Human Exposure to Wild Animals in the Sankuru Province of the Democratic Republic of the Congo

Due to the high level of biological diversity in the Congo Basin and human population dependence on bushmeat, the DRC represents an ideal location for expanding knowledge on wild animal exposures and thus the potential for transmission of zoonotic pathogens. However, limited information exists on patterns and extent of contact with wildlife in such communities. Using a cross-sectional study, 14 villages in the Sankuru Province of the DRC were surveyed between August and September 2007. Villagers ≥ 1 year of age and at home of the time of the survey were eligible and enrolled to describe and assess factors associated with animal exposures (both activity and type of animal). Among respondents, 91% reported exposure to rodents, 89% to duikers, 78% to non-human primates (NHPs), and 32% reported contact with bats in the month prior to the survey. The most frequently reported activities included eating (95%), cooking (70%), and butchering or skinning of animals (55%). The activities and animals to which subjects had contact varied by sex and age. Moreover, we observed a high correlation of the same activities across animal types. In this and other populations that rely on bushmeat, there is a high frequency of exposure to multiple animal species through various modalities. In the event of future zoonotic disease outbreaks, effective public health interventions and campaigns that mitigate the risk of animal contact during outbreaks need to be broad to include various modes of contact and should be directed to both men and women across all age groups. As available information is limited, further studies are necessary to better understand the complex relationships and exposures individuals have with animals.     

Biomethanation of low pH petrochemical wastewater using up-flow fixed-film anaerobic bioreactors

Anaerobic digestion of wastewater from a petrochemical plant, manufacturing Nylon-6 was studied in continuously fed up-flow fixed-film column reactors using different biomass support materials such as bonechar, charcoal, bricks, plastic beads and polyurethane foam under varying hydraulic and organic loading rates. Experimental results showed bonechar as the best support material with high biomass-retaining capacity because of its high specific surface area (53.35m²g^–1 of bedding material) and pore specific volume (0.244cm³g^–1 of bedding material). This system could treat waste water at hydraulic retention times (HRT) as low as 2.5 days with organic loading rates as high as 21.76kg COD m^–3 day^–1 using acidic feed of pH 2.5 resulting in a 95% COD reduction with biogas production of 11.76m³ m^–3 of reactor volume day^–1. Total alkalinity of 1700mg CaCO₃ l^–1 and pH of 7.5 of the treated wastewater were observed at 2.5 days HRT, indicating that methanogenesis appear to be alkalizing step and wastewater with pH as low as 2.5 can be treated as such without neutralization with retention of methanogenic biomass on bonechar.     

Identification of Small-Molecule Inhibitors against Meso-2, 6-Diaminopimelate Dehydrogenase from Porphyromonas gingivalis

Species-specific antimicrobial therapy has the potential to combat the increasing threat of antibiotic resistance and alteration of the human microbiome. We therefore set out to demonstrate the beginning of a pathogen-selective drug discovery method using the periodontal pathogen Porphyromonas gingivalis as a model. Through our knowledge of metabolic networks and essential genes we identified a “druggable” essential target, meso-diaminopimelate dehydrogenase, which is found in a limited number of species. We adopted a high-throughput virtual screen method on the ZINC chemical library to select a group of potential small-molecule inhibitors. Meso-diaminopimelate dehydrogenase from P. gingivalis was first expressed and purified in Escherichia coli then characterized for enzymatic inhibitor screening studies. Several inhibitors with similar structural scaffolds containing a sulfonamide core and aromatic substituents showed dose-dependent inhibition. These compounds were further assayed showing reasonable whole-cell activity and the inhibition mechanism was determined. We conclude that the establishment of this target and screening strategy provides a model for the future development of new antimicrobials.     

MiST: A new approach to variant detection in deep sequencing datasets

MiST is a novel approach to variant calling from deep sequencing data, using the inverted mapping approach developed for Geoseq. Reads that can map to a targeted exonic region are identified using exact matches to tiles from the region. The reads are then aligned to the targets to discover variants. MiST carefully handles paralogous reads that map ambiguously to the genome and clonal reads arising from PCR bias, which are the two major sources of errors in variant calling. The reduced computational complexity of mapping selected reads to targeted regions of the genome improves speed, specificity and sensitivity of variant detection. Compared with variant calls from the GATK platform, MiST showed better concordance with SNPs from dbSNP and genotypes determined by an exonic-SNP array. Variant calls made only by MiST confirm at a high rate (>90%) by Sanger sequencing. Thus, MiST is a valuable alternative tool to analyse variants in deep sequencing data.     

A female with five chambers

Netherlands Heart Journal -     

C6-Ceramide Nanoliposomes Target the Warburg Effect in Chronic Lymphocytic Leukemia

Ceramide is a sphingolipid metabolite that induces cancer cell death. When C6-ceramide is encapsulated in a nanoliposome bilayer formulation, cell death is selectively induced in tumor models. However, the mechanism underlying this selectivity is unknown. As most tumors exhibit a preferential switch to glycolysis, as described in the “Warburg effect”, we hypothesize that ceramide nanoliposomes selectively target this glycolytic pathway in cancer. We utilize chronic lymphocytic leukemia (CLL) as a cancer model, which has an increased dependency on glycolysis. In CLL cells, we demonstrate that C6-ceramide nanoliposomes, but not control nanoliposomes, induce caspase 3/7-independent necrotic cell death. Nanoliposomal ceramide inhibits both the RNA and protein expression of GAPDH, an enzyme in the glycolytic pathway, which is overexpressed in CLL. To confirm that ceramide targets GAPDH, we demonstrate that downregulation of GAPDH potentiates the decrease in ATP after ceramide treatment and exogenous pyruvate treatment as well as GAPDH overexpression partially rescues ceramide-induced necrosis. Finally, an in vivo murine model of CLL shows that nanoliposomal C6-ceramide treatment elicits tumor regression, concomitant with GAPDH downregulation. We conclude that selective inhibition of the glycolytic pathway in CLL cells with nanoliposomal C6-ceramide could potentially be an effective therapy for leukemia by targeting the Warburg effect.     

The choreography of multidrug export

Multidrug transporters have a crucial role in causing the drug resistance that can arise in infectious micro-organisms and tumours. These integral membrane proteins mediate the export of a broad range of unrelated compounds from cells, including antibiotics and anticancer agents, thus reducing the concentration of these compounds to subtoxic levels in target cells. In spite of intensive research, it is not clear exactly how multidrug transporters work. The present review focuses on recent advancements in the biochemistry and structural biology of bacterial and human multidrug ABC (ATP-binding cassette) transporters. These advancements point to a common mechanism in which polyspecific drug-binding surfaces in the membrane domains are alternately exposed to the inside and outside surface of the membrane in response to the ATP-driven dimerization of nucleotide-binding domains and their dissociation following ATP hydrolysis.     

Bioemulsifier production by Streptomyces sp. S22 isolated from garden soil

Out of 45 actinomycetes isolated from garden soil, pond water and air; fifteen showed good emulsification activity. Streptomyces sp. S22 isolated from garden soil produced maximum bioemulsifier with 0.5% (v/v) sunflower oil during stationary phase at 37 degrees C, pH 6 and 250 rev/min. Emulsification activity was maximum (320 EU/ml) with sunflower oil as substrate. Partially purified bioemulsifier from Streptomyces sp. S22 was a peptidoglycolipid containing lipid (51.25%), protein (30%), non-reducing sugar (17.75%) and reducing sugar (1%). The yield of partially purified bioemulsifier was 1.6 g/l and reduced the surface tension of water by 23.09 mN/m. The bioemulsifier produced by Streptomyces sp. S22 was stable at room temperature for seven days.