Machine learning enhances prediction of plants as potential sources of antimalarials.

Plants are a rich source of bioactive compounds and a number of plant-derived antiplasmodial compounds have been developed into pharmaceutical drugs for the prevention and treatment of malaria, a major public health challenge. However, identifying plants with antiplasmodial potential can be time-consuming and costly. One approach for selecting plants to investigate is based on ethnobotanical knowledge which, though having provided some major successes, is restricted to a relatively small group of plant species. Machine learning, incorporating ethnobotanical and plant trait data, provides a promising approach to improve the identification of antiplasmodial plants and accelerate the search for new plant-derived antiplasmodial compounds. In this paper we present a novel dataset on antiplasmodial activity for three flowering plant families - Apocynaceae, Loganiaceae and Rubiaceae (together comprising c. 21,100 species) - and demonstrate the ability of machine learning algorithms to predict the antiplasmodial potential of plant species. We evaluate the predictive capability of a variety of algorithms - Support Vector Machines, Logistic Regression, Gradient Boosted Trees and Bayesian Neural Networks - and compare these to two ethnobotanical selection approaches - based on usage as an antimalarial and general usage as a medicine. We evaluate the approaches using the given data and when the given samples are reweighted to correct for sampling biases. In both evaluation settings each of the machine learning models have a higher precision than the ethnobotanical approaches. In the bias-corrected scenario, the Support Vector classifier performs best - attaining a mean precision of 0.67 compared to the best performing ethnobotanical approach with a mean precision of 0.46. We also use the bias correction method and the Support Vector classifier to estimate the potential of plants to provide novel antiplasmodial compounds. We estimate that 7677 species in Apocynaceae, Loganiaceae and Rubiaceae warrant further investigation and that at least 1300 active antiplasmodial species are highly unlikely to be investigated by conventional approaches. While traditional and Indigenous knowledge remains vital to our understanding of people-plant relationships and an invaluable source of information, these results indicate a vast and relatively untapped source in the search for new plant-derived antiplasmodial compounds.

Effects of Sodium Monensin on Copper Metabolism of Brazilian Santa Inês Sheep Submitted to Different Dietary Copper.

This study aimed to evaluate the influence of sodium monensin on the hepatic accumulation of copper in sheep. Twenty-four Santa Inês crossbred sheep were used and allocated in a 2 × 2 factorial experiment with six repetitions and considering the factors dietary copper (basal and high) and supplementation (with and without sodium monensin). Thus, four homogeneous groups were formed: control (basal diet); monensin (Mon), 30 ppm of monensin; copper (Cu), 10 10 mg/kg BW per day of copper; monensin + copper (MonCu). The experimental period lasted 14 weeks. Liver and bile samples were collected at the beginning and end of the experiment to determine mineral element concentrations, and weekly blood samples for biochemical, hematological, and mineral evaluation. Liver copper concentrations at the beginning of the experiment did not vary between groups, while mean liver copper concentrations at the end of the experiment were higher in the MonCu, Cu, and Mon groups when compared to the control. At the end of the study, hepatic copper concentration was influenced by copper (p = 0.0001) and monensin (p = 0.0003) supplementation. Copper-supplemented groups had reduced liver iron contents (p = 0.0287) and increased copper concentrations in bile. The biochemical evaluation showed increased serum GGT and AST activity (p < 0.05) in the Cu and MonCu groups from the eleventh week on compared to the control and Mon groups. The increase in activity of these enzymes was influenced by copper supplementation (p = 0.0340). Monensin interferes positively with the hepatic accumulation of copper and the supplementation of this additive may predispose sheep to copper poisoning.

Snakebite incidence in rural sub-Saharan Africa might be severely underestimated.

Snakebites in sub-Saharan Africa account for 20,000 to 32,000 annual deaths. But since most data is retrieved from hospital or incomplete central databases, and many victims do not seek hospital treatment or prefer traditional remedies, the current numbers are likely underestimated. In order to reduce snakebite incidence by 50% by 2030 as targeted by World Health Organization, it is crucial to accurately quantify and understand the current rates of snakebite incidence, which can only be reliably measured through household surveys. In this study, we interviewed 1037 households in nine communities in Cabo Delgado, northern Mozambique. Our aim was to quantify true snakebite incidence and under-reporting, by comparing the total number of snakebites reported to our team during household surveys with the subset of reports that reached health centers. We additionally quantified snakebite incidence in terms of species, location of the attack, type of treatment, season, and gender of the victims. These data allow us to propose conservative extrapolations of snakebite incidence and mortality for the province of Cabo Delgado and for Mozambique. Of all snakebites reported in the surveys (N = 296), most incidents were treated exclusively by traditional doctors (N = 174; 59%) and 25% were not seen by any doctor. Most bites occurred on farms and during the rainy season. Using a conservative estimation where we assume our results to be extrapolatable for the whole of rural Mozambique, but considering snakebites in urban areas to be inexistent, we propose that in Cabo Delgado, every year at least 6124 people are victims of snakebites, of which at least 791 result in deaths. In Mozambique, we extrapolated that every year at least 69,261 people are victims of snakebite, of which at least 8950 result in death (one in eight snakebites is fatal). Our estimates are the first for Mozambique based on data retrieved in the country, and despite being an underestimation they increase snakebite incidence levels ten-fold and the number of deaths by 30-fold. Urgent and widespread surveys are needed to further assess the full extent of snakebites in sub-Saharan Africa, explore regional patterns and develop mitigation plans.

Rapid evolution of post-zygotic reproductive isolation is widespread in Arctic plant lineages.

BACKGROUND AND AIMS: The Arctic tundra, with its extreme temperatures and short growing season, is evolutionarily young and harbours one of the most species-poor floras on Earth. Arctic species often show little phenotypic and genetic divergence across circumpolar ranges. However, strong intraspecific post-zygotic reproductive isolation (RI) in terms of hybrid sterility has frequently evolved within selfing Arctic species of the genus Draba. Here we assess whether incipient biological species are common in the Arctic flora. METHODS: We conducted an extensive crossing experiment including six species representing four phylogenetically distant families collected across the circumpolar Arctic. We crossed conspecific parental populations representing different spatial scales, raised 740 F1 hybrids to maturity and measured fertility under laboratory conditions. We examined genetic divergence between populations for two of these species (Cardamine bellidifolia and Ranunculus pygmaeus). KEY RESULTS: In five of the six species, we find extensive reduction in pollen fertility and seed set in F1 hybrids; 219 (46 %) of the 477 F1 hybrids generated between parents separated by ≥427 km had <20 % pollen fertility. Isolation with migration (IM) and *BEAST analyses of sequences of eight nuclear genes in C. bellidifolia suggests that reproductively isolated populations of this species diverged during, or even after, the last glaciation. Likewise, Arctic populations of R. pygmaeus were genetically very similar despite exhibiting strongly reduced fertility in crosses, suggesting that RI evolved recently also in this species. CONCLUSION: We show that post-zygotic RI has developed multiple times within taxonomically recognized Arctic species belonging to several distantly related lineages, and that RI may have developed over just a few millennia. Rapid and widespread evolution of incipient biological species in the Arctic flora might be associated with frequent bottlenecks due to glacial cycles, and/or selfing mating systems, which are common in the harsh Arctic environment where pollinators are scarce.

Species perceived to be dangerous are more likely to have distinctive local names.

BACKGROUND: Species with direct uses, such as sources of food, shelter, building material and medicine tend to have more specific local names. But could the same apply for species that people fear? METHODS: To address this question, here we explore the behavior and perception of species diversity and dangerousness through a survey of 1037 households in nine villages in Cabo Delgado, northern Mozambique. We compare people's knowledge of snakes with that of lizards and amphibians. RESULTS: We find that northern Mozambicans know four to five times more local names for snakes than for lizards and frogs, despite the local species richness of snakes being comparable to the diversity of lizards and frogs. We further find that local knowledge was on par with the academic literature regarding snakebite symptoms. CONCLUSIONS: Our results suggest that fear can increase the level of specificity in naming species among indigenous communities, which could lead to biases in the mapping and protection of species that include data from citizen reports.

Historical chemical annotations of Cinchona bark collections are comparable to results from current day high-pressure liquid chromatography technologies.

ETHNOPHARMACOLOGICAL RELEVANCE: Species of the genus Cinchona (Rubiaceae) have been used in traditional medicine, and as a source for quinine since its discovery as an effective medicine against malaria in the 17th century. Despite being the sole cure of malaria for almost 350 years, little is known about the chemical diversity between and within species of the antimalarial alkaloids found in the bark. Extensive historical Cinchona bark collections housed at the Royal Botanic Gardens, Kew, UK, and in other museums may shed new light on the alkaloid chemistry of the Cinchona genus and the history of the quest for the most effective Cinchona barks. AIM OF THE STUDY: We used High-Pressure Liquid Chromatography (HPLC) coupled with fluorescence detection (FLD) to reanalyze a set of Cinchona barks originally annotated for the four major quinine alkaloids by John Eliot Howard and others more than 150 years ago. MATERIALS AND METHODS: We performed an archival search on the Cinchona bark collections in the Economic Botany Collection housed in Kew, focusing on those with historical alkaloid content information. Then, we performed HPLC analysis of the bark samples to separate and quantify the four major quinine alkaloids and the total alkaloid content using fluorescence detection. Correlations between historic and current annotations were calculated using Spearman's rank correlation coefficient, before paired comparisons were performed using Wilcox rank sum tests. The effects of source were explored using generalized linear modelling (GLM), before the significance of each parameter in predicting alkaloid concentrations were assessed using chi-square tests as likelihood ratio testing (LRT) models. RESULTS: The total alkaloid content estimation obtained by our HPLC analysis was comparatively similar to the historical chemical annotations made by Howard. Additionally, the quantity of two of the major alkaloids, quinine and cinchonine, and the total content of the four alkaloids obtained were significantly similar between the historical and current day analysis using linear regression. CONCLUSIONS: This study demonstrates that the historical chemical analysis by Howard and current day HPLC alkaloid content estimations are comparable. Current day HPLC analysis thus provide a realistic estimate of the alkaloid contents in the historical bark samples at the time of sampling more than 150 years ago. Museum collections provide a powerful but underused source of material for understanding early use and collecting history as well as for comparative analyses with current day samples.

Dietary Zinc Supplementation to Prevent Chronic Copper Poisoning in Sheep.

The aim of this study was to evaluate whether zinc (Zn) supplementation protects against hepatic copper (Cu) accumulation in copper-loaded sheep. Forty cross-bred lambs were assigned to five experimental groups. These included the control group (C) and four treatment groups that received Cu and/or Zn supplementation (dry matter (DM) basis) over 14 weeks, as follows: Cu (450 mg Cu/kg); Zn-35 (450 mg Cu + 35 mg Zn/kg); Zn-150 (450 mg Cu + 150 mg Zn/kg); and Zn-300 (450 mg Cu + 300 mg Zn/kg). Blood, liver, and bile samples were obtained for mineral determination by inductively coupled plasma optical emission spectrometry (ICP⁻OES). The hepatic metallothionein (MT) concentrations were also determined. At the end of the experiment, hepatic Cu concentrations were higher in all Cu-supplemented groups than in C. Hepatic Cu accumulation was lower in the groups receiving the Zn supplementation than in the Cu group, although the difference was only statistically significant (66%) in the Zn-300 group. The MT concentrations tended to be higher (almost two-fold) in the Zn groups (but were not dose related) than in the C and Cu groups, and they were related to hepatic Zn concentrations. Zn supplementation at 300 mg/kg DM is useful for preventing excessive hepatic Cu accumulation in sheep exposed to high dietary concentrations of Cu.

Endemic palm species shed light on habitat shifts and the assembly of the Cerrado and Restinga floras.

Species expansions into new habitats are often associated with physiological adaptations, for instance when rain forest lineages colonize dry habitats. Although such shifts have been documented for the Brazilian savanna (Cerrado), little is known about the biogeographic origin of species occupying an extreme South American habitat type, the coastal dunes (Restinga). We examined the formation of this poorly known, endangered habitat by reconstructing the evolutionary history of two endemic species. Due to the proposed recency and uniqueness of this habitat, we hypothesized that Restinga species of the palm genus Allagoptera to be recently evolved and to present derived morphological characters. To detect habit shifts in absolute time, we used one plastid and nine nuclear genes to reconstruct the phylogenetic and biogeographic history of Allagoptera. We used light microscopy and stable isotope analysis to explore whether morphological adaptations occurred concomitantly with habitat shifts. Phylogenetic relationships were well supported and we found ancestral lineages of Allagoptera to be widely distributed throughout habitats that are currently occupied by extant species. Over the last ca. 7Ma Allagoptera has shifted its preference to increasingly dry habitats. Coincident with the colonization of the Cerrado and Restinga, morphological adaptations also evolved, including subterranean stems that are fire-resistant and long underground stem and root systems that facilitate water access. We did not find differences in metabolic pathway or modifications to pollen morphology when compared to other palm lineages. Assuming that the evolutionary history of Allagoptera is indicative of the habitat in which it occurs, our results infer a recent origin for Cerrado species. Although little is known about the formation of the Restinga habitat, our results also suggest a longer history than currently proposed; with an origin of Restinga habitats dating back to the Late Pliocene.