Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment

A rapidly increasing number of chemicals, or their degradation products, are being recognized as possessing estrogenic activity, albeit usually weak. We have found that effluent from sewage treatment works contains a chemical, or mixture of chemicals, that induces vitellogenin synthesis in male fish maintained in the effluent, thus indicating that the effluent is estrogenic. The effect was extremely pronounced and occurred at all sewage treatment works tested. The nature of the chemical or chemicals causing the effect is presently not known. However, we have tested a number of chemicals known to be estrogenic to mammals and have shown that they are also estrogenic to fish; that is, no species specificity was apparent. Many of these weakly estrogenic chemicals are known to be present in effluents. Further, a mixture of different estrogenic chemicals was considerably more potent than each of the chemicals when tested individually, suggesting that enhanced effects could occur when fish are exposed simultaneously to various estrogenic chemicals (as is likely to occur in rivers receiving effluent). Subsequent work should determine whether exposure to these chemicals at the concentrations present in the environment leads to any deleterious physiological effects

Non-Abelian discrete gauge symmetries in 4d string models

We study the realization of non-Abelian discrete gauge symmetries in 4d field theory and string theory compactifications. The underlying structure generalizes the Abelian case, and follows from the interplay between gaugings of non-Abelian isometries of the scalar manifold and field identifications making axion-like fields periodic. We present several classes of string constructions realizing non-Abelian discrete gauge symmetries. In particular, compactifications with torsion homology classes, where non-Abelianity arises microscopically from the Hanany-Witten effect, or compactifications with non-Abelian discrete isometry groups, like twisted tori. We finally focus on the more interesting case of magnetized branes in toroidal compactifications and quotients thereof (and their heterotic and intersecting duals), in which the non-Abelian discrete gauge symmetries imply powerful selection rules for Yukawa couplings of charged matter fields. In particular, in MSSM-like models they correspond to discrete flavour symmetries constraining the quark and lepton mass matrices, as we show in specific examples.Comment: 58 pages; minor typos corrected and references adde

Required duration of mass ivermectin treatment for onchocerciasis elimination in Africa: a comparative modelling analysis.

BACKGROUND: The World Health Organization (WHO) has set ambitious targets for the elimination of onchocerciasis by 2020–2025 through mass ivermectin treatment. Two different mathematical models have assessed the feasibility of reaching this goal for different settings and treatment scenarios, namely the individual-based microsimulation model ONCHOSIM and the population-based deterministic model EPIONCHO. In this study, we harmonize some crucial assumptions and compare model predictions on common outputs. METHODS: Using a range of initial endemicity levels and treatment scenarios, we compared the models with respect to the following outcomes: 1) model-predicted trends in microfilarial (mf) prevalence and mean mf intensity during 25 years of (annual or biannual) mass ivermectin treatment; 2) treatment duration needed to bring mf prevalence below a provisional operational threshold for treatment interruption (pOTTIS, i.e. 1.4 %), and 3) treatment duration needed to drive the parasite population to local elimination, even in the absence of further interventions. Local elimination was judged by stochastic fade-out in ONCHOSIM and by reaching transmission breakpoints in EPIONCHO. RESULTS: ONCHOSIM and EPIONCHO both predicted that in mesoendemic areas the pOTTIS can be reached with annual treatment, but that this strategy may be insufficient in very highly hyperendemic areas or would require prolonged continuation of treatment. For the lower endemicity levels explored, ONCHOSIM predicted that the time needed to reach the pOTTIS is longer than that needed to drive the parasite population to elimination, whereas for the higher endemicity levels the opposite was true. In EPIONCHO, the pOTTIS was reached consistently sooner than the breakpoint. CONCLUSIONS: The operational thresholds proposed by APOC may have to be adjusted to adequately reflect differences in pre-control endemicities. Further comparative modelling work will be conducted to better understand the main causes of differences in model-predicted trends. This is a pre-requisite for guiding elimination programmes in Africa and refining operational criteria for stopping mass treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-1159-9) contains supplementary material, which is available to authorized users

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders.

Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability

Methylphenidate Treatment in Children with Borderline IQ and Mental Retardation: Analysis of Three Aggregated Studies

Objective: To determine response of low-IQ children with attention deficit hyperactivity disorder (ADHD) symptoms to methylphenidate (MPH). Methods: An aggregated analysis was conducted in 90 children with low IQ who received the same dose regimen of MPH in three independent, placebo-controlled studies. Active drug and placebo were given from 2 to 4 weeks each. Outcome measures included teacher and parent ratings on standardized behavior scales (mean n = 84), performance on computer-controlled cognitive-motor tests (n = 62), and measures of cardiovascular response (n = 85). Results: Both teachers and parents rated the children consistently as being improved on subscales assessing attention, overactivity, and conduct problems. Some 44% of the subjects showed at least a 30% reduction compared with placebo on teacher ratings. MPH improved accuracy on several cognitive tests, response speed was increased on some, and seat activity declined for one of three tests; heart rate was mildly increased (3.9 beats/minute) with MPH. Analyses of IQ and mental age as moderator variables suggested that lower functional level (especially lower IQ) may be associated with a less favorable response to MPH. Conclusions: Children with low IQ and ADHD clearly respond to MPH, but their rate of beneficial response appears to be well under that of normal-IQ children and more varied. Different attentional mechanisms may moderate response to psychostimulants

Measured estimates of semi-natural terrestrial NPP in Great Britain: comparison with modelled values, and dependence on atmospheric nitrogen deposition

Plant growth in nitrogen (N)-limited, unfertilised terrestrial ecosystems should respond to additional N inputs from atmospheric deposition (Ndep). We investigated this for sites in Great Britain (GB) by compiling 796 estimates of net primary productivity (NPP) from measured biomass production over the period 1932-2014, although the great majority were for 1995 onwards. The sites were largely vegetated with shrubs, grass and bracken, and had a wide range of Ndep (0.5 – 3.3. gN m-2 a-1 in 2000). The measured NPP estimates were compared with calculated values from the biogeochemical ecosystem model N14CP, which predicts that NPP depends strongly upon Ndep. The measured and modelled average total NPP values (gC m-2 a-1) from all data were 387 (standard deviation, SD = 193) and 377 (SD = 72) respectively. Measured and modelled averages for vegetation classes followed the sequence: broadleaved trees ~ needle-leaved trees > herbs (rough grassland + bracken) ~ shrubs. After averaging measured values for sites in individual model grid cells (5 km x 5 km) with 10 or more replicates, the measured and modelled NPP values were correlated (n=26, r2=0.22, p=0.011), with a slope close to unity. Significant linear relationships were found between measured ln NPP and cumulative Ndep for both herbs (n=298, p=0.021) and shrubs (n=473, p=0.006), with slopes comparable to those predicted with the model. The results suggest that semi-natural NPP in GB depends positively upon Ndep, in a manner that agrees quantitatively with N14CP predictions. Calculations with the model, using modelled temporal variation in Ndep, indicate that fertilisation by Ndep caused average increases in semi-natural NPP over the period 1800 to 2010 of 30% for shrubs, 71% for herbs, and 91% for broadleaved trees. Combined with previous published results for forests, our findings suggest a general and widespread vegetation response to fertilisation by Ndep

Topical Hpmc/s-nitrosoglutathione Solution Decreases Inflammation And Bone Resorption In Experimental Periodontal Disease In Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor, which exerts antioxidant, anti-inflammatory, and microbicidal actions. Intragingival application of GSNO was already shown to decrease alveolar bone loss, inflammation and oxidative stress in an experimental periodontal disease (EPD) model. In the present study, we evaluated the potential therapeutic effect of topical applications of hydroxypropylmethylcellulose (HPMC)/GSNO solutions on EPD in Wistar rats. EPD was induced by placing a sterilized nylon (3.0) thread ligature around the cervix of the second left upper molar of the animals, which received topical applications of a HPMC solutions containing GSNO 2 or 10 mM or vehicle (HPMC solution), 1 h prior to the placement of the ligature and then twice daily until sacrifice on day 11. Treatment with HPMC/ GSNO 10 mM solution significantly reduced alveolar bone loss, oxidative stress and TNF-alpha e IL-1 beta levels in the surrounding gingival tissue, and led to a decreased transcription of RANK and TNF-alpha genes and elevated bone alkaline phosphatase, compared to the HPMC group. In conclusion, topical application of HPMC/GSNO solution is a potential treatment to reduce inflammation and bone loss in periodontal disease.11National Council for Scientific and Technological Development - CNPq [478380/2011-9, 309390/2011-7]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Preserved neural dynamics across animals performing similar behaviour

Animals of the same species exhibit similar behaviours that are advantageously adapted to their body and environment. These behaviours are shaped at the species level by selection pressures over evolutionary timescales. Yet, it remains unclear how these common behavioural adaptations emerge from the idiosyncratic neural circuitry of each individual. The overall organization of neural circuits is preserved across individuals1 because of their common evolutionarily specified developmental programme2-4. Such organization at the circuit level may constrain neural activity5-8, leading to low-dimensional latent dynamics across the neural population9-11. Accordingly, here we suggested that the shared circuit-level constraints within a species would lead to suitably preserved latent dynamics across individuals. We analysed recordings of neural populations from monkey and mouse motor cortex to demonstrate that neural dynamics in individuals from the same species are surprisingly preserved when they perform similar behaviour. Neural population dynamics were also preserved when animals consciously planned future movements without overt behaviour12 and enabled the decoding of planned and ongoing movement across different individuals. Furthermore, we found that preserved neural dynamics extend beyond cortical regions to the dorsal striatum, an evolutionarily older structure13,14. Finally, we used neural network models to demonstrate that behavioural similarity is necessary but not sufficient for this preservation. We posit that these emergent dynamics result from evolutionary constraints on brain development and thus reflect fundamental properties of the neural basis of behaviour

Prediction of salt balances in irrigated soils along the lower Vaal River, South Africa

In arid and semi-arid regions irrigation tends to degrade soil and water quality through salt accumulation with devastating effects on some crops. This is, according to irrigators, also the case along the lower Vaal River in South Africa. Properly calibrated and tested salinity models could assist the agricultural community in improving salinity management under irrigation.This paper reports on, firstly, salt balances of soils in this region being irrigated for different time periods, and secondly, salt content changes that can be expected as a consequence of future irrigation. Two empirical models, viz. a general and specific salt-balance model were used together with existing water- and soil-quality data to generate such information. The soils selected for this study had been irrigated for periods of between 17 to 53 years. Over these periods addition of salts as a result of farming practices varied between 79 and 280 t·ha-1, with irrigation water being the major contributor. Between 78% to 87% of the salts added to the soils had been leached from the root zone Despite these large amounts of salts that have been removed, certain irrigation practices have promoted the build-up of salts in some of the soils. The freely drained sandy soils irrigated by centre pivot are of particular interest. Poor management of this system can reduce crop yields. On account of inadequate leaching salts are building up to levels that impair the potential evapotranspiration level of maize. Predictions also show that irrigation should rather be withdrawn from soils with poor internal drainage properties, such as the Arcadia soil at Spitskop. In contrast, flood irrigation on certain duplex soils, such as the Valsrivier at Vaalharts, with relatively good internal drainage properties, can improve their quality.Keywords: drained soils, root zone, soil quality, undrained soils, water qualit