Purpose: The purpose of the study was to investigate the effect of γ,n-irradiation of the mouse head on the brain cells damage, behavior, and cognition and to examine the possibility of using lactoferrin (LF) to alleviate radiation-induced impairments.
Materials And Methods: Mouse heads were irradiated in a beam of neutrons and gamma rays from the IR-8 nuclear reactor. The brain cells of control and irradiated mice were isolated using Percoll.
The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function.
View Article and Find Full Text PDFNeurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), represent debilitating conditions with complex, poorly understood pathologies. Epichaperomes, pathologic protein assemblies nucleated on key chaperones, have emerged as critical players in the molecular dysfunction underlying these disorders. In this study, we introduce the synthesis and characterization of clickable epichaperome probes, PU-TCO, positive control, and PU-NTCO, negative control.
View Article and Find Full Text PDFThis manuscript explores the intricate role of acetylcholine-activated inward rectifier potassium (K) channels in the pathogenesis of atrial fibrillation (AF), a common cardiac arrhythmia. It delves into the molecular and cellular mechanisms that underpin AF, emphasizing the vital function of K channels in modulating the atrial action potential and facilitating arrhythmogenic conditions. This study underscores the dual nature of K activation and its genetic regulation, revealing that specific variations in potassium channel genes, such as Kir3.
View Article and Find Full Text PDFThe intricate protein-chaperone network is vital for cellular function. Recent discoveries have unveiled the existence of specialized chaperone complexes called epichaperomes, protein assemblies orchestrating the reconfiguration of protein-protein interaction networks, enhancing cellular adaptability and proliferation. This study delves into the structural and regulatory aspects of epichaperomes, with a particular emphasis on the significance of post-translational modifications in shaping their formation and function.
View Article and Find Full Text PDFIon channels activity is regulated through soluble guanylate cyclase (sGC) and adenylate cyclase (AC) pathways, while phosphodiesterases (PDE) control the intracellular levels of cAMP and cGMP. Here we applied RNA transcriptome sequencing to study changes in the gene expression of the sGC, AC, and PDE isoforms in isolated rat ventricular cardiomyocytes under conditions of microgravity and hypergravity. Our results demonstrate that microgravity reduces the expression of sGC isoform genes, while hypergravity increases their expression.
View Article and Find Full Text PDFThe mechanoelectrical feedback in the heart is based on the work of mechanically gated (MGCs) and mechanosensitive (MSCs) channels. Since microgravity alters the heart's morphological and physiological properties, we hypothesized that the expression of both MGCs and MSCs would be affected. We employed RNA transcriptome sequencing to investigate changes in the gene transcript levels of MGCs and MSCs in isolated rat ventricular cardiomyocytes under control conditions and in a simulated microgravity environment.
View Article and Find Full Text PDFNanomaterials (Basel)
December 2023
Coherent spin dynamics of electrons in CdSe colloidal nanoplatelets are investigated by time-resolved pump-probe Faraday rotation at room and cryogenic temperatures. We measure electron spin precession in a magnetic field and determine -factors of 1.83 and 1.
View Article and Find Full Text PDFSince hypergravity changes the morphological and physiological properties of the heart, it was assumed that the expression of ion channels that respond to cell stretching or compressing, mechanically gated channels (MGC) and mechanosensitive channels (MSC), would be affected. Using RNA transcriptome sequencing, the change in the number of transcripts for MGC and MSC genes was studied in isolated rat ventricular cardiomyocytes under 4g hypergravity for 5 days. It was shown for the first time that hypergravity induces changes in the number of transcripts of MGC genes: an increase for TRPC1, TRPC3, TRPM7, TRPP1 (PKD1), TRPP2 (PKD2), TMEM63A, TMEM63B, but a decrease for TRPV2, Piezo1, Piezo2.
View Article and Find Full Text PDFBackground: The study aimed to identify transcripts of specific ion channels in rat ventricular cardiomyocytes and determine their potential role in the regulation of ionic currents in response to mechanical stimulation. The gene expression levels of various ion channels in freshly isolated rat ventricular cardiomyocytes were investigated using the RNA-seq technique. We also measured changes in current through Ca1.
View Article and Find Full Text PDFBull Exp Biol Med
September 2023
Parameters of non-spatial and spatial memory were evaluated in sexually mature offspring of outbred rats (females and males F0) consuming a 10% ethanol solution for 30 weeks before mating. We found a significant increase in the recognition index in F1 males and its decrease in F1 females in the novel object recognition test. During the first days of the experiment in T-maze, a decrease in spatial memory was revealed in F1 males, which remained at the trend level until the end of testing; no significant deviations were detected in F1 females.
View Article and Find Full Text PDFUnder normal conditions, heat shock proteins work in unison through dynamic protein interactions collectively referred to as the "chaperome." Recent work revealed that during cellular stress, the functional interactions of the chaperome are modified to form the "epichaperome," which results in improper protein folding, degradation, aggregation, and transport. This study is the first to investigate this novel mechanism of protein dishomeostasis in traumatic brain injury (TBI).
View Article and Find Full Text PDFOptical alignment and optical orientation of excitons are studied experimentally on an ensemble of core/shell CdSe/CdS colloidal nanoplatelets. Linear and circular polarization of photoluminescence during resonant excitation of excitons is measured at cryogenic temperatures and with magnetic fields applied in the Faraday geometry. The developed theory addresses the optical alignment and optical orientation of excitons in colloidal nanocrystals, taking into account both bright and dark exciton states in the presence of strong electron-hole exchange interaction and the random in-plane orientation of nanoplatelets within the ensemble.
View Article and Find Full Text PDFEpichaperomes are disease-associated pathologic scaffolds, composed of tightly bound chaperones, co-chaperones, and other factors. They mediate anomalous protein-protein interactions inside cells, which aberrantly affects the function of protein networks, and in turn, cellular phenotypes. Epichaperome study necessitates the implementation of methods that retain these protein complexes in their native cellular states for analysis.
View Article and Find Full Text PDFSystems-level assessments of protein-protein interaction (PPI) network dysfunctions are currently out-of-reach because approaches enabling proteome-wide identification, analysis, and modulation of context-specific PPI changes in native (unengineered) cells and tissues are lacking. Herein, we take advantage of chemical binders of maladaptive scaffolding structures termed epichaperomes and develop an epichaperome-based 'omics platform, epichaperomics, to identify PPI alterations in disease. We provide multiple lines of evidence, at both biochemical and functional levels, demonstrating the importance of these probes to identify and study PPI network dysfunctions and provide mechanistically and therapeutically relevant proteome-wide insights.
View Article and Find Full Text PDFProtein-assembly defects due to an enrichment of aberrant conformational protein variants are emerging as a new frontier in therapeutics design. Understanding the structural elements that rewire the conformational dynamics of proteins and pathologically perturb functionally oriented ensembles is important for inhibitor development. Chaperones are hub proteins for the assembly of multiprotein complexes and an enrichment of aberrant conformers can affect the cellular proteome, and in turn, phenotypes.
View Article and Find Full Text PDFPurpose: Currently there are no effective diagnostic methods for the control of neuroinflammation before manifestation of cognitive impairment after head irradiation. The translocator protein (TSPO) is highly expressed in glial cells upon brain damage, therefore we compared the changes in the number of cells with high TSPO expression in the brain and peripheral blood during radiation-induced neuroinflammation.
Materials And Methods: Hippocampal cytokines mRNA expression and the content of cells with high TSPO expression in the brain and peripheral blood monocytes were analyzed up to eight months after mice head γ-irradiation at a dose of 2 Gy or 8Gy.
In this paper, we studied the role of the crystal structure in spheroidal CdSe nanocrystals on the band-edge exciton fine structure. Ensembles of zinc blende and wurtzite CdSe nanocrystals are investigated experimentally by two optical techniques: fluorescence line narrowing (FLN) and time-resolved photoluminescence. We argue that the zero-phonon line evaluated by the FLN technique gives the ensemble-averaged energy splitting between the lowest bright and dark exciton states, while the activation energy from the temperature-dependent photoluminescence decay is smaller and corresponds to the energy of an acoustic phonon.
View Article and Find Full Text PDFThe coherent spin dynamics of electrons in CdSe nanocrystals embedded in a glass matrix with diameters from 3.3 up to 6.1 nm are investigated by time-resolved Faraday ellipticity at room and cryogenic temperatures.
View Article and Find Full Text PDFThe 3D reconstruction of 100 μm- and 600 μm-thick fibrous poly-L/L-lactide scaffolds was performed by confocal laser scanning microscopy and supported by scanning electron microscopy and showed that the density of the fibers on the side adjacent to the electrode is higher, which can affect cell diffusion, while the pore size is generally the same. Bone marrow mesenchymal stem cells cultured in a 600 μm-thick scaffold formed colonies and produced conditions for cell differentiation. An in vitro study of stem cells after 7 days revealed that cell proliferation and hepatocyte growth factor release in the 600 μm-thick scaffold were higher than in the 100 μm-thick scaffold.
View Article and Find Full Text PDFAcute-on-chronic liver failure (ACLF) of varying grades was assessed in 110 patients with alcoholic liver cirrhosis using the on-line CLIF-C ACLF Calculator ( www.efclif.com/scientific-activity/score-calculators/clif-c-aclf ); fragments of cytokeratin-18, TNFα, IL-1β, IL-4, IL-6, and IL-8 were also assayed.
View Article and Find Full Text PDFWhile initial theories on quantum confinement in colloidal quantum dots (QDs) led to analytical band gap/size relations or sizing functions, numerical methods describe size quantization more accurately. However, because of the lack of reliable sizing functions, researchers fit experimental band gap/size data sets using models with redundant, physically meaningless parameters that break down upon extrapolation. Here, we propose a new sizing function based on a proportional correction for nonparabolic bands.
View Article and Find Full Text PDFCancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours.
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