Project description:The unprecedented magnitude of the 2013-2016 Makona Ebola virus (M-EBOV) epidemic likely resulted from multiple epidemiologic factors that set it apart from previous outbreaks. Nonetheless, genetic adaptations that distinguish M-EBOV from previous isolates may also have contributed to the scale of the epidemic. Of particular interest is a M-EBOV glycoprotein (GP) variant, GP-A82V, that was first detected at the inflection point of the 2013-2016 outbreak - when the number of cases increased exponentially - and which completely supplanted the earlier M-EBOV sequence. We found that, as compared with the earlier strain, GP-A82V increased the ability of M-EBOV to fuse with and infect cells of primate origin, including human blood dendritic cells, without altering innate immune signaling in target cells. Residue 82 is located at the NPC1-binding site on M-EBOV GP and the increased infectivity of GP-A82V was restricted to cells from species in which the NPC1 orthologue bears primate-defining residues at the critical interface. We utilized HIV-derived lentiviral vectors pseudotyped with founder and A82V containing M-EBOV GPs to explore the potential that this modification alters how human monocyte-derived dendritic cells (MDDCs) respond to EBOV GP stimulation.
Project description:The Ashanti Dwarf Pig (ADP) of Ghana is an endangered pig breed with hardy and disease resistant traits. Characterisation of animal genetic resources provides relevant data for their conservation and sustainable use for food security and economic development. We investigated the origin and phylogenetic status of the local ADP of Ghana and their crosses with modern commercial breeds based on mtDNA, MC1R and Y-chromosome sequence polymorphisms, and genome-wide SNP genotyping. The study involved 164 local pigs sampled from the three agro-ecological zones of Ghana. Analyses of the mitochondrial D-loop region and Y-chromosome sequences revealed that the ADP of Ghana has both European and Asian genetic signatures. The ADP also displays considerable variation in the MC1R gene. Black coat colour is the most predominant within the breed, with the dominant black alleles of both Asian and European origin contributing to the majority of alleles in the pool. European alleles for spotting are present at a low frequency in the sample set, and may account for the occurrence of spotted piglets in some APD litters. Other colour variants may be due to epistatic interactions with additional coat colour loci, or mutations. The wide variations in coat colour patterns suggest that morphology alone cannot be used to adequately characterise Ghanaian local pigs. PCA analysis of SNP genotyping data revealed a strong location effect on clustering of local Ghanaian pigs. Based on this work, we recommend that further studies be carried out on more local pigs to find out the effect of admixture on important adaptive and economic traits of the ADP and other local Sus breeds in Africa to help develop a sustainable conservation programmes to prevent the decline of this genetic resource.
Project description:Anopheles gambiae S form adults were drawn from the GAH laboratory colony that originated from the Ahafo region in Ghana. The GAH colony exhibits extensive insecticide resistance (bendiocarb, DDT, dieldrin, permethrin, deltamethrin). Gene expression was compared between blood-fed and sugar-fed females (3 hours after feeding) using a custom array focussing on around 300 detoxification-related genes.
Project description:Neutrophils are crucial mediators of host defense and are recruited to the central nervous system in large numbers during acute bacterial meningitis caused by S. pneumoniae. Neutrophils can release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures and mainly consist of decondensed DNA and neutrophil-derived antimicrobial proteins. We report the extensive presence of NETs in the cerebrospinal fluid of patients with pneumococcal meningitis, and absence of NETs in other forms of meningitis caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the cerebrospinal fluid. Importantly, disrupting NETs using DNase I significantly reduced bacterial load, demonstrating that NETs contribute to the pathogenesis of pneumococcal meningitis in vivo. Targeting NETs using DNase may represent a novel indication for an already approved drug as a non-antibiotic therapeutic option to treat acute pneumococcal meningitis.