Actively growing cells maintain a dynamic, far from equilibrium order through metabolism. Under starvation stress or under stress of exposure to the analog of the anabiosis autoinducer (4-hexylresorcinol), cells go into a dormant state (almost complete lack of metabolism) or even into a mummified state. In a dormant state, cells are forced to use the physical mechanisms of DNA protection. The architecture of DNA in the dormant and mummified state of cells was studied by x-ray diffraction of synchrotron radiation and transmission electron microscopy (TEM). Diffraction experiments indicate the appearance of an ordered organization of DNA. TEM made it possible to visualize the type of DNA ordering. Intracellular nanocrystalline, liquid-crystalline, and folded nucleosome-like structures of DNA have been found. The structure of DNA within a cell in an anabiotic dormant state and dormant state (starvation stress) coincides (forms nanocrystalline structures). Data suggest the universality of DNA condensation by a protein Dps for a dormant state, regardless of the type of stress. The mummified state is very different in structure from the dormant state (has no ordering within a cell). It turned out that it is possible to visualize DNA conformation in toroidal and liquid crystal structures in which there is either no or a very small amount of the Dps protein. Observation of the DNA conformation in nanocrystals and folded nucleosome-like structures so far has been inconclusive. The methodological advances described will facilitate high-resolution visualization of the DNA conformation in the near future.
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http://dx.doi.org/10.1007/s12551-023-01122-0 | DOI Listing |
Prostate cancer (PCa) is mainly managed with androgen deprivation therapy (ADT), but this often leads to a dormant state and subsequent relapse as lethal castration-resistant prostate cancer (CRPC). Using our unique PCa patient-derived xenograft (PDX) dormancy models, we investigated this critical dormant phase and discovered a selective increase in B7-H4 expression during the dormancy period following mouse host castration. This finding is supported by observations in clinical specimens of PCa patients treated with ADT.
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January 2025
Children's Hospital of Philadelphia & University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States.
Philadelphia chromosome-like B-cell acute lymphoblastic leukemia (Ph-like ALL) is driven by genetic alterations that induce constitutive kinase signaling and is associated with chemoresistance and high relapse risk in children and adults. Preclinical studies in the most common CRLF2-rearranged/JAK pathway-activated Ph-like ALL subtype have shown variable responses to JAK inhibitor-based therapies, suggesting incomplete oncogene addiction and highlighting a need to elucidate alternative biologic dependencies and therapeutic vulnerabilities, while the ABL-class Ph-like ALL subtype appears preferentially sensitive to SRC/ABL- or PDGFRB-targeting inhibitors. Which patients may be responsive versus resistant to tyrosine kinase inhibitor (TKI)-based precision medicine approaches remains a critical knowledge gap.
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January 2025
U.S. Geological Survey, Geology, Minerals, Energy, and Geophysics Science Center, Moffett Field, Moffett Field, California, USA.
Climate change is inducing wide-scale permafrost thaw in the Arctic and subarctic, triggering concerns that long-dormant pathogens could reemerge from the thawing ground and initiate epidemics or pandemics. Viruses, as opposed to bacterial pathogens, garner particular interest because outbreaks cannot be controlled with antibiotics, though the effects can be mitigated by vaccines and newer antiviral drugs. To evaluate the potential hazards posed by viral pathogens emerging from thawing permafrost, we review information from a diverse range of disciplines.
View Article and Find Full Text PDFCancer Cell Int
January 2025
Department of Otolaryngology, Pudong Gongli Hospital, Shanghai, 200135, China.
Background: Specific molecular mechanisms by which AURKA promoted LSCC metastasis were still unknown.
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Nat Commun
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Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production.
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