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Sample records for putative environmental-endocrine disruptors

  1. Environmental endocrine disruptors: A proposed classification scheme

    Energy Technology Data Exchange (ETDEWEB)

    Fur, P.L. de; Roberts, J. [Environmental Defense Fund, Washington, DC (United States)

    1995-12-31

    A number of chemicals known to act on animal systems through the endocrine system have been termed environmental endocrine disruptors. This group includes some of the PCBs and TCDDs, as well as lead, mercury and a large number of pesticides. The common feature is that the chemicals interact with endogenous endocrine systems at the cellular and/or molecular level to alter normal processes that are controlled or regulated by hormones. Although the existence of artificial or environmental estrogens (e.g. chlordecone and DES) has been known for some time, recent data indicate that this phenomenon is widespread. Indeed, anti-androgens have been held responsible for reproductive dysfunction in alligator populations in Florida. But the significance of endocrine disruption was recognized by pesticide manufacturers when insect growth regulators were developed to interfere with hormonal control of growth. Controlling, regulating or managing these chemicals depends in no small part on the ability to identify, screen or otherwise know that a chemical is an endocrine disrupter. Two possible classifications schemes are: using the effects caused in an animal, or animals as an exposure indicator; and using a known screen for the point of contact with the animal. The former would require extensive knowledge of cause and effect relationships in dozens of animal groups; the latter would require a screening tool comparable to an estrogen binding assay. The authors present a possible classification based on chemicals known to disrupt estrogenic, androgenic and ecdysone regulated hormonal systems.

  2. Developments in the EPA Computational Toxicology Program to Identify Environmental Endocrine Disruptors ( Environmental Endocrine Disruptors Gordon Conference)

    Science.gov (United States)

    Presentation at the Environmental Endocrine Disruptors Gordon Conference in Newry, ME June 22, 2016 to give an overview of the use of high throughput screening and high throughput toxicokinetics to build models for endocrine disruption by environmental chemicals for estrogen rece...

  3. Organic synthetic environmental endocrine disruptors: structural classes and metabolic fate.

    Science.gov (United States)

    Schmidt, Jan; Peterlin-Mašič, Lucija

    2012-12-01

    Endocrine disruption is the modification of the endocrine system causing harmful effects in healthy subjects or their offspring. Physiological endocrine hormones act at very low plasma concentrations, and certain chemicals known as endocrine disrupting compounds (EDCs) are suspected of modifying endocrine function at similarly low concentrations. In our review we focus mainly on the structural classes of organic synthetic environmental endocrine disruptors and their common structural elements that enable them to interact with estrogen signalling. EDCs can affect estrogenic signalling directly through interaction with estrogen receptors (ERs) or indirectly through transcription factors such as the aryl hydrocarbon receptor (AhR) or by modulation of critical metabolic enzymes engaged in estrogen biosynthesis and metabolism. However, some structural elements can also pose a great risk of cytotoxicity and genotoxicity, especially after biotransformation to reactive metabolites.

  4. Light at night as an environmental endocrine disruptor.

    Science.gov (United States)

    Russart, Kathryn L G; Nelson, Randy J

    2017-09-06

    Environmental endocrine disruptors (EEDs) are often consequences of human activity; however, the effects of EEDs are not limited to humans. A primary focus over the past ∼30years has been on chemical EEDs, but the repercussions of non-chemical EEDs, such as artificial light at night (LAN), are of increasing interest. The sensitivity of the circadian system to light and the influence of circadian organization on overall physiology and behavior make the system a target for disruption with widespread effects. Indeed, there is increasing evidence for a role of LAN in human health, including disruption of circadian regulation and melatonin signaling, metabolic dysregulation, cancer risk, and disruption of other hormonally-driven systems. These effects are not limited to humans; domesticated animals as well as wildlife are also exposed to LAN, and at risk for disrupted circadian rhythms. Here, we review data that support the role of LAN as an endocrine disruptor in humans to be considered in treatments and lifestyle suggestions. We also present the effects of LAN in other animals, and discuss the potential for ecosystem-wide effects of artificial LAN. This can inform decisions in agricultural practices and urban lighting decisions to avoid unintended outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Environmental endocrine disruptors: Effects on the human male reproductive system.

    Science.gov (United States)

    Sweeney, M F; Hasan, N; Soto, A M; Sonnenschein, C

    2015-12-01

    Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine-related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward.

  6. Biodegradation Characteristics of Environmental Endocrine Disruptor Di-n-butyl Phthalate

    Institute of Scientific and Technical Information of China (English)

    LIN WANG; QI-FANG LUO

    2005-01-01

    Objective The biodegradation characteristics of di-n-butyl phthalate (DBP), an environmental endocrine disruptor, were studied by the method of dominant bacteria and immobilized microorganisms. Methods Taking DBP as the only carbon source to acclimatize the collected activated sludge, the concentration of DBP increased progressively in the process of acclimatization. Plate streaking was used to separate 1 strain of the degradation dominant bacteria after acclimatization. Better conditions to degrade DBP by the bacterium could be obtained through orthogonal experiments and the bacterium was identified. Then the acclimated activated sludge was made to immobilize the microorganism using polyvinyl alcohol as entrapment agent. The immobilized microorganism degraded DBP at different conditions. Results The appropriate conditions to degrade DBP by the dominant bacteria were: degradation time, 32 h; DBP concentration, 200 mg/L; rate of shaking incubator, 100 r/min; pH, 7 and temperature, 30℃. DBP could be degraded by more than 95% under such conditions. The bacteria were identified as pseudomonas. The proliferated immobilized microorganisms degraded DBP more effectively and more adapted to temperature and pH than the free acclimated activated sludge. Conclusion One strain of DBP degradation dominant bacteria was separated from the acclimatized activated sludge. It could grow with DBP as the only carbon source and energy, and degraded DBP effectively. After having been immobilized and proliferated, the dominant bacteria could keep a higher biological activity and degrade DBP more effectively than activated sludge.

  7. Long-term effects of environmental endocrine disruptors on reproductive physiology and behavior

    Directory of Open Access Journals (Sweden)

    Heather B Patisaul

    2009-06-01

    Full Text Available It is well established that, over the course of development, hormones shape the vertebrate brain such that sex specific physiology and behaviors emerge. Much of this occurs in discrete developmental windows that span gestation through the prenatal period, although it is now becoming clear that at least some of this process continues through puberty. Perturbation of this developmental progression can permanently alter the capacity for reproductive success. Wildlife studies have revealed that exposure to endocrine disrupting compounds (EDCs, either naturally occurring or man made, can profoundly alter reproductive physiology and ultimately impact entire populations. Laboratory studies in rodents and other species have elucidated some of the mechanisms by which this occurs and strongly indicate that humans are also vulnerable to disruption. Use of hormonally active compounds in human medicine has also unfortunately revealed that the developing fetus can be exposed to and affected by endocrine disruptors, and that it might take decades for adverse effects to manifest. Research within the field of environmental endocrine disruption has also contributed to the general understanding of how early life experiences can alter reproductive physiology and behavior through non-genomic, epigenetic mechanisms such as DNA methylation and histone acetylation. These types of effects have the potential to impact future generations if the germ line is affected. This review provides an overview of how exposure to EDCs, particularly those that interfere with estrogen action, impacts reproductive physiology and behaviors in vertebrates.

  8. 环境内分泌干扰物与kisspeptin系统%Environmental endocrine disruptors and kisspeptin system

    Institute of Scientific and Technical Information of China (English)

    张莹(综述); 陈瑞敏(审校)

    2014-01-01

    环境内分泌干扰物( environmental endocrine disruptors,EED)对性发育的影响越来越受到关注。 Kisspeptin系统是EED干扰下丘脑-垂体-性腺轴新靶点。 EED的雌激素特性使其能够对kisspeptin系统产生影响,从而导致一系列改变,如青春启动时间改变、生育障碍及代谢紊乱。目前主要对三种干扰kisspeptin信号传导途径的EED进行了研究,包括双酚A、多氯联苯和植物雌激素染料异黄酮。%Environmental endocrine disruptors have garnered considerable attention in recent years be-cause of their endocrine disruption on sex development disorders. Kisspeptin system might be a novel target for endocrine disruption at the hypothalamic-pituitary-gonad axis. Environmental endocrine disruptors′estrogenic properties make them capable of interacting with the kisspeptin system,and then confer lifelong consequences in-cluding altered pubertal timing, infertility, and metabolic disorders. To date, three compounds have been well studied for their capacity to interfere with kisspeptin signaling pathways:BPA,PCB mixtures,and the phytoestro-gen GEN.

  9. Environmental endocrine disruptors and developmental abnormalities in wildlife; Kankyo horumon (gaiinsei naibunpi kakuran kagaku busshitsu) no kankyo seibutsu ni taisuru eikyo

    Energy Technology Data Exchange (ETDEWEB)

    Iguchi, T. [Yokohama City Univ., Yokohama (Japan)

    1998-04-15

    The environmental endocrine disruptor, or the so-called environmental hormone, is outlined. Hormones are secreted from endocrine glands in trace amounts, transported by blood, and exert influence on the target organs and distal cells, this to sustain constancy in living organisms. There are two types: peptide hormones which are rows of amino acids and steroid hormones which are composed of cholesterol. Endocrine disruptors are chemical substances discharged into the environment which, once taken into human organisms, disrupt endocrine systems, some acting like female sex hormones and others resisting male sex hormones. Many a wild animal are found affected by them. They are accumulating in human organisms too. Synthesized chemical substances such as DDT, PCB, dioxins, and alkylphenols present in the water system affect a fish by disrupting its endocrine, immunity, nerve, growth, and regeneration. Embryos and larvae are quite susceptible, easy to turn abnormal. Voices are high across the world for the study of environmental endocrine disruptors. Introduced in this report are some animal experiments, typical cases of impact on the ecosystem, and systems for detecting environmental endocrine disruptors. 36 refs., 1 tab.

  10. 内分泌干扰物生物检测研究进展%Review of Bioassay Methods of Environmental Endocrine Disruptors Detection

    Institute of Scientific and Technical Information of China (English)

    张慧珠

    2014-01-01

    The problem of environmental endocrine disruptors has become a global issue.Several bioassay methods of endocrine disruptors are overviewed.The trends of bioassay methods are prospected.%介绍了发光细菌法、重组基因酵母法、免疫分析法、细胞增殖法、受体结合活性法、卵黄蛋白法、酵母双杂交法等几种环境中内分泌干扰物的生物检测技术及研究进展,并提出了展望。

  11. Exposure levels of environmental endocrine disruptors in mother-newborn pairs in China and their placental transfer characteristics.

    Directory of Open Access Journals (Sweden)

    Lu-Xi Li

    Full Text Available There is a growing concern about the potential health effects of exposure to various environmental chemicals during pregnancy and infancy. The placenta is expected to be an effective barrier protecting the developing embryo against some endocrine disruptors (EDs circulating in maternal blood. The current study was designed to assess in utero exposure levels of non-persistent organic pollutants (non-POPs and persistent organic pollutants (POPs in Chinese newborns and potential role of placenta barrier against fetal exposure to these commonly-used environmental endocrine disruptors. A total of 230 newborn-mother pairs were enrolled during 2010-2011, 201 pairs of which were recruited from Shanghai, and the other 29 pairs came from Wenzhou. Maternal blood, cord blood, and meconium specimens were collected in the subject population from Shanghai and analyzed for non-POPs, including mono-2-ethylhexyl phthalate (MEHP, octylphenol (OP and 4-nonylphenol (4-NP. A total of 19 polybrominated diphenyl ethers (PBDEs congeners, which belong to POPs, were detected in maternal and cord blood specimens from the other 29 pairs. Fetal-maternal ratios (F-M ratios and regression coefficients were presented to assess potential function of placenta on barricading the mother/fetal transfer of these EDs. Concentrations of the detected non-POPs in cord blood samples were approximately 20% lower than those in maternal blood, and regression coefficients of which were all over 0.80. In contrast, PBDEs levels in cord blood samples were significantly higher than those in maternal blood. MEHP levels in meconium were much higher than those in cord blood samples, and highly correlated. Therefore, observations demonstrated that the placental barrier slightly decreased the fetal exposure to most non-POPs, while PBDEs seemed to be totally transferred across the placenta and finally reached the fetus. For in utero exposure assessment of Di-2-ethylhexyl phthalate (DEHP, MEHP level in

  12. 环境内分泌干扰物对生殖健康的影响%Effect of environmental endocrine disruptors on fertility

    Institute of Scientific and Technical Information of China (English)

    刘超

    2007-01-01

    @@ 近年来,世界各国发表了许多关于男性及雄性动物生殖功能下降的报道.具有内分泌活性的环境污染物质--"环境内分泌干扰物"(environmental endocrine disruptors,EED),是否可导致男性生殖功能障碍备受关注.

  13. Testing Potential Effect of Environmental Endocrine Disruptors in Cow Milk on Reproductive Index in Female Rats

    Institute of Scientific and Technical Information of China (English)

    XIANG-MING LI; DAVAASAMBUU GANMAA; LI-QIANG QIN; AKIO SATO

    2005-01-01

    Objective To study the effect of endocrine disruptor chemicals in cow milk on female reproductive system. Methods A two-generation reproduction was conducted according to U. S. FDA standard. Milk was fed in special bottle to Wistar rats of both sexes through two successive generations (F0 and F1) in the milk group while artificial milk was fed to rats in the control group. Twenty-four rats of each sex were mated in each group. Measurements were made according to this guideline. Results Reproductive parameters in the milk group such as fertility index, gestation index, weights of uterus and ovary, days of vaginal opening, estrous cycles, histological morphological changes were comparable to those in the control group. However, the means of body weight had some differences. The body weight gains increased significantly in the milk-treated group in F1 and F2 generation compared with those in the control group. The concentration of insulin-like growth factor-1 (IGF-1) in blood in the milk group was comparable to that in the control group, but the standard deviation changed greatly in the milk-treated rats. Conclusion Endocrine disruptor chemicals in milk have no severe effects on the female reproductive system.

  14. Negative role of the environmental endocrine disruptors in the human neurodevelopment

    Directory of Open Access Journals (Sweden)

    Luca Roncati

    2016-08-01

    Full Text Available The endocrine disruptors (EDs are able to influence the endocrine system, mimicking or antagonizing hormonal molecules. They are bio-persistent for their degradation resistance in the environment. Our research group has investigated by gas chromatography-mass spectrometry (GC-MS the EDs presence in 35 brain samples, coming from 27 cases of sudden intrauterine unexplained death syndrome (SIUDS and 8 cases of sudden infant death syndrome (SIDS, collected by centralization in the last year (2015. More in detail, a mixture of 25 EDs has been subjected to analytical procedure, following standard protocols. Among the target analytes, some organochlorine pesticides (OCPs, that is α-chlordane, γ-chlordane, heptachlor, p,p-DDE, p,p-DDT, and the two most commonly used organophosphorus pesticides (OPPs, chlorpyrifos and chlorfenvinfos, have been found in 7 and 3 samples, respectively. The analytical procedure used to detect the presence of environmental EDs in cortex samples has been successfully implemented on SIUDS and SIDS victims. The environmental EDs have been found to be able to overcome the placental barrier, reaching also the basal ganglia assigned to the control of the vital functions. This finding, related to the OPPs bio-persistence, implies a conceptual redefinition of the fetal-placental and fetal blood-brain barriers: not real safety barriers, but simply time-deferral mechanisms of absorption.

  15. Negative Role of the Environmental Endocrine Disruptors in the Human Neurodevelopment.

    Science.gov (United States)

    Roncati, Luca; Termopoli, Veronica; Pusiol, Teresa

    2016-01-01

    The endocrine disruptors (EDs) are able to influence the endocrine system, mimicking or antagonizing hormonal molecules. They are bio-persistent for their degradation resistance in the environment. Our research group has investigated by gas chromatography-mass spectrometry (GC-MS) the EDs presence in 35 brain samples, coming from 27 cases of sudden intrauterine unexplained death syndrome (SIUDS) and 8 cases of sudden infant death syndrome (SIDS), collected by centralization in the last year (2015). More in detail, a mixture of 25 EDs has been subjected to analytical procedure, following standard protocols. Among the target analytes, some organochlorine pesticides, that is α-chlordane, γ-chlordane, heptachlor, p,p-DDE, p,p-DDT, and the two most commonly used organophosphorus pesticides (OPPs), chlorpyrifos and chlorfenvinfos, have been found in seven and three samples, respectively. The analytical procedure used to detect the presence of environmental EDs in cortex samples has been successfully implemented on SIUDS and SIDS victims. The environmental EDs have been found to be able to overcome the placental barrier, reaching also the basal ganglia assigned to the control of the vital functions. This finding, related to the OPPs bio-persistence, implies a conceptual redefinition of the fetal-placental and fetal blood-brain barriers: not real safety barriers but simply time-deferral mechanisms of absorption.

  16. 环境内分泌干扰物与儿童性早熟发病的关系%Correlation between environmental endocrine disruptors and onset of precocious puberty in children

    Institute of Scientific and Technical Information of China (English)

    朱琳; 蔡德培

    2011-01-01

    Environmental endocrine disruptors are pollutants of many chemical classes,which are ubiquitous and persistent in the environment and can exert adverse effects on the endocrine system. Environmental endocrine disruptors are easily absorbed by the body, but not excreted. They are synergistic and hereditary. Therefore,environmental endocrine disruptors will severely destroy public health. Environmental endocrine disruptors, bringing about changes in morphology and function of the hypothalamus-pituitary-gonadal axis, interfering with the metabolism and transportation of estrogen, improve estrogen levels. They can activate estrogen receptor and enhance its sensitivity. By these means, environmental endocrine disruptors lead to early puberty development.%环境内分泌干扰物是普遍存在于环境中的一类化学物质,能够造成机体内分泌系统功能紊乱.环境内分泌干扰物易被机体吸收而不易排出,相互之间具有协同作用,且具有遗传性及传代性,因此能严重影响人类的健康.环境内分泌干扰物可以导致下丘脑-垂体-性腺轴形态和功能的改变,影响其调节功能;干扰雌激素的代谢及转运,提高体内雌激素水平;激活雌激素受体,增强其敏感性,从而导致青春期发育提前.

  17. Effects of Environmental Endocrine Disruptors on Mother and Child Health%环境内分泌干扰物对母婴健康影响研究进展

    Institute of Scientific and Technical Information of China (English)

    潘洪明

    2012-01-01

    在概述环境内分泌干扰物的基础上,从通过与核受体结合的基因作用及非基因信号通路作用方面阐述了环境内分泌干扰物的作用机制,并探讨了环境内分泌干扰物对母婴健康的影响,包括对母亲的影响及对胎儿、婴儿的影响方面。同时强调应重视其对激素水平不稳定的孕期母体及敏感初期生命的影响。%On the basis of an overview of environmental endocrine disruptors, the action mechanism of environmental endocrine disruptors is introduced from the aspects of gene function with nuclear receptor and non-gene signaling pathway. The effect of environmental endocrine disruptors on maternal and child health is also discussed, including the effects on mother, fetus n and infant. Meanwhile, it also emphasizes that the effect of environmental endocrine disrupto~ on mother with unstable hormone levels and sensitive early life should be paid great attention.

  18. 环境内分泌干扰物对胚胎发育调控基因DNA甲基化的影响%Effect of environmental endocrine disruptors on DNA methylation of embryonic developmental regulating gene

    Institute of Scientific and Technical Information of China (English)

    赵岩

    2011-01-01

    DNA methylation is an important genetic modification and an important part of epigenetics. Many studies have confirmed that environmental endocrine disruptors can affect the level of DNA methylation. The effect of environmental disruptors on DNA methylation has become the research focus of embryonic development. In order to provide reference for future mechanism study, we reviewed the effect of environmental endocrine disruptors (EED) on DNA methylation of embryonic developmental regulating gene.%DNA甲基化(DNA methylation)是一种重要的遗传修饰,是表观遗传学研究的重要内容.许多研究证实环境内分泌干扰物能够影响DNA甲基化的水平,有关环境内分泌干扰物对DNA甲基化的影响已经成为当前胚胎发育学的研究热点.本文就环境内分泌干扰物(environmental endocrine disruptor,EED)对胚胎发育调控基因DNA甲基化的影响进行综述,为今后的机制性研究提供参考.

  19. A two-sided tale : the influence of environmental endocrine disruptors and sperm chromatin status on male fertility

    OpenAIRE

    Santos Tavares, Renata

    2014-01-01

    Tese de doutoramento em Biologia, na especialidade de Biologia Celular apresentada à Faculdade de Ciências e Tecnologia da Universidade de Coimbra A exposição a contaminantes ambientais, em particular a disruptores endócrinos, tem sido associada a uma diminuição da qualidade espermática e a uma tendência acrescida de cancro testicular e anomalias nos órgãos reprodutores masculinos, dados que sugerem estes compostos como potenciais causadores de disfunção reprodutora masculina e infertilida...

  20. 环境内分泌干扰物研究进展%Progress in Research of Environmental Endocrine Disruptors

    Institute of Scientific and Technical Information of China (English)

    刘艳平; 孙苏欣

    2010-01-01

    @@ 近年来,关于外源性化学物质干扰人类和动物的内分泌系统、影响健康和生殖的研究与日俱增,欧盟、美国、日本经济合作与发展组织,以及世界野生动物基金会等很多发达国家和地区的政府组织和非政府组织正致力于环境内分泌干扰物(Environmental Endocrine Distuping Chemicals,EEDCs)方面的研究,并相继发表了专题报告.所谓环境内分泌干扰物,是指能改变内分泌系统功能,从而对整个集体或其后代或其(亚)群体引起有害的健康效应的一种外源性物质或混合物.在我国,对EEDCs的研究也逐渐受到重视,但是总体来说,我国对EEDCs的研究还比较薄弱,需要借鉴国际上已有的先进技术和经验[1].

  1. Environmental endocrine disruptors and disorder of sexual development%环境内分泌干扰物和儿童性发育障碍

    Institute of Scientific and Technical Information of China (English)

    陈立芬

    2014-01-01

    儿童性发育障碍是成因复杂、临床表现多样的一类疾病,近年来发病率逐渐上升,发病机制正被不断揭示.环境内分泌干扰物被认为可以干扰正常性别分化过程,导致性发育障碍的产生.该文主要综述环境内分泌干扰物干扰性别分化过程的机制,探讨环境内分泌干扰物和儿童性发育障碍发病之间的关系.%Disorder of sexual development(DSD) refers to a group of diseases with various causes and phenotypes.It has attracted great worldwide as the incidence is rising and the life-long consequences accompanying.Environmental endocrine disruptors(EED) are thought to have an impact of the sex differentiation process and induce disorder of sexual development.This review summarizes the mechanism of DSD that associated with EED and focus on the relationship between DSD and EED.

  2. Phytotoxic, clastogenic and bioaccumulation effects of the environmental endocrine disruptor bisphenol A in various crops grown hydroponically.

    Science.gov (United States)

    Ferrara, Giuseppe; Loffredo, Elisabetta; Senesi, Nicola

    2006-04-01

    The effects of the endocrine disruptor bisphenol A (BPA) at concentrations of 10 and 50 mg l(-1) were evaluated on the germination and morphology, micronuclei (MN) content in root tip cells and BPA bioaccumulation of hydroponic seedlings of broad bean (Vicia faba L.), tomato (Lycopersicon esculentum Mill.), durum wheat (Triticum durum Desf.) and lettuce (Lactuca sativa L.) after 6 and 21 days of growth. In general, BPA at any dose used did not inhibit germination and early growth (6 days) of seedlings of the species examined, with the exception of primary root length of tomato which decreased at the higher BPA dose. In contrast, an evident phytotoxicity was induced by BPA in all species after 21 days of growth with evident morphological anomalies and significant reductions of the lengths and fresh and dry weights of shoots and roots of seedlings. With respect to the nutrient medium without seedlings, BPA concentration decreased markedly during the growth period in the presence of broad bean and tomato seedlings, and limitedly in the presence of durum wheat and, especially, lettuce. Further, the presence of BPA measured in roots and shoots of broad bean and tomato after 21-day growth indicated that bioaccumulation of BPA had occurred. The number of MN in broad bean and durum wheat root tip cells increased markedly by treatment with BPA at both concentrations, thus suggesting a potential clastogenic activity of BPA in these species.

  3. Environmental endocrine disruptors and abnormalities of sexual differentiation and sexual development inchildren%环境内分泌干扰物与儿童性分化、性发育异常

    Institute of Scientific and Technical Information of China (English)

    李祥婷; 蔡德培

    2011-01-01

    环境内分泌干扰物是普遍存在于环境中的一类外源性化学物质,这些物质可干扰体内天然激素的合成、释放、转运、与受体结合、代谢及清除等各个方面,干扰正常激素维持体内平衡和调节发育过程的作用.环境内分泌干扰物被证实是引起儿童性分化、性发育异常的重要致病因素.环境内分泌干扰物可扰乱下丘脑-垂体-性腺轴,干扰雄激素的生物合成、转运、与受体结合、代谢和清除以及通过环境-基因的交互作用来影响儿童的性分化、性发育进程.%Environmental endocrine disruptors are pollutants of many exogenous chemical classes,which are ubiquitous and persistent in the environment and can interfere with the body 's natural steroidogenesis,secretion,transport,and receptor binding,biotransformation and removal of other aspects,thus,they may disturb normal hormone maintaining the organism 's balance and regulating development process.Therefore,exposure to these pollutants is one of the biggest factors that induce sex differentiation and sexual abnormality in children,which has been proved by many data from epidemiological researches.Environmental endocrine disruptors may influence the sexual differentiation and sexual development process of children by disturbing the hypothalamus-pituitary-gonadal axis and affecting the biosynthesis,transport,receptor binding,metabolism and clearance of androgen as well as interacting with genes.

  4. 环境内分泌干扰物与儿童性发育异常的相关性研究%Correlation of environmental endocrine disruptors and child sexual abnormalities

    Institute of Scientific and Technical Information of China (English)

    黄旭峰; 谢忠罗; 黄正国; 方燕兰

    2014-01-01

    目的:观察分析环境内分泌干扰物与儿童性发育异常的相关性。方法:选取我院从2010年3月至2013年3月专科门诊收治的性发育异常患儿共45例,同时选取同时期的正常儿童作为对照组共45例进行对比。采取入选受试者的血液样本检测其中的环境内分泌干扰物的含量情况。结果:观察组患儿的环境内分泌干扰物的含量明显要高于对照组儿童,其中辛基酚(OP)的保留时间为13.822min,双酚 A 的保留时间为11.942min。观察组有53.3%的患儿被检测出其体内含有辛基酚明显要高于对照组的6.67%;而观察组有48.9%的患儿其体内含有双酚 A,明显要高于对照组儿童的8.89%。气相色谱中 DBP 的保留时间为13.623min,DEHP 的保留时间为16.830min。其中观察组中有62.2%的患者检测出其体内含有 DBP,明显高于对照组的8.89%,两组儿童对比有显著性差异;而 DEHP 则有57.8%的观察组患儿的血清中能够被检测到,明显要高于对照组的13.3%。结论:环境内分泌干扰素与儿童性发育异常的发生有着一定的相关性,应该尽量避免或者减少儿童接触环境内分泌干扰物,减少其对儿童性发育的影响。%Objectives:To observe the correlation of environmental endocrine disruptors and child sexual abnormalities.Methods:45 children with sexual abnormality admitted into our hospital from March 2010 to March 2013 were selected as the observation group,while 45 normal children in our hospital in the same period were cho-sen as the control group.The blood samples were tested to detect the content of environmental endocrine disruptors. Results:The content of environmental endocrine disruptors in the observation group was observed to be significantly higher than the control group,with the retention time of octylphenol (OP)and bisphenol A being 13.822min and 11.942min respectively.53.3 % of the children in observation

  5. 环境内分泌干扰物引致儿童性发育异常的研究进展%Research progress of environmental endocrine disruptors causing child sexual dysplasia

    Institute of Scientific and Technical Information of China (English)

    蔡德培

    2013-01-01

    At present, the normal children have extensively exposed to the pollution of environmental endocrine disruptors ( EEDs ). There is a close relationship between EEDs and the onset of child sexual dysplasia, which is one of the important factors inducing the disease. It ought to attract the sufficient attention of the government to perfect the decrees and policy related to industries and environmental protection as quickly as possible so as to put an end of the environmental pollution from the sources of these pernicious materials. In addition, the effective preventive and therapeutic regimes which suit our national situation ought to be formulated, including therapeutic intervention with medicaments. It has been verified that the proper therapeutic regime of traditional Chinese herbal medicine (TCHM) could have antagonistic effect on the estrogen-like activity of EEDs obviously. The TCHM could exert antagonistic effect against the estrogen-like activity of EEDs via regulative effect to estrogen receptor, estrogen synthetase and growth factors on the target organs.%  当前,正常儿童较普遍地暴露于环境内分泌干扰(environmental endocrine disruptors, EEDS),而 EEDs 与儿童性发育异常的发病有密切关系,是其重要的致病因素之一。这应引起政府足够重视,尽快完善相关产业及环保方面的政策法规,从源头上杜绝这些有害物质造成的环境污染;另一方面应积极制定适合国情的有效防治方案,包括采用药物进行治疗干预。已证实恰当的中药治疗方案对EEDs的拟雌激素活性具有显著的拮抗作用,中药可通过对靶器官上雌激素受体、雌激素合成酶及生长因子的调节作用,发挥其对 EEDs 拟雌激素活性的拮抗作用。

  6. 环境内分泌干扰物与人类健康专题研究中的几个问题%Comments on Study of Environmental Endocrine Disruptors and Human Health

    Institute of Scientific and Technical Information of China (English)

    吴德生

    2002-01-01

    @@ 近10年来,全世界对环境中广泛存在的能干扰人类和野生生物内分泌系统功能继而产生健康有害后果的化学物--环境内分泌干扰物(environmental endocrine disruptor chemicals,EDCs)产生了极大的关注.这主要是由于:①在某些野生生物、鱼、生态系统中观察到明显的有害效应;②人类与内分泌有关的疾病和健康不良后果的发生率不断增加;③在动物实验中已经证实某些环境化学物,可引起内分泌活性的干扰,并产生相应的有害效应.这些关注曾刺激了许多国家政府、国际机构、科学社团、化学工业、有兴趣的公众设立研究项目、组织会议和工作组,并针对相关事件组成专家组、委员会致力于对EDC事件的研究和评价.

  7. THE HEALTH EFFECTS AND RELATED MECHANISM OF ENVIRONMENTAL ENDOCRINE DISRUPTORS%环境内分泌干扰物质的健康影响与作用机制

    Institute of Scientific and Technical Information of China (English)

    时国庆; 李栋; 卢晓坤; 王海鸥; 刘丽琴; 魏巍; 宣劲松

    2011-01-01

    本文综述了环境内分泌干扰物质与人或动物生殖发育、行为智力、免疫功能、肥胖、糖尿病、癌症等异常或疾病的相关性及相关作用机制,讨论了其"低剂量效应"和"复合效应",对本领域今后发展的方向进行了探讨.%Environmental endocrine disruptors (EDs) are widely distributed in the environment, and can threat the human and wildlife health by interfering with the normal endocrine balance. This paper reviews the “low-dose effect”, the “mixture effects” of EDs, and the adverse effects and related mechanisms of EDs on human or animal reproduction and development, behavior and intelligence, immune function, obesity, diabetes, cancer and other abnormalities or related diseases. The direction of future development in this field is also discussed.

  8. Review on Effects of Environmental Endocrine Disruptor Nonylphenol on Nervous System of Organisms%环境内分泌干扰物壬基酚对神经系统影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    俞捷; 张镖; 许洁

    2013-01-01

    Nonylphenol (NP) is an environmental endocrine disruptor with estrogen-like effects, and the attentions to its global ecological pollution are increasing. The review discussed the toxic effects of NP on the nervous system of organisms with evidences provided by domestic and international toxicological studies in recent years. At the individual or cell level, NP could induce dysfunction of dopamine neurons and cholinergic systems, resulting in lipid peroxidation of cerebral tissue, apoptosis of nerve cells, as well as neurobehavioral disorders in animals.%壬基酚作为一种环境内分泌干扰物,其所造成的全球生态污染受到越来越多的关注.本文以近年来国内外的毒理学研究资料为依据,综述其对神经系统的影响,认为在整体和细胞水平,壬基酚可干扰机体多巴胺和胆碱能系统,致脑组织脂质过氧化,促神经细胞凋亡,影响动物神经行为等.

  9. 环境内分泌干扰物对子代健康影响的研究进展%Research progress in the effect of environmental endocrine disruptors on the health of the offspring

    Institute of Scientific and Technical Information of China (English)

    朱颖帆; 楼毅云; 袁牧; 金帆

    2015-01-01

    环境内分泌干扰物(environmental endocrine disruptors,EEDs)是一类存在于环境中能改变机体内分泌功能并对机体、子代或亚群引起有害效应的化学物质.包括拟雌激素类、拟睾酮类、拟甲状腺素类、拟其他内分泌功能类.这些化合物广泛存在于日常生活和工作的环境中,可通过多种途径和方式主动或被动进入动物和人体内,而有些EEDs还可通过脐带血进入胎儿体内.大量实验及流行病学资料表明EEDs可引起子代早产、低出生体质量、肥胖、代谢紊乱、泌尿生殖系统异常等方面异常.

  10. Assessment Methods and Biological Detection Techniques for Environmental Endocrine Disruptors (EDCs)%环境内分泌干扰物的评价方法及其生物检测技术

    Institute of Scientific and Technical Information of China (English)

    夏洁; 苏冠勇; 于红霞; 张效伟

    2013-01-01

    With the rapid development of analysis instruments and techniques,many organic chemicals have been frequently detected in various environmental media and foods in recent years.Their concentration level is low,and toxicological studies show that some of them might cause adverse effect to living organisms even at such a low concentration,especially for Environment Endocrine Disruptors (EDCs).It is very important to successfully identify and manage these low-level harmful chemicals in complex environment samples.Taking EDCs as study objects,the potential risks of EDCs are summarized based on literature research in recent years,especially for the mechanisms of action,evaluation criteria and biological detection techniques of different EDCs,which will contribute to the screening and risk identification of harmful materials in environment.%由于化学分析设备与技术的不断提高,大量的有机化学物质不断地从环境介质和食品中被检出.尽管这些物质的浓度很低,但是毒理学的研究表明,一些环境内分泌干扰物质(Environmental Endocrine Disruptors,EDCs)在很低浓度就能导致生物健康负效应.如何在种类众多的环境化学物质,以及在成分复杂的环境提取物中识别具有低剂量效应的有害物质并加以管理十分重要.本文以EDCs为对象,结合近几年来的文献,综述了其可能造成的危害,重点分析了EDCs的作用机制、筛选评估方法及生物检测技术,旨在为今后环境有害物质的筛选与风险识别研究提供借鉴.

  11. 武汉地区水中环境内分泌干扰物的污染情况及其对人体的影响%Analysis on pollution of environmental endocrine disruptors in water in Wuhan area and its influence on human body

    Institute of Scientific and Technical Information of China (English)

    叶超; 刘燕群; 游浩

    2013-01-01

    Wuhan area has rich water resource and vast water area, while water is closely related to people's daily lives. So the water pollution is very important to life quality of residents in Wuhan, and the scientists pay more attention to the water environment in Wuhan area. In recent years, the pollution of environmental endocrine disruptors in Wuhan area has become more serious, and the environmental endocrine disruptors more and more attracted people's attention. The environmental endocrine disruptors, which include estrone (El) , 17 α-acetylene estrone (EE2) , estradiol (E2) , diethylstilbestrol (DES) , nonylphenol (NP) , octyl phenol ( OP) , bisphenol A ( BPA) , Di-n-Butyl phthalate( DBP) and di-(2-ethylhcxyl) phthalate ( DEHP) , widely distribute in Wuhan area, and have different effect on human body. The paper makes a brief analysis on pollution of environmental endocrine disruptors in Wuhan area and its influence on human body.%武汉水资源总量丰富,水域面在,而水又与人们的日常生活息息相关,因而武汉的水环境污染情况对武汉人的生活状况十分重要,武汉地区的水环境也一直是科学家们的重要关注对象.近年来武汉地区环境内分泌干扰物污染情况比较严重,环境内分泌干扰物越来越引起人们的重视.环境内分泌干扰物有很多种,如雌酮(EI)、17α-乙炔雌酮(EE2)、雌二醇(E2)、已烯雌酚(DES)、壬基本分、辛基酚(OP)、双酚A(BPA)、酞酸二正丁酯(DBP)、酞酸二(2-乙基己基)酯(DEHP)等,它们在武汉的分布情况各有不同,对人体的影响也不一样,在这里就武汉地区环境内分泌干扰物的污染情况及其对人体的影响进行简要分析.

  12. 环境内分泌干扰物暴露与儿童肥胖的研究进展%Research progress of the effect of environmental endocrine disruptor chemicals on obesity in children

    Institute of Scientific and Technical Information of China (English)

    吴浪; 许韶君

    2016-01-01

    环境内分泌干扰物(endocrine disruptor chemicals,EDCs)在环境中无处不在,通过污染的食物、水及暴露于EDCs的日常使用物品而被人体吸收,并可在人类的血液、尿液中检测到EDCs及其代谢产物.近年来,肥胖发生率逐年增加,已成为世界各国面临的一个严重公共卫生问题.大量研究表明,EDCs会干扰机体内脂肪代谢并可能引发肥胖.笔者对该因素与儿童肥胖之间关联的研究进展综述如下.

  13. 环境内分泌干扰物对性激素合成相关酶基因调控网络的不良影响%The effect of environmental endocrine disruptors on gene regulative networks related to steroidogenesis

    Institute of Scientific and Technical Information of China (English)

    高连连

    2012-01-01

    环境内分泌干扰物(environmental endocrine disruptor,EED)是具有干扰机体内分泌系统的一类外源性化学物质.研究表明性激素合成相关酶基因是EED的重要靶点.性激素合成与代谢的失衡可致机体生殖障碍、性分化、性发育异常及某些癌症的发病风险增加等.其中类固醇合成急性调节蛋白、芳香化酶等是性激素合成的限速酶及关键酶,这些酶及蛋白又受一系列转录因子及信号通路的调控.基于在性激素合成中的特殊作用,这些酶、转录因子及信号通路等组成的基因调控网络与EED之间的关系备受关注.遗传背景的差异性可影响机体对EED的敏感性.该文就近年来性激素合成相关酶基因的调控以及EED对其产生的不良影响作一综述.%Environmental endocrine disruptors (EED) are pollutants of many exogenous chemicals,which have the potential to disrupt endocrine functions in exposed organisms.The enzymes increasingly involved in the steroid biosynthesis pathway are being recognized as important targets for the actions of various endocrine disrupting chemicals.Interferences with steroid biosynthesis may result in impaired reproduction,alterations in sexual differentiation,sexual development and the development of certain cancers.Aromatase ( CYP19 ) and steroidogenic acute regulatory protein regulated by some transcriptional factors and signalling pathway are considered as the key and rate-limiting enzymes.Given their key role in the formation of steroid hormones,gene regulatory networks of enzymes related to steroidogenesis are gaining interest as molecular targets.Differences in genetic background can affect body's sensitivity to EED.This review will provide an overview of the enzymes involved in steroidogenesis,their cellular and molecular regulation,as well as the adverse effect of EED on them.

  14. Environmental endocrine disruptors in farm animal reproduction: research and reality.

    Science.gov (United States)

    Magnusson, U

    2012-08-01

    In this review, possible comparative advantages of studying endocrine disruption in farm animals vs laboratory rodents are discussed. First, using farm animals, the generality of findings in laboratory rodents are challenged. Farm animals may in certain aspects be better models for humans than laboratory rodents, and sometimes there might be methodological advantages in using farm animals. Second, there are several in vitro studies based on cell-culture systems from sows and cows where the effects of chemicals on sex steroid secretion can be measured and maturation and fertilization of oocytes may be assessed. These in vitro systems are powerful tools for dissecting the mechanisms of action for endocrine-disrupting chemicals. Third, in a set of recent in vivo studies using sheep, goats and pigs, in which very different exposure regimens to endocrine-disrupting chemicals have been used, a full panel of reproductive parameters pertinent to farm animals were assessed. Clinically, it is suggested that endocrine disruption in farm animals should be considered when impaired reproduction could be linked to change in source of feed or pasture. Finally, epigenetic and toxicogenomic approaches can be particularly rewarding in elucidating endocrine disruption in future farm animal studies.

  15. The Establishment of Environmental Endocrine Disruptors Induced Precocious Puberty Macaca Fascicularis Model and the Intervention of Yin Nourishing Fire Purging Chinese Materia Medica%由环境内分泌干扰物引致食蟹猴性早熟疾病模型建立及滋阴泻火中药治疗干预的实验研究

    Institute of Scientific and Technical Information of China (English)

    朱琳; 蔡德培

    2012-01-01

    目的 建立灵长类--食蟹猴的由环境内分泌干扰物(environmental endocrine disruptors,EEDs)引致的性早熟疾病模型,验证滋阴泻火中药对EEDs拟雌激素活性的拮抗作用.方法 (1)不同月龄组青春前期雌性食蟹猴喂饲高、低剂量EEDs,通过观察EEDs拟雌激素作用,以确定最佳月龄、染毒剂量及染毒时间.(2)15只青春前期雌性食蟹猴随机分为染毒组、治疗组及对照组,每组5只.染毒组喂饲壬基酚(nonylphenol,4-NP)及双酚A(bisphenol,BPA),治疗组将染毒物质及滋阴泻火中药合剂同时喂饲,对照组喂饲溶剂玉米油.疗程4周.疗程完成时,检测血清雌激素水平、阴道脱落细胞成熟指数,取出子宫,测定其子宫湿重、子宫内膜及环形平滑肌厚度、子宫内膜上皮细胞及腺上皮细胞高度.结果 (1)20月龄为最佳染毒月龄,低剂量EEDs为最佳染毒剂量,4周为最佳染毒时间.(2)与对照组比较,染毒组血清雌激素水平明显升高,阴道脱落细胞成熟指数显著增加,子宫湿重、子宫内膜厚度及环形平滑肌厚度、子宫内膜上皮细胞及腺上皮细胞高度显著增加(P<0.05).与染毒组比较,治疗组上述指标均显著降低(P<0.05).结论 本研究成功地建立了灵长类--食蟹猴由EEDs引致性早熟的疾病模型,证实了EEDs具有显著的拟雌激素活性,并验证了滋阴泻火中药合剂对其拟雌激素活性具有显著的拮抗作用.%Objective To establish the environmental endocrine disruptors (EEDs) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica (YNFPCMM) against the estrogenic effects. Methods (1) The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs' estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. (2) Fifteen female prepubescent monkeys were

  16. Endocrine Disruptors

    Science.gov (United States)

    ... adjust the font size, or print this page. Endocrine Disruptors Table of Contents Health Studies & Clinical Trials What ... Disruptors General Information For Educators Related Topics Introduction Endocrine Disruptors Introduction Endocrine disruptors are chemicals that may interfere ...

  17. 环境内分泌干扰物对青春前期雄性大鼠性腺发育的不良影响及益肾填精方的治疗作用%Adverse Effect of Environmental Endocrine Disruptors on Gonadal Development of Prepubertal Male Rats and Therapeutic Effect of Bushen Tianjing Recipe on It

    Institute of Scientific and Technical Information of China (English)

    李祥婷; 蔡德培

    2013-01-01

    目的 复制SD雄性大鼠由环境内分泌干扰物(environmental endocrine disruptors,EEDs)引致的性腺发育不良(gonadal dysgenesis,GD)模型,验证益肾填精方对EEDs抗雄激素活性的拮抗作用.方法 3周龄雄性SD大鼠70只随机分为7 组:对照组(喂饲玉米油)、模型A组[邻苯二甲酸二(2-乙基己基)酯(di-2-ethylhexylphthalate,DEHP)500 mg/kg]、中药A组(DEHP 500 mg/kg +益肾填精方40 mL /kg)、模型B组[氯氰菊酯(Cypermethrin,CYP)80 mg/kg]、中药B组(CYP 80 mg/kg +益肾填精方40 mL /kg)、模型C组(DEHP 500 mg/kg+CYP 80 mL/kg)及中药C组(DEHP 500 mg/kg+CYP 80 mg/kg +益肾填精方40 mL/kg),每组10只.每天灌胃1次,共30天.于末次染毒24 h后处死动物,测定大鼠体重、睾丸湿重,并计算睾丸系数;测定血清睾酮(testosterone,T)水平;制备睾丸病理组织切片,光镜观察其组织学改变,电镜观察生殖细胞超微结构的变化.结果 与对照组比较,各模型组及各中药组大鼠体重增加量差异无统计学意义(P >0.05),各模型组睾丸下降时间及包皮分离时间均明显延迟(P <0.01);模型A组及模型C组睾丸重量减轻,血清T降低;模型A组睾丸系数降低(P <0.01).与相应模型组比较,各中药组睾丸下降时间及包皮分离时间均提前(P <0.01);中药A组睾丸重量、睾丸系数及T水平均增加(P <0.01),中药B组T水平明显升高(P <0.05).结论 应用DEHP剂CYP成功地复制了GD大鼠模型,证实EEDs具有显著的抗雄激素活性,并验证了益肾填精方对其抗雄激素活性具有显著的拮抗作用.

  18. 环境内分泌干扰物对性分化和性发育的神经内分泌调控网络的影响%Effects of environmental endocrine disruptors on neuroendocrine regulatory networks related to sexual differentiation and sexual development:a review of recent studies

    Institute of Scientific and Technical Information of China (English)

    高连连; 蔡德培

    2012-01-01

    Environmental endocrine disrupters (EEDs) are pollutants of many exogenous chemical classes, which are ubiquitous and persistent in the environment and can interfere with the neuroendocrine systems,disturb body's natural steroidogenesis, secretion, and receptor binding,removal of other aspects, thus lead to abnormal development of the human bodies and their progenies. Neuroendocrine regulatory networks, especially the regulatory networks of the hypothalamus play vital roles in sexual differentiation and the process of puberty. When neuroendocrine homeostasis is disrupted by environmental endocrine chemicals, a variety of perturbations about sexual differentiation and sexual development can ensue,particularly when endocrine disruption occurs during critical developmental periods. Emerging evidences have shown that the brain can be the direct targets of EEDs. Among neuroendocrine regulatory networks, gonadotropin-releasing hormone (GnRH) neurons, the kisspeptin/GPR54 system, glial cells, and brain aromatase are significantly disrupted by EEDs. Besides, EEDs also have trans —generational effects. This article will provide an overview of the effect of environmental endocrine disruption on neuroendocrine regulatory networks related to sexual differentiation and sexual development.%环境内分泌干扰物(environmental endocrine disrupters,EEDs)是环境中存在的一大类外源性化合物,可干扰机体神经内分泌系统,影响体内天然激素的合成、释放及与受体结合、代谢等过程,进而导致机体及其子代异常发育.神经内分泌调控网络(尤其是下丘脑调控网络)在机体性分化、性发育中发挥关键作用.神经内分泌系统稳态的失衡可致一系列的异常发育,尤其是处于性发育关键时期的胚胎期与青春期.越来越多的研究表明,大脑是EEDs直接作用位点,神经内分泌调控网络中受EEDs显著干扰的主要有促性腺激素释放激素(gonadotropin-releasing hormone,GnRH)

  19. 在线固相萃取-超高效液相色谱-串联质谱法测定乳制品中双酚A等4种内分泌干扰物%Determination of 4 Environmental Endocrine Disruptors Involving Bisphenol A in Dairy Products by On-line Solid Phase Extraction Coupled with Liquid Chromatography-Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    张品; 张晶; 陈洁君; 段鹤君; 邵兵

    2014-01-01

    A simple analytical method by means of on-line solid phase extraction followed liquid chromatography-tandem mass spectrometry ( SPE-LC-MS/MS) was developed for the simultaneous quantitation of 4 endocrine disruptors ( triclosan, triclocarban, bisphenol A and nonylphenol) in dairy products. Infant formula and milk samples were dissolved in acetic acid buffer and hydrolyzed by β-glucuronidase/arylsulfatase. Acetonitrile was used as the extract. Then, the mixture was freeze-centrifuged for 10 min and the supernatant was diluted with water, and analyzed via on-line SPE-LC-MS/MS. The sample extracts were concentrated by an Xbridge C8 cartridge and separated on a BEH C18 column with a gradient mobile phase of methanol and water; then analyzed by triple quadrupole mass spectrometry. Mass acquisition was conducted under negative electrospray ionization mode. Quantification was performed by isotopic internal standard calibration. Acceptable linearity (R2>0. 99) was achieved over the range of 0. 005-5. 0 μg/L, with limits of quantification of 0. 03-1. 0μg/kg. Average recoveries of four target compounds (spiked at three concentration levels) ranged from 80. 2%-106. 7%,with relative standard deviation less than 15%. Due to its rapidity, simplicity, and high sensitivity, the method is suitable for the analysis of endocrine disruptors in dairy products. It has been applied in the analysis of raw milk and milk products collected in Beijing. As a result, nonylphenol was found with a high detectable frequency.%建立了乳制品中三氯生、三氯卡班、双酚A和壬基酚4种内分泌干扰物的在线固相萃取超高压液相色谱-串联质谱(On-line SPE LC-MS/MS)检测方法。液态乳制品或奶粉样品中加入乙酸缓冲液,目标物经β-葡糖醛酸苷肽酶/芳基磺酸酯酶酶解后,用乙腈提取,冷冻离心10 min后,取上清液,用水稀释,在线固相萃取串联质谱法测定。样品溶液经Xbridge C8柱富集,BEH C18色谱柱分离,甲醇和

  20. Effects of environmental endocrine disruptors and phytoestrogens on the kisspeptin system.

    Science.gov (United States)

    Patisaul, Heather B

    2013-01-01

    Sex steroid hormones, most notably estradiol, play a pivotal role in the sex-specific organization and function of the kisspeptin system. Endocrine--disrupting compounds are anthropogenic or naturally occurring compounds that interact with steroid hormone signaling. Thus, these compounds have the potential to disrupt the sexually dimorphic ontogeny and function of kisspeptin signaling pathways, resulting in adverse effects on neuroendocrine physiology. This chapter reviews the small but growing body of evidence for endocrine disruption of the kisspeptin system by the exogenous estrogenic compounds bisphenol A, polychlorinated biphenyl mixtures, and the phytoestrogen genistein. Disruption is region, sex, and compound specific, and associated with shifts in the timing of pubertal onset, irregular estrous cycles, and altered sociosexual behavior. These effects highlight that disruption of kisspeptin signaling pathways could have wide ranging effects across multiple organ systems, and potentially underlies a suite of adverse human health trends including precocious female puberty, idiopathic infertility, and metabolic syndrome.

  1. Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Ediz Yeşilkaya

    2008-10-01

    Full Text Available Endocrine disruptors are of special interest because they mimic, block, or in some way alter the activity of endogenous chemicals that are synthesized by the endocrine system. Besides many other organs, they especially affect the urinary system and the thyroid glands. Endocrine-disrupting chemicals are typically identified as compounds that can interact with oestrogen or androgen receptors and thus act as agonists or antagonists of endogenous hormones. During the last decade, numerous studies have been published, reporting an increase in reproductive organ anomalies, as well as in testicular cancer, and a decline in the relative number of male births, and in semen quality. In this review, the effects of endocrine distruptors on the reproductive health are discussed in the light of the recent literature. (Journal of Current Pediatrics 2008; 6: 76-82

  2. Endocrine Disruptors

    Directory of Open Access Journals (Sweden)

    Paolo F. Ricci

    2015-11-01

    Full Text Available Law and science combine in the estimation of risks from endocrine disruptors (EDs and actions for their regulation. For both, dose–response models are the causal link between exposure and probability (or percentage change of adverse response. The evidence that leads to either regulations or judicial decrees is affected by uncertainty and limited knowledge, raising difficult policy issues that we enumerate and discuss. In the United States, some courts have dealt with EDs, but causation based on animal studies has been a stumbling block for plaintiffs seeking compensation, principally because those courts opt for epidemiological evidence. The European Union (EU has several regulatory tools and ongoing research on the risks associated with bisphenol A, under the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH Regulation and other regulations or directives. The integration of a vast (in kind and in scope number of research papers into a statement of causation for either policy or to satisfy legal requirements, in both the United States and the EU, relies on experts. We outline the discursive dilemma and issues that may affect consensus-based results and a Bayesian causal approach that accounts for the evolution of information, yielding both value of information and flexibility associated with public choices.

  3. Exposure to environmental endocrine disrupting compounds and men's health.

    Science.gov (United States)

    Meeker, John D

    2010-07-01

    Human exposure to environmental endocrine disrupting compounds (EDCs) have received increased attention in recent years due to the documentation of widespread exposure to a number of EDCs among the general population, experimental data demonstrating endocrine-related effects on reproduction, development, metabolism, and cancer, and observations for increasing trends (as well as geographic trends) in endocrine-related disorders among populations. However, human studies of exposure to most environmental EDCs in relation to adverse health outcomes remain limited. This review focuses on the human data generated to date on the relationship between exposures to environmental EDCs and men's health. The agents discussed here, which include polychlorinated biphenyls (PCBs), pesticides, phthalates, bisphenol A (BPA), and polybrominated diphenyl ethers (PBDEs), were chosen based on their exposure prevalence and the presence of existing human data in studies of male reproductive health, altered reproductive and thyroid hormone levels, diabetes and/or metabolic syndrome, and endocrine-related cancers. Taken together, the epidemiologic data on the environmental EDCs suggest that there may be associations between exposure and adverse health outcomes in men. However, the limited human data, and in many instances inconsistent data across studies, highlight the need for further research on these chemicals. Future longitudinal molecular epidemiology studies with appropriately designed exposure assessments are needed to determine potential causal relationships, to identify the most important time windows/life stages of exposure, and to define individual susceptibility factors for adverse effects on men's health in response to exposure.

  4. Many Putative Endocrine Disruptors Inhibit Prostaglandin Synthesis

    DEFF Research Database (Denmark)

    Kristensen, David M.; Skalkam, Maria L.; Audouze, Karine Marie Laure

    2011-01-01

    Background: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine disrupting compounds (EDCs) share a high...... of endocrine disruption. Results: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis and it was correlated with a reduced testosterone production. The inhibition of PG synthesis occurs...

  5. 环境内分泌干扰物研究进展%Progress in research of environmental endocrine disruptors

    Institute of Scientific and Technical Information of China (English)

    井长勤; 穆灵敏; 张光谋

    2005-01-01

    环境内分泌干扰物对人类健康的影响日益受到人们的重视.本文阐述了环境内分泌干扰物的概念、来源、分类、生物学效应、作用机制,并对未来的研究做了展望.存在于人类生活环境中的环境内分泌干扰物种类繁多,对人类和动物造成了许多不良的影响,应加强对环境内分泌干扰物的研究和预防.

  6. Considerations for estimating daily intake values of non-persistent environmental endocrine disruptors based on urinary biomonitoring data

    DEFF Research Database (Denmark)

    Søeborg, Tue; Frederiksen, Hanne; Andersson, Anna-Maria

    2014-01-01

    IntroductionHuman exposure to chemicals may be estimated by back-calculating urinary concentrations resulting from biomonitoring studies if knowledge of the chemical's toxicokinetic properties is available.AimTo review available toxicokinetic data for back-calculating urinary concentrations into ...

  7. Developmental Exposure to Endocrine Disruptors and the Obesity Epidemic

    Science.gov (United States)

    Newbold, Retha R.; Padilla-Banks, Elizabeth; Snyder, Ryan J.; Phillips, Terry M.; Jefferson, Wendy N.

    2007-01-01

    Xenobiotic and dietary compounds with hormone-like activity can disrupt endocrine signaling pathways that play important roles during perinatal differentiation and result in alterations that are not apparent until later in life. Evidence implicates developmental exposure to environmental hormone-mimics with a growing list of health problems. Obesity is currently receiving needed attention since it has potential to overwhelm health systems worldwide with associated illnesses such as diabetes and cardiovascular disease. Here, we review the literature that proposes an association of exposure to environmental endocrine disrupting chemicals with the development of obesity. We describe an animal model of developmental exposure to diethylstilbestrol (DES), a potent perinatal endocrine disruptor with estrogenic activity, to study mechanisms involved in programming an organism for obesity. This experimental animal model provides an example of the growing scientific field termed “the developmental origins of adult disease” and suggests new targets of abnormal programming by endocrine disrupting chemicals. PMID:17321108

  8. Recent Advances on .Sample Pretreatment of Environmental Endocrine Disrupting Chemicals%环境内分泌干扰物前处理方法研究新进展

    Institute of Scientific and Technical Information of China (English)

    司秀荣; 徐东耀

    2011-01-01

    环境内分泌干扰物因其能够紊乱生物体正常内分泌功能而引起人们的广泛关注,然而内分泌干扰物在水环境中浓度极低,水体中复杂机质的干扰较大,在分析监测前一般要经过样品前处理过程,以起到富集痕量组分、消除基体干扰、提高方法灵敏度的作用。针对不同环境样品中内分泌干扰物的前处理方法不同,分别介绍了液体、固体或类固体环境样品的前处理技术,提出了各前处理方法的优缺点,总结并展望了环境内分泌干扰物样品前处理方法的发展方向。%Environmental endocrine disruptors because of their organism to normal endocrine function disorder caused wide-spread concern. However, environmental endocrine disruptors are in low concentrations in the water environment, water quality in-terlerences complex machine. Betore the analysis ol general monitoring ot the sample pre - treatment process to go through to play the enrichment of trace components, eliminating the matrix interference and increase sensitivity of the method's role. In the pres-ent paper, based on the various environmental samples, the pretreatment techniques for liquid, solid or solid -like environmental samples were introduced respectively. Their research advances were reviewed and pros - and - cons of each pretreatment method were discussed respectively. The prospect of sample pretreatment of environmental EDCs was presented.

  9. Exposure to modern, widespread environmental endocrine disrupting chemicals and their effect on the reproductive potential of women: an overview of current epidemiological evidence.

    Science.gov (United States)

    Karwacka, Anetta; Zamkowska, Dorota; Radwan, Michał; Jurewicz, Joanna

    2017-07-31

    Growing evidence indicates that exposure to widespread, environmental contaminants called endocrine disruptors (EDCs) negatively affects animal and human reproductive health and has been linked to several diseases including infertility. This review aims to evaluate the impact of environmental exposure to endocrine disrupting chemicals [phthalates, parabens, triclosan, bisphenol A (BPA), organochlorine (PCBs) and perfluorinated (PFCs) compounds] on the reproductive potential among women, by reviewing most recently published literature. Epidemiological studies focusing on EDCs exposure and reproductive potential among women for the last 16 years were identified by a search of the PUBMED, MEDLINE, EBSCO and TOXNET literature databases. The results of the presented studies show that exposure to EDCs impacts the reproductive potential in women, measured by ovarian reserve and by assisted reproductive technology outcomes. Exposure to environmental endocrine disrupting chemicals decrease: (i) oestradiol levels (BPA); (ii) anti-Müllerian hormone concentrations (PCBs); (iii) antral follicle count (BPA, parabens, phthalates); (iv) oocyte quality (BPA, triclosan, phthalates, PCBs); (v) fertilization rate (PFCs, PCBs); (vi) implantation (BPA, phthalates, PCBs); (vii) embryo quality (triclosan, PCBs, BPA); (viii) rate of clinical pregnancy and live births (parabens, phthalates). The studies were mostly well-designed and used prospective cohorts with the exposure assessment based on the biomarker of exposure. Considering the suggested health effects, more epidemiological data is urgently needed to confirm the presented findings.

  10. Estrogenic compounds -endocrine disruptors

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2011-11-01

    Full Text Available Endocrine disruptors (polychlorinated biphenyls, dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions.

  11. Neuroendocrine targets of endocrine disruptors.

    Science.gov (United States)

    Gore, Andrea C

    2010-01-01

    The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, as well as stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine organs, play critical roles in the ability of an organism to respond to its environment under normal circumstances. When neuroendocrine homeostasis is disrupted by environmental endocrine-disrupting chemicals, a variety of perturbations can ensue, particularly when endocrine disruption occurs during critical developmental time periods. This article will discuss the evidence for environmental endocrine disruption of neuroendocrine systems and the effects on endocrine and reproductive functions.

  12. 内分泌干扰物生物检测研究进展%Review of Bioassay Methods of Environmental Endocrine Disruptors Detection

    Institute of Scientific and Technical Information of China (English)

    张慧珠

    2014-01-01

    介绍了发光细菌法、重组基因酵母法、免疫分析法、细胞增殖法、受体结合活性法、卵黄蛋白法、酵母双杂交法等几种环境中内分泌干扰物的生物检测技术及研究进展,并提出了展望.

  13. Binding modes of environmental endocrine disruptors to human serum albumin: insights from STD-NMR, ITC, spectroscopic and molecular docking studies.

    Science.gov (United States)

    Yang, Hongqin; Huang, Yanmei; Liu, Jiuyang; Tang, Peixiao; Sun, Qiaomei; Xiong, Xinnuo; Tang, Bin; He, Jiawei; Li, Hui

    2017-09-11

    Given that bisphenols have an endocrine-disrupting effect on human bodies, thoroughly exposing their potential effects at the molecular level is important. Saturation transfer difference (STD) NMR-based binding studies were performed to investigate the binding potential of two bisphenol representatives, namely, bisphenol B (BPB) and bisphenol E (BPE), toward human serum albumin (HSA). The relative STD (%) suggested that BPB and BPE show similar binding modes and orientations, in which the phenolic rings were spatially close to HSA binding site. ITC analysis results showed that BPB and BPE were bound to HSA with moderately strong binding affinity through electrostatic interactions and hydrogen bonds. The order of binding affinity of HSA for two test bisphenols is as follows: BPE > BPB. The results of fluorescence competitive experiments using 5-dimethylaminonaphthalene-1-sulfonamide and dansylsarcosine as competitors, combined with molecular docking indicated that both bisphenols are prone to attach to the binding site II in HSA. Spectroscopic results (FT-IR, CD, synchronous and 3D fluorescence spectra) showed that BPB/BPE induces different degrees of microenvironmental and conformational changes to HSA.

  14. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Brieño-Enríquez

    Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  15. Fetal and neonatal endocrine disruptors.

    Science.gov (United States)

    Unüvar, Tolga; Büyükgebiz, Atilla

    2012-06-01

    Endocrine disruptors are substances commonly encountered in every setting and condition in the modern world. It is virtually impossible to avoid the contact with these chemical compounds in our daily life. Molecules defined as endocrine disruptors constitute an extremely heterogeneous group and include synthetic chemicals used as industrial solvents/lubricants and their by-products. Natural chemicals found in human and animal food (phytoestrogens) also act as endocrine disruptors. Different from adults, children are not exposed only to chemical toxins in the environment but may also be exposed during their intrauterine life. Hundreds of toxic substances, which include neuro-immune and endocrine toxic chemical components that may influence the critical steps of hormonal, neurological and immunological development, may affect the fetus via the placental cord and these substances may be excreted in the meconium. Children and especially newborns are more sensitive to environmental toxins compared to adults. Metabolic pathways are immature, especially in the first months of life. The ability of the newborn to metabolize, detoxify and eliminate many toxins is different from that of the adults. Although exposures occur during fetal or neonatal period, their effects may sometimes be observed in later years. Further studies are needed to clarify the effects of these substances on the endocrine system and to provide evidence for preventive measures.

  16. Study on Testicular Toxicity of 2-Bromopropane, an Environmental Endocrine Disrupter

    Institute of Scientific and Technical Information of China (English)

    李卫华; 范奇元; 张蕴辉; 申立军; 吴晓云; 丁训诚

    2000-01-01

    Objective 2-Bromopropane (2-BP ) is considered as a kind of environmental endocrine disrupters (EDs). Its reproductive and hematopoietic toxicity has aroused the attention of international toxicologists during the past five years. In the present study, we aimed to determine experimentally the testicular toxicity of 2-BP in male rats.Materials & Methods Forty SD male rats were divided into four groups of 10 rats each. The rats were intra-abdominally administered 2-BP once per day for 5 days continuously at the doses of 1 800 mg/kg, 600 mg/kg, 200 mg/kg and normal saline,respectively. The rats were dissected one week after the first administration.Results The body weight, absolute testes weight and relative testes weight of the rats in 1 800 mg/kg dose group decreased significantly with comparison to those of the control group, while the weight of accessory gonads showed no significant change. With the increase of dosage, the seminiferous tubules damage rate aggravated while the ratio of spermatogonia in total germ cells fell with P<0. 05. The seminiferous tubule area of rats in 1 800 mg/kg group also reduced significantly. Under light microscopic examination, the spermatogonia of administered rats showed degeneration and chromatin condensation. The nucleus of spermatocytes appeared hyperchromatic and pyknotic. Obvious testicular damage could be found in rats of high dose group, including large amount of spermatogonia necrosis or loss and reduced spermatocyte number. The electron microscopic findings were similar to those of the light microscopy, except that typical morphological change was found in the middle dose group: the structure of spermatogonia was destroyed, mitochondrion and endoplasmic reticulum scattered outside, nucleus disintegrated; some of the spermatocytes' membrane became unclear,chromatin condensed and cogulation necrosis appeared; the nuclear membrane of round spermatids also showed slight damage.Conclusion The results indicated that testis was

  17. [Endocrine disruptors and obesity: obesogens].

    Science.gov (United States)

    García-Mayor, Ricardo V; Larrañaga Vidal, Alejandra; Docet Caamaño, Maria F; Lafuente Giménez, Anunciación

    2012-04-01

    Incidence and prevalence of owerweight and obesity have greatly increased over the past three decades in almost all countries around the world. This phenomenon is not easily explained by lifestyle changes in populations with very different initial habits. This has led to consider the influence of other factors, the so-called endocrine disruptors, and more specifically obesogens. This study reviewed the available evidence about polluting chemical substances which may potentially be obesogens in humans: DES, genistein, bisphenol A, organotins (TBT, TPT), and phthalates. The first three groups of substances mainly act upon estrogen receptors, while organotins and phthalates activate PPARγ. It was concluded that evidence exists of the obesogenic effect of these chemical substances in tissues and experimental animals, but few data are available in humans.

  18. [Environmental contaminants and endocrine disruptors].

    Science.gov (United States)

    Fontenele, Eveline Gadelha Pereira; Martins, Manoel Ricardo Alves; Quidute, Ana Rosa Pinto; Montenegro, Renan Magalhães

    2010-02-01

    The toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reduction of its possible damages.

  19. Health surveillance and endocrine disruptors

    Directory of Open Access Journals (Sweden)

    Waissmann William

    2002-01-01

    Full Text Available The author discusses the extreme relevance of research on the presence of endocrine disruptors (EDs in products of interest to health surveillance (HS. Focusing on EDs, the author highlights the urgency of changes already under way in the direction of HS. The shift should be from product and product-registration approaches to the productive process and its realization in consumption, generation of contaminants, and alterations in the health of workers and the overall population. He briefly describes: regulatory gaps for dealing with EDs; difficulty in evaluating risk and suspension of the production and use of products with its characteristics and the need, as exemplified by such products, to enhance the inter-relationship among all stakeholders and to turn HS into a state-of-the-art technological setting, associated with the academic community and accountable to the public. The author reports on measures already taken in relation to EDs, including the establishment of a reference laboratory for analyzing persistent organic pollutants (POPs, interruption of the use of various POPs in Brazil and an initial review of requirements for registering pesticides under the Brazilian National Health Surveillance Agency (ANVISA.

  20. Health surveillance and endocrine disruptors

    Directory of Open Access Journals (Sweden)

    William Waissmann

    2002-04-01

    Full Text Available The author discusses the extreme relevance of research on the presence of endocrine disruptors (EDs in products of interest to health surveillance (HS. Focusing on EDs, the author highlights the urgency of changes already under way in the direction of HS. The shift should be from product and product-registration approaches to the productive process and its realization in consumption, generation of contaminants, and alterations in the health of workers and the overall population. He briefly describes: regulatory gaps for dealing with EDs; difficulty in evaluating risk and suspension of the production and use of products with its characteristics and the need, as exemplified by such products, to enhance the inter-relationship among all stakeholders and to turn HS into a state-of-the-art technological setting, associated with the academic community and accountable to the public. The author reports on measures already taken in relation to EDs, including the establishment of a reference laboratory for analyzing persistent organic pollutants (POPs, interruption of the use of various POPs in Brazil and an initial review of requirements for registering pesticides under the Brazilian National Health Surveillance Agency (ANVISA.

  1. Effect of Endocrine Disruptor Pesticides: A Review

    Directory of Open Access Journals (Sweden)

    Benoit Roig

    2011-06-01

    Full Text Available Endocrine disrupting chemicals (EDC are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air. For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  2. Effect of endocrine disruptor pesticides: a review.

    Science.gov (United States)

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-06-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

  3. Effect of Endocrine Disruptor Pesticides: A Review

    Science.gov (United States)

    Mnif, Wissem; Hassine, Aziza Ibn Hadj; Bouaziz, Aicha; Bartegi, Aghleb; Thomas, Olivier; Roig, Benoit

    2011-01-01

    Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health. PMID:21776230

  4. 75 FR 70248 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening

    Science.gov (United States)

    2010-11-17

    .... List of Subjects Environmental protection, Chemicals, Drinking water, Endocrine disruptors, Pesticides... AGENCY Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening AGENCY... chemicals and substances for which EPA intends to issue test orders under the Endocrine Disruptor...

  5. 75 FR 70557 - Endocrine Disruptor Screening Program; Draft Policies and Procedures for Screening Safe Drinking...

    Science.gov (United States)

    2010-11-17

    ... Protection Agency Endocrine Disruptor Screening Program; Draft Policies and Procedures for Screening Safe..., 2010 / Notices#0;#0; ] ENVIRONMENTAL PROTECTION AGENCY Endocrine Disruptor Screening Program; Draft... requiring Tier 1 screening under the Endocrine Disruptor Screening Program (EDSP) of substances for...

  6. Verifying of endocrine disruptor chemical affect to the mouse testes: can raman spectroscopy support histology study?

    Science.gov (United States)

    Andriana, Bibin B.; Oshima, Yusuke; Takanezawa, Sota; Tay, Tat W.; Rosawati Soeratman, Catherine Linda; Alam, Mohammad S.; Mitsuoka, Hiroki; Zhu, Xiao B.; Suzuki, Toshiaki; Yamamoto, Yuko S.; Tsunekawa, Naoki; Kanai, Yoshiakira; Kurohmaru, Masamichi; Sato, Hidetoshi

    2009-02-01

    One of suspect environmental endocrine disruptors that affect mouse male reproduction by altering the morphology of Sertoli cells and spermatogenic cells is phthalate. The effects of mono(2-ethylhexyl)phthalate (MEHP), one of metabolites of di(2-ethylhexyl)phthalate , on immature mouse testes in vivo were examined. We have recently shown that MEHP induced Sertoli cells necrosis and spermatogenic cells apoptosis in mice by TUNEL method, F-actin staining, and ultrastructural study, but there is no data for biochemical changing of testes due to those methods could not explore. To verify in detail of it, we conducted Raman spectroscopy study with 785 nm wavelength laser line, 50mW of laser power and 3 minutes of exposure time to analysis the MEHP-treated testicular tissue, which has been fixatived by 4% paraformaldehyde (PFA). Five weeks old (5 w.o) male mice were used in this experiment. As the results, the alterations were observed by Raman spectroscopy that there are significantly differences of DNA, actin filament, type IV collagen and amide I between control group (0 μM MEHP) and treatment group (100 μM MEHP). These results significantly support histology staining observation (such as the apoptotic spermatogenic cells which is associated with DNA fragmentation and F-actin disruption) and ultrastructural observation (such as mitochondria rupture and disintegration of nucleus membrane). Raman spectroscopy can be used for 4% PFA-fixatived tissue observation. However, we recommend that Raman spectroscopy may be able to be expanded as an armamentarium not just for the clarification of histology staining and ultrastructural study, but furthermore, it may be as a non-invasion assessment for screening animal tissue toxicity of chemical in future.

  7. Zearalenone as an endocrine disruptor in humans.

    Science.gov (United States)

    Kowalska, Karolina; Habrowska-Górczyńska, Dominika Ewa; Piastowska-Ciesielska, Agnieszka Wanda

    2016-12-01

    Zearalenone (ZEA), a fungal mycotoxin, is present in a wide range of human foods. Many animal studies have found ZEA to possess a disruptive effect on the hormonal balance, mainly due to its similarity to naturally-occurring estrogens. With increasing consciousness of the adverse effects of endocrine disruptors on human health, it is becoming more important to monitor ZEA concentrations in food and identify its potential effects on human health. Based on a review of recent studies on animal models and molecular pathways in which ZEA is reported to have an influence on humans, we postulate that ZEA might act as an endocrine disruptor in humans in a similar way to animals. Moreover, its endocrine-disrupting effect might be also a causative factor in carcinogenesis. This review article summarizes the latest knowledge about the influence of ZEA on the human hormonal balance. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Estrogenic endocrine disruptors: Molecular mechanisms of action.

    Science.gov (United States)

    Kiyama, Ryoiti; Wada-Kiyama, Yuko

    2015-10-01

    A comprehensive summary of more than 450 estrogenic chemicals including estrogenic endocrine disruptors is provided here to understand the complex and profound impact of estrogen action. First, estrogenic chemicals are categorized by structure as well as their applications, usage and effects. Second, estrogenic signaling is examined by the molecular mechanism based on the receptors, signaling pathways, crosstalk/bypassing and autocrine/paracrine/homeostatic networks involved in the signaling. Third, evaluation of estrogen action is discussed by focusing on the technologies and protocols of the assays for assessing estrogenicity. Understanding the molecular mechanisms of estrogen action is important to assess the action of endocrine disruptors and will be used for risk management based on pathway-based toxicity testing.

  9. Effect of Endocrine Disruptor Pesticides: A Review

    OpenAIRE

    Benoit Roig; Olivier Thomas; Aghleb Bartegi; Wissem Mnif; Aicha Bouaziz; Aziza Ibn Hadj Hassine

    2011-01-01

    International audience; Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soi...

  10. Parma consensus statement on metabolic disruptors

    OpenAIRE

    Heindel, Jerrold J.; Frederick S Vom Saal; Blumberg, Bruce; Bovolin, Patrizia; Calamandrei, Gemma; Ceresini, Graziano; Cohn, Barbara A.; Fabbri, Elena; Gioiosa, Laura; Kassotis, Christopher; Legler, Juliette; La Merrill, Michele; Rizzir, Laura; Machtinger, Ronit; Mantovani, Alberto

    2015-01-01

    © 2015 Heindel et al. A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attenti...

  11. 环境内分泌干扰物复合效应研究进展%Research Advance in Joint Effects of Environmental Endocrine Disrupting Chemicals

    Institute of Scientific and Technical Information of China (English)

    王春花; 蒋萍; 胡伟; 王玉秋

    2011-01-01

    As the constant progress has been made in environmental toxicology, scientists begin to pay more attention to lowdose and multi-chemicals pollutions. Environmental endocrine disrupting chemicals (EEDCs) are such pollutants which are characteristic of variety, complexity and low exposing dose. The present paper reviewed the recent researches on joint effects of EEDCs during the past two decades, predicted the further studies in this field, and also discussed the importance of establishment of detection and evaluation system which is proper in China.%随着环境毒理学的不断发展,低剂量复合污染问题逐渐成为研究热点.近年来,越来越多的环境内分泌干扰物(environmental endocrine disrupting chemicals,EEDCs)进入人们视线,这类物质以其种类繁多、暴露剂量低、作用复杂等特性引起广泛关注.该文综述了EEDCs复合效应的研究进展,预测了今后可能的研究方向.并提出建立我国特有的EEDCs检测评估体系的重要性.

  12. Progress on detection and analysis method of environmental endocrine disruptors%环境内分泌干扰物分析方法的研究与进展

    Institute of Scientific and Technical Information of China (English)

    赵利霞; 林金明

    2006-01-01

    本文对近5年来国内外环境内分泌干扰物的研究进展进行了综述,包括环境内分泌干扰物的分类、样品前处理技术、检测技术等,并对环境内分泌干扰物分析的发展进行了总结和展望,引用文献286篇.

  13. 环境内分泌干扰物对儿童生长发育与健康的影响%Influences of environmental endocrine disruptors on growth, development and health of children

    Institute of Scientific and Technical Information of China (English)

    徐勇; 杨鲁静

    2003-01-01

    @@ 保护儿童免受化学毒物的危害是对现代社会的一大挑战.当今世界, 儿童有接触近15 000种大量生产的化学合成物质的危险[1].其中许多化学物质广泛分布于环境之中.

  14. 环境内分泌干扰物与前列腺疾病的研究现况%Research Progress on Environmental Endocrine Disruptors and Prostate Diseases

    Institute of Scientific and Technical Information of China (English)

    陈姣

    2014-01-01

    前列腺疾病是男性泌尿生殖系统的常见病,包括前列腺增生、前列腺癌等,多发生于中老年男性.前列腺是性激素依赖器官,其生长、分化等过程均需要性激素的调控.目前,环境中存在多种内分泌干扰物,可干扰体内正常内分泌激素的合成、释放、结合、代谢等,从而影响机体内环境稳态、生殖、发育及行为.研究表明,某些环境内分泌干扰物可影响前列腺疾病的发生和发展,本文对影响前列腺疾病的常见环境内分泌干扰物进行分类阐述,认为今后应加强相关人群资料的积累和人群流行病学的研究,探讨其发病机制,明确各类内分泌干扰物与前列腺疾病之间的关联.

  15. 应用胚胎干细胞模型研究环境内分泌干扰物胚胎毒性的展望%Research Progress of Environmental Endocrine Disruptors on Embryotoxicity by Embryonic Stem Cell Test

    Institute of Scientific and Technical Information of China (English)

    马明月

    2016-01-01

    动物实验研究证明,环境内分泌干扰物具有一定的胚胎毒性,但动物实验具有一定的局限性,寻找替代动物实验的体外实验模型至关重要.目前,胚胎干细胞已成为发育毒性实验的一种崭新受试对象,能灵敏、准确地评价有害物质的毒性作用.根据胚胎干细胞特性发展起来的胚胎干细胞模型,可评价环境内分泌干扰物的潜在胚胎毒性和致畸性.

  16. Energy disruptors: rising stars in anticancer therapy?

    Science.gov (United States)

    Bost, F; Decoux-Poullot, A-G; Tanti, J F; Clavel, S

    2016-01-01

    The metabolic features of tumor cells diverge from those of normal cells. Otto Warburg was the first to observe that cancer cells dramatically increase their glucose consumption to generate ATP. He also claimed that cancer cells do not have functional mitochondria or oxidative phosphorylation (OXPHOS) but simply rely on glycolysis to provide ATP to the cell, even in the presence of oxygen (aerobic glycolysis). Several studies have revisited this observation and demonstrated that most cancer cells contain metabolically efficient mitochondria. Indeed, to sustain high proliferation rates, cancer cells require functional mitochondria to provide ATP and intermediate metabolites, such as citrate and cofactors, for anabolic reactions. This difference in metabolism between normal and tumors cells causes the latter to be more sensitive to agents that can disrupt energy homeostasis. In this review, we focus on energy disruptors, such as biguanides, 2-deoxyglucose and 5-aminoimidazole-4-carboxamide ribonucleotide, that interfere with the main metabolic pathways of the cells, OXPHOS, glycolysis and glutamine metabolism. We discuss the preclinical data and the mechanisms of action of these disruptors at the cellular and molecular levels. Finally, we consider whether these drugs can reasonably contribute to the antitumoral therapeutic arsenal in the future. PMID:26779810

  17. Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) Final Report

    Science.gov (United States)

    The EDSTAC Report was developed through a deliberative process that encouraged the development of consensus solutions to complex problems and issues related to developing an Endocrine Disruptor Screening Program.

  18. Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue?

    OpenAIRE

    Magnusson, Ulf; Persson, Sara

    2015-01-01

    Contents The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive sys...

  19. Ten Putative Contributors to the Obesity Epidemic

    Science.gov (United States)

    McAllister, Emily J.; Dhurandhar, Nikhil V.; Keith, Scott W.; Aronne, Louis J.; Barger, Jamie; Baskin, Monica; Benca, Ruth M.; Biggio, Joseph; Boggiano, Mary M.; Eisenmann, Joe C.; Elobeid, Mai; Fontaine, Kevin R.; Gluckman, Peter; Hanlon, Erin C.; Katzmarzyk, Peter; Pietrobelli, Angelo; Redden, David T.; Ruden, Douglas M.; Wang, Chenxi; Waterland, Robert A.; Wright, Suzanne M.; Allison, David B.

    2010-01-01

    The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects, as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic. PMID:19960394

  20. Analysis of a ToxCast™ HTS Toxicity Signature for putative Vascular Disruptor Compounds

    Science.gov (United States)

    Recent studies have shown the importance of blood vessel formation during embryo development and the strong correlation to developmental toxicity. Several developmental toxicants, such as thalidomide, have been identified which specifically target the forming embryonic vasculatur...

  1. Investigating potential for effects of environmental endocrine disrupters on wild populations of amphibians in UK and Japan: status of historical databases and review of methods.

    Science.gov (United States)

    Pickford, Daniel B; Larroze, Severine; Takase, Minoru; Mitsui, Naoko; Tooi, Osamu; Santo, Noriaki

    2007-01-01

    Concern over global declines among amphibians has resulted in increased interest in the effects of environmental contaminants on amphibian populations, and more recently, this has stimulated research on the potential adverse effects of environmental endocrine disrupters in amphibians. Laboratory studies of the effects of single chemicals on endocrine-relevant endpoints in amphibian, mainly anuran, models are valuable in characterizing sensitivity at the individual level and may yield useful bioassays for screening chemicals for endocrine toxicity (for example, thyroid disrupting activity). Nevertheless, in the UK and Japan as in many other countries, it has yet to be demonstrated unequivocally that the exposure of native amphibians to endocrine disrupting environmental contaminants results in adverse effects at the population level. Assessing the potential of such effects is likely to require an ecoepidemiological approach to investigate associations between predicted or actual exposure of amphibians to (endocrine disrupting) environmental contaminants and biologically meaningful responses at the population level. In turn, this demands recent but relatively long-term population trend data. We review two potential sources of such data for widespread UK anurans that could be used in such investigations: records for common frogs and common toads in several databases maintained by the Biological Records Centre (UK Government Centre for Ecology and Hydrology), and adult toad count data from 'Toads on Roads' schemes registered with the UK wildlife charity 'Froglife'. There were little abundance data in the BRC databases that could be used for this purpose, while count data from the Toads on Roads schemes is potentially confounded by the effects of local topology on the detection probabilities and operation of nonchemical anthropogenic stressors. For Japan, local and regional surveys of amphibians and national ecological censuses gathering amphibian data were reviewed to

  2. 75 FR 81605 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Science.gov (United States)

    2010-12-28

    ... CONTACT. List of Subjects Environmental protection, Endocrine disruptors, Screening assays, Weight-of... From the Federal Register Online via the Government Publishing Office ENVIRONMENTAL PROTECTION AGENCY Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for...

  3. 76 FR 60022 - Endocrine Disruptor Screening Program; Weight-of-Evidence Guidance Document; Notice of Availability

    Science.gov (United States)

    2011-09-28

    ... protection, Endocrine disruptors, Screening assays, Weight-of-evidence. ] Dated: September 22, 2011. Stephen... AGENCY Endocrine Disruptor Screening Program; Weight-of-Evidence Guidance Document; Notice of Availability AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA's Endocrine...

  4. The effects of nanomaterials as endocrine disruptors.

    Science.gov (United States)

    Iavicoli, Ivo; Fontana, Luca; Leso, Veruscka; Bergamaschi, Antonio

    2013-08-14

    In recent years, nanoparticles have been increasingly used in several industrial, consumer and medical applications because of their unique physico-chemical properties. However, in vitro and in vivo studies have demonstrated that these properties are also closely associated with detrimental health effects. There is a serious lack of information on the potential nanoparticle hazard to human health, particularly on their possible toxic effects on the endocrine system. This topic is of primary importance since the disruption of endocrine functions is associated with severe adverse effects on human health. Consequently, in order to gather information on the hazardous effects of nanoparticles on endocrine organs, we reviewed the data available in the literature regarding the endocrine effects of in vitro and in vivo exposure to different types of nanoparticles. Our aim was to understand the potential endocrine disrupting risks posed by nanoparticles, to assess their underlying mechanisms of action and identify areas in which further investigation is needed in order to obtain a deeper understanding of the role of nanoparticles as endocrine disruptors. Current data support the notion that different types of nanoparticles are capable of altering the normal and physiological activity of the endocrine system. However, a critical evaluation of these findings suggests the need to interpret these results with caution since information on potential endocrine interactions and the toxicity of nanoparticles is quite limited.

  5. Human infertility: are endocrine disruptors to blame?

    Science.gov (United States)

    Marques-Pinto, André; Carvalho, Davide

    2013-01-01

    Over recent decades, epidemiological studies have been reporting worrisome trends in the incidence of human infertility rates. Extensive detection of industrial chemicals in human serum, seminal plasma and follicular fluid has led the scientific community to hypothesise that these compounds may disrupt hormonal homoeostasis, leading to a vast array of physiological impairments. Numerous synthetic and natural substances have endocrine-disruptive effects, acting through several mechanisms. The main route of exposure to these chemicals is the ingestion of contaminated food and water. They may disturb intrauterine development, resulting in irreversible effects and may also induce transgenerational effects. This review aims to summarise the major scientific developments on the topic of human infertility associated with exposure to endocrine disruptors (EDs), integrating epidemiological and experimental evidence. Current data suggest that environmental levels of EDs may affect the development and functioning of the reproductive system in both sexes, particularly in foetuses, causing developmental and reproductive disorders, including infertility. EDs may be blamed for the rising incidence of human reproductive disorders. This constitutes a serious public health issue that should not be overlooked. The exposure of pregnant women and infants to EDs is of great concern. Therefore, precautionary avoidance of exposure to EDs is a prudent attitude in order to protect humans and wildlife from permanent harmful effects on fertility. PMID:23985363

  6. Enamel hypomineralization due to endocrine disruptors.

    Science.gov (United States)

    Jedeon, Katia; Marciano, Clémence; Loiodice, Sophia; Boudalia, Sofiane; Canivenc Lavier, Marie-Chantal; Berdal, Ariane; Babajko, Sylvie

    2014-08-01

    There has been increasing concerns over last 20 years about the potential adverse effects of endocrine disruptors (EDs). Bisphenol A (BPA), genistein (G) and vinclozolin (V) are three widely used EDs having similar effects. Tooth enamel has recently been found to be an additional target of BPA that may be a causal agent of molar incisor hypomineralization (MIH). However, populations are exposed to many diverse EDs simultaneously. The purpose of this study was therefore to assess the effects of the combination of G, V and BPA on tooth enamel. Rats were exposed daily in utero and after birth to low doses of EDs mimicking human exposure during the critical fetal and suckling periods when amelogenesis takes place. The proportion of rats presenting opaque areas of enamel hypomineralization was higher when rats were treated with BPA alone than with a combination of EDs. The levels of mRNAs encoding the main enamel proteins varied with BPA treatment alone and did not differ significantly between controls and combined treatment groups. In vitro, rat ameloblastic HAT-7 cells were treated with the three EDs. BPA induced enamelin and reduced klk4 expression, G had no such effects and V reduced enamelin expression. These findings suggest that combinations of EDs may affect enamel less severely than BPA alone, and indicate that enamel hypomineralization may differ according to the characteristics of the ED exposure.

  7. 75 FR 77869 - Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Extension...

    Science.gov (United States)

    2010-12-14

    ... water, Endocrine disruptors, Pesticides and pests. Dated: December 8, 2010. Stephen A. Owens, Assistant... AGENCY Endocrine Disruptor Screening Program; Second List of Chemicals for Tier 1 Screening; Extension of... Endocrine Disruptor Screening Program's (EDSP) second list of chemicals for Tier 1 screening. This...

  8. 77 FR 15101 - Results From Inert Ingredient Test Orders Issued Under EPA's Endocrine Disruptor Screening...

    Science.gov (United States)

    2012-03-14

    ..., Endocrine disruptors, Pesticides and pests. Dated: February 17, 2012. Lois Rossi, Director, Registration... AGENCY Results From Inert Ingredient Test Orders Issued Under EPA's Endocrine Disruptor Screening Program... EPA's Endocrine Disruptor Screening Program (EDSP) and the Federal Food, Drug, and Cosmetic Act...

  9. 77 FR 12297 - Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening...

    Science.gov (United States)

    2012-02-29

    ... Subjects Environmental protection, EDSP, Endocrine Disruptors Screening Program, FFDCA orders, List 1... AGENCY Petition To Demonstrate Paperwork Reduction Act Compliance of the Endocrine Disruptor Screening... Request (ICR) of the first list of 67 chemicals to receive orders under the Endocrine Disruptor...

  10. Endocrine Disruptors in Domestic Animal Reproduction: A Clinical Issue?

    Science.gov (United States)

    Magnusson, Ulf; Persson, Sara

    2015-09-01

    The objective of this review was to discuss whether endocrine disruption is a clinical concern in domestic animal reproduction. To that end, we firstly summarize the phenomenon of endocrine disruption, giving examples of the agents of concern and their effects on the mammalian reproductive system. Then there is a brief overview of the literature on endocrine disruptors and domestic animal reproduction. Finally, the clinical implications of endocrine disruptors on the reproductive system of farm animals as well as in dogs and cats are discussed. It is concluded that the evidence for clinical cases of endocrine disruption by chemical pollutants is weak, whereas for phytooestrogens, it is well established. However, there is concern that particular dogs and cats may be exposed to man-made endocrine disruptors.

  11. [Endocrine disruptors are a novel direction of endocrinologic scientific investigation].

    Science.gov (United States)

    Iaglova, N V; Iaglov, V V

    2012-01-01

    Endocrine disruptors are exogenous anthropogenic chemicals (pesticides, herbicides, polychlorinated biphenyls, bisphenol A, polybrominated diphenyl ethers, phthalates and others), that are able to bind hormonal receptors of endocrine and other cells in vivo and act like hormones. These substances disrupt endocrine regulation of metabolism, reproduction and adaptive reactions of organisms and promote human and animal endocrine disorders.

  12. Epigenetic transgenerational actions of endocrine disruptors and male fertility.

    Science.gov (United States)

    Anway, Matthew D; Cupp, Andrea S; Uzumcu, Mehmet; Skinner, Michael K

    2005-06-01

    Transgenerational effects of environmental toxins require either a chromosomal or epigenetic alteration in the germ line. Transient exposure of a gestating female rat during the period of gonadal sex determination to the endocrine disruptors vinclozolin (an antiandrogenic compound) or methoxychlor (an estrogenic compound) induced an adult phenotype in the F1 generation of decreased spermatogenic capacity (cell number and viability) and increased incidence of male infertility. These effects were transferred through the male germ line to nearly all males of all subsequent generations examined (that is, F1 to F4). The effects on reproduction correlate with altered DNA methylation patterns in the germ line. The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology.

  13. Exposición humana a disruptores endocrinos

    Directory of Open Access Journals (Sweden)

    A. Rivas

    2004-01-01

    Full Text Available Numerosos estudios han asociado las patologías observadas en distintas especies animales y en el hombre con la exposición a contaminantes medio ambientales con actividad hormonal. Se ha acuñado el término de disruptores endocrinos (Endocrine Disrupting Chemicals / EDCs para definir el conjunto de compuestos químicos que interaccionan con el sistema endocrino, sobre el que inducen efectos potencialmente debidos a su capacidad para:1 mimetizar la acción de las hormonas endógenas; 2 antagonizar la acción de las hormonas; 3 alterar su patrón de síntesis y metabolismo; o bien 4 modular los niveles de los receptores correspondientes.La exposición humana a disruptores endocrinos es universal y puede provenir de numerosas fuentes. Además, los compuestos acumulados en la grasa son transmitidos a la descendencia a través de la madre durante la gestación y después de la lactancia.Los efectos sobre la salud humana de la exposicición continua a los disruptores endocrinos necesitan ser investigados en más profundidad.

  14. Hormones and endocrine disruptors in human seminal plasma.

    Science.gov (United States)

    Hampl, R; Kubatova, J; Heracek, J; Sobotka, V; Starka, L

    2013-07-01

    Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

  15. The use of metabolising systems for in vitro testing of endocrine disruptors.

    Science.gov (United States)

    Jacobs, M N; Janssens, W; Bernauer, U; Brandon, E; Coecke, S; Combes, R; Edwards, P; Freidig, A; Freyberger, A; Kolanczyk, R; Mc Ardle, C; Mekenyan, O; Schmieder, P; Schrader, T; Takeyoshi, M; van der Burg, B

    2008-10-01

    Legislation and prospective legislative proposals in for instance the USA, Europe, and Japan require, or may require that chemicals are tested for their ability to disrupt the hormonal systems of mammals. Chemicals found to test positive are considered to be endocrine active substances (EAS) and may be putative endocrine disruptors (EDs). To date, there is still little or no experience with incorporating metabolic and toxicokinetic aspects into in vitro tests for EAS. This is a situation in sharp contrast to genotoxicity testing, where in vitro tests are routinely conducted with and without metabolic capacity. Originally prepared for the Organisation of Economic Cooperation and Development (OECD), this detailed review paper reviews why in vitro assays for EAS should incorporate mammalian systems of metabolism and metabolic enzyme systems, and indicates how this could be done. The background to ED testing, the available test methods, and the role of mammalian metabolism in the activation and the inactivation of both endogenous and exogenous steroids are described. The available types of systems are compared, and the potential problems in incorporating systems in in vitro tests for EAS, and how these might be overcome, are discussed. Lastly, some recommendations for future activities are made.

  16. 78 FR 35922 - Endocrine Disruptor Screening Program; Final Second List of Chemicals and Substances for Tier 1...

    Science.gov (United States)

    2013-06-14

    ... as a list of known or likely endocrine disruptors. Nothing in the approach for generating the second... as a list of known or likely endocrine disruptors nor characterized as such. Some commenters also... potential only, it should neither be construed as a list of known or likely endocrine disruptors...

  17. Exposición humana a disruptores endocrinos

    OpenAIRE

    2004-01-01

    Numerosos estudios han asociado las patologías observadas en distintas especies animales y en el hombre con la exposición a contaminantes medio ambientales con actividad hormonal. Se ha acuñado el término de disruptores endocrinos (Endocrine Disrupting Chemicals / EDCs) para definir el conjunto de compuestos químicos que interaccionan con el sistema endocrino, sobre el que inducen efectos potencialmente debidos a su capacidad para:1) mimetizar la acción de las hormonas endógenas; 2) ...

  18. Endocrine disruptors and female cancer: Informing the patients (Review).

    Science.gov (United States)

    Del Pup, Lino; Mantovani, Alberto; Luce, Amalia; Cavaliere, Carla; Facchini, Gaetano; Di Francia, Raffaele; Caraglia, Michele; Berretta, Massimiliano

    2015-07-01

    Pollutants altering the endocrine system, known as endocrine disruptors (ED), may modify the risk of female cancers. The carcinogenic effect of ED on humans has been confirmed by experimental studies for various substances including pesticides, DDT, dioxins, phthalates, bisphenol A, diethylstilbestrol, as well as heavy metals, but it is difficult to quantify precisely for several reasons hereby reviewed. Carcinogenesis is a complex and multifactorial mechanism that manifests itself over a long period of time, making difficult the detection of the specific contribution of the pollutants, whose absorbed dose is often unknown. The combined effect of various substances leads to complex interactions whose outcome is difficult to predict. These substances may accumulate and carry out their harmful effect on critical periods of life, probably also at doses considered harmless to an adult. ED can also have epigenetic adverse effects on the health of future generations. In conclusion, the carcinogenic effects of endocrine disruptors on female cancer types is plausible although additional studies are needed to clarify their mechanisms and entities. In the last part of the review we suggest ways to reduce ED exposure as it is mandatory to implement necessary measures to limit exposure, particularly during those periods of life most vulnerable to the impact of oncogenic environmental causes, such as the embryonic period and puberty.

  19. The impact of endocrine disruptors on endocrine targets.

    Science.gov (United States)

    Diamanti-Kandarakis, E; Palioura, E; Kandarakis, S A; Koutsilieris, M

    2010-07-01

    Endocrine disruption represents one of the most controversial environmental issues of our époque. So far, many substances, both natural and artificial, have been recognized to interfere with endocrine signaling pathways. In intact laboratory animals, this interaction has been documented to generate adverse health outcomes by impairing normal functions. With regard to humans, evidence is limited and inconsistent to clearly establish a causal inference, however, accumulating data incriminate endocrine disrupting chemicals to reproductive disorders and disturbed thyroid homeostasis. Recently, as a result of animal models and preliminary human studies, a new area of interest has arisen concerning the implication of endocrine disruptors in the etiology of obesity and diabetes, the two major, life-threatening, epidemics of modern world. This article reviews the evidence linking endocrine disrupting chemicals to a broad spectrum of clinical perturbations from reproduction and thyroid to metabolic regulation.

  20. Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Hatagima Ana

    2002-01-01

    Full Text Available Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.

  1. Carcinogenetic mechanisms of endocrine disruptors in female cancers (Review).

    Science.gov (United States)

    Del Pup, Lino; Mantovani, Alberto; Cavaliere, Carla; Facchini, Gaetano; Luce, Amalia; Sperlongano, Pasquale; Caraglia, Michele; Berretta, Massimiliano

    2016-08-01

    Endocrine disruptors (EDs) are pollutants that alter the endocrine system and are involved in carcinogenesis. EDs have multiple and complex levels of action. They can affect the synthesis, release and transport of natural hormones. In target tissues, EDs can reduce or increase the effects of natural hormones on their receptors and change signaling cascades. When ED exposure happens at critical periods of life, from embryo to puberty, they can act at doses considered safe for an adult. Furthermore, their epigenetic effects can also influence the cancer risk of future generations. The cancer mechanisms of known EDs are hereby reviewed, There are thousands of newly introduced substances whose potential endocrine-disrupting and cancer effects are completely unknown. Although there are still gaps in our knowledge, these data support the urgent need for health and environmental policies aimed at protecting the public and in particular, the developing fetus and women of reproductive age.

  2. Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Ana Hatagima

    2002-04-01

    Full Text Available Epidemiological studies have estimated that approximately 80% of all cancers are related to environmental factors. Individual cancer susceptibility can be the result of several host factors, including differences in metabolism, DNA repair, altered expression of tumor suppressor genes and proto-oncogenes, and nutritional status. Xenobiotic metabolism is the principal mechanism for maintaining homeostasis during the body's exposure to xenobiotics. The balance of xenobiotic absorption and elimination rates in metabolism can be important in the prevention of DNA damage by chemical carcinogens. Thus the ability to metabolize and eliminate xenobiotics can be considered one of the body's first protective mechanisms. Variability in individual metabolism has been related to the enzymatic polymorphisms involved in activation and detoxification of chemical carcinogens. This paper is a contemporary literature review on genetic polymorphisms involved in the metabolism of endocrine disruptors potentially related to cancer development.

  3. Human exposure to endocrine disruptors and breast milk.

    Science.gov (United States)

    Stefanidou, M; Maravelias, C; Spiliopoulou, C

    2009-09-01

    Endocrine system is one of the most sensitive communication networks of the human body which influences all aspects of human health and well-being, including reproductive potential, cognitive functions, thyroid and metabolism, digestion and hormonal balance. In recent years basic laboratory research has been focused on the potential relationship between environmental contaminants and cellular endocrine function. Environmental contaminants are ubiquitous in the environment, alter endocrine physiology and produce endocrine disruption without acting as classic toxicants. These endocrine disruptors (EDCs) are lipophilic and stored for long periods of time in the adipose tissue. Maternal exposure to EDCs during pregnancy and lactation has as a result the exposure of the fetus and neonate through placenta and breast milk. It has been recognized that human milk is the best natural food for neonates providing immunologic, developmental and practical advantages throughout childhood. However, contamination of human milk by the presence of environmental toxicants is widespread through the past decades due to inadequately controlled pollution. Persistent pesticides, chemical solvents and others tend to invade slowly the environment, to bioaccumulate in the food chain and to have long half-lives in animals and humans. During the past fifteen years, the scientific interest has been focused on xenoestrogens, i.e.,environmental chemicals with estrogen disrupting activity. Certain adverse health and reproductive outcomes are attributed to these chemicals in wildlife, in laboratory animals, as well as in humans. Although most toxic agents are hazardous in high doses, the human health risks associated with EDCs concern exposure to low doses. The human health risks that may be associated with these low-level but constant exposures are still largely unknown and highly controversial. In this paper, we review available data on environmental chemicals present in breast milk that may

  4. The menace of endocrine disruptors on thyroid hormone physiology and their impact on intrauterine development.

    Science.gov (United States)

    Mastorakos, George; Karoutsou, Eftychia I; Mizamtsidi, Maria; Creatsas, George

    2007-06-01

    The delivery of the appropriate thyroid hormones quantity to target tissues in euthyroidism is the result of unopposed synthesis, transport, metabolism, and excretion of these hormones. Thyroid hormones homeostasis depends on the maintenance of the circulating 'free' thyroid hormone reserves and on the development of a dynamic balance between the 'free' hormones reserves and those of the 'bound' hormones with the transport proteins. Disturbance of this hormone system, which is in constant interaction with other hormone systems, leads to an adaptational counter-response targeting to re-establish a new homeostatic equilibrium. An excessive disturbance is likely to result, however, in hypo- or hyper- thyroid clinical states. Endocrine disruptors are chemical substances forming part of 'natural' contaminating agents found in most ecosystems. There is abundant evidence that several key components of the thyroid hormones homeostasis are susceptible to the action of endocrine disruptors. These chemicals include some chlorinated organic compounds, polycyclic aromatic hydrocarbons, herbicides, and pharmaceutical agents. Intrauterine exposure to endocrine disruptors that either mimic or antagonize thyroid hormones can produce permanent developmental disorders in the structure and functioning of the brain, leading to behavioral changes. Steroid receptors are important determinants of the consequences of endocrine disruptors. Their interaction with thyroid hormones complicates the effect of endocrine disruptors. The aim of this review is to present the effect of endocrine disruptors on thyroid hormones physiology and their potential impact on intrauterine development.

  5. A review on endocrine disruptors and their possible impacts on human health.

    Science.gov (United States)

    Kabir, Eva Rahman; Rahman, Monica Sharfin; Rahman, Imon

    2015-07-01

    Endocrine disruption is a named field of research which has been very active for over 10 years, although the effects of endocrine disruptors in wildlife have been studied mainly in vast since the 1940s. A large number of chemicals have been identified as endocrine disruptors and humans can be exposed to them either due to their occupations or through dietary and environmental exposure (water, soil and air). Endocrine disrupting chemicals are compounds that alter the normal functioning of the endocrine system of both humans and wildlife. In order to understand the vulnerability and risk factors of people due to endocrine disruptors as well as the remedies for these, methods need to be developed in order to predict effects on populations and communities from the knowledge of effects on individuals. For several years there have been a growing interest on the mechanism and effect of endocrine disruptors and their relation with environment and human health effect. This paper, based on extensive literature survey, briefly studies the progress mainly in human to provide information concerning causative substances, mechanism of action, ubiquity of effects and important issues related to endocrine disruptors. It also reviews the current knowledge of the potential impacts of endocrine disruptors on human health so that the effects can be known and remedies applied for the problem as soon as possible.

  6. Multi-residue analytical method for the determination of endocrine disruptors and related compounds in river and waste water using dual column liquid chromatography switching system coupled to mass spectrometry.

    Science.gov (United States)

    Gorga, Marina; Petrovic, Mira; Barceló, Damià

    2013-06-21

    The present study describes a novel, fully automated method, based on column switching using EQuan™ columns for an integrated sample preconcentration and liquid chromatography coupled to tandem mass spectrometry (LC-LC-MS/MS). The method allows the unequivocal identification and quantification of the most relevant environmental endocrine disruptors compounds (EDCs) and compounds suspected to be EDCs, such as natural and synthetic estrogens and their conjugates, antimicrobials, parabens, bisphenol A, alkylphenolic compounds, benzotriazoles, and organophosphorus flame retardants, in surface river water and wastewater samples. Applying this technique, water samples were directly injected into the chromatographic system and the target compounds were concentrated into the loading column. Thereafter, the analytes were transferred into the analytical column for subsequent detection by MS-MS (QqQ). A comparative study employing three types of columns, with different chemical modifications, was performed in order to determine the optimal column that allowed maximum retention and subsequent elution of the analytes. Using this new optimized methodology a fast and easy online methodology for the analysis of EDCs in surface river water and wastewater with low limits of quantification (LOQ) was obtained. LOQs ranged from 0.008 to 1.54 ng/L for surface river water and from 0.178/0.364 to 12.5/25.0 ng/L (except for alkylphenol monoethoxylates) for effluent/influent waste water. Moreover, employing approximately 1h, a complete analysis was performed which was significant improvement in comparison to other methods reported previously. This method was used to track the presence and fate of target compounds in the Ebro River which is the most important river in Spain whose intensive agricultural and industrial activities concentrate mainly close to the main cities in the basin, deteriorating soil and water quality.

  7. Endocrine disruptors and spontaneous premature labor: a case control study

    Directory of Open Access Journals (Sweden)

    Swaby Cheryl

    2007-11-01

    Full Text Available Abstract Background Premature labor is a poorly understood condition. Estrogen is thought to play a key role and therefore the labor process may be affected by endocrine disruptors. We sought to determine whether or not an environmental toxicant, DDE, or dietary derived endocrine disruptors, daidzein and genistein, are associated with spontaneous preterm labor. Methods Cases were defined as primiparous patients having a preterm delivery at or before 35 weeks following the spontaneous onset of labor. Controls were defined as primiparous women who delivered on the same day as the cases but at term gestation. Over approximately 1 year, 26 cases and 52 controls were recruited. Subjects agreed to have blood tests on day one postpartum for DDE and for the phytoestrogens genistein and daidzein. Results The mean concentration of DDE was similar in the case and control groups: 4.29 vs 4.32 ng/g lipid p = .85. In the case group, 13/26 had detectable levels of daidzein (range 0.20 – 1.56 ng/ml compared to 25/52 controls (range 0.21 – 3.26 ng/ml. The mean concentration of daidzein was similar in cases compared to controls: 0.30 vs .34 ng/ml p = 0.91. Of the case group,14/26 had detectable levels of genistein (range 0.20 – 2.19 ng/ml compared to 32/52 controls (range 0.21 – 2.55 ng/ml. The mean concentration of genistein was similar in cases compared to controls: 0.39 vs 0.31 ng/ml, p = 0.61. Conclusion The serum levels of DDE in this population were found to be low. There appears to be no relationship between serum concentrations of DDE, daidzein, and genistein and spontaneous preterm labor in our population. The inability to identify an effect may be related to the comparatively low concentrations of DDE in our population and the rapid and variable reduction of phytoestrogens from women in labor.

  8. The endocrine disruptors among the environmental risk factors for stillbirth

    Energy Technology Data Exchange (ETDEWEB)

    Roncati, Luca, E-mail: emailmedical@gmail.com [Provincial Health Care Services, Institute of Pathology, Santa Maria del Carmine Hospital, Rovereto, TN (Italy); Department of Diagnostic and Clinical Medicine and of Public Health, University of Modena and Reggio Emilia, Modena, MO (Italy); Piscioli, Francesco; Pusiol, Teresa [Provincial Health Care Services, Institute of Pathology, Santa Maria del Carmine Hospital, Rovereto, TN (Italy)

    2016-09-01

    Persistent organic pollutants have been lately taken into consideration for their adverse effects, as possible stillbirth contributors; stillbirth can be in fact considered the most dramatic pregnancy complication. Congenital abnormalities account for few stillbirths and many related disorders are potentially modifiable or often coexist, such as maternal infections, non-communicable diseases, lifestyle factors and maternal age. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour. For this reason, many current efforts are focusing on the study of endocrine disruptor (ED) placental transfer, to better understand the in utero exposure dynamics. In this regard, our research group has investigated, by gas chromatography–mass spectrometry, the EDs presence in brain samples of 24 stillbirths, collected over a 3-year period (2012–2014), coming from the Northeast Italy, a notorious area devoted to apple cultivation. Surprisingly, organochlorine pesticides (OCPs), well-known EDs, have been detected in 11 samples. Apart from the noteworthy evidence of pesticides' bio-persistence, this finding implies a redefinition of the placental barrier concept: not a real safety system, but a time-deferral mechanism of absorption. The term ‘placental barrier’ in fact refers to a 4-membrane structure, made up by two epithelial layers, which exactly lining the chorionic villi, and by two endothelial layers, belonging to the feeding vessels for the fetus. It is an effective barrier only for a low administration of water-soluble substances, which encounter obstacle to cross four instead of two membranes. High doses of water-soluble compounds can reach appreciable concentration in the fetal blood, and the lipid-soluble chemicals, such as EDs, are able to pass the placental barrier, through a simple mechanism of passive diffusion, even in minimal concentrations. After crossing the placental barrier

  9. [Endocrine disruptors: echoes of congress of Endocrinology in 2012].

    Science.gov (United States)

    Nassouri, A S; Archambeaud, F; Desailloud, R

    2012-10-01

    The increased prevalence of certain diseases, along with the development of new technologies and industrialization raised the possibility of the involvement of environmental factors, industrial products, nutritional factors, infections, drugs... and endocrine disruptors. These factors may interfere via signaling pathways specific to the organism. Endocrine Disrupting Chemicals (EDCs) have been redefined by the Endocrine Society in 2012 as "exogenous chemical, or mixture of chemicals, that can interfere with any aspect of hormone action". They have therefore potentially deleterious effects on development, growth, metabolism, reproduction, the nervous, immune and cardiovascular systems. Therefore, they constitute a real public health issue. Their long half-life may explain delayed effects and their often lipophilic character may promote maternofetal transmission. Except diethylstilbestrol (DES), few formal proofs have been made on the direct role of EDCs ; arguments are based on cross-sectional studies, in vitro models and animal models. Basic research puts insight into mechanisms of action of EDCs but many questions remain unanswered. Epidemiological data are difficult to interpret because of interindividual differences in susceptibility to EDCs and of nonlinear/nonmonotonique action (as opposed to toxic dose effect), multiple interactions between environmental agents (additive effects and/or synergistic and/or antagonists), the role of the window of exposure, latency, and the possibility of transgenerational effects.

  10. Cosmetics as endocrine disruptors: are they a health risk?

    Science.gov (United States)

    Nicolopoulou-Stamati, Polyxeni; Hens, Luc; Sasco, Annie J

    2015-12-01

    Exposure to chemicals from different sources in everyday life is widespread; one such source is the wide range of products listed under the title "cosmetics", including the different types of popular and widely-advertised sunscreens. Women are encouraged through advertising to buy into the myth of everlasting youth, and one of the most alarming consequences is in utero exposure to chemicals. The main route of exposure is the skin, but the main endpoint of exposure is endocrine disruption. This is due to many substances in cosmetics and sunscreens that have endocrine active properties which affect reproductive health but which also have other endpoints, such as cancer. Reducing the exposure to endocrine disruptors is framed not only in the context of the reduction of health risks, but is also significant against the background and rise of ethical consumerism, and the responsibility of the cosmetics industry in this respect. Although some plants show endocrine-disrupting activity, the use of well-selected natural products might reduce the use of synthetic chemicals. Instruments dealing with this problem include life-cycle analysis, eco-design, and green labels; in combination with the committed use of environmental management systems, they contribute to "corporate social responsibility".

  11. Effects of endocrine disruptors on developmental and reproductive functions.

    Science.gov (United States)

    Brevini, Tiziana A L; Zanetto, Simona Bertola; Cillo, Fabiana

    2005-03-01

    Endocrine disruptors (EDs) are exogenous environmental molecules that may affect the synthesis, secretion, transport, metabolism, binding, action, and catabolism of natural hormones in the body. EDs may thus interact with the endocrine system of animals and humans and can exert this effect even when present in minute amounts. EDs have adverse impacts on a number of developmental functions in wildlife and humans. Critical periods of urogenital tract and nervous system development in-utero and during early post-natal life are especially sensitive to hormonal disruption. Furthermore a wide range of hormone-dependent organs (pituitary gland, hypothalamus, reproductive tract) are targets of EDs disrupting effects in adult subjects, possibly resulting in cell transformation and cancer. At present about 60 chemicals have been identified and characterized as EDs and belong to three main groups: (a) synthetic compounds utilized in industry, agriculture and consumer products; (b) synthetic molecules used as pharmaceutical drugs and (c) natural chemicals found in human and animal food (phytoestrogens). In the present review we will give special attention to the family of Polychlorinated biphenyls (also indicated as PCBs) because of their persistence in the environment, ability to concentrate up the food chain, continued detection in environmental matrices, and ability to be stored in the adipose tissue of animals as well as humans. The detrimental effects of these compounds, and of EDs more in general, on health and reproduction will be discussed, presenting experimental data aimed at understanding the molecular mechanisms involved in their action.

  12. Acid exposure is an immune disruptor in adult Rana pipiens.

    Science.gov (United States)

    Vatnick, Itzick; Andrews, Jaime; Colombo, Matthew; Madhoun, Hareth; Rameswaran, Muthuramanan; Brodkin, Marc A

    2006-01-01

    Acidic environments are physiological stressors for amphibians. The objective of the present study was to document the effect of an acidic environment on innate immune system function under controlled experimental conditions in Rana pipiens. We developed an in vivo assay, by injecting a suspension of 1-microm fluorescent beads in fluid thioglycollate, to induce peritonitis. The number of peritoneal exudate leukocytes and their phagocytic activity did not increase with thioglycollate injection when frogs were exposed to pH 5.5 compared to when frogs were exposed to pH 7.0. An environment of pH 5.5 disrupted the inflammatory response of frogs compared to an environment of pH 7.0; at pH 5.5, more nonphagocytic leukocytes and fewer highly phagocytic leukocytes were found compared to those in frogs exposed to pH 7.0. Frogs stimulated by thioglycollate injection and exposed to pH 5.5 had a 50% increase in cells that did not exhibit phagocytosis and a 4- to 10-fold reduction in the number of highly phagocytic cells. This is evidence that acid exposure functions as an immune disruptor in adult R. pipiens under laboratory conditions.

  13. Properties of irradiated PVC plasticized with non-endocrine disruptor

    Science.gov (United States)

    Hutzler, Beatriz W.; Machado, Luci D. B.; Lugão, Ademar B.; Villavicencio, Anna.-Lucia C. H.

    2000-03-01

    Polyvinylchloride (PVC) is under heavy attack from environmentalist groups due to the use of plasticizers and its recycling difficulties. Chloro-organics and phtalates are considered now as ubiquitous global contaminants due to their potential as weak endocrine disruptor and huge consumption. In order to make PVC acceptable for the irradiation processing industry in the long term, non-toxic plasticizers should be used. PVC was added with dioctyl phtalate (DOP) and epoxy soybean oil (ESO) and irradiated up to 50 kGy. Mechanical properties, optical properties and viscosity were measured and compared. The elongation and mechanical strength were under the usual range and they didn't show any significant change in the studied range of irradiation dose. All the samples showed a weak yellowing effect after irradiation and the molecular weight measured by viscosimetry showed only negligible changes. In conclusion, DOP and ESO were shown to be effective in stabilizing the radiolytic abstraction of HCl from PVC. Both plasticizers imparted good color stability and overall properties to the products.

  14. 8种环境内分泌干扰物对多囊卵巢综合征胰岛素抵抗的影响%Effects of eight environmental endocrine disruptors on insulin resistance in patients with polycystic ovary syndrome: a preliminary investigation

    Institute of Scientific and Technical Information of China (English)

    李婷婷; 邱东升; 韩代文; 胡蓉; 许良智; 陈永亨; 邓红梅; 梁春营; 刘颖; 刘晓芳; 张静; 康德英

    2011-01-01

    Objective To investigate the relationship between 8 endocrine-disrupting chemicals in the serum and insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods This study was conducted among 60 patients with PCOS, including 23 with insulin resistance (PCOS-IR) and 37 without insulin resistance (PCOS-NIR), and 29 non-PCOS women seeking medical attention for infertility or menstrual disorder (control group). The serum levels of 6 phthalic acid esters (PEAs), bisphenol A (BPA) and octylphenol (OP) were measured in all the subjects. Results The levels of PAEs, BPA and OP showed no significant differences between PCOS patients and the control group (P>0.05). The serum level of OP was significantly lower in patients PCOS-IR than in those with PCOS-NIR (47.89 ng/ml vs 60.24 ng/ml, P<0.05). Conclusion PEAs and BPA do not produce obvious effect on the pathogenesis of PCOS or contribute to insulin resistance, but OP may play a role in insulin resistance in PCOS patients.%目的 通过检测多囊卵巢综合征(PCOS)患者血中8种环境内分泌干扰物,初步探讨其与PCOS胰岛素抵抗的关系.方法 分别测定60例PCOS患者(PCOS-IR组23例和PCOS-NIR组37例)及29例输卵管性不育、男性不育、月经紊乱原因就诊非PCOS非胰岛素抵抗对照组血清中的六种邻苯二甲酸酯类(PAEs)、双酚A(BPA)及辛基酚(OP)的含量,SPSS16.0软件进行统计分析.结果 六种PEAs、BPA在PCOS与非PCOS对照组间以及PCOS-IR与PCOS-NIR之间差异均无明显统计学意义(P>0.05).OP在PCOS与非PCOS对照组间差异无明显统计学意义(P>0.05),但在PCOS-IR与PCOS-NIR之间差异有统计学意义(P<0.05),且OP在PCOS-IR组含量低于在PCOS-NIR组含量.结论 PEAs、BPA对PCOS的发病及胰岛素抵抗无明显影响,OP则可能对PCOS胰岛素抵抗有影响.

  15. Endocrine disruptors and estrogenic effects on male reproductive axis

    Institute of Scientific and Technical Information of China (English)

    Suresh C. Sikka; Run Wang

    2008-01-01

    Endocrine disruptors (e.g., polychlorinated biphenyls [PCBs], dichlorodiphenyl-trichloroethane [DDT], dioxin,and some pesticides) are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones,inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions.The development of intra-cytoplasmic sperm injection (ICSI) is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology,biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. Clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.

  16. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors

    Science.gov (United States)

    Lloyd, David J.; St Jean, David J.; Kurzeja, Robert J. M.; Wahl, Robert C.; Michelsen, Klaus; Cupples, Rod; Chen, Michelle; Wu, John; Sivits, Glenn; Helmering, Joan; Komorowski, Renée; Ashton, Kate S.; Pennington, Lewis D.; Fotsch, Christopher; Vazir, Mukta; Chen, Kui; Chmait, Samer; Zhang, Jiandong; Liu, Longbin; Norman, Mark H.; Andrews, Kristin L.; Bartberger, Michael D.; van, Gwyneth; Galbreath, Elizabeth J.; Vonderfecht, Steven L.; Wang, Minghan; Jordan, Steven R.; Véniant, Murielle M.; Hale, Clarence

    2013-12-01

    Glucose homeostasis is a vital and complex process, and its disruption can cause hyperglycaemia and type II diabetes mellitus. Glucokinase (GK), a key enzyme that regulates glucose homeostasis, converts glucose to glucose-6-phosphate in pancreatic β-cells, liver hepatocytes, specific hypothalamic neurons, and gut enterocytes. In hepatocytes, GK regulates glucose uptake and glycogen synthesis, suppresses glucose production, and is subject to the endogenous inhibitor GK regulatory protein (GKRP). During fasting, GKRP binds, inactivates and sequesters GK in the nucleus, which removes GK from the gluconeogenic process and prevents a futile cycle of glucose phosphorylation. Compounds that directly hyperactivate GK (GK activators) lower blood glucose levels and are being evaluated clinically as potential therapeutics for the treatment of type II diabetes mellitus. However, initial reports indicate that an increased risk of hypoglycaemia is associated with some GK activators. To mitigate the risk of hypoglycaemia, we sought to increase GK activity by blocking GKRP. Here we describe the identification of two potent small-molecule GK-GKRP disruptors (AMG-1694 and AMG-3969) that normalized blood glucose levels in several rodent models of diabetes. These compounds potently reversed the inhibitory effect of GKRP on GK activity and promoted GK translocation both in vitro (isolated hepatocytes) and in vivo (liver). A co-crystal structure of full-length human GKRP in complex with AMG-1694 revealed a previously unknown binding pocket in GKRP distinct from that of the phosphofructose-binding site. Furthermore, with AMG-1694 and AMG-3969 (but not GK activators), blood glucose lowering was restricted to diabetic and not normoglycaemic animals. These findings exploit a new cellular mechanism for lowering blood glucose levels with reduced potential for hypoglycaemic risk in patients with type II diabetes mellitus.

  17. Effects of two endocrine disruptors Prochloraz and Ethinylestradiol on development of Rana Temporaria

    DEFF Research Database (Denmark)

    Brande-Lavridsen, Nanna; Christensen-Dalsgaard, Jakob; Korsgaard, Bodil

    2009-01-01

    on the effect of endocrine disruptors on the sexsteroid axis and reproductive function. However, another hormone system, the thyroid hormone axis may equally well be affected by xenobiotics. Thyroid hormones are essential in stimulating all aspects of amphibian metamorphosis and thyroid hormone disruptors may...... of phenotypic males. Moreover, ethinylestradiol caused estrogen-dependent induction of the egg yolk precursor protein vitellogenin. These results show that gonadal development and vitellogenin induction may be used as biomarkers for detection of endocrine disrupting chemicals. Most studies have focused...

  18. Endocrine disruptors: a new scientific role for clinical pharmacologists? Impact on human health, wildlife, and the environment.

    Science.gov (United States)

    Lathers, Claire M

    2002-01-01

    It is important for the clinical pharmacologist to understand the potential human health implications of exposure to environmental chemicals that may act as hormonally active agents. It is necessary to have an understanding of how pharmaceutical and personal care products and other chemicals affect the ecosystem of planet Earth and to understand how they may negatively contribute to human disease. Clinical pharmacologists must understand the various definitions of endocrine disruptors and be able to "decipher" these terms for their patients. Understanding the need for the EPA endocrine disruptor screening program and possessing knowledge of the screening assays used to assess endocrine activity potential are two essential components relevant to the topic of endocrine disruptors. Clinical pharmacologists have an opportunity to play an important role in resolving the question of what role endocrine disruptors play in initiating human disease since some scientists argue that the present evidence is not compelling. Clinical pharmacologists can also play an important role in the evaluation of the risk assessment and use of risk management and risk communication tools required to address public health concerns related to actions of endocrine disruptors. It is important that clinical pharmacologists work with veterinary clinical pharmacologists, toxicologists, industrial chemists, regulators, the scientific community, the general public, and environmental groups to understand the impact of endocrine disruptors on human health, wildlife, and the environment with an ultimate goal to minimize and/or alleviate the unwanted, detrimental effects of the endocrine disruptors.

  19. Selenium hyperaccumulation offers protection from cell disruptor herbivores

    Directory of Open Access Journals (Sweden)

    Quinn Colin F

    2010-08-01

    protective effect of hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.

  20. A study on the degradation of endocrine disruptors and dioxins by ozonation and advanced oxidation processes

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, S.; Kenmochi, Y.; Tutumi, K.; Tanaka, T. [Ebara Corp., Fujisawa (Japan)

    2003-07-01

    Recently, enhancement and development of treatment technologies related to contaminated water environment by endocrine disruptors such as bisphenol-A(BPA), estradiol(E2) and dioxins have become a focus of attention. In this study, the influence of O{sub 3} dosage and the forms of endocrine disruptors on the degradability during O{sub 3} treatment and AOP treatment were investigated. A reaction kinetic evaluation of these processes was also carried out. In this study, the endocrine disruptors were classified into 2 groups: (1) DXNs: dioxins and (2) EDs: endocrine disruptors other than dioxins. For the case of DXNs decomposition, highly concentrated DXNs from incinerator washwater were degraded by UV/O{sub 3} combined treatment. Influence of O{sub 3} dosage and forms of DXNs on the reaction rate constant were evaluated. For the case of EDs decomposition, the effect of O{sub 3} dosage on the reaction rate constant were investigated during O{sub 3} treatment of secondary treated sewage. Also, a degradability comparison was made for the above 2 groups. (orig.)

  1. Session 2 – Identification of endocrine disruptors and amendments of standard information requirements

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Holbech, Henrik

    2014-01-01

    Discussions regarding regulation of endocrine disruptors (EDs) and combination effects are ongoing in Europe. Among the central topics of discussion are establishment of criteria for identification of EDs, whether there is a threshold for endocrine disrupting effects and how EDs should be handled...

  2. 75 FR 67963 - Endocrine Disruptor Screening Program (EDSP); Announcing the Availability of a Draft for Weight...

    Science.gov (United States)

    2010-11-04

    .... 321(q)(1)). List of Subjects Environmental protection, Endocrine disruptors, Screening assays, Weight...] [FR Doc No: 2010-27897] ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2010-0877; FRL-8849-8] Endocrine...-tiered paradigm for screening and testing chemicals for endocrine activity (i.e., estrogen, androgen,...

  3. Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

    Science.gov (United States)

    Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

    2017-05-02

    This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

  4. [The crisis of the hormonal system: the health-effects of endocrine disruptors].

    Science.gov (United States)

    Csaba, György

    2017-09-01

    The endocrine disruptors are natural or arteficial molecules wich are present in the animal (human) environment and entering into the organism. They are bound by hormone receptors, simulating or inhibiting the normal hormonal message. This way they are able to stimulate or hinder the function of the given cell, as well as the synthesis and transport of hormones or receptors. They can cause faulty hormonal imprinting in critical periods of development with lifelong consequences, as alteration of hormone-influenced cell functions, inclination to or manifestation of diseases, so they have medical importance. The number of endocrine disruptors as well as their amount are large and continously growing. Numerous, in adult age manifested disease (e.g. malignant tumors) can be deduced to perinatal harms. Their long-lasting effect can cause the alteration of basal human developmental characteristics (e.g. start of menarche). Vitamins A and D are hormones (exohormones) and could be endocrine disruptors. Perinatal imprinting caused by endocrine disruptors is transmitted to the progenies epigenetically, which also can influence the drug-sensitivity of offspring' receptors. If the epigenetic change is continuously transmitted to the progeny generations, this could have human-evolutionary importance. Orv Hetil. 2017; 158(37): 1443-1451.

  5. The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

    NARCIS (Netherlands)

    Plotan, M.; Elliot, C.T.; Scippo, M.L.; Müller, M.; Antignac, J.P.; Malone, E.; Bovee, T.F.H.; Mitchell, S.; Connolly, L.

    2011-01-01

    The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to en

  6. Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences

    Science.gov (United States)

    Quagliariello, Vincenzo; Rossetti, Sabrina; Cavaliere, Carla; Di Palo, Rossella; Lamantia, Elvira; Castaldo, Luigi; Nocerino, Flavia; Ametrano, Gianluca; Cappuccio, Francesca; Malzone, Gabriella; Montanari, Micaela; Vanacore, Daniela; Romano, Francesco Jacopo; Piscitelli, Raffaele; Iovane, Gelsomina; Pepe, Maria Filomena; Berretta, Massimiliano; D'Aniello, Carmine; Perdonà, Sisto; Muto, Paolo; Botti, Gerardo; Ciliberto, Gennaro; Veneziani, Bianca Maria; De Falco, Francesco; Maiolino, Piera; Caraglia, Michele; Montella, Maurizio; Iaffaioli, Rosario Vincenzo; Facchini, Gaetano

    2017-01-01

    This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the worlds leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease. PMID:28389628

  7. Exposición a disruptores endocrinos y alteraciones del tracto urogenital masculino (criptorquidia e hipospadias Exposure to endocrine disruptors and male urogenital tract malformations [cryptorchidism and hypospadias

    Directory of Open Access Journals (Sweden)

    Mariana F. Fernández

    2007-12-01

    Full Text Available Antecedentes: Se ha sugerido que la exposición maternoinfantil a compuestos hormonalmente activos (disruptores endocrinos tiene en la etapa intrauterina una de sus fases más comprometidas. Objetivo: Revisar los estudios epidemiológicos, nacionales e internacionales, publicados entre 1990 y el primer trimestre de 2006, que tuvieran como hipótesis la asociación entre la exposición humana a disruptores endocrinos y el riesgo de criptorquidia e hipospadias. Métodos: Se han buscado artículos en MEDLINE/PubMed mediante las palabras clave: disruptores endocrinos, xenoestrógenos, pesticidas organoclorados y criptorquidia e hipospadias. La selección de los 16 trabajos incluidos se hizo atendiendo al diseño y la población de estudio, las medidas de exposición empleadas, los criterios de exclusión e inclusión establecidos y el análisis estadístico utilizado. Resultados y conclusiones: Aunque los estudios aquí revisados no son concluyentes para confirmar la asociación entre disruptores endocrinos y riesgo de malformación del tracto genitourinario, tampoco demuestran la falta de tal asociación. Por este motivo parece razonable sugerir que este aspecto de la patología hormonal debería investigarse más en profundidad, resolviendo, al menos, el diagnóstico adecuado de los individuos y la estimación de la exposición a múltiples compuestos químicos, contaminantes ambientales, que actúan conjuntamente a través de mecanismos similares a las hormonas endógenas.Background: It has been proposed that the intrauterine period of child-mother exposure to hormonally active compounds (endocrine disruptors is of critical importance. Objective: We reviewed all Spanish and English-language epidemiological studies published between 1990 and the first trimester of 2006 that studied the possible association between human exposure to chemical compounds and the risk of cryptorchidism and/or hypospadias. Methods: The MEDLINE (PubMed database was

  8. Selecting appropriate animal models and experimental designs for endocrine disruptor research and testing studies.

    Science.gov (United States)

    Stokes, William S

    2004-01-01

    Evidence that chemicals in the environment may cause developmental and reproductive abnormalities in fish and wildlife by disrupting normal endocrine functions has increased concern about potential adverse human health effects from such chemicals. US laws have now been enacted that require the US Environmental Protection Agency (EPA) to develop and validate a screening program to identify chemicals in food and water with potential endocrine-disrupting activity. EPA subsequently proposed an Endocrine Disruptor Screening Program that uses in vitro and in vivo test systems to identify chemicals that may adversely affect humans and ecologically important animal species. However, the endocrine system can be readily modulated by many experimental factors, including diet and the genetic background of the selected animal strain or stock. It is therefore desirable to minimize or avoid factors that cause or contribute to experimental variation in endocrine disruptor research and testing studies. Standard laboratory animal diets contain high and variable levels of phytoestrogens, which can modulate physiologic and behavioral responses similar to both endogenous estrogen as well as exogenous estrogenic chemicals. Other studies have determined that some commonly used outbred mice and rats are less responsive to estrogenic substances than certain inbred mouse and rat strains for various estrogen-sensitive endpoints. It is therefore critical to select appropriate biological models and diets for endocrine disruptor studies that provide optimal sensitivity and specificity to accomplish the research or testing objectives. An introduction is provided to 11 other papers in this issue that review these and other important laboratory animal experimental design considerations in greater detail, and that review laboratory animal and in vitro models currently being used or evaluated for endocrine disruptor research and testing. Selection of appropriate animal models and experimental design

  9. Report: EPA’s Endocrine Disruptor Screening Program Should Establish Management Controls to Ensure More Timely Results

    Science.gov (United States)

    Report #11-P-0215, May 3, 2011. Fourteen years after passage of the FQPA and Safe Drinking Water Act amendments, EPA’s EDSP has not determined whether any chemical is a potential endocrine disruptor.

  10. Disruptores endocrinos utilizados en la industria textil-confección en España Endocrine disruptors used in textile industry in Spain

    OpenAIRE

    Rafael Gadea; Laura Mundemurra; Tatiana Santos; Ruth Jiménez; Ana M. García

    2009-01-01

    Introducción: Los disruptores endocrinos son sustancias químicas que pueden alterar el sistema hormonal. Estas sustancias se utilizan en distintos procesos de la industria del textil-confección. Objetivos: Identificar las sustancias con efectos de disrupción endocrina utilizados en la industria del textil y la confección en España para prevenir la exposición de los trabajadores a estas sustancias. Material y métodos: En el estudio participaron 65 empresas de siete comunidades autónomas, selec...

  11. Global pollution by organochlorinated endocrine disruptors - possible challenge for mankind at the onset of millennium.

    Science.gov (United States)

    Langer, P

    2015-01-01

    Author of this review submits a comprehensive report of his long-lasting research regarding the global pollution by endocrine disruptors (EDs), EDs and diabetes and obesity, EDs and the thyroid in highly polluted Slovakia, Ah-receptor: the central pivot responsible for such global "EDs disaster", EDs and immune system, EDs and testosterone, EDs in mothers and newborns, EDs and human genome, and EDs at the beginning of the millennium.

  12. Effect of Sediment Humic Substances on Sorption of Selected Endocrine Disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Sun, W. L., E-mail: sunweiling@iee.pku.edu.cn; Ni, J. R.; Liu, T. T. [The Key Laboratory of Water and Sediment Sciences, Ministry of Education, Department of Environmental Engineering, Peking University (China)

    2006-12-15

    Characterizing sorption processes is essential to understand the environmental distribution and toxicity potential of endocrine disruptors in terrestrial and aquatic systems. The sorption behaviors of three endocrine disruptors (bisphenol A (BPA), 17{beta}-estradiol (E2), and 17{alpha}-ethynylestradiol (EE2)) on sediments were investigated using batch techniques. Samples were taken from some representative reaches in several major Chinese rivers. More attention has been paid to the effect of sediment organic components on the sorption of BPA, E2, and EE2. The results show that the sediment organic carbon-normalized partition coefficients (K{sub oc}(sed)) for three endocrine disruptors are in the order of EE2 > E2 > BPA, which corresponds to the octanol-water partitioning coefficients (logK{sub ow}) of the compounds. Moreover, the K{sub oc} values for humic substances (K{sub oc}(hs)) are comparable with the K{sub oc}(sed) values and highly dependent on the physico-chemical properties of humic substances in sediments. The UV absorptivity at 272 nm (A{sub 272}), which suggests the abundance of aromatic rings in humic substance structure, correlates well with the K{sub oc}(hs) values. In addition, the infrared spectra of the humic substances extracted from sediments show four strong bands centered at 3,400 cm{sup -1}, 1,625 cm{sup -1}, 1,390 cm{sup -1}, and 1,025 cm{sup -1}. The K{sub oc}(hs) values have a positive linear relation with the peak area ratio for peak at 1,025 cm{sup -1} and a negative linear relation with the peak area ratio between peaks at 1,625 cm{sup -1} and 1,025 cm{sup -1}. Hence, the hydrogen bonds play a critical role to the sorption of selected endocrine disruptors.

  13. Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

    OpenAIRE

    Hyun Yang; Eui-Bae Jeung; Kyung-Chul Choi; Beum-Soo An; Eui-Man Jung

    2012-01-01

    Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by b...

  14. 环境污染对几类水生无脊椎动物内分泌功能扰乱的研究现状%Current status of environmental endocrine disruption in selected aquatic invertebrates

    Institute of Scientific and Technical Information of China (English)

    Enmin ZOU

    2003-01-01

    . It is also inappropriate to suggest that an endocrine disrupting effect in a non-deuterostome invertebrate can be used as a marker to monitor environmental endocrine disruption in vertebrates.

  15. Endocrine disruptors, travel-associated illness, and media violence: important health considerations for children and adolescents.

    Science.gov (United States)

    Pattishall, Amy E; Spector, Nancy D

    2010-12-01

    This article addresses three important topics that are part of contemporary life for children: endocrine disruptors, hazards of international travel, and the impact of media violence on children and adolescents. Practitioners will learn about phthalates and Bisphenol-A as endocrine disruptors. In published studies, elevated phthalates were associated with an increase in pubertal gynecomastia and premature thelarche. Bisphenol-A was judged by the Food and Drug Administration as having some concern for potential effects on brain, behavior, and prostate gland in fetuses, infants, and young children: hence, the decision to take reasonable steps to reduce exposure of infants. In travel-related diseases, diarrheal disease (primarily Campylobacter and Salmonella), dermatologic conditions (animal bites), systemic febrile illness (malaria and dengue fever), and respiratory illnesses predominate. Children and adolescents spend more than 7 h using media per day. The degree to which media violence can be linked to behavior is not conclusive, but the prevention message for practitioners is important because parents can have an important mitigating effect. Endocrine disruptors, travel-related diseases, and media violence are part of modern day life for our children. Pediatricians need to stay abreast of recent findings and have access to up-to-date resources to assist them in providing contemporary advice and guidance to patients and families.

  16. Drug residues and endocrine disruptors in drinking water: risk for humans?

    Science.gov (United States)

    Touraud, Evelyne; Roig, Benoit; Sumpter, John P; Coetsier, Clémence

    2011-11-01

    The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, β-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion.

  17. Annelid Endocrine Disruptors and a Survey of Invertebrate FMRFamide-Related Peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2005-01-01

    There is a growing body of literature describing the actions of endocrine disruptors on annelids. These pollutants cause decreases in growth and reproductive output, delay sexual maturation, and inhibit the immune system in annelids. More studies are needed to determine the mechanisms that underlie these responses. Most invertebrate endocrine disruptor research focuses on steroids. In recent years many new invertebrate peptide hormones including those related to the molluscan peptide FMRFamide have been identified. Since the storage of these peptides can be inhibited by steroids during insect metamorphosis, they may be affected by endocrine disruptors. Therefore, it is worthwhile to give a brief overview of this peptide family to those studying endocrine disruption in invertebrates with the hope that they may begin to consider these peptides in their future research. In 1977 Price and Greenberg isolated FMRFamide from the cerebral ganglia of the clam, Macrocallista nimbosa. Since then researchers have used bioassays and immunoassays to identify a large number of FMRFamide-related peptides (FaRPs) from many invertebrate phyla. Even more peptides are predicted by the FaRP genes that have been sequenced. FaRPs have a variety of functions and act as neurotransmitters, neuromodulators, or neurohormones. Each function is species and tissue specific. Most FaRP receptors are linked to a second messenger system. However, at least one is a ligand gated sodium channel. On going studies are examining FaRPs from the molecular to organismal level.

  18. 宁波市内河几种酚类环境激素的污染状况及分布特征%Pollution and Distribution of Phenolic Endocrine Disruptors in Water Columns and Sediments in Ningbo Inner River

    Institute of Scientific and Technical Information of China (English)

    程军蕊; 徐继荣; 刘英; 张锐; 张秋芳

    2014-01-01

    应用固相萃取、超声萃取及高效液相色谱法对宁波市内河10个采样点的壬基酚、辛基酚和双酚 A 进行了检测.结果表明:宁波市内河水体及沉积物中均不同程度地检出了壬基酚和双酚 A,辛基酚的检出率约为50%;壬基酚、辛基酚和双酚 A 在内河水体中的浓度最大值分别为4.516μg·L-1、0.384μg·L-1和1.594μg·L-1,在沉积物(干重)中的含量最大值分别为0.811μg·g-1、0.139μg·g-1和0.223μg·g-1.江北大河、宁大内河及护城河的水体与沉积物中的浓度值较高,城湾水库、姚江及后西河相对较低;水体及沉积物中3种酚类环境激素的浓度值夏季低于冬季,水体和沉积物中的污染物浓度存在正相关关系.宁波市内河受到3种酚类环境激素的污染,对水生生物具有一定的生态风险.%Distributions of nonylphenol, octylphenol and bisphenol A in water columns and sediments at ten sample collecting stations in Ningbo Inner River were investigated using the method of high performance liquid chromatography coupled with ultrasonication extraction and solid phase extraction. It was found that NP and BPA are widely scattered in Ningbo Inner River, and the detection rates of both OP in water columns and sediments were about 50%. The highest concentrations of NP, OP and BPA were measured as 4.516μg·L-1, 0.384μg·L-1, 1.594 μg·L-1 in the river water samples, and 0.811 μg·g-1, 0.139 μg·g-1, 0.223 μg·g-1 in the sediments samples, respectively. The concentrations of the three phenolic endocrine disruptors were found to be higher in Jiangbei River, Ningda River and Hucheng River, and relatively lower in Chengwan Reservoir, Yao River and Houxi River, and with the higher concentration in winter than in summer. There was also a positive concentration correlation, although insignificant, among the three pollutants in water columns and sediments, The result shows that exposure to the phenolic environmental

  19. Disruptores endocrinos utilizados en la industria textil-confección en España Endocrine disruptors used in textile industry in Spain

    Directory of Open Access Journals (Sweden)

    Rafael Gadea

    2009-03-01

    Full Text Available Introducción: Los disruptores endocrinos son sustancias químicas que pueden alterar el sistema hormonal. Estas sustancias se utilizan en distintos procesos de la industria del textil-confección. Objetivos: Identificar las sustancias con efectos de disrupción endocrina utilizados en la industria del textil y la confección en España para prevenir la exposición de los trabajadores a estas sustancias. Material y métodos: En el estudio participaron 65 empresas de siete comunidades autónomas, seleccionadas mediante acuerdo entre las organizaciones empresariales y sindicales del sector. Técnicos de salud laboral de las federaciones sindicales visitaron las empresas participantes y recogieron información sobre los productos químicos utilizados mediante observación de etiquetas y fichas de datos de seguridad y mediante entrevistas con técnicos de prevención, trabajadores designados, delegados de prevención y trabajadores utilizando cuestionarios estandarizados. Resultados: Las empresas participantes cubren un amplio rango de actividades propias del sector, siendo la mayoría de ellas de tamaño medio (entre 51 y 250 trabajadores, n=39. Se identificaron diecisiete sustancias diferentes con efectos de disrupción endocrina utilizadas en distintos puestos de trabajo, incluyendo preparación de fibras y tejidos, lavado, tintado o acabado textil, entre otros. Conclusiones: Serían necesarios estudios que permitieran cuantificar el nivel de exposición en los puestos identificados para priorizar las medidas preventivas necesarias.Introduction: Endocrine disruptors are chemicals which can affect hormonal system in human beings. These substances are used in several processes in the textile industry. Objectives: Identifying chemicals with endocrine disruption potential used in Spanish textile industry to promoting risk prevention in exposed workers. Material and methods: The study includes 65 companies located in seven different Spanish regions

  20. Nuevos disruptores endocrinos: su importancia en la población pediátrica New endocrine disruptors: their importance in pediatric population

    Directory of Open Access Journals (Sweden)

    Juan Manuel Alfaro Velásquez

    2005-04-01

    Full Text Available Los cambios de nuestro hábitat en los últimos 40 años han generado contactos frecuentes con sustancias químicas tanto naturales como sintéticas que funcionan como disruptores endocrinos; son ejemplos los pesticidas ampliamente usados tras la introducción del DDT, los derivados petroquímicos en la industria del plástico, las medicinas sintéticas, y el volumen creciente de artículos de vestuario, aseo, cosmética y transporte. En cada uno de los grupos anotados hay señales de actividad de algún disruptor endocrino sea directamente o a través de sus derivados. La controversia inicial se centró principalmente en los compuestos químicamente similares a los estrógenos y en todos aquellos con actividad antiandrógenos o antitiroidea, debido a que se sospechaba que dañaban el ADN; recientemente se han estudiado otros compuestos y condiciones de vida que no lesionan el genoma pero sí interactúan con enzimas y sus metabolitos. Entre los efectos potenciales de estas sustancias cabe mencionar los siguientes: anomalías intrauterinas por daños del tejido fetal en formación; cambios del fenotipo genital al nacer y diversas manifestaciones clínicas durante la adolescencia; además, no pueden perderse de vista los efectos sobre las generaciones futuras. Los disruptores endocrinos son compuestos que pueden modular tanto la expresión endocrina e inmune del afectado como la homeostasis, la reproducción, el desarrollo y el comportamiento y tienen efectos sobre los tejidos reproductivos masculino y femenino, la fertilidad, la función tiroidea y el sistema nervioso central. Changes in the environment that have taken place during the last 40 years have generated frequent contacts with natural and synthetic chemical products with potential endocrine-disrupting roles; among them: the intensive use of pesticides after the introduction of DDT, the petrochemical derivatives of the plastic industry, the synthetic medicines and the growing market of

  1. Mixture Effects of 3 Mechanistically Different Steroidogenic Disruptors (Prochloraz, Genistein, and Ketoconazole) in the H295R Cell Assay

    DEFF Research Database (Denmark)

    Nielsen, Frederik Knud; Hansen, Cecilie Hurup; Fey, Jennifer Anna

    2015-01-01

    Mixture effects of 3 model endocrine disruptors, prochloraz, ketoconazole, and genistein, on steroidogenesis were tested in the adrenocortical H295R cell line. Seven key steroid hormones (pregnenolone, progesterone, dehydroepiandrosterone, androstenedione, testosterone, estrone, and 17β...... the H295R cell line was suitable for evaluating mixture toxicity of endocrine disruptors with different modes of action. The compounds were chosen because they interfere with steroidogenesis in different ways. They all individually decrease the concentrations of the main sex steroids downstream...... with the H295R cell assay is a useful tool also for studying how mixtures of endocrine disruptors with differing modes of action interfere with the steroidogenic pathway and that existing models like concentration addition are insufficient in such cases. Furthermore, for end points where compounds exert...

  2. Adsorption of pharmaceutical compounds and an endocrine disruptor from aqueous solutions by carbon materials.

    Science.gov (United States)

    Sotelo, José L; Rodríguez, Araceli R; Mateos, María M; Hernández, Sergio D; Torrellas, Silvia A; Rodríguez, Juan G

    2012-01-01

    Adsorption has been used to study the removal of atenolol, caffeine, diclofenac and isoproturon, pharmaceutical compounds as emerging contaminants and an endocrine disruptor from ultrapure water and a municipal wastewater treatment plant effluent with three carbonaceous materials: activated carbon, multiwalled carbon nanotubes and carbon nanofibers. The adsorption capacities were studied in the temperature range of 25-65°C and pH range from 3 to 9. Several model isotherms were used to model the adsorption equilibrium data. Also, the competitive adsorption was evaluated.

  3. Characterization of the interactions between endocrine disruptors and aquatic humic substances from tropical rivers

    Energy Technology Data Exchange (ETDEWEB)

    Botero, Wander G. [Universidade Federal de Alagoas (UFAL), Arapiraca, AL (Brazil); Oliveira, Luciana C. de [Universidade Federal de Sao Carlos (UFSCar), Sorocaba, SP (Brazil); Cunha, Bruno B.; Oliveira, Lilian K. de; Goveia, Danielle; Fraceto, Leonardo F.; Rosa, Andre Henrique, E-mail: ahrosa@sorocaba.unesp.b [UNESP, Sorocaba, SP (Brazil). Dept. de Engenharia do Meio Ambiente; Rocha, Julio Cesar [UNESP, Araraquara, SP (Brazil). Inst. de Quimica. Dept. de Quimica Analitica

    2011-07-01

    Interactions between two endocrine disruptors (ED) and aquatic humic substances (AHS) from tropical rivers were studied using an ultrafiltration system equipped with a 1 kDa cut-off cellulose membrane to separate free ED from the fraction bound in the AHS. Quantification of 17{alpha}-ethynylestradiol and bisphenol A was performed using gas chromatography-mass spectrometry (GC-MS). The times required for establishment of equilibrium between the AHS and the ED were ca. 30 min, and complexation capacities for 17{alpha}-ethynylestradiol and bisphenol A were 18.53 and 2.07 mg g{sup -1} TOC, respectively. The greater interaction of AHS with 17{alpha}-ethynylestradiol, compared to bisphenol A, was due to the presence of hydrogen in the structure of 17{alpha}-ethynylestradiol, which could interact with ionized oxygenated groups of the AHS. The results indicate that AHS can strongly influence the transport and reactivity of endocrine disruptors in aquatic systems. (author)

  4. Our stolen figures: the interface of sexual differentiation, endocrine disruptors, maternal programming, and energy balance.

    Science.gov (United States)

    Schneider, Jill E; Brozek, Jeremy M; Keen-Rhinehart, Erin

    2014-06-01

    This article is part of a Special Issue "Energy Balance". The prevalence of adult obesity has risen markedly in the last quarter of the 20th century and has not been reversed in this century. Less well known is the fact that obesity prevalence has risen in domestic, laboratory, and feral animals, suggesting that all of these species have been exposed to obesogenic factors present in the environment. This review emphasizes interactions among three biological processes known to influence energy balance: Sexual differentiation, endocrine disruption, and maternal programming. Sexual dimorphisms include differences between males and females in body weight, adiposity, adipose tissue distribution, ingestive behavior, and the underlying neural circuits. These sexual dimorphisms are controlled by sex chromosomes, hormones that masculinize or feminize adult body weight during perinatal development, and hormones that act during later periods of development, such as puberty. Endocrine disruptors are natural and synthetic molecules that attenuate or block normal hormonal action during these same developmental periods. A growing body of research documents effects of endocrine disruptors on the differentiation of adipocytes and the central nervous system circuits that control food intake, energy expenditure, and adipose tissue storage. In parallel, interest has grown in epigenetic influences, including maternal programming, the process by which the mother's experience has permanent effects on energy-balancing traits in the offspring. This review highlights the points at which maternal programming, sexual differentiation, and endocrine disruption might dovetail to influence global changes in energy balancing traits.

  5. Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination.

    Science.gov (United States)

    Chang, Hung-Shu; Anway, Matthew D; Rekow, Stephen S; Skinner, Michael K

    2006-12-01

    Embryonic exposure to the endocrine disruptor vinclozolin at the time of gonadal sex determination was previously found to promote transgenerational disease states. The actions of vinclozolin appear to be due to epigenetic alterations in the male germline that are transmitted to subsequent generations. Analysis of the transgenerational epigenetic effects on the male germline (i.e. sperm) identified 25 candidate DNA sequences with altered methylation patterns in the vinclozolin generation sperm. These sequences were identified and mapped to specific genes and noncoding DNA regions. Bisulfite sequencing was used to confirm the altered methylation pattern of 15 of the candidate DNA sequences. Alterations in the epigenetic pattern (i.e. methylation) of these genes/DNA sequences were found in the F2 and F3 generation germline. Therefore, the reprogramming of the male germline involves the induction of new imprinted-like genes/DNA sequences that acquire an apparent permanent DNA methylation pattern that is passed at least through the paternal allele. The expression pattern of several of the genes during embryonic development were found to be altered in the vinclozolin F1 and F2 generation testis. A number of the imprinted-like genes/DNA sequences identified are associated with epigenetic linked diseases. In summary, an endocrine disruptor exposure during embryonic gonadal sex determination was found to promote an alteration in the epigenetic (i.e. induction of imprinted-like genes/DNA sequences) programming of the male germline, and this is associated with the development of transgenerational disease states.

  6. Emergent contaminants: Endocrine disruptors and their laccase-assisted degradation - A review.

    Science.gov (United States)

    Barrios-Estrada, Carlos; de Jesús Rostro-Alanis, Magdalena; Muñoz-Gutiérrez, Blanca Delia; Iqbal, Hafiz M N; Kannan, Soundarapandian; Parra-Saldívar, Roberto

    2017-09-11

    Herein, an effort has been made to highlight the trends of the state-of-the-art of laccase-assisted degradation of emerging contaminants at large and endocrine disruptors in particular. Since first described in the 19th century, laccase has received particular interest for inter- and multidisciplinary investigations due to its uniqueness and remarkable biotechnological applicability. There has always been a paramount concern over the widespread occurrences of various pollutant types, around the globe. Therefore, pollution free processes are gaining ground all over the world. With ever increasing scientific knowledge, socioeconomic awareness, human health-related issues and ecological apprehensions, people are more concerned about the widespread environmental pollutants. In this context, the occurrences of newly identified pollutants so-called "emerging contaminants - ECs" in our main water bodies is of continued and burning concern worldwide. Undoubtedly, various efforts have already been made to tackle this challenging ECs concern though using different approaches including physical and chemical, however, each has considerable limitations. In this review, we present information on how laccase-assisted approach can change this limited tendency of physical and chemical based approaches. A special focus has been given to the laccase-assisted systems including pristine laccase, laccase-mediator catalyzed system and immobilized-laccase catalyzed system that promotes the endocrine disruptors removal. Towards the end, a list of outstanding questions and research gaps are given that can pave the way for future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Inverse Effects on Growth and Development Rates by Means of Endocrine Disruptors in African Clawed Frog Tadpoles ("Xenopus Laevis")

    Science.gov (United States)

    Hackney, Zachary Carl

    2007-01-01

    Previous work on fish, frogs, and salamanders, showed the ability for estrogen (EE2) and anthropogenic endocrine disruptors to skew sex ratios and cause hermaphrodism. This study addressed the effects of estrogens on growth and development rates of African clawed frog tadpoles ("Xenopus laevis") during their gender determination stages. The…

  8. Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

    Directory of Open Access Journals (Sweden)

    Mingyue Zhang

    2015-11-01

    Full Text Available Background: Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds. Methods: In this study, BPA and phytoestrogens in urine specimens (n = 256 collected from children in China were measured by liquid chromatography (LC-tandem mass spectrometry (MS/MS. Results: BPA was detected in most specimens, with a geometric mean concentration of 1.58 ng/mL. For the first time, levels of urinary phytoestrogens in Chinese children were reported. Daidzein and enterolactone are the typical isoflavones and lignans compounds in urine, respectively. Conclusions: Relatively high levels of urinary BPA indicate an increasing risk of BPA exposure to Chinese children. Urinary concentrations of daidzein in Chinese children are higher when compared with those reported in the U.S. children, while concentrations of urinary enterolactone and enterodiols are significantly lower. This suggests a significant difference in phytoestrogen intake between the children from China and from the U.S.

  9. Steroids and endocrine disruptors--History, recent state of art and open questions.

    Science.gov (United States)

    Hampl, Richard; Kubátová, Jana; Stárka, Luboslav

    2016-01-01

    This introductory chapter provides an overview of the levels and sites at which endocrine disruptors (EDs) affect steroid actions. In contrast to the special issue of Journal of Steroid Biochemistry and Molecular Biology published three years ago and devoted to EDs as such, this paper focuses on steroids. We tried to point to more recent findings and opened questions. EDs interfere with steroid biosynthesis and metabolism either as inhibitors of relevant enzymes, or at the level of their expression. Particular attention was paid to enzymes metabolizing steroid hormones to biologically active products in target cells, such as aromatase, 5α-reductase and 3β-, 11β- and 17β-hydroxysteroid dehydrogenases. An important target for EDs is also steroid acute regulatory protein (StAR), responsible for steroid precursor trafficking to mitochondria. EDs influence receptor-mediated steroid actions at both genomic and non-genomic levels. The remarkable differences in response to various steroid-receptor ligands led to a more detailed investigation of events following steroid/disruptor binding to the receptors and to the mapping of the signaling cascades and nuclear factors involved. A virtual screening of a large array of EDs with steroid receptors, known as in silico methods (≡computer simulation), is another promising approach for studying quantitative structure activity relationships and docking. New data may be expected on the effect of EDs on steroid hormone binding to selective plasma transport proteins, namely transcortin and sex hormone-binding globulin. Little information is available so far on the effects of EDs on the major hypothalamo-pituitary-adrenal/gonadal axes, of which the kisspeptin/GPR54 system is of particular importance. Kisspeptins act as stimulators for hormone-induced gonadotropin secretion and their expression is regulated by sex steroids via a feed-back mechanism. Kisspeptin is now believed to be one of the key factors triggering puberty in

  10. Efficiencies of freshwater and estuarine constructed wetlands for phenolic endocrine disruptor removal in Taiwan.

    Science.gov (United States)

    Hsieh, Chi-Ying; Yang, Lei; Kuo, Wen-Chien; Zen, Yi-Peng

    2013-10-01

    We examined the distribution and removal efficiencies of phenolic endocrine disruptors (EDs), namely nonylphenol diethoxylates (NP2EO), nonylphenol monoethoxylates (NP1EO), nonylphenol (NP), and octylphenol (OP), in wastewater treated by estuarine and freshwater constructed wetland systems in Dapeng Bay National Scenic Area (DBNSA) and along the Dahan River in Taiwan. Water samples were taken bimonthly at 30 sites in three estuarine constructed wetlands (Datan, Pengcun and Linbian right bank (A and B)) in DBNSA, for eight sampling campaigns. The average removal efficiencies were in the range of 3.13-97.3% for wetlands in DBNSA. The highest average removal occurred in the east inlet to the outlet of the Tatan wetland. The most frequently detected compound was OP (57.7%), whose concentration was up to 1458.7 ng/L in DBNSA. NP was seen in only 20.5% of the samples. The temporal variation of EDs showed a decrease across seasons, where summer>spring>winter>autumn in these constructed wetlands. The removal efficiencies of EDs by estuarine wetlands, in decreasing order, were Datan>Pengcun>Linbian right bank in DBNSA. Water samples collected at 18 sites in three freshwater constructed wetlands (Daniaopi, Hsin-Hai I, and Hsin-Hai II) along the riparian area of Dahan River. NP2EO was the most abundant compound, with a concentration of up to 11,200 ng/L. Removal efficiencies ranged from 55% to 91% for NP1EO, NP2EO, and NP in Hsin-Hai I. The average removal potential of EDs in freshwater constructed wetlands, in decreasing order, was Hsin-Hai II>Daniaopi>Hsin-Hai I constructed wetlands. The lowest concentrations of the selected compounds were observed in the winter. The highest removal efficiency of the selected phenolic endocrine disruptors was achieved by Hsin-Hai I wetland. The calculated risk quotients used to evaluate the ecological risk were up to 30 times higher in the freshwater wetlands along Dahan River than in the estuarine (DBNSA) constructed wetlands, indicating

  11. Impacto de los disruptores endocrinos en la salud y el medio ambiente.

    Directory of Open Access Journals (Sweden)

    Alina Falero Morejón

    2005-01-01

    Full Text Available Los disruptores endocrinos comprenden diferentes sustancias químicas con efectos adversos sobre la salud de los organismos vivos o su progenie, como consecuencia de alteraciones en la función endocrina. Abarca un conjunto diverso y heterogéneo de compuestos químicos, capaces de alterar el equilibrio hormonal. Entre ellas se encuentran sustancias persistentes, bioacumulativas y organohalógenas que incluyen algunos plaguicidas (fungicidas, herbicidas e insecticidas, sustancias químicas industriales, otros productos sintéticos y algunos metales pesados. Muchas de estas sustancias han sido vertidas al medio ambiente, sin tener en cuenta el impacto provocado por su acción perturbadora sobre el sistema endocrino de los animales, incluidos los seres humanos. La valoración cuantitativa de su impacto constituye un tema de gran interés para la comunidad científica actual, dada su alta incidencia sobre la salud humana y animal y la escasa información sobre la producción, uso y aplicaciones de los compuestos químicos, incluidos bajo esta denominación. Por otra parte, no se dispone de tests adecuados para su identificación y catalogación. La estrategia para conocer los efectos provocados por los disruptores en la salud humana y el medio ambiente debe estar encaminada a la obtención de información sobre las sustancias que se sospechen con propiedades de disruptores endocrinos, al desarrollo y validación de métodos de ensayo para la obtención de datos toxicológicos sobre las sustancias con insuficiente información y a la adaptación de la legislación existente sobre ensayos, evaluación y usos de tales sustancias. Este trabajo tiene como objetivo brindar una información lo mas actualizada posible acerca de un problema de gran incidencia ambiental, con vistas a contribuir a la comprensión de la magnitud del mismo.

  12. Endocrine disruptors and female fertility: focus on (bovine) ovarian follicular physiology.

    Science.gov (United States)

    Petro, E M L; Leroy, J L M R; Van Cruchten, S J M; Covaci, A; Jorssen, E P A; Bols, P E J

    2012-12-01

    Throughout the previous century, the production, use and, as a result, presence of chemicals in the environment increased enormously. Consequently, humans and animals are exposed to a wide variety of chemical substances of which some possess the ability to disrupt the endocrine system in the body, thereby denominated as "endocrine disrupting chemicals" (EDCs) or "endocrine disruptors". Because the reproductive system is a target organ for endocrine disruption, EDCs are postulated as one of the possible causes of human subfertility. Within the reproductive system, the ovarian follicle can be considered as an extremely fragile microenvironment where interactions between the oocyte and its surrounding somatic cells are essential to generate a fully competent oocyte. In this review, we explore how EDCs can interfere with the well-balanced conditions in the ovarian follicle. In addition, we highlight the bovine ovarian follicle as an alternative in vitro model for EDC and broader toxicology research.

  13. Long term impact of the endocrine disruptor tributyltin on male fertility following a single acute exposure.

    Science.gov (United States)

    Mitra, Sumonto; Srivastava, Ankit; Khandelwal, Shashi

    2017-10-01

    Declining rate of human fertility is a growing concern, where lifestyle and environmental factors play an important role. We recently demonstrated that tributyltin (TBT), an omnipresent endocrine disruptor, affects testicular cells in vitro. In this study, male Wistar rats were gavaged a single dose of 10, 20, and 30 mg/kg TBT-chloride (TBTC) (to mimic accidental exposure in vivo) and sacrificed on day 3 and day 7, respectively. TBT bioavailability was evaluated by estimating total tin content, and essential metal levels were analyzed along with redox molecules (ROS and GSH/GSSG) to understand the effect on physiological conditions. Blood-testicular barrier (BTB) disruption, levels of associated proteins and activity of proteolytic enzymes were evaluated to understand the effect on BTB. Histological analysis of tissue architecture and effect on protein expression of steroidogenic, stress and apoptotic markers were also evaluated. Widespread TBTC pollution can be an eventual threat to male fertility worldwide. © 2017 Wiley Periodicals, Inc.

  14. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  15. Identification of Chemical Vascular Disruptors During Development Using An Integrative Predictive Toxicity Model and Zebrafish and in Vitro Functional Angiogenesis Assays.

    Science.gov (United States)

    Identification of chemical vascular disruptors during development using an integrative predictive toxicity model and zebrafish and in vitro functional angiogenesis assays Chemically-induced vascular toxicity during embryonic development can result in a wide range of adverse pre...

  16. New-tools to assess the toxicological hazard of endocrine disruptor organoclorine contaminants in Mediterranean cetaceans

    Energy Technology Data Exchange (ETDEWEB)

    M. Cristina Fossi; Marsili, L.; Casini, S. [Dept. of Environmental Sciences, Univ. of Siena (Italy)

    2004-09-15

    The Mediterranean top predators, and particularly cetacean odontocetes, accumulate high concentrations of organochlorine contaminants (OCs), incurring high toxicological risk. Some organochlorine compounds, now with worldwide distribution, are known as endocrine disrupting chemicals (EDCs). Four types of organochlorine endocrine disruptors are commonly found in Mediterranean cetaceans: (1) environmental estrogens, (2) environmental androgens, (3) anti-estrogens and (4) anti-androgens. Endocrine disruptors act by mimicking sex steroid hormones, both estrogens and androgens, by binding to hormone receptors or influencing cell pathways (environmental estrogens and androgens), or by blocking and altering hormone receptor binding (anti-estrogens, antiandrogens). Environmental estrogens are the most common and most widely studied EDCs. The relative estrogenic power of these chemicals, identified by in vitro and in vivo screening methods is rather weak (10{sup -3} or less) compared with the reference power of 17-estradiol or DES. However, the high levels of organochlorine compounds detected in marine mammals, particularly in pinnipeds and odontocetes, and consequently, the high levels of organochlorines with ED capacity, cannot be ignored. Here the hypothesis that some Mediterranean cetaceans (Stenella coeruleoalba, Delphinus delphis, Tursiops truncatus and Balaenoptera physalus) are ''potentially at risk'' due to organochlorines with endocrine disrupting capacity is investigated using new non-lethal tools. As ''diagnostic'' tool we use benzo(a)pyrene monooxygenase (CYP1A1) activity in skin biopsies (non-lethal biomarker) as a potential indicator of exposure to organochlorines, with special reference to the compounds with endocrine disrupting capacity. As ''prognostic'' tool we propose the immunofluorescence technique in fibroblast cell cultures, for a qualitative and quantitative evaluation of the target

  17. Genotyping sex in the amphibian, Xenopus (Silurana) tropicalis, for endocrine disruptor bioassays.

    Science.gov (United States)

    Olmstead, Allen W; Lindberg-Livingston, Annelie; Degitz, Sigmund J

    2010-06-01

    Endocrine disrupting compounds have been shown to alter gonad differentiation in both male and female individuals in amphibian, avian, fish, invertebrate, and reptile species. In some cases, these affected individuals are completely sex reversed and are morphologically indistinguishable from normal individuals of the opposite sex. Detecting shifts in sex ratios following chemical exposure often requires large numbers of organisms to achieve the necessary statistical power, especially in those species with genetic sex determination and homomorphic sex chromosomes (such as amphibians and many fish). The ability to assess the genetic sex of individuals would allow for detection of sex reversal (genotype-phenotype mismatches) that have greater statistical power compared to examining changes in sex ratios. Utilizing amplified fragment length polymorphisms (AFLPs), we developed a method for genotyping sex in the amphibian, Xenopus (Silurana) tropicalis, that can be incorporated into endocrine disruptor screening assays that examine the effects of chemicals on gonad differentiation. AFLPs from 512 primer pairs were assessed in one spawn of X. tropicalis. Each primer pair yielded, on average, 100 fragments. In total 17 sex-linked AFLPs were identified, isolated, and sequenced. A recombination map of these AFLPs was generated using over 300 individuals with four AFLPs having a recombination rate of 0% with regard to sex. A BLASTn search of the X. tropicalis genome using these AFLP sequences resulted in identification of sex-linked scaffolds. Areas of these scaffolds were searched for additional polymorphisms that could be utilized for genotyping sex. Retrospective and prospective strategies for incorporating genotyping sex in endocrine disruptor bioassays with X. tropicalis were developed. A Monte Carlo simulation comparing analyzing data as sex ratio shifts versus assessment of sex reversal using genotyping demonstrates the increase in statistical power that can be

  18. The effects of estrogenic and androgenic endocrine disruptors on the immune system of fish: a review.

    Science.gov (United States)

    Milla, Sylvain; Depiereux, Sophie; Kestemont, Patrick

    2011-03-01

    During the last decade, a number of studies have shown that, in addition to their classically described reproductive function, estrogens and androgens also regulate the immune system in teleosts. Today, several molecules are known to interfere with the sex-steroid signaling. These chemicals are often referred to as endocrine disrupting contaminants (EDCs). We review the growing evidence that these compounds interfere with the fish immune system. These studies encompass a broad range of approaches from field studies to those at the molecular level. This integrative overview improves our understanding of the various endocrine-disrupting processes triggered by these chemicals. Furthermore, the research also explains why fish that have been exposed to EDCs are more sensitive to pathogens during gametogenesis. In this review, we first discuss the primary actions of sex-steroid-like endocrine disruptors in fish and the specificity of the fish immune system in comparison to mammals. Then, we review the known interactions between the immune system and EDCs and interpret the primary effects of sex steroids (estrogens and androgens) and their related endocrine disruptors on immune modulation. The recent literature suggests that immune parameters may be used as biomarkers of contamination by EDCs. However, caution should be used in the assessment of such immunotoxicity. In particular, more attention should be paid to the specificity of these biomarkers, the external/internal factors influencing the response, and the transduction pathways induced by these molecules in fish. The use of the well-known mammalian models provides a useful guide for future research in fish.

  19. The endocrine disruptor diethylstilbestrol induces adipocyte differentiation and promotes obesity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Chan-Juan; Cheng, Xue-Jia; Xia, Hong-Fei, E-mail: hongfeixia@yahoo.com.cn; Ma, Xu

    2012-08-15

    Epidemiology studies indicate that exposure to endocrine disruptors during developmental “window” contributes to adipogenesis and the development of obesity. Implication of endocrine disruptor such as diethylstilbestrol (DES) on adipose tissue development has been poorly investigated. Here we evaluated the effects of DES on adipocyte differentiation in vitro and in vivo, and explored potential mechanism involved in its action. DES induced 3T3-L1 preadipocyte differentiation in a dose-dependent manner, and activated the expression of estrogen receptor (ER) and peroxisome proliferator-acivated receptor (PPAR) γ as well as its target genes required for adipogenesis in vitro. ER mediated the enhancement of DES-induced PPARγ activity. Moreover, DES perturbed key regulators of adipogenesis and lipogenic pathway in vivo. In utero exposure to low dose of DES significantly increased body weight, liver weight and fat mass in female offspring at postnatal day (PND) 60. In addition, serum triglyceride and glucose levels were also significantly elevated. These results suggest that perinatal exposure to DES may be expected to increase the incidence of obesity in a sex-dependent manner and can act as a potential chemical stressor for obesity and obesity-related disorders. -- Highlights: ► DES induced adipocyte differentiation in a dose-dependent manner in 3T3-L1 cells. ► DES activated adipogenic critical regulators and markers in vitro and in vivo. ► Perinatal exposure to DES led to the obese phenotype in female offspring. ► DES might be a potential chemical stressor for obesity and obesity-related disorders.

  20. The application of reporter gene assays for the detection of endocrine disruptors in sport supplements

    Energy Technology Data Exchange (ETDEWEB)

    Plotan, Monika; Elliott, Christopher T. [Institute of Agri-Food and Land Use, School of Biological Sciences, Queen' s University Belfast, Belfast BT95AG, Northern Ireland (United Kingdom); Scippo, Marie Louise [Department of Food Sciences, University of Liege, 4000 Liege (Belgium); Muller, Marc [Molecular Biology and Genetic Engineering GIGA-R, University of Liege, 4000 Liege (Belgium); Antignac, Jean-Philippe [LABERCA, ENVN, USC INRA 2013, BP 50707, 44 307, Nantes (France); Malone, Edward [The State Laboratory, Young' s Cross, Celbridge, Co. Kildare (Ireland); Bovee, Toine F.H. [RIKILT Institute of Food Safety, P.O. Box 230, AE Wageningen 6700 (Netherlands); Mitchell, Samuel [Agri-Food and Biosciences Institute, Belfast BT9 5PX (United Kingdom); Connolly, Lisa, E-mail: l.connolly@qub.ac.uk [Institute of Agri-Food and Land Use, School of Biological Sciences, Queen' s University Belfast, Belfast BT95AG, Northern Ireland (United Kingdom)

    2011-08-26

    The increasing availability and use of sports supplements is of concern as highlighted by a number of studies reporting endocrine disruptor contamination in such products. The health food supplement market, including sport supplements, is growing across the Developed World. Therefore, the need to ensure the quality and safety of sport supplements for the consumer is essential. The development and validation of two reporter gene assays coupled with solid phase sample preparation enabling the detection of estrogenic and androgenic constituents in sport supplements is reported. Both assays were shown to be of high sensitivity with the estrogen and androgen reporter gene assays having an EC{sub 50} of 0.01 ng mL{sup -1} and 0.16 ng mL{sup -1} respectively. The developed assays were applied in a survey of 63 sport supplements samples obtained across the Island of Ireland with an additional seven reference samples previously investigated using LC-MS/MS. Androgen and estrogen bio-activity was found in 71% of the investigated samples. Bio-activity profiling was further broken down into agonists, partial agonists and antagonists. Supplements (13) with the strongest estrogenic bio-activity were chosen for further investigation. LC-MS/MS analysis of these samples determined the presence of phytoestrogens in seven of them. Supplements (38) with androgen bio-activity were also selected for further investigation. Androgen agonist bio-activity was detected in 12 supplements, antagonistic bio-activity was detected in 16 and partial antagonistic bio-activity was detected in 10. A further group of supplements (7) did not present androgenic bio-activity when tested alone but enhanced the androgenic agonist bio-activity of dihydrotestosterone when combined. The developed assays offer advantages in detection of known, unknown and low-level mixtures of endocrine disruptors over existing analytical screening techniques. For the detection and identification of constituent hormonally

  1. [Alteration of thyroid hormone secretion after long-term exposure to low doses of endocrine disruptor DDT].

    Science.gov (United States)

    Iaglova, N V; Iaglov, V V

    2014-01-01

    Endocrine disruptors are exogenous substances that exhibit hormone-like action and consequently disrupt homeostatic action of endogenous hormones. DDT is the most common disruptor. The objective was to evaluate changes in thyroid hormone secretion after long-term exposure to low doses of DDT. The experiment was performed on male Wistar rats. The rats were given DDT at doses of 1.89±0.86 мg/kg/day and 7.77±0.17 мg/kg/day for 6 and 10 weeks. Dose dependent increase of serum total thyroxine, total triiodthyronine, and thyroid peroxidase was revealed after 6 weeks exposure. After 10 weeks free thyroxine secretion was reduced. Such alterations of the thyroid status are typical for iodine deficient goiter. The data obtained indicate that the main mechanism of DDT action includes disruption of thyroxine secretion by thyrocytes, but not inhibition of deiodinase activity and decrease of blood thyroid binding proteins.

  2. Evolutionary biology of plant defenses against herbivory and their predictive implications for endocrine disruptor susceptibility in vertebrates.

    OpenAIRE

    Wynne-Edwards, K E

    2001-01-01

    Hormone disruption is a major, underappreciated component of the plant chemical arsenal, and the historical coevolution between hormone-disrupting plants and herbivores will have both increased the susceptibility of carnivores and diversified the sensitivities of herbivores to man-made endocrine disruptors. Here I review diverse evidence of the influence of plant secondary compounds on vertebrate reproduction, including human reproduction. Three of the testable hypotheses about the evolutiona...

  3. 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.

  4. Determination of endocrine disruptors in Kafue lechwe (Kobus leche kafuensis) samples from the Lochinvar National Park of Zambia.

    Science.gov (United States)

    Sichilongo, Kwenga; Torto, Nelson

    2006-08-01

    Analysis of serum, whole blood and liver tissue samples from Kafue lechwe in the Lochinvar National Park of Zambia for suspected endocrine disrupting compounds revealed high concentrations for some of the compounds. 45 samples of serum, whole blood and liver tissue were extracted by liquid-liquid extraction followed by an analysis using Gas Chromatography-Electron Capture Detection (GC-ECD). The following endocrine disruptors were analyzed: deltamethrin, aldrin, endosulfan, dieldrin, pp-DDD, heptachlor, d-t-allethrin, pp-DDE, endrin and pp-DDT. For all the samples, dieldrin showed the highest concentration ranging from 1.7 to 44.4 microg/ml in serum and whole blood sample extracts and 0.10-5.1 microg/g wet weight in liver sample extracts. The most frequently detected was deltamethrin in 62% of the samples. Percent recoveries in spiked laboratory blanks ranged between 60% and 100% while calculated detection limits ranged from 0.004 to 0.21 microg/ml for all the endocrine disruptors evaluated. Where endocrine disruptors were detected, the concentrations of most of them far exceeded the maximum residue limits (MRLs) and the extraneous maximum residue limits (EMRLs) set by the Codex Alimentarius of the United Nations (UN), Food and Agricultural Organization (FAO).

  5. Putative archaeal viruses from the mesopelagic ocean.

    Science.gov (United States)

    Vik, Dean R; Roux, Simon; Brum, Jennifer R; Bolduc, Ben; Emerson, Joanne B; Padilla, Cory C; Stewart, Frank J; Sullivan, Matthew B

    2017-01-01

    Oceanic viruses that infect bacteria, or phages, are known to modulate host diversity, metabolisms, and biogeochemical cycling, while the viruses that infect marine Archaea remain understudied despite the critical ecosystem roles played by their hosts. Here we introduce "MArVD", for Metagenomic Archaeal Virus Detector, an annotation tool designed to identify putative archaeal virus contigs in metagenomic datasets. MArVD is made publicly available through the online iVirus analytical platform. Benchmarking analysis of MArVD showed it to be >99% accurate and 100% sensitive in identifying the 127 known archaeal viruses among the 12,499 viruses in the VirSorter curated dataset. Application of MArVD to 10 viral metagenomes from two depth profiles in the Eastern Tropical North Pacific (ETNP) oxygen minimum zone revealed 43 new putative archaeal virus genomes and large genome fragments ranging in size from 10 to 31 kb. Network-based classifications, which were consistent with marker gene phylogenies where available, suggested that these putative archaeal virus contigs represented six novel candidate genera. Ecological analyses, via fragment recruitment and ordination, revealed that the diversity and relative abundances of these putative archaeal viruses were correlated with oxygen concentration and temperature along two OMZ-spanning depth profiles, presumably due to structuring of the host Archaea community. Peak viral diversity and abundances were found in surface waters, where Thermoplasmata 16S rRNA genes are prevalent, suggesting these archaea as hosts in the surface habitats. Together these findings provide a baseline for identifying archaeal viruses in sequence datasets, and an initial picture of the ecology of such viruses in non-extreme environments.

  6. Adverse effects of endocrine disruptors on the foetal testis development: focus on the phthalates.

    Directory of Open Access Journals (Sweden)

    Catherine Pairault

    2010-01-01

    Full Text Available There are great concerns about the increasing incidence of abnormalities in male reproductive function. Human sperm counts have markedly dropped and the rate of testicular cancer has clearly augmented over the past four decades. Moreover, the prevalence rates of cryptorchidism and hypospadias are also probably increasing. It has been hypothesized that all these adverse trends in male reproduction result from abnormalities in the development of the testis during foetal and neonatal life. Furthermore, many recent epidemiological, clinical and experimental data suggest that these male reproductive disorders could be due to the effects of xenobiotics termed endocrine disruptors, which are becoming more and more concentrated and prevalent in our environment. Among these endocrine disruptors, we chose to focus this review on the phthalates for different reasons: 1 they are widespread in the environment; 2 their concentrations in many human biological fluids have been measured; 3 the experimental data using rodent models suggesting a reprotoxicity are numerous and are the most convincing; 4 their deleterious effects on the in vivo and in vitro development and function of the rat foetal testis have been largely studied; 5 some epidemiological data in humans suggest a reprotoxic effect at environmental concentrations at least during neonatal life. However, the direct effects of phthalates on human foetal testis have never been explored. Thus, as we did for the rat in the 1990s, we recently developed and validated an organ culture system which allows maintenance of the development of the different cell types of human foetal testis. In this system, addition of 10-4 M MEHP (mono-2-ethylhexyl phthalate, the most produced phthalate, had no effect on basal or LH-stimulated production of testosterone, but it reduced the number of germ cells by increasing their apoptosis, without modification of their proliferation. This is the first experimental demonstration

  7. The Substitution Principle within the REACH Regulation: Nuclear Receptor-Bound Endocrine Disruptors

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    Stefano Lorenzetti

    2017-09-01

    Full Text Available Within the REACH Regulation (EC/1907/2006, the substitution principle for chemicals classified as Substances of Very High Concern (SVHC for either human health or environmental risks has been implemented in order to support their replacement by suitable alternatives. Considering the thousands of chemicals to be tested within the frame of REACH, animal testing by internationally-accepted guidelines sounds unreasonable in terms of the required time, costs as well ethical issues. Hence, REACH recommended also the use of alternative methods to animal experimentation although no validated in silico or in vitro tools were available when regulation entried into force. To search for suitable alternatives to SVHC having an Endocrine Disruptor (ED-like Mode-of-Action (MoA by means of an integrated, tiered in silico-in vitro approach, the EU-granted project LIFE-EDESIA (contract no. LIFE12 ENV/IT/000633 is combining computational-based tools and cell-based bioassays, in order to develop a no-animal testing procedure to screen for chemicals having less or no toxicity in terms of endocrine disruption-like activities. A general view of the no-animal testing approach implementing REACH and the substitution principle will be given, emphasising ligand-nuclear receptor (NR assessment by molecular docking (one of the LIFE-EDESIA in silico approaches and the use of clinical biomarkers in in vitro toxicology to detect ED-like adverse effects in cell-based bioassays.

  8. Bioindication in natural-like aquatic ecosystems: endocrine disruptors in outdoor microcosms. Status-report

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, K.W.; Severin, G.F.

    2002-07-01

    Over the past few decades scientists have shown that the hormone system of a wide range of organisms can be affected by numerous environmental chemicals. Society strongly demands studies about the fate and effects of such endocrine disruptors on the aquatic environment. It has been scientifically accepted that risk assessment studies done in aquatic microcosms can be used to extrapolate the potential impact of the tested compound on natural ecosystems. Realistic exposure situations were simulated and screening methods as well as analytical methods with high accuracy were applied on water and sediment. For the comprehensive risk assessment as many trophic levels as possible have to be investigated. Changes in the population dynamics and the community structure serve as ecotoxicological endpoints. Modelling the concentrations of the chemicals in the different aquatic compartments complements and confirms the analytical diagnostics. A directed design of the analytical procedures according to amount of sample and limits of determination becomes possible. Bridging acute and chronic time scales in effect diagnostics the 'area under the curve' - approach has been followed in combination with multivariate statistics. Haber's rule have been applied to the results about complex effect- and exposure-conditions. In some cases the interpretation of results becomes more easy and clear by this approach. (orig.)

  9. Biomarker Genes for Detecting Estrogenic Activity of Endocrine Disruptors via Estrogen Receptors

    Directory of Open Access Journals (Sweden)

    Hyun Yang

    2012-02-01

    Full Text Available Endocrine disruptors (EDs are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D9k (CaBP-9k, that may be used to assess estrogenic activity of EDs.

  10. [Endocrine disruptors: hormone-active chemicals from the environment: a risk to humans?].

    Science.gov (United States)

    Klingmüller, Dietrich; Alléra, A

    2011-05-01

    Many substances from the technical and natural environment can cause damage to the endocrine system. Animal tests show that so-called endocrine disruptors (ED), such as pesticides, fungicides, plasticizers (phthalates), bisphenol A (BPA), and organotin compounds can interfere with the endocrine system. In humans, it is difficult to attribute such changes to specific ED. Nevertheless, in vitro studies with human cells and tissues clearly show that ED are able to interfere with endogenous hormones, i. e. affecting the steroid hormone metabolism and intracellular signaling. Several clinical studies show that humans are also affected, including reproductive disorders like reduction of spermatogenesis, decreased testosterone production or malformation of the genitals or induction of tumors like mammary carcinoma. Facing the body of reports documenting the effects of ED, the European Union supported--inter alia--COMPRENDO, a project addressing risk assessment of particular ED in human and wildlife species, while the FDA supports the industry's actions to stop producing BPA-containing baby bottles and infant feeding cups. Some ED show an u-shaped dose response curve and specific ED have effects at levels dramatically lower than thought relevant to traditional toxicology, a phenomenon termed "Low Dose Impact". Further research is needed to clarify whether the observed findings represent associations or causal results.

  11. In vitro steroid profiling system for the evaluation of endocrine disruptors.

    Science.gov (United States)

    Nakano, Yosuke; Yamashita, Toshiyuki; Okuno, Masashi; Fukusaki, Eiichiro; Bamba, Takeshi

    2016-09-01

    Endocrine disruptors (ED) are chemicals that affect various aspects of the endocrine system, often leading to the inhibition of steroidogenesis. Current chemical safety policies that restrict human exposure to such chemicals describe often time-consuming and costly methods for the evaluation of ED effects. We aimed to develop an effective tool for accurate phenotypic chemical toxicology studies. We developed an in vitro ED evaluation system using gas chromatography/mass spectrometry (GC/MS/MS) methods for metabolomic analysis of multi-marker profiles. Accounting for sample preparation and GC/MS/MS conditions, we established a screening method that allowed the simultaneous analysis of 17 steroids with good reproducibility and a linear calibration curve. Moreover, we applied the developed system to H295R human adrenocortical cells exposed to forskolin and prochloraz in accordance with the Organization for Economic Cooperation and Development (OECD) guidelines and observed dose-dependent variations in steroid profiles. While the OECD guidelines include only testosterone and 17β-estradiol, our system enabled a comprehensive and highly sensitive analysis of steroid profile alteration due to ED exposure. The application of our ED evaluation screen could be economical and provide novel insights into the hazards of ED exposure to the endocrine system.

  12. Endocrine disruptors in water filters used in the Rio dos Sinos Basin region, Southern Brazil.

    Science.gov (United States)

    Furtado, C M; von Mühlen, C

    2015-05-01

    The activated carbon filter is used in residences as another step in the treatment of drinking water, based on a physical-chemical process to absorb pollutants that are not removed in conventional treatment. Endocrine disruptors (EDCs) are exogenous substances or mixtures of substances that acts on the endocrine system similarly to the endogenously produced hormones, triggering malfunctions and harmful changes to human and animal health. The objective of the present work was to study EDCs through semi-quantitative analysis of residential water filters collected in the region of Rio dos Sinos basin, focusing on two specific classes: hormones and phenols. The solid phase extraction principle was used for the extraction of compounds and gas chromatography coupled with mass spectrometry for the separation and characterization of EDCs. Four samples of residential filters collected from public water distribution and artesian wells, from the cities of Novo Hamburgo and São Leopoldo were analysed. Using the developed methodology, it was possible to detect and comparatively quantify selected EDCs in all studied samples, which indicates the presence of these contaminants in drinking water from different sources.

  13. Effects of endocrine disruptors in the development of the female reproductive tract.

    Science.gov (United States)

    Costa, Elaine Maria Frade; Spritzer, Poli Mara; Hohl, Alexandre; Bachega, Tânia A S S

    2014-03-01

    Environmental agencies have identified a growing number of environmental contaminants that have endocrine disrupting activity, and these can become a major public health problem. It is suggested that endocrine disruptors could account for the higher-than-expected increase in the prevalence of some non-communicable diseases, such as obesity, diabetes, thyroid diseases, and some cancers. Several endocrine Disrupting Chemicals (EDCs), such as pesticides, bisphenol A, phthalates, dioxins, and phytoestrogens, can interact with the female reproductive system and lead to endocrine disruption. Initially, it was assumed that EDCs exert their effects by binding to hormone receptors and transcription factors, but it is currently known that they may also alter the expression of enzymes involved in the synthesis or catabolism of steroids. Biomonitoring studies have identified these compounds in adults, children, pregnant women, and fetuses. Among the diseases of the female reproductive tract associated with EDCs exposure are the following: precocious puberty, polycystic ovary syndrome, and premature ovarian failure. The different populations of the world are exposed to a great number of chemicals through different routes of infection; despite the various available studies, there is still much doubt regarding the additive effect of a mixture of EDCs with similar mechanisms of action.

  14. Removal of a type of endocrine disruptors-di-n-butyl phthalate from water by ozonation

    Institute of Scientific and Technical Information of China (English)

    LI Hai-yan; QU Jiu-hui; LIU Hui-juan

    2006-01-01

    Ozonation of synthetic water containing a type of endocrine disruptor-di-n-butyl phthalate (DBP) was examined. Key impact factors such as pH, temperature, ionic strength, ozone dosage and initial DBP concentration were investigated. In addition, the activities of radicals on uncatalysed and catalysed ozonation were studied. The degradation intermediate products were followed and the kinetic of the ozonation were assessed as well. Results revealed that ozonation of DBP followed two mechanisms. Firstly, the reaction rate of direct ozonation was slower at lower pH, temperature, and ionic strength. Secondly, when these factors were increased for indirect radical reaction, higher percentage of DBP was removed with the increase of the initial ozone dosage and the decrease of the initial DBP concentration. In addition, tert-butanol, humic substances and Fe(Ⅱ) affected DBP ozonation through the radical pathway. It was determined that ozonation was restrained by adding tert-butanol for its radical inhibition effect. Furthermore, humic substances enhanced the reaction to some extent, but a slight negative effect would be encountered if the optimum dosage was exceeded. As a matter of fact, Mn(Ⅱ) affected the ozonation by "active sites" mechanism. In the experiment, three different kinds of intermediate products were produced during ozonation, but the amount of products for each one of them decreased as pH, temperature,ionic strength and initial ozone dosage increased. A kinetic equation of the reaction between ozone and DBP was obtained.

  15. Esterification of vertebrate like steroids in molluscs: a target of endocrine disruptors?

    Science.gov (United States)

    Giusti, Arnaud; Joaquim-Justo, Célia

    2013-11-01

    Alterations of the reproductive organs of gastropod molluscs exposed to pollutants have been reported in natural populations for more than 40 years. In some cases, these impacts have been linked to exposure to endocrine-disrupting chemicals (EDCs), which are known to induce adverse impacts on vertebrates, mainly by direct binding to steroid receptors or by altering hormone synthesis. Investigations on the mechanisms of action of endocrine disruptors in molluscs show that EDCs induce modifications of endogenous titres of androgens (e.g., testosterone, androstenedione) and oestrogens (e.g., 17ß-oestradiol). Alterations of the activity of enzymes related to steroid metabolism (i.e., cytochrome P-450 aromatase, acyltransferases) are also often observed. In bivalves and gastropods, fatty acid esterification of steroids might constitute the major regulation of androgen and oestrogen homeostasis. The present review indicates that metabolism of steroid hormones to fatty acid esters might be a target of synthetic EDCs. Alterations of this process would impact the concentrations of free, potentially bioactive, form of steroids.

  16. Endocrine disruptors and the tumor microenvironment: A new paradigm in breast cancer biology.

    Science.gov (United States)

    Burks, Hope; Pashos, Nicholas; Martin, Elizabeth; Mclachlan, John; Bunnell, Bruce; Burow, Matthew

    2017-12-05

    Breast cancer is one of the most frequently diagnosed malignancies in women and is characterized by predominantly estrogen dependent growth. Endocrine disruptors (EDCs) have estrogenic properties which have been shown to increase breast cancer risk. While the direct effects of EDCs on breast cancer cell biology and tumor progression have been well studied, the roles for EDCs on tumor microenvironment composition, signaling and structure are incompletely defined. Estrogen targeting of tumor stromal cells can drive paracrine signaling to breast cancer cells regulating tumorigenesis and progression. Additionally, estrogen and estrogen receptor signaling has been shown to alter breast architecture and extracellular matrix component synthesis. Unsurprisingly, EDCs have been shown to induce structural changes in the mammary gland as well as increased collagen fibers in the tissue stroma. Previous work demonstrates that human mesenchymal stem cells (hMSC) are essential components of the tumor microenvironment and are direct targets of both estrogens and EDCs. Furthermore, estrogen-stem cell cross talk has been implicated in breast cancer progression and results in increased tumor cell proliferation, angiogenesis and invasion. This review aims to dissect the possible relationship and mechanisms between EDCs, the tumor microenvironment, and breast cancer progression. Copyright © 2016. Published by Elsevier B.V.

  17. Electrochemical performance of porous diamond-like carbon electrodes for sensing hormones, neurotransmitters, and endocrine disruptors.

    Science.gov (United States)

    Silva, Tiago A; Zanin, Hudson; May, Paul W; Corat, Evaldo J; Fatibello-Filho, Orlando

    2014-12-10

    Porous diamond-like carbon (DLC) electrodes have been prepared, and their electrochemical performance was explored. For electrode preparation, a thin DLC film was deposited onto a densely packed forest of highly porous, vertically aligned multiwalled carbon nanotubes (VACNT). DLC deposition caused the tips of the carbon nanotubes to clump together to form a microstructured surface with an enlarged surface area. DLC:VACNT electrodes show fast charge transfer, which is promising for several electrochemical applications, including electroanalysis. DLC:VACNT electrodes were applied to the determination of targeted molecules such as dopamine (DA) and epinephrine (EP), which are neurotransmitters/hormones, and acetaminophen (AC), an endocrine disruptor. Using simple and low-cost techniques, such as cyclic voltammetry, analytical curves in the concentration range from 10 to 100 μmol L(-1) were obtained and excellent analytical parameters achieved, including high analytical sensitivity, good response stability, and low limits of detection of 2.9, 4.5, and 2.3 μmol L(-1) for DA, EP, and AC, respectively.

  18. Biomarker genes for detecting estrogenic activity of endocrine disruptors via estrogen receptors.

    Science.gov (United States)

    Jung, Eui-Man; An, Beum-Soo; Yang, Hyun; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-03-01

    Endocrine disruptors (EDs) are compounds used in various industrial products, drugs, and cosmetics. They can be found in the environment and disturb the endocrine and reproductive systems, resulting in adverse effects to humans and wildlife such as birth defects and developmental disorders. Since several EDs have a structure similar to that of endogenous steroid hormones such as estrogens, they intend to have an affinity for steroid hormone receptors and alter hormone-mediated metabolism by binding to these receptors. EDs are therefore a global concern and assays should be developed to efficiently determine whether these compounds are detrimental to biological systems. Diverse experimental methods may help determine the endocrine disrupting potential of EDs and evaluate the adverse effects of a single and/or combination of these reagents. Currently, biomarkers have been employed to objectively measure EDs potency and understand the underlying mechanisms. Further studies are required to develop ideal screening methods and biomarkers to determine EDs potency at environmentally relevant concentrations. In this review, we describe the biomarkers for estrogenicity of EDs identified both in vitro and in vivo, and introduce a biomarker, cabindin-D(9k) (CaBP-9k), that may be used to assess estrogenic activity of EDs.

  19. Population Survey of Iodine Deficiency and Environmental Disruptors of Thyroid Function in Young Children in Haiti.

    Science.gov (United States)

    von Oettingen, Julia E; Brathwaite, Tesha D; Carpenter, Christopher; Bonnell, Ric; He, Xuemei; Braverman, Lewis E; Pearce, Elizabeth N; Larco, Philippe; Larco, Nancy Charles; Jean-Baptiste, Eddy; Brown, Rosalind S

    2017-02-01

    Iodine deficiency is the leading cause of preventable neurodevelopmental delay in children worldwide and a possible public health concern in Haiti. To determine the prevalence of iodine deficiency in Haitian young children and its influence by environmental factors. Cross-sectional study, March through June 2015. Community churches in 3 geographical regions in Haiti. 299 healthy Haitian children aged 9 months to 6 years; one-third each enrolled in a coastal, mountainous, and urban region. Urinary iodide, serum thyrotropin (TSH), goiter assessment, and urinary perchlorate and thiocyanate. Mean age was 3.3±1.6 years, with 51% female, median family income USD 30/week, and 16% malnutrition. Median urinary iodide levels were normal in coastal (145 μg/L, interquartile range [IQR] 97 to 241) and urban regions (187 μg/L, IQR 92 to 316), but revealed mild iodine deficiency in a mountainous region (89 μg/L, IQR 56 to 129), P < 0.0001. Grade 1 goiters were palpated in 2 children, but TSH values were normal. Urinary thiocyanate and perchlorate concentrations were not elevated. Predictors of higher urinary iodide included higher urinary thiocyanate and perchlorate, breastfeeding, and not living in a mountainous region. Areas of mild iodine deficiency persist in Haiti's mountainous regions. Exposure to two well-understood environmental thyroid function disruptors is limited.

  20. Removal of a combination of endocrine disruptors from aqueous systems by seedlings of radish and ryegrass.

    Science.gov (United States)

    Gattullo, C Eliana; Cunha, Bruno Barboza; Rosa, André H; Loffredo, Elisabetta

    2013-01-01

    Endocrine disruptors (EDs) are widespread in the environment, especially aquatic systems, and cause dangerous effects on wildlife and humans. This work was aimed to assess the capacity of radish (Raphanus sativus L.) and ryegrass (Lolium perenne L.) seedlings to tolerate and remove two combinations of EDs containing bisphenol A (BPA), 17alpha-ethynilestradiol (EE2), and linuron from four aqueous media: distilled water, a solution of natural organic matter (NOM), a lake water and a river water. Seeds of the two species were germinated in each contaminated medium and, at the end of germination, the seedling growth was evaluated by biometric measurements and residual EDs were quantified by chromatographic analysis. Biometric measurements revealed that the phytotoxicity of the two combinations of EDs depended on the medium used. Radish showed a discrete tolerance in distilled water and lake water but was inhibited in the solution of NOM and river water. Ryegrass was negatively affected mainly in river water. The concentration of each ED appeared significantly reduced in all media in the presence of seedlings of both species, but not in the blanks without plants. In 5 days, radish removed up to 88% of BPA, 100% of EE2 and 42% of linuron, and in 6 days ryegrass removed up to 92% of BPA, 74% of EE2 and 16% of linuron. The considerable removal capacity of radish and ryegrass in all media tested encourages the use of phytoremediation to remove EDs from waters.

  1. Estrogenic endocrine disruptors present in sports supplements. A risk assessment for human health.

    Science.gov (United States)

    Plotan, Monika; Elliott, Christopher T; Frizzell, Caroline; Connolly, Lisa

    2014-09-15

    Sports supplements are becoming a regular dietary addition for consumers who view such products as a means of improving their health and performance. Previously estrogenic endocrine disruptors (EDs) were detected in 80% of 116 sports supplements investigated by biological in vitro reporter gene assays (RGAs). The aim of this study was to quantify the hormonal activity in 50 of these sports supplement samples using a validated estrogen RGA and perform an exposure and risk assessment for human health. Results showed that 17β-estradiol equivalent levels were higher than those reported as being present in the typical human omnivore diet in 33 of the sports supplements and higher than the acceptable daily intake (ADI) in 13 of these products. The highest activity samples presented a potential to influence the human daily exposure to 17β-estradiol like activity in various risk groups with a predicted hormonal impact of greatest concern in young boys and postmenopausal women. In conclusion, consumers of sports supplements may be exposed to high levels of estrogenic EDs.

  2. Coexpression of nuclear receptors and histone methylation modifying genes in the testis: implications for endocrine disruptor modes of action.

    Directory of Open Access Journals (Sweden)

    Alison M Anderson

    Full Text Available BACKGROUND: Endocrine disruptor chemicals elicit adverse health effects by perturbing nuclear receptor signalling systems. It has been speculated that these compounds may also perturb epigenetic mechanisms and thus contribute to the early origin of adult onset disease. We hypothesised that histone methylation may be a component of the epigenome that is susceptible to perturbation. We used coexpression analysis of publicly available data to investigate the combinatorial actions of nuclear receptors and genes involved in histone methylation in normal testis and when faced with endocrine disruptor compounds. METHODOLOGY/PRINCIPAL FINDINGS: The expression patterns of a set of genes were profiled across testis tissue in human, rat and mouse, plus control and exposed samples from four toxicity experiments in the rat. Our results indicate that histone methylation events are a more general component of nuclear receptor mediated transcriptional regulation in the testis than previously appreciated. Coexpression patterns support the role of a gatekeeper mechanism involving the histone methylation modifiers Kdm1, Prdm2, and Ehmt1 and indicate that this mechanism is a common determinant of transcriptional integrity for genes critical to diverse physiological endpoints relevant to endocrine disruption. Coexpression patterns following exposure to vinclozolin and dibutyl phthalate suggest that coactivity of the demethylase Kdm1 in particular warrants further investigation in relation to endocrine disruptor mode of action. CONCLUSIONS/SIGNIFICANCE: This study provides proof of concept that a bioinformatics approach that profiles genes related to a specific hypothesis across multiple biological settings can provide powerful insight into coregulatory activity that would be difficult to discern at an individual experiment level or by traditional differential expression analysis methods.

  3. [Endocrine disruptors in food contact articles and baby toys with their transition].

    Science.gov (United States)

    Kawamura, Yoko

    2010-01-01

    A number of endocrine disruptors have been reported in food contact articles and baby toys mainly during the second half of the 1990s. Bisphenol A, nonylphenol, phthalates, styrene dimers and trimers, and their transision are described in this article. Bisphenol A was found in polycarbonate tableware, nursing bottles and the epoxy resin coating of cans, therefore, it was also found in the canned foods and drinks. Polycarbonate is now only slightly used for tableware or nursing bottles in Japan because consumers refused them. The can manufacturers changed their coating material to the low bisphenol A resin or PET films and voluntarily regulate its migration limit to under 5 or 10 ng/ml. Nonylphenol was found in most PVC wrapping films and gloves. It was generated from an oxidant, tris (nonylphenyl) phosphite. PVC wrapping film was extensively used in markets, thus many kinds of foods were contaminated. Among them, fillet or minced fish and meat contained it at high levels. In 2000, manufacturers voluntarily changed their composition and all wrapping films in Japan no longer contain nonylphenol. Di(2-ethylhexyl) phthalate (DEHP) was found in PVC gloves, which contaminated packed lunches and hospital meals at high levels. The government prohibited these gloves for all food contact use in 2000, moreover, other PVC food contact articles containing DEHP were prohibited for contact use with fatty foods in 2002. DEHP was also found in PVC toys which was prohibited in 2002. Styrene dimers and trimers were found in PS products, which migrated into cupped noodles after cooking. No changes have been made in them. In Japan, the exposure to bisphenol A, nonylphenol and DEHP have been significantly reduced and people also have more concerns with the safety of food contact articles.

  4. Degradation of endocrine disruptor bisphenol A in drinking water by ozone oxidation

    Institute of Scientific and Technical Information of China (English)

    XU Bin; GAO Naiyun; RUI Min; WANG Hong; WU Haihui

    2007-01-01

    The ozone oxidation of endocrine disruptor bisphenol A in drinking water was investigated.A stainless completely mixed reactor was employed to carry out the degradation experiments by means of a batch model.With an initial concentration of 11.0 mg/L,the removal efficiencies of BPA (bisphenol A) could be measured up to 70%,82%,and 90% when the dosages of ozone were 1,1.5,and 2 mg/L,respectively.The impacts on BPA degradation under the conditions of different ozone dosages,water background values,BPA initial concentrations,and ozone adding time were analyzed.The results showed that ozone dosage plays a dominant role during the process of BPA degradation,while the impact of the contact time could be ignored.UV wavelength scanning was used to confirm that the by-products were produced,which could be absorbed at UV254.The value of UV254 was observed to have changed during the ozonation process.Based on the change of UV254,it could be concluded that BPA is not completely degraded at low ozone dosage,while shorter adding time of total ozone dosage,high ozone dosage,and improvement of dissolved ozone concentration greatly contribute to the extent of BPA degradation.The effects of applied H2O2 dose in ozone oxidation of BPA were also examined in this study.The O3-H2O2 processes proved to have similar effects on the degradation of BPA by ozone oxidation.

  5. Presence of endocrine disruptors in freshwater in the northern Antarctic Peninsula region.

    Science.gov (United States)

    Esteban, S; Moreno-Merino, L; Matellanes, R; Catalá, M; Gorga, M; Petrovic, M; López de Alda, M; Barceló, D; Silva, A; Durán, J J; López-Martínez, J; Valcárcel, Y

    2016-05-01

    The increasing human presence in Antarctica and the waste it generates is causing an impact on the environment at local and border scale. The main sources of anthropic pollution have a mainly local effect, and include the burning of fossil fuels, waste incineration, accidental spillage and wastewater effluents, even when treated. The aim of this work is to determine the presence and origin of 30 substances of anthropogenic origin considered to be, or suspected of being, endocrine disruptors in the continental waters of the Antarctic Peninsula region. We also studied a group of toxic metals, metalloids and other elements with possible endocrine activity. Ten water samples were analyzed from a wide range of sources, including streams, ponds, glacier drain, and an urban wastewater discharge into the sea. Surprisingly, the concentrations detected are generally similar to those found in other studies on continental waters in other parts of the world. The highest concentrations of micropollutants found correspond to the group of organophosphate flame retardants (19.60-9209ngL(-1)) and alkylphenols (1.14-7225ngL(-1)); and among toxic elements the presence of aluminum (a possible hormonal modifier) (1.7-127µgL(-1)) is significant. The concentrations detected are very low and insufficient to cause acute or subacute toxicity in aquatic organisms. However, little is known as yet of the potential sublethal and chronic effects of this type of pollutants and their capacity for bioaccumulation. These results point to the need for an ongoing system of environmental monitoring of these substances in Antarctic continental waters, and the advisability of regulating at least the most environmentally hazardous of these in the Antarctic legislation.

  6. The Stapled AKAP Disruptor Peptide STAD-2 Displays Antimalarial Activity through a PKA-Independent Mechanism.

    Directory of Open Access Journals (Sweden)

    Briana R Flaherty

    Full Text Available Drug resistance poses a significant threat to ongoing malaria control efforts. Coupled with lack of a malaria vaccine, there is an urgent need for the development of new antimalarials with novel mechanisms of action and low susceptibility to parasite drug resistance. Protein Kinase A (PKA has been implicated as a critical regulator of pathogenesis in malaria. Therefore, we sought to investigate the effects of disrupted PKA signaling as a possible strategy for inhibition of parasite replication. Host PKA activity is partly regulated by a class of proteins called A Kinase Anchoring Proteins (AKAPs, and interaction between HsPKA and AKAP can be inhibited by the stapled peptide Stapled AKAP Disruptor 2 (STAD-2. STAD-2 was tested for permeability to and activity against Plasmodium falciparum blood stage parasites in vitro. The compound was selectively permeable only to infected red blood cells (iRBC and demonstrated rapid antiplasmodial activity, possibly via iRBC lysis (IC50 ≈ 1 μM. STAD-2 localized within the parasite almost immediately post-treatment but showed no evidence of direct association with PKA, indicating that STAD-2 acts via a PKA-independent mechanism. Furosemide-insensitive parasite permeability pathways in the iRBC were largely responsible for uptake of STAD-2. Further, peptide import was highly specific to STAD-2 as evidenced by low permeability of control stapled peptides. Selective uptake and antiplasmodial activity of STAD-2 provides important groundwork for the development of stapled peptides as potential antimalarials. Such peptides may also offer an alternative strategy for studying protein-protein interactions critical to parasite development and pathogenesis.

  7. Biomonitoring of infant exposure to phenolic endocrine disruptors using urine expressed from disposable gel diapers.

    Science.gov (United States)

    Liu, Liangpo; Xia, Tongwei; Zhang, Xueqin; Barr, Dana Boyd; Alamdar, Ambreen; Zhang, Jie; Tian, Meiping; Huang, Qingyu; Shen, Heqing

    2014-08-01

    Infant exposure to endocrine disruptors (EDs) may cause adverse health effects because of their fast growth and development during this life stage. However, collecting urine from infants for exposure assessment using biological monitoring is not an easy task. For this purpose, we evaluated the feasibility of using urine expressed from disposable gel absorbent diapers (GADs) as a matrix for biomonitoring selected phenolic EDs. GADs urine was expressed with the assistance of CaCl(2) and was collected using a device fabricated in our laboratory. The analytes were extracted and concentrated using a liquid-liquid method and their hydroxyl groups were modified by dansyl chloride to enhance their chromatography and detection. Finally, the analytes were measured by high-performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS/MS). The target chemicals were bisphenol A, triclosan, 17 α-ethynylestradiol, the natural hormone estrone, and 17 β-estradiol. The ratio of the CaCl(2) to the urine-wetted gel absorbent, variation of the inter-urination volume, and analyte deposition bias in the diaper were assessed. Analyte blank values in the diapers, the sample storage stabilities, and recoveries of the analytes were also evaluated. The results showed that 70-80 % of the urine could be expressed from the diaper with the assistance of CaCl(2) and 70.5-124 % of the spiked analytes can be recovered in the expressed urine. The limits of detections (LODs) were 0.02-0.27 ng/mL, well within the range for detection in human populations. Our pilot data suggest that infants are widely exposed to the selected EDs.

  8. Exposure assessment of endocrine disruptors in bottled drinking water of Lebanon.

    Science.gov (United States)

    Dhaini, Hassan R; Nassif, Rana M

    2014-09-01

    Bisphenol A (BPA) is a commonly used monomer in various products including bottled water. Numerous studies have reported endocrine adverse effects and neoplasia associated with BPA exposure in animals. However, considerable discrepancies exist among these studies with respect to both the nature of the toxic effects and the threshold dose. In Lebanon, 19-L polycarbonate (PC) bottles of drinking water are widely used in urban areas. The present study aims at assessing BPA human exposure and associated health risks from drinking water in Lebanese. A total of 22 bottled water sources, packaged in PC, were identified from licensed and non-licensed sources. Water samples were analyzed following exposure to sunlight for 72 h. BPA in water was quantified by HPLC, and other potential organic pollutants were screened by GC/MS. Fifty-nine percent of samples showed BPA levels above detection limits (>0.05 ng/mL). The median BPA level was 0.1 ng/mL (range 0.05 to 1.37 ng/mL). The mean BPA level for the total number of samples was 0.169 ng/mL (±0.280). A higher mean BPA level was found in water from licensed companies compared to non-licensed sources, however, not statistically significant. Screening showed the presence of dibutyl-phthalate and dioctyl-phthalate in only two samples. Endocrine disruptors (EDR) are ubiquitous contaminants in bottled water in Lebanon with potential health risk implications. Although estimated exposure levels are below the reference dose (RfD), further studies are needed to quantitate exposure from various sources and to investigate EDR contribution to existing epidemics in the country.

  9. A QSAR model for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors) by nanofiltration membranes.

    Science.gov (United States)

    Yangali-Quintanilla, Victor; Sadmani, Anwar; McConville, Megan; Kennedy, Maria; Amy, Gary

    2010-01-01

    A quantitative structure activity relationship (QSAR) model has been produced for predicting rejection of emerging contaminants (pharmaceuticals, endocrine disruptors, pesticides and other organic compounds) by polyamide nanofiltration (NF) membranes. Principal component analysis, partial least square regression and multiple linear regressions were used to find a general QSAR equation that combines interactions between membrane characteristics, filtration operating conditions and compound properties for predicting rejection. Membrane characteristics related to hydrophobicity (contact angle), salt rejection, and surface charge (zeta potential); compound properties describing hydrophobicity (log K(ow), log D), polarity (dipole moment), and size (molar volume, molecular length, molecular depth, equivalent width, molecular weight); and operating conditions namely flux, pressure, cross flow velocity, back diffusion mass transfer coefficient, hydrodynamic ratio (J(o)/k), and recovery were identified as candidate variables for rejection prediction. An experimental database produced by the authors that accounts for 106 rejection cases of emerging contaminants by NF membranes as result of eight experiments with clean and fouled membranes (NF-90, NF-200) was used to produce the QSAR model. Subsequently, using the QSAR model, rejection predictions were made for external experimental databases. Actual rejections were compared against predicted rejections and acceptable R(2) correlation coefficients were found (0.75 and 0.84) for the best models. Additionally, leave-one-out cross-validation of the models achieved a Q(2) of 0.72 for internal validation. In conclusion, a unified general QSAR equation was able to predict rejections of emerging contaminants during nanofiltration; moreover the present approach is a basis to continue investigation using multivariate analysis techniques for understanding membrane rejection of organic compounds.

  10. Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.

    Science.gov (United States)

    Habert, René; Muczynski, Vincent; Grisin, Tiphany; Moison, Delphine; Messiaen, Sébastien; Frydman, René; Benachi, Alexandra; Delbes, Géraldine; Lambrot, Romain; Lehraiki, Abdelali; N'tumba-Byn, Thierry; Guerquin, Marie-Justine; Levacher, Christine; Rouiller-Fabre, Virginie; Livera, Gabriel

    2014-01-01

    Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk.

  11. Bezafibrate, a lipid-lowering pharmaceutical, as a potential endocrine disruptor in male zebrafish (Danio rerio).

    Science.gov (United States)

    Velasco-Santamaría, Yohana M; Korsgaard, Bodil; Madsen, Steffen S; Bjerregaard, Poul

    2011-09-01

    disruptor due to its effect on the gonadal steroidogenesis and spermatogenesis.

  12. Putative Nitrogen Sensing Systems in Higher Plants

    Institute of Scientific and Technical Information of China (English)

    Hon-Ming Lam; Ying Ann Chiao; Man-Wah Li; Yuk-Kwong Yung; Sang Ji

    2006-01-01

    Nitrogen (N) metabolism is essential for the biosynthesis of vital biomolecules. N status thus exerts profound effects on plant growth and development, and must be closely monitored. In bacteria and fungi, a few sophisticated N sensing systems have been extensively studied. In animals, the ability to receive amino acid signals has evolved to become an integral part of the nervous coordination system. In this review, we will summarize recent developments in the search for putative N sensing systems in higher plants based on homologous systems in bacteria, fungi, and animals. Apparently, although plants have separated and diversified from other organisms during the evolution process, striking similarities can be found in their N sensing systems compared with those of their counterparts; however, our understanding of these systems is still incomplete. Significant modifications of the N sensing systems (including cross-talk with other signal transduction pathways) in higher plants may be a strategy of adaptation to their unique mode of life.

  13. Putative respiratory chain of Porphyromonas gingivalis.

    Science.gov (United States)

    Meuric, Vincent; Rouillon, Astrid; Chandad, Fatiha; Bonnaure-Mallet, Martine

    2010-05-01

    The electron transfer chain in Porphyromonas gingivalis, or periodontopathogens, has not yet been characterized. P. gingivalis, a strict anaerobic bacteria and the second colonizer of the oral cavity, is considered to be a major causal agent involved in periodontal diseases. Primary colonizers create a favorable environment for P. gingivalis growth by decreasing oxygen pressure. Oxygen does not appear to be the final electron acceptor of the respiratory chain. Fumarate and cytochrome b have been implicated as major components of the respiratory activity. However, the P. gingivalis genome shows many other enzymes that could be implicated in aerobic or nitrite respiration. Using bioinformatic tools and literature studies of respiratory pathways, the ATP synthesis mechanism from the sodium cycle and nutrients metabolism, the putative respirasome of P. gingivalis has been proposed.

  14. Research Progresson Disruptor Screening Program (EDSP) in US EPA%EPA内分泌干扰物研究进展

    Institute of Scientific and Technical Information of China (English)

    李敏; 傅桂平; 吕宁; 林荣华; 宗伏霖

    2016-01-01

    本文论述了农药内分泌干扰物的作用机理及对人类及动物的危害.介绍了美国环保署(US EPA)内分泌干扰物筛查项目(Endocrine Disruptor Screening Program,EDSP)的发展历史、主要测评方法、研究进展、对农药登记的影响和后续计划等,为我国开展相关工作提供参考.

  15. Endocrine disruptors in freshwater streams of Hesse, Germany: changes in concentration levels in the time span from 2003 to 2005.

    Science.gov (United States)

    Quednow, Kristin; Püttmann, Wilhelm

    2008-03-01

    Four small freshwater streams in the region known as Hessisches Ried in Germany were investigated with respect to the temporal and spatial concentration variations of the endocrine disruptors bisphenol A (BPA), 4-tert-octylphenol (4-tert-OP), and the technical isomer mixture of 4-nonylphenol (tech.-4-NP). Measured concentrations of the target compounds in the river water samples ranged from marketing and use of nonylphenols. Results from the analysis of additionally collected water samples from sewage treatment plant (STP) effluents indicate that the STPs cannot be the only sources for tech.-4-NP found in the river water.

  16. Introduction of environmental endocrine disrupters; Kankyo horumon ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Nakai, S. [Japan Society for the Promotion of Science, Tokyo (Japan); Hosomi, M. [Tokyo Univ. of Agriculture and Technology, Tokyo (Japan). Faculty of Technology

    1998-11-05

    This paper describes environmental hormones. Hormones are directly secreted from endocrine gland into blood flow, and play an important role of the differentiation of textures of organisms, reproductive function, metabolism, and adjustment of nervous/immunity system. There are some substances with hormone and anti-hormone reactions within the body of organisms, which are discharged as chemical substances in the natural environment by the artificial production activities. These are extrinsic endocrine disrupters, i.e., environmental hormones. There are 67 kinds of doubtful substances. When the environmental hormones work on the certain reaction stage of hormones, the normal action of hormones is disturbed. Various anomalies of wild animals have been reported in the world, which are suggested to be caused by the environmental hormones. Effects are known on the health of Homo sapiens, such as malignant tumor. In the current stage, test methods are under development, by which the presence of endocrine disruption can be screened. The effects depend on the growing stages of organisms, and it is necessary to consider the effects on various generations. 20 refs., 2 figs., 4 tabs.

  17. Evaluation of endocrine disruptor levels in Kafue Lechwe (Kobus leche kafuensis) samples from the Blue Lagoon National Park of Zambia.

    Science.gov (United States)

    Sichilongo, Kwenga; Torto, Nelson

    2009-12-01

    The concentrations of endocrine disruptors were determined in 36 liver tissue, serum and whole blood sample extracts drawn from 15 Blue Lagoon National Park Kafue lechwe. Out of 10 analytes evaluated, 89% of the sample extracts showed very high dieldrin concentrations of between 0.08–100 μg/mL in serum, 0.08–24.8 μg/mL in whole blood and 0.08–4.6 μg/g wet weight in liver tissue extracts. pp-DDE was detected in 83% of the sample extracts at 0.006–5.1 μg/mL in serum, 0.006–8.5 μg/mL in whole blood and 0.006–0.12 μg/g wet weight in liver tissue extracts. There was strong correlation between pp-DDE and dieldrin in all the three matrices. Deltamethrin and endosulfan detected at 50% frequency each. Percent recoveries in spiked laboratory blanks ranged between 60–100% while calculated detection limits ranged from 0.004 to 0.21 μg/mL for all the endocrine disruptors evaluated.

  18. Putative bronchopulmonary flagellated protozoa in immunosuppressed patients.

    Science.gov (United States)

    Kilimcioglu, Ali Ahmet; Havlucu, Yavuz; Girginkardesler, Nogay; Celik, Pınar; Yereli, Kor; Özbilgin, Ahmet

    2014-01-01

    Flagellated protozoa that cause bronchopulmonary symptoms in humans are commonly neglected. These protozoal forms which were presumed to be "flagellated protozoa" have been previously identified in immunosuppressed patients in a number of studies, but have not been certainly classified so far. Since no human cases of bronchopulmonary flagellated protozoa were reported from Turkey, we aimed to investigate these putative protozoa in immunosuppressed patients who are particularly at risk of infectious diseases. Bronchoalveolar lavage fluid samples of 110 immunosuppressed adult patients who were admitted to the Department of Chest Diseases, Hafsa Sultan Hospital of Celal Bayar University, Manisa, Turkey, were examined in terms of parasites by light microscopy. Flagellated protozoal forms were detected in nine (8.2%) of 110 cases. Metronidazole (500 mg b.i.d. for 30 days) was given to all positive cases and a second bronchoscopy was performed at the end of the treatment, which revealed no parasites. In conclusion, immunosuppressed patients with bronchopulmonary symptoms should attentively be examined with regard to flagellated protozoa which can easily be misidentified as epithelial cells.

  19. The Biogeography of Putative Microbial Antibiotic Production.

    Directory of Open Access Journals (Sweden)

    Hélène Morlon

    Full Text Available Understanding patterns in the distribution and abundance of functional traits across a landscape is of fundamental importance to ecology. Mapping these distributions is particularly challenging for species-rich groups with sparse trait measurement coverage, such as flowering plants, insects, and microorganisms. Here, we use likelihood-based character reconstruction to infer and analyze the spatial distribution of unmeasured traits. We apply this framework to a microbial dataset comprised of 11,732 ketosynthase alpha gene sequences extracted from 144 soil samples from three continents to document the spatial distribution of putative microbial polyketide antibiotic production. Antibiotic production is a key competitive strategy for soil microbial survival and performance. Additionally, novel antibiotic discovery is highly relevant to human health, making natural antibiotic production by soil microorganisms a major target for bioprospecting. Our comparison of trait-based biogeographical patterns to patterns based on taxonomy and phylogeny is relevant to our basic understanding of microbial biogeography as well as the pressing need for new antibiotics.

  20. Mechanosensory neurons, cutaneous mechanoreceptors, and putative mechanoproteins.

    Science.gov (United States)

    Del Valle, M E; Cobo, T; Cobo, J L; Vega, J A

    2012-08-01

    The mammalian skin has developed sensory structures (mechanoreceptors) that are responsible for different modalities of mechanosensitivity like touch, vibration, and pressure sensation. These specialized sensory organs are anatomically and functionally connected to a special subset of sensory neurons called mechanosensory neurons, which electrophysiologically correspond with Aβ fibers. Although mechanosensory neurons and cutaneous mechanoreceptors are rather well known, the biology of the sense of touch still remains poorly understood. Basically, the process of mechanosensitivity requires the conversion of a mechanical stimulus into an electrical signal through the activation of ion channels that gate in response to mechanical stimuli. These ion channels belong primarily to the family of the degenerin/epithelium sodium channels, especially the subfamily acid-sensing ion channels, and to the family of transient receptor potential channels. This review compiles the current knowledge on the occurrence of putative mechanoproteins in mechanosensory neurons and mechanoreceptors, as well as the involvement of these proteins on the biology of touch. Furthermore, we include a section about what the knock-out mice for mechanoproteins are teaching us. Finally, the possibilities for mechanotransduction in mechanoreceptors, and the common involvement of the ion channels, extracellular membrane, and cytoskeleton, are revisited.

  1. Mass flows of endocrine disruptors in the Glatt River during varying weather conditions

    Energy Technology Data Exchange (ETDEWEB)

    Jonkers, Niels; Kohler, Hans-Peter E.; Dammshaeuser, Anna [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland); Giger, Walter [Eawag, Swiss Federal Institute of Aquatic Science and Technology, 8600 Duebendorf (Switzerland)], E-mail: giger@eawag.ch

    2009-03-15

    . - Mass balance of endocrine disruptors in a wastewater-river system is strongly influenced by water flow conditions.

  2. Evaluating bioaccumulation of suspected endocrine disruptors into periphytons and benthos in the Tama River.

    Science.gov (United States)

    Takahashi, A; Higashitani, T; Yakou, Y; Saitou, M; Tamamoto, H; Tanaka, H

    2003-01-01

    There are two major routes through which fish are exposed to endocrine disruptors (EDs); one route is through water that is a habitat; the other is through aquatic food such as algae and benthos. Few studies on the bioaccumulation of EDs in food have been conducted. Therefore, we evaluated the concentration in food of nonylphenol (NP), bisphenol A (BPA) and 17beta-estradiol (E2), which were frequently detected in river water and in final discharge of Wastewater Treatment Plants (WWTPs) in Japan. We also evaluated the estrogenicity of samples using recombinant yeast. NP concentrations ranged 0.1-0.4 microg/L in the river water, while they ranged 8-130 microg/kg-wet in the periphytons and 8-140 microg/kg-wet in the benthos. BPA concentrations ranged 0.02-0.15 microg/L in the river water, while they ranged 2-8.8 microg/kg-wet in the periphytons and 0.3-12 microg/kg-wet in the benthos. E2 concentrations ranged 0.0001-0.0076 microg/L in the water, while they ranged 0.09-2.26 microg/kg-wet in the periphytons and benthos. The estrogenicity ranged 0.0001-0.0464 microg-E2equivalent/L in the water, while it ranged 3.4-66.8 microg-E2equivalent/kg-wet in the periphytons and 7.4-5458 microg-E2equivalent/kg-wet in the benthos. Bioaccumulation factors of NP are estimated as 160-650 for the periphytons, and 63-990 for the benthos, respectively. Bioaccumulation factors of BPA are estimated as 18-650 for the periphytons, and 8-170 for the benthos, respectively. Bioaccumulation factors of E2 are estimated as 64-1,200 for the periphytons, and 100-160 for the benthos, respectively. The ratios of the periphytons and the benthos to the water in terms of the estrogenicity were larger than those in terms of the chemicals. In particularly, the ratio of the benthos to the water is about 10(6) in the maximum. The results suggest that food may be a more important route for fish exposed to EDs in water environment.

  3. Occupational exposure to endocrine disruptors and time to pregnancy among couples in a large birth cohort study: the Generation R Study

    NARCIS (Netherlands)

    Snijder, C.A.; Brouwers, M.M.; Jaddoe, V.W.; Hofman, A.; Roeleveld, N.; Burdorf, A.

    2011-01-01

    OBJECTIVE: To study the influence of occupational exposure to endocrine disruptors (EDs) on time to pregnancy (TTP). DESIGN: Cross-sectional analysis within a prospective, population-based cohort study. SETTING: Medical center. PATIENT(S): Mothers and fathers who filled out a questionnaire during mi

  4. Biomonitoring: Guide for the Use of Biological Endpoints in Monitoring Species, Habitats, and Projects

    Science.gov (United States)

    2007-11-01

    Disruptors . Pages 369-430 in: R. Kendall, R. Dickerson, J. Geisy, and W. Suk, eds., Principles and Processes for Evaluating Endocrine Disruptors ...Olympia, WA. Sheffield, S.R., J.M. Matter, B.A. Rattner, and P.D. Guiney 1998. Fish and Wildlife Species as Sentinels of Environmental Endocrine

  5. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    Directory of Open Access Journals (Sweden)

    Brophy James T

    2012-11-01

    Full Text Available Abstract Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration. Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82; bars-gambling (OR = 2.28; 95% CI, 0.94-5.53; automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88, food canning (OR = 2.35; 95% CI, 1.00-5.53, and metalworking (OR = 1.73; 95% CI, 1.02-2.92. Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4 and food canning (OR = 5.70; 95% CI, 1.03-31.5. Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and

  6. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    Science.gov (United States)

    2012-01-01

    Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5). Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and

  7. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case-control study.

    Science.gov (United States)

    Brophy, James T; Keith, Margaret M; Watterson, Andrew; Park, Robert; Gilbertson, Michael; Maticka-Tyndale, Eleanor; Beck, Matthias; Abu-Zahra, Hakam; Schneider, Kenneth; Reinhartz, Abraham; Dematteo, Robert; Luginaah, Isaac

    2012-11-19

    Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case-control design, exposure effects were estimated using conditional logistic regression. Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5). These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work

  8. Deposition patterns and transport mechanisms for the endocrine disruptor 4-nonylphenol across the Sierra Nevada Mountains, California.

    Science.gov (United States)

    Lyons, Rebecca; Van de Bittner, Kyle; Morgan-Jones, Sean

    2014-12-01

    Dust and particulate distribution patterns are shifting as global climate change brings about longer drought periods. Particulates act as vehicles for long range transport of organic pollutants, depositing at locations far from their source. Nonylphenol, a biodegradation product of nonylphenol polyethoxylate, is a known endocrine disruptor. Nonylphenol polyethoxylate enters the environment as an inert ingredient in pesticide sprays, potentially traveling great distances from its application site. This is of concern when a highly agricultural region, California's Central Valley, lies adjacent to sensitive areas like the Eastern Sierra Nevada Mountains. The distribution and transport mechanisms for 4-nonylphenol were investigated in Eastern Sierra Nevada canyons. Regions close to canyon headwalls showed trace amounts of 4-nonylphenol in surface water, snow, and atmospheric deposition. Exposed areas had yearly average concentrations as high as 9 μg/L. Distribution patterns are consistent with particulate-bound transport. This suggests with increasing drought periods, higher levels of persistent organic pollutants are likely.

  9. Distrubution of the Endocrine Disruptor Nonylphenol and the Effects of Topographical Sheilding in an Eastern Sierra Nevada Mountain Drainage

    Science.gov (United States)

    Lyons, R. A.; Van de Bittner, K.; Morgan Jones, S.

    2013-12-01

    Nonylphenol is a biodegradation product of nonylphenol polyethoxylates, a pervasive compound used in many industrial processes and notably in pesticides as a surfactant. Nonylphenol has been shown to act as an endocrine disruptor at low concentrations. It causes hermaphrodism, birth defects, and high mortality in fish, frogs and other amphibians. The Sierra Nevada Mountains separate the Central Valley in the west from the high desert of Mono Country on the east side of the state of California. The Central Valley represents some of the most heavily cultivated agricultural land in the United States. San Joaquin County alone had an annual pesticide use of over 8 million pounds in 2009 according to the Pesticide Action Network, compared with 4800 pounds in Mono County the same year. Fragile alpine ecosystems in the Sierra Nevadas may be highly susceptible to the effects of endocrine disruptors like nonylphenol. The distribution of nonylphenol is affected by localized topography in a steep walled montane canyon in the Eastern Sierra Nevada Mountains, Convict Creek canyon. The concentration of nonylphenol in snow and surface water increases as the elevation in Convict Creek canyon decreases in an easterly direction from not detectable at the highest elevations to as much as .01mg/L in water and 1.8 mg/L in snow at the lowest elevations. The steep head wall of Convict Creek canyon, facing southeast, provides shielding to the higher elevation lakes from deposition of compounds and particulate matter. As a canyon becomes less steep and broader, more nonylphenol is deposited. Identifying these deposition patterns may assist in determining amphibian and fish populations that are at higher risk of negative impact from these compounds.

  10. Development of a new adsorbent from agro-industrial waste and its potential use in endocrine disruptor compound removal

    Energy Technology Data Exchange (ETDEWEB)

    Rovani, Suzimara; Censi, Monique T.; Pedrotti, Sidnei L.; Lima, Éder C.; Cataluña, Renato; Fernandes, Andreia N., E-mail: andreia.fernandes@ufrgs.br

    2014-04-01

    Highlights: • Development of a new adsorbent from agro-industrial waste. • Characterization by chemical and spectroscopic methods. • Alternative for the treatment of effluents that contain estrogens. • The AC adsorbent was successfully employed as solid phase adsorbent for the preconcentration of E2 and EE2 from aqueous solutions. - Abstract: A new activated carbon (AC) material was prepared by pyrolysis of a mixture of coffee grounds, eucalyptus sawdust, calcium hydroxide and soybean oil at 800 °C. This material was used as adsorbent for the removal of the endocrine disruptor compounds 17β-estradiol (E2) and 17α-ethinylestradiol (EE2) from aqueous solutions. The carbon material was characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR), N{sub 2} adsorption/desorption curves and point of zero charge (pH{sub PZC}). Variables including the initial pH of the adsorbate solutions, adsorbent masses and contact time were optimized. The optimum range of initial pH for removal of endocrine disruptor compounds (EDC) was 2.0–11.0. The kinetics of adsorption were investigated using general order, pseudo first-order and pseudo-second order kinetic models. The Sips isotherm model gave the best fits of the equilibrium data (298 K). The maximum amounts of E2 and EE2 removed at 298 K were 7.584 (E2) and 7.883 mg g{sup −1} (EE2) using the AC as adsorbent. The carbon adsorbent was employed in SPE (solid phase extraction) of E2 and EE2 from aqueous solutions.

  11. 环境内分泌干扰物与儿童性早熟发病的关系*%The relationship of the environment endocrine disruptors with precocious puberty

    Institute of Scientific and Technical Information of China (English)

    蔡德培; 乔丽丽; 郑力行

    2013-01-01

      目的:探讨环境内分泌干扰物(EEDs)与儿童性早熟发病的关系.方法:收集2005年3月至2005年9月在性早熟专科门诊就诊的初诊患儿110例及正常儿童100例.采用高效液相色谱及气相色谱分析法测定性早熟患儿及正常儿童血清中辛基酚(OP)、双酚A(BPA)和邻苯二甲酸二丁酯(DBP)的含量.同时测定患儿的子宫、卵巢体积和血清雌二醇(E2)含量.将血清EEDs含量与靶器官发育的指标作相关性分析.结果:正常儿童中,5.0%血清检测到OP(中位数,下同)为2.72 ng/ml,2.0%检测到BPA(2.11 ng/ml),4.0%检测到DBP(0.52 ng/ml);性早熟患儿中,33.6%血清检测到OP(7.38 ng/ml),40.9%检测到BPA(9.15 ng/ml),27.3%检测到DBP(2.76 ng/ml).性早熟患儿血清中EEDs含量显著高于正常儿童(P<0.001).患儿血清OP、BPA、DBP含量与其子宫体积均呈显著正相关(P<0.05或0.01),血清OP、DBP含量与其卵巢体积均呈显著正相关(P<0.05或0.01).结论:当前的正常儿童已有一部分暴露于EEDs,性早熟患儿EEDs的暴露程度比正常儿童严重得多.EEDs与性早熟的发病密切相关,是其重要的致病因素之一.%ABSTRACT Objective:To explore the relationship of the environmental endocrine disruptors(EEDs) with the onset of precocious puberty. Method:The blood samples were collected from 110 cases of precocious puberty and 100 cases of normal children who initially visited the precocious puberty outpatient department from March to Sept. 2005. The concentrations of octylphenol (OP), bisphenol A (BPA) and di-n-butyl phthalate (DBP) in the serum were measured with high performance liquid chromatography(HPLC) and gas chromatography. The volume of uterus and ovary, and the content of estradiol (E2) in the serum of precocious puberty were determined at the same time. The contents of EEDs in the serums and the indices of the target organs were analyzed by the methods of correlation and regression. Result:In normal control group

  12. Putative Corneal Neuralgia Responding to Vitamin D Supplementation

    Directory of Open Access Journals (Sweden)

    Eric L. Singman

    2013-09-01

    Full Text Available A patient with putative corneal neuralgia was incidentally discovered to have hypovitaminosis D. Supplementation of vitamin D appears to have led to a resolution of the patient's pain, whereas other efforts to treat the patient were unsuccessful.

  13. Proposal of how to update the standard information requirements in REACH, PPPR and BPR – a testing strategy for identification of endocrine disruptors

    DEFF Research Database (Denmark)

    Holbech, Henrik; Bjerregaard, Poul; Hass, Ulla

    This presentation is based on a project prepared by the Danish Centre on Endocrine Disrupters (CEHOS) for the Danish EPA. The project aim to provide a science based input to the on-going work in EU with regard to endocrine disruptors, i.e. the development of criteria for identification, REACH...... review on EDs and the revised strategy for the future work on endocrine disruptors, focusing on adequate detection of substances with endocrine disrupting properties under various legislative frameworks, including REACH (EC No 1907/2006), the Plant Protection Products Regulation (PPPR) (EC No 1107....../2009) and the Biocidal Products Regulation (BPR) (EC No 528/2012). There are currently no specific information requirements or testing strategies with regard to endocrine disruption in REACH and other relevant legislations. However, in relation to biocides and recently also to plant protection products, indications...

  14. Reduced graphene oxide-silver nanoparticle composite as visible light photocatalyst for degradation of colorless endocrine disruptors.

    Science.gov (United States)

    Bhunia, Susanta Kumar; Jana, Nikhil R

    2014-11-26

    Sunlight-induced degradation of organic pollutants is an ideal approach for environmental pollution control and wastewater treatment. Although a variety of photocatalysts have been designed toward this goal, efficient degradation of colorless organic pollutants by visible light is a challenging issue. Here, we show that a reduced graphene oxide (rGO)-based composite with silver nanoparticle (rGO-Ag) can act as an efficient visible-light photocatalyst for the degradation of colorless organic pollutants. We have developed a simple, large-scale synthesis method for rGO-Ag and used it for the degradation of three well-known endocrine disruptors (phenol, bisphenol A, and atrazine) under UV and visible light. It is found that photocatalytic efficiency by rGO-Ag under visible light is significantly higher compared to that of rGO or silver nanoparticles. It is proposed that Ag nanoparticles offer visible-light-induced excitation of silver plasmons, and conductive rGO offers efficient charge separation and thus induces oxidative degradation of the organic pollutant. This approach can be extended for sunlight-induced degradation of different organic pollutants.

  15. Marinopyrrole derivatives with sulfide spacers as selective disruptors of Mcl-1 binding to pro-apoptotic protein Bim.

    Science.gov (United States)

    Cheng, Chunwei; Liu, Yan; Balasis, Maria E; Garner, Thomas P; Li, Jerry; Simmons, Nicholas L; Berndt, Norbert; Song, Hao; Pan, Lili; Qin, Yong; Nicolaou, K C; Gavathiotis, Evripidis; Sebti, Said M; Li, Rongshi

    2014-07-29

    A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ) assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM), whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1) for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis) and inhibited cell proliferation.

  16. Liquid-phase exfoliated graphene as highly-sensitive sensor for simultaneous determination of endocrine disruptors: diethylstilbestrol and estradiol.

    Science.gov (United States)

    Hu, Lintong; Cheng, Qin; Chen, Danchao; Ma, Ming; Wu, Kangbing

    2015-01-01

    It is quite important to develop convenient and rapid analytical methods for trace levels of endocrine disruptors because they heavily affect health and reproduction of humans and animals. Herein, graphene was easily prepared via one-step exfoliation using N-methyl-2-pyrrolidone as solvent, and then used to construct an electrochemical sensor for highly-sensitive detection of diethylstilbestrol (DES) and estradiol (E2). On the surface of prepared graphene film, two independent and greatly-increased oxidation waves were observed at 0.28V and 0.49V for DES and E2. The remarkable signal enlargements indicated that the detection sensitivity was improved significantly. The influences of pH value, amount of graphene and accumulation time on the oxidation signals of DES and E2 were discussed. As a result, a highly-sensitive and rapid electrochemical method was newly developed for simultaneous detection of DES and E2. The values of detection limit were evaluated to be 10.87 nM and 4.9 nM for DES and E2. Additionally, this new method was successfully used in lake water samples and the accuracy was satisfactory.

  17. Possible Roles of B1 Cells and Environmental Estrogens (Endocrine Disruptors in the Development of Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Sho Ishikawa

    2005-01-01

    Full Text Available Autoimmune diseases as well as type-I allergic diseases have markedly increased in the past 30 years. Environmental estrogens or endocrine disruptors are possibly involved in the etiology of the increase in autoimmune diseases as one of environmental factors. In aged BWF1 mice, a murine model for SLE, B lymphocyte chemoattractant (BLC/CXCL13 is ectopically and highly expressed in target organs such as the thymus and kidney. B1 cells, a specialized cell population that are distinguished from conventional B cells (B2 cells by their origin, cell surface phenotype, unique tissue distribution, self-reactivity, etc., preferentially migrate towards BLC. Aberrant B1 cell trafficking to the target organs may result in activation of autoreactive CD4 T cells, autoantibody production, and impaired mucosal immunity in the gut during the development of SLE. Interestingly, B1 cells show a higher sensitivity to environmental estrogens than conventional B (B2 cells to produce autoantibodies. Thus, B1 cell can be a useful target for evaluating the pathological significance of environmental estrogens in the development of autoimmune diseases.

  18. Liquid-phase exfoliated graphene as highly-sensitive sensor for simultaneous determination of endocrine disruptors: Diethylstilbestrol and estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Lintong; Cheng, Qin [Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Chen, Danchao; Ma, Ming [Ningbo Entry-exit Inspection and Quarantine Bureau of China, Ningbo 315012 (China); Wu, Kangbing, E-mail: kbwu@hust.edu.cn [Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2015-02-11

    Graphical abstract: - Highlights: • A novel electrochemical sensor was developed for diethylstilbestrol and estradiol. • Graphene prepared by solvent exfoliation greatly enhances the detection sensitivity. • The newly-developed method has promising application and the accuracy is good. - Abstract: It is quite important to develop convenient and rapid analytical methods for trace levels of endocrine disruptors because they heavily affect health and reproduction of humans and animals. Herein, graphene was easily prepared via one-step exfoliation using N-methyl-2-pyrrolidone as solvent, and then used to construct an electrochemical sensor for highly-sensitive detection of diethylstilbestrol (DES) and estradiol (E2). On the surface of prepared graphene film, two independent and greatly-increased oxidation waves were observed at 0.28 V and 0.49 V for DES and E2. The remarkable signal enlargements indicated that the detection sensitivity was improved significantly. The influences of pH value, amount of graphene and accumulation time on the oxidation signals of DES and E2 were discussed. As a result, a highly-sensitive and rapid electrochemical method was newly developed for simultaneous detection of DES and E2. The values of detection limit were evaluated to be 10.87 nM and 4.9 nM for DES and E2. Additionally, this new method was successfully used in lake water samples and the accuracy was satisfactory.

  19. Endocrine disruptors in freshwater streams of Hesse, Germany: Changes in concentration levels in the time span from 2003 to 2005

    Energy Technology Data Exchange (ETDEWEB)

    Quednow, Kristin [J. W. Goethe University Frankfurt am Main, Institute of Atmospheric and Environmental Sciences, Department of Environmental Analytical Chemistry, Georg-Voigt-Strasse 14, 60054 Frankfurt (Germany)], E-mail: quednow@kristall.uni-frankfurt.de; Puettmann, Wilhelm [J. W. Goethe University Frankfurt am Main, Institute of Atmospheric and Environmental Sciences, Department of Environmental Analytical Chemistry, Georg-Voigt-Strasse 14, 60054 Frankfurt (Germany)

    2008-03-15

    Four small freshwater streams in the region known as Hessisches Ried in Germany were investigated with respect to the temporal and spatial concentration variations of the endocrine disruptors bisphenol A (BPA), 4-tert-octylphenol (4-tert-OP), and the technical isomer mixture of 4-nonylphenol (tech.-4-NP). Measured concentrations of the target compounds in the river water samples ranged from <20 ng/l to 1927 ng/l, <10 ng/l to 770 ng/l, and <10 ng/l to 420 ng/l for BPA, 4-tert-OP and tech.-4-NP, respectively. BPA levels were, with the exception of two samples, below the predicted no-effect concentration (PNEC) for water organisms. Tech.-4-NP concentrations showed a significant tendency of decreasing concentrations during the sampling period. This is mainly attributed to the implementation of the European Directive 2003/53/EG, which restricts both the marketing and use of nonylphenols. Results from the analysis of additionally collected water samples from sewage treatment plant (STP) effluents indicate that the STPs cannot be the only sources for tech.-4-NP found in the river water. - Concentrations of 4-nonylphenols in rivers of Hessisches Ried in Germany decreased in the sampling period from September 2003 to September 2005.

  20. Hypothesis-driven weight of evidence framework for evaluating data within the US EPA's Endocrine Disruptor Screening Program.

    Science.gov (United States)

    Borgert, Christopher J; Mihaich, Ellen M; Ortego, Lisa S; Bentley, Karin S; Holmes, Catherine M; Levine, Steven L; Becker, Richard A

    2011-11-01

    "Weight of Evidence" (WoE) approaches are often used to critically examine, prioritize, and integrate results from different types of studies to reach general conclusions. For assessing hormonally active agents, WoE evaluations are necessary to assess screening assays that identify potential interactions with components of the endocrine system, long-term reproductive and developmental toxicity tests that define adverse effects, mode of action studies aimed at identifying toxicological pathways underlying adverse effects, and toxicity, exposure and pharmacokinetic data to characterize potential risks. We describe a hypothesis-driven WoE approach for hormonally active agents and illustrate the approach by constructing hypotheses for testing the premise that a substance interacts as an agonist or antagonist with components of estrogen, androgen, or thyroid pathways or with components of the aromatase or steroidogenic enzyme systems for evaluating data within the US EPA's Endocrine Disruptor Screening Program. Published recommendations are used to evaluate data validity for testing each hypothesis and quantitative weightings are proposed to reflect two data parameters. Relevance weightings should be derived for each endpoint to reflect the degree to which it probes each specific hypothesis. Response weightings should be derived based on assay results from the test substance compared to the range of responses produced in the assay by the appropriate prototype hormone and positive and negative controls. Overall WoE scores should be derived based on response and relevance weightings and a WoE narrative developed to clearly describe the final determinations.

  1. On-Line Derivatization Gas Chromatography Ion Trap Mass Spectrometry for Determination of Endocrine Disruptors in Surface Water

    Energy Technology Data Exchange (ETDEWEB)

    Tzing, Shin-Hwa; Chang, Jia-Yaw; Ling, Yong-Chien

    2004-03-31

    A method has been developed for the determination of endocrine disruptors (EDs) (containing hydroxyl groups) in surface water from different sources. The surface water samples from different sites including school and local dormitory sewage effluents, lake water and river water were collected and analyzed. In this method, the pretreated sample is directly analyzed by GC-MS using on-line derivatization, where tetramethylammonium hydroxide (TMA-OH) was used as the derivatizing agent. Use of large-volume direct sample introduction (DSI) and co-injection of the sample and TMAOH avoids external contaminations as observed in conventional derivatization protocols. Additionally, the use of chemical ionization (CI) and CI-MS/MS could enable detection of EDs at lower concentrations and reduce the matrices' interference thereby enhancing detection sensitivity of EDs for quantification. In this work, the use of dichloromethane as CI reagent for EDs is reported for the first time and could detect EDs to concentrations as low as 0.5 pg/mL. The recovery ranged from 74 to 112 % and the relative standard derivations for replicate analyses ranged from 5 to 17 %. We hope that this method will be applicable for routine analysis of EDs with hydroxyl functional groups.

  2. Metabolic and immune impairments induced by the endocrine disruptors benzo[a]pyrene and triclosan in Xenopus tropicalis.

    Science.gov (United States)

    Regnault, Christophe; Willison, John; Veyrenc, Sylvie; Airieau, Antinéa; Méresse, Patrick; Fortier, Marlène; Fournier, Michel; Brousseau, Pauline; Raveton, Muriel; Reynaud, Stéphane

    2016-07-01

    Despite numerous studies suggesting that amphibians are highly sensitive to cumulative anthropogenic stresses, the role played by endocrine disruptors (EDs) in the decline of amphibian populations remains unclear. EDs have been extensively studied in adult amphibians for their capacity to disturb reproduction by interfering with the sexual hormone axis. Here, we studied the in vivo responses of Xenopus tropicalis males exposed to environmentally relevant concentrations of each ED, benzo[a]pyrene (BaP) and triclosan (TCS) alone (10 μg L(-1)) or a mixture of the two (10 μg L(-1) each) over a 24 h exposure period by following the modulation of the transcription of key genes involved in metabolic, sexual and immunity processes and the cellular changes in liver, spleen and testis. BaP, TCS and the mixture of the two all induced a marked metabolic disorder in the liver highlighted by insulin resistance-like and non-alcoholic fatty liver disease (NAFLD)-like phenotypes together with hepatotoxicity due to the impairment of lipid metabolism. For TCS and the mixture, these metabolic disorders were concomitant with modulation of innate immunity. These results confirmed that in addition to the reproductive effects induced by EDs in amphibians, metabolic disorders and immune system disruption should also be considered.

  3. Marinopyrrole Derivatives with Sulfide Spacers as Selective Disruptors of Mcl-1 Binding to Pro-Apoptotic Protein Bim

    Directory of Open Access Journals (Sweden)

    Chunwei Cheng

    2014-07-01

    Full Text Available A series of novel marinopyrroles with sulfide and sulphone spacers were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-xL, was evaluated using ELISA assays. Fluorescence-quenching (FQ assays confirmed the direct binding of marinopyrroles to Mcl-1. Benzyl- and benzyl methoxy-containing sulfide derivatives 4 and 5 were highly potent dual Mcl-1/Bim and Bcl-xL/Bim disruptors (IC50 values of 600 and 700 nM, whereas carboxylate-containing sulfide derivative 9 exhibited 16.4-fold more selectivity for disrupting Mcl-1/Bim over Bcl-xL/Bim binding. In addition, a nonsymmetrical marinopyrrole 12 is as equally potent as the parent marinopyrrole A (1 for disrupting both Mcl-1/Bim and Bcl-xL/Bim binding. Some of the derivatives were also active in intact human breast cancer cells where they reduced the levels of Mcl-1, induced programd cell death (apoptosis and inhibited cell proliferation.

  4. MG53-IRS-1 (Mitsugumin 53-Insulin Receptor Substrate-1) Interaction Disruptor Sensitizes Insulin Signaling in Skeletal Muscle.

    Science.gov (United States)

    Lee, Hyun; Park, Jung-Jin; Nguyen, Nga; Park, Jun Sub; Hong, Jin; Kim, Seung-Hyeob; Song, Woon Young; Kim, Hak Joong; Choi, Kwangman; Cho, Sungchan; Lee, Jae-Seon; Kim, Bong-Woo; Ko, Young-Gyu

    2016-12-23

    Mitsugumin 53 (MG53) is an E3 ligase that interacts with and ubiquitinates insulin receptor substrate-1 (IRS-1) in skeletal muscle; thus, an MG53-IRS-1 interaction disruptor (MID), which potentially sensitizes insulin signaling with an elevated level of IRS-1 in skeletal muscle, is an excellent candidate for treating insulin resistance. To screen for an MID, we developed a bimolecular luminescence complementation system using an N-terminal luciferase fragment fused with IRS-1 and a C-terminal luciferase fragment fused with an MG53 C14A mutant that binds to IRS-1 but does not have E3 ligase activity. An MID, which was discovered using the bimolecular luminescence complementation system, disrupted the molecular association of MG53 with IRS-1, thus abolishing MG53-mediated IRS-1 ubiquitination and degradation. Thus, the MID sensitized insulin signaling and increased insulin-elicited glucose uptake with an elevated level of IRS-1 in C2C12 myotubes. These data indicate that this MID holds promise as a drug candidate for treating insulin resistance. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. TBT e imposex en Galicia: los efectos de un disruptor endocrino en poblaciones de gasterópodos marinos

    Directory of Open Access Journals (Sweden)

    R. Barreiro

    2004-01-01

    Full Text Available En este artículo se resume la experiencia de nuestro grupo de investigación en el campo de los efectos de un disruptor endocrino androgenizante (el tributilo de estaño, más conocido como TBT por su abreviatura del inglés tributyltin en gasterópodos marinos del litoral gallego. Nuestras investigaciones sobre este tema comenzaron en 1996 y continúan en la actualidad. Después de una breve introducción sobre qué es el TBT y su problemática, se resumen los principales hallazgos conseguidos con nuestro trabajo, que se basan principalmente en el estudio de los efectos en el gasterópodo carnívoro Nucella lapillus con alguna información adicional para otras especies como el carroñero Nassarius reticulatus. Nuestro trabajo abarca tanto la bioacumulación de contaminante, la manifestación de un biomarcador específico de los efectos del TBT (masculinización de hembras, conocido como imposex en poblaciones naturales y en experiencias de trasplante, el estudio de la presencia de individuos genéticamente más resistentes a los efectos del TBT y algunos datos de ecología molecular sobre la estructuración poblacional y capacidad de dispersión de Nucella lapillus.

  6. Biodegradation of pharmaceuticals and endocrine disruptors with oxygen, nitrate, manganese (IV), iron (III) and sulfate as electron acceptors

    Science.gov (United States)

    Schmidt, Natalie; Page, Declan; Tiehm, Andreas

    2017-08-01

    Biodegradation of pharmaceuticals and endocrine disrupting compounds was examined in long term batch experiments for a period of two and a half years to obtain more insight into the effects of redox conditions. A mix including lipid lowering agents (e.g. clofibric acid, gemfibrozil), analgesics (e.g. diclofenac, naproxen), beta blockers (e.g. atenolol, propranolol), X-ray contrast media (e.g. diatrizoic acid, iomeprol) as well as the antiepileptic carbamazepine and endocrine disruptors (e.g. bisphenol A, 17α-ethinylestradiol) was analyzed in batch tests in the presence of oxygen, nitrate, manganese (IV), iron (III), and sulfate. Out of the 23 selected substances, 14 showed a degradation of > 50% of their initial concentrations under aerobic conditions. The beta blockers propranolol and atenolol and the analgesics pentoxifylline and naproxen showed a removal of > 50% under anaerobic conditions. In particular naproxen proved to be degradable with oxygen and under most anaerobic conditions, i.e. with manganese (IV), iron (III), or sulfate. The natural estrogens estriol, estrone and 17β-estradiol showed complete biodegradation under aerobic and nitrate-reducing conditions, with a temporary increase of estrone during transformation of estriol and 17β-estradiol. Transformation of 17β-estradiol under Fe(III)-reducing conditions resulted in an increase of estriol as well. Concentrations of clofibric acid, carbamazepine, iopamidol and diatrizoic acid, known for their recalcitrance in the environment, remained unchanged.

  7. Validation and application of reporter gene assays for the determination of estrogenic and androgenic endocrine disruptor activity in sport supplements.

    Science.gov (United States)

    Plotan, Monika; Elliott, Christopher T; Oplatowska, Michalina; Connolly, Lisa

    2012-07-01

    Previously developed estrogen and androgen mammalian reporter gene assays (RGAs) were assessed for their potential use as a quantitative screening method in the detection of estrogenic and androgenic endocrine disruptors (EDs) in sport supplements. The validation of both RGAs coupled with dispersive solid phase extraction (dSPE) was performed in accordance with European Commission Decision EC/2002/6579 for biological screening methods. Decision limits (CCα) and detection capabilities (CCβ) were established for both the estrogen and androgen RGAs. All samples were compliant with CCα and CCβ in both bioassays. Recovery rates were 96 % for 17β-estradiol and 115 % for dihydrotestosterone as obtained in their corresponding RGA. Both estrogens and androgens were stable in samples for more than 3 weeks, when stored at -20 °C. Specificity, good repeatability (coefficients of variation (CV), 12-25 %), reproducibility and robustness of both bioassays were also observed. Four different ED modes of action were determined for estrogens and androgens in 53 sport supplements, using the validated RGAs. This study revealed that 89 % of the investigated sport supplements contained estrogenic EDs and 51 % contained androgenic compounds. In conclusion, both bioassays are suitable for sport supplement screening of estrogenic and androgenic EDs.

  8. Pesticide chlorpyrifos acts as an endocrine disruptor in adult rats causing changes in mammary gland and hormonal balance.

    Science.gov (United States)

    Ventura, Clara; Nieto, María Rosa Ramos; Bourguignon, Nadia; Lux-Lantos, Victoria; Rodriguez, Horacio; Cao, Gabriel; Randi, Andrea; Cocca, Claudia; Núñez, Mariel

    2016-02-01

    Endocrine disruptors (EDs) are compounds that interfere with hormone regulation and influence mammary carcinogenesis. We have previously demonstrated that the pesticide chlorpyrifos (CPF) acts as an ED in vitro, since it induces human breast cancer cells proliferation through estrogen receptor alpha (ERα) pathway. In this work, we studied the effects of CPF at environmental doses (0.01 and 1mg/kg/day) on mammary gland, steroid hormone receptors expression and serum steroid hormone levels. It was carried out using female Sprague-Dawley 40-days-old rats exposed to the pesticide during 100 days. We observed a proliferating ductal network with a higher number of ducts and alveolar structures. We also found an increased number of benign breast diseases, such as hyperplasia and adenosis. CPF enhanced progesterone receptor (PgR) along with the proliferating cell nuclear antigen (PCNA) in epithelial ductal cells. On the other hand, the pesticide reduced the expression of co-repressors of estrogen receptor activity REA and SMRT and it decreased serum estradiol (E2), progesterone (Pg) and luteinizing hormone (LH) levels. Finally, we found a persistent decrease in LH levels among ovariectomized rats exposed to CPF. Therefore, CPF alters the endocrine balance acting as an ED in vivo. These findings warn about the harmful effects that CPF exerts on mammary gland, suggesting that this compound may act as a risk factor for breast cancer.

  9. A putative viral defence mechanism in archaeal cells

    DEFF Research Database (Denmark)

    Lillestøl, Reidun K; Redder, Peter; Garrett, Roger Antony

    2006-01-01

    in cells, and that both the mode of inhibition of viral propagation and the mechanism of adding spacer-repeat units to clusters, are dependent on RNAs transcribed from the clusters. Moreover, the putative inhibitory apparatus (piRNA-based) may be evolutionarily related to the interference RNA systems (si...

  10. Putative Lineage of Novel African Usutu Virus, Central Europe

    Centers for Disease Control (CDC) Podcasts

    2015-10-15

    Sarah Gregory reads an abridged version of "Putative Lineage of Novel African Usutu Virus, Central Europe.".  Created: 10/15/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/15/2015.

  11. Putative golden proportions as predictors of facial esthetics in adolescents.

    NARCIS (Netherlands)

    Kiekens, R.M.A.; Kuijpers-Jagtman, A.M.; Hof, M.A. van 't; Hof, BE van 't; Maltha, J.C.

    2008-01-01

    INTRODUCTION: In orthodontics, facial esthetics is assumed to be related to golden proportions apparent in the ideal human face. The aim of the study was to analyze the putative relationship between facial esthetics and golden proportions in white adolescents. METHODS: Seventy-six adult laypeople

  12. Scientific Opinion on the hazard assessment of endocrine disruptors: Scientific criteria for identification of endocrine disruptors and appropriateness of existing test methods for assessing effects mediated by these substances on human health and the environment

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Scientific Committee (SC

    2013-03-01

    Full Text Available Upon request of the European Commission, the Scientific Committee (SC of the European Food Safety Authority reviewed existing information related to the testing and assessment of endocrine active substances (EASs and endocrine disruptors (EDs. This work was conducted by a working group of experts in endocrinology, risk assessment and toxicology, together with observers from other EU agencies, namely EMA, ECHA and EEA. To distinguish between EDs and other groups of substances with different modes of action, it was concluded that an ED is defined by three criteria: the presence of i an adverse effect in an intact organism or a (subpopulation; ii an endocrine activity; and iii a plausible causal relationship between the two. As scientific criteria for adversity have not been generally defined, specific criteria for endocrine disrupting effects could not be identified. Hence, expert judgement is required to assess on a case-by-case basis the (ecotoxicological relevance of changes at the molecular to individual and/or (subpopulation level following exposure to an EAS. The SC concluded that a reasonably complete suite of standardised assays for testing the effects of EASs is (or will soon be available for the oestrogenic, androgenic, thyroid and steroidogenic modalities in mammals and fish, with fewer tests for birds and amphibians. Shortcomings in current tests and for other endocrine modalities and species were reviewed. Critical effect, severity, (irreversibility and potency aspects are part of the hazard characterisation of EDs. To inform on risk and level of concern for the purpose of risk management decisions, risk assessment (taking into account hazard and exposure data/predictions makes best use of available information. Levels of concern are not determined exclusively by risk assessment but also by protection goals set by the risk management.

  13. [Determination of four phenolic endocrine disruptors in environmental water samples by high performance liquid chromatography-fluorescence detection using dispersive liquid-liquid microextraction coupled with derivatization].

    Science.gov (United States)

    Wang, Xiaoyan; Qi, Weimei; Zhao, Xian'en; Lü, Tao; Wang, Xiya; Zheng, Longfang; Yan, Yehao; You, Jinmao

    2014-06-01

    To achieve accurate, fast and sensitive detection of phenolic endocrine disruptors in small volume of environmental water samples, a method of dispersive liquid-liquid microextraction (DLLME) coupled with fluorescent derivatization was developed for the determination of bisphenol A, nonylphenol, octylphenol and 4-tert-octylphenol in environmental water samples by high performance liquid chromatography-fluorescence detection (HPLC-FLD). The DLLME and derivatization conditions were investigated, and the optimized DLLME conditions for small volume of environmental water samples (pH 4.0) at room temperature were as follows: 70 microL chloroform as extraction solvent, 400 microL acetonitrile as dispersing solvent, vortex mixing for 3 min, and then high-speed centrifugation for 2 min. Using 2-[2-(7H-dibenzo [a, g] carbazol-7-yl)-ethoxy] ethyl chloroformate (DBCEC-Cl) as precolumn derivatization reagent, the stable derivatives of the four phenolic endocrine disruptors were obtained in pH 10.5 Na2CO3-NaHCO3 buffer/acetonitrile at 50 degrees C for 3 min, and then separated within 10 min by HPLC-FLD. The limits of detection (LODs) were in the range of 0.9-1.6 ng/L, and the limits of quantification (LOQs) were in the range of 3.8-7.1 ng/L. This method had perfect linearity, precision and recovery results, and showed obvious advantages and practicality comparing to the previously reported methods. It is a convenient and validated method for the routine analysis of phenolic endocrine disruptors in waste water of paper mill, lake water, domestic wastewater, tap water, etc.

  14. The U.S. federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996.

    Science.gov (United States)

    Reiter, L W; DeRosa, C; Kavlock, R J; Lucier, G; Mac, M J; Melillo, J; Melnick, R L; Sinks, T; Walton, B T

    1998-03-01

    The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and

  15. High content screening biosensor assay to identify disruptors of p53-hDM2 protein-protein interactions.

    Science.gov (United States)

    Hua, Yun; Strock, Christopher J; Johnston, Paul A

    2015-01-01

    This chapter describes the implementation of the p53-hDM2 protein-protein interaction (PPI) biosensor (PPIB) HCS assay to identify disruptors of p53-hDM2 PPIs. Recombinant adenovirus expression constructs were generated bearing the individual p53-GFP and hDM2-RFP PPI partners. The N-terminal p53 transactivating domain that contains the binding site for hDM2 is expressed as a GFP fusion protein that is targeted and anchored in the nucleolus of infected cells by a nuclear localization (NLS) sequence. The p53-GFP biosensor is localized to the nucleolus to enhance and facilitate the image acquisition and analysis of the PPIs. The N-terminus of hDM2 encodes the domain for binding to the transactivating domain of p53, and is expressed as a RFP fusion protein that includes both an NLS and a nuclear export sequence (NES). In U-2 OS cells co-infected with both adenovirus constructs, the binding interactions between hDM2 and p53 result in both biosensors becoming co-localized within the nucleolus. Upon disruption of the p53-hDM2 PPIs, the p53-GFP biosensor remains in the nucleolus while the shuttling hDM2-RFP biosensor redistributes into the cytoplasm. p53-hDM2 PPIs are measured by acquiring fluorescent images of cells co-infected with both adenovirus biosensors on an automated HCS imaging platform and using an image analysis algorithm to quantify the relative distribution of the hDM2-RFP shuttling component of the biosensor between the cytoplasm and nuclear regions of compound treated cells.

  16. A multi-residue method for characterization of endocrine disruptors in gaseous and particulate phases of ambient air

    Science.gov (United States)

    Alliot, Fabrice; Moreau-Guigon, Elodie; Bourges, Catherine; Desportes, Annie; Teil, Marie-Jeanne; Blanchard, Martine; Chevreuil, Marc

    2014-08-01

    A number of semi-volatile compounds occur in indoor air most of them being considered as potent endocrine disruptors and thus, exerting a possible impact upon health. To assess their concentration levels in indoor air, we developed and validated a method for sampling and multi-residue analysis of 58 compounds including phthalates, polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), parabens, bisphenol A (BPA) and tetrabromobisphenol A (TBBPA) in gaseous and particulate phases of air. We validated each step of procedures from extraction until analysis. Matrice spiking were performed at extraction, fractionation and purification stages. The more volatile compounds were analyzed with a gas chromatography system coupled with a mass spectrometer (GC/MS) or with a tandem mass spectrometer (GC/MS/MS). The less volatile compounds were analyzed with a liquid chromatography system coupled with a tandem mass spectrometer (LC/MS/MS). Labeled internal standard method was used ensuring high quantification accuracy. The instrumental detection limits were under 1 pg for all compounds and therefore, a limit of quantification averaging 1 pg m-3 for the gaseous and the particulate phases and a volume of 150 m3, except for phthalates, phenol compounds and BDE-209. Satisfactory recoveries were found except for phenol compounds. That method was successfully applied to several indoor air samples (office, apartment and day nursery) and most of the targeted compounds were quantified, mainly occurring in the gaseous phase. The most abundant were phthalates (up to 918 ng m-3 in total air), followed by PCBs > parabens > BPA > PAHs > PBDEs.

  17. Construction of high sensitive detection system for endocrine disruptors with yeast n-alkane-assimilating Yarrowia lipolytica.

    Science.gov (United States)

    Cho, Eun-Min; Lee, Haeng-Seog; Eom, Chi-Yong; Ohta, Akinori

    2010-11-01

    To construct a highly sensitive detection system for endocrine disruptors, we have compared the activity of promoters with the ALK1, ICL1, RPS7 and TEF1 for heterologous gene in Yarrowia lipolytica. The promoters were introduced into the upstream of lacZ or hERalpha reporter gene, respectively, and the activity was evaluated by beta-galactosidase assay by lacZ or western blot analysis by hERalpha. The expression analysis revealed that the ALK1 and ICL1 promoter were induced by n-decane and by EtOH, respectively. The constitutive promoter of RPS7 and TEF1 showed mostly high level of expression in the presence of glucose and glycerol, respectively. Particularly, the TEF1 promoter showed the highest beta-galactosidase activity and a significant signal by western blotting with the anti-estrogen receptor compared with the other promoters. Moreover, the detection system was constructed with promoters were linked to the upstream of expression vector for hERalpha gene transformed into the Y. lipolytica with a chromosome-integrated lacZ reporter gene under the control of estrogen response elements (EREs). It was indicated that a combination of pTEF1p-hERalpha and CXAU1-2XERE was the most effective system for the E2-dependent induction of the beta-galactosidase activity. This system showed the highest beta-galactosidase activity at 10-6 M E2 and the activity could be detected at even the concentration of 10-10 M E2. As the result, we constructed a strongly sensitive detection system with Y. lipolitica to evaluate recognized/suspected ED chemicals, such as natural/synthetic hormones, pesticides, and commercial chemicals. The results demonstrate the utility, sensitivity and reproducibility of the system for characterizing environmental estrogens.

  18. Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors

    Energy Technology Data Exchange (ETDEWEB)

    Bedia, Carmen, E-mail: carmen.bedia@idaea.csic.es; Dalmau, Núria, E-mail: nuria.dalmau@idaea.csic.es; Jaumot, Joaquim, E-mail: joaquim.jaumot@idaea.csic.es; Tauler, Romà, E-mail: roma.tauler@idaea.csic.es

    2015-07-15

    Endocrine disruptors (EDs) are a class of environmental toxic molecules able to interfere with the normal hormone metabolism. Numerous studies involve EDs exposure to initiation and development of cancers, including prostate cancer. In this work, three different EDs (aldrin, aroclor 1254 and chlorpyrifos (CPF)) were investigated as potential inducers of a malignant phenotype in DU145 prostate cancer cells after a chronic exposure. Epithelial to mesenchymal transition (EMT) induction, proliferation, migration, colony formation and release of metalloproteinase 2 (MMP-2) were analyzed in 50-day exposed cells to the selected EDs. As a result, aldrin and CPF exposure led to an EMT induction (loss of 16% and 14% of E-cadherin levels, respectively, compared to the unexposed cells). Aroclor and CPF presented an increased migration (134% and 126%, respectively), colony formation (204% and 144%, respectively) and MMP-2 release (137% in both cases) compared to the unexposed cells. An untargeted lipidomic analysis was performed to decipher the lipids involved in the observed transformations. As general results, aldrin exposure showed a global decrease in phospholipids and sphingolipids, and aroclor and CPF showed an increase of certain phospholipids, glycosphingolipids as well as a remarkable increase of some cardiolipin species. Furthermore, the three exposures resulted in an increase of some triglyceride species. In conclusion, some significant changes in lipids were identified and thus we postulate that some lipid compounds and lipid metabolic pathways could be involved in the acquisition of the malignant phenotype in exposed prostate cancer cells to the selected EDs. - Highlights: • Aldrin, aroclor and chlorpyrifos induced an aggressive phenotype in DU145 cells. • An untargeted lipidomic analysis has been performed on chronic exposed cells. • Lipidomic results showed changes in specific lipid species under chronic exposure. • These lipids may have a role in the

  19. Plastics derived endocrine disruptors (BPA, DEHP and DBP induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

    Directory of Open Access Journals (Sweden)

    Mohan Manikkam

    Full Text Available Environmental compounds are known to promote epigenetic transgenerational inheritance of adult onset disease in subsequent generations (F1-F3 following ancestral exposure during fetal gonadal sex determination. The current study was designed to determine if a mixture of plastic derived endocrine disruptor compounds bisphenol-A (BPA, bis(2-ethylhexylphthalate (DEHP and dibutyl phthalate (DBP at two different doses promoted epigenetic transgenerational inheritance of adult onset disease and associated DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to either the "plastics" or "lower dose plastics" mixture during embryonic days 8 to 14 of gonadal sex determination and the incidence of adult onset disease was evaluated in F1 and F3 generation rats. There were significant increases in the incidence of total disease/abnormalities in F1 and F3 generation male and female animals from plastics lineages. Pubertal abnormalities, testis disease, obesity, and ovarian disease (primary ovarian insufficiency and polycystic ovaries were increased in the F3 generation animals. Kidney and prostate disease were only observed in the direct fetally exposed F1 generation plastic lineage animals. Analysis of the plastics lineage F3 generation sperm epigenome previously identified 197 differential DNA methylation regions (DMR in gene promoters, termed epimutations. A number of these transgenerational DMR form a unique direct connection gene network and have previously been shown to correlate with the pathologies identified. Observations demonstrate that a mixture of plastic derived compounds, BPA and phthalates, can promote epigenetic transgenerational inheritance of adult onset disease. The sperm DMR provide potential epigenetic biomarkers for transgenerational disease and/or ancestral environmental exposures.

  20. Disruptores endocrinos. El caso particular de los xenobióticos estrogénicos. I Estrógenos naturales Endocrine disrupters. The case of estrogen xenobiotics

    OpenAIRE

    P. Martín Olmedo; M. F. Fernández Cabrera; N. Olea Serrano

    2001-01-01

    El interés de la comunidad científica por la exposición humana a sustancias químicas capaces de alterar el equilibrio hormonal -disruptores endocrinos— ha crecido al mismo tiempo que se han presentado pruebas de las con- secuencias de la exposición a estas sustancias sobre poblaciones animales. Como ha ocurrido en ocasiones anteriores, los datos observacionales en poblaciones animales han sido lo suficientemente sugerentes como para inducir entre los clínicos cierto grado de preocupación, por...

  1. Estudio translacional de los efectos del disruptor endocrino di(2-etilhexil) ftalto (DEHP) sobre la función reproductiva femenina en un modelo animal ovino

    OpenAIRE

    Herreros Guerra, María Ángeles

    2009-01-01

    En la actualidad, existe una creciente preocupación causada por las evidencias encontradas acerca del efecto de los ftalatos, sustancias ampliamente usadas en la industria de fabricación de plásticos, como disruptores endocrinos. Concretamente, el di(2-etilhexil) ftalato (DEHP) es un compuesto muy utilizado como componente de materiales plásticos (tipo policloruro de vinilo, PVC), que posee una elevada tendencia a liberarse de la matriz plástica, por lo que los animales y el hombre se encuent...

  2. Putative melatonin receptors in a human biological clock

    Energy Technology Data Exchange (ETDEWEB)

    Reppert, S.M.; Weaver, D.R.; Rivkees, S.A.; Stopa, E.G.

    1988-10-07

    In vitro autoradiography with /sup 125/I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific /sup 125/I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific /sup 125/I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific /sup 125/I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.

  3. Trypanosoma brucei: a putative RNA polymerase II promoter.

    Science.gov (United States)

    Bayele, Henry K

    2009-12-01

    RNA polymerase II (pol II) promoters are rare in the African trypanosome Trypanosoma brucei because gene regulation in the parasite is complex and polycistronic. Here, we describe a putative pol II promoter and its structure-function relationship. The promoter has features of an archetypal eukaryotic pol II promoter including putative canonical CCAAT and TATA boxes, and an initiator element. However, the spatial arrangement of these elements is only similar to yeast pol II promoters. Deletion mapping and transcription assays enabled delineation of a minimal promoter that could drive orientation-independent reporter gene expression suggesting that it may be a bidirectional promoter. In vitro transcription in a heterologous nuclear extract revealed that the promoter can be recognized by the basal eukaryotic transcription complex. This suggests that the transcription machinery in the parasite may be very similar to those of other eukaryotes.

  4. Chromosomal Abnormalities and Putative Susceptibility Genes in Autism Spectrum Disorders

    DEFF Research Database (Denmark)

    Nielsen, Mette Gilling

    Autism spectrum disorders (ASDs) is a heterogeneous group of neurodevelopmental disorders with a significant genetic component as shown by family and twin studies. However, only a few genes have repeatedly been shown to be involved in the development of ASDs. The aim of this study has been...... to identify possible ASD susceptibility genes. Genome screens in ASD patients suggest possible susceptibility gene regions on almost every chromosome. We identified four ASD patients with chromosomal rearrangements, two of which were familial rearrangements involving one of these putative susceptibility gene......) was performed for all four patients. By combination of these methods we identified several putative susceptibility genes for ASDs. Expression patterns were established for several of these genes by Quantitative PCR (Q-PCR) or in situ hybridization and one gene was sequenced in 157 ASD patients. Our results...

  5. Cloning of partial putative gonadotropin hormone receptor sequence from fish

    Indian Academy of Sciences (India)

    G Kumaresan; T Venugopal; A Vikas; T J Pandian; S M Athavan

    2000-03-01

    A search for the presence of mariner-like elements in the Labeo rohita genome by polymerase chain reaction led to the amplification of a partial DNA sequence coding for a putative transmembrane domain of gonadotropin hormone receptor. The amplified DNA sequence shows a high degree of homology to the available turkey and human luteinizing and follicle stimulating hormone receptor coding sequences. This is the first report on cloning such sequences of piscine origin.

  6. A putative role for apelin in the etiology of obesity.

    Science.gov (United States)

    Rayalam, Srujana; Della-Fera, Mary Anne; Krieg, Paul A; Cox, Christopher M; Robins, Allan; Baile, Clifton A

    2008-04-11

    Apelin, the endogenous ligand of the G protein-coupled APJ receptor has been shown to promote tumor angiogenesis. However, the effect of apelin on inducing angiogenesis in adipose tissue has not been investigated. In this review, we propose a putative role for apelin in promoting angiogenesis in adipose tissue. We further propose that targeting adipose tissue vasculature by blocking apelin signaling with anti-apelin antibodies will lead not only to inhibition of angiogenesis in adipose tissue but also to decreased adiposity.

  7. Isolation and Identification of Putative Oral Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Min; ZHAO Yan-Hua; TANG Xiao-Fei

    2011-01-01

    Objective: To isolate and characterize putative cancer stem cells in Tea8113 oral squmous cell carcinoma cell line. Methods: Putative cancer stem cells were isolated by limited dilution assay in Tea8113 cell line. Biological features of putative cancer stem cells were detected by MTT assay, flow cytometry, immunofluorescence, Colony Forming Efficiency assays, cell motility assay and in vivo tumor formation experiment. Results: Compared with untreated Tea8113 cells, the putative cancer stem cells proliferated more quickly and showed heteroploid cell cycle,higher G0/G1-arrested cells, higher CFE and higher expression levels of ABCG2 belonged to tumor stem cell phenotypes. The putative cancer stem cells had stronger capacity to generate tumors in vivo. Conclusion: The holoclone cells have higher proliferation and self-renewal abilities, which may be cancer stem cells existed in Tea8113 oral squmous cell carcinoma cell line.%目的:分离鉴定口腔鳞癌细胞系Tca8113中的肿瘤干细胞.方法:利用有限稀释的方法分离Tca8113细胞系中的肿瘤干细胞.通过MTT法、流式细胞技术、细胞免疫荧光、克隆形成率分析、细胞迁移能力检测和裸鼠皮下成瘤实验确定分离得到的肿瘤干细胞的生物学特点.结果:分离得到的紧密型克隆肿瘤细胞表现为异倍体样细胞周期,大部分细胞处于G0/G1期,增殖能力、克隆形成率和体外迁移能力都明显高于未分离的肿瘤细胞.紧密型克隆肿瘤细胞肿瘤干细胞标记物ABCG2表达也高于未分离的肿瘤细胞,并且具有更强的裸鼠皮下成瘤能力.结论:我们分离得到的紧密型克隆细胞具有较强的细胞增殖和自我更新能力,可能就是口腔鳞癌细胞系Tca8113中的肿瘤干细胞.

  8. The molecular mechanism of bisphenol A (BPA as an endocrine disruptor by interacting with nuclear receptors: insights from molecular dynamics (MD simulations.

    Directory of Open Access Journals (Sweden)

    Lanlan Li

    Full Text Available Bisphenol A (BPA can interact with nuclear receptors and affect the normal function of nuclear receptors in very low doses, which causes BPA to be one of the most controversial endocrine disruptors. However, the detailed molecular mechanism about how BPA interferes the normal function of nuclear receptors is still undiscovered. Herein, molecular dynamics simulations were performed to explore the detailed interaction mechanism between BPA with three typical nuclear receptors, including hERα, hERRγ and hPPARγ. The simulation results and calculated binding free energies indicate that BPA can bind to these three nuclear receptors. The binding affinities of BPA were slightly lower than that of E2 to these three receptors. The simulation results proved that the binding process was mainly driven by direct hydrogen bond and hydrophobic interactions. In addition, structural analysis suggested that BPA could interact with these nuclear receptors by mimicking the action of natural hormone and keeping the nuclear receptors in active conformations. The present work provided the structural evidence to recognize BPA as an endocrine disruptor and would be important guidance for seeking safer substitutions of BPA.

  9. Multi-residue analysis of free and conjugated hormones and endocrine disruptors in rat testis by QuEChERS-based extraction and LC-MS/MS.

    Science.gov (United States)

    Pouech, Charlène; Tournier, Mikaël; Quignot, Nadia; Kiss, Agneta; Wiest, Laure; Lafay, Florent; Flament-Waton, Marie-Magdeleine; Lemazurier, Emmanuel; Cren-Olivé, Cécile

    2012-03-01

    Endocrine disrupting compounds (EDCs) are suspected to be responsible for many disorders of the human reproductive system. To establish a causality relationship between exposure to endocrine disruptors and disease, experiments on animals must be performed with improved or new analytical tools. Therefore, a simple, rapid, and effective multi-residue method was developed for the determination of four steroid hormones (i.e., testosterone, androstenedione, estrone, and estradiol), glucuronide and sulfate conjugates of estrone and estradiol and four endocrine disruptors in rat testis (i.e., bisphenol A, atrazine, and active metabolites of methoxychlor and vinclozolin). The sample preparation procedure was based on the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach. An analytical method was then developed to quantify these compounds at ultra-trace levels by liquid chromatography coupled to tandem mass spectrometry. The QuEChERS extraction was optimized with regard to the acetonitrile/water ratio used in the extraction step, the choice of the cleanup method and the acetonitrile/hexane ratio used in the cleanup step. The optimized extraction method exhibited recoveries between 89% and 108% for all tested compounds except the conjugates (31% to 58%). The detection limits of all compounds were below 20 ng g(-1) of wet weight of testis. The method was subsequently applied to determine the levels of hormones and EDCs in seven rat testis samples.

  10. Warming modulates the effects of the endocrine disruptor progestin levonorgestrel on the zebrafish fitness, ovary maturation kinetics and reproduction success.

    Science.gov (United States)

    Cardoso, P G; Rodrigues, D; Madureira, T V; Oliveira, N; Rocha, M J; Rocha, E

    2017-10-01

    Interactive effects between multiple stressors, namely climate drivers (e.g., temperature) and chemical pollution (e.g., endocrine disruptors) are poorly studied. Here, it was for the first time evaluated the combinatory effects of temperature and a synthetic progestin, levonorgestrel (LNG), on the fitness and reproductive-related endpoints of zebrafish (Danio rerio). A multi-factorial design was implemented by manipulating both temperature [setting as baseline an ambient temperature of 27 °C, against warming (+3 °C)] and LNG levels (10 ngL(-1) and 1000 ngL(-1)). Groups of males and females were exposed sub-acutely, for 21-days. Increased temperature caused an overall decrease in the females' gonadosomatic index (GSI), during the pre-reproduction phase, LNG did not affect GSI. In addition, fecundity (number of ovulated eggs) was negatively affected by both temperature and LNG, being the effect of the latter more intense. Fish exposed to the highest LNG concentration (at both temperatures) did not reproduce, but also in those exposed to the lowest dose of progestin at a higher temperature, a complete reproductive failure occurred. These results reflect what was observed in the stereological analysis of the ovary maturation stages prior to reproduction. Accordingly, the higher the LNG concentration, the lower the degree of maturation of the ovary. This was exacerbated by the higher temperature. As to embryonated eggs, they hatched significantly faster at higher temperatures, but exposure to 10 ngL(-1) of LNG (at 27 °C) reduced significantly the hatching rate, comparing to control. Further, the recrudescence of the ovary 48 h after spawning seems to be not affected by both stressors. Our data suggest that in a future scenario of global warming and synthetic hormones exposure, the reproduction of fish species, such as the zebrafish, can be endangered, which can put at risk their success, and consequently affect the structure and functioning of associated

  11. Supramolecular composite materials from cellulose, chitosan, and cyclodextrin: facile preparation and their selective inclusion complex formation with endocrine disruptors.

    Science.gov (United States)

    Duri, Simon; Tran, Chieu D

    2013-04-23

    We have successfully developed a simple one-step method of preparing high-performance supramolecular polysaccharide composites from cellulose (CEL), chitosan (CS), and (2,3,6-tri-O-acetyl)-α-, β-, and γ-cyclodextrin (α-, β-, and γ-TCD). In this method, [BMIm(+)Cl(-)], an ionic liquid (IL), was used as a solvent to dissolve and prepare the composites. Because a majority (>88%) of the IL used was recovered for reuse, the method is recyclable. XRD, FT-IR, NIR, and SEM were used to monitor the dissolution process and to confirm that the polysaccharides were regenerated without any chemical modifications. It was found that unique properties of each component including superior mechanical properties (from CEL), excellent adsorption for pollutants and toxins (from CS), and size/structure selectivity through inclusion complex formation (from TCDs) remain intact in the composites. Specifically, the results from kinetics and adsorption isotherms show that whereas CS-based composites can effectively adsorb the endocrine disruptors (polychlrophenols, bisphenol A), their adsorption is independent of the size and structure of the analytes. Conversely, the adsorption by γ-TCD-based composites exhibits a strong dependence on the size and structure of the analytes. For example, whereas all three TCD-based composites (i.e., α-, β-, and γ-TCD) can effectively adsorb 2-, 3-, and 4-chlorophenol, only the γ-TCD-based composite can adsorb analytes with bulky groups including 3,4-dichloro- and 2,4,5-trichlorophenol. Furthermore, the equilibrium sorption capacities for the analytes with bulky groups by the γ-TCD-based composite are much higher than those by CS-based composites. Together, these results indicate that the γ-TCD-based composite with its relatively larger cavity size can readily form inclusion complexes with analytes with bulky groups, and through inclusion complex formation, it can strongly adsorb many more analytes and has a size/structure selectivity compared to

  12. Molecular genetics: DNA analysis of a putative dog clone.

    Science.gov (United States)

    Parker, Heidi G; Kruglyak, Leonid; Ostrander, Elaine A

    2006-03-09

    In August 2005, Lee et al. reported the first cloning of a domestic dog from adult somatic cells. This putative dog clone was the result of somatic-cell nuclear transfer from a fibroblast cell of a three-year-old male Afghan hound into a donor oocyte provided by a dog of mixed breed. In light of recent concerns regarding the creation of cloned human cell lines from the same institution, we have undertaken an independent test to determine the validity of the claims made by Lee et al..

  13. Putative cryptoendolithic life in Devonian pillow basalt, Rheinisches Schiefergebirge, Germany.

    Science.gov (United States)

    Peckmann, J; Bach, W; Behrens, K; Reitner, J

    2008-03-01

    Middle Devonian (Givetian) pillow basalt and inter-pillow breccia from the Rheinisches Schiefergebirge in Germany were found to contain putative biogenic filaments that indicate that life once proliferated within these volcanic rocks. Mineralized filaments are found in carbonate amygdules (vesicles filled by carbonate cement) in the volcanic rock, where they started to form on the internal surface of the once water-filled vesicles. Biogenicity of the filaments is indicated by (1) their size and shape resembling modern microorganisms including a constant diameter along the length of curved filaments, (2) their independence of crystal faces or cleavage planes, (3) branching patterns reminiscent of modern microorganisms, and (4) their spatial clustering and preferential occurrence close to the margin of pillows and in the inter-pillow breccias. A time lag between the deposition of pillow basalt and the activity of endoliths is revealed by the sequence of carbonate cements filling the amygdules. The putative filamentous microorganisms thrived after the formation of early fibrous rim cement, but before later equant calcite spar filled most of the remaining porosity. Microbial clay authigenesis analogous to the encrustation of prokaryotes in modern iron-rich environments led to the preservation of filaments. The filaments predominantly consist of the clay minerals chamosite and illite. Having dwelled in water-filled vesicles, the Devonian basalt-hosted filaments apparently represent cryptoendoliths. This finding suggests that a previously unrecognized niche for life exists within volcanic rock.

  14. Putative golden proportions as predictors of facial esthetics in adolescents.

    Science.gov (United States)

    Kiekens, Rosemie M A; Kuijpers-Jagtman, Anne Marie; van 't Hof, Martin A; van 't Hof, Bep E; Maltha, Jaap C

    2008-10-01

    In orthodontics, facial esthetics is assumed to be related to golden proportions apparent in the ideal human face. The aim of the study was to analyze the putative relationship between facial esthetics and golden proportions in white adolescents. Seventy-six adult laypeople evaluated sets of photographs of 64 adolescents on a visual analog scale (VAS) from 0 to 100. The facial esthetic value of each subject was calculated as a mean VAS score. Three observers recorded the position of 13 facial landmarks included in 19 putative golden proportions, based on the golden proportions as defined by Ricketts. The proportions and each proportion's deviation from the golden target (1.618) were calculated. This deviation was then related to the VAS scores. Only 4 of the 19 proportions had a significant negative correlation with the VAS scores, indicating that beautiful faces showed less deviation from the golden standard than less beautiful faces. Together, these variables explained only 16% of the variance. Few golden proportions have a significant relationship with facial esthetics in adolescents. The explained variance of these variables is too small to be of clinical importance.

  15. CRYSTAL STRUCTURE ANALYSIS OF A PUTATIVE OXIDOREDUCTASE FROM KLEBSIELLA PNEUMONIAE

    Energy Technology Data Exchange (ETDEWEB)

    Baig, M.; Brown, A.; Eswaramoorthy, S.; Swaminathan, S.

    2009-01-01

    Klebsiella pneumoniae, a gram-negative enteric bacterium, is found in nosocomial infections which are acquired during hospital stays for about 10% of hospital patients in the United States. The crystal structure of a putative oxidoreductase from K. pneumoniae has been determined. The structural information of this K. pneumoniae protein was used to understand its function. Crystals of the putative oxidoreductase enzyme were obtained by the sitting drop vapor diffusion method using Polyethylene glycol (PEG) 3350, Bis-Tris buffer, pH 5.5 as precipitant. These crystals were used to collect X-ray data at beam line X12C of the National Synchrotron Light Source (NSLS) at Brookhaven National Laboratory (BNL). The crystal structure was determined using the SHELX program and refi ned with CNS 1.1. This protein, which is involved in the catalysis of an oxidation-reduction (redox) reaction, has an alpha/beta structure. It utilizes nicotinamide adenine dinucleotide phosphate (NADP) or nicotine adenine dinucleotide (NAD) to perform its function. This structure could be used to determine the active and co-factor binding sites of the protein, information that could help pharmaceutical companies in drug design and in determining the protein’s relationship to disease treatment such as that for pneumonia and other related pathologies.

  16. 环境内分泌干扰物对健康影响的研究进展

    Institute of Scientific and Technical Information of China (English)

    王簃兰

    2003-01-01

    @@ 环境内分泌干扰物(environmental endocrine disruptors)英文又名EDCs(endocrine disrupting chemicals)、EDs(endocrine disruptors).早在1936年,Dodds等已发现了羟基联苯化合物具有雌激素活性.20世纪40年代4,4'-二羟基二苯烷烃的雌激素活性得到进一步证实.

  17. Quantifying ER Function Using High-Throughput Imaging in Breast and Other Cancer Cells

    Science.gov (United States)

    2008-09-01

    and in the analysis of environmental endocrine disruptors . Methodology/Principal Findings. We report the development of a high throughput (HT) image... endocrine disruptors , demonstrated that nuclear translocation and nuclear “speckling” were linked with transcriptional output, and specific ligands were...also plays crucial roles in the development of breast cancer, and in some way, all endocrine -based treatments target ER_ (1). ER_ mediates estrogen

  18. Exceptional error minimization in putative primordial genetic codes

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2009-11-01

    Full Text Available Abstract Background The standard genetic code is redundant and has a highly non-random structure. Codons for the same amino acids typically differ only by the nucleotide in the third position, whereas similar amino acids are encoded, mostly, by codon series that differ by a single base substitution in the third or the first position. As a result, the code is highly albeit not optimally robust to errors of translation, a property that has been interpreted either as a product of selection directed at the minimization of errors or as a non-adaptive by-product of evolution of the code driven by other forces. Results We investigated the error-minimization properties of putative primordial codes that consisted of 16 supercodons, with the third base being completely redundant, using a previously derived cost function and the error minimization percentage as the measure of a code's robustness to mistranslation. It is shown that, when the 16-supercodon table is populated with 10 putative primordial amino acids, inferred from the results of abiotic synthesis experiments and other evidence independent of the code's evolution, and with minimal assumptions used to assign the remaining supercodons, the resulting 2-letter codes are nearly optimal in terms of the error minimization level. Conclusion The results of the computational experiments with putative primordial genetic codes that contained only two meaningful letters in all codons and encoded 10 to 16 amino acids indicate that such codes are likely to have been nearly optimal with respect to the minimization of translation errors. This near-optimality could be the outcome of extensive early selection during the co-evolution of the code with the primordial, error-prone translation system, or a result of a unique, accidental event. Under this hypothesis, the subsequent expansion of the code resulted in a decrease of the error minimization level that became sustainable owing to the evolution of a high

  19. Research on Endocrine Disruptors

    Science.gov (United States)

    EPA researchers are developing innovative approaches, tools, models and data to improve the understanding of potential risks to human health and wildlife from chemicals that could disrupt the endocrine system.

  20. Glifosato como desregulador endócrino químico / Glyphosate as an endocrine chemical disruptor

    Directory of Open Access Journals (Sweden)

    Renata Marino Romano

    2009-08-01

    Full Text Available ResumoDesreguladores endócrinos são moléculas exógenas ambientais que podem afetar a síntese, secreção, transporte, metabolismo, ligação, ação e catabolismo de hormônios naturais do organismo, podendo exercer seu efeito mesmo quando em mínimas quantidades. O glifosato é um herbicida utilizado no combate às plantas daninhas prejudiciais a diversas culturas, bastante efetivo, não seletivo e pós-emergente que inibe o crescimento da planta através da interferência com a produção de aminoácidos aromáticos essenciais pela inibição da fotossíntese. Em baixas concentrações não tóxicas ele causa efeito de desregulação sobre a enzima aromatase em células de placenta humana in vitro, reduzindo a atividade da enzima aromatase e reduzindo a expressão da proteína StAR (proteína de regulação rápida da esteroidogênese. Acontaminação do solo e da água tanto fluvial como subterrânea, pelo intenso uso do glifosato, pode levar a distúrbios reprodutivos, além da possibilidade da persistência de resíduos destas substâncias no sangue, na carne, no leite, na urina e nas fezes dos animais levando à recontaminação do solo e podendo chegar ao consumo humano. O objetivo desta revisão é apresentar informações atuais sobre a toxicologia do glifosato e a sua importância sobre a saúde humana, suscitando o debate nessa área, uma vez que a legislação brasileira ainda não contempla o controle desse tipo de efeito tóxico.AbstractEndocrine disruptors (EDs are exogenous molecular factors that may affect the synthesis, secretion, transport, metabolism, binding, action, and catabolism of the body’s natural hormones. They are able to produce their effect even when they are present in minimum quantities. Glyphosate is an herbicide used to combat weeds that are harmful to different plants. It is very effective, non-selective and post-emergent, inhibiting the plant growth by interfering with the production of essential

  1. Health surveillance and endocrine disruptors Vigilância sanitária e desreguladores endócrinos

    Directory of Open Access Journals (Sweden)

    William Waissmann

    2002-04-01

    Full Text Available The author discusses the extreme relevance of research on the presence of endocrine disruptors (EDs in products of interest to health surveillance (HS. Focusing on EDs, the author highlights the urgency of changes already under way in the direction of HS. The shift should be from product and product-registration approaches to the productive process and its realization in consumption, generation of contaminants, and alterations in the health of workers and the overall population. He briefly describes: regulatory gaps for dealing with EDs; difficulty in evaluating risk and suspension of the production and use of products with its characteristics and the need, as exemplified by such products, to enhance the inter-relationship among all stakeholders and to turn HS into a state-of-the-art technological setting, associated with the academic community and accountable to the public. The author reports on measures already taken in relation to EDs, including the establishment of a reference laboratory for analyzing persistent organic pollutants (POPs, interruption of the use of various POPs in Brazil and an initial review of requirements for registering pesticides under the Brazilian National Health Surveillance Agency (ANVISA.Descreve-se como da maior relevância, o estudo da presença de "desreguladores endócrinos" (DE em produtos sob interesse da vigilância sanitária (VS. Demonstra-se, tendo como foco os DE, como são urgentes as mudanças, já iniciadas, de direcionamento da VS. De abordagens centradas nos produtos e em ações cartoriais, há que se verter tanto para a análise do processo produtivo, de sua realização no consumo, na geração de contaminantes e nas alterações da saúde de trabalhadores e da população em geral. São descritas, de modo sucinto: deficiências normativas para o enfrentamento dos DE; a dificuldade de avaliação do risco que representam e a suspensão da produção e uso de produtos com suas características e; a

  2. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents.

    Science.gov (United States)

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Gérard, Arlette; Bourguignon, Jean-Pierre

    2015-07-01

    Puberty presents remarkable individual differences in timing reaching over 5 years in humans. We put emphasis on the two edges of the age distribution of pubertal signs in humans and point to an extended distribution towards earliness for initial pubertal stages and towards lateness for final pubertal stages. Such distortion of distribution is a recent phenomenon. This suggests changing environmental influences including the possible role of nutrition, stress and endocrine disruptors. Our ability to assess neuroendocrine effects and mechanisms is very limited in humans. Using the rodent as a model, we examine the impact of environmental factors on the individual variations in pubertal timing and the possible underlying mechanisms. The capacity of environmental factors to shape functioning of the neuroendocrine system is thought to be maximal during fetal and early postnatal life and possibly less important when approaching the time of onset of puberty.

  3. Does cancer start in the womb? altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors.

    Science.gov (United States)

    Soto, Ana M; Brisken, Cathrin; Schaeberle, Cheryl; Sonnenschein, Carlos

    2013-06-01

    We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to diethylstilbestrol resulted in clear cell carcinoma of the vagina and breast cancer. In this review the effects of the endocrine disruptor bisphenol-A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer.

  4. Basal ganglia calcification as a putative cause for cognitive decline

    Directory of Open Access Journals (Sweden)

    João Ricardo Mendes de Oliveira

    Full Text Available ABSTRACT Basal ganglia calcifications (BGC may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients

  5. Probing the putative active site of YjdL

    DEFF Research Database (Denmark)

    Jensen, Johanne Mørch; Ismat, Fouzia; Szakonyi, Gerda;

    2012-01-01

    YjdL from E. coli is an unusual proton-coupled oligopeptide transporter (POT). Unlike prototypical POTs, dipeptides are preferred over tripeptides, in particular dipeptides with a positively charged C-terminal residue. To further understand this difference in peptide specificity, the sequences...... of YjdL and YdgR, a prototypical E. coli POT, were compared in light of the crystal structure of a POT from Shewanella oneidensis. Several residues found in the putative active site were mutated and the activities of the mutated variants were assessed in terms of substrate uptake assays, and changes...... pocket that opens towards the extracellular space. The C-terminal side chain faces in the opposite direction into a sub pocket that faces the cytoplasm. These data indicated a stabilizing effect on a bulky N-terminal residue by an Ala281Phe variant and on the dipeptide backbone by Trp278...

  6. Novel putative mechanisms to link circadian clocks to healthy aging.

    Science.gov (United States)

    Popa-Wagner, Aurel; Catalin, Bogdan; Buga, Ana-Maria

    2015-08-01

    The circadian clock coordinates the internal physiology to increase the homeostatic capacity thereby providing both a survival advantage to the system and an optimization of energy budgeting. Multiple-oscillator circadian mechanisms are likely to play a role in regulating human health and may contribute to the aging process. Our aim is to give an overview of how the central clock in the hypothalamus and peripheral clocks relate to aging and metabolic disorders, including hyperlipidemia and hyperglycemia. In particular, we unravel novel putative mechanisms to link circadian clocks to healthy aging. This review may lead to the design of large-scale interventions to help people stay healthy as they age by adjusting daily activities, such as feeding behavior, and or adaptation to age-related changes in individual circadian rhythms.

  7. Ballistic gelatin as a putative substrate for EEG phantom devices

    CERN Document Server

    Hairston, W David; Yu, Alfred B

    2016-01-01

    Phantom devices allow the human variable to be controlled for in order to allow clear comparison and validation of biomedical imaging hardware and software. There is currently no standard phantom for electroencephalography (EEG). To be useful, such a device would need to: (a) accurately recreate the real and imaginary components of scalp electrical impedance, (b) contain internal emitters to create electrical dipoles, and (c) be easily replicable across various labs and research groups. Cost-effective materials, which are conductive, repeatable, and easily formed are a missing key enabler for EEG phantoms. Here, we explore the use of ballistics gelatin, an inexpensive, easily-formable and repeatable material, as a putative substrate by examining its electrical properties and physical stability over time. We show that varied concentrations of NaCl salt relative to gelatin powder shifts the phase/frequency response profile, allowing for selective tuning of the material electrical properties.

  8. Putative benefits of microalgal astaxanthin on exercise and human health

    Directory of Open Access Journals (Sweden)

    Marcelo P. Barros

    2011-04-01

    Full Text Available Astaxanthin (ASTA is a pinkish-orange carotenoid produced by microalgae, but also commonly found in shrimp, lobster and salmon, which accumulate ASTA from the aquatic food chain. Numerous studies have addressed the benefits of ASTA for human health, including the inhibition of LDL oxidation, UV-photoprotection and prophylaxis of bacterial stomach ulcers. ASTA is recognized as a powerful scavenger of reactive oxygen species (ROS, especially those involved in lipid peroxidation. Both aerobic and anaerobic exercise are closely related to overproduction of ROS in muscle tissue. Post-exercise inflammatory processes can even exacerbate the oxidative stress imposed by exercise. Thus, ASTA is suggested here as a putative nutritional alternative/coadjutant for antioxidant therapy to afford additional protection to muscle tissues against oxidative damage induced by exercise, as well as for an (overall integrative redox re-balance and general human health.

  9. Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration.

    Science.gov (United States)

    Kariyazono, Yudai; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Narimatsu, Shizuo; Fujimura, Masatake; Takeda, Tomoki; Yamada, Hideyuki

    2015-12-01

    The effects of endocrine disruptors on testicular steroidogenesis in fetal rats were investigated in a study involving in utero exposure. In the major part of this study, pregnant rats at gestational day (GD)15 were given a single oral administration of the test substance, and then the expression of the following mRNAs in GD20 fetuses was determined: testicular steroidogenic acute-regulatory protein (StAR), a cholesterol transporter mediating the rate-limiting step of steroidogenesis, a ß-subunit of pituitary luteinizing hormone (LH), and a regulator of gonadal steroidogenesis. Among the substances tested, only di(2-ethylhexyl)phthalate (DEHP) reduced the expression of fetal testicular StAR. The others listed below exhibited little effect on fetal StAR: 2,2',4,4'-tetrabromodiphenylether, tributyltin chloride, atrazine, permethrin, cadmium chloride (Cd), lead acetate (Pb) and methylmercury (CH3HgOH). None of them, including DEHP, lacked the ability to reduce the expression of pituitary LHß mRNA. The present study also examined the potential of metals as modifiers of fetal steroidogenesis by giving them to pregnant dams in drinking water during GD1 and GD20. Under these conditions, Cd and Pb at a low concentration (0.01 ppm) significantly attenuated the fetal testicular expression of StAR mRNA without a concomitant reduction in LHß. No such effect was detected with CH3HgOH even at 1 ppm. These results suggest that: 1) DEHP, Cd and Pb attenuate the fetal production of sex steroids by directly acting on the testis, and 2) chronic treatment during the entire gestational period is more useful than a single administration for determining the hazardous effect of a suspected endocrine disruptor on fetal steroidogenesis.

  10. Cryptic species in putative ancient asexual darwinulids (Crustacea, Ostracoda.

    Directory of Open Access Journals (Sweden)

    Isa Schön

    Full Text Available BACKGROUND: Fully asexually reproducing taxa lack outcrossing. Hence, the classic Biological Species Concept cannot be applied. METHODOLOGY/PRINCIPAL FINDINGS: We used DNA sequences from the mitochondrial COI gene and the nuclear ITS2 region to check species boundaries according to the evolutionary genetic (EG species concept in five morphospecies in the putative ancient asexual ostracod genera, Penthesilenula and Darwinula, from different continents. We applied two methods for detecting cryptic species, namely the K/θ method and the General Mixed Yule Coalescent model (GMYC. We could confirm the existence of species in all five darwinulid morphospecies and additional cryptic diversity in three morphospecies, namely in Penthesilenula brasiliensis, Darwinula stevensoni and in P. aotearoa. The number of cryptic species within one morphospecies varied between seven (P. brasiliensis, five to six (D. stevensoni and two (P. aotearoa, respectively, depending on the method used. Cryptic species mainly followed continental distributions. We also found evidence for coexistence at the local scale for Brazilian cryptic species of P. brasiliensis and P. aotearoa. Our ITS2 data confirmed that species exist in darwinulids but detected far less EG species, namely two to three cryptic species in P. brasiliensis and no cryptic species at all in the other darwinulid morphospecies. CONCLUSIONS/SIGNIFICANCE: Our results clearly demonstrate that both species and cryptic diversity can be recognized in putative ancient asexual ostracods using the EG species concept, and that COI data are more suitable than ITS2 for this purpose. The discovery of up to eight cryptic species within a single morphospecies will significantly increase estimates of biodiversity in this asexual ostracod group. Which factors, other than long-term geographic isolation, are important for speciation processes in these ancient asexuals remains to be investigated.

  11. Putative regulatory factors associated with intramuscular fat content.

    Directory of Open Access Journals (Sweden)

    Aline S M Cesar

    Full Text Available Intramuscular fat (IMF content is related to insulin resistance, which is an important prediction factor for disorders, such as cardiovascular disease, obesity and type 2 diabetes in human. At the same time, it is an economically important trait, which influences the sensorial and nutritional value of meat. The deposition of IMF is influenced by many factors such as sex, age, nutrition, and genetics. In this study Nellore steers (Bos taurus indicus subspecies were used to better understand the molecular mechanisms involved in IMF content. This was accomplished by identifying differentially expressed genes (DEG, biological pathways and putative regulatory factors. Animals included in this study had extreme genomic estimated breeding value (GEBV for IMF. RNA-seq analysis, gene set enrichment analysis (GSEA and co-expression network methods, such as partial correlation coefficient with information theory (PCIT, regulatory impact factor (RIF and phenotypic impact factor (PIF were utilized to better understand intramuscular adipogenesis. A total of 16,101 genes were analyzed in both groups (high (H and low (L GEBV and 77 DEG (FDR 10% were identified between the two groups. Pathway Studio software identified 13 significantly over-represented pathways, functional classes and small molecule signaling pathways within the DEG list. PCIT analyses identified genes with a difference in the number of gene-gene correlations between H and L group and detected putative regulatory factors involved in IMF content. Candidate genes identified by PCIT include: ANKRD26, HOXC5 and PPAPDC2. RIF and PIF analyses identified several candidate genes: GLI2 and IGF2 (RIF1, MPC1 and UBL5 (RIF2 and a host of small RNAs, including miR-1281 (PIF. These findings contribute to a better understanding of the molecular mechanisms that underlie fat content and energy balance in muscle and provide important information for the production of healthier beef for human consumption.

  12. Serum estrogen and its metabolites in pregnant women exposed to dioxins and polychlorinated biphenyls (PCBs)

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shuli; Chang, Y.C.; Li, C.M.; Chou, W.L. [National Health Research Insts., Kaohsiung (Taiwan). Div. of Environmental Health and Occupational Medicine; Chao, H.R.; Guo, Y.L. [National Chung Kung Univ., Tainan (Taiwan). Inst. of Environmental Medicine

    2004-09-15

    Dioxins and PCBs are environmental endocrine disruptors that have half-life of 7-10 years in human bodies and have toxicities including carcinogenesis. Studies showed a high estrogen 4-/2- hydroxylation ratio appears to be a marker for neoplasm. The aim is to examine dioxin and PCBs body burden1 in relation to estrogen metabolites and catabolites.

  13. In Utero Influences, Breast Stem Cells, and Breast Cancer Risk Factors

    Science.gov (United States)

    2011-08-01

    genes due to prenatal exposures of other mitogens including environmental endocrine disruptors . REFERENCES 1. Brisken C, Socolovsky M, Lodish...enhanced myocardial contractility in mice with severe IGF-1 deficiency. J Clin Invest 1996;98:2648-55. 5. Nandi S. Endocrine control of a mammary-gland

  14. The impact of pesticides on male fertility.

    NARCIS (Netherlands)

    Roeleveld, N.; Bretveld, R.

    2008-01-01

    PURPOSE OF REVIEW: Observations in several Western countries point toward a decline in semen quality which may be associated with exposure to environmental endocrine disruptors such as several frequently used pesticides. The scarce literature on the effects of pesticides on male fertility will be re

  15. Putative uremic encephalopathy in horses: five cases (1978-1998).

    Science.gov (United States)

    Frye, M A; Johnson, J S; Traub-Dargatz, J L; Savage, C J; Fettman, M J; Gould, D H

    2001-02-15

    To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.

  16. Phytophthora infestans specific phosphorylation patterns and new putative control targets.

    Science.gov (United States)

    Frades, Itziar; Andreasson, Erik

    2016-04-01

    In this study we applied biomathematical searches of gene regulatory mechanisms to learn more about oomycete biology and to identify new putative targets for pesticides or biological control against Phytophthora infestans. First, oomycete phylum-specific phosphorylation motifs were found by discriminative n-gram analysis. We found 11.600 P. infestans specific n-grams, mapping 642 phosphoproteins. The most abundant group among these related to phosphatidylinositol metabolism. Due to the large number of possible targets found and our hypothesis that multi-level control is a sign of usefulness as targets for intervention, we identified overlapping targets with a second screen. This was performed to identify proteins dually regulated by small RNA and phosphorylation. We found 164 proteins to be regulated by both sRNA and phosphorylation and the dominating functions where phosphatidylinositol signalling/metabolism, endocytosis, and autophagy. Furthermore we performed a similar regulatory study and discriminative n-gram analysis of proteins with no clear orthologs in other species and proteins that are known to be unique to P. infestans such as the RxLR effectors, Crinkler (CRN) proteins and elicitins. We identified CRN proteins with specific phospho-motifs present in all life stages. PITG_12626, PITG_14042 and PITG_23175 are CRN proteins that have species-specific phosphorylation motifs and are subject to dual regulation.

  17. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2016-08-31

    An overarching goal in molecular biology is to gain an understanding of the mechanistic basis underlying biochemical systems. Success is critical if we are to predict effectively the outcome of drug treatments and the development of abnormal phenotypes. However, data from most experimental studies is typically noisy and sparse. This allows multiple potential mechanisms to account for experimental observations, and often devising experiments to test each is not feasible. Here, we introduce a novel strategy that discriminates among putative models based on their repertoire of qualitatively distinct phenotypes, without relying on knowledge of specific values for rate constants and binding constants. As an illustration, we apply this strategy to two synthetic gene circuits exhibiting anomalous behaviors. Our results show that the conventional models, based on their well-characterized components, cannot account for the experimental observations. We examine a total of 40 alternative hypotheses and show that only 5 have the potential to reproduce the experimental data, and one can do so with biologically relevant parameter values.

  18. Putative role of Tat-Env interaction in HIV infection.

    Science.gov (United States)

    Poon, Selina; Moscoso, Carlos G; Xing, Li; Kan, Elaine; Sun, Yide; Kolatkar, Prasanna R; Vahlne, Anders G; Srivastava, Indresh K; Barnett, Susan W; Cheng, R Holland

    2013-09-24

    To study the complex formed between Tat protein and Env soluble trimeric immunogen, and compare with previously determined structures of Env native trimers and Env-CD4m complexes. The soluble Env trimer was used to mimic the spike glycoprotein on the virus surface for the study. To overcome limitations of other structural determination methods, cryoelectron microscopy was employed to image the complex, and single particle reconstruction was utilized to reconstruct the structure of the complex from collected micrographs. Molecular modeling of gp120-Tat was performed to provide atomic coordinates for docking. Images were preprocessed by multivariate statistical analysis to identify principal components of variation then submitted for reconstruction. Reconstructed structures were docked with modeled gp120-Tat atomic coordinates to study the positions of crucial epitopes. Analysis of the Env-Tat complex demonstrated an intermediate structure between Env native trimers and Env-CD4m structures. Docking results indicate that the CD4-binding site and the V3 loop are exposed in the Env-Tat complex. The integrin-binding sequence in Tat was also exposed in Env-Tat docking. The intermediate structure induced by Tat-interaction with Env could potentially provide an explanation for increased virus infection in the presence of Tat protein. Consequently, exposure of CD4-binding sites and a putative integrin-binding sequence on Tat in the complex may provide a new avenue for rational design of an effective HIV vaccine. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins

  19. Phosphoglycerate Dehydrogenase: Potential Therapeutic Target and Putative Metabolic Oncogene

    Directory of Open Access Journals (Sweden)

    Cheryl K. Zogg

    2014-01-01

    Full Text Available Exemplified by cancer cells’ preference for glycolysis, for example, the Warburg effect, altered metabolism in tumorigenesis has emerged as an important aspect of cancer in the past 10–20 years. Whether due to changes in regulatory tumor suppressors/oncogenes or by acting as metabolic oncogenes themselves, enzymes involved in the complex network of metabolic pathways are being studied to understand their role and assess their utility as therapeutic targets. Conversion of glycolytic intermediate 3-phosphoglycerate into phosphohydroxypyruvate by the enzyme phosphoglycerate dehydrogenase (PHGDH—a rate-limiting step in the conversion of 3-phosphoglycerate to serine—represents one such mechanism. Forgotten since classic animal studies in the 1980s, the role of PHGDH as a potential therapeutic target and putative metabolic oncogene has recently reemerged following publication of two prominent papers near-simultaneously in 2011. Since that time, numerous studies and a host of metabolic explanations have been put forward in an attempt to understand the results observed. In this paper, I review the historic progression of our understanding of the role of PHGDH in cancer from the early work by Snell through its reemergence and rise to prominence, culminating in an assessment of subsequent work and what it means for the future of PHGDH.

  20. Small intestinal mucosa expression of putative chaperone fls485

    Directory of Open Access Journals (Sweden)

    Raupach Kerstin

    2010-03-01

    Full Text Available Abstract Background Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa. Methods fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies. Results fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c. Conclusions Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.

  1. Small intestinal mucosa expression of putative chaperone fls485.

    Science.gov (United States)

    Reinartz, Andrea; Ehling, Josef; Franz, Susanne; Simon, Verena; Bravo, Ignacio G; Tessmer, Claudia; Zentgraf, Hanswalter; Lyer, Stefan; Schneider, Ursula; Köster, Jan; Raupach, Kerstin; Kämmerer, Elke; Klaus, Christina; Tischendorf, Jens J W; Kopitz, Jürgen; Alonso, Angel; Gassler, Nikolaus

    2010-03-07

    Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. fls485 coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze fls485 expression in human small intestinal mucosa. fls485 expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several in situ techniques and usage of newly synthesized mouse monoclonal antibodies. fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c. Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.

  2. Putative impact of RNA editing on drug discovery.

    Science.gov (United States)

    Decher, Niels; Netter, Michael F; Streit, Anne K

    2013-01-01

    Virtually all organisms use RNA editing as a powerful post-transcriptional mechanism to recode genomic information and to increase functional protein diversity. The enzymatic editing of pre-mRNA by ADARs and CDARs is known to change the functional properties of neuronal receptors and ion channels regulating cellular excitability. However, RNA editing is also an important mechanism for genes expressed outside the brain. The fact that RNA editing breaks the 'one gene encodes one protein' hypothesis is daunting for scientists and a probable drawback for drug development, as scientists might search for drugs targeting the 'wrong' protein. This possible difficulty for drug discovery and development became more evident from recent publications, describing that RNA editing events have profound impact on the pharmacology of some common drug targets. These recent studies highlight that RNA editing can cause massive discrepancies between the in vitro and in vivo pharmacology. Here, we review the putative impact of RNA editing on drug discovery, as RNA editing has to be considered before using high-throughput screens, rational drug design or choosing the right model organism for target validation.

  3. Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias

    Institute of Scientific and Technical Information of China (English)

    Fang Hongbo; Liu Jing; Guo Dan; Liu Peixiang; Zhao Yongliang

    2014-01-01

    Background Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological types.The hypermethylation of the TGFBI promoter,as one of the main regulatory mechanisms,is associated with TGFBI silencing.In this study,we used a methylation-specific PCR (MSP) method to evaluate the methylation status of the TGFBI promoter in human leukemias.Methods Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia call lines and clinical samples.Genomic DNA was isolated from peripheral blood mononuclear cells from leukemia patients,bisulfite-converted,and analyzed by the MSP method.Results Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment reexpressed TGFBI at a substantially increased level in most of leukemia cell lines tested.Furthermore,a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia samples.Conclusion The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia,which provides a useful diagnostic marker for clinical management of human leukemias.

  4. Expression and characterization of rice putative PAUSED gene

    Institute of Scientific and Technical Information of China (English)

    Chengguo Yao; Liangfa Ge; Wei Li; Botao Zhao; Chaoqun Li; Kangcheng Ruan; Hongxuan Lin; Youxin Jin

    2008-01-01

    In Arab idopsis, PA USED ( PSD ) encodes the ortholog of loslp/ exportin-t, which mediates the nuclear export of transfer RNA (tRNA) in yeast and mammals. However, in monocot plants such as rice, knowledge of the corresponding ortholog is limited, and its effects on growth development and productivity remain unknown. In this study, we verified a rice transfer-DNA insertional mutantpsd line and analyzed its phenotypes;the mutant displayed severe morphological defects including retarded development and low fertility compared with wild-type rice. Examining intronless tRNA-Tyr and intron-containing pre-tRNA-Ala expression levels in cytoplasmic and nuclear fraction with Northern blot analysis between wild -type and mutant leaf tissue suggested that rice PSD might be involved in tRNA export from the nucleus to the cytoplasm.Additionally, reverse transcription-polymerase chain reaction analysis revealed that PSD transcript was expressed throughout normal rice plant development, and subcellular localization assays showed that rice PSD protein was present in both the nucleus and cytoplasm. In summary, our data implied that the putative PSD gene might be indispensable for normal rice development and its function might be the same as that ofArabidopsis PSD.

  5. Conformational study of a putative HLTV-1 retroviral protease inhibitor.

    Science.gov (United States)

    Llido, S; d'Estaintot, B L; Dautant, A; Geoffre, S; Picard, P; Precigoux, G

    1993-05-01

    The crystal structure of prolyl-glutaminyl-valyl-statyl-alanyl-leucine (Pro-Gln-Val-Sta-Ala-Leu, C(32)H(57)N(7)0(9).5H(2)0, M(r) = 683.9 + 90.1), a putative HTLV-1 protease inhibitor based on one of the consensus retroviral protease cleavage sequences, and containing the statine residue [(4S,3S)-4-amino-3-hydroxy-6-methylheptanoic acid], has been determined by X-ray diffraction. The same molecule has been modelled in the active site of the HTLV-1 protease and both conformations have been compared. The peptide crystallizes as a pentahydrate in space group P2(1) with a = 10.874(2), b = 9.501(2), c = 21.062(5) A, beta = 103.68 (1) degrees, Z = 2, V= 2114.3 A(3), D(x) = 1.21 g cm(-3), micro = 8.02 cm(-1), T= 293 K, lambda(Cu Kalpha) = 1.5418 A. The structure has been refined to an R value of 0.070 for 2152 observed reflections. The peptide main chain can be described as extended and adopts the usual zigzag conformation from the prolyl to the statyl residue. The main difference in conformation between the individual observed and modelled molecules is located on the Sta, Ala and Leu residues with the main chain of the modelled molecule rotated by about 180 degrees as compared to the observed conformation in the crystal state.

  6. A new putative sigma factor of Myxococcus xanthus.

    Science.gov (United States)

    Apelian, D; Inouye, S

    1993-06-01

    A third putative sigma factor gene, sigC, has been isolated from Myxococcus xanthus by using the sigA gene (formerly rpoD of M. xanthus) as a probe. The nucleotide sequence of sigC has been determined, and an open reading frame of 295 residues (M(r) = 33,430) has been identified. The deduced amino acid sequence of sigC exhibits the features which are characteristic of other bacterial sigma factors. The characterization of a sigC-lacZ strain has demonstrated that sigC expression is induced immediately after cells enter into the developmental cycle and is dramatically reduced at the onset of sporulation. A deletion mutant of sigC grows normally in vegetative culture and is able to develop normally. However, in contrast to the wild-type cells, the sigC deletion mutant cells became capable of forming fruiting bodies and myxospores on semirich agar plates. This suggests that sigC may play a role in expression of genes involved in negatively regulating the initiation of fruiting body formation.

  7. Efecto de los disruptores endocrinos en la reproducción de los peces: medición del diámetro de los ovocitos vitelogénicos

    OpenAIRE

    2016-01-01

    Con el fin de analizar el efecto de los disruptores endocrinos en los peces, el siguiente proyecto plantea realizar un estudio histológico de una colección de muestras de gónadas y la medición del diámetro de los ovocitos vitelogenicos. El estudio se realizó en tres zonas diferentes con el propósito de comparar los resultados obtenidos.

  8. The aerosols' fate in a putative ammonia ocean on Titan

    Science.gov (United States)

    Ramírez, S. I.; Coll, P.; Buch, A.; Brassé, C.; Poch, O.; Raulin, F.

    2010-04-01

    A laboratory study on the chemical transformation of Titan's aerosol analogues placed under putative surface conditions of the satellite was performed. The surface of Titan was one of the targets of the Cassini-Huygens mission and of several of the Cassini orbiter instruments, especially ISS, VIMS and Radar. The first images revealed an interesting solid surface with features that suggest aeolian, tectonic, fluvial processes and even an impact structure[1]. Since then, more detailed descriptions of dunes, channels, lakes, impact craters and cryovolcanic structures have been documented[2]. The existence of an internal liquid water ocean, containing a few percent ammonia has been proposed[2, 3]. It has also been proposed that ammonia-water mixtures can erupt from the putative subsurface ocean leading to cryovolcanism[4]. The Cassini Titan Radar Mapper obtained Synthetic Aperture Radar (SAR) images during 2004 and 2005 that revealed a highly complex geology occurring at Titan's surface[5], among which cryovolcanic features play a central role. The composition of the cryomagma is mainly proposed to be a mixture of water ice and ammonia[6, 7, 8], although ammonia has not been directly detected on Titan, but suggested by recent Cassini-VIMS observations[9]. In order to understand the role that ammonia may play on the chemical transformation of atmospheric aerosols once they reach the surface, we designed the following protocol: laboratory analogues of Titan's aerosols were synthesized from a N2:CH4 (98:2) mixture irradiated under a continuous flow regime of 845 sccm inside which, a cold plasma of 180 W was established. The synthesized analogues were recovered and partitioned in several 10.0 mg samples that were placed in 4.0 mL-volume of aqueous ammonia solutions (25.00, 12.50, 6.25 and 3.125%) at different temperatures (298, 277, 253 and 93 K) for 10 weeks. After a derivatization process performed to the aerosols' refractory phase with N

  9. Molecular diagnosis of putative Stargardt disease probands by exome sequencing

    Directory of Open Access Journals (Sweden)

    Strom Samuel P

    2012-08-01

    Full Text Available Abstract Background The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. Methods We performed whole exome sequencing (WES of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. Results Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. Conclusions Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques.

  10. A putatively novel form of spontaneous coordination in neural activity.

    Science.gov (United States)

    Hermer-Vazquez, Raymond; Hermer-Vazquez, Linda; Srinivasan, Sridhar

    2009-04-06

    We simultaneously recorded local field potentials from three sites along the olfactory-entorhinal axis in rats lightly anesthetized with isoflurane, as part of another experiment. While analyzing the initial data from that experiment with spectrograms, we discovered a potentially novel form of correlated neural activity, with near-simultaneous occurrence across the three widely separated brain sites. After validating their existence further, we named these events Synchronous Frequency Bursts (SFBs). Here we report our initial investigations into their properties and their potential functional significance. In Experiment 1, we found that SFBs have highly regular properties, consisting of brief (approximately 250 ms), high amplitude bursts of LFP energy spanning frequency ranges from the delta band (1-4 Hz) to at least the low gamma band (30-50 Hz). SFBs occurred almost simultaneously across recording sites, usually with onsets sites. While the SFBs had fairly typical, exponentially decaying power spectral density plots, their coherence structure was unusual, with high peaks in several narrow frequency ranges and little coherence in other bands. In Experiment 2, we found that SFBs occurred far more often under light anesthesia than deeper anesthetic states, and were especially prevalent as the animals regained consciousness. Finally, in Experiment 3 we showed that SFBs occur simultaneously at a significant rate across brain sites from putatively different functional subsystems--olfactory versus motor pathways. We suggest that SFBs do not carry information per se, but rather, play a role in coordinating activity in different frequency bands, potentially brain-wide, as animals progress from sleep or anesthesia toward full consciousness.

  11. Tissue factor residues that putatively interact with membrane phospholipids.

    Directory of Open Access Journals (Sweden)

    Ke Ke

    Full Text Available Blood clotting is initiated by the two-subunit enzyme consisting of the plasma protease, factor VIIa (the catalytic subunit, bound to the integral membrane protein, tissue factor (the regulatory subunit. Molecular dynamics simulations have predicted that certain residues in the tissue factor ectodomain interact with phosphatidylserine headgroups to ensure optimal positioning of the tissue factor/factor VIIa complex relative to its membrane-bound protein substrates, factors IX and X. In this study, we individually mutated to alanine all the putative phosphatidylserine-interactive residues in the tissue factor ectodomain and measured their effects on tissue factor cofactor function (activation of factors IX and X by tissue factor/factor VIIa, and clotting of plasma. Some tissue factor mutants exhibited decreased activity in all three assays, with the most profound defects observed from mutations in or near the flexible loop from Lys159 to Gly164. The decreased activity of all of these tissue factor mutants could be partially or completely overcome by increasing the phosphatidylserine content of tissue factor-liposomes. Additionally, yeast surface display was used to screen a random library of tissue factor mutants for enhanced factor VIIa binding. Surprisingly, mutations at a single amino acid (Lys165 predominated, with the Lys165→Glu mutant exhibiting a 3-fold enhancement in factor VIIa binding affinity. Our studies reveal the functional contributions of residues in the C-terminal half of the tissue factor ectodomain that are implicated in interacting with phosphatidylserine headgroups to enhance tissue factor cofactor activity, possibly by allosterically modulating the conformation of the adjacent substrate-binding exosite region of tissue factor.

  12. A putative viral defence mechanism in archaeal cells

    Directory of Open Access Journals (Sweden)

    Reidun Lillestøl

    2006-01-01

    Full Text Available Clusters of regularly spaced direct repeats, separated by unconserved spacer sequences, are ubiquitous in archaeal chromosomes and occur in some plasmids. Some clusters constitute around 1% of chromosomal DNA. Similarly structured clusters, generally smaller, also occur in some bacterial chromosomes. Although early studies implicated these clusters in segregation/partition functions, recent evidence suggests that the spacer sequences derive from extrachromosomal elements, and, primarily, viruses. This has led to the proposal that the clusters provide a defence against viral propagation in cells, and that both the mode of inhibition of viral propagation and the mechanism of adding spacer-repeat units to clusters, are dependent on RNAs transcribed from the clusters. Moreover, the putative inhibitory apparatus (piRNA-based may be evolutionarily related to the interference RNA systems (siRNA and miRNA, which are common in eukarya. Here, we analyze all the current data on archaeal repeat clusters and provide some new insights into their diverse structures, transcriptional properties and mode of structural development. The results are consistent with larger cluster transcripts being processed at the centers of the repeat sequences and being further trimmed by exonucleases to yield a dominant, intracellular RNA species, which corresponds approximately to the size of a spacer. Furthermore, analysis of the extensive clusters of Sulfolobus solfataricus strains P1 and P2B provides support for the presence of a flanking sequence adjoining a cluster being a prerequisite for the incorporation of new spacer-repeat units, which occurs between the flanking sequence and the cluster. An archaeal database summarizing the data will be maintained at http://dac.molbio.ku.dk/dbs/SRSR/.

  13. Putative Risk Factors in Developmental Dyslexia: A Case-Control Study of Italian Children

    Science.gov (United States)

    Mascheretti, Sara; Marino, Cecilia; Simone, Daniela; Quadrelli, Ermanno; Riva, Valentina; Cellino, Maria Rosaria; Maziade, Michel; Brombin, Chiara; Battaglia, Marco

    2015-01-01

    Although dyslexia runs in families, several putative risk factors that cannot be immediately identified as genetic predict reading disability. Published studies analyzed one or a few risk factors at a time, with relatively inconsistent results. To assess the contribution of several putative risk factors to the development of dyslexia, we conducted…

  14. Putative Risk Factors in Developmental Dyslexia: A Case-Control Study of Italian Children

    Science.gov (United States)

    Mascheretti, Sara; Marino, Cecilia; Simone, Daniela; Quadrelli, Ermanno; Riva, Valentina; Cellino, Maria Rosaria; Maziade, Michel; Brombin, Chiara; Battaglia, Marco

    2015-01-01

    Although dyslexia runs in families, several putative risk factors that cannot be immediately identified as genetic predict reading disability. Published studies analyzed one or a few risk factors at a time, with relatively inconsistent results. To assess the contribution of several putative risk factors to the development of dyslexia, we conducted…

  15. Strength Analysis on Recoilless Improvised Explosive Device Disruptor Tube%无后坐力爆炸物销毁器身管强度分析

    Institute of Scientific and Technical Information of China (English)

    龚建华; 邢春洪; 乔晓辉; 李慧

    2014-01-01

    为了满足大口径无后坐力爆炸物销毁器一体化、轻量化设计要求,建立一种基于非线性有限元方法的无后坐力爆炸物销毁器瞬态动力模型。依据无后坐力爆炸物销毁器两端对称的结构特点和膛压变化过程,理论分析了其身管强度,并采用非线性有限元方法,对身管整体强度进行数值仿真及验证。结果表明:新型无后坐力爆炸物销毁器身管在一体化设计的前提下,整体强度满足材料弹性极限要求,并且具有足够的安全系数,弹仓部可以减少其壁厚,以实现其轻量化。该研究为大口径无后坐力爆炸物销毁器和排爆机器人身管的设计提供理论依据。%In order to meet the requirement of the integration and light weight design on the recoilless improvised explosive device (IED), the transient dynamics model was established by the nonlinear finite element method. According to the symmetrical structure and chamber pressure of the recoilless IED disruptor, the strengths were obtained by the theoretical analysis and verified by the nonlinear finite element model. The results illustrated that the maximum strength meets the material elastic limit requirement and the thickness of the tube could be diminished under the requirement of the light weight, which provided theoretical foundation for the heavy caliber recoilless IED disruptor and explosive ordnance disposal (EOD) robot.

  16. Putative functions of extracellular matrix glycoproteins in secondary palate morphogenesis

    Science.gov (United States)

    d'Amaro, Rocca; Scheidegger, Rolf; Blumer, Susan; Pazera, Pawel; Katsaros, Christos; Graf, Daniel; Chiquet, Matthias

    2012-01-01

    Cleft palate is a common birth defect in humans. Elevation and fusion of paired palatal shelves are coordinated by growth and transcription factors, and mutations in these can cause malformations. Among the effector genes for growth factor signaling are extracellular matrix (ECM) glycoproteins. These provide substrates for cell adhesion (e.g., fibronectin, tenascins), but also regulate growth factor availability (e.g., fibrillins). Cleft palate in Bmp7 null mouse embryos is caused by a delay in palatal shelf elevation. In contrast, palatal shelves of Tgf-β3 knockout mice elevate normally, but a cleft develops due to their failure to fuse. However, nothing is known about a possible functional interaction between specific ECM proteins and Tgf-β/Bmp family members in palatogenesis. To start addressing this question, we studied the mRNA and protein distribution of relevant ECM components during secondary palate development, and compared it to growth factor expression in wildtypewild type and mutant mice. We found that fibrillin-2 (but not fibrillin-1) mRNA appeared in the mesenchyme of elevated palatal shelves adjacent to the midline epithelial cells, which were positive for Tgf-β3 mRNA. Moreover, midline epithelial cells started expressing fibronectin upon contact of the two palatal shelves. These findings support the hypothesis that fibrillin-2 and fibronectin are involved in regulating the activity of Tgf-β3 at the fusing midline. In addition, we observed that tenascin-W (but not tenascin-C) was misexpressed in palatal shelves of Bmp7-deficient mouse embryos. In contrast to tenascin-C, tenascin-W secretion was strongly induced by Bmp7 in embryonic cranial fibroblasts in vitro. These results are consistent with a putative function for tenascin-W as a target of Bmp7 signaling during palate elevation. Our results indicate that distinct ECM proteins are important for morphogenesis of the secondary palate, both as downstream effectors and as regulators of Tgf

  17. Comparison of activation media and pyrolysis temperature for activated carbons development by pyrolysis of potato peels for effective adsorption of endocrine disruptor bisphenol-A.

    Science.gov (United States)

    Arampatzidou, Anastasia C; Deliyanni, Eleni A

    2016-03-15

    Activated carbon prepared from potato peels, a solid waste by product has been studied for the adsorption of an endocrine disruptor, Bisphenol-A, from aqueous solutions. The potato peels biomass was activated with H3PO4, KOH and ZnCl2 in order the effect of the activation agent to be evaluated. The activated biomass was carbonized at 400, 600 and/or 800 °C in order the effect of carbonization temperature on the texture, surface chemistry and adsorption properties to be found. The activated carbons prepared were characterized by nitrogen adsorption, Scanning Electron Microscope, thermal analysis and Fourier Transform Infrared Spectroscopy. Equilibrium adsorption data followed both Langmuir and Freundlich isotherms. Adsorption followed second order rate kinetics. The adsorption capacity calculated from the Langmuir isotherm was found 454.62 mg g(-1) at an initial pH 3 at 25 °C for the phosphoric acid activated carbon carbonized at 400 °C that proved to be the best adsorbent.

  18. Endocrine disruptors in sludge wastewater treatment plants: environmental complications - doi: 10.4025/actascitechnol.v35i2.10619

    Directory of Open Access Journals (Sweden)

    Aldo Pacheco Ferreira

    2013-04-01

    Full Text Available Concern over exposure to endocrine disruptors (EDs and impacts on wildlife and human has gradually increased in importance in recent years. Wastewater systematically receives most if not all of these chemicals, so a deeper understanding of the fate of EDs in environment is sorely needed. We evaluated EDs concentration in the affluent and effluent from the Sludge Wastewater Treatment Plants (SWTPs Penha and Ilha do Governador. It was used as evaluation parameter the determination of some target compounds, such as: alkylphenols, 17β-estradiol, bisphenol A; complementing with measures of physical and chemical parameters: temperature, pH, dissolved oxygen, total suspended solids, volatile suspended solids, and total chemical oxygen demand. Samples were collected along the line of treatment of each SWTP, and after laboratory procedures, analyzed by LC-MS/MS and ELISA techniques. In some samples, we verified concentrations of chemical compounds with potential to disrupt the endocrine system of living organisms. Therefore, the release of this effluent, even within the effluent discharge standards (BRASIL, 2005 or in condition to be purified by the water course, may lead to physiological changes in the organisms of the receptor water body.  

  19. Endocrine disruptors and other inhibitors of 11β-hydroxysteroid dehydrogenase 1 and 2: Tissue-specific consequences of enzyme inhibition.

    Science.gov (United States)

    Vitku, Jana; Starka, Luboslav; Bicikova, Marie; Hill, Martin; Heracek, Jiri; Sosvorova, Lucie; Hampl, Richard

    2016-01-01

    Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11β-hydroxysteroid dehydrogenase (11βHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11βHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11βHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11βHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.

  20. Assessment of persistant organic pollutants acting as endocrine disruptor chemicals in animal fat, cow milk and lacteous sub-products from Cluj County, Romania

    Directory of Open Access Journals (Sweden)

    Tania Mihăiescu

    2011-06-01

    Full Text Available The present study aimed to quantify the levels of largely distributed organochlorine compounds(pesticides and polychlorinated biphenyls in various biological media of animal origin from Cluj County,Romania. Organochlorine pesticides residues (DDT and its metabolites, aldrin, dieldrin, endrin,hexachlorbenzene, heptachlor, α-hexachlorcyclohexane, β-hexachlorcyclohexane, γ-hexachlorcyclohexaneand δ-hexachlorcyclohexane were detected in 2.3-62.5% cow milk samples, lacteous sub-products andbovine fat tissue samples without exceeding maximum admitted limits according to the 86/363 Directive ofthe European Council. Polychlorinated biphenyls residues (PCB-28, -52, -101, -138, -153 and -180 wereidentified in 42.43-60.87% of analyzed samples with mean values similar to those previously reported inproducts and sub-products of animal origin in other geographical areas from Romania. Hence, the presenceof persistent organic pollutants acting as endocrine disruptors in products and sub-products of animalorigin from Cluj County is confirmed, thus supporting the passage and bio/accumulation of thesecompounds across the trophic chain to the man.

  1. Association between Exposure to Endocrine Disruptors in Drinking Water and Preterm Birth, Taking Neighborhood Deprivation into Account: A Historic Cohort Study

    Directory of Open Access Journals (Sweden)

    Marion Albouy-Llaty

    2016-08-01

    Full Text Available Background: The relationship between preterm birth (PTB and endocrine disruptor exposure in drinking-water has only occasionally been studied. The objective of this work was to investigate the relation between exposure to atrazine metabolites, or atrazine/nitrate mixtures, in drinking-water during pregnancy and prevalence of PTB neonates, while taking neighborhood deprivation into account. Method: A historic cohort study in Deux-Sèvres, France, between 2005 and 2010 with a multiple imputation model for data of exposure to atrazine metabolites and a logistic regression were carried out. Results: We included 13,654 mother/neonate pairs living in 279 different census districts. The prevalence of PTB was 4%. Average atrazine metabolite concentration was 0.019 ± 0.009 (0.014–0.080 µg/L and 39% of mothers lived in less deprived areas. The individual data were associated with risk of PTB. The risk of PTB when exposed to highest concentration of atrazine metabolite adjusted for confounders, was ORa 1.625 95% CI [0.975; 2.710]. Taking, or not, neighborhood deprivation into account did not change the result. Exposure to atrazine/nitrate mixtures remained non-significant. Conclusions: Even if we took neighborhood deprivation into account, we could not show a significant relationship between exposure to atrazine metabolites, or mixtures, in drinking-water during the second trimester of pregnancy and PTB.

  2. Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features

    Directory of Open Access Journals (Sweden)

    Cinzia La Rocca

    2015-10-01

    Full Text Available Internal levels of selected endocrine disruptors (EDs (i.e., perfluorooctane sulfonate (PFOS, perfluorooctanoic acid (PFOA, di-2-ethylhexyl-phthalate (DEHP, mono-(2-ethylhexyl-phthalate (MEHP, and bisphenol A (BPA were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs of same subjects, gene expression levels of a panel of nuclear receptors (NRs, namely estrogen receptor α (ERα estrogen receptor β (ERβ, androgen receptor (AR, aryl hydrocarbon receptor (AhR, peroxisome proliferator-activated receptor γ (PPARγ and pregnane X receptor (PXR were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERβ, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health.

  3. Endocrine disruptors compounds, pharmaceuticals and personal care products in urban wastewater: implications for agricultural reuse and their removal by adsorption process.

    Science.gov (United States)

    Grassi, Mariangela; Rizzo, Luigi; Farina, Anna

    2013-06-01

    In the last years, a lot of emerging contaminants, such as, endocrine disruptors compounds (EDCs), pharmaceuticals, and personal care products (PPCPs) have been detected in wastewater. Because of their toxicity and possible adverse effects on the environment and humans, their release from urban wastewater treatment plants (UWWTPs) effluents should be minimized, particularly when a wastewater reuse for crops irrigation is expected. Many processes have been investigated for advanced treatment of UWWTP effluents as well as for emerging contaminant degradation; among these, adsorption process was successfully used to remove EDCs and PPCPs from wastewater. This article shortly reviews EDCs and PPCPs removal from UWWTP effluents by adsorption process using conventional and non-conventional adsorbents. The fate of EDCs and PPCPs in UWWTPs and the implications for agricultural wastewater reuse has been addressed too. In spite of the adsorption process looking to be a valuable alternative to other advanced technologies for the removal of emerging contaminants from wastewater, some gaps still remain to evaluate the actual feasibility at full scale. However, according to a few studies available in scientific literature on the use of both powdered activated carbon and granular activated carbon at full scale, adsorption process by activated carbon is a promising, potentially effective, and economically feasible solution for producing safe wastewater for agricultural reuse.

  4. Comparison of Individual and Combined Effects of Four Endocrine Disruptors on Estrogen Receptor Beta Transcription in Cerebellar Cell Culture: The Modulatory Role of Estradiol and Triiodo-Thyronine

    Directory of Open Access Journals (Sweden)

    Gergely Jocsak

    2016-06-01

    Full Text Available Background: Humans and animals are continuously exposed to a number of environmental substances that act as endocrine disruptors (EDs. While a growing body of evidence is available to prove their adverse health effects, very little is known about the consequences of simultaneous exposure to a combination of such chemicals; Methods: Here, we used an in vitro model to demonstrate how exposure to bisphenol A, zearalenone, arsenic, and 4-methylbenzylidene camphor, alone or in combination, affect estrogen receptor β (ERβ mRNA expression in primary cerebellar cell cultures. Additionally, we also show the modulatory role of intrinsic biological factors, such as estradiol (E2, triiodo-thyronine (T3, and glial cells, as potential effect modulators; Results: Results show a wide diversity in ED effects on ERβ mRNA expression, and that the magnitude of these ED effects highly depends on the presence or absence of E2, T3, and glial cells; Conclusion: The observed potency of the EDs to influence ERβ mRNA expression, and the modulatory role of E2, T3, and the glia suggests that environmental ED effects may be masked as long as the hormonal milieu is physiological, but may tend to turn additive or superadditive in case of hormone deficiency.

  5. Effects of (Anti) Androgenic Endocrine Disruptors (DEHP and Butachlor) on Immunoglobulin M (IgM) and Leukocytes Counts of Male Rainbow Trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Ahmadivand, Sohrab; Farahmand, Hamid; Mirvaghefi, Alireza; Eagderi, Soheil; Zargar, Ashkan

    2015-06-01

    The effect of two anti-androgenic endocrine disrupting compounds, i.e. the plasticizer di (2-ethylhexyl) phthalate (DEHP) and herbicide butachlor, were evaluated for their effects on immunoglobulin M (IgM) and leukocytes in male rainbow trout. Also, plasma testosterone (T) concentration was measured to confirm their anti-androgenic effects. In the first experiment, trout were treated with 50 mg/kg (body weight) DEHP intraperitoneally, and in the second one, fish were exposed to 0.39 mg/L butachlor for 10 days. The results showed that T concentrations and white blood cells were significantly lower in fish exposed to either DEHP or butachlor compared to control fish (p butachlor (p  0.05). In addition, no significant differences were found in IgM, eosinophil and monocyte parameters in either DEHP or butachlor treatments (p > 0.05). These results confirmed that leukocytes counts can be considered as a novel marker of immunotoxicity triggered by (anti) androgenic endocrine disruptors.

  6. A Cell-Based High-Throughput Assay for Gap Junction Communication Suitable for Assessing Connexin 43-Ezrin Interaction Disruptors Using IncuCyte ZOOM.

    Science.gov (United States)

    Dukic, Aleksandra R; McClymont, David W; Taskén, Kjetil

    2017-01-01

    Connexin 43 (Cx43), the predominant gap junction (GJ) protein, directly interacts with the A-kinase-anchoring protein (AKAP) Ezrin in human cytotrophoblasts and a rat liver epithelial cells (IAR20). The Cx43-Ezrin-protein kinase (PKA) complex facilitates Cx43 phosphorylation by PKA, which triggers GJ opening in cytotrophoblasts and IAR20 cells and may be a general mechanism regulating GJ intercellular communication (GJIC). Considering the importance of Cx43 GJs in health and disease, they are considered potential pharmaceutical targets. The Cx43-Ezrin interaction is a protein-protein interaction that opens possibilities for targeting with peptides and small molecules. For this reason, we developed a high-throughput cell-based assay in which GJIC can be assessed and new compounds characterized. We used two pools of IAR20 cells, calcein loaded and unloaded, that were mixed and allowed to attach. Next, GJIC was monitored over time using automated imaging via the IncuCyte imager. The assay was validated using known GJ inhibitors and anchoring peptide disruptors, and we further tested new peptides that interfered with the Cx43-Ezrin binding region and reduced GJIC. Although an AlphaScreen assay can be used to screen for Cx43-Ezrin interaction inhibitors, the cell-based assay described is an ideal secondary screen for promising small-molecule hits to help identify the most potent compounds.

  7. Contribution of primary and secondary treatment on the removal of benzothiazoles, benzotriazoles, endocrine disruptors, pharmaceuticals and perfluorinated compounds in a sewage treatment plant.

    Science.gov (United States)

    Stasinakis, Athanasios S; Thomaidis, Nikolaos S; Arvaniti, Olga S; Asimakopoulos, Alexandros G; Samaras, Vasilios G; Ajibola, Akinranti; Mamais, Daniel; Lekkas, Themistokles D

    2013-10-01

    The occurrence and fate of 36 emerging contaminants, belonging to five different classes, (benzotriazoles, BTRs; benzothiazoles, BTHs; perfluorinated compounds, PFCs; non-steroidal anti-inflammatory drugs, NSAIDs and endocrine disruptors, EDCs) were investigated in raw, treated wastewater (both particulate and dissolved phases), and in sludge from a sewage treatment plant (STP) in Athens, Greece. The average concentrations of BTRs, BTHs, NSAIDs and EDCs in raw wastewater ranged between 11 ng L(-1) and 7.27 μg L(-1), while PFCs did not exceed 100 ng L(-1). In dewatered sludge, the average concentrations ranged between 0.8 ng g(-1) dw (perfluorohexanoic acid, PFHxA) and 3895 ng g(-1) dw (nonylphenol, NP). The distribution of emerging contaminants between particulate and dissolved phase was different among the compounds. BTRs and BTHs showed lower solid-liquid distribution coefficients (Kd) than all other compounds. For 9 over the 27 compounds detected in influents, the removal efficiency was higher than 70%, while the others either were removed to a lesser extent or detected at higher concentrations in effluents. Based on this, advanced treatment processes should be applied in the future for achieving adequate emerging contaminants removal in STPs. Regarding removal mechanisms, almost 60% of BTRs and 30 to 75% of BTHs were removed in bioreactors, while the contribution of primary and secondary clarifiers was of minor importance. Sorption to primary sludge was a significant mechanism affecting EDCs fate in STP. © 2013 Elsevier B.V. All rights reserved.

  8. Prioritization of putative metabolite identifications in LC-MS/MS experiments using a computational pipeline.

    Science.gov (United States)

    Zhou, Bin; Xiao, Jun Feng; Ressom, Habtom W

    2013-01-01

    One of the major bottle-necks in current LC-MS-based metabolomic investigations is metabolite identification. An often-used approach is to first look up metabolites from databases through peak mass, followed by verification of the obtained putative identifications using MS/MS data. However, the mass-based search may provide inappropriate putative identifications when the observed peak is from isotopes, fragments, or adducts. In addition, a large fraction of peaks is often left with multiple putative identifications. To differentiate these putative identifications, manual verification of metabolites through comparison between biological samples and authentic compounds is necessary. However, such experiments are laborious, especially when multiple putative identifications are encountered. It is desirable to use computational approaches to obtain more reliable putative identifications and prioritize them before performing experimental verification of the metabolites. In this article, a computational pipeline is proposed to assist metabolite identification with improved metabolome coverage and prioritization capability. Multiple publicly available software tools and databases, along with in-house developed algorithms, are utilized to fully exploit the information acquired from LC-MS/MS experiments. The pipeline is successfully applied to identify metabolites on the basis of LC-MS as well as MS/MS data. Using accurate masses, retention time values, MS/MS spectra, and metabolic pathways/networks, more appropriate putative identifications are retrieved and prioritized to guide subsequent metabolite verification experiments.

  9. The Environmental-Endocrine Basis of Gynandromorphism (Intersex in a Crustacean

    Directory of Open Access Journals (Sweden)

    Allen W. Olmstead, Gerald A. LeBlanc

    2007-01-01

    Full Text Available Commensurate with the decline in many crustacean populations has been an accumulation in reports of sexually ambiguous individuals within these populations. The cause of gynandromorphism or intersex among crustaceans is unknown. We show that gynandromorphism in the branchiopod crustacean Daphnia magna is initiated by the sex-determining hormone methyl farnesoate when levels of the hormone are intermediate between low levels that stimulate the production of broods containing all female offspring and high levels that stimulate the production of broods of all male offspring. The incidence of hormonally-induced gynandromorphism was low (0.14% at the maximum stimulatory hormone concentrations but was significantly increased (46-fold when the animals were hormone-treated at 30oC. Some environmental chemicals also can stimulate the gynandromorphic phenotype as we demonstrated with the insecticide pyriproxyfen. Gynandromorphism occurs due to inadequate signaling of male-sex determination since: a gynandromorphs did not occur in a population that was producing only female offspring; and, b conditions that stimulated gynandromorphism also reduced the incidence of male offspring. We suggest that male sex determination normally occurs prior to the first embryonic cleavage. Elevated temperature may alter the timing of sex determination such that methyl farnesoate signaling occurs after the first embryonic cleavage and bilateral gynandromorphism occurs as a consequence of signaling to only one of the daughter cells. These results demonstrate that environmental factors can cause aberrant sex determination via perturbations in methyl farnesoate signaling.

  10. Integrative rodent models for assessing male reproductive toxicity of environmental endocrine active substances

    Directory of Open Access Journals (Sweden)

    Jacques Auger

    2014-02-01

    Full Text Available In the present review, we first summarize the main benefits, limitations and pitfalls of conventional in vivo approaches to assessing male reproductive structures and functions in rodents in cases of endocrine active substance (EAS exposure from the postulate that they may provide data that can be extrapolated to humans. Then, we briefly present some integrated approaches in rodents we have recently developed at the organism level. We particularly focus on the possible effects and modes of action (MOA of these substances at low doses and in mixtures, real-life conditions and at the organ level, deciphering the precise effects and MOA on the fetal testis. It can be considered that the in vivo experimental EAS exposure of rodents remains the first choice for studies and is a necessary tool (together with the epidemiological approach for understanding the reproductive effects and MOA of EASs, provided the pitfalls and limitations of the rodent models are known and considered. We also provide some evidence that classical rodent models may be refined for studying the multiple consequences of EAS exposure, not only on the reproductive axis but also on various hormonally regulated organs and tissues, among which several are implicated in the complex process of mammalian reproduction. Such models constitute an interesting way of approaching human exposure conditions. Finally, we show that organotypic culture models are powerful complementary tools, especially when focusing on the MOA. All these approaches have contributed in a combinatorial manner to a better understanding of the impact of EAS exposure on human reproduction.

  11. Tropomyosin-1, A Putative Tumor-Suppressor and a Biomarker of Human Breast Cancer

    Science.gov (United States)

    2004-10-01

    cDNA. Lobular carcinoma - 2 A polyclonal pan-TM antibody that recognizes multiple TM Phyllodes tumor - 1 Not determined from the initial pathology...AD Award Number: DAMD17-98-1-8162 TITLE: Tropomyosin-1, A Putative Tumor -Suppressor and a Biomarker of Human Breast Cancer PRINCIPAL INVESTIGATOR...4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Tropomyosin-l, A Putative Tumor -Suppressor and a Biomarker DAMD17-98-1-8162 of Human Breast Cancer 6. A UTHOR

  12. Fluoroquinolone-Resistant Haemophilus parasuis Isolates Exhibit More Putative Virulence Factors than Their Susceptible Counterparts

    OpenAIRE

    Zhang, Qiang; Liu, Jiantao; Yan, Shuxian; Yang, Yujie; Zhang, Anding; Jin, Meilin

    2013-01-01

    The prevalence of 23 putative virulence factors among fluoroquinolone-susceptible and -resistant Haemophilus parasuis isolates was analyzed. Putative hemolysin precursor, fimbrial assembly chaperone, and type I site-specific restriction modification system R subunit genes were more prevalent among fluoroquinolone-resistant H. parasuis isolates than among fluoroquinolone-susceptible H. parasuis isolates. Fluoroquinolone resistance may be associated with an increase in the presence of some viru...

  13. Prevalence and characteristics of Streptococcus pneumoniae "putative serotype 6E" isolates from Asian countries.

    Science.gov (United States)

    Baek, Jin Yang; Park, In Ho; So, Thomas Man-kit; Lalitha, M K; Shimono, Nobuyuki; Yasin, Rohani Md; Carlos, Celia C; Perera, Jennifer; Thamlikitkul, Visanu; Hsueh, Po-Ren; Van, Pham Hung; Shibl, Atef M; Song, Jae-Hoon; Ko, Kwan Soo

    2014-12-01

    The prevalence, antimicrobial susceptibility, and genotypes of Streptococcus pneumoniae “putative serotype 6E” isolates from Asian countries were investigated. A total of 244 S. pneumoniae serogroup 6 isolates obtained from 11 Asian countries were included in this study. Of the 244 serogroup 6 isolates, 101 (41.4%) were typed as "putative serotype 6E," followed by serotypes 6A, 6B, 6C, and 6D (27.0, 20.1, 5.7, and 5.7%, respectively). Multilocus sequence typing revealed that clonal complex (CC) 90, including ST90 and its variants, was the most prevalent clonal group of "putative serotype 6E" isolates (n = 63; 62.4%). CC146 and CC315 were also found frequently in some of the countries. Most of the "putative serotype 6E" isolates showed very high resistance rates against cefuroxime, erythromycin, azithromycin, clarithromycin, clindamycin, and trimethoprim/sulfamethoxazole, probably due to their highly resistant to antimicrobials clone, CC90. Our results indicate that “putative serotype 6E” is prevalent in Asian countries. The clonal dissemination of "putative serotype 6E" isolates was also identified.

  14. Characterization of putative effectors from the cereal cyst nematode Heterodera avenae.

    Science.gov (United States)

    Cui, Jiangkuan; Peng, Huan; Qiao, Fen; Wang, Gaofeng; Huang, Wenkun; Wu, Duqign; Peng, Deliang

    2017-09-20

    Few molecular details of effectors of Heterodera avenae parasitism are known. We performed a high-throughput sequencing analysis of the H. avenae transcriptome at five developmental stages. A total of 82,549 unigenes were ultimately obtained, and 747 transcripts showed best hits to genes putatively encoding carbohydrate-active enzymes in plant parasitic nematodes that play an important role in the invasion process. A total of 1480 unigenes were homologous to known phytonematode effectors, and 63 putative novel effectors were identified in the H. avenae transcriptomes. Twenty-three unigenes were analyzed by qRT-PCR and confirmed to be highly expressed during at least one developmental stage. For in situ hybridization, 17 of the 22 tested putative effectors were specifically expressed and located in the subventral gland cells, and five putative novel effectors were specifically expressed in the dorsal gland. Furthermore, 115 transcripts were found to have putative lethal RNA interference (RNAi) phenotypes. Three target genes with lethal RNAi phenotypes and two of the four tested putative effectors were associated with a decrease in the number of cysts through in vitro RNAi technology. These transcriptomic data lay a foundation for further studies of interactions of H. avenae with cereal and H. avenae parasitic control.

  15. Plasmatic concentration of organochlorine lindane acts as metabolic disruptors in HepG2 liver cell line by inducing mitochondrial disorder

    Energy Technology Data Exchange (ETDEWEB)

    Benarbia, Mohammed el Amine [LUNAM Université, Angers (France); Inserm 1063, Angers (France); Macherel, David [LUNAM Université, Angers (France); UMR 1345 IRHS, Angers (France); Faure, Sébastien; Jacques, Caroline; Andriantsitohaina, Ramaroson [LUNAM Université, Angers (France); Inserm 1063, Angers (France); Malthièry, Yves, E-mail: yves.malthiery@univ-angers.fr [LUNAM Université, Angers (France); Inserm 1063, Angers (France)

    2013-10-15

    Lindane (LD) is a persistent environmental pollutant that has been the subject of several toxicological studies. However, concentrations used in most of the reported studies were relatively higher than those found in the blood of the contaminated area residents and effects of low concentrations remain poorly investigated. Moreover, effects on cell metabolism and mitochondrial function of exposure to LD have received little attention. This study was designed to explore the effects of low concentrations of LD on cellular metabolism and mitochondrial function, using the hepatocarcinoma cell line HepG2. Cells were exposed to LD for 24, 48 and 72 h and different parameters linked with mitochondrial regulation and energy metabolism were analyzed. Despite having any impact on cellular viability, exposure to LD at plasmatic concentrations led to an increase of maximal respiratory capacity, complex I activity, intracellular ATP and NO release but decreased uncoupled respiration to ATP synthesis and medium lactate levels. In addition, LD exposure resulted in the upregulation of mitochondrial biogenesis genes. We suggest that, at plasmatic concentrations, LD acts as a metabolic disruptor through impaired mitochondrial function and regulation with an impact on cellular energetic metabolism. In addition, we propose that a cellular assay based on the analysis of mitochondria function, such as described here for LD, may be applicable for larger studies on the effects of low concentrations of xenobiotics, because of the exquisite sensitivity of this organelle. - Highlights: Our data clearly demonstrated in HepG2 cells that exposure at plasmatic low concentrations of LD were able to: • Impair mitochondrial function • Caused alteration on nucleo-mitochondrial cross-talk • Increase nitric oxide release and protein nitration • Impair cellular energetic metabolism and lipid accumulation.

  16. Development of partial life-cycle experiments to assess the effects of endocrine disruptors on the freshwater gastropod Lymnaea stagnalis: a case-study with vinclozolin.

    Science.gov (United States)

    Ducrot, Virginie; Teixeira-Alves, Mickaël; Lopes, Christelle; Delignette-Muller, Marie-Laure; Charles, Sandrine; Lagadic, Laurent

    2010-10-01

    Long-term effects of endocrine disruptors (EDs) on aquatic invertebrates remain difficult to assess, mainly due to the lack of appropriate sensitive toxicity test methods and relevant data analysis procedures. This study aimed at identifying windows of sensitivity to EDs along the life-cycle of the freshwater snail Lymnaea stagnalis, a candidate species for the development of forthcoming test guidelines. Juveniles, sub-adults, young adults and adults were exposed for 21 days to the fungicide vinclozolin (VZ). Survival, growth, onset of reproduction, fertility and fecundity were monitored weekly. Data were analyzed using standard statistical analysis procedures and mixed-effect models. No deleterious effect on survival and growth occurred in snails exposed to VZ at environmentally relevant concentrations. A significant impairment of the male function occurred in young adults, leading to infertility at concentrations exceeding 0.025 μg/L. Furthermore, fecundity was impaired in adults exposed to concentrations exceeding 25 μg/L. Biological responses depended on VZ concentration, exposure duration and on their interaction, leading to complex response patterns. The use of a standard statistical approach to analyze those data led to underestimation of VZ effects on reproduction, whereas effects could reliably be analyzed by mixed-effect models. L. stagnalis may be among the most sensitive invertebrate species to VZ, a 21-day reproduction test allowing the detection of deleterious effects at environmentally relevant concentrations of the fungicide. These results thus reinforce the relevance of L. stagnalis as a good candidate species for the development of guidelines devoted to the risk assessment of EDs.

  17. Evaluation of magnetic nanoparticles to serve as solid-phase extraction sorbents for the determination of endocrine disruptors in milk samples by gas chromatography mass spectrometry.

    Science.gov (United States)

    Synaridou, Maria-Evangelia S; Sakkas, Vasilios A; Stalikas, Constantine D; Albanis, Triantafyllos A

    2014-06-27

    A rapid magnetic solid-phase extraction (MSPE) is proposed based on C18-functionalized magnetic silica nanoparticles as sorbents, for the determination of endocrine disruptors - 20 organochlorine pesticides and 6 polychlorinated biphenyls - in milk samples. Magnetic nanoparticles are characterized by several techniques, such as Scanning Electron Microscopy, X-Ray diffraction, Brunauer-Emmett-Teller and Fourier transform-infrared. The MSPE is performed by dispersion of the Fe3O4@SiO2@C18 nanoparticles in milk samples with sonication, after protein precipitation. Then, the sorbent is collected by applying an external magnetic field and the analytes are desorbed by n-hexane. Several parameters affecting the extraction efficiency of target analytes by the magnetic nanoparticles are investigated, including washing and elution solvents, amount of sorbents, time of extraction and elution, sample and elution solvent volume. The proposed method is optimized by means of experimental design and response surface methodology. When coupled with gas chromatography-mass spectrometry detection and under optimum extraction conditions, average recoveries of target analytes are found to be in the range of 79% to 116%. The proposed MSPE-GC-MS analytical method has a linear calibration curve for all target analytes with coefficients of determination to range from 0.9950 to 0.9999. The limits of quantification are found to be between 0.2 and 1μg/L ensuring compliance with the maximum residue limits established by European Commission and Codex Alimentarius, for OCPs and PCBs residues in milk. The proposed method is applied to the determination of target analytes in milk samples from local markets.

  18. Inhibition of the functional interplay between endoplasmic reticulum (ER) oxidoreduclin-1α (Ero1α) and protein-disulfide isomerase (PDI) by the endocrine disruptor bisphenol A.

    Science.gov (United States)

    Okumura, Masaki; Kadokura, Hiroshi; Hashimoto, Shoko; Yutani, Katsuhide; Kanemura, Shingo; Hikima, Takaaki; Hidaka, Yuji; Ito, Len; Shiba, Kohei; Masui, Shoji; Imai, Daiki; Imaoka, Susumu; Yamaguchi, Hiroshi; Inaba, Kenji

    2014-09-26

    Bisphenol A (BPA) is an endocrine disruptor that may have adverse effects on human health. We recently isolated protein-disulfide isomerase (PDI) as a BPA-binding protein from rat brain homogenates and found that BPA markedly inhibited PDI activity. To elucidate mechanisms of this inhibition, detailed structural, biophysical, and functional analyses of PDI were performed in the presence of BPA. BPA binding to PDI induced significant rearrangement of the N-terminal thioredoxin domain of PDI, resulting in more compact overall structure. This conformational change led to closure of the substrate-binding pocket in b' domain, preventing PDI from binding to unfolded proteins. The b' domain also plays an essential role in the interplay between PDI and ER oxidoreduclin 1α (Ero1α), a flavoenzyme responsible for reoxidation of PDI. We show that BPA inhibited Ero1α-catalyzed PDI oxidation presumably by inhibiting the interaction between the b' domain of PDI and Ero1α; the phenol groups of BPA probably compete with a highly conserved tryptophan residue, located in the protruding β-hairpin of Ero1α, for binding to PDI. Consistently, BPA slowed down the reoxidation of PDI and caused the reduction of PDI in HeLa cells, indicating that BPA has a great impact on the redox homeostasis of PDI within cells. However, BPA had no effect on the interaction between PDI and peroxiredoxin-4 (Prx4), another PDI family oxidase, suggesting that the interaction between Prx4 and PDI is different from that of Ero1α and PDI. These results indicate that BPA, a widely distributed and potentially harmful chemical, inhibits Ero1-PDI-mediated disulfide bond formation.

  19. Microsomal cytochrome P450-3A4 (CYP3A4) nanobiosensor for the determination of 2,4-dichlorophenol-An endocrine disruptor compound

    Energy Technology Data Exchange (ETDEWEB)

    Hendricks, Nicolette R.; Waryo, Tesfaye T.; Arotiba, Omotayo; Jahed, Nazeem; Baker, Priscilla G.L. [SensorLab, Department of Chemistry, University of Western Cape, Moderddam Road, Bellville, Cape Town 7535 (South Africa); Iwuoha, Emmanuel I. [SensorLab, Department of Chemistry, University of Western Cape, Moderddam Road, Bellville, Cape Town 7535 (South Africa)], E-mail: eiwuoha@uwc.ac.za

    2009-02-28

    Cytochrome P450-3A4 (CYP3A4) is a monooxygenase enzyme that plays a major role in the detoxification of bioactive compounds and hydrophobic xenobiotics (e.g. medicines, drugs, environmental pollutants, food supplements and steroids). Physiologically the monooxygenation reactions of this class II, microsomal, b-type heme enzyme, usually requires cytochrome P450 reductase, NADPH. A novel CYP3A4 biosensor system that essentially simplified the enzymatic redox processes by allowing electron transfer between the electrode and the enzyme redox centre to occur, without any need for the physiological redox partners, was developed for the detection of 2,4-dichlorophenol (2,4-DCP), a priority environmental pollutant and an endocrine disruptor. The biosensor, GC/Naf-Co(Sep){sup 3+}/CYP3A4/Naf, was constructed by encapsulating CYP3A4 in a Nafion-cobalt (III) sepulchrate (Naf-Co(Sep){sup 3+}) composite film on a glassy carbon (GC) electrode. The responses of the biosensor to 2,4-dichlorophenol, erythromycin (CYP3A4 native substrate) and ketoconazole (CYP 3A4 natural inhibitor) were studied by cyclic and square wave voltammetric techniques. The detection limit (DL) of the biosensor for 2,4-dichlorophenol was 0.043 {mu}g L{sup -1}, which is by an order of magnitude lower than the EU limit (0.3 {mu}g L{sup -1}) for any pesticide compound in ground water. The biosensor's DL is lower than the U.S. Environmental Protection Agency's drinking water equivalent level (DWEL) value for 2,4-DCP, which is 2 {mu}g L{sup -1}.

  20. 环境内分泌干扰物对睾丸间质细胞功能的影响%The Effects of Endocrine Disruptors on Leydig Cell Function

    Institute of Scientific and Technical Information of China (English)

    杨炜蓉; 王怡; 孙燕

    2012-01-01

    近年来,环境内分泌干扰物(environmental endocrine disrupting chemicals,EDCs)对雄性动物的生殖毒性引起了广泛的关注.大量资料显示EDCs可引起雄性生殖发育障碍,如隐睾、尿道下裂、睾丸癌、精液品质不良等.作者就几种典型的EDCs对睾丸间质细胞分泌睾酮的影响机制作一综述.%During the past decades, the effects of endocrine disrupting compounds (EDCs) on animals and humans has caused wide attention. A large body of information have demonstrated that EDCs can cause the male reproductive developmental disorders such as cryptorchidism, hypospadias, testicular cancer, as well as decreased quality of semen. The aim of this paper is to give an overview of the published literature on the effects of EDCs on leydig cell function and steroidogenesis with particular focus on male reproduction and fertility.

  1. Diversity of secondary endosymbionts among different putative species of the whitefly Bemisia tabaci.

    Science.gov (United States)

    Bing, Xiao-Li; Ruan, Yong-Ming; Rao, Qiong; Wang, Xiao-Wei; Liu, Shu-Sheng

    2013-04-01

    Endosymbionts are important components of arthropod biology. The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic species complex composed of ≥ 28 putative species. In addition to the primary endosymbiont Portiera aleyrodidarum, six secondary endosymbionts (S-endosymbionts), Hamiltonella, Rickettsia, Wolbachia, Cardinium, Arsenophonus and Fritschea, have been identified in B. tabaci thus far. Here, we tested five of the six S-endosymbiont lineages (excluding Fritschea) from 340 whitely individuals representing six putative species from China. Hamiltonella was detected only in the two exotic invaders, Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED). Rickettsia was absent in Asia II 1 and MED, scarce in Asia II 3 (13%), but abundant in Asia II 7 (63.2%), China 1 (84.7%) and MEAM1 (100%). Wolbachia, Cardinium and Arsenophonus were absent in the invasive MEAM1 and MED but mostly abundant in the native putative species. Furthermore, phylogenetic analyses revealed that some S-endosymbionts have several clades and different B. tabaci putative species can harbor different clades of a given S-endosymbiont, demonstrating further the complexity of S-endosymbionts in B. tabaci. All together, our results demonstrate the variation and diversity of S-endosymbionts in different putative species of B. tabaci, especially between invasive and native whiteflies.

  2. Diversity of secondary endosymbionts among different putative species of the whitefly Bemisia tabaci

    Institute of Scientific and Technical Information of China (English)

    Xiao-Li Bing; Yong-Ming Ruan; Qiong Rao; Xiao-Wei Wang; Shu-Sheng Liu

    2013-01-01

    Endosymbionts are important components of arthropod biology.The whitefly Bemisia tabaci (Gennadius) (Hemiptera:Aleyrodidae) is a cryptic species complex composed of≥28 putative species.In addition to the primary endosymbiont Portiera aleyrodidarum,six secondary endosymbionts (S-endosymbionts),Hamiltonella,Rickettsia,Wolbachia,Cardinium,Arsenophonus and Fritschea,have been identified in B.tabaci thus far.Here,we tested five of the six S-endosymbiont lineages (excluding Fritschea) from 340 whitely individuals representing six putative species from China.Hamiltonella was detected only in the two exotic invaders,Middle East-Asia Minor 1 (MEAM 1) and Mediterranean (MED).Rickettsia was absent in Asia Ⅱ 1 and MED,scarce in Asia Ⅱ 3 (13%),but abundant in Asia Ⅱ 7 (63.2%),China 1 (84.7%) and MEAM1 (100%).Wolbachia,Cardinium and Arsenophonus were absent in the invasive MEAM 1 and MED but mostly abundant in the native putative species.Furthermore,phylogenetic analyses revealed that some S-endosymbionts have several clades and different B.tabaci putative species can harbor different clades of a given S-endosymbiont,demonstrating further the complexity of S-endosymbionts in B.tabaci.All together,our results demonstrate the variation and diversity of S-endosymbionts in different putative species ofB.tabaci,especially between invasive and native whiteflies.

  3. Eliciting maltreated and nonmaltreated children's transgression disclosures: narrative practice rapport building and a putative confession.

    Science.gov (United States)

    Lyon, Thomas D; Wandrey, Lindsay; Ahern, Elizabeth; Licht, Robyn; Sim, Megan P Y; Quas, Jodi A

    2014-01-01

    This study tested the effects of narrative practice rapport building (asking open-ended questions about a neutral event) and a putative confession (telling the child an adult "told me everything that happened and he wants you to tell the truth") on 4- to 9-year-old maltreated and nonmaltreated children's reports of an interaction with a stranger who asked them to keep toy breakage a secret (n = 264). Only one third of children who received no interview manipulations disclosed breakage; in response to a putative confession, one half disclosed. Narrative practice rapport building did not affect the likelihood of disclosure. Maltreated children and nonmaltreated children responded similarly to the manipulations. Neither narrative practice rapport building nor a putative confession increased false reports.

  4. Molecular diagnosis of putative Stargardt disease by capture next generation sequencing.

    Science.gov (United States)

    Zhang, Xiao; Ge, Xianglian; Shi, Wei; Huang, Ping; Min, Qingjie; Li, Minghan; Yu, Xinping; Wu, Yaming; Zhao, Guangyu; Tong, Yi; Jin, Zi-Bing; Qu, Jia; Gu, Feng

    2014-01-01

    Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis.

  5. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro

    Institute of Scientific and Technical Information of China (English)

    GAO Nan; CUI GuangHui; WANG ZhiChong; HUANG Bing; GE Jian; LU Rong; ZHANG KeFei; FAN ZhiGang; LU Li; PENG Zhan

    2007-01-01

    Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epidermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immunohistology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epidermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being cocultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

  6. CLONING, SEQUENCE ANALYSIS, AND CHARACTERIZATION OF PUTATIVE BETA-LACTAMASE OF STENOTROPHOMONAS MALTOPHILIA

    Directory of Open Access Journals (Sweden)

    Chong Seng Shueh

    2012-10-01

    Full Text Available The main objective of current study was to explore the function of chromosomal putative beta-lactamase gene (smlt 0115 in clinical Stenotrophomonas maltophilia. Antibiotic susceptibility test (AST screening for current antimicrobial drugs was done and Minimum Inhibitory Concentration (MIC level towards beta-lactams was determined by E-test. Putative beta-lactamase gene of S. maltophilia was amplified via PCR, with specific primers, then cloned into pET-15 expression plasmid and transformed into Escherichia coli BL21. The gene was sequenced and analyzed. The expressed protein was purified by affinity chromatography and the kinetic assay was performed. S. maltophilia ATCC 13637 was included in this experiment. Besides, a hospital strain which exhibited resistant to a series of beta-lactams including cefepime was identified via AST and MIC, hence it was named as S2 strain and was considered in this study. Sequencing result showed that putative beta-lactamase gene obtained from ATCC 13637 and S2 strains were predicted to have cephalosporinase activity by National Center for Biotechnology Information (NCBI blast program. Differences in the sequences of both ATCC 13637 and S2 strains were found via ClustalW alignment software. Kinetic assay proved a cephalosporinase characteristic produced by E. coli BL21 clone that overexpressed the putative beta-lactamase gene cloned under the control of an external promoter. Yet, expressed protein purified from S2 strain had high catalytic activity against beta-lactam antibiotics which was 14-fold higher than expressed protein purified from ATCC 13637 strain. This study represents the characterization analysis of putative beta-lactamase gene (smlt 0115 of S. maltophilia. The presence of the respective gene in the chromosome of S. maltophilia suggested that putative beta-lactamase gene (smlt 0115 of S. maltophilia plays a role in beta-lactamase resistance.

  7. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epi-dermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immuno-histology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epi-dermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being co-cultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

  8. Disruptores endocrinos. El caso particular de los xenobióticos estrogénicos. I Estrógenos naturales Endocrine disrupters. The case of estrogen xenobiotics

    Directory of Open Access Journals (Sweden)

    P. Martín Olmedo

    2001-06-01

    Full Text Available El interés de la comunidad científica por la exposición humana a sustancias químicas capaces de alterar el equilibrio hormonal -disruptores endocrinos— ha crecido al mismo tiempo que se han presentado pruebas de las con- secuencias de la exposición a estas sustancias sobre poblaciones animales. Como ha ocurrido en ocasiones anteriores, los datos observacionales en poblaciones animales han sido lo suficientemente sugerentes como para inducir entre los clínicos cierto grado de preocupación, por si estuvieran produciéndose efectos similares en poblaciones humanas. Si bien es cierto que los datos sobre afectación de poblaciones animales se generan mas fácilmente de forma poblacional que individual, también es verdad que las observaciones individuales en la clínica junto con algunos pocos estudios epidemiológicos han demostrado cierto paralelismo. De hecho, modelos in vitro e in vivo han servido para asignar capacidad mimetizadora hormonal a muchos compuestos químicos, tanto naturales como de producción humana, para los cuales existe riesgo de exposición. En este trabajo se revisan las premisas conceptuales sobre disrupción endocrina y como se llegó a acuñar el término.Interest of the scientific community in chemical substances able to alter the hormone balance –endocrine disrupters- has grown with increasing evidence of the consequences for animal populations of exposure to these substances. As has occurred on previous occasions, observational data on animal populations have been sufficiently suggestive to cause concerns among clinicians that similar effects may be produced in human populations. Although data on the effects on populations of animals are more easily generated than those on individuals, clinical observations on human individuals alongside the few existing epidemiological studies have shown a certain parallelism. Indeed, in vitro and in vivo models have been able to designate many chemical compounds as hormonal

  9. An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors.

    Science.gov (United States)

    Gabb, Henry A; Blake, Catherine

    2016-08-01

    -associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155-1165; http://dx.doi.org/10.1289/ehp.1510529.

  10. An Informatics Approach to Evaluating Combined Chemical Exposures from Consumer Products: A Case Study of Asthma-Associated Chemicals and Potential Endocrine Disruptors

    Science.gov (United States)

    Gabb, Henry A.; Blake, Catherine

    2016-01-01

    exposures from consumer products: a case study of asthma-associated chemicals and potential endocrine disruptors. Environ Health Perspect 124:1155–1165; http://dx.doi.org/10.1289/ehp.1510529 PMID:26955064

  11. Detection of putative new mutacins by bioinformatic analysis using available web tools

    Directory of Open Access Journals (Sweden)

    Nicolas Guillaume G

    2011-07-01

    Full Text Available Abstract In order to characterise new bacteriocins produced by Streptococcus mutans we perform a complete bioinformatic analyses by scanning the genome sequence of strains UA159 and NN2025. By searching in the adjacent genomic context of the two-component signal transduction system we predicted the existence of many putative new bacteriocins' maturation pathways and some of them were only exclusive to a group of Streptococcus. Computational genomic and proteomic analysis combined to predictive functionnal analysis represent an alternative way for rapid identification of new putative bacteriocins as well as new potential antimicrobial drugs compared to the more traditional methods of drugs discovery using antagonism tests.

  12. Occurrence of Putative Pathogenicity Islands in Enterococci from Distinct Species and of Differing Origins▿ †

    OpenAIRE

    Semedo-Lemsaddek, Teresa; Barreto-Crespo, Maria Teresa; Tenreiro, Rogério

    2009-01-01

    Enterococci isolated from ewe's milk and cheese, clinical isolates of human and veterinary origins, and reference strains obtained from culture collections were screened for the occurrence of putative pathogenicity island (PAIs). Results obtained after PCR amplification and hybridization point toward PAI dissemination among enterococci of diverse origins (food/clinical) and species (Enterococcus faecalis/non-E. faecalis).

  13. Cloning and characterization of prunus serotina AGAMOUS, a putative flower homeotic gene

    Science.gov (United States)

    Xiaomei Liu; Joseph Anderson; Paula Pijut

    2010-01-01

    Members of the AGAMOUS subfamily of MADS-box transcription factors play an important role in regulating the development of reproductive organs in flowering plants. To help understand the mechanism of floral development in black cherry (Prunus serotina), PsAG (a putative flower homeotic identity gene) was isolated...

  14. A new putative alphapartitivirus recovered from the powdery mildew fungus Erysiphe palczewskii.

    Science.gov (United States)

    Xiong, Guihong; Qiu, Ping; Li, Cong; Chen, Zhuo; Islam, Saif Ul; Fang, Shouguo; Wu, Zujian; Zhang, Songbai; Du, Zhenguo

    2017-02-27

    Two double-stranded RNAs (dsRNA) likely representing the genome of a novel alphapartitivirus which we provisionally named Erysiphe palczewskii alphapartitivirus 1 (EpV1) were recovered from the powdery mildew fungus E. palczewskii infecting Sophora japonica in Jingzhou, Hubei province of China. The two dsRNAs, 1955 (dsRNA1) and 1917 (dsRNA2) bp in size, respectively, each contains a single open reading frame (ORF) encoding a 585- and 528-aa protein, respectively. The 585-aa protein contains a conserved RNA-dependent RNA polymerase (RdRp) domain and shows significant homology to RdRps of approved or putative partitiviruses, particularly those belonging to the genus Alphapartitivirus. However, it shares an aa sequence identity lower than 80% with its closest relative, the RdRp of the putative alphapartitivirus Grapevine partitivirus, and lower than 60% with the RdRps of other partitiviruses. In a phylogenetic tree constructed with RdRp aa sequences of selected partitiviruses, the putative virus EpV1 clustered with Grapevine partitivirus and formed a well-supported monophyletic clade with known or putative alphapartitiviruses.

  15. A rapid approach to evaluate putative nursery sites for penaeid prawns

    Science.gov (United States)

    Taylor, Matthew D.; Smith, James A.; Boys, Craig A.; Whitney, Hannah

    2016-08-01

    Identifying nursery habitats for an aquatic species generally requires tracing adult individuals back through time and space to the area or habitat in which they developed as juveniles. We develop and trial a study design and analytical approach to evaluate the suitability of using stable isotopes to trace emigrating prawns to putative nursery sites, and evaluate assumptions inherent in the application of the approach using two penaeid species with Type-II life cycles: Penaeus (Melicertus) plebejus and Metapenaeus macleayi. Prawns were collected in putative nursery sites within the Hunter River, Australia, and analysed as composite samples of 6 individuals to provide habitat-specific isotopic signatures. Prawns emigrating from the mouth of the river were used as a proxy for individuals recruiting to the adult population, and assigned to putative nursery sites using a probabilistic mixing model and a simple, distance-based approach. Bivariate (δ15N and δ13C) isotopic data was sufficient to distinguish prawns from different putative nursery sites, and isotopic composition correlated closely with salinity. Approximately 90% of emigrating prawns collected could be assigned to these sites using bivariate isotopic data, and both analytical approaches gave similar results. The design developed here is broadly applicable to a suite of penaeid species, but its application will be most powerful when sampling is also aimed at understanding nursery function by simultaneous monitoring of size structure/growth, density, and trophic relationships within nursery habitats.

  16. Mapping the flow of information within the putative mirror neuron system during gesture observation

    NARCIS (Netherlands)

    Schippers, Marleen B.; Keysers, Christian

    2011-01-01

    The putative mirror neuron system may either function as a strict feed-forward system or as a dynamic control system. A strict feed-forward system would predict that action observation leads to a predominantly temporal -> parietal -> premotor flow of information in which a visual representation is t

  17. Complete Genome Sequence of a Putative Densovirus of the Asian Citrus Psyllid, Diaphorina citri.

    Science.gov (United States)

    Nigg, Jared C; Nouri, Shahideh; Falk, Bryce W

    2016-07-28

    Here, we report the complete genome sequence of a putative densovirus of the Asian citrus psyllid, Diaphorina citri Diaphorina citri densovirus (DcDNV) was originally identified through metagenomics, and here, we obtained the complete nucleotide sequence using PCR-based approaches. Phylogenetic analysis places DcDNV between viruses of the Ambidensovirus and Iteradensovirus genera.

  18. Expression of putative expansin genes in phylloxera (Daktulosphaira vitifoliae Fitch) induced root galls of Vitis spp.

    Science.gov (United States)

    Lawo, N C; Griesser, M; Forneck, A

    Grape phylloxera (Daktulosphaira vitifoliae Fitch) is a serious global pest in viticulture. The insects are sedentary feeders and require a gall to feed and reproduce. The insects induce their feeding site within the meristematic zone of the root tip, where they stay attached, feeding both intra- and intercellularly, and causing damage by reducing plant vigour. Several changes in cell structure and composition, including increased cell division and tissue swelling close to the feeding site, cause an organoid gall called a nodosity to develop. Because alpha expansin genes are involved in cell enlargement and cell wall loosening in many plant tissues it may be anticipated that they are also involved in nodosity formation. To identify expansin genes in Vitis vinifera cv. Pinot noir, we mined for orthologues genes in a comparative analysis. Eleven putative expansin genes were identified and shown to be present in the rootstock Teleki 5C (V. berlandieri Planch. x V. riparia Michx.) using specific PCR followed by DNA sequencing. Expression analysis of young and mature nodosities and uninfested root tips were conducted via quantitative real time PCR (qRT-PCR). Up-regulation was measured for three putative expansin genes (VvEXPA15, -A17 and partly -A20) or down-regulation for three other putative genes (VvEXPA7, -A12, -A20) in nodosities. The present study clearly shows the involvement of putative expansin genes in the phylloxera-root interaction.

  19. A review on the putative association between beta-blockers and depression

    NARCIS (Netherlands)

    Verbeek, D.E.; van Riezen, J.; de Boer, R.A.; van Melle, J.P.; de Jonge, P.

    Several kinds of systematic studies have been conducted verifying the putative association between beta-blockers and depressive symptoms. However, many of these studies had important limitations in their design. In most of the studies, no effect of beta-blockers on depressive symptoms was seen.

  20. A review on the putative association between beta-blockers and depression

    NARCIS (Netherlands)

    Verbeek, D.E.; van Riezen, J.; de Boer, R.A.; van Melle, J.P.; de Jonge, P.

    2011-01-01

    Several kinds of systematic studies have been conducted verifying the putative association between beta-blockers and depressive symptoms. However, many of these studies had important limitations in their design. In most of the studies, no effect of beta-blockers on depressive symptoms was seen. Beca

  1. DETERMINATION OF ROCURONIUM AND ITS PUTATIVE METABOLITES IN BODY-FLUIDS AND TISSUE-HOMOGENATES

    NARCIS (Netherlands)

    KLEEF, UW; PROOST, JH; ROGGEVELD, J

    1993-01-01

    A sensitive and selective HPLC method was developed for the quantification of the neuromuscular blocking agent rocuronium and its putative metabolites (the 17-desacetyl derivative and the N-desallyl derivative of rocuronium) in plasma, urine, bile, tissue homogenates and stoma fluid. Samples were pr

  2. Search strings for the study of putative occupational determinants of disease

    NARCIS (Netherlands)

    S. Mattioli; F. Zanardi; A. Baldasseroni; F. Schaafsma; R.M.T. Cooke; G. Mancini; M. Fierro; C. Santangelo; A. Farioli; S. Fucksia; S. Curti; F.S. Violante; J. Verbeek

    2010-01-01

    Objective To identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of conditions not generally considered to be work related. Methods Based on MeSH definitions and expert knowledge, we selected as candidate search terms the four MeSH terms desc

  3. Search strings for the study of putative occupational determinants of disease

    NARCIS (Netherlands)

    Mattioli, S.; Zanardi, F.; Baldasseroni, A.; Schaafsma, F.; Cooke, R.M.T.; Mancini, G.; Fierro, M.; Santangelo, C.; Farioli, A.; Fucksia, S.; Curti, S.; Violante, F.S.; Verbeek, J.

    2010-01-01

    Objective To identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of conditions not generally considered to be work related. Methods Based on MeSH definitions and expert knowledge, we selected as candidate search terms the four MeSH terms

  4. Isolation of Bartonella quintana from a Woman and a Cat following Putative Bite Transmission▿

    OpenAIRE

    Breitschwerdt, Edward B; Maggi, Ricardo G; Sigmon, Betsy; Nicholson, William L.

    2006-01-01

    We report here the detection of Bartonella quintana, after putative bite transmission, in pre-enrichment blood cultures from a woman and from two feral barn cats. Prospective molecular epidemiological studies are necessary to characterize the risk of human Bartonella quintana infection following cat bites.

  5. Isolation and characterization of 17 different genes encoding putative endopolygalacturonase genes from Rhizopus oryzae

    Science.gov (United States)

    Polygalacturonase enzymes are a valuable aid in the retting of flax for production of linens and, more recently, production of biofuels from citrus wastes. In a search of the recently sequenced Rhizopus oryzae strain 99-880 genome database, 18 putative endopolygalacturonase genes were identified, w...

  6. 农村环境中内分泌干扰物的现状、危害及处理%The Status, Hazards and Handling of Endocrine Disruptors in the Rural Environment

    Institute of Scientific and Technical Information of China (English)

    吴二社; 张松林; 刘焕萍; 刘在平; 卢强

    2011-01-01

    农村环境中大量使用的化肥、农药、防腐剂、添加剂、洗涤剂、激素类药物等,很多属于内分泌干扰物,并且还是持久性污染物,其显著及潜在的危害很大.目前的研究还只是集中于浓度较高时,单种内分泌干扰物对环境和生态所造成的危害方面.而在农村环境中的这些内分泌干扰物(或称类激素物质)浓度却往往比较低、成分复杂、存在范围广,当前还研究较少.由于其中有些物质存在协同效应,在低剂量时既能够表现出毒理学效应,因此其危害不容忽视.笔者就其来源、存在状态、危害和处理措施等方面进行了较为深入地研究和总结,旨在引起对该领域研究和管理的重视.%A large number of chemical fertilizers, pesticide, preservative, additive, detergent, hormone medicine, etc. used massively in rural environment, a lot of endocrine are still permanent pollutant, their significant and potentially very harmful. The current study focused only on high concentration of endocrine disruptors on environmental and ecological hazards caused. But the endocrine disruptors (or called class hormone substance) where in the rural environment, which concentrations are lower, and are often complicated ingredients, and existence range large, which study is less in the current. Because of some material existing synergies effect at lower doses, can either show toxicology effect, so the harm can not allow to be ignored. This article is about the source, state and processing measure of the endocrine disruptors in the rural environment,which carries on to be comparatively deeply researched and summaried, aiming at causing it to research of this domain and attention of management.

  7. Endocrine disruptors targeting ERbeta function.

    Science.gov (United States)

    Swedenborg, E; Pongratz, I; Gustafsson, J-A

    2010-04-01

    Endocrine disruptive chemicals (EDCs) circulating in the environment constitute a risk to ecosystems, wildlife and human health. Oestrogen receptor (ER) alpha and beta are targeted by various kinds of EDCs but the molecular mechanisms and long-term consequences of exposure are largely unknown. Some biological effects of EDCs are mediated by the aryl hydrocarbon receptor (AhR), which is a key player in the cellular defence against xenobiotic substances. Adding complexity to the picture, there is also accumulating evidence that AhR-ER pathways have an intricate interplay at multiple levels. In this review, we discuss some EDCs that affect the oestrogen pathway by targeting ERbeta. Furthermore, we describe some effects of AhR activities on the oestrogen system. Mechanisms as well as potential adverse effects on human health are discussed.

  8. [Contamination, endocrine disruptors and cancer].

    Science.gov (United States)

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-03-01

    Since the mid-twentieth century, many species, very different from each other and located in all areas and comers of the planet, began presenting various alterations, many of which suggested to be related to endocrine disorders. Research has shown that such alterations were caused by exposure to various chemical contaminants that could affect the health and cause serious illnesses. Among them stands a diverse and large group of compounds, with very different chemical structures, capable of altering the hormonal balance, act at very low doses and with different mechanisms of action, that are called "endocrine disrupting chemicals". When released into the environment or as part of objects, food or medicines, constitute a major risk to animals and humans, which produces not only endocrine dysfunctions but also different cancers, which include the most common types. Despite the importance and significance of the impact of these compounds, they are not sufficiently known or understood, so the aim of this review is to show their origin and impact in the field of human health, highlighting their role as inducers of cancer, which has led to multiple clinical and biological investigations.

  9. Endocrine disruptors and congenital anomalies

    Directory of Open Access Journals (Sweden)

    Mônica Rittler

    2002-04-01

    Full Text Available The specialized literature was reviewed concerning the suspected increasing secular trends in the frequency of female births, male genital congenital anomalies, abnormal sperm counts, and testicular cancer. Although no risk factors could be identified yet, the observed sex ratio decline during the last decades has been considered to be an effect of certain pollutants on normal hormone activity, and human reproductive development. Reported increasing trends in the frequencies of hypospadias and cryptorchidism are very difficult to be interpreted due to the large variability in the registered frequency of these malformations due to operational as well as biological reasons.

  10. 职业性内分泌干扰物对职业人群的生殖危害%Reproductive Hazards of Occupational Endocrine Disruptors in Workers

    Institute of Scientific and Technical Information of China (English)

    林向华; 王绵珍; 王治明; 吴德生

    2002-01-01

    @@ 环境中持续存在的可干扰野生动物和人类内分泌系统结构和功能,并产生不良效应的化学物,称为内分泌干扰物(endocrine disruptors,EDs).环境雌激素(environmental estrogents)是具有雌激素样活性,可模拟内源性雌激素的生理作用,或具有拮抗雄激素效应的一类外源性化学物质.环境雌激素是内分泌干扰物中的一大类,它们可对机体产生不良影响,干扰内分泌系统,影响生殖和发育,影响神经系统,破坏免疫系统功能以及诱导肿瘤发生.近年来,不断报道野生动物和人类生殖发育异常现象,学者们推测,环境雌激素及其他内分泌干扰物是造成生殖异常的共同原因[1~3].目前,关于内分泌干扰物和环境雌激素对生殖系统的影响研究已成为国际性热点问题.内分泌干扰物所含种类较多,其分类是一个复杂的问题.1997年美国环保局根据动植物生态、人群流行病学调查和体内、外实验研究结果,将人和动物内分泌干扰相关化学物划分为:已确认的内分泌干扰物、可能的内分泌干扰物和可疑的内分泌干扰物3类[4].根据近年发表的有关论著,笔者认为在职业领域可能存在7类内分泌干扰物:(1)邻苯二甲酸酯;(2)农药;(3)酚类;(4)有机溶剂;(5)金属;(6)高分子化合物单体;(7)抗癌药物.现就上述可能存在的7类内分泌干扰物对职业人群的生殖影响进行综述.

  11. Enantioselective metabolism of the endocrine disruptor pesticide methoxychlor by human cytochromes P450 (P450s): major differences in selective enantiomer formation by various P450 isoforms.

    Science.gov (United States)

    Hu, Yiding; Kupfer, David

    2002-12-01

    Methoxychlor, a currently used pesticide that in mammals elicits proestrogenic/estrogenic activity and reproductive toxicity, has been classified as a prototype endocrine disruptor. Methoxychlor is prochiral, and its metabolites 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane (mono-OH-M); 1,1,1-trichloro- 2-(4-methoxyphenyl)-2-(3, 4-dihydroxyphenyl)ethane (catechol-M); and 1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(3, 4-dihydroxyphenyl)ethane (tris-OH-M) are chiral; whereas 1,1,1-trichloro-2, 2-bis(4-hydroxyphenyl)ethane (bis-OH-M) is achiral. These metabolites are formed during methoxychlor incubation with liver microsomes or recombinant cytochrome p450s (rp450s). Since methoxychlor-metabolite enantiomers may have different estrogenic/antiestrogenic/antiandrogenic activities than corresponding racemates, the possibility that p450s preferentially generate or use R or S enantiomers, was examined. Indeed, rCYP1A2 and r2A6 mono-demethylated methoxychlor primarily into (R)-mono-OH-M at 91 and 75%, respectively, whereas rCYP1A1, 2B6, 2C8, 2C9, 2C19, and 2D6 formed the (S)-enantiomer at 69, 66, 75, 95, 96, and 80%, respectively. However, rCYP3A4, 3A5, and 2B1(rat) weakly demethylated methoxychlor without enantioselectivity. Human liver microsomes generated (S)-mono-OH-M (77-87%), suggesting that CYP1A2 and 2A6 display only minor catalytic contribution. P450 inhibitors demonstrated that CYP2C9 and possibly 2C19 are major hepatic catalysts forming (S)-mono-OH-M, and CYP1A2 is primarily involved in forming the (R)-mono-OH-M. Demethylation rate of (S)-mono-OH-M versus (R)-mono-OH-M forming achiral bis-OH-M by rCYP1A2 was 97/3, compared with 15/85 and 17/83 for rCYP2C9 and 2C19, respectively, indicating opposite substrate enantioselectivity of rCYP1A2 versus 2C9 and 2C19. Also, rCYP1A2 preferentially O-demethylated (R)-catechol-M into (R)-tris-OH-M (at 80%), contrasting r2C9 and r2C19 that yielded (S)-tris-OH-M at 80 and 77%, respectively. Ortho-hydroxylation of

  12. Putative and unique gene sequence utilization for the design of species specific probes as modeled by Lactobacillus plantarum

    Science.gov (United States)

    The concept of utilizing putative and unique gene sequences for the design of species specific probes was tested. The abundance profile of assigned functions within the Lactobacillus plantarum genome was used for the identification of the putative and unique gene sequence, csh. The targeted gene (cs...

  13. Structure, regulation, and putative function of the arginine deiminase system of Streptococcus suis.

    Science.gov (United States)

    Gruening, Petra; Fulde, Marcus; Valentin-Weigand, Peter; Goethe, Ralph

    2006-01-01

    Streptococcus suis is an important cause of infectious diseases in young pigs. Little is known about the virulence factors or protective antigens of S. suis. Recently, we have identified two proteins of the arginine deiminase system (ADS) of S. suis, which were temperature induced and expressed on the streptococcal surface (N. Winterhoff, R. Goethe, P. Gruening, M. Rohde, H. Kalisz, H. E. Smith, and P. Valentin-Weigand, J. Bacteriol. 184:6768-6776, 2002). In the present study, we analyzed the complete ADS of S. suis. Due to their homologies to the recently published S. gordonii ADS genes, the genes for arginine deiminase, ornithine carbamoyl-transferase, and carbamate kinase, which were previously designated adiS, octS, and ckS, respectively, were renamed arcA, arcB, and arcC, respectively. Our data revealed that arcA, arcB, and arcC of the S. suis ADS are transcribed from an operon (arcABC operon). Additionally, putative ADS-associated genes were cloned and sequenced which, however, did not belong to the arcABC operon. These were the flpS gene upstream of the arcABC operon with homology to the flp transcription regulator of S. gordonii and the arcD, arcT, arcH, and argR genes downstream of the arcABC operon with high homologies to a putative arginine-ornithine antiporter, a putative dipeptidase of S. gordonii, a putative beta-N-acetylhexosaminidase of S. pneumoniae, and a putative arginine repressor of S. gordonii, respectively. The transcriptional start point of the arcABC operon was determined, and promoter analysis provided evidence that multiple factors contribute to the regulation of the ADS. Thus, a putative binding site for a transcription regulator of the Crp/Fnr family, an ArgR-binding site, and two cis-acting catabolite response elements were identified in the promoter-operator region of the operon. Consistent with this, we could demonstrate that the ADS of S. suis is inducible by arginine and reduced O2 tension and subject to carbon catabolite

  14. Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers

    Directory of Open Access Journals (Sweden)

    Kevin C. O’Connor

    2006-01-01

    Full Text Available Currently, there is no single test for multiple sclerosis (MS. Diagnosis is confirmed through clinical evaluation, abnormalities revealed by magnetic resonance imaging (MRI, and analysis of cerebrospinal fluid (CSF chemistry. The early and accurate diagnosis of the disease, monitoring of progression, and gauging of therapeutic intervention are important but elusive elements of patient care. Moreover, a deeper understanding of the disease pathology is needed, including discovery of accurate biomarkers for MS. Herein we review putative biomarkers of MS relating to neurodegeneration and contributions to neuropathology, with particular focus on autoimmunity. In addition, novel assessments of biomarkers not driven by hypotheses are discussed, featuring our application of advanced proteomics and metabolomics for comprehensive phenotyping of CSF and blood. This strategy allows comparison of component expression levels in CSF and serum between MS and control groups. Examination of these preliminary data suggests that several CSF proteins in MS are differentially expressed, and thus, represent putative biomarkers deserving of further evaluation.

  15. Hippocampal and thalamic neuronal metabolism in a putative rat model of schizophrenia○

    Institute of Scientific and Technical Information of China (English)

    Guolin Ma; Tianbin Song; Min Chen; Yuan Fu; Yong Xu; Ensen Ma; Wu Wang; Jiang Du; Mingxiong Huang

    2013-01-01

    The transcription factor early growth response protein 3 (EGR3) is involved in schizophrenia. We developed a putative rat model of schizophrenia by transfecting lentiviral particles carrying the Egr3 gene into bilateral hippocampal dentate gyrus. We assessed spatial working memory using the Morris water maze test, and neuronal metabolite levels in bilateral hippocampus and thalamus were determined by 3.0 T proton magnetic resonance spectroscopy. Choline content was significantly greater in the hippocampus after transfection, while N-acetylaspartate and the ratio of N-acetylaspartate to creatine/phosphocreatine in the thalamus were lower than in controls. This study is the first to report evaluation of brain metabolites using 3.0 T proton magnetic resonance spectroscopy in rats transfected with Egr3, and reveals metabolic abnormalities in the hippocampus and thalamus in this putative model of schizophrenia.

  16. Functional characterization of a putative β-lactamase gene in the genome of Zymomonas mobilis.

    Science.gov (United States)

    Rajnish, K Narayanan; Asraf, Sheik Abdul Kader Sheik; Manju, Nagarajan; Gunasekaran, Paramasamy

    2011-12-01

    Zymomonas mobilis ZM4 is resistant to β-lactam antibiotics but there are no reports of a β-lactam resistance gene and its regulation. A putative β-lactamase gene sequence (ZMO0103) in the genome of Z. mobilis showed a 55% amino acid sequence identity with class C β-lactamase genes. qPCR analysis of the β-lactamase transcript indicated a higher level expression of the β-lactamase compared to the relative transcript quantities in antibiotic-susceptible bacteria. The putative β-lactamase gene was cloned, expressed in Escherichia coli BL21 and the product, AmpC, was purified to homogeneity. Its optimal activity was at pH 6 and 30 °C. Further, the β-lactamase had a higher affinity towards penicillins than cephalosporin antibiotics. © Springer Science+Business Media B.V. 2011

  17. Putative Biomarkers and Targets of Estrogen Receptor Negative Human Breast Cancer

    Directory of Open Access Journals (Sweden)

    Stephen W. Byers

    2011-07-01

    Full Text Available Breast cancer is a progressive and potentially fatal disease that affects women of all ages. Like all progressive diseases, early and reliable diagnosis is the key for successful treatment and annihilation. Biomarkers serve as indicators of pathological, physiological, or pharmacological processes. Her2/neu, CA15.3, estrogen receptor (ER, progesterone receptor (PR, and cytokeratins are biomarkers that have been approved by the Food and Drug Administration for disease diagnosis, prognosis, and therapy selection. The structural and functional complexity of protein biomarkers and the heterogeneity of the breast cancer pathology present challenges to the scientific community. Here we review estrogen receptor-related putative breast cancer biomarkers, including those of putative breast cancer stem cells, a minor population of estrogen receptor negative tumor cells that retain the stem cell property of self renewal. We also review a few promising cytoskeleton targets for ER alpha negative breast cancer.

  18. A putative ABC transporter is involved in negative regulation of biofilm formation by Listeria monocytogenes

    DEFF Research Database (Denmark)

    Zhu, Xinna; Long, Fei; Chen, Yonghui

    2008-01-01

    Listeria monocytogenes may persist for long periods in food processing environments. In some instances, this may be due to aggregation or biofilm formation. To investigate the mechanism controlling biofilm formation in the food-borne pathogen L. monocytogenes, we characterized LM-49, a mutant...... with enhanced ability of biofilm-formation generated via transposon Tn917 mutagenesis of L. monocytogenes 4b G. In this mutant, a Tn917 insertion has disrupted the coding region of the gene encoding a putative ATP binding cassette (ABC) transporter permease identical to Lmof2365_1771 (a putative ABC......-transporter permease) presented in the sequenced strain L. monocytogenes str. 4b F2365. This disrupted gene, denoted lm.G_1771, encoded a protein with 10 transmembrane helixes. The revertant, LM-49RE, was obtained by replacing lm.G_1771::Tn917 with lm.G_1771 via homologous recombination. We found that LM-49RE formed...

  19. The solution structure of ChaB, a putative membrane ion antiporter regulator from Escherichia coli

    Directory of Open Access Journals (Sweden)

    Iannuzzi Pietro

    2004-08-01

    Full Text Available Abstract Background ChaB is a putative regulator of ChaA, a Na+/H+ antiporter that also has Ca+/H+ activity in E. coli. ChaB contains a conserved 60-residue region of unknown function found in other bacteria, archaeabacteria and a series of baculoviral proteins. As part of a structural genomics project, the structure of ChaB was elucidated by NMR spectroscopy. Results The structure of ChaB is composed of 3 α-helices and a small sheet that pack tightly to form a fold that is found in the cyclin-box family of proteins. Conclusion ChaB is distinguished from its putative DNA binding sequence homologues by a highly charged flexible loop region that has weak affinity to Mg2+ and Ca2+ divalent metal ions.

  20. Exploring Universal Partnerships and Putative Marriages as Tools for Awarding Partnership Property in Contemporary Family Law

    Directory of Open Access Journals (Sweden)

    Elsje Bonthuys

    2016-12-01

    Full Text Available Following upon the Supreme Court of Appeal's judgment in Butters v Mncora 2012 4 SA 1 (SCA, which broadened the criteria and consequences of universal partnerships in cohabitation relationships, this article investigates the potential of universal partnerships and putative marriages to allocate rights to share in partnership property in other intimate relationships. It traverses several instances in which marriages are not recognised - bigamous marriages, Muslim and Hindu religious marriages and invalid customary marriages – examining whether the wives in these marriages could use universal partnerships and putative marriages to claim a share in property. It then considers the use of universal partnerships to obtain a share of property in civil marriages out of community of property. It concludes by pointing out several issues which are in need of clarification and where the common law should be developed to give effect to fundamental constitutional rights.

  1. Enrichment of putative stem cells from adipose tissue using dielectrophoretic field-flow fractionation

    Science.gov (United States)

    Vykoukal, Jody; Vykoukal, Daynene M.; Freyberg, Susanne; Alt, Eckhard U.; Gascoyne, Peter R. C.

    2009-01-01

    We have applied the microfluidic cell separation method of dielectrophoretic field-flow fractionation (DEP-FFF) to the enrichment of a putative stem cell population from an enzyme-digested adipose tissue derived cell suspension. A DEP-FFF separator device was constructed using a novel microfluidic-microelectronic hybrid flex-circuit fabrication approach that is scaleable and anticipates future low-cost volume manufacturing. We report the separation of a nucleated cell fraction from cell debris and the bulk of the erythrocyte population, with the relatively rare (<2% starting concentration) NG2-positive cell population (pericytes and/or putative progenitor cells) being enriched up to 14-fold. This work demonstrates a potential clinical application for DEP-FFF and further establishes the utility of the method for achieving label-free fractionation of cell subpopulations. PMID:18651083

  2. Composition of the Putative Prepore Complex of Bacillus thuringiensis Cry1Ab Toxin

    Science.gov (United States)

    Nair, Manoj S.; Dean, Donald H.

    2015-01-01

    Prepore formation is hypothesized to be an obligate step in the insertion of Cry1Ab toxin into insect brush border membrane vesicles. We examined the architecture of the putative prepore when isolated using the published protocols [1] [2]. Our results demonstrate that the putative prepore form of Cry1Ab is a combination of receptor proteins attached to the toxin, when purified. The results also suggest that this prepore form as prepared by the methods published is different from other membrane-extracted oligomeric forms of Cry toxins and prepore of other toxins in general. While most other known prepores are composed of multimers of a single protein, the Cry1Ab prepore, as generated, is a protein-receptor complex oligomer and monomers of Cry toxins. PMID:26702367

  3. Identification of putative effector genes and their transcripts in three strains related to 'Candidatus Phytoplasma aurantifolia'.

    Science.gov (United States)

    Anabestani, Ameneh; Izadpanah, Keramat; Abbà, Simona; Galetto, Luciana; Ghorbani, Abozar; Palmano, Sabrina; Siampour, Majid; Veratti, Flavio; Marzachì, Cristina

    2017-06-01

    Molecular mechanisms underlying phytoplasma interactions with host plants are largely unknown. In this study attempts were made to identify effectors of three phytoplasma strains related to 'Ca. P. aurantifolia', crotalaria phyllody (CrP), faba bean phyllody (FBP), and witches' broom disease of lime (WBDL), using information from draft genome of peanut witches' broom phytoplasma. Seven putative effectors were identified in WBDL genome (SAP11, SAP21, Eff64, Eff115, Eff197, Eff211 and EffSAP67), five (SAP11, SAP21, Eff64, Eff99 and Eff197) in CrP and two (SAP11, Eff64) in FBP. No homologs to Eff64, Eff197 and Eff211 in phytoplasmas of other phylogenetic groups were found. SAP11 and Eff64 homologs of 'Ca. P. aurantifolia' strains shared at least 95.9% identity and were detected in the three phytoplasmas, supporting their role within the group. Five of the putative effectors (SAP11, SAP21, Eff64, Eff115, and Eff99) were transcribed from total RNA extracts of periwinkle plants infected with these phytoplasmas. Transcription profiles of selected putative effectors of CrP, FBP and WBDL indicated that SAP11 transcripts were the most abundant in the three phytoplasmas. SAP21 transcript levels were comparable to those of SAP11 for CrP and not measurable for the other phytoplasmas. Eff64 had the lowest transcription level irrespective of sampling date and phytoplasma isolate. Eff115 transcript levels were the highest in WBDL infected plants. This work reports the first sequence information for 14 putative effectors in three strains related to 'Ca. P. aurantifolia', and offers novel insight into the transcription profile of five of them during infection of periwinkle. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. A novel putative auxin carrier family regulates intracellular auxin homeostasis in plants

    OpenAIRE

    2012-01-01

    The phytohormone auxin acts as a prominent signal, providing, by its local accumulation or depletion in selected cells, a spatial and temporal reference for changes in the developmental program. The distribution of auxin depends on both auxin metabolism (biosynthesis, conjugation and degradation) and cellular auxin transport. We identified in silico a novel putative auxin transport facilitator family, called PIN-LIKES (PILS). Here we illustrate that PILS proteins are required for auxin-depend...

  5. ANTIBIOTICS RESISTANCE AND PUTATIVE VIRULENCE FACTORS OF AEROMONAS HYDROPHILA ISOLATED FROM ESTUARY

    OpenAIRE

    Olumide Adedokun Odeyemi; Ahmad Asmat; Gires Usup

    2012-01-01

    This study aim to investigate antibiotics resistance profile and putative virulence factors of Aeromonas hydrophila isolated from estuary. Bacteria used for this study were isolated from water and sediment samples obtained from Sungai Melayu, Johor, Malaysia. Serially diluted 100 µL water and 1g sediment were inoculated on modified Rimler - Shott (mRS) agar. Colonies with distinct cultural characteristics were picked for further studies. Isolates were tested for biofilm productions, protease ...

  6. Bioinformatic Analysis of Putative Gene Products Encoded in SARS-HCoV Genome

    Institute of Scientific and Technical Information of China (English)

    赵心刚; 韩敬东; 宁元亨; 孟安明; 陈晔光

    2003-01-01

    The cause of severe acute respiratory syndrome (SARS) has been identified as a new coronavirus named as SARS-HCoV.Using bioinformatic methods, we have performed a detailed domain search.In addition to the viral structure proteins, we have found that several putative polypeptides share sequence similarity to known domains or proteins.This study may provide a basis for future studies on the infection and replication process of this notorious virus.

  7. Detection of putative periodontopathic bacteria in type 1 diabetic and healthy children: A comparative study

    OpenAIRE

    2013-01-01

    Aim: The aim of this study was to compare and assess the risk of periodontitis due to the presence of four putative periodontopathic bacteria (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Aggregatibacter actinomycetemcomitans) in type 1 diabetic and healthy children. Materials and Methods: Fifty type 1 diabetic and 50 healthy children in the age group of 7-14 years were recruited for the study. Subgingival plaque samples collected from permanent first molars w...

  8. Immunodiagnosis of episomal Banana streak MY virus using polyclonal antibodies to an expressed putative coat protein.

    Science.gov (United States)

    Sharma, Susheel Kumar; Kumar, P Vignesh; Baranwal, Virendra Kumar

    2014-10-01

    A cryptic Badnavirus species complex, known as banana streak viruses (BSV) poses a serious threat to banana production and genetic improvement worldwide. Due to the presence of integrated BSV sequences in the banana genome, routine detection is largely based on serological and nucleo-serological diagnostic methods which require high titre specific polyclonal antiserum. Viral structural proteins like coat protein (CP) are the best target for in vitro expression, to be used as antigen for antiserum production. However, in badnaviruses precise CP sequences are not known. In this study, two putative CP coding regions (p48 and p37) of Banana streak MY virus (BSMYV) were identified in silico by comparison with caulimoviruses, retroviruses and Rice tungro bacilliform virus. The putative CP coding region (p37) was in vitro expressed in pMAL system and affinity purified. The purified fusion protein was used as antigen for raising polyclonal antiserum in rabbit. The specificity of antiserum was confirmed in Western blots, immunosorbent electron microscopy (ISEM) and antigen coated plate-enzyme linked immunosorbent assay (ACP-ELISA). The antiserum (1:2000) was successfully used in ACP-ELISA for specific detection of BSMYV infection in field and tissue culture raised banana plants. The antiserum was also utilized in immuno-capture PCR (IC-PCR) based indexing of episomal BSMYV infection. This is the first report of in silico identification of putative CP region of BSMYV, production of polyclonal antiserum against recombinant p37 and its successful use in immunodetection.

  9. Identification of Putative Coffee Rust Mycoparasites via Single-Molecule DNA Sequencing of Infected Pustules.

    Science.gov (United States)

    James, Timothy Y; Marino, John A; Perfecto, Ivette; Vandermeer, John

    2015-11-13

    The interaction of crop pests with their natural enemies is a fundament to their control. Natural enemies of fungal pathogens of crops are poorly known relative to those of insect pests, despite the diversity of fungal pathogens and their economic importance. Currently, many regions across Latin America are experiencing unprecedented epidemics of coffee rust (Hemileia vastatrix). Identification of natural enemies of coffee rust could aid in developing management strategies or in pinpointing species that could be used for biocontrol. In the present study, we characterized fungal communities associated with coffee rust lesions by single-molecule DNA sequencing of fungal rRNA gene bar codes from leaf discs (≈28 mm(2)) containing rust lesions and control discs with no rust lesions. The leaf disc communities were hyperdiverse in terms of fungi, with up to 69 operational taxonomic units (putative species) per control disc, and the diversity was only slightly reduced in rust-infected discs, with up to 63 putative species. However, geography had a greater influence on the fungal community than whether the disc was infected by coffee rust. Through comparisons between control and rust-infected leaf discs, as well as taxonomic criteria, we identified 15 putative mycoparasitic fungi. These fungi are concentrated in the fungal family Cordycipitaceae and the order Tremellales. These data emphasize the complexity of diverse fungi of unknown ecological function within a leaf that might influence plant disease epidemics or lead to the development of species for biocontrol of fungal disease.

  10. Emissions of putative isoprene oxidation products from mango branches under abiotic stress

    Science.gov (United States)

    Jardine, Kolby J.; Meyers, Kimberly; Abrell, Leif; Alves, Eliane G.; Yanez Serrano, Ana Maria; Kesselmeier, Jürgen; Karl, Thomas; Guenther, Alex; Vickers, Claudia; Chambers, Jeffrey Q.

    2013-01-01

    Although several per cent of net carbon assimilation can be re-released as isoprene emissions to the atmosphere by many tropical plants, much uncertainty remains regarding its biological significance. In a previous study, we detected emissions of isoprene and its oxidation products methyl vinyl ketone (MVK) and methacrolein (MACR) from tropical plants under high temperature/light stress, suggesting that isoprene is oxidized not only in the atmosphere but also within plants. However, a comprehensive analysis of the suite of isoprene oxidation products in plants has not been performed and production relationships with environmental stress have not been described. In this study, putative isoprene oxidation products from mango (Mangifera indica) branches under abiotic stress were first identified. High temperature/light and freeze–thaw treatments verified direct emissions of the isoprene oxidation products MVK and MACR together with the first observations of 3-methyl furan (3-MF) and 2-methyl-3-buten-2-ol (MBO) as putative novel isoprene oxidation products. Mechanical wounding also stimulated emissions of MVK and MACR. Photosynthesis under 13CO2 resulted in rapid (<30min) labelling of up to five carbon atoms of isoprene, with a similar labelling pattern observed in the putative oxidation products. These observations highlight the need to investigate further the mechanisms of isoprene oxidation within plants under stress and its biological and atmospheric significance. PMID:23881400

  11. Cloning and molecular characterization of a putative voltage-gated sodium channel gene in the crayfish.

    Science.gov (United States)

    Coskun, Cagil; Purali, Nuhan

    2016-06-01

    Voltage-gated sodium channel genes and associated proteins have been cloned and studied in many mammalian and invertebrate species. However, there is no data available about the sodium channel gene(s) in the crayfish, although the animal has frequently been used as a model to investigate various aspects of neural cellular and circuit function. In the present work, by using RNA extracts from crayfish abdominal ganglia samples, the complete open reading frame of a putative sodium channel gene has firstly been cloned and molecular properties of the associated peptide have been analyzed. The open reading frame of the gene has a length of 5793 bp that encodes for the synthesis of a peptide, with 1930 amino acids, that is 82% similar to the α-peptide of a sodium channel in a neighboring species, Cancer borealis. The transmembrane topology analysis of the crayfish peptide indicated a pattern of four folding domains with several transmembrane segments, as observed in other known voltage-gated sodium channels. Upon analysis of the obtained sequence, functional regions of the putative sodium channel responsible for the selectivity filter, inactivation gate, voltage sensor, and phosphorylation have been predicted. The expression level of the putative sodium channel gene, as defined by a qPCR method, was measured and found to be the highest in nervous tissue.

  12. Putative periodontopathic bacteria and herpesviruses in pregnant women: a case-control study

    Science.gov (United States)

    Lu, Haixia; Zhu, Ce; Li, Fei; Xu, Wei; Tao, Danying; Feng, Xiping

    2016-01-01

    Little is known about herpesvirus and putative periodontopathic bacteria in maternal chronic periodontitis. The present case-control study aimed to explore the potential relationship between putative periodontopathic bacteria and herpesviruses in maternal chronic periodontitis.Saliva samples were collected from 36 pregnant women with chronic periodontitis (cases) and 36 pregnant women with healthy periodontal status (controls). Six putative periodontopathic bacteria (Porphyromonas gingivalis [Pg], Aggregatibacer actinomycetemcomitans [Aa], Fusobacterium nucleatum [Fn], Prevotella intermedia [Pi], Tannerella forsythia [Tf], and Treponema denticola [Td]) and three herpesviruses (Epstein-Barr virus [EBV], human cytomegalovirus [HCMV], and herpes simplex virus [HSV]) were detected. Socio-demographic data and oral health related behaviors, and salivary estradiol and progesterone levels were also collected. The results showed no significant differences in socio-demographic background, oral health related behaviors, and salivary estradiol and progesterone levels between the two groups (all P > 0.05). The detection rates of included periodontopathic microorganisms were not significantly different between the two groups (all P > 0.05), but the coinfection rate of EBV and Pg was significantly higher in the case group than in the control group (P = 0.028). EBV and Pg coinfection may promote the development of chronic periodontitis among pregnant women. PMID:27301874

  13. Genomic identification of a putative circadian system in the cladoceran crustacean Daphnia pulex

    Science.gov (United States)

    Tilden, Andrea R.; McCoole, Matthew D.; Harmon, Sarah M.; Baer, Kevin N.; Christie, Andrew E.

    2011-01-01

    Essentially nothing is known about the molecular underpinnings of crustacean circadian clocks. The genome of Daphnia pulex, the only crustacean genome available for public use, provides a unique resource for identifying putative circadian proteins in this species. Here, the Daphnia genome was mined for putative circadian protein genes using Drosophila melanogaster queries. The sequences of core clock (e.g. CLOCK, CYCLE, PERIOD, TIMELESS and CRYPTOCHROME 2), clock input (CRYPTOCHROME 1) and clock output (PIGMENT DISPERSING HORMONE RECEPTOR) proteins were deduced. Structural analyses and alignment of the Daphnia proteins with their Drosophila counterparts revealed extensive sequence conservation, particularly in functional domains. Comparisons of the Daphnia proteins with other sequences showed that they are, in most cases, more similar to homologs from other species, including vertebrates, than they are to those of Drosophila. The presence of both CRYPTOCHROME 1 and 2 in Daphnia suggests the organization of its clock may be more similar to that of the butterfly Danaus plexippus than to that of Drosophila (which possesses CRYPTOCHROME 1 but not CRYPTOCHROME 2). These data represent the first description of a putative circadian system from any crustacean, and provide a foundation for future molecular, anatomical and physiological investigations of circadian signaling in Daphnia. PMID:21798832

  14. Phylogeny of algal sequences encoding carbohydrate sulfotransferases, formylglycine-dependent sulfatases and putative sulfatase modifying factors

    Directory of Open Access Journals (Sweden)

    Chai-Ling eHo

    2015-11-01

    Full Text Available Many algae are rich sources of sulfated polysaccharides with biological activities. The physicochemical/rheological properties and biological activities of sulfated polysaccharides are affected by the pattern and number of sulfate moieties. Sulfation of carbohydrates is catalyzed by carbohydrate sulfotransferases (CHSTs while modification of sulfate moieties on sulfated polysaccharides was presumably catalyzed by sulfatases including formylglycine-dependent sulfatases (FGly-SULFs. Post-translationally modification of Cys to FGly in FGly-SULFs by sulfatase modifiying factors (SUMFs is necessary for the activity of this enzyme. The aims of this study are to mine for sequences encoding algal CHSTs, FGly-SULFs and putative SUMFs from the fully sequenced algal genomes and to infer their phylogenetic relationships to their well characterized counterparts from other organisms. Algal sequences encoding CHSTs, FGly-SULFs, SUMFs and SUMF-like proteins were successfully identified from green and brown algae. However, red algal FGly-SULFs and SUMFs were not identified. In addition, a group of SUMF-like sequences with different gene structure and possibly different functions were identified for green, brown and red algae. The phylogeny of these putative genes contributes to the corpus of knowledge of an unexplored area. The analyses of these putative genes contribute towards future production of existing and new sulfated carbohydrate polymers through enzymatic synthesis and metabolic engineering.

  15. Do environmental factors play a role in the aetiology of carcinoma in situ testis and the testicular dysgenesis syndrome?

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Hoei-Hansen, C E; Fisher, J S

    2004-01-01

    development, and may be provoked by external factors such as endocrine disruptors in addition to genetic predisposition. Testicular germ cell tumours (TGCTs), considered the most severe symptom of TDS, have increased in incidence during the last 60 years, to become the most common malignancy in young...... (DBP) suggesting that ubiquitously present environmental endocrine disruptors may play a role in the aetiology of human TDS. So far, no animal model has been able to mimick all the symptoms of TDS including TGCTs although CIS-like cells have been found in a spontaneous testicular neoplasm in a rabbit....

  16. Agricultural pesticides and precocious puberty.

    Science.gov (United States)

    Ozen, Samim; Goksen, Damla; Darcan, Sukran

    2014-01-01

    The onset and course of puberty is under the control of the neuroendocrine system. Factors affecting the regulation of timing and order of this system's functions may alter the onset and course of puberty. Several environmental endocrine disruptors (EDs) with significant influences on the normal course of puberty have been identified. Despite the numerous animal and human studies on EDs that may extensively affect human health, there are still several issues that need to be clarified. This chapter discusses the effects of pesticides, which constitute a significant portion of disruptors and have been increasingly used in agriculture, on precocious puberty.

  17. p,p′-DDE activates CatSper and compromises human sperm function at environmentally relevant concentrations

    OpenAIRE

    Tavares, Renata S.; Mansell, Steven; Barratt, Christopher L. R.; Wilson, Stuart M.; Publicover, Stephen J.; Ramalho-Santos, João

    2013-01-01

    STUDY QUESTION Is the environmental endocrine disruptor p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) able to induce non-genomic changes in human sperm and consequently affect functional sperm parameters? SUMMARY ANSWER p,p′-DDE promoted Ca2+ flux into human sperm by activating CatSper channels even at doses found in human reproductive fluids, ultimately compromising sperm parameters important for fertilization. WHAT IS KNOWN ALREADY p,p′-DDE may promote non-genomic actions and interact di...

  18. Localization of putative carbonic anhydrases in two marine diatoms, Phaeodactylum tricornutum and Thalassiosira pseudonana.

    Science.gov (United States)

    Tachibana, Masaaki; Allen, Andrew E; Kikutani, Sae; Endo, Yuri; Bowler, Chris; Matsuda, Yusuke

    2011-09-01

    It is believed that intracellular carbonic anhydrases (CAs) are essential components of carbon concentrating mechanisms in microalgae. In this study, putative CA-encoding genes were identified in the genome sequences of the marine diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana. Subsequently, the subcellular localizations of the encoded proteins were determined. Nine and thirteen CA sequences were found in the genomes of P. tricornutum and T. pseudonana, respectively. Two of the β-CA genes in P. tricornutum corresponded to ptca1 and ptca2 identified previously. Immunostaining transmission electron microscopy of a PtCA1:YFP fusion expressed in the cells of P. tricornutum clearly showed the localization of PtCA1 within the central part of the pyrenoid structure in the chloroplast. Besides these two β-CA genes, P. tricornutum likely contains five α- and two γ-CA genes, whereas T. pseudonana has three α-, five γ-, four δ-, and one ζ-CA genes. Semi-quantitative reverse transcription PCR performed on mRNA from the two diatoms grown in changing light and CO(2) conditions revealed that levels of six putative α- and γ-CA mRNAs in P. tricornutum did not change between cells grown in air-level CO(2) and 5% CO(2). However, mRNA levels of one putative α-CA gene, CA-VII in P. tricornutum, were reduced in the dark compared to that in the light. In T. pseudonana, mRNA accumulation levels of putative α-CA (CA-1), ζ-CA (CA-3) and δ-CA (CA-7) were analyzed and all levels found to be significantly reduced when cells were grown in 0.16% CO(2). Intercellular localizations of eight putative CAs were analyzed by expressing GFP fusion in P. tricornutum and T. pseudonana. In P. tricornutum, CA-I and II localized in the periplastidial compartment, CA-III, VI, VII were found in the chloroplast endoplasmic reticulum, and CA-VIII was localized in the mitochondria. On the other hand, T. pseudonana CA-1 localized in the stroma and CA-3 was found in the periplasm

  19. A Hypothesis for the Abiotic and Non-Martian Origins of Putative Signs of Ancient Martian Life in ALH84001

    Science.gov (United States)

    Treiman, Allan H.

    2001-01-01

    Putative evidence of martian life in ALH84001 can be explained by abiotic and non-martian processes consistent with the meteorite's geological history. Additional information is contained in the original extended abstract.

  20. Haemolytic and cytotoxic activities of the Tween 80-extracted putative haemolysin of Pasteurella multocida B:2.

    Science.gov (United States)

    Chachra, D; Coote, J G; Parton, R; Jand, S K

    2011-06-02

    The objective of this study was to investigate the haemolytic and cytotoxic activity of Pasteurella multocida B:2 strains, originally from cases of haemorrhagic septicaemia in cattle. All six P. multocida B:2 strains were non-haemolytic on sheep blood agar (SBA) and horse blood agar (HBA) when grown aerobically and on SBA anaerobically but they were haemolytic on HBA when grown anaerobically. No haemolytic activity against horse red blood cells was detected in culture supernates from aerobically or anaerobically grown cultures and only very weak haemolytic activity was obtained in supernates or pellet fractions from sonicated cells. However, after repeated extraction of sonicated cells with Tween 80, haemolytic activity was found in various cell fractions, both Tween-soluble and -insoluble. The Tween-extracted putative haemolysin and other bacterial fractions were also cytotoxic for mouse macrophage-like J774.2 cells. Further characterisation of the putative haemolysin revealed it to be a heat-labile, non-pore-forming protein of molecular weight >10 kDa whose activity was completely destroyed by trypsin and greatly reduced with protease and proteinase K treatment. Congo red also reduced the haemolytic activity. Non-denaturing gel-electrophoresis and RBC agar overlay revealed clear haemolytic zones but suggested that Tween was bound to some component of the P. multocida B:2 fractions and was responsible, to some extent, for the haemolytic activity observed. However, the effect of heat and other reagents on the Tween-extracted fractions and the lack of haemolytic activity in different Tween-extracted cell fractions of organisms other than P. multocida suggested that some proteinaceous component of the organism could indeed act as a haemolysin. This putative haemolysin may be one of the virulence attributes of P. multocida, but its characterisation and role in pathogenesis require further study.

  1. Isolation and characterization of two mitoviruses and a putative alphapartitivirus from Fusarium spp.

    Science.gov (United States)

    Osaki, Hideki; Sasaki, Atsuko; Nomiyama, Koji; Sekiguchi, Hiroyuki; Tomioka, Keisuke; Takehara, Toshiaki

    2015-06-01

    The filamentous fungus Fusarium spp. includes several important plant pathogens. We attempted to reveal presence of double-stranded (ds) RNAs in the genus. Thirty-seven Fusarium spp. at the MAFF collection were analyzed. In the strains of Fusarium coeruleum, Fusarium globosum and Fusarium solani f. sp. pisi, single dsRNA bands were detected. The strains of F. coeruleum and F. solani f. sp. pisi cause potato dry rot and mulberry twig blight, respectively. Sequence analyses revealed that dsRNAs in F. coeruleum and F. globosum consisted of 2423 and 2414 bp, respectively. Using the fungal mitochondrial translation table, the positive strands of these cDNAs were found to contain single open reading frames with the potential to encode a protein of putative 757 and 717 amino acids (molecular mass 88.5 and 84.0 kDa, respectively), similar to RNA-dependent RNA polymerases of members of the genus Mitovirus. These dsRNAs in F. coeruleum and F. globosum were assigned to the genus Mitovirus (family Narnaviridae), and these two mitoviruses were designated as Fusarium coeruleum mitovirus 1 and Fusarium globosum mitovirus 1. On the other hand, a positive strand of cDNA (1950 bp) from dsRNA in F. solani f. sp. pisi contained an ORF potentially encoding a putative RdRp of 608 amino acids (72.0 kDa). The putative RdRp was shown to be related to those of members of the genus of Alphapartitivirus (family Partitiviridae). We coined the name Fusarium solani partitivirus 2 for dsRNA in F. solani f. sp. pisi.

  2. The intracellular mobility of NPY and a putative mitochondrial form of NPY in neuronal cells.

    Science.gov (United States)

    Kaipio, Katja; Pesonen, Ullamari

    2009-01-30

    Preproneuropeptide Y is a precursor peptide to mature neuropeptide Y (NPY), which is a universally expressed peptide in the central and peripheral nervous system. NPY is normally routed to endoplasmic reticulum and secretory vesicles in cells, which secrete NPY. In our previous studies, we found a functional Leucine7 to Proline7 (L7P) polymorphism in the signal peptide sequence of preproNPY. This polymorphism affects the secretion of NPY and causes multiple physiological effects in humans. The sequence of NPY mRNA contains two in frame kozak sequences that allow translation initiation to shift, and translation of two proteins. In addition to mature NPY(1-36) also a putative truncated NPY(17-36) with mitochondrial targeting signal is produced. The purpose of this study was to investigate the protein mobility of the putative mitochondrial fragment and the effect of the L7P polymorphism on the cellular level using GFP tagged constructs. The mobility was studied with fluorescence recovery after photobleaching technique in a neuronal cell line. We found that the mobility of the secretory vesicles with NPY(1-36) in cells with L7P genotype was increased in comparison to vesicle mobility in cells with the more abundant L7L genotype. The mobility in the cells with the putative mitochondrial construct was found to be very low. According to the results of the present study, the mitochondrial truncated peptide stays in the mitochondrion. It can be hypothesized that this could be one of the factors affecting energy balance of the membranes of the mitochondrion.

  3. Identification and characterization of a gene encoding a putative lysophosphatidyl acyltransferase from Arachis hypogaea

    Indian Academy of Sciences (India)

    Si-Long Chen; Jia-Quan Huang; Lei Yong; Yue-Ting Zhang; Xiao-Ping Ren; Yu-Ning Chen; Hui-Fang Jiang; Li-Ying Yan; Yu-Rong Li; Bo-Shou Liao

    2012-12-01

    Lysophosphatidyl acyltransferase (LPAT) is the important enzyme responsible for the acylation of lysophosphatidic acid (LPA), leading to the generation of phosphatidic acid (PA) in plant. Its encoding gene is an essential candidate for oil crops to improve oil composition and increase seed oil content through genetic engineering. In this study, a full-length AhLPAT4 gene was isolated via cDNA library screening and rapid amplification of cDNA ends (RACE); our data demonstrated that AhLPAT4 had 1631 nucleotides, encoding a putative 43.8 kDa protein with 383 amino acid residues. The deduced protein included a conserved acyltransferase domain and four motifs (I–IV) with putative LPA and acyl-CoA catalytic and binding sites. Bioinformatic analysis indicated that AhLPAT4 contained four transmembrane domains (TMDs), localized to the endoplasmic reticulum (ER) membrane; detailed analysis indicated that motif I and motifs II–III in AhLPAT4 were separated by the third TMD, which located on cytosolic and ER luminal side respectively, and hydrophobic residues on the surface of AhLPAT4 protein fold to form a hydrophobic tunnel to accommodate the acyl chain. Subcellular localization analysis confirmed that AhLPAT4 was a cytoplasm protein. Phylogenetic analysis revealed that AhLPAT4 had a high homology (63.7–78.3%) with putative LPAT4 proteins from Glycine max, Arabidopsis thaliana and Ricinus communis. AhLPAT4 was ubiquitously expressed in diverse tissues except in flower, which is almost undetectable. The expression analysis in different developmental stages in peanut seeds indicated that AhLPAT4 did not coincide with oil accumulation.

  4. Identification of putative rhamnogalacturonan-II specific glycosyltransferases in Arabidopsis using a combination of bioinformatics approaches.

    Science.gov (United States)

    Voxeur, Aline; André, Aurélie; Breton, Christelle; Lerouge, Patrice

    2012-01-01

    Rhamnogalacturonan-II (RG-II) is a complex plant cell wall polysaccharide that is composed of an α(1,4)-linked homogalacturonan backbone substituted with four side chains. It exists in the cell wall in the form of a dimer that is cross-linked by a borate di-ester. Despite its highly complex structure, RG-II is evolutionarily conserved in the plant kingdom suggesting that this polymer has fundamental functions in the primary wall organisation. In this study, we have set up a bioinformatics strategy aimed at identifying putative glycosyltransferases (GTs) involved in RG-II biosynthesis. This strategy is based on the selection of candidate genes encoding type II membrane proteins that are tightly coexpressed in both rice and Arabidopsis with previously characterised genes encoding enzymes involved in the synthesis of RG-II and exhibiting an up-regulation upon isoxaben treatment. This study results in the final selection of 26 putative Arabidopsis GTs, including 10 sequences already classified in the CAZy database. Among these CAZy sequences, the screening protocol allowed the selection of α-galacturonosyltransferases involved in the synthesis of α4-GalA oligogalacturonides present in both homogalacturonans and RG-II, and two sialyltransferase-like sequences previously proposed to be involved in the transfer of Kdo and/or Dha on the pectic backbone of RG-II. In addition, 16 non-CAZy GT sequences were retrieved in the present study. Four of them exhibited a GT-A fold. The remaining sequences harbored a GT-B like fold and a fucosyltransferase signature. Based on homologies with glycosyltransferases of known functions, putative roles in the RG-II biosynthesis are proposed for some GT candidates.

  5. Novel mutations in the GH gene (GH1) uncover putative splicing regulatory elements.

    Science.gov (United States)

    Babu, Deepak; Mellone, Simona; Fusco, Ileana; Petri, Antonella; Walker, Gillian E; Bellone, Simonetta; Prodam, Flavia; Momigliano-Richiardi, Patricia; Bona, Gianni; Giordano, Mara

    2014-05-01

    Mutations affecting exon 3 splicing are the main cause of autosomal dominant Isolated GH Deficiency II (IGHDII) by increasing the level of exon 3-skipped mRNA encoding the functionally inactive dominant-negative 17.5-kDa isoform. The exons and introns of the gene encoding GH (GH1) were screened for the presence of mutations in 103 sporadic isolated GH deficiency cases. Four different variations within exon 3 were identified in 3 patients. One carried c.261C>T (p.Pro87Pro) and c.272A>T (p.Glu91Val), the second c.255G>A (p.Pro85Pro) and c.261 C>T, and the third c.246G>C (p.Glu82Asp). All the variants were likely generated by gene conversion from an homologous gene in the GH1 cluster. In silico analysis predicted that positions c.255 and c.272 were included within 2 putative novel exon splicing enhancers (ESEs). Their effect on splicing was confirmed in vitro. Constructs bearing these 2 variants induced consistently higher levels both of transcript and protein corresponding to the 17.5-kDa isoform. When c.255 and c.272 were combined in cis with the c.261 variant, as in our patients, their effect was weaker. In conclusion, we identified 2 variations, c.255G>A and c.272A>T, located in 2 novel putative exon splicing enhancers and affecting GH1 splicing in vitro by increasing the production of alternatively spliced isoforms. The amount of aberrant isoforms is further regulated by the presence in cis of the c.261 variant. Thus, our results evidenced novel putative splicing regulatory elements within exon 3, confirming the crucial role of this exon in mRNA processing.

  6. A Proteomics Approach to Identify New Putative Cardiac Intercalated Disk Proteins.

    Directory of Open Access Journals (Sweden)

    Siddarth Soni

    Full Text Available Synchronous beating of the heart is dependent on the efficient functioning of the cardiac intercalated disk (ID. The ID is composed of a complex protein network enabling electrical continuity and chemical communication between individual cardiomyocytes. Recently, several different studies have shed light on increasingly prevalent cardiac diseases involving the ID. Insufficient knowledge of its composition makes it difficult to study these disease mechanisms in more detail and therefore here we aim expand the ID proteome. Here, using a combination of general membrane enrichment, in-depth quantitative proteomics and an intracellular location driven bioinformatics approach, we aim to discover new putative ID proteins in rat ventricular tissue.General membrane isolation, enriched amongst others also with ID proteins as based on presence of the established markers connexin-43 and n-cadherin, was performed using centrifugation. By mass spectrometry, we quantitatively evaluated the level of 3455 proteins in the enriched membrane fraction (EMF and its counterpart, the soluble cytoplasmic fraction. These data were stringently filtered to generate a final set of 97 enriched, putative ID proteins. These included Cx43 and n-cadherin, but also many interesting novel candidates. We selected 4 candidates (Flotillin-2 (FLOT2, Nexilin (NEXN, Popeye-domain-containg-protein 2 (POPDC2 and thioredoxin-related-transmembrane-protein 2 (TMX2 and confirmed their co-localization with n-cadherin in the ID of human and rat heart cryo-sections, and isolated dog cardiomyocytes.The presented proteomics dataset of putative new ID proteins is a valuable resource for future research into this important molecular intersection of the heart.

  7. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    Science.gov (United States)

    2012-01-01

    Background Arbuscular mycorrhizas (AM) are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis. PMID:23046713

  8. Enrichment of putative human epidermal stem cells based on cell size and collagen type IV adhesiveness

    Institute of Scientific and Technical Information of China (English)

    Juxue Li; Enkui Duan; Chenglin Miao; Weixiang Guo; Liwei Jia; Jiaxi Zhou; Baohua Ma; Sha Peng; Shuang Liu; Yujing Cao

    2008-01-01

    The enrichment and identification of human epidermal stem cells (EpSCs) are of paramount importance for both basic research and clinical application. Although several approaches for the enrichment of EpSCs have been established, enriching a pure population of viable EpSCs is still a challenging task. An improved approach is worth developing to enhance the purity and viability of EpSCs. Here we report that cell size combined with collagen type IV adhesiveness can be used in an improved approach to enrich pure and viable human EpSCs. We separated the rapidly adherent keratinocytes into three populations that range in size from 5-7 μm (population A), to 7-9 μm (population B), to >9 μm (population C) in diameter, and found that human putative EpSCs could be further enriched in population A with the smallest size. Among the three populations, population A displayed the highest density of βl-integrin receptor, contained the highest percentage of cells in G0/G1 phase, showed the highest nucleus to cytoplasm ratio, and possessed the highest colony formation efficiency (CFE). When injected into murine blastocysts, these cells participated in multi-tissue formation. More significantly, compared with a previous approach that sorted putative EpSCs according to pl-integrin antibody staining, the viability of the EpSCs enriched by the improved approach was significantly enhanced. Our results provide a putative strategy for the enrichment of human EpSCs, and encourage further study into the role of cell size in stem cell biology.

  9. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    Directory of Open Access Journals (Sweden)

    Giovannetti Marco

    2012-10-01

    Full Text Available Abstract Background Arbuscular mycorrhizas (AM are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis.

  10. Temporal dynamics and decay of putatively allochthonous and autochthonous viral genotypes in contrasting freshwater lakes.

    Science.gov (United States)

    Hewson, Ian; Barbosa, Jorge G; Brown, Julia M; Donelan, Ryan P; Eaglesham, James B; Eggleston, Erin M; LaBarre, Brenna A

    2012-09-01

    Aquatic viruses play important roles in the biogeochemistry and ecology of lacustrine ecosystems; however, their composition, dynamics, and interactions with viruses of terrestrial origin are less extensively studied. We used a viral shotgun metagenomic approach to elucidate candidate autochthonous (i.e., produced within the lake) and allochthonous (i.e., washed in from other habitats) viral genotypes for a comparative study of their dynamics in lake waters. Based on shotgun metagenomes prepared from catchment soil and freshwater samples from two contrasting lakes (Cayuga Lake and Fayetteville Green Lake), we selected two putatively autochthonous viral genotypes (phycodnaviruses likely infecting algae and cyanomyoviruses likely infecting picocyanobacteria) and two putatively allochthonous viral genotypes (geminiviruses likely infecting terrestrial plants and circoviruses infecting unknown hosts but common in soil libraries) for analysis by genotype-specific quantitative PCR (TaqMan) applied to DNAs from viruses in the viral size fraction of lake plankton, i.e., 0.2 μm > virus > 0.02 μm. The abundance of autochthonous genotypes largely reflected expected host abundance, while the abundance of allochthonous genotypes corresponded with rainfall and storm events in the respective catchments, suggesting that viruses with these genotypes may have been transported to the lake in runoff. The decay rates of allochthonous and autochthonous genotypes, assessed in incubations where all potential hosts were killed, were generally lower (0.13 to 1.50% h(-1)) than those reported for marine virioplankton but similar to those for freshwater virioplankton. Both allochthonous and autochthonous viral genotypes were detected at higher concentrations in subsurface sediments than at the water-sediment interface. Our data indicate that putatively allochthonous viruses are present in lake plankton and sediments, where their temporal dynamics reflect active transport to the lake during

  11. Further insight into reproductive incompatibility between putative cryptic species of the Bemisia tabaci whitefly complex.

    Science.gov (United States)

    Qin, Li; Pan, Li-Long; Liu, Shu-Sheng

    2016-04-01

    The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), with its global distribution and extensive genetic diversity, is now known to be a complex of over 35 cryptic species. However, a satisfactory resolution of the systematics of this species complex is yet to be achieved. Here, we designed experiments to examine reproductive compatibility among species with different levels of mitochondrial cytochrome oxidase I (mtCOI) divergence. The data show that putative species with mtCOI divergence of >8% between them consistently exhibited complete reproductive isolation. However, two of the putative species, Asia II 9 and Asia II 3, with mtCOI divergence of 4.47% between them, exhibited near complete reproductive compatibility in one direction of their cross, and partial reproductive compatibility in the other direction. Together with some recent reports on this topic from the literature, our data indicates that, while divergence in the mtCOI sequences provides a valid molecular marker for species delimitation in most clades, more genetic markers and more sophisticated molecular phylogeny will be required to achieve adequate delimitation of all species in this whitefly complex. While many attempts have been made to examine the reproductive compatibility among genetic groups of the B. tabaci complex, our study represents the first effort to conduct crossing experiments with putative species that were chosen with considerations of their genetic divergence. In light of the new data, we discuss the best strategy and protocols to conduct further molecular phylogenetic analysis and crossing trials, in order to reveal the overall pattern of reproductive incompatibility among species of this whitefly complex.

  12. Evaluation of two putative susceptibility loci for oral clefts in the Danish population

    DEFF Research Database (Denmark)

    Mitchell, L E; Murray, J C; O'Brien, S;

    2001-01-01

    Previous studies suggest that the risk of nonsyndromic cleft lip with or without cleft palate (CL+/-P) and isolated cleft palate (CP) is influenced by genetic variation at several loci and that the relation between specific genetic variants and disease risk may be modified by environmental factors....... The present study evaluated potential associations between CL+/-P and CP and two putative clefting susceptibility loci, MSX1 and TGFB3, using data from a nationwide case-control study conducted in Denmark from 1991 to 1994. The potential effects of interactions between these genes and two common environmental...

  13. Role of putative neurotransmitters in the central gastric antisecretory effect of prostaglandin E2 in rats.

    OpenAIRE

    Puurunen, J.

    1985-01-01

    The role of putative neurotransmitters of the central nervous system in the central gastric antisecretory effect of prostaglandin E2 (PGE2) was investigated in pylorus-ligated rats. Pretreatment of the rats with an intracerebroventricular (i.c.v.) injection of 6-hydroxydopamine (6-OHDA) prevented the antisecretory effect of the i.c.v. administration of PGE2, whereas pretreatment with 5,6-dihydroxytryptamine (5,6-DHT) plus p-chlorophenylalanine (PCPA) had no effect. I.c.v.-administered phentol...

  14. A putative, novel coli surface antigen 8B (CS8B) of enterotoxigenic Escherichia coli.

    Science.gov (United States)

    Njoroge, Samuel M; Boinett, Christine J; Madé, Laure F; Ouko, Tom T; Fèvre, Eric M; Thomson, Nicholas R; Kariuki, Samuel

    2015-10-01

    Enterotoxigenic Escherichia coli (ETEC) strains harbor multiple fimbriae and pili to mediate host colonization, including the type IVb pilus, colonization factor antigen III (CFA/III). Not all colonization factors are well characterized or known in toxin positive ETEC isolates, which may have an impact identifying ETEC isolates based on molecular screening of these biomarkers. We describe a novel coli surface antigen (CS) 8 subtype B (CS8B), a family of CFA/III pilus, in a toxin producing ETEC isolate from a Kenyan collection. In highlighting the existence of this putative CS, we provide the sequence and specific primers, which can be used alongside other ETEC primers previously described.

  15. A specimen of Rhamphorhynchus with soft tissue preservation, stomach contents and a putative coprolite

    Directory of Open Access Journals (Sweden)

    David Hone

    2015-08-01

    Full Text Available Despite being known for nearly two centuries, new specimens of the derived non-pterodactyloid pterosaur Rhamphorhynchus continue to be discovered and reveal new information about their anatomy and palaeobiology. Here we describe a specimen held in the collections of the Royal Tyrrell Museum of Palaeontology, Alberta, Canada that shows both preservation and impressions of soft tissues, and also preserves material interpreted as stomach contents of vertebrate remains and, uniquely, a putative coprolite. The specimen also preserves additional evidence for fibers in the uropatagium.

  16. A putative transglycosylase encoded by SCO4132 influences morphological differentiation and actinorhodin production in Streptomyces coelicolor

    Institute of Scientific and Technical Information of China (English)

    Pengfei Xie; Ana Zeng; Xiaoting Lv; Qiuxiang Cheng; Zhongjun Qin

    2013-01-01

    Here we report that tgdA,a novel gene encoding a putative transglycosylase,affects both the morphological differentiation and the yield of blue-pigmented compound actinorhodin in Streptomyces coelicolor.The tgdA null mutant displays sparse aerial hyphae and irregular spore chains frequently lacking chromosomal DNA.Elevated actinorhodin production coincides with the overexpression of actⅡ-orf4 in mutant.tgdA expression is temporally and developmentally regulated.The tgdA orthologs in Streptomyces avermilitis and Streptomyces lividans also affect differentiation.

  17. Prevalence of Clinical Periodontitis and Putative Periodontal Pathogens among South Indian Pregnant Women

    Directory of Open Access Journals (Sweden)

    Chaitanya Tellapragada

    2014-01-01

    Full Text Available In view of recent understanding of the association of periodontal infections and adverse pregnancy outcomes, the present investigation was undertaken to study the periodontal infections among 390 asymptomatic pregnant women and to find an association of bacterial etiologies with the disease. Prevalence of gingivitis was 38% and clinical periodontitis was 10% among the study population. Subgingival plaque specimens were subjected to multiplex PCR targeting ten putative periodontopathogenic bacteria. Among the periodontitis group, high detection rates of Porphyromonas gingivalis (56%, Prevotella nigrescens (44%, Treponema denticola (32%, and Prevotella intermedius (24% were noted along with significant association with the disease (P<0.05.

  18. A specimen of Rhamphorhynchus with soft tissue preservation, stomach contents and a putative coprolite.

    Science.gov (United States)

    Hone, David; Henderson, Donald M; Therrien, François; Habib, Michael B

    2015-01-01

    Despite being known for nearly two centuries, new specimens of the derived non-pterodactyloid pterosaur Rhamphorhynchus continue to be discovered and reveal new information about their anatomy and palaeobiology. Here we describe a specimen held in the collections of the Royal Tyrrell Museum of Palaeontology, Alberta, Canada that shows both preservation and impressions of soft tissues, and also preserves material interpreted as stomach contents of vertebrate remains and, uniquely, a putative coprolite. The specimen also preserves additional evidence for fibers in the uropatagium.

  19. A comparison of the effects of two putative 5-hydroxytryptamine renal prodrugs in normal man.

    OpenAIRE

    LI KAM WA, T. C.; Freestone, S.; Samson, R. R.; JOHNSTON, N. R.; Lee, M.R.

    1993-01-01

    1. The effects of 1 h intravenous infusions of equimolar amounts of two putative 5-hydroxytryptamine (5-HT) renal prodrugs, 5-hydroxy-L-tryptophan (5-HTP, 10 micrograms kg-1 min-1) and gamma-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP, 16.6 micrograms kg-1 min-1) were examined in five healthy male volunteers in a randomised, placebo-controlled, cross-over study. 2. Both compounds increased urinary excretion of 5-HT and there was greater extra-renal formation of 5-HT following 5-HTP administr...

  20. Behavioural characterisation of rats exposed neonatally to bisphenol-A: responses to a novel environment and to methylphenidate challenge in a putative model of attention-deficit hyperactivity disorder.

    NARCIS (Netherlands)

    Kiguchi, M.; Fujita, S.; Oki, H.; Shimizu, N.; Cools, A.R.; Koshikawa, N.

    2008-01-01

    Neonatal exposure of rats to bisphenol-A, an endocrine disruptor, has recently been proposed as a possible animal model of attention-deficit hyperactivity disorder (ADHD), because such rats exhibit motor hyperactivity. To strengthen the face validity of this animal model, the present study

  1. Behavioural characterisation of rats exposed neonatally to bisphenol-A: responses to a novel environment and to methylphenidate challenge in a putative model of attention-deficit hyperactivity disorder.

    NARCIS (Netherlands)

    Kiguchi, M.; Fujita, S.; Oki, H.; Shimizu, N.; Cools, A.R.; Koshikawa, N.

    2008-01-01

    Neonatal exposure of rats to bisphenol-A, an endocrine disruptor, has recently been proposed as a possible animal model of attention-deficit hyperactivity disorder (ADHD), because such rats exhibit motor hyperactivity. To strengthen the face validity of this animal model, the present study replicate

  2. Disruptores endocrinos. El caso particular de los xenobióticos estrogénicos. II Estrógenos sintéticos Endocrine disrupters. The case of oestrogenic xenobiotics II: synthetic oestrogens

    Directory of Open Access Journals (Sweden)

    P. Martín Olmedo

    2001-11-01

    Full Text Available En los últimos años se ha puesto en evidencia que muchas sustancias químicas de origen antropogénico son capaces de alterar el sistema endocrino de los seres vivos y se ha acuñado el nombre de disruptores endocrinos para definirlas. El número de disruptores endocrinos es una preocupación creciente si se añade a la inclusión de nuevos compuestos químicos, hasta ahora insospechados, la información generada sobre sus precursores, metabolitos y productos de degradación que tan solo ahora empiezan a conocerse. No se ha podido definir una estructura química única que permita clasificar a un compuesto químico como mimetizador de las hormonas sexuales femeninas, de tal manera que estructuras químicas similares a los estrógenos naturales, basados en el ciclopentanoperhidrofenantreno, comparten con los estilbenos, bisfenoles, bifenilos, alquilfenoles, dioxinas, furanos y parabenes su efecto hormonal estrogénico. El reconocimiento de la actividad estrogénica en diferentes modelos biológicos se ha utilizado para actualizar el censo de xenoestrógenos y poner de manifiesto fuentes de exposición humana hasta el momento insospechadas.In recent years, it has been demonstrated that endocrine systems of living beings can be altered by many chemical substances of anthropogenic origin, designated as endocrine disrupters. There are growing concerns about the number of these endocrine disrupters. It has not been possible to define a single chemical structure that allows the classification of a chemical compound as a mimic of female sex hormones, so that chemical structures similar to natural estrogens, based on cyclopentanoperhydrophenanthrene, share their hormonal effect with stilbenes, bisphenols, alkylphenols, dioxins, furans and parabenes. The recognition of estrogenic activity in different biological models has been used to update the list of xenoestrogens and reveal sources of human exposure that were previously unknown. New previously

  3. Putative cholesterol-binding sites in human immunodeficiency virus (HIV) coreceptors CXCR4 and CCR5.

    Science.gov (United States)

    Zhukovsky, Mikhail A; Lee, Po-Hsien; Ott, Albrecht; Helms, Volkhard

    2013-04-01

    Using molecular docking, we identified a cholesterol-binding site in the groove between transmembrane helices 1 and 7 near the inner membrane-water interface of the G protein-coupled receptor CXCR4, a coreceptor for HIV entry into cells. In this docking pose, the amino group of lysine K67 establishes a hydrogen bond with the hydroxyl group of cholesterol, whereas tyrosine Y302 stacks with cholesterol by its aromatic side chain, and a number of residues form hydrophobic contacts with cholesterol. Sequence alignment showed that a similar putative cholesterol-binding site is also present in CCR5, another HIV coreceptor. We suggest that the interaction of cholesterol with these putative cholesterol-binding sites in CXCR4 and CCR5 is responsible for the presence of these receptors in lipid rafts, for the effect of cholesterol on their conformational stability and function, and for the role that cell cholesterol plays in the cell entry of HIV strains that use these membrane proteins as coreceptors. We propose that mutations of residues that are involved in cholesterol binding will make CXCR4 and CCR5 insensitive to membrane cholesterol content. Cholesterol-binding sites in HIV coreceptors are potential targets for steroid drugs that bind to CXCR4 and CCR5 with higher binding affinity than cholesterol, but do not stabilize the native conformation of these proteins.

  4. On the Origin of the Supergiant HI Shell and Putative Companion in NGC 6822

    CERN Document Server

    Cannon, John M; Weisz, Daniel R; Skillman, Evan D; Dolphin, Andrew E; Bigiel, Frank; Cole, Andrew A; de Blok, W J G; Walter, Fabian

    2012-01-01

    We present new Hubble Space Telescope Advanced Camera for Surveys imaging of six positions spanning 5.8 kpc of the HI major axis of the Local Group dIrr NGC 6822, including both the putative companion galaxy and the large HI hole. The resulting deep color magnitude diagrams show that NGC 6822 has formed >50% of its stars in the last ~5 Gyr. The star formation histories of all six positions are similar over the most recent 500 Myr, including low-level star formation throughout this interval and a weak increase in star formation rate during the most recent 50 Myr. Stellar feedback can create the giant HI hole, assuming that the lifetime of the structure is longer than 500 Myr; such long-lived structures have now been observed in multiple systems and may be the norm in galaxies with solid-body rotation. The old stellar populations (red giants and red clump stars) of the putative companion are consistent with those of the extended halo of NGC 6822; this argues against the interpretation of this structure as a bon...

  5. ON THE ORIGIN OF THE SUPERGIANT H I SHELL AND PUTATIVE COMPANION IN NGC 6822

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, John M.; O' Leary, Erin M. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Weisz, Daniel R. [Department of Astronomy, University of Washington, Seattle, WA 98195 (United States); Skillman, Evan D. [Minnesota Institute for Astrophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Dolphin, Andrew E. [Raytheon Company, 1151 East Hermans Road, Tucson, AZ 85706 (United States); Bigiel, Frank [Institut fuer Theoretische Astrophysik, Universitaet Heidelberg, Albert-Ueberle-Str. 2, 69120 Heidelberg (Germany); Cole, Andrew A.; Walter, Fabian [School of Mathematics and Physics, University of Tasmania, Private Bag 37, Hobart 7001, Tasmania (Australia); De Blok, W.J.G., E-mail: jcannon@macalester.edu, E-mail: eoleary@macalester.edu, E-mail: dweisz@astro.washington.edu, E-mail: skillman@astro.umn.edu, E-mail: adolphin@raytheon.com, E-mail: bigiel@uni-heidelberg.de, E-mail: andrew.cole@utas.edu.au, E-mail: edeblok@ast.uct.ac.za, E-mail: walter@mpia.de [Department of Astronomy, University of Cape Town, Rondebosch 7700 (South Africa)

    2012-03-10

    We present new Hubble Space Telescope Advanced Camera for Surveys imaging of six positions spanning 5.8 kpc of the H I major axis of the Local Group dIrr NGC 6822, including both the putative companion galaxy and the large H I hole. The resulting deep color-magnitude diagrams show that NGC 6822 has formed >50% of its stars in the last {approx}5 Gyr. The star formation histories of all six positions are similar over the most recent 500 Myr, including low-level star formation throughout this interval and a weak increase in star formation rate during the most recent 50 Myr. Stellar feedback can create the giant H I hole, assuming that the lifetime of the structure is longer than 500 Myr; such long-lived structures have now been observed in multiple systems and may be the norm in galaxies with solid-body rotation. The old stellar populations (red giants and red clump stars) of the putative companion are consistent with those of the extended halo of NGC 6822; this argues against the interpretation of this structure as a bona fide interacting companion galaxy and against its being linked to the formation of the H I hole via an interaction. Since there is no evidence in the stellar population of a companion galaxy, the most likely explanation of the extended H I structure in NGC 6822 is a warped disk inclined to the line of sight.

  6. Transcriptome-Based Examination of Putative Pollen Allergens of Rice(Oryza sativa ssp.japonica)

    Institute of Scientific and Technical Information of China (English)

    Scott D.Russell; Prem L Bhalla; Mohan B.Singh

    2008-01-01

    Pollen allergens are among the most abundantly transcribed and translated products in the Iife history of plants,and particularly grasses.To identify different pollen allergens in rice,putative allergens were identified in the rice genome and their expression characterized using the Affymetrix 57K rice GeneChip microarray.Among the most abundant pollen-specific candidate transcripts were Ory s 1 beta-expansin.Ory s 2,Ory s 7 EFhand,Ory s 11,Ory s 12 profilin A,Ory s 23,glycosyl hydrolase family 28(polygalacturonase).and FAD binding proteins.Highly expressed pollen proteins are frequently present in multiple copy numbers,sometimes with mirror images Iocated on nearby regions of the opposite DNA strand.Many of these are intronless and inserted as copies that retain nearly exact copies of their regulatory elements.Ory s 23 reflects low variability and high copy number,suggesting recent gene amplification.Some copies contain pseudogenes,which may reflect their origin through activity of retrotransposition;some putative allergenic sequences bear fusion products with repeat sequences of transposable elements(LTRs).The abundance of nearby repetitive sequences,activation of transposable elements.and high production of mRNA transcripts appear to coincide in pollen and may contribute to a syndrome in which highly transcribed proteins may be copied and inserted with streamlined features for translation,including grouping and removaI of introns.

  7. Identification of putative DnaN-binding motifs in plasmid replication initiation proteins.

    Science.gov (United States)

    Dalrymple, Brian P; Kongsuwan, Kritaya; Wijffels, Gene

    2007-01-01

    Recently the plasmid RK2 replication initiation protein, TrfA, has been shown to bind to the beta subunit of DNA Polymerase III (DnaN) via a short pentapeptide with the consensus QL[S/D]LF. A second consensus peptide, the hexapeptide QLxLxL, has also been demonstrated to mediate binding to DnaN. Here we describe the results of a comprehensive survey of replication initiation proteins encoded by bacterial plasmids to identify putative DnaN-binding sites. Both pentapeptide and hexapeptide motifs have been identified in a number of families of replication initiation proteins. The distribution of sites is sporadic and closely related families of proteins may differ in the presence, location, or type of putative DnaN-binding motif. Neither motif has been identified in replication initiation proteins encoded by plasmids that replicate via rolling circles or strand displacement. The results suggest that the recruitment of DnaN to the origin of replication of a replisome by plasmid replication initiation proteins is not generally required for plasmid replication, but that in some cases it may be beneficial for efficiency of replication initiation.

  8. Uncovering the Putative B-Star Binary Companion of the SN 1993J Progenitor

    CERN Document Server

    Fox, Ori D; Van Dyk, Schuyler D; Filippenko, Alexei V; Fransson, Claes; Matheson, Thomas; Cenko, S Bradley; Chandra, Poonam; Dwarkadas, Vikram; Li, Weidong; Parker, Alex H; Smith, Nathan

    2014-01-01

    The Type IIb supernova (SN) 1993J is one of only a few stripped-envelope supernovae with a progenitor star identified in pre-explosion images. SN IIb models typically invoke H envelope stripping by mass transfer in a binary system. For the case of SN 1993J, the models suggest that the companion grew to 22 M_solar and became a source of ultraviolet (UV) excess. Located in M81, at a distance of only 3.6 Mpc, SN 1993J offers one of the best opportunities to detect the putative companion and test the progenitor model. Previously published near-UV spectra in 2004 showed evidence for absorption lines consistent with a hot (B2 Ia) star, but the field was crowded and dominated by flux from the SN. Here we present Hubble Space Telescope (HST) Cosmic Origins Spectrograph (COS) and Wide-Field Camera 3 (WFC3) observations of SN 1993J from 2012, at which point the flux from the SN had faded sufficiently to potentially measure the UV continuum properties from the putative companion. The resulting UV spectrum is consistent ...

  9. Evolution and structural diversification of PILS putative auxin carriers in plants

    Directory of Open Access Journals (Sweden)

    Elena eFeraru

    2012-10-01

    Full Text Available The phytohormone auxin contributes to virtually every aspect of the plant development. The spatiotemporal distribution of auxin depends on a complex interplay between auxin metabolism and intercellular auxin transport. Intracellular auxin compartmentalization provides another link between auxin transport processes and auxin metabolism. The PIN-LIKES (PILS putative auxin carriers localize to the endoplasmic reticulum (ER and contribute to cellular auxin homeostasis. PILS proteins regulate intracellular auxin accumulation, the rate of auxin conjugation and subsequently, affect nuclear auxin signalling. Here, we investigate sequence diversification of the PILS family in Arabidopsis thaliana and provide insights into the evolution of these novel putative auxin carriers in plants. Our data suggest that PILS proteins are conserved throughout the plant lineage and expanded during higher plant evolution. PILS proteins diversified early during plant evolution into three clades. Besides the ancient Clade I encompassing non-land plant species, PILS proteins evolved into two clades. The diversification of Clade II and Clade III occurred already at the level of non-vascular plant evolution and, hence, both clades contain vascular and non-vascular plant species. Nevertheless, Clade III contains fewer non- and increased numbers of vascular plants, indicating higher importance of Clade III for vascular plant evolution. Notably, PILS proteins are distinct and appear evolutionarily older than the prominent PIN-FORMED auxin carriers. Moreover, we revealed particular PILS sequence divergence in Arabidopsis and assume that these alterations could contribute to distinct gene regulations and protein functions.

  10. Characterization of putative multidrug resistance transporters of the major facilitator-superfamily expressed in Salmonella Typhi.

    Science.gov (United States)

    Shaheen, Aqsa; Ismat, Fouzia; Iqbal, Mazhar; Haque, Abdul; De Zorzi, Rita; Mirza, Osman; Walz, Thomas; Rahman, Moazur

    2015-05-01

    Multidrug resistance mediated by efflux pumps is a well-known phenomenon in infectious bacteria. Although much work has been carried out to characterize multidrug efflux pumps in Gram-negative and Gram-positive bacteria, such information is still lacking for many deadly pathogens. The aim of this study was to gain insight into the substrate specificity of previously uncharacterized transporters of Salmonella Typhi to identify their role in the development of multidrug resistance. S. Typhi genes encoding putative members of the major facilitator superfamily were cloned and expressed in the drug-hypersensitive Escherichia coli strain KAM42, and tested for transport of 25 antibacterial compounds, including representative antibiotics of various classes, antiseptics, dyes and detergents. Of the 15 tested putative transporters, STY0901, STY2458 and STY4874 exhibited a drug-resistance phenotype. Among these, STY4874 conferred resistance to at least ten of the tested antimicrobials: ciprofloxacin, norfloxacin, levofloxacin, kanamycin, streptomycin, gentamycin, nalidixic acid, chloramphenicol, ethidium bromide, and acriflavine, including fluoroquinolone antibiotics, which were drugs of choice to treat S. Typhi infections. Cell-based functional studies using ethidium bromide and acriflavine showed that STY4874 functions as a H(+)-dependent exporter. These results suggest that STY4874 may be an important drug target, which can now be tested by studying the susceptibility of a STY4874-deficient S. Typhi strain to antimicrobials.

  11. Mutation analysis of novel human liver-related putative tumor suppressor gene in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Liao; Tsai-Ping Li; Mu-Jun Zhao; Jing Zhao; Hai Song; Pascal Pineau; Agnès Marchio; Anne Dejean; Pierre Tiollais; Hong-Yang Wang

    2003-01-01

    AIM: To find the point mutations meaningful for inactivationof liver-related putative tumor suppressor gene (LPTS) gene,a human novel liver-related putative tumor suppressor geneand telomerase inhibitor in hepatocellular carcinoma.METHODS: The entire coding sequence of LPTS genewas examined for mutations by single strand conformationpolymorphism (SSCP) assay and PCR products directsequencing in 56 liver cancer cell lines, 7 ovarian cancerand 7 head & neck tumor cell lines and 70 pairs of HCCtissues samples. The cDNA fragment coding for the mostfrequent mutant protein was subcloned into GST fusionexpression vector. The product was expressed in E. coliand purified by glutathione-agarose column. Telomericrepeat amplification protocol (TRAP) assays wereperformed to study the effect of point mutation totelomerase inhibitory activity.RESULTS: SSCP gels showed the abnormal shifting bandsand DNA sequencing found that there were 5 differentmutations and/or polymorphisms in 12 tumor cell lineslocated at exon2, exon5 and exon7. The main alterationswere A(778)A/G and A(880)T in exon7. The change in siteof 778 could not be found in HCC tissue samples, while themutation in position 880 was seen in 7 (10 %) cases. Themutation in the site of 880 had no effect on telomeraseinhibitory activity.CONCLUSION: Alterations identified in this study arepolymorphisms of LPTS gene. LPTS mutations occur in HCCbut are infrequent and of little effect on the telomeraseinhibitory function of the protein. Epigenetics, such asmethylation, acetylation, may play the key role in inactivationof LPTS.

  12. Expression of putative virulence factors in the potato pathogen Clavibacter michiganensis subsp. sepedonicus during infection.

    Science.gov (United States)

    Holtsmark, Ingrid; Takle, Gunnhild W; Brurberg, May Bente

    2008-02-01

    The Gram-positive bacterium Clavibacter michiganensis subsp. sepedonicus is the causal agent of bacterial wilt and ring rot of potato. So far, only two proteins have been shown to be essential for virulence, namely a plasmid-encoded cellulase CelA and a hypersensitive response-inducing protein. We have examined the relative expression of CelA and eight putative virulence factors during infection of potato and in liquid culture, using quantitative real-time PCR. The examined putative virulence genes were celB, a cellulase-encoding gene and genes encoding a pectate lyase, a xylanase and five homologues of the Clavibacter michiganensis subsp. michiganensis pathogenicity factor Pat-1 thought to encode a serine protease. Six of the nine assayed genes were up-regulated during infection of potato, including celA, celB, the xylanase gene, and two of the pat genes. The pectate lyase gene showed only slightly elevated expression, whereas three of the five examined pat genes were down-regulated during infection in potato. Interestingly, the two up-regulated pat genes showed a noticeable sequence difference compared to the three down-regulated pat genes. These results reveal several new proteins that are likely to be involved in Clavibacter michiganensis subsp. sepedonicus pathogenicity.

  13. Transcriptome of Aphanomyces euteiches: new oomycete putative pathogenicity factors and metabolic pathways.

    Directory of Open Access Journals (Sweden)

    Elodie Gaulin

    Full Text Available Aphanomyces euteiches is an oomycete pathogen that causes seedling blight and root rot of legumes, such as alfalfa and pea. The genus Aphanomyces is phylogenically distinct from well-studied oomycetes such as Phytophthora sp., and contains species pathogenic on plants and aquatic animals. To provide the first foray into gene diversity of A. euteiches, two cDNA libraries were constructed using mRNA extracted from mycelium grown in an artificial liquid medium or in contact to plant roots. A unigene set of 7,977 sequences was obtained from 18,864 high-quality expressed sequenced tags (ESTs and characterized for potential functions. Comparisons with oomycete proteomes revealed major differences between the gene content of A. euteiches and those of Phytophthora species, leading to the identification of biosynthetic pathways absent in Phytophthora, of new putative pathogenicity genes and of expansion of gene families encoding extracellular proteins, notably different classes of proteases. Among the genes specific of A. euteiches are members of a new family of extracellular proteins putatively involved in adhesion, containing up to four protein domains similar to fungal cellulose binding domains. Comparison of A. euteiches sequences with proteomes of fully sequenced eukaryotic pathogens, including fungi, apicomplexa and trypanosomatids, allowed the identification of A. euteiches genes with close orthologs in these microorganisms but absent in other oomycetes sequenced so far, notably transporters and non-ribosomal peptide synthetases, and suggests the presence of a defense mechanism against oxidative stress which was initially characterized in the pathogenic trypanosomatids.

  14. Regulation of Arabidopsis Early Anther Development by Putative Cell-Cell Signaling Molecules and Transcriptional Regulators

    Institute of Scientific and Technical Information of China (English)

    Yu-Jin Sun; Carey LH Hord; Chang-Bin Chen; Hong Ma

    2007-01-01

    Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS (also called NOZZLE),to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 (DYT1) gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.

  15. Characterization of Putative cis-Regulatory Elements in Genes Preferentially Expressed in Arabidopsis Male Meiocytes

    Directory of Open Access Journals (Sweden)

    Junhua Li

    2014-01-01

    Full Text Available Meiosis is essential for plant reproduction because it is the process during which homologous chromosome pairing, synapsis, and meiotic recombination occur. The meiotic transcriptome is difficult to investigate because of the size of meiocytes and the confines of anther lobes. The recent development of isolation techniques has enabled the characterization of transcriptional profiles in male meiocytes of Arabidopsis. Gene expression in male meiocytes shows unique features. The direct interaction of transcription factors (TFs with DNA regulatory sequences forms the basis for the specificity of transcriptional regulation. Here, we identified putative cis-regulatory elements (CREs associated with male meiocyte-expressed genes using in silico tools. The upstream regions (1 kb of the top 50 genes preferentially expressed in Arabidopsis meiocytes possessed conserved motifs. These motifs are putative binding sites of TFs, some of which share common functions, such as roles in cell division. In combination with cell-type-specific analysis, our findings could be a substantial aid for the identification and experimental verification of the protein-DNA interactions for the specific TFs that drive gene expression in meiocytes.

  16. Identification and site of action of the remaining four putative pseudouridine synthases in Escherichia coli.

    Science.gov (United States)

    Del Campo, M; Kaya, Y; Ofengand, J

    2001-11-01

    There are 10 known putative pseudouridine synthase genes in Escherichia coli. The products of six have been previously assigned, one to formation of the single pseudouridine in 16S RNA, three to the formation of seven pseudouridines in 23S RNA, and three to the formation of three pseudouridines in tRNA (one synthase makes pseudouridine in 23S RNA and tRNA). Here we show that the remaining four putative synthase genes make bona fide pseudouridine synthases and identify which pseudouridines they make. RluB (formerly YciL) and RluE (formerly YmfC) make pseudouridine2605 and pseudouridine2457, respectively, in 23S RNA. RluF (formerly YjbC) makes the newly discovered pseudouridine2604 in 23S RNA, and TruC (formerly YqcB) makes pseudouridine65 in tRNA(Ile1) and tRNA(Asp). Deletion of each of these synthase genes individually had no effect on exponential growth in rich media at 25 degrees C, 37 degrees C, or 42 degrees C. A strain lacking RluB and RluF also showed no growth defect under these conditions. Mutation of a conserved aspartate in a common sequence motif, previously shown to be essential for the other six E. coli pseudouridine synthases and several yeast pseudouridine synthases, also caused a loss of in vivo activity in all four of the synthases studied in this work.

  17. Transcriptome Analysis Reveals Putative Genes Involved in Iridoid Biosynthesis in Rehmannia glutinosa

    Directory of Open Access Journals (Sweden)

    Xianen Li

    2012-10-01

    Full Text Available Rehmannia glutinosa, one of the most widely used herbal medicines in the Orient, is rich in biologically active iridoids. Despite their medicinal importance, no molecular information about the iridoid biosynthesis in this plant is presently available. To explore the transcriptome of R. glutinosa and investigate genes involved in iridoid biosynthesis, we used massively parallel pyrosequencing on the 454 GS FLX Titanium platform to generate a substantial EST dataset. Based on sequence similarity searches against the public sequence databases, the sequences were first annotated and then subjected to Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG based analysis. Bioinformatic analysis indicated that the 454 assembly contained a set of genes putatively involved in iridoid biosynthesis. Significantly, homologues of the secoiridoid pathway genes that were only identified in terpenoid indole alkaloid producing plants were also identified, whose presence implied that route II iridoids and route I iridoids share common enzyme steps in the early stage of biosynthesis. The gene expression patterns of four prenyltransferase transcripts were analyzed using qRT-PCR, which shed light on their putative functions in tissues of R. glutinosa. The data explored in this study will provide valuable information for further studies concerning iridoid biosynthesis.

  18. Mapping the flow of information within the putative mirror neuron system during gesture observation.

    Science.gov (United States)

    Schippers, Marleen B; Keysers, Christian

    2011-07-01

    The putative mirror neuron system may either function as a strict feed-forward system or as a dynamic control system. A strict feed-forward system would predict that action observation leads to a predominantly temporal→parietal→premotor flow of information in which a visual representation is transformed into motor-programs which contribute to action understanding. Instead, a dynamic feedback control system would predict that the reverse direction of information flow predominates because of a combination of inhibitory forward and excitatory inverse models. Here we test which of these conflicting predictions best matches the information flow within the putative mirror neuron system (pMNS) and between the pMNS and the rest of the brain during the observation of comparatively long naturalistic stretches of communicative gestures. We used Granger causality to test the dominant direction of influence. Our results fit the predictions of the dynamic feedback control system: we found predominantly an information flow within the pMNS from premotor to parietal and middle temporal cortices. This is more pronounced during an active guessing task than while passively reviewing the same gestures. In particular, the ventral premotor cortex sends significantly more information to other pMNS areas than it receives during active guessing than during passive observation.

  19. Identification and functional analysis of Penicillium digitatum genes putatively involved in virulence towards citrus fruit.

    Science.gov (United States)

    López-Pérez, Mario; Ballester, Ana-Rosa; González-Candelas, Luis

    2015-04-01

    The fungus Penicillium digitatum, the causal agent of green mould rot, is the most destructive post-harvest pathogen of citrus fruit in Mediterranean regions. In order to identify P. digitatum genes up-regulated during the infection of oranges that may constitute putative virulence factors, we followed a polymerase chain reaction (PCR)-based suppression subtractive hybridization and cDNA macroarray hybridization approach. The origin of expressed sequence tags (ESTs) was determined by comparison against the available genome sequences of both organisms. Genes coding for fungal proteases and plant cell wall-degrading enzymes represent the largest categories in the subtracted cDNA library. Northern blot analysis of a selection of P. digitatum genes, including those coding for proteases, cell wall-related enzymes, redox homoeostasis and detoxification processes, confirmed their up-regulation at varying time points during the infection process. Agrobacterium tumefaciens-mediated transformation was used to generate knockout mutants for two genes encoding a pectin lyase (Pnl1) and a naphthalene dioxygenase (Ndo1). Two independent P. digitatum Δndo1 mutants were as virulent as the wild-type. However, the two Δpnl1 mutants analysed were less virulent than the parental strain or an ectopic transformant. Together, these results provide a significant advance in our understanding of the putative determinants of the virulence mechanisms of P. digitatum.

  20. Unprecedented diversity of catalytic domains in the first four modules of the putative pederin polyketide synthase.

    Science.gov (United States)

    Piel, Jörn; Wen, Gaiping; Platzer, Matthias; Hui, Dequan

    2004-01-03

    Polyketides of the pederin group are highly potent antitumor compounds found in terrestrial beetles and marine sponges. Pederin is used by beetles of the genera Paederus and Paederidus as a chemical defense. We have recently identified a group of putative pederin biosynthesis genes and localized them to the genome of an as yet unculturable Pseudomonas sp. symbiont, the likely true pederin producer. However, this polyketide synthase cluster lacks several genes expected for pederin production. Here we report an additional polyketide synthase encoded on a separate region of the symbiont genome. It contains at least three novel catalytic domains that are predicted to be involved in pederin chain initiation and the formation of an unusual exomethylene bond. The region is bordered by mobility pseudogenes; this suggests that gene transposition led to the disjointed cluster organization. With this work, all putative pederin genes have been identified. Their heterologous expression in a culturable bacterium will provide important insights into how sustainable sources of invertebrate-derived drug candidates can be created.

  1. Biochemical Characterization of Putative Adenylate Dimethylallyltransferase and Cytokinin Dehydrogenase from Nostoc sp. PCC 7120.

    Science.gov (United States)

    Frébortová, Jitka; Greplová, Marta; Seidl, Michael F; Heyl, Alexander; Frébort, Ivo

    2015-01-01

    Cytokinins, a class of phytohormones, are adenine derivatives common to many different organisms. In plants, these play a crucial role as regulators of plant development and the reaction to abiotic and biotic stress. Key enzymes in the cytokinin synthesis and degradation in modern land plants are the isopentyl transferases and the cytokinin dehydrogenases, respectively. Their encoding genes have been probably introduced into the plant lineage during the primary endosymbiosis. To shed light on the evolution of these proteins, the genes homologous to plant adenylate isopentenyl transferase and cytokinin dehydrogenase were amplified from the genomic DNA of cyanobacterium Nostoc sp. PCC 7120 and expressed in Escherichia coli. The putative isopentenyl transferase was shown to be functional in a biochemical assay. In contrast, no enzymatic activity was detected for the putative cytokinin dehydrogenase, even though the principal domains necessary for its function are present. Several mutant variants, in which conserved amino acids in land plant cytokinin dehydrogenases had been restored, were inactive. A combination of experimental data with phylogenetic analysis indicates that adenylate-type isopentenyl transferases might have evolved several times independently. While the Nostoc genome contains a gene coding for protein with characteristics of cytokinin dehydrogenase, the organism is not able to break down cytokinins in the way shown for land plants.

  2. TiD: Standalone software for mining putative drug targets from bacterial proteome.

    Science.gov (United States)

    Gupta, Reena; Pradhan, Dibyabhaba; Jain, Arun Kumar; Rai, Chandra Shekhar

    2017-01-01

    TiD is a standalone application, which relies on basic assumption that a protein must be essential for pathogens survival and non-homologous with host to qualify as putative target. With an input bacterial proteome, TiD removes paralogous proteins, picks essential ones, and excludes proteins homologous with host organisms. The targets illustrate non-homology with at least 40 out of 84 gut microbes, considered safe for human. TiD classifies proposed targets as known, novel and virulent. Users can perform pathway analysis, choke point analysis, interactome analysis, subcellular localization and functional annotations through web servers cross-referenced with the application. Drug targets identified by TiD for Listeria monocytogenes, Bacillus anthracis and Pseudomonas aeruginosa have revealed significant overlaps with previous studies. TiD takes <2h to scan putative targets from a bacterial proteome with ~5000 proteins; hence, we propose it as a useful tool for rational drug design. TiD is available at http://bmicnip.in/TiD/. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. VenomKB, a new knowledge base for facilitating the validation of putative venom therapies.

    Science.gov (United States)

    Romano, Joseph D; Tatonetti, Nicholas P

    2015-11-24

    Animal venoms have been used for therapeutic purposes since the dawn of recorded history. Only a small fraction, however, have been tested for pharmaceutical utility. Modern computational methods enable the systematic exploration of novel therapeutic uses for venom compounds. Unfortunately, there is currently no comprehensive resource describing the clinical effects of venoms to support this computational analysis. We present VenomKB, a new publicly accessible knowledge base and website that aims to act as a repository for emerging and putative venom therapies. Presently, it consists of three database tables: (1) Manually curated records of putative venom therapies supported by scientific literature, (2) automatically parsed MEDLINE articles describing compounds that may be venom derived, and their effects on the human body, and (3) automatically retrieved records from the new Semantic Medline resource that describe the effects of venom compounds on mammalian anatomy. Data from VenomKB may be selectively retrieved in a variety of popular data formats, are open-source, and will be continually updated as venom therapies become better understood.

  4. Small-fragment genomic libraries for the display of putative epitopes from clinically significant pathogens.

    Science.gov (United States)

    Henics, T; Winkler, B; Pfeifer, U; Gill, S R; Buschle, M; von Gabain, A; Meinke, A L

    2003-07-01

    Taking advantage of whole genome sequences of bacterial pathogens in many thriving diseases with global impact, we developed a comprehensive screening procedure for the identification of putative vaccine candidate antigens. Importantly, this procedure relies on highly representative small-fragment genomic libraries that are expressed to display frame-selected epitope-size peptides on a bacterial cell surface and to interact directly with carefully selected disease-relevant high-titer sera. Here we describe the generation of small-fragment genomic libraries of Gram-positive and Gram-negative clinically significant pathogens, including Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus pneumoniae, Enterococcus faecalis, Helicobacter pylori, Chlamydia pneumoniae, the enterotoxigenic Escherichia coli, and Campylobacter jejuni. Large-scale sequencing revealed that the libraries, which provide an average of 20-fold coverage, were random and, as demonstrated with two S. aureus libraries, highly representative. Consistent with the comprehensive nature of this approach is the identification of epitopes that reside in both annotated and putatively novel open reading frames. The use of these libraries therefore allows for the rapid and direct identification of immunogenic epitopes with no apparent bias or difficulty that often associate with conventional expression methods.

  5. Five putative nucleoside triphosphate diphosphohydrolase genes are expressed in Trichomonas vaginalis.

    Science.gov (United States)

    Frasson, Amanda Piccoli; Dos Santos, Odelta; Meirelles, Lúcia Collares; Macedo, Alexandre José; Tasca, Tiana

    2016-01-01

    Trichomonas vaginalis is a protozoan that parasitizes the human urogenital tract causing trichomoniasis, the most common non-viral sexually transmitted disease. The parasite has unique genomic characteristics such as a large genome size and expanded gene families. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) is an enzyme responsible for hydrolyzing nucleoside tri- and diphosphates and has already been biochemically characterized in T. vaginalis. Considering the important role of this enzyme in the production of extracellular adenosine for parasite uptake, we evaluated the gene expression of five putative NTPDases in T. vaginalis. We showed that all five putative TvNTPDase genes (TvNTPDase1-5) were expressed by both fresh clinical and long-term grown isolates. The amino acid alignment predicted the presence of the five crucial apyrase conserved regions, transmembrane domains, signal peptides, phosphorylation and catalytic sites. Moreover, a phylogenetic analysis showed that TvNTPDase sequences make up a clade with NTPDases intracellularly located. Biochemical NTPDase activity (ATP and ADP hydrolysis) is responsive to the serum-restrictive conditions and the gene expression of TvNTPDases was mostly increased, mainly TvNTPDase2 and TvNTPDase4, although there was not a clear pattern of expression among them. In summary, the present report demonstrates the gene expression patterns of predicted NTPDases in T. vaginalis.

  6. Functional characterization of PaLAX1, a putative auxin permease, in heterologous plant systems.

    Science.gov (United States)

    Hoyerová, Klára; Perry, Lucie; Hand, Paul; Lanková, Martina; Kocábek, Tomás; May, Sean; Kottová, Jana; Paces, Jan; Napier, Richard; Zazímalová, Eva

    2008-03-01

    We have isolated the cDNA of the gene PaLAX1 from a wild cherry tree (Prunus avium). The gene and its product are highly similar in sequences to both the cDNAs and the corresponding protein products of AUX/LAX-type genes, coding for putative auxin influx carriers. We have prepared and characterized transformed Nicotiana tabacum and Arabidopsis thaliana plants carrying the gene PaLAX1. We have proved that constitutive overexpression of PaLAX1 is accompanied by changes in the content and distribution of free indole-3-acetic acid, the major endogenous auxin. The increase in free indole-3-acetic acid content in transgenic plants resulted in various phenotype changes, typical for the auxin-overproducing plants. The uptake of synthetic auxin, 2,4-dichlorophenoxyacetic acid, was 3 times higher in transgenic lines compared to the wild-type lines and the treatment with the auxin uptake inhibitor 1-naphthoxyacetic acid reverted the changes caused by the expression of PaLAX1. Moreover, the agravitropic response could be restored by expression of PaLAX1 in the mutant aux1 plants, which are deficient in auxin influx carrier activity. Based on our data, we have concluded that the product of the gene PaLAX1 promotes the uptake of auxin into cells, and, as a putative auxin influx carrier, it affects the content and distribution of free endogenous auxin in transgenic plants.

  7. Sensitivity analysis of the relationship between disease occurrence and distance from a putative source of pollution

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    Emanuela Dreassi

    2008-05-01

    Full Text Available The relation between disease risk and a point source of pollution is usually investigated using distance from the source as a proxy of exposure. The analysis may be based on case-control data or on aggregated data. The definition of the function relating risk of disease and distance is critical, both in a classical and in a Bayesian framework, because the likelihood is usually very flat, even with large amounts of data. In this paper we investigate how the specification of the function relating risk of disease with distance from the source and of the prior distributions on the parameters of the function affects the results when case-control data and Bayesian methods are used. We consider different popular parametric models for the risk distance function in a Bayesian approach, comparing estimates with those derived by maximum likelihood. As an example we have analyzed the relationship between a putative source of environmental pollution (an asbestos cement plant and the occurrence of pleural malignant mesothelioma in the area of Casale Monferrato (Italy in 1987-1993. Risk of pleural malignant mesothelioma turns out to be strongly related to distance from the asbestos cement plant. However, as the models appeared to be sensitive to modeling choices, we suggest that any analysis of disease risk around a putative source should be integrated with a careful sensitivity analysis and possibly with prior knowledge. The choice of prior distribution is extremely important and should be based on epidemiological considerations.

  8. Putative monofunctional type I polyketide synthase units: a dinoflagellate-specific feature?

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    Karsten Eichholz

    Full Text Available Marine dinoflagellates (alveolata are microalgae of which some cause harmful algal blooms and produce a broad variety of most likely polyketide synthesis derived phycotoxins. Recently, novel polyketide synthesase (PKS transcripts have been described from the Florida red tide dinoflagellate Karenia brevis (gymnodiniales which are evolutionarily related to Type I PKS but were apparently expressed as monofunctional proteins, a feature typical of Type II PKS. Here, we investigated expression units of PKS I-like sequences in Alexandrium ostenfeldii (gonyaulacales and Heterocapsa triquetra (peridiniales at the transcript and protein level. The five full length transcripts we obtained were all characterized by polyadenylation, a 3' UTR and the dinoflagellate specific spliced leader sequence at the 5'end. Each of the five transcripts encoded a single ketoacylsynthase (KS domain showing high similarity to K. brevis KS sequences. The monofunctional structure was also confirmed using dinoflagellate specific KS antibodies in Western Blots. In a maximum likelihood phylogenetic analysis of KS domains from diverse PKSs, dinoflagellate KSs formed a clade placed well within the protist Type I PKS clade between apicomplexa, haptophytes and chlorophytes. These findings indicate that the atypical PKS I structure, i.e., expression as putative monofunctional units, might be a dinoflagellate specific feature. In addition, the sequenced transcripts harbored a previously unknown, apparently dinoflagellate specific conserved N-terminal domain. We discuss the implications of this novel region with regard to the putative monofunctional organization of Type I PKS in dinoflagellates.

  9. Dichotomous Distribution of Putative Cholinergic Interneurons in Mouse Accessory Olfactory Bulb

    Science.gov (United States)

    Marking, Sarah; Krosnowski, Kurt; Ogura, Tatsuya; Lin, Weihong

    2017-01-01

    Sensory information processing in the olfactory bulb (OB) relies on diverse populations of bulbar interneurons. In rodents, the accessory OB (AOB) is divided into two bulbar regions, the anterior (aAOB) and posterior (pAOB), which differ substantially in their circuitry connections and associated behaviors. We previously identified and characterized a large number of morphologically diverse cholinergic interneurons in the main OB (MOB) using transgenic mice to visualize the cell bodies of choline acetyltransferase (ChAT-expressing neurons and immunolabeling (Krosnowski et al., 2012)). However, whether there are cholinergic neurons in the AOB is controversial and there is no detailed characterization of such neurons. Using the same line of ChAT(bacterial artificial chromosome, BAC)-enhanced green fluorescent protein (eGFP) transgenic mice, we investigated cholinergic neurons in the AOB. We found significant differences in the number and location of GFP-expressing (GFP+), putative cholinergic interneurons between the aAOB and pAOB. The highest numbers of GFP+ interneurons were found in the aAOB glomerular layer (aGL) and pAOB mitral/tufted cell layer (pMCL). We also noted a high density of GFP+ interneurons encircling the border region of the pMCL. Interestingly, a small subset of glomeruli in the middle of the GL receives strong MCL GFP+ nerve processes. These local putative cholinergic-innervated glomeruli are situated just outside the aGL, setting the boundary between the pGL and aGL. Many but not all GFP+ neurons in the AOB were weakly labeled with antibodies against ChAT and vesicular acetylcholine transporter (VAChT). We further determined if these GFP+ interneurons differ from other previously characterized interneuron populations in the AOB and found that AOB GFP+ interneurons express neither GABAergic nor dopaminergic markers and most also do not express the glutamatergic marker. Similar to the cholinergic interneurons of the MOB, some AOB GFP+ interneurons

  10. Coral bleaching under thermal stress: putative involvement of host/symbiont recognition mechanisms

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    Tambutte Sylvie

    2009-08-01

    Full Text Available Abstract Background Coral bleaching can be defined as the loss of symbiotic zooxanthellae and/or their photosynthetic pigments from their cnidarian host. This major disturbance of reef ecosystems is principally induced by increases in water temperature. Since the beginning of the 1980s and the onset of global climate change, this phenomenon has been occurring at increasing rates and scales, and with increasing severity. Several studies have been undertaken in the last few years to better understand the cellular and molecular mechanisms of coral bleaching but the jigsaw puzzle is far from being complete, especially concerning the early events leading to symbiosis breakdown. The aim of the present study was to find molecular actors involved early in the mechanism leading to symbiosis collapse. Results In our experimental procedure, one set of Pocillopora damicornis nubbins was subjected to a gradual increase of water temperature from 28°C to 32°C over 15 days. A second control set kept at constant temperature (28°C. The differentially expressed mRNA between the stressed states (sampled just before the onset of bleaching and the non stressed states (control were isolated by Suppression Subtractive Hybridization. Transcription rates of the most interesting genes (considering their putative function were quantified by Q-RT-PCR, which revealed a significant decrease in transcription of two candidates six days before bleaching. RACE-PCR experiments showed that one of them (PdC-Lectin contained a C-Type-Lectin domain specific for mannose. Immunolocalisation demonstrated that this host gene mediates molecular interactions between the host and the symbionts suggesting a putative role in zooxanthellae acquisition and/or sequestration. The second gene corresponds to a gene putatively involved in calcification processes (Pdcyst-rich. Its down-regulation could reflect a trade-off mechanism leading to the arrest of the mineralization process under stress

  11. Identification of putative drug targets of Listeria monocytogenes F2365 by subtractive genomics approach

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    Md. Musharaf Hossain

    2013-01-01

    Full Text Available The prolonged and uncontrolled use of antibiotics in treatment against many pathogens causes the multiple drug resistance. The drug resistance of Listeria monocytogenes F2365 has been evolved, which cause a major disease listeriosis. The drug dose limit against that pathogen was also increased for currently prescribed antibiotics and more often combinational therapy was preferred. Therefore, identification of an extensive novel drug target, unique and essential to the microorganism and subjected to its validation and drug development is imperative. Availability of the total proteome of L. monocytogenes F2365 enabled in silico identification of putative common drug targets and their subcellular localization by subtractive genomics approach. In the present work subtractive genomics approach is used to identify vaccine and drug targets of L. monocytogenes F2365 to speed up the rational drug and vaccine design. It has revealed that out of 2821 reference sequences of the pathogen, 744 represent essential proteins and among them 274 are human non-homolog proteins. Besides, all predicted human non-homologs were then analyzed by subcellular localization servers, in which 46 proteins were identified as surface exposed proteins and can be considered as potential drug and vaccine targets for the pathogen. The 3D structure of two human non-homolog putative drug targets, pantothenate kinase (LmPK and holliday junction resolvase-like protein (LmHJR of L. monocytogenes F2365 were generated by homology modeling program Easymodeller 4.0; a GUI version of modeller. Generated structures were also validated by several online servers. The overall stereochemical quality of the model was assessed by Ramachandran plot analysis that was provided by PROCHECK. ProQ, ERRAT, Pro-SA web and VERIFY 3D of SAVES programs were also used to compute several validation parameters during the evaluation of the model. This protein structure information is important in structure

  12. Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous cyanobacteria

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    Cui Hongli

    2012-11-01

    Full Text Available Abstract Background Cyanobacteria are photoautotrophic prokaryotes with wide variations in genome sizes and ecological habitats. Peroxiredoxin (PRX is an important protein that plays essential roles in protecting own cells against reactive oxygen species (ROS. PRXs have been identified from mammals, fungi and higher plants. However, knowledge on cyanobacterial PRXs still remains obscure. With the availability of 37 sequenced cyanobacterial genomes, we performed a comprehensive comparative analysis of PRXs and explored their diversity, distribution, domain structure and evolution. Results Overall 244 putative prx genes were identified, which were abundant in filamentous diazotrophic cyanobacteria, Acaryochloris marina MBIC 11017, and unicellular cyanobacteria inhabiting freshwater and hot-springs, while poor in all Prochlorococcus and marine Synechococcus strains. Among these putative genes, 25 open reading frames (ORFs encoding hypothetical proteins were identified as prx gene family members and the others were already annotated as prx genes. All 244 putative PRXs were classified into five major subfamilies (1-Cys, 2-Cys, BCP, PRX5_like, and PRX-like according to their domain structures. The catalytic motifs of the cyanobacterial PRXs were similar to those of eukaryotic PRXs and highly conserved in all but the PRX-like subfamily. Classical motif (CXXC of thioredoxin was detected in protein sequences from the PRX-like subfamily. Phylogenetic tree constructed of catalytic domains coincided well with the domain structures of PRXs and the phylogenies based on 16s rRNA. Conclusions The distribution of genes encoding PRXs in different unicellular and filamentous cyanobacteria especially those sub-families like PRX-like or 1-Cys PRX correlate with the genome size, eco-physiology, and physiological properties of the organisms. Cyanobacterial and eukaryotic PRXs share similar conserved motifs, indicating that cyanobacteria adopt similar catalytic

  13. Identification of a putative protein profile associated with tamoxifen therapy resistance in breast cancer.

    Science.gov (United States)

    Umar, Arzu; Kang, Hyuk; Timmermans, Annemieke M; Look, Maxime P; Meijer-van Gelder, Marion E; den Bakker, Michael A; Jaitly, Navdeep; Martens, John W M; Luider, Theo M; Foekens, John A; Pasa-Tolić, Ljiljana

    2009-06-01

    Tamoxifen resistance is a major cause of death in patients with recurrent breast cancer. Current clinical factors can correctly predict therapy response in only half of the treated patients. Identification of proteins that are associated with tamoxifen resistance is a first step toward better response prediction and tailored treatment of patients. In the present study we intended to identify putative protein biomarkers indicative of tamoxifen therapy resistance in breast cancer using nano-LC coupled with FTICR MS. Comparative proteome analysis was performed on approximately 5,500 pooled tumor cells (corresponding to approximately 550 ng of protein lysate/analysis) obtained through laser capture microdissection (LCM) from two independently processed data sets (n = 24 and n = 27) containing both tamoxifen therapy-sensitive and therapy-resistant tumors. Peptides and proteins were identified by matching mass and elution time of newly acquired LC-MS features to information in previously generated accurate mass and time tag reference databases. A total of 17,263 unique peptides were identified that corresponded to 2,556 non-redundant proteins identified with > or = 2 peptides. 1,713 overlapping proteins between the two data sets were used for further analysis. Comparative proteome analysis revealed 100 putatively differentially abundant proteins between tamoxifen-sensitive and tamoxifen-resistant tumors. The presence and relative abundance for 47 differentially abundant proteins were verified by targeted nano-LC-MS/MS in a selection of unpooled, non-microdissected discovery set tumor tissue extracts. ENPP1, EIF3E, and GNB4 were significantly associated with progression-free survival upon tamoxifen treatment for recurrent disease. Differential abundance of our top discriminating protein, extracellular matrix metalloproteinase inducer, was validated by tissue microarray in an independent patient cohort (n = 156). Extracellular matrix metalloproteinase inducer levels were

  14. Genome-wide analysis of putative peroxiredoxin in unicellular and filamentous cyanobacteria

    Science.gov (United States)

    2012-01-01

    Background Cyanobacteria are photoautotrophic prokaryotes with wide variations in genome sizes and ecological habitats. Peroxiredoxin (PRX) is an important protein that plays essential roles in protecting own cells against reactive oxygen species (ROS). PRXs have been identified from mammals, fungi and higher plants. However, knowledge on cyanobacterial PRXs still remains obscure. With the availability of 37 sequenced cyanobacterial genomes, we performed a comprehensive comparative analysis of PRXs and explored their diversity, distribution, domain structure and evolution. Results Overall 244 putative prx genes were identified, which were abundant in filamentous diazotrophic cyanobacteria, Acaryochloris marina MBIC 11017, and unicellular cyanobacteria inhabiting freshwater and hot-springs, while poor in all Prochlorococcus and marine Synechococcus strains. Among these putative genes, 25 open reading frames (ORFs) encoding hypothetical proteins were identified as prx gene family members and the others were already annotated as prx genes. All 244 putative PRXs were classified into five major subfamilies (1-Cys, 2-Cys, BCP, PRX5_like, and PRX-like) according to their domain structures. The catalytic motifs of the cyanobacterial PRXs were similar to those of eukaryotic PRXs and highly conserved in all but the PRX-like subfamily. Classical motif (CXXC) of thioredoxin was detected in protein sequences from the PRX-like subfamily. Phylogenetic tree constructed of catalytic domains coincided well with the domain structures of PRXs and the phylogenies based on 16s rRNA. Conclusions The distribution of genes encoding PRXs in different unicellular and filamentous cyanobacteria especially those sub-families like PRX-like or 1-Cys PRX correlate with the genome size, eco-physiology, and physiological properties of the organisms. Cyanobacterial and eukaryotic PRXs share similar conserved motifs, indicating that cyanobacteria adopt similar catalytic mechanisms as eukaryotes. All

  15. Application of endocrine disruptor screening program fish short-term reproduction assay: Reproduction and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus) exposed to Bermuda pond sediment.

    Science.gov (United States)

    Fort, Douglas J; Mathis, Michael; Fort, Chelsea E; Fort, Hayley M; Bacon, Jamie P

    2015-06-01

    A modified tier 1 Endocrine Disruptor Screening Program (EDSP) 21-d fish short-term reproduction assay (FSTRA) was used to evaluate the effects of sediment exposure from freshwater and brackish ponds in Bermuda on reproductive fecundity and endocrine function in fathead minnow (Pimephales promelas) and killifish (Fundulus heteroclitus). Reproductively active male and female fish were exposed to control sediment and sediment from 2 freshwater ponds (fathead minnow) and 2 marine ponds (killifish) contaminated with polyaromatic hydrocarbons and metals via flow-through exposure for 21 d. Reproductive fecundity was monitored daily. At termination, the status of the reproductive endocrine system was assessed by the gonadosomatic index, gonadal histology, plasma steroids (estrogen [E2], testosterone [T], and 11-ketotestosterone [11-KT]), steroidogenic enzymes (aromatase and combined 3β/17β -hydroxysteroid dehydrogenase [3β/17β-HSD]), and plasma vitellogenin (VTG). Decreased reproductive fecundity, lower male body weight, and altered endocrinological measures of reproductive status were observed in both species. Higher plasma T levels in female minnows and 11-KT levels in both male and female minnows and female killifish exposed to freshwater and brackish sediments, respectively. Decreased female E2 and VTG levels and gonadal cytochrome P19 (aromatase) activity were also found in sediment exposed females from both species. No effect on female 3β/17β-HSD activity was found in either species. The FSTRA provided a robust model capable of modification to evaluate reproductive effects of sediment exposure in fish.

  16. Scientific and Regulatory Policy Committee (SRPC) Points to Consider: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors.

    Science.gov (United States)

    Keane, Kevin A; Parker, George A; Regan, Karen S; Picut, Catherine; Dixon, Darlene; Creasy, Dianne; Giri, Dipak; Hukkanen, Renee R

    2015-12-01

    The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program.

  17. Antiviral Activities and Putative Identification of Compounds in Microbial Extracts from the Hawaiian Coastal Waters

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    Yuanan Lu

    2012-02-01

    Full Text Available Marine environments are a rich source of significant bioactive compounds. The Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse microorganisms, including many endemic species. Thirty-eight microbial extracts from Hawaiian coastal waters were evaluated for their antiviral activity against four mammalian viruses including herpes simplex virus type one (HSV-1, vesicular stomatitis virus (VSV, vaccinia virus and poliovirus type one (poliovirus-1 using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed antiviral potencies and three of these nine microbial extracts exhibited significant activity against the enveloped viruses. A secosteroid, 5α(H,17α(H,(20R-beta-acetoxyergost-8(14-ene was putatively identified and confirmed to be the active compound in these marine microbial extracts. These results warrant future in-depth tests on the isolation of these active elements in order to explore and validate their antiviral potential as important therapeutic remedies.

  18. Mycobacterium tuberculosis evolutionary pathogenesis and its putative impact on drug development.

    Science.gov (United States)

    Le Chevalier, Fabien; Cascioferro, Alessandro; Majlessi, Laleh; Herrmann, Jean Louis; Brosch, Roland

    2014-01-01

    Mycobacterium tuberculosis, the etiological agent of human TB, is the most important mycobacterial pathogen in terms of global patient numbers and gravity of disease. The molecular mechanisms by which M. tuberculosis causes disease are complex and the result of host-pathogen coevolution that might have started already in the time of its Mycobacterium canettii-like progenitors. Despite research progress, M. tuberculosis still holds many secrets of its successful strategy for circumventing host defences, persisting in the host and developing resistance, which makes anti-TB treatment regimens extremely long and often inefficient. Here, we discuss what we have learned from recent studies on the evolution of the pathogen and its putative new drug targets that are essential for mycobacterial growth under in vitro or in vivo conditions.

  19. Expression of putative markers of pluripotency in equine embryonic and adult tissues.

    Science.gov (United States)

    Esteves, Cristina L; Sharma, Ruchi; Dawson, Lucy; Taylor, Sarah E; Pearson, Gemma; Keen, John A; McDonald, Kieran; Aurich, Christine; Donadeu, F Xavier

    2014-12-01

    Expression of several putative markers of pluripotency (OCT4, SOX2, NANOG, LIN28A, REX1, DNMT3B and TERT) was examined in a range of equine tissues, including early embryos, induced pluripotent stem cells (iPSCs), testis, adipose- and bone marrow-derived mesenchymal stromal cells (MSCs), and keratinocytes. Transcript levels of all markers were highest in embryos and iPSCs and, except for SOX2, were very low or undetectable in keratinocytes. Mean expression levels of all markers were lower in testis than in embryos or iPSCs and, except for DNMT3B, were higher in testis than in MSCs. Expression of OCT4, NANOG and DNMT3B, but not the other markers, was detected in MSCs. Of all markers analysed, only LIN28A, REX1 and TERT were associated exclusively with pluripotent cells in the horse. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Transcriptome outlier analysis implicates schizophrenia susceptibility genes and enriches putatively functional rare genetic variants.

    Science.gov (United States)

    Duan, Jubao; Sanders, Alan R; Moy, Winton; Drigalenko, Eugene I; Brown, Eric C; Freda, Jessica; Leites, Catherine; Göring, Harald H H; Gejman, Pablo V

    2015-08-15

    We searched a gene expression dataset comprised of 634 schizophrenia (SZ) cases and 713 controls for expression outliers (i.e., extreme tails of the distribution of transcript expression values) with SZ cases overrepresented compared with controls. These outlier genes were enriched for brain expression and for genes known to be associated with neurodevelopmental disorders. SZ cases showed higher outlier burden (i.e., total outlier events per subject) than controls for genes within copy number variants (CNVs) associated with SZ or neurodevelopmental disorders. Outlier genes were enriched for CNVs and for rare putative regulatory variants, but this only explained a small proportion of the outlier subjects, highlighting the underlying presence of additional genetic and potentially, epigenetic mechanisms.

  1. White Matter Abnormalities and Animal Models Examining a Putative Role of Altered White Matter in Schizophrenia

    Directory of Open Access Journals (Sweden)

    Haiyun Xu

    2011-01-01

    Full Text Available Schizophrenia is a severe mental disorder affecting about 1% of the population worldwide. Although the dopamine (DA hypothesis is still keeping a dominant position in schizophrenia research, new advances have been emerging in recent years, which suggest the implication of white matter abnormalities in schizophrenia. In this paper, we will briefly review some of recent human studies showing white matter abnormalities in schizophrenic brains and altered oligodendrocyte-(OL- and myelin-related genes in patients with schizophrenia and will consider abnormal behaviors reported in patients with white matter diseases. Following these, we will selectively introduce some animal models examining a putative role of white matter abnormalities in schizophrenia. The emphasis will be put on the cuprizone (CPZ model. CPZ-fed mice show demyelination and OLs loss, display schizophrenia-related behaviors, and have higher DA levels in the prefrontal cortex. These features suggest that the CPZ model is a novel animal model of schizophrenia.

  2. Identification of a putative tetrasporophyte-specific gene in Gracilaria lemaneiformis (Gracilariales, Rhodophyte)

    Science.gov (United States)

    Ren, Xueying; Zhang, Xuecheng

    2008-08-01

    A putative tetrasporophyte-specific gene, designated as SSH466 (GenBank accession No. DQ019223), was one of the genes identified in this work using suppression subtractive hybridization (SSH) method in Gracilaria lemaneiformis. The full length of the gene was obtained using SMART RACE strategy. Sequence analysis revealed that the gene had 1 019 nucleotides, including an open reading frame of 498 nucleotides encoding 166 amino acid residues, 158 nucleotides of 5' untranslated region and 363 nucleotides of 3' non-coding region. Protein motif and secondary structure prediction showed that there existed a transmembrane domain with a unique β-sheet. Thus, SSH466 protein might be a cross-membrane protein. Sequence homology search in the public GenBank databases did not reveal any significant match with SSH466. Virtual Northern blot analysis confirmed that it was a tetrasporophyte-specific gene.

  3. Comparative genomics study for identification of putative drug targets in Salmonella typhi Ty2.

    Science.gov (United States)

    Batool, Nisha; Waqar, Maleeha; Batool, Sidra

    2016-01-15

    Typhoid presents a major health concern in developing countries with an estimated annual infection rate of 21 million. The disease is caused by Salmonella typhi, a pathogenic bacterium acquiring multiple drug resistance. We aim to identify proteins that could prove to be putative drug targets in the genome of S. typhi str. Ty2. We employed comparative and subtractive genomics to identify targets that are absent in humans and are essential to S. typhi Ty2. We concluded that 46 proteins essential to pathogen are absent in the host genome. Filtration on the basis of drug target prioritization singled out 20 potentially therapeutic targets. Their absence in the host and specificity to S. typhi Ty2 makes them ideal targets for treating typhoid in Homo sapiens. 3D structures of two of the final target enzymes, MurA and MurB have been predicted via homology modeling which are then used for a docking study.

  4. Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge.

    Science.gov (United States)

    Liu, Yaping; Lyle, Stephen; Yang, Zaixin; Cotsarelis, George

    2003-11-01

    Putative epithelial stem cells in the hair follicle bulge are thought to play pivotal roles in the homeostasis, aging, and carcinogenesis of the cutaneous epithelium. Elucidating the role of bulge cells in these processes has been hampered by the lack of gene promoters that target this area with specificity. Here we describe the isolation of the mouse keratin 15 (K15) promoter and demonstrate its utility for preferentially targeting hair follicle bulge cells in adult K15/lacZ transgenic mice. We found that patterns of K15 expression and promoter activity changed with age and correlated with levels of differentiation within the cutaneous epithelium; less differentiated keratinocytes in the epidermis of the neonatal mouse and in the bulge area of the adult mouse preferentially expressed K15. These findings demonstrate the utility of the K15 promoter for targeting epithelial stem cells in the hair follicle bulge and set the stage for elucidating the role of bulge cells in skin biology.

  5. Exploring the putative self-binding property of the human farnesyltransferase alpha-subunit.

    Science.gov (United States)

    Hagemann, Anna; Müller, Grit; Manthey, Iris; Bachmann, Hagen Sjard

    2017-09-26

    Farnesylation is an important post-translational protein modification in eukaryotes. Farnesylation is performed by protein farnesyltransferase, a heterodimer composed of an α- (FTα) and a β-subunit. Recently, homo-dimerization of truncated rat and yeast FTα has been detected, suggesting a new role for FTα homodimers in signal transduction. We investigated the putative dimerization behaviour of human and rat FTα. Different in vitro and in vivo approaches revealed no self-dimerization and a presumably artificial formation of homo-trimers and higher homo-oligomers in vitro. Our study contributes to the clarification of the physiological features of FTase in different species and may be important for the ongoing development of FTase inhibitors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Identification of calcium-transporting ATPases of Entamoeba histolytica and cellular localization of the putative SERCA.

    Science.gov (United States)

    Martinez-Higuera, Aarón; Salas-Casas, Andrés; Calixto-Gálvez, Mercedes; Chávez-Munguía, Bibiana; Pérez-Ishiwara, D Guillermo; Ximénez, Cecilia; Rodríguez, Mario A

    2013-09-01

    Calcium has an important role on signaling of different cellular processes in the protozoa parasite Entamoeba histolytica, including development and pathogenesis. However, the systems that control calcium responses in this parasite are incompletely understood. Calcium-ATPases (Ca(2+)-ATPases) are proteins that play an important role in calcium homeostasis by catalyzing the active efflux of this ion from cytoplasm and are essential to the correct functioning of the cell machinery. Here, we reported the identification of five E. histolytica genes encoding putative Ca(2+)-ATPases, three related to PMCA, and two related to organellar ATPases. RT-PCR assays showed that all those genes are expressed in trophozoites and specific antibodies against the SERCA-like member located this protein in a continuous cytoplasmic network, supporting the hypothesis that it corresponds to the Ca(2+)-ATPase responsible to sequester calcium in the endoplasmic reticulum of this parasite.

  7. PLCζ or PAWP: revisiting the putative mammalian sperm factor that triggers egg activation and embryogenesis.

    Science.gov (United States)

    Kashir, Junaid; Nomikos, Michail; Swann, Karl; Lai, F Anthony

    2015-05-01

    In mammals, egg activation is initiated by multiple cytosolic Ca(2+) transients (Ca(2+) oscillations) that are triggered following delivery of a putative sperm factor from the fertilizing sperm. The identity of this 'sperm factor' thus holds much significance, not only as a vital component in creating a new life, but also for its potential therapeutic and diagnostic value in human infertility. Recent data have emerged suggesting the sperm factor may be a post-acrosomal sheath WW domain-binding protein (PAWP). However, a significant body of research points to a testis-specific phospholipase C zeta (PLCζ) as the sperm factor. Herein, we examine the evidence presented in favour of PAWP in relation to PLCζ and the requisite physiological properties of the mammalian sperm factor.

  8. Identification of a Putative Tetrasporophyte-Specific Gene in Gracilaria lemaneiformis(Gracilariales, Rhodophyte)

    Institute of Scientific and Technical Information of China (English)

    REN Xueying; ZHANG Xuecheng

    2008-01-01

    A putative tetrasporophyte-specific gene, designated as SSH466 (GenBank accession No. DQ019223), was one of the genes identified in this work using suppression subtractive hybridization (SSH) method in Gracilaria lemaneiformis. The full length of the gene was obtained using SMART RACE strategy. Sequence analysis revealed that the gene had 1 019 nucleotides, including an open reading frame of 498 nucleotides encoding 166 amino acid residues, 158 nucleotides of 5' untranslated region and 363 nucleo- tides of 3' non-coding region. Protein motif and secondary structure prediction showed that there existed a transmembrane domain with a unique β-sheet. Thus, SSH466 protein might be a cross-membrane protein. Sequence homology search in the public GenBank databases did not reveal any significant match with SSH466. Virtual Northern blot analysis confirmed that it was a tetrasporo- phyte-specific gene.

  9. Revision of the stereochemistry of elisabethatriene, a putative biosynthetic intermediate of pseudopterosins.

    Science.gov (United States)

    Nasuda, Masayuki; Ohmori, Miho; Ohyama, Kiyoshi; Fujimoto, Yoshinori

    2012-01-01

    In the past, we have questioned the accuracy of the stereochemistry of elisabethatriene, a putative biosynthetic intermediate of pseudopterosins, in light of the configuration of elisabethatrienol isolated from Pseudopterogorgia elisabethae, which was represented as 1S,4R,9S,11S. We have reinvestigated the stereochemistry of elisabethatriene. Elisabethatriene with the reported 1S,4R,9R,11S configuration was synthesized starting from (-)-isopulegol in its enantiomeric form. The (1)H- and (13)C-NMR data of the synthesized compound differed from those reported for elisabethatriene. In addition to the fact that elisabethatriene is converted into pseudopterosins, this finding has allowed us to propose that elisabethatriene should have the 1S,4R,9S,11S stereochemistry, which is identical to that of elisabethatrienol.

  10. Excitatory amino acid b-N-methylamino-L-alanine is a putative environmental neurotoxin

    Directory of Open Access Journals (Sweden)

    VLADIMIR NEDELJKOV

    2011-04-01

    Full Text Available The amino acid b-N-methylamino-L-alanine (L-BMAA has been associated with the amyotrophic lateral sclerosis/parkinsonism-dementia complex in three distinct western Pacific populations. The putative neurotoxin is produced by cyanobacteria, which live symbiotically in the roots of cycad trees. L-BMAA was thought to be a threat only to those few populations whose diet and medicines rely heavily on cycad seeds. However, the recent discovery that cyanobacteria from diverse terrestrial, freshwater, and saltwater ecosystems around the world produce the toxin requires a reassessment of whether it poses a larger health threat. Therefore, it is proposed that monitoring L-BMAA levels in cyanobacteria-contaminated water supplies might be prudent.

  11. Molecular mapping of the putative gonadoblastoma locus on the Y chromosome.

    Science.gov (United States)

    Salo, P; Kääriäinen, H; Petrovic, V; Peltomäki, P; Page, D C; de la Chapelle, A

    1995-11-01

    Based on the high incidence of gonadoblastoma in females with XY gonadal dysgenesis or 45,X/46,XY mosaicism, the existence of a susceptibility locus on the Y chromosome (GBY) has been postulated. We attempted to map GBY by making use of a recently developed dense map of Y-chromosomal sequence-tagged sites (STSs). In two female patients with gonadoblastoma, small marker chromosomes contained portions of the Y chromosome, and a single region of overlap could be defined extending from probe pDP97 in interval 4B, which contains the centromere, to marker sY182 in interval 5E of the proximal long arm. This interval is contained in a YAC contig that comprises approximately 4 Mb of DNA. Our findings confirm the previous localization of GBY and greatly refine it. The localization of GBY overlaps with the region to which a putative growth determinant, GCY, was recently assigned.

  12. Identification of Pns6, a putative movement protein of RRSV, as a silencing suppressor

    Directory of Open Access Journals (Sweden)

    Lin Qiying

    2010-11-01

    Full Text Available Abstract RNA silencing is a potent antiviral response in plants. As a counterdefense, most plant and some animal viruses encode RNA silencing suppressors. In this study, we showed that Pns6, a putative movement protein of Rice ragged stunt virus (RRSV, exhibited silencing suppressor activity in coinfiltration assays with the reporter green fluorescent protein (GFP in transgenic Nicotiana benthamiana line 16c. Pns6 of RRSV suppressed local silencing induced by sense RNA but had no effect on that induced by dsRNA. Deletion of a region involved in RNA binding abolished the silencing suppressor activity of Pns6. Further, expression of Pns6 enhanced Potato virus × pathogenicity in N. benthamiana. Collectively, these results suggested that RRSV Pns6 functions as a virus suppressor of RNA silencing that targets an upstream step of the dsRNA formation in the RNA silencing pathway. This is the first silencing suppressor to be identified from the genus Oryzavirus.

  13. Analysis of the expression of putatively imprinted genes in bovine peri-implantation embryos

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille Yde; Alexopoulos, N.I.; Cooney, M.A.

    2008-01-01

    imprinted genes (Ata3, Dlk1, Gnas, Grb10, Magel2, Mest-1, Ndn and Sgce) in bovine peri-implantation embryos. Two embryonic developmental stages were examined, Day 14 and Day 21. The gene expression pattern of single embryos was recorded for in vivo, in vitro produced (IVP) and parthenogenetic embryos...... (LOS) in bovine embryos resulting in increased embryonic morbidity and mortality. In the bovine, limited numbers of imprinted genes have been studied and studies have primarily been restricted to pre-implantation stages. This study reports original data on the expression pattern of 8 putatively...... procedures, either by in vitro maturation, fertilization or culture. In conclusion, effects of genomic imprinting and of in vitro procedures for embryo production may influence the success of bovine embryo implantation....

  14. Identification of putative CLE peptide receptors involved in determinate nodulation on soybean.

    Science.gov (United States)

    Mortier, Virginie; Fenta, Berhanu Amsalu; Kunert, Karl; Holsters, Marcelle; Goormachtig, Sofie

    2011-07-01

    CLAVATA3/EMBRYO SURROUNDING REGION (CLE) peptides tightly control the balance between stem cell proliferation and differentiation in several plant developmental processes. Transmission of the CLE peptide signal has been shown to be rather complex. Despite their recent identification, little is known about the receptors by which nodulation-specific CLE peptides, which were identified in soybean, are perceived. Genetic analysis has indicated that the leucine-rich repeat receptor-like kinase NARK of soybean (Glycine max) and its orthologs in other legumes are possible candidates. However, more receptors need to be identified because CLE peptides are often detected by heteromultimeric complexes. Here, we identified two additional putative CLE peptide receptor pairs in the soybean genome with a nodulation-related expression pattern, GmRLK1-GmRLK2 and GmRLK3-GmRLK4, and discuss their role in CLE peptide perception during nodulation.

  15. Sequence Divergence of Microsatellites and Phylogeny Analysis in Tetraploid Cotton Species and Their Putative Diploid Ancestors

    Institute of Scientific and Technical Information of China (English)

    Wang-Zhen GUO; Dong FANG; Wen-Duo YU; Tian-Zhen ZHANG

    2005-01-01

    To determine the level of microsatellite sequence differences and to use the information to construct a phylogenetic relationship for cultivated tetraploid cotton (Gossypium spp.) species and their putative diploid ancestors, 10 genome-derived microsatellite primer pairs were used to amplify eight species,including two tetraploid and six diploid species, in Gossypium. A total of 92 unique amplicons were resolved using polyacrylamide gel electrophoresis. Each amplicon was cloned, sequenced, and analyzed using standard phylogenetic software. Allelic diversities were caused mostly by changes in the number of simple sequence repeat (SSR) motif repeats and only a small proportion resulted from interruption of the SSR motif within the locus for the same genome. The frequency of base substitutions was 0.5%-1.0% in different genomes, with only few indels found. Based on the combined 10 SSR flanking sequence data, the homology of A-genome diploid species averaged 98.9%, even though most of the amplicons were of the same size, and the sequence homology between G. gossypioides (Ulbr.) Standl. and three other D-genome species (G.raimondii Ulbr., G. davidsonii Kell., and G. thurberi Tod.) was 98.5%, 98.6%, and 98.5%, respectively.Phylogenetic trees of the two allotetraploid species and their putative diploid progenitors showed that homoelogous sequences from the A- and D-subgenome were still present in the polyploid subgenomes and they evolved independently. Meanwhile, homoelogous sequence interaction that duplicated loci in the polyploid subgenomes became phylogenetic sisters was also found in the evolutionary history of tetraploid cotton species. The results of the present study suggest that evaluation of SSR variation at the sequence level can be effective in exploring the evolutionary relationships among Gossypuim species.

  16. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition.

    LENUS (Irish Health Repository)

    Baeyens, A

    2002-12-02

    The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%).

  17. Genetic analysis of BIRC4/XIAP as a putative modifier gene of Wilson disease.

    Science.gov (United States)

    Weiss, Karl Heinz; Runz, Heiko; Noe, Barbara; Gotthardt, Daniel Nils; Merle, Uta; Ferenci, Peter; Stremmel, Wolfgang; Füllekrug, Joachim

    2010-12-01

    Wilson disease (WD) is an autosomal-recessive copper overload disorder caused by mutations in the copper-transporting adenosine triphosphatase (ATPase) ATP7B. It presents with a highly variable clinical phenotype ranging from asymptomatic to fulminant hepatic failure or progressive neurological involvement. No clear genotype-phenotype correlation has been established. Thus, variants in modifier genes could have an impact on WD manifestation and severity. Recently, the antiapoptotic protein baculoviral IAP repeat-containing protein 4 BIRC4/XIAP has been suggested as a regulator of copper-induced cell death. With the aim of investigating a putative role of BIRC4/XIAP as modifier gene in individuals with copper overload, we analyzed a WD patient cohort (n = 98) for sequence variants at the BIRC4/XIAP locus. When compared with clinical data, the previously described coding single nucleotide polymorphisms (SNPs) at the BRIC4/XIAP locus (rs28382721, rs28382722, rs28382723, rs5956583, rs28382740, rs12838858, rs28382741) did not correlate with age of onset or clinical presentation in our collective. However, three previously unreported variants in the BIRC4/XIAP gene were identified (c.1-26 T > G; c.1408A > T; p.T470S; c.1019A > G; p.N340S). The two patients with variants leading to amino acid exchanges in the BIRC4/XIAP protein showed a remarkably early disease onset at the age of 5 years. Furthermore, one of these patients was only heterozygous for disease-causing mutations in the ATP7B gene. In summary, these data emphasize the need to further elucidate a role of BIRC4/XIAP variants as putative pathogenetic factors in copper overload disorders.

  18. Identification and Characterization of a Putative Manganese Export Protein in Vibrio cholerae.

    Science.gov (United States)

    Fisher, Carolyn R; Wyckoff, Elizabeth E; Peng, Eric D; Payne, Shelley M

    2016-10-15

    Manganese plays an important role in the cellular physiology and metabolism of bacterial species, including the human pathogen Vibrio cholerae The intracellular level of manganese ions is controlled through coordinated regulation of the import and export of this element. We have identified a putative manganese exporter (VC0022), named mneA (manganese exporter A), which is highly conserved among Vibrio spp. An mneA mutant exhibited sensitivity to manganese but not to other cations. Under high-manganese conditions, the mneA mutant showed an almost 50-fold increase in intracellular manganese levels and reduced intracellular iron relative to those of its wild-type parent, suggesting that the mutant's manganese sensitivity is due to the accumulation of toxic levels of manganese and reduced iron. Expression of mneA suppressed the manganese-sensitive phenotype of an Escherichia coli strain carrying a mutation in the nonhomologous manganese export gene, mntP, further supporting a manganese export function for V. cholerae MneA. The level of mneA mRNA was induced approximately 2.5-fold after addition of manganese to the medium, indicating regulation of this gene by manganese. This study offers the first insights into understanding manganese homeostasis in this important pathogen. Bacterial cells control intracellular metal concentrations by coordinating acquisition in metal-limited environments with export in metal-excess environments. We identified a putative manganese export protein, MneA, in Vibrio cholerae An mneA mutant was sensitive to manganese, and this effect was specific to manganese. The mneA mutant accumulated high levels of intracellular manganese with a concomitant decrease in intracellular iron levels when grown in manganese-supplemented medium. Expression of mneA in trans suppressed the manganese sensitivity of an E. coli mntP mutant. This study is the first to investigate manganese export in V. cholerae. Copyright © 2016, American Society for Microbiology

  19. Expression of putative immune response genes during early ontogeny in the coral Acropora millepora.

    Directory of Open Access Journals (Sweden)

    Eneour Puill-Stephan

    Full Text Available BACKGROUND: Corals, like many other marine invertebrates, lack a mature allorecognition system in early life history stages. Indeed, in early ontogeny, when corals acquire and establish associations with various surface microbiota and dinoflagellate endosymbionts, they do not efficiently distinguish between closely and distantly related individuals from the same population. However, very little is known about the molecular components that underpin allorecognition and immunity responses or how they change through early ontogeny in corals. METHODOLOGY/PRINCIPAL FINDINGS: Patterns in the expression of four putative immune response genes (apextrin, complement C3, and two CELIII type lectin genes were examined in juvenile colonies of Acropora millepora throughout a six-month post-settlement period using quantitative real-time PCR (qPCR. Expression of a CELIII type lectin gene peaked in the fourth month for most of the coral juveniles sampled and was significantly higher at this time than at any other sampling time during the six months following settlement. The timing of this increase in expression levels of putative immune response genes may be linked to allorecognition maturation which occurs around this time in A. millepora. Alternatively, the increase may represent a response to immune challenges, such as would be involved in the recognition of symbionts (such as Symbiodinium spp. or bacteria during winnowing processes as symbioses are fine-tuned. CONCLUSIONS/SIGNIFICANCE: Our data, although preliminary, are consistent with the hypothesis that lectins may play an important role in the maturation of allorecognition responses in corals. The co-expression of lectins with apextrin during development of coral juveniles also raises the possibility that these proteins, which are components of innate immunity in other invertebrates, may influence the innate immune systems of corals through a common pathway or system. However, further studies

  20. Putative Cross-Contamination Routes of Listeria monocytogenes in a Meat Processing Facility in Romania.

    Science.gov (United States)

    Bolocan, Andrei Sorin; Oniciuc, Elena Alexandra; Alvarez-Ordóñez, Avelino; Wagner, Martin; Rychli, Kathrin; Jordan, Kieran; Nicolau, Anca Ioana

    2015-09-01

    Putative routes of Listeria monocytogenes contamination, based on the workflow of the employees, were studied in a meat processing facility by investigating 226 samples collected from food contact surfaces, non-food contact surfaces, raw materials, and ready-to-eat meat products on four occasions over a 1-year period. In total, 19.7% of non-food contact surfaces, 22.9% of food contact surfaces, 45% of raw materials, and 20% of ready-to-eat meat products were positive for L. monocytogenes (analyzed by the International Organization for Standardization standard method ISO 11290). Pulsed-field gel electrophoresis (PFGE) profiles were determined for a representative subset of these isolates, and 11 distinct pulsotypes were identified, two of which were frequently isolated (T4 and T8) and considered persistent. Strains from the various pulsotypes were screened for the presence of bcrABC and qacH, the genes responsible for tolerance responses to quaternary ammonium compounds. Two strains harbored bcrABC, and these strains had a higher benzalkonium chloride tolerance; however, they were not considered persistent strains. The frequently isolated PFGE pulsotype T8 strains were highly adhesive to abiotic surfaces at 10 and 20°C; however, the pulsotype T6 strain, which was isolated only at the last sampling time, had the highest adhesion ability, and the pulsotype T4 strain (the second most persistent pulsotype) had only modest adhesion. Four putative cross-contamination routes were confirmed by mapping the persistent and other isolates. This information could allow a food safety manager to adjust the work flow to improve the hygienic conditions in a meat processing facility. This study revealed the prevalence and persistence of L. monocytogenes strains in a meat processing facility and established the importance of developing strategies to avoid cross-contamination, recalls, and outbreaks of listeriosis.

  1. High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2

    Directory of Open Access Journals (Sweden)

    Hellberg Michael E

    2010-05-01

    Full Text Available Abstract Background Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching. Results In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus, a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella possess proteins structurally similar to tachylectin-2. Conclusions Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1 part of Oculina's innate immunity repertoire, and 2 evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.

  2. Characterization of ERAS, a putative novel human oncogene, in skin and breast

    Energy Technology Data Exchange (ETDEWEB)

    Peña Avalos, B.L. de la

    2014-07-01

    Most human tumors have mutations in genes of the RAS small GTPase protein family. RAS works as a molecular switch for signaling pathways that modulate many aspects of cell behavior, including proliferation, differentiation, motility and death. Oncogenic mutations in RAS prevent GTP hydrolysis, locking RAS in a permanently active state, being the most common mutations in HRAS, KRAS and NRAS. The human RAS family consists of at least 36 different genes, many of which have been scarcely studied. One of these relatively unknown genes is ERAS (ES cell-expressed RAS), which is a constitutively active RAS protein, localized in chromosome X and expressed only in embryonic cells, being undetectable in adult tissues. New high throughput technologies have made it possible to screen complete cancer genomes for identification of mutations associated to cancer. Using the Sleeping Beauty (SB) transposon system, ERAS was identified as a putative novel oncogene in non-melanoma skin and breast cancers. The major aim of this project is to determine the general characteristics of ERAS as a putative novel human oncogene in skin and breast cells. Forced expression of ERAS results in drastic changes in cell shape, proliferation and motility. When ERAS is overexpressed in skin and breast human cells it is mainly localized in the cytoplasmic membrane. ERAS activates the phosphatidylinositol-3-OH kinase (PI3K) pathway but not the mitogen-activated protein kinase (MAPK) pathway. ERAS-expressing cells suffer spontaneous morphologic and phenotypic EMT-like changes, including cytoskeleton reorganization, vimentin and N-cadherin up-regulation and down-regulation of E-cadherin, which can be associated with increased malignancy, and invasive and metastatic potential. Our results suggest that inappropriate expression of ERAS lead to transformation of human cells. (Author)

  3. Putative glycosyltransferases and other plant Golgi apparatus proteins are revealed by LOPIT proteomics.

    Science.gov (United States)

    Nikolovski, Nino; Rubtsov, Denis; Segura, Marcelo P; Miles, Godfrey P; Stevens, Tim J; Dunkley, Tom P J; Munro, Sean; Lilley, Kathryn S; Dupree, Paul

    2012-10-01

    The Golgi apparatus is the central organelle in the secretory pathway and plays key roles in glycosylation, protein sorting, and secretion in plants. Enzymes involved in the biosynthesis of complex polysaccharides, glycoproteins, and glycolipids are located in this organelle, but the majority of them remain uncharacterized. Here, we studied the Arabidopsis (Arabidopsis thaliana) membrane proteome with a focus on the Golgi apparatus using localization of organelle proteins by isotope tagging. By applying multivariate data analysis to a combined data set of two new and two previously published localization of organelle proteins by isotope tagging experiments, we identified the subcellular localization of 1,110 proteins with high confidence. These include 197 Golgi apparatus proteins, 79 of which have not been localized previously by a high-confidence method, as well as the localization of 304 endoplasmic reticulum and 208 plasma membrane proteins. Comparison of the hydrophobic domains of the localized proteins showed that the single-span transmembrane domains have unique properties in each organelle. Many of the novel Golgi-localized proteins belong to uncharacterized protein families. Structure-based homology analysis identified 12 putative Golgi glycosyltransferase (GT) families that have no functionally characterized members and, therefore, are not yet assigned to a Carbohydrate-Active Enzymes database GT family. The substantial numbers of these putative GTs lead us to estimate that the true number of plant Golgi GTs might be one-third above those currently annotated. Other newly identified proteins are likely to be involved in the transport and interconversion of nucleotide sugar substrates as well as polysaccharide and protein modification.

  4. The V-ATPase a2-subunit as a putative endosomal pH-sensor.

    Science.gov (United States)

    Marshansky, V

    2007-11-01

    V-ATPase (vesicular H(+)-ATPase)-driven intravesicular acidification is crucial for vesicular trafficking. Defects in vesicular acidification and trafficking have recently been recognized as essential determinants of various human diseases. An important role of endosomal acidification in receptor-ligand dissociation and in activation of lysosomal hydrolytic enzymes is well established. However, the molecular mechanisms by which luminal pH information is transmitted to the cytosolic small GTPases that control trafficking events such as budding, coat formation and fusion are unknown. Here, we discuss our recent discovery that endosomal V-ATPase is a pH-sensor regulating the degradative pathway. According to our model, V-ATPase is responsible for: (i) the generation of a pH gradient between vesicular membranes; (ii) sensing of intravesicular pH; and (iii) transmitting this information to the cytosolic side of the membrane. We also propose the hypothetical molecular mechanism involved in function of the V-ATPase a2-subunit as a putative pH-sensor. Based on extensive experimental evidence on the crucial role of histidine residues in the function of PSPs (pH-sensing proteins) in eukaryotic cells, we hypothesize that pH-sensitive histidine residues within the intra-endosomal loops and/or C-terminal luminal tail of the a2-subunit could also be involved in the pH-sensing function of V-ATPase. However, in order to identify putative pH-sensitive histidine residues and to test this hypothesis, it is absolutely essential that we increase our understanding of the folding and transmembrane topology of the a-subunit isoforms of V-ATPase. Thus the crucial role of intra-endosomal histidine residues in pH-dependent conformational changes of the V-ATPase a2-isoform, its interaction with cytosolic small GTPases and ultimately in its acidification-dependent regulation of the endosomal/lysosomal protein degradative pathway remain to be determined.

  5. Putative roles for a rhamnose binding lectin in Flavobacterium columnare pathogenesis in channel catfish Ictalurus punctatus.

    Science.gov (United States)

    Beck, Benjamin H; Farmer, Bradley D; Straus, David L; Li, Chao; Peatman, Eric

    2012-10-01

    Columnaris disease, caused by the bacterial pathogen Flavobacterium columnare, continues to be a major problem worldwide and commonly leads to tremendous losses of both wild and cultured freshwater fish, particularly in intensively farmed aquaculture species such as channel catfish. Despite its ecologic and economic impacts, the fundamental molecular mechanisms of the host immune response to this pathogen remain unclear. While F. columnare can induce marked pathologic changes in numerous ectopic tissues, the adhesion of F. columnare to the gill in particular is strongly associated with pathogen virulence and host susceptibility. Recently, in this regard, using RNA-seq expression profiling we found that a rhamnose-binding lectin (RBL) was dramatically upregulated in the gill of fish infected with F. columnare (as compared to naïve fish). Thus, in the present study we sought to further characterize and understand the RBL response in channel catfish (Ictalurus punctatus). We first identified two distinct catfish families with differential susceptibilities to columnaris disease; one family was found to be completely resistant while the other was susceptible (0% mortality versus 18.3% respectively, P catfish RBL that persisted for at least 24 h (P catfish to different doses of the putative RBL ligands l-rhamnose and d-galactose, and found that these sugars, protected channel catfish against columnaris disease, likely through competition with F. columnare binding of host RBL. Finally, we examined the role of nutritional status on RBL regulation and found that RBL expression was upregulated (>120-fold; P < 0.05) in fish fasted for 7 d (as compared to fish fed to satiation daily), yet expression levels returned to those of satiated fish within 4 h after re-feeding. Collectively, these findings highlight putative roles for RBL in the context of columnaris disease and reveal new aspects linking RBL regulation to feed availability.

  6. Putative cross-kingdom horizontal gene transfer in sponge (Porifera mitochondria

    Directory of Open Access Journals (Sweden)

    Ilan Micha

    2006-09-01

    Full Text Available Abstract Background The mitochondrial genome of Metazoa is usually a compact molecule without introns. Exceptions to this rule have been reported only in corals and sea anemones (Cnidaria, in which group I introns have been discovered in the cox1 and nad5 genes. Here we show several lines of evidence demonstrating that introns can also be found in the mitochondria of sponges (Porifera. Results A 2,349 bp fragment of the mitochondrial cox1 gene was sequenced from the sponge Tetilla sp. (Spirophorida. This fragment suggests the presence of a 1143 bp intron. Similar to all the cnidarian mitochondrial introns, the putative intron has group I intron characteristics. The intron is present in the cox1 gene and encodes a putative homing endonuclease. In order to establish the distribution of this intron in sponges, the cox1 gene was sequenced from several representatives of the demosponge diversity. The intron was found only in the sponge order Spirophorida. A phylogenetic analysis of the COI protein sequence and of the intron open reading frame suggests that the intron may have been transmitted horizontally from a fungus donor. Conclusion Little is known about sponge-associated fungi, although in the last few years the latter have been frequently isolated from sponges. We suggest that the horizontal gene transfer of a mitochondrial intron was facilitated by a symbiotic relationship between fungus and sponge. Ecological relationships are known to have implications at the genomic level. Here, an ecological relationship between sponge and fungus is suggested based on the genomic analysis.

  7. Putative cross-kingdom horizontal gene transfer in sponge (Porifera) mitochondria

    Science.gov (United States)

    Rot, Chagai; Goldfarb, Itay; Ilan, Micha; Huchon, Dorothée

    2006-01-01

    Background The mitochondrial genome of Metazoa is usually a compact molecule without introns. Exceptions to this rule have been reported only in corals and sea anemones (Cnidaria), in which group I introns have been discovered in the cox1 and nad5 genes. Here we show several lines of evidence demonstrating that introns can also be found in the mitochondria of sponges (Porifera). Results A 2,349 bp fragment of the mitochondrial cox1 gene was sequenced from the sponge Tetilla sp. (Spirophorida). This fragment suggests the presence of a 1143 bp intron. Similar to all the cnidarian mitochondrial introns, the putative intron has group I intron characteristics. The intron is present in the cox1 gene and encodes a putative homing endonuclease. In order to establish the distribution of this intron in sponges, the cox1 gene was sequenced from several representatives of the demosponge diversity. The intron was found only in the sponge order Spirophorida. A phylogenetic analysis of the COI protein sequence and of the intron open reading frame suggests that the intron may have been transmitted horizontally from a fungus donor. Conclusion Little is known about sponge-associated fungi, although in the last few years the latter have been frequently isolated from sponges. We suggest that the horizontal gene transfer of a mitochondrial intron was facilitated by a symbiotic relationship between fungus and sponge. Ecological relationships are known to have implications at the genomic level. Here, an ecological relationship between sponge and fungus is suggested based on the genomic analysis. PMID:16972986

  8. Bioinformatic selection of putative epigenetically regulated loci associated with obesity using gene expression data.

    Science.gov (United States)

    Turcot, Valérie; Groom, Alexandra; McConnell, James C; Pearce, Mark S; Potter, Catherine; Embleton, Nicholas D; Swan, Daniel C; Relton, Caroline L

    2012-05-10

    There is considerable interest in defining the relationship between epigenetic variation and the risk of common complex diseases. Strategies which assist in the prioritisation of target loci that have the potential to be epigenetically regulated might provide a useful approach in identifying concrete examples of epigenotype-phenotype associations. Focusing on the postulated role of epigenetic factors in the aetiopathogenesis of obesity this report outlines an approach utilising gene expression data and a suite of bioinformatic tools to prioritise a list of target candidate genes for more detailed experimental scrutiny. Gene expression microarrays were performed using peripheral blood RNA from children aged 11-13years selected from the Newcastle Preterm Birth Growth Study which were grouped by body mass index (BMI). Genes showing ≥2.0 fold differential expression between low and high BMI groups were selected for in silico analysis. Several bioinformatic tools were used for each following step; 1) a literature search was carried out to identify whether the differentially expressed genes were associated with adiposity phenotypes. Of those obesity-candidate genes, putative epigenetically regulated promoters were identified by 2) defining the promoter regions, 3) then by selecting promoters with a CpG island (CGI), 4) and then by identifying any transcription factor binding modules covering CpG sites within the CGI. This bioinformatic processing culminated in the identification of a short list of target obesity-candidate genes putatively regulated by DNA methylation which can be taken forward for experimental analysis. The proposed workflow provides a flexible, versatile and low cost methodology for target gene prioritisation that is applicable to multiple species and disease contexts. Copyright © 2012. Published by Elsevier B.V.

  9. Genetic profiling of putative breast cancer stem cells from malignant pleural effusions.

    Science.gov (United States)

    Tiran, Verena; Stanzer, Stefanie; Heitzer, Ellen; Meilinger, Michael; Rossmann, Christopher; Lax, Sigurd; Tsybrovskyy, Oleksiy; Dandachi, Nadia; Balic, Marija

    2017-01-01

    A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of

  10. The Bacillus anthracis chromosome contains four conserved, excision-proficient, putative prophages

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    Sozhamannan Shanmuga

    2006-04-01

    Full Text Available Abstract Background Bacillus anthracis is considered to be a recently emerged clone within the Bacillus cereus sensu lato group. The B. anthracis genome sequence contains four putative lambdoid prophages. We undertook this study in order to understand whether the four prophages are unique to B. anthracis and whether they produce active phages. Results More than 300 geographically and temporally divergent isolates of B. anthracis and its near neighbors were screened by PCR for the presence of specific DNA sequences from each prophage region. Every isolate of B. anthracis screened by PCR was found to produce all four phage-specific amplicons whereas none of the non-B. anthracis isolates, produced more than one phage-specific amplicon. Excision of prophages could be detected by a PCR based assay for attP sites on extra-chromosomal phage circles and for attB sites on phage-excised chromosomes. SYBR-green real-time PCR assays indicated that prophage excision occurs at very low frequencies (2 × 10-5 - 8 × 10-8/cell. Induction with mitomycin C increased the frequency of excision of one of the prophages by approximately 250 fold. All four prophages appear to be defective since, mitomycin C induced culture did not release any viable phage particle or lyse the cells or reveal any phage particle under electron microscopic examination. Conclusion The retention of all four putative prophage regions across all tested strains of B. anthracis is further evidence of the very recent emergence of this lineage and the prophage regions may be useful for differentiating the B. anthracis chromosome from that of its neighbors. All four prophages can excise at low frequencies, but are apparently defective in phage production.

  11. The gene corresponding to the putative Goodpasture antigen is present in Alport's syndrome.

    Science.gov (United States)

    Savige, J A

    1991-08-01

    Alport's syndrome is a heterogeneous group of inherited abnormalities of basement membranes that may result in progressive renal failure, defective hearing and lens abnormalities. The glomerular basement membrane (GBM) characteristically has areas of reduplication, lamellation and attenuation on electron microscopic examination. In the majority of affected males and some females, there is reduced or variable binding of serum from patients with anti-GBM disease (Goodpasture's syndrome) to these basement membranes. These sera contain antibodies directed against the Goodpasture antigen which has been thought to be located in the non-collagenous domain of the alpha3 chain of type IV collagen and is presumed to be important in cross-linking of the collagen molecules. The reduced staining for the Goodpasture antigen suggests that this structure is either absent or masked in Alport's syndrome. We have tested DNA from six unrelated individuals with Alport's syndrome. All had been transplanted for renal failure. The diagnosis of Alport's syndrome was made on the characteristic electron microscopic appearance of the renal basement membranes (n = 4), the presence of sensori-neural deafness (n = 4), a family history of Alport's syndrome (n = 5) and the presence of circulating inhibitable anti-GBM antibody activity post-transplant (n = 2). Oligonucleotides (20mers) corresponding to the 5' and 3' ends of the known 25 amino acid sequence for the putative Goodpasture antigen were used as primers for amplification of genomic DNA. The products were then blotted and probed with an intermediate 19-mer DNA. All Alport's patients contained a 75-bp fragment corresponding to the published peptide sequence for the non-collagenous domain of the alpha 3 chain of type IV collagen, suggesting that a large deletion of this region, the putative Goodpasture antigen, is unlikely to account for the defect in Alport's syndrome.

  12. Coleopteran-specific and putative novel cry genes in Iranian native Bacillus thuringiensis collection.

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    Nazarian, Amin; Jahangiri, Rosa; Jouzani, Gholamreza Salehi; Seifinejad, Ali; Soheilivand, Saeed; Bagheri, Omolbanin; Keshavarzi, Mansoureh; Alamisaeid, Khalil

    2009-10-01

    The characterization of the strains containing Coleopteran-specific and also putative novel cry genes in Iranian native Bacillus thuringiensis collection is presented. Characterization was based on PCR analysis using 31 general and specific primers for cry1B, cry1I, cry3A, cry3B, cry3C, cry7A, cry8A, cry8B, cry8C, cry14, cry18, cry26, cry28, cry34 and cry35 genes, protein band patterns as well as their insecticidal activity on Xanthogaleruca luteola Mull. larvae. Forty six isolates (65.7%) contained minimum one Coleopteran-active cry gene. Based on universal primers, strains containing cry18 and cry26 genes were the most abundant and represent 27.1% and 24% of the isolates, respectively, whereas cry14, cry3, cry28, cry34, cry35, cry7, cry8 genes were less abundant, found in 14.2, 12.5, 10, 7, 7 and 5.6% of the strains, respectively. Based on specific primers, isolates containing cry1I were the most abundant (48.5%). Two strains containing Coleopteran-active cry genes showed higher activity against X. luteola larvae than B. thuringiensis subsp. morrisoni pathovar tenebrionis. Thirty isolates, when assayed for cry1C, cry5, cry6, cry8b, cry9, cry10, cry11, cry18, cry24 and cry35 genes, showed unexpected size bands. Cloning and sequencing of the amplicons allowed both the identification of known cry genes and the detection of putative novel cry1C sequences.

  13. Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology

    Science.gov (United States)

    Li, Ying; Ozment, Tammy; Wright, Gary L.

    2016-01-01

    C1q TNF Related Protein 3 (CTRP3) is a member of a family of secreted proteins that exert a multitude of biological effects. Our initial work identified CTRP3’s promise as an effective treatment for Nonalcoholic fatty liver disease (NAFLD). Specifically, we demonstrated that mice fed a high fat diet failed to develop NAFLD when treated with CTRP3. The purpose of this current project is to identify putative receptors which mediate the hepatic actions of CTRP3. Methods We used Ligand-receptor glycocapture technology with TriCEPS™-based ligand-receptor capture (LRC-TriCEPS; Dualsystems Biotech AG). The LRC-TriCEPS experiment with CTRP3-FLAG protein as ligand and insulin as a control ligand was performed on the H4IIE rat hepatoma cell line. Results Initial analysis demonstrated efficient coupling of TriCEPS to CTRP3. Further, flow cytometry analysis (FACS) demonstrated successful oxidation and crosslinking of CTRP3-TriCEPS and Insulin-TriCEPS complexes to cell surface glycans. Demonstrating the utility of TriCEPS under these conditions, the insulin receptor was identified in the control dataset. In the CTRP3 treated cells a total enrichment of 261 peptides was observed. From these experiments 5 putative receptors for CTRP3 were identified with two reaching statistically significance: Lysosomal-associated membrane protein 1 (LAMP-1) and Lysosome membrane protein 2 (LIMP II). Follow-up Co-immunoprecipitation analysis confirmed the association between LAMP1 and CTRP3 and further testing using a polyclonal antibody to block potential binding sites of LAMP1 prevented CTRP3 binding to the cells. Conclusion The LRC-TriCEPS methodology was successful in identifying potential novel receptors for CTRP3. Relevance The identification of the receptors for CTRP3 are important prerequisites for the development of small molecule drug candidates, of which none currently exist, for the treatment NAFLD. PMID:27727322

  14. A comparative study on efficiency of adult fibroblast, putative embryonic stem cell and lymphocyte as donor cells for production of handmade cloned embryos in goat and characterization of putative ntES cells obtained from these embryos.

    Science.gov (United States)

    Dutta, Rahul; Malakar, Dhruba; Khate, Keviletsu; Sahu, Shailendra; Akshey, Yogesh; Mukesh, Manishi

    2011-09-15

    The main purpose of the experiment was to compare the efficiency of three cell types, namely adult fibroblast, putative embryonic stem (ES) cell, and lymphocyte, as donor cells for somatic cell nuclear transfer by handmade cloning in goats. The outcome clearly shows that putative embryonic stem cells, with a cleavage and blastocyst production rate of 74.69% ± 3.92 and 39.75% ± 3.86, respectively, performs better in comparison to adult fibroblast cell and lymphocyte. Between adult fibroblast cell and lymphocyte no statistically significant difference exists at P II DRB genes of cloned embryos and three donor cells were performed to verify the cloned embryos. The amplified PCR products were subjected to SSCP to confirm their genetic identity. The karyotyping of the cloned embryos showed normal chromosomal status as expected in goat. Significantly, in the second stage of the experiment, the produced cloned embryos were successfully used to derive ntES-like cells. The rate of primary colony formation rate was 62.50% ± 4.62 for fibroblast donor cell derived embryos. The same was 60.60% ± 4.62 for putative ES donor cell derived embryos and 66.66% ± 4.62 for lymphocyte donor cell derived embryos, respectively. The putative ntES colonies were positively characterized for alkaline phosphatase, Oct-4, TRA-1-60, TRA-1-81, Sox-2, and Nanog by Immunocytochemistry and Reverse Transcription PCR. To further validate the stem ness, the produced putative ntES colonies were differentiated to embryoid bodies. Immunocytochemistry revealed that embryoid bodies expressed NESTIN specific for ectodermal lineage; GATA-4 for endodermal lineage and smooth muscle actin-I, and troponin-I specific for mesodermal lineage. The study has established an efficient protocol for putative ntES cell derivation from HMC embryos. It could be of substantial significance as patient specific ntES cells have proven therapeutic significance.

  15. Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle.

    Science.gov (United States)

    Dickerson, Sarah M; Gore, Andrea C

    2007-06-01

    Endocrine disrupting chemicals (EDCs) are natural or synthetic compounds that interfere with the normal function of an organism's endocrine system. Many EDCs are resistant to biodegradation, due to their structural stability, and persist in the environment. The focus of this review is on natural and artificial EDCs that act through estrogenic mechanisms to affect reproductive neuroendocrine systems. This endocrine axis comprises the hypothalamic gonadotropin-releasing hormone (GnRH), pituitary gonadotropins, and gonadal steroid hormones, including estrogens. Although it is not surprising that EDCs that mimic or antagonize estrogen receptors may exert actions upon reproductive targets, the mechanisms for these effects are complex and involve all three levels of the hypothalamic-pituitary-gonadal (HPG) system. Nevertheless, considerable evidence links exposure to estrogenic environmental EDCs with neuroendocrine reproductive deficits in wildlife and in humans. The effects of an EDC are variable across the life cycle of an animal, and are particularly potent when exposure occurs during fetal and early postnatal development. As a consequence, abnormal sexual differentiation, disrupted reproductive function, or inappropriate sexual behavior may be detected later in life. This review will cover the effects of two representative classes of estrogenic EDCs, phytoestrogens and polychlorinated biphenyls (PCBs), on neuroendocrine reproductive function, from molecules to behavior, across the vertebrate life cycle. Finally, we identify the gaps of knowledge in this field and suggest future directions for study.

  16. Genetic diversity of bovine papillomavirus types, including two putative new types, in teat warts from dairy cattle herds.

    Science.gov (United States)

    Lunardi, Michele; de Camargo Tozato, Claudia; Alfieri, Alice Fernandes; de Alcântara, Brígida Kussumoto; Vilas-Boas, Laurival Antonio; Otonel, Rodrigo Alejandro Arellano; Headley, Selwyn Arlington; Alfieri, Amauri Alcindo

    2016-06-01

    Teat papillomatosis affects dairy cows worldwide. Milking can become difficult due to teat warts, and maintaining affected cows in the herds may diminish economic profit in the dairy industry. Currently, 13 bovine papillomavirus (BPV) types have been fully characterized, and numerous putative BPV types have been identified through partial L1 gene PCR. In order to identify the viral types present in warts on the udders of dairy cows, 40 teat lesions from 24 cows from 13 cattle farms in three States of Brazil were evaluated by PV L1 gene PCR. The warts that were evaluated contained sequences from BPVs 6-10, the putative BPV types BAPV9 and BAPV4, and two unreported putative papillomavirus (PV) types, named BPV/BR-UEL6 and BPV/BR-UEL7. In addition, mixed infections and coinfections were identified, since more than one lesion was observed on the udders of 13 cows. Phylogenetic analysis showed that BPV/BR-UEL6 is closely related to BPVs belonging to the genus Xipapillomavirus, while BPV/BR-UEL7 clustered with the previously reported strains Cervus timorensis and Pudu puda PVs, which represent a putative new PV type, and it was only distantly related to xi-, epsilon-, delta- and dyoxi-PVs. These results provide information that will assist in the understanding of the association of BPVs 6, 7, 8, 9, and 10, as well as putative BPV types BAPV4 and BAPV9, with mammary papillomatosis. This is the first characterization of putative novel PV types BPV/BR-UEL6 and BPV/BR-UEL7 in teat warts of dairy cows, highlighting the high genetic diversity of BPVs associated with teat papillomatosis.

  17. Characterization of three putative xylulose 5-phosphate/fructose 6-phosphate phosphoketolases in the cyanobacterium Anabaena sp. PCC 7120.

    Science.gov (United States)

    Moriyama, Takashi; Tajima, Naoyuki; Sekine, Kohsuke; Sato, Naoki

    2015-01-01

    Xylulose 5-phosphate/fructose 6-phosphate phosphoketolase (Xfp) is a key enzyme in the central carbohydrate metabolism in heterofermentative bacteria, in which enzymatic property of Xfps is well characterized. This is not the case in other microbes. The cyanobacterium Anabaena sp. PCC 7120 possesses three putative genes encoding Xfp, all1483, all2567, and alr1850. We purified three putative Xfps as recombinant proteins. The results of gel filtration indicated that these proteins form homomultimer complex. All1483 and All2567 showed phosphoketolase activity, whereas Alr1850 did not show the activity. Kinetic analyses demonstrated that substrates, fructose 6-phosphate and inorganic phosphate, are cooperatively bound to enzymes positively and negatively, respectively.

  18. Isolation and characterization of a new chemokine receptor gene, the putative chicken CXCR1.

    Science.gov (United States)

    Li, Q J; Lu, S; Ye, R D; Martins-Green, M

    2000-10-31

    This study delineates the isolation and characterization of a novel chemokine receptor gene, the putative chicken CXC receptor 1 (cCXCR1). Using a human CXCR1 probe, we isolated several positive clones from a chicken genomic library. One of the clones contained a fragment of approximately 5000bp that hybridized strongly with the hCXCR1 probe. This fragment was sequenced and subjected to a variety of computer analyses. The open reading frame for this gene predicts a seven transmembrane domain protein with all the characteristics of a chemokine receptor and with 67% sequence homology to hCXCR1, 65% to hCXCR2 and also with considerable sequence homology to other human chemokine receptors such as hCXCR4 (50%), hCCR2 (49%) and hCCR1 (49%). However, the homology to a previously isolated potential G-protein-coupled receptor for chickens (AvCRL1) is only 47%. Using 5' RACE, two transcription initiation sites were identified suggesting the potential for the expression of two protein isoforms (I and II) in vivo. The promoter for the putative cCXCR1 contains a variety of consensus transcription factor binding elements that can potentially be involved in the expression of this chicken receptor upon stimulation by stress-inducing agents. RT-PCR analysis was used to determine the pattern of expression of the larger isoform (I) of this receptor in a variety of tissues. This form of the receptor is expressed primarily in the organs of the gastrointestinal tract, tissues that are frequently exposed to stress-inducing agents, but not in the central nervous system, tissues that are protected from insult by the blood barrier. Using the same RT-PCR approach we show that stress-inducing agents, such as 'first-hand' and 'second-hand' cigarette smoke components, tumor promoters and thrombin, differentially stimulate the expression of the isoform I in primary fibroblasts. Thrombin is an enzyme that plays many important roles in thrombosis, angiogenesis and wound healing and exposure to

  19. Multiple functions of mfa-1, a putative pheromone precursor gene of Neurospora crassa.

    Science.gov (United States)

    Kim, Hyojeong; Metzenberg, Robert L; Nelson, Mary Anne

    2002-12-01

    A putative pheromone precursor gene of Neurospora crassa, mfa-1 (which encodes mating factor a-1), was identified as the most abundant clone in starved mycelial and perithecial cDNA libraries. Northern analysis demonstrated high mfa-1 expression in all mating type a tissues and suggested low expression levels in mat A tissues. The mfa-1 gene was expressed as an approximately 1.2-kb transcript predicted to encode a 24-residue peptide, followed by a long 3' untranslated region (3' UTR). The predicted MFA1 sequence showed 100% sequence identity to PPG2 of Sordaria macrospora and structural similarity (a carboxy-terminal CAAX motif) to many hydrophobic fungal pheromone precursors. Mutants with a disrupted open reading frame (ORF) in which the critical cysteine residue had been changed to a nonprenylatable residue, tyrosine (YAAX mutants), were isolated, as were mfa-1 mutants with intact ORFs but multiple mutations in the 3' noncoding region (CAAX mutants). The 3' UTR is required for the full range of mfa-1 gene activity. Both classes of mutants showed delayed and reduced vegetative growth (which was suppressed by supplementation with a minute amount [30 micro M] of ornithine, citrulline, or arginine), as well as aberrant sexual development. When crossed as female parents to wild-type males, the CAAX and YAAX mutants showed greatly reduced ascospore production. No ascospores were produced in homozygous mfa-1 crosses. As males, YAAX mat a mutants were unable to attract wild-type mat A trichogynes (female-specific hyphae) or to initiate sexual development, while CAAX mat a mutants were able to mate and produce sexual progeny despite their inability to attract mat A trichogynes. In the mat A background, both CAAX and YAAX mutants showed normal male fertility but defective vegetative growth and aberrant female sexual development. Thus, the mfa-1 gene appears to have multiple roles in N. crassa development: (i) it encodes a hydrophobic pheromone with a putative farnesylated

  20. Contrasting phenotypes of putative proprioceptive and nociceptive trigeminal neurons innervating jaw muscle in rat

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    Connor Mark

    2005-10-01

    Full Text Available Abstract Background Despite the clinical significance of muscle pain, and the extensive investigation of the properties of muscle afferent fibers, there has been little study of the ion channels on sensory neurons that innervate muscle. In this study, we have fluorescently tagged sensory neurons that innervate the masseter muscle, which is unique because cell bodies for its muscle spindles are in a brainstem nucleus (mesencephalic nucleus of the 5th cranial nerve, MeV while all its other sensory afferents are in the trigeminal ganglion (TG. We examine the hypothesis that certain molecules proposed to be used selectively by nociceptors fail to express on muscle spindles afferents but appear on other afferents from the same muscle. Results MeV muscle afferents perfectly fit expectations of cells with a non-nociceptive sensory modality: Opiates failed to inhibit calcium channel currents (ICa in 90% of MeV neurons, although ICa were inhibited by GABAB receptor activation. All MeV afferents had brief (1 msec action potentials driven solely by tetrodotoxin (TTX-sensitive Na channels and no MeV afferent expressed either of three ion channels (TRPV1, P2X3, and ASIC3 thought to be transducers for nociceptive stimuli, although they did express other ATP and acid-sensing channels. Trigeminal masseter afferents were much more diverse. Virtually all of them expressed at least one, and often several, of the three putative nociceptive transducer channels, but the mix varied from cell to cell. Calcium currents in 80% of the neurons were measurably inhibited by μ-opioids, but the extent of inhibition varied greatly. Almost all TG masseter afferents expressed some TTX-insensitive sodium currents, but the amount compared to TTX sensitive sodium current varied, as did the duration of action potentials. Conclusion Most masseter muscle afferents that are not muscle spindle afferents express molecules that are considered characteristic of nociceptors, but these

  1. PRE AND POST TRAINING EVALUATION ON UNIVERSAL PRECAUTIONS (UP PRACTICES AT PUTAT JAYA HEALTH CENTER, SURABAYA

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    Cholis Bachroen

    2012-11-01

    Full Text Available Praktek untuk mematuhi 'universal precaution' (UP di institusi pelayanan kesehatan (termasuk puskesmas, klinik dsb dimaksudkan untuk melindungi pasien dan petugas kesehatan dari penularan penyakit yang dapat terjadi karena tindakan pelayanan kesehatan yang kurang atau tidak tepat (tidak mengikuti UP. Penyakit  yang mungkin dapat menular dengan tidak ditepatinya UP oleh petugas kesehatan antara lain adalah penyakit yang dapat menular lewat darah (blood bome diseases termasuk HIV/AIDS dan Hepatitis B dan C. Mengingat kepatuhan  terhadap UP di antara petugas kesehatan selama melayani pasien dinilai masih kurang, maka dilaksanakan Pelatihan UP di puskesmas. Study ini dilakukan di Puskesmas Putat Jays yang Juga mempunyai klinik yang khusus melayani Pekerja Seksual Komersial (PSK dalam rangka menekan terjadinya penularan penyakit kelamin dan HIV/AIDS. Puskesmas Putat Jays merupakan sasaran yang strategis karena mempunyat daerah binaan antara lain Lokalisasi (PSK Dolly dan Jarak. Studi evaluatif ini dimaksudkan untuk melihat tingkat kepatuhan petugas terhadap UP selama melayani pasien serta mengkaji adanya perubahan kepatuhan tersebut setelah mendapat pelatihan. Data kualitaltf dan kuantitatif dikumpulkan melalui observasi, in depth interview dan diskusi. Hasil studi menunjukkan bahwa setelah pelatihan, pengetahuan tentang UP secara umum serta kesadaran untuk melindungi pasien dari penularan penyakit meningkat. Penggunaan ulang jarum suntik sudah tidak dilakukan (selalu memakai jarum diposable, spuit dan jarum di-disinfeksi sebelum dibuang serta pelaksanaan disinfeksilsterilisasi telah sesuai dengan prosedur. Data kuantitatif menunjukkan bahwa dengan pelatihan terjadi peningkatan jumlah petugas kesehatan yang mempunyai kebiasaan mencuci tangan secara tepat pada waktu melayani pasien yaitu dari 10% menjadi 90%, mengganti sarung tangan dengan tepat dari 33,3% menjadi 66,67%, memakai 'one hand technique' waktu menutup jarum dari 0% menjadi 100%, dan

  2. Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

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    Robert C Barber

    Full Text Available Although 24 Alzheimer's disease (AD risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1, Vascular Cell Adhesion Molecule 1 (VCAM1, Pancreatic Polypeptide (PP, Beta2 Microglobulin (B2M, Factor VII (F7, Adiponectin (ADN and Tenascin C (TN-C. Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7. Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes, which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point

  3. Discovery of Putative Herbicide Resistance Genes and Its Regulatory Network in Chickpea Using Transcriptome Sequencing

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    Mir A. Iquebal

    2017-06-01

    Full Text Available Background: Chickpea (Cicer arietinum L. contributes 75% of total pulse production. Being cheaper than animal protein, makes it important in dietary requirement of developing countries. Weed not only competes with chickpea resulting into drastic yield reduction but also creates problem of harboring fungi, bacterial diseases and insect pests. Chemical approach having new herbicide discovery has constraint of limited lead molecule options, statutory regulations and environmental clearance. Through genetic approach, transgenic herbicide tolerant crop has given successful result but led to serious concern over ecological safety thus non-transgenic approach like marker assisted selection is desirable. Since large variability in tolerance limit of herbicide already exists in chickpea varieties, thus the genes offering herbicide tolerance can be introgressed in variety improvement programme. Transcriptome studies can discover such associated key genes with herbicide tolerance in chickpea.Results: This is first transcriptomic studies of chickpea or even any legume crop using two herbicide susceptible and tolerant genotypes exposed to imidazoline (Imazethapyr. Approximately 90 million paired-end reads generated from four samples were processed and assembled into 30,803 contigs using reference based assembly. We report 6,310 differentially expressed genes (DEGs, of which 3,037 were regulated by 980 miRNAs, 1,528 transcription factors associated with 897 DEGs, 47 Hub proteins, 3,540 putative Simple Sequence Repeat-Functional Domain Marker (SSR-FDM, 13,778 genic Single Nucleotide Polymorphism (SNP putative markers and 1,174 Indels. Randomly selected 20 DEGs were validated using qPCR. Pathway analysis suggested that xenobiotic degradation related gene, glutathione S-transferase (GST were only up-regulated in presence of herbicide. Down-regulation of DNA replication genes and up-regulation of abscisic acid pathway genes were observed. Study further reveals

  4. Determination and Analysis of the Putative AcaCD-Responsive Promoters of Salmonella Genomic Island 1

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    Olasz, Ferenc; Kiss, János

    2016-01-01

    The integrative genomic island SGI1 and its variants confer multidrug resistance in numerous Salmonella enterica serovariants and several Proteus mirabilis and Acinetobacter strains. SGI1 is mobilized by the IncA/C family plasmids. The island exploits not only the conjugation apparatus of the plasmid, but also utilizes the plasmid-encoded master regulator AcaCD to induce the excision and formation of its transfer-competent form, which is a key step in the horizontal transfer of SGI1. Triggering of SGI1 excision occurs via the AcaCD-dependent activation of xis gene expression. AcaCD binds in Pxis to an unusually long recognition sequence. Beside the Pxis promoter, upstream regions of four additional SGI1 genes, S004, S005, S012 and S018, also contain putative AcaCD-binding sites. Furthermore, SGI1 also encodes an AcaCD-related activator, FlhDCSGI1, which has no known function. Here, we have analysed the functionality of the putative AcaCD-dependent promoter regions and proved their activation by either AcaCD or FlhDCSGI1. Moreover, we provide evidence that both activators act on the same binding site in Pxis and that FlhDCSGI1 is able to complement the acaCD deletion of the IncA/C family plasmid R16a. We determined the transcription start sites for the AcaCD-responsive promoters and showed that orf S004 is expressed probably from a different start codon than predicted earlier. Additionally, expression of S003 from promoter PS004 was ruled out. Pxis and the four SGI1 promoters examined here also lack obvious -35 promoter box and their promoter profile is consistent with the class II-type activation pathway. Although the role of the four additionally analysed AcaCD/FlhDCSGI1-controlled genes in transfer and/or maintenance of SGI1 is not yet clear, the conservation of the whole region suggests the existence of some selection for their functionality. PMID:27727307

  5. Putative molecular mechanism underlying sperm chromatin remodelling is regulated by reproductive hormones

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    Gill-Sharma Manjeet Kaur

    2012-12-01

    Full Text Available Abstract Background The putative regulatory role of the male reproductive hormones in the molecular mechanism underlying chromatin condensation remains poorly understood. In the past decade, we developed two adult male rat models wherein functional deficits of testosterone or FSH, produced after treatments with 20 mg/Kg/d of cyproterone acetate (CPA per os, for a period of 15 days or 3 mg/Kg/d of fluphenazine decanoate (FD subcutaneously, for a period of 60 days, respectively, affected the rate of sperm chromatin decondensation in vitro. These rat models have been used in the current study in order to delineate the putative roles of testosterone and FSH in the molecular mechanism underlying remodelling of sperm chromatin. Results We report that deficits of both testosterone and FSH affected the turnover of polyubiquitylated histones and led to their accumulation in the testis. Functional deficits of testosterone reduced expression of MIWI, the 5-methyl cap binding RNA-binding protein (PIWIlike murine homologue of the Drosophila protein PIWI/P-element induced wimpy testis containing a PAZ/Piwi-Argonaut-Zwille domain and levels of histone deacetylase1 (HDAC1, ubiquitin ligating enzyme (URE-B1/E3, 20S proteasome α1 concomitant with reduced expression of ubiquitin activating enzyme (ube1, conjugating enzyme (ube2d2, chromodomain Y like protein (cdyl, bromodomain testis specific protein (brdt, hdac6 (histone deacetylase6, androgen-dependent homeobox placentae embryonic protein (pem/RhoX5, histones h2b and th3 (testis-specific h3. Functional deficits of FSH reduced the expression of cdyl and brdt genes in the testis, affected turnover of ubiquitylated histones, stalled the physiological DNA repair mechanism and culminated in spermiation of DNA damaged sperm. Conclusions We aver that deficits of both testosterone and FSH differentially affected the process of sperm chromatin remodelling through subtle changes in the ‘chromatin condensation

  6. Localization and transcriptional responses of Chrysoporthe austroafricana in Eucalyptus grandis identify putative pathogenicity factors

    Directory of Open Access Journals (Sweden)

    Ronishree Mangwanda

    2016-12-01

    Full Text Available Chrysoporthe austroafricana is a fungal pathogen that causes the development of stem cankers on susceptible Eucalyptus grandis trees. Clones of E. grandis that are partially resistant and highly susceptible have been identified based on the extent of lesion formation on the stem upon inoculation with C. austroafricana. These interactions have been used as a model pathosystem to enhance our understanding of interactions between pathogenic fungi and woody hosts, which may be different to herbaceous hosts. In previous research, transcriptomics of host responses in these two clones to C. austroafricana suggested roles for salicylic acid and gibberellic acid phytohormone signalling in defense. However, it is unclear how the pathogen infiltrates host tissue and which pathogenicity factors facilitate its spread in the two host genotypes. The aim of this study was to investigate these two aspects of the E. grandis-C. austroafricana interaction and to test the hypothesis that the pathogen possesses mechanisms to modulate the tree phytohormone-mediated defenses. Light microscopy showed that the pathogen occurred in most cell types and structures within infected E. grandis stem tissue. Notably, the fungus appeared to spread through the stem by penetrating cell wall pits. In order to understand the molecular interaction between these organisms and predict putative pathogenicity mechanisms of C. austroafricana, fungal gene expression was studied in vitro and in planta. Fungal genes associated with cell wall degradation, carbohydrate metabolism and phytohormone manipulation were expressed in planta by C. austroafricana. These genes could be involved in fungal spread by facilitating cell wall pit degradation and manipulating phytohormone mediated defense in each host environment, respectively. Specifically, the in planta expression of an ent-kaurene oxidase and salicylate hydroxylase in C. austroafricana suggests putative mechanisms by which the pathogen can

  7. Pyrosequencing of the Camptotheca acuminata transcriptome reveals putative genes involved in camptothecin biosynthesis and transport

    Directory of Open Access Journals (Sweden)

    Sun Yongzhen

    2011-10-01

    Full Text Available Abstract Background Camptotheca acuminata is a Nyssaceae plant, often called the "happy tree", which is indigenous in Southern China. C. acuminata produces the terpenoid indole alkaloid, camptothecin (CPT, which exhibits clinical effects in various cancer treatments. Despite its importance, little is known about the transcriptome of C. acuminata and the mechanism of CPT biosynthesis, as only few nucleotide sequences are included in the GenBank database. Results From a constructed cDNA library of young C. acuminata leaves, a total of 30,358 unigenes, with an average length of 403 bp, were obtained after assembly of 74,858 high quality reads using GS De Novo assembler software. Through functional annotation, a total of 21,213 unigenes were annotated at least once against the NCBI nucleotide (Nt, non-redundant protein (Nr, Uniprot/SwissProt, Kyoto Encyclopedia of Genes and Genomes (KEGG, and Arabidopsis thaliana proteome (TAIR databases. Further analysis identified 521 ESTs representing 20 enzyme genes that are involved in the backbone of the CPT biosynthetic pathway in the library. Three putative genes in the upstream pathway, including genes for geraniol-10-hydroxylase (CaPG10H, secologanin synthase (CaPSCS, and strictosidine synthase (CaPSTR were cloned and analyzed. The expression level of the three genes was also detected using qRT-PCR in C. acuminata. With respect to the branch pathway of CPT synthesis, six cytochrome P450s transcripts were selected as candidate transcripts by detection of transcript expression in different tissues using qRT-PCR. In addition, one glucosidase gene was identified that might participate in CPT biosynthesis. For CPT transport, three of 21 transcripts for multidrug resistance protein (MDR transporters were also screened from the dataset by their annotation result and gene expression analysis. Conclusion This study produced a large amount of transcriptome data from C. acuminata by 454 pyrosequencing. According to

  8. The impact of endocrine disruptors on membrane fatty acid composition of carp organs%内分泌干扰物对鲤鱼器官细胞膜脂肪酸组分的影响

    Institute of Scientific and Technical Information of China (English)

    张翔; 荆博宇; 袁小英; 郭栋生

    2014-01-01

    选择雌二醇、双酚A和邻苯二甲酸二丁酯等3种内分泌干扰物以及睾酮对鲤鱼染毒,研究了不同处理对鲤鱼肝胰脏、性腺和脑细胞膜中脂肪酸组成和含量的影响以及腺苷酸环化酶活性的变化。结果表明,内分泌干扰物暴露可使不同组织器官细胞膜中饱和脂肪酸含量升高,不饱和脂肪酸含量降低,不饱和脂肪酸中双键的数目减少;其结果可能会对组织器官细胞膜的结构、功能产生一定的影响。在肝胰脏和性腺中,睾酮暴露和雌二醇暴露在细胞膜饱和脂肪酸含量方面表现为效应相一致;只在不饱和脂肪酸花生四烯酸( AA)和二十二碳六烯酸( DHA)含量方面表现为效应相拮抗。酶活性测定结果表明,影响细胞内脂肪酸代谢进而影响细胞膜结构和功能的机理可能与细胞膜腺苷酸环化酶活性发生改变相关。%Three kinds of endocrine disruptors estradiol, bisphenol A, dibutyl phthalate and testosterone were exposed at carp, and the effect of them on the content and composition of fatty acid in cell membrane and adenylate cyclase activity in cell of carp hepatopancreas, gonads and brain had been studied. The result showed that to three organs of carp, the exposure of endocrine disruptors can make the contents of saturated fatty acid increased; unsaturated fatty acid decreased in cell membranes, and make the number of double bonds lowered in unsaturated fatty acid. As a result, the structure and function of cell membranes in organs were possibly affected. In hepatopancreas and gonads, the effect of testosterone exposure was consistent with the effect of estradiol exposure in saturated fatty acid content, but is antagonistic with it in the content of unsaturated fatty acid arachidonic acid and docosahexaenoic acid. The result of enzyme activity assay showed that the mechanism of fatty acid metabolism change for exposure, thereby affecting the structure and

  9. Flucloxacillin, still the empirical choice for putative Staphylococcus aureus infections in intensive care units in the Netherlands.

    NARCIS (Netherlands)

    Rijnders, M.I.; Deurenberg, R.H.; Boumans, M.L.; Hoogkamp-Korstanje, J.A.A.; Beisser, P.S.; Stobberingh, E.E.

    2009-01-01

    OBJECTIVES: To determine the usefulness of flucloxacillin as empirical therapy for putative Staphylococcus aureus infections in intensive care unit (ICU) patients in the Netherlands, the antibiotic resistance of S. aureus isolates from ICUs over a 13 year period was investigated. METHODS: From 1996

  10. Potential role of transient receptor potential channel M5 in sensing putative pheromones in mouse olfactory sensory neurons.

    Science.gov (United States)

    Oshimoto, Arisa; Wakabayashi, Yoshihiro; Garske, Anna; Lopez, Roberto; Rolen, Shane; Flowers, Michael; Arevalo, Nicole; Restrepo, Diego

    2013-01-01

    Based on pharmacological studies of chemosensory transduction in transient receptor potential channel M5 (TRPM5) knockout mice it was hypothesized that this channel is involved in transduction for a subset of putative pheromones in mouse olfactory sensory neurons (OSNs). Yet, in the same study an electroolfactogram (EOG) in the mouse olfactory epithelium showed no significant difference in the responses to pheromones (and odors) between wild type and TRPM5 knockout mice. Here we show that the number of OSNs expressing TRPM5 is increased by unilateral naris occlusion. Importantly, EOG experiments show that mice lacking TRPM5 show a decreased response in the occluded epithelia to putative pheromones as opposed to wild type mice that show no change upon unilateral naris occlusion. This evidence indicates that under decreased olfactory sensory input TRPM5 plays a role in mediating putative pheromone transduction. Furthermore, we demonstrate that cyclic nucleotide gated channel A2 knockout (CNGA2-KO) mice that show substantially decreased or absent responses to odors and pheromones also have elevated levels of TRPM5 compared to wild type mice. Taken together, our evidence suggests that TRPM5 plays a role in mediating transduction for putative pheromones under conditions of reduced chemosensory input.

  11. A Synthetic Peptide with the Putative Iron Binding Motif of Amyloid Precursor Protein (APP) Does Not Catalytically Oxidize Iron

    NARCIS (Netherlands)

    Honarmand Ebrahimi, K.; Hagedoorn, P.L.; Hagen, W.R.

    2012-01-01

    The β-amyloid precursor protein (APP), which is a key player in Alzheimer's disease, was recently reported to possess an Fe(II) binding site within its E2 domain which exhibits ferroxidase activity [Duce et al. 2010, Cell 142: 857]. The putative ligands of this site were compared to those in the fer

  12. Enhancement of Cry19Aa Mosquitocidal Activity against Aedes aegypti by Mutations in the Putative Loop Regions of Domain II

    OpenAIRE

    Abdullah, Mohd Amir F.; Donald H Dean

    2004-01-01

    Improvements in the mosquitocidal activity of Bacillus thuringiensis Cry19Aa were achieved by protein engineering of putative surface loop residues in domain II through rational design. The improvement of Aedes toxicity in Cry19Aa was 42,000-fold and did not affect its toxicity against Anopheles or Culex.

  13. Evidence for Conformational Protection of Nitrogenase against Oxygen in Gluconacetobacter diazotrophicus by a Putative FeSII Protein

    OpenAIRE

    Ureta, Alejandro; Nordlund, Stefan

    2002-01-01

    The mechanisms protecting nitrogenase in Gluconacetobacter diazotrophicus from damage by oxygen were studied. Evidence is provided suggesting that in G. diazotrophicus these mechanisms include respiratory protection as well as conformational protection in which a putative FeSII Shethna protein is involved.

  14. Evidence for conformational protection of nitrogenase against oxygen in Gluconacetobacter diazotrophicus by a putative FeSII protein.

    Science.gov (United States)

    Ureta, Alejandro; Nordlund, Stefan

    2002-10-01

    The mechanisms protecting nitrogenase in Gluconacetobacter diazotrophicus from damage by oxygen were studied. Evidence is provided suggesting that in G. diazotrophicus these mechanisms include respiratory protection as well as conformational protection in which a putative FeSII Shethna protein is involved.

  15. Machine learning techniques to identify putative genes involved in nitrogen catabolite repression in the yeast Saccharomyces cerevisiae

    Science.gov (United States)

    Kontos, Kevin; Godard, Patrice; André, Bruno; van Helden, Jacques; Bontempi, Gianluca

    2008-01-01

    Background Nitrogen is an essential nutrient for all life forms. Like most unicellular organisms, the yeast Saccharomyces cerevisiae transports and catabolizes good nitrogen sources in preference to poor ones. Nitrogen catabolite repression (NCR) refers to this selection mechanism. All known nitrogen catabolite pathways are regulated by four regulators. The ultimate goal is to infer the complete nitrogen catabolite pathways. Bioinformatics approaches offer the possibility to identify putative NCR genes and to discard uninteresting genes. Results We present a machine learning approach where the identification of putative NCR genes in the yeast Saccharomyces cerevisiae is formulated as a supervised two-class classification problem. Classifiers predict whether genes are NCR-sensitive or not from a large number of variables related to the GATA motif in the upstream non-coding sequences of the genes. The positive and negative training sets are composed of annotated NCR genes and manually-selected genes known to be insensitive to NCR, respectively. Different classifiers and variable selection methods are compared. We show that all classifiers make significant and biologically valid predictions by comparing these predictions to annotated and putative NCR genes, and by performing several negative controls. In particular, the inferred NCR genes significantly overlap with putative NCR genes identified in three genome-wide experimental and bioinformatics studies. Conclusion These results suggest that our approach can successfully identify potential NCR genes. Hence, the dimensionality of the problem of identifying all genes involved in NCR is drastically reduced. PMID:19091052

  16. A systematic review of amyloid-beta peptides as putative mediators of the association between affective disorders and Alzheimer's disease

    DEFF Research Database (Denmark)

    Abbasowa, L.; Heegaard, N. H. H.

    2014-01-01

    Background: Affective disorders are associated with an increased occurrence of cognitive deficits and have been linked to cognitive impairment and Alzheimer's disease. The putative molecular mechanisms involved in these associations are however not clear. The aim of this systematic review was to ...

  17. PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70-KILODALTON HEAT SHOCK PROTEIN HSPA2

    Science.gov (United States)

    THE PUTATIVE CREATINE KINASE M-ISOFORM IN HUMAN SPERM IS IDENTIFIED AS THE 70 kDa HEAT SHOCK PROTEIN HSPA2* Gabor Huszar1, Kathryn Stone2, David Dix3 and Lynne Vigue11The Sperm Physiology Laboratory, Department of Obstetrics and Gynecology, 2 W.M. Keck Foundatio...

  18. Promoter activity of a putative pollen monosaccharide transporter in Petunia hybrida and characterisation of a transposon insertion mutant

    NARCIS (Netherlands)

    Garrido, D.; Busscher-Lange, J.; Tunen, van A.J.

    2006-01-01

    For the growth of the male reproductive cells of plants, the pollen, the presence of sufficient sucrose or monosaccharides is of vital importance. From Petunia hybrida a pollen-specific putative monosaccharide transporter designated PMT1 (for petunia monosaccharide transporter) has been identified p

  19. Complete Genome Sequence of the Filamentous Fungus Aspergillus westerdijkiae Reveals the Putative Biosynthetic Gene Cluster of Ochratoxin A

    Science.gov (United States)

    Chakrabortti, Alolika; Li, Jinming

    2016-01-01

    Ochratoxin A (OTA) is a common mycotoxin that contaminates food and agricultural products. Sequencing of the complete genome of Aspergillus westerdijkiae, a major producer of OTA, reveals more than 50 biosynthetic gene clusters, including a putative OTA biosynthetic gene cluster that encodes a dozen of enzymes, transporters, and regulatory proteins. PMID:27635003

  20. CYP2C subfamily, primarily CYP2C9, catalyses the enantioselective demethylation of the endocrine disruptor pesticide methoxychlor in human liver microsomes: use of inhibitory monoclonal antibodies in P450 identification.

    Science.gov (United States)

    Hu, Y; Krausz, K; Gelboin, H V; Kupfer, D

    2004-02-01

    1. The endocrine disruptor pesticide methoxychlor undergoes O-demethylation by mammalian liver microsomes forming chiral mono-phenolic (1,1,1-trichloro-2-(4-hydroxyphenyl)-2-(4-methoxyphenyl)ethane, i.e. mono-OH-M) and achiral bis-phenolic oestrogenic metabolites. Human liver microsomes (HLM) generated primarily the S-mono-OH-M. 2. Inhibitory monoclonal antibodies (MAb) identified those P450s catalysing the enantioselective O-demethylation of methoxychlor. In HLM, O-demethylation was inhibited by MAb anti-2C9 (30-40%), diminishing the per cent of S-mono-OH-M from about 80 to 55-60%. MAb anti-CYP1A2, 2A6, 2B6, 2C8, 2C19, 2D6 and 3A4 did not affect the demethylation rate in HLM. Nevertheless, MAb anti-CYP1A2 decreased the formation of R-mono-OH-M from 21-23 to 10-17%, indicating that CYP1A2 exhibits a role in generating the R-enantiomer. 3. Among cDNA-expressed human P450s (supersomes), CYP2C19 was the most active in demethylation, but in HLM, CYP2C19 appeared inactive (no inhibition by MAb anti-CYP2C19). There was a substantial difference in the per cent inhibition of demethylation by MAb anti-CYP2C9 and anti-rat CYP2C (MAb inhibiting all human CYP2C forms) and in altering the enantioselectivity, suggesting that demethylation by combined CYP2C8, 2C18 and 2C19 was significant (20-30%). 4. Polymorphism of methoxychlor demethylation was examined with supersomes and HLM-expressing CYP2C9 allelic variants. CYP2C9*1 and 2C9*2 were highly active; however, CYP2C9*3 appeared inactive.