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African swine fever virus (ASFV) is the etiological agent of ASF, a fatal hemorrhagic fever that affects domestic pigs. There is currently no vaccine against ASFV, making it a significant threat to the pork industry. The ASFV genome sequence has been published; however, about half of ASFV open reading frames have not been characterized in terms of their structure and function despite being essential for our understanding of ASFV pathogenicity. The present study reports the three-dimensional structure and function of uncharacterized protein, pB263R (NP_042780.1), an open reading frame found in all ASFV strains. Sequence-based profiling and hidden Markov model search methods were used to identify remote pB263R homologs. Iterative Threading ASSEmbly Refinement (I-TASSER) was used to model the three-dimensional structure of pB263R. The posterior probability of fold family assignment was calculated using TM-fold, and biological function was assigned using TM-site, RaptorXBinding, Gene Ontology, and TM-align. Our results suggests that pB263R has the features of a TATA-binding protein and is thus likely to be involved in viral gene transcription.

BackgroundAfrican trypanosomes are protozoan parasites that cause “sleeping sickness” in humans and a similar disease in livestock. Trypanosomes also infect laboratory mice and three major quantitative trait loci (QTL) that regulate survival time after infection with T. congolense have been identified in two independent crosses between susceptible A/J and BALB/c mice, and the resistant C57BL/6. These were designated Tir1, Tir2 and Tir3 for Trypanosoma infection response, and range in size from 0.9–12 cM.Principal FindingsMapping loci regulating survival time after T. congolense infection in an additional cross revealed that susceptible C3H/HeJ mice have alleles that reduce survival time after infection at Tir1 and Tir3 QTL, but not at Tir2. Next-generation resequencing of a 6.2 Mbp region of mouse chromosome 17, which includes Tir1, identified 1,632 common single nucleotide polymorphisms (SNP) including a probably damaging non-synonymous SNP in Pram1 (PML-RAR alpha-regulated adaptor molecule 1), which was the most plausible candidate QTL gene in Tir1. Genome-wide comparative genomic hybridisation identified 12 loci with copy number variants (CNV) that correlate with differential gene expression, including Cd244 (natural killer cell receptor 2B4), which lies close to the peak of Tir3c and has gene expression that correlates with CNV and phenotype, making it a strong candidate QTL gene at this locus.ConclusionsBy systematically combining next-generation DNA capture and sequencing, array-based comparative genomic hybridisation (aCGH), gene expression data and SNP annotation we have developed a strategy that can generate a short list of polymorphisms in candidate QTL genes that can be functionally tested.

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The consumption of khat (Catha Edulis, Forsk) is on the rise despite the much publicized associated deleterious health effects. How chemicals present in khat, affect various physiological and biochemical processes requires further scrutiny. A clear understanding of these processes will provide an avenue for countering khat-driven negative effects using appropriate pharmacological and/or nutritional interventions.Aim of the study: The current study investigated the effect of khat on vital physiological and biochemical processes such as oxidative stress, inflammation and immune responses and the role of Coenzyme-Q 10 (CoQ 10 ), a potent antioxidant and anti-inflammatory, in modulating any negative effects due to khat exposure. Methodology: Three (3) weeks old forty (40) Swiss albino mice were randomly assigned into four treatment groups (n ¼ 10). The first group was the control that was not administered with khat or CoQ 10 . The second group received 200 mg/kg body weight (b/w) of CoQ 10 , while the third group received 1500 mg/kg b/w of khat extract and finally the forth group was co-treated with 200 mg/kg b/w of CoQ 10 and 1500 mg/kg b/w of khat extract. The experiment was conducted for 90 days after which samples were collected for physiological and biochemical analyses.Results: The effects of khat and CoQ 10 on the weights of brain, liver, kidney and spleen was determined. Administration of khat decreased the levels of RBCs and its subtypes (MCV, MCH, RDW-SD and RDW-CV), a clear indicator of khat-induced normochromic microcytic anemia. White blood cells (lymphocytes, monocytes, neutrophils and eosinophil) which are vital in responding to infections were markedly elevated by khat. Moreover, these results provide evidence for khat-induced liver and kidney injury as shown by increased biomarkers; AST, ALT, GGT and creatinine respectively. Standard histopathological analysis confirmed this finding for khat-driven liver and kidney injury. Further studies showed evidence for khat-induced inflammation and oxidative stress as depicted by increased levels of the pro-inflammatory cytokine TNF-alpha and elevation of GSH in the brain, liver and spleen. Remarkably, this is the first study to demonstrate the potential of CoQ 10 in ameliorating khat-induced negative effects as outlined. CoQ 10 supplementation restored the khat-induced reduction in RBC subtypes, and was protective against liver and kidney injury as shown by the appropriate biomarkers and standard histopathology analysis. The other significant finding was the CoQ 10 -driven normalization of GSH and TNF-α levels, indicating a protective effect from khat-driven oxidative stress and inflammation respectively. Conclusion: From this study, we conclude that CoQ 10 may be useful in nullifying khat-driven deleterious events among chronic khat users.