Biology subjects

Stankovic, M.

Publications and source records attributed to Stankovic, M..

3 recordsLinked to original sources

bioRxiv2025

Integrative spatial and multi-omic profiling in bladder cancer links L1 retrotransposition to extrachromosomal DNA, genomic instability, and viral mimicry response

Bladder cancer is one of the most frequent cancers and shows high recurrence rates. Despite recent advances, key knowledge gaps remain in understanding the molecular mechanisms of disease progression, which would support the development of early detection methods and effective personalized treatments. We apply integrated multi-omics and spatial analyses in a cohort of 49 bladder cancer patients to comprehensively profile genetic, epigenetic, transcriptomic, and spatial features of bladder cancer, alongside cell-free DNA blood analysis. Combining low-pass whole-genome cell-free DNA sequencing, Oxford Nanopore long-read tumor DNA sequencing, RNA-sequencing, and spatial transcriptomics, we provide insights into molecular alterations driving bladder cancer. We show frequent somatic LINE-1 (L1) insertions, with up to more than 500 insertions per tumor. We find that L1 insertions are active and occur early in bladder cancer development. We link aberrant somatic L1 insertion in bladder cancer with downstream genomic rearrangements and chromosomal instability, with an excess of structural variants and extrachromosomal DNA (ecDNA) in patients with particularly high L1 counts. By detecting ecDNA within tissue architecture using spatial transcriptomics, we identify the localization of ecDNA to distinct spatial clusters with differential expression of APOBEC3B and immune response pathways. These results, combined with replication timing analysis and gene set enrichment analysis (GSEA), offer evidence for the previously hypothesized viral mimicry response to L1 retrotransposition, mediated via APOBEC3B-editing, the cGAS-STING pathway, and RIG-I and MDA5 responses.

cancer biology↗

bioRxiv2025

Targeting anterior cingulate cortex with tDCS: an overview and analysis of electric field magnitude

The anterior cingulate cortex (ACC) is a brain region with a key role in various cognitive, emotional, and sensory processes. Given its extensive functional repertoire, modulating ACC activity to enhance cognitive functioning and alleviate symptoms of certain clinical conditions holds great potential. Over the past decades, transcranial direct current stimulation (tDCS) has gained popularity due to its ability to non-invasively affect the cortical excitability. Nevertheless, using tDCS to target regions located beneath superficial cortical areas, such as the ACC, could pose a challenge due to the unpredictable distribution of the electric field (E-field). To systematize the current state of evidence regarding the use of tDCS to modulate ACC activity, we conducted a systematic review focusing on analyzing the E-field distribution across the brain and its magnitude within the ACC as the region of interest. Our goal was to review the stimulation parameters used thus far and examine whether the E-field characteristics are linked to the observed effects. After the literature search and study selection, 14 studies were included in the review. Most of the studies were sham-controlled single-session experiments aiming to modulate specific cognitive processes in healthy adults. The most prominent process of interest was cognitive control, and most of the included studies observed behavioural effects. Our results show that cathodal stimulation led to significant results more frequently, regardless of E-field magnitude in ACC or specificity of E-field distribution throughout the brain. When it comes to anodal tDCS, more focal stimulation of the ACC was associated with a higher frequency of significant effects. We discuss these findings considering diverse methodological designs, the (un)specificity of ACC targeting, and other factors that could contribute to the variability of tDCS effects across studies.

neuroscience↗

bioRxiv2022

Extraction of individual associative memory related dominant theta frequency for personalized transcranial brain stimulation

Non-invasive brain stimulation (NIBS) has gained increased interest in research and therapy of associative memory (AM) and its impairments. However, the one-size-fits-all approach yields inconsistent findings, thus putting forward the need for the development of personalized frequency-modulated NIBS protocols to increase the focality and the effectiveness of the interventions. There have been only a few attempts to deliver theta frequency-personalized tES. The current study explores the feasibility of determining dominant individual theta-band frequency (ITF) based on AM task evoked EEG activity. In a sample of 42 healthy young adults, we extracted the frequencies (2-15 Hz, in 0.5 Hz steps) with the highest event-related spectral perturbation from the EEG recorded during successful encoding in the AM task. The developed method for extraction of the dominant theta-band frequency based on the AM-evoked EEG changes is able to reliably determine the AM-related ITF and can be used for personalization of the oscillatory NIBS techniques.

neuroscience↗