Motivation: Morphology of the cell nucleus has been used as a key indicator of disease state and prognosis, but typically without quantitative rigor. It is also not well understood how nuclear morphology varies with time across different genetic backgrounds in healthy cells. To help answer these questions we measured the size and shape of nuclei in cell-cycle-synchronized primary human fibroblasts from 6 different individuals at 32 time points over a 75 hour period.
Results: The nucleus was modeled as an ellipsoid and its dynamics analyzed. Shape and volume changed significantly over this time. Two prominent frequencies were found in the 6 individuals: a 17 hour period consistent with the cell cycle and a 26 hour period. Our findings suggest that the shape of the nucleus changes over time and thus any time-invariant shape property may provide a misleading characterization of cellular populations at different phases of the cell cycle. The proposed methodology provides a general method to analyze morphological change using multiple time points even for non-live-cell experiments.
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http://dx.doi.org/10.1080/19491034.2015.1095432 | DOI Listing |
Geroscience
January 2025
Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Aging is influenced by a complex interplay of multifarious factors, including an individual's genetics, environment, and lifestyle. Notably, high altitude may impact aging and age-related diseases through exposures such as hypoxia and ultraviolet (UV) radiation. To investigate this, we mined risk exposure data (summary exposure value), disease burden data (disability-adjusted life years (DALYs)), and death rates and life expectancy from the Global Health Data Exchange (GHDx) and National Data Management Center for Health of Ethiopia for each subnational region of Ethiopia, a country with considerable differences in the living altitude.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, N-7491, Trondheim, Norway.
The cytotoxic mechanisms of thymidylate synthase inhibitors, such as the multitarget antifolate pemetrexed, are not yet fully understood. Emerging evidence indicates that combining pemetrexed with histone deacetylase inhibitors (HDACi) may enhance therapeutic efficacy in non-small cell lung cancer (NSCLC). To explore this further, A549 NSCLC cells were treated with various combinations of pemetrexed and the HDACi MS275 (Entinostat), and subsequently assessed for cell viability, cell cycle changes, and genotoxic markers.
View Article and Find Full Text PDFLife Sci Alliance
March 2025
https://ror.org/00hj54h04 Interdisciplinary Life Sciences Graduate Programs, The University of Texas at Austin, Austin, TX, USA
Breast cancer stem cells (CSCs) are difficult to therapeutically target, but continued efforts are critical given their contribution to tumor heterogeneity and treatment resistance in triple-negative breast cancer. CSC properties are influenced by metabolic stress, but specific mechanisms are lacking for effective drug intervention. Our previous work on TFEB suggested a key function in CSC metabolism.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Laboratory of Immunogenetics, Pennington Biomedical Research Center, Baton Rouge, LA, 70808, USA; Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address:
Pancreatic islet β-cells express the Cpt1a gene, which encodes the enzyme carnitine palmitoyltransferase 1A (CPT1A), an enzyme that facilitates entry of long chain fatty acids into the mitochondria. Because fatty acids are required for glucose-stimulated insulin secretion, we tested the hypothesis that CPT1A is essential to support islet β-cell function and mass. In this study, we describe genetic deletion of Cpt1a in pancreatic tissue (Cpt1a) using C57BL/6J mice.
View Article and Find Full Text PDFArch Oral Biol
December 2024
University of Brasília, Brasília, Laboratory of Oral Histopathology, Health Sciences Faculty, Brazil. Electronic address:
Objective: This in vitro study aimed to analyze the effects of ionizing radiation on immortalized human osteoblast-like cells (SaOS-2) and further assess their cellular response in co-culture with fibroblasts. These analyses, conducted in both monoculture and co-culture, are based on two theoretical models of osteoradionecrosis - the theory of hypoxia and cellular necrosis and the theory of the radiation-induced fibroatrophic process.
Design: SaOS-2 cells were exposed to ionizing radiation and evaluated for cell viability, nitric oxide (NO) production, cellular morphology, wound healing, and gene expression related to the PI3K-AKT-mTOR pathway.
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