Biology subjects

Kelmanson, I. V.

Publications and source records attributed to Kelmanson, I. V..

3 recordsLinked to original sources

bioRxiv2024

Thermogenetics for cardiac pacing

Cardiac arrhythmias are common disorders that can be fatal. Modern methods of treating bradyarrhythmias include the implantation of pacemakers and cardioverter-defibrillators. However, implantable devices can cause various complications related to the electrodes installed inside the heart, including infection. Less invasive heart rhythm modulation could be beneficial for some cohorts of patients. Here, we demonstrate an alternative approach to heart pacing based on thermogenetics. We used adeno-associated viruses to deliver genetic human transient receptor potential subfamily V member 1 (TRPV1), a heat-sensitive cation channel, into isolated cardiomyocytes and the mouse heart. This allowed us to induce action potentials and control contractility using short heat pulses delivered by infrared laser illumination. Using this approach, we demonstrated the thermogenetic pacing of isolated cardiomyocytes in vitro and in the mouse heart in vivo. Our results demonstrate the potential of thermogenetics for developing therapeutic strategies for heart rhythm modulation.

synthetic biology↗

bioRxiv2023

Non-canonical D1-D2 rearrangements are bimodal and represent a conservative hidden stage of VDJ recombination in TCR beta locus

T-cell receptor (TCR) diversity is generated by VDJ recombination. The classical course of TCR beta (TRB) chain production starts with D and J segment recombination and finishes with subsequent recombination between the resulting DJ junction and V segment. In this study, we performed deep sequencing of poorly explored incomplete TRBD1 to TRBD2 rearrangements in T-cell genomic DNA. We reconstructed full repertoires of human incomplete TRB DD rearrangements and validated its authenticity by detecting excision circles with RSS (recombination signal sequence) junctions for the first time. The identified rearrangements generated in compliance with the classical 12/23 rule are common for humans, rats, and mice and contain typical VDJ recombination footprints. Detected bimodal distribution of DD junctions indicates two active recombination sites producing long and short DD rearrangements. Unlike long DD rearrangements, the short ones have unusual origin resulting from non-canonical intrachromosomal RSSs junctions formation. Identified DD rearrangements lead to deleting J1 and C1 segments and creating diverse hybrid D segments, which recombine further with J2 and V segments. Resulting functional TRB VDDJ rearrangements are present in the memory T-cells subset proving its participation in antigen recognition.

immunology↗

bioRxiv2023

Comment on 'Connexins evolved after early chordates lost innexin diversity'

Gap junctional (GJ) intercellular channels are an important way of intercellular communication. Currently, two unrelated families of GJ proteins, innexins/pannexins, and connexins, are known, either or both of which are present in most multicellular animals. A striking exception is the echinoderms which have functional GJs but until recently were believed to be lacking both innexins and connexins, which suggests the presence of the third, yet the unknown family of GJ proteins. In the recent work Welzel and Schuster (Welzel and Schuster, 2022) have reported several putative innexins and one connexin from echinoderms, therefore undermining such a hypothesis. Here we provide evidence showing that all reported connexin and innexin sequences from echinoderms are cross-species contaminations, indicating that a search for a third GJ protein family is still a subject of immediate scientific research interest.

evolutionary biology↗