Biology subjects

Kowalczyk, M.

Publications and source records attributed to Kowalczyk, M..

9 recordsLinked to original sources

bioRxiv2025

On-Body Measure of Reaction Time Correlates With Intoxication Level

Excessive alcohol use has profound effects on individual health and healthcare systems worldwide. Despite this, there is currently no system or device that can detect robustly the physiologic and functional effects of alcohol-based impairment in real-world conditions. A practical, on-body, device capable of rapidly and accurately determining the functional capacity of an individual to drive, before they can start the ignition of the automobile, is required. The goal of this pilot study was to evaluate the effect of acute alcohol intoxication on premotor time (PMT) and reaction time (RT), both highly sensitive of individual cognition, as evaluated by the Pison Technology wrist-worn wearable. Nineteen participants were included in the study, 14 subjects who consumed alcohol sufficient to raise blood alcohol concentration (BAC) to 0.12% within a 30-minute period and 5 controls who did not consume alcohol. Changes in reaction time data were correlated with blood alcohol levels as measured by breathalyzer testing, identifying a statistically significant difference between those participants under the legal limit and those over the legal limit. Both group and individual analyses confirmed that as the BAC increased in subjects, the PMT also increased. The PMT also decreased as the BAC returned to levels under the legal intoxication threshold (0.08%). A significant effect of BAC levels on changes in PMT at the p < 0.05 level for two conditions. This study demonstrated the first use case of an on-body, neuro-physiological sensor capable of detecting sensitive changes of reaction time, in real time, that serves as an easy-to-measure proxy for blood alcohol content and impairment.

neuroscience↗

bioRxiv2024

A worldwide ENIGMA study on epilepsy-related gray and white matter compromise across the adult lifespan

ObjectivesTemporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. MethodsWe studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. ResultsIn TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. ConclusionsThis study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

neuroscience↗

bioRxiv2021

Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

neuroscience↗

bioRxiv2021

Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide enigma study

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

neuroscience↗

bioRxiv2021

Biosynthesis of benzoxazinoids in rye (Secale cereale L.) - where does the story begin?

According to current opinion, the first step of benzoxazinoids (BXs) synthesis, that is, the conversion of indole-3-glycerol phosphate to indole, occurs exclusively in the photosynthesising parts of plants. However, the results of our previous work and some other studies suggest that this process may also occur in the roots. In this study, we provide evidence that the first step of BXs synthesis does indeed occur in the roots of rye seedlings. We detected ScBx1 transcripts, BX1 enzyme, and six BXs (2-hydroxy-1,4-benzoxazin-3-one, 2,4-dihydroxy-1,4-benzoxazin-3-one, (2R)-2-O-{beta}-d-glucopyranosyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one glucoside, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one glucoside, and 6-methoxy-2-benzoxazolinone) in the roots developed from seeds deprived of the coleoptile at 2 days after sowing (i.e., roots without contact with aerial parts). In roots regenerated in vitro, both ScBx1 transcripts and BX1 enzyme were detected at a low but still measurable levels. Thus, BXs are able to be synthesised in both the roots and above-ground parts of rye plants. HighlightThe first step benzoxazinoids synthesis occurs in both the above-ground parts and roots of rye plants. Benzoxazinoids can be synthesised de novo in roots, independently of plants photosynthesising parts.

molecular biology↗

bioRxiv2020

Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies.

neuroscience↗

bioRxiv2019

A cellular taxonomy of the bone marrow stroma in homeostasis and leukemia demonstrates cancer-crosstalk with stroma to impair normal tissue function

Stroma is a poorly defined non-parenchymal component of virtually every organ with key roles in organ development, homeostasis and repair. Studies of the bone marrow stroma have defined individual populations in the stem cell niche regulating hematopoietic regeneration and capable of initiating leukemia. Here, we use single-cell RNA-seq to define a cellular taxonomy of the mouse bone marrow stroma and its perturbation by malignancy. We identified seventeen stromal subsets expressing distinct hematopoietic regulatory genes, spanning new fibroblastic, and osteoblastic subpopulations. Emerging acute myeloid leukemia resulted in impaired osteogenic differentiation and reduced production of hematopoietic regulatory molecules necessary for normal hematopoiesis. Thus, cancer can affect tissue stroma in which they reside to disadvantage normal parenchymal cells. Our taxonomy of the regulatory stromal compartment provides experimental support for a model where malignant clone is not a destroyer of normal tissue but an architect of it, remodeling tissue stroma to enable emergent cancer.

cell biology↗

bioRxiv2018

Cryo-Electron tomography 3D structure and nanoscale model of Arabidopsis thaliana cell wall

Using cryo-electron tomography of vitrified sections of one month-old Arabidopsis thaliana inflorescence stem tissue, we visualized primary and secondary cell walls of xylem tissue. Extensive quantitative and statistical analysis of segmented 3D tomographic data allowed geometrically idealized 3D-CAD model building of prototypic microfibrils, cross-links, and their supramolecular microfibril 3D organization. We propose a prototypic microfibril model where a cellulose core is heavily decorated by a thin sheath of hemicellulose with infrequent but sturdy hemicellulose-based cross-links. Such prototypic microfibrils then adopt a rather unexpected 3D supramolecular organization of high order and complexity. We discuss a possible new role for lignin in plant cell walls at low concentrations with lignin not acting as a matrix but rather as a reinforcement of microfibrils and cross-links. Extensive computational simulations of mechanical properties further revealed that this 3D organization of the cell wall is not optimized for load bearing but instead for flexibility and ductility.\n\nOne Sentence SummaryCryo-electron tomography and mechanical simulations revealed cell wall 3D architecture, optimized for flexibility/ductility.

plant biology↗

bioRxiv2018

Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection

ObjectiveThe process of manually marking up epileptic spikes for simultaneous electroencephalogram (EEG) and resting state functional MRI (rsfMRI) analysis in epilepsy studies is a tedious and subjective task for a human expert. The aim of this study was to evaluate whether automatic EEG spike detection can facilitate EEG-rsfMRI analysis, and to assess its potential as a clinical tool in epilepsy.\n\nMethodsWe implemented a fast algorithm for detection of uniform interictal epileptiform discharges (IEDs) in one-hour scalp EEG recordings of 19 refractory focal epilepsy datasets (from 16 patients) who underwent a simultaneous EEG-rsfMRI recording. Our method was based on matched filtering of an IED template (derived from human markup) used to automatically detect other similar EEG events. We comprehensively compared simultaneous EEG-rsfMRI results between automatic IED detection and standard analysis with human EEG markup only.\n\nResultsIn contrast to human markup, automatic IED detection takes a much shorter time to detect IEDs and export an output text file containing spike timings. In 13/19 focal epilepsy cases, statistical EEG-rsfMRI maps based on automatic spike detection method were comparable with human markup, and in 6/19 focal epilepsy cases it revealed additional brain regions not seen with human EEG markup. Additional events detected by our automated method independently revealed similar patterns of activation to a human markup. Overall, automatic IED detection provides greater statistical power in EEG-rsfMRI analysis compared to human markup in a short timeframe.\n\nConclusionsAutomatic spike detection is a simple and fast method that can reproduce comparable and, in some cases, even superior results compared to the common practice of manual EEG markup in EEG-rsfMRI analysis of epilepsy.\n\nSignificanceOur study shows that IED detection algorithms can be effectively used in epilepsy clinical settings. This work further helps in translating EEG-rsfMRI research into a fast, reliable and easy-to-use clinical tool for epileptologists. Our IED detection approach will be publicly available as a MATLAB package at: https://github.com/omidvarnia/Automatic_focal_spike_detection.\n\nHighlightsO_LIAutomatic spike detection increases the number of detected uniform epileptic interictal discharges and enhances statistical power of EEG-rsfMRI inter-subject variability maps,\nC_LIO_LIAutomatic spike detection can identify additional activated brain regions with presumed epileptogenic focus not seen in standard analysis based on human markup,\nC_LIO_LIAutomatic spike detection can shorten the IED identification process.\nC_LI

neuroscience↗