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Biology subjects

Kolawole, A.

Publications and source records attributed to Kolawole, A..

3 recordsLinked to original sources

EFFECT OF METHANOL STEM-BARK EXTRACT OF Erythrina senegalensis ON SERUM ALBUMIN LEVEL OF CARBON TETRACHLORIDE INDUCED LIVER DAMAGE IN WISTAR ALBINO RATS.

IntroductionPrevious investigations already established the pharmacological importance of Erythrina senegalensis. The current study was conducted to determine the effect of methanol stem-bark extract of Erythrina senegalensis (MEES) on serum albumin level of carbon tetrachloride (CCl4) induced liver damage in wistar rats. MethodThirty wister rats of either sex weighing were randomly divided into six groups of five rats each. Group 1 served as the control received standard pelleted rat feed with normal distilled water. Group 2-6 were administered 30% CCl4 1ml/kg body weight in liquid paraffin at 72hrs interval. Group 2 was untreated while group 3 was orally treated with standard drug salymarin for 14days. Group 4-6 were orally treated respectively with 100, 300 and 500mg/kg body weight of the MEES. ResultThe phytochemical analysis of the MEES indicated the presence of saponins, phenols, flavonoids, and tannins while the acute toxicity test showed no adverse reaction within the test population at a dose range of 200-2000mg/kg body weight. Unlike the control, inducement of CCL4 to Group2-6 indicated significant changes (p < 0.05) in the serum albumin level and hematological parameters. However, treatment with silymarin and increasing doses of the MEES restore the changes. The histopathological studies also reveal that increasing concentration of administered doses of the MEES significantly (p < 0.05) reduces cell necrosis around central vein. ConclusionThe findings reveal that MEES at recommended doses can serve as alternative source for the development of safe, effective, and affordable liver-supplement drug.

biochemistry↗

Human norovirus infection of primary B cells triggers immune activation in vitro

Human norovirus (HNoV) is a global health and socio-economic burden, estimated to infect every individual at least five times during their lifetime. The underlying mechanism for the potential lack of long-term immune protection from HNoV infections is not understood and prompted us to investigate HNoV susceptibility of primary human B cells and its functional impact. Primary B cells isolated from whole-blood were infected with HNoV-positive stool samples and harvested 3 days post infection (dpi) to assess viral RNA yield by RT-qPCR. A 3-18 fold increase in HNoV RNA yield was observed in 50-60% donors. Infection was further confirmed in B cells derived from splenic and lymph node biopsies. Next, we characterized infection of whole-blood derived B cells by flow cytometry in specific functional B cell subsets (naive CD27-IgD+, memory switched CD27+IgD-, memory unswitched CD27+IgD+ and double-negative CD27-IgD-). While susceptibility of subsets was similar, we observed changes in B cell subsets distribution upon infection that were recapitulated after treatment with HNoV virus-like particles and mRNA encoding for HNoV NS1-2 protein. Importantly, treatment of immortalized BJAB B cell lines with the predicted recombinant NS1 protein triggered cell proliferation, increased ATP production, and induced metabolic changes, as detected by means of CFSE/Ki67 staining, seahorse analysis and metabolomics, respectively. These data demonstrate the susceptibility of primary B cells to HNoV infection and suggest that the secreted NS1 protein affects B cell function, proliferation and metabolism in vitro, which could have implications for viral pathogenesis and immune response in vivo. ImportanceHuman norovirus (HNoV) is the most prevalent causative agent of gastroenteritis worldwide. Infection results in a self-limiting disease that can become chronic and severe in the immunocompromised, elderly and infants. There are currently no approved therapeutic and preventative strategies to limit the health and socio-economic burden associated with HNoV infections. Moreover, HNoV does not elicit life-long immunity as repeat infections are common, presenting a challenge for vaccine development. Given the importance of B cells for humoral immunity, we investigated susceptibility and impact of HNoV infection on human B cells. We found that HNoV replicates in human primary B cells derived from blood, spleen and lymph nodes specimens and induces functional changes in B cells, mediated in part by the non-structural protein NS1. Because of the secreted nature of NS1, we put forward the hypothesis that HNoV infection can modulate bystander B cell function with potential implications in systemic immune response.

microbiology↗

Tuning the course of evolution on the biophysical fitness landscape of an RNA virus

Predicting viral evolution remains a major challenge with profound implications for public health. Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics device, the \"Evolution Chip\", which propagates millions of independent viral sub-populations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs shape viral evolution.

evolutionary biology↗