Biology subjects

Molnar, M.

Publications and source records attributed to Molnar, M..

7 recordsLinked to original sources

bioRxiv2026

Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis

An administration of 3 hydroxy-butyrate (3-OHB) in experimental animals or humans is associated with an increase of cardiac output (CO), but whether this hemodynamic benefit reflects direct myocardial inotropy or heart unloading due to peripheral vasodilation remains unclear. It is also unknown if myocardial effects are due to engagement of receptor-mediated inotropic response, or due to improvement of myocardial bioenergetics. To address these questions, we studied integrated cardiovascular response (pressure-volume analysis of the left ventricle) and isolated left ventricular (LV) trabeculae from normotensive male HanSD rats (age 20-30 weeks) after administration of 3-OHB (1 mmol/l) and drugs targeting adrenergic and cAMP-dependent signaling - metoprolol, adenylyl cyclase inhibitor 2,5-dideoxyadenosine and isoprenaline, during Tyrode solution perfusion and 1 Hz pacing. Pressure-volume analysis demonstrated increased left ventricular end-systolic elastance (+34%), improved ventriculo-arterial coupling (+65%) and increased LV efficiency (+28%), indicating direct inotropic effect of 3OHB. In isolated LV trabeculae, 3-OHB increased twitch force in both groups, but increase was greater in healthy hearts (+55.8%) than in the HF group (+35.6%) (p = 0.014). The inotropic effect of 3-OHB was not further augmented by coadministration of isoprenaline and was not attenuated by beta-1 adrenergic blockade or cAMP inhibition. Results suggest that 3-OHB directly improves LV inotropy and by a mechanism that is independent of receptor-mediated beta-adrenergic signaling, most consistent with a direct bioenergetic pathway. These findings support 3-OHB as a candidate inotropic agent with a mechanistic profile distinct from conventional cAMP-dependent inotropes.

physiology↗

bioRxiv2026

Multiple overlapping SNARE complexes drive endosome maturation in Drosophila nephrocytes

Endosomal maturation determines whether internalized cargo is recycled or degraded, yet the molecular logic governing early endosomal fusion remains poorly defined. This process is often depicted as a linear Rab5-to-Rab7 transition mediated by a single, ordered SNARE pathway, but extensive redundancy in mammalian systems has obscured pathway architecture. Here, using Drosophila nephrocytes as a genetically tractable in vivo model with minimal SNARE redundancy, we show that early endosome maturation is driven by multiple parallel, non-interchangeable SNARE-dependent pathways. We first resolve a long-standing discrepancy in Syntaxin 7 family orthology, demonstrating that the Drosophila protein previously termed Syx7/Avl is functionally analogous to mammalian STX12 rather than STX7, while late endosomal and lysosomal fusion is mediated by a distinct Syntaxin 7 homolog (Syx13). Based on this reclassification, we define a Syx12L-Snap29-Ykt6 complex that drives canonical homotypic early endosomal fusion. In addition, we identify two related SNARE assemblies - Syx7L-Snap29-Ykt6 and Syx7L-Snap29-Vamp7-that promote later stages of endosomal and lysosomal fusion with distinct Rab GTPase requirements. These partially compensatory complexes remain active when the canonical pathway is disrupted, producing divergent morphological outcomes, including the formation of aberrant endolysosomal swirls. We establish Snap29 as a central Qbc-SNARE integrating all endosomal fusion routes and uncover a dual role for Ykt6 in promoting maturation while also participating in endosomal recycling. Together, our findings revise the prevailing model of endosome maturation, revealing a network of parallel, regulated fusion pathways that confer robustness and plasticity to the endolysosomal system.

cell biology↗

bioRxiv2025

Murder in cold blood? Forensic and bioarchaeological identification of the skeletal remains of Bela, Duke of Macso (c. 1245-1272)

In 1915, the remains of a male were discovered in a 13th-century monastery on Margaret Island, Budapest. Historical context suggested that the remains may belong to Duke Bela of Macso (c. 1245-1272), grandson of King Bela IV of Hungary (House of Arpad) and son of Duke Rostislav (Rurik dynasty). We applied a complex approach to identify the individual and reconstruct the circumstances of his death. Radiocarbon dating, when adjusted for freshwater reservoir effects linked to a high-protein diet, placed the burial in the mid-13th century. Skeletal features corresponded to a young adult male. Stable isotope and dental calculus analyses indicated a high-status diet rich in animal proteins and C3 cereals. Ancient DNA confirmed descent from King Bela III (Arpad dynasty) and Y-chromosomal affiliation with the Rurikid lineage. Forensic evidence revealed 26 perimortem injuries, suggesting a coordinated, premeditated assassination involving at least three assailants. The pattern of injuries indicates both planning and intense emotional involvement. Our findings provide the first genetic identification of a medieval royal, and resolve a century-old archaeological question, and illustrate the power of integrating multidisciplinary methods to confirm historical hypotheses and reconstruct violent deaths from the past with unprecedented detail. TeaserWith unprecedented details, this study shows the impact of integrating multidisciplinary methods to confirm historical hypotheses and reconstruct violent deaths from the past.

genetics↗

bioRxiv2024

The Rab7-Epg5 and Rab39-ema modules cooperately position autophagosomes for efficient lysosomal fusions

Macroautophagy, a major self-degradation pathway in eukaryotic cells, utilizes autophagosomes to transport self-material to lysosomes for degradation. While microtubular transport is crucial for the proper function of autophagy, the exact roles of factors responsible for positioning autophagosomes remain incompletely understood. In this study, we performed a loss-of-function genetic screen targeting genes potentially involved in microtubular motility. A genetic background that blocks autophagosome-lysosome fusions was used to accurately analyze autophagosome positioning. We discovered that pre-fusion autophagosomes move towards the non-centrosomal microtubule organizing center (ncMTOC) in Drosophila fat cells, which requires a dynein-dynactin complex. This process is regulated by the small GTPases Rab7 and Rab39 together with their adaptors: Epg5 and ema, respectively. The dynein-dependent movement of vesicles toward the nucleus/ncMTOC is essential for efficient autophagosomal fusions with lysosomes and subsequent degradation. Remarkably, altering the balance of kinesin and dynein motors changes the direction of autophagosome movement, indicating a competitive relationship where normally dynein-mediated transport prevails. Since pre-fusion lysosomes were positioned similarly to autophagosomes, it indicates that pre-fusion autophagosomes and lysosomes converge at the ncMTOC, which increases the efficiency of vesicle fusions.

cell biology↗

bioRxiv2024

Functional brain adaptations during speech processing in 4-month-old bilingual infants

Language learning is influenced by both neural development and environmental experiences. This work investigates the influence of early bilingual experience on the neural mechanisms underlying speech processing in 4-month-old infants. We study how an early environmental factor such as bilingualism interacts with neural development by comparing monolingual and bilingual infants brain responses to speech. We used functional near-infrared spectroscopy (fNIRS) to measure 4-month-old Spanish-Basque bilingual and Spanish monolingual infants brain responses while they listened to forward (FW) and backward (BW) speech stimuli in Spanish. We reveal distinct neural signatures associated with bilingual adaptations, including increased engagement of bilateral inferior frontal and temporal regions during speech processing in bilingual infants, as opposed to left hemispheric specialization observed in monolingual infants. This study provides compelling evidence of bilingualism-induced brain adaptations during speech processing in infants as young as four months. These findings emphasize the role of early language experience in shaping neural plasticity during infancy suggesting that bilingual exposure at this young age profoundly influences the neural mechanisms underlying speech processing. Research HighlightsO_LIThis research sheds light on the intricate relationship between language learning, neural maturation, and environmental factors in early infancy. C_LIO_LIBilingual infants exhibit unique functional brain adaptations during speech processing as early as 4 months of age. C_LIO_LIThis study underscores the critical role of language experience in shaping the developing brain. C_LIO_LIThese findings have implications for our understanding of language acquisition and neuroplasticity in infants growing up in bilingual environments. C_LI

neuroscience↗

bioRxiv2023

Complex-specific subunits of endosomal tethering factors determine the balance between HOPS/CORVET complexes

The endolysosomal tethering complexes HOPS and CORVET play pivotal roles in the homo- and heterotypic fusion of early and late endosomes, respectively, and HOPS also mediates the fusion of lysosomes with incoming vesicles including late endosomes and autophagosomes. These heterohexameric complexes share their four core subunits that assemble with additional two, complex-specific subunits. These features and the similar structure of the complexes allow the formation of hybrid complexes, and the complex specific subunits may compete for binding to the core. In our study, we decided to gain insight into how human HOPS and CORVET complexes form. We found that the overexpression of CORVET-specific Vps8 or Tgfbrap1 decreased the amount of core proteins Vps11 and Vps18 that are assembled with HOPS-specific subunits Vps41 or Vps39, which suggests reduced amount of intracellular HOPS. In line with this, we observed that the level of lipidated LC3 protein was elevated in these cells and the autophagic cargo p62 showed accumulation in cells overexpressing Vps8, suggesting failure in autophagosome-lysosome fusion in line with loss of HOPS function. In contrast, overexpression of HOPS-specific Vps39 or Vps41 did not affect the levels of these autophagic markers. Finally, we found that a hybrid complex containing Vps39 and Vps8 could be formed in HEK293 cells.

cell biology↗

bioRxiv2020

Monolingual and bilingual infants rely on the same brain networks: Evidence from resting-state functional connectivity

This study examines whether bilingual exposure has a profound effect on the functional organization of the developing human brain during infancy. Recent behavioural research attests that monolingual vs. bilingual experience affects cognitive and linguistic processes already during the first months of life. However, to what extent the intrinsic organization of the infant human brain adapts to monolingual vs. bilingual environments is unclear. We measured spontaneous hemodynamic brain activity using functional near-infrared spectroscopy (fNIRS) in a large cohort (N=99) of 4-month-old monolingual and bilingual infants. We implemented well-established analysis approaches of functional brain imaging that enabled us to reveal the functional organization of the infant brain in large-scale cortical networks, and to perform group-level comparisons (i.e., monolingual vs. bilingual groups) in a reliable manner. Our results revealed no differences between the intrinsic functional organization of the developing monolingual and bilingual infant brain at 4 months of age.

neuroscience↗