The widespread occurrence of feminized male fish downstream of some UK Wastewater Treatment Works (WwTWs) has been associated with exposure to estrogenic and potentially antiandrogenic (AA) ...contaminants in the effluents. In this study, profiling of AA contaminants in WwTW effluents and fish was conducted using HPLC in combination with in vitro androgen receptor transcription screens. Analysis of extracts of wastewater effluents revealed complex profiles of AA activity comprising 21–53 HPLC fractions. Structures of bioavailable antiandrogens were identified by exposing rainbow trout to a WwTW effluent and profiling the bile for AA activity using yeast (anti-YAS) and mammalian-based (AR-CALUX) androgen receptor transcription screens. The predominant fractions with AA activity in both androgen receptor screens contained the germicides chlorophene and triclosan, and together these contaminants accounted for 51% of the total anti-YAS activity in the fish bile. Other AA compounds identified in bile included chloroxylenol, dichlorophene, resin acids, napthols, oxybenzone, 4-nonylphenol, and bisphenol A. Pure standards of these compounds were active in the androgen receptor screens at potencies relative to flutamide of between 0.1 and 13.0. Thus, we have identified, for the first time, a diverse range of AA chemicals in WwTWs that are bioavailable to fish and which need to be assessed for their risk to the reproductive health of these organisms and other aquatic biota.
► Different fish species differ in their responsiveness to estrogens. ► Estrogen responsiveness in receptor transactivation assays equate well with responses in vivo. ► Estrogen receptor ...transactivation assays are effective screening tools for estrogenic substances.
Exposure to estrogenic chemicals discharged into the aquatic environment has been shown to induce feminization in wild freshwater fish and although fish species have been reported to differ in their susceptibility for these effects, empirical studies that directly address this hypothesis are lacking. In this study, in vitro ERα activation assays were applied in a range of fish species used widely in chemical testing (including, zebrafish, fathead minnow, medaka) and/or as environmental monitoring species (including, roach, stickleback, carp) to assess their comparative responsiveness to natural (estrone, estradiol, estriol) and synthetic (17α-ethinylestradiol (EE2), diethylstilbestrol (DES)) estrogens. In vivo exposures to EE2 via the water (nominal 2 and 10ng/L for 7 days) were also conducted for seven fish species to compare their responsiveness for hepatic vitellogenin (VTG) mRNA induction (an ER mediated response). Of the fish species tested, zebrafish ERα was found to be the most responsive and carp and stickleback ERα the least responsive to natural steroid estrogens. This was also the case for exposure to EE2 with an ERα-mediated response sensitivity order of zebrafish>medaka>roach>fathead minnow>carp>stickleback. For VTG mRNA induction in vivo, the order of species responsiveness was: rainbow trout (not tested in the ERα activation assays)>zebrafish>fathead minnow>medaka>roach>stickleback>carp. Overall, the responses to steroid estrogens in vitro via ERα compared well with those seen in vivo (VTG induction for exposure to EE2) showing in vitro screening of chemicals using fish ERα-mediated responses indicative of estrogenic responses (VTG induction) in vivo.
Exposure of fish to wastewater treatment works (WwTWs) effluents can result in reproductive anomalies consistent with exposure to estrogenic compounds. However, UK WwTWs effluents also contain ...compounds with androgen receptor activities which may contribute to reproductive dysfunction in fish. A toxicity identification and evaluation (TIE) approach was used to profile (anti)androgenic compounds in bile of fish exposed to two WwTWs effluents. Extracts of bile from exposed fish and effluent were fractionated by liquid chromatography and tested for (anti)androgenic activity using a yeast androgen receptor transcription screen (YAS). A number of bile fractions contained (anti)androgenic activity unique to the effluent-exposed fish. Some of these fractions contained di(chloromethyl)anthracene or dichlorophene, and these contaminants showed antagonistic activity in the YAS when tested as pure compounds. No androgenic activity was detected in the effluents, but TIE analysis of bile revealed a number of androgenic fractions which contained testosterone metabolites that were unique to effluent-exposed fish. This is the first work reported on the nature of some of the (anti)androgenic compounds that bioaccumulate in fish from WwTWs effluents and indicates that other contaminants, besides estrogenic substances, need to be considered for their potential to contribute to the disruption of reproductive system of fish in UK waters.
Estrogenic chemicals are major contaminants of surface waters and can threaten the sustainability of natural fish populations. Characterization of the global molecular mechanisms of toxicity of ...environmental contaminants has been conducted primarily in model species rather than species with limited existing transcriptomic or genomic sequence information. We aimed to investigate the global mechanisms of toxicity of an endocrine disrupting chemical of environmental concern 17β-estradiol (E2) using high-throughput RNA sequencing (RNA-Seq) in an environmentally relevant species, brown trout (Salmo trutta). We exposed mature males to measured concentrations of 1.94, 18.06, and 34.38 ng E2/l for 4 days and sequenced three individual liver samples per treatment using an Illumina HiSeq 2500 platform. Exposure to 34.4 ng E2/L resulted in 2,113 differentially regulated transcripts (FDR < 0.05). Functional analysis revealed upregulation of processes associated with vitellogenesis, including lipid metabolism, cellular proliferation, and ribosome biogenesis, together with a downregulation of carbohydrate metabolism. Using real-time quantitative PCR, we validated the expression of eight target genes and identified significant differences in the regulation of several known estrogen-responsive transcripts in fish exposed to the lower treatment concentrations (including esr1 and zp2.5). We successfully used RNA-Seq to identify highly conserved responses to estrogen and also identified some estrogen-responsive transcripts that have been less well characterized, including nots and tgm2l. These results demonstrate the potential application of RNA-Seq as a valuable tool for assessing mechanistic effects of pollutants in ecologically relevant species for which little genomic information is available.
•Historical metal exposure is linked to altered transcriptional responses to copper.•Stickleback from metal-rich areas have higher basal transcription of genes encoding metallothioneins.•These ...changes are heritable to the F1 generation in laboratory conditions.
Some fish populations inhabiting contaminated environments show evidence of increased chemical tolerance, however the mechanisms contributing to this tolerance, and whether this is heritable, are poorly understood. We investigated the responses of two populations of wild three-spined stickleback (Gasterosteus aculeatus) with different histories of contaminant exposure to an oestrogen and copper, two widespread aquatic pollutants. Male stickleback originating from two sites, the River Aire, with a history of complex pollution discharges, and Siblyback Lake, with a history of metal contamination, were depurated and then exposed to copper (46μg/L) and the synthetic oestrogen ethinyloestradiol (22ng/L). The hepatic transcriptomic response was compared between the two populations and to a reference population with no known history of exposure (Houghton Springs, Dorset). Gene responses included those typical for both copper and oestrogen, with no discernable difference in response to oestrogen between populations. There was, however, some difference in the magnitude of response to copper between populations. Siblyback fish showed an elevated baseline transcription of genes encoding metallothioneins and a lower level of metallothionein induction following copper exposure, compared to those from the River Aire. Similarly, a further experiment with an F1 generation of Siblyback fish bred in the laboratory found evidence for elevated transcription of genes encoding metallothioneins in unexposed fish, together with an altered transcriptional response to 125μg/L copper, compared with F1 fish originating from the clean reference population exposed to the same copper concentration. These data suggest that the stickleback from Siblyback Lake have a differential response to copper, which is inherited by the F1 generation in laboratory conditions, and for which the underlying mechanism may include an elevation of baseline transcription of genes encoding metallothioneins. The genetic and/or epigenetic mechanisms contributing to this inherited alteration of metallothionein transcription have yet to be established.
Whether the implementation of additional treatments for the removal of estrogens from wastewater treatment works (WwTWs) effluents will eliminate their feminizing effects in exposed wildlife has yet ...to be established, and this information is crucial for future decisions on investment into WwTWs. Here, granular activated carbon (GAC), ozone (O3), and chlorine dioxide (ClO2) were investigated for their effectiveness in reducing steroidal estrogen levels in a WwTW effluent and assessments made on the associated estrogenic and reproductive responses in fathead minnows (Pimephales promelas) exposed for 21 days. All treatments reduced the estrogenicity of the standard-treated (STD) effluent, but with different efficacies; ranging between 70−100% for total estrogenicity and 53−100% for individual steroid estrogens. In fish exposed to the GAC- and ClO2- (but not O3-) treated effluents, there was no induction of plasma vitellogenin (VTG) or reduction in the weight of the fatpad, a secondary sex character in males, as occurred for fish exposed to STD effluent. This finding suggests likely benefits of employing these treatment processes for the reproductive health in wild fish populations living in rivers receiving WwTW discharges. Exposure of pair-breeding minnows to the GAC-treated effluent, however, resulted in a similar inhibition of egg production to that occurring for exposure to the STD effluent (34−40%). These data, together with a lack of effect on egg production of the estrogen, ethinylestradiol (10 ng/L), alone, suggest that chemical/physical properties of the effluents rather than their estrogenicity were responsible for the reproductive effect and that these factor(s) were not remediated for through GAC treatment. Collectively, our findings illustrate the importance of assessing integrative biological responses, rather than biomarkers alone, in the assessment and improvement of WwTW technologies for the protection of wild fish populations.
Many factors have been considered in evaluations of the risk−benefit balance of hormone replacement therapy (HRT), used for treating menopausal symptoms in women, but not its potential risks for the ...environment. We investigated the possible environmental health implications of conjugated equine estrogens (CEEs), the most common components of HRT, including their discharge into the environment, their uptake, potency, and ability to induce biological effects in wildlife. Influents and effluents from four UK sewage treatment works (STWs), and bile of effluent-exposed fish, were screened for six equine estrogens. In vitro estrogen receptor (ER) activation assays were applied in humans and fish to compare their potencies, followed by in vivo exposures of fish to equine estrogens and evaluation of bioaccumulation, estrogenic responses, and ER gene expression. The equine estrogen equilenin (Eqn), and its metabolite 17β-dihydroequilenin (17β-Eqn), were detected by tandem GC-MSMS in all STW influent samples and 83% of STW effluent samples analyzed, respectively, at low concentrations (0.07−2.6 ng/L) and were taken-up into effluent-exposed fish. As occurs in humans, these estrogens bound to and activated the fish ERs, with potencies at ERα 2.4−3490% of that for 17β-estradiol. Exposure of fish for 21 days to Eqn and 17β-Eqn induced estrogenic responses including hepatic growth and vitellogenin production at concentrations as low as 0.6−4.2 ng/L. Associated with these effects were inductions of hepatic ERα and ERβ1 gene expression, suggesting ER-mediated mechanism(s) of action. These data provide evidence for the discharge of equine estrogens from HRT into the aquatic environment and highlight a strong likelihood that these compounds contribute to feminization in exposed wildlife.
Osteopathic distinctiveness is a result of professional education, identity formation, training, credentialing, and qualifications. With the advancement of a single graduate medical education (GME) ...accreditation system and the continued growth of the osteopathic medical profession, osteopathic distinctiveness and professional identity are seen as lacking clarity and pose a challenge.
To achieve consensus on a succinct definition of osteopathic distinctiveness and to identify steps to more clearly define and advance that distinctiveness, particularly in professional self-regulation, a representative group of osteopathic medical students, residents, physicians, and members of the licensing, GME, and undergraduate medical education (UME) communities convened the 2019 United States Osteopathic Medical Regulatory Summit in February 2019. Key features of osteopathic distinctiveness were discussed. Growth in the profession; changes in health care delivery, technology, and demographics within the profession and patient communities; and associated challenges and opportunities for osteopathic medical practice and patients were considered.
Osteopathic medicine is a distinctive practice that brings unique, added value to patients, the public, and the health care community at large. A universal definition and common understanding of that distinctiveness is lacking. Efforts to unify messaging that defines osteopathic distinctiveness, to align the distinctive elements of osteopathic medical education and professional self-regulation across a continuum, and to advance research on care and educational program outcomes are critical to the future of the osteopathic medical profession.
(1) Convene a task force of groups represented at the Summit to develop a succinct and consistent message defining osteopathic distinctiveness. (2) Demonstrate uniqueness of the profession through research demonstrating efficacy of care and patient outcomes, adding to the public good. (3) Harmonize GME and UME by beginning to align entrustable professional activities with UME milestones. (4) Convene representatives from osteopathic specialty colleges and certification boards to define curricular elements across GME, certification, and osteopathic continuous certification. (5) Build on the Project in Osteopathic Medical Education and Empathy study.
Estrogenic chemicals are major contaminants of surface waters and can threaten the sustainability of natural fish populations. Characterization of the global molecular mechanisms of toxicity of ...environmental contaminants has been conducted primarily in model species rather than species with limited existing transcriptomic or genomic sequence information. We aimed to investigate the global mechanisms of toxicity of an endocrine disrupting chemical of environmental concern 17beta-estradiol (E2) using high-throughput RNA sequencing (RNA-Seq) in an environmentally relevant species, brown trout (Salmo trutta). We exposed mature males to measured concentrations of 1.94, 18.06, and 34.38 ng E2/l for 4 days and sequenced three individual liver samples per treatment using an Illumina HiSeq 2500 platform. Exposure to 34.4 ng E2/L resulted in 2,113 differentially regulated transcripts (FDR < 0.05). Functional analysis revealed upregulation of processes associated with vitellogenesis, including lipid metabolism, cellular proliferation, and ribosome biogenesis, together with a downregulation of carbohydrate metabolism. Using real-time quantitative PCR, we validated the expression of eight target genes and identified significant differences in the regulation of several known estrogen-responsive transcripts in fish exposed to the lower treatment concentrations (including esr1 and zp2.5). We successfully used RNA-Seq to identify highly conserved responses to estrogen and also identified some estrogen-responsive transcripts that have been less well characterized, including nots and tgm2l. These results demonstrate the potential application of RNA-Seq as a valuable tool for assessing mechanistic effects of pollutants in ecologically relevant species for which little genomic information is available.
Book reviews and notes Johnson, Nick; Tribe, Diana M. R.; Giles, M. ...
The Law Teacher,
19/1/1/, Letnik:
19, Številka:
3
Book Review
Recenzirano
SWEET & MAXWELL'S LAW FILES. General Editor, PHILLIP H. KENNY. File 1 Land Law: Cohabiting Owners (1984, £2.95).
File 2 Trusts: The Fitzkenton Estate (1984, £2.95).
File 3 Tort: From Accident to ...Liability (1984, £2.95).
File 4 Land Law: Neighbours in Law (1985, £2.95).
File 5 Trusts: Trustees of the Fitzkenton Estate (1985, £2.95).
File 6 Tort: Liability of an Industrialist (1985, £2.95).
File 7 Contract: Striking a Bargain (1985, £2.95). (The Files are available in packs of ten at £29.50 per pack).
THE MODERN ENGLISH LEGAL SYSTEM. By P. F. SMITH and S. H. BAILEY. Sweet & Maxwell. 1984. xxxix and 780 pp. (inc. index). £16.00 (paperback); £30.00 (hardback).
THE CIVIL COURT IN ACTION. Second edition. By DAVID BARNARD. Butterworths. 1985. xv and 350 pp. (inc. index). £16 (hardback); £11.95 (paperback).
SUCCESS WITHOUT TEARS (SWOT), SERIES published by Financial Training Publications Ltd., 1985, paperback.
COMPANY LAW. By ALLAN BLAKE and HELEN J. BOND. 186 pp. £7.50.
CONSTITUTIONAL AND ADMINISTRATIVE LAW. By ROBERT G. LEE. 189 pp. £5.95.
LAW OF EVIDENCE. By C. J. CARR and S. J. BEAUMONT. 200 pp. £7.50.
LAW OF TORTS. By PETER CLARK and GRAHAM STEPHENSON. 165 pp. £6.95.
THE STATE, THE LAW, AND THE FAMILY-CRITICAL PERSPECTIVES. Edited by MICHAEL D. A. FREEMAN. Tavistock Publications Sweet & Maxwell, xi and 318 pp. (inc. index). £7.95.
LEGAL FOUNDATIONS OF THE WELFARE STATE. By ROSS CRANSTON. Weidenfeld and Nicolson. xxxiv and 453 pp. (inc. index). £12.95.
POLITICAL TRIALS IN BRITAIN. By PETER HAIN. Penguin. 320 pp. £3.50.
THE POLITICS OF THE JUDICIARY. Third edition. By J. A. G. GRIFFITH. Fontana. 250 pp. £3.50.
MORE ROUGH JUSTICE. By PETER HILL, MARTIN YOUNG and TOM
SARGANT. Penguin. 251 pp. £2.50.
AN INTRODUCTION TO THE LAW OF OBLIGATIONS. By A. M. TETTENBORN. Butterworths. 1984. 238 pp. (inc. index). £10.95 (soft cover); £16.50 (hard cover).
1. 1983J 1 A.C. 520. See particularly A. S. Burrows, "Contract, Tort and Restitution-A Satisfactory Division or Not?" 99 L.Q.R. 217; Jon Holgoak, "Tort and Contract After Junior Books", 99 L.Q.R. 591.
2. However the writer does discuss alternative systems of compensation at the end of Chapter 7.
3. "If any general theme runs through the law of obligations, as that of 'wealth' permeates the law of property, it can only be the very general (and rather inconsequential) one that it provides the fabric of legal control without which social life would be impossible".
LAND LAW. Third edition. By PATRICK J. DALTON. Pitman. 1983. xliii & 377 pp. £9.95).
SEARCHES AND ENQUIRIES: A CONVEYANCER'S GUIDE. By FRANCES SILVERMAN. Butterworths. 1985. xxii & 442 pp. £22.50 (paperback).
EVANS: THE LAW OF LANDLORD AND TENANT. Second edition. By P. F. SMITH. Butterworths. 1985. xlvii & 505 pp. £25.00 (hardback); £14.95 (paperback).
SENTENCING-THEORY, LAW AND PRACTICE. By NIGEL WALKER. Butterworths. 510 pp. £18.95 (paperback); £27.00 (hard cover). A PRACTICAL APPROACH TO SENTENCING. By CHRISTOPHER J. EMMINS. Financial Training Ltd. 350 pp. £12.95 (paperback); £18.00 (hard cover).
VICTIMS IN THE CRIMINAL JUSTICE SYSTEM. By JOANNA SHAPLAND, JON WILLMORE and PETER DUFF. Gower: Cambridge Studies in Criminology. 1985. 203 pp. (inc. references & index). £8.95 (limp).
CONSUMERS AND THE LAW. Second edition. By ROSS CRANSTON. Weidenfeld & Nicolson. 1984. xli & 503 pp. (inc. index). £10.95.
A PRACTICAL GUIDE TO PACKAGE HOLIDAY LAW AND CONTRACTS. By J. NELSON-JONES and P. STEWART. Fourmat Publishing. 1985. xvii and 219 pp. (inc. index). £12.95.
WORDPROCESSING: A WRITER'S GUIDE. By EDMOND McGOVERN. Exeter Globefield Press. 1985. 32 pp. £1.90.
AN INTRODUCTION TO ADMINISTRATIVE LAW. By NEIL HAWKE. ESC Publishing Ltd. 1984. xxix and 255 pp. (inc. index). £17.20 (hardback); £9.95 (paperback).
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