Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay

Copyright @ 2001 Environmental Health PerspectivesWe used a recombinant yeast estrogen assay to assess the activity of 73 phenolic additives that are used as sunscreens, preservatives, disinfectants, antioxidants, flavorings, or for perfumery. Thirty-two of these compounds displayed activity: 22 with potencies relative to 17 beta -estradiol, ranging from 1/3,000 to -estradiol. Forty-one compounds were inactive. The major criteria for activity appear to be the presence of an unhindered phenolic OH group in a para position and a molecular weight of 140-250 Da.This work was supported in part under contract with the U.K. Department of Trade and Industry as part of the Government Chemist Programme

Re-evaluation of the first synthetic estrogen, 1-keto-1,2,3,4-tetrahydrophenanthrene, and bisphenol A, using both the ovariectomised rat model used in 1933 and additional assays

1-Keto-1,2,3,4-tetrahydrophenanthrene (THP-1) was reported by Cook et al in 1933 as the first synthetic estrogen. Estrogenic activity was assessed by the induction of vaginal cornification in ovariectomised rats. The corresponding 4-isomer (THP-4) was shown to be inactive. Both chemicals have been re-synthesised and assessed for hormonal activity. Each chemical bound weakly and to the same extent to isolated estrogen receptors, but only at high concentrations. However, they each lacked estrogenic or anti-estrogenic activity when evaluated in vitro using a yeast hER assay, and both failed to induce vaginal cornification or uterotrophic effects in ovariectomised rats. THP-1, and to a lesser extent THP-4, were shown to possess weak androgenic and anti-androgenic activity in vitro when evaluated using an hAR yeast assay. Estrogenic activity for bisphenol A (BPA) was subsequently demonstrated by Dodds and Lawson (1936) using the same ovariectomised rat protocol, and this activity has been confirmed and supplemented by positive uterotrophic effects for BPA in the same bioassays. The present results illustrate the complexity of deriving conclusions regarding the hormonal activities of chemicals. First, some activities observed in isolated hormonal receptor binding assays may not be expressed in functional hormonal assays. This indicates the need for functional hormonal assays in any screening programme. Second, that activities observed for a chemical in one hormonal assay may not be reflected in related hormonal assays. This indicates the need to define assay protocols with some precision when incorporating them into screening batteries. Finally, that some literature reports of hormonal activity for chemicals may not be capable of independent confirmation under apparently identical conditions of test. This illustrates the need to use lists of hormonally active chemicals with car

The rodent uterotrophic assay: Critical protocol features, studies with nonyl phenols, and comparison with a yeast estrogenicity assay

The major protocol features of the immature rat uterotrophic assay have been evaluated using a range of reference chemicals. The protocol variables considered include the selection of the test species and route of chemical administration, the age of the test animals, the maintenance diet used, and the specificity of the assay for estrogens. It is concluded that three daily oral administrations of test chemicals to 21- to 22-day-old rats, followed by determination of absolute uterus weights on the fourth day, provide a sensitive and toxicologically relevant in vivo estrogenicity assay. Rats are favored over mice for reasons of toxicological practice, but the choice of test species is probably not a critical protocol variable, as evidenced by the similar sensitivity of rats and mice to the uterotrophic activity of methoxychlor. Vaginal opening is shown to be a useful, but nondefinitive, adjunct to the uterotrophic assay. The ability of test chemicals to reduce or abolish the uterotrophic response of estradiol is suggested to provide a useful extension of the uterotrophic assay for the purpose of detecting antiestrogens. The results of a series of studies on the environmental estrogen nonyl phenol (NP), and its linear isomer n -nonyl phenol, confirm that branching of the aliphatic side chain is important for activity. 17beta-Desoxyestradiol is shown to be of similar activity to estradiol in the uterotrophic assay and is suggested to represent the "parent" estrogen of NP. Benzoylation of NP and 17-desoxyestradiol did not affect their uterotrophic activity, in contrast to the enhancing effect of benzoylation on estradiol. Selected chemicals shown to be active in the immature rat uterotrophic assay were also evaluated in an in vitro yeast human estrogen receptor transactivation assay. Most of the chemicals gave similar qualitative responses to those seen in the uterotrophic assay, and the detection of the estrogen methoxychlor by the yeast assay evidenced a degree of intrinsic metabolic competence. However, the assay had a reduced ability (compared to rodents) to hydrolyze the benzoate ester of estradiol, and the estrogenic benzoate derivative of NP was not active in the yeast assay. These last results indicate that current metabolic deficiencies of in vitro estrogenicity assays will limit the value of negative data for the immediate future. The results described illustrate the intrinsic complexity of evaluating chemicals for estrogenic activities and confirm the need for rigorous attention to experimental design and criteria for assessing estrogenic activity

Reciprocal relationships in collective flights of homing pigeons

Collective motion of bird flocks can be explained via the hypothesis of many wrongs, and/or, a structured leadership mechanism. In pigeons, previous studies have shown that there is a well-defined hierarchical structure and certain specific individuals occupy more dominant positions --- suggesting that leadership by the few individuals drives the behavior of the collective. Conversely, by analyzing the same data-sets, we uncover a more egalitarian mechanism. We show that both reciprocal relationships and a stratified hierarchical leadership are important and necessary in the collective movements of pigeon flocks. Rather than birds adopting either exclusive averaging or leadership strategies, our experimental results show that it is an integrated combination of both compromise and leadership which drives the group's movement decisions.Comment: 7 pages, 5 figure

The consequences of feminization in breeding groups of wild fish

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.BACKGROUND: The feminization of nature by endocrine-disrupting chemicals (EDCs) is a key environmental issue affecting both terrestrial and aquatic wildlife. A crucial and as yet unanswered question is whether EDCs have adverse impacts on the sustainability of wildlife populations. There is widespread concern that intersex fish are reproductively compromised, with potential population-level consequences. However, to date, only in vitro sperm quality data are available in support of this hypothesis. OBJECTIVE: The aim of this study was to examine whether wild endocrine-disrupted fish can compete successfully in a realistic breeding scenario. METHODS: In two competitive breeding experiments using wild roach (Rutilus rutilus), we used DNA microsatellites to assign parentage and thus determine reproductive success of the adults. RESULTS: In both studies, the majority of intersex fish were able to breed, albeit with varying degrees of success. In the first study, where most intersex fish were only mildly feminized, body length was the only factor correlated with reproductive success. In the second study, which included a higher number of more severely intersex fish, reproductive performance was negatively correlated with severity of intersex. The intersex condition reduced reproductive performance by up to 76% for the most feminized individuals in this study, demonstrating a significant adverse effect of intersex on reproductive performance. CONCLUSION: Feminization of male fish is likely to be an important determinant of reproductive performance in rivers where there is a high prevalence of moderately to severely feminized males.Funding for this work was derived through the Endocrine Disruption in Catchments project, which was supported by the U.K. Department for Environment Food and Rural Affairs and the U.K. Environment Agency

Continuous theory of active matter systems with metric-free interactions

We derive a hydrodynamic description of metric-free active matter: starting from self-propelled particles aligning with neighbors defined by "topological" rules, not metric zones, -a situation advocated recently to be relevant for bird flocks, fish schools, and crowds- we use a kinetic approach to obtain well-controlled nonlinear field equations. We show that the density-independent collision rate per particle characteristic of topological interactions suppresses the linear instability of the homogeneous ordered phase and the nonlinear density segregation generically present near threshold in metric models, in agreement with microscopic simulations.Comment: Submitted to Physical Review Letter

Configuration development study of the X-24C hypersonic research airplane

Bottom line results were made of a three-phase study to determine the feasibility of designing, building, and operating, and maintaining an air-launched high performance aircraft capable of cruising at speeds up to Mach 8 for short durations. The results show that Lockalloy heat-sink structure affords the capability for a 'work-horse' vehicle which can serve as an excellent platform for this research. It was further concluded that the performance of a blended wing body configuration surpassed that of a lifting body design for typical X-24C missions. The cost of a two vehicle program, less engines, B-52 modification and contractor support after delivery, can be kept within $70M (in Jan. 1976 dollars)

On the Necessary Memory to Compute the Plurality in Multi-Agent Systems

We consider the Relative-Majority Problem (also known as Plurality), in which, given a multi-agent system where each agent is initially provided an input value out of a set of $k$ possible ones, each agent is required to eventually compute the input value with the highest frequency in the initial configuration. We consider the problem in the general Population Protocols model in which, given an underlying undirected connected graph whose nodes represent the agents, edges are selected by a globally fair scheduler. The state complexity that is required for solving the Plurality Problem (i.e., the minimum number of memory states that each agent needs to have in order to solve the problem), has been a long-standing open problem. The best protocol so far for the general multi-valued case requires polynomial memory: Salehkaleybar et al. (2015) devised a protocol that solves the problem by employing $O(k 2^k)$ states per agent, and they conjectured their upper bound to be optimal. On the other hand, under the strong assumption that agents initially agree on a total ordering of the initial input values, Gasieniec et al. (2017), provided an elegant logarithmic-memory plurality protocol. In this work, we refute Salehkaleybar et al.'s conjecture, by providing a plurality protocol which employs $O(k^{11})$ states per agent. Central to our result is an ordering protocol which allows to leverage on the plurality protocol by Gasieniec et al., of independent interest. We also provide a $\Omega(k^2)$-state lower bound on the necessary memory to solve the problem, proving that the Plurality Problem cannot be solved within the mere memory necessary to encode the output.Comment: 14 pages, accepted at CIAC 201

The dynamics of audience applause

The study of social identity and crowd psychology looks at how and why individual people change their behaviour in response to others. Within a group, a new behaviour can emerge first in a few individuals before it spreads rapidly to all other members. A number of mathematical models have been hypothesized to describe these social contagion phenomena, but these models remain largely untested against empirical data. We used Bayesian model selection to test between various hypotheses about the spread of a simple social behaviour, applause after an academic presentation. Individuals' probability of starting clapping increased in proportion to the number of other audience members already ‘infected’ by this social contagion, regardless of their spatial proximity. The cessation of applause is similarly socially mediated, but is to a lesser degree controlled by the reluctance of individuals to clap too many times. We also found consistent differences between individuals in their willingness to start and stop clapping. The social contagion model arising from our analysis predicts that the time the audience spends clapping can vary considerably, even in the absence of any differences in the quality of the presentations they have heard

How can the nanostructure affect the charge transport in PLED?

In polymer light emitting diodes (PLEDs) each semiconducting polymer chain consists of a large number of conjugated segments linked by kinks or twists and each one of them behaves like a separated straight strand. The length and orientation of the conjugated strands relative to the electrodes surface depend on the deposition conditions used. Atomistic results have shown that the molecular properties of the conjugated strands depend on their length, which can affect the electronic processes involved in PLEDs. The aim of this work is to study the influence of the average conjugation length within the polymer layer on charge injection, trapping and recombination in PLEDs for all polymer strand orientations relative to the electrodes surface obtained experimentally by different techniques. For that purpose we use a mesoscopic model that considers the morphology and the molecular properties of the polymer. Our results show that by increasing the average conjugation length of the active polymer layer the amount of charge injected into the device increases and the recombination probability occurs preferentially in segments longer than the average conjugation length, both effects having implications on the performance of polymer LEDs.Fundação para a Ciência e a Tecnologia (FCT) – Programa Operacional “Ciência , Tecnologia, Inovação” – POCTI/CTM/41574/2001, CONC-REEQ/443/EEI/2005 e SFRH/BD/22143/2005European Community Fund FEDE