Biology subjects

Sabirova, D.

Publications and source records attributed to Sabirova, D..

4 recordsLinked to original sources

bioRxiv2026

Genomic insights into the human gut commensal Megasphaera elsdenii: Relatedness and metabolic potential compared to animal isolates

Megasphaera elsdenii is best known as a prominent lactate consumer within the rumen microbial community in livestock, and its metabolic properties are relatively well studied. In humans, it can be isolated from healthy donors feces and, more often, from patients feces with diverse inflammatory conditions. Genetic diversity of this species is poorly understood, and it is currently unclear whether human and animal gut isolates are genetically related and perform the same metabolic function. In this study, we compared 86 M. elsdenii genomes from human feces (as a proxy for the human gut) to those of animal gut isolates. Phylogenetic analysis revealed that human and animal gut lineages intermingle within a single, genetically homogeneous branch, lacking any host-specific clustering. Human gut lineages shared most of their genes and biochemical pathways with those of swine and cattle gut isolates, despite differences in their digestive tracts. Neither unsupervised nor supervised approaches identified any notable differences in encoded pathways between different host-specific gut lineages. Genome-scale metabolic modeling suggests that human and animal gut lineages likely share identical carbon and energy source requirements. Moreover, the requirements for lactate and acetate were conserved across all studied samples, regardless of the host. Finally, we found no virulence genes, and lactate utilization remains a plausible explanation for M. elsdenii accumulation in the host intestine. IMPORTANCEMegasphaera elsdenii is considered a commensal in the human gut and animal rumen. However, M. elsdenii tends to be more abundant in patients feces with diverse inflammatory conditions. As we know little about the strain diversity and biology of human gut lineages, comparisons with better-studied animal isolates can be informative. In this study, we compared human gut M. elsdenii genomes to those from better-studied isolates from ruminant and non-ruminant animal hosts. Human gut samples associated with patients and healthy donors were genetically very similar to gut isolates from animals and may have shared a common origin. We found that human and animal gut lineages have a similar genomic makeup and metabolic potential, and that neither group harbors virulence genes. We hypothesize that M. elsdenii is a benign commensal that grows in response to lactate accumulation in the inflamed gut.

microbiology↗

bioRxiv2025

Neurophysiological mechanisms of immersive virtual reality influence segmental motor reflexes

Immersive virtual reality (VR) technologies are being increasingly applied in clinical settings, physiotherapy, and neurorehabilitation due to their potential to modulate neurophysiological functions. However, the mechanistic basis of VRs effects on human motor systems, especially the impact of emotionally charged VR experiences on segmental spinal reflex excitability, remains unclear. This study aimed to compare the effects of immersive VR stimulation with different emotional tones, the Jendrassik maneuver, and transcranial magnetic stimulation on spinal motor center excitability in healthy adults. H-reflex and M-response amplitudes in the soleus muscle were measured during tibial nerve stimulation under control conditions, during the Jendrassik maneuver, subthreshold magnetic stimulation, and while participants viewed VR videos evoking fear, excitement, or relaxation. The experimental design randomized condition order for each participant. The principal finding was that emotionally salient VR content, particularly scenes inducing fear, produced clear lateralized effects on the spinal motor system. Specifically, inhibitory effects on reflex excitability were observed in the dominant limb, while facilitatory changes occurred in the non-dominant limb. These patterns suggest that immersive VR may differentially engage descending modulatory systems, influencing both sympathoadrenal and corticospinal pathways. In contrast, traditional neuromodulatory interventions did not alter reflex parameters compared to control. The results highlight the unique multimodal influence of immersive VR on sensorimotor regulation and support its incorporation into advanced neurorehabilitation protocols.

physiology↗

bioRxiv2024

Hedgehog signaling controls cytotoxic T cell migration in the tumour microenvironment.

Cytotoxic T lymphocytes effectively eliminate cancer cells. Their abundance in the tumour microenvironment is one of the strongest pan-cancer predictors of clinical response. Here, we show that Hedgehog (Hh) signaling regulates T cell migration into tumours. Using conditional knockout mouse models of central Hh signaling components Ihh, Smo and Gli1 in CD8 T cells, we show that Smo deletion greatly impairs the anti-tumour response in vivo due to diminished CD8 T cell migration into the tumour microenvironment. The migration defect is mediated exclusively by Smo, both in in vivo cancer models and in vitro migration assays. This effect is independent of the canonical Hh pathway and relies on the GPCR function of Smo to regulate the migration of murine and human CD8 T cells via RhoA. Hh signaling is critical during embryonic development and adult stem cell homeostasis, but is also amplified in multiple cancer types. Hh inhibitors targeting SMO have been clinically-approved and shown efficacy in the treatment of Hh-driven basal cell carcinoma and medulloblastoma but have failed in clinical trials in other solid cancers with upregulated Hh signaling. We demonstrate that SMO inhibitors specifically decrease CD8 T cell migration into the tumour microenvironment, both in murine cancer models and resected BCCs from patients treated with the SMO inhibitor vismodegib, providing the first mechanistic explanation as to why Hh inhibitors have failed in solid cancers. Our data establishes a novel link between Hh inhibition in vivo and the anti-tumour immune response and reveals a fundamental mechanism controlling T cell migration. The work provides the basis for improved Hh targeting approaches in the clinic and new entry points into enhancing migration in T cell therapies.

immunology↗

bioRxiv2023

A DNA condensation code for linker histones

Linker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fibre of nucleosomal "beads on a string". The result is a heterogeneous condensed state with local properties that range from dynamic, irregular and liquid-like, to stable and regular structures (the 30-nm fibre), which in turn impact chromatin-dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly disordered C-terminal tail, which is the most variable region of the protein, both between species, and within the various subtypes and cell-type specific variants of a given organism. We have developed an in-vitro model system comprising linker histone tail and linker DNA, which although very minimal, displays surprisingly complex behaviour, and is sufficient to model the known states of linker-histone-condensed chromatin: disordered "fuzzy" complexes ("open" chromatin), dense liquid-like assemblies (dynamic condensates) and higher-order structures (organised 30-nm fibres). A crucial advantage of such a simple model is that it allows the study of the various condensed states by NMR, CD and scattering methods. Moreover, it allows capture of the thermodynamics underpinning the transitions between states through calorimetry. We have leveraged this to rationalise the distinct condensing properties of linker histone subtypes and variants across species that are encoded by the amino acid content of their C-terminal tails. Three properties emerge as key to defining the condensed state: charge density, lysine/arginine ratio, and proline-free regions, and we evaluate each separately using a strategic mutagenesis approach.

biophysics↗