Biology subjects

Biro, P.

Publications and source records attributed to Biro, P..

6 recordsLinked to original sources

bioRxiv2026

Flightless I and LRRFIP work together to regulate lateral growth of the sarcomeres in Drosophila

Myofibrils are structurally highly conserved elements of the cardiac and striated muscles. The striking commonalities in their basic organization principles emerge during myofibrillogenesis when the initially formed premyofibrils grow in length and width to attain their final dimensions, characteristic of each muscle type. Although the molecular composition of the myofibrils is well known, the mechanisms governing their growth remain poorly understood, particularly those driving peripheral thickening. Here, we show that two cardiac disease associated proteins, Flightless I and LRRFIP, are required for lateral integration of the myofilaments that is essential for circumferential myofibril growth in the Drosophila flight muscle. Genetic and biochemical analysis reveal that these proteins form multimeric complexes enriched at the barbed end of the actin filaments. Furthermore, we found that the Flightless I/LRRFIP complex acts in a formin dependent manner. Together, our findings demonstrate that Flightless I and LRRFIP cooperate to promote the spatially controlled integration of peripheral actin filaments at the Z-disc, uncovering a key step in myofibril maturation.

cell biology↗

bioRxiv2025

Subsequent memory effect in the inferior frontal gyrus revealed by fNIRS

A central finding in memory research is the subsequent memory effect, which describes consistent neural differences during encoding between events that are later remembered versus those that are forgotten, which has been reliably replicated with both EEG and fMRI for the past decades. Replicating the subsequent memory effect using fNIRS could enable research opportunities that are difficult to pursue with other methods, including studies with children, patient populations, or experiments in highly naturalistic settings. Therefore, our study investigated whether the prefrontal cortex is differentially involved in subsequently remembered versus subsequently forgotten stimuli using fNIRS. Our results showed that in particular channels mapping onto the inferior frontal gyrus showed more activation during encoding of subsequently remembered events compared to subsequently forgotten events. These results demonstrate that fNIRS can reliably capture the subsequent memory effect, providing new opportunities to study memory mechanisms across diverse populations and real-world contexts.

neuroscience↗

bioRxiv2025

From one schema to another: How the prefrontal cortex responds to conflicting information

Over time, we develop event schemas or scripts that shape our expectations about what typically happens in certain contexts. However, even after forming a memory about a certain event, we are often exposed to related information about that same event at later points in time. This additional information sometimes causes one to have to re-evaluate the interpretation of the original event. Over a two-day fNIRS experiment, participants were exposed to events that were subsequently updated with schema-congruent or schemaincongruent additional details. These schema-incongruent additional details make those events more fitting to another schema than originally was the case, meaning that participants would need to dissociate that event from the original schema and re-integrate it with another schema. The fNIRS results showed stronger PFC activity for events updated with schema-congruent compared to schema-incongruent details. When specifically looking at those events that were updated with schema-incongruent details, our results suggest that dissociating an event from the original schema and re-integrating it with another schema was accompanied by an initial PFC decrease early in the trial followed by a PFC increase later in the trial. This was a distinctly different pattern compared to trials in which participants failed to re-integrate the event with another schema, which showed delayed PFC increase with lower amplitude and no initial PFC decrease. Our results refine our understanding of mechanisms of adaptive memory updating in the face of conflicting information.

neuroscience↗

bioRxiv2025

A myofilament lattice model of Drosophila flight muscle sarcomeres based on multiscale morphometric analysis during development

The indirect flight muscle is a widely used model for studying sarcomere structure and muscle development due to its extremely regular architecture. Nevertheless, precise measurement of the basic sarcomeric parameters remains a challenge even in this greatly ordered tissue. In this study, we identified several factors affecting measurement reliability and developed a software tool for precise, high-throughput measurement of sarcomere length and myofibril width. The accuracy of this new tool was validated against simulated images and blinded manual measurements. To extend the scope of this morphometric analysis to the sub-sarcomeric scale, we used electron and super-resolution microscopy to quantify myofilament number and filament length during myofibrillogenesis. These results provided novel insights into the dynamics of sarcomere growth, and enabled us to construct a refined model of sarcomere growth reaching to the level of individual myofilaments and providing a spatial framework for interpreting molecular localization data. These findings enhance our understanding of sarcomere assembly and offer a foundation for future studies of muscle development and function. SUMMARY STATEMENTThis study identifies factors influencing sarcomere size measurements, introduces a validated tool for precise analysis, and presents a comprehensive model of Drosophila flight muscle sarcomere growth during muscle development.

developmental biology↗

bioRxiv2024

Mild hyperthermia-induced thermogenesis in the endoplasmic reticulum defines stress response mechanisms

Previous studies reported that a mild, non-protein denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed that the master regulator of the UPR, the IRE1 (inositol-requiring enzyme 1) protein is clustered as a result of UPR activation in a human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, a temperature-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we detected significant intracellular thermogenesis in mouse embryonic fibroblast (MEF) cells. Temperatures reached at least 8{degrees}C higher than the external environment (40{degrees}C), resulting in exceptionally high ER temperatures similar to those previously described for mitochondria. Mild heat-induced thermogenesis in the ER of MEF cells was likely due to the uncoupling of the Ca2+/ATPase (SERCA) pump. The high ER temperatures initiated a pronounced cytosolic heat shock response in MEF cells, which was significantly lower in U2OS cells in which both the ER thermogenesis and SERCA pump uncoupling were absent. Our results suggest that, depending on intrinsic cellular properties, mild hyperthemia-induced intracellular thermogenesis defines the cellular response mechanism, and determines the outcome of hyperthermic stress.

cell biology↗

bioRxiv2021

Oxoglutarate dehydrogenase coordinates myofibril growth by maintaining amino acid homeostasis

Myofibrils are long intracellular cables specific to muscles, composed mainly of actin and myosin filaments. The actin and myosin filaments are organized into repeated units called sarcomeres, which form the myofibril cables. Muscle contraction is achieved by the simultaneous shortening of sarcomeres and for a highly coordinated contraction to occur all sarcomeres should have the same size. Muscles have evolved a variety of ways to ensure sarcomere homogeneity, one example being the controlled oligomerization of Zasp proteins that sets the diameter of the myofibril. To understand how Zasp proteins effect myofibril growth, we looked for Zasp-binding proteins at the Z-disc. We found that the E1 subunit of the oxoglutarate dehydrogenase complex is recruited to the Z-disc by Zasp52 and is required to sustain myofibril growth. By making specific mutants, we show that its enzymatic activity is important for myofibril growth, and that the other two subunits of the complex are also required for myofibril formation. Using super resolution microscopy, we revealed the overall organization of the complex at the Z-disc. Then, using metabolomic analysis, we uncovered an amino acid balance defect affecting protein synthesis, that we also confirmed by genetic tools. In summary, we show that Zasp controls the local amino acid pool responsible for myofibril growth by recruiting the OGDH complex to the Z-disc.

cell biology↗