Biology subjects

Sokolova, O.

Publications and source records attributed to Sokolova, O..

5 recordsLinked to original sources

bioRxiv2026

THE ROLE OF LIQUID CRYSTAL ORDERING IN THE STRUCTURAL ORGANIZATION OF DNA IN BACTERIA.

This paper presents and critically reviews the results of original and some literature based experimental studies conducted by the authors last years on the structural organization of DNA in dormant (starvation stress), anabiotic dormant (4 HR treatment) E. coli cells, as well as the K12 {Delta}dps strain, which lacks the Dps protein (Dps null E. coli). The experimental data includes small-angle synchrotron radiation diffraction (SAXS) and transmission electron microscopy (TEM) data. Synchrotron radiation diffraction experiments on K12{Delta}dps cells allowed us to conclude that peaks at 44.3, 22.1, and 14.8 angstrom resolutions are associated exclusively with ordered DNA organization. Peaks at 44.3, 22.1, and 14.8 angstrom resolutions are also observed for samples of dormant (starvation stress) cells and anabiotically dormant cells. Therefore, this ordered DNA organization also applies to samples of dormant and anabiotically dormant cells. A model is proposed that considers the ordered DNA organization in the cell as a cholesteric liquid crystal. The powder diffraction pattern calculated based on this model is compared with experimental small angle X ray scattering (SAXS) data obtained on Dps-null cell samples. The model completely reproduces the key features of the experimental diffraction pattern from Dps-null cell samples. Accordingly, the cholesteric liquid crystal model corresponds to DNA packaging in dormant and anabiotically dormant cells. Cholesteric liquid crystal ordering should be further considered in all models of cellular DNA packaging. To address the question of which structural organization of DNA predominates in the cell: the cholesteric liquid crystal or nanocrystalline or whether they coexist and fully manifest themselves under different external conditions, it is necessary to utilize the latest methodological advances in structural analysis.

biophysics↗

bioRxiv2026

Mitigation of imprinted antibody responses in elderly COVID-19 highly vaccinated individuals

SARS-CoV-2 continues to evolve from the Omicron serotype, with BA.2.86 sublineage JN.1 and descendants predominating in 2025-26 and recent emergence of the highly divergent BA.3.2 saltation variant. Elderly individuals continue to be at greatest risk of clinical complications from COVID-19, yet contemporary data on kinetics of immune potency and breadth following multiple vaccinations remain limited in this group. We studied a cohort of forty-three healthy older adults (median age = 85 years, IQR 75-88, 40% female). Using both pseudotyped virus (PVNT) and surrogate virus (SVNT) neutralization-based assays, we demonstrate that JN.1 and KP.2 vaccinations six months apart elicit high potency neutralization across all studied variants except BA.3.2.2, where titres were around 2-3 fold lower. Waning of serum neutralizing activity was modest between vaccine doses, suggesting sustained immunity following multiple vaccines. Importantly, the half-life of serum neutralization against Wu-1 (179 days) was substantially longer compared to JN.1 subvariants (43.7-70.1days), consistent with imprinted and longer-lived Wu-1-specific responses. Furthermore, half-life for BA.3.2.2 neutralisation was prolonged at 107 days compared to JN.1 subvariants, implicating imprinted ancestral variant targeting antibodies in neutralization of this saltation variant. While absolute neutralization titers remained highest against ancestral Wu-1 at all timepoints due to multiple historical exposures and accumulation, the recall responses after the recent KP.2 vaccine revealed a shift in immunodominance: neutralization against full-length Wu-1 spike was not boosted, whereas all tested JN.1 descendants and BA.3.2.2 showed significant boosts, indicating that immune imprinting against ancestral Wu-1 was partially overcome. These data indicate that in the elderly, protective neutralizing antibody responses against recent VOC can be achieved, with alleviation of immune imprinting and reduction of waned responses through biannual, strain-updated booster vaccines. Imprinted antibodies against ancestral pre Omicron variants may still be relevant for protection against further highly immune evasive variants such as BA.3.2.2, highlighting that careful characterisation of population level COVID-19 humoral immunity is still warranted.

microbiology↗

bioRxiv2022

Mechanism of Curaxin-dependent Nucleosome Unfolding by FACT

Human FACT (FACT) is a multifunctional histone chaperone involved in transcription, replication and DNA repair. Curaxins are anticancer compounds that induce FACT- dependent nucleosome unfolding and trapping of FACT in the chromatin of cancer cells (c-trapping) through an unknown molecular mechanism. Here, we analyzed the effects of curaxin CBL0137 on nucleosome unfolding by FACT using spFRET and electron microscopy. By itself, FACT adopted multiple conformations, including a novel, compact, four-domain state in which the previously unresolved NTD of the SPT16 subunit of FACT was localized, apparently stabilizing a compact configuration. Multiple, primarily open conformations of FACT-nucleosome complexes were observed during curaxin-supported nucleosome unfolding. The structures of intermediates suggest "decision points" in the unfolding/folding pathway where FACT can either promote disassembly or assembly of nucleosomes, with the outcome possibly being influenced by additional factors. The data suggest novel mechanisms of nucleosome unfolding by FACT and c-trapping by curaxins.

cancer biology↗

bioRxiv2020

Morphological peculiarities of DNA-protein complexes in dormant Escherichia coli cells, subjected to prolonged starvation

One of the adaptive strategies for the constantly changing conditions of the environment utilized in bacterial cells involves the condensation of DNA in complex with the DNA-binding protein, Dps. With the use of electron microscopy and electron tomography, we observed several morphologically different types of DNA condensation in dormant Escherichia coli cells, namely: nanocrystalline, liquid crystalline, and the folded nucleosome-like. We confirmed the presence of both Dps and DNA in all of the ordered structures using EDX analysis. The comparison of EDX spectra obtained for the three different ordered structures revealed that in nanocrystalline formation the majority of Dps protein is tightly bound to nucleoid DNA. We demonstrated that the population of the dormant cell is structurally heterogeneous, which allows cells to respond flexibly to environmental changes. It increases the ability of the whole bacterial population to survive under extreme stress conditions.

cell biology↗

bioRxiv2017

ALPK1 And TIFA Dependent Innate Immune Response Triggered By The Helicobacter Pylori Type IV Secretion System

Activation of transcription factor NF-{kappa}B is a hallmark of infection with the gastric pathogen Helicobacter pylori and associated with inflammation and carcinogenesis. Genome-wide RNAi screening revealed numerous hits involved in H. pylori-, but not IL-1{beta}- and TNF-- dependent NF-{kappa}B regulation. Pathway analysis including CRISPR/Cas9-knockout and recombinant protein technology, immunofluorescence microscopy, immunoblotting, mass spectrometry and mutant H. pylori strains, identified the H. pylori metabolite D-glycero-{beta}-D-manno-heptose 1,7-bisphosphate ({beta}HBP) as a cagPAI type IV secretion system (T4SS)-dependent effector of NF-{kappa}B activation in infected cells. Upon pathogen-host cell contact, TIFA forms large complexes (TIFAsomes) including interacting host factors, such as TRAF2. NF-{kappa}B activation, TIFA phosphorylation as well as TIFAsome formation depended on a functional ALPK1 kinase, highlighting the ALPK1-TIFA axis as core of a novel innate immune pathway. ALPK1-TIFA-mediated NF-{kappa}B activation was independent of CagA protein translocation, indicating that CagA translocation and HBP delivery to host cells are distinct features of the pathogens T4SS.

molecular biology↗