Biology subjects

Bogdanov, A.

Publications and source records attributed to Bogdanov, A..

6 recordsLinked to original sources

bioRxiv2026

Quantum transduction from electron spin state to a signaling state in a wild-type LOV photoreceptor

1Whether coherent spin dynamics can control biological regulation remains an open question. Here we show that the electron spin state in the wild-type Avena sativa phototropin 1 Light-Oxygen-Voltage domain 2 (AsLOV2) modulates FMN-cysteine photoadduct formation, the covalent bond that defines its signaling state. Although AsLOV2 was thought magnetically inactive, we observe a magnetic field effect (MFE) on its fluorescence, emerging above ~100 mT and strengthening to 1300 mT. The MFE establishes a spin-correlated radical pair on the photoadduct pathway, one rendered inaccessible to direct spectroscopy by the same strong coupling that sets the high-field onset. It arises from g-factor asymmetry within the closely spaced FMN-cysteine radical pair overcoming its dipolar coupling to drive coherent singlet-triplet interconversion. We furthermore observe an MFE in UV-Vis absorption that, unlike fluorescence, shows the field modulates productive bond formation itself. LOV domains are ubiquitous biological regulators, suggesting that quantum transduction relying on radical pairs as molecular qubits may be a general property among natural and engineered photoreceptors.

biophysics↗

bioRxiv2025

The forbidden doubling: exploring rare spermatocyte polyploidy in mammals

We studied rare cases of over-ploid spermatocytes using advanced immunocytochemical methods and a cross-species approach for the first time. In subterranean rodents Ellobius tancrei, E. alaicus, E. talpinus, and Nannospalax leucodon tetraploid spermatocytes exhibited specific features during meiotic prophase I, including symmetric and asymmetric chromosome quadrivalents with partner-switching, extended asynapsis, altered recombination patterns, and variable chromatin inactivation. Notably, the quadrivalents were capable of assembling shelterin complexes at chromosome ends, which are connected to the nuclear envelope through the SUN-KASH complex as in normal spermatocytes. Anomalies suggest that meiotic checkpoints potentially triggered by failed synapsis or incomplete sex chromosome silencing may act to prevent the progression of polyploid spermatocytes.

genetics↗

bioRxiv2024

Pattern-based genome mining guides discovery of the antibiotic indanopyrrole A from a marine streptomycete.

Terrestrial actinomycetes in the genus Streptomyces have long been recognized as prolific producers of small molecule natural products, including many clinically important antibiotics and cytotoxic agents. Although Streptomyces can also be isolated from marine environments, their potential for natural product biosynthesis remains underexplored. The MAR4 clade of largely marine-derived Streptomyces has been a rich source of novel halogenated natural products of diverse structural classes. To further explore the biosynthetic potential of this group, we applied pattern-based genome mining leading to the discovery of the first halogenated pyrroloketoindane natural products, indanopyrrole A (1) and B (2), and the bioinformatic linkage of these compounds to an orphan biosynthetic gene cluster (BCG) in 20 MAR4 genomes. Indanopyrrole A displays potent broad-spectrum antibiotic activity against clinically relevant pathogens. A comparison of the putative indanopyrrole BGC with that of the related compound indanomycin provides new insights into the terminal cyclization and offloading mechanisms in pyrroloketoindane biosynthesis. Broader searches of public databases reveal the rarity of this BGC while also highlighting opportunities for discovering additional compounds in this uncommon class. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/620887v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@14d6080org.highwire.dtl.DTLVardef@fa89b5org.highwire.dtl.DTLVardef@66fdddorg.highwire.dtl.DTLVardef@1a4f7f9_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2023

Cell-penetrating peptide and cationic liposomes mediated siRNA delivery to arrest growth of chronic myeloid leukemia cells in vitro

Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs against BCR-ABL, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model. The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2X3-DOPE-DSPE-PEG2000 (0.62% mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

molecular biology↗

bioRxiv2023

Small Molecule in situ Resin Capture - an Organism Independent Strategy for Natural Product Discovery.

Microbial natural products remain an important resource for drug discovery. Yet, commonly employed discovery techniques are plagued by the rediscovery of known compounds, the relatively few microbes that can be cultured, and laboratory growth conditions that do not elicit biosynthetic gene expression among myriad other challenges. Here we introduce a culture independent approach to natural product discovery that we call the Small Molecule In situ Resin Capture (SMIRC) technique. SMIRC exploits in situ environmental conditions to elicit compound production and represents a new approach to access poorly explored chemical space by capturing natural products directly from the environments in which they are produced. In contrast to traditional methods, this compound-first approach can capture structurally complex small molecules across all domains of life in a single deployment while relying on Nature to provide the complex and poorly understood environmental cues needed to elicit biosynthetic gene expression. We illustrate the effectiveness of SMIRC in marine habitats with the discovery of numerous new compounds and demonstrate that sufficient compound yields can be obtained for NMR-based structure assignment. Two new compound classes are reported including one novel carbon skeleton that possesses a functional group not previously observed among natural products and a second that possesses potent biological activity. We introduce expanded deployments, in situ cultivation, and metagenomics as methods to facilitate compound discovery, enhance yields, and link compounds to producing organisms. This compound first approach can provide unprecedented access to new natural product chemotypes with broad implications for drug discovery. Significance StatementPharmaceutically relevant microbial natural products have traditionally been discovered using a microbe-first approach in which bioassays are used to guide the isolation of active compounds from crude culture extracts. While once productive, it is now widely recognized that this approach fails to access the vast chemical space predicted from microbial genomes. Here, we report a new approach to natural product discovery in which compounds are captured directly from the environments in which they are produced. We demonstrate the applications of this technique with the isolation and identification of both known and new compounds including several that possess new carbon skeletons and one with promising biological activity.

biochemistry↗

bioRxiv2021

Synergy between vesicular and non-vesicular gliotransmission regulates synaptic plasticity and working memory

Astrocytes are an active element of brain signalling, capable of release of small molecule gliotransmitters by vesicular and channel-mediated mechanisms. However, specific physiological roles of astroglial exocytosis of glutamate and D-Serine remain controversial. Our data demonstrate that cortical astrocytes can release glutamate and D-Serine by combination of SNARE-dependent exocytosis and non-vesicular mechanisms dependent on TREK-1 and Best1 channels. Astrocyte-derived glutamate and D-serine elicited complex multicomponent phasic response in neocortical pyramidal neurons, which is mediated by extra-synaptic GluN2B receptors. Impairment of either pathway of gliotransmission (in the TREK1 KO, Best-1 KO or dnSNARE mice) strongly affected the NMDAR-dependent long-term synaptic plasticity in the hippocampus and neocortex. Moreover, impairment of astroglial exocytosis in dnSNARE mice led to the deficit in the spatial working memory which was rescued by environmental enrichment. We conclude that synergism between vesicular and non-vesicular gliotransmission is crucial for astrocyte-neuron communication and astroglia-driven regulation of synaptic plasticity and memory. HighlightsO_LIAstrocytes in situ release glutamate via exocytosis and channel-mediated release. C_LIO_LIAstroglia-derived glutamate and D-Serine activate phasic NMDAR currents in neurons C_LIO_LIBoth vesicular and non-vesicular gliotransmission are required for synaptic plasticity C_LIO_LIImpaired exocytosis of gliotransmitters causes deficit in working memory C_LI

neuroscience↗