Accumulating evidence suggests that p21(Cip1) located in the cytoplasm might play a role in promoting transformation and tumor progression. Here we show that oncogenic H-RasV12 contributes to the loss of actin stress fibers by inducing cytoplasmic localization of p21(Cip1), which uncouples Rho-GTP from stress fiber formation by inhibiting Rho kinase (ROCK). Concomitant with the loss of stress fibers in Ras-transformed cells, there is a decrease in the phosphorylation level of cofilin, which is indicative of a compromised ROCK/LIMK/cofilin pathway. Inhibition of MEK in Ras-transformed NIH3T3 results in restoration of actin stress fibers accompanied by a loss of cytoplasmic p21(Cip1), and increased phosphorylation of cofilin. Ectopic expression of cytoplasmic but not nuclear p21(Cip1) in Ras-transformed cells was effective in preventing stress fibers from being restored upon MEK inhibition and inhibited phosphorylation of cofilin. p21(Cip1) was also found to form a complex with ROCK in Ras-transformed cells in vivo. Furthermore, inhibition of the PI 3-kinase pathway resulted in loss of p21(Cip1) expression accompanied by restoration of phosphocofilin, which was not accompanied by stress fiber formation. These results suggest that restoration of cofilin phosphorylation in Ras-transformed cells is necessary but not sufficient for stress fiber formation. Our findings define a novel mechanism for coupling cytoplasmic p21(Cip1) to the control of actin polymerization by compromising the Rho/ROCK/LIMK/cofilin pathway by oncogenic Ras. These studies suggest that localization of p21(Cip1) to the cytoplasm in transformed cells contributes to pathways that favor not only cell proliferation, but also cell motility thereby contributing to invasion and metastasis.
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Sci Rep
January 2025
Neuroscience Graduate Program, The Ohio State University, Columbus, OH, 43210, USA.
Postpartum depression (PPD) affects up to 20% of new mothers and has adverse consequences for the well-being of both mother and child. Exposure to stress during pregnancy as well as dysregulation in the mesolimbic dopamine (DA) reward system and its upstream modulator oxytocin (OT) have been independently linked to PPD. However, no studies have directly examined DA or OT signaling in the postpartum brain after gestational stress.
View Article and Find Full Text PDFLow Urin Tract Symptoms
January 2025
Farwaniya Hospital, Farwaniya, Kuwait.
Objectives: During holmium laser enucleation of the prostate (HOLEP), blunt dissection (BD) by pushing the tip of the scope may exert mechanical force on the sphincter that could be avoided by adopting laser dissection (LD). This study evaluates the continence recovery in consecutive patients who underwent BD and LD.
Methods: A prospective cohort of patients who underwent LD was compared with a retrospective control that underwent BD.
PLoS Comput Biol
January 2025
Department of Mechanical Engineering & Materials Science, Washington University, St. Louis, Missouri, United States of America.
Cell collectives, like other motile entities, generate and use forces to move forward. Here, we ask whether environmental configurations alter this proportional force-speed relationship, since aligned extracellular matrix fibers are known to cause directed migration. We show that aligned fibers serve as active conduits for spatial propagation of cellular mechanotransduction through matrix exoskeleton, leading to efficient directed collective cell migration.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Chile.
Background: Chronic exposition to stressor factors has been postulated as a cause of structural changes in the brain in the context of dementia. One of these changes can be the fiber integrity loss, that can be measured by diffusion tensor imaging (DTI). We obtained DTI whole brain metrics to relate them with allostatic load in subjects of a chilean cohort of cognitive complaint subjects.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
City University of Hong Kong, Department of Chemistry, 83 Tat Chee Avenue, Hong Kong, HONG KONG.
Li metal batteries (LMBs), particularly with a limited Li metal anode and a 5V-class cathode, offer significantly higher energy density compared to the state-of-the-art Li-ion batteries. However, the limited Li anode poses severe challenges to cycling stability due to low efficiency and large volume expansion issues associated with Li. Herein, we design a lightweight and functionalized host composed of Sn nanoparticles embedded into necklace-like B,N,F-doped carbon macroporous fibers (Sn@B/N/F-CMFs) toward anode-less 5V-class LMBs.
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