Biology subjects

Kharchenko, V.

Publications and source records attributed to Kharchenko, V..

6 recordsLinked to original sources

bioRxiv2025

Dual-Resonance Shapes REM Sleep: A Mechanistic Link Between Homeostasis, Circadian Phase, and Sleep Deficit.

How circadian and homeostatic processes interact to shape REM sleep architecture remains unresolved. Here, we empirically confirm the existence of a conserved resonance curve governing REM episode duration, as previously predicted by the wave model of sleep dynamics. This curve emerges from two converging resonance states - homeostatic and circadian - that form a stable framework across conditions. Their relative phase and amplitude determine REM structure, producing bell-shaped, linear, or bimodal profiles. The model reproduces REM dynamics during regular sleep, extension, and post-deprivation recovery. Crucially, REM duration alone provides an experimentally accessible readout: simultaneously revealing circadian phase and quantifying sleep deficit as additional hours needed to restore homeostatic equilibrium. Together, these findings reposition REM duration from a descriptive to a diagnostic marker, and a mechanistic signal, linking sleep architecture to the dynamic interplay of internal regulatory systems. Summary sentenceREM episode duration emerges as a dual readout of circadian phase and sleep deficit, reflecting the interaction of homeostatic and circadian resonance processes.

neuroscience↗

bioRxiv2025

Homeostatic Forces Shaping the Daily Pattern of Sleep Propensity.

The discrepancy between high sleep need and the ability to initiate sleep underlies insomnia, the most prevalent sleep disorder, whose nature remains obscure. Sleep need increases monotonically with prolonged wakefulness, as reflected in the rising intensity of sleep after varying wake intervals. In contrast, sleep propensity - the ability to transition from wake to sleep - follows a bimodal pattern, peaking in the mid-afternoon, dipping in the evening, and rising again near bedtime. Previously, we demonstrated that sleep structure dynamics can be effectively modeled using probability waves. Here, we extend this wave model of homeostatic regulation of sleep to the period of wakefulness and show that its extrapolation predicts the bimodal pattern of wake-to-sleep transitions. This pattern arises from the interplay of two key factors in state transitions: wake-state instability and interaction strength between states. While wake-state instability increases monotonically, interaction strength follows a bimodal pattern. Their combined effect produces a bimodal probability of state transitions, aligning closely with experimental data. The mid-afternoon peak corresponds to maximal interaction at the homeostatic equilibrium of sleep and wake states, whereas the evening dip reflects minimal interaction, counteracting high wake-state instability. An exponential rise in both factors by the end of the day facilitates sleep onset at bedtime. Our experimental findings on sleep deprivation support the model predictions. Understanding the relationship between sleep need and ability to initiate sleep may offer valuable insights for optimizing daytime performance and sleep quality in both health and disease. Statement of significanceMonotonic increase in sleep need throughout the day contrasts sharply with the bimodal pattern of the ability to fall asleep, referred to as sleep propensity. This phenomenon, inherent to normal sleep physiology, may also underlie major insomnias - inability to fall asleep despite high sleep need. We applied the wave model of sleep dynamics to unveil how the bimodal daily sleep propensity pattern can emerge from the non-linear changes in homeostatic strength of interaction between the wake and sleep states.

neuroscience↗

bioRxiv2023

Invariant relationship unites REM and NonREM sleep.

Establishing structural and functional links between two distinct types of sleep, rapid-eye-movement (REM) and non-REM (NREM), that alternate and form several sleep cycles per night, has posed a significant challenge. Here we demonstrate a simple invariant relationship where the product of the duration of NREM sleep episode and intensity of subsequent REM sleep episode remains constant over successive sleep cycles of normal human sleep. This Sleep Cycle Invariant (SCI), previously predicted by a quantitative model of sleep dynamics, supports the structural and functional unity of NREM and REM sleep. The significance of SCI for understanding normal sleep and sleep disorders is highlighted by alterations in REM sleep intensity and NREM sleep episode duration being a hallmark of major depression. One-Sentence SummaryThe duration of NREM sleep and intensity of REM sleep have an invariant relationship across normal sleep cycles of one night.

neuroscience↗

bioRxiv2022

Zinc ions prevent a-synuclein aggregation by enhancingchaperone function of human serum albumin

Metal ions present in cellular microenvironment have been implicated as drivers of aggregation of amyloid forming proteins. Zinc (Zn2+) ions have been reported to directly interact with -synuclein (AS), a causative agent of Parkinsons disease and other neurodegenerative diseases, and promote its aggregation. AS is a small intrinsically disordered protein (IDP) i.e., understanding molecular factors that drive its misfolding and aggregation has been challenging since methods used routinely to study protein structure are not effective for IDPs. Here, we report the atomic details of Zn2+ binding to AS at physiological conditions using proton-less NMR techniques that can be applied to highly dynamic systems like IDPs. We also examined how human serum albumin (HSA), the most abundant protein in human blood, binds to AS and whether Zn2+ and/or ionic strength affect this. We conclude that Zn2+ enhances the anti-aggregation chaperoning role of HSA that relies on protecting the hydrophobic N-terminal and NAC regions of AS, rather than polar negatively charged C-terminus. This suggested a previously undocumented role of Zn2+ in HSA function and AS aggregation.

biophysics↗

bioRxiv2021

Molecular basis of UHRF1 allosteric activation for synergistic histone modification binding by PI5P

Chromatin marks are recognized by distinct binding modules many of which are embedded in multidomain proteins or complexes. How the different protein functionalities of complex chromatin modulators are regulated is often unclear. Using a combination of biochemical, biophysical and structural approaches we delineated the regulation of the H3unmodified and H3K9me binding activities of the multidomain UHRF1 protein. The phosphoinositide PI5P interacts with two distant flexible linker regions of UHRF1 in a mode that is dependent on the polar head group and the acyl part of the phospholipid. The associated conformational rearrangements stably position the H3unmodified and H3K9me3 histone recognition modules of UHRF1 for multivalent and synergistic binding of the H3 tail. Our work highlights a novel molecular function for PI5P outside of the context of lipid mono- or bilayers and establishes a molecular paradigm for the allosteric regulation of complex, multidomain chromatin modulators by small cellular molecules.

biochemistry↗

bioRxiv2020

Molecular Basis for the Adaptive Evolution of Environment Sensing by H-NS Proteins

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression, and hence toxicity and biological responses, to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less NMR spectroscopy and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the mechanism for H-NS-mediated environmental sensing and suggests that it resulted from the exaptation of an ancestral protein feature.

biochemistry↗