Biology subjects

Kiss, T.

Publications and source records attributed to Kiss, T..

7 recordsLinked to original sources

bioRxiv2026

Low-intensity ultrasound drives offline neuromodulation through passive membrane mechanisms in synaptically isolated hippocampal neurons

Low-intensity ultrasound alters neuronal excitability long after exposure ends, but the basis of this offline effect is unclear and most proposed mechanisms require synaptic receptors. We recorded from cultured mouse hippocampal neurons in whole-cell current clamp, before and 20 min after 1 min of 850 kHz continuous-wave ultrasound at 0.5 W/cm2 or sham, with synaptic transmission blocked throughout, each neuron re-patched. Sonicated neurons remained intact and firing, yet depolarized, with smaller action potentials and more noise. A passive-membrane fit showed reduced capacitance and a depolarized leak reversal potential in every sonicated cell, with a shortened time constant and no detectable change in input conductance, while sham cells showed no significant change. Changes in the time constant and reversal potential, both independent of membrane area, indicate a modification of the membrane itself rather than a loss of area. Brief ultrasound therefore leaves a lasting, receptor-independent imprint on passive membrane properties.

neuroscience↗

bioRxiv2026

An Epstein-Barr virus-encoded snoRNA directs 2'-O-methylation of human rRNAs to control translation and the viral lytic switch

Epstein-Barr virus (EBV) establishes life-long latency in human B-cells yet the molecular strategies that balance its persistence with lytic replication remain incompletely understood. Here, we identify the EBV-encoded small nucleolar RNA, v-snoRNA1, as a bona fide 2'-O-methylation guide that directs methylation of host ribosomal RNAs at 18S-C621 and 28S-U1760, two conserved residues in the ribosomal A-site. V-snoRNA1-mediated hypermethylation impairs 18S rRNA maturation and compromises translational fidelity and output, resulting in slower cellular proliferation. Infection with a v-snoRNA1 deleted virus ({Delta}v-snoRNA1) leads to enhanced protein synthesis and increased proliferation, together with extensive rewiring of host and viral gene expression. This rewiring includes suppression of immune and interferon pathways and alterations in transcription factor activities important for B-cell differentiation. Importantly, we find that v-snoRNA1 is required to facilitate viral production. Our findings reveal a molecular strategy by which EBV directly controls translation to promote infection.

molecular biology↗

bioRxiv2026

Rejuvenation of the Aged Cerebrovascular System via Protein Corona-Guided Fusogenic Liposome Delivery

Brain vascular aging is increasingly recognized as a critical therapeutic target for age-related cognitive decline. Oxidative stress, bioenergetic dysfunction, and molecular damage play central roles in the progression of vascular aging, contributing to cerebrovascular dysfunction and impaired cognitive function. While naturally occurring polyphenols such as resveratrol (RSV) have demonstrated potential in mitigating aging-related pathologies, their poor bioavailability and limited brain targeting efficiency significantly constrain their therapeutic impact. As a result, high doses or advanced drug delivery strategies are necessary to achieve meaningful physiological effects. We introduce a novel nanocarrier system designed to enhance RSV delivery to the cerebral endothelium by leveraging the natural formation of an apolipoprotein E (ApoE)-enriched protein corona around fusogenic liposomes (FL) in vivo. These nanoparticles directly fuse with cytoplasmic cell membranes and thus evade endocytosis. We found that once in the circulation FL spontaneously acquire a protein corona, which is highly enriched in ApoE, a key ligand for brain endothelial low-density lipoprotein receptors (LDLR). Based on this observation, we engineered an ApoE-functionalized protein corona around FL (ApoE-FL) to systematically evaluate whether this mechanism could be exploited for targeted brain delivery. Following optimization and physicochemical characterization, the RSV-loaded liposomes were evaluated in vitro using human cerebral microvascular endothelial cells and in vivo C57BL/6 aged mice to assess their therapeutic potential. Both FL and engineered ApoE-FL liposomal delivery systems exhibited a strong affinity for endothelial cell membranes in vitro. The knockdown of the ApoE receptor, low-density lipoprotein receptor-related protein 1 (LRP1), significantly reduced liposomal docking. Microscopy analysis revealed that both ApoE-FL and non-functionalized FL directly fused with endothelial plasma membranes, thus bypassing intracellular organelles and minimizing lysosomal degradation. This suggests that the naturally formed ApoE corona in vivo may contribute to efficient cerebrovascular targeting, a property successfully replicated by the engineered ApoE corona strategy. In vivo biodistribution and kinetic studies demonstrated that especially ApoE-FL achieved enhanced brain-targeting efficiency, prolonged cerebrovascular retention, and extended targeting distance along the arteriovenous axis. This emphasizes that fusogenic liposomes effectively engage almost the entire microvascular network, including capillaries and post-capillary venules. Functionally, fusogenic liposome-delivered RSV improved blood-brain barrier (BBB) integrity, enhanced neurovascular coupling (NVC) responses, and promoted brain vascularization in aged mice. Single-cell RNA sequencing (scRNA-seq) revealed enhanced endothelial angiogenesis and barrier protective transcriptional profiles in cerebrovascular cells treated with ApoE-FL/RSV, suggesting a molecular basis for the observed vascular benefits. Liposomal RSV delivery achieved near-complete cerebrovascular and cognitive rejuvenation in aged mice applying a 2000-fold lower RSV dose than oral administration used as control sample. Thus, ApoE-FL liposomes exhibited exceptionally high delivery efficiency in deeper brain regions, further expanding their therapeutic potential. These findings underscore the importance of targeted drug delivery in optimizing therapeutic outcomes and establish ApoE-functionalized fusogenic liposomes as a promising strategy for mitigating brain vascular aging and cognitive decline. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/709925v1_ufig1.gif" ALT="Figure 1000"> View larger version (52K): org.highwire.dtl.DTLVardef@acad5borg.highwire.dtl.DTLVardef@a96e3borg.highwire.dtl.DTLVardef@18405aeorg.highwire.dtl.DTLVardef@90e349_HPS_FORMAT_FIGEXP M_FIG C_FIG

animal behavior and cognition↗

bioRxiv2025

Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming and increased inflammation in the aging brain

Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses revealed that aging promotes lipid droplet accumulation in brain ECs. These lipid-laden brain ECs exhibit a transcriptomic signature indicative of impaired blood-brain barrier function, increased cellular senescence, and inflammation in aging. Furthermore, lipid accumulation is associated with an altered metabolic phenotype characterized by increased fatty acid oxidation and decreased glycolysis, and impaired mitochondrial electron transport chain activity in the ECs of the aging brain. We have also validated lipid accumulation in aged ECs in vivo. Collectively, our findings indicate that lipid accumulation drives structural, functional, and metabolic impairments in the brain ECs, likely contributing to cerebrovascular aging. Understanding the mechanisms underlying lipid accumulation-induced endothelial dysfunction may offer novel therapeutic strategies for mitigating microvascular dysfunction and cognitive decline in aging.

neuroscience↗

bioRxiv2025

Optimal inter-electrode distances for maximizing single unit yield per electrode in neural recordings

State-of-the-art high-density multielectrode arrays enable the recording of simultaneous spiking activity from hundreds of neurons. Although significant efforts have been dedicated to enhancing neural recording devices and developing more efficient sorting algorithms, there has been relatively less focus on the allocation of microelectrodes--a factor that undeniably affects spike sorting effectiveness and ultimately the total number of detected neurons. Here, we systematically examined the relationship between optimal electrode spacing and spike sorting efficiency by creating virtual sparser layouts from high-density recordings through spatial downsampling. We assessed spike sorting performance by comparing the quantity of well-isolated single units per electrode in sparse configurations across various brain regions (neocortex and thalamus) and species (rat, mouse, and human). Enabling the theoretical estimation of optimal electrode arrangements, we complement experimental results with a geometrical modeling framework. Contrary to the general assumption that higher electrode density inherently leads to more efficient sorting, both our theoretical and experimental results reveal a clear optimum for electrode spacing specific to species and regions. We demonstrate that carefully choosing optimal electrode distances could yield a total of 1.7 to 3 times increase in spike sorting efficiency. These findings emphasize the necessity of species- and region-specific microelectrode design optimization.

neuroscience↗

bioRxiv2024

Drought influences the fungal community structure, diversity, and functionality inhabiting the grapevine xylem and enhances the abundance of Phaeomoniella chlamydospora

The productivity of grapevines in Mediterranean regions faces significant threats from global warming, which may intensify competition for water resources. Recent research highlights the impact of water deficit on the root-associated microbiota of grapevines, particularly organisms capable of mitigating abiotic and biotic stressors. This study explores the influence of drought on the structure, diversity, and functionality of xylem- inhabiting fungal communities of grapevine, with a focus on the fungal pathogen Phaeomoniella chlamydospora associated with esca and Petri diseases. One-year-old grapevine rootlings grown under greenhouse conditions were subjected to three water regimes: severe water deficit (SWD) at 25% of field capacity, moderate water deficit (MWD) at 50% of field capacity, and no water deficit (AWD) at 100% of field capacity. Wood samples were non-destructively collected before planting (t0) and one (t1) and two (t2) growing seasons after planting from the bottom, medium, and apical parts of the rootstock. Fungal composition and P. chlamydospora abundance were assessed using ITS high-throughput amplicon sequencing (HTAS) and droplet-digital PCR (ddPCR), respectively. The induced water stress not only altered the diversity and composition of the fungal microbiome in the xylem vessels but also affected co- occurrence networks, resulting in less complex networks with fewer correlations between taxa, potentially increasing grapevine vulnerability to various biotic and abiotic stresses. SWD significantly reduced microbial diversity, leading to a shift in the abundance of pathotrophs such as P. chlamydospora in the xylem. This underscores the interconnectedness between water stress, microbiome dynamics, and plant health. The combination of compromised plant defenses, altered physiological conditions, and shifts in the surrounding microbial community may create conditions conducive to increased P. chlamydospora abundance in the xylem vessels of young vines following water stress.

microbiology↗

bioRxiv2021

Light spectra trigger divergent gene expression in barley cultivars

Light spectra influence barley development, causing a diverse range of responses among cultivars that are poorly understood. Here, we exposed three barley genotypes with different light sensitivities to two light sources: fluorescent bulbs, over-representing green and red wavebands, and metal halide lamps, with a more balanced spectrum. We used RNA sequencing to identify the main genes and pathways involved in the different responses, and RT-qPCR to validate the expression values. Different grades of sensitivity to light spectra were associated with transcriptional reprogramming, plastid signals, and photosynthesis. The genotypes were especially divergent in the expression of genes regulated by transcription factors from MADS-box, WRKY, and NAC families, and in specific photoreceptors such as phytochromes and cryptochromes. Variations in light spectra also affected the expression of circadian clock, flowering time, and frost tolerance genes, among others, resembling plant responses to temperature. The relation between PPD-H1, HvVRN1, and HvFT1 expression might explain genotypic differences. Light-sensitive genotypes experienced a partial reversion of the vernalization process and senescence-related stress under the less favorable light quality conditions. The observed light-quality sensitivities reveal a complex mechanism of adaptation to regions with specific light quality features and/or possible regulation of light spectra in plant development during early spring. HighlightDevelopment genes were affected by light quality in the barley varieties tested. Different grades of sensitivity were related to the expression of transcription factors, senescence, light signaling and cold-regulated genes.

plant biology↗