Natural product hybrid and its superacid synthesized analogues: Dodoneine and its derivatives show selective inhibition of carbonic anhydrase isoforms I,III, XIII and XIV

The natural product dodoneine (a dihydropyranone phenolic compound), extracted from African mistletoe Agelanthus dodoneifolius, has been investigated as inhibitor of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. By using superacid chemistry, analogues of the lactone phenolic hybrid lead compound have been synthesized and tested as CA inhibitors. Small chemical modifications of the basic scaffold revealed strong changes in the selectivity profile against different CA isoforms. These new compounds selectively inhibited isoforms CA I (K_Is in the range of 0.13–0.76 μM), III (K_Is in the range of 5.13–10.80 μM), XIII (K_Is in the range of 0.34–0.96 μM) and XIV (K_Is in the range of 2.44–7.24 μM), and can be considered as new leads, probably acting as non-zinc-binders, similar to other phenols/lactones investigated earlier.     

Functional Characteristics of the Naked Mole Rat μ-Opioid Receptor

While humans and most animals respond to µ-opioid receptor (MOR) agonists with analgesia and decreased aggression, in the naked mole rat (NMR) opioids induce hyperalgesia and severe aggression. Single nucleotide polymorphisms in the human mu-opioid receptor gene (OPRM1) can underlie altered behavioral responses to opioids. Therefore, we hypothesized that the primary structure of the NMR MOR may differ from other species. Sequencing of the NMR oprm1 revealed strong homology to other mammals, but exposed three unique amino acids that might affect receptor-ligand interactions. The NMR and rat oprm1 sequences were cloned into mammalian expression vectors and transfected into HEK293 cells. Radioligand binding and 3''-5''-cyclic adenosine monophosphate (cAMP) enzyme immunoassays were used to compare opioid binding and opioid-mediated cAMP inhibition. At normalized opioid receptor protein levels we detected significantly lower [3H]DAMGO binding to NMR compared to rat MOR, but no significant difference in DAMGO-induced cAMP inhibition. Strong DAMGO-induced MOR internalization was detectable using radioligand binding and confocal imaging in HEK293 cells expressing rat or NMR receptor, while morphine showed weak or no effects. In summary, we found minor functional differences between rat and NMR MOR suggesting that other differences e.g. in anatomical distribution of MOR underlie the NMR''s extreme reaction to opioids.     

Infection and Co-infection with Helminths and Plasmodium among School Children in C?te d’Ivoire: Results from a National Cross-Sectional Survey

Background

Helminth infection and malaria remain major causes of ill-health in the tropics and subtropics. There are several shared risk factors (e.g., poverty), and hence, helminth infection and malaria overlap geographically and temporally. However, the extent and consequences of helminth-Plasmodium co-infection at different spatial scales are poorly understood.

Methodology

This study was conducted in 92 schools across Côte d’Ivoire during the dry season, from November 2011 to February 2012. School children provided blood samples for detection of Plasmodium infection, stool samples for diagnosis of soil-transmitted helminth (STH) and Schistosoma mansoni infections, and urine samples for appraisal of Schistosoma haematobium infection. A questionnaire was administered to obtain demographic, socioeconomic, and behavioral data. Multinomial regression models were utilized to determine risk factors for STH-Plasmodium and Schistosoma-Plasmodium co-infection.

Principal Findings

Complete parasitological and questionnaire data were available for 5,104 children aged 5-16 years. 26.2% of the children were infected with any helminth species, whilst the prevalence of Plasmodium infection was 63.3%. STH-Plasmodium co-infection was detected in 13.5% and Schistosoma-Plasmodium in 5.6% of the children. Multinomial regression analysis revealed that boys, children aged 10 years and above, and activities involving close contact to water were significantly and positively associated with STH-Plasmodium co-infection. Boys, wells as source of drinking water, and water contact were significantly and positively associated with Schistosoma-Plasmodium co-infection. Access to latrines, deworming, higher socioeconomic status, and living in urban settings were negatively associated with STH-Plasmodium co-infection; whilst use of deworming drugs and access to modern latrines were negatively associated with Schistosoma-Plasmodium co-infection.

Conclusions/Significance

More than 60% of the school children surveyed were infected with Plasmodium across Côte d’Ivoire, and about one out of six had a helminth-Plasmodium co-infection. Our findings provide a rationale to combine control interventions that simultaneously aim at helminthiases and malaria.     

Bayesian Risk Mapping and Model-Based Estimation of Schistosoma haematobium–Schistosoma mansoni Co-distribution in C?te d′Ivoire

Background

Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d′Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species.

Methodology

We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d′Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium–S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines.

Principal Findings

We estimated that 8.9% of school-aged children in Côte d′Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country.

Conclusions/Significance

We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d′Ivoire and a strong empirical basis for a rational targeting of control interventions.     

When time and numerosity interfere: the longer the more, and the more the longer

There is strong evidence that magnitudes in different dimensions can interfere. A majority of previous studies on the interaction of temporal magnitudes on numerosity showed no interfering effect, while many studies have reported the interference of numerosity on judgement of temporal magnitudes. We speculated that this one-way interference is confounded by the magnitudes used in the studies. We used a methodology that allowed us to study this interaction reciprocally. Moreover, we selected magnitudes for two dimensions that enabled us to detect their interfering effects. Participants had to either judge which of two successive sets of items was more numerous (numerosity judgement task), or which set of items was presented longer (duration judgement task). We hypothesised that a longer presentation of a set will be judged as being more numerous, and vice versa, a more numerous set will be judged as being presented longer. Results confirmed our hypothesis. A positive correlation between duration of presentation and judged numerosity as well as a positive correlation between the number of items and judged duration of presentation was found. This observation supports the idea that duration and numerosity judgements are not completely independent and implies the existence of (partly) generalised and abstract components in the magnitude representations.     

Ants as Indicators of the Success of Rehabilitation Efforts in Deposits of Gold Mining Tailings

The evaluation of the success of restoration efforts is an essential step for environmental monitoring programs, providing reliable and intricate information on the response of biotic and abiotic elements of ecosystem following the restoration programs adopted. The aim of this study was to evaluate the efficacy of different rehabilitation efforts after gold mining activities using ants as bioindicators. We tested the following hypotheses: (1) the ant species richness and composition vary with the technique of revegetation and (2) the number of epigaeic and hypogaeic ant species increases with resources. We selected four tailing dumps from gold mining, one spontaneously revegetated (“Natural”) and the other three areas with different rehabilitation techniques, namely: Grassy 2005—rehabilitation with grasses in 2005; Grassy 2006—rehabilitation with grasses in 2006, and Shrubby 2004—rehabilitation with grasses, herbaceous, and shrubs in 2004. Ants were sampled using epigaeic and hypogaeic pitfall traps. Species accumulation curves show that the “Natural” area has a higher number of species. We found differences in species composition of epigaeic and hypogaeic ants among the different areas sampled. We conclude that Camponotus fastigatus can be taken as a good indicator of environmental rehabilitation in areas impacted by mining activities. Moreover, Ectatomma edentatum, Dorymyrmex brunneus, Crematogaster evallans, and Solenopsis invicta can also indicate that the rehabilitation process is not yet completed.     

Can ants be used as indicators of environmental impacts caused by arsenic?

We evaluated ants as bioindicators of environmental impacts caused by arsenic residuals in the soil. We tested the hypotheses that the presence of arsenic in the soil affects: (1) estimates of resources and habitat condition for arboreal and epigaeic ants; (2) species richness of arboreal and epigaeic ants and (3) arboreal and epigaeic ant species composition. Ants were sampled at an inactivated raticide factory in Nova Lima, Minas Gerais, Brasil, which used arsenic as one of its main byproducts. The following environmental variables were measured: bioavailable arsenic concentration in the soil, the number and density of tree species, plant cover and leaf litter depth. The species richness of arboreal ants decreased with increased bioavailable arsenic concentration whilst epigaeic ants increased with arsenic. Arboreal ants were positively related to the number of tree species, which in turn were negatively affected by arsenic. We verified which ants are good bioindicators of arsenic. Independent verification of the influence of arsenic on background environmental variables was fundamental in defining responses of ant communities, as well as in identifying the most effective pathways for the recovery of biological communities in degraded areas.     

Natural history and demography of <Emphasis Type="BoldItalic">Thalpomys lasiotis</Emphasis> (Thomas, 1916), a rare and endemic species from the Brazilian savanna

Hairy-eared cerrado mouse Thalpomys lasiotis is an endemic species of the cerrado biome. It can be found in open habitats, but its distribution is patchy and population numbers are unknown. In this paper, we describe, for the first time, aspects related to the ecology and natural history of T. lasiotis, detailing demographic parameters such as population densities, reproduction, home range, and longevity of this endemic and rare species. We captured, marked, and recaptured 55 individuals of T. lasiotis in águas Emendadas Ecological Station, located in the northeast of the Federal District, Brazil. We found significant differences on population numbers and densities between the dry and wet seasons. Densities and population numbers apparently are affected by the seasonality of food resources. Moreover, the breeding season is seasonal, and both males and females were reproductively active during the wet season. T. lasiotis showed a permanence time ranging from 2–9 months, which means that individuals can survive for at least 9 months in natural habitats. The home ranges of males and females of T. lasiotis were not significantly different. However, males have larger home ranges than females and the mean distance moved by males was higher than the distance moved by females, which is consistent with the hypothesis that males belonging to polygynous species tend to move greater distances to avoid agonistic encounters and to search sexual partners.