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Predicting the joint algal toxicity of multi-component s-triazine mixtures at low-effect concentrations of individual toxicants.

Herbicidal s-triazines are widespread contaminants of surface waters. They are highly toxic to algae and other primary producers in aquatic systems. This results from their specific interference with photosynthetic electron transport. Risk assessment for aquatic biota has to consider situations of simultaneous exposure to various of these toxicants. In tests with freshwater algae we predicted and determined the toxicity of multiple mixtures of 18 different s-triazines. The toxicity parameter was the inhibition of reproduction of Scenedesmus vacuolatus. Concentration-response analyses were performed for single toxicants and for mixtures containing all 18 s-triazines in two different concentration ratios. Experiments were designed to allow a valid statistical description of the entire concentration-response relationships, including the low concentration range down to EC1. Observed effects and effect concentrations of mixtures were compared to predictions of mixture toxicity. Predictions were calculated from the concentration-response functions of individual s-triazines by applying the concepts of concentration addition and independent action (response addition) alternatively. Predictions based on independent action tend to underestimate the overall toxicity of s-triazine mixtures. In contrast, the concept of concentration addition provides highly accurate predictions of s-triazine mixture toxicity, irrespective of the effect level under consideration and the concentration ratio of the mixture components. This also holds true when the mixture components are present in concentrations below their individual NOEC values. Concentrations statistically estimated to elicit non-significant effects of only 1% still contribute to the overall toxicity. When present in a multi-component mixture they can co-operate to give a severe joint effect. Applicability of the findings obtained with s-triazines to mixtures of other contaminants in aquatic systems and consequences for risk assessment procedures are discussed.

Chlorophyta↗

Valproate-associated reproductive and metabolic abnormalities: are epileptic women at greater risk than bipolar women?

OBJECTIVE: Evidence indicates that valproate (VPA) may have an adverse impact on reproductive endocrine and metabolic functions in women with epilepsy. This study explores whether the association of VPA with reproductive endocrine abnormalities is applicable to women with bipolar disorder (BD) or is unique to women with epilepsy. METHODS: Thirty female patients aged 18-40 years with a DSM-IV diagnosis of BD (15 on lithium monotherapy and 15 on VPA monotherapy or VPA in combination with lithium therapy) and 15 with idiopathic generalized epilepsy (IGE) on VPA monotherapy were evaluated for reproductive endocrine functioning and metabolic parameters. RESULTS: The menarche age, mean length of menstrual cycle and mean length of menses were not significantly different between groups. None of the bipolar patients on lithium, three (20%) of the bipolar patients on VPA and seven (47%) of the epileptic patients on VPA reported menstrual disturbances. Hirsutism scores of the epilepsy group were significantly higher than those bipolar women, regardless of treatment. Serum total testosterone levels were significantly higher in patients (both with BD and with IGE) treated with VPA than in those treated with lithium. Serum FSH levels were significantly lower and LH-to-FSH ratio was significantly higher in patients with epilepsy than in patients with BD, regardless of treatment. The weight parameters and lipid values investigated did not differ significantly between the groups. CONCLUSION: The study supports the conclusion that VPA may be associated with menstrual abnormalities and increased total testosterone levels in both bipolar and epileptic patients although women with BD did not show clinical features of hyperandrogenism (menstrual abnormalities, hirsutism and truncal obesity) as did frequently as women with epilepsy.

Adult↗

Population dynamics in echinococcosis and cysticercosis: evaluation of the biological parameters of Taenia hydatigena and T. ovis and comparison with those of Echinococcus granulosus.

An evaluation has been made of the biological and epidemiological parameters that determine the basic reproductive rates of Taenia hydatigena and T. ovis. These host-parasite systems are characterized by (i) no overcrowding in either host; (ii) no parasite-induced mortality of either host; (iii) no density-dependent constraint in the definitive host, but a strong, rapidly mobilized, short-acting immunity in the intermediate host and (iv) egg production which, in the natural environment, is high enough to prevent superinfection. It is considered that tapeworms with these characteristics are more stable to fluctuations in environmental conditions and to control measures such as dog dosing, than species which have a low egg production and infectivity such as Echinococcus granulosus. Reciprocal immunity exists between T. hydatigena and T. ovis in sheep. Exposure to T. hydatigena suppresses infection by T. ovis, but not by E. granulosus. This has important epidemiological consequences where these parasites co-exist.

Animals↗

Detection of second hydration shells in ionic solutions by XANES: computed spectra for Ni2+ in water based on molecular dynamics.

A general procedure to compute X-ray absorption near-edge structure (XANES) spectra within multiple-scattering theory starting from molecular dynamics (MD) structural data has been developed and applied to the study of a Ni(2+) aqueous solution. This method allows one to perform a quantitative analysis of the XANES spectra of disordered systems using a proper description of the thermal and structural fluctuations. The XANES spectrum of Ni(2+) in aqueous solution has been calculated using the structural information obtained from the MD simulations without carrying out any minimization in the structural parameter space. A very good reproduction of the experimental data was obtained including the second-shell water molecules in the calculation, thus showing that the second hydration shell provides a detectable contribution to the XANES spectra of ionic solutions. The analysis including the first-shell cluster only permitted us to quantitatively determine the effect of disorder on the amplitude of the XANES spectra for molecular complexes. These results simultaneously confirm the reliability of the procedure and the structural results obtained from MD simulations. The combination of MD and XANES is found to be very helpful to get important new insights into the quantitative estimation of structural properties of disordered systems.

Journal Article↗

The diversity of parasites.

Parasitism is one of the most successful modes of life displayed by living organisms, as measured by how often it evolved and how many parasitic species are presently in existence. Studying the diversity of parasites is particularly relevant because sympatric diversification may be important in some parasite taxa, and because of the opportunity for independent tests of evolutionary hypotheses in the many separate lineages in which parasitism evolved. Our incomplete knowledge of existing parasite species--the result of a range of phenomena that includes inadequate sampling effort or the lumping of different cryptic species under one name--is not always a major obstacle for the study of parasite diversity. Patterns in the diversity of parasites may be associated with either host or parasite characteristics. The distribution of parasite diversity among host taxa does not simply reflect the species diversity of the host taxa themselves; life history and ecological traits of hosts appear to play important roles. These may determine the likelihood that hosts are colonized by parasite species over evolutionary time. It is not yet clear whether some host traits also favor intrahost speciation and diversification of parasites, and the formation of new parasite species. Certain features of parasites may also be associated with speciation and diversification. Only parasite body size has received much attention; the patterns observed are not greatly different from those of free-living species, with small-bodied parasite taxa being more speciose than related large-bodied taxa. Epidemiological parameters such as the basic reproductive rate of parasites, or R0, can also generate predictions regarding the distribution or evolution of parasite diversity. For instance, parasite taxa characterized by high R0 values may be more speciose than related taxa with lower values of R0; such predictions remain untested. Large-scale biogeographical patterns of diversity have only been well studied for metazoan parasites of marine fish; for these parasites, latitudinal patterns can be explained by effects of temperature on speciation rates and epidemiological variables, though other causes are possible. The emphasis for future research must shift from pattern description to the elucidation of the processes responsible for the structure and diversity of parasite faunas. A better integration of ecological and historical (or phylogenetic) approaches to the study of parasite diversity should make this objective possible.

Animals↗

Estimating the immunity coverage required to prevent epidemics in a community of households.

An estimation of the immunity coverage needed to prevent future outbreaks of an infectious disease is considered for a community of households. Data on outbreak size in a sample of households from one epidemic are used to derive maximum likelihood estimates and confidence bounds for parameters of a stochastic model for disease transmission in a community of households. These parameter estimates induce estimates and confidence bounds for the basic reproduction number and the critical immunity coverage, which are the parameters of main interest when aiming at preventing major outbreaks in the future. The case when individuals are homogeneous, apart from the size of their household, is considered in detail. The generalization to the case with variable infectivity, susceptibility and/or mixing behaviour is discussed more briefly. The methods are illustrated with an application to data on influenza in Tecumseh, Michigan.

Journal Article↗

Influence of undernutrition during gestation and suckling on development and sexual maturity in the rat.

The effects of undernourishment during gestation and suckling on rats subsequently fed ad libitum for 4 mo after weaning are explored. We measured the following: weight at birth and over a 5-mo period; sexual behavior of adult males; curiosity; basal physical activity; morphometric measures; organ weights (absolute and relative) including brain, testicles and seminal vesicles in males 5 mo of age; and the O2 uptake of some brain and glandular structures in males at 5 mo of age. Body weight of the malnourished animals was consistently lower than that of the controls. Compared to controls sexual behavior in undernourished males was significantly reduced, while curiosity test and basal physical activity were increased. The absolute weights of all organs (except the pituitary gland) were significantly lower in malnourished males at 5 mo than in controls. Compared to controls, relative weight of brain was greater and that of seminal vesicles was less in the male rats. Oxygen uptake was significantly lower in the pituitary gland and testicles of malnourished males than of controls. In view of these results, it can be concluded that malnutrition in utero and while suckling affects fundamental parameters of both development and reproductive function in the male offspring 4 mo after feeding ad libitum is begun at weaning.

Animals↗

Quantification of in vivo replicative capacity of HIV-1 in different compartments of infected cells.

Based on a mathematical model, we analyze the dynamics of CD4+ cells, actively, latently, persistently, and defectively infected cells and plasma virus after initiation of antiretroviral therapy in 14 HIV-1-infected asymptomatic patients. By simultaneous fitting of our model to clinical data of plasma HIV-1 RNA, peripheral blood mononuclear cell (PBMC)-gag RNA, proviral DNA, and CD4+ cell counts, we estimate kinetic parameters to determine the basic reproductive rate (R0) of the virus in different infected cell compartments as a measure of the replicative capacity of the virus in vivo. We find that the basic reproductive rate is larger than 1 before treatment only in actively infected cells (mean R0(act) approximately 2.46) indicating that only in this compartment the virus can maintain an ongoing infection. In latently and persistently infected cells the basic reproductive rate is considerably smaller (R0(lat) approximately 0.03 and R0(pers) approximately 0.008, respectively) indicating that these compartments contribute little to the total basic reproductive rate and cannot maintain an ongoing infection in absence of actively infected cells.

Anti-HIV Agents↗

Sequence evaluation of four pooled-tissue normalized bovine cDNA libraries and construction of a gene index for cattle.

An essential component of functional genomics studies is the sequence of DNA expressed in tissues of interest. To provide a resource of bovine-specific expressed sequence data and facilitate this powerful approach in cattle research, four normalized cDNA libraries were produced and arrayed for high-throughput sequencing. The libraries were made with RNA pooled from multiple tissues to increase efficiency of normalization and maximize the number of independent genes for which sequence data were obtained. Target tissues included those with highest likelihood to have impact on production parameters of animal health, growth, reproductive efficiency, and carcass merit. Success of normalization and inter- and intralibrary redundancy were assessed by collecting 6000-23,000 sequences from each of the libraries (68,520 total sequences deposited in GenBank). Sequence comparison and assembly of these sequences was performed in combination with 56,500 other bovine EST sequences present in the GenBank dbEST database to construct a cattle Gene Index (available from The Institute for Genomic Research at http://www.tigr.org/tdb/tgi.shtml). The 124,381 bovine ESTs present in GenBank at the time of the analysis form 16,740 assemblies that are listed and annotated on the Web site. Analysis of individual library sequence data indicates that the pooled-tissue approach was highly effective in preparing libraries for efficient deep sequencing.

Animals↗

Tracking factors modulating cytoplasmic incompatibilities in the mosquito Culex pipiens.

Wolbachia are maternally inherited endosymbiotic bacteria that infect many arthropod species and may induce cytoplasmic incompatibility (CI), resulting in abortive embryonic development. One Wolbachia host, Culex pipiens complex mosquitoes, displays high levels of variability in both CI crossing types (cytotypes) and DNA markers. We report here an analysis of 14 mosquito strains, containing 13 Wolbachia variants, and with 13 different cytotypes. Cytotypes were Wolbachia-dependent, as antibiotic treatment rendered all strains tested compatible. Cytotype distributions were independent of geographical distance between sampling sites and host subspecies, suggesting that Wolbachia does not promote a reproductive isolation depending on these parameters. Backcross analysis demonstrated a mild restoring effect of the nuclear genome, indicating that CI is mostly cytoplasmically determined for some crosses. No correlation was found between the phenotypic and genotypic variability of 16 WO prophage and transposon markers, except for the WO prophage Gp15 gene, which encodes a protein similar to a bacterial virulence factor. However, Gp15 is partially correlated with CI expression, suggesting that it could be just linked to a CI gene.

Animals↗

The genetic architecture of male colour differences between a sympatric Lake Malawi cichlid species pair.

The genetic basis of traits involved in reproductive isolation is a key parameter in models of sympatric speciation by sexual selection, a potential mechanism driving the explosive radiation of East African cichlids. Analysis of hybrid crosses between two sympatric Lake Malawi cichlid species, representing the extremes of the extant colour distribution, generated Castle-Wright estimates of four to seven loci controlling colour differences. Segregation patterns deviated from a purely additive model with a significant contribution from dominance, and possibly also epistasis. Evidence was found for a strong influence of autosomal loci. As departures from simple additive variation could effect the operation of models of sympatric speciation, dominance and epistasis should not be neglected.

Animals↗

Chronic ethanol intake may delay the onset of gossypol-induced infertility in the male rat.

Parameters were obtained from the reproductive organs of ethanol-fed, gossypol-treated Sprague Dawley rats. The experimental animals were fed either on a normal (15.17%) or low protein (8.00%) diet. Measurements included reproductive organ weights, seminal characteristics, serum concentration of testosterone and histological, stereological and histomorphometric evaluation of the testis. The testis size, length and diameter of the seminiferous tubule had the least values in the protein-malnourished, gossypol-treated rats (3.01 +/- 0.26 g, 0.56 +/- 0.03 m, 281.34 +/- 11.30 microns), in comparison to corresponding animals which had received ethanol simultaneously with gossypol (3.40 +/- 0.25, 0.71 +/- 0.06 m, 314.42 +/- 11.61 microns). As gossypol and ethanol are both associated with reduced reproductive capacity, this unexpected but interesting finding lends support to the hypothesis that either a normal dietary protein or ethanol consumption may modify the action of gossypol on body tissues, including the testis. This effect, presumably mediated through changes caused to the bioavailability of gossypol, modifies its antifertility activity. The present observation further highlights the need to consider the concurrent administration of other drugs, such as alcohol, and the nutritional status in the evaluation of gossypol for various potential uses.

Alcoholism↗

Efficacy and effects of short- and medium-term contraception in the common marmoset (Callithrix jacchus) using melengestrol acetate implants.

This study examines the effect of melengestrol acetate (MGA) implants on reproductive function and various biochemical parameters, ovarian activity, and uterine morphology in ten female common marmosets implanted for either 6-8 or 19-21 months. Measures of body weight, concentrations of urinary glucose and blood liver enzymes were taken. Ovarian activity was assessed by analysis of urinary progestin levels and ultrasound examinations of the ovaries. Ultrasonography was also used to evaluate uterine morphology. MGA was highly effective in preventing pregnancies in the study animals. No changes in biochemical parameters were found; however, seven females developed a substantial weight gain during the study. Follicular development was not suppressed, as indicated by the presence of antral follicles, luteinized structures, and elevated urinary progestin levels. The uteri of the MGA-treated subjects were moderately enlarged with a thickened endometrium that showed a marked change in structural appearance indicative of hypertrophy and decidualization. After implant removal these changes quickly disappeared and all females ovulated within 3 weeks and conceived within 4 months post-treatment. MGA appears to be an acceptable contraceptive in the marmoset, although non-steroidal methods should be evaluated as possible potential alternatives.

Animals↗

Changing paradigms in insect social evolution: insights from halictine and allodapine bees.

Until the 1980s theories of social insect evolution drew strongly on halictine and allodapine bees. However, that early work suffered from a lack of sound phylogenetic inference and detailed information on social behavior in many critical taxa. Recent studies have changed our understanding of these bee groups in profound ways. It has become apparent that forms of social organization, caste determination, and sex allocation are more labile and complex than previously thought, although the terminologies for describing them are still inadequate. Furthermore, the unexpected complexity means that many key parameters in kin selection and reproductive skew models remain unquantified, and addressing this lack of information will be formidable. At the same time, phylogenetic questions have become more tractable, and DNA sequence-based studies have resolved questions that earlier studies could not resolve, radically changing our understanding of the number of origins and losses of sociality in these bees.

Animals↗

Regulatory issues of importance to developing anti-HIV therapeutics.

In the United States, before clinical trials with new drugs can proceed, an Investigational New Drug (IND) application must be submitted to the Food and Drug Administration. Applications for drugs intended for the treatment of HIV-related diseases are reviewed by the Division of Anti-Viral Drug Products (DAVDP) within the Center for Drug Evaluation and Research. IND applications must contain adequate preclinical studies to support the safety of the proposed clinical trials. Essential for demonstrating safety are animal toxicology studies in which the drug has been administered in doses, by the route(s) of administration, and over a length of time equivalent to the corresponding parameters proposed for clinical trials. Reproductive toxicology/teratology studies should be conducted early in the development of the drug. Other nonclinical toxicology studies, such as carcinogenicity bioassays, are usually conducted concurrently with clinical trials. The DAVDP has developed a Pre-IND program to assist sponsors in preparing the best preclinical research to support the development of new drugs.

Animals↗

Lepidium meyenii (Maca) increases litter size in normal adult female mice.

BACKGROUND: Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. METHODS: Adult female Balb/C mice were divided at random into three main groups: i) Reproductive indexes group, ii) Implantation sites group and iii) Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO) day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. RESULTS: Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. CONCLUSION: Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to enhance female fertility.

Animals↗

Density-dependent productivity depression in Pyrenean Bearded Vultures: implications for conservation.

The main objective of many conservation programs is to increase population size by improving a species' survival and reproduction. However, density dependence of demographic parameters may confound this approach. In this study we used a 25-year data set on Bearded Vultures (Gypaetus barbatus) in Spain to evaluate the consequences of population growth on reproductive performance. Unlike its coefficient of variation (cv), mean annual productivity decreased with increasing population size. After controlling for territorial heterogeneity, productivity also was negatively related to the distance to the nearest conspecific breeding pair and to supplementary feeding points where floaters congregate. These results suggest that vulture populations are regulated as posited by the site-dependency hypothesis: as the population increases, average productivity decreases because progressively poorer territories are used. The combined effects of the shrinkage of territories and the presence of floaters around supplementary feeding points seem to be the main causes of productivity decline and are therefore the main determinants of territory quality. This has conservation implications, especially concerning the role of supplementary feeding points. Supplementary feeding should be reviewed given that its usefulness in reducing preadult mortality has not yet been proved and its effect on productivity, as our results suggest, is negative.

Animals↗

Influence of dimethoate on acetylcholinesterase activity and locomotor function in terrestrial isopods.

Locomotor behavior in terrestrial organisms is crucial for burrowing, avoiding predators, food seeking, migration, and reproduction; therefore, it is a parameter with ecological relevance. Acetylcholinesterase (AChE) is a nervous system enzyme inhibited by several compounds and widely used as an exposure biomarker in several organisms. Moreover, changes in energy reserves also may indicate an exposure to a stress situation. The aim of this study is to link biomarkers of different levels of biological organization in isopods exposed to increasing doses of dimethoate in semifield conditions. Locomotor parameters, AChE activity, and energy reserves (lipid, glycogen, and protein contents) were evaluated in the isopod Porcellio dilatatus after 48-h and 10-d exposure to dimethoate-contaminated soil. Results showed a clear impairment of both locomotor and AChE activity during the entire study, although effects were more pronounced after 48 h. Most locomotor parameters and AChE activity showed a clear dose-response relationship. By contrast, no clear trend was observed on energetic components. A positive and significant relationship was found between AChE activity and those locomotor parameters indicating activity, and the opposite was observed with those locomotor parameters indicating confusion and disorientation. The results obtained in this study enhance the importance of linking biochemical responses to parameters with ecological relevance at individual level, the value of locomotor behavior as an important marker to assess effects of toxicants, and also the usefulness and the acquisition of ecological relevance by AChE as a biomarker, by linking it with ecologically relevant behavioral parameters.

Acetylcholinesterase↗