Molecular docking: A potential tool to aid ecotoxicity testing in environmental risk assessment of pharmaceuticals

A cocktail of human pharmaceuticals pollute aquatic environments and there is considerable scientific uncertainty about the effects that this may have on aquatic organisms. Human drug target proteins can be highly conserved in non target species suggesting that similar modes of action (MoA) may occur. The aim of this work was to explore whether molecular docking offers a potential tool to predict the effects of pharmaceutical compounds on non target organisms. Three highly prescribed drugs, diclofenac, ibuprofen and levonorgestrel which regularly pollute freshwater environments were used as examples. Their primary drug targets are cyclooxygenase 2 (COX2) and progesterone receptor (PR). Molecular docking experiments were performed using these drugs and their primary drug target homologues for Danio rerio, Salmo salar, Oncorhynchus mykiss, Xenopus tropicalis, Xenopus laevis and Daphnia pulex. The results show that fish and frog COX2 enzymes are likely to bind diclofenac and ibuprofen in the same way as humans but that D. pulex would not. Binding will probably lead to inhibition of COX function and reduced prostaglandin production. Levonorgestrel was found to bind in the same binding pocket of the progesterone receptor in frogs and fish as the human form. This suggests implications for the fecundity of fish and frogs which are exposed to levonorgestrel. Chronic ecotoxicological effects of these drugs reported in the literature support these findings. Molecular docking may provide a valuable tool for ecotoxicity tests by guiding selection of test species and incorporating the MoA of drugs for relevant chronic test end points in environmental risk assessments.     

Prenatal measurement of the fetal cerebellum and cisterna cerebellomedullaris by ultrasound

The fetal cerebellum can be visualized with ultrasound throughout the second trimester. We describe a technique for measuring the transverse and anteroposterior cerebellar diameters and the measurement of the cisterna magna in the same plane between 14 and 32 weeks gestation. Nomograms for these measurements against gestational age showed good correlation, and narrow confidence limits for the transverse cerebellar diameter. The transverse cerebellar diameter was also measured directly in 79 fetuses after mid-trimester abortion and the measurements obtained were compared with the ultrasound TCD nomogram. Good correlation, was obtained between the post mortem measurements and the ultrasound TCD nomogram. Routine use of these measurements and nomograms should prove valuable in the diagnosis of congenital abnormality of the posterior fossa and may also be of use in assessing the effect of severe intrauterine growth retardation and other insults on cerebellar growth and development. The narrow confidence limits obtained with the TCD nomogram should enable it to be used with confidence in clinical practice.     

Trisomy 7 in chorionic villi: Follow-up studies of pregnancy,normal child,and placental clonal anomalies

Cytogenetic study of chorionic villi sampled because of advanced maternal age revealed, after overnight culture, an apparently non-mosaic trisomy 7. Amniocentesis showed exclusively normal mitoses, and the pregnancy continued normally. One hundred mitoses from cord blood of the normal newborn revealed a non-mosaic 46,XX complement. No cells with a proven trisomy 7 were found in cultures from either of two biopsies of the morphologically normal placenta, but the peripheral biopsy showed in multiple cultures an abnormal clone: 47,XX, + 20,-2,-21, + t(2;21)(p13;q22). To our knowledge, this is the first case of non-mosaic trisomy 7 detected on CVS which has had follow-up studies of amniotic fluid, cord blood, and term placenta.     

Paternal investment in Poecilimon veluchianus bushcrickets: beneficial effects of nuptial feeding on offspring viability

In most bushcrickets, males transfer a large spermatophore during copulation that is afterwards consumed by the female. In some species this nuptial gift enhances offspring fitness and is therefore believed to function as paternal investment. To determine whether this is the case, I examined whether a male's own offspring benefit from spermatophore consumption in the bushcricket Poecilimon veluchianus. Females that consumed a spermatophore produced offspring with increased residuals of dry weight compared to females that were prevented from feeding on the spermatophore. This beneficial effect of spermatophore consumption occurred within the first 4 days after copulation. An increased dry weight indicates higher energy reserves because offspring dry weight correlates significantly with the lifespan of starved larvae and because spermatophore consumption increased the lifespan of starved offspring. During egg-laying, females apply a liquid substance to the soil that hardens and probably serves as protection for the egg clutch. The amount of this substance correlated with the number of eggs laid but did not differ between spermatophore treatments. In P. veluchianus, females mate frequently and there is last-male sperm precedence. The spermatophore thus only constitutes paternal investment when offspring produced before female remating benefit from spermatophore consumption. The dry weight of offspring increased during the first 4 days after spermatophore consumption and thus within the natural remating interval. This shows that the spermatophore has a paternal investment function in addition to its already known sperm protection function. Received: 15 May 1998 / Accepted after revision: 11 October 1998     

Kenntnisdefizite bei Stoffeigenschaften und ihre Folgen

The data situation to chemical substances is unsatisfactory— in spite of in part considerable efforts in the last decades. One knows still very little on the subject of the dangerous characteristics of chemical substances. The consequences of this ignorance have primarily the employees to carry. They get sick due to a dealing with substances whose characteristics were not completely enlightened. But as well the enterprises have to suffer under it, after all, lose her experienced staff member and have to pay the costs about the Berufsgenossenschaften for these knowledge deficits. In the EU, the future European chemical policy is therefore discussed. The contribution explains the range of the sicknesses through dealing with substances with unknown characteristics.     

Sicherheitsdatenblätter — Eine Anleitung zum sicheren Umgang?

The European Union Guideline 2001/58/EG (safety data sheet guideline) states that the safety data sheet shall enable professional users to take the necessary measures for the protection of health and safety at the workplace as well as of the environment. According to this guideline, the employer should be in the position to determine whether hazardous chemical agents do exist at the workplace, and to assesses the risk to health and safety of workers arising from their use. Can the employer actually rely on the safety data sheet? Have the present data sheets really instructed how to safely handle and manage dangerous compounds? Are the numerously arising occupational illnesses by dangerous substances just a consequence of a careless handling? This question is also important in the discussion on REACH, the new European Chemicals Policy. This paper reveals the strengths and the weaknesses as well as the potential of manufacturer information.     

Baboon loud calls advertise male quality: acoustic features and their relation to rank,age, and exhaustion

Free-ranging adult male baboons give loud two-syllable wahoo calls during dawn choruses, interactions between groups, when chasing females, and in aggressive interactions with other males. Previous research has shown that the rate and duration of these contest wahoos are correlated with a males competitive ability: high-ranking males call more often, call at faster rates, and call for longer bouts than do low-ranking males. Here we report that acoustic features of wahoos also reveal information about male competitive ability. High-ranking males give wahoos with higher fundamental frequencies (F0) and longer hoo syllables. Within-subject analyses revealed that, as males fall in rank, the hoo syllables tend to shorten within a period of months. As males age and continue to fall in rank, F0 declines, hoo syllables shorten, and formant dispersion decreases. Independent of age and rank, within bouts of calling F0 declines and hoo syllables become shorter. Because wahoos are often given while males are running or leaping through trees, variation in these acoustic features may function as an indicator of a males stamina. The acoustic features of contest wahoos thus potentially allow listeners to assess a males competitive ability.Communicated by C. Nunn     

An actor game on implementation of environmental quality standards for nitrogen in a Swedish agricultural catchment

Despite political efforts, diffuse pollution from agriculture continues to be the single largest source of nitrogen (N) emissions into the aquatic environment in many countries and regions. This fact, and the recent enactment of a new Swedish environmental code, led to the design of a study targeted at the evaluation of new N pollution abatement strategies. An actor game was chosen as the key component of the study, with a focus on four major goals: to test the implementability of legally binding environmental quality standards for nitrate concentration in groundwater and N transport to the sea, to find sets of agriculturally feasible and cost-effective measures to decrease N loads, to investigate the possibilities for collective action through negotiated and institutionalized actor cooperation, and to investigate the role of mathematical modeling in environmental N management. Characteristics from the agriculturally dominated catchment of Genevads?n (224 km2) on the southwest coast of Sweden served as the playing field for the actor game. The most noteworthy result from the study was that it appeared to be possible to meet ambitious environmental N standards with less economically drastic measures than anticipated by most of the participants. The actor game was shown to be a good method for learning about the new Swedish environmental code and its application and for gaining deeper insight into the issues of N management. In addition, the actor game functioned as an arena for gaining a more thorough understanding of the views of different stakeholders.     

Male control of sperm transfer dynamics in a spermatophore-donating bushcricket

In many animal species, male and female interests often differ when it comes to decisions over mating and fertilization. However, it is intrinsically difficult to determine the degree to which males and females exert control over the various processes that determine the outcome of reproductive interactions, and thus to predict how such conflicts will be resolved. For example, in species where sperm are transferred to females via a spermatophore or other external sperm packaging device, it is unclear which sex determines subsequent sperm transfer dynamics to the female reproductive tract. To address this question, we used a reciprocal cross experimental design in a bushcricket species (Poecilimon veluchianus) comprising two subspecies differing in the dynamics of sperm transfer. The reciprocal crosses show that in these bushcrickets the timing of sperm transfer in inter-subspecies crosses closely resemble those typical of the subspecies of the male partner, indicating that it is the properties of the spermatophore rather than its handling by the female that determine sperm transfer dynamics. There was neither a significant female influence nor any indication of an interaction between males and females with regard to the number of sperm transferred after a set interval. Our study suggests that males rather than females appear to control the timing of the insemination process in this species.     

New expansions in old clades: population genetics and phylogeny of Gnatholepis species (Teleostei: Gobioidei) in the Pacific

Species of the reef goby genus Gnatholepis exhibit enormous geographic ranges with little evidence of population segregation detectable based on mitochondrial DNA. To determine if genetic differentiation is evident with more rapidly evolving markers, seven microsatellite loci were screened from the species Gnatholepis anjerensis and G. scapulostigma and population segregation was tested among fish from across the South Pacific. Both AMOVA and pairwise F _ST analyses showed that, in concordance with previous mitochondrial results, most genetic variance occurs within individual populations, as population differentiation is evident only over the largest distances (>3,700 km). This result is contrasted with previous studies demonstrating that despite their relatively long larval periods, some gobiid fishes exhibit population differentiation on small (<100 km) geographic scales. Coalescence analysis showed that current Pacific populations of these species originated in the Pleistocene, presumably related to sea level fluctuations associated with episodes of glaciation. However, rate analysis based on a phylogeny of Gnatholepis species indicates that the species themselves are much older, consistent with a complex history of rapid, short-term population contractions and expansions, with corresponding rapid dispersal.