Biology subjects

Petrova, T.

Publications and source records attributed to Petrova, T..

6 recordsLinked to original sources

bioRxiv2026

Sex differences in brain metabolism assessed with whole-brain magnetic resonance spectroscopic imaging

Sex differences in brain disorders span age at onset, symptom profiles, disease course and treatment response, and may partly reflect underlying differences in cellular metabolism. Indeed, in vivo evidence of sex-related neurometabolic variation remains sparse, with heterogenous and conflicting findings. Using fast high-resolution whole-brain three-dimensional magnetic resonance spectroscopic imaging, we mapped five brain metabolites in three independent cohorts of healthy participants (total n = 114). In a discovery sample of adolescents scanned at 3 Tesla (3T) (n = 61), males showed higher total N-acetylaspartate (tNAA) across widespread gray matter regions. Regional analyses further revealed opposing sex patterns with a complementary higher total creatine (tCr) observed in females, motivating examination of their ratio as an integrative metabolic index. The tNAA/tCr ratio was consistently higher in males in the discovery sample and this finding was replicated across two independent young-adult samples (3T, n = 26; 7T, n = 27), with a widespread gray and white matter distribution. This tNAA/tCr ratio may link neuronal mitochondrial metabolism with cellular energy buffering, positioning it as a potential index of bioenergetic balance relevant for conditions showing both sex differences and altered neurometabolism, notably multiple sclerosis, Alzheimer disease, and psychosis. Together, these findings reveal a reproducible, distributed metabolic sexual dimorphism in the human brain, and underscore the importance of accounting for sex-specific neurometabolic profiles in studies of brain health and disease.

neuroscience↗

bioRxiv2026

A Whole-Genome and Ancient DNA Perspective on the Drivers of Genetic Diversity and Structure in Palearctic True Lemmings

True lemmings (genus Lemmus) underwent substantial range shifts during the Late Pleistocene and the Pleistocene-Holocene transition, but the impact of these events on present-day diversity remains poorly understood. Here, we used whole-genome sequencing data from modern and ancient samples across the Palearctic range to address this knowledge gap. Reconstruction of autosomal phylogeny revealed that Palearctic true lemmings exhibit relatively shallow genetic structure, contrasting with the deep divergence inferred from mitochondrial genomes. Genetic variation largely follows an isolation-by-distance pattern, and no elevated nuclear divergence was detected between the major mitochondrial lineages. Window-based phylogenetic analyses identified several peripheral populations with high concordance factors, including Norway and Amur lemmings. The high degree of phylogenetic concordance along the genome in these populations is likely a consequence of postglacial bottlenecks and isolation, as indicated by reduced heterozygosity and the presence of runs of homozygosity in them. Overall, our results indicate that the modern genomic structure of Palearctic lemmings was shaped primarily by range fragmentation and population isolation following the broad distribution of the genus during the Last Glacial Maximum. Thus, the current genetic structure appears to represent only a fraction of the Late Pleistocene true lemming diversity. This is illustrated by a genetically distinct ancient specimen ([~]40 ka BP) from the Indigirka River basin that does not cluster with any modern lineage. From a taxonomic perspective, these findings do not support strong species-level differentiation among the major Palearctic lineages and highlight the discrepancy between mitochondrial and nuclear patterns of diversity within the genus.

evolutionary biology↗

bioRxiv2025

Determination of the water network surrounding the type I pilus from E. coli by cryo-electron microscopy

Type 1 pili are protein filamentous surface structures of Gram-negative bacteria that mediate adhesion to host and play a crucial role in infection. Here, we report the cryogenic electron microscopy structure of the type 1 pilus from E. coli K-12 comprising 15 subunits of the major protein pilin FimA. The final resolution of EM reconstruction was estimated to be in the range from 2.09 to 2.30 [A], which is higher than that of the previously published structure. This improvement in the resolution enabled us to refine side-chain conformations to reliably determine the distances between the side-chain residues participating in the intersubunit interactions, and determine a network of water molecules surrounding the pilus rod. The analysis revealed that water contributes to intersubunit stabilization both through discrete bridging interactions and through extended hydrogen-bonded clusters, thereby supporting both the rigidity and flexibility of the filament. Comparison with a homologous high-resolution pilus model from enterotoxigenic E. coli showed that nearly all "conserved" water molecules i.e., those that are present at equivalent positions in different subunits of our model occupy also equivalent positions across the two structures, under-scoring their functional relevance. At the same time, sequence-specific differences in hydration patterns were observed. These findings highlight the structural and functional importance of water in pilus architecture and provide a more detailed molecular framework for understanding bacterial adhesion. SynopsisThe improvement in the resolution of the Cryo-EM reconstruction for type I pilus from E. coli made it possible to determine the positions of water molecules surrounding the pilus rod and reveal a more detailed picture of interactions between different subunits of the rod.

molecular biology↗

bioRxiv2021

c-MAF maintains the transcriptional program of enterocyte zonation and the balance of absorptive/intestinal secretory cell types

Small intestinal villi are structural and functional units uniquely adapted to the nutrient absorption in higher vertebrates. Villus enterocytes are organized in spatially resolved "zones" dedicated to specialized tasks such anti-bacterial protection, and absorption of amino-acids, carbohydrates and lipids. The molecular mechanisms specifying villus zonation are incompletely understood. We report that inactivation of transcription factor c-MAF, highly expressed in mature lower and mid-villus enterocytes, perturbed the entire villus zonation program, by increasing the expression of regulators of carbohydrate and bile acid metabolism and transport, while suppressing genes related to amino acid and lipid absorption. Maf inactivation under homeostatic conditions expanded tuft cells and led to compensatory gut lengthening, preventing body weight loss. However, delayed enterocyte maturation in the absence of Maf impaired body weight recovery after acute intestinal injury, resulting in reduced survival. Our results identify c-MAF as a novel regulator of small intestinal villus zonation program, while highlighting the importance of coordination between stem/progenitor and differentiation programs for intestinal regeneration. Summaryc-MAF is expressed in differentiated enterocytes. c-MAF loss alters enterocyte zonation leading to a compensatory gut remodelling and tuft cell expansion. Upon acute intestinal injury mice deficient for c-MAF cannot recover due to lack of nutrient transport and compensatory lengthening.

cell biology↗

bioRxiv2020

IL-23 production is regulated via an MSK1/2 - CREB dependent signaling pathway downstream of Toll like receptors.

IL-23 is an IL-12 family cytokine that is important in promoting Th17 responses and has been strongly linked to autoimmunity and psoriasis. It is a heterodimeric cytokine made up of a p19 subunit unique to IL-23 and a p40 subunit that is shared with IL-12. We show here that in response to LPS, the induction of IL-23p19 mRNA is regulated by a MSK1/2 - CREB dependent pathway downstream of ERK1/2 and p38 MAPK. Knockout of MSK1/2 resulted in a decrease in both IL-23p19 mRNA transcription and IL-23 secretion in GM-CSF differentiated bone marrow cells. Similar effects were seen when the MSK1/2 phosphorylation site in CREB was mutated to alanine. Stimulation with PGE2 promotes the nuclear localisation of CRTC3, a co-activator for CREB. In combination with LPS, PGE2 promoted IL-23p19 mRNA transcription and this was blocked by knockdown of CRTC3. Imiquimod induced skin inflammation in mice has been used as a model for psoriasis and is dependent on IL-23. While MSK1/2 knockout reduced the induction of IL-23 in vivo following i.p. injection of LPS, the knockout mice were not protected from Imiquimod induced skin inflammation. MSK1/2 knockout did not reduce the induction of IL-17 producing {gamma}{delta}T cells following Imiquimod treatment, although MSK1/2 knockout did reduce the levels of these cells in mice receiving a control cream. The lack of protection in the Imiquimod model may be due to the known anti-inflammatory roles or MSKs, such as its contribution to the induction of IL-10.

immunology↗

bioRxiv2020

Systematic analysis of mutational spectra associated with DNA repair deficiency in C. elegans

Genome integrity is particularly important in germ cells to faithfully preserve genetic information across generations. As yet little is known about the contribution of various DNA repair pathways to prevent mutagenesis. Using the C. elegans model we analyse mutational spectra that arise in wild-type and 61 DNA repair and DNA damage response mutants cultivated over multiple generations. Overall, 44% of lines show >2-fold increased mutagenesis with a broad spectrum of mutational outcomes including changes in single or multiple types of base substitutions induced by defects in base excision or nucleotide excision repair, or elevated levels of 50-400 bp deletions in translesion polymerase mutants rev-3(pol {zeta}) and polh-1(pol {eta}). Mutational signatures associated with defective homologous recombination fall into two classes: 1) mutants lacking brc-1/BRCA1 or rad-51/RAD51 paralogs show elevated base substitutions, indels and structural variants, while 2) deficiency for MUS-81/MUS81 and SLX-1/SLX1 nucleases, and HIM-6/BLM, HELQ-1/HELQ and RTEL-1/RTEL1 helicases primarily cause structural variants. Genome-wide investigation of mutagenesis patterns identified elevated rates of tandem duplications often associated with inverted repeats in helq-1 mutants, and a unique pattern of translocation events involving homeologous sequences in rip-1 paralog mutants. atm-1/ATM DNA damage checkpoint mutants harboured complex structural variants enriched in subtelomeric regions, and chromosome end-to-end fusions. Finally, while inactivation of the p53-like gene cep-1 did not affect mutagenesis, combined brc-1 cep-1 deficiency displayed increased, locally clustered mutagenesis. In summary, we provide a global view of how DNA repair pathways prevent germ cell mutagenesis.

genomics↗