Biology subjects

Lenart, P.

Publications and source records attributed to Lenart, P..

16 recordsLinked to original sources

bioRxiv2026

Temporal compression of gonadal growth preserves reproductive timing and soma-to-germline scaling under stress

How organisms maintain timely reproduction under stress is central to life history plasticity and remains an unmet challenge in biomedicine. Life history theory predicts that organisms preserve fitness across environments by reallocating resources between somatic and reproductive growth, yet direct tests of this prediction have been limited by the lack of longitudinal life history data. Here, using Caenorhabditis elegans, we combine longitudinal video microscopy of gonadal growth, mathematical modelling, and genetic perturbations to show that reproductive timing is preserved through temporally dynamic control of reproductive organ growth. Under stress, the onset of gonad growth was delayed early in development but later accelerated relative to somatic growth, thereby preserving reproductive-to-somatic size ratios at adulthood. Modelling suggests this delay-and-acceleration strategy to minimize the time to maturity under stress. Consistently, disrupting compensatory gonadal growth acceleration, either through genetic perturbation of the JNK/p38 stress signalling pathway or by uncoupling of reproductive and somatic development, reduced gonad size and delayed reproduction. Together, our results show that reproductive robustness under stress arises from dynamic regulation of reproductive growth rather than a fixed shift in resource allocation, defining a previously unrecognized mechanistic principle for environmentally plastic sexual maturation.

developmental biology↗

bioRxiv2026

Cnidarian oocytes reveal conserved actin-driven mechanisms of female meiosis

Oocyte meiosis is a specialized form of cell division adapted to produce a single haploid egg for fertilization. Diverse actin-driven mechanisms have essential roles in supporting these highly asymmetric divisions of the large oocyte. Whether these represent exotic adaptations in individual species or whether actin has broadly conserved functions in animal oocytes remains unclear. To address this, we established live-imaging assays, combined with targeted perturbations and biophysical modeling, in the non-bilaterian jellyfish Clytia hemisphaerica. We show that in Clytia, a nuclear F-actin network stabilizes the large oocyte nucleus. Upon meiotic entry, a transient F-actin shell forms to facilitate nuclear envelope rupture, followed by chromosome congression driven by the collapse of the nuclear F-actin network and capture by microtubules. Finally, the forming spindle is transported to the cell periphery by cytoplasmic flows produced by a wave of cortical contraction. Together, the presence of these actin-driven mechanisms in a basal metazoan evidence their ancient origin, establishing a metazoan complement of conserved molecular modules required for oocyte divisions.

cell biology↗

bioRxiv2026

Proximity labeling at H3K9me3 reveals VRK-1 regulate global chromatin distribution in C. elegans

Heterochromatin marked by histone H3 lysine 9 di- or trimethylation (H3K9me2/3) underpins transcriptional silencing and nuclear organization, yet its full complement of associated proteins remains incompletely defined. Here, we apply ChromID proximity labelling with the mouse HP1{beta} chromodomains to map the H3K9me3-proximal proteome in Caenorhabditis elegans, recovering known heterochromatin factors alongside previously uncharacterized candidates. We pursued one such candidate, the vaccinia-related kinase VRK-1, because of its established but poorly understood links to chromatin organization. Intriguingly, VRK-1 dynamically relocates from a broad nuclear distribution to the nuclear periphery upon azide or heat stress. Following these stresses, bulk chromatin exhibits similarly increased peripheral enrichment and apparent compaction, as assessed by radial fluorescence profiles. Although VRK-1 is not necessary for stress-induced chromatin reorganization, decompaction and repositioning of chromatin away from the nuclear envelope during recovery requires VRK-1. VRK-1 depletion leads to persistent perinuclear chromatin retention and compromises post-stress survival. Furthermore, loss of VRK-1 catalytic activity results in over-retention of chromatin at the nuclear periphery under normal growth conditions; this phenotype can be reversed by depletion of a key VRK-1 substrate at the nuclear envelope BAF-1. Our findings identify VRK-1 as a key regulator that controls the interaction of chromatin with the nuclear lamina through regulation of BAF-1.

cell biology↗

bioRxiv2025

AutoSTED: An automated workflow for STED super-resolution imaging of cell nuclei

The traditional microscopy workflow involves manual selection of objects one after the other. This is not only time consuming, but inevitably introduces human bias. Here, we describe a workflow, AutoSTED for identification of cell nuclei on wide-field fluorescence images and subsequent automated imaging of these nuclei at super-resolution by Stimulated Emission Depletion (STED) microscopy. We demonstrate that in an overnight run we are able to image hundreds of cells selected without bias. The resolution afforded by STED allowed straightforward identification and counting of individual nuclear pore complexes (NPCs), and enabled us to automatically extract parameters such as NPC density under different experimental conditions. Together, we illustrate how automation enables optimal use of instrument time to produce large unbiased datasets.

cell biology↗

bioRxiv2025

Direct mechanical communication of cellular to nuclear shape in oocytes

The mechanical properties of the cytoplasm and nucleoplasm are crucial for the correct and robust functioning of a cell and play a key role in understanding how mechanical signals are transferred to the nucleus. Here, we demonstrate remarkable shape mimicry between the cellular and nuclear shape of oocytes, following the externally applied deformation without direct contact between the cell cortex and the nucleus. This effect arises from a surprisingly soft and fluid-like nucleoplasm that is barely resisting any external strain, while the viscoelastic cytoplasm drives shape transmission. Comparative studies in jellyfish, starfish, and mouse oocytes reveal that lower cytoplasmic elasticity in jellyfish leads to reduced nuclear shape mimicry, highlighting the role of cytoplasmic mechanics in nuclear deformation. Significance StatementMechanosensing of the nucleus is, in addition to chemical signalling, an important factor in gene expression. Although nuclei are often thought to be rigid inclusions in the cytoplasm of a cell, we show that in oocytes nuclei are much more deformable. Using a combination of intranuclear, intracellular and extracellular measurements, we attribute our findings to a fine balance between the soft nucleoplasm surrounded by an elastic shell and the viscoelastic properties of the cytoplasm.

biophysics↗

bioRxiv2024

Plk1 inhibition delays mitotic entry revealing prophase-specific changes to the phosphoproteome

Polo-like kinase 1 (plk1) is a conserved regulator of cell division. During prophase, plk1 phosphorylates direct substrates and is involved in activation of the cyclin-dependent kinase 1 (cdk1). However, the exact functions of plk1 in prophase remain incompletely understood. By testing several cell lines and small-molecule inhibitors, we confirm that plk1 inhibition causes a delay in mitotic entry. We show that cells are delayed in a prophase-like state displaying progressively condensing chromosomes, increased microtubule dynamics, reorganization of the actin cortex, while the nuclear envelope remains intact. We show that during this prolonged prophase cdk1 activity increases gradually over several hours with individual cells stochastically reaching the entry threshold, explaining the highly variable timing of mitotic entry. We then use phosphoproteomics to characterize this prolonged prophase state revealing for the first time phosphosites specific to prophase including several regulators of chromatin organization and the cytoskeleton. Together, we show that plk1 functions as a catalyst of prophase to prometaphase transition, and by using plk1 inhibition as a tool, we identify early changes in the phosphoproteome as the cell prepares for division.

cell biology↗

bioRxiv2023

Phosphoproteomics identifies targets of Mos-MAPK regulating translation and spindle organization in oocyte meiosis

The Mos kinase activates the ERK/MAPK pathway during oocyte meiosis, controlling essential meiotic functions in species across metazoa. However, despite its significance, the molecular targets of Mos-MAPK remain largely unidentified. Here, we addressed this question using starfish oocytes ideally suited to combine cellular assays with phosphoproteomics. This revealed CPE-mediated mRNA polyadenylation as a prominent target of Mos-MAPK, and we show that translation is required to drive the second meiotic division. Secondly, we identify a well-defined subset of cytoskeletal regulators as targets of Mos-MAPK. We show that this regulation is critical to ensure the asymmetry of meiotic divisions primarily by reducing the growth of astral microtubules. This allows positioning of the spindle directly beneath the cortex and prevents the separation of spindle poles in anaphase, thereby minimizing polar body size. Thus, by phosphoproteomics we reveal molecular modules controlled by Mos-MAPK explaining how this single, conserved kinase can act as a switch between the mitotic and meiotic division programs.

cell biology↗

bioRxiv2023

Learning accelerates the evolution of slow aging but obstructs negligible senescence

BackgroundFor most animals, intrinsic senescence-induced mortality increases with age, while deaths from extrinsic threats, such as predation or accidents, decline during development as individuals grow and mature. Age-dependent modulation of extrinsic mortality is known to influence the evolution of aging, yet how the timing of mortality shapes evolutionary forces remains poorly understood. ResultsTo address this, we developed two complementary mathematical models that integrate survival benefits arising during development with the progressive increase in mortality associated with senescence. Agent-based simulations and deterministic analyses revealed a strong and consistent influence of the timing of developmental survival benefits on their evolutionary impact: early-life survival benefits reduced the selection for slower aging, while late-acting benefits enhanced it. This difference arises because early-life benefits more strongly accelerate population growth than late-life benefits, diminishing the relative evolutionary advantage of increased longevity. ConclusionsOur results underscore the importance of mortality timing in the evolution of aging and provide a theoretical framework for connecting developmental trajectories to aging dynamics.

evolutionary biology↗

bioRxiv2021

Biological Factors and Self-Perception of Stress Predict Human Freeze-Like Responses in the Context of Self-Defence Training and Personal Experience with Violence

Many animals react to threatening stimuli such as a predator attacks by freezing. However, little experimental research investigated freeze response in humans. Here, we have employed practices commonly used in self-defence training to create two unique scenarios simulating armed physical attacks. Sixty healthy men volunteers divided into three groups of twenty (untrained, trained but unexperienced, trained and experienced) underwent these scenarios accompanied by measurement of biochemical, physiological, and psychological markers of stress. All participants also underwent an fMRI session during which they observed neutral and negative images from the International Affective Picture System (IAPS). Our results show that scenarios simulating physical attacks can induce a freeze-like response in men. In addition, we demonstrate that while electrodermal activity (EDA), subjective stress perception, and brain activity in fMRI predict freeze-like response in men, their effect on freeze-like response is entirely dependent on the level of training and experience of a given individual.

neuroscience↗

bioRxiv2021

TACSTD2 upregulation is an early reaction to lung infection

TACSTD2 encodes a transmembrane glycoprotein Trop2 commonly overexpressed in carcinomas. While the Trop2 protein was discovered already in 1981 and first antibody-drug conjugate targeting Trop2 were recently approved cancer therapy, the physiological role of Trop2 is still not fully understood. In this article, we show that TACSTD2/Trop2 expression is evolutionarily conserved in lungs of various vertebrates. By analysis of publicly available transcriptomic data we demonstrate that TACSTD2 level consistently increases in lungs infected with miscellaneous pathogens. Single cell and subpopulation based transcriptomic data revealed that the major source of TACSTD2 transcript are lung epithelial cells and their progenitors and that TACSTD2 is induced directly in lung epithelial cells following infection. This increase may represent a mechanism to maintain/restore epithelial barrier function and contribute to regeneration process in infected/damaged lungs.

cell biology↗

bioRxiv2020

Learning Mitigates Genetic Drift

Genetic drift is a basic evolutionary principle describing random changes in allelic frequencies, with far-reaching consequences in various topics ranging from species conservation efforts to speciation. The conventional approach assumes that genetic drift has the same effect on all populations undergoing the same change in size, regardless of different behaviors and history of the populations. However, here we reason that processes leading to a systematic increase of individuals chances of survival, such as learning or immunological memory, can mitigate the effects of genetic drift even if the overall mortality rate in the population does not change. We further test this notion in an agent-based model monitoring allele frequencies in a population of prey, either able or not able to learn. Importantly, both these populations start with the same effective size and have the same and constant overall mortality rates. Our results demonstrate that even under these conditions, learning can mitigate drift if generations overlap. Furthermore, this effect holds regardless if the population is haploid or diploid or whether it reproduces sexually or asexually. Therefore, our findings demonstrate that learning is an overlooked factor affecting the effective population size. These findings may be of importance not only for basic evolutionary theory but also for other fields using the concept of genetic drift.

evolutionary biology↗

bioRxiv2020

Predation Has Small, Short-Term, and in Certain Conditions Random Effect on the Evolution of Aging

The pace of aging varies considerably in nature. Historically, scientists focused mostly on why and how has aging evolved, while only a few studies explored mechanisms driving evolution of specific rates of aging. Here we develop an agent-based model simulating evolution of aging in prey subject to predation. Our results suggest that predation affects the pace of aging in prey only if young, vivid animals are not much more likely to escape predators than the old ones. However, even this effect slowly vanishes when the predator diet composition evolves, too. Furthermore, evolution of a specific aging rate, in our model, is driven mainly by a single parameter, the strength of a trade-off between aging and fecundity. Indeed, in absence of this trade-off the evolutionary impacts of predation on the prey aging rate appear random. Our model produces several testable predictions which may be useful for other areas of aging research.

evolutionary biology↗

bioRxiv2018

An F-actin shell ruptures the nuclear envelope by sorting pore-dense and pore-free membranes in meiosis of starfish oocytes

The nucleus of oocytes, traditionally referred to as the germinal vesicle, is unusually large and its nuclear envelope (NE) is densely packed with nuclear pore complexes (NPCs) stockpiled for embryonic development. We have shown that breakdown of this specialized NE during meiosis of starfish oocytes is mediated by an Arp2/3-nucleated F-actin shell, in contrast to microtubule-driven tearing in somatic cells. The detailed mechanism of how the cytoskeletal forces disrupt the NE remains poorly understood in any system. Here, we address the mechanism of F-actin-driven NE rupture by using live-cell and correlated super-resolution light and electron microscopy. We show that actin is nucleated within the lamina and sprouts filopodia-like spikes towards the nuclear membranes forcing lamina and nuclear membranes apart. These F-actin spikes protrude pore-free nuclear membranes, whereas the adjoining membrane stretches accumulate packed NPCs associated with the still-intact lamin network. NPC conglomerates sort into a distinct tubular-vesicular membrane network, while breaks appear in pore-free, ER-like regions. Together, our work reveals a novel function for Arp2/3-mediated membrane shaping in NE rupture that is likely to have broad relevance in regulating NE dynamics in diverse other contexts such as nuclear rupture frequently observed in cancer cells.

cell biology↗

bioRxiv2018

Evolution favors aging in populations with assortative mating and strong pathogen pressure

Since at first sight aging seems to be omnipresent, many authors to this very day regard it as an inevitable consequence of the laws of physics. However, studies published in the past two decades have conclusively shown that a number of organisms do not age, or at least do not age on a scale comparable with other aging organisms. This disparity leads us to question why aging evolved in some organisms and not in others. We thus present a mathematical model which simulates evolution in a sexually reproducing population composed of aging and non-aging individuals. We have observed that aging individuals may outcompete non-aging individuals if they have a higher starting fertility or if the main mating pattern in the population is assortative mating. Furthermore, stronger pathogen pressure was found to help the aging phenotype when compared to the non-aging phenotype. Last but not least, the aging phenotype was found to more easily outcompete the non-aging one or to resist the dominance of the latter for a longer period of time in populations composed of dimorphic sexually reproducing individuals compared to populations of hermaphrodites. Our findings are consistent with both classical evolutionary theories of aging and with evolutionary theories of aging which assume the existence of an aging program. They can thus potentially work as a bridge between these two opposing views, suggesting that the truth in fact lies somewhere in between.\n\nSignificance StatementThis study presents the first mathematical model which simulates the evolution of aging in a population of sexually reproducing organisms. Our model shows that aging individuals may outcompete non-aging individuals in several scenarios known to occur in nature. Our work thus provides important insight into the question why aging has evolved in most, but not all, organisms.

evolutionary biology↗

bioRxiv2018

F-actin patches nucleated on chromosomes coordinate capture by microtubules in oocyte meiosis

Capture of each and every chromosome by spindle microtubules is essential to prevent chromosome loss and aneuploidy. In somatic cells, astral microtubules search and capture chromosomes forming lateral attachments to kinetochores. However, this mechanism alone is insufficient in large oocytes. We have previously shown that a contractile F-actin network is additionally required to collect chromosomes scattered in the 70-m starfish oocyte nucleus. How this F-actin-driven mechanism is coordinated with microtubule capture remained unknown. Here, we show that after nuclear envelope breakdown Arp2/3-nucleated F-actin patches form around chromosomes in a Ran-GTP-dependent manner, and we propose that these structures sterically block kinetochore-microtubule attachments. Once F-actin-driven chromosome transport is complete, coordinated disassembly of these F-actin patches allows synchronous capture by microtubules. Our observations indicate that this coordination is necessary, as early capture of chromosomes by microtubules would interfere with F-actin-driven transport leading to chromosome loss and formation of aneuploid eggs.

cell biology↗

bioRxiv2017

Mortality Data Suggests that Men Are More Fragile but Women Age Faster

Women on average live longer than men, which seems to suggest that women also age slower than men. However, the potential difference in pace of aging between sexes is a relatively controversial topic, and both positions \"women age slower\" and \"women and men age at the same pace\" have found some support. We thus employ mathematical methods previously established in model organisms to compare the pace of aging between the sexes using freely available mortality data from 13 countries. Our results support hypothesis that men age faster than women.

physiology↗