Biology subjects

Popov, P.

Publications and source records attributed to Popov, P..

4 recordsLinked to original sources

bioRxiv2026

Neuronal avalanches in awake macaque V1 and V4

Neuronal avalanches are cascades of synchronised activity whose sizes follow power law. Analyses of avalanches shed light on cortical dynamics operating near a critical point. In awake monkeys, avalanches were found in motor and premotor cortex, where they are invariant to temporal binning, detection threshold and the number of electrodes employed. Whether awake primate early visual cortex, which receives strong structured afferent drive, shares these properties has not been tested. We analyzed a public 1,024-channel resting-state dataset from V1 and V4 of two macaques. In both animals avalanche sizes followed power laws over more than 10-fold range, the exponent scaled with bin width as alpha proportional to delta-t to the power beta (beta = -0.045 and -0.031), and the distributions ended at a cutoff proportional to the number of electrodes analysed. Raising the detection threshold from 1.5 to 4.5 standard deviations (SDs) removed over 99% of events but changed alpha by only 0.02-0.05 per SD, whereas randomly removing the same events destroyed the power law. Per-electrode shuffling abolished all heavy tails. Eye closure shifted alpha, beta and the branching ratio by less than predefined equivalence bounds, far below the reproducible differences between recording sites. Avalanche organisation therefore extends to awake early visual cortex.

neuroscience↗

bioRxiv2026

Deep in vivo brain metabolomics maps vulnerability-associated and cocaine-induced neurochemical states

Innate temperament affects vulnerability to substance use disorders (SUDs). Identifying the neurochemistry that differentiates temperaments, alongside the metabolic impact of drugs of abuse, can provide new insights into pathways to SUD and treatments. We show that heritable emotional temperaments associated with SUD vulnerability are encoded by distinct extracellular neurochemical states in the living brain. We apply untargeted metabolomics to microdialysis samples to define the chemical composition of the living brain metabolome with unprecedented depth. Using two phenotypes from a rodent model of diverging temperaments linked to SUDs, dialysate samples were collected before and after acute exposure to cocaine (15 mg/kg, i.p.). Metabolomic analysis revealed previously unknown basal differences in stress-response, bioenergetics, and amino acid neurotransmitters and their related pathways between the two phenotypes. Cocaine administration also had a profound impact on the metabolome, altering amino acid, purine, and arachidonic acid pathways along with cognition-related metabolites. Despite these broad metabolomic changes, cocaine administration narrowed several pre-existing differences between phenotypes, highlighting divergent responses across genetic lines. These findings demonstrate that in vivo metabolomics not only offers novel insights into the neurochemistry underlying temperament and drug response but also serves as framework to advance a systems-level understanding of other brain-related disorders.

neuroscience↗

bioRxiv2022

Structural basis for receptor selectivity and inverse agonism in S1P5 receptors

The bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PR) - S1P1-5. S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads to side effects. In this article, we describe a 2.2 [A] resolution room temperature crystal structure of the human S1P5 receptor in complex with a selective inverse agonist determined by serial femtosecond crystallography (SFX) at the Pohang Accelerator Laboratory X-Ray Free Electron Laser (PAL-XFEL) and analyze its structure-activity relationship data. The structure demonstrates a unique ligand-binding mode, involving an allosteric subpocket, which clarifies the receptor subtype selectivity and provides a template for structure-based drug design. Together with previously published S1PR structures in complex with antagonists and agonists, the new S1P5-inverse agonist structure sheds light on the activation mechanism and reveals structural determinants of the inverse agonism in the S1PR-family.

biophysics↗

bioRxiv2020

Spatiotemporal identification of druggable binding sites using deep learning

Identification of novel protein binding sites expands < > and opens new opportunities for drug discovery. Generally, presence or absence of a binding site depends on the three-dimensional conformation of a protein, making binding site identification resemble to object detection problem in computer vision. Here we introduce a computational approach for the large-scale detection of protein binding sites, named BiteNet, that considers protein conformations as the 3D-images, binding sites as the objects on these images to detect, and conformational ensembles of proteins as the 3D-videos to analyze. BiteNet is suitable for spatiotemporal detection of hard-to-spot allosteric binding sites, as we showed for conformation-specific binding site of the epidermal growth factor receptor, oligomer-specific binding site of the ion channel, and binding sites in G protein-coupled receptors. BiteNet outperforms state-of-the-art methods both in terms of accuracy and speed, taking about 1.5 minute to analyze 1000 conformations of a protein with 2000 atoms. BiteNet is available at https://github.com/i-Molecule/bitenet.

bioinformatics↗