WorldWideScience

Sample records for cellular xenobiotic defense

  1. Studies on defense mechanism against xenobiotics in rats, using gold as a model

    International Nuclear Information System (INIS)

    Sugawa-Katayama, Yohko; Kojima, Akiko; Nakano, Yukihiro.

    1994-01-01

    For self-protection, a living organism has a special mechanism to prevent xenobiotics from being absorbed through the gastrointestinal tract. This led to the present study on the defense mechanism of the gastrointestinal tract where foods are digested and absorbed. The results obtained from this study showed that 1) starvation caused an insufficiency of the defense mechanism against xenobiotics in jejunal absorptive cells and Kupffer cells, 2) after refeeding diets, a reparative process occurred at the damaged cell sites, resulting in recovery of the defense mechanism against xenobiotics, and 3) a 5% fat diet seemed to be the best fat level for recovery of the defense mechanism against xenobiotics. In the nutritional point of view, the 5% fat diet is equivalent to 0.11 in fat energy ratio (fat energy/total energy of the diet). These data suggest that a diet with a much lower fat energy (equivalent to 0.11) can give a good effect on recovery of the defense mechanism against xenobiotics in the gastrointestinal tract and the liver. (author)

  2. Conservation and divergence of chemical defense system in the tunicate Oikopleura dioica revealed by genome wide response to two xenobiotics

    Directory of Open Access Journals (Sweden)

    Yadetie Fekadu

    2012-02-01

    Full Text Available Abstract Background Animals have developed extensive mechanisms of response to xenobiotic chemical attacks. Although recent genome surveys have suggested a broad conservation of the chemical defensome across metazoans, global gene expression responses to xenobiotics have not been well investigated in most invertebrates. Here, we performed genome survey for key defensome genes in Oikopleura dioica genome, and explored genome-wide gene expression using high density tiling arrays with over 2 million probes, in response to two model xenobiotic chemicals - the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP the pharmaceutical compound Clofibrate (Clo. Results Oikopleura genome surveys for key genes of the chemical defensome suggested a reduced repertoire. Not more than 23 cytochrome P450 (CYP genes could be identified, and neither CYP1 family genes nor their transcriptional activator AhR was detected. These two genes were present in deuterostome ancestors. As in vertebrates, the genotoxic compound BaP induced xenobiotic biotransformation and oxidative stress responsive genes. Notable exceptions were genes of the aryl hydrocarbon receptor (AhR signaling pathway. Clo also affected the expression of many biotransformation genes and markedly repressed genes involved in energy metabolism and muscle contraction pathways. Conclusions Oikopleura has the smallest number of CYP genes among sequenced animal genomes and lacks the AhR signaling pathway. However it appears to have basic xenobiotic inducible biotransformation genes such as a conserved genotoxic stress response gene set. Our genome survey and expression study does not support a role of AhR signaling pathway in the chemical defense of metazoans prior to the emergence of vertebrates.

  3. Cytotoxic effects and aromatase inhibition by xenobiotic endocrine disrupters alone and in combination

    International Nuclear Information System (INIS)

    Benachour, Nora; Moslemi, Safa; Sipahutar, Herbert; Seralini, Gilles-Eric

    2007-01-01

    Xenobiotics may cause long-term adverse effects in humans, especially at the embryonic level, raising questions about their levels of exposure, combined effects, and crucial endpoints. We are interested in the possible interactions between xenobiotic endocrine disrupters, cellular viability and androgen metabolism. Accordingly, we tested aroclor 1254 (A1254), atrazine (AZ), o,p'-DDT, vinclozolin (VZ), p,p'-DDE, bisphenol A (BPA), chlordecone (CD), nonylphenol (NP), tributylin oxide (TBTO), and diethylstilbestrol (DES) for cellular toxicity against human embryonic 293 cells, and activity against cellular aromatase, but also on placental microsomes and on the purified equine enzyme. Cellular viability was affected in 24 h by all the xenobiotics with a threshold at 50 μM (except for TBTO and DES, 10 μM threshold), and aromatase was inhibited at non-toxic doses. In combination synergism was observed reducing the threshold values of toxicity to 4-10 μM, and aromatase activity by 50% in some cases. In placental microsomes the most active xenobiotics rapidly inhibited microsomal aromatase in a manner independent of NADPH metabolism. Prolonged exposures to low doses in cells generally amplified by 50 times aromatase inhibition. These xenobiotics may act by inhibition of the active site or by allosteric effects on the enzyme. Bioaccumulation is a feature of some xenobiotics, especially chlordecone, DDT and DDE, and low level chronic exposures can also affect cell signaling mechanisms. This new information about the mechanism of action of these xenobiotics will assist in improved molecular design with a view to providing safer compounds for use in the (human) environment

  4. The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification.

    Directory of Open Access Journals (Sweden)

    Read Pukkila-Worley

    2014-05-01

    Full Text Available Metazoans protect themselves from environmental toxins and virulent pathogens through detoxification and immune responses. We previously identified a small molecule xenobiotic toxin that extends survival of Caenorhabditis elegans infected with human bacterial pathogens by activating the conserved p38 MAP kinase PMK-1 host defense pathway. Here we investigate the cellular mechanisms that couple activation of a detoxification response to innate immunity. From an RNAi screen of 1,420 genes expressed in the C. elegans intestine, we identified the conserved Mediator subunit MDT-15/MED15 and 28 other gene inactivations that abrogate the induction of PMK-1-dependent immune effectors by this small molecule. We demonstrate that MDT-15/MED15 is required for the xenobiotic-induced expression of p38 MAP kinase PMK-1-dependent immune genes and protection from Pseudomonas aeruginosa infection. We also show that MDT-15 controls the induction of detoxification genes and functions to protect the host from bacteria-derived phenazine toxins. These data define a central role for MDT-15/MED15 in the coordination of xenobiotic detoxification and innate immune responses.

  5. The evolutionarily conserved mediator subunit MDT-15/MED15 links protective innate immune responses and xenobiotic detoxification.

    Science.gov (United States)

    Pukkila-Worley, Read; Feinbaum, Rhonda L; McEwan, Deborah L; Conery, Annie L; Ausubel, Frederick M

    2014-05-01

    Metazoans protect themselves from environmental toxins and virulent pathogens through detoxification and immune responses. We previously identified a small molecule xenobiotic toxin that extends survival of Caenorhabditis elegans infected with human bacterial pathogens by activating the conserved p38 MAP kinase PMK-1 host defense pathway. Here we investigate the cellular mechanisms that couple activation of a detoxification response to innate immunity. From an RNAi screen of 1,420 genes expressed in the C. elegans intestine, we identified the conserved Mediator subunit MDT-15/MED15 and 28 other gene inactivations that abrogate the induction of PMK-1-dependent immune effectors by this small molecule. We demonstrate that MDT-15/MED15 is required for the xenobiotic-induced expression of p38 MAP kinase PMK-1-dependent immune genes and protection from Pseudomonas aeruginosa infection. We also show that MDT-15 controls the induction of detoxification genes and functions to protect the host from bacteria-derived phenazine toxins. These data define a central role for MDT-15/MED15 in the coordination of xenobiotic detoxification and innate immune responses.

  6. Inhibition of cellular efflux pumps involved in multi xenobiotic resistance (MXR) in echinoid larvae as a possible mode of action for increased ecotoxicological risk of mixtures

    NARCIS (Netherlands)

    Drs Anselmo, H.M.R.; Berg, van den J.H.J.; Rietjens, I.; Murk, A.J.

    2012-01-01

    In marine organisms the multi xenobiotic resistance (MXR) mechanism via e.g. P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) is an important first line of defense against contaminants by pumping contaminants out of the cells. If compounds would impair the MXR mechanism, this

  7. Role of Free Radicals, Oxidative Stress and Xenobiotics in Carcinogenesis by Environmental Pollutants

    Directory of Open Access Journals (Sweden)

    Dibyajyoti Saha

    2014-09-01

    Full Text Available Carcinogenesis by many small molecular weight chemicals involves either a direct action of the chemical on cellular DNA or metabolism of the parent chemical to an active or ultimate form, which can than react with cellular DNA to produce a permanent chemical change in a DNA structure. A free radical is an atom or molecule that has one or more unpaired electron(s. These are highly reactive species capable of wide spread, indiscriminate oxidation and per oxidation of proteins, lipids and DNA which can lead to significant cellular damage and even tissue and/or organ failure. . Oxidative stress is a leading cause to damage cells by oxidation. The rate at which oxidative damage is induced (input and the rate at which it is efficiently repaired and removed (output. Xenobiotics are a compound that is foreign to the body. Xenobiotics can produce a variety of biological effects, including pharmacologic responses, toxicity, genes, immunologic reactions and cancer. Oxidative stress is a leading cause to damage cells by oxidation. The rate at which oxidative damage is induced (input and the rate at which it is efficiently repaired and removed (output. This communication highlights the role of carcinogens as environmental pollutants with the possible mechanism of free radicals, oxidative stress and xenobiotics.

  8. (Systemic) phototoxicity of drugs and other xenobiotics.

    Science.gov (United States)

    Beijersbergen van Henegouwen, G M

    1991-08-01

    Xenobiotics extensively used in drugs, cosmetics, food and agricultural chemicals can produce adverse biological effects. These toxic effects are separated into classes, e.g. hepatotoxicity, genotoxicity and neurotoxicity. Skin allergy, part of immunotoxicity, is also a subdivision of toxicology. When light is an essential condition for toxicity, the xenobiotic is called phototoxic. Thus it fits into the logic of toxicology that photoallergic compounds are a subdivision of phototoxic compounds. Phototoxicons as a group do not differ from the group of phototherapeutics with regard to their eventual biological effects. The primary photoreactions, secondary molecular processes, biomolecules involved and cellular and tissue damage are similar. The difference between the two groups is in the appreciation of the photobiological effects: adverse vs. desired. The aim of research is to determine the part of the molecular structure which makes a given compound phototoxic. With that knowledge the structure of the phototoxicon can be changed. This can result in a derivative which still has the desired properties of the parent compound, but is no longer phototoxic. This aim can be reached by combining data from both in vitro and in vivo research. The variety and number of phototoxic compounds is large. This, together with the limited research effort devoted to this subject so far, means that for most phototoxic xenobiotics a relationship between structure and in vivo photoreactivity is not available. In this review, emphasis is placed on xenobiotics whose in vitro and in vivo photochemistry have been studied. Furthermore, possible phototoxic effects which do not concern the skin but involve inner organs (systemic effects) are considered. References in this review mostly concern investigations over the last 10 years. For older literature or for additional information, references to other reviews are given. Important groups of phototoxic xenobiotics not dealt with in this article

  9. Retrofit Strategies for Incorporating Xenobiotic Metabolism into High Throughput Screening Assays (EMGS)

    Science.gov (United States)

    The US EPA’s ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to a mischaracterization...

  10. Xenobiotic Metabolism and Gut Microbiomes.

    Directory of Open Access Journals (Sweden)

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  11. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver.

    Science.gov (United States)

    Cavin, C; Marin-Kuan, M; Langouët, S; Bezençon, C; Guignard, G; Verguet, C; Piguet, D; Holzhäuser, D; Cornaz, R; Schilter, B

    2008-04-01

    Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.

  12. Xenobiotics and the Glucocorticoid Receptor

    International Nuclear Information System (INIS)

    Gulliver, Linda S M

    2017-01-01

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  13. Xenobiotics and the Glucocorticoid Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Gulliver, Linda S M, E-mail: linda.gulliver@otago.ac.nz

    2017-03-15

    Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid

  14. Current knowledge of detoxification mechanisms of xenobiotic in honey bees.

    Science.gov (United States)

    Gong, Youhui; Diao, Qingyun

    2017-01-01

    The western honey bee Apis mellifera is the most important managed pollinator species in the world. Multiple factors have been implicated as potential causes or factors contributing to colony collapse disorder, including honey bee pathogens and nutritional deficiencies as well as exposure to pesticides. Honey bees' genome is characterized by a paucity of genes associated with detoxification, which makes them vulnerable to specific pesticides, especially to combinations of pesticides in real field environments. Many studies have investigated the mechanisms involved in detoxification of xenobiotics/pesticides in honey bees, from primal enzyme assays or toxicity bioassays to characterization of transcript gene expression and protein expression in response to xenobiotics/insecticides by using a global transcriptomic or proteomic approach, and even to functional characterizations. The global transcriptomic and proteomic approach allowed us to learn that detoxification mechanisms in honey bees involve multiple genes and pathways along with changes in energy metabolism and cellular stress response. P450 genes, is highly implicated in the direct detoxification of xenobiotics/insecticides in honey bees and their expression can be regulated by honey/pollen constitutes, resulting in the tolerance of honey bees to other xenobiotics or insecticides. P450s is also a key detoxification enzyme that mediate synergism interaction between acaricides/insecticides and fungicides through inhibition P450 activity by fungicides or competition for detoxification enzymes between acaricides. With the wide use of insecticides in agriculture, understanding the detoxification mechanism of insecticides in honey bees and how honeybees fight with the xenobiotis or insecticides to survive in the changing environment will finally benefit honeybees' management.

  15. Xenobiotic-induced apoptosis: significance and potential application as a general biomarker of response

    Science.gov (United States)

    Sweet, Leonard I.; Passino-Reader, Dora R.; Meier, Peter G.; Omann, Geneva M.

    1999-01-01

    The process of apoptosis, often coined programmed cell death, involves cell injury induced by a variety of stimuli including xenobiotics and is morphologically, biochemically, and physiologically distinct from necrosis. Apoptotic death is characterized by cellular changes such as cytoplasm shrinkage, chromatin condensation, and plasma membrane asymmetry. This form of cell suicide is appealing as a general biomarker of response in that it is expressed in multiple cell systems (e.g. immune, neuronal, hepatal, intestinal, dermal, reproductive), is conserved phylogenetically (e.g. fish, rodents, birds, sheep, amphibians, roundworms, plants, humans), is modulated by environmentally relevant levels of chemical contaminants, and indicates a state of stress of the organism. Further, apoptosis is useful as a biomarker as it serves as a molecular control point and hence may provide mechanistic information on xenobiotic stress. Studies reviewed here suggest that apoptosis is a sensitive and early indicator of acute and chronic chemical stress, loss of cellular function and structure, and organismal health. Examples are provided of the application of this methodology in studies of health of lake trout (Salvelinus namaycush) in the Laurentian Great Lakes.

  16. Microbial transformation of xenobiotics for environmental ...

    African Journals Online (AJOL)

    Microbial transformation of xenobiotics for environmental bioremediation. ... anaerobic and reductive biotransformation by co-metabolic processes and an overview of ... of xenobiotic compounds in context to the modern day biotechnology.

  17. Comparison of xenobiotic-metabolising human, porcine, rodent, and piscine cytochrome P450

    International Nuclear Information System (INIS)

    Burkina, Viktoriia; Rasmussen, Martin Krøyer; Pilipenko, Nadezhda; Zamaratskaia, Galia

    2017-01-01

    Highlights: • The percent identity of porcine, murine and piscine CYPs was compared with human CYPs. • Main similarities and differences were reviewed. • Understanding of molecular mechanisms of CYP system will provide further insights into the CYP regulatory processes, and responses to different factors. - Abstract: Cytochrome P450 proteins (CYP450s) are present in most domains of life and play a critical role in the metabolism of endogenous compounds and xenobiotics. The effects of exposure to xenobiotics depend heavily on the expression and activity of drug-metabolizing CYP450s, which is determined by species, genetic background, age, gender, diet, and exposure to environmental pollutants. Numerous reports have investigated the role of different vertebrate CYP450s in xenobiotic metabolism. Model organisms provide powerful experimental tools to investigate Phase I metabolism. The aim of the present review is to compare the existing data on human CYP450 proteins (1–3 families) with those found in pigs, mice, and fish. We will highlight differences and similarities and identify research gaps which need to be addressed in order to use these species as models that mimic human traits. Moreover, we will discuss the roles of nuclear receptors in the cellular regulation of CYP450 expression in select organisms.

  18. Prediction of bacterial growth on xenobiotics

    DEFF Research Database (Denmark)

    Brock, Andreas Libonati; Kästner, Matthias; Trapp, Stefan

    2016-01-01

    to attain predictions closer to the experimentally observed yields [3]. However, this knowledge is seldom known for xenobiotics in the environment but is needed to assess the turnover leading to biomass production, i.e. for sludge production or biogenic residues. The objectives of the present study were...... method, we evaluated it with both simple substrates (e.g. acetate, methanol, and glyoxylate) and xenobiotics (e.g 2,4-D, linuron, carbofuran, carbon tetrachloride, and toluene). Experimental data for the simple substrates were taken from [4], for xenobiotics from [6] and own experimental data. For simple...... substrates, our approach predicts yields close to experimental values and also for xenobiotics the yield predictions for most of the compounds are close to the experimentally obtained values.Overall, with our method we were able to obtain yield predictions close to experimental values with a minimum of input...

  19. LC-MS-BASED METABOLOMICS OF XENOBIOTIC-INDUCED TOXICITIES

    Directory of Open Access Journals (Sweden)

    Chi Chen

    2013-01-01

    Full Text Available Xenobiotic exposure, especially high-dose or repeated exposure of xenobiotics, can elicit detrimental effects on biological systems through diverse mechanisms. Changes in metabolic systems, including formation of reactive metabolites and disruption of endogenous metabolism, are not only the common consequences of toxic xenobiotic exposure, but in many cases are the major causes behind development of xenobiotic-induced toxicities (XIT. Therefore, examining the metabolic events associated with XIT generates mechanistic insights into the initiation and progression of XIT, and provides guidance for prevention and treatment. Traditional bioanalytical platforms that target only a few suspected metabolites are capable of validating the expected outcomes of xenobiotic exposure. However, these approaches lack the capacity to define global changes and to identify unexpected events in the metabolic system. Recent developments in high-throughput metabolomics have dramatically expanded the scope and potential of metabolite analysis. Among all analytical techniques adopted for metabolomics, liquid chromatography-mass spectrometry (LC-MS has been most widely used for metabolomic investigations of XIT due to its versatility and sensitivity in metabolite analysis. In this review, technical platform of LC-MS-based metabolomics, including experimental model, sample preparation, instrumentation, and data analysis, are discussed. Applications of LC-MS-based metabolomics in exploratory and hypothesis-driven investigations of XIT are illustrated by case studies of xenobiotic metabolism and endogenous metabolism associated with xenobiotic exposure.

  20. Approaching Resonant Absorption of Environmental Xenobiotics Harmonic Oscillation by Linear Structures

    Directory of Open Access Journals (Sweden)

    Cornelia A. Bulucea

    2012-03-01

    Full Text Available Over the last several decades, it has become increasingly accepted that the term xenobiotic relates to environmental impact, since environmental xenobiotics are understood to be substances foreign to a biological system, which did not exist in nature before their synthesis by humans. In this context, xenobiotics are persistent pollutants such as dioxins and polychlorinated biphenyls, as well as plastics and pesticides. Dangerous and unstable situations can result from the presence of environmental xenobiotics since their harmful effects on humans and ecosystems are often unpredictable. For instance, the immune system is extremely vulnerable and sensitive to modulation by environmental xenobitics. Various experimental assays could be performed to ascertain the immunotoxic potential of environmental xenobiotics, taking into account genetic factors, the route of xenobiotic penetration, and the amount and duration of exposure, as well as the wave shape of the xenobiotic. In this paper, we propose an approach for the analysis of xenobiotic metabolism using mathematical models and corresponding methods. This study focuses on a pattern depicting mathematically modeled processes of resonant absorption of a xenobiotic harmonic oscillation by an organism modulated as an absorbing oscillator structure. We represent the xenobiotic concentration degree through a spatial concentration vector, and we model and simulate the oscillating regime of environmental xenobiotic absorption. It is anticipated that the results could be used to facilitate the assessment of the processes of environmental xenobiotic absorption, distribution, biotransformation and removal within the framework of compartmental analysis, by establishing appropriate mathematical models and simulations.

  1. Genomic interrogation of mechanism(s) underlying cellular responses to toxicants

    International Nuclear Information System (INIS)

    Amin, Rupesh P.; Hamadeh, Hisham K.; Bushel, Pierre R.; Bennett, Lee; Afshari, Cynthia A.; Paules, Richard S.

    2002-01-01

    Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information

  2. Cellular defense against UVB-induced phototoxicity by cytosolic NADP+-dependent isocitrate dehydrogenase

    International Nuclear Information System (INIS)

    Jo, Seung-Hee; Lee, So-Hyun; Suk Chun, Hang; Min Lee, Su; Koh, Ho-Jin; Lee, Sung-Eun; Chun, Jang-Soo; Park, Jeen-Woo; Huh, Tae-Lin

    2002-01-01

    Ultraviolet (UV) radiation is known as a major cause of skin photoaging and photocarcinogenesis. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species. Recently, we have shown that NADP + -dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study we investigated the role of cytosolic form of NADP + -dependent isocitrate dehydrogenase (IDPc) against UV radiation-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to UVB (312 nm), the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly overexpressed IDPc exhibited enhanced resistance against UV radiation, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against UV radiation-induced oxidative injury

  3. Cellular defense against UVB-induced phototoxicity by cytosolic NADP(+)-dependent isocitrate dehydrogenase.

    Science.gov (United States)

    Jo, Seung-Hee; Lee, So-Hyun; Chun, Hang Suk; Lee, Su Min; Koh, Ho-Jin; Lee, Sung-Eun; Chun, Jang-Soo; Park, Jeen-Woo; Huh, Tae-Lin

    2002-03-29

    Ultraviolet (UV) radiation is known as a major cause of skin photoaging and photocarcinogenesis. Many harmful effects of UV radiation are associated with the generation of reactive oxygen species. Recently, we have shown that NADP(+)-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study we investigated the role of cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc) against UV radiation-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to UVB (312 nm), the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly overexpressed IDPc exhibited enhanced resistance against UV radiation, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against UV radiation-induced oxidative injury. (c)2002 Elsevier Science (USA).

  4. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Energy Technology Data Exchange (ETDEWEB)

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  5. Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

    Science.gov (United States)

    Kim, Sun Yee; Park, Jeen-Woo

    2003-03-01

    Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

  6. In silico prediction of xenobiotic metabolism in humans

    Energy Technology Data Exchange (ETDEWEB)

    Mu, Fangping [Los Alamos National Laboratory

    2009-01-01

    Xenobiotic metabolism in humans is catalyzed by a few enzymes with broad substrate specificities, which provide the overall broad chemical specificity for nearly all xenobiotics that humans encounter. Xenobiotic metabolism are classified into functional group biotransformations. Based on bona fide reactions and negative examples for each reaction class, support vector machine (SVM) classifiers are built. The input to SVM is a set of atomic and molecular features to define the electrostatic, steric, energetic, geometrical and topological environment of the atoms in the reaction center under the molecule. Results show that the overall sensitivity and specificity of classifiers is around 87%.

  7. Potential for anaerobic conversion of xenobiotics

    DEFF Research Database (Denmark)

    Mogensen, Anders Skibsted; Dolfing, J.; Haagensen, Frank

    2003-01-01

    This review covers the latest research on the anaerobic biodegradation of aromatic xenobiotic compounds, with emphasis on surfactants, polycyclic aromatic hydrocarbons, phthalate esters, polychlorinated biphenyls, halogenated phenols, and pesticides. The versatility of anaerobic reactor systems...... regarding the treatment of xenobiotics is shown with the focus on the UASB reactor, but the applicability of other reactor designs for treatment of hazardous waste is also included. Bioaugmentation has proved to be a viable technique to enhance a specific activity in anaerobic reactors and recent research...

  8. P-glycoprotein Inhibition by the Agricultural Pesticide Propiconazole and Its Hydroxylated Metabolites: Implications for Pesticide-Drug Interactions.

    Science.gov (United States)

    The human efflux transporter P-glycoprotein (P-gp; MDR1) functions an important cellular defense system against a variety of xenobiotics; however, little information exists on whether environmental chemicals interact with P-gp. Conazoles provide a unique challenge to exposure ass...

  9. The cuticle and plant defense to pathogens

    Directory of Open Access Journals (Sweden)

    Jean-Pierre eMetraux

    2014-06-01

    Full Text Available The cuticle provides a physical barrier against water loss and protects against irradiation, xenobiotics and pathogens. Components of the cuticle are perceived by invading fungi and activate developmental processes during pathogenesis. In addition, cuticle alterations of various types induce a syndrome of reactions that often results in resistance to necrotrophs. This article reviews the current knowledge on the role of the cuticle in relation to the perception of pathogens and activation of defenses.

  10. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

    Directory of Open Access Journals (Sweden)

    Nadine T Nehme

    2011-03-01

    Full Text Available Two NF-kappaB signaling pathways, Toll and immune deficiency (imd, are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial peptides, which are important components of a humoral defense response. However, it is less clear to what extent macrophage-like hemocytes contribute to host defense.In order to dissect the relative importance of humoral and cellular defenses after septic injury with three different gram-positive bacteria (Micrococcus luteus, Enterococcus faecalis, Staphylococcus aureus, we used latex bead pre-injection to ablate macrophage function in flies wildtype or mutant for various Toll and imd pathway components. We found that in all three infection models a compromised phagocytic system impaired fly survival--independently of concomitant Toll or imd pathway activation. Our data failed to confirm a role of the PGRP-SA and GNBP1 Pattern Recognition Receptors for phagocytosis of S. aureus. The Drosophila scavenger receptor Eater mediates the phagocytosis by hemocytes or S2 cells of E. faecalis and S. aureus, but not of M. luteus. In the case of M. luteus and E. faecalis, but not S. aureus, decreased survival due to defective phagocytosis could be compensated for by genetically enhancing the humoral immune response.Our results underscore the fundamental importance of both cellular and humoral mechanisms in Drosophila immunity and shed light on the balance between these two arms of host defense depending on the invading pathogen.

  11. Addressing the Impact of Environmental Xenobiotics in Coal-Fired Flue Gas

    Directory of Open Access Journals (Sweden)

    Cornelia A. Bulucea

    2015-03-01

    Full Text Available Dangerous and unstable situations can result from the presence of environmental xenobiotics since their harmful effects on humans and ecosystems are often unpredictable, and building awareness of the environmental risk should be a main concern of humankind. The environmental xenobiotics in the flue gas from a fossil fuel-fired electrical generating station, such as particulate matter (PM, sulfur dioxide (SO2, nitrogen oxides (NOx, and carbon dioxide (CO2, are analyzed in this study, since these xenobiotics are persistent pollutants. Mathematical models of the environmental pollutant vector, estimating the emission factors specific to fossil fuel combustion, are applied to the operation of thermal units in the Turceni electrical generating station, each of which produces a net electrical power of 330 MW. For each stack gas component in the pollutant vector, emission factors and pollutant concentrations are determined. A pattern is also examined depicting the mathematically modelled processes of resonant absorption of an environmental xenobiotic harmonic oscillation by an organism modulated as an absorbing oscillator structure. The xenobiotic concentration degree is represented through a spatial concentration vector, which allows further modelling and simulation of the oscillating regime of environmental xenobiotic absorption.

  12. Effect of thiabendazole on some rat hepatic xenobiotic metabolising enzymes

    NARCIS (Netherlands)

    Price, R.J.; Scott, M.P.; Walters, D.G.; Stierum, R.H.; Groten, J.P.; Meredith, C.; Lake, B.G.

    2004-01-01

    The effect of thiabendazole (TB) on some rat hepatic xenobiotic metabolising enzymes has been investigated. Male Sprague-Dawley rats were fed control diet or diets containing 102-5188 ppm TB for 28 days. As a positive control for induction of hepatic xenobiotic metabolism, rats were also fed diets

  13. Cellular and exosome mediated molecular defense mechanism in bovine granulosa cells exposed to oxidative stress.

    Directory of Open Access Journals (Sweden)

    Mohammed Saeed-Zidane

    Full Text Available Various environmental insults including diseases, heat and oxidative stress could lead to abnormal growth, functions and apoptosis in granulosa cells during ovarian follicle growth and oocyte maturation. Despite the fact that cells exposed to oxidative stress are responding transcriptionally, the potential release of transcripts associated with oxidative stress response into extracellular space through exosomes is not yet determined. Therefore, here we aimed to investigate the effect of oxidative stress in bovine granulosa cells in vitro on the cellular and exosome mediated defense mechanisms. Bovine granulosa cells were aspirated from ovarian follicles and cultured in DMEM/F-12 Ham culture medium supplemented with 10% exosome-depleted fetal bovine serum. In the first experiment sub-confluent cells were treated with 5 μM H2O2 for 40 min to induce oxidative stress. Thereafter, cells were subjected to ROS and mitochondrial staining, cell proliferation and cell cycle assays. Furthermore, gene and protein expression analysis were performed in H2O2-challenged versus control group 24 hr post-treatment using qRT-PCR and immune blotting or immunocytochemistry assay, respectively. Moreover, exosomes were isolated from spent media using ultracentrifugation procedure, and subsequently used for RNA isolation and qRT-PCR. In the second experiment, exosomes released by granulosa cells under oxidative stress (StressExo or those released by granulosa cells without oxidative stress (NormalExo were co-incubated with bovine granulosa cells in vitro to proof the potential horizontal transfer of defense molecules from exosomes to granulosa cells and investigate any phenotype changes. Exposure of bovine granulosa cells to H2O2 induced the accumulation of ROS, reduced mitochondrial activity, increased expression of Nrf2 and its downstream antioxidant genes (both mRNA and protein, altered the cell cycle transitions and induced cellular apoptosis. Granulosa cells

  14. A Liver-Centric Multiscale Modeling Framework for Xenobiotics.

    Directory of Open Access Journals (Sweden)

    James P Sluka

    Full Text Available We describe a multi-scale, liver-centric in silico modeling framework for acetaminophen pharmacology and metabolism. We focus on a computational model to characterize whole body uptake and clearance, liver transport and phase I and phase II metabolism. We do this by incorporating sub-models that span three scales; Physiologically Based Pharmacokinetic (PBPK modeling of acetaminophen uptake and distribution at the whole body level, cell and blood flow modeling at the tissue/organ level and metabolism at the sub-cellular level. We have used standard modeling modalities at each of the three scales. In particular, we have used the Systems Biology Markup Language (SBML to create both the whole-body and sub-cellular scales. Our modeling approach allows us to run the individual sub-models separately and allows us to easily exchange models at a particular scale without the need to extensively rework the sub-models at other scales. In addition, the use of SBML greatly facilitates the inclusion of biological annotations directly in the model code. The model was calibrated using human in vivo data for acetaminophen and its sulfate and glucuronate metabolites. We then carried out extensive parameter sensitivity studies including the pairwise interaction of parameters. We also simulated population variation of exposure and sensitivity to acetaminophen. Our modeling framework can be extended to the prediction of liver toxicity following acetaminophen overdose, or used as a general purpose pharmacokinetic model for xenobiotics.

  15. Xenobiotics and the Human Gut Microbiome: Metatranscriptomics Reveal the Active Players

    OpenAIRE

    Ursell, Luke K.; Knight, Rob

    2013-01-01

    The human gut microbiome plays an important role in the metabolism of xenobiotics. In a recent issue of Cell, Maurice et al. identify the active members of the gut microbiome and show how gene expression profiles change within the gut microbial community in response to antibiotics and host-targeted xenobiotics.

  16. Estimation of aerial deposition and foliar uptake of xenobiotics: Assessment of current models

    Energy Technology Data Exchange (ETDEWEB)

    Link, S.O.; Fellows, R.J.; Cataldo, D.A.; Droppo, J.G.; Van Voris, P.

    1987-10-01

    This report reviews existing mathematical and/or computer simulation models that estimate xenobiotic deposition to and transport through (both curricular and stomatal) vegetative surfaces. The report evaluates the potential for coupling the best of those models to the existing Uptake, Translocation, Accumulation, and Biodegradation model to be used for future xenobiotic exposure assessments. Here xenobiotic compounds are defined as airborne contaminants, both organic and gaseous pollutants, that are introduced into the environment by man. Specifically this document provides a detailed review of the state-of-the-art models that addressed aerial deposition of particles and gases to foliage; foliar and cuticular transport, metabolism, and uptake of organic xenobiotics; and stomatal transport of gaseous and volatile organic xenobiotic pollutants. Where detailed information was available, parameters for each model are provided on a chemical by chemical as well as species by species basis. Sufficient detail is provided on each model to assess the potential for adapting or coupling the model to the existing UTAB plant exposure model. 126 refs., 6 figs., 10 tabs.

  17. Metabolic and redox barriers in the skin exposed to drugs and xenobiotics.

    Science.gov (United States)

    Korkina, Liudmila

    2016-01-01

    Growing exposure of human skin to environmental and occupational hazards, to numerous skin care/beauty products, and to topical drugs led to a biomedical concern regarding sustainability of cutaneous chemical defence that is essential for protection against intoxication. Since skin is the largest extra-hepatic drug/xenobiotic metabolising organ where redox-dependent metabolic pathways prevail, in this review, publications on metabolic processes leading to redox imbalance (oxidative stress) and its autocrine/endocrine impact to cutaneous drug/xenobiotic metabolism were scrutinised. Chemical and photo-chemical skin barriers contain metabolic and redox compartments: their protective and homeostatic functions. The review will examine the striking similarity of adaptive responses to exogenous chemical/photo-chemical stressors and endogenous toxins in cutaneous metabolic and redox system; the role(s) of xenobiotics/drugs and phase II enzymes in the endogenous antioxidant defence and maintenance of redox balance; redox regulation of interactions between metabolic and inflammatory responses in skin cells; skin diseases sharing metabolic and redox problems (contact dermatitis, lupus erythematosus, and vitiligo) Due to exceptional the redox dependence of cutaneous metabolic pathways and interaction of redox active metabolites/exogenous antioxidants with drug/xenobiotic metabolism, metabolic tests of topical xenobiotics/drugs should be combined with appropriate redox analyses and performed on 3D human skin models.

  18. Molecular, cellular, and tissue impact of depleted uranium on xenobiotic-metabolizing enzymes.

    Science.gov (United States)

    Gueguen, Yann; Rouas, Caroline; Monin, Audrey; Manens, Line; Stefani, Johanna; Delissen, Olivia; Grison, Stéphane; Dublineau, Isabelle

    2014-02-01

    Enzymes that metabolize xenobiotics (XME) are well recognized in experimental models as representative indicators of organ detoxification functions and of exposure to toxicants. As several in vivo studies have shown, uranium can alter XME in the rat liver or kidneys after either acute or chronic exposure. To determine how length or level of exposure affects these changes in XME, we continued our investigation of chronic rat exposure to depleted uranium (DU, uranyl nitrate). The first study examined the effect of duration (1-18 months) of chronic exposure to DU, the second evaluated dose dependence, from a level close to that found in the environment near mining sites (0.2 mg/L) to a supra-environmental dose (120 mg/L, 10 times the highest level naturally found in the environment), and the third was an in vitro assessment of whether DU exposure directly affects XME and, in particular, CYP3A. The experimental in vivo models used here demonstrated that CYP3A is the enzyme modified to the greatest extent: high gene expression changed after 6 and 9 months. The most substantial effects were observed in the liver of rats after 9 months of exposure to 120 mg/L of DU: CYP3A gene and protein expression and enzyme activity all decreased by more than 40 %. Nonetheless, no direct effect of DU by itself was observed after in vitro exposure of rat microsomal preparations, HepG2 cells, or human primary hepatocytes. Overall, these results probably indicate the occurrence of regulatory or adaptive mechanisms that could explain the indirect effect observed in vivo after chronic exposure.

  19. Xenobiotic metabolism in the fourth dimension: PARtners in time.

    Science.gov (United States)

    Green, Carla B; Takahashi, Joseph S

    2006-07-01

    A significant portion of the transcriptome in mammals, including the PAR bZIP transcription factors DBP, HLF, and TEF, is under circadian clock control. In this issue of Cell Metabolism, Gachon and colleagues (Gachon et al., 2006) show that disruption of these three genes in mice alters gene expression patterns of many proteins involved in drug metabolism and in liver and kidney responses to xenobiotic agents. Triple mutant mice have severe physiological deficits, including increased hypersensitivity to xenobiotic agents and premature aging, highlighting the profound effect the circadian clock has on this important response system.

  20. Integrated modelling of two xenobiotic organic compounds

    DEFF Research Database (Denmark)

    Lindblom, Erik Ulfson; Gernaey, K.V.; Henze, Mogens

    2006-01-01

    This paper presents a dynamic mathematical model that describes the fate and transport of two selected xenobiotic organic compounds (XOCs) in a simplified representation. of an integrated urban wastewater system. A simulation study, where the xenobiotics bisphenol A and pyrene are used as reference...... compounds, is carried out. Sorption and specific biological degradation processes are integrated with standardised water process models to model the fate of both compounds. Simulated mass flows of the two compounds during one dry weather day and one wet weather day are compared for realistic influent flow...... rate and concentration profiles. The wet weather day induces resuspension of stored sediments, which increases the pollutant load on the downstream system. The potential of the model to elucidate important phenomena related to origin and fate of the model compounds is demonstrated....

  1. Influence of TiO{sub 2} nanoparticles on cellular antioxidant defense and its involvement in genotoxicity in HepG2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Petkovic, Jana; Zegura, Bojana; Filipic, Metka, E-mail: metka.filipic@nib.si [Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, SI-1000 Ljubljana (Slovenia)

    2011-07-06

    We investigated the effects of two types of TiO{sub 2} nanoparticles (<25 nm anatase, TiO{sub 2}-An; <100 nm rutile, TiO{sub 2}-Ru) on cellular antioxidant defense in HepG2 cells. We previously showed that in HepG2 cells, TiO{sub 2} nanoparticles are not toxic, although they induce oxidative DNA damage, production of intracellular reactive oxygen species, and up-regulation of mRNA expression of DNA-damage-responsive genes (p53, p21, gadd45{alpha} and mdm2). In the present study, we measured changes in mRNA expression of several antioxidant enzymes: catalase, superoxide dismutase, glutathione peroxidase, nitric oxide synthase, glutathione reductase and glutamate-cysteine ligase. As reduced glutathione has a central role in cellular antioxidant defense, we determined the effects of TiO{sub 2} nanoparticles on changes in the intracellular glutathione content. To confirm a role for glutathione in protection against TiO{sub 2}-nanoparticle-induced DNA damage, we compared the extent of TiO{sub 2}-nanoparticle-induced DNA damage in HepG2 cells that were glutathione depleted with buthionine-(S,R)-sulfoximine pretreatment and in nonglutathione-depleted cells. Our data show that both types of TiO{sub 2} nanoparticles up-regulate mRNA expression of oxidative-stress-related genes, with TiO{sub 2}-Ru being a stronger inducer than TiO{sub 2}-An. Both types of TiO{sub 2} nanoparticles also induce dose-dependent increases in intracellular glutathione levels, and in glutathione-depleted cells, TiO{sub 2}-nanoparticle-induced DNA damage was significantly greater than in nonglutathione-depleted cells. Interestingly, the glutathione content and the extent of DNA damage were significantly higher in TiO{sub 2}-An- than TiO{sub 2}-Ru-exposed cells. Thus, we show that TiO{sub 2} nanoparticles cause activation of cellular antioxidant processes, and that intracellular glutathione has a critical role in defense against this TiO{sub 2}-nanoparticle-induced DNA damage.

  2. The biochemistry and molecular biology of xenobiotic polymer degradation by microorganisms.

    Science.gov (United States)

    Kawai, Fusako

    2010-01-01

    Research on microbial degradation of xenobiotic polymers has been underway for more than 40 years. It has exploited a new field not only in applied microbiology but also in environmental microbiology, and has greatly contributed to polymer science by initiating the design of biodegradable polymers. Owing to the development of analytical tools and technology, molecular biological and biochemical advances have made it possible to prospect for degrading microorganisms in the environment and to determine the mechanisms involved in biodegradation when xenobiotic polymers are introduced into the environment and are exposed to microbial attack. In this review, the molecular biological and biochemical aspects of the microbial degradation of xenobiotic polymers are summarized, and possible applications of potent microorganisms, enzymes, and genes in environmental biotechnology are suggested.

  3. Xenophagic pathways and their bacterial subversion in cellular self-defense - παντα ρει - everything is in flux.

    Science.gov (United States)

    Radomski, Nadine; Rebbig, Annica; Leonhardt, Ralf M; Knittler, Michael R

    2017-11-02

    Autophagy is an evolutionarily ancient and highly conserved eukaryotic mechanism that targets cytoplasmic material for degradation. Autophagic flux involves the formation of autophagosomes and their degradation by lysosomes. The process plays a crucial role in maintaining cellular homeostasis and responds to various environmental conditions. While autophagy had previously been thought to be a non-selective process, it is now clear that it can also selectively target cellular organelles, such as mitochondria (referred to as mitophagy) and/or invading pathogens (referred to as xenophagy). Selective autophagy is characterized by specific substrate recognition and requires distinct cellular adaptor proteins. Here we review xenophagic mechanisms involved in the recognition and autolysosomal or autophagolysosomal degradation of different intracellular bacteria. In this context, we also discuss a recently discovered cellular self-defense pathway, termed mito-xenophagy, which occurs during bacterial infection of dendritic cells and depends on a TNF-α-mediated metabolic switch from oxidative phosphorylation to glycolysis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. PROXIMAL: a method for Prediction of Xenobiotic Metabolism.

    Science.gov (United States)

    Yousofshahi, Mona; Manteiga, Sara; Wu, Charmian; Lee, Kyongbum; Hassoun, Soha

    2015-12-22

    Contamination of the environment with bioactive chemicals has emerged as a potential public health risk. These substances that may cause distress or disease in humans can be found in air, water and food supplies. An open question is whether these chemicals transform into potentially more active or toxic derivatives via xenobiotic metabolizing enzymes expressed in the body. We present a new prediction tool, which we call PROXIMAL (Prediction of Xenobiotic Metabolism) for identifying possible transformation products of xenobiotic chemicals in the liver. Using reaction data from DrugBank and KEGG, PROXIMAL builds look-up tables that catalog the sites and types of structural modifications performed by Phase I and Phase II enzymes. Given a compound of interest, PROXIMAL searches for substructures that match the sites cataloged in the look-up tables, applies the corresponding modifications to generate a panel of possible transformation products, and ranks the products based on the activity and abundance of the enzymes involved. PROXIMAL generates transformations that are specific for the chemical of interest by analyzing the chemical's substructures. We evaluate the accuracy of PROXIMAL's predictions through case studies on two environmental chemicals with suspected endocrine disrupting activity, bisphenol A (BPA) and 4-chlorobiphenyl (PCB3). Comparisons with published reports confirm 5 out of 7 and 17 out of 26 of the predicted derivatives for BPA and PCB3, respectively. We also compare biotransformation predictions generated by PROXIMAL with those generated by METEOR and Metaprint2D-react, two other prediction tools. PROXIMAL can predict transformations of chemicals that contain substructures recognizable by human liver enzymes. It also has the ability to rank the predicted metabolites based on the activity and abundance of enzymes involved in xenobiotic transformation.

  5. Measurements of radioactive and xenobiotic substances in the biosphere in the Netherlands 1983

    International Nuclear Information System (INIS)

    1983-01-01

    In this annual report the results and conclusions are given of measurements of radioactive and xenobiotic substances in the biosphere of the Netherlands. The measurements are coordinated by the Coordinating Committee for the Monitoring of Radioactive and Xenobiotic Substances (CCRX)

  6. Symposium overview: alterations in cytokine receptors by xenobiotics.

    Science.gov (United States)

    Cohen, M D; Schook, L B; Oppenheim, J J; Freed, B M; Rodgers, K E

    1999-04-01

    A symposium entitled Alterations in Cytokine Receptors by Xenobiotics was held at the 37th Annual Meeting of the Society of Toxicology (SOT) in Seattle, Washington. The symposium was sponsored by the Immunotoxicology Specialty Section of SOT and was designed to present information on the effect of several different classes of xenobiotics on various aspects of receptor function (i.e., post-receptor signal transduction of receptor expression), or the involvement of cytokine receptors in the action of the toxicant under consideration. This symposium brought together scientists in the area of receptor immunobiology whose expertise in receptor modulation encompassed those major signaling agents involved in the normal immune response, i.e., proinflammatory cytokines, chemokines, interleukins, and interferons. The following is a summary of each of the individual presentations.

  7. Effect of Nine Diets on Xenobiotic Transporters in Livers of Mice

    Science.gov (United States)

    Guo, Ying; Cui, Julia Yue; Lu, Hong; Klaassen, Curtis D.

    2017-01-01

    1. Lifestyle diseases are often caused by inappropriate nutrition habits and attempted to be treated by polypharmacotherapy. Therefore, it is important to determine whether differences in diet affect the disposition of drugs. Xenobiotic transporters in the liver are essential in drug disposition. 2. In the current study, mice were fed one of 9 diets for 3 weeks. The mRNAs of 23 known xenobiotic transporters in livers of mice were quantified by microarray analysis, and validated by branched DNA assay. The mRNAs of 15 transporters were altered by at least one diet. Diet-restriction (10) and the atherogenic diet (10) altered the expression of the most number of transporters, followed by western diet (8), high-fat diet (4), lab chow (2), high-fructose diet (2) and EFA-deficient diet (2), whereas the low n-3 FA diet had no effect on these transporters. Seven of the 11 xenobiotic transporters in the Slc family, three of 4 in the Abcb family, two of 4 in the Abcc family and all 3 in the Abcg family were changed significantly. 3. This first comprehensive study indicates that xenobiotic transporters are altered by diet, and suggests there are likely diet-drug interactions due to changes in the expression of drug transporters. PMID:25566878

  8. Pb-induced cellular defense system in the root meristematic cells of Allium sativum L.

    Science.gov (United States)

    Jiang, Wusheng; Liu, Donghua

    2010-03-02

    Electron microscopy (EM) techniques enable identification of the main accumulations of lead (Pb) in cells and cellular organelles and observations of changes in cell ultrastructure. Although there is extensive literature relating to studies on the influence of heavy metals on plants, Pb tolerance strategies of plants have not yet been fully explained. Allium sativum L. is a potential plant for absorption and accumulation of heavy metals. In previous investigations the effects of different concentrations (10(-5) to 10(-3) M) of Pb were investigated in A. sativum, indicating a significant inhibitory effect on shoot and root growth at 10(-3) to 10(-4) M Pb. In the present study, we used EM and cytochemistry to investigate ultrastructural alterations, identify the synthesis and distribution of cysteine-rich proteins induced by Pb and explain the possible mechanisms of the Pb-induced cellular defense system in A. sativum. After 1 h of Pb treatment, dictyosomes were accompanied by numerous vesicles within cytoplasm. The endoplasm reticulum (ER) with swollen cisternae was arranged along the cell wall after 2 h. Some flattened cisternae were broken up into small closed vesicles and the nuclear envelope was generally more dilated after 4 h. During 24-36 h, phenomena appeared such as high vacuolization of cytoplasm and electron-dense granules in cell walls, vacuoles, cytoplasm and mitochondrial membranes. Other changes included mitochondrial swelling and loss of cristae, and vacuolization of ER and dictyosomes during 48-72 h. In the Pb-treatment groups, silver grains were observed in cell walls and in cytoplasm, suggesting the Gomori-Swift reaction can indirectly evaluate the Pb effects on plant cells. Cell walls can immobilize some Pb ions. Cysteine-rich proteins in cell walls were confirmed by the Gomori-Swift reaction. The morphological alterations in plasma membrane, dictyosomes and ER reflect the features of detoxification and tolerance under Pb stress. Vacuoles are

  9. Pb-induced cellular defense system in the root meristematic cells of Allium sativum L

    Directory of Open Access Journals (Sweden)

    Liu Donghua

    2010-03-01

    Full Text Available Abstract Background Electron microscopy (EM techniques enable identification of the main accumulations of lead (Pb in cells and cellular organelles and observations of changes in cell ultrastructure. Although there is extensive literature relating to studies on the influence of heavy metals on plants, Pb tolerance strategies of plants have not yet been fully explained. Allium sativum L. is a potential plant for absorption and accumulation of heavy metals. In previous investigations the effects of different concentrations (10-5 to 10-3 M of Pb were investigated in A. sativum, indicating a significant inhibitory effect on shoot and root growth at 10-3 to 10-4 M Pb. In the present study, we used EM and cytochemistry to investigate ultrastructural alterations, identify the synthesis and distribution of cysteine-rich proteins induced by Pb and explain the possible mechanisms of the Pb-induced cellular defense system in A. sativum. Results After 1 h of Pb treatment, dictyosomes were accompanied by numerous vesicles within cytoplasm. The endoplasm reticulum (ER with swollen cisternae was arranged along the cell wall after 2 h. Some flattened cisternae were broken up into small closed vesicles and the nuclear envelope was generally more dilated after 4 h. During 24-36 h, phenomena appeared such as high vacuolization of cytoplasm and electron-dense granules in cell walls, vacuoles, cytoplasm and mitochondrial membranes. Other changes included mitochondrial swelling and loss of cristae, and vacuolization of ER and dictyosomes during 48-72 h. In the Pb-treatment groups, silver grains were observed in cell walls and in cytoplasm, suggesting the Gomori-Swift reaction can indirectly evaluate the Pb effects on plant cells. Conclusions Cell walls can immobilize some Pb ions. Cysteine-rich proteins in cell walls were confirmed by the Gomori-Swift reaction. The morphological alterations in plasma membrane, dictyosomes and ER reflect the features of detoxification

  10. Transgenic plants for enhanced biodegradation and phytoremediation of organic xenobiotics.

    Science.gov (United States)

    Abhilash, P C; Jamil, Sarah; Singh, Nandita

    2009-01-01

    Phytoremediation--the use of plants to clean up polluted soil and water resources--has received much attention in the last few years. Although plants have the inherent ability to detoxify xenobiotics, they generally lack the catabolic pathway for the complete degradation of these compounds compared to microorganisms. There are also concerns over the potential for the introduction of contaminants into the food chain. The question of how to dispose of plants that accumulate xenobiotics is also a serious concern. Hence the feasibility of phytoremediation as an approach to remediate environmental contamination is still somewhat in question. For these reasons, researchers have endeavored to engineer plants with genes that can bestow superior degradation abilities. A direct method for enhancing the efficacy of phytoremediation is to overexpress in plants the genes involved in metabolism, uptake, or transport of specific pollutants. Furthermore, the expression of suitable genes in root system enhances the rhizodegradation of highly recalcitrant compounds like PAHs, PCBs etc. Hence, the idea to amplify plant biodegradation of xenobiotics by genetic manipulation was developed, following a strategy similar to that used to develop transgenic crops. Genes from human, microbes, plants, and animals are being used successfully for this venture. The introduction of these genes can be readily achieved for many plant species using Agrobacterium tumefaciens-mediated plant transformation or direct DNA methods of gene transfer. One of the promising developments in transgenic technology is the insertion of multiple genes (for phase 1 metabolism (cytochrome P450s) and phase 2 metabolism (GSH, GT etc.) for the complete degradation of the xenobiotics within the plant system. In addition to the use of transgenic plants overexpressed with P450 and GST genes, various transgenic plants expressing bacterial genes can be used for the enhanced degradation and remediation of herbicides, explosives

  11. Xenobiotics enhance laccase activity in alkali-tolerant γ-proteobacterium JB.

    Science.gov (United States)

    Singh, Gursharan; Batish, Mona; Sharma, Prince; Capalash, Neena

    2009-01-01

    Various genotoxic textile dyes, xenobiotics, substrates (10 µM) and agrochemicals (100 µg/ml) were tested for enhancement of alkalophilic laccase activity in γ-proteobacterium JB. Neutral Red, Indigo Carmine, Naphthol Base Bordears and Sulphast Ruby dyes increased the activity by 3.7, 2.7, 2.6 and 2.3 fold respectively. Xenobiotics/substrates like p-toluidine, 8-hydroxyquinoline and anthracine increased it by 3.4, 2.8 and 2.3 fold respectively. Atrazine and trycyclozole pesticides enhanced the activity by 1.95 and 1.5 fold respectively.

  12. Toxicity of xenobiotics during sulfate, iron, and nitrate reduction in primary sewage sludge suspensions

    DEFF Research Database (Denmark)

    Elsgaard, Lars

    2010-01-01

    The effect and persistence of six organic xenobiotics was tested under sulfate-, iron-, and nitrate-reducing conditions in primary sewage sludge suspensions. The xenobiotics tested were acenaphthene, phenanthrene, di(2-ethylhexyl)phthalate (DEHP), 4-nonylphenol (4-NP), linear alkylbenzene sulfonate...

  13. An activated sludge modeling framework for xenobiotic trace chemicals (ASM-X): assessment of diclofenac and carbamazepine.

    Science.gov (United States)

    Plósz, Benedek Gy; Langford, Katherine H; Thomas, Kevin V

    2012-11-01

    Conventional models for predicting the fate of xenobiotic organic trace chemicals, identified, and calibrated using data obtained in batch experiments spiked with reference substances, can be limited in predicting xenobiotic removal in wastewater treatment plants (WWTPs). At stake is the level of model complexity required to adequately describe a general theory of xenobiotic removal in WWTPs. In this article, we assess the factors that influence the removal of diclofenac and carbamazepine in activated sludge, and evaluate the complexity required for the model to effectively predict their removal. The results are generalized to previously published cases. Batch experimental results, obtained under anoxic and aerobic conditions, were used to identify extensions to, and to estimate parameter values of the activated sludge modeling framework for Xenobiotic trace chemicals (ASM-X). Measurement and simulation results obtained in the batch experiments, spiked with the diclofenac and carbamazepine content of preclarified municipal wastewater shows comparably high biotransformation rates in the presence of growth substrates. Forward dynamic simulations were performed using full-scale data obtained from Bekkelaget WWTP (Oslo, Norway) to evaluate the model and to estimate the level of re-transformable xenobiotics present in the influent. The results obtained in this study demonstrate that xenobiotic loading conditions can significantly influence the removal capacity of WWTPs. We show that the trace chemical retransformation in upstream sewer pipes can introduce considerable error in assessing the removal efficiency of a WWTP, based only on parent compound concentration measurements. The combination of our data with those from the literature shows that solids retention time (SRT) can enhance the biotransformation of diclofenac, which was not the case for carbamazepine. Model approximation of the xenobiotic concentration, detected in the solid phase, suggest that between

  14. Generation Z: Adolescent Xenobiotic Abuse in the 21st Century.

    Science.gov (United States)

    Eggleston, William; Stork, Christine

    2015-12-01

    NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.

  15. Interplay of drug metabolizing enzymes with cellular transporters.

    Science.gov (United States)

    Böhmdorfer, Michaela; Maier-Salamon, Alexandra; Riha, Juliane; Brenner, Stefan; Höferl, Martina; Jäger, Walter

    2014-11-01

    Many endogenous and xenobiotic substances and their metabolites are substrates for drug metabolizing enzymes and cellular transporters. These proteins may not only contribute to bioavailability of molecules but also to uptake into organs and, consequently, to overall elimination. The coordinated action of uptake transporters, metabolizing enzymes, and efflux pumps, therefore, is a precondition for detoxification and elimination of drugs. As the understanding of the underlying mechanisms is important to predict alterations in drug disposal, adverse drug reactions and, finally, drug-drug interactions, this review illustrates the interplay between selected uptake/efflux transporters and phase I/II metabolizing enzymes.

  16. Oxygen and xenobiotic reductase activities of cytochrome P450.

    NARCIS (Netherlands)

    Goeptar, A.R.; Scheerens, H.; Vermeulen, N.P.E.

    1995-01-01

    The oxygen reductase and xenobiotic reductase activities of cytochrome P450 (P450) are reviewed. During the oxygen reductase activity of P450, molecular oxygen is reduced to superoxide anion radicals (O

  17. Application of probiotics in the xenobiotic detoxification therapy

    Energy Technology Data Exchange (ETDEWEB)

    Urban, P L [Isotope Laboratory, Faculty of Biology, Warsaw University, Warsaw (Poland); Kuthan, R T [2 Plant Pathogenesis Group, Institute of Biochemistry and Biophysics, Polish Academy of Science, Warsaw (Poland)

    2004-07-01

    Many applications of probiotics have been described up to date. In this paper, it is hypothesized that probiotic microorganisms can also be used to decrease the xenobiotics intake in humans. The use of probiotic bacteria (e.g. strains of Lactobacillus sp. and Bifidobacterium Sp.) and Yeasts (Saccharomyces sp.) gives the opportunity for detoxification of various elements and compounds, considered as contaminants, directly in the lumen of human intestine. Some of these microorganisms ar known to accumulate cesium, strontium and heavy metals to a great extent and also bind mycotoxins. Certainly, during the up-coming years, their native or genetically modified strains will be a part of treatment protocols in detoxication therapy. The utilization of probiotics, in the both therapy and nutrition of people living in the countries suffering from high food contamination, could result in the reduction of annual xenobiotic dose to be incorporated in their organisms. (author)

  18. Application of probiotics in the xenobiotic detoxification therapy

    International Nuclear Information System (INIS)

    Urban, P.L.; Kuthan, R.T.

    2004-01-01

    Many applications of probiotics have been described up to date. In this paper, it is hypothesized that probiotic microorganisms can also be used to decrease the xenobiotics intake in humans. The use of probiotic bacteria (e.g. strains of Lactobacillus sp. and Bifidobacterium Sp.) and Yeasts (Saccharomyces sp.) gives the opportunity for detoxification of various elements and compounds, considered as contaminants, directly in the lumen of human intestine. Some of these microorganisms ar known to accumulate cesium, strontium and heavy metals to a great extent and also bind mycotoxins. Certainly, during the up-coming years, their native or genetically modified strains will be a part of treatment protocols in detoxication therapy. The utilization of probiotics, in the both therapy and nutrition of people living in the countries suffering from high food contamination, could result in the reduction of annual xenobiotic dose to be incorporated in their organisms. (author)

  19. Review and evaluation of the effects of xenobiotic chemicals on microorganisms in soil. [139 references

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, R.J.; Van Voris, P.

    1988-02-01

    The primary objective was to review and evaluate the relevance and quality of existing xenobiotic data bases and test methods for evaluating direct and indirect effects (both adverse and beneficial) of xenobiotics on the soil microbial community; direct and indirect effects of the soil microbial community on xenobiotics; and adequacy of test methods used to evaluate these effects and interactions. Xenobiotic chemicals are defined here as those compounds, both organic and inorganic, produced by man and introduced into the environment at concentrations that cause undesirable effects. Because soil serves as the main repository for many of these chemicals, it therefore has a major role in determining their ultimate fate. Once released, the distribution of xenobiotics between environmental compartments depends on the chemodynamic properties of the compounds, the physicochemical properties of the soils, and the transfer between soil-water and soil-air interfaces and across biological membranes. Abiotic and biotic processes can transform the chemical compound, thus altering its chemical state and, subsequently, its toxicity and reactivity. Ideally, the conversion is to carbon dioxide, water, and mineral elements, or at least, to some harmless substance. However, intermediate transformation products, which can become toxic pollutants in their own right, can sometimes be formed. 139 refs., 6 figs., 11 tabs.

  20. Apoptosis (programmed cell death) as an indicator of xenobiotic toxicity

    International Nuclear Information System (INIS)

    Bond, G.P.

    1989-01-01

    Xenobiotics alter the frequency and pattern of apoptosis (programmed cell death). Preliminary studies identified the mouse liver, with normally low levels of apoptosis, as a preferable test system to the chicken embryo limb, with normally high levels of apoptosis. The major purposes of these investigations, using the apoptogen and necrogen 1,1-dichloroethylene (DCE), were to determine if increases in apoptosis, (1) could be quantified as a direct result of treatment, (2) were dose- and time-dependent, (3) were independent of necrosis, (4) were associated with mitosis in the control of cell numbers and (5) were limited to specific areas of the liver. To these ends, food-deprived female, CF-1 mice were administered DCE ip under varying experimental conditions. Increased apoptosis occurred in a dose- and time-dependent manner after treatment with 12.5, 40, and 125 mg/kg for 0.5, 1, 2, 4 and 8 hr. Peak effects were observed at 4 hr. Apoptosis occurred only in the midzonal/pericentral areas of the liver. At 12.5 mg/kg, there were no effects on biochemical (alanine transaminase) and morphological indices of necrosis, establishing apoptosis as a separate phenomenon from necrosis. Increased 3 H-thymidine incorporation (DNA synthesis), mitosis and the percentage of octaploid hepatocytes occurred from 24-48 hr after treatment with the apoptotic but non-necrotic dose of 40 mg/kg. Apoptosis only occurred in the midzonal/pericentral areas of the liver after multiple doses with DCE, indicating the zonal selectivity of the response. In conclusion, apoptosis, a normally occurring homeostatic process associated with mitosis in the control of cell numbers, is affected by selected xenobiotics in a dose-dependent manner. Xenobiotic-induced apoptosis in the liver occurs at low doses of xenobiotics which cause no other effects on tissue structure or function

  1. Costs and benefits of priming for defense in Arabidopsis

    NARCIS (Netherlands)

    Hulten, M.H.A. van; Pelser, M.; Loon, L.C. Van; Pieterse, C.M.J.; Ton, J.

    2006-01-01

    Induced resistance protects plants against a wide spectrum of diseases; however, it can also entail costs due to the allocation of resources or toxicity of defensive products. The cellular defense responses involved in induced resistance are either activated directly or primed for augmented

  2. Defense islands in bacterial and archaeal genomes and prediction of novel defense systems.

    Science.gov (United States)

    Makarova, Kira S; Wolf, Yuri I; Snir, Sagi; Koonin, Eugene V

    2011-11-01

    The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic "sinks" that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands.

  3. The pathogen-actin connection: A platform for defense signaling in plants

    Energy Technology Data Exchange (ETDEWEB)

    Day, B; Henty, Jessica L; Porter, K J; Staiger, Chris J

    2011-09-08

    The cytoskeleton, a dynamic network of cytoplasmic polymers, plays a central role in numerous fundamental processes, such as development, reproduction, and cellular responses to biotic and abiotic stimuli. As a platform for innate immune responses in mammalian cells, the actin cytoskeleton is a central component in the organization and activation of host defenses, including signaling and cellular repair. In plants, our understanding of the genetic and biochemical responses in both pathogen and host that are required for virulence and resistance has grown enormously. Additional advances in live-cell imaging of cytoskeletal dynamics have markedly altered our view of actin turnover in plants. In this review, we outline current knowledge of host resistance following pathogen perception, both in terms of the genetic interactions that mediate defense signaling, as well as the biochemical and cellular processes that are required for defense signaling.

  4. Uses and limits of radiotracers in the study of drugs and xenobiotics metabolism

    International Nuclear Information System (INIS)

    Cohen, Y.

    1980-01-01

    This review deals with scientific papers issued in 1977-1978, on labelling of drugs and xenobiotics and their metabolism. It is divided in five parts: site of label; in vivo metabolism in animals and human beings; in vitro metabolism on tissue slices, cells culture, microsomes, membrane receptors; metabolism of xenobiotics: nutrients, food additives, detergents, plastics and fabrics; discussion. Metabolic studies, nowadays, associate radiotracers, stable isotopes with high performing procedures for analytical separation [fr

  5. Genomics and the prediction of xenobiotic toxicity

    International Nuclear Information System (INIS)

    Meyer, Urs-A.; Gut, Josef

    2002-01-01

    The systematic identification and functional analysis of human genes is revolutionizing the study of disease processes and the development and rational use of drugs. It increasingly enables medicine to make reliable assessments of the individual risk to acquire a particular disease, raises the number and specificity of drug targets and explains interindividual variation of the effectiveness and toxicity of drugs. Mutant alleles at a single gene locus for more than 20 drug metabolizing enzymes are some of the best studied individual risk factors for adverse drug reactions and xenobiotic toxicity. Increasingly, genetic polymorphisms of transporter and receptor systems are also recognized as causing interindividual variation in drug response and drug toxicity. However, pharmacogenetic and toxicogenetic factors rarely act alone; they produce a phenotype in concert with other variant genes and with environmental factors. Environmental factors may affect gene expression in many ways. For instance, numerous drugs induce their own and the metabolism of other xenobiotics by interacting with nuclear receptors such as AhR, PPAR, PXR and CAR. Genomics is providing the information and technology to analyze these complex situations to obtain individual genotypic and gene expression information to assess the risk of toxicity

  6. A new research journal to understand the interactions of xenobiotics with living organisms

    Directory of Open Access Journals (Sweden)

    François Gagné

    2012-10-01

    Full Text Available Since its creation in January 2011, the Journal of Xenobiotics (published by PAGEPress, Italy is devoted to the publication of novel research articles in the fields of the occurrence and biochemical effects of xenobiotics on all living organisms. Although xenobiotics are defined firstly as compounds that are foreign to life, compounds of natural origins occuring at concentrations that are not usually found, could also be considered as foreigners since their enhanced occurrence may affect non-target organisms. In this sense, products derived from natural products are well known to have either a beneficial (natural products used as food additives and many pharmaceuticals or detrimental (cyanotoxins impact on the health of an organism. The journal recognizes that these compounds could be either harmful or beneficial to organisms and the interplay between these two aspects is of particular interest...

  7. Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics

    Energy Technology Data Exchange (ETDEWEB)

    Tocchetti, Guillermo Nicolás [Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 570, 2000 Rosario (Argentina); Rigalli, Juan Pablo [Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 570, 2000 Rosario (Argentina); Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Arana, Maite Rocío; Villanueva, Silvina Stella Maris [Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 570, 2000 Rosario (Argentina); Mottino, Aldo Domingo, E-mail: amottino@unr.edu.ar [Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 570, 2000 Rosario (Argentina)

    2016-07-15

    The multidrug resistance-associated protein 2 (MRP2/ABCC2) is a transporter that belongs to the ATP-binding cassette (ABC) superfamily. In the intestine, it is localized to the apical membrane of the enterocyte and plays a key role in limiting the absorption of xenobiotics incorporated orally. MRP2 may also play a role in systemic clearance of xenobiotics available from the serosal side of the intestine. MRP2 transports a wide range of substrates, mainly organic anions conjugated with glucuronic acid, glutathione and sulfate and its expression can be modulated by xenobiotics at transcriptional- and post-transcriptional levels. Transcriptional regulation is usually mediated by a group of nuclear receptors. The pregnane X receptor (PXR) is a major member of this group. Relevant drugs described to up-regulate intestinal MRP2 via PXR are rifampicin, spironolactone and carbamazepine, among others. The constitutive androstane receptor (CAR, NR1I3) was also reported to modulate MRP2 expression, phenobarbital being a typical activator. Dietary compounds, including micronutrients and other natural products, are also capable of regulating intestinal MRP2 expression transcriptionally. We have given them particular attention since the composition of the food ingested daily is not necessarily supervised and may result in interactions with therapeutic drugs. Post-transcriptional regulation of MRP2 activity by xenobiotics, e.g. as a consequence of inhibitory actions, is also described in this review. Unfortunately, only few studies report on drug-drug or nutrient-drug interactions as a consequence of modulation of intestinal MRP2 activity by xenobiotics. Future clinical studies are expected to identify additional interactions resulting in changes in efficacy or safety of therapeutic drugs. - Highlights: • Intestinal MRP2 (ABCC2) expression and activity can be regulated by xenobiotics. • PXR and CAR are major MRP2 modulators through a transcriptional mechanism. • Rifampicin

  8. Drug and xenobiotic biotransformation in the blood-brain barrier: A neglected issue.

    Directory of Open Access Journals (Sweden)

    José A.G. Agúndez

    2014-10-01

    Full Text Available Drug biotransformation is a crucial mechanism for facilitating the elimination of chemicals from the organism and for decreasing their pharmacological activity. Published evidence suggests that brain drug metabolism may play a role in the development of adverse drug reactions and in the clinical response to drugs and xenobiotics. The blood-brain barrier (BBB has been regarded mainly as a physical barrier for drugs and xenobiotics, and little attention has been paid to BBB as a drug-metabolizing barrier. The presence of drug metabolizing enzymes in the BBB is likely to have functional implications because local metabolism may inactivate drugs or may modify the drug's ability to cross the BBB, thus modifying the drug response and the risk of developing adverse drug reactions. In this perspective paper, we discuss the expression of relevant xenobiotic metabolizing enzymes in the brain and in the BBB, and we cover current advances and future directions on the potential role of these BBB drug-metabolizing enzymes as modifiers of drug response.

  9. Xenobiotic effects on intestinal stem cell proliferation in adult honey bee (Apis mellifera L) workers.

    Science.gov (United States)

    Forkpah, Cordelia; Dixon, Luke R; Fahrbach, Susan E; Rueppell, Olav

    2014-01-01

    The causes of the current global decline in honey bee health are unknown. One major group of hypotheses invokes the pesticides and other xenobiotics to which this important pollinator species is often exposed. Most studies have focused on mortality or behavioral deficiencies in exposed honey bees while neglecting other biological functions and target organs. The midgut epithelium of honey bees presents an important interface between the insect and its environment. It is maintained by proliferation of intestinal stem cells throughout the adult life of honey bees. We used caged honey bees to test multiple xenobiotics for effects on the replicative activity of the intestinal stem cells under laboratory conditions. Most of the tested compounds did not alter the replicative activity of intestinal stem cells. However, colchicine, methoxyfenozide, tetracycline, and a combination of coumaphos and tau-fluvalinate significantly affected proliferation rate. All substances except methoxyfenozide decreased proliferation rate. Thus, the results indicate that some xenobiotics frequently used in apiculture and known to accumulate in honey bee hives may have hitherto unknown physiological effects. The nutritional status and the susceptibility to pathogens of honey bees could be compromised by the impacts of xenobiotics on the maintenance of the midgut epithelium. This study contributes to a growing body of evidence that more comprehensive testing of xenobiotics may be required before novel or existing compounds can be considered safe for honey bees and other non-target species.

  10. In silico identification and construction of microbial gene clusters associated with biodegradation of xenobiotic compounds.

    Science.gov (United States)

    Awasthi, Garima; Kumari, Anjani; Pant, Aditya Bhushan; Srivastava, Prachi

    2018-01-01

    Chemical substances not showing any importance in existence of biological systems and causing serious health hazards may be designated as Xenobiotic compound. Elimination or degradation of these unwanted substances is a major issue of concern for current time research. Process of biodegradation is a very important aspect of current research as discussed in current manuscript. Current study focuses on the detailed mining of data for the construction of microbial consortia for wide range of xenobiotics compounds. Intensive literature search was done for the construction of this library. Desired data was retrieved from NCBI in fasta format. Data was analysed through homology approaches by using BLAST. This homology based searched enriched with a great vision that not only bacterial population but many other cheap and potential sources are available for different xenobiotic degradation. Though it was focused that bacterial population covers a major part of biodegradation which is near about 90.6% but algae and fungi are also showing promising future in degradation of some important xenobiotic compounds. Analysis of data reveals that Pseudomonas putida has potential for degrading maximum compounds. Establishment of correlation through cluster analysis signifies that Pseudomonas putida, Aspergillus niger and Skeletonema costatum can have combined traits that can be used in finding out actual evolutionary relationship between these species. These findings may also givea new outcome in terms of much cheaper and eco-friendly source in the area of biodegradation of specified xenobiotic compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Influence of xenobiotics on the microbiological and agrochemical parameters of soddy-podzolic soil

    Science.gov (United States)

    Vakkerov-Kouzova, N. D.

    2010-08-01

    We studied the influence of various chemical compounds, i.e., azobenzene (an insecticide and acaricide), nitrification inhibitors (DCD, dicyandiamide and DMPP, and 3,4-dimetylpyrazolphosphate), and inhibitors of urease activity (HQ-hydroquinone), on the agrochemical and microbiological parameters of a soddy-podzolic soil. It is proved that these xenobiotics are able to influence the agrochemical parameters (the pH and the content of NO{3/-} and NH{4/+}, the microbial activity (the basal respiration, the microbial mass carbon, and the microbial quotient), and the number of bacteria of different physiological groups in soddypodzolic soil. The influence of the xenobiotics was preserved for some time, which testified to their persistence in the soil. Upon cultivating the soil microorganisms in different media, the growth of the heterotrophic bacteria was inhibited, the radial growth velocity was slowed down, and the sporogenesis of the micromycetes was retarded. The toxic effect of the xenobiotics was higher with their increasing concentrations.

  12. A methodology for ranking and hazard identification of xenobiotic organic compounds in urban stormwater

    DEFF Research Database (Denmark)

    Baun, Anders; Eriksson, Eva; Ledin, Anna

    2006-01-01

    The paper presents a novel methodology (RICH, Ranking and Identification of Chemical Hazards) for ranking and identification of xenobiotic organic compounds of environmental concern in stormwater discharged to surface water. The RICHmethod is illustrated as a funnel fitted with different filters...... in hazard/risk assessments, a justified list of stormwater priority pollutants which must be included in hazard/risk assessments, and a list of compounds which may be present in discharged stormwater, but cannot be evaluated due to lack of data. The procedure was applied to 233 xenobiotic organic chemicals...... with xenobiotic organic compounds (XOCs) found in urban stormwater, but it may be transferred to other environmental compartments and problems. Thus, the RICH procedure can be used as a stand-alone tool for selection of potential priority pollutants or it can be integrated in larger priority setting frameworks....

  13. APOBEC3G: a Double Agent in Defense

    OpenAIRE

    Smith, Harold C.

    2011-01-01

    APOBEC3G (A3G) is an effective cellular host defense factor under experimental conditions in which a functional form of the HIV-encoded protein Vif cannot be expressed. Wild type Vif targets A3G for proteasomal degradation and along with it, any host defense advantage A3G might provide is severely diminished or lost. Recent evidence cast doubt on the potency of A3G in host defense and suggested that it could, under some circumstances, promote the emergence of more virulent HIV strains. In thi...

  14. Defense Islands in Bacterial and Archaeal Genomes and Prediction of Novel Defense Systems ▿†‡

    Science.gov (United States)

    Makarova, Kira S.; Wolf, Yuri I.; Snir, Sagi; Koonin, Eugene V.

    2011-01-01

    The arms race between cellular life forms and viruses is a major driving force of evolution. A substantial fraction of bacterial and archaeal genomes is dedicated to antivirus defense. We analyzed the distribution of defense genes and typical mobilome components (such as viral and transposon genes) in bacterial and archaeal genomes and demonstrated statistically significant clustering of antivirus defense systems and mobile genes and elements in genomic islands. The defense islands are enriched in putative operons and contain numerous overrepresented gene families. A detailed sequence analysis of the proteins encoded by genes in these families shows that many of them are diverged variants of known defense system components, whereas others show features, such as characteristic operonic organization, that are suggestive of novel defense systems. Thus, genomic islands provide abundant material for the experimental study of bacterial and archaeal antivirus defense. Except for the CRISPR-Cas systems, different classes of defense systems, in particular toxin-antitoxin and restriction-modification systems, show nonrandom clustering in defense islands. It remains unclear to what extent these associations reflect functional cooperation between different defense systems and to what extent the islands are genomic “sinks” that accumulate diverse nonessential genes, particularly those acquired via horizontal gene transfer. The characteristics of defense islands resemble those of mobilome islands. Defense and mobilome genes are nonrandomly associated in islands, suggesting nonadaptive evolution of the islands via a preferential attachment-like mechanism underpinned by the addictive properties of defense systems such as toxins-antitoxins and an important role of horizontal mobility in the evolution of these islands. PMID:21908672

  15. Hepatocyte-based flow analytical bioreactor for xenobiotics metabolism bioprediction

    Directory of Open Access Journals (Sweden)

    M Helvenstein

    2017-04-01

    Full Text Available The research for new in vitro screening tools for predictive metabolic profiling of drug candidates is of major interest in the pharmaceutical field. The main motivation is to avoid late rejection in drug development and to deliver safer drugs to the market. Thanks to the superparamagnetic properties of iron oxide nanoparticles, a flow bioreactor has been developed which is able to perform xenobiotic metabolism studies. The selected cell line (HepaRG maintained its metabolic competencies once iron oxide nanoparticles were internalized. Based on magnetically trapped cells in a homemade immobilization chamber, through which a flow of circulating phase was injected to transport nutrients and/or the studied xenobiotic, off-line and online (when coupled to a high-performance liquid chromatography chain metabolic assays were developed using diclofenac as a reference compound. The diclofenac demonstrated a similar metabolization profile chromatogram, both with the newly developed setup and with the control situation. Highly versatile, this pioneering and innovative instrumental design paves the way for a new approach in predictive metabolism studies.

  16. Applications of NMR spectroscopy to xenobiotic metabolism

    International Nuclear Information System (INIS)

    Harris, T.M.

    1989-01-01

    Recent years have seen high field NMR spectrometers become commonplace in research laboratories. At the same time, major advances in methodology for structural analysis have occurred, particularly notable among these being the development of two-dimensional spectroscopic techniques. Many applications have been made of NMR spectroscopy in the study of xenobiotic metabolic processes. This deals with two specific applications which have been made in the author's laboratory and involve mechanistic studies of the reactions of the carcinogens ethylene dibromide and aflatoxin with DNA

  17. [THE SYSTEM OF XENOBIOTICS BIOTRANSFORMATION OF HELMINTHS. RESEMBLANCE AND DIFFERENSES FROM SIMILAR HOST SYSTEMS (REWEW)].

    Science.gov (United States)

    Smirnov, L P; Borvinskaya, E V; Suhovskaya, I V

    2016-01-01

    The three phases system xenobiotic biotransformation in cells as prokaryotes as eukaryotes was formed during the process of evolution. Clear and managed function of all three links of this system guarantee the survival of living organisms at alteration of chemical component of environment. Oxidation, reduction or hydrolysis of xenobiotics realize in phase I by insertion or opening reactive and hydrophilic groups in structure of drug molecule. In phase II xenobiotics or their metabolites from phase I conjugate with endogenic compounds, main of there are glutathione, glucuronic acid, amino acids and sulphates. Active transport of substrata, metabolites and conjugates through cell lipid membranes special transport proteins carry out (phase III). The system of xenobiotics biotransformation of helminths has essential differences from the same of vertebrate hosts. In particular, parasites do not reveal the activity of prime oxidases of phase I, such as CYP or FMO, in spite of the genes of these enzymes in DNA. As this phenomenon displays mainly in adult helminths, living in guts of vertebrates, then the hypothesis was formulated that this effect is related with adaptation to conditions of strong deficiency of oxygen, arise in a process of evolution (Kotze et al., 2006). Literature data testify the existence in helminths of unique forms of enzymes of phase II, the investigation of which present doubtless interest in relation with possible role in adaptation to parasitic mode of life. Notwithstanding that many of helminths GST in greater or lesser degree similar with enzymes of M, P, S and О classes of other organisms, nevertheless they have essential structural differences as compared with enzymes of hosts that makes perspective the search of specific anthelminthics vaccines. Transport of xenobiotics is now considered phase III of biotransformation. It was shown that proteins of this phase (ATP binding cassette transporters (ABC ) of parasites) play a key role in efflux

  18. Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling.

    Directory of Open Access Journals (Sweden)

    Sven van Eijl

    Full Text Available BACKGROUND: Human skin has the capacity to metabolise foreign chemicals (xenobiotics, but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS: Label-free proteomic analysis of whole human skin (10 donors was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4-10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these

  19. ABC transporters and xenobiotic defense systems in early life stages of rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Kropf, Christian; Segner, Helmut; Fent, Karl

    2016-01-01

    Embryos of oviparous fish, in contrast to (ovo) viviparous species, develop in the aquatic environment, and therefore need solute transport systems at their body surfaces for maintaining internal homeostasis and defending against potentially harmful substances. We hypothesized that solute transporters undergo changes in tissue distribution from the embryo to the larval stage. We therefore studied the mRNA profiles of eight ABC transporters (abcb1a, abcb1b, abcc1, abcc2, abcc3, abcc4, abcc5, abcg2) and three solute carriers (oatp1d, putative oatp2 putative, mate1) in different body regions (head, yolk sac epithelium, abdominal viscera, skin/muscles) of developing rainbow trout. Additionally, we investigated mRNA levels of phase I (cyp1a, cyp3a) and phase II (gstp, putative ugt1, putative ugt2) biotransformation enzymes. The study covered the developmental period from the eleuthero-embryo stage to the first-feeding larval stage (1-20days post-hatch, dph). At 1dph, transcripts of abcc2, abcc4, abcg2, cyp3a, gstp, putative mate1, and putative oatp2 occurred primarily in the yolk sac epithelium, whereas at later stages expression of these genes was predominantly observed in the abdominal viscera. The functional activity of ABC transporters in fish early life stages was assessed by rhodamine B accumulation assays. Finally, we investigated the potential impact of xenobiotics (clotrimazole, clofibric acid) on the ABC and biotransformation systems of trout early life stages. While clofibric acid had no effect, clotrimazole lead to an increased rhodamine B accumulation. The results provide evidence that the transition from the eleuthero-embryo to the larval stage is accompanied by a major alteration in tissue expression of ABC transporters. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Health and Cellular Impacts of Air Pollutants: From Cytoprotection to Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Karine Andreau

    2012-01-01

    Full Text Available Air pollution as one of the ravages of our modern societies is primarily linked to urban centers, industrial activities, or road traffic. These atmospheric pollutants have been incriminated in deleterious health effects by numerous epidemiological and in vitro studies. Environmental air pollutants are a heterogeneous mixture of particles suspended into a liquid and gaseous phase which trigger the disruption of redox homeostasis—known under the term of cellular oxidative stress—in relation with the establishment of inflammation and cell death via necrosis, apoptosis, or autophagy. Activation or repression of the apoptotic process as an adaptative response to xenobiotics might lead to either acute or chronic toxicity. The purpose of this paper is to highlight the central role of oxidative stress induced by air pollutants and to focus on the subsequent cellular impacts ranging from cytoprotection to cytotoxicity by decreasing or stimulating apoptosis, respectively.

  1. Xenobiotic Modulation of Human Mammary Epithelial Cell Gap Junctional Intercellular Communication and Growth

    National Research Council Canada - National Science Library

    Ruch, Randall

    1999-01-01

    .... These agents also inhibit gap junctional intercellular communication (GJIC). This inhibition may contribute to the enhancement of breast epithelial growth and breast cancer formation by xenobiotics...

  2. Magnetically-modified natural biogenic iron oxides for organic xenobiotics removal

    Czech Academy of Sciences Publication Activity Database

    Šafařík, Ivo; Filip, J.; Horská, Kateřina; Nowakova, M.; Tuček, J.; Šafaříková, Miroslava; Hashimoto, H.; Takada, J.; Zbořil, R.

    2015-01-01

    Roč. 12, č. 2 (2015), s. 673-682 ISSN 1735-1472 R&D Projects: GA MŠk(CZ) LH11111; GA MŠk LH12190 Institutional support: RVO:67179843 Keywords : Biogenic iron oxides * Leptothrix ochracea * Magnetic fluid * Magnetic adsorbents * Xenobiotics Subject RIV: EI - Biotechnology ; Bionics Impact factor: 2.344, year: 2015

  3. Involvement of hepatic xenobiotic related genes in bromadiolone resistance in wild Norway rats, Rattus norvegicus (Berk.)

    DEFF Research Database (Denmark)

    Markussen, Mette Drude; Heiberg, Ann-Charlotte; Alsbo, Carsten

    2007-01-01

    To examine the role of xenobiotic relevant genes in bromadiolone resistance in wild Norway rats (Rattus norvegicus) we compared the constitutive liver gene expression and expression upon bromadiolone administration in bromadiolone resistant and anticoagulant susceptible female rats using a LNA...... expressed in resistant than susceptible rats upon bromadiolone exposure. To establish how bromadiolone affected xenobiotic gene expression in the two strains we compared bromadiolone expression profiles to saline profiles of both strains. Bromadiolone mediated significant up-regulation of Cyp2e1 and Cyp3a3...... expression in the resistant rats whereas the rodenticide conferred down-regulation of Cyp2e1, Cyp3a3 and Gpox1 and induction of Cyp2c12 expression in susceptible rats. Cyp2c13 and Cyp3a2 expression were markedly suppressed in both strains upon treatment. This suggests that xenobiotic relevant enzymes play...

  4. Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes.

    Science.gov (United States)

    Shen, Ding-Wu; Pouliot, Lynn M; Hall, Matthew D; Gottesman, Michael M

    2012-07-01

    Cisplatin is one of the most effective broad-spectrum anticancer drugs. Its effectiveness seems to be due to the unique properties of cisplatin, which enters cells via multiple pathways and forms multiple different DNA-platinum adducts while initiating a cellular self-defense system by activating or silencing a variety of different genes, resulting in dramatic epigenetic and/or genetic alternations. As a result, the development of cisplatin resistance in human cancer cells in vivo and in vitro by necessity stems from bewilderingly complex genetic and epigenetic changes in gene expression and alterations in protein localization. Extensive published evidence has demonstrated that pleiotropic alterations are frequently detected during development of resistance to this toxic metal compound. Changes occur in almost every mechanism supporting cell survival, including cell growth-promoting pathways, apoptosis, developmental pathways, DNA damage repair, and endocytosis. In general, dozens of genes are affected in cisplatin-resistant cells, including pathways involved in copper metabolism as well as transcription pathways that alter the cytoskeleton, change cell surface presentation of proteins, and regulate epithelial-to-mesenchymal transition. Decreased accumulation is one of the most common features resulting in cisplatin resistance. This seems to be a consequence of numerous epigenetic and genetic changes leading to the loss of cell-surface binding sites and/or transporters for cisplatin, and decreased fluid phase endocytosis.

  5. The iron-sulfur cluster assembly network component NARFL is a key element in the cellular defense against oxidative stress.

    Science.gov (United States)

    Corbin, Monique V; Rockx, Davy A P; Oostra, Anneke B; Joenje, Hans; Dorsman, Josephine C

    2015-12-01

    Aim of this study was to explore cellular changes associated with increased resistance to atmospheric oxygen using high-resolution DNA and RNA profiling combined with functional studies. Two independently selected oxygen-resistant substrains of HeLa cells (capable of proliferating at >80% O2, i.e. hyperoxia) were compared with their parental cells (adapted to growth at 20% O2, but unable to grow at >80% O2). A striking consistent alteration found to be associated with the oxygen-resistant state appeared to be an amplified and overexpressed region on chromosome 16p13.3 harboring 21 genes. The driver gene of this amplification was identified by functional studies as NARFL, which encodes a component of the cytosolic iron-sulfur cluster assembly system. In line with this result we found the cytosolic c-aconitase activity as well as the nuclear protein RTEL1, both Fe-S dependent proteins, to be protected by NARFL overexpression under hyperoxia. In addition, we observed a protective effect of NARFL against hyperoxia-induced loss of sister-chromatid cohesion. NARFL thus appeared to be a key factor in the cellular defense against hyperoxia-induced oxidative stress in human cells. Our findings suggest that new insight into age-related degenerative processes may come from studies that specifically address the involvement of iron-sulfur proteins. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Evasion of host immune defenses by human papillomavirus.

    Science.gov (United States)

    Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun

    2017-03-02

    A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Microvillar cell surface as a natural defense system against xenobiotics: a new interpretation of multidrug resistance.

    Science.gov (United States)

    Lange, K; Gartzke, J

    2001-08-01

    The phenomenon of multidrug resistance (MDR) is reinterpreted on the basis of the recently proposed concept of microvillar signaling. According to this notion, substrate and ion fluxes across the surface of differentiated cells occur via transporters and ion channels that reside in membrane domains at the tips of microvilli (MV). The flux rates are regulated by the actin-based cytoskeletal core structure of MV, acting as a diffusion barrier between the microvillar tip compartment and the cytoplasm. The expression of this diffusion barrier system is a novel aspect of cell differentiation and represents a functional component of the natural defense system of epithelial cells against environmental hazardous ions and lipophilic compounds. Because of the specific organization of epithelial Ca(2+) signaling and the secretion, lipophilic compounds associated with the plasma membrane are transferred from the basal to the apical cell surface by a lipid flow mechanism. Drug release from the apical pole occurs by either direct secretion from the cell surface or metabolization by the microvillar cytochrome P-450 system and efflux of the metabolites and conjugation products through the large multifunctional anion channels localized in apical MV. The natural microvillar defense system also provides a mechanistic basis of acquired MDR in tumor cells. The microvillar surface organization is lost in rapidly growing cells such as tumor or embryonic cells but is restored during exposure of tumor cells to cytotoxins by induction of a prolonged G(0)/G(1) resting phase.

  8. Cellular reprogramming through mitogen-activated protein kinases

    Directory of Open Access Journals (Sweden)

    Justin eLee

    2015-10-01

    Full Text Available Mitogen-activated protein kinase (MAPK cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554 in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression – including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding and degradation steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes.

  9. Animal bioavailability of defined xenobiotic lignin metabolites

    International Nuclear Information System (INIS)

    Sandermann, H. Jr.; Arjmand, M.; Gennity, I.; Winkler, R.; Struble, C.B.; Aschbacher, P.W.

    1990-01-01

    Lignin has been recognized as a major component of bound pesticide residues in plants and is thought to be undigestible in animals. Two defined ring-U- 14 C-labeled chloroaniline/lignin metabolites have now been fed to rats, where a release of ∼66% of the bound xenobiotic occurred in the form of simple chloroaniline derivatives. The observed high degree of bioavailability indicates that bound pesticidal residues may possess ecotoxicological significance. In parallel studies, the white-rot fungus Phanerochaete chrysosporium was more efficient, and a soil system was much less efficient, in the degradation of the [ring-U- 14 C]chloroaniline/lignin metabolites

  10. Live-cell Imaging Approaches for the Investigation of Xenobiotic-Induced Oxidant Stress

    Science.gov (United States)

    BACKGROUND: Oxidant stress is arguably a universal feature in toxicology. Research studies on the role of oxidant stress induced by xenobiotic exposures have typically relied on the identification of damaged biomolecules using a variety of conventional biochemical and molecular t...

  11. The Bioavailability of Soluble Cigarette Smoke Extract Is Reduced through Interactions with Cells and Affects the Cellular Response to CSE Exposure.

    Science.gov (United States)

    Bourgeois, Jeffrey S; Jacob, Jeeva; Garewal, Aram; Ndahayo, Renata; Paxson, Julia

    2016-01-01

    Cellular exposure to cigarette smoke leads to an array of complex responses including apoptosis, cellular senescence, telomere dysfunction, cellular aging, and neoplastic transformation. To study the cellular response to cigarette smoke, a common in vitro model exposes cultured cells to a nominal concentration (i.e. initial concentration) of soluble cigarette smoke extract (CSE). However, we report that use of the nominal concentration of CSE as the only measure of cellular exposure is inadequate. Instead, we demonstrate that cellular response to CSE exposure is dependent not only on the nominal concentration of CSE, but also on specific experimental variables, including the total cell number, and the volume of CSE solution used. As found in other similar xenobiotic assays, our work suggests that the effective dose of CSE is more accurately related to the amount of bioavailable chemicals per cell. In particular, interactions of CSE components both with cells and other physical factors limit CSE bioavailability, as demonstrated by a quantifiably reduced cellular response to CSE that is first modified by such interactions. This has broad implications for the nature of cellular response to CSE exposure, and for the design of in vitro assays using CSE.

  12. Avian species differences in the intestinal absorption of xenobiotics (PCB, dieldrin, Hg2+)

    Science.gov (United States)

    Serafin, J.A.

    1984-01-01

    1. Intestinal absorption of a polychlorinated biphenyl, dieldrin, and mercury (from HgCl2) was measured in adult Northern bobwhites, Eastern screech owls, American kestrels, black-crowned night-herons and mallards in vivo by an in situ luminal perfusion technique.2. Bobwhites, screech owls and kestrels absorbed much more of each xenobiotic than black-crowned night-herons and mallards.3. Mallards absorbed less dieldrin and mercury than black-crowned night-herons.4. Mercury absorption by kestrels was more than twice that in screech owls and eight times that observed in mallards.5. Pronounced differences in xenobiotic absorption rates between bobwhites, screech owls and kestrels on the one hand, and black-crowned night-herons and mallards on the other, raise the possibility that absorptive ability may be associated with the phylogenetic classification of birds.

  13. [Hypothetical link between endometriosis and xenobiotics-associated genetically modified food].

    Science.gov (United States)

    Aris, A; Paris, K

    2010-12-01

    Endometriosis is an oestrogen-dependent inflammatory disease affecting 10 % of reproductive-aged women. Often accompanied by chronic pelvic pain and infertility, endometriosis rigorously interferes with women's quality of life. Although the pathophysiology of endometriosis remains unclear, a growing body of evidence points to the implication of environmental toxicants. Over the last decade, an increase in the incidence of endometriosis has been reported and coincides with the introduction of genetically modified foods in our diet. Even though assessments of genetically modified food risk have not indicated any hazard on human health, xenobiotics-associated genetically modified food, such as pesticides residues and xenoproteins, could be harmful in the long-term. The "low-dose hypothesis", accumulation and biotransformation of pesticides-associated genetically modified food and the multiplied toxicity of pesticides-formulation adjuvants support this hypothesis. This review summarizes toxic effects (in vitro and on animal models) of some xenobiotics-associated genetically modified food, such as glyphosate and Cry1Ab protein, and extrapolates on their potential role in the pathophysiology of endometriosis. Their roles as immune toxicants, pro-oxidants, endocrine disruptors and epigenetic modulators are discussed. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  14. MicroRNA regulated defense responses in Triticum aestivum L. during Puccinia graminis f.sp. tritici infection.

    Science.gov (United States)

    Gupta, Om Prakash; Permar, Vipin; Koundal, Vikas; Singh, Uday Dhari; Praveen, Shelly

    2012-02-01

    Plants have evolved diverse mechanism to recognize pathogen attack and triggers defense responses. These defense responses alter host cellular function regulated by endogenous, small, non-coding miRNAs. To understand the mechanism of miRNAs regulated cellular functions during stem rust infection in wheat, we investigated eight different miRNAs viz. miR159, miR164, miR167, miR171, miR444, miR408, miR1129 and miR1138, involved in three different independent cellular defense response to infection. The investigation reveals that at the initiation of disease, accumulation of miRNAs might be playing a key role in hypersensitive response (HR) from host, which diminishes at the maturation stage. This suggests a possible host-fungal synergistic relation leading to susceptibility. Differential expression of these miRNAs in presence and absence of R gene provides a probable explanation of miRNA regulated R gene mediated independent pathways.

  15. Mass fluxes and spatial trends of xenobiotics in the waters of the city of Halle, Germany

    International Nuclear Information System (INIS)

    Reinstorf, F.; Strauch, G.; Schirmer, K.; Glaeser, H.-R.; Moeder, M.; Wennrich, R.; Osenbrueck, K.; Schirmer, M.

    2008-01-01

    The behaviour and the effects of xenobiotics including pharmaceuticals and fragrances in the environment are widely unknown. In order to improve our knowledge, field investigations and modelling approaches for the entire area of the city of Halle/Saale, Germany, were performed. The distribution of the concentration values and mass fluxes are exemplified using indicators such as Bisphenol A, t-Nonylphenol, Carbamacepine, Galaxolide, Tonalide, Gadolinium and isotopes. Concentrations at a magnitude of ng/L to μg/L were found ubiquitously in the ground and surface waters. Using the concentration values, the impact of the city concerning the indicators was not always evident. Only the assessment of the mass fluxes shows significant urban impacts along the city passage. The calculation of the mass fluxes shows increasing values for all investigated xenobiotics during the city passage; only Bisphenol A stagnates. A balance model of water and indicator mass fluxes was built up for the entire city area. - Xenobiotics are ubiquitous in the investigated urban aquatic system and are quantified by a large scale mass balance to find spatial trends

  16. Xenobiotic Modulation of Human Mammary Epithelial Cell Gap junctional Intercellular Communication and Growth

    National Research Council Canada - National Science Library

    Ruch, Randall

    1998-01-01

    ...), phthalate esters, and dioxin have been implicated in this increase. Many xenobiotics such as DDT and PCBs have weak estrogenic activity and may enhance breast cancer formation by an estrogenic effect on breast epithelial cell growth...

  17. Xenobiotic Modulation of Human Mammary Epithelial Cell Gap Junctional Intercellular Communication and Growth

    National Research Council Canada - National Science Library

    Ruch, Randall

    1997-01-01

    ...), phthalate esters, and dioxin have been implicated in this increase. Many xenobiotics such as DDT and PCBs have weak estrogenic activity and may enhance breast cancer formation by an estrogenic effect on breast epithelial cell growth...

  18. Activities of xenobiotic metabolizing enzymes in rat placenta and liver in vitro

    NARCIS (Netherlands)

    Fabian, Eric; Wang, Xinyi; Engel, Franziska; Li, Hequn; Landsiedel, Robert; Ravenzwaay, van Bennard

    2016-01-01

    In order to assess whether the placental metabolism of xenobiotic compounds should be taken into consideration for physiologically-based toxicokinetic (PBTK) modelling, the activities of seven phase I and phase II enzymes have been quantified in the 18-day placenta of untreated Wistar rats. To

  19. Occurrence of xenobiotics in gray water and removal in three biological treatment systems

    NARCIS (Netherlands)

    Hernandez Leal, L.; Vieno, N.; Temmink, B.G.; Zeeman, G.; Buisman, C.J.N.

    2010-01-01

    Eighteen selected xenobiotics related to personal care and household chemicals (UV-filters, fragrances, preservatives, biocides, surfactants) were measured in gray water from 32 houses and in effluents of three different biological treatment systems (aerobic, anaerobic, and combined anaerobic +

  20. Overexpression of long non-coding RNAs following exposure to xenobiotics in the aquatic midge Chironomus riparius

    International Nuclear Information System (INIS)

    Martínez-Guitarte, José-Luis; Planelló, Rosario; Morcillo, Gloria

    2012-01-01

    Non-coding RNAs (ncRNAs) represent an important transcriptional output of eukaryotic genomes. In addition to their functional relevance as housekeeping and regulatory elements, recent studies have suggested their involvement in rather unexpected cellular functions. The aim of this work was to analyse the transcriptional behaviour of non-coding RNAs in the toxic response to pollutants in Chironomus riparius, a reference organism in aquatic toxicology. Three well-characterized long non-coding sequences were studied: telomeric repeats, Cla repetitive elements and the SINE CTRT1. Transcription levels were evaluated by RT-PCR after 24-h exposures to three current aquatic contaminants: bisphenol A (BPA), benzyl butyl phthalate (BBP) and the heavy metal cadmium (Cd). Upregulation of telomeric transcripts was found after BPA treatments. Moreover, BPA significantly activated Cla transcription, which also appeared to be increased by cadmium, whereas BBP did not affect the transcription levels of these sequences. Transcription of SINE CTRT1 was not altered by any of the chemicals tested. These data are discussed in the light of previous studies that have shown a response by long ncRNAS (lncRNAs) to cellular stressors, indicating a relationship with environmental stimuli. Our results demonstrated for the first time the ability of bisphenol A to activate non-coding sequences mainly located at telomeres and centromeres. Overall, this study provides evidence that xenobiotics can induce specific responses in ncRNAs derived from repetitive sequences that could be relevant in the toxic response, and also suggests that ncRNAs could represent a novel class of potential biomarkers in toxicological assessment.

  1. Overexpression of long non-coding RNAs following exposure to xenobiotics in the aquatic midge Chironomus riparius

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Guitarte, Jose-Luis, E-mail: jlmartinez@ccia.uned.es [Grupo de Biologia y Toxicologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, UNED, Senda del Rey 9, 28040 Madrid (Spain); Planello, Rosario; Morcillo, Gloria [Grupo de Biologia y Toxicologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, UNED, Senda del Rey 9, 28040 Madrid (Spain)

    2012-04-15

    Non-coding RNAs (ncRNAs) represent an important transcriptional output of eukaryotic genomes. In addition to their functional relevance as housekeeping and regulatory elements, recent studies have suggested their involvement in rather unexpected cellular functions. The aim of this work was to analyse the transcriptional behaviour of non-coding RNAs in the toxic response to pollutants in Chironomus riparius, a reference organism in aquatic toxicology. Three well-characterized long non-coding sequences were studied: telomeric repeats, Cla repetitive elements and the SINE CTRT1. Transcription levels were evaluated by RT-PCR after 24-h exposures to three current aquatic contaminants: bisphenol A (BPA), benzyl butyl phthalate (BBP) and the heavy metal cadmium (Cd). Upregulation of telomeric transcripts was found after BPA treatments. Moreover, BPA significantly activated Cla transcription, which also appeared to be increased by cadmium, whereas BBP did not affect the transcription levels of these sequences. Transcription of SINE CTRT1 was not altered by any of the chemicals tested. These data are discussed in the light of previous studies that have shown a response by long ncRNAS (lncRNAs) to cellular stressors, indicating a relationship with environmental stimuli. Our results demonstrated for the first time the ability of bisphenol A to activate non-coding sequences mainly located at telomeres and centromeres. Overall, this study provides evidence that xenobiotics can induce specific responses in ncRNAs derived from repetitive sequences that could be relevant in the toxic response, and also suggests that ncRNAs could represent a novel class of potential biomarkers in toxicological assessment.

  2. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a "Central Dogma" for Toxic Mechanisms?

    Science.gov (United States)

    Park, Yeong-Chul; Lee, Sundong; Cho, Myung-Haing

    2014-09-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems.

  3. Cellular Promyelocytic Leukemia Protein Is an Important Dengue Virus Restriction Factor

    OpenAIRE

    Giovannoni, Federico; Damonte, Elsa B.; Garc?a, Cybele C.

    2015-01-01

    The intrinsic antiviral defense is based on cellular restriction factors that are constitutively expressed and, thus, active even before a pathogen enters the cell. The promyelocytic leukemia (PML) nuclear bodies (NBs) are discrete nuclear foci that contain several cellular proteins involved in intrinsic antiviral responses against a number of viruses. Accumulating reports have shown the importance of PML as a DNA virus restriction factor and how these pathogens evade this antiviral activity....

  4. Triclocarban mediates induction of xenobiotic metabolism through activation of the constitutive androstane receptor and the estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Mei-Fei Yueh

    Full Text Available Triclocarban (3,4,4'-trichlorocarbanilide, TCC is used as a broad-based antimicrobial agent that is commonly added to personal hygiene products. Because of its extensive use in the health care industry and resistance to degradation in sewage treatment processes, TCC has become a significant waste product that is found in numerous environmental compartments where humans and wildlife can be exposed. While TCC has been linked to a range of health and environmental effects, few studies have been conducted linking exposure to TCC and induction of xenobiotic metabolism through regulation by environmental sensors such as the nuclear xenobiotic receptors (XenoRs. To identify the ability of TCC to activate xenobiotic sensors, we monitored XenoR activities in response to TCC treatment using luciferase-based reporter assays. Among the XenoRs in the reporter screening assay, TCC promotes both constitutive androstane receptor (CAR and estrogen receptor alpha (ERα activities. TCC treatment to hUGT1 mice resulted in induction of the UGT1A genes in liver. This induction was dependent upon the constitutive active/androstane receptor (CAR because no induction occurred in hUGT1Car(-/- mice. Induction of the UGT1A genes by TCC corresponded with induction of Cyp2b10, another CAR target gene. TCC was demonstrated to be a phenobarbital-like activator of CAR in receptor-based assays. While it has been suggested that TCC be classified as an endocrine disruptor, it activates ERα leading to induction of Cyp1b1 in female ovaries as well as in promoter activity. Activation of ERα by TCC in receptor-based assays also promotes induction of human CYP2B6. These observations demonstrate that TCC activates nuclear xenobiotic receptors CAR and ERα both in vivo and in vitro and might have the potential to alter normal physiological homeostasis. Activation of these xenobiotic-sensing receptors amplifies gene expression profiles that might represent a mechanistic base for

  5. Assessment of the impact of xenobiotic pollutants on the marine organisms: Molecular biomarker approach

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.

    of the organisms to xenobiotic compounds being transformed into reactive oxygen species. Most importantly, the occurrence of DNA strand breaks in marine organisms leading to the loss of DNA integrity is a significant biomarker of marine pollution. The measurement...

  6. Xenobiotic metabolism in human skin and 3D human skin reconstructs: A review

    NARCIS (Netherlands)

    Gibbs, S.; Sandt, J.J.M. van de; Merk, H.F.; Lockley, D.J.; Pendlington, R.U.; Pease, C.K.

    2007-01-01

    In this review, we discuss and compare studies of xenobiotic metabolism in both human skin and 3D human skin reconstructs. In comparison to the liver, the skin is a less studied organ in terms of characterising metabolic capability. While the skin forms the major protective barrier to environmental

  7. Influence of non-hydrophobic factors on the sorption of ionizable xenobiotics to solids

    DEFF Research Database (Denmark)

    Lützhøft, Hans-Christian Holten; Franco, Antonio; Trapp, Stefan

    2011-01-01

    It is well known that xenobiotics sorp to solid phases like soil and sediment, depending on their inherent properties and environmental conditions. Traditionally it was accepted, that the hydrophobicity of the chemical, i.e. the log KOW, as well as the solid’s content of organic carbon (OC) were...

  8. The Simplest Flowchart Stating the Mechanisms for Organic Xenobiotics-induced Toxicity: Can it Possibly be Accepted as a “Central Dogma” for Toxic Mechanisms?

    Science.gov (United States)

    Lee, Sundong; Cho, Myung-Haing

    2014-01-01

    Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. It is estimated that the organic xenobiotics are responsible for approximately 80~90% of chemical-induced toxicity in human population. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. indirect-acting chemicals, cytochrome P450-dependent vs. cytochrome P450-independent biotransformation, reactive intermediates, reactivation, toxicokinetics vs. toxicodynamics, and reversibility vs. irreversibility. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. PMID:25343011

  9. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    International Nuclear Information System (INIS)

    Heck, Julia E.; Moore, Lee E.; Lee, Yuan-Chin A.; McKay, James D.; Hung, Rayjean J.; Karami, Sara; Gaborieau, Valérie; Szeszenia-Dabrowska, Neonila; Zaridze, David G.; Mukeriya, Anush; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Kollárová, Helena; Bencko, Vladimir; Rothman, Nathaniel; Brennan, Paul; Chow, Wong-Ho; Boffetta, Paolo

    2012-01-01

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  10. Xenobiotic Metabolizing Gene Variants and Renal Cell Cancer: A Multicenter Study

    Energy Technology Data Exchange (ETDEWEB)

    Heck, Julia E. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); Moore, Lee E. [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Lee, Yuan-Chin A. [International Agency for Research on Cancer, Lyon (France); Department of Epidemiology, School of Public Health, University of California Los Angeles, Los Angeles, CA (United States); McKay, James D. [International Agency for Research on Cancer, Lyon (France); Hung, Rayjean J. [Samuel Lunenfeld Research Institute of Mount Sinai Hospital, Toronto, ON (Canada); Karami, Sara [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Gaborieau, Valérie [International Agency for Research on Cancer, Lyon (France); Szeszenia-Dabrowska, Neonila [Department of Epidemiology, Institute of Occupational Medicine, Lodz (Poland); Zaridze, David G. [Cancer Research Centre, Institute of Carcinogenesis, Moscow (Russian Federation); Mukeriya, Anush [Cancer Research Centre, Department of Epidemiology, Moscow (Russian Federation); Mates, Dana [Institute of Public Health, Bucharest (Romania); Foretova, Lenka [Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno (Czech Republic); Janout, Vladimir; Kollárová, Helena [Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc (Czech Republic); Bencko, Vladimir [First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Prague, Czech Republic (Czech Republic); Rothman, Nathaniel [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Brennan, Paul [International Agency for Research on Cancer, Lyon (France); Chow, Wong-Ho [Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD (United States); Boffetta, Paolo, E-mail: paolo.boffetta@mssm.edu [International Prevention Research Institute, Lyon (France); Tisch Cancer Institute, Mt. Sinai School of Medicine, New York, NY (United States)

    2012-02-20

    Background: The countries of Central and Eastern Europe have among the highest worldwide rates of renal cell cancer (RCC). Few studies have examined whether genetic variation in xenobiotic metabolic pathway genes may modify risk for this cancer. Methods: The Central and Eastern Europe Renal Cell Cancer study was a hospital-based case–control study conducted between 1998 and 2003 across seven centers in Central and Eastern Europe. Detailed data were collected from 874 cases and 2053 controls on demographics, work history, and occupational exposure to chemical agents. Genes [cytochrome P-450 family, N-acetyltransferases, NAD(P)H:quinone oxidoreductase I (NQO1), microsomal epoxide hydrolase (mEH), catechol-O-methyltransferase (COMT), uridine diphosphate-glucuronosyltransferase (UGT)] were selected for the present analysis based on their putative role in xenobiotic metabolism. Haplotypes were calculated using fastPhase. Odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for country of residence, age, sex, smoking, alcohol intake, obesity, and hypertension. Results: We observed an increased risk of RCC with one SNP. After adjustment for multiple comparisons it did not remain significant. Neither NAT1 nor NAT2 slow acetylation was associated with disease. Conclusion: We observed no association between this pathway and renal cell cancer.

  11. Cellular defense of the avian respiratory system: effects of Pasteurella multocida on respiratory burst activity of avian respiratory tract phagocytes.

    Science.gov (United States)

    Ochs, D L; Toth, T E; Pyle, R H; Siegel, P B

    1988-12-01

    The respiratory tract of healthy chickens contain few free-residing phagocytic cells. Intratracheal inoculation with Pasteurella multocida stimulated a significant (P less than 0.05) migration of cells to the lungs and air sacs of White Rock chickens within 2 hours after inoculation. We found the maximal number of avian respiratory tract phagocytes (22.9 +/- 14.0 x 10(6] at 8 hours after inoculation. Flow cytometric analysis of these cells revealed 2 populations on the basis of cell-size and cellular granularity. One of these was similar in size and granularity to those of blood heterophils. Only this population was capable of generating oxidative metabolites in response to phorbol myristate acetate. The ability of the heterophils to produce hydrogen peroxide, measured as the oxidation of intracellularly loaded 2',7'-dichlorofluorescein, decreased with time after inoculation. These results suggest that the migration of heterophils, which are capable of high levels of oxidative metabolism, to the lungs and air sacs may be an important defense mechanism of poultry against bacterial infections of the respiratory tract.

  12. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression

    NARCIS (Netherlands)

    Nantasanti, Sathidpak; Toussaint, Mathilda J. M.; Youssef, Sameh A.; Tooten, Peter C. J.; de Bruin, Alain

    2016-01-01

    The tumor suppressors Retinoblastoma (Rb) and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC) or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver

  13. Cuticular uptake of xenobiotics into living plants. Part 2: influence of the xenobiotic dose on the uptake of bentazone, epoxiconazole and pyraclostrobin, applied in the presence of various surfactants, into Chenopodium album, Sinapis alba and Triticum aestivum leaves.

    Science.gov (United States)

    Forster, W Alison; Zabkiewicz, Jerzy A; Liu, Zhiqian

    2006-07-01

    This study has determined the uptake of three pesticides, applied as commercial or model formulations in the presence of a wide range of surfactants, into the leaves of three plant species (bentazone into Chenopodium album L. and Sinapis alba L., epoxiconazole and pyraclostrobin into Triticum aestivum L.). The results have confirmed previous findings that the initial dose (nmol mm(-2)) of xenobiotic applied to plant foliage is a strong, positive determinant of uptake. This held true for all the pesticide formulations studied, although surfactant concentration was found to have an effect. The lower surfactant concentrations studied showed an inferior relationship between the amount of xenobiotic applied and uptake. High molecular mass surfactants also produced much lower uptake than expected from the dose uptake equations in specific situations.

  14. Classification and modelling of non-extractable residue (NER) formation of xenobiotics in soil - a synthesis

    DEFF Research Database (Denmark)

    Kästner, M.; Nowak, K. M.; Miltner, A.

    2014-01-01

    This review provides a comprehensive overview about NER formation and attempts to classify the various types. Xenobiotic NER derived from parent pesticides (or other environmental contaminants) and primary metabolites sorbed or entrapped within the soil organic matter (type I) or covalently bound...

  15. Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

    Science.gov (United States)

    Efferth, Thomas; Volm, Manfred

    2017-07-01

    The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

  16. Xenobiotic-metabolizing enzymes in plants and their role in uptake and biotransformation of veterinary drugs in the environment.

    Science.gov (United States)

    Bártíková, Hana; Skálová, Lenka; Stuchlíková, Lucie; Vokřál, Ivan; Vaněk, Tomáš; Podlipná, Radka

    2015-08-01

    Many various xenobiotics permanently enter plants and represent potential danger for their organism. For that reason, plants have evolved extremely sophisticated detoxification systems including a battery of xenobiotic-metabolizing enzymes. Some of them are similar to those in humans and animals, but there are several plant-specific ones. This review briefly introduces xenobiotic-metabolizing enzymes in plants and summarizes present information about their action toward veterinary drugs. Veterinary drugs are used worldwide to treat diseases and protect animal health. However, veterinary drugs are also unwantedly introduced into environment mostly via animal excrements, they persist in the environment for a long time and may impact on the non-target organisms. Plants are able to uptake, transform the veterinary drugs to non- or less-toxic compounds and store them in the vacuoles and cell walls. This ability may protect not only plant themselves but also other organisms, predominantly invertebrates and wild herbivores. The aim of this review is to emphasize the importance of plants in detoxification of veterinary drugs in the environment. The results of studies, which dealt with transport and biotransformation of veterinary drugs in plants, are summarized and evaluated. In conclusion, the risks and consequences of veterinary drugs in the environment and the possibilities of phytoremediation technologies are considered and future perspectives are outlined.

  17. Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review.

    Science.gov (United States)

    Bévalot, Fabien; Cartiser, Nathalie; Bottinelli, Charline; Fanton, Laurent; Guitton, Jérôme

    2016-01-01

    Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

  18. Effects of excess dietary tyrosine or certain xenobiotics on the cholesterogenesis in rats

    International Nuclear Information System (INIS)

    Nagaoka, S.; Masaki, H.; Aoyama, Y.; Yoshida, A.

    1986-01-01

    Comparison of the effects of excess dietary tyrosine, DDT, chlorobutanol (Chloretone) or butylated hydroxyanisole (BHA) on serum cholesterol, hepatic activities of the rate-limiting enzyme of cholesterol synthesis,3-hydroxy-3-methylglutaryl coenzyme A reductase and in vivo rates of the hepatic cholesterol synthesis measured by 3 H 2 O incorporation were investigated in rats. Serum cholesterol concentration was significantly higher in rats fed the DDT, chlorobutanol, BHA or excess tyrosine diets than in rats fed the control diet for 7 days. Serum cholesterol concentration remained higher compared to control rats when excess tyrosine was fed for 21 d. When rats were fed a basal diet after feeding a tyrosine excess diet for 2 wk, liver weight and serum cholesterol level returned to normal within 7 d. The incorporation of 3 H 2 O into liver cholesterol and the activity of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase were greater in rats fed excess tyrosine or certain xenobiotics than in control rats. Present results suggested that the increase in serum cholesterol concentration due to excess dietary tyrosine or certain xenobiotics is mainly attributable to the stimulation of liver cholesterol synthesis

  19. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles

    Energy Technology Data Exchange (ETDEWEB)

    Maradonna, F.; Nozzi, V. [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); Santangeli, S. [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Traversi, I. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università di Genova, 16132 Genova (Italy); Gallo, P. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Dipartimento di Chimica, Istituto Zooprofilattico Sperimentale del Mezzogiorno, 80055 Portici, Napoli (Italy); Fattore, E. [Dipartimento Ambiente e Salute, IRCCS–Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milano (Italy); Mita, D.G. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Mandich, A. [INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy); Dipartimento di Scienze della Terra, dell’Ambiente e della Vita, Università di Genova, 16132 Genova (Italy); Carnevali, O., E-mail: o.carnevali@univpm.it [Dipartimento di Scienze della Vita e dell’Ambiente, Università Politecnica delle Marche, 60131 Ancona (Italy); INBB Consorzio Interuniversitario di Biosistemi e Biostrutture, 00136 Roma (Italy)

    2015-10-15

    Highlights: • Diets contaminated with NP, BPA, or t-OP affect lipid metabolism. • Xenobiotic-contaminated diets induce metabolic disorders. • Hepatic metabolic disorders may be related to environmental pollution. - Abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes

  20. Xenobiotic-contaminated diets affect hepatic lipid metabolism: Implications for liver steatosis in Sparus aurata juveniles

    International Nuclear Information System (INIS)

    Maradonna, F.; Nozzi, V.; Santangeli, S.; Traversi, I.; Gallo, P.; Fattore, E.; Mita, D.G.; Mandich, A.; Carnevali, O.

    2015-01-01

    Highlights: • Diets contaminated with NP, BPA, or t-OP affect lipid metabolism. • Xenobiotic-contaminated diets induce metabolic disorders. • Hepatic metabolic disorders may be related to environmental pollution. - Abstract: The metabolic effects induced by feed contaminated with a lower or a higher concentration of -nonylpnenol (NP), 4-tert-octylphenol (t-OP) or bisphenol A (BPA), three environmental endocrine disruptors, were assessed in juvenile sea bream liver. Histological analysis demonstrated that all these three xenobiotics induced hepatic lipid accumulation and steatosis. These findings prompted analysis of the expression of the major molecules involved in lipid metabolism: peroxisome proliferator activated receptors (which is encoded by ppars), fatty acid synthase (encoded by fas), lipoprotein lipase (encoded by lpl) and hormone-sensitive lipase (encoded by hsl). The enzymes encoded by ppars and fas are in fact responsible for lipid accumulation, whereas lpl- and hsl- encoded proteins play a pivotal role in fat mobilization. The three xenobiotics modulated ppar mRNA expression: pparα mRNA expression was induced by the higher dose of each contaminant; pparβ mRNA expression was upregulated by the lower doses and in BPA2 fish ppary mRNA overexpression was induced by all pollutants. These data agreed with the lipid accumulation profiles documented by histology. Fas mRNA levels were modulated by the two NP doses and the higher BPA concentration. Lpl mRNA was significantly upregulated in all experimental groups except for BPA1 fish while hsl mRNA was significantly downregulated in all groups except for t-OP2 and BPA1 fish. The plasma concentrations of cortisol, the primary stress biomarker, were correlated with the levels of pepck mRNA level. This gene encodes phosphoenolpyruvate carboxykinase which is one of the key enzymes of gluconeogenesis. Pepck mRNA was significantly overexpressed in fish exposed to NP2 and both t-OP doses. Finally, the genes

  1. Free radicals and related reactive species as mediators of tissue injury and disease: implications for Health.

    Science.gov (United States)

    Kehrer, James P; Klotz, Lars-Oliver

    2015-01-01

    A radical is any molecule that contains one or more unpaired electrons. Radicals are normal products of many metabolic pathways. Some exist in a controlled (caged) form as they perform essential functions. Others exist in a free form and interact with various tissue components. Such interactions can cause both acute and chronic dysfunction, but can also provide essential control of redox regulated signaling pathways. The potential roles of endogenous or xenobiotic-derived free radicals in several human pathologies have stimulated extensive research linking the toxicity of numerous xenobiotics and disease processes to a free radical mechanism. In recent years, improvements in analytical methodologies, as well as the realization that subtle effects induced by free radicals and oxidants are important in modulating cellular signaling, have greatly improved our understanding of the roles of these reactive species in toxic mechanisms and disease processes. However, because free radical-mediated changes are pervasive, and a consequence as well as a cause of injury, whether such species are a major cause of tissue injury and human disease remains unclear. This concern is supported by the fact that the bulk of antioxidant defenses are enzymatic and the findings of numerous studies showing that exogenously administered small molecule antioxidants are unable to affect the course of most toxicities and diseases purported to have a free radical mechanism. This review discusses cellular sources of various radical species and their reactions with vital cellular constituents, and provides examples of selected disease processes that may have a free radical component.

  2. Soil-biofilters for elimination of xenobiotics from wastewaters

    DEFF Research Database (Denmark)

    Bester, Kai; Schäfer, D; Janzen, N.

    treatment plants are not designed to eliminate these compounds. Even more of these compounds are discharged by storm waters and combined sewer overflows. It is generally suggested that separating sewers into waste water and rainwater systems might help to improve the situation. However in the last few years...... it has been demonstrated, that storm waters can be heavily polluted with biocides, lubricants and PAHs. In this study we investigated the possibilities to eliminate lipophilic fragrances, bactericides, UV blockers, lubricants etc, as well as more hydrophilic organophosphate flame retardants, biocides...... and other components with low cost soil biofilter techniques suited for on-site decentralised treatment of storm waters and combined sewer overflows. On the other hand the same systems and compounds were tested in for polishing treated waste water in respect of further elimination of xenobiotic compounds....

  3. Bound xenobiotic residues in food commodities of plant and animal origin: IUPAC Reports on Pesticides (40)

    NARCIS (Netherlands)

    Skidmore, M.W.; Paulson, G.D.; Kuiper, H.A.; Ohlin, B.

    1998-01-01

    In order to assess the dietary risk resulting from the use of pesticides or veterinary drugs the nature of the chemical residues on food commodities needs to be determined. Elucidation of the nature of the chemical residue is carried out using radiolabelled studies where the radiolabelled xenobiotic

  4. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Directory of Open Access Journals (Sweden)

    Jinpeng Qi

    Full Text Available Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR by using mathematical framework of kinetic theory of active particles (KTAP. Firstly, we focus on illustrating the profile of Cellular Repair System (CRS instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs and Repair Protein (RP generating, DSB-protein complexes (DSBCs synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  5. Kinetic theory approach to modeling of cellular repair mechanisms under genome stress.

    Science.gov (United States)

    Qi, Jinpeng; Ding, Yongsheng; Zhu, Ying; Wu, Yizhi

    2011-01-01

    Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.

  6. Activity of the Antioxidant Defense System in a Typical Bioinsecticide-and Synthetic Insecticide-treated Cowpea Storage Beetle F. (Coleoptera: Chrysomelidae

    Directory of Open Access Journals (Sweden)

    Ayodele O. Kolawole

    2014-01-01

    Full Text Available The non-enzymatic and enzymatic antioxidant defense systems play a major role in detoxification of pro-oxidant endobiotics and xenobiotics. The possible involvement of beetle non-enzymatic [α-tocopherol, glutathione (GSH, and ascorbic acid] and enzymatic [catalase (CAT, superoxide dismutase (SOD, peroxidase (POX, and polyphenol oxidase (PPO] antioxidant defense system on the insecticidal activity of synthetic insecticides (cypermethrin, 2,2-dicholorovinyl dimethyl phosphate, and λ-cyhalothrin and ethanolic plant extracts of Tithonia diversifolia, Cyperus rotundus, Hyptis suaveolens leaves , and Jatropha Curcas seeds was investigated. 2,2-Dicholorovinyl dimethyl phosphate (DDVP; 200 ppm, LC 50 = 13.24 ppm and T. diversifolia (20,000 ppm resulted in 100% beetle mortality at 96-hour post-treatment. The post-treatments significantly increased the beetle α-tocopherol and GSH contents. Activities of CAT, SOD, POX, and PPO were modulated by the synthetic insecticides and bioinsecticides to diminish the adverse effect of the chemical stresses. Quantitative and qualitative allelochemical compositions of bioinsecticides and chemical structure of synthetic insecticides possibly account and for modulation of their respective enzyme activities. Altogether, oxidative stress was enormous enough to cause maladaptation in insects. This study established that oxidative imbalance created could be the molecular basis of the efficacy of both insecticides and bio-insecticides. Two, there was development of functional but inadequate antioxidant defense mechanism in the beetle.

  7. IL-36/LXR axis modulates cholesterol metabolism and immune defense to Mycobacterium tuberculosis.

    Science.gov (United States)

    Ahsan, Fadhil; Maertzdorf, Jeroen; Guhlich-Bornhof, Ute; Kaufmann, Stefan H E; Moura-Alves, Pedro

    2018-01-24

    Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans. Bacterial infection of macrophages usually triggers strong innate immune mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1 family, IL-36, was recently shown to be involved in cellular defense against Mtb. To unveil the underlying mechanism of IL-36 induced antibacterial activity, we analyzed its role in the regulation of cholesterol metabolism, together with the involvement of Liver X Receptor (LXR) in this process. We report that, in Mtb-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides expression and in Mtb growth restriction. These data provide novel evidence for the importance of IL-36 and cholesterol metabolism mediated by LXR in cellular host defense against Mtb.

  8. Whole body exposure to low-dose γ-radiation enhances the antioxidant defense system

    International Nuclear Information System (INIS)

    Pathak, C.M.; Avti, P.K.; Khanduja, K.L.; Sharma, S.C.

    2008-01-01

    It is believed that the extent of cellular damage by low- radiation dose is proportional to the effects observed at high radiation dose as per the Linear-No-Threshold (LNT) hypothesis. However, this notion may not be true at low-dose radiation exposure in the living system. Recent evidence suggest that the living organisms do not respond to ionizing radiations in a linear manner in the low dose range 0.01-0.5Gy and rather restore the homeostasis both in vivo and in vitro by normal physiological mechanisms such as cellular and DNA repair processes, immune reactions, antioxidant defense, adaptive responses, activation of immune functions, stimulation of growth etc. In this study, we have attempted to find the critical radiation dose range and the post irradiation period during which the antioxidant defense systems in the lungs, liver and kidneys remain stimulated in these organs after whole body exposure of the animals to low-dose radiation

  9. Proteomic approaches to understanding the role of the cytoskeleton in host-defense mechanisms

    Science.gov (United States)

    Radulovic, Marko; Godovac-Zimmermann, Jasminka

    2014-01-01

    The cytoskeleton is a cellular scaffolding system whose functions include maintenance of cellular shape, enabling cellular migration, division, intracellular transport, signaling and membrane organization. In addition, in immune cells, the cytoskeleton is essential for phagocytosis. Following the advances in proteomics technology over the past two decades, cytoskeleton proteome analysis in resting and activated immune cells has emerged as a possible powerful approach to expand our understanding of cytoskeletal composition and function. However, so far there have only been a handful of studies of the cytoskeleton proteome in immune cells. This article considers promising proteomics strategies that could augment our understanding of the role of the cytoskeleton in host-defense mechanisms. PMID:21329431

  10. Markers of individual susceptibility and DNA repair rate in workers exposed to xenobiotics in a tire plant

    Czech Academy of Sciences Publication Activity Database

    Vodička, Pavel; Kumar, R.; Štětina, R.; Musak, L.; Souček, P.; Haufroid, V.; Sasiadek, M.; Vodičková, Ludmila; Naccarati, Alessio; Sediková, J.; Sanyal, S.; Brsiak, V.; Norppa, H.; Buchancová, J.; Hemminki, K.; Kuricová, Miroslava

    2004-01-01

    Roč. 44, - (2004), s. 283-292 ISSN 0893-6692 R&D Projects: GA ČR GA310/01/0802 Institutional research plan: CEZ:AV0Z5039906 Keywords : occupational exposure to xenobiotics Subject RIV: FM - Hygiene Impact factor: 2.000, year: 2004

  11. Basalt fiber reinforced porous aggregates-geopolymer based cellular material

    Science.gov (United States)

    Luo, Xin; Xu, Jin-Yu; Li, Weimin

    2015-09-01

    Basalt fiber reinforced porous aggregates-geopolymer based cellular material (BFRPGCM) was prepared. The stress-strain curve has been worked out. The ideal energy-absorbing efficiency has been analyzed and the application prospect has been explored. The results show the following: fiber reinforced cellular material has successively sized pore structures; the stress-strain curve has two stages: elastic stage and yielding plateau stage; the greatest value of the ideal energy-absorbing efficiency of BFRPGCM is 89.11%, which suggests BFRPGCM has excellent energy-absorbing property. Thus, it can be seen that BFRPGCM is easy and simple to make, has high plasticity, low density and excellent energy-absorbing features. So, BFRPGCM is a promising energy-absorbing material used especially in civil defense engineering.

  12. Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

    Science.gov (United States)

    Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

    2013-01-01

    The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

  13. Towards a continuous two-phase partitioning bioreactor for xenobiotic removal

    Energy Technology Data Exchange (ETDEWEB)

    Tomei, M.Concetta, E-mail: tomei@irsa.cnr.it [Water Research Institute, C.N.R., Via Salaria km 29.300, CP 10, 00015 Monterotondo Stazione, Rome (Italy); Mosca Angelucci, Domenica [Water Research Institute, C.N.R., Via Salaria km 29.300, CP 10, 00015 Monterotondo Stazione, Rome (Italy); Daugulis, Andrew J. [Department of Chemical Engineering, Queen’s University, Kingston, Ontario K7 L 3N6 (Canada)

    2016-11-05

    Highlights: • A prototype of a continuous two-phase partitioning bioreactor was investigated. • The bioreactor contained coiled tubing of a selected extruded polymer, Hytrel 8206. • Mass transfer and removal of a xenobiotic, 4-cholorophenol, were investigated. • Removal efficiencies in the tubing wastewater stream were always ≥ 96%. • Presence of polymer tubing buffered increasing in organic load to the hybrid system. - Abstract: The removal of a xenobiotic (4-chlorophenol) from contaminated water was investigated in a simulated continuous two-phase partitioning bioreactor (C-TPPB), fitted with coiled tubing comprised of a specifically-selected extruded polymer, Hytrel 8206. Wastewater flowed inside the tubing, the pollutant diffused through the tubing wall, and was removed in the aqueous bioreactor phase at typical biological removal rates in the C-TTPB simulated by varying aqueous phase throughput to the reactor. Operating over a range of influent substrate concentrations (500–1500 mg L{sup −1}) and hydraulic retention times in the tubing (4–8 h), overall mass transfer coefficients were 1.7–3.5 × 10{sup −7} m s{sup −1}, with the highest value corresponding to the highest tubing flow rate. Corresponding mass transfer rates are of the same order as biological removal rates, and thus do not limit the removal process. The C-TPPB showed good performance over all organic and hydraulic loading ranges, with removal efficiencies of 4CP in the tubing wastewater stream always ≥96%. Additionally, the presence of the Hytrel tubing was able to buffer increases in organic loading to the hybrid system, enhancing overall process stability. Biological testing of the C-TPPB confirmed the abiotic test results demonstrating even higher 4-chlorophenol removal efficiency (∼99%) in the tubing stream.

  14. Effect of turmeric on xenobiotic metabolising enzymes.

    Science.gov (United States)

    Goud, V K; Polasa, K; Krishnaswamy, K

    1993-07-01

    Diet contains several substances capable of inhibiting chemical carcinogenesis. It is known that such inhibitors may either act directly by scavenging the reactive substances or indirectly by promoting mechanisms which enhance detoxification. Turmeric which contains curcumin both in vitro and in vivo is an active antimutagen. Studies were therefore conducted to evaluate the effects of turmeric on xenobiotic metabolising enzymes in hepatic tissue of rats fed turmeric ranging from 0.5-10% in the diet. Enzymes such as aryl hydrocarbon hydroxylase, UDP glucuronyl transferase and glutathione-S-transferase were assayed after four weeks of turmeric fed diets. No significant differences were seen in the activating enzyme AHH. However, UDPGT was significantly elevated in rats fed 10% turmeric while GSHT registered a significant increase in 5 and 10% turmeric fed diet as compared to controls and 0.5-1.0% turmeric fed animals. The results suggest that turmeric may increase detoxification systems in addition to its anti-oxidant properties. Curcumin perhaps is the active principle in turmeric. Turmeric used widely as a spice would probably mitigate the effects of several dietary carcinogens.

  15. Defense Business Board

    Science.gov (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Business Board Search Search Defense Business Board: Search Search Defense Business Board: Search Defense Business Board Business Excellence in Defense of the Nation Defense Business Board Home Charter Members Meetings Studies Contact Us The Defense

  16. Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

    Science.gov (United States)

    Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

    2011-01-01

    Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

  17. Do heavy metals and metalloids influence the detoxification of organic xenobiotics in plants?

    Science.gov (United States)

    Schröder, Peter; Lyubenova, Lyudmila; Huber, Christian

    2009-11-01

    Mixed pollution with trace elements and organic industrial compounds is characteristic for many spill areas and dumping sites. The danger for the environment and human health from such sites is large, and sustainable remediation strategies are urgently needed. Phytoremediation seems to be a cheap and environmentally sound option for the removal of unwanted compounds, and the hyperaccumulation of trace elements and toxic metals is seemingly independent from the metabolism of organic xenobiotics. However, stress reactions, ROS formation and depletion of antioxidants will also cause alterations in xenobiotic detoxification. Here, we investigate the capability of plants to detoxify chlorophenols via glutathione conjugation in a mixed pollution situation. Typha latifolia and Phragmites australis plants for the present study were grown under greenhouse conditions in experimental ponds. A Picea abies L. suspension culture was grown in a growth chamber. Cadmium sulphate, sodium arsenate and lead chloride in concentrations from 10 to 500 microM were administered to plants. Enzymes of interest for the present study were: glutathione transferase (GST), glutathione reductase, ascorbate peroxidase and peroxidase. Measurements were performed according to published methods. GST spectrophotometric assays included the model substrates CDNB, DCNB, NBC, NBoC and the herbicide Fluorodifen. Heavy metals lead to visible stress symptoms in higher plants. Besides one long-term experiment of 72 days duration, the present study shows time and concentration-dependent plant alterations already after 24 and 72 h Cd incubation. P. abies spruce cell cultures react to CdSO(4) and Na(2)HAsO(4) with an oxidative burst, similar to that observed after pathogen attack or elicitor treatment. Cd application resulted in a reduction in GSH and GSSG contents. When a heavy metal mixture containing Na(2)HAsO(4), CdSO(4) and PbCl(2) was applied to cultures, both GSH and GSSG levels declined. Incubation with

  18. Time-course comparison of xenobiotic activators of CAR and PPARα in mouse liver

    International Nuclear Information System (INIS)

    Ross, Pamela K.; Woods, Courtney G.; Bradford, Blair U.; Kosyk, Oksana; Gatti, Daniel M.; Cunningham, Michael L.; Rusyn, Ivan

    2009-01-01

    Constitutive androstane receptor (CAR) and peroxisome proliferator activated receptor (PPAR)α are transcription factors known to be primary mediators of liver effects, including carcinogenesis, by phenobarbital-like compounds and peroxisome proliferators, respectively, in rodents. Many similarities exist in the phenotypes elicited by these two classes of agents in rodent liver, and we hypothesized that the initial transcriptional responses to the xenobiotic activators of CAR and PPARα will exhibit distinct patterns, but at later time-points these biological pathways will converge. In order to capture the global transcriptional changes that result from activation of these nuclear receptors over a time-course in the mouse liver, microarray technology was used. First, differences in basal expression of liver genes between C57Bl/6J wild-type and Car-null mice were examined and 14 significantly differentially expressed genes were identified. Next, mice were treated with phenobarbital (100 mg/kg by gavage for 24 h, or 0.085% w/w diet for 7 or 28 days), and liver gene expression changes with regards to both time and treatment were identified. While several pathways related to cellular proliferation and metabolism were affected by phenobarbital in wild-type mice, no significant changes in gene expression were found over time in the Car-nulls. Next, we determined commonalities and differences in the temporal response to phenobarbital and WY-14,643, a prototypical activator of PPAR α. Gene expression signatures from livers of wild-type mice C57Bl6/J mice treated with PB or WY-14,643 were compared. Similar pathways were affected by both compounds; however, considerable time-related differences were present. This study establishes common gene expression fingerprints of exposure to activators of CAR and PPARα in rodent liver and demonstrates that despite similar phenotypic changes, molecular pathways differ between classes of chemical carcinogens

  19. Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

    International Nuclear Information System (INIS)

    Karimullina, Elina; Li Yangchun; Ginjupalli, Gautam K.; Baldwin, William S.

    2012-01-01

    Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

  20. Daphnia HR96 is a promiscuous xenobiotic and endobiotic nuclear receptor

    Energy Technology Data Exchange (ETDEWEB)

    Karimullina, Elina [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Institute of Plant and Animal Ecology, Russian Academy of Sciences, Ural Branch, Yekaterinburg 620144 (Russian Federation); Li Yangchun; Ginjupalli, Gautam K. [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Baldwin, William S., E-mail: baldwin@clemson.edu [Environmental Toxicology Program, Clemson University, Clemson, SC 29634 (United States); Biological Sciences, Clemson University, Clemson, SC (United States)

    2012-07-15

    Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics.

  1. The physiology and toxicology of salmonid eggs and larvae in relation to water quality criteria

    International Nuclear Information System (INIS)

    Finn, Roderick Nigel

    2007-01-01

    the presence of ambient humic acid. High temperatures during development may be teratogenic, cause sexual bias, or long-term effects on muscle cellularity. Xenobiotics cause inhibition of neural acetylcholine esterase and carboxylases and disrupt the normal signalling pathways of hormones by binding to relevant receptors and mimicking their actions. A complex suite of genes is activated in response to environmental or parentally transmitted xenobiotics. The primary defense mechanism in embryos involves resistance to uptake but later biotransformation via the aryl hydrocarbon receptor (AHR)-mediated activation of members of the cytochrome mixed-function mono-oxygenase superfamily (CYP1A, CYP2B, and CYP3A) and subsequent glucuronidation or glutathionation. Due to the number of duplicate or triplicate genes coding for intermediates in the signalling pathways, and cross-talk between nuclear orphan receptors and steroid hormone receptors, a large number of complications arise in response to xenobiotic intoxicaton. One such syndrome, known as blue-sac disease causes an anaphylactoid response in hatched larvae due to increased permeability in the vascular endothelium that coincides with AHR-mediated CYP induction. Early embryos also respond to such xenobiotic insults, but apparently have an immature translational control for expression of CYP proteins, which coincides with a lack of excretory organs necessary for the end-point of biotransformation. Other syndromes (M74 and Cayuga) are now associated with thiamine deficiency. Where possible guidelines for water quality criteria are suggested

  2. The physiology and toxicology of salmonid eggs and larvae in relation to water quality criteria

    Energy Technology Data Exchange (ETDEWEB)

    Finn, Roderick Nigel [Department of Biology, University of Bergen, Allegaten 41, N-5020 Bergen (Norway)]. E-mail: nigel.finn@bio.uib.no

    2007-03-30

    the presence of ambient humic acid. High temperatures during development may be teratogenic, cause sexual bias, or long-term effects on muscle cellularity. Xenobiotics cause inhibition of neural acetylcholine esterase and carboxylases and disrupt the normal signalling pathways of hormones by binding to relevant receptors and mimicking their actions. A complex suite of genes is activated in response to environmental or parentally transmitted xenobiotics. The primary defense mechanism in embryos involves resistance to uptake but later biotransformation via the aryl hydrocarbon receptor (AHR)-mediated activation of members of the cytochrome mixed-function mono-oxygenase superfamily (CYP1A, CYP2B, and CYP3A) and subsequent glucuronidation or glutathionation. Due to the number of duplicate or triplicate genes coding for intermediates in the signalling pathways, and cross-talk between nuclear orphan receptors and steroid hormone receptors, a large number of complications arise in response to xenobiotic intoxicaton. One such syndrome, known as blue-sac disease causes an anaphylactoid response in hatched larvae due to increased permeability in the vascular endothelium that coincides with AHR-mediated CYP induction. Early embryos also respond to such xenobiotic insults, but apparently have an immature translational control for expression of CYP proteins, which coincides with a lack of excretory organs necessary for the end-point of biotransformation. Other syndromes (M74 and Cayuga) are now associated with thiamine deficiency. Where possible guidelines for water quality criteria are suggested.

  3. Involvement of oxygen reactive species in the cellular response of carcinoma cells to irradiation

    International Nuclear Information System (INIS)

    Tulard, A.

    2004-06-01

    After a presentation of oxygen reactive species and their sources, the author describes the enzymatic and non-enzymatic anti-oxidative defenses, the physiological roles of oxygen reactive species, the oxidative stress, the water radiolysis, the anti-oxidative enzymes and the effects of ionizing radiations. The author then reports an investigation on the contribution of oxygen reactive species in the cellular response to irradiation, and an investigation on the influence of the breathing chain on the persistence of a radio-induced oxidative stress. He also reports a research on molecular mechanisms involved in the cellular radio-sensitivity

  4. Xenobiotic Compounds Degradation by Heterologous Expression of a Trametes sanguineus Laccase in Trichoderma atroviride.

    Directory of Open Access Journals (Sweden)

    Edgar Balcázar-López

    Full Text Available Fungal laccases are enzymes that have been studied because of their ability to decolorize and detoxify effluents; they are also used in paper bleaching, synthesis of polymers, bioremediation, etc. In this work we were able to express a laccase from Trametes (Pycnoporus sanguineus in the filamentous fungus Trichoderma atroviride. For this purpose, a transformation vector was designed to integrate the gene of interest in an intergenic locus near the blu17 terminator region. Although monosporic selection was still necessary, stable integration at the desired locus was achieved. The native signal peptide from T. sanguineus laccase was successful to secrete the recombinant protein into the culture medium. The purified, heterologously expressed laccase maintained similar properties to those observed in the native enzyme (Km and kcat and kcat/km values for ABTS, thermostability, substrate range, pH optimum, etc. To determine the bioremediation potential of this modified strain, the laccase-overexpressing Trichoderma strain was used to remove xenobiotic compounds. Phenolic compounds present in industrial wastewater and bisphenol A (an endocrine disruptor from the culture medium were more efficiently removed by this modified strain than with the wild type. In addition, the heterologously expressed laccase was able to decolorize different dyes as well as remove benzo[α]pyrene and phenanthrene in vitro, showing its potential for xenobiotic compound degradation.

  5. Proteomic analysis of the defense response of wheat to the powdery mildew fungus, Blumeria graminis f. sp. tritici.

    Science.gov (United States)

    Mandal, Md Siddikun Nabi; Fu, Ying; Zhang, Sheng; Ji, Wanquan

    2014-12-01

    Powdery mildew of wheat is caused by Blumeria graminis f. sp. tritici (Bgt). Although many wheat cultivars resistant to this disease have been developed, little is known about their resistance mechanisms. The aim of this study was to identify proteins showing changes in abundance during the resistance response of the wheat line N0308 infected by Bgt. In two-dimensional electrophoresis analyses, 45 spots on the gels showed significant changes in abundance at 24, 48, and 72 h after inoculation, as compared to non-inoculated plants. Of these 45 proteins, 44 were identified by mass spectrometry analysis using the NCBInr database of Triticum aestivum (26 spots) and closely related species in the Triticum genus (18 spots). These proteins were associated with the defense response, photosynthesis, metabolism, and other cellular processes in wheat. Most of the up-regulated proteins were identified as stress- and defense-related proteins. In particular, the product of a specific powdery mildew resistance gene (Pm3b and its homolog) and some other defense- and pathogenesis-related proteins were overexpressed. The resistance gene product mediates the immune response and coordinates other cellular processes during the resistance response to Bgt.

  6. High-throughput metagenomic analysis of petroleum-contaminated soil microbiome reveals the versatility in xenobiotic aromatics metabolism.

    Science.gov (United States)

    Bao, Yun-Juan; Xu, Zixiang; Li, Yang; Yao, Zhi; Sun, Jibin; Song, Hui

    2017-06-01

    The soil with petroleum contamination is one of the most studied soil ecosystems due to its rich microorganisms for hydrocarbon degradation and broad applications in bioremediation. However, our understanding of the genomic properties and functional traits of the soil microbiome is limited. In this study, we used high-throughput metagenomic sequencing to comprehensively study the microbial community from petroleum-contaminated soils near Tianjin Dagang oilfield in eastern China. The analysis reveals that the soil metagenome is characterized by high level of community diversity and metabolic versatility. The metageome community is predominated by γ-Proteobacteria and α-Proteobacteria, which are key players for petroleum hydrocarbon degradation. The functional study demonstrates over-represented enzyme groups and pathways involved in degradation of a broad set of xenobiotic aromatic compounds, including toluene, xylene, chlorobenzoate, aminobenzoate, DDT, methylnaphthalene, and bisphenol. A composite metabolic network is proposed for the identified pathways, thus consolidating our identification of the pathways. The overall data demonstrated the great potential of the studied soil microbiome in the xenobiotic aromatics degradation. The results not only establish a rich reservoir for novel enzyme discovery but also provide putative applications in bioremediation. Copyright © 2016. Published by Elsevier B.V.

  7. DEFENSE SCIENCE AND TECHNOLOGY Adopting Best Practices Can Improve Innovation Investments and Management

    Science.gov (United States)

    2017-06-01

    Defense Technology Development: Technology Transition Programs Support Military Users, but Opportunities Exist to Improve Measurement of Outcomes, GAO-13... LTE ), for cellular wireless communication applications. They also develop and commercialize numerous technologies used in handsets and tablets. They...17-499 Note: Technology Readiness Levels (TRL) are a tool that DOD, among others, uses to assess technology maturity. TRLs are measured on a scale

  8. Proteomic characterization of an isolated fraction of synthetic proteasome inhibitor (PSI-induced inclusions in PC12 cells might offer clues to aggresomes as a cellular defensive response against proteasome inhibition by PSI

    Directory of Open Access Journals (Sweden)

    Li Xing'an

    2010-08-01

    Full Text Available Abstract Background Cooperation of constituents of the ubiquitin proteasome system (UPS with chaperone proteins in degrading proteins mediate a wide range of cellular processes, such as synaptic function and neurotransmission, gene transcription, protein trafficking, mitochondrial function and metabolism, antioxidant defence mechanisms, and apoptotic signal transduction. It is supposed that constituents of the UPS and chaperone proteins are recruited into aggresomes where aberrant and potentially cytotoxic proteins may be sequestered in an inactive form. Results To determinate the proteomic pattern of synthetic proteasome inhibitor (PSI-induced inclusions in PC12 cells after proteasome inhibition by PSI, we analyzed a fraction of PSI-induced inclusions. A proteomic feature of the isolated fraction was characterized by identification of fifty six proteins including twenty previously reported protein components of Lewy bodies, twenty eight newly identified proteins and eight unknown proteins. These proteins, most of which were recognized as a profile of proteins within cellular processes mediated by the UPS, a profile of constituents of the UPS and a profile of chaperone proteins, are classed into at least nine accepted categories. In addition, prolyl-4-hydroxylase beta polypeptide, an endoplasmic reticulum member of the protein disulfide isomerase family, was validated in the developmental process of PSI-induced inclusions in the cells. Conclusions It is speculated that proteomic characterization of an isolated fraction of PSI-induced inclusions in PC12 cells might offer clues to appearance of aggresomes serving as a cellular defensive response against proteasome inhibition.

  9. Non-targeted, high resolution mass spectrometry strategy for simultaneous monitoring of xenobiotics and endogenous compounds in green sea turtles on the Great Barrier Reef.

    Science.gov (United States)

    Heffernan, Amy L; Gómez-Ramos, Maria M; Gaus, Caroline; Vijayasarathy, Soumini; Bell, Ian; Hof, Christine; Mueller, Jochen F; Gómez-Ramos, Maria J

    2017-12-01

    Chemical contamination poses a threat to ecosystem, biota and human health, and identifying these hazards is a complex challenge. Traditional hazard identification relies on a priori-defined targets of limited chemical scope, and is generally inappropriate for exploratory studies such as explaining toxicological effects in environmental systems. Here we present a non-target high resolution mass spectrometry environmental monitoring study with multivariate statistical analysis to simultaneously detect biomarkers of exposure (e.g. xenobiotics) and biomarkers of effect in whole turtle blood. Borrowing the concept from clinical chemistry, a case-control sampling approach was used to investigate the potential influence of xenobiotics of anthropogenic origin on free-ranging green sea turtles (Chelonia mydas) from a remote, offshore 'control' site; and two coastal 'case' sites influenced by urban/industrial and agricultural activities, respectively, on the Great Barrier Reef in North Queensland, Australia. Multiple biomarkers of exposure, including sulfonic acids (n=9), a carbamate insecticide metabolite, and other industrial chemicals; and five biomarkers of effect (lipid peroxidation products), were detected in case sites. Additionally, two endogenous biomarkers of neuroinflammation and oxidative stress were identified, and showed moderate-to-strong correlations with clinical measures of inflammation and liver dysfunction. Our data filtering strategy overcomes limitations of traditional a priori selection of target compounds, and adds to the limited environmental xenobiotic metabolomics literature. To our knowledge this is the first case-control study of xenobiotics in marine megafauna, and demonstrates the utility of green sea turtles to link internal and external exposure, to explain potential toxicological effects in environmental systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The cellular immune response of Daphnia magna under host-parasite genetic variation and variation in initial dose.

    Science.gov (United States)

    Auld, Stuart K J R; Edel, Kai H; Little, Tom J

    2012-10-01

    In invertebrate-parasite systems, the likelihood of infection following parasite exposure is often dependent on the specific combination of host and parasite genotypes (termed genetic specificity). Genetic specificity can maintain diversity in host and parasite populations and is a major component of the Red Queen hypothesis. However, invertebrate immune systems are thought to only distinguish between broad classes of parasite. Using a natural host-parasite system with a well-established pattern of genetic specificity, the crustacean Daphnia magna and its bacterial parasite Pasteuria ramosa, we found that only hosts from susceptible host-parasite genetic combinations mounted a cellular response following exposure to the parasite. These data are compatible with the hypothesis that genetic specificity is attributable to barrier defenses at the site of infection (the gut), and that the systemic immune response is general, reporting the number of parasite spores entering the hemocoel. Further supporting this, we found that larger cellular responses occurred at higher initial parasite doses. By studying the natural infection route, where parasites must pass barrier defenses before interacting with systemic immune responses, these data shed light on which components of invertebrate defense underlie genetic specificity. © 2012 The Author(s). Evolution© 2012 The Society for the Study of Evolution.

  11. Clonal xenobiotic resistance during pollution-induced toxic injury and hepatocellular carcinogenesis in liver of female flounder (Platichthys flesus (L.))

    NARCIS (Netherlands)

    Koehler, Angela; Alpermann, Tilmann; Lauritzen, Bjarne; van Noorden, Cornelis J. F.

    2004-01-01

    Juvenile and adult female flounder (Platichthys flesus (L.)) were caught either in the estuary of the most polluted European river, the Elbe, or as controls in a reference site to study pollution-induced xenobiotic resistance in their livers in relation to pathological alterations. In juvenile fish,

  12. Immunity, suicide or both? Ecological determinants for the combined evolution of anti-pathogen defense systems.

    Science.gov (United States)

    Iranzo, Jaime; Lobkovsky, Alexander E; Wolf, Yuri I; Koonin, Eugene V

    2015-03-13

    Parasite-host arms race is one of the key factors in the evolution of life. Most cellular life forms, in particular prokaryotes, possess diverse forms of defense against pathogens including innate immunity, adaptive immunity and programmed cell death (altruistic suicide). Coevolution of these different but interacting defense strategies yields complex evolutionary regimes. We develop and extensively analyze a computational model of coevolution of different defense strategies to show that suicide as a defense mechanism can evolve only in structured populations and when the attainable degree of immunity against pathogens is limited. The general principle of defense evolution seems to be that hosts do not evolve two costly defense mechanisms when one is sufficient. Thus, the evolutionary interplay of innate immunity, adaptive immunity and suicide, leads to an equilibrium state where the combination of all three defense strategies is limited to a distinct, small region of the parameter space. The three strategies can stably coexist only if none of them are highly effective. Coupled adaptive immunity-suicide systems, the existence of which is implied by the colocalization of genes for the two types of defense in prokaryotic genomes, can evolve either when immunity-associated suicide is more efficacious than other suicide systems or when adaptive immunity functionally depends on the associated suicide system. Computational modeling reveals a broad range of outcomes of coevolution of anti-pathogen defense strategies depending on the relative efficacy of different mechanisms and population structure. Some of the predictions of the model appear compatible with recent experimental evolution results and call for additional experiments.

  13. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    International Nuclear Information System (INIS)

    Rashid, Kahkashan; Sil, Parames C.

    2015-01-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  14. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Rashid, Kahkashan; Sil, Parames C., E-mail: parames@jcbose.ac.in

    2015-02-01

    The phytochemical, curcumin, has been reported to play many beneficial roles. However, under diabetic conditions, the detail mechanism of its beneficial action in the glucose homeostasis regulatory organ, pancreas, is poorly understood. The present study has been designed and carried out to explore the role of curcumin in the pancreatic tissue of STZ induced and cellular stress mediated diabetes in eight weeks old male Wistar rats. Diabetes was induced with a single intraperitoneal dose of STZ (65 mg/kg body weight). Post to diabetes induction, animals were treated with curcumin at a dose of 100 mg/kg body weight for eight weeks. Underlying molecular and cellular mechanism was determined using various biochemical assays, DNA fragmentation, FACS, histology, immunoblotting and ELISA. Treatment with curcumin reduced blood glucose level, increased plasma insulin and mitigated oxidative stress related markers. In vivo and in vitro experimental results revealed increased levels of proinflammatory cytokines (TNF-α, IL1-β and IFN-γ), reduced level of cellular defense proteins (Nrf-2 and HO-1) and glucose transporter (GLUT-2) along with enhanced levels of signaling molecules of ER stress dependent and independent apoptosis (cleaved Caspase-12/9/8/3) in STZ administered group. Treatment with curcumin ameliorated all the adverse changes and helps the organ back to its normal physiology. Results suggest that curcumin protects pancreatic beta-cells by attenuating inflammatory responses, and inhibiting ER/mitochondrial dependent and independent pathways of apoptosis and crosstalk between them. This uniqueness and absence of any detectable adverse effect proposes the possibility of using this molecule as an effective protector in the cellular stress mediated diabetes mellitus. - Highlights: • STZ induced cellular stress plays a vital role in pancreatic dysfunction. • Cellular stress causes inflammation, pancreatic islet cell death and diabetes. • Deregulation of Nrf-2

  15. Chronic pyelonephritis: Modulation of host defenses by cyclosporin A

    International Nuclear Information System (INIS)

    Findon, G.; Miller, T.E.

    1989-01-01

    Chronic experimental pyelonephritis is characterized by a stable level of infection, which persists for many months. Administration of cyclosporin A (CsA) reactivated previously healed renal lesions and caused a marked increase in bacterial numbers in the kidney. Studies were then carried out to compare the effects of CsA, and the nonselective cytodepletive agents irradiation and cyclophosphamide, on both host defenses and the bacteriologic status of chronically infected kidneys. Two different responses were observed. In animals treated with CsA, bacterial numbers increased markedly, although circulating neutrophil numbers were relatively unaffected. This observation was in contrast to the severe ablation of leukocyte numbers and competence needed to achieve an equivalent effect when irradiation and cyclophosphamide were used. One possible explanation for the adverse effect of CsA on the host-parasite balance in chronic pyelonephritis is that CsA affects mediators that control the inflammatory response or induces a qualitative change in a critical cellular defense compartment

  16. Defense Standardization Program Journal, July/December 2007

    Science.gov (United States)

    2007-12-01

    IeqLuirelleCnlts. About the Authors Robert Stenner , a toxicologist at Pacific Northwest National Laboratory (PNNL), has more than 30 years ot experience...in emergency response, environmental health risk analysis, and human health impact analysis of xenobiotic agents. Dr. Stenner also chairs ASTM

  17. Beyond cellular detoxification: a plethora of physiological roles for MDR transporter homologs in plants

    Science.gov (United States)

    Remy, Estelle; Duque, Paula

    2014-01-01

    Higher plants possess a multitude of Multiple Drug Resistance (MDR) transporter homologs that group into three distinct and ubiquitous families—the ATP-Binding Cassette (ABC) superfamily, the Major Facilitator Superfamily (MFS), and the Multidrug And Toxic compound Extrusion (MATE) family. As in other organisms, such as fungi, mammals, and bacteria, MDR transporters make a primary contribution to cellular detoxification processes in plants, mainly through the extrusion of toxic compounds from the cell or their sequestration in the central vacuole. This review aims at summarizing the currently available information on the in vivo roles of MDR transporters in plant systems. Taken together, these data clearly indicate that the biological functions of ABC, MFS, and MATE carriers are not restricted to xenobiotic and metal detoxification. Importantly, the activity of plant MDR transporters also mediates biotic stress resistance and is instrumental in numerous physiological processes essential for optimal plant growth and development, including the regulation of ion homeostasis and polar transport of the phytohormone auxin. PMID:24910617

  18. Short-term hepatic effects of depleted uranium on xenobiotic and bile acid metabolizing cytochrome P450 enzymes in the rat

    International Nuclear Information System (INIS)

    Gueguen, Y.; Souidi, M.; Baudelin, C.; Dudoignon, N.; Grison, S.; Dublineau, I.; Marquette, C.; Voisin, P.; Gourmelon, P.; Aigueperse, J.

    2006-01-01

    The toxicity of uranium has been demonstrated in different organs, including the kidneys, skeleton, central nervous system, and liver. However, few works have investigated the biological effects of uranium contamination on important metabolic function in the liver. In vivo studies were conducted to evaluate its effects on cytochrome P450 (CYP) enzymes involved in the metabolism of cholesterol and xenobiotics in the rat liver. The effects of depleted uranium (DU) contamination on Sprague-Dawley were measured at 1 and 3 days after exposure. Biochemical indicators characterizing liver and kidney functions were measured in the plasma. The DU affected bile acid CYP activity: 7α-hydroxycholesterol plasma level decreased by 52% at day 3 whereas microsomal CYP7A1 activity in the liver did not change significantly and mitochondrial CYP27A1 activity quintupled at day 1. Gene expression of the nuclear receptors related to lipid metabolism (FXR and LXR) also changed, while PPARα mRNA levels did not. The increased mRNA levels of the xenobiotic-metabolizing CYP3A enzyme at day 3 may be caused by feedback up-regulation due to the decreased CYP3A activity at day 1. CAR mRNA levels, which tripled on day 1, may be involved in this up-regulation, while mRNA levels of PXR did not change. These results indicate that high levels of depleted uranium, acting through modulation of the CYP enzymes and some of their nuclear receptors, affect the hepatic metabolism of bile acids and xenobiotics. (orig.)

  19. Two Horizontally Transferred Xenobiotic Resistance Gene Clusters Associated with Detoxification of Benzoxazolinones by Fusarium Species

    Science.gov (United States)

    Glenn, Anthony E.; Davis, C. Britton; Gao, Minglu; Gold, Scott E.; Mitchell, Trevor R.; Proctor, Robert H.; Stewart, Jane E.; Snook, Maurice E.

    2016-01-01

    Microbes encounter a broad spectrum of antimicrobial compounds in their environments and often possess metabolic strategies to detoxify such xenobiotics. We have previously shown that Fusarium verticillioides, a fungal pathogen of maize known for its production of fumonisin mycotoxins, possesses two unlinked loci, FDB1 and FDB2, necessary for detoxification of antimicrobial compounds produced by maize, including the γ-lactam 2-benzoxazolinone (BOA). In support of these earlier studies, microarray analysis of F. verticillioides exposed to BOA identified the induction of multiple genes at FDB1 and FDB2, indicating the loci consist of gene clusters. One of the FDB1 cluster genes encoded a protein having domain homology to the metallo-β-lactamase (MBL) superfamily. Deletion of this gene (MBL1) rendered F. verticillioides incapable of metabolizing BOA and thus unable to grow on BOA-amended media. Deletion of other FDB1 cluster genes, in particular AMD1 and DLH1, did not affect BOA degradation. Phylogenetic analyses and topology testing of the FDB1 and FDB2 cluster genes suggested two horizontal transfer events among fungi, one being transfer of FDB1 from Fusarium to Colletotrichum, and the second being transfer of the FDB2 cluster from Fusarium to Aspergillus. Together, the results suggest that plant-derived xenobiotics have exerted evolutionary pressure on these fungi, leading to horizontal transfer of genes that enhance fitness or virulence. PMID:26808652

  20. Monocrotophos induces the expression and activity of xenobiotic metabolizing enzymes in pre-sensitized cultured human brain cells.

    Directory of Open Access Journals (Sweden)

    Vinay K Tripathi

    Full Text Available The expression and metabolic profile of cytochrome P450s (CYPs is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y and glial (U373-MG cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC, cyclophosphamide (CPA, ethanol and known neurotoxicant- monocrotophos (MCP, a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against

  1. Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

    International Nuclear Information System (INIS)

    Yang, Hong; Guo, Dong; Obianom, Obinna N.; Su, Tong; Polli, James E.; Shu, Yan

    2017-01-01

    Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd 2+ ). In this study, we aimed to examine whether Cd 2+ is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd 2+ . The cells overexpressing MATEs showed a 2–4 fold increase of Cd 2+ uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K m ) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd 2+ could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC 50 ) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd 2+ out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd 2+ -induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd 2+ and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

  2. Dynamic defense workshop :

    Energy Technology Data Exchange (ETDEWEB)

    Crosby, Sean Michael; Doak, Justin E.; Haas, Jason Juedes.; Helinski, Ryan; Lamb, Christopher C.

    2013-02-01

    On September 5th and 6th, 2012, the Dynamic Defense Workshop: From Research to Practice brought together researchers from academia, industry, and Sandia with the goals of increasing collaboration between Sandia National Laboratories and external organizations, de ning and un- derstanding dynamic, or moving target, defense concepts and directions, and gaining a greater understanding of the state of the art for dynamic defense. Through the workshop, we broadened and re ned our de nition and understanding, identi ed new approaches to inherent challenges, and de ned principles of dynamic defense. Half of the workshop was devoted to presentations of current state-of-the-art work. Presentation topics included areas such as the failure of current defenses, threats, techniques, goals of dynamic defense, theory, foundations of dynamic defense, future directions and open research questions related to dynamic defense. The remainder of the workshop was discussion, which was broken down into sessions on de ning challenges, applications to host or mobile environments, applications to enterprise network environments, exploring research and operational taxonomies, and determining how to apply scienti c rigor to and investigating the eld of dynamic defense.

  3. Technical Soddi Defenses: The Trojan Horse Defense Revisited

    Directory of Open Access Journals (Sweden)

    Chad Steel

    2014-12-01

    Full Text Available In 2004, the Trojan horse defense was at a crossroads, with two child pornography cases where it was successfully employed in the United Kingdom, resulting in acquittals.  The original Trojan horse defense has now become part of the more general “technical SODDI” defense, which includes the possibility of unknown actors using unsecured Wi-Fi connections or having physical access to a computer to perform criminal acts.  In the past ten years, it has failed to be effective in the United States for criminal cases, with no published acquittals in cases where it was the primary defense.  In the criminal cases where it has been used as leverage in plea negotiations, there has been either poor forensics performed by the prosecution or political pressure to resolve a matter.  On the civil side, however, the defense has been wildly successful, effectively shutting down large John Doe copyright infringement litigation against non-commercial violators.  

  4. Isonitrosoacetophenone drives transcriptional reprogramming in Nicotiana tabacum cells in support of innate immunity and defense.

    Directory of Open Access Journals (Sweden)

    Arnaud T Djami-Tchatchou

    Full Text Available Plants respond to various stress stimuli by activating broad-spectrum defense responses both locally as well as systemically. As such, identification of expressed genes represents an important step towards understanding inducible defense responses and assists in designing appropriate intervention strategies for disease management. Genes differentially expressed in tobacco cell suspensions following elicitation with isonitrosoacetophenone (INAP were identified using mRNA differential display and pyro-sequencing. Sequencing data produced 14579 reads, which resulted in 198 contigs and 1758 singletons. Following BLAST analyses, several inducible plant defense genes of interest were identified and classified into functional categories including signal transduction, transcription activation, transcription and protein synthesis, protein degradation and ubiquitination, stress-responsive, defense-related, metabolism and energy, regulation, transportation, cytoskeleton and cell wall-related. Quantitative PCR was used to investigate the expression of 17 selected target genes within these categories. Results indicate that INAP has a sensitising or priming effect through activation of salicylic acid-, jasmonic acid- and ethylene pathways that result in an altered transcriptome, with the expression of genes involved in perception of pathogens and associated cellular re-programming in support of defense. Furthermore, infection assays with the pathogen Pseudomonas syringae pv. tabaci confirmed the establishment of a functional anti-microbial environment in planta.

  5. Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood

    Directory of Open Access Journals (Sweden)

    Laura Llobet

    2015-11-01

    Full Text Available Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis.

  6. Transcription Factor Functional Protein-Protein Interactions in Plant Defense Responses

    Directory of Open Access Journals (Sweden)

    Murilo S. Alves

    2014-03-01

    Full Text Available Responses to biotic stress in plants lead to dramatic reprogramming of gene expression, favoring stress responses at the expense of normal cellular functions. Transcription factors are master regulators of gene expression at the transcriptional level, and controlling the activity of these factors alters the transcriptome of the plant, leading to metabolic and phenotypic changes in response to stress. The functional analysis of interactions between transcription factors and other proteins is very important for elucidating the role of these transcriptional regulators in different signaling cascades. In this review, we present an overview of protein-protein interactions for the six major families of transcription factors involved in plant defense: basic leucine zipper containing domain proteins (bZIP, amino-acid sequence WRKYGQK (WRKY, myelocytomatosis related proteins (MYC, myeloblastosis related proteins (MYB, APETALA2/ ETHYLENE-RESPONSIVE ELEMENT BINDING FACTORS (AP2/EREBP and no apical meristem (NAM, Arabidopsis transcription activation factor (ATAF, and cup-shaped cotyledon (CUC (NAC. We describe the interaction partners of these transcription factors as molecular responses during pathogen attack and the key components of signal transduction pathways that take place during plant defense responses. These interactions determine the activation or repression of response pathways and are crucial to understanding the regulatory networks that modulate plant defense responses.

  7. [Effects of berberine on the recovery of rat liver xenobiotic-metabolizing enzymes after partial hepatectomy].

    Science.gov (United States)

    Zverinsky, I V; Zverinskaya, H G; Sutsko, I P; Telegin, P G; Shlyahtun, A G

    2015-01-01

    We have studied the effect of berberine on the recovery processes of liver xenobiotic-metabolizing function during its compensatory growth after 70% partial hepatectomy. It was found the hepatic ability to metabolize foreign substances are not restored up to day 8. Administration of berberine (10 mg/kg intraperitoneally) for 6 days led to normalization of both cytochrome P450-dependent and flavin-containing monooxygenases. It is suggested that in the biotransformation of berberine involved not only cytochrome P450, but also flavin-containing monooxygenases.

  8. The effects of multiply ionizing gamma irradiations on the xenobiotic metabolizing system in the liver of rats

    International Nuclear Information System (INIS)

    Zavodnik, L.B.; Buko, V.U.

    2009-01-01

    The aim of the work was the studying the effect of multiply low doses of gamma-irradiation in a total doze 1 and 2 Gy on processes lipid peroxidation and xenobiotics metabolizing in rat liver. It was shown the multiply irradiation causes the expressed activation of lipid peroxidation, by increase of TBARS level and dien conjugates. The system of microsomal oxidations was broken at the same time. (authors)

  9. [Study of defense styles, defenses and coping strategies in alcohol-dependent population].

    Science.gov (United States)

    Ribadier, A; Varescon, I

    2017-05-01

    Defense mechanisms have been seen to greatly change over time and across different definitions made by different theoretical currents. Recently with the definition provided by the DSM IV, defense mechanisms have integrated the concept of coping as a defensive factor. These mechanisms are no longer considered just through a psychodynamic approach but also through a cognitive and behavioral one. In recent years, new theories have therefore integrated these two components of the defensive operation. According to Chabrol and Callahan (2013), defense mechanisms precede coping strategies. In individuals with psychopathological disorders, these authors indicate a relative stability of these mechanisms. Also, we asked about the presence of unique characteristics among people with alcohol dependence. Indeed, studies conducted with people with alcohol dependence highlight the presence of a neurotic defense style and some highly immature defenses (projection, acting out, splitting and somatization). In terms of coping strategies, persons with alcohol dependence preferentially use avoidant strategies and strategies focused on emotion. However, although several studies have been conducted to assess coping strategies and defense styles within a population of individuals with an alcohol problem, at the present time none of them has taken into account all these aspects of defense mechanisms. The aim of this study is therefore to study the defenses and defense styles and coping strategies in an alcohol-dependent population. This multicenter study (3 CHU, 1 center of supportive care and prevention in addiction and 1 clinic) received a favorable opinion of an Institutional Review Board (IRB Registration #: 00001072). Eighty alcohol-dependent individuals responded to a questionnaire assessing sociodemographic characteristics and elements related to the course of consumption. Coping strategies were assessed by means of a questionnaire validated in French: the Brief Cope. The Defense

  10. Analysis of putative apoplastic effectors from the nematode, Globodera rostochiensis, and identification of an expansin-like protein that can induce and suppress host defenses.

    Science.gov (United States)

    Ali, Shawkat; Magne, Maxime; Chen, Shiyan; Côté, Olivier; Stare, Barbara Gerič; Obradovic, Natasa; Jamshaid, Lubna; Wang, Xiaohong; Bélair, Guy; Moffett, Peter

    2015-01-01

    The potato cyst nematode, Globodera rostochiensis, is an important pest of potato. Like other pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm, to alter plant cellular functions and successfully infect their hosts. We have generated a library of ORFs encoding putative G. rostochiensis putative apoplastic effectors in vectors for expression in planta. These clones were assessed for morphological and developmental effects on plants as well as their ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins induced developmental phenotypes, whereas predicted cell wall-modifying proteins induced necrosis and chlorosis, consistent with roles in cell fate alteration and tissue invasion, respectively. When directed to the apoplast with a signal peptide, two effectors, an ubiquitin extension protein (GrUBCEP12) and an expansin-like protein (GrEXPB2), suppressed defense responses including NB-LRR signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in species- and sequence-specific manner. Our results are consistent with the scenario whereby potato cyst nematodes secrete effectors that modulate host cell fate and metabolism as well as modifying host cell walls. Furthermore, we show a novel role for an apoplastic expansin-like protein in suppressing intra-cellular defense responses.

  11. Analysis of putative apoplastic effectors from the nematode, Globodera rostochiensis, and identification of an expansin-like protein that can induce and suppress host defenses.

    Directory of Open Access Journals (Sweden)

    Shawkat Ali

    Full Text Available The potato cyst nematode, Globodera rostochiensis, is an important pest of potato. Like other pathogens, plant parasitic nematodes are presumed to employ effector proteins, secreted into the apoplast as well as the host cytoplasm, to alter plant cellular functions and successfully infect their hosts. We have generated a library of ORFs encoding putative G. rostochiensis putative apoplastic effectors in vectors for expression in planta. These clones were assessed for morphological and developmental effects on plants as well as their ability to induce or suppress plant defenses. Several CLAVATA3/ESR-like proteins induced developmental phenotypes, whereas predicted cell wall-modifying proteins induced necrosis and chlorosis, consistent with roles in cell fate alteration and tissue invasion, respectively. When directed to the apoplast with a signal peptide, two effectors, an ubiquitin extension protein (GrUBCEP12 and an expansin-like protein (GrEXPB2, suppressed defense responses including NB-LRR signaling induced in the cytoplasm. GrEXPB2 also elicited defense response in species- and sequence-specific manner. Our results are consistent with the scenario whereby potato cyst nematodes secrete effectors that modulate host cell fate and metabolism as well as modifying host cell walls. Furthermore, we show a novel role for an apoplastic expansin-like protein in suppressing intra-cellular defense responses.

  12. Ballistic missile defense effectiveness

    Science.gov (United States)

    Lewis, George N.

    2017-11-01

    The potential effectiveness of ballistic missile defenses today remains a subject of debate. After a brief discussion of terminal and boost phase defenses, this chapter will focus on long-range midcourse defenses. The problems posed by potential countermeasures to such midcourse defenses are discussed as are the sensor capabilities a defense might have available to attempt to discriminate the actual missile warhead in a countermeasures environment. The role of flight testing in assessing ballistic missile defense effectiveness is discussed. Arguments made about effectiveness by missile defense supporters and critics are summarized.

  13. Modulation of Xenobiotic Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes by ToxCast Chemicals

    Science.gov (United States)

    ToxCast chemicals were assessed for induction or suppression of xenobiotic metabolizing enzyme and transporter gene expression using primary human hepatocytes. The mRNA levels of 14 target and 2 control genes were measured: ABCB1, ABCB11, ABCG2, SLCO1B1, CYP1A1, CYP1A2, CYP2B6, C...

  14. 76 FR 72391 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-11-23

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Revised Defense Logistics Agency...

  15. Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

    Science.gov (United States)

    Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

    2016-04-15

    In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Triclosan affects the microbial community in simulated sewage-drain-field soil and slows down xenobiotic degradation

    Energy Technology Data Exchange (ETDEWEB)

    Svenningsen, Hanne [Department of Geochemistry, Geological Survey of Denmark and Greenland (GEUS), Oster Voldgade 10, DK-1350 Copenhagen K (Denmark); Department of Biology, University of Copenhagen, Solvgade 83H, DK-1307 Copenhagen K (Denmark); Henriksen, Trine [Department of Geochemistry, Geological Survey of Denmark and Greenland (GEUS), Oster Voldgade 10, DK-1350 Copenhagen K (Denmark); Prieme, Anders [Department of Biology, University of Copenhagen, Solvgade 83H, DK-1307 Copenhagen K (Denmark); Johnsen, Anders R., E-mail: arj@geus.dk [Department of Geochemistry, Geological Survey of Denmark and Greenland (GEUS), Oster Voldgade 10, DK-1350 Copenhagen K (Denmark)

    2011-06-15

    Effects of the common antibacterial agent triclosan on microbial communities and degradation of domestic xenobiotics were studied in simulated sewage-drain-field soil. Cultivable microbial populations decreased 22-fold in the presence of 4 mg kg{sup -1} of triclosan, and triclosan-resistant Pseudomonas strains were strongly enriched. Exposure to triclosan also changed the general metabolic profile (Ecoplate substrate profiling) and the general profile (T-RFLP) of the microbial community. Triclosan degradation was slow at all concentrations tested (0.33-81 mg kg{sup -1}) during 50-days of incubation. Mineralization experiments ({sup 14}C-tracers) and chemical analyses (LC-MS/MS) showed that the persistence of a linear alkylbenzene sulfonate (LAS) and a common analgesic (ibuprofen) increased with increasing triclosan concentrations (0.16-100 mg kg{sup -1}). The largest effect was seen for LAS mineralization which was severely reduced by 0.16 mg kg{sup -1} of triclosan. Our findings indicate that environmentally realistic concentrations of triclosan may affect the efficiency of biodegradation in percolation systems. - Highlights: > Triclosan may enter the soil environment through sewage. > Triclosan impacts the microbial community in sewage-drain-field soil. > Triclosan-resistant pseudomonads are strongly enriched. > Degradation of co-occurring LAS and ibuprofen is reduced. - Environmentally realistic triclosan concentrations in percolation systems may reduce the biodegradation of other xenobiotics and select for triclosan-resistant bacteria.

  17. Triclosan affects the microbial community in simulated sewage-drain-field soil and slows down xenobiotic degradation

    International Nuclear Information System (INIS)

    Svenningsen, Hanne; Henriksen, Trine; Prieme, Anders; Johnsen, Anders R.

    2011-01-01

    Effects of the common antibacterial agent triclosan on microbial communities and degradation of domestic xenobiotics were studied in simulated sewage-drain-field soil. Cultivable microbial populations decreased 22-fold in the presence of 4 mg kg -1 of triclosan, and triclosan-resistant Pseudomonas strains were strongly enriched. Exposure to triclosan also changed the general metabolic profile (Ecoplate substrate profiling) and the general profile (T-RFLP) of the microbial community. Triclosan degradation was slow at all concentrations tested (0.33-81 mg kg -1 ) during 50-days of incubation. Mineralization experiments ( 14 C-tracers) and chemical analyses (LC-MS/MS) showed that the persistence of a linear alkylbenzene sulfonate (LAS) and a common analgesic (ibuprofen) increased with increasing triclosan concentrations (0.16-100 mg kg -1 ). The largest effect was seen for LAS mineralization which was severely reduced by 0.16 mg kg -1 of triclosan. Our findings indicate that environmentally realistic concentrations of triclosan may affect the efficiency of biodegradation in percolation systems. - Highlights: → Triclosan may enter the soil environment through sewage. → Triclosan impacts the microbial community in sewage-drain-field soil. → Triclosan-resistant pseudomonads are strongly enriched. → Degradation of co-occurring LAS and ibuprofen is reduced. - Environmentally realistic triclosan concentrations in percolation systems may reduce the biodegradation of other xenobiotics and select for triclosan-resistant bacteria.

  18. Silverleaf whitefly induces salicylic acid defenses and suppresses effectual jasmonic acid defenses.

    Science.gov (United States)

    Zarate, Sonia I; Kempema, Louisa A; Walling, Linda L

    2007-02-01

    The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF.

  19. The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization.

    Science.gov (United States)

    Tokusumi, Yumiko; Tokusumi, Tsuyoshi; Schulz, Robert A

    2017-05-13

    In vertebrates, interaction between the nervous system and immune system is important to protect a challenged host from stress inputs from external sources. In this study, we demonstrate that sensory neurons are involved in the cellular immune response elicited by wasp infestation of Drosophila larvae. Multidendritic class IV neurons sense contacts from external stimuli and induce avoidance behaviors for host defense. Our findings show that inactivation of these sensory neurons impairs the cellular response against wasp parasitization. We also demonstrate that the nociception genes encoding the mechanosensory receptors Painless and Piezo, both expressed in class IV neurons, are essential for the normal cellular immune response to parasite challenge. Copyright © 2017. Published by Elsevier Inc.

  20. Missile Defense: Ballistic Missile Defense System Testing Delays Affect Delivery of Capabilities

    Science.gov (United States)

    2016-04-28

    Page 1 GAO-16-339R Ballistic Missile Defense 441 G St. N.W. Washington, DC 20548 April 28, 2016 Congressional Committees Missile Defense... Ballistic Missile Defense System Testing Delays Affect Delivery of Capabilities For over half a century, the Department of Defense (DOD) has been...funding efforts to develop a system to detect, track, and defeat enemy ballistic missiles. The current system—the Ballistic Missile Defense System

  1. An activated sludge model for xenobiotic organic micro-pollutants (ASM-X)

    DEFF Research Database (Denmark)

    Plósz, Benedek; Lehnberg, K.; Dott, W.

    2010-01-01

    In this paper, we present an evaluation of the process model developed by Plósz et al. (2010a) to predict the fate of antibiotics xenobiotic organic micro-pollutants (XOMs) in activated sludge systems. Instead of spiking the batch reactors with reference substances, observations were made using...... the XOMs content of pre-clarified municipal sewage. Evaluation of the model structure is carried out in dynamic simulations using data obtained in samples taken in a measuring campaign in a full-scale activated sludge wastewater treatment plant (WWTP). Our results suggest that the sorption...... deteriorate; thereby hindering the effluent quality of secondary treatment step, and thereby increasing the XOM mass load on the tertiary treatment step. Besides the impact of different redox conditions, divalent iron-salt dosing used for enhanced phosphorus removal and pH have been identified as potential...

  2. Use of biomarkers to evaluate the ecological risk of xenobiotics associated with agriculture.

    Science.gov (United States)

    Lima, Liana Bezerra Dias de; Morais, Paula Benevides de; Andrade, Ricardo Lopes Tortorela de; Mattos, Luciana Vieira; Moron, Sandro Estevan

    2018-06-01

    This research aimed to evaluate the ecological risk of xenobiotics associated with agricultural activities by determining metal contents and biomarker responses using tucunaré (Cichla sp.) as a bioindicator. The work was conducted in the southwest region of the state of Tocantins, in the cities of Lagoa da Confusão and Pium. Water samples and specimens of Cichla sp. were collected in the Javaés and Formoso Rivers at three collection points (A, B and C). The concentrations of Cd, Pb, Cu, Cr, Mn, Ni and Zn in water and fish were analyzed. In fish, genotoxic, biochemical (glucose serum levels, AST (aspartate aminotransferase) and ALT (alanine aminotransferase) and histological (gills and liver) biomarkers were assessed. In the water, the Cr and Mn concentrations at the three collection points exceeded the values for Class 1 rivers. In the muscle, Cr was above the maximum limit allowed for human consumption at the three collection points, although the values at Points B and C were not significantly different from that at Point A (p > 0.05). At the three collection points, the micronucleus test revealed a low frequency of micronuclei. Significant hyperglycemia and a decrease in the AST activity of the fish collected at Point C was observed. In the gills, the most frequent alterations were at Stages I and II, which indicated mild to moderate damage, and epithelial detachment was the most frequent variation. In the liver tissue, the most frequently observed histological changes were at Stages I and II and included cytoplasmic vacuolization, nuclear hypertrophy, dilated sinusoids and bile stagnation. The integrated evaluation of these biomarkers indicated that fish collected from areas with intense agricultural activities presented adaptive responses that were likely caused by the availability and bioaccumulation of certain xenobiotics in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Importance of Unattached Bacteria and Bacteria Attached to Sediment in Determining Potentials for Degradation of Xenobiotic Organic Contaminants in an Aerobic Aquifer

    DEFF Research Database (Denmark)

    Nielsen, Per Henning; Albrechtsen, Hans-Jørgen; Christensen, Thomas Højlund

    1992-01-01

    The bacterial abundance, distribution, and degradation potential (in terms of degradation versus lack of degradation) for four xenobiotic compounds in an aerobic aquifer sediment have been examined in laboratory and field experiments. The xenobiotic compounds studied were benzene, toluene, o......-xylene, and naphthalene (all at concentrations of approximately 120 pg/liter). The aerobic degradation experiments ran for approximately 90 days at 10°C, which corresponded to the groundwater temperature. At the end of the experiment, the major part of the microbial biomass, quantified as acridine orange direct counts......, was attached to the groundwater sediment (18 x 106 to 25 x 106 cells per g [dry weight]), and only a minor part was unattached in the groundwater (0.6 x 106 to 5.5 x 106 cells per ml). Experiments involving aquifer sediment suspensions showed identical degradation potentials in the laboratory and in the field...

  4. Defense Human Resources Activity > PERSEREC

    Science.gov (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  5. Rb and p53 Liver Functions Are Essential for Xenobiotic Metabolism and Tumor Suppression.

    Directory of Open Access Journals (Sweden)

    Sathidpak Nantasanti

    Full Text Available The tumor suppressors Retinoblastoma (Rb and p53 are frequently inactivated in liver diseases, such as hepatocellular carcinomas (HCC or infections with Hepatitis B or C viruses. Here, we discovered a novel role for Rb and p53 in xenobiotic metabolism, which represent a key function of the liver for metabolizing therapeutic drugs or toxins. We demonstrate that Rb and p53 cooperate to metabolize the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC. DDC is metabolized mainly by cytochrome P450 (Cyp3a enzymes resulting in inhibition of heme synthesis and accumulation of protoporphyrin, an intermediate of heme pathway. Protoporphyrin accumulation causes bile injury and ductular reaction. We show that loss of Rb and p53 resulted in reduced Cyp3a expression decreased accumulation of protoporphyrin and consequently less ductular reaction in livers of mice fed with DDC for 3 weeks. These findings provide strong evidence that synergistic functions of Rb and p53 are essential for metabolism of DDC. Because Rb and p53 functions are frequently disabled in liver diseases, our results suggest that liver patients might have altered ability to remove toxins or properly metabolize therapeutic drugs. Strikingly the reduced biliary injury towards the oxidative stress inducer DCC was accompanied by enhanced hepatocellular injury and formation of HCCs in Rb and p53 deficient livers. The increase in hepatocellular injury might be related to reduce protoporphyrin accumulation, because protoporphrin is well known for its anti-oxidative activity. Furthermore our results indicate that Rb and p53 not only function as tumor suppressors in response to carcinogenic injury, but also in response to non-carcinogenic injury such as DDC.

  6. Investigation of runoff generation from anthropogenic sources with dissolved xenobiotics

    Science.gov (United States)

    Krein, A.; Pailler, J.; Guignard, C.; Iffly, J.; Pfister, L.; Hoffmann, L.

    2009-04-01

    In the experimental Mess basin (35 km2, Luxembourg) dissolved xenobiotics in surface water are used to study the influences of anthropogenic sources like separated sewer systems on runoff generation. Emerging contaminants like pharmaceuticals are of growing interest because of their use in large quantities in human and veterinary medicine. The amounts reaching surface waters depend on rainfall patterns, hydraulic conditions, consumption, metabolism, degradation, and disposal. The behaviour of endocrine disruptors including pharmaceuticals in the aquatic environment is widely unknown. The twelve molecules analyzed belong to three families: the estrogens, the antibiotics (sulfonamides, tetracyclines), and the painkillers (ibuprofen, diclofenac). Xenobiotics can be used as potential environmental tracers for untreated sewerage. Our results show that the concentrations are highly variable during flood events. The highest concentrations are reached in the first flush period, mainly during the rising limb of the flood hydrographs. As a result of the kinematic wave effect the concentration peak occurs in some cases a few hours after the discharge maximum. In floodwater (eleven floods, 66 samples) the highest concentrations were measured for ibuprofen (g/l range), estrone, and diclofenac (all ng/l range). From the tetracycline group, essentially tetracycline itself is of relevance, while the sulfonamides are mainly represented by sulfamethoxazole (all in ng/l range). In the Mess River the pharmaceuticals fluxes during flood events proved to be influenced by hydrological conditions. Different pharmaceuticals showed their concentration peaks during different times of a flood event. An example is the estrone peak that - during summer flash floods - often occurred one to two hours prior to the largest concentrations of the painkillers. This suggests for more sources than the sole storm drainage through the spillway of the single sewage water treatment plant, different

  7. 76 FR 28757 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-05-18

    ... DEPARTMENT OF DEFENSE Office of the Secretary [DOCKET ID DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Notice of Availability (NOA) of Revised...

  8. 76 FR 53119 - Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense...

    Science.gov (United States)

    2011-08-25

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Docket ID: DOD-2011-OS-0055] Defense Logistics Agency Revised Regulation 1000.22, Environmental Considerations in Defense Logistics Agency Actions AGENCY: Defense Logistics Agency, Department of Defense. ACTION: Comment Addressed on Notice of...

  9. 75 FR 76423 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of Defense. ACTION: Notice of Closed Meeting. SUMMARY: Pursuant to the...

  10. 76 FR 28960 - Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting

    Science.gov (United States)

    2011-05-19

    ... DEPARTMENT OF DEFENSE Office of the Secretary Defense Intelligence Agency National Defense Intelligence College Board of Visitors Closed Meeting AGENCY: National Defense Intelligence College, Defense Intelligence Agency, Department of Defense. ACTION: Notice of Closed Meeting. SUMMARY: Pursuant to the...

  11. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Harmit S. Ranhotra

    2016-07-01

    Full Text Available The molecular basis for the regulation of the intestinal barrier is a very fertile research area. A growing body of knowledge supports the targeting of various components of intestinal barrier function as means to treat a variety of diseases, including the inflammatory bowel diseases. Herein, we will summarize the current state of knowledge of key xenobiotic receptor regulators of barrier function, highlighting recent advances, such that the field and its future are succinctly reviewed. We posit that these receptors confer an additional dimension of host-microbe interaction in the gut, by sensing and responding to metabolites released from the symbiotic microbiota, in innate immunity and also in host drug metabolism. The scientific evidence for involvement of the receptors and its molecular basis for the control of barrier function and innate immunity regulation would serve as a rationale towards development of non-toxic probes and ligands as drugs.

  12. Hybrid quadrupole-orbitrap mass spectrometry analysis with accurate-mass database and parallel reaction monitoring for high-throughput screening and quantification of multi-xenobiotics in honey.

    Science.gov (United States)

    Li, Yi; Zhang, Jinzhen; Jin, Yue; Wang, Lin; Zhao, Wen; Zhang, Wenwen; Zhai, Lifei; Zhang, Yaping; Zhang, Yongxin; Zhou, Jinhui

    2016-01-15

    This study reports a rapid, automated screening and quantification method for the determination of multi-xenobiotic residues in honey using ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry (UHPLC-Q-Orbitrap) with a user-built accurate-mass database plus parallel reaction monitoring (PRM). The database contains multi-xenobiotic information including formulas, adduct types, theoretical exact mass and retention time, characteristic fragment ions, ion ratios, and mass accuracies. A simple sample preparation method was developed to reduce xenobiotic loss in the honey samples. The screening method was validated based on retention time deviation, mass accuracy via full scan-data-dependent MS/MS (full scan-ddMS2), multi-isotope ratio, characteristic ion ratio, sensitivity, and positive/negative switching performance between the spiked sample and corresponding standard solution. The quantification method based on the PRM mode is a promising new quantitative tool which we validated in terms of selectivity, linearity, recovery (accuracy), repeatability (precision), decision limit (CCα), detection capability (CCβ), matrix effects, and carry-over. The optimized methods proposed in this study enable the automated screening and quantification of 157 compounds in less than 15 min in honey. The results of this study, as they represent a convenient protocol for large-scale screening and quantification, also provide a research approach for analysis of various contaminants in other matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Quantitative cytochemical analysis of glucose-6-phosphate dehydrogenase activity in living isolated hepatocytes of European flounder for rapid analysis of xenobiotic effects

    NARCIS (Netherlands)

    Winzer, K.; van Noorden, C. J.; Köhler, A.

    2001-01-01

    There is a great need for rapid but reliable assays to determine quantitatively effects of xenobiotics on biological systems in environmental research. Hepatocytes of European flounder are sensitive to low-dose toxic stress. Glucose-6-phosphate dehydrogenase (G6PDH) is the major source of NADPH in

  14. Transforming Defense

    National Research Council Canada - National Science Library

    Lamb, Christopher J; Bunn, M. E; Lutes, Charles; Cavoli, Christopher

    2005-01-01

    .... Despite the resources and attention consumed by the war on terror, and recent decisions by the White House to curtail the growth of defense spending, the senior leadership of the Department of Defense (DoD...

  15. Home - Defense Technology Security Administration

    Science.gov (United States)

    by @dtsamil Defense Technology Security Administration Mission, Culture, and History Executive Official seal of Defense Technology Security Administration Official seal of Defense Technology Security Administration OFFICE of the SECRETARY of DEFENSE Defense Technology Security Administration

  16. Optimizing Active Cyber Defense

    OpenAIRE

    Lu, Wenlian; Xu, Shouhuai; Yi, Xinlei

    2016-01-01

    Active cyber defense is one important defensive method for combating cyber attacks. Unlike traditional defensive methods such as firewall-based filtering and anti-malware tools, active cyber defense is based on spreading "white" or "benign" worms to combat against the attackers' malwares (i.e., malicious worms) that also spread over the network. In this paper, we initiate the study of {\\em optimal} active cyber defense in the setting of strategic attackers and/or strategic defenders. Specific...

  17. Physics of a ballistic missile defense - The chemical laser boost-phase defense

    Science.gov (United States)

    Grabbe, Crockett L.

    1988-01-01

    The basic physics involved in proposals to use a chemical laser based on satellites for a boost-phase defense are investigated. After a brief consideration of simple physical conditions for the defense, a calculation of an equation for the number of satellites needed for the defense is made along with some typical values of this for possible future conditions for the defense. Basic energy and power requirements for the defense are determined. A sumary is made of probable minimum conditions that must be achieved for laser power, targeting accuracy, number of satellites, and total sources for power needed.

  18. Investment in defense and cost of predator-induced defense along a resource gradient

    DEFF Research Database (Denmark)

    Steiner, Uli

    2007-01-01

    An organism's investment in different traits to reduce predation is determined by the fitness benefit of the defense relative to the fitness costs associated with the allocation of time and resources to the defense. Inherent tradeoffs in time and resource allocation should result in differential...... investment in defense along a resource gradient, but competing models predict different patterns of investment. There are currently insufficient empirical data on changes in investment in defensive traits or their costs along resource gradients to differentiate between the competing allocation models....... In this study, I exposed tadpoles to caged predators along a resource gradient in order to estimate investment in defense and costs of defense by assessing predator-induced plasticity. Induced defenses included increased tail depth, reduced feeding, and reduced swimming activity; costs associated...

  19. Unfolding Green Defense

    DEFF Research Database (Denmark)

    Larsen, Kristian Knus

    2015-01-01

    In recent years, many states have developed and implemented green solutions for defense. Building on these initiatives NATO formulated the NATO Green Defence Framework in 2014. The framework provides a broad basis for cooperation within the Alliance on green solutions for defense. This report aims...... to inform and support the further development of green solutions by unfolding how green technologies and green strategies have been developed and used to handle current security challenges. The report, initially, focuses on the security challenges that are being linked to green defense, namely fuel...... consumption in military operations, defense expenditure, energy security, and global climate change. The report then proceeds to introduce the NATO Green Defence Framework before exploring specific current uses of green technologies and green strategies for defense. The report concludes that a number...

  20. Induction of defensive enzymes (isozymes) during defense against ...

    African Journals Online (AJOL)

    user

    2012-09-06

    Sep 6, 2012 ... defense against two different fungal pathogens in pear calli ... study the biochemical changes in relation to plant defense ... relatively easy to manipulate by empirical means, allowing for a ... earlier phase, and the degree of rot was significantly ..... resistance of fruit, and they play an important role in the.

  1. Morphological and Cellular Features of Innate Immune Reaction in Helicobacter pylori Gastritis: A Brief Review

    Directory of Open Access Journals (Sweden)

    Antonio Ieni

    2016-01-01

    Full Text Available Innate and adaptive immunity are both involved in acute and chronic inflammatory processes. The main cellular players in the innate immune system are macrophages, mast cells, dendritic cells, neutrophils, eosinophils, and natural killer (NK, which offer antigen-independent defense against infection. Helicobacter pylori (H. pylori infection presents peculiar characteristics in gastric mucosa infrequently occurring in other organs; its gastric colonization determines a causal role in both gastric carcinomas and mucosa-associated lymphoid tissue lymphoma. In contrast, an active role for Epstein-Barr virus (EBV has been identified only in 9% of gastric carcinomas. The aim of the present review is to discuss the role of cellular morphological effectors in innate immunity during H. pylori infection and gastric carcinogenesis.

  2. Assaying Cellular Viability Using the Neutral Red Uptake Assay.

    Science.gov (United States)

    Ates, Gamze; Vanhaecke, Tamara; Rogiers, Vera; Rodrigues, Robim M

    2017-01-01

    The neutral red uptake assay is a cell viability assay that allows in vitro quantification of xenobiotic-induced cytotoxicity. The assay relies on the ability of living cells to incorporate and bind neutral red, a weak cationic dye, in lysosomes. As such, cytotoxicity is expressed as a concentration-dependent reduction of the uptake of neutral red after exposure to the xenobiotic under investigation. The neutral red uptake assay is mainly used for hazard assessment in in vitro toxicology applications. This method has also been introduced in regulatory recommendations as part of 3T3-NRU-phototoxicity-assay, which was regulatory accepted in all EU member states in 2000 and in the OECD member states in 2004 as a test guideline (TG 432). The present protocol describes the neutral red uptake assay using the human hepatoma cell line HepG2, which is often employed as an alternative in vitro model for human hepatocytes. As an example, the cytotoxicity of acetaminophen and acetyl salicylic acid is assessed.

  3. Multidrug and toxin extrusion proteins mediate cellular transport of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hong; Guo, Dong; Obianom, Obinna N. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Su, Tong [Department of Oral Maxillofacial Surgery, the First Affiliated Hospital, Xiangya Medical School, Central South University, Hunan 410007 (China); Polli, James E. [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States); Shu, Yan, E-mail: yshu@rx.umaryland.edu [Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, MD (United States)

    2017-01-01

    Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. As compared to the extensive research in Cd tissue accumulation, little was known about the elimination of Cd, particularly its toxic form, Cd ion (Cd{sup 2+}). In this study, we aimed to examine whether Cd{sup 2+} is a substrate of multidrug and toxin extrusion proteins (MATEs) that are important in renal xenobiotic elimination. HEK-293 cells overexpressing the human MATE1 (HEK-hMATE1), human MATE2-K (HEK-hMATE2-K) and mouse Mate1 (HEK-mMate1) were used to study the cellular transport and toxicity of Cd{sup 2+}. The cells overexpressing MATEs showed a 2–4 fold increase of Cd{sup 2+} uptake that could be blocked by the MATE inhibitor cimetidine. A saturable transport profile was observed with the Michaelis-Menten constant (K{sub m}) of 130 ± 15.8 μM for HEK-hMATE1; 139 ± 21.3 μM for HEK-hMATE2-K; and 88.7 ± 13.5 μM for HEK-mMate1, respectively. Cd{sup 2+} could inhibit the uptake of metformin, a substrate of MATE transporters, with the half maximal inhibitory concentration (IC{sub 50}) of 97.5 ± 6.0 μM, 20.2 ± 2.6 μM, and 49.9 ± 6.9 μM in HEK-hMATE1, HEK-hMATE2-K, and HEK-mMate1 cells, respectively. In addition, hMATE1 could transport preloaded Cd{sup 2+} out of the HEK-hMATE1 cells, thus resulting in a significant decrease of Cd{sup 2+}-induced cytotoxicity. The present study has provided the first evidence supporting that MATEs transport Cd{sup 2+} and may function as cellular elimination machinery in Cd intoxication. - Highlights: • Cadmium is an environmentally prevalent toxicant. • Little was known regarding the elimination and detoxification of cadmium. • Cadmium ion is here demonstrated as a substrate of MATE transporters. • MATEs may function as cellular elimination machinery in cadmium detoxification.

  4. Defense.gov Special Report: Defense Officials Release Operational Energy

    Science.gov (United States)

    , DOD Operational Energy Strategy DOD's Operational Energy Strategy will guide the Defense Department to operations are among the goals of the Defense Department's operational energy strategy, a senior Pentagon operational energy footprint, experts in solar power, microgrids and "smart" generators recently

  5. 75 FR 52732 - Renewal of Department of Defense Federal Advisory Committee; Missile Defense Advisory Committee

    Science.gov (United States)

    2010-08-27

    ... Committee; Missile Defense Advisory Committee AGENCY: Department of Defense (DoD). ACTION: Renewal of..., the Department of Defense gives notice that it is renewing the charter for the Missile Defense... Director, Missile Defense Agency, independent advice and recommendations on all matters relating to missile...

  6. Phase I to II cross-induction of xenobiotic metabolizing enzymes: A feedforward control mechanism for potential hormetic responses

    International Nuclear Information System (INIS)

    Zhang Qiang; Pi Jingbo; Woods, Courtney G.; Andersen, Melvin E.

    2009-01-01

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  7. Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

    Science.gov (United States)

    Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

    2009-06-15

    Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a

  8. Oxidation and adduct formation of xenobiotics in a microfluidic electrochemical cell with boron doped diamond electrodes and an integrated passive gradient rotation mixer

    NARCIS (Netherlands)

    van den Brink, Floris Teunis Gerardus; Wigger, Tina; Ma, Liwei; Odijk, Mathieu; Olthuis, Wouter; Karst, U.; van den Berg, Albert

    2016-01-01

    Reactive xenobiotic metabolites and their adduct formation with biomolecules such as proteins are important to study as they can be detrimental to human health. Here, we present a microfluidic electrochemical cell with integrated micromixer to study phase I and phase II metabolism as well as protein

  9. Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation

    National Research Council Canada - National Science Library

    Potts, Anthony W

    2007-01-01

    ...% of defense product sales annually. Defense consolidation has diminished the flexibility required for surge capacity, diminished competitive innovations in products, and reduced competitive pricing based on multiple sources for products...

  10. Ethanol cellular defense induce unfolded protein response in yeast

    Directory of Open Access Journals (Sweden)

    Elisabet eNavarro-Tapia

    2016-02-01

    Full Text Available Ethanol is a valuable industrial product and a common metabolite used by many cell types. However, this molecule produces high levels of cytotoxicity affecting cellular performance at several levels. In the presence of ethanol, cells must adjust some of their components, such as the membrane lipids to maintain homeostasis. In the case of microorganism as Saccharomyces cerevisiae, ethanol is one of the principal products of their metabolism and is the main stress factor during fermentation. Although many efforts have been made, mechanisms of ethanol tolerance are not fully understood and very little evidence is available to date for specific signaling by ethanol in the cell. This work studied two Saccharomyces cerevisiae strains, CECT10094 and Temohaya-MI26, isolated from flor wine and agave fermentation (a traditional fermentation from Mexico respectively, which differ in ethanol tolerance, in order to understand the molecular mechanisms underlying the ethanol stress response and the reasons for different ethanol tolerance. The transcriptome was analyzed after ethanol stress and, among others, an increased activation of genes related with the unfolded protein response (UPR and its transcription factor, Hac1p, was observed in the tolerant strain CECT10094. We observed that this strain also resist more UPR agents than Temohaya-MI26 and the UPR-ethanol stress correlation was corroborated observing growth of 15 more strains and discarding UPR correlation with other stresses as thermal or oxidative stress. Furthermore, higher activation of UPR pathway in the tolerant strain CECT10094 was observed using a UPR mCherry reporter. Finally, we observed UPR activation in response to ethanol stress in other S. cerevisiae ethanol tolerant strains as the wine strains T73 and EC1118. This work demonstrates that the UPR pathway is activated under ethanol stress occurring in a standard fermentation and links this response to an enhanced ethanol tolerance. Thus

  11. Cardiac biomarkers as sensitive tools to evaluate the impact of xenobiotics on amphibians: the effects of anionic surfactant linear alkylbenzene sulfonate (LAS).

    Science.gov (United States)

    Jones-Costa, Monica; Franco-Belussi, Lilian; Vidal, Felipe Augusto Pinto; Gongora, Nathália Penteado; Castanho, Luciano Mendes; Dos Santos Carvalho, Cleoni; Silva-Zacarin, Elaine Cristina Mathias; Abdalla, Fabio Camargo; Duarte, Iolanda Cristina Silveira; Oliveira, Classius De; de Oliveira, Cristiane Ronchi; Salla, Raquel Fernanda

    2018-04-30

    Amphibian populations have been experiencing a drastic decline worldwide. Aquatic contaminants are among the main factors responsible for this decline, especially in the aquatic environment. The linear alkylbenzene sulfonate (LAS) is of particular concern, since it represents 84% of the anionic surfactants' trade. In Brazil, the maximal LAS concentration allowed in fresh waters is 0.5mgL -1 , but its potential harmful effects in amphibians remain unknown. Therefore, this study aimed to analyze the effects of a sublethal concentration of LAS (0.5mgL -1 ) for 96h on sensitive cardiac biomarkers of bullfrog tadpoles, Lithobates catesbeianus (Shaw, 1802). For this, we measured the activity level (AL - % of animals), in situ heart rate (f H - bpm), relative ventricular mass (RVM - % of body mass), in vitro myocardial contractility and cardiac histology of the ventricles. Tadpoles' AL and f H decreased in LAS group. In contrast, the RVM increased, as a result of a hypertrophy of the myocardium, which was corroborated by the enlargement of the nuclear measures and the increase of myocytes' diameters. These cellular effects resulted in an elevation of the in vitro contractile force of ventricle strips. Acceleration in the contraction (TPT - ms) also occurred, although no alterations in the time to relaxation (THR -ms) were observed. Therefore, it can be concluded that even when exposed to an environmentally safe concentration, this surfactant promotes several alterations in the cardiac function of bullfrog tadpoles that can impair their development, making them more susceptible to predators and less competitive in terms of reproduction success. Thus, LAS concentrations that are considered safe by Brazilian by regulatory agencies must be revised in order to minimize a drastic impact over amphibian populations. This study demonstrates the relevance of employing cardiac biomarkers at different levels (e.g., morphological, physiological and cellular) to evaluate effects of

  12. Marine Invertebrate Xenobiotic-Activated Nuclear Receptors: Their Application as Sensor Elements in High-Throughput Bioassays for Marine Bioactive Compounds

    Directory of Open Access Journals (Sweden)

    Ingrid Richter

    2014-11-01

    Full Text Available Developing high-throughput assays to screen marine extracts for bioactive compounds presents both conceptual and technical challenges. One major challenge is to develop assays that have well-grounded ecological and evolutionary rationales. In this review we propose that a specific group of ligand-activated transcription factors are particularly well-suited to act as sensors in such bioassays. More specifically, xenobiotic-activated nuclear receptors (XANRs regulate transcription of genes involved in xenobiotic detoxification. XANR ligand-binding domains (LBDs may adaptively evolve to bind those bioactive, and potentially toxic, compounds to which organisms are normally exposed to through their specific diets. A brief overview of the function and taxonomic distribution of both vertebrate and invertebrate XANRs is first provided. Proof-of-concept experiments are then described which confirm that a filter-feeding marine invertebrate XANR LBD is activated by marine bioactive compounds. We speculate that increasing access to marine invertebrate genome sequence data, in combination with the expression of functional recombinant marine invertebrate XANR LBDs, will facilitate the generation of high-throughput bioassays/biosensors of widely differing specificities, but all based on activation of XANR LBDs. Such assays may find application in screening marine extracts for bioactive compounds that could act as drug lead compounds.

  13. Strategic Defense Initiative: Splendid Defense or Pipe Dream? Headline Series No. 275.

    Science.gov (United States)

    Armstrong, Scott; Grier, Peter

    This pamphlet presents a discussion of the various components of President Reagan's Strategic Defense Initiative (SDI) including the problem of pulling together various new technologies into an effective defensive system and the politics of the so-called "star wars" system. An important part of the defense initiative is the…

  14. Molecular and cellular mechanisms of cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Waisberg, Michael; Joseph, Pius; Hale, Beverley; Beyersmann, Detmar

    2003-01-01

    Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd 2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate

  15. Prevalence of xenobiotic substances in first-trimester blood samples from Danish pregnant women: a cross-sectional study.

    Science.gov (United States)

    Aagaard, Sissel Kramer; Larsen, Agnete; Andreasen, Mette Findal; Lesnikova, Iana; Telving, Rasmus; Vestergaard, Anna Louise; Tørring, Niels; Uldbjerg, Niels; Bor, Pinar

    2018-03-03

    The aim of this study was to investigate the prevalence of xenobiotic substances, such as caffeine, nicotine and illicit drugs (eg, cannabis and cocaine), in blood samples from first-trimester Danish pregnant women unaware of the screening. A cross - sectional study examined 436 anonymised residual blood samples obtained during 2014 as part of the nationwide prenatal first-trimester screening programme. The samples were analysed by ultra performance liquid chromatography with high-resolution time-of-flight mass spectrometry. An antenatal clinic in a Danish city with 62 000 inhabitants, where >95% of pregnant women joined the screening programme. The prevalence and patterns of caffeine, nicotine, medication and illicit drug intake during the first trimester of pregnancy. The prevalence of prescription and over-the-counter drug detection was 17.9%, including acetaminophen (8.9%) and antidepressants (3.0%), of which citalopram (0.9%) was the most frequent. The prevalence of illegal drugs, indicators of smoking (nicotine/cotinine) and caffeine was 0.9%, 9.9%, and 76.4%, respectively. Only 17.4% of women had no substance identified in their sample. This study emphasises the need for further translational studies investigating lifestyle habits during pregnancy, as well as the underlying molecular mechanisms through which xenobiotic substances may affect placental function and fetal development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Financial Reporting Procedures for Defense Distribution Depots - Defense Logistics Agency Business Area of the Defense Business Operations Fund

    National Research Council Canada - National Science Library

    Young, Shelton

    1994-01-01

    In our audit of the FY 1993 Financial Statements for the Distribution Depots--Defense Logistics Agency Business Mea of the Defense Business Operations Fund, we evaluated procedures and controls used...

  17. Defense styles of pedophilic offenders.

    Science.gov (United States)

    Drapeau, Martin; Beretta, Véronique; de Roten, Yves; Koerner, Annett; Despland, Jean-Nicolas

    2008-04-01

    This pilot study investigated the defense styles of pedophile sexual offenders. Interviews with 20 pedophiles and 20 controls were scored using the Defense Mechanisms Rating Scales. Results showed that pedophiles had a significantly lower overall defensive functioning score than the controls. Pedophiles used significantly fewer obsessional-level defenses but more major image-distorting and action-level defenses. Results also suggested differences in the prevalence of individual defenses where pedophiles used more dissociation, displacement, denial, autistic fantasy, splitting of object, projective identification, acting out, and passive aggressive behavior but less intellectualization and rationalization.

  18. CHANGING METABOLIC FUNCTIONS IN EXPERIMENTAL ANIMALS AFTER INTRODUCTION OF THE XENOBIOTIC, IMMUNOTROPIC DRUG AND PROBIOTIC

    Directory of Open Access Journals (Sweden)

    Zvyagintseva O.V.

    2015-05-01

    Saccharomyces cerevisiae. The peripheral blood leukocytes were cultured according to the method of Hereford in medium 199 with the addition of fetal calf serum in the absence and in the presence of T-cell mitogen – phytohemagglutinin. Results and discussion. In all studied groups (introduction of the xenobiotic, "Fungidol", probiotic experimental animals revealed a significant increase in the concentrations of ceruloplasmin and haptoglobin on the average in 1,5 times in comparison with the control, indicating the development of the inflammatory process after the toxic action of copper sulphate. During administration of sulphate of copper, the experimental animals showed a reduction in the index of completion of phagocytosis, indicating a failure of the process of endocytosis of bacterial antigens and reduced stimulation index due to the low activity of NADPoxidase system of phagocytes. The introduction of xenobiotic animals was increased 1,2 times compared with the control (23,33±1,38 % the number of transformed cells in the background of mitogenic inducer of cell proliferation. The proliferative activity of hemolytic after the joint action of the xenobiotic and immunotropic drug in cell culture with the mitogen was the highest and exceeded 1,5 times control (23,33±1,38%. After the introduction of copper sulfate and probiotic proliferative activity of hemolytic was also significantly higher spontaneous. Introduction biologic response modifier substance to a greater extent than probiotics stimulate a protective immune processes aimed at combating the negative effect of the xenobiotic. Conclusion. Thus, the introduction of copper sulfate launches in animals a cascade of reactions aimed at the disruption of homeostasis. It is a violation of various physiological processes of digestion, respiration, cell differentiation, water-salt metabolism, metabolism of carbohydrates, proteins, lipids, detoxification of exogenous substrates and metabolites, production of biologically active

  19. Strategic Framework for the Defense Acquisition System Understanding Defense Consolidation

    National Research Council Canada - National Science Library

    Potts, Anthony W

    2007-01-01

    The 1993 policy to promote the consolidation of the United States defense industry began a series of acquisitions and mergers that went beyond the intent of the policy and left the Department of Defense (DoD...

  20. Draft Genome Sequence of Paenibacillus sp. Strain DMB20, Isolated from Alang Ship-Breaking Yard, Which Harbors Genes for Xenobiotic Degradation.

    Science.gov (United States)

    Shah, Binal; Jain, Kunal; Patel, Namrata; Pandit, Ramesh; Patel, Anand; Joshi, Chaitanya G; Madamwar, Datta

    2015-06-11

    Paenibacillus sp. strain DMB20, in cometabolism with other Proteobacteria and Firmicutes, exhibits azoreduction of textile dyes. Here, we report the draft genome sequence of this bacterium, consisting of 6,647,181 bp with 7,668 coding sequences (CDSs). The data presented highlight multiple sets of functional genes associated with xenobiotic compound degradation. Copyright © 2015 Shah et al.

  1. Recognizing Plant Defense Priming

    NARCIS (Netherlands)

    Martinez-Medina, Ainhoa; Flors, Victor; Heil, Martin; Mauch-Mani, Brigitte; Pieterse, Corné M J|info:eu-repo/dai/nl/113115113; Pozo, Maria J; Ton, Jurriaan; van Dam, Nicole M; Conrath, Uwe

    2016-01-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in

  2. Recognizing plant defense priming

    NARCIS (Netherlands)

    Martinez-Medina, A.; Flors, V.; Heil, M.; Mauch-Mani, B.; Pieterse, C.M.J.; Pozo, M.J.; Ton, J.; Van Dam, N.M.; Conrath, U.

    2016-01-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in

  3. Plant defense against insect herbivores

    DEFF Research Database (Denmark)

    Fürstenberg-Hägg, Joel; Zagrobelny, Mika; Bak, Søren

    2013-01-01

    , defense compounds. These bioactive specialized plant defense compounds may repel or intoxicate insects, while defense proteins often interfere with their digestion. Volatiles are released upon herbivory to repel herbivores, attract predators or for communication between leaves or plants, and to induce......Plants have been interacting with insects for several hundred million years, leading to complex defense approaches against various insect feeding strategies. Some defenses are constitutive while others are induced, although the insecticidal defense compound or protein classes are often similar...... defense responses. Plants also apply morphological features like waxes, trichomes and latices to make the feeding more difficult for the insects. Extrafloral nectar, food bodies and nesting or refuge sites are produced to accommodate and feed the predators of the herbivores. Meanwhile, herbivorous insects...

  4. Other Defense Organizations and Defense Finance and Accounting Service Controls Over High-Risk Transactions Were Not Effective

    Science.gov (United States)

    2016-03-28

    Defense Organizations and Defense Finance and Accounting Service Controls Over High-Risk Transactions Were Not Effective M A R C H 2 8 , 2 0 1 6...Defense Organizations and Defense Finance and Accounting Service Controls Over High-Risk Transactions Were Not Effective Visit us at www.dodig.mil... FINANCE AND ACCOUNTING SERVICE DIRECTOR, DEFENSE HEALTH AGENCY SUBJECT: Other Defense Organizations and Defense Finance and Accounting Service

  5. DEFENSE PROGRAMS RISK MANAGEMENT FRAMEWORK

    Directory of Open Access Journals (Sweden)

    Constantin PREDA

    2012-01-01

    Full Text Available For the past years defense programs have faced delays in delivering defense capabilities and budget overruns. Stakeholders are looking for ways to improve program management and the decision making process given the very fluid and uncertain economic and political environment. Consequently, they have increasingly resorted to risk management as the main management tool for achieving defense programs objectives and for delivering the defense capabilities strongly needed for the soldiers on the ground on time and within limited defense budgets. Following a risk management based decision-making approach the stakeholders are expected not only to protect program objectives against a wide range of risks but, at the same time, to take advantage of the opportunities to increase the likelihood of program success. The prerequisite for making risk management the main tool for achieving defense programs objectives is the design and implementation of a strong risk management framework as a foundation providing an efficient and effective application of the best risk management practices. The aim of this paper is to examine the risk management framework for defense programs based on the ISO 31000:2009 standard, best risk management practices and the defense programs’ needs and particularities. For the purposes of this article, the term of defense programs refers to joint defense programs.

  6. Silverleaf Whitefly Induces Salicylic Acid Defenses and Suppresses Effectual Jasmonic Acid Defenses1[W][OA

    Science.gov (United States)

    Zarate, Sonia I.; Kempema, Louisa A.; Walling, Linda L.

    2007-01-01

    The basal defenses important in curtailing the development of the phloem-feeding silverleaf whitefly (Bemisia tabaci type B; SLWF) on Arabidopsis (Arabidopsis thaliana) were investigated. Sentinel defense gene RNAs were monitored in SLWF-infested and control plants. Salicylic acid (SA)-responsive gene transcripts accumulated locally (PR1, BGL2, PR5, SID2, EDS5, PAD4) and systemically (PR1, BGL2, PR5) during SLWF nymph feeding. In contrast, jasmonic acid (JA)- and ethylene-dependent RNAs (PDF1.2, VSP1, HEL, THI2.1, FAD3, ERS1, ERF1) were repressed or not modulated in SLWF-infested leaves. To test for a role of SA and JA pathways in basal defense, SLWF development on mutant and transgenic lines that constitutively activate or impair defense pathways was determined. By monitoring the percentage of SLWF nymphs in each instar, we show that mutants that activate SA defenses (cim10) or impair JA defenses (coi1) accelerated SLWF nymphal development. Reciprocally, mutants that activate JA defenses (cev1) or impair SA defenses (npr1, NahG) slowed SLWF nymphal development. Furthermore, when npr1 plants, which do not activate downstream SA defenses, were treated with methyl jasmonate, a dramatic delay in nymph development was observed. Collectively, these results showed that SLWF-repressed, JA-regulated defenses were associated with basal defense to the SLWF. PMID:17189328

  7. Rethinking Defensive Information Warfare

    National Research Council Canada - National Science Library

    French, Geoffrey S

    2004-01-01

    .... This paper examines defensive tactics and strategies from the German defense in depth that emerged from World War I to the American Active Defense that developed in the Cold War and proposes a new mindset for DIW that draws on these operational concepts from military history.

  8. Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Ines eLassowskat

    2014-10-01

    Full Text Available Mitogen-activated protein kinases (MAPKs target a variety of protein substrates to regulate cellular signaling processes in eukaryotes. In plants, the number of identified MAPK substrates that control plant defense responses is still limited. Here, we generated transgenic Arabidopsis thaliana plants with an inducible system to simulate in vivo activation of two stress-activated MAPKs, MPK3 and MPK6. Metabolome analysis revealed that this artificial MPK3/6 activation (without any exposure to pathogens or other stresses is sufficient to drive the production of major defense-related metabolites, including various camalexin, indole glucosinolate and agmatine derivatives. An accompanying (phosphoproteome analysis led to detection of hundreds of potential phosphoproteins downstream of MPK3/6 activation. Besides known MAPK substrates, many candidates on this list possess typical MAPK-targeted phosphosites and in many cases, the corresponding phosphopeptides were detected by mass spectrometry. Notably, several of these putative phosphoproteins have been reported to be associated with the biosynthesis of antimicrobial defense substances (e.g. WRKY transcription factors and proteins encoded by the genes from the PEN pathway required for penetration resistance to filamentous pathogens. Thus, this work provides an inventory of candidate phosphoproteins, including putative direct MAPK substrates, for future analysis of MAPK-mediated defense control. (Proteomics data are available with the identifier PXD001252 via ProteomeXchange, http://proteomecentral.proteomexchange.org.

  9. 75 FR 65462 - Renewal of Department of Defense Federal Advisory Committee; Department of Defense Military...

    Science.gov (United States)

    2010-10-25

    ... Committee; Department of Defense Military Family Readiness Council AGENCY: Department of Defense (DoD... renewing the charter for the Department of Defense Military Family Readiness Council (hereafter referred to... requirements for the support of military family readiness by the Department of Defense; and (c) evaluate and...

  10. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals.

    Science.gov (United States)

    Prasad, Sahdeo; Gupta, Subash C; Tyagi, Amit K

    2017-02-28

    Extensive research over the past half a century indicates that reactive oxygen species (ROS) play an important role in cancer. Although low levels of ROS can be beneficial, excessive accumulation can promote cancer. One characteristic of cancer cells that distinguishes them from normal cells is their ability to produce increased numbers of ROS and their increased dependence on an antioxidant defense system. ROS are produced as a byproduct intracellularly by mitochondria and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs, xenobiotics, and radiation. ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to cellular transformation, inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic changes in genes, which is helpful in diagnosing diseases. This review considers the role of ROS in the various stages of cancer development. Finally, we provide evidence that nutraceuticals derived from Mother Nature are highly effective in eliminating cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. MicroRNA-Mediated Gene Silencing in Plant Defense and Viral Counter-Defense

    Directory of Open Access Journals (Sweden)

    Sheng-Rui Liu

    2017-09-01

    Full Text Available MicroRNAs (miRNAs are non-coding RNAs of approximately 20–24 nucleotides in length that serve as central regulators of eukaryotic gene expression by targeting mRNAs for cleavage or translational repression. In plants, miRNAs are associated with numerous regulatory pathways in growth and development processes, and defensive responses in plant–pathogen interactions. Recently, significant progress has been made in understanding miRNA-mediated gene silencing and how viruses counter this defense mechanism. Here, we summarize the current knowledge and recent advances in understanding the roles of miRNAs involved in the plant defense against viruses and viral counter-defense. We also document the application of miRNAs in plant antiviral defense. This review discusses the current understanding of the mechanisms of miRNA-mediated gene silencing and provides insights on the never-ending arms race between plants and viruses.

  12. Recognizing Plant Defense Priming.

    Science.gov (United States)

    Martinez-Medina, Ainhoa; Flors, Victor; Heil, Martin; Mauch-Mani, Brigitte; Pieterse, Corné M J; Pozo, Maria J; Ton, Jurriaan; van Dam, Nicole M; Conrath, Uwe

    2016-10-01

    Defense priming conditions diverse plant species for the superinduction of defense, often resulting in enhanced pest and disease resistance and abiotic stress tolerance. Here, we propose a guideline that might assist the plant research community in a consistent assessment of defense priming in plants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Combination of microautoradiography and fluorescence in situ hybridization for identification of microorganisms degrading xenobiotic contaminants.

    Science.gov (United States)

    Yang, Yanru; Zarda, Annatina; Zeyer, Josef

    2003-12-01

    One of the central topics in environmental bioremediation research is to identify microorganisms that are capable of degrading the contaminants of interest. Here we report application of combined microautoradiography (MAR) and fluorescence in situ hybridization (FISH). The method has previously been used in a number of systems; however, here we demonstrate its feasibility in studying the degradation of xenobiotic compounds. With a model system (coculture of Pseudomonas putida B2 and Sphingomonas stygia incubated with [14C] o-nitrophenol), combination of MAR and FISH was shown to be able to successfully identify the microorganisms degrading o-nitrophenol. Compared with the conventional techniques, MAR-FISH allows fast and accurate identification of the microorganisms involved in environmental contaminant degradation.

  14. Antipredator defenses predict diversification rates

    Science.gov (United States)

    Arbuckle, Kevin; Speed, Michael P.

    2015-01-01

    The “escape-and-radiate” hypothesis predicts that antipredator defenses facilitate adaptive radiations by enabling escape from constraints of predation, diversified habitat use, and subsequently speciation. Animals have evolved diverse strategies to reduce the direct costs of predation, including cryptic coloration and behavior, chemical defenses, mimicry, and advertisement of unprofitability (conspicuous warning coloration). Whereas the survival consequences of these alternative defenses for individuals are well-studied, little attention has been given to the macroevolutionary consequences of alternative forms of defense. Here we show, using amphibians as the first, to our knowledge, large-scale empirical test in animals, that there are important macroevolutionary consequences of alternative defenses. However, the escape-and-radiate hypothesis does not adequately describe them, due to its exclusive focus on speciation. We examined how rates of speciation and extinction vary across defensive traits throughout amphibians. Lineages that use chemical defenses show higher rates of speciation as predicted by escape-and-radiate but also show higher rates of extinction compared with those without chemical defense. The effect of chemical defense is a net reduction in diversification compared with lineages without chemical defense. In contrast, acquisition of conspicuous coloration (often used as warning signals or in mimicry) is associated with heightened speciation rates but unchanged extinction rates. We conclude that predictions based on the escape-and-radiate hypothesis must incorporate the effect of traits on both speciation and extinction, which is rarely considered in such studies. Our results also suggest that knowledge of defensive traits could have a bearing on the predictability of extinction, perhaps especially important in globally threatened taxa such as amphibians. PMID:26483488

  15. Planetary Defense

    Science.gov (United States)

    2016-05-01

    4 Abstract Planetary defense against asteroids should be a major concern for every government in the world . Millions of asteroids and...helps make Planetary Defense viable because defending the Earth against asteroids benefits from all the above technologies. So if our planet security...information about their physical characteristics so we can employ the right strategies. It is a crucial difference if asteroids are made up of metal

  16. Arabidopsis flower specific defense gene expression patterns affect resistance to pathogens

    KAUST Repository

    Ederli, Luisa

    2015-02-20

    We investigated whether the Arabidopsis flower evolved protective measures to increase reproductive success. Firstly, analyses of available transcriptome data show that the most highly expressed transcripts in the closed sepal (stage 12) are enriched in genes with roles in responses to chemical stimuli and cellular metabolic processes. At stage 15, there is enrichment in transcripts with a role in responses to biotic stimuli. Comparative analyses between the sepal and petal in the open flower mark an over-representation of transcripts with a role in responses to stress and catalytic activity. Secondly, the content of the biotic defense-associated phytohormone salicylic acid (SA) in sepals and petals is significantly higher than in leaves. To understand whether the high levels of stress responsive transcripts and the higher SA content affect defense, wild-type plants (Col-0) and transgenic plants defective in SA accumulation (nahG) were challenged with the biotrophic fungus Golovinomyces cichoracearum, the causal agent of powdery mildew, and the necrotrophic fungus Botrytis cinerea. NahG leaves were more sensitive than those of Col-0, suggesting that in leaves SA has a role in the defense against biotrophs. In contrast, sepals and petals of both genotypes were resistant to G. cichoracearum, indicating that in the flower, resistance to the biotrophic pathogen is not critically dependent on SA, but likely dependent on the up-regulation of stress-responsive genes. Since sepals and petals of both genotypes are equally susceptible to B. cinerea, we conclude that neither stress-response genes nor increased SA accumulation offers protection against the necrotrophic pathogen. These results are interpreted in the light of the distinctive role of the flower and we propose that in the early stages, the sepal may act as a chemical defense barrier of the developing reproductive structures against biotrophic pathogens.

  17. Ensuring a Strong U.S. Defense for the Future: The National Defense Panel Review of the 2014 Quadrennial Defense Review

    Science.gov (United States)

    2014-07-31

    territorial disputes with China. We note recent moves to station U.S. forces in Darwin , the plan to station a number of Littoral Combat Ships in Singapore...Under Secretary of Defense, Comptroller (C) Charles “Chuck” Hagel Secretary of Defense Mara Karlin Principal Director for Strategy, Policy (P...Support Staff to the Panel Charles Arnold George Sinks U.S. Government Liaison Officers Lori Abele Chief of Staff, Deputy Under Secretary of Defense

  18. Technologies for distributed defense

    Science.gov (United States)

    Seiders, Barbara; Rybka, Anthony

    2002-07-01

    For Americans, the nature of warfare changed on September 11, 2001. Our national security henceforth will require distributed defense. One extreme of distributed defense is represented by fully deployed military troops responding to a threat from a hostile nation state. At the other extreme is a country of 'citizen soldiers', with families and communities securing their common defense through heightened awareness, engagement as good neighbors, and local support of and cooperation with local law enforcement, emergency and health care providers. Technologies - for information exploitation, biological agent detection, health care surveillance, and security - will be critical to ensuring success in distributed defense.

  19. Decolorization of synthetic dyes and textile effluents by basidiomycetous fungi

    Digital Repository Service at National Institute of Oceanography (India)

    Diwaniyan, S.; Kharb, D.; Raghukumar, C.; Kuhad, R.C.

    of their ability to degrade xenobiotic compounds. Owing to extra- cellular non-specific free-radical-based ligninolytic system of WRF, they can completely eliminate a variety of xenobiotics, including synthetic dyes, giving rise to non-toxic compounds (Kuhad et al... and decolorization and ligninolytic enzymes activity was determined in the cell-free supernatant (CS). 2.5 Decolorization Assays The fungal biomass from each 250-ml Erlenmeyer flask was taken after respective incubation period. It was crushed into a paste...

  20. DEFENSE-ATTACK INTERACTION OVER OPTIMALLY DESIGNED DEFENSE SYSTEMS VIA GAMES AND RELIABILITY

    Directory of Open Access Journals (Sweden)

    Isis Didier Lins

    2014-05-01

    Full Text Available This paper analyzes defense systems taking into account the strategic interactions between two rational agents; one of them is interested in designing a defense system against purposeful attacks of the other. The interaction is characterized by a sequential game with perfect and complete information. Reliability plays a fundamental role in both defining agents' actions and in measuring performance of the defense system for which a series-parallel configuration is set up by the defender. The attacker, in turn, focuses on only one defense subsystem in order to maximize her efficiency in attacking. An algorithm involving backward induction is developed to determine the equilibrium paths of the game. Application examples are also provided.

  1. IFPA meeting 2015 workshop report III: nanomedicine applications and exosome biology, xenobiotics and endocrine disruptors and pregnancy, and lipid.

    Science.gov (United States)

    Albrecht, C; Caniggia, I; Clifton, V; Göhner, C; Harris, L; Hemmings, D; Jawerbaum, A; Johnstone, E; Jones, H; Keelan, J; Lewis, R; Mitchell, M; Murthi, P; Powell, T; Saffery, R; Smith, R; Vaillancourt, C; Wadsack, C; Salomon, C

    2016-12-01

    Workshops are an important part of the IFPA annual meeting, as they allow for discussion of specialized topics. At the IFPA meeting 2015 there were twelve themed workshops, three of which are summarized in this report. These workshops were related to various aspects of placental biology but collectively covered areas of pregnancy pathologies and placental metabolism: 1) nanomedicine applications and exosome biology; 2) xenobiotics and endocrine disruptors and pregnancy; 3) lipid mediators and placental function. Copyright © 2016. Published by Elsevier Ltd.

  2. Modelling the Fate of Xenobiotic Trace Chemicals via Wastewater Treatment and Agricultural Resource Reuse

    DEFF Research Database (Denmark)

    Polesel, Fabio

    the comprehension of XTC fate, and thus the predictive capabilities of fate models: (i) at process scale, with a focus on sorption and biological transformation of XTCs in biological treatment systems; (ii) in full-scale WWTPs, assessing the impact of retransformation and WWTP operation on XTC elimination; and (iii......) in integrated WWTP-agricultural systems. Different modelling tools, suiting the specific purposes of our investigations, were developed, extended and/or innovatively applied. Fate models used as reference in this thesis include: the Activated Sludge Modelling framework for Xenobiotics (ASM-X); the generic WWTP...... model SimpleTreat Activity; and the dynamic soil-plant model for fate prediction in agricultural systems. Experimental and model-based observations were combined to assess sorption of ionizable XTCs onto activated sludge and XTC biotransformation in moving bed biofilm reactors (MBBRs). Most XTCs...

  3. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887

    Science.gov (United States)

    Merrill, A. H. Jr; Hoel, M.; Wang, E.; Mullins, R. E.; Hargrove, J. L.; Jones, D. P.; Popova, I. A.; Merrill AH, J. r. (Principal Investigator)

    1990-01-01

    To determine the possible biochemical effects of prolonged weightlessness on liver function, samples of liver from rats that had flown aboard Cosmos 1887 were analyzed for protein, glycogen, and lipids as well as the activities of a number of key enzymes involved in metabolism of these compounds and xenobiotics. Among the parameters measured, the major differences were elevations in the glycogen content and hydroxymethylglutaryl-CoA (HMG-CoA) reductase activities for the rats flown on Cosmos 1887 and decreases in the amount of microsomal cytochrome P-450 and the activities of aniline hydroxylase and ethylmorphine N-demethylase, cytochrome P-450-dependent enzymes. These results support the earlier finding of differences in these parameters and suggest that altered hepatic function could be important during spaceflight and/or the postflight recovery period.

  4. Biomarkers and Environmental Stress: Relevance of Cellular Responses in Determining Adverse Outcomes

    Science.gov (United States)

    Biomarkers are measurable changes in a biological system indicative of an interaction with a chemical, physical, or biological agent. Such changes can be molecular, biochemical, physiological, or histological and can be reflective of either xenobiotic exposures or effects. Molecu...

  5. The US-Russia missile defense dialogue as a factor of the Russian defense policy

    OpenAIRE

    Dmitry Suslov

    2013-01-01

    To a big extent the Russian defense policy and, as a consequence, development of the Russian defense industrial complex, is determined by the prospects of the US missile defense policy and fate of the US-Russia negotiations in this area. As a cooperative solution seems improbable in the observable future, Russia plans to develop certain response measures of military nature, including creation of a new heavy ICBM, and to create its own missile defense by 2015. However, this policy does not see...

  6. Defense Agency Travel Payments at Defense Finance and Accounting Service Indianapolis Center

    National Research Council Canada - National Science Library

    1997-01-01

    The audit objective was to assess the effectiveness of Defense Finance and Accounting Service Indianapolis Center management controls over payments to Defense agency personnel for temporary duty and local travel...

  7. Simulating Quantitative Cellular Responses Using Asynchronous Threshold Boolean Network Ensembles

    Directory of Open Access Journals (Sweden)

    Shah Imran

    2011-07-01

    Full Text Available Abstract Background With increasing knowledge about the potential mechanisms underlying cellular functions, it is becoming feasible to predict the response of biological systems to genetic and environmental perturbations. Due to the lack of homogeneity in living tissues it is difficult to estimate the physiological effect of chemicals, including potential toxicity. Here we investigate a biologically motivated model for estimating tissue level responses by aggregating the behavior of a cell population. We assume that the molecular state of individual cells is independently governed by discrete non-deterministic signaling mechanisms. This results in noisy but highly reproducible aggregate level responses that are consistent with experimental data. Results We developed an asynchronous threshold Boolean network simulation algorithm to model signal transduction in a single cell, and then used an ensemble of these models to estimate the aggregate response across a cell population. Using published data, we derived a putative crosstalk network involving growth factors and cytokines - i.e., Epidermal Growth Factor, Insulin, Insulin like Growth Factor Type 1, and Tumor Necrosis Factor α - to describe early signaling events in cell proliferation signal transduction. Reproducibility of the modeling technique across ensembles of Boolean networks representing cell populations is investigated. Furthermore, we compare our simulation results to experimental observations of hepatocytes reported in the literature. Conclusion A systematic analysis of the results following differential stimulation of this model by growth factors and cytokines suggests that: (a using Boolean network ensembles with asynchronous updating provides biologically plausible noisy individual cellular responses with reproducible mean behavior for large cell populations, and (b with sufficient data our model can estimate the response to different concentrations of extracellular ligands. Our

  8. Nasal cytochrome P4502A: Identification in rats and humans

    Energy Technology Data Exchange (ETDEWEB)

    Thornton-Manning, J.R.; Hotchkiss, J.A. [Michigan State Univ., East Lansing, MI (United States); Ding, Xinxin [Wadsworth Center for Laboratories and Research, Albany, NY (United States)] [and others

    1995-12-01

    The nasal mucosa, the first tissue of contact for inhaled xenobiotics, possesses substantial enobiotic-metabolizing capacti. Enzymes of the nasal cavity may metabolize xenobiotics to innocuous, more water-soluble compounds that are eliminated from the body, or they may bioactivate them to toxic metabolites. These toxic metabolites may find to cellular macromolecules in the nasal cavity or be transported to other parts of the body where they may react. Nasal carcinogenesis in rodents often results from bioactivation of xenobiotics. The increased incidences of nasal tumors associated with certain occupations suggest that xenobiotic bioactivation may be important in human nasal cancer etiology, as well. The increasing popularity of the nose as a route of drug administration makes information concerning nasal drug metabolism and disposition vital to accomplish therapeutic goals. For these reasons, the study of xenobiotic-met abolizing capacity of the nasal cavity is an important area of health-related research. In the present study, we have confirmed the presence of CYP2A6 mRNA in human respiratory mucosa.

  9. SELF-DEFENSE IN KARABAKH CONFLICT?

    Directory of Open Access Journals (Sweden)

    Saeed Bagheri

    2015-01-01

    Full Text Available Use of force is one of the principles of international law which has been banned by the UN Charter and modern constitutions. However, since the enforcement of the UN Charter, self-defense has become the preferred excuse for states to justify their use of force. But applying self-defense requires some conditions. Immediacy is one of the important conditions of self-defense. Immediacy defined as the time span between armed attacks and reaction to it, is the main discourse. This condition requires self defense immediately after the armed conflict or during a rational time span since its occurance.In this respect, the emerging Karabakh Conflict between Armenia and Azerbaijan in the 1990s is important. After Armenia’s armed attacks, Azerbaijan has acted within the scope of legitimate self-defense. But in accordance with UN Security Council cease-fire resolution Azerbaijan has suspended its self-defense actions. However, today, still twenty percent of Azerbaijani territory is still under Armenian occupation. Accordingly, after a long time the validity of Azerbaijan’s right to legitimate self-defense is still subject to arguments.In this article, by comparing two different approaches (strict and board interpretation approaches on the temporal link between the measures of self-defense and the armed attacks (immediacy, the temporal link between the self-defense countermeasures of Azerbaijan and armed attacks by Armenia in Karabakh Conflict will be examined.

  10. Transposable elements are enriched within or in close proximity to xenobiotic-metabolizing cytochrome P450 genes

    Directory of Open Access Journals (Sweden)

    Li Xianchun

    2007-03-01

    Full Text Available Abstract Background Transposons, i.e. transposable elements (TEs, are the major internal spontaneous mutation agents for the variability of eukaryotic genomes. To address the general issue of whether transposons mediate genomic changes in environment-adaptation genes, we scanned two alleles per each of the six xenobiotic-metabolizing Helicoverpa zea cytochrome P450 loci, including CYP6B8, CYP6B27, CYP321A1, CYP321A2, CYP9A12v3 and CYP9A14, for the presence of transposon insertions by genome walking and sequence analysis. We also scanned thirteen Drosophila melanogaster P450s genes for TE insertions by in silico mapping and literature search. Results Twelve novel transposons, including LINEs (long interspersed nuclear elements, SINEs (short interspersed nuclear elements, MITEs (miniature inverted-repeat transposable elements, one full-length transib-like transposon, and one full-length Tcl-like DNA transpson, are identified from the alleles of the six H. zea P450 genes. The twelve transposons are inserted into the 5'flanking region, 3'flanking region, exon, or intron of the six environment-adaptation P450 genes. In D. melanogaster, seven out of the eight Drosophila P450s (CYP4E2, CYP6A2, CYP6A8, CYP6A9, CYP6G1, CYP6W1, CYP12A4, CYP12D1 implicated in insecticide resistance are associated with a variety of transposons. By contrast, all the five Drosophila P450s (CYP302A1, CYP306A1, CYP307A1, CYP314A1 and CYP315A1 involved in ecdysone biosynthesis and developmental regulation are free of TE insertions. Conclusion These results indicate that TEs are selectively retained within or in close proximity to xenobiotic-metabolizing P450 genes.

  11. Toxicological implications of polymorphisms in receptors for xenobiotic chemicals: The case of the aryl hydrocarbon receptor

    International Nuclear Information System (INIS)

    Okey, Allan B.; Franc, Monique A.; Moffat, Ivy D.; Tijet, Nathalie; Boutros, Paul C.; Korkalainen, Merja; Tuomisto, Jouko; Pohjanvirta, Raimo

    2005-01-01

    Mechanistic toxicology has predominantly been focused on adverse effects that are caused by reactive metabolites or by reactive oxygen species. However, many important xenobiotics exert their toxicity, not by generating reactive products, but rather by altering expression of specific genes. In particular, some environmental contaminants target nuclear receptors that function as regulators of transcription. For example, binding of xenobiotic chemicals to steroid receptors is a principle mechanism of endocrine disruption. The aryl hydrocarbon receptor (AHR) mediates toxicity of dioxin-like compounds. In mice, a polymorphism in the AHR ligand-binding domain reduces binding affinity by about 10-fold in the DBA/2 strain compared with the C57BL/6 strain; consequently, dose-response curves for numerous biochemical and toxic effects are shifted about one log to the right in DBA/2 mice. In the Han/Wistar (Kuopio) (H/W) rat strain, a polymorphism causes a deletion of 38 or 43 amino acids from the AHR transactivation domain. This deletion is associated with a greater than 1000-fold resistance to lethality from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Genes in the conventional AH gene battery (e.g. CYP1A1, CYP1A2, CYP1B1, ALDH3A1, NQO1 and UGT1A1) remain responsive to TCDD in H/W rats despite the large deletion. However, the deletion may selectively alter the receptor's ability to dysregulate specific genes that are key to dioxin toxicity. We are identifying these genes using an expression array approach in dioxin-sensitive vs. dioxin-resistant rat strains and lines. Polymorphisms exist in the human AH receptor, but thus far they have not been shown to have any substantial effect on human responses to AHR-ligands

  12. Defense Treaty Inspection Readiness Program

    International Nuclear Information System (INIS)

    Cronin, J.J.; Kohen, M.D.; Rivers, J.D.

    1996-01-01

    The Defense Treaty Inspection Readiness Program (DTIRP) was established by the Department of Defense in 1990 to assist defense facilities in preparing for treaty verification activities. Led by the On-Site Inspection Agency (OSIA), an element of the Department of Defense, DTIRP''s membership includes representatives from other Department of Defense agencies, the Department of Energy (DOE), the Central Intelligence Agency, the Federal Bureau of Investigation, the Department of Commerce, and others. The Office of Safeguards and Security has a significant interest in this program, due to the number of national defense facilities within its purview that are candidates for future inspections. As a result, the Office of Safeguards and Security has taken a very active role in DTIRP. This paper discusses the Office of Safeguards and Security''s increasing involvement in various elements of the DTIRP, ranging from facility assessments to training development and implementation

  13. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  14. Coordination of frontline defense mechanisms under severe oxidative stress.

    Science.gov (United States)

    Kaur, Amardeep; Van, Phu T; Busch, Courtney R; Robinson, Courtney K; Pan, Min; Pang, Wyming Lee; Reiss, David J; DiRuggiero, Jocelyne; Baliga, Nitin S

    2010-07-01

    Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations--this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of gamma rays.

  15. Changes in cytochrome P450 gene expression and enzyme activity induced by xenobiotics in rabbits in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Orsolya Palócz

    2017-06-01

    Full Text Available As considerable inter-species differences exist in xenobiotic metabolism, developing new pharmaceutical therapies for use in different species is fraught with difficulties. For this reason, very few medicines have been registered for use in rabbits, despite their importance in inter alia meat and fur production. We have developed a rapid and sensitive screening system for drug safety in rabbits based on cytochrome P450 enzyme assays, specifically CYP1A1, CYP1A2 and CYP3A6, employing an adaptation of the luciferin-based clinical assay currently used in human drug screening. Short-term (4-h cultured rabbit primary hepatocytes were treated with a cytochrome inducer (phenobarbital and 2 inhibitors (alpha-naphthoflavone and ketoconazole. In parallel, and to provide verification, New Zealand white rabbits were dosed with 80 mg/kg phenobarbital or 40 mg/kg ketoconazole for 3 d. Ketoconazole significantly increased CYP3A6 gene expression and decreased CYP3A6 activity both in vitro and in vivo. CYP1A1 activity was decreased by ketoconazole in vitro and increased in vivo. This is the first report of the inducer effect of ketoconazole on rabbit cytochrome isoenzymes in vivo. Our data support the use of a luciferin-based assay in short-term primary hepatocytes as an appropriate tool for xenobiotic metabolism assays and short-term toxicity testing in rabbits.

  16. Defense Business Transformation

    Science.gov (United States)

    2009-12-01

    Defense Business Transformation by Jacques S. Gansler and William Lucyshyn The Center for Technology and National...REPORT TYPE 3. DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Defense Business Transformation 5a. CONTRACT NUMBER 5b. GRANT NUMBER...vii Part One: DoD Business Transformation

  17. Carcinogen-induced mdr overexpression is associated with xenobiotic resistance in rat preneoplastic liver nodules and hepatocellular carcinomas.

    Science.gov (United States)

    Fairchild, C R; Ivy, S P; Rushmore, T; Lee, G; Koo, P; Goldsmith, M E; Myers, C E; Farber, E; Cowan, K H

    1987-11-01

    We have previously reported the isolation of a human breast cancer cell line resistant to doxorubicin (adriamycin; AdrR MCF-7 cells) that has also developed the phenotype of multidrug resistance (MDR). MDR in this cell line is associated with increased expression of mdr (P glycoprotein) gene sequences. The development of MDR in AdrR MCF-7 cells is also associated with changes in the expression of several phase I and phase II drug-detoxifying enzymes. These changes are remarkably similar to those associated with development of xenobiotic resistance in rat hyperplastic liver nodules, a well-studied model system of chemical carcinogenesis. Using an mdr-encoded cDNA sequence isolated from AdrR MCF-7 cells, we have examined the expression of mdr sequences in rat livers under a variety of experimental conditions. The expression of mdr increased 3-fold in regenerating liver. It was also elevated (3- to 12-fold) in several different samples of rat hyperplastic nodules and in four of five hepatomas that developed in this system. This suggests that overexpression of mdr, a gene previously associated with resistance to antineoplastic agents, may also be involved in the development of resistance to xenobiotics in rat hyperplastic nodules. In addition, although the acute administration of 2-acetylaminofluorene induced an 8-fold increase in hepatic mdr-encoded RNA, performance of a partial hepatectomy either before or after administration of 2-acetylaminofluorene resulted in a greater than 80-fold increase in mdr gene expression over that in normal untreated livers. This represents an important in vivo model system in which to study the acute regulation of this drug resistance gene.

  18. Efficient transfection of Xenobiotic Responsive Element-biosensor plasmid using diether lipid and phosphatidylcholine liposomes in differentiated HepaRG cells.

    Science.gov (United States)

    Demazeau, Maxime; Quesnot, Nicolas; Ripoche, Nicolas; Rauch, Claudine; Jeftić, Jelena; Morel, Fabrice; Gauffre, Fabienne; Benvegnu, Thierry; Loyer, Pascal

    2017-05-30

    In this study, we evaluated cationic liposomes prepared from diether-NH 2 and egg phosphatidylcholine (EPC) for in vitro gene delivery. The impact of the lipid composition, i.e. the EPC and Diether-NH 2 molar ratio, on in vitro transfection efficiency and cytotoxicity was investigated using the human HEK293T and hepatoma HepaRG cells known to be permissive and poorly permissive cells for liposome-mediated gene transfer, respectively. Here, we report that EPC/Diether-NH 2 -based liposomes enabled a very efficient transfection with low cytotoxicity compared to commercial transfection reagents in both HEK293T and proliferating progenitor HepaRG cells. Taking advantage of these non-toxic EPC/Diether-NH 2 -based liposomes, we developed a method to efficiently transfect differentiated hepatocyte-like HepaRG cells and a biosensor plasmid containing a Xenobiotic Responsive Element and a minimal promoter driving the transcription of the luciferase reporter gene. We demonstrated that the luciferase activity was induced by a canonical inducer of cytochrome P450 genes, the benzo[a]pyrene, and two environmental contaminants, the fluoranthene, a polycyclic aromatic hydrocarbon, and the endosulfan, an organochlorine insecticide, known to induce toxicity and genotoxicity in differentiated HepaRG cells. In conclusion, we established a new efficient lipofection-mediated gene transfer in hepatocyte-like HepaRG cells opening new perspectives in drug evaluation relying on xenobiotic inducible biosensor plasmids. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Derek J Nancarrow

    Full Text Available Esophageal adenocarcinoma (EAC has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE, which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2 designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1 and xenobiotic (AKR1C2, AKR1B10 defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.

  20. Development of a Novel Antimicrobial Screening System Targeting the Pyoverdine-Mediated Iron Acquisition System and Xenobiotic Efflux Pumps

    Directory of Open Access Journals (Sweden)

    Kazuki Sato

    2015-04-01

    Full Text Available The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound—ethyl 2-(1-acetylpiperidine-4-carboxamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate—was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method.

  1. Development of a novel antimicrobial screening system targeting the pyoverdine-mediated iron acquisition system and xenobiotic efflux pumps.

    Science.gov (United States)

    Sato, Kazuki; Ushioda, Kenichi; Akiba, Keiji; Matsumoto, Yoshimi; Maseda, Hideaki; Ando, Tasuke; Isogai, Emiko; Nakae, Taiji; Yoneyama, Hiroshi

    2015-04-29

    The iron acquisition systems in Pseudomonas aeruginosa are inducible in response to low-iron conditions and important for growth of this organism under iron limitation. OprM is the essential outer membrane subunit of the MexAB-OprM xenobiotic efflux pump. We designed and constructed a new model antimicrobial screening system targeting both the iron-uptake system and xenobiotic efflux pumps. The oprM gene was placed immediately downstream of the ferri-pyoverdine receptor gene, fpvA, in the host lacking chromosomal oprM and the expression of oprM was monitored by an antibiotic susceptibility test under iron depleted and replete conditions. The recombinant cells showed wild-type susceptibility to pump substrate antibiotics, e.g., aztreonam, under iron limitation and became supersusceptible to them under iron repletion, suggesting that expression of oprM is under control of the iron acquisition system. Upon screening of a chemical library comprising 2952 compounds using this strain, a compound-ethyl 2-(1-acetylpiperidine-4-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate-was found to enhance the efficacy of aztreonam under iron limitation, suggesting that the compound inhibits either the iron acquisition system or the MexAB-OprM efflux pump. This compound was subsequently found to inhibit the growth of wild-type cells in the presence of sublethal amounts of aztreonam, regardless of the presence or absence of dipyridyl, an iron-chelator. The compound was eventually identified to block the function of the MexAB-OprM efflux pump, showing the validity of this new method.

  2. Self-Defense in Karabakh Conflict?

    Directory of Open Access Journals (Sweden)

    Saeed Bagheri

    2015-01-01

    Full Text Available Use of force is one of the principles of international law that has been banned by the UN Charter and modern constitutions. However, since the enforcement of the UN Charter, self-defense has become the preferred excuse for states to justify their use of force. Applying self-defense, however, requires some conditions. Immediacy is one of the important conditions of self-defense. This is defined as the timeframe between armed attacks and reaction to it. This situation requires self-defense immediately after the armed conflict or during a reasonable timeframe since its occurance.In this respect, emerging Karabakh Conflict between Armenia and Azerbaijan in the 1990s is important. In this article, by comparing two different approaches (strict and board interpretation of the temporal link between the measures of self-defense and the armed attacks (immediacy, the temporal link between the self-defense countermeasures of Azerbaijan and attacks by Armenia in Karabakh Conflict will be examined.

  3. Organizing Defense Logistics: What Strategic Structures Should Exist for the Defense Supply Chain

    National Research Council Canada - National Science Library

    Maddox, Edward D

    2005-01-01

    .... The primary research question of this study was: What strategic organizational structures should exist within the Department of Defense to facilitate further integration of the defense supply chain...

  4. Phosphorylation of Isoflavones by Bacillus subtilis BCRC 80517 May Represent Xenobiotic Metabolism.

    Science.gov (United States)

    Hsu, Chen; Wu, Bo-Yuan; Chang, Yu-Chuan; Chang, Chi-Fon; Chiou, Tai-Ying; Su, Nan-Wei

    2018-01-10

    The soy isoflavones daidzein (DAI) and genistein (GEN) have beneficial effects on human health. However, their oral bioavailability is hampered by their low aqueous solubility. Our previous study revealed two water-soluble phosphorylated conjugates of isoflavones, daidzein 7-O-phosphate and genistein 7-O-phosphate, generated via biotransformation by Bacillus subtilis BCRC80517 cultivated with isoflavones. In this study, two novel derivatives of isoflavones, daidzein 4'-O-phosphate and genistein 4'-O-phosphate, were identified by HPLC-ESI-MS/MS and 1 H, 13 C, and 31 P NMR, and their biotransformation roadmaps were proposed. Primarily, isoflavone glucosides were deglycosylated and then phosphorylated predominantly into 7-O-phosphate conjugates with traces of 4'-O-phosphate conjugates. Inevitably, trace quantities of glucosides were converted into 6″-O-succinyl glucosides. GEN was more efficiently phosphorylated than DAI. Nevertheless, the presence of GEN prolonged the time until the exponential phase of cell growth, whereas the other isoflavones showed little effect on cell growth. Our findings provide new insights into the novel microbial phosphorylation of isoflavones involved in xenobiotic metabolism.

  5. Infection and cellular defense dynamics in a novel 17β-estradiol murine model of chronic human group B streptococcus genital tract colonization reveal a role for hemolysin in persistence and neutrophil accumulation.

    Science.gov (United States)

    Carey, Alison J; Tan, Chee Keong; Mirza, Shaper; Irving-Rodgers, Helen; Webb, Richard I; Lam, Alfred; Ulett, Glen C

    2014-02-15

    Genital tract carriage of group B streptococcus (GBS) is prevalent among adult women; however, the dynamics of chronic GBS genital tract carriage, including how GBS persists in this immunologically active host niche long term, are not well defined. To our knowledge, in this study, we report the first animal model of chronic GBS genital tract colonization using female mice synchronized into estrus by delivery of 17β-estradiol prior to intravaginal challenge with wild-type GBS 874391. Cervicovaginal swabs, which were used to measure bacterial persistence, showed that GBS colonized the vaginal mucosa of mice at high numbers (10(6)-10(7) CFU/swab) for at least 90 d. Cellular and histological analyses showed that chronic GBS colonization of the murine genital tract caused significant lymphocyte and PMN cell infiltrates, which were localized to the vaginal mucosal surface. Long-term colonization was independent of regular hormone cycling. Immunological analyses of 23 soluble proteins related to chemotaxis and inflammation showed that the host response to GBS in the genital tract comprised markers of innate immune activation including cytokines such as GM-CSF and TNF-α. A nonhemolytic isogenic mutant of GBS 874391, Δcyle9, was impaired for colonization and was associated with amplified local PMN responses. Induction of DNA neutrophil extracellular traps, which was observed in GBS-infected human PMNs in vitro in a hemolysin-dependent manner, appeared to be part of this response. Overall, this study defines key infection dynamics in a novel murine model of chronic GBS genital tract colonization and establishes previously unknown cellular and soluble defense responses to GBS in the female genital tract.

  6. Shift in aggregation, ROS generation, antioxidative defense, lysozyme and acetylcholinesterase activities in the cells of an Indian freshwater sponge exposed to washing soda (sodium carbonate).

    Science.gov (United States)

    Mukherjee, Soumalya; Ray, Mitali; Ray, Sajal

    2016-09-01

    Washing soda, chemically identified as anhydrous sodium carbonate, is a popular cleaning agent among the rural and urban populations of India which often contaminates the freshwater ponds and lakes, the natural habitat of sponge Eunapius carteri. Present investigation deals with estimation of cellular aggregation, generation of ROS and activities of antioxidant enzymes, lysozyme and acetylcholinesterase in the cells of E. carteri under the environmentally realistic concentrations of washing soda. Prolonged treatment of washing soda inhibited the degree of cellular aggregation. Experimental exposure of 8 and 16mg/l of sodium carbonate for 48h elevated the physiological level of reactive oxygen species (ROS) generation in the agranulocytes, semigranulocytes and granulocytes of E. carteri, whereas, treatment of 192h inhibited the ROS generation in three cellular morphotypes. Activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded to be inhibited under prolonged exposure of washing soda. Washing soda mediated inhibition of ROS generation and depletion in the activities of antioxidant enzymes were indicative to an undesirable shift in cytotoxic status and antioxidative defense in E. carteri. Inhibition in the activity of lysozyme under the treatment of sodium carbonate was suggestive to a severe impairment of the innate immunological efficiency of E. carteri distributed in the washing soda contaminated habitat. Washing soda mediated inhibition in the activity of acetylcholinesterase indicated its neurotoxicity in E. carteri. Washing soda, a reported environmental contaminant, affected adversely the immunophysiological status of E. carteri with reference to cellular aggregation, oxidative stress, antioxidative defense, lysozyme and acetylcholinesterase activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Strategic Defense Initiative Overview

    National Research Council Canada - National Science Library

    1990-01-01

    ... to Third World and other nations. I will then discuss the scope of the SDI effort, the evolving strategic defense system architectures and theater defense, our compliancy with the ABM Treaty, technology spinoffs resulting from SDI...

  8. Summary Report on the Audit of Defense Logistics Agency 1995 Defense Base Realignment and Closure Data Collection Process.

    Science.gov (United States)

    1995-06-19

    VXW-ÄVAVKVX’AWXW/XVXV:*: OFFICE OF THE INSPECTOR GENERAL SUMMARY REPORT ON THE AUDIT OF DEFENSE LOGISTICS AGENCY 1995 DEFENSE BASE REALIGNMENT...FOR DIRECTOR, DEFENSE LOGISTICS AGENCY SUBJECT: Summary Report on the Audit of Defense Logistics Agency 1995 Defense Base Realignment and Closure...the data that DLA provides to support recommendations for the 1995 Commission. The specific objective for the audits was to determine whether the

  9. Effect of psychological intervention in the form of relaxation and guided imagery on cellular immune function in normal healthy subjects. An overview

    DEFF Research Database (Denmark)

    Zachariae, R; Kristensen, J S; Hokland, P

    1991-01-01

    The present study measured the effects of relaxation and guided imagery on cellular immune function. During a period of 10 days 10 healthy subjects were given one 1-hour relaxation procedure and one combined relaxation and guided imagery procedure, instructing the subjects to imagine their immune...... on the immune defense and could form the basis of further studies on psychological intervention and immunological status. Udgivelsesdato: 1990-null...

  10. Putative sugar transporters of the mustard leaf beetle Phaedon cochleariae: their phylogeny and role for nutrient supply in larval defensive glands.

    Directory of Open Access Journals (Sweden)

    Magdalena Stock

    Full Text Available BACKGROUND: Phytophagous insects have emerged successfully on the planet also because of the development of diverse and often astonishing defensive strategies against their enemies. The larvae of the mustard leaf beetle Phaedon cochleariae, for example, secrete deterrents from specialized defensive glands on their back. The secretion process involves ATP-binding cassette transporters. Therefore, sugar as one of the major energy sources to fuel the ATP synthesis for the cellular metabolism and transport processes, has to be present in the defensive glands. However, the role of sugar transporters for the production of defensive secretions was not addressed until now. RESULTS: To identify sugar transporters in P. cochleariae, a transcript catalogue was created by Illumina sequencing of cDNA libraries. A total of 68,667 transcripts were identified and 68 proteins were annotated as either members of the solute carrier 2 (SLC2 family or trehalose transporters. Phylogenetic analyses revealed an extension of the mammalian GLUT6/8 class in insects as well as one group of transporters exhibiting distinctive conserved motifs only present in the insect order Coleoptera. RNA-seq data of samples derived from the defensive glands revealed six transcripts encoding sugar transporters with more than 3,000 counts. Two of them are exclusively expressed in the glandular tissue. Reduction in secretions production was accomplished by silencing two of four selected transporters. RNA-seq experiments of transporter-silenced larvae showed the down-regulation of the silenced transporter but concurrently the up-regulation of other SLC2 transporters suggesting an adaptive system to maintain sugar homeostasis in the defensive glands. CONCLUSION: We provide the first comprehensive phylogenetic study of the SLC2 family in a phytophagous beetle species. RNAi and RNA-seq experiments underline the importance of SLC2 transporters in defensive glands to achieve a chemical defense

  11. Investigation into the fate of C-14-labelled xenobiotics(naphthalene, phenanthrene, 2,4,5,2 ',4',5 '-hexachlorobiphenyl, octachlorostyrene) in Bermudian corals

    OpenAIRE

    Solbakken, Jan Erik; Knap, A.H.; Sleeter, T.D.; Searle, C.E.; Palmork, Karsten H.

    1983-01-01

    Uptake and elimination of 4 labelled lipid-soluble xenobiotics (naphthalene, phenanthrene, 2,4,5,2',4',5'-hexachlorobiphen(yPlC B), octachlorostyrene) were studied in 19 anthozoans and 1 hydrozoan common to Bermudian waters. The concentration of radioactiv~ty In the tissues was determined using liquid scintillation counting. All organisms tested took up radioactivity from the water. However, elimination rates were very slow compared to those of other marine organisms. Naphthale...

  12. Department of Defense perspective

    International Nuclear Information System (INIS)

    Devine, R.

    1985-01-01

    This paper examines radiation instrumentation from the Department of Defense perspective. Radiation survey instruments and calibration, or RADIAC, as it is called in the services, while administratively falling under the Assistant Secretary of Defense for Atomic Energy, has generally been managed at a lower level. The Naval Electronics Systems Command and Army Signal Corp are the two principles in the Department of Defense for RADIAC. The actions of the services are coordinated through the tri-service RADIAC working group, which meets about every year and a half. Several points from this organization are highlighted

  13. ABCG2 Inhibition as a Therapeutic Approach for Overcoming ...

    Indian Academy of Sciences (India)

    Breast cancer resistance protein (BCRP, ABCP or MXR) / ATP-binding cassette subfamily G member 2 (ABCG2) was characterized as a multidrug resistance efflux transporter in 1998. ABCG2 physiologically acts as a part of a self-defense mechanism for the organism; it enhances eliminating of toxic xenobiotic substances ...

  14. The Role of NLR-related Protein 3 Inflammasome in Host Defense and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Chul-Su Yang

    2012-03-01

    Full Text Available Among a number of innate receptors, the nucleotide-binding domain leucine-rich repeat containing (NLR nucleotide oligomerization domain (NOD-like receptor families are involved in the recognition of cytosolic pathogen- or danger-associated molecules. Activation of these specific sets of receptors leads to the assembly of a multiprotein complex, the inflammasome, leading to the activation of caspase-1 and maturation of the cytokines interleukin (IL-1β, IL-18, and IL-33. Among NLRs, NLR-related protein 3 (NLRP3 is one of the best-characterized receptors that activates the inflammasome. There is no doubt that NLRP3 inflammasome activation is important for host defense and effective pathogen clearance against fungal, bacterial, and viral infection. In addition, mounting evidence indicates that the NLRP3 inflammasome plays a role in a variety of inflammatory diseases, including gout, atherosclerosis, and type II diabetes, as well as under conditions of cellular stress or injury. Here, we review recent advances in our understanding of the role of the NLRP3 inflammasome in host defense and various inflammatory diseases.

  15. Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics.

    Science.gov (United States)

    Martin, Hans-Jörg; Breyer-Pfaff, Ursula; Wsol, Vladimir; Venz, Simone; Block, Simone; Maser, Edmund

    2006-03-01

    Members of the aldo-keto reductase (AKR) superfamily have a broad substrate specificity in catalyzing the reduction of carbonyl group-containing xenobiotics. In the present investigation, a member of the aldose reductase subfamily, AKR1B10, was purified from human liver cytosol. This is the first time AKR1B10 has been purified in its native form. AKR1B10 showed a molecular mass of 35 kDa upon gel filtration and SDS-polyacrylamide gel electrophoresis. Kinetic parameters for the NADPH-dependent reduction of the antiemetic 5-HT3 receptor antagonist dolasetron, the antitumor drugs daunorubicin and oracin, and the carcinogen 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) to the corresponding alcohols have been determined by HPLC. Km values ranged between 0.06 mM for dolasetron and 1.1 mM for daunorubicin. Enzymatic efficiencies calculated as kcat/Km were more than 100 mM-1 min-1 for dolasetron and 1.3, 0.43, and 0.47 mM-1 min-1 for daunorubicin, oracin, and NNK, respectively. Thus, AKR1B10 is one of the most significant reductases in the activation of dolasetron. In addition to its reducing activity, AKR1B10 catalyzed the NADP+-dependent oxidation of the secondary alcohol (S)-1-indanol to 1-indanone with high enzymatic efficiency (kcat/Km=112 mM-1 min-1). The gene encoding AKR1B10 was cloned from a human liver cDNA library and the recombinant enzyme was purified. Kinetic studies revealed lower activity of the recombinant compared with the native form. Immunoblot studies indicated large interindividual variations in the expression of AKR1B10 in human liver. Since carbonyl reduction of xenobiotics often leads to their inactivation, AKR1B10 may play a role in the occurrence of chemoresistance of tumors toward carbonyl group-bearing cytostatic drugs.

  16. Salix purpurea Stimulates the Expression of Specific Bacterial Xenobiotic Degradation Genes in a Soil Contaminated with Hydrocarbons.

    Directory of Open Access Journals (Sweden)

    Antoine P Pagé

    Full Text Available The objectives of this study were to uncover Salix purpurea-microbe xenobiotic degradation systems that could be harnessed in rhizoremediation, and to identify microorganisms that are likely involved in these partnerships. To do so, we tested S. purpurea's ability to stimulate the expression of 10 marker microbial oxygenase genes in a soil contaminated with hydrocarbons. In what appeared to be a detoxification rhizosphere effect, transcripts encoding for alkane 1-monooxygenases, cytochrome P450 monooxygenases, laccase/polyphenol oxidases, and biphenyl 2,3-dioxygenase small subunits were significantly more abundant in the vicinity of the plant's roots than in bulk soil. This gene expression induction is consistent with willows' known rhizoremediation capabilities, and suggests the existence of S. purpurea-microbe systems that target many organic contaminants of interest (i.e. C4-C16 alkanes, fluoranthene, anthracene, benzo(apyrene, biphenyl, polychlorinated biphenyls. An enhanced expression of the 4 genes was also observed within the bacterial orders Actinomycetales, Rhodospirillales, Burkholderiales, Alteromonadales, Solirubrobacterales, Caulobacterales, and Rhizobiales, which suggest that members of these taxa are active participants in the exposed partnerships. Although the expression of the other 6 marker genes did not appear to be stimulated by the plant at the community level, signs of additional systems that rest on their expression by members of the orders Solirubrobacterales, Sphingomonadales, Actinomycetales, and Sphingobacteriales were observed. Our study presents the first transcriptomics-based identification of microbes whose xenobiotic degradation activity in soil appears stimulated by a plant. It paints a portrait that contrasts with the current views on these consortia's composition, and opens the door for the development of laboratory test models geared towards the identification of root exudate characteristics that limit the

  17. Acquisition Planning at the Defense Communications Agency.

    Science.gov (United States)

    1984-04-01

    guidelines for interaction are developed under the leadership of DCA agencywide integrators with the participation of personnel from DCA, the Services...Communications System DCSO - Defense Communications System Organizatin . DDN - Defense Data Network DEC - Decision Making DG - Defense Guidance DIA - Defense

  18. PERM Hypothesis: The Fundamental Machinery Able to Elucidate the Role of Xenobiotics and Hormesis in Cell Survival and Homeostasis

    Directory of Open Access Journals (Sweden)

    Salvatore Chirumbolo

    2017-01-01

    Full Text Available In this article the Proteasome, Endoplasmic Reticulum and Mitochondria (PERM hypothesis is discussed. The complex machinery made by three homeostatic mechanisms involving the proteasome (P, endoplasmic reticulum (ER and mitochondria (M is addressed in order to elucidate the beneficial role of many xenobiotics, either trace metals or phytochemicals, which are spread in the human environment and in dietary habits, exerting their actions on the mechanisms underlying cell survival (apoptosis, cell cycle regulation, DNA repair and turnover, autophagy and stress response. The “PERM hypothesis” suggests that xenobiotics can modulate this central signaling and the regulatory engine made fundamentally by the ER, mitochondria and proteasome, together with other ancillary components such as peroxisomes, by acting on the energetic balance, redox system and macromolecule turnover. In this context, reactive species and stressors are fundamentally signalling molecules that could act as negative-modulating signals if PERM-mediated control is offline, impaired or dysregulated, as occurs in metabolic syndrome, degenerative disorders, chronic inflammation and cancer. Calcium is an important oscillatory input of this regulation and, in this hypothesis, it might play a role in maintaining the correct rhythm of this PERM modulation, probably chaotic in its nature, and guiding cells to a more drastic decision, such as apoptosis. The commonest effort sustained by cells is to maintain their survival balance and the proterome has the fundamental task of supporting this mechanism. Mild stress is probably the main stimulus in this sense. Hormesis is therefore re-interpreted in the light of this hypothetical model and that experimental evidence arising from flavonoid and hormesis reasearch.

  19. Relation between serum xenobiotic induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations

    DEFF Research Database (Denmark)

    Long, Manhai; Stronati, Alessanda; Bizzaro, Davide

    2007-01-01

    Persistent organic pollutants (POPs) can interfere with hormone activities and are suspected as endocrine disrupters involved in disorders, e.g. reproductive disorders. We investigated the possible relation between the actual integrated serum xenoestrogenic, xenoandrogenic and aryl hydrocarbon......, but higher xenoandrogenic activity. In contrast, in the European groups, xenobiotic-induced receptor activities were found to be positively correlated with the DNA damage. Further research must elucidate whether altered receptor activities in concerted action with genetic and/or nutrient factors may have...... protecting effect on sperm DNA damage of the Inuit population....

  20. COP21: defense stakes

    International Nuclear Information System (INIS)

    Coldefy, Alain; Hulot, Nicolas; Aichi, Leila; Tertrais, Bruno; Paillard, Christophe-Alexandre; Piodi, Jerome; Regnier, Serge; Volpi, Jean-Luc; Descleves, Emmanuel; Garcin, Thierry; Granholm, Niklas; Wedin, Lars; Pouvreau, Ana; Henninger, Laurent

    2015-01-01

    The 21. Conference of the Parties (COP21) from the UN Framework Convention took place in Paris between November 30 and December 11, 2015. The challenge is to reach a universal agreement of fight against global warming and to control the carbon footprint of human activities. This topic is in the core of the Defense Ministry preoccupations. This special dossier takes stock of the question of defense issues linked with global warming. The dossier comprises 13 papers dealing with: 1 - COP21: defense stakes (Coldefy, A.); 2 - Warfare climate, a chance for peace (Hulot, N.); 3 - COP21 and defense (Aichi, L.); 4 - A war climate? (Tertrais, B.); 5 - Challenges the World has to face in the 21. century (Paillard, C.A.); 6 - Desertification: a time bomb in the heart of Sahel (Piodi, J.); 7 - The infrastructure department of defense in the fight against climate disturbance (Regnier, S.); 8 - Fight against global warming, a chance for the forces? (Volpi, J.L.); 9 - Sea and sustainable development (Descleves, E.); 10 - Rationales of Arctic's surrounding powers (Garcin, T.); 11 - Arctic: strategic stake (Granholm, N.; Wedin, L.); 12 - Strategic impact of Turkey's new energy choices (Pouvreau, A.); 13 - Climate and war: a brief historical outlook (Henninger, L.)

  1. Is flood defense changing in nature? Shifts in the flood defense strategy in six European countries

    Directory of Open Access Journals (Sweden)

    Mathilde Gralepois

    2016-12-01

    Full Text Available In many countries, flood defense has historically formed the core of flood risk management but this strategy is now evolving with the changing approach to risk management. This paper focuses on the neglected analysis of institutional changes within the flood defense strategies formulated and implemented in six European countries (Belgium, England, France, the Netherlands, Poland, and Sweden. The evolutions within the defense strategy over the last 30 years have been analyzed with the help of three mainstream institutional theories: a policy dynamics-oriented framework, a structure-oriented institutional theory on path dependency, and a policy actors-oriented analysis called the advocacy coalitions framework. We characterize the stability and evolution of the trends that affect the defense strategy in the six countries through four dimensions of a policy arrangement approach: actors, rules, resources, and discourses. We ask whether the strategy itself is changing radically, i.e., toward a discontinuous situation, and whether the processes of change are more incremental or radical. Our findings indicate that in the European countries studied, the position of defense strategy is continuous, as the classical role of flood defense remains dominant. With changing approaches to risk, integrated risk management, climate change, urban growth, participation in governance, and socioeconomic challenges, the flood defense strategy is increasingly under pressure to change. However, these changes can be defined as part of an adaptation of the defense strategy rather than as a real change in the nature of flood risk management.

  2. Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma

    International Nuclear Information System (INIS)

    Bièche, Ivan; Girault, Igor; Urbain, Estelle; Tozlu, Sengül; Lidereau, Rosette

    2004-01-01

    Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability. To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a well-defined cohort of 97 ERα-positive postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone. Seven of the 27 genes showed very weak or undetectable expression in both normal and tumoral breast tissues. Among the 20 remaining genes, seven genes (CYP2A6, CYP2B6, FMO5, NAT1, SULT2B1, GSTM3 and ABCC11) showed significantly higher mRNA levels in ERα-positive breast tumors than in normal breast tissue, or showed higher mRNA levels in ERα-positive breast tumors than in ERα-negative breast tumors. In the 97 ERα-positive breast tumor series, most alterations of these seven genes corresponded to upregulations as compared with normal breast tissue, with an incidence ranging from 25% (CYP2A6) to 79% (NAT1). Downregulation was rare. CYP2A6, CYP2B6, FMO5 and NAT1 emerged as new putative ERα-responsive genes in human breast cancer. Relapse-free survival was longer among patients with FMO5-overexpressing tumors or NAT1-overexpressing tumors (P = 0.0066 and P = 0.000052, respectively), but only NAT1 status retained prognostic significance in Cox multivariate regression analysis (P = 0.0013). Taken together, these data point to a role of genes coding for xenobiotic-metabolizing enzymes in breast tumorigenesis, NAT1 being an

  3. THE CONCEPT OF "SMART DEFENSE" IN THE CONTEXT OF AN EFFICIENT DEFENSE PLANNING

    Directory of Open Access Journals (Sweden)

    Teodor FRUNZETI

    2012-01-01

    Full Text Available The international security environment is currently undergoing a series of fundamental changes becoming increasingly complex. Consequently, international actors need to find innovative ways to manage security and defense. The global financial and economic crisis has had a strong impact on military budgets, making it necessary for states and regional and international organizations concerned with such issues to streamline their defense planning and the more so because, in addition to the already consecrated risks and security threats, there are also new challenges. The concepts of “pooling and sharing” and “smart defense” have become, in this context, increasingly popular generating new initiatives in defense planning. However, despite some successes in this regard and their presentation as ideal solutions for managing defense in the current context, these concepts involve a number of difficulties to overcome that sometimes may translate into strategic political military and even economic disadvantages.

  4. 47 CFR 90.411 - Civil defense communications.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Civil defense communications. 90.411 Section 90... PRIVATE LAND MOBILE RADIO SERVICES Operating Requirements § 90.411 Civil defense communications. The... necessary for the implementation of civil defense activities assigned such station by local civil defense...

  5. DCT-based cyber defense techniques

    Science.gov (United States)

    Amsalem, Yaron; Puzanov, Anton; Bedinerman, Anton; Kutcher, Maxim; Hadar, Ofer

    2015-09-01

    With the increasing popularity of video streaming services and multimedia sharing via social networks, there is a need to protect the multimedia from malicious use. An attacker may use steganography and watermarking techniques to embed malicious content, in order to attack the end user. Most of the attack algorithms are robust to basic image processing techniques such as filtering, compression, noise addition, etc. Hence, in this article two novel, real-time, defense techniques are proposed: Smart threshold and anomaly correction. Both techniques operate at the DCT domain, and are applicable for JPEG images and H.264 I-Frames. The defense performance was evaluated against a highly robust attack, and the perceptual quality degradation was measured by the well-known PSNR and SSIM quality assessment metrics. A set of defense techniques is suggested for improving the defense efficiency. For the most aggressive attack configuration, the combination of all the defense techniques results in 80% protection against cyber-attacks with PSNR of 25.74 db.

  6. Missile defense in the United States

    OpenAIRE

    Heurlin, Bertil

    2004-01-01

    The basic arguments of this paper are, first, that the current US-missile defense, being operative from fall 2004, is based upon the former experiences with missile defense, second, that missile defense closely associated with weapons of mass destruction has gained the highest priority in American national security policy due to the 9.11 attacks, and third, that the superior argument for establishing an American missile defense is to maintain global, long term political-strategic superiority....

  7. Strategic Missile Defense & Nuclear Deterrence

    Science.gov (United States)

    Grego, Laura

    The United States has pursued defenses against nuclear-armed long-range ballistic missiles since at least the 1950s. At the same time, concerns that missile defenses could undermine nuclear deterrence and potentially spark an arms race led the United States and Soviet Union to negotiate limits on these systems. The 1972 Anti-Ballistic Missile Treaty constrained strategic missile defenses for thirty years. After abandoning the treaty in 2002, President George W. Bush began fielding the Ground-based Midcourse Defense (GMD) homeland missile defense system on an extremely aggressive schedule, nominally to respond to threats from North Korea and Iran. Today, nearly fifteen years after its initial deployment, the potential and the limits of this homeland missile defense are apparent. Its test record is poor and it has no demonstrated ability to stop an incoming missile under real-world conditions. No credible strategy is in place to solve the issue of discriminating countermeasures. Insufficient oversight has not only exacerbated the GMD system's problems, but has obscured their full extent, which could encourage politicians and military leaders to make decisions that actually increase the risk of a missile attack against the United States. These are not the only costs. Both Russia and China have repeatedly expressed concerns that U.S. missile defenses adversely affect their own strategic capabilities and interests, particularly taken in light of the substantial US nuclear forces. This in turn affects these countries' nuclear modernization priorities. This talk will provide a technical overview of the US strategic missile defense system, and how it relates to deterrence against non-peer adversaries as well as how it affects deterrence with Russia and China and the long-term prospects for nuclear reductions

  8. Defense Mechanisms: A Bibliography.

    Science.gov (United States)

    Pedrini, D. T.; Pedrini, Bonnie C.

    This bibliography includes studies of defense mechanisms, in general, and studies of multiple mechanisms. Defense mechanisms, briefly and simply defined, are the unconscious ego defendants against unpleasure, threat, or anxiety. Sigmund Freud deserves the clinical credit for studying many mechanisms and introducing them in professional literature.…

  9. Understanding the toxic potencies of xenobiotics inducing TCDD/TCDF-like effects.

    Science.gov (United States)

    Şahin, A D; Saçan, M T

    2018-02-01

    Toxic potencies of xenobiotics such as halogenated aromatic hydrocarbons inducing 2,3,7,8-tetrachlorodibenzo-p-dioxin/2,3,7,8-tetrachlorodibenzofuran (TCDD/TCDF)-like effects were investigated by quantitative structure-toxicity relationships (QSTR) using their aryl hydrocarbon receptor (AhR) binding affinity data. A descriptor pool was created using the SPARTAN 10, DRAGON 6.0 and ADMET 8.0 software packages, and the descriptors were selected using QSARINS (v.2.2.1) software. The QSTR models generated for AhR binding affinities of chemicals with TCDD/TCDF-like effects were internally and externally validated in line with the Organization of Economic Co-operation and Development (OECD) principles. The TCDD-based model had six descriptors from DRAGON 6.0 and ADMET 8.0, whereas the TCDF-based model had seven descriptors from DRAGON 6.0. The predictive ability of the generated models was tested on a diverse group of chemicals including polychlorinated/brominated biphenyls, dioxins/furans, ethers, polyaromatic hydrocarbons with fused heterocyclic rings (i.e. phenoxathiins, thianthrenes and dibenzothiophenes) and polyaromatic hydrocarbons (i.e. halogenated naphthalenes and phenanthrenes) with no AhR binding data. For the external set chemicals, the structural coverage of the generated models was 90% and 89% for TCDD and TCDF-like effects, respectively.

  10. Variation in plant defense suppresses herbivore performance

    Science.gov (United States)

    Pearse, Ian; Paul, Ryan; Ode, Paul J.

    2018-01-01

    Defensive variability of crops and natural systems can alter herbivore communities and reduce herbivory. However, it is still unknown how defense variability translates into herbivore suppression. Nonlinear averaging and constraints in physiological tracking (also more generally called time-dependent effects) are the two mechanisms by which defense variability might impact herbivores. We conducted a set of experiments manipulating the mean and variability of a plant defense, showing that defense variability does suppress herbivore performance and that it does so through physiological tracking effects that cannot be explained by nonlinear averaging. While nonlinear averaging predicted higher or the same herbivore performance on a variable defense than on an invariable defense, we show that variability actually decreased herbivore performance and population growth rate. Defense variability reduces herbivore performance in a way that is more than the average of its parts. This is consistent with constraints in physiological matching of detoxification systems for herbivores experiencing variable toxin levels in their diet and represents a more generalizable way of understanding the impacts of variability on herbivory. Increasing defense variability in croplands at a scale encountered by individual herbivores can suppress herbivory, even if that is not anticipated by nonlinear averaging.

  11. Tactile defensiveness and stereotyped behaviors.

    Science.gov (United States)

    Baranek, G T; Foster, L G; Berkson, G

    1997-02-01

    This study explores the constructs of stereotyped behaviors (e.g., repetitive motor patterns, object manipulations, behavioral rigidities) and tactile defensiveness as relevant to occupational therapy theory and practice and attempts to test their purported relationships in children with developmental disabilities. Twenty-eight children with developmental disabilities and autism were assessed on eight factors of stereotyped behavior via a questionnaire and by four measures of tactile defensiveness. The subjects' scores from the questionnaire were correlated with their scores on the tactile defensiveness measures to see what, if any, relationship among these behaviors exists. Significant relationships emerged from the data, indicating that subjects with higher levels of tactile defensiveness were also more likely to evidence rigid or inflexible behaviors, repetitive verbalizations, visual stereotypes, and abnormal focused affections that are often associated with autism. No significant association was found between motor and object stereotypes and tactile defensiveness. These relationships could not be explained solely by maturational factors. The results suggest that clinicians should include observations of stereotyped behaviors, particularly behavioral rigidities, in conjunction with assessments of sensory defensiveness because these are related phenomena that may pose unique challenges for children with developmental disabilities and autism. Further study is needed to determine the causal mechanisms responsible for these relationships.

  12. Mode of Action and Human Relevance Analysis for Nuclear Receptor-Mediated Liver Toxicity: A Case Study with Phenobarbital as a Model Constitutive Androstane Receptor (CAR) Activator

    Science.gov (United States)

    The constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are key nuclear receptors involved in the regulation of cellular responses. to exposure to many xenobiotics and various physiological processes. Phenobarbital (PB) is a non­ genotoxic i...

  13. Mood States Associated with Induced Defensiveness.

    Science.gov (United States)

    Jaderlund, Natasha Slesnick; Waldron, Holly Barrett

    1994-01-01

    Compared effects of neutral and defensive mood induction in 70 students reporting conflicted versus nonconflicted families for presence of hostility, aggression, fear, anxiety, and sadness. Found that defensive students from high-conflict families reported stronger negative emotions than did neutral high-conflict and defensive low-conflict…

  14. 22 CFR 120.9 - Defense service.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Defense service. 120.9 Section 120.9 Foreign... Defense service. (a) Defense service means: (1) The furnishing of assistance (including training) to..., educational, or information publications and media of all kinds, training aid, orientation, training exercise...

  15. Cellular Homeostasis and Antioxidant Response in Epithelial HT29 Cells on Titania Nanotube Arrays Surface

    Directory of Open Access Journals (Sweden)

    Rabiatul Basria SMN Mydin

    2017-01-01

    Full Text Available Cell growth and proliferative activities on titania nanotube arrays (TNA have raised alerts on genotoxicity risk. Present toxicogenomic approach focused on epithelial HT29 cells with TNA surface. Fledgling cell-TNA interaction has triggered G0/G1 cell cycle arrests and initiates DNA damage surveillance checkpoint, which possibly indicated the cellular stress stimuli. A profound gene regulation was observed to be involved in cellular growth and survival signals such as p53 and AKT expressions. Interestingly, the activation of redox regulator pathways (antioxidant defense was observed through the cascade interactions of GADD45, MYC, CHECK1, and ATR genes. These mechanisms furnish to protect DNA during cellular division from an oxidative challenge, set in motion with XRRC5 and RAD50 genes for DNA damage and repair activities. The cell fate decision on TNA-nanoenvironment has been reported to possibly regulate proliferative activities via expression of p27 and BCL2 tumor suppressor proteins, cogent with SKP2 and BCL2 oncogenic proteins suppression. Findings suggested that epithelial HT29 cells on the surface of TNA may have a positive regulation via cell-homeostasis mechanisms: a careful circadian orchestration between cell proliferation, survival, and death. This nanomolecular knowledge could be beneficial for advanced medical applications such as in nanomedicine and nanotherapeutics.

  16. Defense waste management plan

    International Nuclear Information System (INIS)

    1983-06-01

    Defense high-level waste (HLW) and defense transuranic (TRU) waste are in interim storage at three sites, namely: at the Savannah River Plant, in South Carolina; at the Hanford Reservation, in Washington; and at the Idaho National Engineering Laboratory, in Idaho. Defense TRU waste is also in interim storage at the Oak Ridge National Laboratory, in Tennessee; at the Los Alamos National Laboratory, in New Mexico; and at the Nevada Test Site, in Nevada. (Figure E-2). This document describes a workable approach for the permanent disposal of high-level and transuranic waste from atomic energy defense activities. The plan does not address the disposal of suspect waste which has been conservatively considered to be high-level or transuranic waste but which can be shown to be low-level waste. This material will be processed and disposed of in accordance with low-level waste practices. The primary goal of this program is to utilize or dispose of high-level and transuranic waste routinely, safely, and effectively. This goal will include the disposal of the backlog of stored defense waste. A Reference Plan for each of the sites describes the sequence of steps leading to permanent disposal. No technological breakthroughs are required to implement the reference plan. Not all final decisions concerning the activities described in this document have been made. These decisions will depend on: completion of the National Environmental Policy Act process, authorization and appropriation of funds, agreements with states as appropriate, and in some cases, the results of pilot plant experiments and operational experience. The major elements of the reference plan for permanent disposal of defense high-level and transuranic waste are summarized

  17. The methodological defense of realism scrutinized.

    Science.gov (United States)

    Wray, K Brad

    2015-12-01

    I revisit an older defense of scientific realism, the methodological defense, a defense developed by both Popper and Feyerabend. The methodological defense of realism concerns the attitude of scientists, not philosophers of science. The methodological defense is as follows: a commitment to realism leads scientists to pursue the truth, which in turn is apt to put them in a better position to get at the truth. In contrast, anti-realists lack the tenacity required to develop a theory to its fullest. As a consequence, they are less likely to get at the truth. My aim is to show that the methodological defense is flawed. I argue that a commitment to realism does not always benefit science, and that there is reason to believe that a research community with both realists and anti-realists in it may be better suited to advancing science. A case study of the Copernican Revolution in astronomy supports this claim. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Priming of antiherbivore defensive responses in plants

    Institute of Scientific and Technical Information of China (English)

    Jinwon Kim; Gary W.Felton

    2013-01-01

    Defense priming is defined as increased readiness of defense induction.A growing body of literature indicates that plants (or intact parts of a plant) are primed in anticipation of impending environmental stresses,both biotic and abiotic,and upon the following stimulus,induce defenses more quickly and strongly.For instance,some plants previously exposed to herbivore-inducible plant volatiles (HIPVs) from neighboring plants under herbivore attack show faster or stronger defense activation and enhanced insect resistance when challenged with secondary insect feeding.Research on priming of antiherbivore defense has been limited to the HIPV-mediated mechanism until recently,but significant advances were made in the past three years,including non-HIPV-mediated defense priming,epigenetic modifications as the molecular mechanism of priming,and others.It is timely to consider the advances in research on defense priming in the plantinsect interactions.

  19. Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Poulomi; Keating, Aileen F., E-mail: akeating@iastate.edu

    2012-06-15

    The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants. -- Highlights: ► Summary of ovotoxicant action during ovotoxicity. ► Discussion of impact of biotransformation on chemical toxicity. ► Identification of knowledge gaps in chemical metabolism.

  20. Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics

    Directory of Open Access Journals (Sweden)

    Francesco Gatto

    2016-07-01

    Full Text Available Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.

  1. Impact of environmental exposures on ovarian function and role of xenobiotic metabolism during ovotoxicity

    International Nuclear Information System (INIS)

    Bhattacharya, Poulomi; Keating, Aileen F.

    2012-01-01

    The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants. -- Highlights: ► Summary of ovotoxicant action during ovotoxicity. ► Discussion of impact of biotransformation on chemical toxicity. ► Identification of knowledge gaps in chemical metabolism.

  2. Differential stimulation of antioxidant defense in various organs of mice after whole body exposure to low-dose gamma radiation

    International Nuclear Information System (INIS)

    Pathak, C.M.; Avti, P.K.; Khanduja, K.L.; Sharma, S.C.

    2007-01-01

    It has been generally considered that any dose of ionizing radiation is detrimental to the living organisms, however low the radiation dose may be. The much relied upon 'Linear-No-Threshold' (LNT) hypothesis dose not have any convincing experimental evidence regarding the damaging effects at very low-doses and low-dose rates. Generally, the deleterious biological effects have been inferred theoretically by extrapolating the known effects of high radiation dose to low-dose range. Recently, it has been reported that the living organisms do not respond to ionizing radiations in a linear manner in the low-dose range 0.01-0.50 Gy and rather restore the homeostasis both in-vivo and in-vitro by normal physiological mechanisms such as, cellular and DNA repair processes, immune reactions, antioxidant defense, adaptive responses, activation of immune functions; stimulation of growth etc. In this study, we have attempted to find: (i) the critical radiation dose range and the post irradiation period during which the antioxidant defense systems in the lungs, liver and kidneys remain stimulated; and (ii) to evaluate the degree to which these defense mechanisms remain stimulated in these organs after whole body exposure of the animal to low-dose radiation

  3. Policy implications of the Strategic Defense Initiative

    International Nuclear Information System (INIS)

    Goodwin, R.C.

    1991-01-01

    Specific topics include: the technological feasibility of proposed components and architectures; the compatibility of the proposed systems with existing and proposed arms control agreements, with special emphasis upon the ABM Treaty, Outer Space Treaty, the Defense and Space Treaty, and the START Treaty; the compatibility of proposed systems with classical warfare doctrine and the four modern strategic nuclear doctrines of Massive Retaliation, Assured Destruction, Countervailing and Flexible Response; the economics of strategic defense including an assessment of overall governmental spending, of the suballocation for defense, and of the feasibility of defensive systems which are cost-effective at the margin; and, in summary, an assessment of the New Strategic Concept which balances arms control, offensive forces, and defensive forces. This study falls within the realm of defense policy analysis in that it attempts to determine whether the administration's proposed Strategic Defense Initiative, as well as the long-term strategic defensive systems derived from SDI research, constitute efficient, desirable allocation of scarce government resources - especially in a period of seemingly relaxed superpower tensions and numerous demands upon those resources

  4. Acetaminophen induces xenobiotic-metabolizing enzymes in rat: Impact of a uranium chronic exposure.

    Science.gov (United States)

    Rouas, Caroline; Souidi, Maâmar; Grandcolas, Line; Grison, Stephane; Baudelin, Cedric; Gourmelon, Patrick; Pallardy, Marc; Gueguen, Yann

    2009-11-01

    The extensive use of uranium in civilian and military applications increases the risk of human chronic exposure. Uranium is a slightly radioactive heavy metal with a predominantly chemical toxicity, especially in kidney but also in liver. Few studies have previously shown some effects of uranium on xenobiotic-metabolizing enzymes (XME) that might disturb drug pharmacokinetic. The aim of this study was to determine whether a chronic (9 months) non-nephrotoxic low dose exposure to depleted uranium (DU, 1mg/rat/day) could modify the liver XME, using a single non-hepatotoxic acetaminophen (APAP) treatment (50mg/kg). Most of XME analysed were induced by APAP treatment at the gene expression level but at the protein level only CYP3A2 was significantly increased 3h after APAP treatment in DU-exposed rats whereas it remained at a basal level in unexposed rats. In conclusion, these results showed that a chronic non-nephrotoxic DU exposure specially modify CYP3A2 after a single therapeutic APAP treatment. Copyright © 2009 Elsevier B.V. All rights reserved.

  5. Neural and Cellular Mechanisms of Fear and Extinction Memory Formation

    Science.gov (United States)

    Orsini, Caitlin A.; Maren, Stephen

    2012-01-01

    Over the course of natural history, countless animal species have evolved adaptive behavioral systems to cope with dangerous situations and promote survival. Emotional memories are central to these defense systems because they are rapidly acquired and prepare organisms for future threat. Unfortunately, the persistence and intrusion of memories of fearful experiences are quite common and can lead to pathogenic conditions, such as anxiety and phobias. Over the course of the last thirty years, neuroscientists and psychologists alike have attempted to understand the mechanisms by which the brain encodes and maintains these aversive memories. Of equal interest, though, is the neurobiology of extinction memory formation as this may shape current therapeutic techniques. Here we review the extant literature on the neurobiology of fear and extinction memory formation, with a strong focus on the cellular and molecular mechanisms underlying these processes. PMID:22230704

  6. Application of Various Statistical Models to Explore Gene-Gene Interactions in Folate, Xenobiotic, Toll-Like Receptor and STAT4 Pathways that Modulate Susceptibility to Systemic Lupus Erythematosus.

    Science.gov (United States)

    Rupasree, Yedluri; Naushad, Shaik Mohammad; Varshaa, Ravi; Mahalakshmi, Govindaraj Swathika; Kumaraswami, Konda; Rajasekhar, Liza; Kutala, Vijay Kumar

    2016-02-01

    In view of our previous studies showing an independent association of genetic polymorphisms in folate, xenobiotic, and toll-like receptor (TLR) pathways with the risk for systemic lupus erythematosus (SLE), we have developed three statistical models to delineate complex gene-gene interactions between folate, xenobiotic, TLR, and signal transducer and activator of transcription 4 (STAT4) signaling pathways in association with the molecular pathophysiology of SLE. We developed additive, multifactor dimensionality reduction (MDR), and artificial neural network (ANN) models. The additive model, although the simplest, suggested a moderate predictability of 30 polymorphisms of these four pathways (area under the curve [AUC] 0.66). MDR analysis revealed significant gene-gene interactions among glutathione-S-transferase (GST)T1 and STAT4 (rs3821236 and rs7574865) polymorphisms, which account for moderate predictability of SLE. The MDR model for specific auto-antibodies revealed the importance of gene-gene interactions among cytochrome P450, family1, subfamily A, polypeptide 1 (CYP1A1) m1, catechol-O-methyltransferase (COMT) H108L, solute carrier family 19 (folate transporter), member 1 (SLC19A1) G80A, estrogen receptor 1 (ESR1), TLR5, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), thymidylate synthase (TYMS). and STAT4 polymorphisms. The ANN model for disease prediction showed reasonably good predictability of SLE risk with 30 polymorphisms (AUC 0.76). These polymorphisms contribute towards the production of SSB and anti-dsDNA antibodies to the extent of 48 and 40%, respectively, while their contribution for the production of antiRNP, SSA, and anti-cardiolipin antibodies varies between 20 and 30%. The current study highlighted the importance of genetic polymorphisms in folate, xenobiotic, TLR, and STAT4 signaling pathways as moderate predictors of SLE risk and delineates the molecular pathophysiology associated with these single nucleotide

  7. Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

    Science.gov (United States)

    Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

  8. The Integration Role of European Defense Procurement in Achieving a More Competitive and Stronger European Defense Equipment Market

    Science.gov (United States)

    2015-06-01

    and systems, even monopolistic ) essence of the supply side of the defense market . There are only a few suppliers that can meet today’s complex...DEFENSE PROCUREMENT IN ACHIEVING A MORE COMPETITIVE AND STRONGER EUROPEAN DEFENSE EQUIPMENT MARKET by Kiril O. Angelov June 2015 Thesis Advisor...COMPETITIVE AND STRONGER EUROPEAN DEFENSE EQUIPMENT MARKET 5. FUNDING NUMBERS 6. AUTHOR(S) Kiril O. Angelov 7. PERFORMING ORGANIZATION NAME(S) AND

  9. Microfilament Contraction Promotes Rounding of Tunic Slices: An Integumentary Defense System in the Colonial Ascidian Aplidium yamazii.

    Science.gov (United States)

    Hirose, E; Ishii, T

    1995-08-01

    In Aplidium yamazii, when a slice of a live colony (approximately 0.5 mm thick) was incubated in seawater for 12 h, the slice became a round tunic fragment. This tunic rounding was inhibited by freezing of the slices, incubation with Ca2+-Mg2+ -free seawater, or addition of cytochalasin B. Staining of microfilaments in the slices with phalloidin-FITC showed the existence of a cellular network in the tunic. Contraction of this cellular network probably promotes rounding of the tunic slice. In electron microscopic observations, a new tunic cuticle regenerated at the surface of the round tunic fragments; the tunic cuticle did not regenerate in newly sliced specimens nor in specimens in which rounding was experimentally inhibited. Based on these results, an integumentary defense system is proposed in this species as follows. (1) When the colony is wounded externally, contraction of the cellular network promotes tunic contraction around the wound. (2) The wound is almost closed by tunic contraction. (3) Tunic contraction increases the density of the filamentous components of the tunic at the wound, and it may accelerate the regeneration of tunic cuticle there.

  10. Report to the Congressional Defense Committees: Status of the Department of Defense's Business Transformation Efforts

    National Research Council Canada - National Science Library

    2008-01-01

    ...). It directs the Secretary of Defense to provide the Congressional Defense Committees with an annual report on the Department's business transformation efforts and compliance with the requirements of the law...

  11. 22 CFR 120.6 - Defense article.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Defense article. 120.6 Section 120.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL TRAFFIC IN ARMS REGULATIONS PURPOSE AND DEFINITIONS § 120.6 Defense article. Defense article means any item or technical data designated in § 121.1 of this subchapter...

  12. Vaccination of koalas (Phascolarctos cinereus) with a recombinant chlamydial major outer membrane protein adjuvanted with poly I:C, a host defense peptide and polyphosphazine, elicits strong and long lasting cellular and humoral immune responses.

    Science.gov (United States)

    Khan, Shahneaz Ali; Waugh, Courtney; Rawlinson, Galit; Brumm, Jacqui; Nilsson, Karen; Gerdts, Volker; Potter, Andrew; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

    2014-10-07

    Chlamydial infections are wide spread in koalas across their range and a solution to this debilitating disease has been sought for over a decade. Antibiotics are the currently accepted therapeutic measure, but are not an effective treatment due to the asymptomatic nature of some infections and a low efficacy rate. Thus, a vaccine would be an ideal way to address this infectious disease threat in the wild. Previous vaccine trials have used a three-dose regimen; however this is very difficult to apply in the field as it would require multiple capture events, which are stressful and invasive processes for the koala. In addition, it requires skilled koala handlers and a significant monetary investment. To overcome these challenges, in this study we utilized a polyphosphazine based poly I:C and a host defense peptide adjuvant combined with recombinant chlamydial major outer membrane protein (rMOMP) antigen to induce long lasting (54 weeks) cellular and humoral immunity in female koalas with a novel single immunizing dose. Immunized koalas produced a strong IgG response in plasma, as well as at mucosal sites. Moreover, they showed high levels of C. pecorum specific neutralizing antibodies in the plasma as well as vaginal and conjunctival secretions. Lastly, Chlamydia-specific lymphocyte proliferation responses were produced against both whole chlamydial elementary bodies and rMOMP protein, over the 12-month period. The results of this study suggest that a single dose rMOMP vaccine incorporating a poly I:C, host defense peptide and polyphosphazine adjuvant is able to stimulate both arms of the immune system in koalas, thereby providing an alternative to antibiotic treatment and/or a three-dose vaccine regime. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. STRUCTURING DEFENSE POLICIES FOR THE DEFENSE AND CONTROL OF STRATEGIC NATURAL RESOURCES

    Directory of Open Access Journals (Sweden)

    GABRIEL DE PAULA

    2018-02-01

    Full Text Available During the last decade, there has been a reconfiguration of a new geopolitical scenario. This new scenario focus on the assessment about strategic natural resources (oil, gas and water, and less important, biodiversity, food and fertile land and its spatial condition (the resources are in a territory which is politically defined by boundaries or zone of influence. The scenario in South America is not far from that international dynamic, which affects in different levels the strategic lines of national defense policies in Brazil, Venezuela and (in less degree Argentina. In that way, competence and confluence scenarios are defined, which may have variability in the conflict level, such as a military confrontation or cooperation mechanisms (as the South America Defense Council. These scenarios are geographically located in: oil and gas basins, Amazonas, water resources, Antarctica, Atlantic Ocean and fertile land. The defense strategies set parameters for the design of the armed forces, as far as the hypothesis of conflicts above-mentioned applied. Thus, the defense administration reconfigured the capabilities of the Armed Forces (logistic, personnel, doctrine, resources, surveillance, in order to achieve the mission of control the regions where availability of natural resources exists.

  14. Immune defense in leaf-cutting ants

    DEFF Research Database (Denmark)

    Armitage, Sophie A O; Broch, Jens F; Marín, Hermogenes Fernández

    2011-01-01

    To ameliorate the impact of disease, social insects combine individual innate immune defenses with collective social defenses. This implies that there are different levels of selection acting on investment in immunity, each with their own trade-offs. We present the results of a cross......-fostering experiment designed to address the influences of genotype and social rearing environment upon individual and social immune defenses. We used a multiply mating leaf-cutting ant, enabling us to test for patriline effects within a colony, as well as cross-colony matriline effects. The worker's father influenced...... both individual innate immunity (constitutive antibacterial activity) and the size of the metapleural gland, which secretes antimicrobial compounds and functions in individual and social defense, indicating multiple mating could have important consequences for both defense types. However, the primarily...

  15. Coactivator PGC-1α regulates the fasting inducible xenobiotic-metabolizing enzyme CYP2A5 in mouse primary hepatocytes

    International Nuclear Information System (INIS)

    Arpiainen, Satu; Jaervenpaeae, Sanna-Mari; Manninen, Aki; Viitala, Pirkko; Lang, Matti A.; Pelkonen, Olavi; Hakkola, Jukka

    2008-01-01

    The nutritional state of organisms and energy balance related diseases such as diabetes regulate the metabolism of xenobiotics such as drugs, toxins and carcinogens. However, the mechanisms behind this regulation are mostly unknown. The xenobiotic-metabolizing cytochrome P450 (CYP) 2A5 enzyme has been shown to be induced by fasting and by glucagon and cyclic AMP (cAMP), which mediate numerous fasting responses. Peroxisome proliferator-activated receptor γ coactivator (PGC)-1α triggers many of the important hepatic fasting effects in response to elevated cAMP levels. In the present study, we were able to show that cAMP causes a coordinated induction of PGC-1α and CYP2A5 mRNAs in murine primary hepatocytes. Furthermore, the elevation of the PGC-1α expression level by adenovirus mediated gene transfer increased CYP2A5 transcription. Co-transfection of Cyp2a5 5' promoter constructs with the PGC-1α expression vector demonstrated that PGC-1α is able to activate Cyp2a5 transcription through the hepatocyte nuclear factor (HNF)-4α response element in the proximal promoter of the Cyp2a5 gene. Chromatin immunoprecipitation assays showed that PGC-1α binds, together with HNF-4α, to the same region at the Cyp2a5 proximal promoter. In conclusion, PGC-1α mediates the expression of CYP2A5 induced by cAMP in mouse hepatocytes through coactivation of transcription factor HNF-4α. This strongly suggests that PGC-1α is the major factor mediating the fasting response of CYP2A5

  16. Ballistic Missile Defense in Europe

    OpenAIRE

    Sarihan, Ali; Bush, Amy; Summers, Lawrence; Thompson, Brent; Tomasszewski, Steven

    2009-01-01

    This paper will build on ballistic missile defense in Europe. In the first part, a brief historical overview will place the current public management issue into light. This is followed by a discussion of the main actors in the international debate, the problems that arise and the available options and recommendations to address missile defense. In the second part, differences between George W. Bush and Barack H. Obama will analyze under the title “Ballistic Missile Defense in Europe: Evolving...

  17. Defense Logistics Agency Revenue Eliminations

    National Research Council Canada - National Science Library

    1996-01-01

    The issue of revenue eliminations was identified during our work on the Defense Logistics Agency portion of the Audit of Revenue Accounts in the FY 1996 Financial Statements of the Defense Business Operations Fund...

  18. Defense Dollars and Sense: A Common Cause Guide to the Defense Budget Process.

    Science.gov (United States)

    Rovner, Mark

    Designed to increase public awareness of military spending, this 5-part guide examines the process and problems of preparing the national defense budget. The publication begins with a brief overview of the 1984 defense budget. Major military programs, trends in budgeting, and key concerns in budget formulation are explored. Graphs and charts…

  19. Ballistic Missile Defense

    OpenAIRE

    Mayer, Michael

    2011-01-01

    At the 2010 NATO summit in Lisbon, the alliance decided to move forward on the development of a territorial ballistic missile defense (BMD) system and explore avenues for cooperation with Russia in this endeavor. Substantial progress on BMD has been made over the past decade, but some questions remain regarding the ultimate strategic utility of such a system and whether its benefi ts outweigh the possible opportunity costs. Missile defense has been a point of contention between the US and its...

  20. Defensive Federal Litigation

    Science.gov (United States)

    1998-08-20

    requires that all affirmative defenses be pleaded in the answer. The rule lists 19 specific affirmative defenses, such as estoppel , laches, res judicata...Brown, 22 F.3d 516 (2d Cir. 1994); Poole v. Rourke, 779 F. Supp. 1546 (E.D. Cal. 1991). 3-40 potential collateral estoppel .4. effect of the district...the back pay claim, which was over $10,000, to the Court of Claims. The court of appeals found that ൸Collateral estoppel prohibits relitigation of

  1. Website Fingerprinting Defenses at the Application Layer

    Directory of Open Access Journals (Sweden)

    Cherubin Giovanni

    2017-04-01

    Full Text Available Website Fingerprinting (WF allows a passive network adversary to learn the websites that a client visits by analyzing traffic patterns that are unique to each website. It has been recently shown that these attacks are particularly effective against .onion sites, anonymous web servers hosted within the Tor network. Given the sensitive nature of the content of these services, the implications of WF on the Tor network are alarming. Prior work has only considered defenses at the client-side arguing that web servers lack of incentives to adopt countermeasures. Furthermore, most of these defenses have been designed to operate on the stream of network packets, making practical deployment difficult. In this paper, we propose two application-level defenses including the first server-side defense against WF, as .onion services have incentives to support it. The other defense is a lightweight client-side defense implemented as a browser add-on, improving ease of deployment over previous approaches. In our evaluations, the server-side defense is able to reduce WF accuracy on Tor .onion sites from 69.6% to 10% and the client-side defense reduces accuracy from 64% to 31.5%.

  2. The Art and Science of Defense Logistics

    Science.gov (United States)

    1995-04-01

    The Art And Science Of Defense Logistics CSC 1995 SUBJECT AREA - Logistics THE ART AND SCIENCE OF DEFENSE LOGISTICS...Government EXECUTIVE SUMMARY Title: The Art and Science of Defense Logistics Author: Major S. I. Schuler, USMC Research Questions: 1...00-1995 4. TITLE AND SUBTITLE The Art And Science Of Defense Logistics 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6

  3. Mobilization and Defense Management Technical Reports Series. A Framework for Increasing Defense Production by Reducing Perceived Opportunity Costs.

    Science.gov (United States)

    1983-05-01

    advertising. Traditionally defense marketing and advertising focused on decision makers within the defense conuunity and Congress. While it appears that...focus may be- starting to change, marketing and advertising remain highly directed and concentrated in defense oriented media. marketing was oriented to

  4. Cellular gravity

    NARCIS (Netherlands)

    F.C. Gruau; J.T. Tromp (John)

    1999-01-01

    textabstractWe consider the problem of establishing gravity in cellular automata. In particular, when cellular automata states can be partitioned into empty, particle, and wall types, with the latter enclosing rectangular areas, we desire rules that will make the particles fall down and pile up on

  5. Space-based ballistic-missile defense

    International Nuclear Information System (INIS)

    Bethe, H.A.; Garwin, R.L.; Gottfried, K.; Kendall, H.W.

    1984-01-01

    This article, based on a forthcoming book by the Union for Concerned Scientists, focuses on the technical aspects of the issue of space-based ballistic-missile defense. After analysis, the authors conclude that the questionable performance of the proposed defense, the ease with which it could be overwhelmed or circumvented, and its potential as an antisatellite system would cause grievous damage to the security of the US if the Strategic Defense Initiative were to be pursued. The path toward greater security lies in quite another direction, they feel. Although research on ballistic-missile defense should continue at the traditional level of expenditure and within the constraints of the ABM Treaty, every effort should be made to negotiate a bilateral ban on the testing and use of space weapons. The authors think it is essential that such an agreement cover all altitudes, because a ban on high-altitude antisatellite weapons alone would not viable if directed energy weapons were developed for ballistic-missile defense. Further, the Star Wars program, unlikely ever to protect the entire nation against a nuclear attack, would nonetheless trigger a major expansion of the arms race

  6. Effects and mechanisms of 3α,5α,-THP on emotion, motivation, and reward functions involving pregnane xenobiotic receptor

    Directory of Open Access Journals (Sweden)

    Cheryl A Frye

    2012-01-01

    Full Text Available Progestogens [progesterone (P4 and its products] play fundamental roles in the development and/or function of the central nervous system during pregnancy. We, and others, have investigated the role of pregnane neurosteroids for a plethora of functional effects beyond their pro-gestational processes. Emerging findings regarding the effects, mechanisms, and sources of neurosteroids have challenged traditional dogma about steroid action. How the P4 metabolite and neurosteroid, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP, influences cellular functions and behavioral processes involved in emotion/affect, motivation, and reward, is the focus of the present review. To further understand these processes, we have utilized an animal model assessing the effects, mechanisms, and sources of 3α,5α-THP. In the ventral tegmental area (VTA, 3α,5α-THP has actions to facilitate affective, and motivated, social behaviors through non-traditional targets, such as GABA, glutamate, and dopamine receptors. 3α,5α-THP levels in the midbrain VTA both facilitate, and/or are enhanced by, affective and social behavior. The pregnane xenobiotic receptor (PXR mediates the production of, and/or metabolism to, various neurobiological factors. PXR is localized to the midbrain VTA of rats. The role of PXR to influence 3α,5α-THP production from central biosynthesis, and/or metabolism of peripheral P4, in the VTA, as well as its role to facilitate, or be increased by, affective/social behaviors is under investigation. Investigating novel behavioral functions of 3α,5α-THP extends our knowledge of the neurobiology of progestogens, relevant for affective/social behaviors, and their connections to systems that regulate affect and motivated processes, such as those important for stress regulation and neuropsychiatric disorders (anxiety, depression, schizophrenia, drug dependence. Thus, further understanding of 3α,5α-THP’s role and mechanisms to enhance affective and motivated

  7. Report of the Defense Science Board/Defense Policy Board Task Force On Theater Missile Defense

    National Research Council Canada - National Science Library

    1996-01-01

    ... also tackled the controversial subject of the ABM Treaty and its effect on theater missile defenses Subsequent to its interim report, which expressed strong concerns about the demarcation path the US...

  8. Concentrations, patterns and metabolites of organochlorine pesticides in relation to xenobiotic phase I and II enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea

    International Nuclear Information System (INIS)

    Routti, Heli; Bavel, Bert van; Letcher, Robert J.; Arukwe, Augustine; Chu Shaogang; Gabrielsen, Geir W.

    2009-01-01

    The present study investigates the concentrations and patterns of organochlorine pesticides (OCPs) and their metabolites in liver and plasma of two ringed seal populations (Phoca hispida): lower contaminated Svalbard population and more contaminated Baltic Sea population. Among OCPs, p,p'-DDE and sum-chlordanes were the highest in concentration. With increasing hepatic contaminant concentrations and activities of xenobiotic-metabolizing enzymes, the concentrations of 3-methylsulfonyl-p,p'-DDE and the concentration ratios of pentachlorophenol/hexachlorobenzene increased, and the toxaphene pattern shifted more towards persistent Parlar-26 and -50 and less towards more biodegradable Parlar-44. Relative concentrations of the chlordane metabolites, oxychlordane and -heptachlorepoxide, to sum-chlordanes were higher in the seals from Svalbard compared to the seals from the Baltic, while the trend was opposite for cis- and trans-nonachlor. The observed differences in the OCP patterns in the seals from the two populations are probably related to the catalytic activity of xenobiotic-metabolizing enzymes, and also to differences in dietary exposure. - Contrasting patterns of organochlorine pesticides in two ringed seal populations.

  9. Concentrations, patterns and metabolites of organochlorine pesticides in relation to xenobiotic phase I and II enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea

    Energy Technology Data Exchange (ETDEWEB)

    Routti, Heli, E-mail: heli.routti@npolar.n [Norwegian Polar Institute, Polar Environmental Centre, 9296 Tromso (Norway); Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, 20014 Turku (Finland); Bavel, Bert van [MTM Research Centre, Orebro University, 70182 Orebro (Sweden); Letcher, Robert J. [Wildlife Toxicology and Disease Program, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3 (Canada); Arukwe, Augustine [Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim (Norway); Chu Shaogang [Wildlife Toxicology and Disease Program, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3 (Canada); Gabrielsen, Geir W. [Norwegian Polar Institute, Polar Environmental Centre, 9296 Tromso (Norway)

    2009-08-15

    The present study investigates the concentrations and patterns of organochlorine pesticides (OCPs) and their metabolites in liver and plasma of two ringed seal populations (Phoca hispida): lower contaminated Svalbard population and more contaminated Baltic Sea population. Among OCPs, p,p'-DDE and sum-chlordanes were the highest in concentration. With increasing hepatic contaminant concentrations and activities of xenobiotic-metabolizing enzymes, the concentrations of 3-methylsulfonyl-p,p'-DDE and the concentration ratios of pentachlorophenol/hexachlorobenzene increased, and the toxaphene pattern shifted more towards persistent Parlar-26 and -50 and less towards more biodegradable Parlar-44. Relative concentrations of the chlordane metabolites, oxychlordane and -heptachlorepoxide, to sum-chlordanes were higher in the seals from Svalbard compared to the seals from the Baltic, while the trend was opposite for cis- and trans-nonachlor. The observed differences in the OCP patterns in the seals from the two populations are probably related to the catalytic activity of xenobiotic-metabolizing enzymes, and also to differences in dietary exposure. - Contrasting patterns of organochlorine pesticides in two ringed seal populations.

  10. Impact of uranium (U) on the cellular glutathione pool and resultant consequences for the redox status of U.

    Science.gov (United States)

    Viehweger, Katrin; Geipel, Gerhard; Bernhard, Gert

    2011-12-01

    Uranium (U) as a redox-active heavy metal can cause various redox imbalances in plant cells. Measurements of the cellular glutathione/glutathione disulfide (GSH/GSSG) by HPLC after cellular U contact revealed an interference with this essential redox couple. The GSH content remained unaffected by 10 μM U whereas the GSSG level immediately increased. In contrast, higher U concentrations (50 μM) drastically raised both forms. Using the Nernst equation, it was possible to calculate the half-cell reduction potential of 2GSH/GSSG. In case of lower U contents the cellular redox environment shifted towards more oxidizing conditions whereas the opposite effect was obtained by higher U contents. This indicates that U contact causes a consumption of reduced redox equivalents. Artificial depletion of GSH by chlorodinitrobenzene and measuring the cellular reducing capacity by tetrazolium salt reduction underlined the strong requirement of reduced redox equivalents. An additional element of cellular U detoxification mechanisms is the complex formation between the heavy metal and carboxylic functionalities of GSH. Because two GSH molecules catalyze electron transfers each with one electron forming a dimer (GSSG) two UO(2) (2+) are reduced to each UO(2) (+) by unbound redox sensitive sulfhydryl moieties. UO(2) (+) subsequently disproportionates to UO(2) (2+) and U(4+). This explains that in vitro experiments revealed a reduction to U(IV) of only around 33% of initial U(VI). Cellular U(IV) was transiently detected with the highest level after 2 h of U contact. Hence, it can be proposed that these reducing processes are an important element of defense reactions induced by this heavy metal.

  11. NAD(P)H-dependent quinone oxidoreductase 1 (NQO1) and cytochrome P450 oxidoreductase (CYP450OR) differentially regulate menadione-mediated alterations in redox status, survival and metabolism in pancreatic β-cells.

    Science.gov (United States)

    Gray, Joshua P; Karandrea, Shpetim; Burgos, Delaine Zayasbazan; Jaiswal, Anil A; Heart, Emma A

    2016-11-16

    NQO1 (NAD(P)H-quinone oxidoreductase 1) reduces quinones and xenobiotics to less-reactive compounds via 2-electron reduction, one feature responsible for the role of NQO1 in antioxidant defense in several tissues. In contrast, NADPH cytochrome P450 oxidoreductase (CYP450OR), catalyzes the 1-electron reduction of quinones and xenobiotics, resulting in enhanced superoxide formation. However, to date, the roles of NQO1 and CYP450OR in pancreatic β-cell metabolism under basal conditions and oxidant challenge have not been characterized. Using NQO1 inhibition, over-expression and knock out, we have demonstrated that, in addition to protection of β-cells from toxic concentrations of the redox cycling quinone menadione, NQO1 also regulates the basal level of reduced-to-oxidized nucleotides, suggesting other role(s) beside that of an antioxidant enzyme. In contrast, over-expression of NADPH cytochrome P450 oxidoreductase (CYP450OR) resulted in enhanced redox cycling activity and decreased cellular viability, consistent with the enhanced generation of superoxide and H 2 O 2 . Basal expression of NQO1 and CYP450OR was comparable in isolated islets and liver. However, NQO1, but not CYP450OR, was strongly induced in β-cells exposed to menadione. NQO1 and CYP450OR exhibited a reciprocal preference for reducing equivalents in β-cells: while CYP450OR preferentially utilized NADPH, NQO1 primarily utilized NADH. Together, these results demonstrate that NQO1 and CYP450OR reciprocally regulate oxidant metabolism in pancreatic β-cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. 76 FR 22681 - Defense Logistics Agency (DLA) Address Directory

    Science.gov (United States)

    2011-04-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary Defense Logistics Agency (DLA) Address Directory AGENCY: Department of Defense. ACTION: Notice. SUMMARY: The Defense Logistics Agency (DLA) is updating... Directory: Defense Logistics Agency Headquarters, Andrew T. McNamara Building, 8725 John J. Kingman Road...

  13. Active Computer Network Defense: An Assessment

    Science.gov (United States)

    2001-04-01

    sufficient base of knowledge in information technology can be assumed to be working on some form of computer network warfare, even if only defensive in...the Defense Information Infrastructure (DII) to attack. Transmission Control Protocol/ Internet Protocol (TCP/IP) networks are inherently resistant to...aims to create this part of information superiority, and computer network defense is one of its fundamental components. Most of these efforts center

  14. Chemical Screening for Bioactivated Electrophilic Metabolites Using Alginate Immobilization of Metabolic Enzymes (AIME) (SOT)

    Science.gov (United States)

    The US EPA's ToxCast program is designed to assess chemical perturbations of molecular and cellular endpoints using a variety of high-throughput screening (HTS) assays. However, existing HTS assays have limited or no xenobiotic metabolism which could lead to a mischaracterization...

  15. 32 CFR 13.4 - Duties and responsibilities of the defense.

    Science.gov (United States)

    2010-07-01

    ... COMMISSIONS RESPONSIBILITIES OF THE CHIEF DEFENSE COUNSEL, DETAILED DEFENSE COUNSEL, AND CIVILIAN DEFENSE COUNSEL § 13.4 Duties and responsibilities of the defense. (a) Regular duties. The Defense shall perform... 32 National Defense 1 2010-07-01 2010-07-01 false Duties and responsibilities of the defense. 13.4...

  16. 78 FR 17176 - Federal Acquisition Regulation; Defense Base Act

    Science.gov (United States)

    2013-03-20

    ... Regulation; Defense Base Act AGENCIES: Department of Defense (DoD), General Services Administration (GSA... the Defense Base Act. DATES: Interested parties should submit written comments to the Regulatory... Act as extended by the Defense Base Act. II. Discussion and Analysis The Defense Base Act of 1941...

  17. Cellular MR Imaging

    Directory of Open Access Journals (Sweden)

    Michel Modo

    2005-07-01

    Full Text Available Cellular MR imaging is a young field that aims to visualize targeted cells in living organisms. In order to provide a different signal intensity of the targeted cell, they are either labeled with MR contrast agents in vivo or prelabeled in vitro. Either (ultrasmall superparamagnetic iron oxide [(USPIO] particles or (polymeric paramagnetic chelates can be used for this purpose. For in vivo cellular labeling, Gd3+- and Mn2+- chelates have mainly been used for targeted hepatobiliary imaging, and (USPIO-based cellular imaging has been focused on imaging of macrophage activity. Several of these magneto-pharmaceuticals have been FDA-approved or are in late-phase clinical trials. As for prelabeling of cells in vitro, a challenge has been to induce a sufficient uptake of contrast agents into nonphagocytic cells, without affecting normal cellular function. It appears that this issue has now largely been resolved, leading to an active research on monitoring the cellular biodistribution in vivo following transplantation or transfusion of these cells, including cell migration and trafficking. New applications of cellular MR imaging will be directed, for instance, towards our understanding of hematopoietic (immune cell trafficking and of novel guided (stem cell-based therapies aimed to be translated to the clinic in the future.

  18. Strengthening Nordic-Baltic Defense Capabilities

    DEFF Research Database (Denmark)

    Breitenbauch, Henrik Ø.

    2014-01-01

    and troubling challenge to the way international security has been structured in Europe since the end of the Cold War. While most of the existing defense cooperation with a view of strengthening defense capabilities has been carried out within the internationally renowned framework of NORDEFCO...

  19. 76 FR 71467 - Defense Federal Acquisition Regulation Supplement; Extension of Department of Defense Mentor...

    Science.gov (United States)

    2011-11-18

    ... Defense Mentor-Prot[eacute]g[eacute] Pilot Program (DFARS Case 2011-D050) AGENCY: Defense Acquisition... applications under the DoD Mentor-Prot[eacute]g[eacute] Pilot Program for new mentor-prot[eacute]g[eacute] agreements and the date mentors may incur costs and/or receive credit towards fulfilling their small business...

  20. 6 CFR 25.8 - Government contractor Defense.

    Science.gov (United States)

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Government contractor Defense. 25.8 Section 25.8...-TERRORISM BY FOSTERING EFFECTIVE TECHNOLOGIES § 25.8 Government contractor Defense. (a) Criteria for... applicability of the government contractor defense. In determining whether to issue such Certification, the...

  1. Programmable cellular arrays. Faults testing and correcting in cellular arrays

    International Nuclear Information System (INIS)

    Cercel, L.

    1978-03-01

    A review of some recent researches about programmable cellular arrays in computing and digital processing of information systems is presented, and includes both combinational and sequential arrays, with full arbitrary behaviour, or which can realize better implementations of specialized blocks as: arithmetic units, counters, comparators, control systems, memory blocks, etc. Also, the paper presents applications of cellular arrays in microprogramming, in implementing of a specialized computer for matrix operations, in modeling of universal computing systems. The last section deals with problems of fault testing and correcting in cellular arrays. (author)

  2. Biotransformation and induction: implications for toxicity, bioaccumulation and monitoring of environmental xenobiotics in fish

    International Nuclear Information System (INIS)

    Kleinow, K.M.; Melancon, M.J.; Lech, J.J.

    1987-01-01

    Biotransformation of xenobiotics in fish occurs by many of the same reactions as in mammals. These reactions have been shown to affect the bioaccumulation, persistence, residue dynamics, and toxicity of select chemicals in fish. P-450-dependent monooxygenase activity of fish can be induced by polycyclic aromatic hydrocarbons, but phenobarbital-type agents induce poorly, if at all. Fish monooxygenase activity exhibits ideal temperature compensation and sex-related variation. Induction of monooxygenase activity by polycyclic aromatic hydrocarbons can result in qualitative as well as quantitative changes in the metabolic profile of a chemical. Induction can also alter toxicity. In addition, multiple P-450 isozymes have been described for several fish species. The biotransformation productions of certain chemicals have been related to specific P-450 isozymes, and the formation of these products can be influenced by induction. Exposure of fish to low levels of certain environmental contaminants has resulted in induction of specific monooxygenase activities and monitoring of such activities has been suggested as a means of identifying areas of pollutant exposure in the wild

  3. Defense Primer: DOD Contractors

    Science.gov (United States)

    2017-02-10

    functions, from intelligence analysis or software development to landscaping or food service. Why does DOD use individual contractors? Going back to...that provide professional services, from research to management support. The bulk of contractors—more than 70%—provide products, and these include...10 U.S.C. Part IV: Service, Supply, and Procurement. CRS Products CRS In Focus IF10548, Defense Primer: U.S. Defense Industrial Base, by Daniel

  4. Defense Primer: The National Defense Budget Function (050)

    Science.gov (United States)

    2017-03-17

    individual policy activities. Subfunctions are assigned a numeric identifier (ending in a single digit ) related to the function to which they belong...operations, equipment repair, and maintenance of defense facilities, healthcare costs, and administration. 24% Military Personnel (MILPERS) Pay and

  5. Student Papers on Strategic Defense Initiative.

    Science.gov (United States)

    1985-01-01

    895. 3. "Scientific Canvas" AWST, p. 19. 4. Halliday, p. 548. 5. William Shiner, Lasers (New York: Mc Graw -Hill, 1980), p. 21. - 30...and Design. New York: Mc Graw -Hill, 1980. U.S. Department of Defense. The Strategic Defense Ini- tiative: Defensive Technologies Study. Washington...Armageddon," Armed Forces Journal, February 1983, p. 30. 7. David Baker, The Shape of Wars to Come (Cambridge: Patrick Stephens , Ltd, 1981), p. 109

  6. Mining the plant-herbivore interface with a leafmining Drosophila of Arabidopsis

    Science.gov (United States)

    Whiteman, Noah K.; Groen, Simon C.; Chevasco, Daniela; Bear, Ashley; Beckwith, Noor; Gregory, T. Ryan; Denoux, Carine; Mammarella, Nicole; Ausubel, Frederick M.; Pierce, Naomi E.

    2010-01-01

    Experimental infections of Arabidopsis thaliana (Arabidopsis) with genomically characterized plant pathogens such as Pseudomonas syringae have facilitated dissection of canonical eukaryotic defense pathways and parasite virulence factors. Plants are also attacked by herbivorous insects, and the development of an ecologically relevant genetic model herbivore that feeds on Arabidopsis will enable the parallel dissection of host defense and reciprocal resistance pathways such as those involved in xenobiotic metabolism. An ideal candidate is Scaptomyza flava, a drosophilid fly whose leafmining larvae are true herbivores that can be found in nature feeding on Arabidopsis and other crucifers. Here we describe the eukaryotic life cycle of S. flava on Arabidopsis, and use multiple approaches to characterize the response of Arabidopsis to S. flava attack. Oviposition choice tests and growth performance assays on different Arabidopsis ecotypes, defense-related mutants, and hormone and chitin-treated plants revealed significant differences in host preference and variation in larval performance across Arabidopsis accessions. The jasmonate (JA) and glucosinolate pathways in Arabidopsis are important in mediating quantitative resistance against S. flava, and priming with JA or chitin resulted in increased resistance. Expression of xenobiotic detoxification genes was reduced in S. flava larvae reared on Arabidopsis JA signaling mutants, and increased in plants pre-treated with chitin. These results and future research directions are discussed in the context of developing a genetic model system to analyze insect/plant interactions. PMID:21073583

  7. Functioning of Microsomal Cytochrome P450s: Murburn Concept Explains the Metabolism of Xenobiotics in Hepatocytes.

    Science.gov (United States)

    Manoj, Kelath Murali; Parashar, Abhinav; Gade, Sudeep K; Venkatachalam, Avanthika

    2016-01-01

    Using oxygen and NADPH, the redox enzymes cytochrome P450 (CYP) and its reductase (CPR) work in tandem to carry out the phase I metabolism of a vast majority of drugs and xenobiotics. As per the erstwhile understanding of the catalytic cycle, binding of the substrate to CYP's heme distal pocket allows CPR to pump electrons through a CPR-CYP complex. In turn, this trigger (a thermodynamic push of electrons) leads to the activation of oxygen at CYP's heme-center, to give Compound I, a two-electron deficient enzyme reactive intermediate. The formation of diffusible radicals and reactive oxygen species (DROS, hitherto considered an undesired facet of the system) was attributed to the heme-center. Recently, we had challenged these perceptions and proposed the murburn ("mured burning" or "mild unrestricted burning") concept to explain heme enzymes' catalytic mechanism, electron-transfer phenomena and the regulation of redox equivalents' consumption. Murburn concept incorporates a one-electron paradigm, advocating obligatory roles for DROS. The new understanding does not call for high-affinity substrate-binding at the heme distal pocket of the CYP (the first and the most crucial step of the erstwhile paradigm) or CYP-CPR protein-protein complexations (the operational backbone of the erstwhile cycle). Herein, the dynamics of reduced nicotinamide nucleotides' consumption, peroxide formation and depletion, product(s) formation, etc. was investigated with various controls, by altering reaction variables, environments and through the incorporation of diverse molecular probes. In several CYP systems, control reactions lacking the specific substrate showed comparable or higher peroxide in milieu, thereby discrediting the foundations of the erstwhile hypothesis. The profiles obtained by altering CYP:CPR ratios and the profound inhibitions observed upon the incorporation of catalytic amounts of horseradish peroxidase confirm the obligatory roles of DROS in milieu, ratifying

  8. Inducible defenses against herbivory and fouling in seaweeds

    Science.gov (United States)

    Pereira, Renato Crespo; Costa, Erica da Silva; Sudatti, Daniela Bueno; da Gama, Bernardo Antonio Perez

    2017-04-01

    Secondary metabolites play an important ecological role as a defense mechanism in seaweeds. Chemical defenses are well known to change in response to herbivory, but other driving factors, either biotic or abiotic, are often neglected. Epibiosis may not only reduce seaweed fitness, but also increase attractiveness to consumers, and thus defense production should also be triggered by epibionts. In this study, three Southwestern Atlantic seaweeds, Gracilaria cearensis, Pterocladiella capillacea (Rhodophyceae) and Codium decorticatum (Chlorophyceae) were investigated in laboratory bioassays designed to test whether the action of herbivory or simulated epibiosis influences chemical defenses. Crossed induction experiments were also performed in order to assess whether herbivore induction influences antifouling chemical defense, as well as whether epibiont induction would affect defense against herbivores. The effect of laboratory conditions on seaweeds in the absence of field stimuli was also investigated by comparing consumption of artificial food with extracts from acclimatized and non-acclimatized seaweeds (i.e., natural defense levels). Only the green seaweed C. decorticatum exhibited inducible antifouling defenses triggered by simulated epibiosis, but not by herbivores. In the other seaweeds there was no induction either by herbivory or simulated epibiosis. Acclimatization did not affect C. decorticatum defenses. However, non-acclimatized G. cearensis artificial foods were preferred over acclimatized ones, while extracts from acclimatized P. capillacea increased herbivore consumption, highlighting the need to acclimatize seaweeds before the main induction experiments. This is the first report of inducible defenses due to simulated fouling in seaweeds.

  9. Metabolism Retrofit Strategies for ToxCast Assays (BOSC)

    Science.gov (United States)

    The EPA’s ToxCast program utilizes a wide variety of high-throughput screening assays (HTS) to assess chemical perturbations of molecular and cellular endpoints. A limitation of many HTS assays used for toxicity assessment is the lack of xenobiotic metabolism (XM) which precludes...

  10. 2015 Assessment of the Ballistic Missile Defense System (BMDS)

    Science.gov (United States)

    2016-04-01

    Director, Operational Test and Evaluation 2015 Assessment of the Ballistic Missile Defense System (BMDS...Evaluation (DOT&E) as they pertain to the Ballistic Missile Defense System (BMDS). Congress specified these requirements in the fiscal year 2002 (FY02...systems are the Ground-based Midcourse Defense (GMD), Aegis Ballistic Missile Defense (Aegis BMD), Terminal High-Altitude Area Defense (THAAD), and

  11. Defense radioactive waste management

    International Nuclear Information System (INIS)

    Hindman, T.B. Jr.

    1988-01-01

    The Office of Defense Programs (DP), U.S. Department of Energy, is responsible for the production of nuclear weapons and materials for national defense. Pursuant to this mission, DP operates a large industrial complex that employs over 60,000 people at various installations across the country. As a byproduct of their activities, these installations generate radioactive, hazardous, or mixed wastes that must be managed in a safe and cost-effective manner in compliance with all applicable Federal and STate environmental requirements. At the Federal level such requirements derive primarily from the Atomic Energy Act, the Resource Conservation and Recovery Act (RCRA), the comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and the Superfund Amendments and Reauthorization Act (SARA). Responsibility for DP activities in connection with the disposal of defense wastes is consolidated within the Office of Defense Waste and Transportation Management (DWTM). This paper discusses these activities which consist of five principal elements: the environmental restoration of inactive DP facilities and sites, the processing storage and disposal of wastes associated with ongoing operations at active DP facilities, research and development directed toward the long-term disposal of radioactive, hazardous, mixed wastes, technology development directly supporting regulatory compliance, and the development of policies, procedures, and technologies for assuring the safe transportation of radioactive and hazardous materials

  12. 47 CFR 22.970 - Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone...

    Science.gov (United States)

    2010-10-01

    ...-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. 22.970 Section... MOBILE SERVICES Cellular Radiotelephone Service § 22.970 Unacceptable interference to part 90 non-cellular 800 MHz licensees from cellular radiotelephone or part 90-800 MHz cellular systems. (a) Definition...

  13. Defense AT&L Magazine A Publication of the Defense Acquisition University. Volume 34, Number 2, DAU 183

    National Research Council Canada - National Science Library

    Turk, Wayne; Wynn, Michael W; Schaeffer, Mark D; Walsh, John; Kratz, Louise A; Ward, Dan; Brown, David; McVay, Tammi

    2005-01-01

    .... As the flagship publication of the Defense Acquisition University, Defense AT AND L also disseminates information on training and education, continuous learning, and e-Learning to those acquisition...

  14. Defense AT&L Magazine A Publication of the Defense Acquisition University. Volume 34, Number 1, DAU 182

    National Research Council Canada - National Science Library

    Gadeken, Owen C; Quaid, Chris; Ward, Dan; Liss, Steven; Lambert, Cathy; Li, Alan; Parmer, Shailesh; Hurt, Hayden; Sumpter, LeAntha; Malnick, Kathy

    2005-01-01

    .... As the flagship publication of the Defense Acquisition University, Defense AT AND L also disseminates information on training and education, continuous learning, and e-Learning to those acquisition...

  15. Defense AT&L Magazine: A Publication of the Defense Acquisition University. Volume 34, Number 3, DAU 184

    National Research Council Canada - National Science Library

    Chedister, Robert W; Leach, Richard; Route, Ronald; Knott, Claudia; Turk, Wayne; Quaid, Chris; Ward, Dan; Geurts, James F

    2005-01-01

    .... As the flagship publication of the Defense Acquisition University, Defense AT AND L also disseminates information on training and education, continuous learning, and e-Learning to those acquisition...

  16. Defense AT&L Magazine A Publication of the Defense Acquisition University. Volume 33, Number 5, DAU 181

    National Research Council Canada - National Science Library

    Wynn, Michael; Gadeken, Owen C; Triggs, Marcia; Wengrowski, Bruno S

    2004-01-01

    .... As the flagship publication of the Defense Acquisition University, Defense AT AND L also disseminates information on training and education, continuous learning, and e-Learning to those acquisition...

  17. Defense AT&L Magazine A Publication of the Defense Acquisition University. Volume 33, Number 6, DAU 181

    National Research Council Canada - National Science Library

    Horn, John F; Ronis, Sheila R; Vann, Sandy; Sylvester, Richard K

    2005-01-01

    .... As the flagship publication of the Defense Acquisition University, Defense AT AND L also disseminates information on training and education, continuous learning, and e-Learning to those acquisition...

  18. Defense AT&L Magazine: A Publication of the Defense Acquisition University. Volume 33, Number 4, DAU 180

    National Research Council Canada - National Science Library

    Bryan, Harry W; Pezzano, Anthony; Burke, Peter; Davis, Jerry; Vanleer, Keisha; Howe, Keith B; Rippere, Richard B; Ward, Daniel; McGrath, Elizabeth A

    2004-01-01

    .... As the flagship publication of the Defense Acquisition University, Defense AT AND L also disseminates information on training and education, continuous learning, and e-Learning to those acquisition...

  19. Heterogeneous cellular networks

    CERN Document Server

    Hu, Rose Qingyang

    2013-01-01

    A timely publication providing coverage of radio resource management, mobility management and standardization in heterogeneous cellular networks The topic of heterogeneous cellular networks has gained momentum in industry and the research community, attracting the attention of standardization bodies such as 3GPP LTE and IEEE 802.16j, whose objectives are looking into increasing the capacity and coverage of the cellular networks. This book focuses on recent progresses,  covering the related topics including scenarios of heterogeneous network deployment, interference management i

  20. HOMA: Israel's National Missile Defense Strategy (Abridged Version)

    National Research Council Canada - National Science Library

    Lailari, Guermantes

    2002-01-01

    ... (Hebrew for Fortress Wall), Chapter 1 discusses the fundamentals of missile defense and the reason why Israel's missile defense system affects US national security interests, Chapter 2 describes Israel's missile defense...

  1. Department of Defense PERSEREC (DOD PERSEREC)

    Data.gov (United States)

    Social Security Administration — The purpose of this agreement is for SSA to verify SSN information for Defense Manpower Data Center (DMDC) of the Department of Defense. DMDC will use the SSA data...

  2. 47 CFR 22.909 - Cellular markets.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular markets...

  3. Defense Transuranic Waste Program Strategy Document

    International Nuclear Information System (INIS)

    1984-01-01

    The Defense Transuranic Waste Program (DTWP) Strategy Document presents the general strategy for managing transuranic (TRU) waste materials generated during defense and research activities regulated by the US Department of Energy. The Strategy Document includes discussion of objectives and activities relating to the entire Defense Transuranic Waste Program. However, the primary focus is on the specific management responsibilities of the Transuranic Waste Lead Organization (TLO). The document also includes an updated summary of progress on TLO-managed activities over the past year

  4. Trade Costs, Conflicts, and Defense Spending

    OpenAIRE

    Seitz, Michael; Tarasov, Alexander; Zakharenko, Roman

    2013-01-01

    This paper develops a quantitative model of trade, military conflicts, and defense spending. Trade liberalization between two countries reduces probability of an armed conflict between them, causing both to cut defense spending. This in turn causes a domino effect on defense spending by other countries. As a result, both countries and the rest of the world are better off. We estimate the model using data on trade, conflicts, and military spending. We find that, after reduction of costs of tra...

  5. Sandia National Laboratories: National Security Missions: Defense Systems

    Science.gov (United States)

    ; Technology Defense Systems & Assessments About Defense Systems & Assessments Program Areas Audit Sandia's Economic Impact Licensing & Technology Transfer Browse Technology Portfolios ; Culture Work-Life Balance Special Programs Nuclear Weapons Defense Systems Global Security Energy Facebook

  6. Defensive behaviours in innovation teams: how project teams discuss defensiveness and its relationship with innovation resilience behaviour and project success

    NARCIS (Netherlands)

    Oeij, P.R.A.; Dhondt, S.; Gaspersz, J.B.R.; Vuuren, T. van

    2016-01-01

    Project team members and project leaders of innovation projects were interviewed about the possible presence of defensive behaviours within the team. While investigating defensive behaviour can be done validly by observation techniques, to talk about defensiveness within a team often leads to

  7. 12 CFR 411.500 - Secretary of Defense.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Secretary of Defense. 411.500 Section 411.500 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES NEW RESTRICTIONS ON LOBBYING Exemptions § 411.500 Secretary of Defense. (a) The Secretary of Defense may exempt, on a case-by-case basis, a covered...

  8. Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.

    Science.gov (United States)

    van der Sluis, Rencia; Erasmus, Elardus

    2016-10-01

    Activation of fatty acids by the acyl-CoA synthetases (ACSs) is the vital first step in fatty acid metabolism. The enzymatic and physiological characterization of the human xenobiotic/medium chain fatty acid: CoA ligases (ACSMs) has been severely neglected even though xenobiotics, such as benzoate and salicylate, are detoxified through this pathway. This review will focus on the nomenclature and substrate specificity of the human ACSM ligases; the biochemical and enzymatic characterization of ACSM1 and ACSM2B; the high sequence homology of the ACSM2 genes (ACSM2A and ACSM2B) as well as what is currently known regarding disease association studies. Several discrepancies exist in the current literature that should be taken note of. For example, the single nucleotide polymorphisms (SNPs) reported to be associated with aspirin metabolism and multiple risk factors of metabolic syndrome are incorrect. Kinetic data on the substrate specificity of the human ACSM ligases are non-existent and currently no data exist on the influence of SNPs on the enzyme activity of these ligases. One of the biggest obstacles currently in the field is that glycine conjugation is continuously studied as a one-step process, which means that key regulatory factors of the two individual steps remain unknown.

  9. Defense Reutilization and Marketing Manual

    Science.gov (United States)

    1990-03-01

    H -3 E Responsibilities of Defense Reutilization and Marketing Regions (D R M s...at Defense electronic products which produce radiation Reutilization and Marketing Offices, para- when energized. Among the principal radi- graph F... Sporting Equipment 7820 Games , Toys, and Wheeled Goods 7830 Recreational and Gymnastic Equipment 7910 Floor Polishers and Vacuum Cleaning Equipment

  10. Study on defensive security concepts and policies

    International Nuclear Information System (INIS)

    1993-01-01

    The report begins by describing the background against which the proposal for the study emerged-the welcome developments brought about by the end of the cold war but also the emergence of new threats and the reappearance of long-standing problems. The study proceeds to examine current trends in the international security environment and how they may influence the peaceful settlement of dispute and the effecting of restraint and a defensive orientation in the development, maintenance and use of armed forces. A discussion of the substance and main features of defensive security concepts and policies follows. Existing studies and models designed to eliminate the offensive character of military force postures by effecting a defensive orientation of capabilities are surveyed. In addition, the study discusses political and military aspects of defensive security, pointing out how defensive security differs from those existing models

  11. 77 FR 11367 - Defense Federal Acquisition Regulation Supplement; Extension of the Department of Defense Mentor...

    Science.gov (United States)

    2012-02-24

    ... Defense Mentor-Prot[eacute]g[eacute] Pilot Program (DFARS Case 2012-D024) AGENCY: Defense Acquisition... applications under the DoD Mentor-Prot[eacute]g[eacute] Pilot Program for new mentor-prot[eacute]g[eacute] agreements and the date mentors may incur costs and/or receive credit towards fulfilling their small business...

  12. Genetic Variation in the Nuclear and Organellar Genomes Modulates Stochastic Variation in the Metabolome, Growth, and Defense

    Science.gov (United States)

    Joseph, Bindu; Corwin, Jason A.; Kliebenstein, Daniel J.

    2015-01-01

    Recent studies are starting to show that genetic control over stochastic variation is a key evolutionary solution of single celled organisms in the face of unpredictable environments. This has been expanded to show that genetic variation can alter stochastic variation in transcriptional processes within multi-cellular eukaryotes. However, little is known about how genetic diversity can control stochastic variation within more non-cell autonomous phenotypes. Using an Arabidopsis reciprocal RIL population, we showed that there is significant genetic diversity influencing stochastic variation in the plant metabolome, defense chemistry, and growth. This genetic diversity included loci specific for the stochastic variation of each phenotypic class that did not affect the other phenotypic classes or the average phenotype. This suggests that the organism's networks are established so that noise can exist in one phenotypic level like metabolism and not permeate up or down to different phenotypic levels. Further, the genomic variation within the plastid and mitochondria also had significant effects on the stochastic variation of all phenotypic classes. The genetic influence over stochastic variation within the metabolome was highly metabolite specific, with neighboring metabolites in the same metabolic pathway frequently showing different levels of noise. As expected from bet-hedging theory, there was more genetic diversity and a wider range of stochastic variation for defense chemistry than found for primary metabolism. Thus, it is possible to begin dissecting the stochastic variation of whole organismal phenotypes in multi-cellular organisms. Further, there are loci that modulate stochastic variation at different phenotypic levels. Finding the identity of these genes will be key to developing complete models linking genotype to phenotype. PMID:25569687

  13. Polyphenol Oxidase as a Biochemical Seed Defense Mechanism

    Directory of Open Access Journals (Sweden)

    E. Patrick Fuerst

    2014-12-01

    Full Text Available Seed dormancy and resistance to decay are fundamental survival strategies, which allow a population of seeds to germinate over long periods of time. Seeds have physical, chemical, and biological defense mechanisms that protect their food reserves from decay-inducing organisms and herbivores. Here, we hypothesize that seeds also possess enzyme-based biochemical defenses, based on induction of the plant defense enzyme, polyphenol oxidase (PPO, when wild oat (Avena fatua L. caryopses and seeds were challenged with seed-decaying Fusarium fungi. These studies suggest that dormant seeds are capable of mounting a defense response to pathogens. The pathogen-induced PPO activity from wild oat was attributed to a soluble isoform of the enzyme that appeared to result, at least in part, from proteolytic activation of a latent PPO isoform. PPO activity was also induced in wild oat hulls (lemma and palea, non-living tissues that cover and protect the caryopsis. These results are consistent with the hypothesis that seeds possess inducible enzyme-based biochemical defenses arrayed on the exterior of seeds and these defenses represent a fundamental mechanism of seed survival and longevity in the soil. Enzyme-based biochemical defenses may have broader implications since they may apply to other defense enzymes as well as to a diversity of plant species and ecosystems.

  14. Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

    International Nuclear Information System (INIS)

    Dairou, Julien; Petit, Emile; Ragunathan, Nilusha; Baeza-Squiban, Armelle; Marano, Francelyne; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2009-01-01

    Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and β-naphthylamine (β-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating that inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H 2 O 2 or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.

  15. The time point of β-catenin knockout in hepatocytes determines their response to xenobiotic activation of the constitutive androstane receptor

    International Nuclear Information System (INIS)

    Ganzenberg, Katrin; Singh, Yasmin; Braeuning, Albert

    2013-01-01

    The constitutive androstane receptor (CAR) controls the expression of drug-metabolizing enzymes and regulates hepatocyte proliferation. Studies with transgenic mice with an early postnatal conditional hepatocyte-specific knockout of the β-catenin gene Ctnnb1 revealed that β-catenin deficiency decreases the magnitude of induction of drug-metabolizing enzymes by CAR activators, abrogates zonal differences in the hepatocytes’ susceptibility to these compounds, and impacts on hepatocyte proliferation. These data, however, do not allow distinguishing between effects caused by β-catenin deficiency during postnatal liver development and acute effects of β-catenin deficiency in the adult animal at the time point of CAR activation. Therefore, CAR activation was now studied in a different mouse model allowing for the hepatocyte-specific knockout of β-catenin in adult mice. Treatment of these mice with 3 mg/kg body weight of the model CAR activator 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) confirmed previous findings related to the coordinate regulation of drug metabolism by β-catenin and CAR. More importantly, the present study clarified that the impact of β-catenin signaling on CAR-mediated enzyme induction in the liver is not merely due to developmental defects caused by a postnatal lack of β-catenin, but depends on the presence of β-catenin at the time point of xenobiotic treatment. The study also revealed interesting differences between the two mouse models: hepatic zonation of TCPOBOP-dependent induction of drug-metabolizing enzymes was restored in mice with late knockout of β-catenin, and the strong proliferative response of female mice was exclusively abolished when using animals with a late β-catenin knockout. This suggests a β-catenin-dependent postnatal priming of hepatocytes during postnatal liver development, later affecting the proliferative response of adult animals to CAR-activating xenobiotics

  16. Review of defense display research programs

    Science.gov (United States)

    Tulis, Robert W.; Hopper, Darrel G.; Morton, David C.; Shashidhar, Ranganathan

    2001-09-01

    Display research has comprised a substantial portion of the defense investment in new technology for national security for the past 13 years. These investments have been made by the separate service departments and, especially, via several Defense Research Projects Agency (DARPA) programs, known collectively as the High Definition Systems (HDS) Program (which ended in 2001) and via the Office of the Secretary of Defense (OSD) Defense Production Act (DPA) Title III Program (efforts ended in 2000). Using input from the Army, Navy, and Air Force to focus research and identify insertion opportunities, DARPA and the Title III Program Office have made investments to develop the national technology base and manufacturing infrastructure necessary to meet the twin challenge of providing affordable displays in current systems and enabling the DoD strategy of winning future conflicts by getting more information to all participants during the battle. These completed DARPA and DPA research and infrastructure programs are reviewed. Service investments have been and are being made to transition display technology; examples are described. Display science and technology (S&T) visions are documented for each service to assist the identification of areas meriting consideration for future defense research.

  17. 75 FR 43156 - Federal Advisory Committee; Missile Defense Advisory Committee

    Science.gov (United States)

    2010-07-23

    ... DEPARTMENT OF DEFENSE Office of the Secretary Federal Advisory Committee; Missile Defense Advisory Committee AGENCY: Missile Defense Agency (MDA), DoD. ACTION: Notice of closed meeting. SUMMARY: Under the... Defense announces that the Missile Defense Advisory Committee will meet on August 4 and 5, 2010, in...

  18. Defense Agencies Cash Management in the Defense Business Operations Fund

    National Research Council Canada - National Science Library

    Lane, F

    1997-01-01

    The primary audit objective was to determine whether the Fund Balance With Treasury Account on the Consolidated Financial Statements of the Defense Business Operations Fund for FY 1996 was presented...

  19. Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses

    DEFF Research Database (Denmark)

    Sørensen, Ole E.; Clemmensen, Stine N; Dahl, Sara L

    2014-01-01

    immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally......Papillon-Lefèvre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked......CAP-18 into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent...

  20. Soviet civil defense is inadequate and meaningless

    International Nuclear Information System (INIS)

    Kaplan, F.M.

    1985-01-01

    In this paper, the author argues that Soviet civil defense plans exist primarily on paper and are used to pacify the Soviet people, not as plans to survive and prevail in a nuclear confrontation with the U.S. The author describes how the Soviet people have little faith in the civil defense programs. They don't believe they can survive an attack. Furthermore, he says the Soviets have never staged an evacuation exercise in any major city nor, even in smaller towns, has an entire community been evacuated. The author says there are numerous problems with the shelter programs as well. Very few existing shelters have any food stocks, only a few more have any water. There is little evidence that Soviet leaders have planned their economy with civil defense in mind. Nor - given the blatant inadequacies of Soviet civil defense programs, the marked vulnerabilities of the Soviet economy, and the intrinsic limitation and uncertainties about civil defense generally - is there much basis for claiming that Soviet leaders, even in desperate straits, would risk war with the United States while counting on civil defense measures to limit the damage wreaked on the Soviet Union

  1. Biomechanics of cellular solids.

    Science.gov (United States)

    Gibson, Lorna J

    2005-03-01

    Materials with a cellular structure are widespread in nature and include wood, cork, plant parenchyma and trabecular bone. Natural cellular materials are often mechanically efficient: the honeycomb-like microstructure of wood, for instance, gives it an exceptionally high performance index for resisting bending and buckling. Here we review the mechanics of a wide range of natural cellular materials and examine their role in lightweight natural sandwich structures (e.g. iris leaves) and natural tubular structures (e.g. plant stems or animal quills). We also describe two examples of engineered biomaterials with a cellular structure, designed to replace or regenerate tissue in the body.

  2. Management Data Used to Manage the Defense Logistics Agency Supply Management Division of the Defense Business Operations Fund

    National Research Council Canada - National Science Library

    1994-01-01

    The Defense Logistics Agency Supply Management Division (the Division) of the Defense Business Operations Fund provides supplies and logistics services to DoD Components and other (Government agencies...

  3. Status of defense radioactive waste disposal activities

    International Nuclear Information System (INIS)

    Wade, T.W.

    1988-01-01

    The Office of Defense Programs, U.S. Department of Energy, is responsible for the production of nuclear weapons and materials for national defense. As a byproduct to their activities, nuclear production facilities have generated, and will continue to generate, certain radioactive, hazardous, or mixed wastes that must be managed and disposed of in a safe and cost-effective manner. Compliance with all applicable Federal and State regulations is required. This paper describes the principal elements that comprise Defense Programs' approach to waste management and disposal. The status of high-level, transuranic, and low-level radioactive waste disposal is set forth. Defense Programs' activities in connection with the environmental restoration of inactive facilities and with the safe transport of waste materials are summarized. Finally, the principal challenges to realizing the goals set for the defense waste program are discussed in terms of regulatory, public acceptance, technical, and budget issues

  4. Plant antiherbivore defenses in Fabaceae species of the Chaco.

    Science.gov (United States)

    Lima, T E; Sartori, A L B; Rodrigues, M L M

    2017-01-01

    The establishment and maintenance of plant species in the Chaco, one of the widest continuous areas of forests in the South American with sharp climatic variations, are possibly related to biological features favoring plants with particular defenses. This study assesses the physical and chemical defenses mechanisms against herbivores of vegetative and reproductive organs. Its analyses of 12 species of Fabaceae (Leguminosae) collected in remnants of Brazilian Chaco shows that 75% present structural defense characters and 50% have chemical defense - defense proteins in their seeds, like protease inhibitors and lectins. Physical defenses occur mainly on branches (78% of the species), leaves (67%), and reproductive organs (56%). The most common physical characters are trichomes and thorns, whose color represents a cryptic character since it does not contrast with the other plant structures. Defense proteins occur in different concentrations and molecular weight classes in the seeds of most species. Protease inhibitors are reported for the first time in seeds of: Albizia niopoides, Anadenanthera colubrina, Mimosa glutinosa, Prosopis rubriflora, and Poincianella pluviosa. The occurrence of physical and chemical defenses in members of Fabaceae indicate no associations between defense characters in these plant species of the Chaco.

  5. Inducible defenses stay up late: temporal patterns of immune gene expression in Tenebrio molitor.

    Science.gov (United States)

    Johnston, Paul R; Makarova, Olga; Rolff, Jens

    2013-12-06

    The course of microbial infection in insects is shaped by a two-stage process of immune defense. Constitutive defenses, such as engulfment and melanization, act immediately and are followed by inducible defenses, archetypically the production of antimicrobial peptides, which eliminate or suppress the remaining microbes. By applying RNAseq across a 7-day time course, we sought to characterize the long-lasting immune response to bacterial challenge in the mealworm beetle Tenebrio molitor, a model for the biochemistry of insect immunity and persistent bacterial infection. By annotating a hybrid de novo assembly of RNAseq data, we were able to identify putative orthologs for the majority of components of the conserved insect immune system. Compared with Tribolium castaneum, the most closely related species with a reference genome sequence and a manually curated immune system annotation, the T. molitor immune gene count was lower, with lineage-specific expansions of genes encoding serine proteases and their countervailing inhibitors accounting for the majority of the deficit. Quantitative mapping of RNAseq reads to the reference assembly showed that expression of genes with predicted functions in cellular immunity, wound healing, melanization, and the production of reactive oxygen species was transiently induced immediately after immune challenge. In contrast, expression of genes encoding antimicrobial peptides or components of the Toll signaling pathway and iron sequestration response remained elevated for at least 7 days. Numerous genes involved in metabolism and nutrient storage were repressed, indicating a possible cost of immune induction. Strikingly, the expression of almost all antibacterial peptides followed the same pattern of long-lasting induction, regardless of their spectra of activity, signaling possible interactive roles in vivo. Copyright © 2014 Johnston et al.

  6. Priming Arabidopsis for defense : Molecular and ecological aspects

    NARCIS (Netherlands)

    van Hulten, M.H.A.

    2009-01-01

    Plants are capable to enhance basal defense strategies against harmful organisms upon the perception of certain stimuli. This enhanced resistance is not necessarily accompanied by direct activation of defenses, but often depends on a sensitization of the plant tissue to express defenses faster

  7. Status of DOE defense waste management policy

    International Nuclear Information System (INIS)

    Oertel, K.G.; Scott, R.S.

    1983-01-01

    This paper very briefly traces the statutory basis for DOE management of atomic energy defense activity wastes, touches on the authority of the Federal agencies involved in the regulation of defense nuclear waste management, and addresses the applicable regulations and their status. This background sets the stage for a fairly detailed discussion of management and disposal strategies of the Defense Waste and Byproducts Management Program

  8. Cellular Reflectarray Antenna

    Science.gov (United States)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  9. Defense styles explain psychiatric symptoms: an empirical study.

    Science.gov (United States)

    Holi, M M; Sammallahti, P R; Aalberg, V A

    1999-11-01

    To examine the relation between psychiatric symptoms and defense mechanisms, we administered two questionnaires, the Symptom Check-list 90 (SCL-90) and the Defense Style Questionnaire (DSQ) to 122 psychiatric out-patients and to a community sample of 337 subjects. Using regression analysis, we found that 51.8% of the variation in subject's Global Severity Index value could be explained by his defense style. Of the three defense styles, the immature style explained most of the variation in the symptoms. We found little overall evidence for specific connections between particular defenses and symptoms. Projection and dissociation were central in most of the symptom dimensions. We compared patients and controls with the same level of general symptom severity and found that patients used significantly more devaluation and splitting, and controls used significantly more altruism and idealization. Whether defenses predispose to certain symptomatology or are one of its aspects is discussed.

  10. Mathematical Modeling of Tuberculosis Bacillary Counts and Cellular Populations in the Organs of Infected Mice

    Science.gov (United States)

    Bru, Antonio; Cardona, Pere-Joan

    2010-01-01

    Background Mycobacterium tuberculosis is a particularly aggressive microorganism and the host's defense is based on the induction of cellular immunity, in which the creation of a granulomatous structure has an important role. Methodology We present here a new 2D cellular automata model based on the concept of a multifunctional process that includes key factors such as the chemokine attraction of the cells; the role of innate immunity triggered by natural killers; the presence of neutrophils; apoptosis and necrosis of infected macrophages; the removal of dead cells by macrophages, which induces the production of foamy macrophages (FMs); the life cycle of the bacilli as a determinant for the evolution of infected macrophages; and the immune response. Results The results obtained after the inclusion of two degrees of tolerance to the inflammatory response triggered by the infection shows that the model can cover a wide spectrum, ranging from highly-tolerant (i.e. mice) to poorly-tolerant hosts (i.e. mini-pigs or humans). Conclusions This model suggest that stopping bacillary growth at the onset of the infection might be difficult and the important role played by FMs in bacillary drainage in poorly-tolerant hosts together with apoptosis and innate lymphocytes. It also shows the poor ability of the cellular immunity to control the infection, provides a clear protective character to the granuloma, due its ability to attract a sufficient number of cells, and explains why an already infected host can be constantly reinfected. PMID:20886087

  11. Defense Acquisitions Acronyms and Terms

    Science.gov (United States)

    2012-12-01

    DR Decision Review DRMO Defense Reutilization Marketing Office DRPM Direct Reporting Program Manager DSAA Defense Security Assistance Agency...STE Special Test Equipment STEP Simulation, Test, and Evaluation Process STLDD Software Top Level Design Document STP Software Test Plan STPR...established catalog or market prices for specific tasks under standard commercial terms and conditions; this does not include services sold based

  12. Aluminium-induced excessive ROS causes cellular damage and metabolic shifts in black gram Vigna mungo (L.) Hepper.

    Science.gov (United States)

    Chowra, Umakanta; Yanase, Emiko; Koyama, Hiroyuki; Panda, Sanjib Kumar

    2017-01-01

    Aluminium-induced oxidative damage caused by excessive ROS production was evaluated in black gram pulse crop. Black gram plants were treated with different aluminium (Al 3+ ) concentrations (10, 50 and 100 μM with pH 4.7) and further the effects of Al 3+ were characterised by means of root growth inhibition, histochemical assay, ROS content analysis, protein carbonylation quantification and 1 H-NMR analysis. The results showed that aluminium induces excessive ROS production which leads to cellular damage, root injury, stunt root growth and other metabolic shifts. In black gram, Al 3+ induces cellular damage at the earliest stage of stress which was characterised from histochemical analysis. From this study, it was observed that prolonged stress can activate certain aluminium detoxification defence mechanism. Probably excessive ROS triggers such defence mechanism in black gram. Al 3+ can induce excessive ROS initially in the root region then transported to other parts of the plant. As much as the Al 3+ concentration increases, the rate of cellular injury and ROS production also increases. But after 72 h of stress, plants showed a lowered ROS level and cellular damage which indicates the upregulation of defensive mechanisms. Metabolic shift analysis also showed that the black gram plant under stress has less metabolic content after 24 h of treatment, but gradually, it was increased after 72 h of treatment. It was assumed that ROS played the most important role as a signalling molecule for aluminium stress in black gram.

  13. 75 FR 77849 - Closed Meeting of the Missile Defense Advisory Committee

    Science.gov (United States)

    2010-12-14

    ... DEPARTMENT OF DEFENSE Office of the Secretary Closed Meeting of the Missile Defense Advisory Committee AGENCY: Department of Defense; Missile Defense Agency (MDA). ACTION: Notice. SUMMARY: Under the... Defense announces that the following Federal advisory committee meeting of the Missile Defense Advisory...

  14. 75 FR 77848 - Closed Meeting of the Missile Defense Advisory Committee

    Science.gov (United States)

    2010-12-14

    ... DEPARTMENT OF DEFENSE Office of the Secretary Closed Meeting of the Missile Defense Advisory Committee AGENCY: Department of Defense; Missile Defense Agency (MDA). ACTION: Notice. SUMMARY: Under the... Defense announces that the following Federal advisory committee meeting of the Missile Defense Advisory...

  15. Linearizable cellular automata

    International Nuclear Information System (INIS)

    Nobe, Atsushi; Yura, Fumitaka

    2007-01-01

    The initial value problem for a class of reversible elementary cellular automata with periodic boundaries is reduced to an initial-boundary value problem for a class of linear systems on a finite commutative ring Z 2 . Moreover, a family of such linearizable cellular automata is given

  16. Electromagnetic cellular interactions.

    Science.gov (United States)

    Cifra, Michal; Fields, Jeremy Z; Farhadi, Ashkan

    2011-05-01

    Chemical and electrical interaction within and between cells is well established. Just the opposite is true about cellular interactions via other physical fields. The most probable candidate for an other form of cellular interaction is the electromagnetic field. We review theories and experiments on how cells can generate and detect electromagnetic fields generally, and if the cell-generated electromagnetic field can mediate cellular interactions. We do not limit here ourselves to specialized electro-excitable cells. Rather we describe physical processes that are of a more general nature and probably present in almost every type of living cell. The spectral range included is broad; from kHz to the visible part of the electromagnetic spectrum. We show that there is a rather large number of theories on how cells can generate and detect electromagnetic fields and discuss experimental evidence on electromagnetic cellular interactions in the modern scientific literature. Although small, it is continuously accumulating. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Photovoltaics in the Department of Defense

    International Nuclear Information System (INIS)

    Chapman, R.N.

    1997-01-01

    This paper documents the history of photovoltaic use within the Department of Defense leading up to the installation of 2.1 MW of photovoltaics underway today. This history describes the evolution of the Department of Defense's Tri-Service Photovoltaic Review Committee and the committee's strategic plan to realize photovoltaic's full potential through outreach, conditioning of the federal procurement system, and specific project development. The Photovoltaic Review Committee estimates photovoltaic's potential at nearly 4,000 MW, of which about 700 MW are considered to be cost-effective at today's prices. The paper describes photovoltaic's potential within the Department of Defense, the status and features of the 2.1-MW worth of photovoltaic systems under installation, and how these systems are selected and implemented. The paper also documents support provided to the Department of Defense by the Department of Energy dating back to the late 70s. copyright 1997 American Institute of Physics

  18. Cyanobacterial defense mechanisms against foreign DNA transfer and their impact on genetic engineering

    Directory of Open Access Journals (Sweden)

    Karina Stucken

    2013-01-01

    Full Text Available Cyanobacteria display a large diversity of cellular forms ranging from unicellular to complex multicellular filaments or aggregates. Species in the group present a wide range of metabolic characteristics including the fixation of atmospheric nitrogen, resistance to extreme environments, production of hydrogen, secondary metabolites and exopolysaccharides. These characteristics led to the growing interest in cyanobacteria across the fields of ecology, evolution, cell biology and biotechnology. The number of available cyanobacterial genome sequences has increased considerably in recent years, with more than 140 fully sequenced genomes to date. Genetic engineering of cyanobacteria is widely applied to the model unicellular strains Synechocystis sp. PCC 6803 and Synechococcus elongatus PCC 7942. However the establishment of transformation protocols in many other cyanobacterial strains is challenging. One obstacle to the development of these novel model organisms is that many species have doubling times of 48 h or more, much longer than the bacterial models E. coli or B. subtilis. Furthermore, cyanobacterial defense mechanisms against foreign DNA pose a physical and biochemical barrier to DNA insertion in most strains. Here we review the various barriers to DNA uptake in the context of lateral gene transfer among microbes and the various mechanisms for DNA acquisition within the prokaryotic domain. Understanding the cyanobacterial defense mechanisms is expected to assist in the development and establishment of novel transformation protocols that are specifically suitable for this group.

  19. Natural Marine and Synthetic Xenobiotics Get on Nematode's Nerves: Neuro-Stimulating and Neurotoxic Findings in Caenorhabditis elegans.

    Science.gov (United States)

    Lieke, Thora; Steinberg, Christian E W; Ju, Jingjuan; Saul, Nadine

    2015-05-06

    Marine algae release a plethora of organic halogenated compounds, many of them with unknown ecological impact if environmentally realistic concentrations are applied. One major compound is dibromoacetic acid (DBAA) which was tested for neurotoxicity in the invertebrate model organism Caenorhabditis elegans (C. elegans). This natural compound was compared with the widespread synthetic xenobiotic tetrabromobisphenol-A (TBBP-A) found in marine sediments and mussels. We found a neuro-stimulating effect for DBAA; this is contradictory to existing toxicological reports of mammals that applied comparatively high dosages. For TBBP-A, we found a hormetic concentration-effect relationship. As chemicals rarely occur isolated in the environment, a combination of both organobromines was also examined. Surprisingly, the presence of DBAA increased the toxicity of TBBP-A. Our results demonstrated that organohalogens have the potential to affect single organisms especially by altering the neurological processes, even with promoting effects on exposed organisms.

  20. Defense mechanisms in schizotypal, borderline, antisocial, and narcissistic personality disorders.

    Science.gov (United States)

    Perry, J Christopher; Presniak, Michelle D; Olson, Trevor R

    2013-01-01

    Numerous authors have theorized that defense mechanisms play a role in personality disorders. We reviewed theoretical writings and empirical studies about defenses in schizotypal, borderline, antisocial, and narcissistic personality disorders, developing hypotheses about these differential relationships. We then examined these hypotheses using dynamic interview data rated for defenses in a study of participants (n = 107) diagnosed with these four personality disorder types. Overall, the prevalence of immature defenses was substantial, and all four disorders fit within the broad borderline personality organization construct. Defenses predicted the most variance in borderline and the least variance in schizotypal personality disorder, suggesting that dynamic factors played the largest role in borderline and the least in schizotypal personality. Central to borderline personality were strong associations with major image-distorting defenses, primarily splitting of self and other's images, and the hysterical level defenses, dissociation and repression. Narcissistic and antisocial personality disorders shared minor image-distorting defenses, such as omnipotence or devaluation, while narcissistic also used splitting of self-images and antisocial used disavowal defenses like denial. Overall, differential relationships between specific defenses and personality disorder types were largely consistent with the literature, and consistent with the importance that the treatment literature ascribes to working with defenses.

  1. Transcriptome Analysis of the Carmine Spider Mite, Tetranychus cinnabarinus (Boisduval, 1867 (Acari: Tetranychidae, and Its Response to β-Sitosterol

    Directory of Open Access Journals (Sweden)

    Chunya Bu

    2015-01-01

    Full Text Available Tetranychus cinnabarinus (Acari: Tetranychidae is a worldwide polyphagous agricultural pest that has the title of resistance champion among arthropods. We reported previously the identification of the acaricidal compound β-sitosterol from Mentha piperita and Inula japonica. However, the acaricidal mechanism of β-sitosterol is unclear. Due to the limited genetic research carried out, we de novo assembled the transcriptome of T. cinnabarinus using Illumina sequencing and conducted a differential expression analysis of control and β-sitosterol-treated mites. In total, we obtained >5.4 G high-quality bases for each sample with unprecedented sequencing depth and assembled them into 22,941 unigenes. We identified 617 xenobiotic metabolism-related genes involved in detoxification, binding, and transporting of xenobiotics. A highly expanded xenobiotic metabolic system was found in mites. T. cinnabarinus detoxification genes—including carboxyl/cholinesterase and ABC transporter class C—were upregulated after β-sitosterol treatment. Defense-related proteins, such as Toll-like receptor, legumain, and serine proteases, were also activated. Furthermore, other important genes—such as the chloride channel protein, cytochrome b, carboxypeptidase, peritrophic membrane chitin binding protein, and calphostin—may also play important roles in mites’ response to β-sitosterol. Our results demonstrate that high-throughput-omics tool facilitates identification of xenobiotic metabolism-related genes and illustration of the acaricidal mechanisms of β-sitosterol.

  2. Should the Department of Defense Transfer the Defense Logistics Agency's Map Functions to the Defense Working Capital Fund

    National Research Council Canada - National Science Library

    Zimmerman, Donald

    2000-01-01

    .... The functions cost about $25 million annually and are funded by operations and maintenance (O&M) dollars. This study analyzed if the functions should be transferred to the Defense Working Capital Fund...

  3. Happiness and Defense Styles in Psychiatrists.

    Science.gov (United States)

    Machado, Leonardo; Tavares, Hermano; Petribú, Kátia; Pinto, Tiago; Cantilino, Amaury

    2016-03-01

    The aim of this study was to measure happiness in a sample of Brazilian psychiatrists and correlate it with the defense styles used by them and sociodemographic data. This study was observational, cross-sectional, and analytical. Data were collected through self-administered questionnaires by Brazilian psychiatrists who participated in the XXXII Brazilian Congress of Psychiatry, 2014. In this sample of psychiatrists, happiness levels were high (scoring 5.69 of a total of 7), and mature defense styles prevailed, especially humor and anticipation. In a multivariate analysis, having children, good sleep quality, increased sexual interest, and use of defense styles such as humor, anticipation, and idealization all showed a positive relationship with happiness; on the other hand, using defense style such as acting out or annulment demonstrated a negative relationship with happiness. Despite the well-known professional burden that they bear, Brazilian psychiatrists surveyed presented, in general, high levels of subjective well-being and happiness.

  4. Hijacking of host cellular functions by an intracellular parasite, the microsporidian Anncaliia algerae.

    Directory of Open Access Journals (Sweden)

    Johan Panek

    Full Text Available Intracellular pathogens including bacteria, viruses and protozoa hijack host cell functions to access nutrients and to bypass cellular defenses and immune responses. These strategies have been acquired through selective pressure and allowed pathogens to reach an appropriate cellular niche for their survival and growth. To get new insights on how parasites hijack host cellular functions, we developed a SILAC (Stable Isotope Labeling by Amino Acids in Cell culture quantitative proteomics workflow. Our study focused on deciphering the cross-talk in a host-parasite association, involving human foreskin fibroblasts (HFF and the microsporidia Anncaliia algerae, a fungus related parasite with an obligate intracellular lifestyle and a strong host dependency. The host-parasite cross-talk was analyzed at five post-infection times 1, 6, 12 and 24 hours post-infection (hpi and 8 days post-infection (dpi. A significant up-regulation of four interferon-induced proteins with tetratricopeptide repeats IFIT1, IFIT2, IFIT3 and MX1 was observed at 8 dpi suggesting a type 1 interferon (IFN host response. Quantitative alteration of host proteins involved in biological functions such as signaling (STAT1, Ras and reduction of the translation activity (EIF3 confirmed a host type 1 IFN response. Interestingly, the SILAC approach also allowed the detection of 148 A. algerae proteins during the kinetics of infection. Among these proteins many are involved in parasite proliferation, and an over-representation of putative secreted effectors proteins was observed. Finally our survey also suggests that A. algerae could use a transposable element as a lure strategy to escape the host innate immune system.

  5. Cruise Missile Defense

    National Research Council Canada - National Science Library

    Hichkad, Ravi R; Bolkcom, Christopher

    2005-01-01

    Congress has expressed interest in cruise missile defense for years. Cruise missiles (CMs) are essentially unmanned attack aircraft -- vehicles composed of an airframe, propulsion system, guidance system, and weapons payload...

  6. Cruise Missile Defense

    National Research Council Canada - National Science Library

    Hichkad, Ravi R; Bolkcom, Christopher

    2004-01-01

    Congress has expressed interest in cruise missile defense for years. Cruise missiles (CMs) are essentially unmanned attack aircraft -- vehicles composed of an airframe, propulsion system, guidance system, and weapons payload...

  7. The Identification of Xenobiotics in the New UK Context of Drinking Water Safety Planning and Related Environmental Legislation

    International Nuclear Information System (INIS)

    Hayes, C. R.; Keirle, R. S.; Lobley, A.

    2008-01-01

    Recent European environmental legislation (the Water Framework Directive, the Environmental Liability Directive, and the REACH Regulation) should provide better protection of terrestrial water bodies but their focus is on the more conspicuous pollutants, as opposed to the large number of xenobiotic micro-pollutants that are increasingly being detected in the urban water cycle. The development of Drinking Water Safety Plans (DWSPs), as promoted by the World Health Organization, utilises a proactive risk assessment-risk management approach that necessarily should include micro-pollutants, although currently in the UK micro-pollutants have largely been ignored. The generic assessment of the risks posed by micro-pollutants is proposed and will require a consensus on analytical screening methods, sampling points and frequencies, and a method for prioritising concern, and would enable DWSPs to take fuller account of the risks posed

  8. Cellular Particle Dynamics simulation of biomechanical relaxation processes of multi-cellular systems

    Science.gov (United States)

    McCune, Matthew; Kosztin, Ioan

    2013-03-01

    Cellular Particle Dynamics (CPD) is a theoretical-computational-experimental framework for describing and predicting the time evolution of biomechanical relaxation processes of multi-cellular systems, such as fusion, sorting and compression. In CPD, cells are modeled as an ensemble of cellular particles (CPs) that interact via short range contact interactions, characterized by an attractive (adhesive interaction) and a repulsive (excluded volume interaction) component. The time evolution of the spatial conformation of the multicellular system is determined by following the trajectories of all CPs through numerical integration of their equations of motion. Here we present CPD simulation results for the fusion of both spherical and cylindrical multi-cellular aggregates. First, we calibrate the relevant CPD model parameters for a given cell type by comparing the CPD simulation results for the fusion of two spherical aggregates to the corresponding experimental results. Next, CPD simulations are used to predict the time evolution of the fusion of cylindrical aggregates. The latter is relevant for the formation of tubular multi-cellular structures (i.e., primitive blood vessels) created by the novel bioprinting technology. Work supported by NSF [PHY-0957914]. Computer time provided by the University of Missouri Bioinformatics Consortium.

  9. Autophagy as a defense strategy against stress: focus on Paracentrotus lividus sea urchin embryos exposed to cadmium.

    Science.gov (United States)

    Chiarelli, Roberto; Martino, Chiara; Agnello, Maria; Bosco, Liana; Roccheri, Maria Carmela

    2016-01-01

    Autophagy is used by organisms as a defense strategy to face environmental stress. This mechanism has been described as one of the most important intracellular pathways responsible for the degradation and recycling of proteins and organelles. It can act as a cell survival mechanism if the cellular damage is not too extensive or as a cell death mechanism if the damage/stress is irreversible; in the latter case, it can operate as an independent pathway or together with the apoptotic one. In this review, we discuss the autophagic process activated in several aquatic organisms exposed to different types of environmental stressors, focusing on the sea urchin embryo, a suitable system recently included into the guidelines for the use and interpretation of assays to monitor autophagy. After cadmium (Cd) exposure, a heavy metal recognized as an environmental toxicant, the sea urchin embryo is able to adopt different defense mechanisms, in a hierarchical way. Among these, autophagy is one of the main responses activated to preserve the developmental program. Finally, we discuss the interplay between autophagy and apoptosis in the sea urchin embryo, a temporal and functional choice that depends on the intensity of stress conditions.

  10. Emotional exhaustion and defense mechanisms in intensive therapy unit nurses.

    Science.gov (United States)

    Regan, Anna; Howard, Ruth A; Oyebode, Jan R

    2009-05-01

    Contrary to its original conceptualization, research has found that emotional demands do not lead to burnout in nurses. According to psychoanalytic theory, unconscious defense mechanisms may protect nurses from conscious awareness of work-related anxiety. This prevents self-report and may explain research findings. The maturity of defense style influences how anxiety is managed. Immature defenses prevent the conscious processing necessary for resolution of anxiety. Therefore, it is hypothesized that the use of immature defenses will lead to emotional exhaustion. This cross-sectional study used questionnaires to explore the defense mechanisms of 87 Intensive Therapy Unit nurses. Although the sample endorsed a predominantly mature defense style, the use of immature defenses predicted emotional exhaustion. Also, lower levels of reported stress associated with emotional demands predicted emotional exhaustion. Although this strongly implies the mediating role of immature defense mechanisms, the results were not statistically significant.

  11. 77 FR 34357 - Missile Defense Advisory Committee; Notice of Closed Meeting

    Science.gov (United States)

    2012-06-11

    ... DEPARTMENT OF DEFENSE Office of the Secretary Missile Defense Advisory Committee; Notice of Closed Meeting AGENCY: Missile Defense Agency (MDA), Department of Defense. ACTION: Notice of closed meeting... Missile Defense Advisory Committee will take place. DATES: Tuesday, June 12, 2012 through Wednesday, June...

  12. 76 FR 71556 - Missile Defense Advisory Committee; Notice of Closed Meeting

    Science.gov (United States)

    2011-11-18

    ... DEPARTMENT OF DEFENSE Office of the Secretary Missile Defense Advisory Committee; Notice of Closed Meeting AGENCY: Missile Defense Agency (MDA), Department of Defense. ACTION: Notice of closed meeting... Missile Defense Advisory Committee will take place. DATES: Tuesday, December 13, 2011 through Wednesday...

  13. 76 FR 45783 - Missile Defense Advisory Committee; Notice of Closed Meeting

    Science.gov (United States)

    2011-08-01

    ... DEPARTMENT OF DEFENSE Office of the Secretary Missile Defense Advisory Committee; Notice of Closed Meeting AGENCY: Department of Defense; Missile Defense Agency (MDA). ACTION: Notice of closed meeting... Missile Defense Advisory Committee will take place. DATES: Tuesday, August 16, 2011 through Thursday...

  14. Design and Acquisition of Software for Defense Systems

    Science.gov (United States)

    2018-02-14

    embrace of iterative development has benefited bottom lines and cost , schedule, and testing performance, while the Department and its defense industrial...February 2018 CLEARED FOR OPEN PUBLICATION February 14, 2018 DEPARTMENT OF DEFENSE OFFICE OF PREPUBLICATION AND SECURITY REVIEW...Force concluded that the Department of Defense would benefit from the implementation of continuous iterative development best practices as software

  15. Cost of space-based laser ballistic missile defense.

    Science.gov (United States)

    Field, G; Spergel, D

    1986-03-21

    Orbiting platforms carrying infrared lasers have been proposed as weapons forming the first tier of a ballistic missile defense system under the President's Strategic Defense Initiative. As each laser platform can destroy a limited number of missiles, one of several methods of countering such a system is to increase the number of offensive missiles. Hence it is important to know whether the cost-exchange ratio, defined as the ratio of the cost to the defense of destroying a missile to the cost to the offense of deploying an additional missile, is greater or less than 1. Although the technology to be used in a ballistic missile defense system is still extremely uncertain, it is useful to examine methods for calculating the cost-exchange ratio. As an example, the cost of an orbiting infrared laser ballistic missile defense system employed against intercontinental ballistic missiles launched simultaneously from a small area is compared to the cost of additional offensive missiles. If one adopts lower limits to the costs for the defense and upper limits to the costs for the offense, the cost-exchange ratio comes out substantially greater than 1. If these estimates are confirmed, such a ballistic missile defense system would be unable to maintain its effectiveness at less cost than it would take to proliferate the ballistic missiles necessary to overcome it and would therefore not satisfy the President's requirements for an effective strategic defense. Although the method is illustrated by applying it to a space-based infrared laser system, it should be straightforward to apply it to other proposed systems.

  16. Photochemistry and photobiology of actinic erythema: defensive and reparative cutaneous mechanisms

    Directory of Open Access Journals (Sweden)

    A.C. Tedesco

    1997-05-01

    Full Text Available Sunlight is part of our everyday life and most people accept it as beneficial to our health. With the advance of our knowledge in cutaneous photochemistry, photobiology and photomedicine over the past four decades, the terrestrial solar radiation has become a concern of dermatologists and is considered to be a major damaging environmental factor for our skin. Most photobiological effects (e.g., sunburn, suntanning, local and systemic immunosuppression, photoaging or dermatoheliosis, skin cancer and precancer, etc. are attributed to ultraviolet radiation (UVR and more particularly to UVB radiation (290-320 nm. UVA radiation (320-400 nm also plays an important role in the induction of erythema by the photosensitized generation of reactive oxygen species (singlet oxygen (1O2, superoxide (O2.- and hydroxyl radicals (.OH that damage DNA and cellular membranes, and promote carcinogenesis and the changes associated with photoaging. Therefore, research efforts have been directed at a better photochemical and photobiological understanding of the so-called sunburn reaction, actinic or solar erythema. To survive the insults of actinic damage, the skin appears to have different intrinsic defensive mechanisms, among which antioxidants (enzymatic and non-enzymatic systems play a pivotal role. In this paper, we will review the basic aspects of the action of UVR on the skin: a photochemical reactions resulting from photon absorption by endogenous chromophores; b the lipid peroxidation phenomenon, and c intrinsic defensive cutaneous mechanisms (antioxidant systems. The last section will cover the inflammatory response including mediator release after cutaneous UVR exposure and adhesion molecule expression

  17. Innate defense regulator peptide 1018 in wound healing and wound infection.

    Directory of Open Access Journals (Sweden)

    Lars Steinstraesser

    Full Text Available Innate defense regulators (IDRs are synthetic immunomodulatory versions of natural host defense peptides (HDP. IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

  18. 32 CFR 13.3 - Office of the Chief Defense Counsel.

    Science.gov (United States)

    2010-07-01

    ... COMMISSIONS RESPONSIBILITIES OF THE CHIEF DEFENSE COUNSEL, DETAILED DEFENSE COUNSEL, AND CIVILIAN DEFENSE... II of the Affidavit And Agreement By Civilian Defense Counsel at Appendix B to 32 CFR part 14. (5... incur confidentiality obligations in the context of fulfilling their supervisory responsibilities with...

  19. 75 FR 9588 - Defense Intelligence Agency Advisory Board; Closed Meeting

    Science.gov (United States)

    2010-03-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary Defense Intelligence Agency Advisory Board; Closed Meeting AGENCY: Defense Intelligence Agency, DoD. ACTION: Notice of closed meeting. SUMMARY: Pursuant to... Law 94-409, notice is hereby given that the Defense Intelligence Agency Advisory Board, will meet on...

  20. Defense Acquisition Reform: Background, Analysis, and Issues for Congress

    Science.gov (United States)

    2014-05-23

    provided to CRS by Semiconductor Industry, October, 2013. 33 Zachary Fryer- Biggs , “Looking Beyond Defense: Firms Grow Revenue—By Diversifying,” DefenseNews...was chartered based on the authority set forth in Section 854 of the John Warner National Defense Authorization Act for 2007 (P.L. 109-364). See...Secretary of Defense for Acquisition, Technology, and Logistics John Young echoed this sentiment, stating “the enterprise will often pressure acquisition

  1. Department of Defense Agency Financial Report for FY 2011

    Science.gov (United States)

    2011-11-01

    able to distribute resources across hospitals and clinics within a market to meet the needs of the entire population of eligible beneficiaries. In...WRAMC), Washington, DC. This entailed construction of a new community hospital and a dental clinic at Fort Belvoir and an expansion of the National...Department of Defense DSB Defense Science Board DSS Defense Security Service DTM Directive-type Memorandum DTS Defense Travel System EBF Education

  2. 76 FR 13991 - Meeting of the Department of Defense Wage Committee

    Science.gov (United States)

    2011-03-15

    ... DEPARTMENT OF DEFENSE Office of the Secretary Meeting of the Department of Defense Wage Committee... meetings of the Department of Defense Wage Committee. DATES: Tuesday, April 5, 2011, and Tuesday, April 19... FURTHER INFORMATION CONTACT: Chairman, Department of Defense Wage Committee, 4000 Defense Pentagon...

  3. Changes in defensive functioning in a case of avoidant personality disorder.

    Science.gov (United States)

    Presniak, Michelle D; Olson, Trevor R; Porcerelli, John H; Dauphin, V Barry

    2010-03-01

    This case study is based upon data from a male patient with Avoidant Personality Disorder who was in psychoanalytic treatment for 5 years. Defense mechanism use was assessed by 3 coders using the Defense Mechanisms Rating Scales. Session transcripts from intake, each year of therapy, and 1-year follow-up were used for the ratings. Over the course of psychoanalysis and follow-up, the patient's Overall Defensive Functioning and High-Adaptive defense level use increased and his use of the Disavowal defense level and Fantasy decreased. The pattern of change throughout treatment was also assessed. The patient's Overall Defensive Functioning decreased initially, followed by an increase through year 4. Overall Defensive Functioning decreased again prior to termination before increasing to its highest level at follow-up. The results demonstrated changes consistent with hypotheses and theory, including overall improvement in defensive functioning, an initial regression of defensive functioning, decline in functioning immediately prior to termination, and continued improvement posttermination. This pattern of defense change highlights the importance of assessing defenses in treatment research. PsycINFO Database Record (c) 2010 APA, all rights reserved

  4. Immune defense and host life history.

    Science.gov (United States)

    Zuk, Marlene; Stoehr, Andrew M

    2002-10-01

    Recent interest has focused on immune response in an evolutionary context, with particular attention to disease resistance as a life-history trait, subject to trade-offs against other traits such as reproductive effort. Immune defense has several characteristics that complicate this approach, however; for example, because of the risk of autoimmunity, optimal immune defense is not necessarily maximum immune defense. Two important types of cost associated with immunity in the context of life history are resource costs, those related to the allocation of essential but limited resources, such as energy or nutrients, and option costs, those paid not in the currency of resources but in functional or structural components of the organism. Resource and option costs are likely to apply to different aspects of resistance. Recent investigations into possible trade-offs between reproductive effort, particularly sexual displays, and immunity have suggested interesting functional links between the two. Although all organisms balance the costs of immune defense against the requirements of reproduction, this balance works out differently for males than it does for females, creating sex differences in immune response that in turn are related to ecological factors such as the mating system. We conclude that immune response is indeed costly and that future work would do well to include invertebrates, which have sometimes been neglected in studies of the ecology of immune defense.

  5. Removal of Antibiotics in Biological Wastewater Treatment Systems—A Critical Assessment Using the Activated Sludge Modeling Framework for Xenobiotics (ASM-X)

    DEFF Research Database (Denmark)

    Polesel, Fabio; Andersen, Henrik Rasmus; Trapp, Stefan

    2016-01-01

    Many scientific studies present removal efficiencies for pharmaceuticals in laboratory-, pilot-, and full-scale wastewater treatment plants, based on observations that may be impacted by theoretical and methodological approaches used. In this Critical Review, we evaluated factors influencing...... observed removal efficiencies of three antibiotics (sulfamethoxazole, ciprofloxacin, tetracycline) in pilot- and full-scale biological treatment systems. Factors assessed include (i) retransformation to parent pharmaceuticals from e.g., conjugated metabolites and analogues, (ii) solid retention time (SRT......), (iii) fractions sorbed onto solids, and (iv) dynamics in influent and effluent loading. A recently developed methodology was used, relying on the comparison of removal efficiency predictions (obtained with the Activated Sludge Model for Xenobiotics (ASM-X)) with representative measured data from...

  6. THE DEFENSE PLANNING SYSTEMS AND THEIR IMPLICATIONS

    Directory of Open Access Journals (Sweden)

    Laszlo STICZ

    2010-01-01

    Full Text Available Defense planning in the Alliance is a fundamental element of the arrangements which enable its member countries to enjoy the crucial political, military and resource advantages of collective defense and other common military efforts to enhance security and stability. In this respect, the aim of this paper is to outline the role of the Armed Forces and the specific processes aiming to achieve the ultimate goal of a nation regarding national security, with focus on defense planning and the PDPS.

  7. Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.

    Science.gov (United States)

    Gao, Chao; Zhang, Long; Zhang, Ye; Wallace, Darren P; Lopez-Soler, Reynold I; Higgins, Paul J; Zhang, Wenzheng

    2017-11-01

    Urinary tract infection (UTI) is a broad term referring to an infection of the kidneys, ureters, bladder, and/or urethra. Because of its prevalence, frequent recurrence, and rising resistance to antibiotics, UTI has become a challenge in clinical practice. Autosomal-dominant polycystic kidney disease (ADPKD) is the most common monogenic disorder of the kidney and is characterized by the growth of fluid-filled cysts in both kidneys. Progressive cystic enlargement, inflammation, and interstitial fibrosis result in nephron loss with subsequent decline in kidney function. ADPKD patients frequently develop UTI; however, the cellular and molecular mechanisms responsible for the high UTI incidence in ADPKD patients remain virtually unaddressed. Emerging evidence suggests that α-intercalated cells (α-ICs) of the collecting ducts function in the innate immune defense against UTI. α-ICs inhibit bacterial growth by acidifying urine and secreting neutrophil gelatinase-associated lipocalin (NGAL) that chelates siderophore-containing iron. It is necessary to determine, therefore, if ADPKD patients with recurrent UTI have a reduced number and/or impaired function of α-ICs. Identification of the underlying cellular and molecular mechanisms may lead to the development of novel strategies to reduce UTI in ADPKD. Copyright © 2017 the American Physiological Society.

  8. Dynamic behavior of cellular materials and cellular structures: Experiments and modeling

    Science.gov (United States)

    Gao, Ziyang

    Cellular solids, including cellular materials and cellular structures (CMS), have attracted people's great interests because of their low densities and novel physical, mechanical, thermal, electrical and acoustic properties. They offer potential for lightweight structures, energy absorption, thermal management, etc. Therefore, the studies of cellular solids have become one of the hottest research fields nowadays. From energy absorption point of view, any plastically deformed structures can be divided into two types (called type I and type II), and the basic cells of the CMS may take the configurations of these two types of structures. Accordingly, separated discussions are presented in this thesis. First, a modified 1-D model is proposed and numerically solved for a typical type II structure. Good agreement is achieved with the previous experimental data, hence is used to simulate the dynamic behavior of a type II chain. Resulted from different load speeds, interesting collapse modes are observed, and the parameters which govern the cell's post-collapse behavior are identified through a comprehensive non-dimensional analysis on general cellular chains. Secondly, the MHS specimens are chosen as an example of type I foam materials because of their good uniformity of the cell geometry. An extensive experimental study was carried out, where more attention was paid to their responses to dynamic loadings. Great enhancement of the stress-strain curve was observed in dynamic cases, and the energy absorption capacity is found to be several times higher than that of the commercial metal foams. Based on the experimental study, finite elemental simulations and theoretical modeling are also conducted, achieving good agreements and demonstrating the validities of those models. It is believed that the experimental, numerical and analytical results obtained in the present study will certainly deepen the understanding of the unsolved fundamental issues on the mechanical behavior of

  9. Landscape Variation in Plant Defense Syndromes across a Tropical Rainforest

    Science.gov (United States)

    McManus, K. M.; Asner, G. P.; Martin, R.; Field, C. B.

    2014-12-01

    Plant defenses against herbivores shape tropical rainforest biodiversity, yet community- and landscape-scale patterns of plant defense and the phylogenetic and environmental factors that may shape them are poorly known. We measured foliar defense, growth, and longevity traits for 345 canopy trees across 84 species in a tropical rainforest and examined whether patterns of trait co-variation indicated the existence of plant defense syndromes. Using a DNA-barcode phylogeny and remote sensing and land-use data, we investigated how phylogeny and topo-edaphic properties influenced the distribution of syndromes. We found evidence for three distinct defense syndromes, characterized by rapid growth, growth compensated by defense, or limited palatability/low nutrition. Phylogenetic signal was generally lower for defense traits than traits related to growth or longevity. Individual defense syndromes were organized at different taxonomic levels and responded to different spatial-environmental gradients. The results suggest that a diverse set of tropical canopy trees converge on a limited number of strategies to secure resources and mitigate fitness losses due to herbivory, with patterns of distribution mediated by evolutionary histories and local habitat associations. Plant defense syndromes are multidimensional plant strategies, and thus are a useful means of discerning ecologically-relevant variation in highly diverse tropical rainforest communities. Scaling this approach to the landscape level, if plant defense syndromes can be distinguished in remotely-sensed data, they may yield new insights into the role of plant defense in structuring diverse tropical rainforest communities.

  10. Statistical mechanics of cellular automata

    International Nuclear Information System (INIS)

    Wolfram, S.

    1983-01-01

    Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of ''elementary'' cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to p definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions approx. =1.59 or approx. =1.69. With ''random'' initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed

  11. Proteoliposomes as Tool for Assaying Membrane Transporter Functions and Interactions with Xenobiotics

    Directory of Open Access Journals (Sweden)

    Annamaria Tonazzi

    2013-09-01

    Full Text Available Proteoliposomes represent a suitable and up to date tool for studying membrane transporters which physiologically mediate absorption, excretion, trafficking and reabsorption of nutrients and metabolites. Using recently developed reconstitution strategies, transporters can be inserted in artificial bilayers with the same orientation as in the cell membranes and in the absence of other interfering molecular systems. These methodologies are very suitable for studying kinetic parameters and molecular mechanisms. After the first applications on mitochondrial transporters, in the last decade, proteoliposomes obtained with optimized methodologies have been used for studying plasma membrane transporters and defining their functional and kinetic properties and structure/function relationships. A lot of information has been obtained which has clarified and completed the knowledge on several transporters among which the OCTN sub-family members, transporters for neutral amino acid, B0AT1 and ASCT2, and others. Transporters can mediate absorption of substrate-like derivatives or drugs, improving their bioavailability or can interact with these compounds or other xenobiotics, leading to side/toxic effects. Therefore, proteoliposomes have recently been used for studying the interaction of some plasma membrane and mitochondrial transporters with toxic compounds, such as mercurials, H2O2 and some drugs. Several mechanisms have been defined and in some cases the amino acid residues responsible for the interaction have been identified. The data obtained indicate proteoliposomes as a novel and potentially important tool in drug discovery.

  12. 77 FR 62469 - Defense Logistics Agency Freedom of Information Act Program

    Science.gov (United States)

    2012-10-15

    ... DEPARTMENT OF DEFENSE Office of the Secretary 32 CFR Part 300 Defense Logistics Agency 32 CFR Part 1285 RIN 0790-AI87 [Docket ID: DOD-2012-OS-0019] Defense Logistics Agency Freedom of Information Act Program AGENCY: Defense Logistics Agency, DoD. ACTION: Proposed rule. SUMMARY: The Defense Logistics...

  13. Wireless Cellular Mobile Communications

    OpenAIRE

    Zalud, V.

    2002-01-01

    In this article is briefly reviewed the history of wireless cellular mobile communications, examined the progress in current second generation (2G) cellular standards and discussed their migration to the third generation (3G). The European 2G cellular standard GSM and its evolution phases GPRS and EDGE are described somewhat in detail. The third generation standard UMTS taking up on GSM/GPRS core network and equipped with a new advanced access network on the basis of code division multiple ac...

  14. Quadrennial Defense Review, National Defense Authorizatin Act for Fiscal Year 2000

    National Research Council Canada - National Science Library

    2002-01-01

    Objectives of Overall JS QDR Effort Develop a QDR process that will shape defense policies Ensure the process is strategy-based, not budget-based Define a force structure responsive to the national...

  15. Applying Rapid Acquisition Policy Lessons for Defense Innovation

    Science.gov (United States)

    2017-12-21

    import- ing Silicon Valley- style innovation practices to its acquisition process, it is im- portant to assess an organization’s ability to...these efforts. Keywords: defense acquisition, defense procurement, rapid acquisition, de- fense innovation, program management , organizational culture...Device De- feat Organization, JIEDDO, Rapid Equipping Force, REF Silicon Valley- style innovation is a hot topic in the Department of De-fense (DOD). For

  16. Embryonic treatment with xenobiotics disrupts steroid hormone profiles in hatchling red-eared slider turtles (Trachemys scripta elegans).

    Science.gov (United States)

    Willingham, E; Rhen, T; Sakata, J T; Crews, D

    2000-01-01

    Many compounds in the environment capable of acting as endocrine disruptors have been assayed for their developmental effects on morphogenesis; however, few studies have addressed how such xenobiotics affect physiology. In the current study we examine the effects of three endocrine-disrupting compounds, chlordane, trans-nonachlor, and the polychlorinated biphenyl (PCB) mixture Aroclor 1242, on the steroid hormone concentrations of red-eared slider turtle (Trachemys scripta elegans) hatchlings treated in ovo. Basal steroid concentrations and steroid concentrations in response to follicle-stimulating hormone were examined in both male and female turtles treated with each of the three compounds. Treated male turtles exposed to Aroclor 1242 or chlordane exhibited significantly lower testosterone concentrations than controls, whereas chlordane-treated females had significantly lower progesterone, testosterone, and 5[alpha]-dihydrotestosterone concentrations relative to controls. The effects of these endocrine disruptors extend beyond embryonic development, altering sex-steroid physiology in exposed animals. Images Figure 1 Figure 2 PMID:10753091

  17. MSAT and cellular hybrid networking

    Science.gov (United States)

    Baranowsky, Patrick W., II

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  18. Managing Quadrennial Defense Review Integration: An Overview

    National Research Council Canada - National Science Library

    Schrader, John

    2001-01-01

    ...). The lessons learned from the 1997 Quadrennial Defense Review (QDR 1997) included the need for leadership guidance and integration of analytic activities to sort through the myriad issues that are always confronting the Department of Defense...

  19. COMPETITIVENESS OF DEFENSE INDUSTRY IN TURKEY

    Directory of Open Access Journals (Sweden)

    Hakki BILGEN

    2010-01-01

    Full Text Available Turkey has created some opportunities for the organisations in the defense industry to generate a suitable business and to ensure its sustainability. The domestic coverage ratio of defense system need in 2010 is aimed as 50%. To achieve this target depends on the defense industry competitiveness. In this study, the development plans, strategies and foreign trade are examined. Its contribution which has an important place in the research and development investment, is not at the level expected in Turkey’s economy. Turkey occupies 47th position in World Competitiveness Scoreboard, and 61st position in Global Competitiveness Index in 2009. The index factors are investigated to understand the competitiveness according to the Porter’s diamond model, applied in Turkey for the first time. As a result, the competitiveness analysis of Turkish defense industry is carried out and its global place and competitive advantage are exposed. Therefore, a framework is made to introduce a guide for decision-making by using a widely-accepted model, and to contribute to the plans and strategies

  20. Antiviral Defense Mechanisms in Honey Bees

    Science.gov (United States)

    Brutscher, Laura M.; Daughenbaugh, Katie F.; Flenniken, Michelle L.

    2015-01-01

    Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID:26273564

  1. Department of Defense high power laser program guidance

    Science.gov (United States)

    Muller, Clifford H.

    1994-06-01

    The DoD investment of nominally $200 million per year is focused on four high power laser (HPL) concepts: Space-Based Laser (SBL), a Ballistic Missile Defense Organization effort that addresses boost-phase intercept for Theater Missile Defense and National Missile Defense; Airborne Laser (ABL), an Air Force effort that addresses boost-phase intercept for Theater Missile Defense; Ground-Based Laser (GBL), an Air Force effort addressing space control; and Anti-Ship Missile Defense (ASMD), a Navy effort addressing ship-based defense. Each organization is also supporting technology development with the goal of achieving less expensive, brighter, and lighter high power laser systems. These activities represent the building blocks of the DoD program to exploit the compelling characteristics of the high power laser. Even though DoD's HPL program are focused and moderately strong, additional emphasis in a few technical areas could help reduce risk in these programs. In addition, a number of options are available for continuing to use the High-Energy Laser System Test Facility (HELSTF) at White Sands Missile Range. This report provides a brief overview and guidance for the five efforts which comprise the DoD HPL program (SBL, ABL, GBL, ASMD, HELSTF).

  2. Modulation of xenobiotic biotransformation system and hormonal responses in Atlantic salmon (Salmo salar) after exposure to tributyltin (TBT).

    Science.gov (United States)

    Mortensen, Anne Skjetne; Arukwe, Augustine

    2007-04-01

    Multiple biological effects of tributyltin (TBT) on juvenile salmon have been investigated. Fish were exposed for 7 days to waterborne TBT at nominal concentrations of 50 and 250 microg/L dissolved in dimethyl sulfoxide (DMSO). Hepatic samples were analyzed for gene expression patterns in the hormonal and xenobiotic biotransformation pathways using validated real-time PCR method. Immunochemical and several cytochrome P450 (CYP)-mediated enzyme activity (ethoxyresorufin: EROD, benzyloxyresorufin: BROD, methoxyresorufin: MROD and pentoxyresorufin: PROD) assays were analyzed. Our data show that TBT produced concentration-specific decrease of estrogen receptor-alpha (ERalpha), vitellogenin (Vtg), zona radiata protein (Zr-protein) and increase of estrogen receptor-beta (ERbeta) and androgen receptor-beta (ARbeta) in the hormonal pathway. In the xenobiotic biotransformation pathway, TBT produced apparent increase and decrease at respective low and high concentration, on aryl hydrocarbon receptor-alpha (AhRalpha), AhR nuclear translocator (ARNT) and AhR repressor (AhRR) mRNA. The expression of CYP1A1 and GST showed a TBT concentration-dependent decrease. The AhRbeta, CYP3A and uridine diphosphoglucuronosyl transferase (UGT) mRNA expressions were significantly induced after exposure to TBT. Immunochemical analysis of CYP3A and CYP1A1 protein levels confirmed the TBT effects observed at the transcriptional levels. The effect of TBT on the biotransformation enzyme gene expressions partially co-related but did not directly parallel enzyme activity levels for EROD, BROD, MROD and PROD. In general, these findings confirm previous reports on the endocrine effects of TBT, in addition to effects on hepatic CYP1A isoenzyme at the transcriptional level that transcends to protein and enzymatic levels. The induced expression patterns of CYP3A and UGT mRNA after TBT exposure, suggest the involvement of CYP3A and UGT in TBT metabolism in fish. The effect of TBT on CYP3A is proposed to

  3. Perturbations of amino acid metabolism associated with glyphosate-dependent inhibition of shikimic acid metabolism affect cellular redox homeostasis and alter the abundance of proteins involved in photosynthesis and photorespiration.

    Science.gov (United States)

    Vivancos, Pedro Diaz; Driscoll, Simon P; Bulman, Christopher A; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H

    2011-09-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway.

  4. Next Generation Nuclear Plant Defense-in-Depth Approach

    International Nuclear Information System (INIS)

    Wallace, Edward G.; Fleming, Karl N.; Burns, Edward M.

    2009-01-01

    The purpose of this paper is to (1) document the definition of defense-in-depth and the pproach that will be used to assure that its principles are satisfied for the NGNP project and (2) identify the specific questions proposed for preapplication discussions with the NRC. Defense-in-depth is a safety philosophy in which multiple lines of defense and conservative design and evaluation methods are applied to assure the safety of the public. The philosophy is also intended to deliver a design that is tolerant to uncertainties in knowledge of plant behavior, component reliability or operator performance that might compromise safety. This paper includes a review of the regulatory foundation for defense-in-depth, a definition of defense-in-depth that is appropriate for advanced reactor designs based on High Temperature Gas-cooled Reactor (HTGR) technology, and an explanation of how this safety philosophy is achieved in the NGNP.

  5. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  6. Cellular decomposition in vikalloys

    International Nuclear Information System (INIS)

    Belyatskaya, I.S.; Vintajkin, E.Z.; Georgieva, I.Ya.; Golikov, V.A.; Udovenko, V.A.

    1981-01-01

    Austenite decomposition in Fe-Co-V and Fe-Co-V-Ni alloys at 475-600 deg C is investigated. The cellular decomposition in ternary alloys results in the formation of bcc (ordered) and fcc structures, and in quaternary alloys - bcc (ordered) and 12R structures. The cellular 12R structure results from the emergence of stacking faults in the fcc lattice with irregular spacing in four layers. The cellular decomposition results in a high-dispersion structure and magnetic properties approaching the level of well-known vikalloys [ru

  7. Cellular Antiviral Factors that Target Particle Infectivity of HIV-1.

    Science.gov (United States)

    Goffinet, Christine

    2016-01-01

    In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.

  8. Air defense planning for an area with the use of very short range air defense sets

    Directory of Open Access Journals (Sweden)

    Tadeusz Pietkiewicz

    2017-12-01

    Full Text Available This paper presents a heuristic method of planning the deployment of very short-range anti-air missile and artillery sets (VSHORAD around an area (‘protected area’ in order to protect it. A function dependent on the distance between the earliest feasible points of destroying targets and the centre of the protected area was taken as an objective function. This is a different indicator from those commonly used in the literature, and based on the likelihood of a defense zone penetration by means of an air attack (MAA: the kill probability of the MAA and the probability of area losses. The model constraints resulted directly from the restrictions imposed by real air defense systems and the nature of the area being defended. This paper assumes that the VSHORAD system operates as a part of a general, superordinate air defense command and control system based on the idea of network-centric warfare, which provides the VSHORAD system with a recognized air picture, air defense plans, and combat mission specifications. The presented method has been implemented. The final part of the paper presents the computational results. Keywords: optimal planning, air defense system, area installation protection, deployment of very short range anti-air missile and artillery sets (VSHORAD

  9. Effect of Cissus quadrangularis on gastric mucosal defensive factors in experimentally induced gastric ulcer-a comparative study with sucralfate.

    Science.gov (United States)

    Jainu, Mallika; Devi, C S Shyamala

    2004-01-01

    Cissus quadrangularis is an indigenous plant commonly mentioned in Ayurveda for treatment of gastric ulcers. The ulcer-protective effect of a methanolic extract of C. quadrangularis (CQE) was comparable to that of the reference drug sucralfate. Further, gastric juice and mucosal studies showed that CQE at a dose of 500 mg/kg given for 10 days significantly increased the mucosal defensive factors like mucin secretion, mucosal cell proliferation, glycoproteins, and life span of cells. The present investigation suggests that CQE not only strengthens mucosal resistance against ulcerogens but also promotes healing by inducing cellular proliferation. Thus, CQE has potential usefulness for treatment of peptic ulcer disease.

  10. Cognitive defenses and compliance with radiation treatment in cancer patients

    International Nuclear Information System (INIS)

    Karassik, B.M.

    1989-01-01

    The present study was undertaken to investigate the relationships between four cognitive defenses and compliance with radiation therapy in cancer patients. The role of accurate self-report of usage of each of the defenses was examined as well. A distinction between direct-action and emotion-focused coping was utilized to conceptualize the possible relationships between compliance and the defenses. Based on the proposals of Heilbrun and Renert (1986) regarding the relative evasiveness of the defenses and available evidence from the compliance literature, it was predicted that noncompliant patients would show more repression, projection, and denial and less rationalization than compliant patients. In addition, based upon the findings of Heilbrun and Pepe (1985) that related self-deception to effectiveness of the defenses in dealing with stress, predictions were also made regarding differences in accuracy of reported defense usage by compliant and noncompliant patients. Noncompliant repressors and projectors and compliant rationalizers were predicted to be less aware of their respective use of these defenses than their compliant counterparts; noncompliant deniers were predicted to be more aware of the use of this defense than compliant deniers

  11. Precipitation affects plant communication and defense.

    Science.gov (United States)

    Pezzola, Enrico; Mancuso, Stefano; Karban, Richard

    2017-06-01

    Anti-herbivore defense shows high levels of both inter- and intraspecific variability. Defending against herbivores may be costly to the plant when it requires a tradeoff in allocation between defense and other missed opportunities, such as reproduction. Indeed, the plastic expression of defensive traits allows the plant to invest resources in defense only when the risk of being damaged actually increases, avoiding wasted resources. Plants may assess risk by responding to volatile cues emitted by neighbors that are under attack. Most plastic responses likely depend on environmental conditions. In this experiment, we investigated the effect of water availability on resistance induced by volatile cues in sagebrush. We found that plants receiving additional water over summer and/or volatile cues from neighbor donor plants showed reduced herbivore damage compared to control plants. Interestingly, we found no evidence of interactions between additional water and volatile cues. We performed an inferential analysis comparing historical records of the levels of herbivore damage during different years that had different temperature and precipitation accumulations. Results confirmed findings from the experiment, as the regression model indicated that sagebrush was better defended during wetter and hotter seasons. Reports from the literature indicated that sagebrush is extremely sensitive to water availability in the soil. We suggest that water availability may directly affect resistance of herbivory as well as sensitivity to cues of damage. Costs and benefits of allocating resources to defensive traits may vary with environmental conditions. © 2017 by the Ecological Society of America.

  12. Natural Marine and Synthetic Xenobiotics Get on Nematode’s Nerves: Neuro-Stimulating and Neurotoxic Findings in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Thora Lieke

    2015-05-01

    Full Text Available Marine algae release a plethora of organic halogenated compounds, many of them with unknown ecological impact if environmentally realistic concentrations are applied. One major compound is dibromoacetic acid (DBAA which was tested for neurotoxicity in the invertebrate model organism Caenorhabditis elegans (C. elegans. This natural compound was compared with the widespread synthetic xenobiotic tetrabromobisphenol-A (TBBP-A found in marine sediments and mussels. We found a neuro-stimulating effect for DBAA; this is contradictory to existing toxicological reports of mammals that applied comparatively high dosages. For TBBP-A, we found a hormetic concentration-effect relationship. As chemicals rarely occur isolated in the environment, a combination of both organobromines was also examined. Surprisingly, the presence of DBAA increased the toxicity of TBBP-A. Our results demonstrated that organohalogens have the potential to affect single organisms especially by altering the neurological processes, even with promoting effects on exposed organisms.

  13. The Xenobiotic Transporter Mdr1 Enforces T Cell Homeostasis in the Presence of Intestinal Bile Acids.

    Science.gov (United States)

    Cao, Wei; Kayama, Hisako; Chen, Mei Lan; Delmas, Amber; Sun, Amy; Kim, Sang Yong; Rangarajan, Erumbi S; McKevitt, Kelly; Beck, Amanda P; Jackson, Cody B; Crynen, Gogce; Oikonomopoulos, Angelos; Lacey, Precious N; Martinez, Gustavo J; Izard, Tina; Lorenz, Robin G; Rodriguez-Palacios, Alex; Cominelli, Fabio; Abreu, Maria T; Hommes, Daniel W; Koralov, Sergei B; Takeda, Kiyoshi; Sundrud, Mark S

    2017-12-19

    CD4 + T cells are tightly regulated by microbiota in the intestine, but whether intestinal T cells interface with host-derived metabolites is less clear. Here, we show that CD4 + T effector (Teff) cells upregulated the xenobiotic transporter, Mdr1, in the ileum to maintain homeostasis in the presence of bile acids. Whereas wild-type Teff cells upregulated Mdr1 in the ileum, those lacking Mdr1 displayed mucosal dysfunction and induced Crohn's disease-like ileitis following transfer into Rag1 -/- hosts. Mdr1 mitigated oxidative stress and enforced homeostasis in Teff cells exposed to conjugated bile acids (CBAs), a class of liver-derived emulsifying agents that actively circulate through the ileal mucosa. Blocking ileal CBA reabsorption in transferred Rag1 -/- mice restored Mdr1-deficient Teff cell homeostasis and attenuated ileitis. Further, a subset of ileal Crohn's disease patients displayed MDR1 loss of function. Together, these results suggest that coordinated interaction between mucosal Teff cells and CBAs in the ileum regulate intestinal immune homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Microbial Genomics: The Expanding Universe of Bacterial Defense Systems.

    Science.gov (United States)

    Forsberg, Kevin J; Malik, Harmit S

    2018-04-23

    Bacteria protect themselves against infection using multiple defensive systems that move by horizontal gene transfer and accumulate in genomic 'defense islands'. A recent study exploited these features to uncover ten novel defense systems, substantially expanding the catalog of bacterial defense systems and predicting the discovery of many more. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Effects of Gain/Loss Framing in Cyber Defense Decision-Making

    Energy Technology Data Exchange (ETDEWEB)

    Bos, Nathan; Paul, Celeste; Gersh, John; Greenberg, Ariel; Piatko, Christine; Sperling, Scott; Spitaletta, Jason; Arendt, Dustin L.; Burtner, Edwin R.

    2016-10-24

    Cyber defense requires decision making under uncertainty. Yet this critical area has not been a strong focus of research in judgment and decision-making. Future defense systems, which will rely on software-defined networks and may employ ‘moving target’ defenses, will increasingly automate lower level detection and analysis, but will still require humans in the loop for higher level judgment. We studied the decision making process and outcomes of 17 experienced network defense professionals who worked through a set of realistic network defense scenarios. We manipulated gain versus loss framing in a cyber defense scenario, and found significant effects in one of two focal problems. Defenders that began with a network already in quarantine (gain framing) used a quarantine system more than those that did not (loss framing). We also found some difference in perceived workload and efficacy. Alternate explanations of these findings and implications for network defense are discussed.

  16. PTSD as a criminal defense: a review of case law.

    Science.gov (United States)

    Berger, Omri; McNiel, Dale E; Binder, Renée L

    2012-01-01

    Posttraumatic stress disorder (PTSD) has been offered as a basis for criminal defenses, including insanity, unconsciousness, self-defense, diminished capacity, and sentencing mitigation. Examination of case law (e.g., appellate decisions) involving PTSD reveals that when offered as a criminal defense, PTSD has received mixed treatment in the judicial system. Courts have often recognized testimony about PTSD as scientifically reliable. In addition, PTSD has been recognized by appellate courts in U.S. jurisdictions as a valid basis for insanity, unconsciousness, and self-defense. However, the courts have not always found the presentation of PTSD testimony to be relevant, admissible, or compelling in such cases, particularly when expert testimony failed to show how PTSD met the standard for the given defense. In cases that did not meet the standard for one of the complete defenses, PTSD has been presented as a partial defense or mitigating circumstance, again with mixed success.

  17. On Three Defenses of Sentimentalism

    OpenAIRE

    Iwasa, Noriaki

    2013-01-01

    This essay shows that a moral sense or moral sentiments alone cannot identify appropriate morals. To this end, the essay analyzes three defenses of Francis Hutcheson’s, David Hume’s, and Adam Smith’s moral sense theories against the relativism charge that a moral sense or moral sentiments vary across people, societies, cultures, or times. The first defense is the claim that there is a universal moral sense or universal moral sentiments. However, even if they exist, a moral sense or moral sent...

  18. Protease inhibitor (PI) mediated defense in leaves and flowers of pigeonpea (protease inhibitor mediated defense in pigeonpea).

    Science.gov (United States)

    Padul, Manohar V; Tak, Rajesh D; Kachole, Manvendra S

    2012-03-01

    More than 200 insect pests are found growing on pigeonpea. Insects lay eggs, attack and feed on leaves, flowers and developing pods. Plants have developed elaborate defenses against these insect pests. The present work evaluates protease inhibitor (PI) based defense of pigeonpea in leaves and flowers. PIs in the extracts of these tender tissues were detected by using gel X-ray film contact print method. Up to three PIs (PI-3, PI-4 and PI-5) were detected in these tissues as against nine (PI-1-PI-9) in mature seeds. PI-3 is the major component of these tissues. Mechanical wounding, insect chewing, fungal pathogenesis and application of salicylic acid induced PIs in pigeonpea in these tissues. Induction was found to be local as well as systemic but local response was stronger than systemic response. During both local and systemic induction, PI-3 appeared first. In spite of the presence and induction of PIs in these tender tissues and seeds farmers continue to suffer yield loses. This is due to the weak expression of PIs. However the ability of the plant to respond to external stimuli by producing defense proteins does not seem to be compromised. This study therefore indicates that PIs are components of both constitutive and inducible defense and provide a ground for designing stronger inducible defense (PIs or other insect toxin based) in pigeonpea. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  19. Scavenging of free-radical metabolites of aniline xenobiotics and drugs by amino acid derivatives: toxicological implications of radical-transfer reactions.

    Science.gov (United States)

    Michail, Karim; Baghdasarian, Argishti; Narwaley, Malyaj; Aljuhani, Naif; Siraki, Arno G

    2013-12-16

    We investigated a novel scavenging mechanism of arylamine free radicals by poly- and monoaminocarboxylates. Free radicals of arylamine xenobiotics and drugs did not react with oxygen in peroxidase-catalyzed reactions; however, they showed marked oxygen uptake in the presence of an aminocarboxylate. These free-radical intermediates were identified using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) spectrometry. Diethylenetriaminepentaacetic acid (DTPA), a polyaminocarboxylate, caused a concentration-dependent attenuation of N-centered radicals produced by the peroxidative metabolism of arylamines with the subsequent formation of secondary aliphatic carbon-centered radicals stemming from the cosubstrate molecule. Analogously, N,N-dimethylglycine (DMG) and N-methyliminodiacetate (MIDA), but not iminodiacetic acid (IDA), demonstrated a similar scavenging effect of arylamine-derived free radicals in a horseradish peroxidase/H2O2 system. Using human promyelocytic leukemia (HL-60) cell lysate as a model of human neutrophils, DTPA, MIDA, and DMG readily reduced anilinium cation radicals derived from the arylamines and gave rise to the corresponding carbon radicals. The rate of peroxidase-triggered polymerization of aniline was studied as a measure of nitrogen-radical scavenging. Although, IDA had no effect on the rate of aniline polymerization, this was almost nullified in the presence of DTPA and MIDA at half of the molar concentration of the aniline substrate, whereas a 20 molar excess of DMPO caused only a partial inhibition. Furthermore, the yield of formaldehyde, a specific reaction endproduct of the oxidation of aminocarboxylates by aniline free-radical metabolites, was quantitatively determined. Azobenzene, a specific reaction product of peroxidase-catalyzed free-radical dimerization of aniline, was fully abrogated in the presence of DTPA, as confirmed by GC/MS. Under aerobic conditions, a radical-transfer reaction

  20. Defense Finance and Accounting Service Commercial Activities Program

    National Research Council Canada - National Science Library

    1999-01-01

    .... This report evaluated the Defense Finance and Accounting Service competitive sourcing process and reviewed the adequacy of the Defense Finance and Accounting Service management control program...

  1. Defense.gov Special Report: Hagel Bids Farewell

    Science.gov (United States)

    Africa. Story Major Components of Hagel's Leadership During his tenure, Defense Secretary Chuck Hagel prudence, careful leadership and personal compassion. "What our budget proposal and defense strategy Relationship With India Understanding the importance of a rising and democratic India to the future security

  2. Cellular automata analysis and applications

    CERN Document Server

    Hadeler, Karl-Peter

    2017-01-01

    This book focuses on a coherent representation of the main approaches to analyze the dynamics of cellular automata. Cellular automata are an inevitable tool in mathematical modeling. In contrast to classical modeling approaches as partial differential equations, cellular automata are straightforward to simulate but hard to analyze. In this book we present a review of approaches and theories that allow the reader to understand the behavior of cellular automata beyond simulations. The first part consists of an introduction of cellular automata on Cayley graphs, and their characterization via the fundamental Cutis-Hedlund-Lyndon theorems in the context of different topological concepts (Cantor, Besicovitch and Weyl topology). The second part focuses on classification results: What classification follows from topological concepts (Hurley classification), Lyapunov stability (Gilman classification), and the theory of formal languages and grammars (Kůrka classification). These classifications suggest to cluster cel...

  3. Analysis of Defense Industry Consolidation Effects on Program Acquisition Costs

    National Research Council Canada - National Science Library

    Hoff, Russell V

    2007-01-01

    .... This thesis examines whether cost changes are evident following consolidation within the defense industry by conducting a regression analysis of Major Defense Acquisition Programs across 13 broad defense market sectors...

  4. Concept of a nuclear defense and disarmament; Concept d'une defense nucleaire et desarmement

    Energy Technology Data Exchange (ETDEWEB)

    Grandperrier, Catherine

    2011-02-09

    Today, disarmament and proliferation control stakes have to deal with the economical and political interests of the development of the civil and military nuclear industry. This book addresses the question of the future of the nuclear defense in France and in the rest of the world at a time when two trends, the abolitionist one and the traditional one, are in opposition. Between disarmament and nuclear exaggeration, tomorrow's defense strategy will have to find its way. (J.S.)

  5. Chemical defense of early life stages of benthic marine invertebrates.

    Science.gov (United States)

    Lindquist, Niels

    2002-10-01

    Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

  6. Defense Contract Management Command Capitalization of Fixed Assets

    National Research Council Canada - National Science Library

    Young, Shelton

    1997-01-01

    The audit objective was to determine whether the Defense Logistics Agency and the Defense Finance and Accounting Service had implemented effective management control procedures and complied with laws...

  7. Defense.gov Special Report: 2013 Fiscal Budget

    Science.gov (United States)

    Department of Defense Submit Search 2013 Fiscal Budget Published Feb. 13, 2012 Top Stories Budget Proposal Slows Cost Growth, Pentagon Leaders Say The Defense Department's proposed fiscal 2013 budget request Department officials told a Senate panel. Story Officials Seek Construction Funds, More BRAC in Budget

  8. Defense: FY2017 Budget Request, Authorization, and Appropriations

    Science.gov (United States)

    2016-04-12

    adjusted the limits on defense and non-defense spending —each time adjusting only the limits for the two succeeding years. 13 Nevertheless, each of... employee hour worked . The Bureau of Labor Statistics reports the ECI which is computed from compensation cost data collected from a sample of jobs...with $9.6 billion in mandatory spending , brought the Administration’s total FY2017 National Defense budget request to $619.5 billion. In shaping the

  9. Perspective on methods to calculate a fee for disposal of defense high-level waste in combined (civilian/defense) repositories

    International Nuclear Information System (INIS)

    1986-12-01

    The Department of Energy intends to send the high-level waste from defense operations to combined civilian/defense repositories for disposal. The federal government must pay a fee to cover its fair share of the cost for the disposal system. This report provides an overview perspective on the defense high-level waste (DHLW) quantities and characteristics and on potential alternatives for calculation and payment of the disposal fee. Information on the DHLW expected from government sites includes the number of waste canisters, radioactivity, thermal decay power, mass of defense reactor fuel, and total electrical energy-equivalents. Ranges in quantities are shown where different operating scenarios are being considered. Several different fee determination methods are described and fees for different quantities of waste are estimated. Information is also included on possible payment alternatives, production and shipping schedules, and credits which could be applied to the fee

  10. A perillyl alcohol-conjugated analog of 3-bromopyruvate without cellular uptake dependency on monocarboxylate transporter 1 and with activity in 3-BP-resistant tumor cells.

    Science.gov (United States)

    Chen, Thomas C; Yu, Jiali; Nouri Nigjeh, Eslam; Wang, Weijun; Myint, Phyo Thazin; Zandi, Ebrahim; Hofman, Florence M; Schönthal, Axel H

    2017-08-01

    The anticancer agent 3-bromopyruvate (3-BP) is viewed as a glycolytic inhibitor that preferentially kills glycolytic cancer cells through energy depletion. However, its cytotoxic activity is dependent on cellular drug import through transmembrane monocarboxylate transporter 1 (MCT-1), which restricts its anticancer potential to MCT-1-positive tumor cells. We created and characterized an MCT-1-independent analog of 3-BP, called NEO218. NEO218 was synthesized by covalently conjugating 3-BP to perillyl alcohol (POH), a natural monoterpene. The responses of various tumor cell lines to treatment with either compound were characterized in the presence or absence of supplemental pyruvate or antioxidants N-acetyl-cysteine (NAC) and glutathione (GSH). Drug effects on glyceraldehyde 3-phosphate dehydrogenase (GAPDH) enzyme activity were investigated by mass spectrometric analysis. The development of 3-BP resistance was investigated in MCT-1-positive HCT116 colon carcinoma cells in vitro. Our results show that NEO218: (i) pyruvylated GAPDH on all 4 of its cysteine residues and shut down enzymatic activity; (ii) severely lowered cellular ATP content below life-sustaining levels, and (iii) triggered rapid necrosis. Intriguingly, supplemental antioxidants effectively prevented cytotoxic activity of NEO218 as well as 3-BP, but supplemental pyruvate powerfully protected cells only from 3-BP, not from NEO218. Unlike 3-BP, NEO218 exerted its potent cytotoxic activity irrespective of cellular MCT-1 status. Treatment of HCT116 cells with 3-BP resulted in prompt development of resistance, based on the emergence of MCT-1-negative cells. This was not the case with NEO218, and highly 3-BP-resistant cells remained exquisitely sensitive to NEO218. Thus, our study identifies a mechanism by which tumor cells develop rapid resistance to 3-BP, and presents NEO218 as a superior agent not subject to this cellular defense. Furthermore, our results offer alternative interpretations of previously

  11. MIMO Communication for Cellular Networks

    CERN Document Server

    Huang, Howard; Venkatesan, Sivarama

    2012-01-01

    As the theoretical foundations of multiple-antenna techniques evolve and as these multiple-input multiple-output (MIMO) techniques become essential for providing high data rates in wireless systems, there is a growing need to understand the performance limits of MIMO in practical networks. To address this need, MIMO Communication for Cellular Networks presents a systematic description of MIMO technology classes and a framework for MIMO system design that takes into account the essential physical-layer features of practical cellular networks. In contrast to works that focus on the theoretical performance of abstract MIMO channels, MIMO Communication for Cellular Networks emphasizes the practical performance of realistic MIMO systems. A unified set of system simulation results highlights relative performance gains of different MIMO techniques and provides insights into how best to use multiple antennas in cellular networks under various conditions. MIMO Communication for Cellular Networks describes single-user,...

  12. Computer Network Defense and Attack: Information Warfare in the Department of Defense

    National Research Council Canada - National Science Library

    Best, Carole

    2001-01-01

    .... This paper will discuss current computer network defense and attack policy in the context of ends, ways and means, explain what is lacking in current policy and offer recommendations for improvement...

  13. Cost Effective Regional Ballistic Missile Defense

    Science.gov (United States)

    2016-02-16

    deploying advanced air defense systems18, such as the Russian S-300 and S-500, and concealing them in hardened, camouflaged sites, such as extensive... Russian objections to the European Phased Adaptive Approach (EPAA) and fund homeland defense priorities.39 Furthermore, the PTSS system was also... Theatre Ballistic Missile Defence Capability Becomes Operational,” Jane’s Missiles & Rockets, 1 February 2011. 55 Joseph W. Kirschbaum, REGIONAL MISSILE

  14. Forager bees (Apis mellifera) highly express immune and detoxification genes in tissues associated with nectar processing.

    Science.gov (United States)

    Vannette, Rachel L; Mohamed, Abbas; Johnson, Brian R

    2015-11-09

    Pollinators, including honey bees, routinely encounter potentially harmful microorganisms and phytochemicals during foraging. However, the mechanisms by which honey bees manage these potential threats are poorly understood. In this study, we examine the expression of antimicrobial, immune and detoxification genes in Apis mellifera and compare between forager and nurse bees using tissue-specific RNA-seq and qPCR. Our analysis revealed extensive tissue-specific expression of antimicrobial, immune signaling, and detoxification genes. Variation in gene expression between worker stages was pronounced in the mandibular and hypopharyngeal gland (HPG), where foragers were enriched in transcripts that encode antimicrobial peptides (AMPs) and immune response. Additionally, forager HPGs and mandibular glands were enriched in transcripts encoding detoxification enzymes, including some associated with xenobiotic metabolism. Using qPCR on an independent dataset, we verified differential expression of three AMP and three P450 genes between foragers and nurses. High expression of AMP genes in nectar-processing tissues suggests that these peptides may contribute to antimicrobial properties of honey or to honey bee defense against environmentally-acquired microorganisms. Together, these results suggest that worker role and tissue-specific expression of AMPs, and immune and detoxification enzymes may contribute to defense against microorganisms and xenobiotic compounds acquired while foraging.

  15. 75 FR 22753 - Federal Advisory Committee; Defense Science Board; Charter Renewal

    Science.gov (United States)

    2010-04-30

    ... Deputy Secretary of Defense; the Under Secretary of Defense for Acquisition, Technology and Logistics... complex technology problems facing the Department of Defense in such areas as research, engineering, and... official. The Under Secretary of Defense for Acquisition, Technology and Logistics shall be authorized to...

  16. Soviet debate on missile defense

    Energy Technology Data Exchange (ETDEWEB)

    Parrott, B.

    1987-04-01

    Although the Strategic Defense Initiative (SDI) is meant to cope with the danger of a Soviet nuclear attack, the recent US debate over SDI has paid surprisingly little attention to Soviet views of ballistic missile defense. Despite the existence of a substantial body of pertinent scholarship, the debate has failed to take adequate account of major changes in Soviet ballistic missile defense policy since the mid-1960s. It has also neglected the links between current Soviet military policy and broader Soviet political and economic choices. The Soviets regard SDI not as a novel undertaking to reduce the risks of nuclear war but as an extension of the geopolitical competition between the superpowers. This competition has been dominated in the 1980s, in the Soviet view, by sharply increased US assertiveness and the decline of detente. Viewing SDI as a manifestation of these general trends, Soviet decision makers find the prospect of an unregulated race in ballistic missile defenses and military space technologies deeply unsettling. The deterioration of superpower relations has raised serious doubts in Moscow about the wisdom of Soviet external policy during the 1970s and has provoked sharp internal differences over policy toward the US. Already highly suspicious of the Reagan administration, the elite is united by a general conviction that SDI is an American gambit that may ultimately undercut past Soviet strategic gains and pose a grave new threat to Soviet security. 14 references.

  17. Modulation of xenobiotic metabolising enzymes by anticarcinogens-focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Pool-Zobel, Beatrice [Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University Jena, 07743 Jena (Germany)]. E-mail: b8pobe@uni-jena.de; Veeriah, Selvaraju [Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University Jena, 07743 Jena (Germany); Boehmer, Frank-D. [Institute of Molecular Cell Biology, University Hospital, Friedrich Schiller University Jena, 07743 Jena (Germany)

    2005-12-11

    There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione S-transferases [GST]), which primarily catalyze conjugation reactions. The conjugation of electrophilic Phase I intermediates with glutathione, for instance, frequently results in detoxification. Several possible colon carcinogens may serve as substrates for GST isoenzymes that can have marked substrate specificity. The conjugated products could be less toxic/genotoxic if GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown that the induction of GSTs by antioxidants enables experimental animals to tolerate exposure to carcinogens. One important mechanism of GST induction involves an antioxidant-responsive response element (ARE) and the transcription factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch-like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate expression of Phase II genes via interaction with the ARE. GSTs are also induced by butyrate, a product of gut flora-derived fermentation of plant foods, which may act via different mechanisms, e.g. by increasing histone acetylation. GSTs are expressed with high inter-individual variability in human colonocytes, which points to large differences in cellular susceptibility to xenobiotics. Enhancing expression of GSTs in human colon tissue could therefore contribute to reducing cancer risks. However, it has not been demonstrated in humans that this mechanism is associated with cancer prevention. In the

  18. Modulation of xenobiotic metabolising enzymes by anticarcinogens-focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis

    International Nuclear Information System (INIS)

    Pool-Zobel, Beatrice; Veeriah, Selvaraju; Boehmer, Frank-D.

    2005-01-01

    There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione S-transferases [GST]), which primarily catalyze conjugation reactions. The conjugation of electrophilic Phase I intermediates with glutathione, for instance, frequently results in detoxification. Several possible colon carcinogens may serve as substrates for GST isoenzymes that can have marked substrate specificity. The conjugated products could be less toxic/genotoxic if GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown that the induction of GSTs by antioxidants enables experimental animals to tolerate exposure to carcinogens. One important mechanism of GST induction involves an antioxidant-responsive response element (ARE) and the transcription factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch-like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate expression of Phase II genes via interaction with the ARE. GSTs are also induced by butyrate, a product of gut flora-derived fermentation of plant foods, which may act via different mechanisms, e.g. by increasing histone acetylation. GSTs are expressed with high inter-individual variability in human colonocytes, which points to large differences in cellular susceptibility to xenobiotics. Enhancing expression of GSTs in human colon tissue could therefore contribute to reducing cancer risks. However, it has not been demonstrated in humans that this mechanism is associated with cancer prevention. In the

  19. 75 FR 71080 - Closed Meeting of the Department of Defense Wage Committee

    Science.gov (United States)

    2010-11-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary Closed Meeting of the Department of Defense Wage... closed meetings of the Department of Defense Wage Committee. DATES: Tuesday, December 14, 2010; at 10 a.m... obtained by writing to the Chairman, Department of Defense Wage Committee, 4000 Defense Pentagon...

  20. Extracellular Alkalinization as a Defense Response in Potato Cells.

    Science.gov (United States)

    Moroz, Natalia; Fritch, Karen R; Marcec, Matthew J; Tripathi, Diwaker; Smertenko, Andrei; Tanaka, Kiwamu

    2017-01-01

    A quantitative and robust bioassay to assess plant defense response is important for studies of disease resistance and also for the early identification of disease during pre- or non-symptomatic phases. An increase in extracellular pH is known to be an early defense response in plants. In this study, we demonstrate extracellular alkalinization as a defense response in potatoes. Using potato suspension cell cultures, we observed an alkalinization response against various pathogen- and plant-derived elicitors in a dose- and time-dependent manner. We also assessed the defense response against a variety of potato pathogens, such as protists ( Phytophthora infestans and Spongospora subterranea ) and fungi ( Verticillium dahliae and Colletotrichum coccodes ). Our results show that extracellular pH increases within 30 min in proportion to the number of pathogen spores added. Consistently with the alkalinization effect, the higher transcription level of several defense-related genes and production of reactive oxygen species was observed. Our results demonstrate that the alkalinization response is an effective marker to study early stages of defense response in potatoes.

  1. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

    International Nuclear Information System (INIS)

    Benderitter, M.; Assem, M.; Maupoil, V.

    1995-01-01

    During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab

  2. Cash Management in the Defense Working Capital Funds

    National Research Council Canada - National Science Library

    1997-01-01

    ... (formerly the Defense Business Operations Fund) was identified during our audit of the Fund Balance With Treasury Account of the FY 1996 Consolidated Financial Statements of the Defense Business Operations Fund...

  3. The Role of Oxidative Stress in Carcinogenesis Induced by Metals and Xenobiotics

    International Nuclear Information System (INIS)

    Henkler, Frank; Brinkmann, Joep; Luch, Andreas

    2010-01-01

    In addition to a wide range of adverse effects on human health, toxic metals such as cadmium, arsenic and nickel can also promote carcinogenesis. The toxicological properties of these metals are partly related to generation of reactive oxygen species (ROS) that can induce DNA damage and trigger redox-dependent transcription factors. The precise mechanisms that induce oxidative stress are not fully understood. Further, it is not yet known whether chronic exposures to low doses of arsenic, cadmium or other metals are sufficient to induce mutations in vivo, leading to DNA repair responses and/or tumorigenesis. Oxidative stress can also be induced by environmental xenobiotics, when certain metabolites are generated that lead to the continuous release of superoxide, as long as the capacity to reduce the resulting dions (quinones) into hydroquinones is maintained. However, the specific significance of superoxide-dependent pathways to carcinogenesis is often difficult to address, because formation of DNA adducts by mutagenic metabolites can occur in parallel. Here, we will review both mechanisms and toxicological consequences of oxidative stress triggered by metals and dietary or environmental pollutants in general. Besides causing DNA damage, ROS may further induce multiple intracellular signaling pathways, notably NF-κB, JNK/SAPK/p38, as well as Erk/MAPK. These signaling routes can lead to transcriptional induction of target genes that could promote proliferation or confer apoptosis resistance to exposed cells. The significance of these additional modes depends on tissue, cell-type and is often masked by alternate oncogenic mechanisms being activated in parallel

  4. 75 FR 33587 - Federal Advisory Committee; Department of Defense Wage Committee

    Science.gov (United States)

    2010-06-14

    ... Wage Committee AGENCY: Department of Defense (DoD). ACTION: Notice of closed meeting. SUMMARY: Pursuant... hereby given that the Department of Defense Wage Committee will meet on July 13, 2010, in Rosslyn... writing to the Chairman, Department of Defense Wage Committee, 4000 Defense Pentagon, Washington, DC 20301...

  5. 75 FR 44231 - Federal Advisory Committee; Department of Defense Wage Committee

    Science.gov (United States)

    2010-07-28

    ... Wage Committee AGENCY: Department of Defense (DoD). ACTION: Notice of closed meeting. SUMMARY: Pursuant... hereby given that a closed meeting of the Department of Defense Wage Committee will be held on August 24..., Department of Defense Wage Committee, 4000 Defense Pentagon, Washington, DC 20301- 4000. SUPPLEMENTARY...

  6. 75 FR 28786 - Federal Advisory Committee; Department of Defense Wage Committee

    Science.gov (United States)

    2010-05-24

    ... Wage Committee AGENCY: Department of Defense (DoD). ACTION: Notice of closed meeting. SUMMARY: Pursuant... hereby given that a closed meeting of the Department of Defense Wage Committee will be held on June 15..., Department of Defense Wage Committee, 4000 Defense Pentagon, Washington, DC 20301- 4000. SUPPLEMENTARY...

  7. 75 FR 40796 - Federal Advisory Committee; Department of Defense Wage Committee

    Science.gov (United States)

    2010-07-14

    ... Wage Committee AGENCY: Department of Defense (DoD). ACTION: Notice of closed meeting. SUMMARY: Pursuant... hereby given that a closed meeting of the Department of Defense Wage Committee will be held on August 10..., Department of Defense Wage Committee, 4000 Defense Pentagon, Washington, DC 20301- 4000. SUPPLEMENTARY...

  8. Cellular communications a comprehensive and practical guide

    CERN Document Server

    Tripathi, Nishith

    2014-01-01

    Even as newer cellular technologies and standards emerge, many of the fundamental principles and the components of the cellular network remain the same. Presenting a simple yet comprehensive view of cellular communications technologies, Cellular Communications provides an end-to-end perspective of cellular operations, ranging from physical layer details to call set-up and from the radio network to the core network. This self-contained source forpractitioners and students represents a comprehensive survey of the fundamentals of cellular communications and the landscape of commercially deployed

  9. 76 FR 72245 - Implementation of Defense Trade Cooperation Treaties

    Science.gov (United States)

    2011-11-22

    ... equipment sold under a contract in the amount of $25,000,000 or more (currently required for amounts of $14... equipment sold under a contract in the amount in the amount of $25,000,000 or more, or for defense articles... the Defense Trade Cooperation Treaty between the United States and Australia and the Defense Trade...

  10. Magnetohydrodynamics cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu.

    1990-02-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  11. Magnetohydrodynamic cellular automata

    Energy Technology Data Exchange (ETDEWEB)

    Hatori, Tadatsugu [National Inst. for Fusion Science, Nagoya (Japan)

    1990-03-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author).

  12. Magnetohydrodynamic cellular automata

    International Nuclear Information System (INIS)

    Hatori, Tadatsugu

    1990-01-01

    There has been a renewal of interest in cellular automata, partly because they give an architecture for a special purpose computer with parallel processing optimized to solve a particular problem. The lattice gas cellular automata are briefly surveyed, which are recently developed to solve partial differential equations such as hydrodynamics or magnetohydrodynamics. A new model is given in the present paper to implement the magnetic Lorentz force in a more deterministic and local procedure than the previous one. (author)

  13. Modeling cellular systems

    CERN Document Server

    Matthäus, Franziska; Pahle, Jürgen

    2017-01-01

    This contributed volume comprises research articles and reviews on topics connected to the mathematical modeling of cellular systems. These contributions cover signaling pathways, stochastic effects, cell motility and mechanics, pattern formation processes, as well as multi-scale approaches. All authors attended the workshop on "Modeling Cellular Systems" which took place in Heidelberg in October 2014. The target audience primarily comprises researchers and experts in the field, but the book may also be beneficial for graduate students.

  14. Federal Aviation Administration's behavioral research program for defense against hijackings.

    Science.gov (United States)

    Dailey, J T; Pickrel, E W

    1975-04-01

    Behavioral research has been significant contributions to the government's successful program for defense against hijackers. Today's boarding gate defenses have a leading role in that program, but they were rejected until creation of the behavioral profile made selective search feasible. Metal detectors now make search of all travelers practical but with increasing involvement of boarding gate employees, so a behavioral program is used to monitor their performance. Experience shows that some persons have penetrated boarding gate defenses, so another requirement was in-flight defenses. Flightpersonnel had defeated some past hijackers, so a behavioral analysis of past hijackings was used to identify tactics for in-flight defense. These were incorporated into training programs and distributed to all U.S. airlines, many government organizations, and foreign carriers. Research continues for updating these and developing new courses for special needs, such as defense against gangs.

  15. Limited response of ponderosa pine bole defenses to wounding and fungi.

    Science.gov (United States)

    Gaylord, Monica L; Hofstetter, Richard W; Kolb, Thomas E; Wagner, Michael R

    2011-04-01

    Tree defense against bark beetles (Curculionidae: Scolytinae) and their associated fungi generally comprises some combination of constitutive (primary) and induced (secondary) defenses. In pines, the primary constitutive defense against bark beetles consists of preformed resin stored in resin ducts. Induced defenses at the wound site (point of beetle entry) in pines may consist of an increase in resin flow and necrotic lesion formation. The quantity and quality of both induced and constitutive defenses can vary by species and season. The inducible defense response in ponderosa pine is not well understood. Our study examined the inducible defense response in ponderosa pine using traumatic mechanical wounding, and wounding with and without fungal inoculations with two different bark beetle-associated fungi (Ophiostoma minus and Grosmannia clavigera). Resin flow did not significantly increase in response to any treatment. In addition, necrotic lesion formation on the bole after fungal inoculation was minimal. Stand thinning, which has been shown to increase water availability, had no, or inconsistent, effects on inducible tree defense. Our results suggest that ponderosa pine bole defense against bark beetles and their associated fungi is primarily constitutive and not induced.

  16. Cellular Angiofibroma of the Nasopharynx.

    Science.gov (United States)

    Erdur, Zülküf Burak; Yener, Haydar Murat; Yilmaz, Mehmet; Karaaltin, Ayşegül Batioğlu; Inan, Hakki Caner; Alaskarov, Elvin; Gozen, Emine Deniz

    2017-11-01

    Angiofibroma is a common tumor of the nasopharynx region but cellular type is extremely rare in head and neck. A 13-year-old boy presented with frequent epistaxis and nasal obstruction persisting for 6 months. According to the clinical symptoms and imaging studies juvenile angiofibroma was suspected. Following angiographic embolization total excision of the lesion by midfacial degloving approach was performed. Histological examination revealed that the tumor consisted of staghorn blood vessels and irregular fibrous stroma. Stellate fibroblasts with small pyknotic to large vesicular nuclei were seen in a highly cellular stroma. These findings identified cellular angiofibroma mimicking juvenile angiofibroma. This article is about a very rare patient of cellular angiofibroma of nasopharynx.

  17. Tricking the guard: exploiting plant defense for disease susceptibility.

    Science.gov (United States)

    Lorang, J; Kidarsa, T; Bradford, C S; Gilbert, B; Curtis, M; Tzeng, S-C; Maier, C S; Wolpert, T J

    2012-11-02

    Typically, pathogens deploy virulence effectors to disable defense. Plants defeat effectors with resistance proteins that guard effector targets. We found that a pathogen exploits a resistance protein by activating it to confer susceptibility in Arabidopsis. The guard mechanism of plant defense is recapitulated by interactions among victorin (an effector produced by the necrotrophic fungus Cochliobolus victoriae), TRX-h5 (a defense-associated thioredoxin), and LOV1 (an Arabidopsis susceptibility protein). In LOV1's absence, victorin inhibits TRX-h5, resulting in compromised defense but not disease by C. victoriae. In LOV1's presence, victorin binding to TRX-h5 activates LOV1 and elicits a resistance-like response that confers disease susceptibility. We propose that victorin is, or mimics, a conventional pathogen virulence effector that was defeated by LOV1 and confers virulence to C. victoriae solely because it incites defense.

  18. Extraribosomal l13a is a specific innate immune factor for antiviral defense.

    Science.gov (United States)

    Mazumder, Barsanjit; Poddar, Darshana; Basu, Abhijit; Kour, Ravinder; Verbovetskaya, Valentina; Barik, Sailen

    2014-08-01

    We report a novel extraribosomal innate immune function of mammalian ribosomal protein L13a, whereby it acts as an antiviral agent. We found that L13a is released from the 60S ribosomal subunit in response to infection by respiratory syncytial virus (RSV), an RNA virus of the Pneumovirus genus and a serious lung pathogen. Unexpectedly, the growth of RSV was highly enhanced in L13a-knocked-down cells of various lineages as well as in L13a knockout macrophages from mice. In all L13a-deficient cells tested, translation of RSV matrix (M) protein was specifically stimulated, as judged by a greater abundance of M protein and greater association of the M mRNA with polyribosomes, while general translation was unaffected. In silico RNA folding analysis and translational reporter assays revealed a putative hairpin in the 3'untranslated region (UTR) of M mRNA with significant structural similarity to the cellular GAIT (gamma-activated inhibitor of translation) RNA hairpin, previously shown to be responsible for assembling a large, L13a-containing ribonucleoprotein complex that promoted translational silencing in gamma interferon (IFN-γ)-activated myeloid cells. However, RNA-protein interaction studies revealed that this complex, which we named VAIT (respiratory syncytial virus-activated inhibitor of translation) is functionally different from the GAIT complex. VAIT is the first report of an extraribosomal L13a-mediated, IFN-γ-independent innate antiviral complex triggered in response to virus infection. We provide a model in which the VAIT complex strongly hinders RSV replication by inhibiting the translation of the rate-limiting viral M protein, which is a new paradigm in antiviral defense. The innate immune mechanisms of host cells are diverse in nature and act as a broad-spectrum cellular defense against viruses. Here, we report a novel innate immune mechanism functioning against respiratory syncytial virus (RSV), in which the cellular ribosomal protein L13a is released

  19. Why even good defenses may be bad

    International Nuclear Information System (INIS)

    Glaser, C.L.

    1984-01-01

    The current debate over whether an effective ballistic missile defense (BMD) is technically feasible and whether it could be developed and deployed has left most of the advocacy up to those supporting a BMD program. The author emphasizes the issues beyond technical feasibility in his conclusion that assured destruction may still be preferable to perfect defense in terms of reducing the probability of nuclear war. After examining a number of possible scenarios involving the US and Soviet Union, the positions of allies, and the possibility of clandestine bombs, he sees no reason to expect that a defense system would be less vulnerable or have fewer uncertainties. 29 references

  20. 76 FR 28001 - Meeting of the Department of Defense Wage Committee

    Science.gov (United States)

    2011-05-13

    ... DEPARTMENT OF DEFENSE Office of the Secretary Meeting of the Department of Defense Wage Committee... Department of Defense Wage Committee will be held on Tuesday, June 14, 2011, and Tuesday, June 28, 2011, at... and practices of the Department of Defense and the detailed wage data to be considered were obtained...