Biology subjects

Morozov, D.

Publications and source records attributed to Morozov, D..

4 recordsLinked to original sources

bioRxiv2025

Towards MR-based interrogation of the hypoxia-driven insulin resistance mechanism: Adipocytes size estimation.

Obesity is a major risk factor for type 2 diabetes, yet not all individuals with obesity develop metabolic disease, underscoring the need for mechanistic biomarkers. Adipocyte hypertrophy is a hypothesized driver of insulin resistance, but current methods for quantifying adipocyte size are invasive. Here, we propose and validate a non-invasive MRI approach based on "short diffusion time" diffusion-weighted MR spectroscopy to estimate adipocyte size in vivo. Monte Carlo simulations confirmed the methods accuracy across a physiologic range of adipocyte sizes (20 - 150 m) and signal-to-noise ratios (SNR > 40). We applied this technique to the epididymal white adipose tissue (eWAT) of rats using in vivo 4.7T and ex vivo 11.7T MRI. Adipocyte sizes derived from diffusion MRI showed good agreement with histology, with minor systematic underestimation corrected by empirical factors. This approach does not require complex modeling or high diffusion weighting, increasing its translatability to the laboratory and clinical settings. Diffusion MRI may serve as a non-invasive "virtual biopsy" to monitor adipocyte morphology and improve understanding of obesity-related metabolic dysfunction.

bioengineering↗

bioRxiv2020

State space discovery in spatial representation circuits with persistent cohomology

Persistent cohomology is a powerful technique for discovering topological structure in data. Strategies for its use in neuroscience are still undergoing development. We comprehensively and rigorously assess its performance in simulated neural recordings of the brains spatial representation system. Grid, head direction, and conjunctive cell populations each span low-dimensional topological structures embedded in high-dimensional neural activity space. We evaluate the ability for persistent cohomology to discover these structures for different dataset dimensions, variations in spatial tuning, and forms of noise. We quantify its ability to decode simulated animal trajectories contained within these topological structures. We also identify regimes under which mixtures of populations form product topologies that can be detected. Our results reveal how dataset parameters affect the success of topological discovery and suggest principles for applying persistent cohomology, as well as persistent homology, to experimental neural recordings.

neuroscience↗

bioRxiv2020

Illuminating a Phytochrome Paradigm - a Light-Activated Phosphatase in Two-Component Signaling Uncovered

Bacterial phytochrome photoreceptors usually belong to two-component signaling systems which transmit environmental stimuli to a response regulator through a histidine kinase domain. Phytochromes switch between red light-absorbing and far-red light-absorbing states. Despite exhibiting extensive structural responses during this transition, the model bacteriophytochrome from Deinococcus radiodurans (DrBphP) lacks detectable kinase activity. Here, we resolve this long-standing conundrum by comparatively analyzing the interactions and output activities of DrBphP and a bacteriophytochrome from Agrobacterium fabrum (AgP1). Whereas AgP1 acts as a conventional histidine kinase, we identify DrBphP as a light-sensitive phosphatase. While AgP1 binds its cognate response regulator only transiently, DrBphP does so strongly, which is rationalized at the structural level. Our data pinpoint two key residues affecting the balance between kinase and phosphatase activities, which immediately bears on photoreception and two-component signaling. The opposing output activities in two highly similar bacteriophytochromes inform the use of light-controllable histidine kinases and phosphatases for optogenetics.

biochemistry↗

bioRxiv2019

The primary structural photoresponse of phytochrome proteins captured by a femtosecond X-ray laser

Phytochrome proteins control the growth, reproduction, and photosynthesis of plants, fungi, and bacteria. Light is detected by a bilin cofactor, but it remains elusive how this leads to activation of the protein through structural changes. We present serial femtosecond X-ray crystallographic data of the chromophore-binding domains of a bacterial phytochrome at delay times of 1 ps and 10 ps after photoexcitation. The structures reveal a twist of the D-ring, which lead to partial detachment of the chromophore from the protein. Unexpectedly, the conserved so-called pyrrole water is photodissociated from the chromophore, concomitant with movement of the A-ring and a key signalling aspartate. The changes are wired together by ultrafast backbone and water movements around the chromophore, channeling them into signal transduction towards the output domains. We suggest that the water dissociation is key to the phytochrome photoresponse, explaining the earliest steps of how plants, fungi and bacteria sense red light.

biophysics↗