Biology subjects

Knight, V. B.

Publications and source records attributed to Knight, V. B..

3 recordsLinked to original sources

bioRxiv2022

Post-Translational Tubulin Modifications in Differentiated Human Neural Stem Cells

The tubulin protein fulfills a variety of cellular functions that range from chromosomal separation to locomotion. Functional diversity is achieved through the expression of specific tubulin isotypes in different cell types or developmental time periods. Post-translational modifications (PTMs) of tubulin also are vital for specific intracellular tasks, such as binding and recruiting motor proteins. In neurons, the isotypic expression profile for tubulin is well characterized, and the importance of PTMs for proper neuronal function has gained recent attention due to their implication in neurodegenerative disorders. In contrast, the role of tubulin specializations in the specification of neural cell fate has received minimal attention and studies of tubulin PTMs and isotypes in neuroglia such as astrocytes are relatively few. To bridge this knowledge gap, we undertook an analysis of PTMs in neurons and astrocytes derived from the federally approved H9 hESC-derived human neural stem cell (hNSC) line. In hNSCs, basal cells can be directed to assume neural fate as neurons or astrocytes by specifying different media growth conditions. Immunocytochemical methods, fluorescent antibody probes, and confocal microscopy facilitated image acquisition of fluorescent signals from class III {beta}-tubulin ({beta}III-tubulin), acetylated tubulin, and polyglutamylated tubulin. Fluorescent probe intensities were assessed with the EBImage package for the statistical programming language R, and compared using Students t-tests. Qualitative analysis indicated that {beta}III-tubulin, acetylated tubulin, and polyglutamylated tubulin were expressed to some degree in basal hNSCs and their media-differentiated hNSC neuronal and astroglial progeny. In media-differentiated hNSC astrocyte progeny, quantification and statistical analysis of fluorescence probe intensity showed that acetylated tubulin/ {beta}III-tubulin ratios were greater than the ratio for polyglutamylated tubulin/ {beta}III-tubulin. These findings represent a snapshot of the dynamic and varied changes in the tubulin expression profile during the specification of neural cell fate. Results imply that investigations of tubulin PTMs have the potential to advance our understanding of the generation and regeneration of nervous tissue.

neuroscience↗

bioRxiv2022

A Xenopus neuromast bioassay for chemical ototoxicity

BackgroundOtotoxic chemicals can impair the senses of hearing and balance in mammals through irreversible damage to the mechanosensory bundles of inner ear hair cells. Fish and amphibians are useful models for investigating ototoxicity because their inner ear hair cells, like those of mammals, are susceptible to damage by ototoxins. Moreover, amphibian mechanosensation is augmented by a lateral line organ on the body surface that comprises external mechanosensory hair cells. The lateral line hair cells are arranged in clusters (neuromasts) and are structurally and functionally similar to inner ear hair cells, but are more accessible for experimental manipulation. Herein, we implemented neuromasts of the amphibian (Xenopus) lateral line as an organ system for evaluating the effects of ototoxic chemicals, such as antibiotics, on mechanosensory hair cell bundles. MethodsWe examined the ultrastructure of larval Xenopus laevis neuromasts with scanning electron microscopy (SEM) after larvae were continuously exposed to ototoxic aminoglycoside antibiotics at sub-lethal concentrations (gentamicin; streptomycin; neomycin) for 72 hours. ResultsSEM images demonstrated that 72 hours of exposure to antibiotic concentrations greater than 25 {micro}M reduced the hair cell bundle number in lateral line neuromasts. ConclusionTherapeutic drug studies will benefit from the incorporation of bioassay strategies that evaluate ototoxicity across multiple species including genera of amphibian origin such as Xenopus. Our outcomes support the use of the Xenopus lateral line for identification of potential ototoxic chemicals and suggest that Xenopus neuromast hair cell bundles can withstand antibiotic exposure. The Xenopus bioassay presented here can be incorporated into drug discovery methodology as a high-resolution phenotypic screen for ototoxic effects. Summary statementDamage to sensory cells of the inner ear by chemical agents such as antibiotics contributes to the growing global prevalence of disorders of hearing and balance. Our results demonstrate that the Xenopus lateral line, in conjunction with SEM, affords an accessible organ system for otoxicity screens during the drug discovery pipeline.

neuroscience↗

bioRxiv2021

Hunter-gatherer foraging networks promote information transmission

Central-place foraging, where foragers return to a central location (or home), is a key feature of hunter-gatherer social organization. Central-place foraging could have significantly changed hunter-gatherers use of space and mobility, and altered social networks and increased opportunities for information exchange. We evaluated whether central-place foraging patterns facilitate information transmission and considered the potential roles of environmental conditions and mobility strategies. We built an agent-based central-place foraging model where agents move according to a simple optimal foraging rule, and can encounter other agents as they move across the environment. They either forage close to their home within a given radius or move the location of their home to new areas. We analyzed the interaction networks arising across different environments and mobility strategies. We found that, at intermediate levels of environmental heterogeneity and mobility, central-place foraging increased global and local network efficiencies as well as the rate of contagion-based information transmission (simple and complex). We also assessed the effect of population density on the resultant networks and found that central-place mobility strategies can further improve information transmission in larger populations. Our findings suggest that the combination of foraging and movement strategies, as well as the underlying environmental conditions that characterized early human societies, may have been a crucial precursor in our species unique capacity to innovate, accumulate and rely on complex culture.

evolutionary biology↗