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Horvath, B.

Publications and source records attributed to Horvath, B..

11 recordsLinked to original sources

From Scalp to Source: Precise Phase Retrieval of Intracerebral Epileptic Sources Based on Surface EEG

Accurate phase tracking of deep-brain activity is critical for effective closed-loop and phase-locked neuromodulation therapies. However, direct access to deep neural phase through intracranial recordings remains clinically restrictive due to the invasiveness. Here we validate and clinically benchmark the Gabor-Nelson (GN) dipole estimation method for reconstructing deep-brain oscillatory phase from non-invasive scalp EEG. GN is a geometry-based, imaging-independent approach that offers computationally efficient dipole reconstruction and has rarely been applied to source-level phase estimation in human neuroscience. We compared GN with an established MRI-informed Inverse Solution (IS) method using a three-stage reconstruction pipeline consisting of dipole modeling, dimensionality reduction, and frequency-dependent phase-delay correction. Validation is performed using (i) cadaveric recordings, where known ground-truth seizure waveforms were replayed through implanted deep electrodes, and (ii) simultaneous scalp EEG and SEEG recordings in human patients, where pseudo-ground truth was approximated via the intracranial contacts. GN achieved phase accuracy and signal fidelity comparable to IS across both datasets despite requiring no anatomical imaging. In cadaver recordings, phase-corrected reconstruction correlations exceeded r > 0.91 and {Delta}{Phi} < 9{degrees} in mean phase error. In patient SEEG data, GN reached up to r {approx} 0.80 with phase offsets suitable for neuromodulatory timing. GN offers a viable, low-barrier, imaging-independent alternative to traditional inverse modeling for non-invasive seizure phase tracking. This framework opens pathways for scalable, phase-locked and closed-loop stimulation therapies in epilepsy and potentially other network-based brain disorders.

neuroscience↗

Maternal high-fat diet drives sex-specific microglia remodeling of serotonergic reward circuits

Maternal nutrition shapes offspring brain development and influences neurodevelopmental disorder risk, but the underlying mechanisms remain unclear. In mice, maternal high-fat diet exposure disrupted microglia-serotonin interactions during a critical postnatal period, producing persistent, sex-specific mesolimbic alterations. Male but not female offspring showed increased serotonergic fiber density in the nucleus accumbens (NAc), coincident with reduced microglial phagocytosis of serotonergic projections. Microglial 5-HT2C receptor signaling is a key regulator of this process. Viral over expression in microglia, mimicking diet-induced upregulation, was sufficient to cause serotonergic hyperinnervation. By adulthood, male offspring displayed increased NAc serotonin release and projection-specific changes in dorsal raphe physiology. These circuit alterations accelerated reward-motivated learning, a phenotype reproduced by chemogenetic activation of NAc-projecting serotonergic neurons. Together, these findings reveal a novel mechanism by which maternal diet programs serotonergic circuit assembly and behavior in a sex-specific manner, providing a potential link between early-life metabolic inflammation and lifelong serotonergic dysfunction.

neuroscience↗

Morphological and genetic heterogeneity in Aedes aegypti (Diptera: Culicidae) populations across diverse landscapes in West Africa

Native to sub-Saharan Africa, Aedes aegypti has spread across the globe and is now one of the most significant vectors of arboviruses worldwide. However, data on the ranges of its populations remain sparse, and the genetic variability and ecological adaptability in West Africa are still poorly understood. In this study, we characterized the morphological and genetic diversity of Ae. aegypti across four landscape types (urban, peri-urban, rural, and sylvatic sites) in three West African countries (Burkina Faso, Cote dIvoire, and Ghana). Ae. aegypti exhibited significant variation in abdominal scaling patterns across countries and landscape types, with the sylvatic and urban populations in Burkina Faso displaying the highest proportions of white scales (>50% white scales), while black scales predominated among those from Cote dIvoire and Ghana (>80% black scales). Wing shape displayed limited differentiation between the countries, landscape types, and genetic clusters. Bayesian analysis indicated high gene flow among populations, with notable outliers observed in sylvatic sites from Burkina Faso and admixture patterns suggesting possible human-mediated dispersal. Additionally, two major mitochondrial lineages, clades A and B, were identified. Most samples were categorized under clade B, showing no evidence of clustering by country or landscape type. In contrast, clade A comprised primarily sylvatic specimens from Burkina Faso and a single urban individual from Cote dIvoire. These findings highlight the complex interplay of genetic, environmental, and ecological factors shaping the variations in Ae. aegypti populations in West Africa. They provide insights into the phenotypic and genetic diversity of Ae. aegypti, offering valuable implications for understanding arbovirus transmission dynamics and formulating targeted interventions against arboviral diseases.

ecology↗

Non-vectorial Integration of Intersectional Short-Pulse Stimulation Enables Enhanced Deep Brain Modulation and Effective Seizure Control

Transcranial electrical stimulation (TES) holds promise to treat neurological disorders, but its efficacy is limited by poor spatial focality and depth of penetration. Here, we examined the potential utility of Intersectional Short-Pulse (ISP) stimulation of deeper brain penetration. Using computational modeling and in vivo patch-clamp recordings in rats, we demonstrate that neurons integrate ISP-induced electric fields in a non-vectorial manner. This mechanism allows ISP to overcome some limits of conventional TES, achieving spatially limited stimulation across cortical and subcortical structures. In a rat model of temporal lobe epilepsy, closed-loop ISP stimulation significantly outperformed conventional TES in reducing seizure duration and severity. ISP reduced hippocampal seizure duration by 49% and 41% compared to sham stimulation and conventional TES and significantly reduced motor seizure severity. Our findings demonstrate that ISP stimulation can rapidly terminate hippocampal seizures, offering a potential new approach for non-invasive neuromodulation with applications across diverse neurologic and psychiatric disorders.

neuroscience↗

Entamoeba histolytica extracellular vesicles drive pro-inflammatory monocyte signaling

The parasitic protozoan Entamoeba histolytica secretes extracellular vesicles (EVs), but so far little is known about their function in the interaction with the host immune system. Infection with E. histolytica trophozoites can lead to formation of amebic liver abscesses (ALAs), in which pro-inflammatory immune responses of Ly6Chi monocytes contribute to liver damage. Men exhibit a more severe pathology as the result of higher monocyte recruitment and a stronger immune response. To investigate the role of EVs and pathogenicity in the host immune response, we studied the effect of EVs secreted by low pathogenic EhA1 and highly pathogenic EhB2 amebae on monocytes. Size and quantity of isolated EVs from both clones were similar. However, they differed in their proteome and miRNA cargo, providing insight into factors potentially involved in amebic pathogenicity. In addition, EVs were enriched in proteins with signaling peptides compared with the total protein content of trophozoites. Exposure to EVs from both clones induced monocyte activation and a pro-inflammatory immune response as evidenced by increased surface presentation of the activation marker CD38 and upregulated gene expression of key signaling pathways (including NF-{kappa}B, IL-17 and TNF signaling). The release of pro-inflammatory cytokines was increased in EV-stimulated monocytes and more so in male-than in female-derived cells. While EhA1 EV stimulation caused elevated myeloperoxidase (MPO) release by both monocytes and neutrophils, EhB2 EV stimulation did not, indicating the protective role of MPO during amebiasis. Collectively, our results suggest that parasite-released EVs contribute to the male-biased immunopathology mediated by pro-inflammatory monocytes during ALA formation. Author summaryParasites communicate with their host via small membranous extracellular vesicles (EVs) that can shuttle cargo and thus information between cells. The protozoan parasite Entamoeba histolytica releases EVs but not much is known about their role in the interaction with the host immune system. Infection with E. histolytica can lead to amebic liver abscess (ALA) formation. Innate immune cells, particularly monocytes, contribute to liver damage by releasing microbicidal factors. Men have a more severe ALA pathology as the result of a stronger monocyte immune response. In this study, we analyzed the effect of EVs from differently virulent E. histolytica clones on monocytes to better understand their interaction. EVs of both clones were similar in size and quantity but differed in their cargo, which provides information on factors potentially involved in pathogenicity. Monocytes responded to EVs of both clones in a pro-inflammatory manner that reflected the immune processes occurring during ALA in vivo, including the bias towards the male sex. Only EVs of amebae with low pathogenicity, and not those released by the highly pathogenic clone, elicited secretion of the granular enzyme myeloperoxidase, which plays a protective role during ALA. Overall, our data suggest that EVs may contribute to liver injury.

immunology↗

A polytypic species revisited: Phylogenetic and morphological variation, taxonomic status, and geographical distribution of Trachops (Chiroptera: Phyllostomidae)

The taxonomic status of the neotropical bat genus Trachops has been reevaluated through an integrated study that incorporates morphological, morphometric, and molecular data across its extensive geographic range. Our research, which included previously unexamined regions, revealed substantial insights into the diversity within Trachops. The results support the elevation of T. cirrhosus ehrhardti to species status, due to genetic and morphological differences in southeastern Brazil specimens. Conversely, our comprehensive analysis found insufficient evidence to maintain the subspecific distinction of T. c. coffini, which lacks diagnosable morphological characters and is not genetically distinct from T. c. cirrhosus across its distribution range. Additionally, our findings challenge the previous belief of a latitudinal differentiation in body size for Trachops cirrhosus, as specimens from western South America and northeastern South America exhibit similar sizes to those from Central America. These results underscore the importance of revising the taxonomic framework for this bat genus, contributing to a more precise understanding of its evolutionary relationships, and further enhancing conservation efforts, considering the potential threats to the newly recognized T. ehrhardti in the imperiled Atlantic Forest of Brazil.

zoology↗

Targeted mutagenesis of Medicago truncatula Nodule-specific Cysteine-rich (NCR) genes using the Agrobacterium rhizogenes-mediated CRISPR/Cas9 system

The host-produced nodule specific cysteine-rich (NCR) peptides control the terminal differentiation of endosymbiotic rhizobia in the nodules of IRLC legumes. Although the Medicago truncatula genome encodes about 700 NCR peptides, only few of them have been proved to be crucial for nitrogen-fixing symbiosis. In this study, we applied the CRISPR/Cas9 gene editing technology to generate knock-out mutants of NCR genes for which no genetic or functional data were previously available. We have developed a workflow to analyse the mutation and the symbiotic phenotype of individual nodules formed on Agrobacterium rhizogenes-mediated transgenic hairy roots. The selected NCR genes were successfully edited by the CRISPR/Cas9 system and nodules formed on knockout hairy roots showed wild type phenotype indicating that peptides NCR068, NCR089, NCR128 and NCR161 are not essential for symbiosis between M. truncatula Jemalong and Sinorhizobium medicae WSM419. We regenerated stable mutants edited for the NCR068 from hairy roots obtained from A. rhizogenes-mediated transformation. The analysis of the symbiotic phenotype of stable ncr068 mutants showed that peptide NCR068 is not required for symbiosis with S. meliloti strains 2011 and FSM-MA either. Our study reports that gene editing can help to elicit the role of particular NCRs in symbiotic nitrogen fixation.

plant biology↗

The Medicago truncatula nodule-specific cysteine-rich peptides, NCR343 and NCR-new35 are required for the maintenance of rhizobia in nitrogen-fixing nodules.

In the nodules of Inverted Repeat-Lacking Clade legumes, including M. truncatula, nitrogen-fixing rhizobia undergo terminal differentiation resulting in elongated and endoreduplicated bacteroids specialised for nitrogen fixation. This irreversible transition of rhizobia is mediated by host produced nodule-specific cysteine-rich (NCR) peptides, of which about 700 are encoded in the M. truncatula genome. Some of these NCR peptides, NCR169, NCR211 and NCR247, are essential for nitrogen-fixing symbiosis. The analysis of bacteroid and symbiotic host cell differentiation revealed that the symbiotic phenotype of M. truncatula mutants, Mtsym19, Mtsym20 and NF-FN9363, were defective likewise in the formerly studied ncr mutants, Mtdnf4-1 and Mtdnf7-2. The incomplete differentiation of bacteroids triggered premature senescence of rhizobia in the nitrogen fixation zones of mutant nodules. Mtsym19 and Mtsym20 mutants are defective in the same peptide NCR-new35 and the lack of NCR343 is responsible for the ineffective symbiosis of NF-FN9363. The activity of NCR-new35 is significantly lower and limited to the transition zone of the nodule compared with other crucial NCRs. The fluorescent protein-tagged version of NCR343 and NCR-new35 localize to the symbiotic compartment. Our discovery added two additional members to the group of NCR genes essential for nitrogen-fixing symbiosis in M. truncatula.

plant biology↗

Sailing in rough waters: examining volatility of fMRI noise

BackgroundThe assumption that functional magnetic resonance imaging (fMRI) noise has constant volatility has recently been challenged by studies examining heteroscedasticity arising from head motion and physiological noise. The present study builds on this work using latest methods from the field of financial mathematics to model fMRI noise volatility. MethodsMulti-echo nd human fMRI scans were used and realised volatility was estimated. The Hurst parameter H [isin] (0, 1), which governs the roughness/irregularity of realised volatility time series, was estimated. Calibration of H was performed pathwise, using well-established neural network calibration tools. ResultsIn all experiments the volatility calibrated to values within the rough case, H < 0.5, and on average fMRI noise was very rough with 0.03 < H < 0.05. Some edge effects were also observed, whereby H was larger near the edges of the phantoms. DiscussionThe findings suggest that fMRI volatility is not only non-constant, but also substantially more irregular than a standard Brownian motion. Thus, further research is needed to examine the impact such pronounced oscillations in the volatility of fMRI noise have on data analyses.

neuroscience↗

The Medicago truncatula Vacuolar Iron Transporter-Like proteins VTL4 and VTL8 deliver iron to endosymbiotic bacteria at different stages of the infection process

The symbiotic relationship between legumes and rhizobium bacteria in root nodules has a high demand for iron. The host plant is known to provide iron to developing bacteroids, but questions remain regarding which transporters are involved. Here, we characterize two Vacuolar Iron Transporter-Like (VTL) proteins in Medicago truncatula that are specifically expressed during nodule development. VTL4 is mostly expressed during early infection and the protein was localized to membranes and the infection thread. vtl4 mutants were delayed in nodule development. VTL8 is closely related to SEN1 in Lotus japonicus and expressed in the late stages of bacteroid differentiation. The VTL8 protein was localized to the symbiosome membrane. A mutant line lacking the tandemly-arranged VTL4 - VTL8 genes, named 13U, was unable to develop functional nodules and failed to fix nitrogen, which was restored by expression of VTL8 alone. Using a newly developed lux reporter to monitor iron status of the bacteroids, a slight decrease in luminescence was observed in vtl4 mutants and a strong decrease in the 13U mutant. Iron transport capability of VTL4 and VTL8 was shown by yeast complementation. Taken together, these data indicate that VTL-type transporters are the main route for delivering iron to symbiotic rhizobia.

plant biology↗

Evolution of exploitative interactions during diversification in Bacillus subtilis biofilms

Microbial biofilms are tightly packed, heterogeneous structures that serve as arenas for social interactions. Studies on Gram negative models reveal that during evolution in structured environments like biofilms, isogenic populations commonly diversify into phenotypically and genetically distinct variants. These variants can settle in alternative biofilm niches and develop new types of interactions that greatly influence population productivity. Here, we explore the evolutionary diversification of pellicle biofilms of the Gram positive, spore-forming bacterium Bacillus subtilis. We discover that - similarly to other species - B. subtilis diversifies into distinct colony variants. These variants dramatically differ in biofilm formation abilities and expression of biofilm-related genes. In addition, using a quantitative approach, we reveal striking differences in surface complexity and hydrophobicity of the evolved colony types. Interestingly, one of the morphotypes completely lost the ability of independent biofilm formation and evolved to hitchhike with other morphotypes with improved biofilm forming abilities. Genome comparison suggests that major phenotypic transformations between the morphotypes can be triggered by subtle genetic differences. Our work demonstrates how positive complementarity effects and exploitative interactions intertwine during evolutionary diversification in biofilms.

microbiology↗