Biology subjects

Akimov, V.

Publications and source records attributed to Akimov, V..

6 recordsLinked to original sources

bioRxiv2026

Glucocorticoid signalling exerts distinct lineage-permissive and dose-dependent disruptive actions during human osteoblast differentiation

At physiological levels glucocorticoid (GC) signalling within the osteoblast lineage has been proposed to be required for skeletal homeostasis, whereas supraphysiological activation supresses bone formation and causes bone loss. While these observations suggest that GC exert dose- and context-dependent effects, the molecular mechanisms underlying these opposing actions remain unresolved. Here we systematically dissected the receptor-, lineage-, and concentration-dependent effects of GC signalling on human bone marrow stromal cell (BMSC) differentiation using integrated transcriptional, epigenomic, and functional analyses. Our findings suggest that GC opposing effects are not simply due to a GR dose-response but instead reflect distinct context- and concentration-dependent modes of action. During early BMSC differentiation, the cellular context induced GR-dependent licensing of lineage-specific gene and enhancer programs. The adverse effects of high-dose GC developed over time and could not be predicted from the early transcriptional response. We found that high-dose GC caused osteoblast maturation arrest, accompanied with a cellular stress response sustained by myeloid zinc finger 1 (MZF1) also identified as an endogenous inhibitor of osteoblast differentiation.

molecular biology↗

bioRxiv2025

Interoceptive training enhances emotional awareness and body image perception: evidence from improved heartbeat detection and psychological outcomes

The conscious integration of interoceptive signals, such as heartbeats and breathing, is essential for emotional regulation, self-awareness, and stress resilience. We conducted a controlled trial implementing a 5-day biofeedback-guided interoceptive training program to assess its impact on interoceptive accuracy (IAc) and psychological dimensions of bodily and mental perception. The experimental group showed significant improvements in IAc compared to controls, reflecting enhanced detection of heartbeats. Training increased scores on two MAIA subscales: "Awareness of Negative Emotional States" and "Not Distracting". These outcomes suggest the intervention enhanced participants capacity to acknowledge and engage with unpleasant bodily sensations without resorting to avoidance or distraction strategies. A trend toward improved body image perception emerged in the experimental group, with gains correlating with reductions in depressive symptoms, underscoring the interplay between bodily awareness and emotional well-being. These findings underscore that targeted interoceptive training represents a powerful tool for refining awareness of internal states, enhancing attentional control, and optimizing emotional processing. By bridging bodily signals and affective experiences, this approach offers a pathway for innovative, evidence-based therapies to bolster emotional resilience and address conditions rooted in dysregulated emotional states, such as anxiety, depression, and stress-related disorders.

physiology↗

bioRxiv2024

Deep Proteome Profiling of Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects roughly 1 in 3 adults and is a leading cause of liver transplants and liver related mortality. A deeper understanding of disease pathogenesis is essential to assist in developing blood-based biomarkers. Here, we use data-independent acquisition mass spectrometry to assess disease-state associated protein profiles in human liver, blood plasma, and white adipose tissue (WAT). In liver, we find that MASLD is associated with an increased abundance of proteins involved in immune response and extracellular matrix (ECM) and a decrease in proteins involved in metabolism. Cell type deconvolution of the proteome indicate liver endothelial and hepatic stellate cells as main source of the ECM rearrangements, and hepatocytes as the major contributor to the changes in liver metabolism. In the blood, profiles of several MASLD-associated proteins that correlate with their expression in WAT rather than liver yet could serve as suitable liver disease predictors in a multi-protein panel marker. Moreover, our proteomics-based logistic regression models consistently outperform existing methods for predicting MASLD and liver fibrosis from human blood samples.

systems biology↗

bioRxiv2023

Pulmonary maternal immune activation does not extend through the placenta but leads to fetal metabolic adaptation

Maternal immune system activation (MIA) during pregnancy can disrupt the fetal environment, causing postnatal susceptibility to disorders. How the placenta and the fetus respond to acute MIA over time is unknown. Here, we characterized the response to acute maternal pulmonary inflammation across time in maternal and fetal organs using multi-omics. Unlike maternal organs which mounted strong innate immune responses, the placenta upregulated tissue-integrity genes, likely to prevent fetal exposure to infections, and downregulated growth-associated genes. Subsequently, the placenta upregulated biosynthesis and endoplasmic reticulum stress genes in order to return to homeostasis. These responses likely protected the fetus, since we observed no immune response in fetal liver. Instead, likely due to nutrient depletion, the fetal liver displayed metabolic adaptations, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. Our study shows, for the first time, the integrated temporal response to pulmonary MIA across maternal and fetal organs.

genomics↗

bioRxiv2022

Ester-linked ubiquitin sites formed by HOIL-1 in TLR7 signaling include four novel ubiquitin dimers

The E3 ligase HOIL-1 forms ester bonds in vitro between ubiquitin and serine/threonine residues in proteins. Here, we exploit UbiSite technology to identify serine and threonine residues undergoing HOIL-1 catalysed ubiquitylation in macrophages stimulated with R848, an activator of the TLR7/8 heterodimer. We identify Thr12, Thr14, Ser20 and Thr22 of ubiquitin as amino acid residues forming ester bonds with the C-terminal carboxylate of another ubiquitin molecule, increasing from 8 to 12 the different types of ubiquitin dimer formed in cells. We also identify Ser175 of IRAK4, Ser136, Thr163 and Ser168 of IRAK2 and Thr141 of MyD88 as further sites of HOIL-1-catalysed ubiquitylation together with lysine residues in these proteins that also undergo R848-dependent ubiquitylation. These findings establish that the ubiquitin chains attached to components of myddosomes are initiated by both ester and isopeptide bonds. Ester bond formation takes place within the proline, serine, threonine-rich (PST) domains of IRAK2 and IRAK4 and the intermediate domain of MyD88. The ubiquitin molecules attached to Lys162, Thr163 and Ser168 of IRAK2 are attached to different IRAK2 molecules.

biochemistry↗

bioRxiv2022

TBK1 phosphorylation activates LIR-dependent degradation of the inflammation repressor TNIP1

Limitation of excessive inflammation due to selective degradation of pro-inflammatory proteins is one of the cytoprotective functions attributed to autophagy. In the current study, we highlight that selective autophagy also plays a vital role in promoting the establishment of a robust inflammatory response. Under inflammatory conditions, here TLR3-activation by poly(I:C) treatment, the inflammation repressor TNIP1 (TNFAIP3 interacting protein 1) is phosphorylated by TBK1 (Tank-binding kinase 1) activating a LIR motif that leads to the selective autophagy-dependent degradation of TNIP1, supporting expression of pro-inflammatory genes and proteins. Thus, similarly as in cancer, autophagy may play a dual role in controlling inflammation depending on the exact state and timing of the inflammatory response. SummaryAutophagy is well known for its anti-inflammatory effects. Here, we highlight that selective, autophagy-dependent degradation of the inflammation repressor TNIP1 supports pro-inflammatory gene and protein expression. Similarly as in cancer, autophagy appears to play a dual role in controlling inflammation.

cell biology↗