How cells respond to dynamic environmental changes is crucial for understanding fundamental biological processes and cell physiology. In this study, we developed an experimental and quantitative analytical framework to explore how dynamic stress gradients that change over time regulate cellular volume, signaling activation, and growth phenotypes. Our findings reveal that gradual stress conditions substantially enhance cell growth compared to conventional acute stress. This growth advantage correlates with a minimal reduction in cell volume dependent on the dynamic of stress. We explain the growth phenotype with our finding of a logarithmic signal transduction mechanism in the yeast Mitogen-Activated Protein Kinase (MAPK) osmotic stress response pathway. These insights into the interplay between gradual environments, cell volume change, dynamic cell signaling, and growth, advance our understanding of fundamental cellular processes in gradual stress environments.
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http://dx.doi.org/10.1101/2023.12.05.570188 | DOI Listing |
Viruses
December 2024
Department of Microbiology, Virology, and Immunology, I. Horbachevsky Ternopil National Medical University, 46001 Ternopil, Ukraine.
Metformin, a widely used antidiabetic medication, has emerged as a promising broad-spectrum antiviral agent due to its ability to modulate cellular pathways essential for viral replication. By activating AMPK, metformin depletes cellular energy reserves that viruses rely on, effectively limiting the replication of pathogens such as influenza, HIV, SARS-CoV-2, HBV, and HCV. Its role in inhibiting the mTOR pathway, crucial for viral protein synthesis and reactivation, is particularly significant in managing infections caused by HIV, CMV, and EBV.
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December 2024
Department of Biological Sciences, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606, USA.
During virus infection, the activation of the antiviral endoribonuclease, ribonuclease L (RNase L), by a unique ligand 2'-5'-oilgoadenylate (2-5A) causes the cleavage of single-stranded viral and cellular RNA targets, restricting protein synthesis, activating stress response pathways, and promoting cell death to establish broad antiviral effects. The immunostimulatory dsRNA cleavage products of RNase L activity (RL RNAs) recruit diverse dsRNA sensors to activate signaling pathways to amplify interferon (IFN) production and activate inflammasome, but the sensors that promote cell death are not known. In this study, we found that DEAH-box polypeptide 15 (DHX15) and retinoic acid-inducible gene I (Rig-I) are essential for apoptosis induced by RL RNAs and require mitochondrial antiviral signaling (MAVS), c-Jun amino terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK) for caspase-3-mediated intrinsic apoptosis.
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November 2024
Laboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, Argentina.
, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the family. In dogs (), common signs of infection include conjunctivitis, digital hyperkeratosis and neuropathologies. Even with vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes have been an interesting and promising area in new therapeutic drugs research in recent years.
View Article and Find Full Text PDFVaccines (Basel)
December 2024
College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, especially when it involves the central nervous system (CNS). Tuberculous meningitis (TBM), a severe manifestation of TB, is linked to high mortality rates and long-term neurological complications, further exacerbated by drug resistance and immune evasion mechanisms employed by Mycobacterium tuberculosis (Mtb). Although pulmonary TB remains the primary focus of research, MDR-TBM introduces unique challenges in diagnosis, treatment, and patient outcomes.
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November 2024
Department of Social and Environmental Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Background/objectives: Although the protective effects of zinc against COVID-19 are documented, its impact on COVID-19 vaccine immunogenicity remains unknown.
Methods: We conducted a prospective study involving a cohort of 79 Japanese individuals (aged 21-56 years; comprising three subcohorts) and measured their serum zinc levels pre-vaccination and anti-SARS-CoV-2 IgM/IgG levels pre- and post-vaccination over 4 months.
Results: Serum zinc concentrations ranged between 74-140 and 64-113 μg/dL in male and female individuals, respectively, with one male and 11 female participants exhibiting subclinical zinc deficiency (60-80 μg/dL).
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