Biology subjects

Martinovic, J.

Publications and source records attributed to Martinovic, J..

9 recordsLinked to original sources

bioRxiv2026

Placental prostaglandin signaling disrupts barrier integrity and relays an acute inflammatory signal to the fetus.

Maternal inflammation during pregnancy is a major risk factor for adverse neurodevelopmental outcomes, yet the mechanisms linking maternal immune activation (MIA) to placenta-fetal brain axis dysfunction remain unclear. Using a poly-(I:C) mouse model, we show that MIA rapidly disrupts placental-blood barrier (PBB) integrity by disrupting pericyte-endothelium coupling within 48 hours, leading to increased placental permeability detected by in vivo MRI. We identify a prostaglandin E2 (PGE2)-dependent pathway involving cyclooxygenase-2 (COX2) and prostaglandin E-synthase (mPGES1) as a key mediator of this effect. Pharmacological inhibition of COX2 prevented MIA-induced structural and functional changes. In vitro explant studies confirmed that PGE2 acts via the EP3 receptor to disrupt pericyte-endothelium interactions, while ex vivo perfusion demonstrated that in addition to its local effects on PBB structure, placenta-derived PGE2 enters the fetal circulation. Finally, similar vascular alterations were observed in human placentas from pregnancies with severe maternal inflammation. These findings reveal a conserved inflammatory mechanism that compromises PBB integrity and may relay signals to the fetal brain, highlighting potential therapeutic targets for neuroprotection during prenatal inflammation. One Sentence SummaryMaternal immune activation during pregnancy disrupts placental vascular integrity through a COX2-dependent prostaglandin E2 pathway, which compromises the placenta-blood barrier and relays inflammatory signals to the fetus, identifying potential therapeutic targets for neuroprotection.

developmental biology↗

bioRxiv2026

Cognition does not automatically influence perception: Evidence from neural encoding of colours belonging to different categories

The firmest evidence in favour of models that posit early high-level influences of cognition on perception comes from electroencephalography (EEG). Enhanced early, pre-attentive processing of light and dark blue feature changes compared to light and dark green changes was reported in Greek speakers, who have two basic terms for blue (ghalazio/ble). In the present three-experiment study, we systematically re-evaluate this evidence and test an alternative model that the early difference waves in the human EEG instead mainly reflect contrast adaptation phenomena. We use the same classical oddball paradigm presenting alternating standards and deviants that systematically differ in colour and/or luminance and chromatic contrast. We then calculate the visual mismatch negativity (vMMN), a putative index of pre-attentive feature change processing and predictive coding derived from EEG data, by subtracting the activity elicited by standards from that elicited by task-irrelevant deviants. Our experiments demonstrate the following: 1) vMMN is driven by contrast adaptation, being observable only in the presence of contrast differences between the stimuli and not reliably observed for categorically different hues equated in contrast; 2) there is no reliable difference between green- and blue-related difference waves in speakers (Russian) with two basic blue colour categories, the difference waves, again, being driven by contrast rather than their categorical content. Our findings are highly significant for the debate concerning the interface between perception and cognition, as the absence of early categorical effects speaks against models that predict Whorfian-type pre-attentive cognitive influences on perception. Significance statementThe Whorfian hypothesis posits that basic language categories alter ones perception of the world in a fundamental manner. Some of the most compelling evidence in favour of this hypothesis came from electrophysiological responses that indicated early differences between speakers of languages with different number of basic colour categories. The brain response taken as an indicator of these differences was considered to be a robust marker of early, pre-attentive processing and predictive coding. In the current multi-experiment study, we present evidence that early electrophysiological differences to colour reflect signatures of hue, saturation and luminance contrast and adaptation to this contrast, rather than of linguistic categories. This means that evidence in favour of early, pre-attentive categorical colour perception has been significantly eroded.

neuroscience↗

bioRxiv2025

Colour desaturation in the periphery is explained by general mechanisms of contrast sensitivity and constancy

Colors appear less saturated in the visual periphery than in the fovea. We revisit this well-known phenomenon by characterizing parafoveal perceived contrast as a function of size. Observers (n = 20) matched perceived contrast of a parafoveally presented comparison disc (2{degrees} -0.33{degrees}) to a standard 2{degrees} disc. For chromatic stimuli, desaturation increased with decreasing size. Unexpectedly, a similar amount of desaturation occurred for luminance-defined discs, once their perceived contrast was adjusted to match the standard chromatic discs. Desaturation was reduced as standard stimulus contrast increased, in line with contrast constancy theory, which predicts constant appearance for stimuli that are sufficiently distant from threshold. Since chromatic contrast sensitivity is reduced away from the fovea, contrast constancy is unachievable within the monitor gamut. In conclusion and somewhat counter-intuitively, the appearance of color and luminance in the periphery is affected similarly, governed by general laws of contrast sensitivity and constancy. Public Significance StatementIn the early stages of visual signal processing, color and luminance (achromatic) information are separated. If we overgeneralize on the basis of such early separation, we may conclude that the desaturated appearance of small and peripherally presented color stimuli is specific to color processing mechanisms. Here we show that this is not the case and that chromatic and achromatic stimuli are processed similarly when presented in the periphery, implying that such processing is governed by more general contrast-processing mechanisms. Our work provides the basis for a better understanding of how the visual system builds a unified experience of color appearance across chromatic and achromatic dimensions from the information on contrast present in the image.

neuroscience↗

bioRxiv2024

CHARACTERISING REPRESENTATIONS OF HUE AND SATURATION IN THE CORTEX USING INFORMATION DECODING

One of the enduring questions in the field of colour vision research revolves around how features of colour appearance, such as hue and saturation are represented in the brain. While considerable progress has been made in understanding the transformation of physical colour signals during early processing stages, the mechanisms by which these signals are recombined in later processing, ultimately giving rise to our perceptual experience of colour, remain elusive. A promising avenue for capturing these representations involves decoding from EEG signals. We captured EEG signals in response to 8 evenly spaced isoluminant colours at two saturation levels, taken from a perceptually uniform CIE Lab colour space. Surprisingly, our main finding challenges the expectation that representations of colours that are perceptually more similar elicit more similar signals. Instead, our results show that isoluminant hues perceived as maximally dissimilar tend to evoke the most similar EEG signals, which is in line with predictions derived from opponent theory. Additionally, decoding performs better for lower saturation than for higher saturation hues, contrary to expectations that more distinct hue representations would be associated with highly saturated hues but in line with prediction of magnified differences in latency and amplitude of EEG signals between low-level opponent mechanisms at lower contrast levels. Finally, our findings also highlight the non- uniformity of the cortical representation space for isoluminant colour, indicating that neighbouring hues exhibit varying degrees of similarity. Put together, the results show that low-level features, such as contrast and cone-opponency, drive the EEG response to colour.

neuroscience↗

bioRxiv2024

Integrated Database of Force-Field Parameters, Experimental Measurements and Molecular Dynamics Simulations

Molecular Dynamic (MD) simulation is a vital theoretical tool for exploring nucleic acids (RNA, DNA), proteins and other (bio)molecular systems, generating vast amounts of data daily. Efficient storage and possible reuse of this data is a persistent challenge. Here, we introduce IDA (Integrated DAtabase of force fields and datasets from experiments and MD simulations), an innovative database scheme for datasets from various types of MD simulations. IDA supports outputs from different MD approaches, i.e., standard MD simulations, importance sampling techniques, simulated annealing, and other enhanced sampling methods including replica-exchange simulations. IDA also houses a collection of molecule-specific force fields (FFs) and experimental datasets. Uploaded MD outputs, FFs, and experimental data are integrated in a standardized format, allowing efficient data mining and extraction of valuable insights from the extensive data generated by diverse MD simulations. With the data and metadata holdings of IDA, and the prospective assignment of persistent identifiers, our work aims to make key steps towards making MD data FAIR (findable, accessible, interoperable, reusable).

bioinformatics↗

bioRxiv2024

Humanized in vivo bone marrow models orchestrate multi-lineage human hematopoietic cell development

Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate differentiation and preservation of hematopoietic stem/progenitor cells (HSPCs). Although murine BM has been extensively analyzed, the human BM microenvironment remains less understood. Immune-deficient murine models have enabled the analysis of molecular and cellular regulation of human HSPCs, which remains limited as human hematopoietic cells develop in xenogenic microenvironments. In this study, we thoroughly characterized a humanized (h) in vivo BM model, based on mesenchymal stromal cell (MSC) differentiation (called hOssicles (hOss)), and hematopoietic cell compartments generated 3 months post-transplant of CD34+ cells using single-cell RNA sequencing and cellular barcoding. Serial isolation of MSCs and HSPCs from hOss and transplant experiments revealed the dynamic nature of these hBM niches. hOss altered human hematopoietic development by modulating myeloid/lymphoid cell production and HSPC levels. Clonal tracking highlighted hematopoietic cell cross-talks between the murine BM and hOss, indicating the multipotent or more restricted lineage origin of human hematopoiesis shared in the BM sites.

cell biology↗

bioRxiv2024

Prediction of Aggregation Prone Regions in Proteins Using Deep Neural Networks and Their Suppression by Computational Design

Identification of aggregation-prone regions in proteins and their suppression through mutations is a powerful strategy to enhance protein solubility and yield, significantly expanding their application potential. Here, we developed a deep neural network-based predictor AggreProt, that generates a residue-level aggregation profile for protein sequences. The model outperformed or matched current state-of-the-art algorithms, as validated on two independent datasets comprising hexapeptides and full-length proteins with annotated aggregation-prone regions. We further validated the model experimentally using a set of 34 hexapeptides identified in the model protein haloalkane dehalogenase LinB, along with seven proteins from the AmyPro database. Experimental results agreed with our predictions in 79% of cases and also revealed inaccuracies in some database annotations. Finally, the algorithms utility was demonstrated by identifying aggregation-prone regions in the LinB enzyme and designing mutations to suppress aggregation in its exposed regions. The resulting variants exhibited reduced aggregation propensity, improved solubility, and up to a 100% increase in yield compared to the wild type. AggreProt is freely available to the scientific community via a user- friendly web server: https://loschmidt.chemi.muni.cz/aggreprot.

bioinformatics↗

bioRxiv2023

Attention to Colour: Spotlight in Hue Space

Biological systems must allocate limited perceptual resources to relevant elements in their environment. This often requires simultaneous selection of multiple elements from the same feature dimension (e.g., colour). To establish the determinants of divided attentional selection of colour, we conducted an experiment that used multicoloured displays with four overlapping random dot kinematograms that differed only in hue. We manipulated (1) requirement to focus attention to a single colour or divide it between two colours; (2) distances of distractor hues from target hues in a perceptual colour space. We conducted a behavioural and an electroencephalographic experiment, in which each colour was tagged by a specific flicker frequency and driving its own steady-state visual evoked potential. Behavioural and neural indices of attention showed several major consistencies. Concurrent selection halved the neural signature of target enhancement observed for single targets, consistent with an approximately equal division of limited resources between two hue-selective foci. Distractors interfered with behavioural performance in a context-dependent fashion but their effects were asymmetric, indicating that perceptual distance did not adequately capture attentional distance. These asymmetries point towards an important role of higher-level mechanisms such as categorisation and grouping-by-colour in determining the efficiency of attentional allocation in complex, multi-coloured scenes.

neuroscience↗

bioRxiv2021

Decoding of EEG signals reveals non-uniformities in the neural geometry of colour

The idea of colour opponency maintains that colour vision arises through the comparison of two chromatic mechanisms, red versus green (RG) and yellow versus blue (YB). The four unique hues, red, green, blue, and yellow, are assumed to appear at the null points of these the two chromatic systems. However, whether unique hues have a distinct signature that can be reliably discerned in neural activity is still an open question. Here we hypothesise that, if unique hues represent a tractable cortical state, they should elicit more robust activity compared to non-unique hues. We use a spatiotemporal decoding approach to reconstruct an activation space for a set of unique and intermediate hues across a range of luminance values. We show that electroencephalographic (EEG) responses carry robust information about isoluminant unique hues within a 100-300 ms window from stimulus onset. Decoding is possible in both passive and active viewing tasks, but is compromised when concurrent high luminance contrast is added to the colour signals. The efficiency of hue decoding is not entirely predicted by their mutual distance in a nominally uniform perceptual colour space. Instead, the encoding space shows pivotal non-uniformities which suggest that anisotropies in neurometric hue-spaces are likely to represent perceptual unique hues. Furthermore, the neural code for hue temporally coincides with the neural code for luminance contrast, thus explaining why potential neural correlates of unique hues have remained so elusive until now.

neuroscience↗