Browsing by Author "Khan, Zeina S. (TTU)"

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Curbing Breast Cancer by Altering V-ATPase Action on F-Actin, Heterochromatin, ETV7 and mTORC2 Signaling
(2024) Khan, Zeina S. (TTU); Hussain, Fazle (TTU)
Background/Aims: Motivated by the vacuolar proton pump’s importance in cancer, we investigate the effects of proton pump inhibition on breast cancer cell migration and proliferation, F-actin polymerization, lamin A/C, heterochromatin, and ETV7 expressions, nuclear size and shape, and AKT/mTOR signaling. Methods: Lowly metastatic MCF7 and highly metastatic MDA-MB-231 breast cancer cells were treated with 120 nM of proton pump inhibitor Bafilomycin A1 for 24 hours. Cell migration was studied with wound- scratch assays, ATP levels with a chemiluminescent assay; cell proliferation was quantified by a cell area expansion assay. Nuclear size and shape were determined using DAPI nuclear stain and fluorescence microscopy. The levels of F-actin, lamin A/C, heterochromatin, and ETV7 were quantified using both immunocytochemistry and western blots; p-mTORC1, p-mTORC2, mTOR, p-AKT, and AKT were measured by western blots. Results: We reveal that proton pump inhibition reduces F-actin polymerization, cell migration, proliferation, and increases heterochromatin in both lowly and highly metastatic cells. Surprisingly, Bafilomycin decreases lamin A/C in both cell lines. Inhibition has different effects on ETV7 expression in lowly and highly metastatic cells, as well as nuclear area, perimeter, and circularity. Bafilomycin also significantly decreases p-mTORC1, p-MTORC2, and MTOR expression in both cell lines, whereas it significantly decreases p-AKT in lowly metastatic cells and surprisingly significantly increases p-AKT in highly metastatic cells. Our proton pump inhibition protocol reduces V-ATPase levels (~25%) within three hours. V-ATPase levels vary in time for both control and inhibited cells, and inhibition reduces cellular ATP. Conclusions: Proton pumps promote F-actin polymerization and decrease heterochromatin, facilitating invasion. These pumps also upregulate both mTORC1 and mTORC2, thus highlighting the relevance of vacuolar proton pumps as metastatic cancer targets.
Locomotion of C. elegans: A piecewise-harmonic curvature representation of nematode behavior
(2012) Padmanabhan, Venkat (TTU); Khan, Zeina S. (TTU); Solomon, Deepak E. (TTU); Armstrong, Andrew (TTUHSC); Rumbaugh, Kendra P. (TTUHSC); Vanapalli, Siva A. (TTU); Blawzdziewicz, Jerzy (TTU)
Caenorhabditis elegans, a free-living soil nematode, displays a rich variety of body shapes and trajectories during its undulatory locomotion in complex environments. Here we show that the individual body postures and entire trails of C. elegans have a simple analytical description in curvature representation. Our model is based on the assumption that the curvature wave is generated in the head segment of the worm body and propagates backwards. We have found that a simple harmonic function for the curvature can capture multiple worm shapes during the undulatory movement. The worm body trajectories can be well represented in terms of piecewise sinusoidal curvature with abrupt changes in amplitude, wavevector, and phase. © 2012 Padmanabhan et al.
Modeling the change in European and US COVID-19 death rates
(2022) Khan, Zeina S. (TTU); Bussel, Frank Van (TTU); Hussain, Fazle (TTU)
Motivated by several possible differences in Covid-19 virus strains, age demographics, and face mask wearing between continents and countries, we focussed on changes in Covid death rates in 2020. We have extended our Covid-19 multicompartment model (Khan et al., 2020) to fit cumulative case and death data for 49 European countries and 52 US states and territories during the recent pandemic, and found that the case mortality rate had decreased by at least 80% in most of the US and at least 90% in most of Europe. We found that death rate decreases do not have strong correlations to other model parameters (such as contact rate) or other standard state/national metrics such as population density, GDP, and median age. Almost all the decreases occurred between mid-April and mid-June 2020, which corresponds to the time when many state and national lockdowns were relaxed resulting in surges of new cases. We examine here several plausible causes for this drop—improvements in treatment, face mask wearing, new virus strains, testing, potentially changing demographics of infected patients, and changes in data collection and reporting—but none of their effects are as significant as the death rate changes suggest. In conclusion, this work shows that a two death rate model is effective in quantifying the reported drop in death rates.