances students' professional competitiveness by providing students with valuable research skills as they work on a problem to which they can relate.

  12. Brain processing of biologically relevant odors in the awake rat, as revealed by manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Benoist Lehallier

    Full Text Available BACKGROUND: So far, an overall view of olfactory structures activated by natural biologically relevant odors in the awake rat is not available. Manganese-enhanced MRI (MEMRI is appropriate for this purpose. While MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages. METHODOLOGY/PRINCIPAL FINDINGS: Odors of male fox feces and of chocolate flavored cereals were used to stimulate conscious rats previously treated by intranasal instillation of manganese (Mn. MEMRI activation maps showed Mn enhancement all along the primary olfactory cortex. Mn enhancement elicited by male fox feces odor and to a lesser extent that elicited by chocolate odor, differed from that elicited by deodorized air. This result was partly confirmed by c-Fos immunohistochemistry in the piriform cortex. CONCLUSION/SIGNIFICANCE: By providing an overall image of brain structures activated in awake rats by odorous stimulation, and by showing that Mn enhancement is differently sensitive to different stimulating odors, the present results demonstrate the interest of MEMRI for functional studies of olfaction in the primary olfactory cortex of laboratory small animals, under conditions close to natural perception. Finally, the factors that may cause the variability of the MEMRI signal in response to different odor are discussed.

  13. Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure.

    Science.gov (United States)

    Korashy, Hesham M; Attafi, Ibraheem M; Famulski, Konrad S; Bakheet, Saleh A; Hafez, Mohammed M; Alsaad, Abdulaziz M S; Al-Ghadeer, Abdul Rahman M

    2017-02-01

    Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these

  14. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca; Yauk, Carole L., E-mail: Carole.Yauk@hc-sc.gc.ca; White, Paul A., E-mail: Paul.White@hc-sc.gc.ca; Halappanavar, Sabina, E-mail: Sabina.Halappanavar@hc-sc.gc.ca

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I

  15. Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: relevance to human cancer risk.

    Science.gov (United States)

    Labib, Sarah; Guo, Charles H; Williams, Andrew; Yauk, Carole L; White, Paul A; Halappanavar, Sabina

    2013-12-01

    Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50, and 75 mgBaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans.

  16. Biological Effects of Clinically Relevant CoCr Nanoparticles in the Dura Mater: An Organ Culture Study

    Directory of Open Access Journals (Sweden)

    Iraklis Papageorgiou

    2014-06-01

    Full Text Available Medical interventions for the treatment of spinal disc degeneration include total disc replacement and fusion devices. There are, however, concerns regarding the generation of wear particles by these devices, the majority of which are in the nanometre sized range with the potential to cause adverse biological effects in the surrounding tissues. The aims of this study were to develop an organ culture model of the porcine dura mater and to investigate the biological effects of CoCr nanoparticles in this model. A range of histological techniques were used to analyse the structure of the tissue in the organ culture. The biological effects of the CoCr wear particles and the subsequent structural changes were assessed using tissue viability assays, cytokine assays, histology, immunohistochemistry, and TEM imaging. The physiological structure of the dura mater remained unchanged during the seven days of in vitro culture. There was no significant loss of cell viability. After exposure of the organ culture to CoCr nanoparticles, there was significant loosening of the epithelial layer, as well as the underlying collagen matrix. TEM imaging confirmed these structural alterations. These structural alterations were attributed to the production of MMP-1, -3, -9, -13, and TIMP-1. ELISA analysis revealed that there was significant release of cytokines including IL-8, IL-6, TNF-α, ECP and also the matrix protein, tenascin-C. This study suggested that CoCr nanoparticles did not cause cytotoxicity in the dura mater but they caused significant alterations to its structural integrity that could lead to significant secondary effects due to nanoparticle penetration, such as inflammation to the local neural tissue.

  17. Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

    Science.gov (United States)

    Kim, Myung-Hee Y.; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2014-01-01

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

  18. Climate change and occupational allergies: an overview on biological pollution, exposure and prevention.

    Science.gov (United States)

    D'Ovidio, Maria Concetta; Annesi-Maesano, Isabella; D'Amato, Gennaro; Cecchi, Lorenzo

    2016-01-01

    Climate change, air pollution, temperature increase and other environmental variables are modifying air quality, contributing to the increase of prevalence of allergic respiratory diseases. Allergies are complex diseases characterized by multilevel interactions between individual susceptibility, response to immune modulation and environmental exposures to physical, chemical and biological agents. Occupational allergies introduce a further complexity to these relationships by adding occupational exposure to both the indoor and outdoor ones in the living environment. The aim of this paper is to overview climate-related allergy affecting environmental and occupational health, as literature data are scanty in this regard, and to suggest a management model of this risk based on a multidisciplinary approach, taking the case of biological pollution, with details on exposure and prevention. The management of climate-related occupational allergy should take into account preventive health strategies, environmental, public and occupational interventions, as well as to develop, implement, evaluate, and improve guidelines and standards protecting workers health under changing climatic conditions; new tools and strategies based on local conditions will have to be developed. Experimental studies and acquisition of environmental and personal data have to be matched to derive useful information for the scope of occupational health and safety.

  19. The Role of Molecular Biology in the Biomonitoring of Human Exposure to Chemicals

    Directory of Open Access Journals (Sweden)

    Balam Muñoz

    2010-11-01

    Full Text Available Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies. Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk. However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk. Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics. In this review, we discuss the role of the following common techniques: (1 Use of cell cultures; (2 evaluation of gene expression; (3 the “omic” sciences (genomics, transcriptomics, proteomics and metabolomics and (4 bioinformatics. We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions.

  20. The role of molecular biology in the biomonitoring of human exposure to chemicals.

    Science.gov (United States)

    Muñoz, Balam; Albores, Arnulfo

    2010-11-12

    Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies. Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk. However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk. Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics. In this review, we discuss the role of the following common techniques: (1) Use of cell cultures; (2) evaluation of gene expression; (3) the "omic" sciences (genomics, transcriptomics, proteomics and metabolomics) and (4) bioinformatics. We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions.

  1. The Role of Molecular Biology in the Biomonitoring of Human Exposure to Chemicals

    Science.gov (United States)

    Muñoz, Balam; Albores, Arnulfo

    2010-01-01

    Exposure to different substances in an occupational environment is of utmost concern to global agencies such as the World Health Organization and the International Labour Organization. Interest in improving work health conditions, particularly of those employees exposed to noxious chemicals, has increased considerably and has stimulated the search for new, more specific and selective tests. Recently, the field of molecular biology has been indicated as an alternative technique for monitoring personnel while evaluating work-related pathologies. Originally, occupational exposure to environmental toxicants was assessed using biochemical techniques to determine the presence of higher concentrations of toxic compounds in blood, urine, or other fluids or tissues; results were used to evaluate potential health risk. However, this approach only estimates the presence of a noxious chemical and its effects, but does not prevent or diminish the risk. Molecular biology methods have become very useful in occupational medicine to provide more accurate and opportune diagnostics. In this review, we discuss the role of the following common techniques: (1) Use of cell cultures; (2) evaluation of gene expression; (3) the “omic” sciences (genomics, transcriptomics, proteomics and metabolomics) and (4) bioinformatics. We suggest that molecular biology has many applications in occupational health where the data can be applied to general environmental conditions. PMID:21151453

  2. Biological monitoring and questionnaire for assessing exposure to ethylenebisdithiocarbamates in a multicenter European field study.

    Science.gov (United States)

    Fustinoni, S; Campo, L; Liesivuori, J; Pennanen, S; Vergieva, T; van Amelsvoort, Lgpm; Bosetti, C; Van Loveren, H; Colosio, C

    2008-09-01

    This study deals with pesticide exposure profile in some European countries with a specific focus on ethylenebisdithiocarbamates (EBDC). In all, 55 Bulgarian greenhouse workers, 51 Finnish potato farmers, 48 Italian vineyard workers, 42 Dutch floriculture farmers, and 52 Bulgarian zineb producers entered the study. Each group was matched with a group of not occupationally exposed subjects. Exposure data were gained through self-administered questionnaires and measuring ethylenethiourea (ETU) in two spot urine samples collected, respectively, before the beginning of seasonal exposure (T0), and after 30 days, at the end of the exposure period (T30). Controls underwent a similar protocol. Study agriculture workers were involved in mixing and loading pesticides, application of pesticide mixture with mechanical or manual equipments, re-entry activities, and cleaning equipments. Chemical workers were involved in synthesis, quality controls, and packing activities. The number of pesticides to whom these subjects were exposed varied from one (zineb production) to eight (potato farmers). The use of personal protective devices was variegate and regarded both aerial and dermal penetration routes. EBDC exposure, assessed by T30 urinary ETU, was found to follow the order: greenhouse workers, zineb producers, vineyard workers, potato farmers, floriculture farmers with median levels of 49.6, 23.0, 11.8, 7.5, and 0.9 microg/g creatinine; the last group having ETU at the same level of controls (approximately 0.5 microg/g creatinine). Among agriculture workers, pesticide application, especially using manual equipment, seems to be the major determinant in explaining internal dose. Although the analysis of self-administered questionnaires evidenced difficulties especially related to lack and/or poor quality of reported data, biological monitoring confirms to be a powerful tool in assessing pesticide exposure.

  3. Structural, Chemical and Biological Aspects of Antioxidants for Strategies Against Metal and Metalloid Exposure

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    Swaran J. S. Flora

    2009-01-01

    Full Text Available Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and many others. Human studies are limited in this regard. Under certain conditions, surprisingly, the antioxidant supplements may exhibit pro-oxidant properties and even worsen metal induced toxic damage. To date, the evidence is insufficient to recommend antioxidant supplements in subject with exposure to metals. Prospective, controlled clinical trials on safety and effectiveness of different therapeutic antioxidant strategies either individually or in combination with chelating agent are indispensable. The present review focuses on structural, chemical and biological aspects of antioxidants particularly related to their chelating properties.

  4. Alkali Metal Ion Complexes with Phosphates, Nucleotides, Amino Acids, and Related Ligands of Biological Relevance. Their Properties in Solution.

    Science.gov (United States)

    Crea, Francesco; De Stefano, Concetta; Foti, Claudia; Lando, Gabriele; Milea, Demetrio; Sammartano, Silvio

    2016-01-01

    Alkali metal ions play very important roles in all biological systems, some of them are essential for life. Their concentration depends on several physiological factors and is very variable. For example, sodium concentrations in human fluids vary from quite low (e.g., 8.2 mmol dm(-3) in mature maternal milk) to high values (0.14 mol dm(-3) in blood plasma). While many data on the concentration of Na(+) and K(+) in various fluids are available, the information on other alkali metal cations is scarce. Since many vital functions depend on the network of interactions occurring in various biofluids, this chapter reviews their complex formation with phosphates, nucleotides, amino acids, and related ligands of biological relevance. Literature data on this topic are quite rare if compared to other cations. Generally, the stability of alkali metal ion complexes of organic and inorganic ligands is rather low (usually log K  Na(+) > K(+) > Rb(+) > Cs(+). For example, for citrate it is: log K ML = 0.88, 0.80, 0.48, 0.38, and 0.13 at 25 °C and infinite dilution. Some considerations are made on the main aspects related to the difficulties in the determination of weak complexes. The importance of the alkali metal ion complexes was also studied in the light of modelling natural fluids and in the use of these cations as probes for different processes. Some empirical relationships are proposed for the dependence of the stability constants of Na(+) complexes on the ligand charge, as well as for correlations among log K values of NaL, KL or LiL species (L = generic ligand).

  5. Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

    Science.gov (United States)

    Monopoli, Marco P; Walczyk, Dorota; Campbell, Abigail; Elia, Giuliano; Lynch, Iseult; Bombelli, Francesca Baldelli; Dawson, Kenneth A

    2011-03-02

    It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.

  6. Biological effects of exposure to static electric fields in humans and vertebrates: a systematic review.

    Science.gov (United States)

    Petri, Anne-Kathrin; Schmiedchen, Kristina; Stunder, Dominik; Dechent, Dagmar; Kraus, Thomas; Bailey, William H; Driessen, Sarah

    2017-04-17

    High-voltage direct current (HVDC) lines are the technology of choice for the transport of large amounts of energy over long distances. The operation of these lines produces static electric fields (EF), but the data reviewed in previous assessments were not sufficient to assess the need for any environmental limit. The aim of this systematic review was to update the current state of research and to evaluate biological effects of static EF. Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) recommendations, we collected and evaluated experimental and epidemiological studies examining biological effects of exposure to static EF in humans (n = 8) and vertebrates (n = 40). There is good evidence that humans and animals are able to perceive the presence of static EF at sufficiently high levels. Hair movements caused by electrostatic forces may play a major role in this perception. A large number of studies reported responses of animals (e.g., altered metabolic, immunologic or developmental parameters) to a broad range of static EF strengths as well, but these responses are likely secondary physiological responses to sensory stimulation. Furthermore, the quality of many of the studies reporting physiological responses is poor, which raises concerns about confounding. The weight of the evidence from the literature reviewed did not indicate that static EF have adverse biological effects in humans or animals. The evidence strongly supported the role of superficial sensory stimulation of hair and skin as the basis for perception of the field, as well as reported indirect behavioral and physiological responses. Physical considerations also preclude any direct effect of static EF on internal physiology, and reports that some physiological processes are affected in minor ways may be explained by other factors. While this literature does not support a level of concern about biological effects of exposure to static EF, the conditions

  7. Fractal structures of single-walled carbon nanotubes in biologically relevant conditions: role of chirality vs. media conditions.

    Science.gov (United States)

    Khan, Iftheker A; Aich, Nirupam; Afrooz, A R M Nabiul; Flora, Joseph R V; Schierz, P Ariette; Ferguson, P Lee; Sabo-Attwood, Tara; Saleh, Navid B

    2013-11-01

    Aggregate structure of covalently functionalized chiral specific semiconducting single-walled carbon nanotubes (SWNTs) was systematically studied employing static light scattering (SLS). Fractal dimensions (Df) of two specific chirality SWNTs-SG65 and SG76 with (6, 5) and (7, 6) chiral enrichments-were measured under four biological exposure media conditions, namely: Dulbecco's Modified Eagle Medium (DMEM), Minimum Essential Medium (MEM), Roswell Park Memorial Institute (RPMI) 1640 medium, and 0.9% saline solution. The SWNTs exhibited chiral dependence on Df with SG65 showing more fractal or loosely bound aggregate structures, i.e., lower Df values (range of 2.24±0.03 to 2.64±0.05), compared to the SG76 sample (range of 2.58±0.13 to 2.90±0.08). All the Df values reported are highly reproducible, measured from multiple SLS runs and estimated with 'random block-effects' statistical analysis that yielded all p values to be fractal aggregates. Moreover, presence of fetal bovine serum (FBS) and bovine serum albumin (BSA), used to mimic the in vitro cell culture condition, reduced the Df values, i.e., created more fractal structures. Steric hindrance to aggregation was identified as the key mechanism for creating the fractal structures. Also, increase in FBS concentration from 1% to 10% resulted in increasingly lower Df values.

  8. Biologically relevant chemical space navigator: from patent and structure-activity relationship analysis to library acquisition and design.

    Science.gov (United States)

    Rabal, Obdulia; Oyarzabal, Julen

    2012-12-21

    A new and versatile visualization tool, based on a descriptor accounting for ligand-receptor interactions (LiRIf), is introduced for guiding medicinal chemists in analyzing the R-groups from a congeneric series. Analysis is performed in a reference-independent scenario where the whole biologically relevant chemical space (BRCS) is represented. Using a real project-based data set, we show the impact of this tool on four key navigation strategies for the drug discovery process. First, this navigator analyzes competitors' patents, including a comparison of patents coverage and the identification of the most frequent fragments. Second, the tool analyzes the structure-activity relationship (SAR) leading to the representation of reference-independent activity landscapes that enable the identification not only of critical ligand-receptor interactions (LRI) and substructural features but also of activity cliffs. Third, this navigator enables comparison of libraries, thus selecting commercially available molecules that complement unexplored spaces or areas of interest. Finally, this tool also enables the design of new analogues, which is based on reaction types and the exploration purpose (focused or diverse), selecting the most appropriate reagents.

  9. Anthropogenic climate change and allergen exposure: The role of plant biology.

    Science.gov (United States)

    Ziska, Lewis H; Beggs, Paul J

    2012-01-01

    Accumulation of anthropogenic gases, particularly CO(2), is likely to have 2 fundamental effects on plant biology. The first is an indirect effect through Earth's increasing average surface temperatures, with subsequent effects on other aspects of climate, such as rainfall and extreme weather events. The second is a direct effect caused by CO(2)-induced stimulation of photosynthesis and plant growth. Both effects are likely to alter a number of fundamental aspects of plant biology and human health, including aerobiology and allergic diseases, respectively. This review highlights the current and projected effect of increasing CO(2) and climate change in the context of plants and allergen exposure, emphasizing direct effects on plant physiologic parameters (eg, pollen production) and indirect effects (eg, fungal sporulation) related to diverse biotic and abiotic interactions. Overall, the review assumes that future global mitigation efforts will be limited and suggests a number of key research areas that will assist in adapting to the ongoing challenges to public health associated with increased allergen exposure.

  10. Adverse biological effects of Milan urban PM looking for suitable molecular markers of exposure

    Directory of Open Access Journals (Sweden)

    Mantecca Paride

    2012-01-01

    Full Text Available The results presented summarise the ones obtained in the coordinated research project Tosca, which extensively analysed the impact of Milan urban PM on human health. The molecular markers of exposure and effects of seasonally and size-fractionated PMs (summer and winter PM10, PM2.5 were investigated in in vitro (human lung cell lines and in vivo (mice systems. The results obtained by the analyses of cytotoxic, pro-inflammatory and genotoxic parameters demonstrate that the biological responses are strongly dependent upon the PM samples seasonal and dimensional variability, that ultimately reflect their chemical composition and source. In fact summer PM10, enriched in crustal elements and endotoxins, was the most cytotoxic and pro-inflammatory fraction, while fine winter PMs induced genotoxic effects and xenobiotic metabolizing enzymes (like CYP1B1 production, likely as a consequence of the higher content in combustion derived particles reach in PAHs and heavy toxic metals. These outcomes outline the need of a detailed knowledge of the PMs physico-chemical composition on a local scale, coupled with the biological hazard directly associated to PM exposure. Apparently this is the only way allowing scientists and police-makers to establish the proper relationships between the respirable PM quantity/quality and the health outcomes described by clinicians and epidemiologists.

  11. Systematic review of biological effects of exposure to static electric fields. Part II: Invertebrates and plants.

    Science.gov (United States)

    Schmiedchen, Kristina; Petri, Anne-Kathrin; Driessen, Sarah; Bailey, William H

    2017-09-27

    The construction of high-voltage direct current (HVDC) lines for the long-distance transport of energy is becoming increasingly popular. This has raised public concern about potential environmental impacts of the static electric fields (EF) produced under and near HVDC power lines. As the second part of a comprehensive literature analysis, the aim of this systematic review was to assess the effects of static EF exposure on biological functions in invertebrates and plants and to provide the basis for an environmental impact assessment of such exposures. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used to guide the methodological conduct and reporting. Thirty-three studies - 14 invertebrate and 19 plant studies - met the eligibility criteria and were included in this review. The reported behavioral responses of insects and planarians upon exposure strongly suggest that invertebrates are able to perceive the presence of a static EF. Many other studies reported effects on physiological functions that were expressed as, for example, altered metabolic activity or delayed reproductive and developmental stages in invertebrates. In plants, leaf damage, alterations in germination rates, growth and yield, or variations in the concentration of essential elements, for example, have been reported. However, these physiological responses and changes in plant morphology appear to be secondary to surface stimulation by the static EF or caused by concomitant parameters of the electrostatic environment. Furthermore, all of the included studies suffered from methodological flaws, which lowered credibility in the results. At field levels encountered from natural sources or HVDC lines (effects of static EF on other biological functions in invertebrates and plants. At far higher field levels (> 35kV/m), adverse effects on physiology and morphology, presumably caused by corona-action, appear to be more likely. Higher quality studies are needed to

  12. Occupational exposure to contaminated biological material: perceptions and feelings experienced among dental students

    Directory of Open Access Journals (Sweden)

    Camila PINELLI

    Full Text Available INTRODUCTION: Dental students may be a particularly vulnerable group exposed to the risk of acquiring infections through occupational injuries.OBJECTIVE: To investigate the perceptions with regard to their occupational exposure to potentially infectious biologic materials.MATERIAL AND METHOD: Interviews were conducted by means of a script with open questions. The speeches were recorded, transcribed and qualitative analysis was performed with the aid of QUALIQUANTISOFT® software. The Collective Subject Discourse (CSD was obtained.RESULT: The feeling most frequently experienced was related to the fear of contagion. Most accidents occurred during the handling of sharp dental instruments. Respondents attributed the occurrence of accidents especially the lack of attention, carelessness while handling sharp instruments, and lack of use of Personal Protective Equipment. As regards the measures taken right after the exposure, they "washed the local area". Other respondents reported they "continued the dental treatment". They complained mostly about the fear of having been infected, and because they had to leave the faculty to take blood exams for HIV screening. As part of the learning experience the injured reported they paid more attention when handling sharp instruments. The students informed that any type of injury due to contact with contaminated material must be notified. However, they were neglectful about reporting their own injury.CONCLUSION: Education strategies for preventive measures related to occupational exposure must be restructured, because the knowledge and the fear of contagion among dental students were not always sufficient for a complete adherence to treatment protocols and notification.

  13. Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

    Science.gov (United States)

    Kim, Myung-Hee Y.; Wu, Honglu; Hada, Megumi; Cucinotta, Francis

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET g or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ‘‘biological Bragg curve’’ is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called “overkill”. F. A. Cucinotta, I. Plante, A. L. Ponomarev, and M. Y. Kim, Nuclear Interactions in Heavy Ion Transport and Event

  14. Comparative Analysis of Whole-Genome Gene Expression Changes in Cultured Human Embryonic Stem Cells in Response to Low, Clinical Diagnostic Relevant, and High Doses of Ionizing Radiation Exposure

    Science.gov (United States)

    Sokolov, Mykyta; Nguyen, Van; Neumann, Ronald

    2015-01-01

    The biological effects of low-dose ionizing radiation (LDIR) exposure in humans are not comprehensively understood, generating a high degree of controversy in published literature. The earliest stages of human development are known to be among the most sensitive to stress exposures, especially genotoxic stresses. However, the risks stemming from exposure to LDIR, particularly within the clinical diagnostic relevant dose range, have not been directly evaluated in human embryonic stem cells (hESCs). Here, we describe the dynamics of the whole genome transcriptional responses of different hESC lines to both LDIR and, as a reference, high-dose IR (HDIR). We found that even doses as low as 0.05 Gy could trigger statistically significant transient changes in a rather limited subset of genes in all hESCs lines examined. Gene expression signatures of hESCs exposed to IR appear to be highly dose-, time-, and cell line-dependent. We identified 50 genes constituting consensus gene expression signature as an early response to HDIR across all lines of hESC examined. We observed substantial differences in biological pathways affected by either LDIR or HDIR in hESCs, suggesting that the molecular mechanisms underpinning the responses of hESC may fundamentally differ depending on radiation doses. PMID:26133243

  15. Clinicopathological variables of sporadic schwannomas of peripheral nerve in 291 patients and expression of biologically relevant markers.

    Science.gov (United States)

    Young, Eric D; Ingram, Davis; Metcalf-Doetsch, William; Khan, Dilshad; Al Sannaa, Ghadah; Le Loarer, Francois; Lazar, Alexander J F; Slopis, John; Torres, Keila E; Lev, Dina; Pollock, Raphael E; McCutcheon, Ian E

    2017-09-08

    OBJECTIVE While sporadic peripheral schwannomas (SPSs) are generally well treated with surgery, their biology is not well understood. Consequently, treatment options are limited. The aim of this study was to provide a comprehensive description of SPS. The authors describe clinicopathological features and treatment outcomes of patients harboring these tumors, and they assess expression of biomarkers using a clinically annotated tissue microarray. Together, these data give new insight into the biology and management of SPS. METHODS Patients presenting with a primary SPS between 1993 and 2011 (n = 291) were selected from an institutional registry to construct a clinical database. All patients underwent follow-up, and short- and long-term outcomes were assessed. Expression of relevant biomarkers was assessed using a new tissue microarray (n = 121). RESULTS SPSs were generally large (mean 5.5 cm) and frequently painful at presentation (55%). Most patients were treated with surgery (80%), the majority of whom experienced complete resolution (52%) or improvement (18%) of their symptoms. Tumors that were completely resected (85%) did not recur. Some patients experienced short-term (16%) and long-term (4%) complications postoperatively. Schwannomas expressed higher levels of platelet-derived growth factor receptor-β (2.1) than malignant peripheral nerve sheath tumors (MPNSTs) (1.5, p = 0.004) and neurofibromas (1.33, p = 0.007). Expression of human epidural growth factor receptor-2 was greater in SPSs (0.91) than in MPNSTs (0.33, p = 0.002) and neurofibromas (0.33, p = 0.026). Epidural growth factor receptor was expressed in far fewer SPS cells (10%) than in MPNSTs (58%, p SPSs more frequently expressed cytoplasmic survivin (66% of tumor cells) than normal nerve (46% of cells), but SPS expressed nuclear survivin in fewer tumor cells than in MPNSTs (24% and 50%, respectively; p = 0.018). CONCLUSIONS Complete resection is curative for SPS. Left untreated, however, these

  16. Electronic noses for monitoring benzene occupational exposure in biological samples of Egyptian workers

    Directory of Open Access Journals (Sweden)

    Ehab I. Mohamed

    2013-02-01

    Full Text Available Objectives: Benzene is commonly emitted in several industries, leading to widespread environmental and occupational exposure hazards. While less toxic solvents have been substituted for benzene, it is still a component of petroleum products and is a trace impurity in industrial products resulting in continued higher occupational exposures in industrial settings in developing countries. Materials and Methods: We investigated the potential use of an electronic nose (e-nose to monitor the headspace volatiles in biological samples from benzene-exposed Egyptian workers and non-exposed controls. The study population comprised 150 non-smoking male workers exposed to benzene and an equal number of matching non-exposed controls. We determined biomarkers of benzene used to estimate exposure and risk including: benzene in exhaled air and blood; and its urinary metabolites such as phenol and muconic acid using gas chromatography technique and a portable e-nose. Results: The average benzene concentration measured in the ambient air of the workplace of all studied industrial settings in Alexandria, Egypt; was 97.56±88.12 μg/m3 (range: 4.69–260.86 μg/m3. Levels of phenol and muconic acid were signifi cantly (p < 0.001 higher in both blood and urine of benzene-exposed workers as compared to non-exposed controls. Conclusions: The e-nose technology has successfully classifi ed and distinguished benzene-exposed workers from non-exposed controls for all measured samples of blood, urine and the exhaled air with a very high degree of precision. Thus, it will be a very useful tool for the low-cost mass screening and early detection of health hazards associated with the exposure to benzene in the industry.

  17. Tyrosyl radicals in dehaloperoxidase: how nature deals with evolving an oxygen-binding globin to a biologically relevant peroxidase.

    Science.gov (United States)

    Dumarieh, Rania; D'Antonio, Jennifer; Deliz-Liang, Alexandria; Smirnova, Tatyana; Svistunenko, Dimitri A; Ghiladi, Reza A

    2013-11-15

    Dehaloperoxidase (DHP) from Amphitrite ornata, having been shown to catalyze the hydrogen peroxide-dependent oxidation of trihalophenols to dihaloquinones, is the first oxygen binding globin that possesses a biologically relevant peroxidase activity. The catalytically competent species in DHP appears to be Compound ES, a reactive intermediate that contains both a ferryl heme and a tyrosyl radical. By simulating the EPR spectra of DHP activated by H2O2, Thompson et al. (Thompson, M. K., Franzen, S., Ghiladi, R. A., Reeder, B. J., and Svistunenko, D. A. (2010) J. Am. Chem. Soc. 132, 17501-17510) proposed that two different radicals, depending on the pH, are formed, one located on either Tyr-34 or Tyr-28 and the other on Tyr-38. To provide additional support for these simulation-based assignments and to deduce the role(s) that tyrosyl radicals play in DHP, stopped-flow UV-visible and rapid-freeze-quench EPR spectroscopic methods were employed to study radical formation in DHP when three tyrosine residues, Tyr-28, Tyr-34, and Tyr-38, were replaced either individually or in combination with phenylalanines. The results indicate that radicals form on all three tyrosines in DHP. Evidence for the formation of DHP Compound I in several tyrosine mutants was obtained. Variants that formed Compound I showed an increase in the catalytic rate for substrate oxidation but also an increase in heme bleaching, suggesting that the tyrosines are necessary for protecting the enzyme from oxidizing itself. This protective role of tyrosines is likely an evolutionary adaptation allowing DHP to avoid self-inflicted damage in the oxidative environment.

  18. Predicting Subtype Selectivity for Adenosine Receptor Ligands with Three-Dimensional Biologically Relevant Spectrum (BRS-3D)

    Science.gov (United States)

    He, Song-Bing; Ben Hu; Kuang, Zheng-Kun; Wang, Dong; Kong, De-Xin

    2016-11-01

    Adenosine receptors (ARs) are potential therapeutic targets for Parkinson’s disease, diabetes, pain, stroke and cancers. Prediction of subtype selectivity is therefore important from both therapeutic and mechanistic perspectives. In this paper, we introduced a shape similarity profile as molecular descriptor, namely three-dimensional biologically relevant spectrum (BRS-3D), for AR selectivity prediction. Pairwise regression and discrimination models were built with the support vector machine methods. The average determination coefficient (r2) of the regression models was 0.664 (for test sets). The 2B-3 (A2B vs A3) model performed best with q2 = 0.769 for training sets (10-fold cross-validation), and r2 = 0.766, RMSE = 0.828 for test sets. The models’ robustness and stability were validated with 100 times resampling and 500 times Y-randomization. We compared the performance of BRS-3D with 3D descriptors calculated by MOE. BRS-3D performed as good as, or better than, MOE 3D descriptors. The performances of the discrimination models were also encouraging, with average accuracy (ACC) 0.912 and MCC 0.792 (test set). The 2A-3 (A2A vs A3) selectivity discrimination model (ACC = 0.882 and MCC = 0.715 for test set) outperformed an earlier reported one (ACC = 0.784). These results demonstrated that, through multiple conformation encoding, BRS-3D can be used as an effective molecular descriptor for AR subtype selectivity prediction.

  19. Exposure factors for marine eutrophication impacts assessment based on a mechanistic biological model

    DEFF Research Database (Denmark)

    Cosme, Nuno Miguel Dias; Koski, Marja; Hauschild, Michael Zwicky

    2015-01-01

    Emissions of nitrogen (N) from anthropogenic sources enrich marine waters and promote planktonic growth. This newly synthesised organic carbon is eventually exported to benthic waters where aerobic respiration by heterotrophic bacteria results in the consumption of dissolved oxygen (DO...... routes from primary (cell aggregates) and secondary producers (faecal pellets, carcasses, and active vertical transport). Carbon export production (PE) and ecosystems eXposure Factors (XF), which represents a nitrogen-to-oxygen 'conversion' potential, were estimated at a spatial resolution of 66 large...... is essential to estimate a marine eutrophication impacts indicator in Life Cycle Impact Assessment (LCIA) of anthropogenic-N emissions. Every relevant process was modelled and the uncertainty of the driving parameters considered low suggesting valid applicability in characterisation modelling in LCIA....

  20. Design, Development, and Psychometric Analysis of a General, Organic, and Biological Chemistry Topic Inventory Based on the Identified Main Chemistry Topics Relevant to Nursing Clinical Practice

    Science.gov (United States)

    Brown, Corina E.

    2013-01-01

    This two-stage study focused on the undergraduate nursing course that covers topics in general, organic, and biological (GOB) chemistry. In the first stage, the central objective was to identify the main concepts of GOB chemistry relevant to the clinical practice of nursing. The collection of data was based on open-ended interviews of both nursing…

  1. Exposure pathways and biological receptors: baseline data for the canyon uranium mine, Coconino County, Arizona

    Science.gov (United States)

    Hinck, Jo E.; Linder, Greg L.; Darrah, Abigail J.; Drost, Charles A.; Duniway, Michael C.; Johnson, Matthew J.; Méndez-Harclerode, Francisca M.; Nowak, Erika M.; Valdez, Ernest W.; Van Riper, Charles; Wolff, S.W.

    2014-01-01

    Recent restrictions on uranium mining within the Grand Canyon watershed have drawn attention to scientific data gaps in evaluating the possible effects of ore extraction to human populations as well as wildlife communities in the area. Tissue contaminant concentrations, one of the most basic data requirements to determine exposure, are not available for biota from any historical or active uranium mines in the region. The Canyon Uranium Mine is under development, providing a unique opportunity to characterize concentrations of uranium and other trace elements, as well as radiation levels in biota, found in the vicinity of the mine before ore extraction begins. Our study objectives were to identify contaminants of potential concern and critical contaminant exposure pathways for ecological receptors; conduct biological surveys to understand the local food web and refine the list of target species (ecological receptors) for contaminant analysis; and collect target species for contaminant analysis prior to the initiation of active mining. Contaminants of potential concern were identified as arsenic, cadmium, chromium, copper, lead, mercury, nickel, selenium, thallium, uranium, and zinc for chemical toxicity and uranium and associated radionuclides for radiation. The conceptual exposure model identified ingestion, inhalation, absorption, and dietary transfer (bioaccumulation or bioconcentration) as critical contaminant exposure pathways. The biological survey of plants, invertebrates, amphibians, reptiles, birds, and small mammals is the first to document and provide ecological information on .200 species in and around the mine site; this study also provides critical baseline information about the local food web. Most of the species documented at the mine are common to ponderosa pine Pinus ponderosa and pinyon–juniper Pinus–Juniperus spp. forests in northern Arizona and are not considered to have special conservation status by state or federal agencies; exceptions

  2. Whack-A-Mole Model: Towards unified description of biological effect caused by radiation-exposure

    CERN Document Server

    Manabe, Yuichiro; Tsunoyama, Yuichi; Nakajima, Hiroo; Nakamura, Issei; Bando, Masako

    2014-01-01

    We present a novel model to estimate biological effects caused by artificial radiation exposure, Whack-a-mole (WAM) model. It is important to take account of the recovery effects during the time course of the cellular reactions. The inclusion of the dose-rate dependence is essential in the risk estimation of low dose radiation, while nearly all the existing theoretical models relies on the total dose dependence only. By analyzing the experimental data of the relation between the radiation dose and the induced mutation frequency of 5 organisms, mouse, drosophila, chrysanthemum, maize and tradescantia, we found that all the data can be reproduced by WAM model. Most remarkably, a scaling function, which is derived from WAM model, consistently accounts for the observed mutation frequencies of 5 organisms. This is the first rationale to account for the dose rate dependence as well as to give a unified understanding of a general feature of organisms.

  3. Whack-A-Mole Model: Towards a Unified Description of Biological Effects Caused by Radiation Exposure

    Science.gov (United States)

    Manabe, Yuichiro; Wada, Takahiro; Tsunoyama, Yuichi; Nakajima, Hiroo; Nakamura, Issei; Bando, Masako

    2015-04-01

    We present a novel model to for estimating biological effects caused by artificial radiation exposure, i.e., the Whack-A-Mole (WAM) model. It is important to take into account the recovery effects during the time course of cellular reactions. The inclusion of dose-rate dependence is essential in the risk estimation of low-dose radiation, while nearly all the existing theoretical models rely on the total dose dependence only. By analyzing experimental data of the relationship between the radiation dose and the induced mutation frequency of five organisms, namely, mouse, Drosophila, chrysanthemum, maize, Tradescantia, we found that all the data can be reproduced by the WAM model. Most remarkably, a scaling function, which is derived from the WAM model, consistently accounts for the observed mutation frequencies of the five organisms. This is the first rationale to account for the dose rate dependence as well as to provide a unified understanding of a general feature of organisms.

  4. MULTIVARIATE ANALYSIS OF RELATIONSHIPS BETWEEN IODINE BIOLOGICAL EXPOSURE AND SUBCLINICAL THYROID DYSFUNCTIONS

    Institute of Scientific and Technical Information of China (English)

    Wei Chong; Zhong-yan Shan; Wei Sun; Wei-ping Teng

    2005-01-01

    Objective To assess the relationships between iodine biological exposure and subclinical thyroid dysfunctions. Methods The cross-sectional survey was performed to obtain the epidemiologic data of population in three communities with different iodine biological exposure: mild iodine deficiency [median urinary iodine concentration (MUI) of 50 99g/L], more than adequate iodine intake (MUI of 200-299 μg/L), and excessive iodine intake (MUI over 300 μg/L). Univariate and multivariate analysis (logistic regression analysis) were used to analyze the risk factors of subclinical hypothyroidism and subclinical hyperthyroidism. Results Logistic regression analysis with sex and age controlled suggested that more than adequate iodine intake (OR = 3.172, P = 0.0004) and excessive iodine intake (OR = 6.391, P = 0.0001) increased the risk of subclinical hypothyroidism, while excessive iodine intake decreased the risk of subclinical hyperthyroidism (OR = 0.218, P= 0.0001). Logistic regression analysis including interaction of iodine intake and antibodies [tryroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)] suggested that excessive iodine intake was an independent risk factor of subclinical hypothyroidism (OR = 6.360, P = 0.0001), but independent protect factor of subclinical hyperthyroidism (OR = 0.193, P = 0.0001). More than adequate iodine intake and it's interaction with TgAb increased the risk of subclinical hypothyroidism independently, in addition, it decreased the risk of subclinical hyperthyroidism at the present of TPOAb. Conclusion Both excessive iodine intake and more than adequate iodine intake could increase risk of subclinical hypo thyroidism, supplement of iodine should be controlled to ensure MUI within the safe range.

  5. Synthesis of fluorophore encapsulated silica nanoparticles for the evaluation of the biological fate and toxicity of food relevant nanoparticles

    Science.gov (United States)

    Zane, Andrew Paul

    We show that commercially available TiO2, SiO2, and ZnO nanoparticles are all internalized by C2BBe1 intestinal epithelial cells, but do not appear to be toxic, even after long term repeat-exposures. When particles were exposed to a simulated digestion protocol mimicking the stomach and intestinal environment, TiO2 particles did show mild toxicity by MTT assay, indicating a decrease in metabolic activity. IR spectra of these particles indicate presence of material from the digestion media, and these absorbed species may be responsible for the effects noted. Though the three particles were not significantly toxic, we note internalization by the intestinal epithelial cells, opening a possibility for absorption into circulation where they may localize in organs throughout the body. This will be observed by functionalizing the particles with fluorophores, after which they can be measured via fluorescence. To optimize the quantum yield efficiency, and thus the brightness, of one such fluorophore, we seek to improve a microwave synthesis of CdSe/CdS/ZnS quantum dots our lab has previously reported. By coupling the microwave reactor to a fluorescence spectrometer via fiber optic cables, we were able to monitor the development of the particles throughout the microwave heating. Time-dependent fluorescence shows the development of an early fluorescence peak at 502 nm attributed to CdSe cores. We then note two isosbestic points which we attribute to the development of CdS layer around CdSe cores, and eventually the formation of outer ZnS shell. We utilize this in situ monitoring along with a study of various nucleation temperatures ranging from 0 to 100°C, and pre-and-post microwave heating UV exposure treatments to obtain optimized CdSe/CdS/ZnS particles with a QY of 40%. This is an improvement over our previous particles' 13% QY, and the highest yet reported for an aqueous synthesis of CdSe/ZnS type particles. Finally, we incorporate these QDs as well as two organic

  6. Allergy and asthma: Effects of the exposure to particulate matter and biological allergens.

    Science.gov (United States)

    Baldacci, S; Maio, S; Cerrai, S; Sarno, G; Baïz, N; Simoni, M; Annesi-Maesano, I; Viegi, G

    2015-09-01

    The prevalence of asthma and allergies including atopy has increased during the past decades, particularly in westernized countries. The rapid rise in the prevalence of such diseases cannot be explained by genetic factors alone. Rapid urbanization and industrialization throughout the world have increased air pollution and population exposures, so that most epidemiologic studies are focusing on possible links between air pollution and respiratory diseases. Furthermore, a growing body of evidence shows that chemical air pollution may interact with airborne allergens enhancing the risk of atopic sensitization and exacerbation of symptoms in sensitized subjects. These phenomena are supported by current in vitro and animal studies showing that the combined exposure to air pollutants and allergens may have a synergistic or additive effect on asthma and allergies, although there is an insufficient evidence about this link at the population level. Further research is needed in order to elucidate the mechanisms by which pollutants and biological allergens induce damage in exposed subjects. The abatement of the main risk factors for asthma and allergic diseases may achieve huge health benefits. Thus, it is important to raise awareness of respiratory allergies as serious chronic diseases which place a heavy burden on patients and on society as a whole.

  7. Quantitative measurement of porphyrins in biological tissues and evaluation of tissue porphyrins during toxicant exposures.

    Science.gov (United States)

    Woods, J S; Miller, H D

    1993-10-01

    Porphyrins are formed in most eukaryotic tissues as intermediates in the biosynthesis of heme. Assessment of changes in tissue porphyrin levels occurring in response to the actions of various drugs or toxicants is potentially useful in the evaluation of chemical exposures and effects. The present paper describes a rapid and sensitive method for the extraction and quantitation of porphyrins in biological tissues which overcomes difficulties encountered in previously described methods, particularly the loss of porphyrins during extraction and interference of porphyrin quantitation by coeluting fluorescent tissue constituents. In this procedure 8- through 2-carboxyl porphyrins are quantitatively extracted from tissue homogenates using HCl and methanol and are subsequently separated from potentially interfering contaminants by sequential methanol/phosphate elution on a C-18 preparatory column. Porphyrins are then separated and measured by reversed-phase high-performance liquid chromatography and spectrofluorometric techniques. Recovery of tissue porphyrins using this method is close to 100% with an intraassay variability of less than 10%. We have employed this procedure to measure liver and kidney porphyrin concentrations in male Fischer rats and to define the distinctive changes in tissue porphyrin patterns associated with treatment with the hepatic and renal porphyrinogenic chemicals, allylisopropylacetamide, and methyl mercury hydroxide, respectively. This method is applicable to the measurement of tissue porphyrin changes resulting from drug or toxicant exposures in clinical, experimental or environmental assessments.

  8. BIOLOGICAL AND HEALTH EFFECTS OF EXPOSURE TO ELECTROMAGNETIC FIELD FROM MOBILE COMMUNICATIONS SYSTEMS

    Directory of Open Access Journals (Sweden)

    Masao TAKI

    2001-01-01

    Full Text Available Mobile communication devices are sources of radiofrequency (RF electromagnetic field (EMF that are common in daily life and can cause strong exposure to the head. Possible adverse health effects, especially on brain functions, have been of great concern among the general public since the explosive penetration of this technology began in the 1990's. The exposure complies with current safety guidelines. The established knowledge of biological effects of RF does not provide any evidence for anecdotally reported effects such as memory loss or causing brain tumors. However, there is no way to prove the absolute absence of such effects. The enormous efforts have been made to search for such unknown effects and ascertain the safety of this technology. Recent research on the possible effects of RF-EMF on the brain is briefly summarized here to show what is known and what remains unknown. The evidence reported so far indicates few effects that could possibly damage human health seriously. Only slight changes in physiological function in the brain may exist, but variation of the data is too great to believe that the exposure actually has the potential to affect function. The health risk, if any, at an individual level, would be very low in consideration of the available evidence. However, if mobile phone fields were actually hazardous, the very large number of mobile phone users could mean that, even if the individual risk were very low, the impact on public health could be considerable. This is the most important reason why so many efforts are being made in this issue.

  9. Use of portable microbial samplers for estimating inhalation exposure to viable biological agents.

    Science.gov (United States)

    Yao, Maosheng; Mainelis, Gediminas

    2007-01-01

    Portable microbial samplers are being increasingly used to determine the presence of microbial agents in the air; however, their performance characteristics when sampling airborne biological agents are largely unknown. In addition, it is unknown whether these samplers could be used to assess microbial inhalation exposure according to the particle sampling conventions. This research analyzed collection efficiencies of MAS-100, Microflow, SMA MicroPortable, Millipore Air Tester, SAS Super 180, BioCulture, and RCS High Flow portable microbial samplers when sampling six bacterial and fungal species ranging from 0.61 to 3.14 microm in aerodynamic diameter. The efficiencies with which airborne microorganisms were deposited on samplers' collection medium were compared to the particle inhalation and lung deposition convention curves. When sampling fungi, RCS High Flow and SAS Super 180 deposited 80%-90% of airborne spores on agar - highest among investigated samplers. Other samplers showed collection efficiencies of 10%-60%. When collecting bacteria, RCS High Flow and MAS-100 collected 20%-30%, whereas other samplers collected less than 10% of these bioparticles. Comparison of samplers' collection efficiencies with particle inhalation convention curves showed that RCS High Flow and SAS Super 180 could be used to assess inhalation exposure to particles larger than 2.5 microm, such as fungal spores. Performance of RCS High Flow sampler was also reflective of the particle lung deposition pattern when sampling both bacteria and fungi. MAS-100 and SAS Super 180 matched the total deposition curve fairly well when collecting bacterial and fungi species, respectively. For other tested samplers, we observed substantial discrepancies between their performances and particle deposition efficiencies in the lung. The results show that feasibility of applying portable microbial samplers for exposure assessment depends on a particular sampler model and microbial species.

  10. Evaluation of exposure to PAHs in asphalt workers by environmental and biological monitoring.

    Science.gov (United States)

    Campo, Laura; Buratti, Marina; Fustinoni, Silvia; Cirla, Piero E; Martinotti, Irene; Longhi, Omar; Cavallo, Domenico; Foà, Vito

    2006-09-01

    In the present article we assessed exposure to polycyclic aromatic hydrocarbons (PAHs) in Italian asphalt workers (AW, n = 100), exposed to bitumen fumes and diesel exhausts, and in roadside construction workers (CW, n = 47), exposed to diesel exhausts, by means of environmental and biological monitoring. 1-hydroxypyrene (OH-Py) was determined in urine spot samples collected, respectively, after 2 days of vacation (baseline), before, and at the end of the monitored work shift, in the second part of the workweek. Median airborne levels during the work shift of 15 PAHs (both vapor and particulate phases), from naphthalene (NAP) to indeno(1,2,3-cd)pyrene, ranged from below 0.03 to 426 ng/m(3). Median excretion values of OH-Py in baseline, before- and end-shift samples were 228, 402, and 690 ng/L for AW and 260, 304, and 378 ng/L for CW. Lower values were found in nonsmokers compared to smokers (e.g., in AW 565 and 781 versus 252 and 506 ng/L in before-shift and end-shift samples, respectively). In all subjects a weak correlation between personal exposure to the sum of airborne 15 PAHs and OH-Py was observed (r = 0.30). The results of this article show that AW experienced a moderate occupational exposure to airborne PAHs, resulting in a significant increase of urinary OH-Py during the workday and the workweek. The contribution of working activities to internal dose was in the same order of magnitude of the contribution of cigarette smoking.

  11. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    Science.gov (United States)

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both pamphetamine exposure persisted after adjustment for all known cardiovascular risk factors (pamphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  12. Hair as a biological indicator of drug use, drug abuse or chronic exposure to environmental toxicants.

    Science.gov (United States)

    Boumba, Vassiliki A; Ziavrou, Kallirroe S; Vougiouklakis, Theodore

    2006-01-01

    In recent years hair has become a fundamental biological specimen, alternative to the usual samples blood and urine, for drug testing in the fields of forensic toxicology, clinical toxicology and clinical chemistry. Moreover, hair-testing is now extensively used in workplace testing, as well as, on legal cases, historical research etc. This article reviews methodological and practical issues related to the application of hair as a biological indicator of drug use/abuse or of chronic exposure to environmental toxicants. Hair structure and the mechanisms of drug incorporation into it are commented. The usual preparation and extraction methods as well as the analytical techniques of hair samples are presented and commented on. The outcomes of hair analysis have been reviewed for the following categories: drugs of abuse (opiates, cocaine and related, amphetamines, cannabinoids), benzodiazepines, prescribed drugs, pesticides and organic pollutants, doping agents and other drugs or substances. Finally, the specific purpose of the hair testing is discussed along with the interpretation of hair analysis results regarding the limitations of the applied procedures.

  13. Establishing the "Biological Relevance" of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels.

    Science.gov (United States)

    Gray, Leon Earl; Furr, Johnathan; Tatum-Gibbs, Katoria R; Lambright, Christy; Sampson, Hunter; Hannas, Bethany R; Wilson, Vickie S; Hotchkiss, Andrew; Foster, Paul M D

    2016-01-01

    Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that relatively large reductions in fetal testosterone (T) levels and testis gene expression may be required to adversely affect reproductive development (Hannas, B. R., Lambright, C. S., Furr, J., Evans, N., Foster, P. M., Gray, E. L., and Wilson, V. S. (2012). Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency. Toxicol. Sci. 125, 544-557). The objectives of this study were (1) to model the relationships between changes in fetal male rat plasma testosterone (PT), T levels in the testis (TT), T production (PROD), and testis gene expression with the reproductive malformation rates, and (2) to quantify the "biologically relevant reductions" (BRRs) in fetal T necessary to induce adverse effects in the offspring. In the fetal experiment, Harlan Sprague-Dawley rats were dosed with dipentyl phthalate (DPeP) at 0, 11, 33, 100, and 300 mg/kg/day from gestational days (GD) 14-18 and fetal testicular T, PT levels, and T Prod and gene expression were assessed on GD 18. In the postnatal experiment, rats were dosed with DPeP from GD 8-18 and reproductive development was monitored through adulthood. The dose-response curves for TT levels (ED(50) = 53 mg/kg) and T PROD (ED(50) = 45 mg/kg) were similar, whereas PT was reduced at ED50 = 19 mg/kg. When the reductions in TPROD and Insl3 mRNA were compared with the postnatal effects of in utero DPeP, dose-related reproductive alterations were noted when T PROD and Insl3 mRNA were reduced by >45% and 42%, respectively. The determination of BRR levels may enable risk assessors to utilize fetal endocrine data to help establish points of departure for

  14. Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design

    Energy Technology Data Exchange (ETDEWEB)

    Dodd, D.E.; Frank, F.R.; Fowler, E.H.; Troup, C.M.; Milton, R.M.

    1987-06-01

    Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration. MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC/sub 50/ tests with 14-day postexposure follow-up were conducted, and the LC/sub 50/ (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs. Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.

  15. The relevance of commuter and work/school exposure in an epidemiological study on traffic-related air pollution.

    Science.gov (United States)

    Ragettli, Martina S; Phuleria, Harish C; Tsai, Ming-Yi; Schindler, Christian; de Nazelle, Audrey; Ducret-Stich, Regina E; Ineichen, Alex; Perez, Laura; Braun-Fahrländer, Charlotte; Probst-Hensch, Nicole; Künzli, Nino

    2015-01-01

    Exposure during transport and at non-residential locations is ignored in most epidemiological studies of traffic-related air pollution. We investigated the impact of separately estimating NO2 long-term outdoor exposures at home, work/school, and while commuting on the association between this marker of exposure and potential health outcomes. We used spatially and temporally resolved commuter route data and model-based NO2 estimates of a population sample in Basel, Switzerland, to assign individual NO2-exposure estimates of increasing complexity, namely (1) home outdoor concentration; (2) time-weighted home and work/school concentrations; and (3) time-weighted concentration incorporating home, work/school and commute. On the basis of their covariance structure, we estimated the expectable relative differences in the regression slopes between a quantitative health outcome and our measures of individual NO2 exposure using a standard measurement error model. The traditional use of home outdoor NO2 alone indicated a 12% (95% CI: 11-14%) underestimation of related health effects as compared with integrating both home and work/school outdoor concentrations. Mean contribution of commuting to total weekly exposure was small (3.2%; range 0.1-13.5%). Thus, ignoring commute in the total population may not significantly underestimate health effects as compared with the model combining home and work/school. For individuals commuting between Basel-City and Basel-Country, ignoring commute may produce, however, a significant attenuation bias of 4% (95% CI: 4-5%). Our results illustrate the importance of including work/school locations in assessments of long-term exposures to traffic-related air pollutants such as NO2. Information on individuals' commuting behavior may further improve exposure estimates, especially for subjects having lengthy commutes along major transportation routes.

  16. Biological effects of long-term exposure to low dose-rate radiation -- Comparisons of WAM model and LQ model

    CERN Document Server

    Wada, Takahiro; Nakamura, Issei; Tsunoyama, Yuichi; Nakajima, Hiroo; Bando, Masako

    2015-01-01

    Newly proposed Whack-A-Mole (WAM) model which is to be used to estimate the biological effects of artificial radiations is compared with conventionally used Linear-Quadratic model. Basic properties of WAM model are discussed emphasizing on the dose-rate dependence. By adopting the parameters that are determined to fit the mega mouse experiments, biological effects of long-term exposure to extremely low dose-rate radiation are discussed. In WAM model, the effects of the long-term exposure show a saturation property, which makes a clear distinction from the LNT hypothesis which predicts a linear increase of the effects with time.

  17. Animal models of nicotine exposure: relevance to second-hand smoking, electronic cigarette use and compulsive smoking

    Directory of Open Access Journals (Sweden)

    Ami eCohen

    2013-06-01

    Full Text Available Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine and that a large proportion of smokers eventually become dependent on nicotine. In humans, nicotine acutely produces positive reinforcing effects, including mild euphoria, whereas a nicotine abstinence syndrome with both somatic and affective components is observed after chronic nicotine exposure. Animal models of nicotine self-administration and chronic exposure to nicotine have been critical in unveiling the neurobiological substrates that mediate the acute reinforcing effects of nicotine and emergence of a withdrawal syndrome during abstinence. However, important aspects of the transition from nicotine abuse to nicotine dependence, such as the emergence of increased motivation and compulsive nicotine intake following repeated exposure to the drug, have only recently begun to be modeled in animals. Thus, the neurobiological mechanisms that are involved in these important aspects of nicotine addiction remain largely unknown. In this review, we describe the different animal models available to date and discuss recent advances in animal models of nicotine exposure and nicotine dependence. This review demonstrates that novel animal models of nicotine vapor exposure and escalation of nicotine intake provide a unique opportunity to investigate the neurobiological effects of second-hand nicotine exposure, electronic cigarette use and the mechanisms that underlie the transition from nicotine use to compulsive nicotine intake.

  18. Multi-biological defects caused by lead exposure exhibit transferable properties from exposed parents to their progeny in Caenorhabditis elegans

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Whether the multi-biological toxicity from lead exposure could be transferred to progeny has not been clarified. In the present study, we explored the Caenorhabditis elegans to analyze the multiple toxicities from lead exposure and their possibly transferable properties. The lead exposure could cause series of severe multi-biological defects with a concentration-dependent manner by affecting the endpoints of life span, development, reproduction and locomotion behaviors in nematodes. Moreover, most of these toxicities could be transferred to progeny from lead exposed animals and some of the defects in progeny appeared even more severe than in their parents, such as the body sizes and mean life spans. We summarized the defects caused by lead exposure into three groups according to their transferable properties or rescue patterns. That is, the defects caused by lead exposure could be largely, or partially, or became even more severe in progeny animals. Therefore, our results suggest that lead exposure can cause severely multi-biological defects, and most of these multiple toxicities can be considered as transferable for exposed animals in C. elegans.

  19. Contaminant mixtures and repoductive health: Developmental toxicity effects in rats after mixed exposure to environmentally relevant endocrine disrupting chemicals, with focus on effects in females

    DEFF Research Database (Denmark)

    Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Hass, Ulla

    disorders or later onset adult diseases. However, experimental evidence on the effects of developmental exposure to environmentally relevant endocrine disrupting chemicals in females has been missing attention. Since chemical exposure can affect female reproductive development it is important to investigate......Background: In toxicological testing, effects of endocrine disrupters are in most cases more thoroughly investigated in males than in females. In males the hypothesis of testicu lar dysgenesis syndrome (TDS) proposes that there is a common origin in fetal life of the increase in frequency observed...... in later years of for example incidence of boys born with hypospadias and young men with low semen quality in the human male population. Furthermore, it has been observed in animal studies that exposure during fetal life to endocrine disrupters may lead to similar adverse reproductive effects. It has been...

  20. Visualization and identification of health space, based on personalized molecular phenotype and treatment response to relevant underlying biological processes

    NARCIS (Netherlands)

    Bouwman, J.; Vogels, J.T.W.E.; Wopereis, S.; Rubingh, C.M.; Bijlsma, S.; Ommen, B. van

    2012-01-01

    Background: Being able to visualize multivariate biological treatment effects can be insightful. However the axes in visualizations are often solely defined by variation and thus have no biological meaning. This makes the effects of treatment difficult to interpret. Methods: A statistical

  1. The non-ionizing electromagnetic field: Derivation of valid biological exposure metrics from Maxwell's equations of electromagnetism

    Science.gov (United States)

    Lundquist, Marjorie

    2003-03-01

    Standards for protecting health from exposure to non-ionizing electromagnetic radiation treat the power density (magnitude of Poynting vector) as the biological exposure metric. For a static electric or magnetic field, the presumed metric is field strength. Scientifically valid expressions for such exposure metrics have been derived theoretically [1]. Three regimes exist for which different expressions are obtained: high frequencies (where electric and magnetic fields are tightly coupled), low frequencies (where these fields are separable), and static fields (where time derivatives are zero). Unexpected results are obtained: * There are two exposure metrics: one for thermal, another for athermal effects. * In general, these two metrics are different. Only for a plane wave is the same metric (power density) valid for both effects. * Exposure metrics used today for static fields are invalid! These findings also apply in the ionizing portion of the electromagnetic spectrum. [1] Wireless Phones and Health II: State of the Science. G. Carlo, ed. NY: Kluwer Academic Publishers, 2000; Chapter 4.

  2. Retrospective assessment of radiation exposure using biological dosimetry: chromosome painting, electron paramagnetic resonance and the glycophorin a mutation assay.

    Science.gov (United States)

    Kleinerman, R A; Romanyukha, A A; Schauer, D A; Tucker, J D

    2006-07-01

    Biological monitoring of dose can contribute important, independent estimates of cumulative radiation exposure in epidemiological studies, especially in studies in which the physical dosimetry is lacking. Three biodosimeters that have been used in epidemiological studies to estimate past radiation exposure from external sources will be highlighted: chromosome painting or FISH (fluorescence in situ hybridization), the glycophorin A somatic mutation assay (GPA), and electron paramagnetic resonance (EPR) with teeth. All three biodosimeters have been applied to A-bomb survivors, Chernobyl clean-up workers, and radiation workers. Each biodosimeter has unique advantages and limitations depending upon the level and type of radiation exposure. Chromosome painting has been the most widely applied biodosimeter in epidemiological studies of past radiation exposure, and results of these studies provide evidence that dose-related translocations persist for decades. EPR tooth dosimetry has been used to validate dose models of acute and chronic radiation exposure, although the present requirement of extracted teeth has been a disadvantage. GPA has been correlated with physically based radiation dose after high-dose, acute exposures but not after low-dose, chronic exposures. Interindividual variability appears to be a limitation for both chromosome painting and GPA. Both of these techniques can be used to estimate the level of past radiation exposure to a population, whereas EPR can provide individual dose estimates of past exposure. This paper will review each of these three biodosimeters and compare their application in selected epidemiological studies.

  3. Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design.

    OpenAIRE

    Dodd, D E; Frank, F R; Fowler, E H; Troup, C M; Milton, R M

    1987-01-01

    Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration (...

  4. Microdosimetric analysis confirms similar biological effectiveness of external exposure to gamma-rays and internal exposure to 137Cs, 134Cs, and 131I.

    Directory of Open Access Journals (Sweden)

    Tatsuhiko Sato

    Full Text Available The risk of internal exposure to 137Cs, 134Cs, and 131I is of great public concern after the accident at the Fukushima-Daiichi nuclear power plant. The relative biological effectiveness (RBE, defined herein as effectiveness of internal exposure relative to the external exposure to γ-rays is occasionally believed to be much greater than unity due to insufficient discussions on the difference of their microdosimetric profiles. We therefore performed a Monte Carlo particle transport simulation in ideally aligned cell systems to calculate the probability densities of absorbed doses in subcellular and intranuclear scales for internal exposures to electrons emitted from 137Cs, 134Cs, and 131I, as well as the external exposure to 662 keV photons. The RBE due to the inhomogeneous radioactive isotope (RI distribution in subcellular structures and the high ionization density around the particle trajectories was then derived from the calculated microdosimetric probability density. The RBE for the bystander effect was also estimated from the probability density, considering its non-linear dose response. The RBE due to the high ionization density and that for the bystander effect were very close to 1, because the microdosimetric probability densities were nearly identical between the internal exposures and the external exposure from the 662 keV photons. On the other hand, the RBE due to the RI inhomogeneity largely depended on the intranuclear RI concentration and cell size, but their maximum possible RBE was only 1.04 even under conservative assumptions. Thus, it can be concluded from the microdosimetric viewpoint that the risk from internal exposures to 137Cs, 134Cs, and 131I should be nearly equivalent to that of external exposure to γ-rays at the same absorbed dose level, as suggested in the current recommendations of the International Commission on Radiological Protection.

  5. Microdosimetric analysis confirms similar biological effectiveness of external exposure to gamma-rays and internal exposure to 137Cs, 134Cs, and 131I.

    Science.gov (United States)

    Sato, Tatsuhiko; Manabe, Kentaro; Hamada, Nobuyuki

    2014-01-01

    The risk of internal exposure to 137Cs, 134Cs, and 131I is of great public concern after the accident at the Fukushima-Daiichi nuclear power plant. The relative biological effectiveness (RBE, defined herein as effectiveness of internal exposure relative to the external exposure to γ-rays) is occasionally believed to be much greater than unity due to insufficient discussions on the difference of their microdosimetric profiles. We therefore performed a Monte Carlo particle transport simulation in ideally aligned cell systems to calculate the probability densities of absorbed doses in subcellular and intranuclear scales for internal exposures to electrons emitted from 137Cs, 134Cs, and 131I, as well as the external exposure to 662 keV photons. The RBE due to the inhomogeneous radioactive isotope (RI) distribution in subcellular structures and the high ionization density around the particle trajectories was then derived from the calculated microdosimetric probability density. The RBE for the bystander effect was also estimated from the probability density, considering its non-linear dose response. The RBE due to the high ionization density and that for the bystander effect were very close to 1, because the microdosimetric probability densities were nearly identical between the internal exposures and the external exposure from the 662 keV photons. On the other hand, the RBE due to the RI inhomogeneity largely depended on the intranuclear RI concentration and cell size, but their maximum possible RBE was only 1.04 even under conservative assumptions. Thus, it can be concluded from the microdosimetric viewpoint that the risk from internal exposures to 137Cs, 134Cs, and 131I should be nearly equivalent to that of external exposure to γ-rays at the same absorbed dose level, as suggested in the current recommendations of the International Commission on Radiological Protection.

  6. Environmentally Relevant Chronic Low-Dose Tritium and Gamma Exposures do not Increase Somatic Intrachromosomal Recombination in pKZ1 Mouse Spleen.

    Science.gov (United States)

    Bannister, Laura; Serran, Mandy; Bertrand, Lindsey; Klokov, Dmitry; Wyatt, Heather; Blimkie, Melinda; Gueguen, Yann; Priest, Nicholas; Jourdain, Jean-René; Sykes, Pamela

    2016-12-01

    The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision. In this study, we investigated potential cytotoxic and genotoxic effects in mouse spleen after one month and eight months of chronic exposure to low-dose tritiated water (HTO). The dose regimes studied were designed to mimic human chronic consumption of HTO at levels of 10 kBq/l, 1 MBq/l and 20 MBq/l. The total doses from these radiation exposures ranged from 0.01 to 180 mGy. We also compared the biological effects of exposure to HTO with equivalent exposure to external whole-body (60)Co gamma rays. Changes in spleen weight and somatic intrachromosomal recombination (DNA inversions) in spleen tissue of pKZ1(Tg/+) mice were monitored. Our results showed no overall changes in either spleen organ weights and no increase mouse splenic intrachromosomal recombination frequencies, indicating that current drinking water standards for tritium exposure in the form of HTO are likely to be adequately protective against cytotoxic and genotoxic damage in spleen. These results demonstrate no evidence for cytotoxicity or genotoxicity in mouse spleen following chronic exposures to HTO activities (or equivalent gamma doses) up to 20 MBq/L.

  7. Effectiveness of personal protective equipment: Relevance of dermal and inhalation exposure to chlorpyrifos among pest control operators

    NARCIS (Netherlands)

    Jagt, K. van der; Tielemans, E.; Links, I.; Brouwer, D.; Hemmen, J. van

    2004-01-01

    This study assessed the effectiveness of a custom fit personal protective equipment (PPE) program aimed at reducing occupational exposure to pesticides. The intervention study was carried out on 15 pest control operators (PCOs) during mixing/loading and application of chlorpyrifos. Each worker was m

  8. Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects

    Science.gov (United States)

    Perchlorate exposure and association with iron homeostasis and other biological functions among NHANES 2005-2008 subjects Schreinemachers DM, Ghio AJ, Cascio WE, Sobus JR. U.S. EPA, RTP, NC, USA Perchlorate (ClO4-), an environmental pollutant, is a known thyroid toxicant and...

  9. Best practices for the use and exchange of invertebrate biological control genetic resources relevant for food and agriculture

    Science.gov (United States)

    Biological control is an important and environmentally preferred management option for invasive insect pests and weeds. Implementation of new international regulations governing exchange of genetic materials impacts the availability of candidate biocontrol agents, and exchange policies need to be ca...

  10. REE incorporation and behaviour in aquatic turtles as a consequence of environmental exposure and biological processes

    Science.gov (United States)

    Censi, P.; Randazzo, L. A.; D'Angelo, S.; Cuttitta, A.; Saiano, F.

    2012-04-01

    features in whole blood samples suggest that behaviour of these elements can be influenced by vital effects, probably related to the phosphate deposition during formation of turtle skeleton. In order to corroborate this suggestion a portion of esoskeleton sample coming from an Emys trinacris individual was analysed and REE concentrations normalised to the environmental water. Observed features of REE pattern from this material strongly agree with above the mentioned hypothesis being MREE enriched, from Nd to Ho, with respect to LREE and HREE. Therefore collected data indicate that REE contents in blood of Emys trinacris is influenced by exposure to environmental conditions but elemental behaviour in whole blood is driven by biological processes, probably associated to formation of esoskeleton that can be subjected to the incorporation of radionuclides.

  11. The REPAIR Project: Examining the Biological Impacts of Sub-Background Radiation Exposure within SNOLAB, a Deep Underground Laboratory.

    Science.gov (United States)

    Thome, Christopher; Tharmalingam, Sujeenthar; Pirkkanen, Jake; Zarnke, Andrew; Laframboise, Taylor; Boreham, Douglas R

    2017-07-19

    Considerable attention has been given to understanding the biological effects of low-dose ionizing radiation exposure at levels slightly above background. However, relatively few studies have been performed to examine the inverse, where natural background radiation is removed. The limited available data suggest that organisms exposed to sub-background radiation environments undergo reduced growth and an impaired capacity to repair genetic damage. Shielding from background radiation is inherently difficult due to high-energy cosmic radiation. SNOLAB, located in Sudbury, Ontario, Canada, is a unique facility for examining the effects of sub-background radiation exposure. Originally constructed for astroparticle physics research, the laboratory is located within an active nickel mine at a depth of over 2,000 m. The rock overburden provides shielding equivalent to 6,000 m of water, thereby almost completely eliminating cosmic radiation. Additional features of the facility help to reduce radiological contamination from the surrounding rock. We are currently establishing a biological research program within SNOLAB: Researching the Effects of the Presence and Absence of Ionizing Radiation (REPAIR project). We hypothesize that natural background radiation is essential for life and maintains genomic stability, and that prolonged exposure to sub-background radiation environments will be detrimental to biological systems. Using a combination of whole organism and cell culture model systems, the effects of exposure to a sub-background environment will be examined on growth and development, as well as markers of genomic damage, DNA repair capacity and oxidative stress. The results of this research will provide further insight into the biological effects of low-dose radiation exposure as well as elucidate some of the processes that may drive evolution and selection in living systems. This Radiation Research focus issue contains reviews and original articles, which relate to the

  12. Characterization of biological aerosol exposure risks from automobile air conditioning system.

    Science.gov (United States)

    Li, Jing; Li, Mingzhen; Shen, Fangxia; Zou, Zhuanglei; Yao, Maosheng; Wu, Chang-yu

    2013-09-17

    Although use of automobile air conditioning (AC) was shown to reduce in-vehicle particle levels, the characterization of its microbial aerosol exposure risks is lacking. Here, both AC and engine filter dust samples were collected from 30 automobiles in four different geographical locations in China. Biological contents (bacteria, fungi, and endotoxin) were studied using culturing, high-throughput gene sequence, and Limulus amebocyte lysate (LAL) methods. In-vehicle viable bioaerosol concentrations were directly monitored using an ultraviolet aerodynamic particle sizer (UVAPS) before and after use of AC for 5, 10, and 15 min. Regardless of locations, the vehicle AC filter dusts were found to be laden with high levels of bacteria (up to 26,150 CFU/mg), fungi (up to 1287 CFU/mg), and endotoxin (up to 5527 EU/mg). More than 400 unique bacterial species, including human opportunistic pathogens, were detected in the filter dusts. In addition, allergenic fungal species were also found abundant. Surprisingly, unexpected fluorescent peaks around 2.5 μm were observed during the first 5 min use of AC, which was attributed to the reaerosolization of those filter-borne microbial agents. The information obtained here can assist in minimizing or preventing the respiratory allergy or infection risk from the use of automobile AC system.

  13. Biological effects of in vitro THz radiation exposure in human foetal fibroblasts.

    Science.gov (United States)

    De Amicis, Andrea; Sanctis, Stefania De; Cristofaro, Sara Di; Franchini, Valeria; Lista, Florigio; Regalbuto, Elisa; Giovenale, Emilio; Gallerano, Gian Piero; Nenzi, Paolo; Bei, Roberto; Fantini, Massimo; Benvenuto, Monica; Masuelli, Laura; Coluzzi, Elisa; Cicia, Cristina; Sgura, Antonella

    2015-11-01

    In recent years, terahertz (THz) radiation has been widely used in a variety of applications: medical, security, telecommunications and military areas. However, few data are available on the biological effects of this type of electromagnetic radiation and the reported results, using different genetic or cellular assays, are quite discordant. This multidisciplinary study focuses on potential genotoxic and cytotoxic effects, evaluated by several end-points, associated with THz radiation. For this purpose, in vitro exposure of human foetal fibroblasts to low frequency THz radiation (0.1-0.15THz) was performed using a Compact Free Electron Laser. We did not observe an induction of DNA damage evaluated by Comet assay, phosphorylation of H2AX histone or telomere length modulation. In addiction, no induction of apoptosis or changes in pro-survival signalling proteins were detected. Moreover, our results indicated an increase in the total number of micronuclei and centromere positive micronuclei induction evaluated by CREST analysis, indicating that THz radiation could induce aneugenic rather than clastogenic effects, probably leading to chromosome loss. Furthermore, an increase of actin polymerization observed by ultrastructural analysis after THz irradiation, supports the hypothesis that an abnormal assembly of spindle proteins could lead to the observed chromosomal malsegregation.

  14. Exposure to Environmentally Relevant Concentrations of Genistein during Activation Does Not Affect Sperm Motility in the Fighting Fish Betta splendens

    Directory of Open Access Journals (Sweden)

    Ethan D. Clotfelter

    2014-01-01

    Full Text Available Sperm collected from male fighting fish Betta splendens were activated in control water, water containing the ion-channel blocker gadolinium (a putative positive control, or water containing the isoflavone phytoestrogen genistein to determine the effects of acute genistein exposure on male reproductive function. Computer-assisted sperm analysis was used to quantify the proportion of sperm that were motile and the swimming velocity of those sperm. The highest concentration of gadolinium (100 μM tested was effective at reducing sperm motility and velocity, but neither concentration of genistein tested (3.7 nM or 3.7 μM significantly affected these sperm parameters. Our findings suggest that acute exposure to waterborne phytoestrogens during activation does not reduce the motility of fish sperm.

  15. Exposure to environmentally relevant concentrations of genistein during activation does not affect sperm motility in the fighting fish Betta splendens.

    Science.gov (United States)

    Clotfelter, Ethan D; Gendelman, Hannah K

    2014-01-01

    Sperm collected from male fighting fish Betta splendens were activated in control water, water containing the ion-channel blocker gadolinium (a putative positive control), or water containing the isoflavone phytoestrogen genistein to determine the effects of acute genistein exposure on male reproductive function. Computer-assisted sperm analysis was used to quantify the proportion of sperm that were motile and the swimming velocity of those sperm. The highest concentration of gadolinium (100 μ M) tested was effective at reducing sperm motility and velocity, but neither concentration of genistein tested (3.7 nM or 3.7 μ M) significantly affected these sperm parameters. Our findings suggest that acute exposure to waterborne phytoestrogens during activation does not reduce the motility of fish sperm.

  16. Exposure to Environmentally Relevant Concentrations of Genistein during Activation Does Not Affect Sperm Motility in the Fighting Fish Betta splendens

    OpenAIRE

    Clotfelter, Ethan D.; Hannah K Gendelman

    2014-01-01

    Sperm collected from male fighting fish Betta splendens were activated in control water, water containing the ion-channel blocker gadolinium (a putative positive control), or water containing the isoflavone phytoestrogen genistein to determine the effects of acute genistein exposure on male reproductive function. Computer-assisted sperm analysis was used to quantify the proportion of sperm that were motile and the swimming velocity of those sperm. The highest concentration of gadolinium (100 ...

  17. Free radical release and HSP70 expression in two human immune-relevant cell lines after exposure to 1800 MHz radiofrequency radiation.

    Science.gov (United States)

    Lantow, M; Schuderer, J; Hartwig, C; Simkó, M

    2006-01-01

    The goal of this study was to investigate whether radiofrequency (RF) electromagnetic-field (EMF) exposure at 1800 MHz causes production of free radicals and/or expression of heat-shock proteins (HSP70) in human immune-relevant cell systems. Human Mono Mac 6 and K562 cells were used to examine free radical release after exposure to incubator control, sham, RF EMFs, PMA, LPS, heat (40 degrees C) or co-exposure conditions. Several signals were used: continuous-wave, several typical modulations of the Global System for Mobile Communications (GSM): GSM-non DTX (speaking only), GSM-DTX (hearing only), GSM-Talk (34% speaking and 66% hearing) at specific absorption rates (SARs) of 0.5, 1.0, 1.5 and 2.0 W/kg. Heat and PMA treatment induced a significant increase in superoxide radical anions and in ROS production in the Mono Mac 6 cells when compared to sham and/or incubator conditions. No significant differences in free radical production were detected after RF EMF exposure or in the respective controls, and no additional effects on superoxide radical anion production were detected after co-exposure to RF EMFs+PMA or RF EMFs+LPS. The GSM-DTX signal at 2 W/kg produced a significant difference in free radical production when the data were compared to sham because of the decreasing sham value. This difference disappeared when data were compared to the incubator controls. To determine the involvement of heat-shock proteins as a possible inhibitor of free radical production, we investigated the HSP70 expression level after different RF EMF exposures; no significant effects were detected.

  18. Selecting cost effective and policy-relevant biological indicators for European monitoring of soil biodiversity and ecosystem function

    NARCIS (Netherlands)

    Griffiths, B.S.; Römbke, J.; Schmelz, R.M.; Scheffczyk, A.; Faber, J.H.; Bloem, J.; Peres, G.; Cluzeau, D.; Chabbi, A.; Suhadolc, M.; Sousa, J.P.; Silva, da P.M.; Carvalho, F.; Mendes, S.; Morais, P.; Francisco, R.; Pereira, C.; Bonkowski, M.; Geisen, Stefan; Bardgetti, R.D.; Vries, De F.T.; Bolger, T.; Dirilgen, T.; Schmidt, O.; Winding, Anne; Hendriksen, Nicolien; Johansen, A.; Philippot, L.; Plassart, P.; Bru, D.; Thomson, B.M.; Griffiths, R.I.; Bailey, Megan; Keith, A.; Rutgers, M.; Mulder, Christian; Hannula, S.E.; Creamer, Rachel; Stone, D.

    2016-01-01

    Soils provide many ecosystem services that are ultimately dependent on the local diversity and belowground abundance of organisms. Soil biodiversity is affected negatively by many threats and there is a perceived policy requirement for the effective biological monitoring of soils at the European lev

  19. Selecting cost effective and policy-relevant biological indicators for European monitoring of soil biodiversity and ecosystem function

    NARCIS (Netherlands)

    Griffiths, B.s.; Römbke, J.; Schmelz, R.m.; Scheffczyk, A.; Faber, J.h.; Bloem, Jaap; Pérès, G.; Cluzeau, D.; Chabbi, A.; Suhadolc, M.; Sousa, J.p.; Martins Da Silva, P.; Carvalho, F.; Mendes, S.; Morais, P.; Francisco, R.; Pereira, C.; Bonkowski, M.; Geisen, S.; Bardgett, R.d.; De Vries, F.t.; Bolger, T.; Dirilgen, T.; Schmidt, O.; Winding, A.; Hendriksen, N.b.; Johansen, A.; Philippot, L.; Plassart, P.; Bru, D.; Thomson, B.; Griffiths, R.i.; Bailey, M.j.; Keith, A.; Rutgers, M.; Mulder, C.; Hannula, S.e.; Creamer, R.; Stone, D.

    2016-01-01

    Soils provide many ecosystem services that are ultimately dependent on the local diversity and below ground abundance of organisms. Soil biodiversity is affected negatively by many threats and there is a perceived policy requirement for the effective biological monitoring of soils at the European le

  20. Childhood exposure to violence and lifelong health: clinical intervention science and stress-biology research join forces.

    Science.gov (United States)

    Moffitt, Terrie E

    2013-11-01

    Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child's body, alterations that may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people.

  1. Practical Method for Determining Free Erythrocyte Protoporphyrin as a Biological Marker of Exposure to Inorganic Lead

    OpenAIRE

    Gloria Marilé Ávalos Ávalos

    2014-01-01

    Background: there are various exposure biomarkers for assessing occupational exposure to inorganic lead including the determination of blood lead levels and free erythrocyte protoporphyrin. Objective: to determine the practical and comparative reliability of a simple spectrophotometric method for determining free erythrocyte protoporphyrin as a biomarker of inorganic lead exposure. Methods: a group of 40 lead-exposed workers with different levels of exposure was studied. A blood sample was co...

  2. Emissions of Per- and Polyfluoroalkyl Substances in a Textile Manufacturing Plant in China and Their Relevance for Workers' Exposure.

    Science.gov (United States)

    Heydebreck, Franziska; Tang, Jianhui; Xie, Zhiyong; Ebinghaus, Ralf

    2016-10-04

    The manufacturing of high-performance fabrics requires numerous chemical treatment steps that involve the use of per- and polyfluoroalkyl substances (PFASs) to protect apparel against water, stain, and oil penetration. However, air and wastewater emissions of PFASs generated during this manufacturing are a potential threat to both factory workers and the environment. We investigated the occurrence and distribution of PFASs in wastewater, air, airborne particles, and settled dust in a textile manufacturing plant in China. PFOA and PFDA or their precursor compounds 8:2 FTOH and 10:2 FTOH were the dominant compounds in all environmental media tested, revealing that long-chain PFASs were preferably used for the manufacturing of functional garments. Besides, PFASs were detected along the textile manufacturing chain, indicating that they were used as durable water repellents and as surfactants in, for example, coating agents. The workers' exposure to FTOHs via air inhalation was up to 5 orders of magnitude higher than the background exposure of the general western population. To the best of our knowledge, this is the first study providing information regarding the emission of PFASs during the manufacturing of textiles via various environmental media.

  3. A relevant exposure to a food matrix contaminated environmentally by polychlorinated biphenyls induces liver and brain disruption in rats.

    Science.gov (United States)

    Ounnas, Fayçal; Privé, Florence; Lamarche, Fréderic; Salen, Patricia; Favier-Hininger, Isabelle; Marchand, Philippe; Le Bizec, Bruno; Venisseau, Anais; Batandier, Cécile; Fontaine, Eric; de Lorgeril, Michel; Demeilliers, Christine

    2016-10-01

    Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants present in dietary fats. Most studies evaluating PCB effects have been conducted with a single compound or a mixture of PCBs given as a single acute dose. The purpose of this study was to evaluate in vivo PCB toxicity in a realistic model of exposure: a low daily dose of PCBs (twice the tolerable daily intake (TDI)), chronically administered (8 weeks) to rats in contaminated goat milk. Liver and brain PCB toxicities were investigated by evaluating oxidative stress status and mitochondrial function. PCB toxicity in the liver was also estimated by transaminase enzymatic activity. This study shows that even at low doses, chronic PCB exposure resulted in a statistically significant reduction of mitochondrial function in liver and brain. In the liver, oxygen consumption in the condition of adenosine triphosphate (ATP) production (state 3) decreased by 22-29% (p food complex mixture of environmental origin) resulted in multiple disruptions in the liver and brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. RNA sequencing analysis of transcriptional change in the freshwater mussel Elliptio complanata after environmentally relevant sodium chloride exposure

    Science.gov (United States)

    Robertson, Laura S.; Galbraith, Heather S.; Iwanowicz, Deborah; Blakeslee, Carrie J.; Cornman, Robert S.

    2017-01-01

    To identify potential biomarkers of salt stress in a freshwater sentinel species, we examined transcriptional responses of the common mussel Elliptio complanata to controlled sodium chloride (NaCl) exposures. Ribonucleic acid sequencing (RNA-Seq) of mantle tissue identified 481 transcripts differentially expressed in adult mussels exposed to 2 ppt NaCl (1.2 ppt chloride) for 7 d, of which 290 had nonoverlapping intervals. Differentially expressed gene categories included ion and transmembrane transport, oxidoreductase activity, maintenance of protein folding, and amino acid metabolism. The rate-limiting enzyme for synthesis of taurine, an amino acid frequently linked to osmotic stress in aquatic species, was upregulated, as was the transmembrane ion pump sodium/potassium adenosine 5′-triphosphatase. These patterns confirm a primary transcriptional response to the experimental dose, albeit likely overlapping with nonspecific secondary stress responses. Substantial involvement of the heat shock protein 70 chaperone family and the water-transporting aquaporin family was not detected, however, in contrast to some studies in other bivalves. A subset of the most significantly regulated genes was confirmed by quantitative polymerase chain reaction in an independent sample. Cluster analysis showed separation of mussels exposed to 2 ppt NaCl from control mussels in multivariate space, but mussels exposed to 1 ppt NaCl were largely indistinguishable from controls. Transcriptome-scale analysis of salt exposure under laboratory conditions efficiently identified candidate biomarkers for further functional analysis and field validation

  5. Surface modifications of fusion reactor relevant materials on exposure to fusion grade plasma in plasma focus device

    Energy Technology Data Exchange (ETDEWEB)

    Niranjan, Ram, E-mail: niranjan@barc.gov.in [Applied Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Rout, R.K.; Srivastava, R. [Applied Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Chakravarthy, Y. [Laser and Plasma Technology Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Mishra, P. [Materials Processing Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Kaushik, T.C.; Gupta, Satish C. [Applied Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2015-11-15

    Graphical abstract: - Highlights: • Exposure of materials (W, Ni, SS, Mo and Cu) to fusion plasma in a plasma focus device. • The erosion and the formations of blisters, pores, craters, micro-cracks after irradiation. • The structural phase transformation in the SS sample after irradiation. • The surface layer alloying of the samples with the plasma focus anode material. - Abstract: An 11.5 kJ plasma focus (PF) device was used here to irradiate materials with fusion grade plasma. The surface modifications of different materials (W, Ni, stainless steel, Mo and Cu) were investigated using various available techniques. The prominent features observed through the scanning electron microscope on the sample surfaces were erosions, cracks, blisters and craters after irradiations. The surface roughness of the samples increased multifold after exposure as measured by the surface profilometer. The X-ray diffraction analysis indicated the changes in the microstructures and the structural phase transformation in surface layers of the samples. We observed change in volumes of austenite and ferrite phases in the stainless steel sample. The energy dispersive X-ray spectroscopic analysis suggested alloying of the surface layer of the samples with elements of the PF anode. We report here the comparative analysis of the surface damages of materials with different physical, thermal and mechanical properties. The investigations will be useful to understand the behavior of the perspective materials for future fusion reactors (either in pure form or in alloy) over the long operations.

  6. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yingchen29@yahoo.com.cn [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Yan, X.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Department of Radiation Safety, Beijing Institute of Nuclear and Chemical Safety, 14 Guan-cun, Dongcheng District, Beijing 100077 (China); Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China)

    2011-09-15

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of {sup 60}Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of {sup 60}Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0{sup -3}D{sup 2}. Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy {gamma}-irradiation from a supra-high dose {sup 60}Co gamma-ray accident.

  7. The relevance of polar surface area (PSA) in rationalizing biological properties of several cis-diamminemalonatoplatinum(II) derivatives.

    Science.gov (United States)

    Caron, Giulia; Ermondi, Giuseppe; Gariboldi, Marzia B; Monti, Elena; Gabano, Elisabetta; Ravera, Mauro; Osella, Domenico

    2009-10-01

    A panel of six cis-diamminemalonatoplatinum(II) derivatives were designed and synthesized, and their physicochemical properties and in vitro biological activity were experimentally evaluated and studied in silico. All the complexes showed higher IC(50) values (> or =20 microM) than those observed for cisplatin and its malonato analogue on three different human tumor cell lines, namely A2780 ovarian carcinoma, A549 lung carcinoma, and MCF-7 breast carcinoma. In silico studies revealed that polar surface area (PSA) is the best descriptor to explain the poor biological activity observed for this series of new compounds, which in turn is likely due to poor cellular uptake. This finding is in line with general rules that assign a major role to PSA in characterizing the transport properties of drugs, in the actual case of antiproliferative metallopharmaceuticals.

  8. Neutron Exposures in Human Cells: Bystander Effect and Relative Biological Effectiveness

    Science.gov (United States)

    Seth, Isheeta; Schwartz, Jeffrey L.; Stewart, Robert D.; Emery, Robert; Joiner, Michael C.; Tucker, James D.

    2014-01-01

    Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (pbystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. PMID:24896095

  9. Neutron exposures in human cells: bystander effect and relative biological effectiveness.

    Science.gov (United States)

    Seth, Isheeta; Schwartz, Jeffrey L; Stewart, Robert D; Emery, Robert; Joiner, Michael C; Tucker, James D

    2014-01-01

    Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (pbystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0 ± 0.13 for micronuclei and 5.8 ± 2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety.

  10. The levels of kerosene components in biological samples after repeated dermal exposure to kerosene in rats.

    Science.gov (United States)

    Fujihara, Junko; Hieda, Yoko; Tsujino, Yoshio; Xue, Yuying; Takayama, Koji; Kimura, Kojiro; Dekio, Satoshi

    2004-04-01

    The current study was experimentally investigated using rats whether or not kerosene components are accumulated from daily repeated dermal exposure. Rats received daily 1h-exposure to kerosene for 5 days (5K), daily 1h-exposure for 4 days and left for 1 day (4KL), a single 1h-exposure (1K), a single 1h-exposure and left for 1 day (1KL), or a single 1h-exposure, sacrificed and left dead for 1 day (1KLD). Kerosene components, trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) in blood and tissues were determined by GC-MS. In blood, almost the same concentrations of TMBs were detected in the rats sacrificed immediately after exposure (5K, 1K and 1KLD), and only trace levels were detected in the rats sacrificed 1 day after exposure (4 and 1KL). Almost the same levels of AHCs in blood were detected among groups except for the rats sacrificed 1 day after a single exposure (1KL), in which AHCs were slightly lower. These results suggest that (1) AHCs tend to be accumulated from daily exposure, while TMBs do not, (2) the proportions of detected kerosene components in blood can be an indicator of whether the last exposure occurred just before death or not, (3) the kerosene levels last at least 1 day without blood circulation.

  11. The relevance of biological dosimetry in controversial judgements about low level effects in populations; Die Aussagekraft der biologischen Dosimetrie bei Kontroversen ueber Strahlenfolgen im Niederdosisbereich

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz-Feuerhake, Inge

    2009-07-01

    Radiation-specific structural chromosome aberrations include dicentric chromosomes which are most sensitive to prove exposures in individuals and cohorts of persons. The reasons are their very low spontaneous rate and their instability which leads to a kind of equilibrium because no relevant accumulation occurs during lifetime by natural or civil exposures. The doubling dose in case of an acute homogenous whole body exposure is about 10 mSv. For example, a review about findings in populations exposed by Chernobyl fallout is presented which shows, that the dose estimates of UNSCEAR and WHO are not reliable. While these result even for highly contaminated regions in values in the range of a few mSv, the aberration rates in many and numerous samples of the population showed a multifold elevation compared to normal background rates. An underestimation of the true exposure by the physical calculation in the range of 1-2 orders of magnitude must be considered. Similar conclusions can be drawn for the accident of Three Mile Island in 1979, the effects near nuclear establishments in regular conditions and for air craft personnel. (orig.)

  12. A piecewise regression approach for determining biologically relevant hydraulic thresholds for the protection of fish at river infrastructure

    Energy Technology Data Exchange (ETDEWEB)

    Boys, Craig A.; Robinson, Wayne; Miller, Brett; Pflugrath, Brett D.; Baumgartner, Lee J.; Navarro, Anna; Brown, Richard S.; Deng, Zhiqun

    2016-05-13

    Barotrauma injury can occur when fish are exposed to rapid decompression during downstream passage through river infrastructure. A piecewise regression approach was used to objectively quantify barotrauma injury thresholds in two physoclistous species (Murray cod Maccullochella peelii and silver perch Bidyanus bidyanus) following simulated infrastructure passage in barometric chambers. The probability of injuries such as swim bladder rupture; exophthalmia; and haemorrhage and emphysema in various organs increased as the ratio between the lowest exposure pressure and the acclimation pressure (ratio of pressure change RPCE/A) fell. The relationship was typically non-linear and piecewise regression was able to quantify thresholds in RPCE/A that once exceeded resulted in a substantial increase in barotrauma injury. Thresholds differed among injury types and between species but by applying a multi-species precautionary principle, the maintenance of exposure pressures at river infrastructure above 70% of acclimation pressure (RPCE/A of 0.7) should sufficiently protect downstream migrating juveniles of these two physoclistous species. These findings have important implications for determining the risk posed by current infrastructures and informing the design and operation of new ones.

  13. Effect of Co-Existing Biologically Relevant Molecules and Ions on DNA Photocleavage Caused by Pyrene and its Derivatives

    Directory of Open Access Journals (Sweden)

    Hongtao Yu

    2005-04-01

    Full Text Available Inorganic ions, coenzymes, amino acids, and saccharides could co-exist with toxic environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs, in the cell. The presence of these co-existing chemicals can modulate the toxicity of the PAHs. One of the genotoxic effects by PAHs is light-induced cleavage, or photocleavage, of DNA. The effect of inorganic ions I-, Na+, Ca2+, Mg2+, Fe3+, Mn2+, Cu2+, and Zn2+ and biological molecules riboflavin, histidine, mannitol, nicotinamide adenine dinucleotide (NAD, glutathione, and glutamic acid on the DNA photocleavage by pyrene, 1-hydroxypyrene (1-HP, and 1-aminopyrene (1-AP, is studied. The non-transition metal ions Na+, Ca2+, and Mg2+, usually have very little inhibitory effects, while the transition metal ions Fe3+, Cu2+, and Zn2+ enhance, Mn2+ inhibits the DNA photocleavage. The effect by biological molecules is complex, depending on the photochemical reaction mechanisms of the compounds tested (1-AP, 1-HP and pyrene and on the chemical nature of the added biological molecules. Riboflavin, histidine, and mannitol enhance DNA photocleavage by all three compounds, except that mannitol has no effect on the photocleavage of DNA by pyrene. Glutathione inhibits the DNA photocleavage by 1-AP and 1-HP, but has no effect on that by pyrene. NAD enhances the DNA photocleavage by 1-AP, but has no effect on that by 1-HP and pyrene. Glutamic acid enhances the DNA photocleavage by 1-AP and pyrene, but inhibits that by 1-HP. These results show that the co-existing chemicals may have a profound effect on the toxicity of PAHs, or possibly on the toxicity of many other chemicals. Therefore, if one studies the toxic effects of PAHs or other toxic chemicals, the effect of the co-existing chemicals or ions needs to be considered.

  14. Exposure to ethylene oxide in hospitals: biological monitoring and influence of glutathione S-transferase and epoxide hydrolase polymorphisms.

    Science.gov (United States)

    Haufroid, Vincent; Merz, Brigitte; Hofmann, Annette; Tschopp, Alois; Lison, Dominique; Hotz, Philippe

    2007-04-01

    Ethylene oxide is considered as a human carcinogen. A biomarker of exposure would be a useful instrument to assess the risk in occupationally exposed workers. This cross-sectional study aimed at examining (a) whether the urinary excretion of a metabolite of ethylene oxide, 2-hydroxyethyl mercapturic acid (HEMA), could be used for monitoring occupational exposure and (b) whether glutathione S-transferase (GST) and epoxide hydrolase genotypes influenced biological monitoring. Exposure to ethylene oxide was measured by personal sampling in 80 hospital workers (95% of those eligible). HEMA concentrations were determined in three urine samples (baseline, end of shift, and next morning) by liquid chromatography with tandem mass spectrometry. GSTs (GSTT1, GSTM1, and GSTP1) and epoxide hydrolase (EPHX1) were also genotyped. The influence of exposure, genotypes, and several other factors was examined in multiple regression analyses. Exposure was always <1 parts per million. On a group basis, exposure and a non-null GSTT1 genotype increased the HEMA concentrations in the urine sample collected at the end of the shift and these factors remained statistically significant after considering possible confounding or modifying factors.

  15. The hazard assessment of nanostructured CeO{sub 2}-based mixed oxides on the zebrafish Danio rerio under environmentally relevant UV-A exposure

    Energy Technology Data Exchange (ETDEWEB)

    Jemec, Anita, E-mail: anita.jemec@bf.uni-lj.si [National Institute of Chemistry, Laboratory for Environmental Sciences and Engineering, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); University of Ljubljana, Biotechnical Faculty, Department of Biology, Večna pot 111, SI-1000 Ljubljana (Slovenia); Djinović, Petar; Črnivec, Ilja Gasan Osojnik; Pintar, Albin [National Institute of Chemistry, Laboratory for Environmental Sciences and Engineering, Hajdrihova 19, SI-1001 Ljubljana (Slovenia)

    2015-02-15

    The effect of nanomaterials on biota under realistic environmental conditions is an important question. However, there is still a lack of knowledge on how different illumination conditions alter the toxicity of some photocatalytic nanomaterials. We have investigated how environmentally relevant UV-A exposure (intensity 8.50 ± 0.61 W/m{sup 2}, exposure dose 9.0 J/cm{sup 2}) affected the toxicity of cerium oxide (CeO{sub 2})-based nanostructured materials to the early-life stages of zebrafish Danio rerio. Pure cerium oxide (CeO{sub 2}), copper–cerium (CuO–CeO{sub 2}) (with a nominal 10, 15 and 20 mol.% CuO content), cerium–zirconium (CeO{sub 2}–ZrO{sub 2}) and nickel and cobalt (Ni–Co) deposited over CeO{sub 2}–ZrO{sub 2} were tested. It was found that under both illumination regimes, none of the tested materials affected the normal development or induced mortality of zebrafish early-life stages up to 100 mg/L. Only in the case of CuO–CeO{sub 2}, the growth of larvae was decreased (96 h LOEC values for CuCe10, CuCe15 and CuCe20 were 50, 50 and 10 mg/L, respectively). To conclude, CeO{sub 2}-based nanostructured materials are not severely toxic to zebrafish and environmentally relevant UV-A exposure does not enhance their toxicity. - Highlights: • CeO{sub 2}–ZrO{sub 2} nanomaterials and pure CeO{sub 2} (up to 100 mg/L) were not harmful to zebrafish. • Only CuO modified CeO{sub 2} affected the growth of zebrafish larvae. • UV-A radiation did not enhance the toxicity of tested nanomaterials.

  16. Comparative analyses of built environment exposures relevant to health of greenhouse gas emissions reduction strategies in Serbia

    Directory of Open Access Journals (Sweden)

    Stefanović Sandra P.

    2014-01-01

    Full Text Available Paper presents comparative analysis of residential indoor air pollutant concentration change over future specified time horizon, implementing building physical and thermal retrofit measures, thus creating pollution mitigation scenarios for existing Belgrade and Nis housing stock followed by greenhouse gas emission reduction scenarios up to 2050. Regarding specified mitigation scenarios, the set of typical housing unit models has been generated which define existing housing stock of Belgrade and Nis. Extensive monitoring of physical and thermal parameters as well as detailed socio-technical survey of selected households was performed and used as an initial modeling input. Relationship between environment pollution and building performances was investigated, with respect to indooroutdoor sources of pollution, thermal and physical properties of the stock samples and occupant’s behavior. As a final output, indoor pollutant concentrations for each of the modelled cases was obtained and validated against the available data. This housing modelling framework has been created in order to develop an assessment of present and future exposure and health impact quantity regarding single/multiple scenario interventions introduced to the housing stock. This paper provides each strategy guidelines for taking measures towards achieving the healthier indoor environments. [FP7-ENV-2010: PURGE-Public health impacts in urban environments of greenhouse gas emissions reduction strategies, Project number: 265325, financed by the European Commission

  17. SysBioCube: A Data Warehouse and Integrative Data Analysis Platform Facilitating Systems Biology Studies of Disorders of Military Relevance.

    Science.gov (United States)

    Chowbina, Sudhir; Hammamieh, Rasha; Kumar, Raina; Chakraborty, Nabarun; Yang, Ruoting; Mudunuri, Uma; Jett, Marti; Palma, Joseph M; Stephens, Robert

    2013-01-01

    SysBioCube is an integrated data warehouse and analysis platform for experimental data relating to diseases of military relevance developed for the US Army Medical Research and Materiel Command Systems Biology Enterprise (SBE). It brings together, under a single database environment, pathophysio-, psychological, molecular and biochemical data from mouse models of post-traumatic stress disorder and (pre-) clinical data from human PTSD patients.. SysBioCube will organize, centralize and normalize this data and provide an access portal for subsequent analysis to the SBE. It provides new or expanded browsing, querying and visualization to provide better understanding of the systems biology of PTSD, all brought about through the integrated environment. We employ Oracle database technology to store the data using an integrated hierarchical database schema design. The web interface provides researchers with systematic information and option to interrogate the profiles of pan-omics component across different data types, experimental designs and other covariates.

  18. [Methodological aspects in environmental and biological monitoring of exposure to low doses of benzene: problems and possible solutions].

    Science.gov (United States)

    Tranfo, Giovanna; Paci, Enrico; Fustinoni, Silvia; Barbieri, Anna; Carrieri, Mariella

    2013-01-01

    This paper aims to examine some methods to measure human exposure to benzene, both in life and occupational environments, through environmental and biological monitoring, examining the critical issues and optimal conditions of use. The overall performance of environmental monitoring, from the analytical point of view, strongly depend on the choice of an appropriate method of sampling and analysis. Urinary SPMA and t, t-MA are the biomarkers listed by ACGIH to evaluate occupational exposure: most of the recent studies use HPLC with tandem mass spectrometry, but since t, t-MA is present in the urine in larger quantities it is also determinable with UV detectors. The urinary benzene is an index not officially included in the list of the ACGIH BEIs, but it is useful to assess exposure and benzene at low concentrations, that most frequently are found today in the occupational and life environments.

  19. Predictive variables for the biological behaviour of basal cell carcinoma of the face: relevance of morphometry of the nuclei.

    Science.gov (United States)

    Appel, T; Bierhoff, E; Appel, K; von Lindern, J-J; Bergé, S; Niederhagen, B

    2003-06-01

    We did a morphometric analysis of 130 histological sections of basal cell carcinoma (BCC) of the face to find out whether morphometric variables in the structure of the nuclei of BCC cells could serve as predictors of the biological behaviour. We considered the following variables: maximum and minimum diameters, perimeter, nuclear area and five form factors that characterise and quantify the shape of a structure (axis ratio, shape factor, nuclear contour index, nuclear roundness and circumference ratio). We did a statistical analysis of primary and recurring tumours and four histology-based groups (multifocal superficial BCCs, nodular BCCs, sclerosing BCCs and miscellaneous forms) using a two-sided t test for independent samples. Multifocal superficial BCCs showed significantly smaller values for the directly measured variables (maximum and minimum diameters, perimeter and nuclear area). Morphometry could not distinguish between primary and recurring tumours.

  20. Evaluation of some procedures relevant to the determination of trace elemental components in biological materials by destructive neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Berry, D.L.

    1979-01-01

    The development of a simplified procedure for the analysis of biological materials by destructive neutron activation analysis (DNAA) is described. The sample manipulations preceding gamma ray assay were investigated as five specific stages of processing: (1) pre-irradiation treatment; (2) sample irradiation; (3) removal of the organic matrix; (4) removal of interfering radioactivities; and (5) concentration and separation of analyte activities. Each stage was evaluated with respect to susceptibility to sample contamination, loss of trace elemental components, and compatibility with other operations in the overall DNAA procedures. A complete DNAA procedure was proposed and evaluated for the analysis of standard bovine liver and blood samples. The DNAA system was effective for the determination of As, Cu, Fe, Hg, Mo, Rb, Sb, Se, and Zn without yield determinations and with a minimum turn-around time of approximately 3 days.

  1. Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance.

    Science.gov (United States)

    Hutmacher, Dietmar Werner; Holzapfel, Boris Michael; De-Juan-Pardo, Elena Maria; Pereira, Brooke Anne; Ellem, Stuart John; Loessner, Daniela; Risbridger, Gail Petuna

    2015-12-01

    In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

  2. [Exposure to biologic hazards in rehabilitation: analysis of the perceived risk and of the educational needs of nurses and physiotherapists].

    Science.gov (United States)

    Papalia, Francesco; Monami, Stefano; Antonelli, Leone; Magnavita, Nicola; Marchi, Edda

    2007-01-01

    Nurses and physiotherapists who work in a Rehabilitation Centre are exposed to biologic hazards due to the close physical contact they have with their patients, who are often affected by contagious infectious diseases. The perceived risk amongst these workers is a significant element in establishing an effective prevention plan and in evaluating educational needs and was therefore investigated in this survey. An anonymous self-administered questionnaire, structured in four subsections for a total of twenty four multiple-choice questions was used. The evaluated variables included knowledge of pathogen transmission pathways, modes of exposure to such pathogens, knowledge of universal precautions and of ways in which to deal with known exposure. Physiotherapists, more so than nurses, have a partial and insufficient knowledge of biologic hazards. The main reason for this gap can be found in the school curriculum for such professionals, in which, in comparison to other graduate degree courses (medicine, nursing) a much smaller amount of course time is allotted to the topic of biologic hazards and risk prevention. In order to practice effective risk management it is therefore necessary for the employer to commit to providing specific on-site education and training to its workers. For this purpose, our centre has developed specific educational activities and internal procedures which can be shared on the topic of biologic hazards and risk management.

  3. Neutron exposures in human cells: bystander effect and relative biological effectiveness.

    Directory of Open Access Journals (Sweden)

    Isheeta Seth

    Full Text Available Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy, and irradiated-cell conditioned media (ICCM was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control, 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (p<0.0001. These data indicate that neutrons do not induce a bystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0 ± 0.13 for micronuclei and 5.8 ± 2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety.

  4. A biologically inspired psychometric function for accuracy of visual identification as a function of exposure duration

    DEFF Research Database (Denmark)

    Petersen, Anders; Andersen, Tobias

    The psychometric function of letter identification is typically described as a function of stimulus intensity. However, the effect of stimulus exposure duration on letter identification remains poorly described. This is surprising because the effect of exposure duration has played a central role ...

  5. Exposure to trauma-relevant pictures is associated with tachycardia in victims who had experienced an intense peritraumatic defensive response: the tonic immobility

    Directory of Open Access Journals (Sweden)

    Rita de Cassia Soares Alves

    2014-12-01

    Full Text Available Tonic immobility is an involuntary, last-ditch defensive reaction characterized by physical inactivity in a context of inescapable threat that has been described in many species, including humans. The occurrence of this defensive response is a predictor of the severity of psychiatric disorders and may be considered as an index of an intense reaction to a traumatic event. Here, we investigated whether the retrospective reports of peritraumatic tonic immobility reaction in participants exposed to a traumatic event would modify their cardiac responses to pictures related to their trauma. Using a questionnaire of life-threating events, we selected students who experienced violent crime as their most intense trauma and students who had never experienced a violent crime trauma, but experienced other traumatic events. All participants completed a questionnaire that estimated the intensity of tonic immobility during their most intense trauma. Electrocardiographic recordings were collected during exposure to pictures. Participants viewed emotional pictures (human attack with guns and neutral pictures. These emotional stimuli were selected to be trauma-relevant to the violent crime group and non trauma-relevant to the no violent crime trauma group. Violent crime group showed a positive correlation between heart rate changes after viewing trauma-related pictures and tonic immobility scores. We observed that low tonic immobility scores were associated with bradycardia and high scores with tachycardia in response to trauma-relevant pictures. For the no violent crime group, no significant correlation was detected. These results suggest that the relevance of the stimuli and the magnitude of the defensive response during a previous trauma event were important factors triggering more intense defensive responses.

  6. Biological Production of a Hydrocarbon Fuel Intermediate Polyhydroxybutyrate (PHB) from a Process Relevant Lignocellulosic Derived Sugar (Poster)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.; Mittal, A.; Mohagheghi, A.; Johnson, D. K.

    2014-04-01

    PHAs are synthesized by many microorganisms to serve as intracellular carbon storage molecules. In some bacterial strains, PHB can account for up to 80% of cell mass. In addition to its application in the packaging sector, PHB also has great potential as an intermediate in the production of hydrocarbon fuels. PHB can be thermally depolymerized and decarboxylated to propene which can be upgraded to hydrocarbon fuels via commercial oligomerization technologies. Cupriavidus necator is the microorganism that has been most extensively studied and used for PHB production on an industrial scale; However the substrates used for producing PHB are mainly fructose, glucose, sucrose, fatty acids, glycerol, etc., which are expensive. In this study, we demonstrate production of PHB from a process relevant lignocellulosic derived sugar stream, i.e., saccharified slurry from pretreated corn stover. The strain was first investigated in shake flasks for its ability to utilize glucose, xylose and acetate. In addition, the strain was also grown on pretreated lignocellulose hydrolyzate slurry and evaluated in terms of cell growth, sugar utilization, PHB accumulation, etc. The mechanism of inhibition in the toxic hydrolysate generated by the pretreatment and saccharification process of biomass, was also studied.

  7. Structure, Properties, and Biological Relevance of the DNA and RNA G-Quadruplexes: Overview 50 Years after Their Discovery.

    Science.gov (United States)

    Dolinnaya, N G; Ogloblina, A M; Yakubovskaya, M G

    2016-12-01

    G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding-unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA-RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.

  8. A Method for Quantifying the Acute Health Impacts of Residential Non-Biological Exposure Via Inhalation

    Energy Technology Data Exchange (ETDEWEB)

    Logue, Jennifer M. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max H. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Singer, Bret C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-01

    The inability to monetize the health costs of acute exposures in homes and the benefits of various control options is a barrier to justifying policies and approaches that can reduce exposure and improve health.We synthesized relationships between short-term outdoor concentration changes and health outcomes to estimate the health impacts of short-term in-home exposures. Damage and cost impacts of specific health outcomes were taken from the literature. We assessed the impact of vented and non-vented residential natural gas cooking burners on Southern California occupants for two pollutants (NO2 and CO).

  9. Examining waterborne and dietborne routes of exposure and their contribution to biological response patterns in fathead minnow (Pimephales promelas)

    Energy Technology Data Exchange (ETDEWEB)

    Rozon-Ramilo, Lisa D., E-mail: lisa.ramilo@usask.ca [University of Saskatchewan, Toxicology Centre, 44 Campus Drive, Saskatoon, Saskatchewan S7N 5B3 (Canada); Dube, Monique G., E-mail: moniqe.dube@usask.ca [University of Saskatchewan, School of Environment and Sustainability, 117 Science Place, Saskatoon, Saskatchewan S7N 2X8 (Canada); Squires, Allison J., E-mail: allison.squires@usask.ca [University of Saskatchewan, Toxicology Centre, 44 Campus Drive, Saskatoon, Saskatchewan S7N 5B3 (Canada); Niyogi, Som, E-mail: som.niyogi@usask.ca [University of Saskatchewan, Department of Biology, 112 Science Place, Saskatoon, Saskatchewan S7N 5E2 (Canada)

    2011-10-15

    total egg production and cumulative spawning events were significantly affected by both waterborne and dietborne exposures, with maximum effect found in the multi-trophic streams. These results suggest that under environmentally relevant exposure conditions, trophic transfer of metals may lead to greater reproductive effects and increased metal toxicity in fish. It also indicates that metals are assimilated in tissues differently depending on the quality of the food (live vs. frozen). Overall, it appears that the multi-trophic bioassay provides an important link between the laboratory and field, which may allow for a more realistic assessment of the true impact of MME's in the environment.

  10. Spontaneous encapsulation and concentration of biological macromolecules in liposomes: an intriguing phenomenon and its relevance in origins of life.

    Science.gov (United States)

    de Souza, Tereza Pereira; Fahr, Alfred; Luisi, Pier Luigi; Stano, Pasquale

    2014-12-01

    One of the main open questions in origin of life research focuses on the formation, by self-organization, of primitive cells composed by macromolecular compounds enclosed within a semi-permeable membrane. A successful experimental strategy for studying the emergence and the properties of primitive cells relies on a synthetic biology approach, consisting in the laboratory assembly of cell models of minimal complexity (semi-synthetic minimal cells). Despite the recent advancements in the construction and characterization of synthetic cells, an important physical aspect related to their formation is still not well known, namely, the mechanism of solute entrapment inside liposomes (in particular, the entrapment of macromolecules). In the past years, we have investigated this phenomenon and here we shortly review our experimental results. We show how the detailed cryo-transmission electron microscopy analyses of liposome populations created in the presence of ferritin (taken as model protein) or ribosomes have revealed that a small fraction of liposomes contains a high number of solutes, against statistical expectations. The local (intra-liposomal) macromolecule concentration in these liposomes largely exceeds the bulk concentration. A similar behaviour is observed when multi-molecular reaction mixtures are used, whereby the reactions occur effectively only inside those liposomes that have entrapped high number of molecules. If similar mechanisms operated in early times, these intriguing results support a scenario whereby the formation of lipid compartments plays an important role in concentrating the components of proto-metabolic systems-in addition to their well-known functions of confinement and protection.

  11. Aberrant E-cadherin and gamma-catenin expression in malignant mesothelioma and its diagnostic and biological relevance.

    Science.gov (United States)

    Orecchia, Sara; Schillaci, Francesca; Salvio, Michela; Libener, Roberta; Betta, Pier-Giacomo

    2004-08-01

    Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined and the role of the cadherin-catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and alpha-, beta- and gamma-catenins was studied in nine human MM cell lines and five human mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin and alpha- and beta-catenins. All but one MM cell line were N-cadherin-positive and all of them were also positive for alpha- and beta-catenins. E-cadherin was found in six (66.7%) and gamma-catenin in seven (77.8%) MM cell lines. Five of these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was also P-cadherin-positive. Double immunofluorescence staining revealed the plasma membrane co-localisation of both cadherin types in MM cell lines that co-expressed E- and N-cadherin or E- and P-cadherin, respectively. Immunoprecipitation showed complexes of beta-catenin with both cadherin types when co-expressed. The results point to upregulation of E-cadherin and gamma-catenin in most MM cases and demonstrate that cadherin expression is more heterogeneous and less mutually exclusive in MM compared with the mesothelium, although the biological significance of this finding remains unclear.

  12. Human urinary biomarkers of dioxin exposure: Analysis by metabolomics and biologically driven data dimensionality reduction

    OpenAIRE

    Jeanneret, Fabienne; Boccard, Julien; Badoud, Flavia; Sorg, Olivier; Tonoli, David; Pelclova, Daniela; Vlckova, Stepanka; Rutledge, Douglas N; Samer, Caroline Flora; Hochstrasser, Denis; Saurat, Jean-Hilaire; Rudaz, Serge

    2013-01-01

    Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers submitted to severe dioxin occupational exposure in a herbicide production plant in the late 1960s. Experiments were carried out with ultra-high pressure liquid chromatography (U...

  13. A multicomponent bioactive tissue-engineered blood vessel: Fabrication, mechanical evaluation and biological evaluation with physiological-relevant conditions

    Science.gov (United States)

    Bonani, Walter

    The high long-term failure rate of synthetic vascular grafts in the replacement of small vessels is known to be associated with the lack of physiological signals to vascular cells causing adverse hemodynamic, inflammatory or coagulatory events. Current studies focus on developing engineered vascular devices with ability of directing cell activity in vitro and in vivo for tissue regeneration. It is also known that controlled molecule release from scaffolds can dramatically increase the scaffold ability of directing cell activities in vitro and in vivo for tissue regeneration. To address the mechanical and biological problems associated with graft materials, we demonstrated a degradable polyester-fibroin composite tubular scaffolds which shows well-integrated nanofibrous structure, endothelial-conducive surface and anisotropic mechanical property, suitable as engineered vascular constructs. Tissue regeneration needs not only functional biomolecules providing signaling cues to cells and guide tissue remodeling, but also an adequate modality of molecule delivery. In fact, healthy tissue formation requires specific signals at well-defined place and time. To develop scaffolds with multi-modal presentation of biomolecules, we patterned electrospun nanofibers over the thickness of the 3-dimensional scaffolds by programming the deposition of interpenetrating networks of degradable polymers poly(a-caprolactone) and poly(lactide-co-glycolide) acid in tailored proportion. Fluorescent model molecules, drug and growth factors were embedded in the polymeric fibers with different techniques and release profiles were obtained and discussed. Fabrication process resulted in precise gradient patterns of materials and functional biomolecules throughout the thickness of the scaffold. These graded materials showed programmable spatio-temporal control over the release. Molecule release profiles on each side of the scaffolds were used to determine the separation efficiency of molecule

  14. Endogenous expression of ASLV viral proteins in specific pathogen free chicken embryos: relevance for the developmental biology research field

    Directory of Open Access Journals (Sweden)

    Canto-Soler M Valeria

    2010-10-01

    Full Text Available Abstract Background The use of Specific Pathogen Free (SPF eggs in combination with RCAS retrovirus, a member of the Avian Sarcoma-Leukosis Virus (ASLV family, is of standard practice to study gene function and development. SPF eggs are certified free of infection by specific pathogen viruses of either exogenous or endogenous origin, including those belonging to the ASLV family. Based on this, SPF embryos are considered to be free of ASLV viral protein expression, and consequently in developmental research studies RCAS infected cells are routinely identified by immunohistochemistry against the ASLV viral proteins p19 and p27. Contrary to this generally accepted notion, observations in our laboratory suggested that certified SPF chicken embryos may endogenously express ASLV viral proteins p19 and p27. Since these observations may have significant implications for the developmental research field we further investigated this possibility. Results We demonstrate that certified SPF chicken embryos have transcriptionally active endogenous ASLV loci (ev loci capable of expressing ASLV viral proteins, such as p19 and p27, even when those loci are not capable of producing viral particles. We also show that the extent of viral protein expression in embryonic tissues varies not only among flocks but also between embryos of the same flock. In addition, our genetic screening revealed significant heterogeneity in ev loci composition even among embryos of the same flock. Conclusions These observations have critical implications for the developmental biology research field, since they strongly suggest that the current standard methodology used in experimental studies using the chick embryo and RCAS vectors may lead to inaccurate interpretation of results. Retrospectively, our observations suggest that studies in which infected cells have been identified simply by pan-ASLV viral protein expression may need to be considered with caution. For future studies, they

  15. Biological monitoring as a valid tool to assess occupational exposure to mixtures of 2,4-:2,6-toluene diisocyanate.

    Science.gov (United States)

    De Palma, G; Cortesi, Ilenia; Ghitti, Roberta; Festa, Denise; Bergonzi, R; Apostoli, P

    2012-01-01

    Despite its advantages over environmental monitoring, biological monitoring of exposure to 2,4-:2,6-toluene diisocyanate (TDI) mixtures is still underused. The present study was designed in order to evaluate the feasibility and reliability of biological monitoring in a factory producing polyurethane foam blocks. Airborne TDI isomers were sampled by both static and personal pumps and determined by HPLC with fluorimetric detection. Specific metabolites 2,4- and 2,6-toluenediamine (TDA) were determined by gas chromatography-mass spectrometry on hydrolysed urine samples collected from 16 workers at the beginning of the workweek and both before (BS) and at the end (ES) of the 4th workday. Additional samples were collected at the end of the 1st half-shift and at the beginning of the 2nd half-shift in 5 workers. In the foam production shop, TDI values were on average about 20 microg/m3, with higher levels in the 2nd half-shift and peak levels in workers operating along the polymerization tunnel. Average TDI levels were significantly correlated with ES TDA concentrations (p values at the beginning of the workweek (higher than in unexposed subjects) and by their elevation in subsequent BS samples. The study demonstrates the feasibility and reliability of biological monitoring in workers exposed to 2,4-:2, 6-TDI mixtures. This approach can provide information about both the daily and weekly exposure levels.

  16. Contamination of indoor dust and air by polychlorinated biphenyls and brominated flame retardants and relevance of non-dietary exposure in Vietnamese informal e-waste recycling sites.

    Science.gov (United States)

    Tue, Nguyen Minh; Takahashi, Shin; Suzuki, Go; Isobe, Tomohiko; Viet, Pham Hung; Kobara, Yuso; Seike, Nobuyasu; Zhang, Gan; Sudaryanto, Agus; Tanabe, Shinsuke

    2013-01-01

    This study investigated the occurrence of polychlorinated biphenyls (PCBs), and several additive brominated flame retardants (BFRs) in indoor dust and air from two Vietnamese informal e-waste recycling sites (EWRSs) and an urban site in order to assess the relevance of these media for human exposure. The levels of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCD), 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE) and decabromodiphenyl ethane (DBDPE) in settled house dust from the EWRSs (130-12,000, 5.4-400, 5.2-620 and 31-1400 ng g(-1), respectively) were significantly higher than in urban house dust but the levels of PCBs (4.8-320 ng g(-1)) were not higher. The levels of PCBs and PBDEs in air at e-waste recycling houses (1000-1800 and 620-720 pg m(-3), respectively), determined using passive sampling, were also higher compared with non-e-waste houses. The composition of BFRs in EWRS samples suggests the influence from high-temperature processes and occurrence of waste materials containing older BFR formulations. Results of daily intake estimation for e-waste recycling workers are in good agreement with the accumulation patterns previously observed in human milk and indicate that dust ingestion contributes a large portion of the PBDE intake (60%-88%), and air inhalation to the low-chlorinated PCB intake (>80% for triCBs) due to their high levels in dust and air, respectively. Further investigation of both indoor dust and air as the exposure media for other e-waste recycling-related contaminants and assessment of health risk associated with exposure to these contaminant mixtures is necessary.

  17. Insight into the Local Solvent Environment of Biologically Relevant Iron-nitroysl Systems through Two-Dimensional Infrared Spectroscopy

    Science.gov (United States)

    Brookes, Jennifer Faith

    Iron-nitrosyl systems, particularly in the form of heme proteins, with their iron metal active sites play an important role in biological systems. Heme proteins act as storage, transporters, and receptors for nitric oxide (NO), a signaling molecule that is important in immune, nervous, and cardiovascular systems of mammals. By better understanding the local environment of the active site of NO binding heme proteins we can gain insight into disease in which the NO pathways have been implicated. This is an important step to being able to develop pharmaceuticals targeting NO pathways in humans. Sodium nitroprusside ((SNP, Na2[Fe(CN)5is NO]·2H 2O) investigated as a model system for the active site of nitric oxide binding heme proteins. Using two-dimensional infrared spectroscopy (2D IR) to obtain dephasing dynamics of the nitrosyl stretch (nuNO) in a series of solvents we are able to better understand the local environment of the more complicated metalloproteins. Rigorous line shape analysis is performed by using nonlinear response theory to simulate 2D IR spectra which are then fit to experimental data in an iterative process to extract frequency-frequency correlation functions (FFCFs). The time scales obtained are then correlated to empirical solvent polarity parameters. The analysis of the 2D IR lineshapes reveal that the spectral diffusion timescale of the nuNO in SNP varies from 0.8 -- 4 ps and is negatively correlated with the empirical solvent polarity scales. We continue to investigate NO binding of metalloproteins through 2D IR experiments on nitrophorin 4 (NP4). NP4 is a pH-sensitive NO transporter protein present in the salivary gland of the blood sucking insect Rhodius prolixus which undergoes a pH sensitive structural change between a closed and open conformation allowing for the storage and delivery of NO. The two structures are observed spectroscopically as two distinct pH-dependent nu NO frequencies at ~1904 and ~1917 cm-1. We obtain FFCFs by globally

  18. A biologically inspired psychometric function for accuracy of visual identification as a function of exposure duration

    DEFF Research Database (Denmark)

    Petersen, Anders; Andersen, Tobias

    The psychometric function of letter identification is typically described as a function of stimulus intensity. However, the effect of stimulus exposure duration on letter identification remains poorly described. This is surprising because the effect of exposure duration has played a central role......-Z) was presented at the centre of the screen. Exposure duration was varied from 5 to 210 milliseconds. The letter was followed by a pattern mask. Three subjects each completed 54,080 trials in a 26-Alternative Forced Choice procedure. We compared the exponential, the gamma and the Weibull psychometric functions......, all of these having a temporal offset included, as well as the ex-Gaussian, and finally a new psychometric function, motivated from single-neuron studies by (Albrecht, Geisler, Frazor & Crane, 2002). The new psychometric function stands out by having a nonmonotonous hazard rate which is initially...

  19. Biological monitoring of occupational exposure to different chromium compounds at various valency states

    Energy Technology Data Exchange (ETDEWEB)

    Mutti, A.; Pedroni, C.; Arfini, G.; Franchini, I.; Minoia, C.; Micoli, G.; Baldi, C.

    1984-01-01

    Chromium concentrations in the air were measured in seven different workroom environments, where exposure to water soluble hexavalent or trivalent compounds was expected. Urinary excretion of chromium was measured before and after the same arbitrarily chosen working day. End-of-shift urinary chromium and its increase above pre-exposure levels were closely related to the concentration of water soluble chromium (VI) in the air. The values corresponding to 50 micrograms m-3 in the air, which is the current threshold limit value in most countries, were 29.8 and 12.2 micrograms g-1 of creatinine, respectively. Urinary chromium in workers exposed to water insoluble chromates or to water soluble chromic (III) sulphate was definitely higher than that observed in subjects not occupationally exposed to chromium compounds, but it cannot be recommended as short-term exposure test for evaluation of the job-related hazard.

  20. An alternative viewpoint to the biological effects of low-level exposures

    Energy Technology Data Exchange (ETDEWEB)

    Cook, R.R. [Dow Corning Corp., Midland, MI (United States)

    1995-12-31

    The effects of low-level exposures to toxic chemicals and radiations are presumed to be similar to those associated with higher level exposures. There is a growing body of evidence that this assumption is incorrect. Through a series of data-based examples, this paper challenges the assumptions inherent to the current toxics model and offers three alternatives: nonlinear dose response in which the effects seen at low levels may be interpreted as paradoxical, or even beneficial; a holistic model in which the outcome is the whole animal; and a trade-off model in which the unit of study is the population and not an individual.

  1. Study of genetic damage in the Japanese oyster induced by an environmentally-relevant exposure to diuron: evidence of vertical transmission of DNA damage.

    Science.gov (United States)

    Barranger, A; Akcha, F; Rouxel, J; Brizard, R; Maurouard, E; Pallud, M; Menard, D; Tapie, N; Budzinski, H; Burgeot, T; Benabdelmouna, A

    2014-01-01

    genitors to short exposures to diuron at medium environmental concentrations. The analysis of POCIS showed that oysters were exposed to integrated concentrations as low as 0.2 and 0.3 μg L(-1), emphasizing the relevance of the results obtained and the risk associated to chemical contamination for oyster recruitment and fitness.

  2. Imino [4+4] cycloaddition products as exclusive and biologically relevant acrolein-amine conjugates are intermediates of 3-formyl-3,4-dehydropiperidine (FDP), an acrolein biomarker.

    Science.gov (United States)

    Takamatsu, Masayuki; Fukase, Koichi; Kurbangalieva, Almira; Tanaka, Katsunori

    2014-11-15

    We demonstrated synthetically that the eight-membered heterocycles 2,6,9-triazabicyclo[3.3.1]nonanes and 1,5-diazacyclooctanes are the initial and exclusive products of the reaction, through an imino [4+4] cycloaddition, of biologically relevant amines with acrolein. The stabilities of the aminoacetals within the eight-membered heterocycles determined whether the product was subsequently transformed gradually into the 3-formyl-3,4-dehydropiperidine (FDP), which is widely used as an oxidative stress marker. The reactivity profiles discovered in this study suggested that some of the imino [4+4] cycloaddition products are reactive intermediates of FDP and contribute to the mechanisms underlying the oxidative stress response to acrolein.

  3. Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 GSTT1

    NARCIS (Netherlands)

    Delft, J.H.M. van; Steenwinkel, M.-J.S.T.; Asten, J.G. van; Vogel, N. de; Bruijntjes-Rozier, T.C.D.M.; Schouten, T.; Cramers, P.; Maas, L.; Herwijnen, M.H. van; Schooten, F.-J. van; Hopmans, P.M.J.

    2001-01-01

    Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. Objective: Thi

  4. Biological monitoring the exposure to polycyclic aromatic hydrocarbons of coke oven workers in relation to smoking and genetic polymorphisms for GSTM1 GSTT1

    NARCIS (Netherlands)

    Delft, J.H.M. van; Steenwinkel, M.-J.S.T.; Asten, J.G. van; Vogel, N. de; Bruijntjes-Rozier, T.C.D.M.; Schouten, T.; Cramers, P.; Maas, L.; Herwijnen, M.H. van; Schooten, F.-J. van; Hopmans, P.M.J.

    2001-01-01

    Occupational exposure to polycyclic aromatic hydrocarbons (PAH) increases the risk of developing lung cancer. Human exposure is often demonstrated by increased internal levels of PAH metabolites and of markers for early biological effects, like DNA adducts and cytogenetic aberrations. Objective: Thi

  5. Biological monitoring of embrio-fetal exposure to methamidophos or chlorothalonil on rat development.

    Science.gov (United States)

    de Castro, V L; Chiorato, S H; Pinto, N F

    2000-12-01

    Maternal exposure to pesticides during the pre-implantation and very early post-implantation periods of pregnancy is correlated with numerous adverse effects on the offspring and in reproductive parameters like an increase in resorption, a decrease in fetal survival and weight, and teratogenic effects. Although the epidemiological evidence is inconclusive as regards the risk of the adverse outcome of pregnancy and developmental toxicity events, the use of biomarkers in exposure assessment may contribute to recognizing a potential health impairment. The present study evaluated the influence of prenatal oral exposure to an insecticide (1.0 mg methamidophos/kg) or a fungicide (200.0 mg chlorothalonil/kg) during gestation days 1 to 6 on maturational and behavioral aspects of offspring development of rats. The pesticides did not affect the body weight gain of dams and offspring, nor did the exposure affect the weight of gravid uterus, fetus, placenta and ovary. There were no observed alterations in the swimming behavior tested at postnatal days 7, 14 and 21, but the pesticides interfered with physical and maturational development landmarks of offspring according to age, showing subtle effects on behavioral and physical development. These findings show the importance of categorizing developmental effects, establishing the relationship between age and important performances, to recognize potential impacts on human populations.

  6. Biological monitoring of pesticide exposures in residents living near agricultural land

    Directory of Open Access Journals (Sweden)

    Galea Karen S

    2011-11-01

    Full Text Available Abstract Background There is currently a lack of reliable information on the exposures of residents and bystanders to pesticides in the UK. Previous research has shown that the methods currently used for assessing pesticide exposure for regulatory purposes are appropriate for farm workers 1. However, there were indications that the exposures of bystanders may sometimes be underestimated. The previous study did not collect data for residents. Therefore, this study aims to collect measurements to determine if the current methods and tools are appropriate for assessing pesticide exposure for residents living near agricultural fields. Methods/design The study will recruit owners of farms and orchards (hereafter both will be referred to as farms that spray their agricultural crops with certain specified pesticides, and which have residential areas in close proximity to these fields. Recruited farms will be asked to provide details of their pesticide usage throughout the spray season. Informed consenting residents (adults (18 years and over and children(aged 4-12 years will be asked to provide urine samples and accompanying activity diaries during the spraying season and in additionfor a limited number of weeks before/after the spray season to allow background pesticide metabolite levels to be determined. Selected urine samples will be analysed for the pesticide metabolites of interest. Statistical analysis and mathematical modelling will use the laboratory results, along with the additional data collected from the farmers and residents, to determine systemic exposure levels amongst residents. Surveys will be carried out in selected areas of the United Kingdom over two years (2011 and 2012, covering two spraying seasons and the time between the spraying seasons. Discussion The described study protocol was implemented for the sample and data collection procedures carried out in 2011. Based on experience to date, no major changes to the protocol are

  7. Carbon nanotubes – Characteristic of the substance, biological effects and occupational exposure levels

    Directory of Open Access Journals (Sweden)

    Anna Maria Świdwińska-Gajewska

    2017-04-01

    Full Text Available Carbon nanotubes (CNTs are a diverse group of nano-objects in terms of structure, size (length, diameter, shape and characteristics. The growing interest in these structures is due to the increasing number of people working in exposure to CNTs. Occupational exposure to carbon nanotubes may occur in research laboratories, as well as in plants producing CNTs and their nanocomposites. Carbon nanotubes concentration at the emission source may reach 107 particles/cm3. These values, however, are considerably reduced after the application of adequate ventilation. Animal studies suggest that the main route of exposure is inhalation. Carbon nanotubes administered orally are largely excreted in the feces. In animals exposed by inhalation, CNTs caused mainly inflammation, as a result of oxidative stress, leading above all to changes in the lungs. The main effect of animal dermal exposure is oxidative stress causing local inflammation. In animals exposed by ingestion the mild or no toxicity was observed. Carbon nanotubes did not induce mutations in the bacterial tests, but they were genotoxic in a series of tests on cells in vitro, as well as in exposed mice in vivo. Embryotoxicity of nanotubes depends mainly on their modifications and carcinogenicity – primarily on the CNT size and its rigidity. Occupational exposure limits for CNTs proposed by world experts fall within the range of 1–80 μg/m3. The different effects of various kinds of CNT, leads to the conclusion that each type of nanotube should be treated as a separate substance with individual estimation of hygienic normative. Med Pr 2017;68(2:259–276

  8. Biological Monitoring of Occupational Exposure to Polycyclic Aromatic Hydrocarbons at an Electric Steel Foundry in Tunisia.

    Science.gov (United States)

    Campo, Laura; Hanchi, Mariem; Olgiati, Luca; Polledri, Elisa; Consonni, Dario; Zrafi, Ines; Saidane-Mosbahi, Dalila; Fustinoni, Silvia

    2016-07-01

    Occupational exposures during iron and steel founding have been classified as carcinogenic to humans, and the exposure to polycyclic aromatic hydrocarbons (PAHs) in this industrial setting may contribute to cancer risk. The occupational exposure to PAHs was assessed in 93 male workers at an electric steel foundry in Tunisia by biomonitoring, with the aims of characterizing the excretion profile and investigating the influence of job title and personal characteristics on the biomarkers. Sixteen 2-6 ring unmetabolized PAHs (U-PAHs) and eight hydroxylated PAH metabolites (OHPAHs) were analyzed by gas chromatography-triple quadrupole tandem mass spectrometry and liquid chromatography triple quadrupole tandem mass spectrometry, respectively. Among U-PAHs, urinary naphthalene (U-NAP) was the most abundant compound (median level: 643ng l(-1)), followed by phenanthrene (U-PHE, 18.5ng l(-1)). Urinary benzo[a]pyrene (U-BaP) level was <0.30ng l(-1) Among OHPAHs, 2-hydroxynaphthalene (2-OHNAP) was the most abundant metabolite (2.27 µg l(-1)). Median 1-hydroxypyrene (1-OHPYR) was 0.52 µg l(-1) Significant correlations among urinary biomarkers were observed, with Pearson's r ranging from 0.177 to 0.626. 1-OHPYR was correlated to benzo[a]pyrene, but not to five- and six-rings PAHs. A multiple linear regression model showed that job title was a significant determinant for almost all U-PAHs. In particular, employees in the steel smelter workshop had higher levels of high-boiling U-PAHs and lower levels of low-boiling U-PAHs than those of workers with other job titles. Among OHPAHs, this model was significant only for naphthols and 1-hydroxyphenanthrene (1-OHPHE). Smoking status was a significant predictor for almost all biomarkers. Among all analytes, U-PHE and 1-OHPHE were the less affected by tobacco smoke, and they were significantly correlated with both low- and high-molecular-weight compounds, and their levels were related to job titles, so they could be proposed as suitable

  9. Human biological monitoring for exposure assessment in response to an incident involving hazardous materials

    NARCIS (Netherlands)

    Scheepers, P.T.J.; Brederode, N.E. van; Bos, P.M.J.; Nijhuis, N.J.; Weerdt, R.H. van de; Woude, I. van der; Eggens, M.L.

    2014-01-01

    Biological monitoring in humans (HBM) is widely used in the field of occupational and environmental health. In the situation of an unexpected release of hazardous materials HBM may contribute to the medical support and treatment of exposed individuals from the general population or of emergency

  10. Static magnetic fields: A summary of biological interactions, potential health effects, and exposure guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Tenforde, T.S.

    1992-05-01

    Interest in the mechanisms of interaction and the biological effects of static magnetic fields has increased significantly during the past two decades as a result of the growing number of applications of these fields in research, industry and medicine. A major stimulus for research on the bioeffects of static magnetic fields has been the effort to develop new technologies for energy production and storage that utilize intense magnetic fields (e.g., thermonuclear fusion reactors and superconducting magnet energy storage devices). Interest in the possible biological interactions and health effects of static magnetic fields has also been increased as a result of recent developments in magnetic levitation as a mode of public transportation. In addition, the rapid emergence of magnetic resonance imaging as a new clinical diagnostic procedure has, in recent years, provided a strong rationale for defining the possible biological effects of magnetic fields with high flux densities. In this review, the principal interaction mechanisms of static magnetic fields will be described, and a summary will be given of the present state of knowledge of the biological, environmental, and human health effects of these fields.

  11. Contextual Hub Analysis Tool (CHAT: A Cytoscape app for identifying contextually relevant hubs in biological networks [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Tanja Muetze

    2016-08-01

    Full Text Available Highly connected nodes (hubs in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT, which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest.   Availability: CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store (http://apps.cytoscape.org/apps/chat.

  12. Pass the salt: physiological consequences of ecologically relevant hyposmotic exposure in juvenile gummy sharks (Mustelus antarcticus) and school sharks (Galeorhinus galeus)

    Science.gov (United States)

    Morash, Andrea J.; Mackellar, Sara R. C.; Tunnah, Louise; Barnett, David A.; Stehfest, Kilian M.; Semmens, Jayson M.; Currie, Suzanne

    2016-01-01

    Estuarine habitats are frequently used as nurseries by elasmobranch species for their protection and abundant resources; however, global climate change is increasing the frequency and severity of environmental challenges in these estuaries that may negatively affect elasmobranch physiology. Hyposmotic events are particularly challenging for marine sharks that osmoconform, and species-specific tolerances are not well known. Therefore, we sought to determine the effects of an acute (48 h) ecologically relevant hyposmotic event (25.8 ppt) on the physiology of two juvenile shark species, namely the school shark (Galeorhinus galeus), listed by the Australian Environmental Protection and Biodiversity Conservation Act as ‘conservation dependent’, and the gummy shark (Mustelus antarcticus), from the Pittwater Estuary (Australia). In both species, we observed a decrease in plasma osmolality brought about by selective losses of NaCl, urea and trimethylamine N-oxide, as well as decreases in haemoglobin, haematocrit and routine oxygen consumption. Heat-shock protein levels varied between species during the exposure, but we found no evidence of protein damage in any of the tissues tested. Although both species seemed to be able to cope with this level of osmotic challenge, overall the school sharks exhibited higher gill Na+/K+-ATPase activity and ubiquitin concentrations in routine and experimental conditions, a larger heat-shock protein response and a smaller decrease in routine oxygen consumption during the hyposmotic exposure, suggesting that there are species-specific responses that could potentially affect their ability to withstand longer or more severe changes in salinity. Emerging evidence from acoustic monitoring of sharks has indicated variability in the species found in the Pittwater Estuary during hyposmotic events, and together, our data may help to predict species abundance and distribution in the face of future global climate change. PMID:27757235

  13. Phytotoxicity effects and biological responses of Arabidopsis thaliana to 2,3,7,8-tetrachlorinated dibenzo-p-dioxin exposure.

    Science.gov (United States)

    Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad

    2014-06-01

    Dioxins are persistent organic pollutants. Their bioaccumulation in the food chain makes dioxins a considerable risk for human health. The use of plants for removing toxic organic compounds, including dioxins, is a safe and efficient strategy. Herein we studied the toxicity effects and the biological responses in Arabidopsis thaliana to 2',3',7',8'-tetrachlorinated dibenzo-p-dioxin (TCDD) exposure. First, TCDD-induced toxicity was demonstrated using several parameters including, a decrease in seed germination, a loss in fresh weight with a striking decrease in chlorophyll content, but not in carotenoids, and an augmentation in the biomass of the lateral roots system, but not in the elongation of the primary root. Uptake of TCDD by Arabidopsis was confirmed. Responses to TCDD-exposure were marked by an enhanced level of hydrogen peroxide H2O2 production and a massive stimulation of anti-oxidative enzyme activities. Moreover, a significant variation in the transcript level of transcription factor genes, bHLH, MYB and AP2-EREBP was detected in Arabidopsis shoot and an up-regulation of WRKY, MYB and IAA was observed in the root. Our results illustrate the TCDD-induced toxicity effects and the biological responses of Arabidopsis to TCDD. Better understanding of the plants ability to detoxifydioxins would help to improve their use as a safe bioremediators.

  14. Biological system responses to zearalenone mycotoxin exposure by integrated metabolomic studies.

    Science.gov (United States)

    Liu, Guangmang; Yan, Tao; Wang, Jing; Huang, Zhiqing; Chen, Xiaoling; Jia, Gang; Wu, Caimei; Zhao, Hua; Xue, Bai; Xiao, Liang; Tang, Jiayong

    2013-11-20

    This study aims to investigate the effect of zearalenone supplementation on rat metabolism. Rats received biweekly intragastric administration of zearalenone mycotoxin (3 mg/kg body weight) for 2 weeks. Urine and plasma samples after zearalenone administration were analyzed by NMR-based metabolomics. Zearalenone exposure significantly elevated the plasma levels of glucose, lactate, N-acetyl glycoprotein, O-acetyl glycoprotein, and propionate but reduced the plasma levels of tyrosine, branched-chain amino acids, and choline metabolites. Zearalenone supplementation decreased the urine levels of butyrate, lactate, and nicotinate. However, it increased the urine levels of allantoin, choline, and N-methylnicotinamide at 0-8 h after the last zearalenone administration and those of 1-methylhistidine, acetoacetate, acetone, and indoxyl sulfate at 8-24 h after the last zearalenone administration. These results suggest that zearalenone exposure can cause oxidative stress and change common systemic metabolic processes, including cell membrane metabolism, protein biosynthesis, glycolysis, and gut microbiota metabolism.

  15. Psychological dysfunctions in lead-exposed workers. Relation to biological parameters of exposure

    Energy Technology Data Exchange (ETDEWEB)

    Grandjean, P.; Arnvig, E.; Beckmann, J.

    1978-12-01

    Insidious neurotoxic effects of lead have been studied in a population of 42 lead-exposed workers and a reference group of 22 comparable workers with no lead exposure. The age of the individuals ranged from 18 to 50 years. The complete Wechler Adult Intelligence Scale, as well as psychomotor and memory tests, was included in the test battery. The exposure was assessed by means of the lead concentration in blood and hair and the ratio between zinc protoporphyrin and hemoglobin in the blood. Significant differences were found between the two groups of workers, especially concerning long-term memory, verbal and visuospatial abstraction, and psychomotor speed. Blood lead and zinc protoporphyrin appeared to correlate better with the intellectual impairment than did hair lead.

  16. Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure

    OpenAIRE

    Flora, Swaran J.S

    2009-01-01

    Oxidative stress contributes to the pathophysiology of exposure to heavy metals/metalloid. Beneficial renal effects of some medications, such as chelation therapy depend at least partially on the ability to alleviate oxidative stress. The administration of various natural or synthetic antioxidants has been shown to be of benefit in the prevention and attenuation of metal induced biochemical alterations. These include vitamins, N-acetylcysteine, α-lipoic acid, melatonin, dietary flavonoids and...

  17. Analysis of the Exposure Levels and Potential Biologic Effects of the PAVE PAWS Radar System.

    Science.gov (United States)

    1979-01-01

    purported effects of microwave exposure, cataract induction is the only irreversible alteration repgted to have occurred in humans as a result of accidental ...Czerski12 ) described the cases of two long-term radar technicians wh2 were accidentally exposed to microwave power densities of 30-70 mW/cmZ. These power...of the children had never revealed a harmful effect. OTHER EFFECTS There is no evidence of significant microwave-induced immunologic, cerebrovascular

  18. Biologic indicators of exposure to cadmium and lead palmerton, Pennsylvania. Part 2. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Sarasua, S.M.; McGeehin, M.A.; Stallings, F.L.; Terracciano, G.L.; Amler, R.W.

    1995-05-01

    In Part 2 of this study, no difference was reported in the results of medical tests of the blood, liver, kidney, and immune systems of participants living in the two study areas. No relationships was found between exposure to cadmium and lead and the immune, liver, and blood system tests. No community wide medical action is needed in Palmerton based on the results of this study. No further site-specific health studies are recommended.

  19. Molecular change signal-to-noise criteria for interpreting experiments involving exposure of biological systems to weakly interacting electromagnetic fields.

    Science.gov (United States)

    Vaughan, Timothy E; Weaver, James C

    2005-05-01

    We describe an approach to aiding the design and interpretation of experiments involving biological effects of weakly interacting electromagnetic fields that range from steady (dc) to microwave frequencies. We propose that if known biophysical mechanisms cannot account for an inferred, underlying molecular change signal-to-noise ratio, (S/N)gen, of a observed result, then there are two interpretation choices: (1) there is an unknown biophysical mechanism with stronger coupling between the field exposure and the ongoing biochemical process, or (2) the experiment is responding to something other than the field exposure. Our approach is based on classical detection theory, the recognition that weakly interacting fields cannot break chemical bonds, and the consequence that such fields can only alter rates of ongoing, metabolically driven biochemical reactions, and transport processes. The approach includes both fundamental chemical noise (molecular shot noise) and other sources of competing chemical change, to be compared quantitatively to the field induced change for the basic case that the field alters a single step in a biochemical network. Consistent with pharmacology and toxicology, we estimate the molecular dose (mass associated with field induced molecular change per mass tissue) resulting from illustrative low frequency field exposures for the biophysical mechanism of voltage gated channels. For perspective, we then consider electric field-mediated delivery of small molecules across human skin and into individual cells. Specifically, we consider the examples of iontophoretic and electroporative delivery of fentanyl through skin and electroporative delivery of bleomycin into individual cells. The total delivered amount corresponds to a molecular change signal and the delivery variability corresponds to generalized chemical noise. Viewed broadly, biological effects due to nonionizing fields may include animal navigation, medical applications, and environmental

  20. Biological monitoring of pyrethroid exposure of pest control workers in Japan.

    Science.gov (United States)

    Wang, Dong; Kamijima, Michihiro; Imai, Ryota; Suzuki, Takayoshi; Kameda, Yohei; Asai, Kazumi; Okamura, Ai; Naito, Hisao; Ueyama, Jun; Saito, Isao; Nakajima, Tamie; Goto, Masahiro; Shibata, Eiji; Kondo, Takaaki; Takagi, Kenji; Takagi, Kenzo; Wakusawa, Shinya

    2007-11-01

    Synthetic pyrethroids such as cypermethrin, deltamethrin and permethrin, which are usually used in pest control operations, are metabolized to 3-phenoxybenzoic acid (3-PBA) and excreted in urine. Though 3-PBA can be used to assess exposure to pyrethroids, there are few reports describing urinary 3-PBA levels in Japan. This study aimed to investigate the seasonal variation of the exposure levels of pyrethroids and the concentration of urinary 3-PBA among pest control operators (PCOs) in Japan. The study subjects were 78 and 66 PCOs who underwent a health examination in December 2004 and in August 2005, respectively. 3-PBA was determined using gas chromatography-mass spectrometry. The geometric mean concentration of urinary 3-PBA in winter (3.9 microg/g creatinine) was significantly lower than in summer (12.2 microg/g creatinine) (p0.05), respectively. A significant association of 3-PBA levels and pyrethroid spraying was thus observed only in winter. In conclusion, the results of the present study show that the exposure level of pyrethroids among PCOs in Japan assessed by monitoring urinary 3-PBA was higher than that reported in the UK but comparable to that in Germany. Further research should be accumulated to establish an occupational reference value in Japan.

  1. Occupational exposure and biological evaluation of lead in Iranian workers-a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Kourosh Sayehmiri

    2016-09-01

    Full Text Available Introduction: Lead exposure is considered as a global health problem. The irreparable harmful effects of this heavy metal on human have been proven in various studies. Comparing to general population, workers in related industries are more exposed to lead. Several studies have investigated lead occupational exposure and its biological evaluation in Iran; however there is no overall estimate. Thus, the present study was conducted to determine the occupational exposure to lead and its biological evaluation in Iranian workers, using systematic review and meta-analysis. Material and Method: This study was carried out based on information obtained from databases including Magiran, Iranmedex, SID, Medlib, Trials Register, Scopus, Pubmed, Science Direct, Cochran, Embase, Medline, Web of Science, Springer, Online Library Wiley, and Google Scholar from 1991 to 2016, using standard key words. All of the reviewed papers which met the inclusion criteria have been evaluated. Data combination was performed according to Random Effects Model using Stata software version 11.1. Result: In the 34 qualified studies, the mean blood lead level (BLL concentration in Iranian workers was estimated 42.8µg/dl (95% CI: 35.15-50.49. The minimum and maximum BLL were belonged to west (28.348µg/dl and center (45.928µg/dl regions of Iran, respectively. Considering different occupations, the lowest mean value was reported in textile industry workers (12.3 µg/dl, while the highest value was for zinc-lead mine workers (72.6 µg/dl. Mean breathing air lead level of Iranian workers reported in 4 studies was estimated 0.23 mg/m3 (95% CI: 0.14-0.33. Conclusion: According to the high concentration of BLL and breathing air, it is recommended to increase protective measures and frequent screening. Scheduled clinical and paraclinical examination should also be performed for workers.

  2. Occupational cosmic radiation exposure in Portuguese airline pilots: study of a possible correlation with oxidative biological markers.

    Science.gov (United States)

    Silva, Rodrigo; Folgosa, Filipe; Soares, Paulo; Pereira, Alice S; Garcia, Raquel; Gestal-Otero, Juan Jesus; Tavares, Pedro; Gomes da Silva, Marco D R

    2013-05-01

    Several studies have sought to understand the health effects of occupational exposure to cosmic radiation. However, only few biologic markers or associations with disease outcomes have so far been identified. In the present study, 22 long- and 26 medium-haul male Portuguese airline pilots and 36 factory workers who did not fly regularly were investigated. The two groups were comparable in age and diet, were non-smokers, never treated with ionizing radiation and other factors. Cosmic radiation exposure in pilots was quantified based on direct monitoring of 51 flights within Europe, and from Europe to North and South America, and to Africa. Indirect dose estimates in pilots were performed based on the SIEVERT (Système informatisé d'évaluation par vol de l'exposition au rayonnement cosmique dans les transports aériens) software for 6,039 medium- and 1,366 long-haul flights. Medium-haul pilots had a higher cosmic radiation dose rate than long-haul pilots, that is, 3.3 ± 0.2 μSv/h and 2.7 ± 0.3 μSv/h, respectively. Biological tests for oxidative stress on blood and urine, as appropriate, at two time periods separated by 1 year, included measurements of antioxidant capacity, total protein, ferritin, hemoglobin, creatinine and 8-hydroxy-2-deoxyguanosine (8OHdG). Principal components analysis was used to discriminate between the exposed and unexposed groups based on all the biological tests. According to this analysis, creatinine and 8OHdG levels were different for the pilots and the unexposed group, but no distinctions could be made among the medium- and the long-haul pilots. While hemoglobin levels seem to be comparable between the studied groups, they were directly correlated with ferritin values, which were lower for the airline pilots.

  3. Barrier function and natural moisturizing factor levels after cumulative exposure to a fruit-derived organic acid and a detergent: different outcomes in atopic and healthy skin and relevance for occupational contact dermatitis in the food industry.

    Science.gov (United States)

    Angelova-Fischer, Irena; Hoek, Anne-Karin; Dapic, Irena; Jakasa, Ivone; Kezic, Sanja; Fischer, Tobias W; Zillikens, Detlef

    2015-12-01

    Fruit-derived organic compounds and detergents are relevant exposure factors for occupational contact dermatitis in the food industry. Although individuals with atopic dermatitis (AD) are at risk for development of occupational contact dermatitis, there have been no controlled studies on the effects of repeated exposure to multiple irritants, relevant for the food industry, in atopic skin. The aim of the study was to investigate the outcomes of repeated exposure to a fruit-derived organic acid and a detergent in AD compared to healthy volunteers. The volunteers were exposed to 2.0% acetic acid (AcA) and/or 0.5% sodium lauryl sulfate (SLS) in controlled tandem repeated irritation test. The outcomes were assessed by measurements of erythema, transepidermal water loss (TEWL) and natural moisturizing factor (NMF) levels. In the AD volunteers, repeated AcA exposure led to barrier disruption and significant TEWL increase; no significant differences after the same exposure in the healthy controls were found. Repeated exposure to SLS and the irritant tandems enhanced the reactions and resulted in a significantly higher increase in TEWL in the AD compared to the control group. Cumulative irritant exposure reduced the NMF levels in both groups. Differences in the severity of irritant-induced barrier impairment in atopic individuals contribute to the risk for occupational contact dermatitis in result of multiple exposures to food-derived irritants and detergents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Exposures of zebrafish through diet to three environmentally relevant mixtures of PAHs produce behavioral disruptions in unexposed F1 and F2 descendant.

    Science.gov (United States)

    Vignet, Caroline; Joassard, Lucette; Lyphout, Laura; Guionnet, Tiphaine; Goubeau, Manon; Le Menach, Karyn; Brion, François; Kah, Olivier; Chung, Bon-Chu; Budzinski, Hélène; Bégout, Marie-Laure; Cousin, Xavier

    2015-11-01

    The release of polycyclic aromatic hydrocarbons (PAHs) into the environment has increased very substantially over the last decades. PAHs are hydrophobic molecules which can accumulate in high concentrations in sediments acting then as major secondary sources. Fish contamination can occur through contact or residence nearby sediments or though dietary exposure. In this study, we analyzed certain physiological traits in unexposed fish (F1) issued from parents (F0) exposed through diet to three PAH mixtures at similar and environmentally relevant concentrations but differing in their compositions. For each mixture, no morphological differences were observed between concentrations. An increase in locomotor activity was observed in larvae issued from fish exposed to the highest concentration of a pyrolytic (PY) mixture. On the contrary, a decrease in locomotor activity was observed in larvae issued from heavy oil mixture (HO). In the case of the third mixture, light oil (LO), a reduction of the diurnal activity was observed during the setup of larval activity. Behavioral disruptions persisted in F1-PY juveniles and in their offspring (F2). Endocrine disruption was analyzed using cyp19a1b:GFP transgenic line and revealed disruptions in PY and LO offspring. Since no PAH metabolites were dosed in larvae, these findings suggest possible underlying mechanisms such as altered parental signaling molecule and/or hormone transferred in the gametes, eventually leading to early imprinting. Taken together, these results indicate that physiological disruptions are observed in offspring of fish exposed to PAH mixtures through diet.

  5. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  6. Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array.

    Science.gov (United States)

    Price, Magda E; Cotton, Allison M; Lam, Lucia L; Farré, Pau; Emberly, Eldon; Brown, Carolyn J; Robinson, Wendy P; Kobor, Michael S

    2013-03-03

    Measurement of genome-wide DNA methylation (DNAm) has become an important avenue for investigating potential physiologically-relevant epigenetic changes. Illumina Infinium (Illumina, San Diego, CA, USA) is a commercially available microarray suite used to measure DNAm at many sites throughout the genome. However, it has been suggested that a subset of array probes may give misleading results due to issues related to probe design. To facilitate biologically significant data interpretation, we set out to enhance probe annotation of the newest Infinium array, the HumanMethylation450 BeadChip (450 k), with >485,000 probes covering 99% of Reference Sequence (RefSeq) genes (National Center for Biotechnology Information (NCBI), Bethesda, MD, USA). Annotation that was added or expanded on includes: 1) documented SNPs in the probe target, 2) probe binding specificity, 3) CpG classification of target sites and 4) gene feature classification of target sites. Probes with documented SNPs at the target CpG (4.3% of probes) were associated with increased within-tissue variation in DNAm. An example of a probe with a SNP at the target CpG demonstrated how sample genotype can confound the measurement of DNAm. Additionally, 8.6% of probes mapped to multiple locations in silico. Measurements from these non-specific probes likely represent a combination of DNAm from multiple genomic sites. The expanded biological annotation demonstrated that based on DNAm, grouping probes by an alternative high-density and intermediate-density CpG island classification provided a distinctive pattern of DNAm. Finally, variable enrichment for differentially methylated probes was noted across CpG classes and gene feature groups, dependant on the tissues that were compared. DNAm arrays offer a high-throughput approach for which careful consideration of probe content should be utilized to better understand the biological processes affected. Probes containing SNPs and non-specific probes may affect the

  7. Biological monitoring of exposure to polycyclic aromatic hydrocarbons by determination of unmetabolized compounds in urine.

    Science.gov (United States)

    Campo, Laura; Addario, Liliana; Buratti, Marina; Scibetta, Licia; Longhi, Omar; Valla, Carla; Cirla, Piero E; Martinotti, Irene; Foà, Vito; Fustinoni, Silvia

    2006-04-10

    In this paper we evaluated the possibility to assess occupational exposure to polycyclic aromatic hydrocarbons (PAHs) measuring unmetabolized PAHs in urine. With this aim, 24 road paving (RP) workers, exposed to bitumen fumes, and 6 road construction workers (CW), exposed to diesel exhausts, were investigated. Median personal exposure to low boiling PAHs (from naphthalene to pyrene) during the work shift ranged from 0.5 to 369 ng/m(3), with naphthalene as the most abundant compound. Three urine samples were collected for each worker: baseline (after 2 days of vacation), before- and end-shift samples (in the second part of the work week). The following urinary compounds were measured by headspace-solid phase microextraction GC/MS: naphthalene (U-NAP), acenaphthylene (U-ACY), acenaphthene (U-ACE), fluorene (U-FLE), phenanthrene (U-PHE), anthracene (U-ANT), fluoranthene (U-FLU), pyrene (U-PYR). Urinary PAHs were detected in almost all samples. Median levels for U-NAP, U-PHE, U-PYR and U-FLE in end-shift samples were 82, 48, 54 and 21 ng/L in RP and 69, 14, 24 and 15 ng/L in CW, respectively. Significant differences in the levels of U-PHE, U-FLU and U-PYR were found between RP and CW (p<0.05). Moreover in RP samples the urinary excretion of most analytes increased during the work shift (p<0.05). These results suggest that urinary PAHs may be useful biomarkers of occupational exposure.

  8. UV effects on the primary productivity of picophytoplankton: biological weighting functions and exposure response curves of Synechococcus

    Science.gov (United States)

    Neale, P. J.; Pritchard, A. L.; Ihnacik, R.

    2014-05-01

    A model that predicts UV effects on marine primary productivity using a biological weighting function (BWF) coupled to the photosynthesis-irradiance response (BWF/P-E model) has been implemented for two strains of the picoplanktonic cyanobacteria Synechococcus, WH7803 and WH8102, which were grown at two irradiances (77 and 174 μmol m-2 s-1 photosynthetically available radiation (PAR)) and two temperatures (20 and 26 °C). The model was fit using photosynthesis measured in a polychromatic incubator with 12 long-pass filter configurations with 50% wavelength cutoffs ranging from 291 to 408 nm, giving an effective wavelength range of 280-400 nm. Examination of photosynthetic response vs. weighted exposure revealed that repair rate progressively increases at low exposure but reaches a maximum rate above a threshold exposure ("Emax"). Adding Emax as a parameter to the BWF/P-E model provided a significantly better fit to Synechococcus data than the existing "E" or "T" models. Sensitivity to UV inhibition varied with growth conditions for both strains, but this was mediated mainly by variations in Emax for WH8102 while both the BWF and Emax changed for WH7803. Higher growth temperature was associated with a considerable reduction in sensitivity, consistent with an important role of repair in regulating sensitivity to UV. Based on nominal water column conditions (noon, solstice, 23° latitude, "blue" water), the BWFEmax/P-E model estimates that UV + PAR exposure inhibits Synechococcus photosynthesis from 78 to 91% at 1 m, and integrated productivity to 150 m 17-29% relative to predicted rates in the absence of inhibition.

  9. Chemical and biological risk assessment of chronic exposure to PAH contaminated sediments

    Energy Technology Data Exchange (ETDEWEB)

    Means, J.; McMillin, D.; Kondapi, N. [Louisiana State Univ., Baton Rouge, LA (United States)

    1995-12-31

    Chronically contaminated sediments represent a long-term source of mixtures of contaminants, exposing aquatic ecosystems to PAH through desorption and bioaccumulation. Chronic toxicity assessments must address potential of these bond contaminants. Environmental impacts and ecological health hazards of sediment-bound normal, alkylated and heterocyclic aromatic hydrocarbons are functions of their entry into aquatic food webs and are controlled by both abiotic and biotic factors. Laboratory and field microcosm exposures of fish and invertebrates were conducted followed by assessments of effects using chemical analysis and biomarkers of potential genotoxic effects. Chemical analysis of accumulated residues of 62 individual PAH were conducted in oysters, Crassostrea virginica exposed to PAH contaminated sediments in the field. The rates and equilibrium bioaccumulation constants for each were determined. Fish were exposed to the same contaminated sediments in laboratory and field exposures. Measurements of ethoxy-resorufin-o-deethylase activity induction as well as alterations in the expression of the p53 tumor suppressor gene were performed on exposed fish liver samples. EROD activities were increased significantly relative to unexposed and laboratory/field control sediment-exposed fish, however, the responses of individuals were highly variable. Fundulus grandis or Gambusia affinis, exposed to contaminated sediments in the laboratory, revealed changes in the expression of the p53 tumor suppressor gene. The degree to which mutations within the gene occurred was assessed using PCR followed by measurement of single stranded DNA polymorphisms using gel electrophoresis chromatography.

  10. Catecholamines are the key for explaining the biological relevance of insulin-melatonin antagonisms in type 1 and type 2 diabetes.

    Science.gov (United States)

    Peschke, E; Hofmann, K; Pönicke, K; Wedekind, D; Mühlbauer, E

    2012-05-01

    In this paper, we analyze the biological relevance of melatonin in diabetogenesis. As has recently been demonstrated, melatonin decreases insulin secretion via specific melatonin receptor isoforms (MT1 and MT2) in the pancreatic β-cells. In addition, type 2 diabetic rats, as well as patients, exhibit decreased melatonin levels, whereas the levels in type 1 diabetic rats are increased. The latter effects were normalized by insulin substitution, which signifies that a specific receptor-mediated insulin-melatonin antagonism exists. These results are in agreement with several recent genome-wide association studies, which have identified a number of single nucleotide polymorphisms in the MTNR1B gene, encoding the MT2 receptor, that were closely associated with a higher prognostic risk of developing type 2 diabetes. We hypothesize that catecholamines, which decrease insulin levels and stimulate melatonin synthesis, control insulin-melatonin interactions. The present results support this assertion as we show that catecholamines are increased in type 1 but are diminished in type 2 diabetes. Another important line of inquiry involves the fact that melatonin protects the β-cells against functional overcharge and, consequently, hinders the development of type 2 diabetes. In this context, it is striking that at advanced ages, melatonin levels are reduced and the incidence of type 2 diabetes is increased. Thus, melatonin appears to have a protective biological role. Here, we strongly repudiate misconceptions, resulting from observations that melatonin reduces the plasma insulin level, that the blockage of melatonin receptors would be of benefit in the treatment of type 2 diabetes.

  11. Biological bases of the maximum permissible exposure levels of the UK laser standard BS 4803 1983

    CERN Document Server

    MacKinlay, Alistair F

    1983-01-01

    The use of lasers has increased greatly over the past 15 years or so, to the extent that they are now used routinely in many occupational and public situations. There has been an increasing awareness of the potential hazards presented by lasers and substantial efforts have been made to formulate safety standards. In the UK the relevant Safety Standard is the British Standards Institution Standard BS 4803. This Standard was originally published in 1972 and a revision has recently been published (BS 4803: 1983). The revised standard has been developed using the American National Standards Institute Standard, ANSI Z136.1 (1973 onwards), as a model. In other countries, national standards have been similarly formulated, resulting in a large measure of international agreement through participation in the work of the International Electrotechnical Commission (IEC). The bases of laser safety standards are biophysical data on threshold injury effects, particularly on the retina, and the development of theoretical mode...

  12. Biological stress responses induced by alpha radiation exposure in Lemna minor

    Energy Technology Data Exchange (ETDEWEB)

    Van Hoeck, A.; Horemans, N.; Van Hees, M.; Nauts, R. [Belgian Nuclear Research Centre SCK-CEN (Belgium); Knapen, D.; Blust, R. [University of Antwerp (Belgium)

    2014-07-01

    To enhance the robustness of radiation protection criteria for biota, additional information on the biological impact of radionuclides on non-human biota is needed. In particular the effects of alpha emitting isotopes have been poorly studied within a radioecological contextual though they exhibit a high linear energy transfer which can cause significant biological damage when taken up by organisms. Therefore, it is not only essential to measure alpha radiation toxicity, but also try to understand the underlying mechanisms of this stressor. The current study aimed to contribute to a better knowledge of the fundamental processes regulating alpha radiation stress response mechanisms in higher plants. {sup 241}Am was primarily selected as it is an almost pure alpha emitter and, as a daughter nuclide of {sup 241}Pu, it will become one of the dominant pollutants in plutonium affected areas. The aquatic macrophyte Lemna minor has proven its value in eco-toxicological research as representative of higher aquatic plants (OECD guideline nr. 221) and will be used to analyze alpha radiation stress in plant systems. An individual growth inhibition test was set up by means of single dose-response curve in order to identify the Effective Dose Rates (EDR-values) for frond size and biomass. As the mean path length is small for alpha particles, the accumulation of the radionuclide inside species represents almost exclusively the dosimetry. Therefore, quantification of {sup 241}Am uptake and {sup 241}Am distribution were evaluated separately for roots and fronds taking the activity concentrations of growth medium into account. Taken together with the respective dose conversion coefficients from the ERICA tool, this allowed to construct an accurate dosimetric model to determine internal and external dose rates. Different standard media were tested on growth rate and biomass to analyse the amount of {sup 241}Am taken up by the plants exposed from 2.5 to 100 kBq/L. From these

  13. Combined exposures: an update from the International Commission on Biological Effects of Noise.

    Science.gov (United States)

    Leroux, Tony; Klaeboe, Ronny

    2012-01-01

    International Commission on Biological Effects of Noise (ICBEN) Team 8 deals with the effects of combined "agents" in the urban and work place settings. Results presented at the ICBEN conference indicate that some pesticides, more specifically the organophosphates, and a wider range of industrial chemicals are harmful to the auditory system at concentrations often found in occupational settings. Effects of occupational noise on hearing are exacerbated by toluene and possibly by carbon monoxide. Several of the chemicals studied found to be potentially toxic not only to hair cells in the cochlea but also to the auditory nerve. In urban environments, team 8 focuses on additive and synergetic effects of ambient stressors. It was argued that noise policies need to pay attention to grey areas with intermediate noise levels. Noteworthy is also stronger reactions to vibrations experienced in the evening and during the night. An innovative event-based model for sound perception was presented.

  14. Activation of biologically relevant levels of reactive oxygen species by Au/g-C3N4 hybrid nanozyme for bacteria killing and wound disinfection.

    Science.gov (United States)

    Wang, Zhenzhen; Dong, Kai; Liu, Zhen; Zhang, Yan; Chen, Zhaowei; Sun, Hanjun; Ren, Jinsong; Qu, Xiaogang

    2017-01-01

    As common reactive oxygen species, H2O2 is widely used for bacterial inactivation and wound disinfection. However, the concentrations used are always higher than physiological levels, which frequently result in potential toxicity to healthy tissue and even delay wound healing. Here we report highly efficient nanozyme hybrids that are capable of activating biologically relevant concentrations of H2O2 for defending bacterial infections. The integration of AuNPs with ultrathin graphitic carbon nitride (g-C3N4) provides excellent peroxidase-activity, which can catalyze the decomposition of H2O2 to OH radicals much more efficiently, allowing the use of bio-safety levels of H2O2 for the first time. Furthermore, our system not only exhibits striking bactericidal performance against both DR Gram-negative and DR Gram-positive bacteria, but also shows high efficiency in breaking down the existing DR-biofilms and prevented formation of new biofilms in vitro. More importantly, in vivo experiments indicate that our system could significantly prevent bacterial infections and accelerate the healing rate of wounds.

  15. Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro-edenite.

    Science.gov (United States)

    Ledda, Caterina; Loreto, Carla; Pomara, Cristoforo; Rapisarda, Giuseppe; Fiore, Maria; Ferrante, Margherita; Bracci, Massimo; Santarelli, Lory; Fenga, Concettina; Rapisarda, Venerando

    2016-05-01

    A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanning electron microscopy (SEM) examination. The lymph-nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8-41µm in length and 0.4-1.39µm in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance.

  16. An experimental system for controlled exposure of biological samples to electrostatic discharges.

    Science.gov (United States)

    Marjanovič, Igor; Kotnik, Tadej

    2013-12-01

    Electrostatic discharges occur naturally as lightning strokes, and artificially in light sources and in materials processing. When an electrostatic discharge interacts with living matter, the basic physical effects can be accompanied by biophysical and biochemical phenomena, including cell excitation, electroporation, and electrofusion. To study these phenomena, we developed an experimental system that provides easy sample insertion and removal, protection from airborne particles, observability during the experiment, accurate discharge origin positioning, discharge delivery into the sample either through an electric arc with adjustable air gap width or through direct contact, and reliable electrical insulation where required. We tested the system by assessing irreversible electroporation of Escherichia coli bacteria (15 mm discharge arc, 100 A peak current, 0.1 μs zero-to-peak time, 0.2 μs peak-to-halving time), and gene electrotransfer into CHO cells (7 mm discharge arc, 14 A peak current, 0.5 μs zero-to-peak time, 1.0 μs peak-to-halving time). Exposures to natural lightning stroke can also be studied with this system, as due to radial current dissipation, the conditions achieved by a stroke at a particular distance from its entry are also achieved by an artificial discharge with electric current downscaled in magnitude, but similar in time course, correspondingly closer to its entry.

  17. SAR measurement due to mobile phone exposure in a simulated biological media.

    Science.gov (United States)

    Behari, J; Nirala, Jay Prakash

    2012-09-01

    The specific absorption rate (SAR) measurements are carried out for compliance testing of personal 3G Mobile phone. The accuracy of this experimental setup has been checked by comparing the SAR in 10 gm of simulated tissue and an arbitrary shaped box. This has been carried out using a 3G mobile Phone at 1718.5 MHz, in a medium simulating brain and muscle phantom. The SAR measurement system consists of a stepper motor to move a monopole E-field probe in two dimensions inside an arbitrary shaped box. The phantom is filled with appropriate frequency-specific fluids with measured electrical properties (dielectric constant and conductivity). That is close to the average for gray and white matters of the brain at the frequencies of interest (1718.5 MHz). Induced fields are measured using a specially designed monopole probe in its close vicinity. The probe is immersed in the phantom material. The measured data for induced fields are used to compute SAR values at various locations with respect to the mobile phone location. It is concluded that these SAR values are position dependent and well below the safety criteria prescribed for human exposure.

  18. Biological impact of high-dose and dose-rate radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Maliev, V.; Popov, D. [Russian Academy of Science, Vladicaucas (Russian Federation); Jones, J.; Gonda, S. [NASA -Johnson Space Center, Houston (United States); Prasad, K.; Viliam, C.; Haase, G. [Antioxida nt Research Institute, Premier Micronutrient Corporation, Novato (United States); Kirchin, V. [Moscow State Veterinary and Biotechnology Acade my, Moscow (Russian Federation); Rachael, C. [University Space Research Association, Colorado (United States)

    2006-07-01

    Experimental anti-radiation vaccine is a power tool of immune - prophylaxis of the acute radiation disease. Existing principles of treatment of the acute radiation dis ease are based on a correction of developing patho-physiological and biochemical processes within the first days after irradiation. Protection from radiation is built on the general principles of immunology and has two main forms - active and passive immunization. Active immunization by the essential radiation toxins of specific radiation determinant (S.D.R.) group allows significantly reduce the lethality and increase duration of life among animals that are irradiated by lethal and sub-lethal doses of gamma radiation.The radiation toxins of S.D.R. group have antigenic properties that are specific for different forms of acute radiation disease. Development of the specific and active immune reaction after intramuscular injection of radiation toxins allows optimize a manifestation of a clinical picture and stabilize laboratory parameters of the acute radiation syndromes. Passive immunization by the anti-radiation serum or preparations of immune-globulins gives a manifestation of the radioprotection effects immediately after this kind of preparation are injected into organisms of mammals. Providing passive immunization by preparations of anti-radiations immune-globulins is possible in different periods of time after radiation. Providing active immunization by preparations of S.D.R. group is possible only to achieve a prophylaxis goal and form the protection effects that start to work in 18 - 35 days after an injection of biological active S.D.R. substance has been administrated. However active and passive immunizations by essential anti-radiation toxins and preparations of gamma-globulins extracted from a hyper-immune serum of a horse have significantly different medical prescriptions for application and depend on many factors like a type of radiation, a power of radiation, absorption doses, a time of

  19. Integration of biological monitoring, environmental monitoring and computational modelling into the interpretation of pesticide exposure data: introduction to a proposed approach.

    Science.gov (United States)

    Colosio, Claudio; Rubino, Federico M; Alegakis, Athanasios; Ariano, Eugenio; Brambilla, Gabri; Mandic-Rajcevic, Stefan; Metruccio, Francesca; Minoia, Claudio; Moretto, Angelo; Somaruga, Chiara; Tsatsakis, Aristidis; Turci, Roberta; Vellere, Francesca

    2012-08-13

    Open field, variability of climatic and working conditions, and the use of complex mixtures of pesticides makes biological and environmental monitoring in agriculture, and therefore risk assessment and management, very complicated. A need of pointing out alternative risk assessment approaches, not necessarily based on measures, but simple, user-friendly and reliable, feasible also in the less advanced situations and in particular in small size enterprises, arises. This aim can be reached through a combination of environmental monitoring, biological monitoring and computational modelling. We have used this combination of methods for the creation of "exposure and risk profiles" to be applied in specific exposure scenarios, and we have tested this approach on a sample of Italian rice and maize herbicide applicators. We have given specific "toxicity scores" to the different products used and we have identified, for each of the major working phases, that is mixing and loading, spraying, maintenance and cleaning of equipment, the main variables affecting exposure and inserted them into a simple algorithm, able to produce "exposure indices". Based on the combination of toxicity indices and exposure indices it is possible to obtain semiquantitative estimates of the risk levels experienced by the workers in the exposure scenarios considered. Results of operator exposure data collected under real-life conditions can be used to validate and refine the algorithms; moreover, the AOEL derived from pre-marketing studies can be combined to estimate tentative biological exposure limits for pesticides, useful to perform individual risk assessment based on technical surveys and on simple biological monitoring. A proof of principle example of this approach is the subject of this article.

  20. Clinically relevant hydrogel-based on hyaluronic acid and platelet rich plasma as a carrier for mesenchymal stem cells: Rheological and biological characterization.

    Science.gov (United States)

    Vadalà, Gianluca; Russo, Fabrizio; Musumeci, Maria; D'Este, Matteo; Cattani, Caterina; Catanzaro, Giuseppina; Tirindelli, Maria Cristina; Lazzari, Lorenza; Alini, Mauro; Giordano, Rosaria; Denaro, Vincenzo

    2016-12-26

    Intervertebral disc regeneration is quickly moving towards clinical applications. However, it is still missing an ideal injectable hydrogel to support mesenchymal stem cells (MSC) delivery. Herein, a new injectable hydrogel composed of platelet rich plasma (PRP) and hyaluronic acid (HA) blended with batroxobin (BTX) as gelling agent, was designed to generate a clinically relevant cell carrier for disc regeneration. PRP/HA/BTX blend was tested for rheological properties. Amplitude sweep, frequency sweep, and rotational measurements were performed and viscoelastic properties were evaluated. Human MSC encapsulated in PRP/HA/BTX hydrogel were cultured in both growing medium and medium with or without TGF-β1 up to day 21. The amount of glycosaminoglycan was evaluated. Quantitative gene expression evaluation for collagen type II, aggrecan, and Sox 9 was also performed. Rheological tests showed that the hydrogel jellifies in 15 min 20°C and in 3 min at 37°C. Biological test showed that MSCs cultured in the hydrogel maintain high cell viability and proliferation. Human MSC within the hydrogel cultured with or without TGF-β1 showed significantly higher GAG production compared to control medium. Moreover, MSCs in the hydrogel underwent differentiation to chondrocyte-like cells with TGF-β1, as shown by histology and gene expression analysis. This novel hydrogel improves viability and proliferation of MSCs supporting the differentiation process toward chondrocyte-like cells. Rheology tests showed optimal gelation kinetics at room temperature for manipulation and faster gelation after transplantation (37°C). The clinical availability of all components of the hydrogel will allow a rapid translation of this regenerative approach into the clinical scenario. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Effect of Organic Solvents and Biologically Relevant Ions on the Light-Induced DNA Cleavage by Pyrene and Its Amino and Hydroxy Derivatives

    Directory of Open Access Journals (Sweden)

    Hongtao Yu

    2002-09-01

    Full Text Available Abstract: Polycyclic aromatic hydrocarbons (PAHs are a class of carcinogenic compounds that are both naturally and artificially produced. Many PAHs are pro-carcinogens that require metabolic activation. Recently, it has been shown that PAH can induce DNA single strand cleavage and formation of PAH-DNA covalent adduct upon irradiation with UVA light. The light-induced DNA cleavage parallels phototoxicity in one instance. The DNA photocleavage efficiency depends on the structure of the PAHs. This article reports the effect of both organic solvents and the presence of biologically relevant ions, Na+, Mg2+, Ca2+, K+, Fe3+, Cu2+, Zn+2, Mn2+, and I-, on the light-induced DNA cleavage by pyrene, 1-hydroxypyrene and 1-aminopyrene. Since both 1-hydroxypyrene (0.6 μM and 1-aminopyrene (6 μM dissolve well in the minimum organic solvents used (2% methanol, dimethylsulfoxide, and dimethylformamide, increasing the amount of the organic solvent resulted in the decrease of the amount of DNA single strand cleavage caused by the combination effect of 1-hydroxy or 1-aminopyrene and UVA light. The result with the less watersoluble pyrene shows that increase of the amount of the organic solvent can increase the amount of DNA single strand DNA photocleavage cause by the combination of pyrene and UVA light. Therefore, there are two effects by the organic solvents: (i to dissolve PAH and (ii to quench DNA photocleavage. The presence of Fe3+ and Zn2+ enhances, while the presence of Ca2+ and Mn2+ inhibits the DNA photocleavage caused by 1-aminopyrene and UVA light. Other metal ions have minimal effect. This means that the effect of ions on DNA photocleavage by PAHs is complex. The presence of KI enhances DNA photocleavage. This indicates that the triplet-excited state of 1-aminopyrene is involved in causing DNA cleavage

  2. Discovery of Anti-inflammatory Ingredients in Chinese Herbal Formula Kouyanqing Granule based on Relevance Analysis between Chemical Characters and Biological Effects.

    Science.gov (United States)

    Liu, Hong; Zheng, Yan-fang; Li, Chu-yuan; Zheng, Yu-ying; Wang, De-qin; Wu, Zhong; Huang, Lin; Wang, Yong-gang; Li, Pei-bo; Peng, Wei; Su, Wei-wei

    2015-12-10

    Kouyanqing Granule (KYQG) is a traditional Chinese herbal formula composed of Flos lonicerae (FL), Radix scrophulariae (RS), Radix ophiopogonis (RO), Radix asparagi (RA), and Radix et rhizoma glycyrrhizae (RG). In contrast with the typical method of separating and then biologicalily testing the components individually, this study was designed to establish an approach in order to define the core bioactive ingredients of the anti-inflammatory effects of KYQG based on the relevance analysis between chemical characters and biological effects. Eleven KYQG samples with different ingredients were prepared by changing the ratios of the 5 herbs. Thirty-eight ingredients in KYQG were identified using Ultra-fast liquid chromatography-Diode array detector-Quadrupole-Time-of-flight-Tandem mass spectrometry (UFLC-DAD-Q-TOF-MS/MS) technology. Human oral keratinocytes (HOK) were cultured for 24 hours with 5% of Cigarette smoke extract (CSE) to induce inflammation stress. Interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumour necrosis factor-α (TNF-α) were evaluated after treatment with the eleven KYQG samples. Grey relational analysis(GRA), Pearson's correlations (PCC), and partial least-squares (PLS) were utilized to evaluate the contribution of each ingredient. The results indicated that KYQG significantly reduced interleukin-1β, interleukin-6, interleukin-8, and tumour necrosis factor-α levels, in which lysine, γ-aminobutyric acid, chelidonic acid, tyrosine, harpagide, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isoquercitrin, luteolin-7-o-glucoside, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, angoroside C, harpagoside, cinnamic acid, and ruscogenin play a vital role.

  3. Beta-defensin-2 protein is a serum biomarker for disease activity in psoriasis and reaches biologically relevant concentrations in lesional skin.

    Directory of Open Access Journals (Sweden)

    Patrick A M Jansen

    Full Text Available BACKGROUND: Previous studies have extensively documented antimicrobial and chemotactic activities of beta-defensins. Human beta-defensin-2 (hBD-2 is strongly expressed in lesional psoriatic epidermis, and recently we have shown that high beta-defensin genomic copy number is associated with psoriasis susceptibility. It is not known, however, if biologically and pathophysiologically relevant concentrations of hBD-2 protein are present in vivo, which could support an antimicrobial and proinflammatory role of beta-defensins in lesional psoriatic epidermis. METHODOLOGY/PRINCIPAL FINDINGS: We found that systemic levels of hBD-2 showed a weak but significant correlation with beta defensin copy number in healthy controls but not in psoriasis patients with active disease. In psoriasis patients but not in atopic dermatitis patients, we found high systemic hBD-2 levels that strongly correlated with disease activity as assessed by the PASI score. Our findings suggest that systemic levels in psoriasis are largely determined by secretion from involved skin and not by genomic copy number. Modelling of the in vivo epidermal hBD-2 concentration based on the secretion rate in a reconstructed skin model for psoriatic epidermis provides evidence that epidermal hBD-2 levels in vivo are probably well above the concentrations required for in vitro antimicrobial and chemokine-like effects. CONCLUSIONS/SIGNIFICANCE: Serum hBD-2 appears to be a useful surrogate marker for disease activity in psoriasis. The discrepancy between hBD-2 levels in psoriasis and atopic dermatitis could explain the well known differences in infection rate between these two diseases.

  4. The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals : A simulation study

    NARCIS (Netherlands)

    Vermeer, Niels S.; Ebbers, Hans C.; Straus, Sabine M J M; Leufkens, Hubert G M; Egberts, Toine C G; De Bruin, Marie L.

    2016-01-01

    Background and Objective: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR) re

  5. Evaluation of perturbations in serum thyroid hormones during human pregnancy due to dietary iodide and perchlorate exposure using a biologically based dose-response model.

    Science.gov (United States)

    Lumen, Annie; Mattie, David R; Fisher, Jeffrey W

    2013-06-01

    A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 µg/day and an environmentally relevant exposure of perchlorate (~0.1 µg/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 µg/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32.2 µg/kg/day. As iodide intake was lowered to 75 µg/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 µg/kg/day for daily iodide intake of 250-75 µg/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.

  6. Self-reported Occupational Exposures Relevant for Cancer among 28,000 Offshore Oil Industry Workers Employed between 1965 and 1999.

    Science.gov (United States)

    Stenehjem, Jo S; Friesen, Melissa C; Eggen, Tone; Kjærheim, Kristina; Bråtveit, Magne; Grimsrud, Tom K

    2015-01-01

    The objective of this study was to examine self-reported frequency of occupational exposure reported by 28,000 Norwegian offshore oil workers in a 1998 survey. Predictors of self-reported exposure frequency were identified to aid future refinements of an expert-based job-exposure-time matrix (JEM). We focus here on reported frequencies for skin contact with oil and diesel; exposure to oil vapor from shaker, to exhaust fumes, vapor from mixing chemicals used for drilling, natural gas, chemicals used for water injection and processing, and to solvent vapor. Exposure frequency was reported by participants as the exposed proportion of the work shift, defined by six categories, in their current or last position offshore (between 1965 and 1999). Binary Poisson regression models with robust variance were used to examine the probabilities of reporting frequent exposure (≥¼ vs. <¼ of work shift) according to main activity, time period, supervisory position, type of company, type of installation, work schedule, and education. Holding a non-supervisory position, working shifts, being employed in the early period of the offshore industry, and having only compulsory education increased the probability of reporting frequent exposure. The identified predictors and group-level patterns may aid future refinement of the JEM previously developed for the present cohort.

  7. Reactions of potent antitumor complex trans-[Ru(III)Cl4(indazole)2]- with a DNA-relevant nucleobase and thioethers: insight into biological action.

    Science.gov (United States)

    Egger, Alexander; Arion, Vladimir B; Reisner, Erwin; Cebrián-Losantos, Berta; Shova, Sergiu; Trettenhahn, Günter; Keppler, Bernhard K

    2005-01-10

    Reactions of the complex trans-[RuCl(4)(Hind)(2)](-) (Hind = indazole), which is of clinical relevance today, with both the DNA model nucleobase 9-methyladenine (made) and the thioethers R(2)S (R = Me, Et), as models of the methionine residue in biological molecules possibly acting as nitrogen-competing sulfur-donor ligands for ruthenium atom, have been investigated to get insight into details of mechanism leading to antitumor activity. Three novel ruthenium complexes, viz., [Ru(III)Cl(3)(Hind)(2)(made)], 1, [Ru(II)Cl(2)(Hind)(2)(Me(2)S)(2)], 2, and [Ru(II)Cl(2)(Hind)(2)(Et(2)S)(2)], 3, have been isolated as solids. Oxidation of 2 and 3 with hydrogen peroxide in the presence of 12 M HCl in chloroform afforded the monothioether adducts, viz., [Ru(III)Cl(3)(Hind)(2)(Me(2)S)], 4, and [Ru(III)Cl(3)(Hind)(2)(Et(2)S)], 5. By dissolution of 2 or 3 in DMSO, replacement of both R(2)S ligands by DMSO molecules occurred with isolation of trans,trans,trans-[Ru(II)Cl(2)(Hind)(2)(DMSO)(2)], 6. The products were characterized by elemental analysis, IR, UV-vis, electrospray mass spectrometry, cyclic voltammetry, and X-ray crystallography (1.CH(2)Cl(2).CH(3)OH and 1.1.1H(2)O.0.9CH(3)OH, 2, and 5). The first crystallographic evidence for the monofunctional coordination of the 9-methyladenine ligand to ruthenium via N7 and the self-pairing of the complex molecules via H-bonding, using the usual Watson-Crick pairing donor and acceptor sites of two adjacent 9-methyladenine ligands, is reported. The electrochemical behavior of 1-5 has been studied in DMF and DMSO by cyclic voltammetry. The redox potential values have been interpreted on the basis of the Lever's parametrization method. The E(L) parameter was estimated for 9-methyladenine at 0.18 V, showing that this ligand behaves as a weaker net electron donor than imidazole (E(L) = 0.12 V). The kinetics of the reductively induced stepwise replacement of chlorides by DMF in 4 and 5 were studied by digital simulation of the cyclic

  8. Biological monitoring of dermal and air exposure to cobalt at a Swedish hard metal production plant: does dermal exposure contribute to uptake?

    Science.gov (United States)

    Klasson, Maria; Lindberg, Magnus; Bryngelsson, Ing-Liss; Arvidsson, Helena; Pettersson, Carin; Husby, Bente; Westberg, Håkan

    2017-10-01

    Occupational exposure to cobalt is well established in hard metal manufacture. Cobalt is known to cause contact allergy, asthma, hard metal lung disease, and lung cancer. The relationship between skin exposure and uptake determined in blood has not been extensively investigated. To examine whether skin and inhalable air exposure to cobalt contributes to uptake, determined as cobalt in blood, in a hard metal manufacturing factory. The amount of cobalt on the skin found with an acid wash technique, the air concentrations of inhalable cobalt and cobalt blood concentrations were determined and correlated in exposed workers. We found a significant rank correlation for cobalt concentrations on the skin, in inhalable air, and in blood (0.376-0.498). Multiple linear regression showed significant regression coefficients for cobalt skin exposure and blood (B = 0.01, p exposure levels at different air concentrations caused a 3-14% increase in blood levels. Our data suggest that skin exposure to cobalt in the hard metal industry could affect the total uptake at the same order of magnitude as air exposure. © 2017 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.

  9. Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.

    Science.gov (United States)

    Fracchiolla, Nicola Stefano; Todoerti, Katia; Bertazzi, Pier Alberto; Servida, Federica; Corradini, Paolo; Carniti, Cristiana; Colombi, Antonio; Cecilia Pesatori, Angela; Neri, Antonino; Deliliers, Giorgio Lambertenghi

    2011-04-28

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic diseases, diabetes, infertility, cancers and immunotoxicity. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 257 differentially modulated probe sets, identifying 221 well characterized genes. A large part of these resulted associated to cell adhesion and/or angiogenesis and to transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems. Our data support a role of dioxin in the neoplastic transformation of hemopoietic stem cells and in immune modulation processes after in vivo exposure, as indicated by the epidemiologic data in dioxin accidentally exposed populations, providing a molecular basis for it. In addition, TCDD alters genes associated to glucidic and lipidic metabolisms, to GABAergic transmission or involved in male and female fertility, thus providing a possible explanation of the diabetogenic, dyslipidemic, neurologic and fertility effects induced by TCDD in vivo exposure.

  10. An occupational hygiene investigation of exposure to acrylamide and the role for urinary S-carboxyethyl-cysteine (CEC) as a biological marker.

    Science.gov (United States)

    Bull, Peter J; Brooke, Richard K; Cocker, John; Jones, Katharine; Warren, Nicholas

    2005-11-01

    Acrylamide has a range of toxicological hazards including neurotoxicity and reproductive toxicity; however, occupational risk management is driven by its genotoxic and carcinogenic potential (it is classified within the EU as a Category 2 carcinogen, R45 and Category 2 mutagen, R46). Since there is the potential for skin absorption and systemic toxicity, biological monitoring may be a useful aid for the assessment of exposure via inhalation, ingestion and dermal absorption. However, there are currently no biological monitoring guidance values (BMGVs). This study describes an extensive survey of potential workplace exposure to acrylamide at the Ciba (Bradford) site to gather data suitable for a BMGV. This manufacturing site is typical within the industry as a whole and includes a cross section of activities and tasks representative of acrylamide exposure. Acrylamide is used in the manufacture of polyacrylamide based products for applications in water treatment; oil and mineral extraction; paper, paint and textile processes. Workers (62 plus 6 controls) with varying potential exposures provided a total of 275 pre shift and 247 post-shift urine samples along with 260 personal air samples. A small non-exposed control group was similarly monitored. Urine samples were analysed for S-carboxyethyl-cysteine (CEC). Airborne, surface and glove samples were analysed for acrylamide. Inhalation exposures were well controlled with values consistently below one-tenth of the UK Workplace Exposure Limit. Engineering controls, personal protective equipment and work practice, all contributed to good control of occupational exposure. CEC was found in urine samples from both exposed workers and non-occupationally exposed controls. At the low levels of exposure found, smoking made a significant contribution to urinary CEC levels. Nevertheless a correlation between urinary CEC and airborne acrylamide was found. A mixed effects model incorporating inhalation concentrations of acrylamide

  11. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure

    Science.gov (United States)

    Henderson, Thomas; Nilles, Matthew L.; Kwilas, Steve A.; Josleyn, Matthew D.; Hammerbeck, Christopher D.; Schiltz, James; Royals, Michael; Ballantyne, John; Hooper, Jay W.; Bradley, David S.

    2015-01-01

    Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product

  12. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

    Directory of Open Access Journals (Sweden)

    Nicole Haese

    biological product capable of preventing a lethal disease when administered post-exposure.

  13. Chromosomal analysis and application of biological dosimetry in two cases of apparent over exposure; Analisis cromosomico y aplicacion de la dosimetria biologica en dos casos de aparente sobreexposicion

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Brena V, M. [Departamento de Biologia, ININ A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    2002-07-01

    The gamma radiation calibration curve of {sup 60} Co is used which was generated in the ININ Laboratory of Biology to calculate the exposure dose of two workers whose dosemeters marked values above of the limit allowed. The analysis indicates that in a first case, the aberrations frequency corresponded to the basal value, therefore there is not over exposure. The aberrations frequency of the second case is lightly above to the basal value and therefore the probability favors to what the physical dosimetry indicates. (Author)

  14. Exposure to perfluorononanoic acid combined with a low-dose mixture of 14 human-relevant compounds disturbs energy/lipid homeostasis in rats

    DEFF Research Database (Denmark)

    Skov, Kasper; Kongsbak, Kristine Grønning; Hadrup, Niels

    2015-01-01

    differentially affected across study groups. In the liver, expression of 182 and 203 genes—mainly related to energy homeostasis and lipid metabolism—were differentially expressed upon exposure to PFNA alone or PFNA + Mix, respectively. In general, Mix alone affected lipid metabolism evident in blood plasma.......0125 mg/kg/day) or mid (0.25 mg/kg/day) doses, or a combination of Mix and PFNA. In blood plasma, 63 and 64 metabolites were significantly changed upon exposure to Mix alone or PFNA + Mix, respectively. Twelve of the metabolites were identified and comprised mainly lipids, with various lipid classes...

  15. Prenatal exposure to a polychlorinated biphenyl (PCB congener influences fixation duration on biological motion at 4-months-old: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Hirokazu Doi

    Full Text Available Adverse effects of prenatal exposure to polychlorinated biphenyl (PCB congeners on postnatal brain development have been reported in a number of previous studies. However, few studies have examined the effects of prenatal PCB exposure on early social development. The present study sought to increase understanding of the neurotoxicity of PCBs by examining the relationship between PCB congener concentrations in umbilical cord blood and fixation patterns when observing upright and inverted biological motion (BM at four-months after birth. The development of the ability to recognize BM stimuli is considered a hallmark of socio-cognitive development. The results revealed a link between dioxin-like PCB #118 concentration and fixation pattern. Specifically, four-month-olds with a low-level of prenatal exposure to PCB #118 exhibited a preference for the upright BM over inverted BM, whereas those with a relatively high-level of exposure did not. This finding supports the proposal that prenatal PCB exposure impairs the development of social functioning, and indicates the importance of congener-specific analysis in the risk analysis of the adverse effects of PCB exposure on the brain development.

  16. Environmental noise exposure, early biological risk and mental health in nine to ten year old children: a cross-sectional field study

    Directory of Open Access Journals (Sweden)

    Stansfeld Stephen A

    2011-05-01

    Full Text Available Abstract Background Previous research suggests that children born prematurely or with a low birth weight are more vulnerable to the mental health effects of ambient neighbourhood noise; predominantly road and rail noise, at home. This study used data from the Road Traffic and Aircraft Noise Exposure and Children's Cognition and Health (RANCH study to see if this finding extends to aircraft and road traffic noise at school. Methods Children and their parents from schools around three European airports were selected to represent a range of aircraft and road traffic noise exposure levels. Birth weight and gestation period were merged to create a dichotomous variable assessing 'early biological risk'. Mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ. Complete data were available for 1900 primary school children. Results Children who were 'at risk' (i.e. low birth weight or premature birth were rated as having more conduct problems and emotional symptoms and poorer overall mental health than children not at risk. However, there was no interaction between aircraft or road traffic noise exposure at school and early biological risk. Conclusions Data from the RANCH study suggests that children with early biological risk are not more vulnerable to the effects of aircraft or road traffic noise at school on mental health than children without this risk; however they are more likely to have mental ill-health.

  17. Improving performance of HVAC systems to reduce exposure to aerosolized infectious agents in buildings; recommendations to reduce risks posed by biological attacks.

    Science.gov (United States)

    Hitchcock, Penny J; Mair, Michael; Inglesby, Thomas V; Gross, Jonathan; Henderson, D A; O'Toole, Tara; Ahern-Seronde, Joa; Bahnfleth, William P; Brennan, Terry; Burroughs, H E Barney; Davidson, Cliff; Delp, William; Ensor, David S; Gomory, Ralph; Olsiewski, Paula; Samet, Jonathan M; Smith, William M; Streifel, Andrew J; White, Ronald H; Woods, James E

    2006-01-01

    The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon. The Working Group was composed of subject matter experts in air filtration, building ventilation and pressurization, air conditioning and air distribution, biosecurity, building design and operation, building decontamination and restoration, economics, medicine, public health, and public policy. The group focused on functions of the heating, ventilation, and air conditioning systems in commercial or public buildings that could reduce the risk of exposure to deleterious aerosols following biological attacks. The Working Group's recommendations for building owners are based on the use of currently available, off-the-shelf technologies. These recommendations are modest in expense and could be implemented immediately. It is also the Working Group's judgment that the commitment and stewardship of a lead government agency is essential to secure the necessary financial and human resources and to plan and build a comprehensive, effective program to reduce exposure to aerosolized infectious agents in buildings.

  18. The effect of exposure misclassification in spontaneous ADR reports on the time to detection of product-specific risks for biologicals

    DEFF Research Database (Denmark)

    Vermeer, Niels S; Ebbers, Hans C; Straus, Sabine M J M;

    2016-01-01

    BACKGROUND AND OBJECTIVE: The availability of accurate product-specific exposure information is essential in the pharmacovigilance of biologicals, because differences in the safety profile may emerge between products containing the same active substance. In spontaneous adverse drug reaction (ADR......) reports, drug exposure may, however, be misclassified, that is, attributed to the incorrect product. The aim of this study was to explore the effect of exposure misclassification on the time to detection of product-specific risks in spontaneous reporting systems. METHODS: We used data simulations...... reports may result in a delayed detection of product-specific risks, particularly in the detection of weak drug-event associations. Our findings can help inform the future implementation and refinement of product-specific and batch-specific signal detection procedures....

  19. An Introductory Characterization of a Combat-Casualty-Care Relevant Swine Model of Closed Head Injury Resulting from Exposure to Explosive Blast

    Science.gov (United States)

    2009-07-08

    Richard Bauman, Geoffrey Ling, Lawrence Tong, Adolph Januszkiewicz , Denes Agoston, Nihal Delanerolle, Young Kim, Dave Ritzel, Randy Bell, James Ecklund...of Closed Head Injury Resulting from Exposure to Explosive Blast* Richard A. Bauman,1 Geoffrey Ling,2 Lawrence Tong,3 Adolph Januszkiewicz ,4 Denes...inflammation, and neuronal death cascades. J. Neurotrauma 26, 901-911. Ananiadou, O., Bibou, K ., Drossos, G., Bai, M., Haj-Yahia, S., Charchardi, A., and

  20. Heterorhabditis bacteriophora (Rhabditida: Heterorhabditidae) HP88 for biological control of Rhipicephalus microplus (Acari: Ixodidae): the effect of different exposure times of engorged females to the nematodes.

    Science.gov (United States)

    Monteiro, Caio Márcio de Oliveira; Prata, Márcia Cristina de Azevedo; Faza, Aline; Batista, Elder Simões de Paula; Dolinski, Cláudia; Furlong, John

    2012-04-30

    The aim of this study was to assess the influence of different exposure times of engorged female the Rhipicephalus microplus to infective juveniles of Heterorhabditis bacteriophora isolate HP88. The engorged females were divided into seven groups (six treatments and one control) of 20 ticks each with statistically similar average weights (p>0.05) and exposed to concentrations of 300 nematodes/tick for periods of 3, 6, 12, 24, 48 and 72 h. The following biological parameters were monitored: pre-oviposition period; egg mass weight; hatching percentage; and efficacy of treatment. There was no influence of the exposure time on the pre-oviposition period (p>0.05), while there were significant differences (pcontrol group with respect to the egg mass weight, and 24h for hatching percentage. Treatment efficacy reached 100% after exposure for 48 and 72 h. These results demonstrate that infective juveniles of H. bacteriophora HP88, under laboratory conditions, interfere in the majority of the biological parameters of the non-parasitic phase of engorged R. microplus females when the exposure time is greater than or equal to 24h.

  1. Role of quantity of additional food to predators as a control in predator-prey systems with relevance to pest management and biological conservation.

    Science.gov (United States)

    Srinivasu, P D N; Prasad, B S R V

    2011-10-01

    Necessity to understand the role of additional food as a tool in biological control programs is being increasingly felt, particularly due to its eco-friendly nature. A thorough mathematical analysis in this direction revealed the vital role of quality and quantity of the additional food in the controllability of the predator-prey systems. In this article controllability of the additional food--provided predator-prey system is studied from perspectives of pest eradication and biological conservation. Time optimal paths have been constructed to drive the state of the system to a desired terminal state by choosing quantity of the additional food as control variable. The theory developed in this article has been illustrated by solving problems related to pest eradication and biological conservation.

  2. Perinatal exposure to lead (Pb) promotes Tau phosphorylation in the rat brain in a GSK-3β and CDK5 dependent manner: Relevance to neurological disorders.

    Science.gov (United States)

    Gąssowska, Magdalena; Baranowska-Bosiacka, Irena; Moczydłowska, Joanna; Tarnowski, Maciej; Pilutin, Anna; Gutowska, Izabela; Strużyńska, Lidia; Chlubek, Dariusz; Adamczyk, Agata

    2016-03-10

    Hyperphosphorylation of Tau is involved in the pathomechanism of neurological disorders such as Alzheimer's, Parkinson's diseases as well as Autism. Epidemiological data suggest the significance of early life exposure to lead (Pb) in etiology of disorders affecting brain function. However, the precise mechanisms by which Pb exerts neurotoxic effects are not fully elucidated. The purpose of this study was to evaluate the effect of perinatal exposure to low dose of Pb on the Tau pathology in the developing rat brain. Furthermore, the involvement of two major Tau-kinases: glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5) in Pb-induced Tau modification was evaluated. Pregnant female rats were divided into control and Pb-treated group. The control animals were maintained on drinking water while females from the Pb-treated group received 0.1% lead acetate (PbAc) in drinking water, starting from the first day of gestation until weaning of the offspring. During the feeding of pups, mothers from the Pb-treated group were still receiving PbAc. Pups of both groups were weaned at postnatal day 21 and then until postnatal day 28 received only drinking water. 28-day old pups were sacrificed and Tau mRNA and protein level as well as Tau phosphorylation were analyzed in forebrain cortex (FC), cerebellum (C) and hippocampus (H). Concomitantly, we examined the effect of Pb exposure on GSK-3β and CDK5 activation. Our data revealed that pre- and neonatal exposure to Pb (concentration of Pb in whole blood below 10μg/dL, considered safe for humans) caused significant increase in the phosphorylation of Tau at Ser396 and Ser199/202 with parallel rise in the level of total Tau protein in FC and C. Tau hyperphosphorylation in Pb-treated animals was accompanied by elevated activity of GSK-3β and CDK5. Western blot analysis revealed activation of GSK-3β in FC and C as well as CDK5 in C, via increased phosphorylation of Tyr-216 and calpain-dependent p25

  3. Methodological issues in the biological monitoring of urinary benzene and S-phenylmercapturic acid at low exposure levels.

    Science.gov (United States)

    Fustinoni, Silvia; Campo, Laura; Mercadante, Rosa; Manini, Paola

    2010-10-01

    Biological monitoring of low level exposure to pollutants is a very challenging analytical activity, and the quality of results is difficult to assess, especially when a certified reference material is unavailable. The aim of this work was to evaluate the reliability of the assays used to measure urinary benzene (Benz-U) and S-phenylmercapturic acid (SPMA), by applying an internal quality control protocol. Urine spot samples from 705 subjects who were either members of the general urban population, gasoline station attendants, or refinery plant workers were assayed for Benz-U and SPMA, using GC/MS and LC/MS/MS, with quantification limits of 15 ng/L and 0.10 μg/L. The median Benz-U concentration was 263 ng/L (60-2789 ng/L, 5th-95th percentile), and the median SPMA concentration was 0.19 μg/L (<0.1-2.5 μg/L, 5th-95th percentile). Linearity of both assays was good, but a less-than-proportional response was found for SPMA concentrations below 1 μg/L. Between-run precision and accuracy for Benz-U concentration determination were assessed using quality controls at 120 ng/L and 1000 ng/L and were 10.3% and 4.8%, and 104.8% and 98.9%, respectively; while the precision and accuracy for SPMA concentration determination at 0.3 μg/L, 2.5 μg/L, and 20 μg/L were 40.3%, 6.2%, and 6.2%, and 48.3%, 96.3%, and 98.8%, respectively. Precision, estimated using duplicates of unknown samples, was 13.4% for Benz-U and 26.5% for SPMA analyses. Control charts for the means of the slope of the linear calibration curve of Benz-U showed good stability of the means over a five-year period. For SPMA, a two-laboratory comparison revealed acceptable agreement between ln-transformed data pairs, with a slope of the linear regression of 0.863 (confidence interval 0.774-0.952), null intercept, and a Pearson's r value of 0.844. Reliable results were obtained for Benz-U analyses over the entire concentration range, and for high and medium SPMA levels. However, the determination of SPMA

  4. Biological Monitoring of Inhaled Nanoparticles in Patients: An Appealing Approach To Study Causal Link between Human Respiratory Pathology and Exposure to Nanoparticles.

    Science.gov (United States)

    Forest, Valérie; Vergnon, Jean-Michel; Pourchez, Jérémie

    2017-09-18

    Although necessary, in vitro and in vivo studies are not fully successful at predicting nanomaterials toxicity. We propose to associate such assays to the biological monitoring of nanoparticles in clinical samples to get more relevant data on the chemical and physical nature and dose of nanoparticles found in humans. The concept is to establish the load of nanoparticles in biological samples of patients. Then, by comparing samples from different patient groups, nanoparticles of interest could be identified and a potential link between a given nanoparticle type and toxicity could be suggested. It must be confirmed by investigating the biological effects induced by these nanoparticles using in vitro or in vivo models (mechanistic or dose-response studies). This translational approach from the bedside to the bench and vice versa could allow a better understanding of the nanoparticle effects and mechanisms of toxicity that can contribute, at least in part, to a disease.

  5. Environmentally relevant bouts of cooling stimulate corticosterone secretion in free-living eastern bluebird (Sialia sialis) nestlings: potential links between maternal behavior and corticosterone exposure in offspring.

    Science.gov (United States)

    Lynn, Sharon E; Kern, Michael D

    2014-01-15

    In vertebrates, exposure to stressful stimuli or to elevated glucocorticoids early in development can contribute to phenotypic variation that may have significant fitness consequences. In species with altricial young, offspring may be partially buffered from elevations in glucocorticoids by a period of low glucocorticoid responsiveness to stressors coupled with high levels of parental care. Because altricial young depend heavily on their parents for warmth, parental brooding behavior could buffer offspring from glucocorticoid exposure associated with cooling. We studied eastern bluebirds (Sialia sialis) with two goals: (1) to determine whether an experimental drop in body temperature such as that which might occur when a brooding female is off the nest was sufficient to stimulate glucocorticoid secretion in young chicks, and (2) to examine the extent to which chicks experienced such bouts of cooling in the field. We subjected chicks to treatments simulating nest temperatures while females were brooding or absent from the nest. We also recorded chick surface temperatures and ambient temperatures at nests during the first week of the brood period. Reductions of surface temperature of less than 10°C significantly elevated corticosterone secretion in chicks as young as 5days old, and thermal and hormonal responses of chicks to cooling increased in an age-dependent manner. One quarter of broods experienced repeated, natural bouts of cooling of this magnitude or greater in the nest. Our data suggest that natural variations in maternal brooding patterns can result in differential exposure of offspring to glucocorticoids, and this may have important phenotypic consequences later in life.

  6. [The assessment of risk for xylene exposure in a laboratory of anatomy: comparison between computational models and environmental and biological monitoring].

    Science.gov (United States)

    Fustinoni, S; Campo, L; Pasini, R; De Comite, A; Missineo, P; Riboldi, L; Bertazzi, P A

    2012-01-01

    Exposure to xylene in a pathology laboratory was evaluated using two algorithms: Stoffenmanager and Archi.me.de. The results were compared with those obtained by applying the environmental and biological monitoring of the exposure. The use of models required a period of self-learning and, for Stoffenmanager, knowledge of the English language. Information on the toxicity and safety of xylene, available from the medial and safety data sheets, and the conditions and amount of use, obtained through a survey and interviews with operators, have been imputed. Stoffenmanager estimated low the inhalation exposure and medium the dermal exposure, with a value of personal exposure during the work shift of 1.4 mg/m3. A.r.chi.me.d.e. estimated negligible the risk to health. These ratings are consistent with those obtained using the experimental approach. This result, combined with the simplicity and low cost, makes the algorithms very interesting tools for the assessment of chemical risk in the workplace.

  7. Histopathological effects of chronic aqueous exposure to bis(tri-n-butyltin)oxide (TBTO) to environmentally relevant concentrations reveal thymus atrophy in European flounder (Platichthys flesus)

    Energy Technology Data Exchange (ETDEWEB)

    Grinwis, G.C.M., E-mail: g.c.m.grinwis@uu.n [Department of Pathobiology, Faculty of Veterinary Medicine University of Utrecht, P.O. Box 80.158, 3508 TD Utrecht (Netherlands); Wester, P.W. [Laboratory for Toxicology, Pathology and Genetics, National Institute for Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven (Netherlands); Vethaak, A.D. [Deltares, Unit Coastal and Marine Systems, P.O. Box 177, 2600 MH Delft (Netherlands)

    2009-10-15

    Although the use of tributyltin in antifouling paints has been banned, this compound is still a serious pollutant of the marine environment. This paper describes a unique study in which European flounder (Platichthys flesus) were chronically (8 months) exposed to bis(tri-n-butyltin)oxide (TBTO) in the water under controlled laboratory conditions. Residue levels in selected tissues (liver, muscle) and general health status indices were measured and the effects on several organs (gills, liver, mesonephros, ovary/testis, spleen, and gastrointestinal tract) were examined histopathologically. Additionally, morphometric analysis of the thymus was performed. The major finding is that exposure of flounder to 5 mug TBTO/l over a period of 8 months, resulting in body burdens comparable to high field levels, induced significant reduction of thymus volume, possibly affecting immunocompetence of the animals. Chronic exposure of European flounder to tributyltin is therefore likely to affect the general health status of this species in heavily polluted aquatic environments. - Current levels of tributyltin antifouling contamination are still likely to affect the general health status of estuarine flatfish in heavily polluted environments.

  8. Kinetics of nickel bioaccumulation and its relevance to selected cellular processes in leaves of Elodea canadensis during short-term exposure.

    Science.gov (United States)

    Maleva, Maria G; Malec, Przemysław; Prasad, Majeti Narasimha Vara; Strzałka, Kazimierz

    2016-03-01

    Elodea canadensis is an aquatic macrophyte used widely as a bioindicator for the monitoring of water quality and in the phytoremediation of metal-contaminated waters. This study considers the kinetics of nickel bioaccumulation and changes in accompanying metabolic and stress-related physiological parameters. These include photosynthetic activity, pigment content, the accumulation of thiol-containing compounds, thiobarbituric acid-reactive substance (TBARS) products, and the activity of selected antioxidant enzymes (catalase, glutathione reductase, superoxide dismutase). Elodea leaves accumulated nickel according to pseudo-second-order kinetics, and the protective responses followed a time sequence which was related to the apparent rates of nickel accumulation. The applicability of second-order kinetics to the Ni uptake by Elodea leaves during the first 8 h of exposure to the metal suggested that the passive binding of metal ions (chemisorption) was a rate-limiting step at the initial phase of Ni accumulation. This phase was accompanied by an increase in photosynthetic activity together with elevated photosynthetic pigments and protein synthesis, the enhanced activity of antioxidant enzymes, and increased thiol concentration. In contrast, there was a decrease in metabolic activity upon the accumulation of TBARS, and the decline in enzyme activity was observed in the saturation phase of Ni accumulation (8-24 h). These results show that a correlation exists between the protective response and the apparent kinetic rate of Ni uptake. Thus, the time of exposure to the toxicant is a crucial factor in the activation of specific mechanisms of Ni detoxification and stress alleviation.

  9. Biological characterization of radiation exposure and dose estimates for inhaled uranium milling effluents. Annual progress report April 1, 1982-March 31, 1983

    Energy Technology Data Exchange (ETDEWEB)

    Eidson, A.F.

    1984-05-01

    The problems addressed are the protection of uranium mill workers from occupational exposure to uranium through routine bioassay programs and the assessment of accidental worker exposures. Comparisons of chemical properties and the biological behavior of refined uranium ore (yellowcake) are made to identify important properties that influence uranium distribution patterns among organs. These studies will facilitate calculations of organ doses for specific exposures and associated health risk estimates and will identify important bioassay procedures to improve evaluations of human exposures. A quantitative analytical method for yellowcake was developed based on the infrared absorption of ammonium diuranate and U/sub 3/O/sub 8/ mixtures in KBr. The method was applied to yellowcake samples obtained from six operating mills. The composition of yellowcake from the six mills ranged from nearly pure ammonium diuranate to nearly pure U/sub 3/O/sub 8/. The composition of yellowcake samples taken from lots from the same mill was only somewhat less variable. Because uranium mill workers might be exposed to yellowcake either by contamination of a wound or by inhalation, a study of retention and translocation of uranium after subcutaneous implantation in rats was done. The results showed that 49% of the implanted yellowcake cleared from the body with a half-time (T sub 1/2) in the body of 0.3 days, and the remainder was cleared with a T sub 1/2 of 11 to 30 days. Exposures of Beagle dogs by nose-only inhalation to aerosols of commercial yellowcake were completed. Biochemical indicators of kidney dysfunction that appeared in blood and urine 4 to 8 days after exposure to the more soluble yellowcake showed significant changes in dogs, but levels returned to normal by 16 days after exposure. No biochemical evidence of kidney dysfunction was observed in dogs exposed to the less soluble yellowcake form. 18 figures, 9 tables.

  10. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    Science.gov (United States)

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-01

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  11. Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer

    DEFF Research Database (Denmark)

    Brooks, Susan A; Carter, Tracey M; Bennett, Eric P;

    2007-01-01

    understood, may mediate the synthesis of varied glycoforms of cellular proteins with different biological activities. Disruptions in glycosylation are a common feature of cancer and may have functional significance. Immunocytochemistry with confocal scanning laser microscopy was employed to detect members......,475). They stably synthesise varying levels, consistent with origin and phenotype, of aberrantly glycosylated glycoproteins featuring exposed, terminal GalNAc residues, including the cancer-associated Tn antigen, which, in numerous studies, have been associated with metastatic competence and poor cancer prognosis...

  12. Integration of pharmacokinetic and NRF2 system biology models to describe reactive oxygen species production and subsequent glutathione depletion in liver microfluidic biochips after flutamide exposure.

    Science.gov (United States)

    Leclerc, Eric; Hamon, Jeremy; Legendre, Audrey; Bois, Frederic Y

    2014-10-01

    We present a systems biology analysis of rat primary hepatocytes response after exposure to 10 μM and 100 μM flutamide in liver microfluidic biochips. We coupled an in vitro pharmacokinetic (PK) model of flutamide to a system biology model of its reactive oxygen species (ROS) production and scavenging by the Nrf2 regulated glutathione production. The PK model was calibrated using data on flutamide kinetics, hydroxyflutamide and glutathione conjugates formation in microfluidic conditions. The parameters of Nrf2-related gene activities and the subsequent glutathione depletion were calibrated using microarray data from our microfluidic experiments and literature information. Following a 10 μM flutamide exposure, the model predicted a recovery time to baseline levels of glutathione (GSH) and ROS in agreement with our experimental observations. At 100 μM, the model predicted that metabolism saturation led to an important accumulation of flutamide in cells, a high ROS production and complete GSH depletion. The high levels of ROS predicted were consistent with the necrotic switch observed by transcriptomics, and the high cell mortality we had experimentally observed. The model predicted a transition between recoverable GSH depletion and deep GSH depletion at about 12.5 μM of flutamide (single perfusion exposure). Our work shows that in vitro biochip experiments can provide supporting information for complex in silico modeling including data from extra cellular and intra cellular levels. We believe that this approach can be an efficient strategy for a global integrated methodology in predictive toxicology.

  13. Relevance of a combined process coupling electro-Fenton and biological treatment for the remediation of sulfamethazine solutions – Application to an industrial pharmaceutical effluent

    OpenAIRE

    Mansour, Dorsaf; Fourcade, Florence; Soutrel, Isabelle; Hauchard, Didier; Bellakhal, Nizar; Amrane, Abdeltif

    2014-01-01

    International audience; A combined process coupling an electro-Fenton pretreatment and a biological degradation was implemented in order to mineralize synthetic and industrial pharmaceutical effluents, containing a veterinary antibiotic, sulfamethazine (SMT). The electro-Fenton pretreatment of SMT synthetic solution was first examined and the obtained results showed total SMT degradation after 30 min of electrolysis at pH 3, 18°C, 500 mA and an initial SMT concentration of 0.2 mM, while the l...

  14. Dioxin-related compounds in breast milk of women from Vietnamese e-waste recycling sites: levels, toxic equivalents and relevance of non-dietary exposure.

    Science.gov (United States)

    Tue, Nguyen Minh; Katsura, Kana; Suzuki, Go; Tuyen, Le Huu; Takasuga, Takumi; Takahashi, Shin; Viet, Pham Hung; Tanabe, Shinsuke

    2014-08-01

    Although informal e-waste recycling sites (EWRSs) are hotspots of both polychlorinated and polybrominated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs and PBDD/Fs), human exposure to the latter has not been studied in details. This study investigated the accumulation levels and profiles of dioxin-related compounds (DRCs) in breast milk samples from women living in two Vietnamese EWRSs and estimated the intake contribution from e-waste-related exposure. Screening results using Dioxin-Responsive Chemically Activated LUciferase gene eXpression assay (DR-CALUX) showed higher dioxin-like (DL) activities in samples from the EWRS Bui Dau than in those from the EWRS Trang Minh and a reference site (2.3-10 vs 1.7-4.8 and 0.60-5.7 pg CALUX-TEQ/g lipid, n=10, 6 and 9, respectively). Chemical analysis results of selected samples show that the WHO-TEQ levels of PCDD/Fs, DL-PCBs and PBDD/Fs in EWRS samples were not significantly higher than in those from the reference site (0.22-7.4 vs 1.1-3.0 pg/g lipid) and within the Vietnamese background range, but women involved in recycling accumulated higher concentrations of PCDFs (13-15 vs 2.3-8.8 pg/g lipid) and PBDFs (1.1-1.5 vs <1.1 pg/g lipid). By comparing the DRC profile in milk of these women with the reported profile in house dust from the same site, dust ingestion was estimated to contribute most of the intake for tetraBDF, 37 per cent to 55 per cent for penta-octaCDFs, but less than twenty per cent for PCDDs and DL-PCBs, and 26 per cent for total WHO-TEQs. The DL activities in some EWRS milk samples were not fully explained by chemical data, suggesting contribution from unidentified compounds. The estimated WHO-TEQ intake doses for breastfed infants (1.3-33 pg/kg/d) mostly exceeded the tolerable value, especially for those living in the EWRSs; and unidentified DRCs might increase further the dioxin-related health risk.

  15. QEEN Workshop: "Quantifying Exposure to Engineered Nano-materials from Manufactured Products": Write Up Biological Tissues and Media

    Science.gov (United States)

    The measurement and characterization of nanomaterials in biological tissues is complicated by a number of factors including: the sensitivity of the assay to small sized particles or low concentrations of materials; the ability to distinguish different forms and transformations of...

  16. Identification of clinically relevant protein targets in prostate cancer with 2D-DIGE coupled mass spectrometry and systems biology network platform.

    Directory of Open Access Journals (Sweden)

    Ramesh Ummanni

    Full Text Available Prostate cancer (PCa is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24 compared to benign (n = 21 prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.

  17. Chronic exposure to cigarette smoke during gestation results in altered cholinesterase enzyme activity and behavioral deficits in adult rat offspring: potential relevance to schizophrenia.

    Science.gov (United States)

    Zugno, Alexandra I; Fraga, Daiane B; De Luca, Renata D; Ghedim, Fernando V; Deroza, Pedro F; Cipriano, Andreza L; Oliveira, Mariana B; Heylmann, Alexandra S A; Budni, Josiane; Souza, Renan P; Quevedo, João

    2013-06-01

    Prenatal cigarette smoke exposure (PCSE) has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. The present study investigated locomotor activity and cholinesterase enzyme activity in rats, following PCSE and/or ketamine treatment in adulthood. Pregnant female Wistar rats were exposed to 12 commercially filtered cigarettes per day for a period of 28 days. We evaluated motor activity and cholinesterase activity in the brain and serum of adult male offspring that were administered acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg), which serves as an animal model of schizophrenia. To determine locomotor activity, we used the open field test. Cholinesterase activity was assessed by hydrolysis monitored spectrophotometrically. Our results show that both PCSE and ketamine treatment in the adult offspring induced increase of locomotor activity. Additionally, it was observed increase of acetylcholinesterase and butyrylcholinesterase activity in the brain and serum, respectively. We demonstrated that animals exposed to cigarettes in the prenatal period had increased the risk for psychotic symptoms in adulthood. This also occurs in a dose-dependent manner. These changes provoke molecular events that are not completely understood and may result in abnormal behavioral responses found in neuropsychiatric disorders, such as schizophrenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Stebbings, J.H.; Peterson, D.P.; Johnson, S.A.; Kumar, R.; Goun, B.D.; Janssen, I.; Trier, J.E.

    1993-03-01

    This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease in blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account.

  19. [Environmental and biological monitoring of exposure to PAHs in Taranto coke-oven workers and in two groups of the general population from Apulia].

    Science.gov (United States)

    Campo, L; Vimercati, L; Carrus, A; Bisceglia, L; Pesatori, A C; Bertazzi, P A; Assennato, G; Fustinoni, S

    2012-01-01

    The exposure to PAHs was assessed by personal air sampling and urinary 1-hydroxypyrene (1-OHP) in 100 coke-oven workers (CW) of the Taranto plant and in subjects from the general population living close (NC, 18) and far away (FC, 15) from the plant. Median airborne benzo[a]pyrene (BaP) and 1-OHP levels were 152, 1.5, and 3.6 ng/m3 and 2.0, 0.5 and 0.6 microg/g creatinine in CW, NC, and FC, respectively. BaP exposure exceeded the German acceptable (70 ng/m3) and tolerable (700 ng/m3) limit risk based values in 82 and 11% of CW and the European target value for ambient air (1 ng/m3) in about 65% of NC and FC. 1-OHP levels exceed the proposed biological limit value for the coke-oven industry (4.4 microg/g crt) in 21% of CW and the Italian reference value (0.3 microg/g crt) in about 90% of NC and FC. The exposure resulted lower than in the past, but this study highlights that PAHs exposure from the coke plant still poses a health risk for workers and the general population.

  20. Lead exposures and biological responses in military weapons systems: Aerosol characteristics and acute lead effects among US Army artillerymen: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Stebbings, J.H.; Peterson, D.P.; Johnson, S.A.; Kumar, R.; Goun, B.D.; Janssen, I.; Trier, J.E.

    1993-03-01

    This study was to determine the concentration and chemical nature of lead (Pb) aerosols produced during the firing of artillery and to determine the exposures and biological responses of crew members exposed to lead aerosols during such firing. The concentrations of lead-containing aerosols at crew positions depended on wind conditions, with higher concentrations when firing into a head wind. Aerosol concentrations were highest in the muzzle blast zone. Concentrations of lead in the blood of crew members rose during the first 12 days of exposure to elevated airborne lead concentrations and then leveled off. There was no rapid decrease in blood lead concentrations after completion of firing. Small decreases in hematocrit and small increases in free erythrocyte porphyrin were correlated with increasing exposure to airborne lead. These changes were reversed by seven weeks after firing. Changes in nerve conduction velocity had borderline statistical significance to airborne lead exposure. In measuring nerve conduction velocity, differences in skin temperature must be taken into account.

  1. Elements determination of clinical relevance in biological tissues Dmd{sup mdx}/J dystrophic mice strains investigated by NAA; Determinacao de elementos de relevancia clinica em tecidos biologicos de camundongos distroficos Dmd{sup mdx}/J por AAN

    Energy Technology Data Exchange (ETDEWEB)

    Metairon, Sabrina

    2012-07-01

    In this work the determination of chemistry elements in biological tissues (whole blood, bones and organs) of dystrophic mice, used as animal model of Duchenne Muscular Dystrophy (DMD), was performed using analytical nuclear technique. The aim of this work was to determine reference values of elements of clinical (Ca, Cl, K, Mg, Na) and nutritional (Br and S) relevance in whole blood, tibia, quadriceps and hearts from Dmdmdx/J (10 males and 10 females) dystrophic mice and C57BL/6J (10 males) control group mice, using Neutron Activation Analysis technique (NAA). To show in more details the alterations that this disease may cause in these biological tissues, correlations matrixes of the DMD{sup mdx}/J mouse strain were generated and compared with C57BL/6J control group. For this study 119 samples of biological tissue were irradiated in the IEA-R1 nuclear reactor at IPEN (Sao Paulo, Brazil). The concentrations of these elements in biological tissues of Dmd{sup mdx}/J and C57B/6J mice are the first indicative interval for reference values. Moreover, the alteration in some correlation coefficients data among the elements in the health status and in the diseased status indicates a connection between these elements in whole blood, tibia, quadriceps and heart. These results may help the researchers to evaluate the efficiency of new treatments and to compare the advantages of different treatment approaches before performing tests in patients with muscular dystrophy. (author)

  2. Combined exposure to agriculture pesticides, paraquat and maneb, induces alterations in the N/OFQ-NOPr and PDYN/KOPr systems in rats: Relevance to sporadic Parkinson's disease.

    Science.gov (United States)

    Bastías-Candia, Sussy; Di Benedetto, Manuela; D'Addario, Claudio; Candeletti, Sanzio; Romualdi, Patrizia

    2015-01-01

    Despite several years of research, the aetiology of Parkinson's disease (PD) is quite far from being solved. In PD, as well as in other neurodegenerative disorders, it has been proposed that the combination of multiple factors might contribute to the onset of the disease. Indeed, several authors have suggested that environmental factors, such as pollutants and chemicals, might be associated with the onset of several neurodegenerative disorders. On the other hand, several studies have described that the nociceptin/orphanin-NOP and prodynorphin-KOP opioid systems are implicated in the pathology of Parkinson's disease. Considering the nonrestricted commercial availability and common use of several pesticides, such as paraquat and maneb, in agriculture of less developed countries, the aim of our study was to investigate the involvement of nociceptin/orphanin-NOP and prodynorphin-KOP systems in a chronic paraquat and maneb animal model of Parkinson's disease. Our results showed that after paraquat/maneb (5/15 mg kg(-1) ) treatment, a significant reduction in tyrosine hydroxylase (TH) levels, the rate-limiting enzyme for dopamine synthesis, was observed. Also, the association of paraquat and maneb (5/15 mg kg(-1) ) induced an increase in nociceptin/orphanin and a decrease of prodynorphin gene expression levels in the substantia nigra with a down-regulation of NOP and KOP receptors after both treatments in the substantia nigra and caudate putamen. These data further confirm that paraquat and maneb toxicity can modulate gene expression of the nociceptin/orphanin-NOP receptor and prodynorphin-KOP receptor systems in the substantia nigra and caudate putamen, offering further support to the hypothesis that chronic exposure to these agrochemicals might be implicated in the mechanisms underlying sporadic Parkinson's disease. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 656-663, 2015.

  3. Density functional theory estimation of isotope fractionation of Fe, Ni, Cu, and Zn among species relevant to geochemical and biological environments

    Science.gov (United States)

    Fujii, Toshiyuki; Moynier, Frédéric; Blichert-Toft, Janne; Albarède, Francis

    2014-09-01

    This paper reports the values of reduced partition function ratios (as 1000 ln β) for Fe, Ni, Cu, and Zn bound to a number of inorganic and organic ligands. We used Density Functional Techniques to update the existing data and calculate ln β for new ligands. This work allows for the mass-dependent isotope fractionation to be predicted for various inorganic (hydrated cation, hydroxide, chloride, sulfate, sulfide, phosphate) and organic (citrate, amino acid) complexes of Fe, Ni, Cu, and Zn. Isotope fractionation among coexisting complexes of these metals was evaluated from the ln β values in a variety of geochemical and biological environments. The results provide a framework for interpretation of isotope fractionation observed in seawater and chemical sediments, in the roots and aerial parts of plants, and among the organs and body fluids of mammals.

  4. DNA double-strand breaks as potential indicators for the biological effects of ionising radiation exposure from cardiac CT and conventional coronary angiography: a randomised, controlled study

    Energy Technology Data Exchange (ETDEWEB)

    Geisel, Dominik; Zimmermann, Elke; Rief, Matthias; Greupner, Johannes; Hamm, Bernd [Charite Medical School, Department of Radiology, Berlin (Germany); Laule, Michael; Knebel, Fabian [Charite Medical School, Department of Cardiology, Berlin (Germany); Dewey, Marc [Charite Medical School, Department of Radiology, Berlin (Germany); Charite, Institut fuer Radiologie, Berlin (Germany)

    2012-08-15

    To prospectively compare induced DNA double-strand breaks by cardiac computed tomography (CT) and conventional coronary angiography (CCA). 56 patients with suspected coronary artery disease were randomised to undergo either CCA or cardiac CT. DNA double-strand breaks were assessed in fluorescence microscopy of blood lymphocytes as indicators of the biological effects of radiation exposure. Radiation doses were estimated using dose-length product (DLP) and dose-area product (DAP) with conversion factors for CT and CCA, respectively. On average there were 0.12 {+-} 0.06 induced double-strand breaks per lymphocyte for CT and 0.29 {+-} 0.18 for diagnostic CCA (P < 0.001). This relative biological effect of ionising radiation from CCA was 1.9 times higher (P < 0.001) than the effective dose estimated by conversion factors would have suggested. The correlation between the biological effects and the estimated radiation doses was excellent for CT (r = 0.951, P < 0.001) and moderate to good for CCA (r = 0.862, P < 0.001). One day after radiation, a complete repair of double-strand breaks to background levels was found in both groups. Conversion factors may underestimate the relative biological effects of ionising radiation from CCA. DNA double-strand break assessment may provide a strategy for individualised assessments of radiation. (orig.)

  5. Estrogenic Effects in the Immature Rat Uterus after Dietary Exposure to Ethinylestradiol and Zearalenone Using a Systems Biology Approach

    NARCIS (Netherlands)

    Heneweer, M.; Houtman, R.; Poortman, J.H.; Groot, M.J.; Maliepaard, C.A.; Peijnenburg, A.A.C.M.

    2007-01-01

    Residues of illegally used hormones are regularly detected in animal products, feed, or cocktails recovered at farms. In order to better understand the effects of dietary exposure to ethinyl estradiol (EE2, 0.03¿1 µg/kg body weight [bw]) and zearalenone (ZEA, 0.03¿1 mg/kg bw), an immature rat

  6. Measuring tobacco smoke exposure: quantifying nicotine/cotinine concentration in biological samples by colorimetry, chromatography and immunoassay methods.

    Science.gov (United States)

    Dhar, Preeti

    2004-04-01

    Procedures to assess tobacco smoke exposure are reviewed and biomarkers used for determining the smoking status of an individual are compared. Methods used to extract these biomarkers from saliva, urine, and blood and the advantages and disadvantages of the assays are discussed. Finally, the procedures used to measure the levels of cortisol, a stress hormone speculated to be linked to nicotine metabolism, are discussed.

  7. The Fluid-Mosaic Model of Membrane Structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years.

    Science.gov (United States)

    Nicolson, Garth L

    2014-06-01

    In 1972 the Fluid-Mosaic Membrane Model of membrane structure was proposed based on thermodynamic principals of organization of membrane lipids and proteins and available evidence of asymmetry and lateral mobility within the membrane matrix [S. J. Singer and G. L. Nicolson, Science 175 (1972) 720-731]. After over 40years, this basic model of the cell membrane remains relevant for describing the basic nano-structures of a variety of intracellular and cellular membranes of plant and animal cells and lower forms of life. In the intervening years, however, new information has documented the importance and roles of specialized membrane domains, such as lipid rafts and protein/glycoprotein complexes, in describing the macrostructure, dynamics and functions of cellular membranes as well as the roles of membrane-associated cytoskeletal fences and extracellular matrix structures in limiting the lateral diffusion and range of motion of membrane components. These newer data build on the foundation of the original model and add new layers of complexity and hierarchy, but the concepts described in the original model are still applicable today. In updated versions of the model more emphasis has been placed on the mosaic nature of the macrostructure of cellular membranes where many protein and lipid components are limited in their rotational and lateral motilities in the membrane plane, especially in their natural states where lipid-lipid, protein-protein and lipid-protein interactions as well as cell-matrix, cell-cell and intracellular membrane-associated protein and cytoskeletal interactions are important in restraining the lateral motility and range of motion of particular membrane components. The formation of specialized membrane domains and the presence of tightly packed integral membrane protein complexes due to membrane-associated fences, fenceposts and other structures are considered very important in describing membrane dynamics and architecture. These structures along

  8. Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure

    DEFF Research Database (Denmark)

    Mason, Anna J.; Giusti, Valerio; Green, Stuart

    2011-01-01

    The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any in...... interactions between the effects of biological damage induced by high- and low-linear energy transfer (LET) dose components, in this 'mixed field' irradiation, was also examined......The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any...

  9. (41)Ca in tooth enamel. Part I: a biological signature of neutron exposure in atomic bomb survivors.

    Science.gov (United States)

    Wallner, A; Rühm, W; Rugel, G; Nakamura, N; Arazi, A; Faestermann, T; Knie, K; Maier, H J; Korschinek, G

    2010-08-01

    The detection of (41)Ca atoms in tooth enamel using accelerator mass spectrometry is suggested as a method capable of reconstructing thermal neutron exposures from atomic bomb survivors in Hiroshima and Nagasaki. In general, (41)Ca atoms are produced via thermal neutron capture by stable (40)Ca. Thus any (41)Ca atoms present in the tooth enamel of the survivors would be due to neutron exposure from both natural sources and radiation from the bomb. Tooth samples from five survivors in a control group with negligible neutron exposure were used to investigate the natural (41)Ca content in tooth enamel, and 16 tooth samples from 13 survivors were used to estimate bomb-related neutron exposure. The results showed that the mean (41)Ca/Ca isotope ratio was (0.17 +/- 0.05) x 10(-14) in the control samples and increased to 2 x 10(-14) for survivors who were proximally exposed to the bomb. The (41)Ca/Ca ratios showed an inverse correlation with distance from the hypocenter at the time of the bombing, similar to values that have been derived from theoretical free-in-air thermal-neutron transport calculations. Given that gamma-ray doses were determined earlier for the same tooth samples by means of electron spin resonance (ESR, or electron paramagnetic resonance, EPR), these results can serve to validate neutron exposures that were calculated individually for the survivors but that had to incorporate a number of assumptions (e.g. shielding conditions for the survivors).

  10. Using Vitek MALDI-TOF mass spectrometry to identify species belonging to the Acinetobacter calcoaceticus-Acinetobacter baumannii complex: a relevant alternative to molecular biology?

    Science.gov (United States)

    Pailhoriès, Hélène; Daure, Sophie; Eveillard, Matthieu; Joly-Guillou, Marie-Laure; Kempf, Marie

    2015-10-01

    Acinetobacter baumannii belongs to the Acinetobacter calcoaceticus-baumannii complex (Acb) containing 2 other pathogenic species: Acinetobacter pittii and Acinetobacter nosocomialis. Identification of these bacteria remains problematic despite the use of matrix-assisted laser ionization time-of-flight mass spectrometry (MALDI-TOF MS). Here, we enriched the SARAMIS™ database of the Vitek MS® plus mass spectrometer to improve the identification of species of the Acb complex. For each species, we incremented reference spectra. Then, a SuperSpectrum was created based on the selection of 40 specific masses. In a second step, we validated reference spectra and SuperSpectra with 100 isolates identified by rpoB gene sequencing. All the isolates were correctly identified by MALDI-TOF MS with the database we created as compared to the identifications obtained by rpoB sequencing. Our database enabled rapid and reliable identification of the pathogen species belonging to the Acb complex. Identification by MALDI-TOF MS with our database is a good alternative to molecular biology.

  11. Biological assessments of a mixture of endocrine disruptors at environmentally relevant concentrations in water following UV/H{sub 2}O{sub 2} oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, P.-J. [Department of Civil and Environmental Engineering, Duke University (United States); Integrated Toxicology Program, Nicolas School of Environment and Earth Science, Duke University (United States); Rosenfeldt, Erik J. [Department of Civil and Environmental Engineering, Duke University (United States); Kullman, Seth W. [Integrated Toxicology Program, Nicolas School of Environment and Earth Science, Duke University (United States); Hinton, David E. [Integrated Toxicology Program, Nicolas School of Environment and Earth Science, Duke University (United States); Linden, Karl G. [Department of Civil and Environmental Engineering, Duke University (United States)]. E-mail: kglinden@duke.edu

    2007-04-15

    Numerous studies have investigated degradation of individual endocrine disrupting compounds (EDCs) in lab or natural waters. However, natural variations in water matrices and mixtures of EDCs in the environment may confound analysis of the treatment efficiency. Because chemical based analytical methods cannot represent the combined or synergistic activities between water quality parameters and/or the EDC mixtures at environmentally relevant concentrations ({mu}g L{sup -1}-ng L{sup -1}), bioanalytical assessments of residual estrogenic activity in treated water were used to evaluate the performance of the UV based advanced oxidation process for estrogenic contaminants in water. Four EDCs including estradiol (E{sub 2}), ethinyl estradiol (EE{sub 2}), bisphenol-A (BPA) and nonylphenol (NP) were spiked individually or as a mixture at {mu}g L{sup -1}-ng L{sup -1} in laboratory or natural river water. The removal rates of estrogenic activity were quantitatively evaluated by in vitro yeast estrogen screen (YES) and in vivo Vitellogenin (VTG) assays with Japanese medaka fish (Oryzias latipes). UV in combination with 10 ppm H{sub 2}O{sub 2} as an oxidation process was capable of decreasing in vitro and in vivo estrogenic activity, however, in vivo estrogenic activity of the EDC mixture in natural water was not completely removed at UV fluence up to 2000 mJ cm{sup -2}. The removal rates of in vitro estrogenic activity of the EDC mixtures were lower than those observed for single compounds, and slower in natural waters, likely due to lower steady-state concentrations of hydroxyl radicals ({center_dot}OH) in the presence of {center_dot}OH scavengers from the water matrix and EDC mixture.

  12. Effect of biologically relevant ions on the corrosion products formed on alloy AZ31B: an improved understanding of magnesium corrosion.

    Science.gov (United States)

    Jang, Yongseok; Collins, Boyce; Sankar, Jagannathan; Yun, Yeoheung

    2013-11-01

    Simulated physiological solutions mimicking human plasma have been utilized to study the in vitro corrosion of biodegradable metals. However, corrosion and corrosion product formation are different for different solutions with varied responses and, hence, the prediction of in vivo degradation behavior is not feasible based on these studies alone. This paper reports the role of physiologically relevant salts and their concentrations on the corrosion behavior of a magnesium alloy (AZ31B) and subsequent corrosion production formation. Immersion tests were performed for three different concentrations of Ca(2+), HPO4(2-), HCO3(-) to identify the effect of each ion on the corrosion of AZ31B assessed at 1, 3 and 10 days. Time-lapse morphological characterization of the samples was performed using X-ray computed tomography and scanning electron microscopy. The chemical composition of the surface corrosion products was determined by electron dispersive X-ray spectroscopy and X-ray diffraction. The results show that: (1) calcium is not present in the corrosion product layer when only Cl(-) and OH(-) anions are available; (2) the presence of phosphate induces formation of a densely packed amorphous magnesium phosphate corrosion product layer when HPO4(2-) and Cl(-) are present in solution; (3) octacalcium phosphate and hydroxyapatite (HAp) are deposited on the surface of the magnesium alloy when HPO4(2-) and Ca(2+) are present together in NaCl solution (this coating limits localized corrosion and increases general corrosion resistance); (4) addition of HCO3(-) accelerates the overall corrosion rate, which increases with increasing bicarbonate concentration; (5) the corrosion rate decreases due to the formation of insoluble HAp on the surface when HCO3(-), Ca(2+), and HPO4(2-) are present together.

  13. Studies to assess the biological relevance of anti-Tamm-Horsfall protein antibodies detected by direct-binding enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Hunt, J S; Groufsky, A; Lynn, K L

    1987-11-01

    1. A role has been suggested for anti-Tamm-Horsfall protein (THP) antibodies in renal disease based on the results of immunoassays of pathological sera. The putative autoantibodies have not been isolated from such sera nor have definitive inhibition studies of their binding been carried out. We have carried out such studies using rabbit anti-THP antibodies as control reagents. 2. Urinary THP prepared by salt precipitation was used to prepare four immunoabsorbent columns by covalent coupling to CNBr-activated Sepharose 4B. After washing with a variety of dissociating agents to remove any non-covalently bound subunit THP, each column was incubated with normal and immune rabbit serum. Fractions washed and eluted from columns were tested for anti-THP antibodies by enzyme-linked immunosorbent assay (ELISA) and THP antigen by radioimmunoassay, and showed NH4SCN (3 mol/l) and guanidine hydrochloride (GuHCl) (6 mol/l) equivalent and sodium dodecyl sulphate (20 g/l) to be inferior in their capacity to produce immunoabsorbent THP capable of isolating specific antibodies from immune rabbit serum. 3. The column treated with GuHCl (6 mol/l) was used further in attempts to isolate putative anti-THP antibodies from five patients, who had a history of urinary tract infections and whose sera showed strong binding by ELISA. 4. Results from direct and inhibition ELISA experiments on fractions collected after washing and elution with all sera suggested that the putative human anti-THP antibodies were of very low affinity and/or directed against non-subunit THP. 5. The pathological relevance of human anti-THP antibodies measured by ELISA remains to be established.

  14. Elemental Speciation as an Essential Part of Formulating Exposure Assessments that Support Risk Estimates

    Science.gov (United States)

    The chemical form specific toxicity of arsenic has caused scientists to move toward species specific assessments with an emphasis on biological relevance of an exposure. For example, numerous studies on the occurrence of arsenic in rice have documented the exposure potential fro...

  15. Heme versus non-heme iron-nitroxyl {FeN(H)O}⁸ complexes: electronic structure and biologically relevant reactivity.

    Science.gov (United States)

    Speelman, Amy L; Lehnert, Nicolai

    2014-04-15

    Researchers have completed extensive studies on heme and non-heme iron-nitrosyl complexes, which are labeled {FeNO}(7) in the Enemark-Feltham notation, but they have had very limited success in producing corresponding, one-electron reduced, {FeNO}(8) complexes where a nitroxyl anion (NO(-)) is formally bound to an iron(II) center. These complexes, and their protonated iron(II)-NHO analogues, are proposed key intermediates in nitrite (NO2(-)) and nitric oxide (NO) reducing enzymes in bacteria and fungi. In addition, HNO is known to have a variety of physiological effects, most notably in the cardiovascular system. HNO may also serve as a signaling molecule in mammals. For these functions, iron-containing proteins may mediate the production of HNO and serve as receptors for HNO in vivo. In this Account, we highlight recent key advances in the preparation, spectroscopic characterization, and reactivity of ferrous heme and non-heme nitroxyl (NO(-)/HNO) complexes that have greatly enhanced our understanding of the potential biological roles of these species. Low-spin (ls) heme {FeNO}(7) complexes (S = 1/2) can be reversibly reduced to the corresponding {FeNO}(8) species, which are stable, diamagnetic compounds. Because the reduction is ligand (NO) centered in these cases, it occurs at extremely negative redox potentials that are at the edge of the biologically feasible range. Interestingly, the electronic structures of ls-{FeNO}(7) and ls-{FeNO}(8) species are strongly correlated with very similar frontier molecular orbitals (FMOs) and thermodynamically strong Fe-NO bonds. In contrast, high-spin (hs) non-heme {FeNO}(7) complexes (S = 3/2) can be reduced at relatively mild redox potentials. Here, the reduction is metal-centered and leads to a paramagnetic (S = 1) {FeNO}(8) complex. The increased electron density at the iron center in these species significantly decreases the covalency of the Fe-NO bond, making the reduced complexes highly reactive. In the absence of

  16. Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes.

    Science.gov (United States)

    Raju, Raghavan; Dalakas, Marinos C

    2005-08-01

    To explore the biological significance of gene expression in the pathogenesis of inflammatory myopathies, we performed microarray experiments followed by real-time PCR and immunohistochemistry on muscle biopsies obtained before and after therapy from patients with dermatomyositis (DM) who improved and patients with inclusion body myositis (sIBM) who did not improve after controlled trials with three monthly intravenous immunoglobulin (IVIg) infusions. The pretreatment biopsies showed high expression of immunoglobulin, adhesion molecules, chemokines and cytokine genes in both sIBM and DM (sIBM > DM). In the repeated biopsies of DM patients who clinically improved, 2206 genes were downregulated more than 1.5-fold; in contrast, 1700 of the same genes remained unchanged in sIBM patients who did not improve. Genes markedly downregulated in DM, but not sIBM, were interleukin 22, Kallmann syndrome 1 (KAL-1), an adhesion molecule shown for the first time in muscle, ICAM-1, complement C1q, and several structural protein genes. Because mRNA for KAL-1 was selectively upregulated in vitro by transforming growth factor (TGF) beta1, a fibrogenic cytokine immunolocalized in the endomysial connective tissue of pretreatment DM muscles, the downregulation of both TGF-beta and KAL-1 after IVIg only in DM suggests that these molecules have a functional role in connective tissue proliferation and fibrosis. The improved muscles of DM, but not sIBM, showed upregulation of chemokines CXCL9 (Mig) and CXCL11, and several immunoglobulin-related genes, suggesting an effect on muscle remodelling and regeneration. The results suggest that IVIg modulates several immunoregulatory or structural muscle genes, but only a subset of them associated with inflammatory mediators, fibrosis and muscle remodelling are connected with the clinical response. Gene arrays, when combined with clinical assessments, may provide important information in the pathogenesis of inflammatory myopathies.

  17. Effects of type of smoking (pipe, cigars or cigarettes) on biological indices of tobacco exposure and toxicity.

    Science.gov (United States)

    Funck-Brentano, Christian; Raphaël, Mathilde; Lafontaine, Michel; Arnould, Jean-Pierre; Verstuyft, Céline; Lebot, Martine; Costagliola, Dominique; Roussel, Ronan

    2006-10-01

    Although all forms of smoking are harmful, smoking pipes or cigars is associated with lower exposure to the lethal products of tobacco products and lower levels of morbidity and mortality than smoking cigarettes. Cytochrome P-450-1A (CYP1A) is a major pathway activating carcinogens from tobacco smoke. Our primary aim was to compare CYP1A2 activity in individuals smoking pipes or cigars only, cigarettes only and in non-smokers. We studied 30 smokers of pipes or cigars only, 28 smokers of cigarettes only, and 30 non-smokers male subjects matched for age. CYP1A2 activity was assessed as the caffeine metabolic ratio in plasma. One-day urine collection was used for determining exposure to products of tobacco metabolism. Nitrosamine and benzo[a]pyrene DNA adducts were measured in lymphocytes. CYP1A2 activity was greater (ptobacco metabolism than cigarette smoking and to an absence of CYP1A2 induction. Cigarette smoking was the only independent predictor of CYP1A2 activity in smokers. However, inhalation behaviour, rather than the type of tobacco smoked, may be the key factor linked to the extent of tobacco exposure and CYP1A2 induction. Our results provide a reasonable explanation for the results of epidemiological studies showing pipe or cigar smoking to present fewer health hazards than cigarette smoking.

  18. Evaluation of Functionality and Biological Responses of Mytilus galloprovincialis after Exposure to Quaternium-15 (Methenamine 3-Chloroallylochloride).

    Science.gov (United States)

    Pagano, Maria; Capillo, Gioele; Sanfilippo, Marilena; Palato, Simon; Trischitta, Francesca; Manganaro, Antonio; Faggio, Caterina

    2016-01-01

    Although the irritant effects of quaternium-15 have been established, little is known about the toxicological consequences induced by this xenobiotic on aquatic invertebrates. The present article reports toxicological, histological and physiological effects of quaternium-15 following the exposure of Mytilus galloprovincialis for 18 days at three different concentrations (0.1, 1.0 and 2.0 mg/L). The results demonstrate that at higher concentrations histological damages to M. galloprovincialis gills occur, like melanosis, light exfoliations, increase of mucus production and infiltrative inflammation. In addition digestive gland cells of M. galloprovincialis, were not able to perform the regulation volume decrease (RVD) owing to osmotic stress following the exposure to the preservative. Overall, this first study on quaternium-15 highlights that it can jeopardize both the morphology and vital physiological processes in marine invertebrates, depending on the duration of exposure and the concentration of the preservative, indicating that further studies are necessary to increase our knowledge about the effects of this substance, commonly added to our products of daily use.

  19. Biological monitoring of occupational exposure to 1-bromopropane by means of urinalysis for 1-bromopropane and bromide ion.

    Science.gov (United States)

    Kawai, T; Takeuchi, A; Miyama, Y; Sakamto, K; Zhang, Z W; Higashikawa, K; Ikeda, M

    2001-01-01

    The purposes of the present study are (1) to develop a sensitive analytical method to measure 1-bromopropane (1-BP) in urine, (2) to examine if 1-BP or bromide ion (Br) in urine is a useful biomarker of exposure to 1-BP, and (3) to identify the lowest 1-BP exposure concentration the method thus established can biomonitor. A factory survey was carried out on Friday, and 33 workers (all men) in cleaning and painting workshops participated; each worker was equipped with a diffusive sampler (carbon cloth KF-1500 as an adsorbent) to monitor 1-BP vapour for an 8-h shift, and offered a urine sample at the end of the shift for measurement of 1-BP and Br in urine. In addition, 10 non-exposed men offered urine samples as controls. The performance of the carbon cloth diffusive sampler was examined to confirm that the sampler is suitable for monitoring time-weighted average 1-BP vapour exposure. A head-space GC technique was employed for analysis of 1-BP in urine, whereas Br in urine was analysed by ECD-GC after derivatization to methyl bromide. The workers were exposed to vapours of seven other solvents (i.e. toluene, xylenes, ethylbenzene, acetone, etc.) in addition to 1-BP vapour; the 1-BP vapour concentration was 1.4 ppm as GM and 28 ppm as the maximum. Multiple regression analysis however showed that 1-BP was the only variable that influenced urinary 1-BP significantly. There was a close correlation between 1-BP in urine and 1-BP in air; the correlation coefficient (r) was >0.9 with a narrow variation range, and the regression line passed very close to the origin so that 2 ppm 1-BP exposure can be readily biomonitored. The correlation of Br in urine with 1-BP in air was also significant, but the r (about 0.7) was smaller than that for 1-BP, and the background Br level was also substantial (about 8 mg l(-1)). Thus, it was concluded that 1-BP in end-of-shift urine is a reliable biomarker of occupational exposure to 1-BP vapour, and that Br in urine is less reliable.

  20. External and internal exposure to polycyclic aromatic hydrocarbons (PAH) among workers in the production of fire-proof materials - proposal of a biological monitoring guidance value.

    Science.gov (United States)

    Preuss, Ralf; Rossbach, Bernd; Wilhelm, Michael; Brüning, Thomas; Angerer, Jürgen

    2006-11-01

    In 1999, we introduced the German polycyclic aromatic hydrocarbons (PAH) study. The study was designed as a nation-wide investigation on workers exposed to PAH. One aim of the study was to establish biological monitoring guidance values (BMGVs) for different branches. Here, we report on the production of fire-proof materials. This branch of industry is typically confronted with high exposure to PAH and with PAH-induced occupational (cancer) diseases. One hundred and thirty-five employees participated in the course of seven sampling dates in four different plants in Germany. External exposure was determined by personal air monitoring of the 16 EPA-PAH. Human biological monitoring was accomplished by the determination of 1-hydroxypyrene and monohydroxyphenanthrenes in post-shift spot urine samples. Concentrations of PAH in the air of the workplaces ranged up to 1102.6microg/m(3). Maximum benzo[a]pyrene concentration was 38.2microg/m(3). The internal PAH exposure of workers was much higher compared with that of the general population. Median concentration for 1-hydroxypyrene was 6.4microg/g creatinine (maximum 279.6, 90th percentile 23.9microg/g creatinine) and for the sum of monohydroxyphenanthrene metabolites 13.3microg/g creatinine (maximum 313.4, 90th percentile 70.8microg/g creatinine). The following BMGVs for the non-smokers of this branch of industry are proposed: for 1-hydroxypyrene 18microg/g creatinine and for the sum of hydroxyphenanthrenes 77microg/g creatinine in urine measured at the end of the shift.

  1. Assessment of biological changes of continuous whole body exposure to static magnetic field and extremely low frequency electromagnetic fields in mice.

    Science.gov (United States)

    Hashish, A H; El-Missiry, M A; Abdelkader, H I; Abou-Saleh, R H

    2008-11-01

    The question whether static magnetic fields (SMFs) and extremely low frequency electromagnetic fields (ELF-EMF) cause biological effects is of special interest. We investigated the effects of continuous whole body exposure to both fields for 30 days on some liver and blood parameters in mice. Two exposure systems were designed; the first produced a gradient SMF while the second generated uniform 50 Hz ELF-EMF. The results showed a gradual body weight loss when mice were exposed to either field. This is coupled with a significant decrease (Pglutathione-S-transferase activity and lipid peroxidation level in the liver were significantly increased while a significant decrease in hepatic gluthathione content was recorded. A significant decrease in the counts of monocytes, platelets, peripheral lymphocytes as well as splenic total, T and B lymphocytes levels was observed for SMF and ELF-EMF exposed groups. The granulocytes percentage was significantly increased. The results indicate that there is a relation between the exposure to SMF or ELF-EMF and the oxidative stress through distressing redox balance leading to physiological disturbances.

  2. How dependent are molecular and atomic properties on the electronic structure method? Comparison of Hartree-Fock, DFT, and MP2 on a biologically relevant set of molecules.

    Science.gov (United States)

    Matta, Chérif F

    2010-04-30

    This article compares molecular properties and atomic properties defined by the quantum theory of atoms in molecules (QTAIM) obtained from three underlying levels of theory: MP2(full), density functional theory (DFT) (B3LYP), and Hartree-Fock (H-F). The same basis set (6-311++G(d,p)) has been used throughout the study. The calculations and comparisons were applied to a set of 30 small molecules representing common fragments of biological molecules. The molecular properties investigated are the energies and the electrostatic moments (up to and including the quadrupoles), and the atomic properties include electron populations (and atomic charge), atomic dipolar and quadrupolar polarizations, atomic volumes, and corrected and raw atomic energies. The Cartesian distance between dipole vectors and the Frobenius distance between the quadrupole tensors calculated at the three levels of theory provide a measure of their correlation (or lack thereof). With the exception of energies (atomic and molecular), it is found that both DFT and H-F are in excellent agreement with MP2, especially with regards to the electrostatic mutipoles up to the quadrupoles, but DFT and MP2 agree better in almost all studied properties (with the exception of molecular geometries). QTAIM properties whether obtained from H-F, DFT(B3LYP), or MP2 calculations when used in the construction of empirical correlations with experiment such as quantitative structure-activity-(or property)-relationships (QSAR/QSPR) are equivalent (because the properties calculated at the three levels are very highly correlated among themselves with r(2) typically >0.95, and therefore preserving trends). These results suggest that the massive volume of results that were published in the older literature at the H-F level is valid especially when used to study trends or in QSAR or QSPR studies, and, as long as our test set of molecules is representative, there is no pressing need to re-evaluate them at other levels of theory

  3. Computational biology

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2011-01-01

    Computation via biological devices has been the subject of close scrutiny since von Neumann’s early work some 60 years ago. In spite of the many relevant works in this field, the notion of programming biological devices seems to be, at best, ill-defined. While many devices are claimed or proved t...

  4. EMF exposure assessment in the Finnish garment industry: evaluation of proposed EMF exposure metrics.

    Science.gov (United States)

    Hansen, N H; Sobel, E; Davanipour, Z; Gillette, L M; Niiranen, J; Wilson, B W

    2000-01-01

    Recently published studies indicate that having worked in occupations that involve moderate to high electromagnetic field (EMF) exposure is a risk factor for neurodegenerative diseases, including Alzheimer's disease. In these studies, the occupational groups most over-represented for EMF exposure comprised seamstresses, dressmakers, and tailors. Future epidemiologic studies designed to evaluate the possibility of a causal relationship between exposure to EMF and a neuro degenerative disease endpoint such as incidence of Alzheimer's disease, will benefit from the measurement of electromagnetic field metrics with potential biological relevance. Data collection methodology in such studies would be highly dependent upon how the metrics are defined. In this research the authors developed and demonstrated (1) protocols for collecting EMF exposure data suitable for estimating a variety of exposure metrics that may have biological relevance, and (2) analytical methods for calculation of these metrics. The authors show how exposure might be estimated under each of the three prominent EMF health-effects mechanism theories and evaluate the assertion that relative exposure ranking is dependent on which mechanism is assumed. The authors also performed AC RMS magnetic flux density measurements, confirming previously reported findings. The results indicate that seamstresses, as an occupational group, should be considered for study of the possible health effects of long-term EMF exposure.

  5. A review of air quality, biological indicators and health effects of second-hand waterpipe smoke exposure

    OpenAIRE

    Kumar, Sumit R.; Davies, Shelby; Weitzman, Michael; Sherman, Scott

    2014-01-01

    Objective There has been a rapid increase in the use of waterpipe tobacco and non-tobacco based shisha in many countries. Understanding the impact and effects of second-hand smoke (SHS) from cigarette was a crucial factor in reducing cigarette use, leading to clean indoor air laws and smoking bans. This article reviews what is known about the effects of SHS exposure from waterpipes. Data sources We used PubMed and EMBASE to review the literature. Articles were grouped into quantitative measur...

  6. Biological effects of short-term, high-concentration exposure to methyl isocyanate. II. Blood chemistry and hematologic evaluations.

    OpenAIRE

    Troup, C M; Dodd, D E; Fowler, E H; Frank, F R

    1987-01-01

    Human, rat, and guinea pig packed erythrocytes exposed to 100, 500, or 1000 ppm of methyl isocyanate (MIC) vapor in vitro showed a concentration-related inhibition of cholinesterase (ChE) activity. Rat and guinea pig packed erythrocytes showed an almost complete inhibition of ChE activity at 2000 ppm. In vitro exposures of human and guinea pig blood to 1000 or 2000 ppm of MIC vapor resulted in qualitative alterations in the electrophoretic mobility of hemoglobin (Hb) as measured by citrated a...

  7. Effects of glyphosate-based herbicides on survival, development, growth and sex ratios of wood frog (Lithobates sylvaticus) tadpoles. II: agriculturally relevant exposures to Roundup WeatherMax® and Vision® under laboratory conditions.

    Science.gov (United States)

    Lanctôt, C; Navarro-Martín, L; Robertson, C; Park, B; Jackman, P; Pauli, B D; Trudeau, V L

    2014-09-01

    Glyphosate-based herbicides are currently the most commonly used herbicides in the world. They have been shown to affect survival, growth, development and sexual differentiation of tadpoles under chronic laboratory exposures but this has not been investigated under more environmentally realistic conditions. The purpose of this study is (1) to determine if an agriculturally relevant exposure to Roundup WeatherMax®, a relatively new and understudied formulation, influences the development of wood frog tadpoles (Lithobates sylvaticus) through effects on the mRNA levels of genes involved in the control of metamorphosis; (2) to compare results to the well-studied Vision® formulation (containing the isopropylamine salt of glyphosate [IPA] and polyethoxylated tallowamine [POEA] surfactant) and to determine which ingredient(s) in the formulations are responsible for potential effects on development; and (3) to compare results to recent field studies that used a similar experimental design. In the present laboratory study, wood frog tadpoles were exposed to an agriculturally relevant application (i.e., two pulses) of Roundup WeatherMax® and Vision® herbicides as well as the active ingredient (IPA) and the POEA surfactant of Vision®. Survival, development, growth, sex ratios and mRNA levels of genes involved in tadpole metamorphosis were measured. Results show that Roundup WeatherMax® (2.89 mg acid equivalent (a.e.)/L) caused 100% mortality after the first pulse. Tadpoles treated with a lower concentration of Roundup WeatherMax® (0.21 mg a.e./L) as well as Vision® (2.89 mg a.e./L), IPA and POEA had an increased condition factor (based on length and weight measures in the tadpoles) relative to controls at Gosner stage (Gs) 36/38. At Gs42, tadpoles treated with IPA and POEA had a decreased condition factor. Also at Gs42, the effect on condition factor was dependent on the sex of tadpoles and significant treatment effects were only detected in males. In most cases

  8. Minimally invasive transcriptome profiling in salmon: Detection of biological response in rainbow trout caudal fin following exposure to environmental chemical contaminants

    Energy Technology Data Exchange (ETDEWEB)

    Veldhoen, Nik; Stevenson, Mitchel R. [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055, STN CSC, Victoria, BC V8W 3P6 (Canada); Skirrow, Rachel C. [Pacific and Yukon Laboratory for Environmental Testing, Pacific Environmental Science Centre, Environment Canada, 2645 Dollarton Highway, North Vancouver, BC V7H 1B1 (Canada); Rieberger, Kevin J. [Environmental Sustainability and Strategic Policy Division, Water Protection and Sustainability Branch, British Columbia Ministry of Environment, P.O. Box 9362 Stn Prov Govt, Victoria, BC V8W 9M2 (Canada); Aggelen, Graham van [Pacific and Yukon Laboratory for Environmental Testing, Pacific Environmental Science Centre, Environment Canada, 2645 Dollarton Highway, North Vancouver, BC V7H 1B1 (Canada); Meays, Cynthia L. [Environmental Sustainability and Strategic Policy Division, Water Protection and Sustainability Branch, British Columbia Ministry of Environment, P.O. Box 9362 Stn Prov Govt, Victoria, BC V8W 9M2 (Canada); Helbing, Caren C., E-mail: chelbing@uvic.ca [Department of Biochemistry and Microbiology, University of Victoria, P.O. Box 3055, STN CSC, Victoria, BC V8W 3P6 (Canada)

    2013-10-15

    Highlights: •A minimally-invasive tail fin biopsy assay was developed for use in fish. •Quantitative real time polymerase reaction provided gene expression readout. •Results were comparable to classical liver tissue responses. •The approach was used on two salmonid species and can be coupled with genomic sex determination using an additional biopsy for maximal information. -- Abstract: An increasing number of anthropogenic chemicals have demonstrated potential for disruption of biological processes critical to normal growth and development of wildlife species. Both anadromous and freshwater salmon species are at risk of exposure to environmental chemical contaminants that may affect migratory behavior, environmental fitness, and reproductive success. A sensitive metric in determination of the presence and impact of such environmental chemical contaminants is through detection of changes in the status of gene transcript levels using a targeted quantitative real-time polymerase chain reaction assay. Ideally, the wildlife assessment strategy would incorporate conservation-centered non-lethal practices. Herein, we describe the development of such an assay for rainbow trout, Oncorhynchus mykiss, following an acute 96 h exposure to increasing concentrations of either 17α-ethinyl estradiol or cadmium. The estrogenic screen included measurement of mRNA encoding estrogen receptor α and β isoforms, vitellogenin, vitelline envelope protein γ, cytochrome p450 family 19 subfamily A, aryl hydrocarbon receptor, and the stress indicator, catalase. The metal exposure screen included evaluation of the latter two mRNA transcripts along with those encoding the metallothionein A and B isoforms. Exposure-dependent transcript abundance profiles were detected in both liver and caudal fin supporting the use of the caudal fin as a non-lethally obtained tissue source. The potential for both transcriptome profiling and genotypic sex determination from fin biopsy was extended, in

  9. The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

    Science.gov (United States)

    Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

    2013-08-12

    resistant to short-term high-dose irradiation. This discrepancy is reconcilable based on the differences in the experimental conditions. We are just beginning to understand the biological effects of long-term low-dose exposures in animals. Further research is necessary to accurately assess the possible biological effects of the accident.

  10. Application of translocation, γ-H2AX, and Sam68 as a biological indicators for the assessment of radiation exposure in nuclear power plant workers

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Kwang Hee; Park, Hyung Sun; Nam, Seon Young [Korea Hydro Nuclear Power Co., Seoul (Korea, Republic of)

    2014-05-15

    This study showed that confirmation of the initial dose estimated by dicentric analysis is provided by the subsequent FISH analysis for translocation frequency and provides further evidence for the valid use of FISH as a retrospective biological dosimeter. The IAEA manual on cytogenetic dosimetry recommends a halftime value of 3 y to correct for the decrease of dicentrics in case of delayed sampling based on the patient data of Buckton. Support for this comes from the cytogenetic follow up of an individual exposed to tritium, which also indicated a decline in dicentrics with a half-time of ∼3 y. Naturally, the RBE of tritium, as well as other kinds of ionizing radiation, depends on the dose, exposure conditions, and studied parameters. The information about the RBE of tritium that is most important from an applied standpoint is that associated with the range of low doses. In our study, the dose dependence of tritium RBE was not identified because of very low dose Tritium (< 1mSv). However, The strong smooth relationship between translocation yield and age is shown in Table 2. The translocation yields reported here are only slightly lower than already published. The implication is that the increase of yield with age could be due to environmental factors, to a natural aging process or both. In addition, we confirmed that γ-H2AX and Sam68 associated with DNA damage and apoptosis, can be new biological indicators for radiation exposure. Radiation workers are exposed to ionizing radiation from various sources. Ionizing radiation produces several types of DNA lesion, including DNA base alterations, DNA. DNA cross-links, and single- and double-strand breaks. As a protocol for biological dosimetry recommended by IAEA (2001), the analysis of solid stained dicentric chromosomes has been used since the mid 1960s. The intervening years have seen great improvements bringing the technique to a point where dicentric analysis has become a routine component of the radiological

  11. Biological exposure limit in bone metabolism damage induced by co-exposure to fluorine and arsenic from coal burning%燃煤氟砷致骨代谢损伤的生物暴露限值初探

    Institute of Scientific and Technical Information of China (English)

    曾奇兵; 喻仙; 杨鋆; 洪峰

    2012-01-01

    Objective To study the biological exposure limit in bone metabolism damage caused by coexposure to fluorine and arsenic from coal burning in exposed population.Methods One hundred and ninety-eight cases of fluoride and arsenic co-exposed people from Liuchang village,Qinzhen city,Guizhou province were enrolled in the study.Urinary fluorine (UF),urinary arsenic (UAs),urinary hydroxyproline (UHYP),ross-linked Ntelopeptides of type Ⅰ collagen(UNTX) and bone strength index(STI) were detected.BMDS Version 2.1 software was used to calculate UF,UAs benchmark dose (BMD) and its lower confidence limit (BMDL) on the damage of bone metabolism caused by co-exposure to fluorine and arsenic from coal burning.Results The BMD and BMDL range of UF caused by co-exposure to fluorine and arsenic from coal burning were 0.68-1.35 mg/g Cr,0.57-1.11 mg/g Cr.The BMD and BMDL range of UAs caused by co-exposure to fluorine and arsenic from coal burning were 8.36-18.77 μg/g Cr,7.12-15.40 μg/g Cr.Conclusion The biological exposure limits of UF and UAs for bone metabolism toxicity are proposed as 0.57 mg/g Cr and 7.12 μg/g Cr in co-exposure to fluoride and arsenic from coal burning,respectively.%目的 探讨燃煤氟砷致暴露人群骨代谢损伤的生物暴露限值(BEL).方法 2009年选择贵州省清镇市流长乡198例氟砷联合暴露者作为调查对象,分别检测尿氟、尿砷及骨代谢效应标志尿羟脯氨酸(UHYP)和尿Ⅰ型胶原交联氨基末端肽(UNTX)、骨强度指数(STI).应用BMDS Version 2.1软件计算燃煤氟砷致骨代谢损伤的尿氟、尿砷基准剂量(BMD)及其可信限下限(BMDL).结果 氟、砷混合暴露引起骨代谢损伤的尿氟BMD及BMDL范围分别为0.68 ~ 1.35 mg/g Cr和0.57 ~ 1.11 mg/g Cr;尿砷BMD及BMDL范围分别为8.36 ~ 18.77 μg/g Cr和7.12 ~ 15.40 μg/g Cr.结论 建议燃煤氟砷混合暴露引起骨代谢损伤的生物暴露限值,尿氟为0.57 mg/g Cr,尿砷为7.12 μg/g Cr.

  12. Previous exposure to biologics and C-reactive protein are associated with the response to tacrolimus in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Iago Rodríguez-Lago

    Full Text Available Background and aims: Inflammatory bowel disease is a chronic disorder of the gastrointestinal tract. Tacrolimus is a calcineurin inhibitor used in the prophylaxis of rejection after a solid organ transplant. There is some evidence for its use in inflammatory bowel disease, although there is a lack of information about the patients who will benefit the most with this drug and the prognostic factors for a favorable response. Material and Methods: We performed a multicentric retrospective study evaluating all the patients who have received tacrolimus in the last 10 years as a treatment for IBD in our area. Results: A total of 20 patients, 12 with Crohn's disease and 8 with ulcerative colitis, were included in four hospitals. The two most common indications were steroid-dependency and fistulizing Crohn's disease. The median time receiving tacrolimus was 11 months. In 12 patients the treatment was stopped. The main reasons for drug withdrawal were absence or loss of response. The median clinical follow-up was 35.5 months. Overall, a 25% achieved clinical remission and 40% were in partial response. Biologic-naïve patients demonstrated a significantly better remission rate as compared with those that were not (80 vs. 7%. Patients who achieved remission were more likely to have a significant reduction in C-reactive protein values 1 month after starting the drug. Seven patients required surgery during the follow- up period. Conclusions: Patients naïve to biologics showed a significantly better response to tacrolimus. A reduction in C-reactive protein one month after starting this drug was associated with clinical remission.

  13. Cholesterol enrichment of human monocyte/macrophages induces surface exposure of phosphatidylserine and the release of biologically-active tissue factor-positive microvesicles.

    Science.gov (United States)

    Liu, Ming-Lin; Reilly, Michael P; Casasanto, Peter; McKenzie, Steven E; Williams, Kevin Jon

    2007-02-01

    Biologically significant amounts of two procoagulant molecules, phosphatidylserine (PS) and tissue factor (TF), are transported by monocyte/macrophage-derived microvesicles (MVs). Because cellular cholesterol accumulation is an important feature of atherosclerotic vascular disease, we now examined effects of cholesterol enrichment on MV release from human monocytes and macrophages. Cholesterol enrichment of human THP-1 monocytes, alone or in combination with lipopolysaccharide (LPS), tripled their total MV generation, as quantified by flow cytometry based on particle size and PS exposure. The subset of these MVs that were also TF-positive was likewise increased by cellular cholesterol enrichment, and these TF-positive MVs exhibited a striking 10-fold increase in procoagulant activity. Moreover, cholesterol enrichment of primary human monocyte-derived macrophages also increased their total as well as TF-positive MV release, and these TF-positive MVs exhibited a similar 10-fold increase in procoagulant activity. To explore the mechanisms of enhanced MV release, we found that cholesterol enrichment of monocytes caused PS exposure on the cell surface by as early as 2 hours and genomic DNA fragmentation in a minority of cells by 20 hours. Addition of a caspase inhibitor at the beginning of these incubations blunted both cholesterol-induced apoptosis and MV release. Cholesterol enrichment of human monocyte/macrophages induces the generation of highly biologically active, PS-positive MVs, at least in part through induction of apoptosis. Cholesterol-induced monocyte/macrophage MVs, both TF-positive and TF-negative, may be novel contributors to atherothrombosis.

  14. Biological monitoring of human exposure to coal tar. Urinary mutagenicity assays and analytical determination of polycyclic aromatic hydrocarbon metabolites in urine.

    Science.gov (United States)

    Clonfero, E; Jongeneelen, F; Zordan, M; Levis, A G

    1990-01-01

    The mutagenicity of urine extracts from anode plant workers exposed to coal tar pitch volatiles and non-smoking psoriatic patients treated with coal tar applications and UV light (Goeckermann regimen), was determined by the plate incorporation assay and the fluctuation test employing Salmonella typhimurium strain TA98 in the presence of rat liver post-mitochondrial fractions and deconjugating enzymes. The levels of total polycyclic aromatic hydrocarbons (PAHs) and of a marker metabolite of pyrene (1-hydroxypyrene) were determined in the urine of the same subjects. Both the occupational and in particular the therapeutic exposure to coal tar resulted in clear increases in urinary levels of PAH metabolites as compared to unexposed subjects. The level of 1-hydroxypyrene in the urine samples was comparable to or even greater than the corresponding level of total PAHs, indicating a poor recovery of PAH metabolites for this method. Following treatment with coal tar, most of the psoriatic patients excreted clearly increased levels of mutagens in their urine, w