Macrophage migration inhibitory factor in Nodding syndrome

Nodding syndrome (NS) is a catastrophic and enigmatic childhood epilepsy, accompanied by multiple neurological impairments and neuroinflammation. Of all the infectious, environmental and psychological factors associated with NS, the major culprit is Onchocerca Volvulus (Ov)–a parasitic worm transmitted to human by blackflies. NS seems to be an ’Autoimmune Epilepsy’ in light of the recent findings of deleterious autoimmune antibodies to Glutamate receptors and to Leiomodin-I in NS patients. Moreover, we recently found immunogenetic fingerprints in HLA peptide-binding grooves associate with protection or susceptibility to NS. Macrophage migration inhibitory factor (MIF) is an immune-regulatory cytokine playing a central role in modulating innate and adaptive immunity. MIF is also involved in various pathologies: infectious, autoimmune and neurodegenerative diseases, epilepsy and others. Herein, two functional polymorphisms in the MIF gene, a −794 CATT_5–8 microsatellite repeat and a −173 G/C single-nucleotide polymorphism, were assessed in 49 NS patients and 51 healthy controls from South Sudan. We also measured MIF plasma levels in established NS patients and healthy controls. We discovered that the frequency of the high-expression MIF -173C containing genotype was significantly lower in NS patients compared to healthy controls. Interestingly however, MIF plasma levels were significantly elevated in NS patients than in healthy controls. We further demonstrated that the HLA protective and susceptibility associations are dominant over the MIF association with NS. Our findings suggest that MIF might have a dual role in NS. Genetically controlled high-expression MIF genotype is associated with disease protection. However, elevated MIF in the plasma may contribute to the detrimental autoimmunity, neuroinflammation and epilepsy.     

Do microplastics impair male dominance interactions in fish? A test of the vector hypothesis

Microplastics (MPs) are widespread in aquatic environments and have become a critical environmental issue in recent years due to their adverse impacts on the physiology, reproduction, and survival of aquatic animals. Exposure to MPs also has the potential to induce sub‐lethal behavioral changes that can affect individual fitness, but these effects are understudied. Many plastic additives introduced during the manufacture of MPs are known endocrine‐disrupting chemicals (EDCs) that mimic the action of natural hormones, alter sexual and competitive behavior, and impair reproductive success in fish. In addition, EDCs and other aquatic contaminants may adhere to MPs in the environment, the latter of which may serve as transport vectors for these compounds (i.e., the vector hypothesis). In this study, we staged territorial contests between control males, and males exposed to virgin MP particles or to MPs previously immersed in one of two environmentally relevant concentrations of 17‐alpha ethinyl estradiol (EE2; 5 ng/L and 25 ng/L) to evaluate the independent and synergistic effects of exposure to MPs and a common environmental estrogen on male–male aggression and competitive territory acquisition in a freshwater fish, Pimephales promelas. Short‐term (30 days) dietary exposure to MPs did not impair the ability of males to successfully compete for and obtain a breeding territory. Overall levels of aggression in control and exposed males were also similar across trial series. These results help to fill a critical knowledge gap regarding the direct and indirect (vector‐borne) effects of MPs on the reproductive behavior of aquatic vertebrates in freshwater systems.     

A Mathematical Model of the Tuberculosis Epidemic

Acta Biotheoretica - Tuberculosis has continued to retain its title as “the captain among these men of death”. This is evident as it is the leading cause of death globally from a single...     

Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum

A parallel synthetic strategy to the 9-aminoacridine scaffold of the classical anti-malarial drug quinacrine (2) is presented. The method features a new route to 9-chloroacridines that utilizes triflates of salicylic acid derivatives, which are commercially available in a variety of substitution patterns. The route allows ready variation of the two diversity elements present in this class of molecules: the tricyclic aromatic heterocyclic core, and the disubstituted diamine sidechain. In this study, a library of 175 compounds was designed, although only 93 of the final products had purities acceptable for screening. Impurity was generally due to incomplete removal of 9-acridones (18), a degradation product of the 9-chloroacridine synthetic intermediates. The library was screened against two strains of Plasmodium falciparum, including a model of the drug-resistant parasite, and six novel compounds were found to have IC(50) values in the low nanomolar range.     

Oogenesis in the date stone beetle, Coccotrypes dactyliperda, depends on symbiotic bacteria

Abstract.  It has been suggested that sex ratio distorting symbionts are involved in the sex determination and female-biased sex ratios observed in strongly inbred scolytid beetles. Coccotrypes dactyliperda (Coleoptera: Scolytinae) is a species in which mother-son- and sib-mating occur inside the date seeds it inhabits, and the sex ratios produced are highly skewed toward females. In the present study, polymerase chain reaction (PCR) techniques and antibiotic treatments are applied to determine the possible role of Bacteria in this system. PCR with primers specifically designed to target the 16S rDNA gene in all Bacteria reveals the presence of Wolbachia and Rickettsia in control beetles, but not in antibiotic-treated individuals. Virgin females fed with antibiotics lay no eggs, and no sign of oogenesis is detected compared with all-male progeny of virgin control females. Mated females fed with antibiotics lay significantly fewer eggs than control females, with a strong effect of female age at the time of antibiotic feeding on the number of eggs laid. The study suggests that symbiotic bacteria are not involved in female-biased sex ratios but are required for oogenesis in C. dactyliperda . The specific role each of the bacteria ( Wolbachia and Rickettsia ) plays in the oogenesis remains to be determined.     

The impact of host species and vector control measures on the fitness of African malaria vectors

Many malaria vector mosquitoes in Africa have an extreme preference for feeding on humans. This specialization allows them to sustain much higher levels of transmission than elsewhere, but there is little understanding of the evolutionary forces that drive this behaviour. In Tanzania, we used a semi-field system to test whether the well-documented preferences of the vectors, Anopheles arabiensis and Anopheles gambiae sensu stricto (s.s.) for cattle and humans, respectively, are predicted by the fitness they obtain from host-seeking on these species relative to other available hosts. Mosquito fitness was contrasted, when humans were fully exposed and when they were protected by a typical bednet. The fitness of both vectors varied between host species. The predicted relationship between host preference and fitness was confirmed in An. arabiensis, but not in An. gambiae s.s., whose fitness was similar on humans and other mammals. Use of typical, imperfect bednets generated only minor reductions in An. gambiae s.s. feeding success and fitness on humans, but was predicted to generate a significant reduction in the lifetime reproductive success of An. arabiensis on humans relative to cows. This supports the hypothesis that such human-protective measures could additionally benefit malaria control by increasing selection for zoophily in vectors.     

Episodic outbreaks of small mammals influence predator community dynamics in an east African savanna ecosystem

Little is known about the dynamics of small mammals in tropical savanna: a critical gap in our understanding of Africa's best known ecosystems. Historical evidence suggested small mammals peak in abundance (outbreak) in Serengeti National Park (SNP), as in agricultural systems. We asked 1) what are bottom–up drivers of small mammals and 2) do predators have top–down effects? We documented dynamics of small mammals, birds of prey, and mammalian carnivores in SNP and agricultural areas. We used climatic fluctuations and differences between unmodified and agricultural systems as perturbations to examine trophic processes, key to understanding responses to climate change and increasing human pressures. Data were derived from intermittent measures of abundance collected 1968–1999, combined with systematic sampling 2000–2010 to construct a 42‐year time series. Data on abundance of black‐shouldered kites (1968–2010), eight other species of rodent‐eating birds (1997–2010), and 10 carnivore species (1993–2010) were also collated. Outbreaks occurred every 3–5 years in SNP, with low or zero abundance between peaks. There was a positive relationship between rainfall in the wet season and 1) small mammal abundance and 2) the probability of an outbreak, both of which increased with negative Southern Oscillation Index values. Rodent‐eating birds and carnivores peaked 6–12 months after small mammals. In agricultural areas, abundance remained higher than in natural habitats. Abundances of birds of prey and mammalian carnivores were extremely low in these areas and not related to small mammal abundance. Small mammals are an important food resource for higher trophic levels in the Serengeti ecosystem. Changes in climate and land use may alter their future dynamics, with cascading consequences for higher trophic levels, including threatened carnivores. Although outbreaks cause substantial damage to crops in agricultural areas, small mammals also play a vital role in maintaining some of the diversity and complexity found in African savanna ecosystems.