The precise regulation of transcription is required for embryonic development, adult tissue turnover, and regeneration. Epigenetic modifications play a crucial role in orchestrating and regulating the transcription of genes. These modifications are important in the transition of pluripotent stem cells and their progeny.
View Article and Find Full Text PDFThe precise regulation of transcription is required for embryonic development, adult tissue turnover, and regeneration. Epigenetic modifications play a crucial role in orchestrating and regulating the transcription of genes. These modifications are important in the transition of pluripotent stem cells and their progeny.
View Article and Find Full Text PDFBackground And Purpose: The impact of radiotherapy (RT) at ultra high vs conventional dose rate (FLASH vs CONV) on the generation and repair of DNA double strand breaks (DSBs) is an important question that remains to be investigated. Here, we tested the hypothesis as to whether FLASH-RT generates decreased chromosomal translocations compared to CONV-RT.
Materials And Methods: We used two FLASH validated electron beams and high-throughput rejoin and genome-wide translocation sequencing (HTGTS-JoinT-seq), employing S.
Comet assay provides the opportunity to detect and characterize DNA strand breaks. Cellular lysing followed by embedding in agarose slide is used to visualize under an electrical current migration patterns corresponding to DNA fragments of different sizes. Here we describe the process of detecting and characterizing DNA damage by Comet assay on planarians, which is a model organism commonly used to understand the process of whole-body regeneration, stem cell regulation, and adult tissue maintenance.
View Article and Find Full Text PDFExposure to high levels of ionizing γ radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity and the re-establishment of stem cell activity in tissues damaged by ionizing radiation. We show that subthreshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally γ-irradiated tissues of the planarian flatworm Schmidtea mediterranea.
View Article and Find Full Text PDFWhole planarian chromosome squash allows researchers to qualitatively analyze chromosome integrity. Treatment with colchicine is used to halt dividing cells within metaphase and does not require amputation or tissue puncturing. In combination with acetic-orcein, a stain-fixative for chromosomes, this strategy is suitable for animals with friable tissues caused by drug treatment, radiation, and RNA interference phenotypes.
View Article and Find Full Text PDFTissue homeostasis relies on the timely renewal of cells that have been damaged or have surpassed their biological age. Nonetheless, the underlying molecular mechanism coordinating tissue renewal is unknown. The planarian harbors a large population of stem cells that continuously divide to support the restoration of tissues throughout the body.
View Article and Find Full Text PDFProtein ADP-ribosylation is a reversible post-translational modification (PTM) process that plays fundamental roles in cell signaling. The covalent attachment of ADP ribose polymers is executed by PAR polymerases (PARP) and it is essential for chromatin organization, DNA repair, cell cycle, transcription, and replication, among other critical cellular events. The process of PARylation or polyADP-ribosylation is dynamic and takes place across many tissues undergoing renewal and repair, but the molecular mechanisms regulating this PTM remain mostly unknown.
View Article and Find Full Text PDFCandida albicans is one of the most common fungal pathogens of humans. Currently, there are limitations in the evaluation of C. albicans infection in existing animal models, especially in terms of understanding the influence of specific infectious stages of the fungal pathogen on the host.
View Article and Find Full Text PDFFaithful renewal of aging and damaged tissues is central to organismal lifespan. Stem cells (SCs) generate the cellular progeny that replenish adult tissues across the body but this task becomes increasingly compromised over time. The age related decline in SC-mediated tissue maintenance is a multifactorial event that commonly affects genome integrity.
View Article and Find Full Text PDFMechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to a systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body.
View Article and Find Full Text PDFBackground: Akt (PKB) is a serine threonine protein kinase downstream of the phosphoinositide 3-kinase (PI3K) pathway. In mammals, Akt is ubiquitously expressed and is associated with regulation of cellular proliferation, metabolism, cell growth and cell death. Akt has been widely studied for its central role in physiology and disease, in particular cancer where it has become an attractive pharmacological target.
View Article and Find Full Text PDFCellular fate decisions are influenced by their topographical location in the adult body. For instance, tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. However, the molecular underpinnings of these regional differences are unknown.
View Article and Find Full Text PDFBiochim Biophys Acta
October 2015
Cell cycle regulation through the manipulation of endogenous membrane potentials offers tremendous opportunities to control cellular processes during tissue repair and cancer formation. However, the molecular mechanisms by which biophysical signals modulate the cell cycle remain underappreciated and poorly understood. Cells in complex organisms generate and maintain a constant voltage gradient across the plasma membrane known as the transmembrane potential.
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