Biology subjects

Szabo, E.

Publications and source records attributed to Szabo, E..

6 recordsLinked to original sources

bioRxiv2026

Recognizing dUTPase as a mitotic factor essential for early embryonic development

dUTPase is universally regarded as a metabolic sanitizing enzyme that protects genomes by preventing the incorporation of uracil into DNA. Despite its essentiality across eukaryotes, no function beyond nucleotide sanitization has been demonstrated. Here, we uncover a conserved, non-canonical role for dUTPase as a regulator of mitosis. Using Drosophila and mouse models, we demonstrate that dUTPase loss causes early embryonic lethality characterized by severe mitotic failure that, cannot be rescued by disabling uracil-DNA repair, uncoupling dUTPase essentiality from DNA repair pathways. Mechanistically, dUTPase dynamically associates with the mitotic spindle and centrosomes, and its depletion induces centrosome amplification and chromosome segregation defects. Beyond cell division, dUTPase dosage bidirectionally controls cell migration, linking its mitotic function to cellular behaviors relevant for metastasis. Together, our findings redefine dUTPase as a moonlighting mitotic factor that coordinates centrosome integrity and spindle dynamics, expanding its known repertoire beyond nucleotide metabolism. HighlightsdUTPase deficiency leads to mitotic defects during early embryonic development in both Drosophila and mouse models dUTPase shows dynamic spatiotemporal localization associated with microtubules through mitosis dUTPase is essential for the normal number and intracellular localization of centrosomes dUTPase deficiency counteracts while its overexpression enhances cell migration

molecular biology↗

bioRxiv2021

Cryptic survival and an unexpected recovery of the long-tailed mayfly Palingenia longicauda (Olivier, 1791) (Ephemeroptera: Palingeniidae) in Southeastern Europe.

O_LIOnce widespread in the large European rivers, Palingenia longicauda underwent a drastic range contraction as a result of the intense pollution and hydromorphological interventions of the 19th and 20th centuries. For the last decades it was considered to be restricted only to the Tisa River and its tributaries, and to the Raba River, but new reports indicated its presence in the Danube River in Hungary, in the Danube Delta in Romania and Ukraine, and in the Prut River in the Republic of Moldova. C_LIO_LIThe objective of this study is to analyze the phylogeographic pattern between the two main eco-regions (Pannon and Pontic) of the species distribution, based on the combined mitochondrial COI (472 bp) and 16S (464 bp) sequences generated for individuals collected in Romania and Ukraine, and from publicly available ones, representing the Tisa catchment populations. C_LIO_LIThe presence of viable populations in the Danube Delta and on the Prut River in Romania is confirmed, and additional presence on the Mure{square} and Bega rivers from Romania, and on the Styr and Horyn rivers in Northern Ukraine is shown. C_LIO_LIThe phylogeographic results indicate that the presence of the analyzed populations are not the result of recent founding events from the Pannon region, confirming the survival and expansion of cryptic local lineages. C_LIO_LIThe recent recovery of the species may be related to the improvement of water quality as a result of the implementation of the EU Water Framework Directive and the EU Floods Directive after 2000. C_LI

ecology↗

bioRxiv2021

Young domestic chicks spontaneously represent the absence of objects

Absence is a notion that is usually captured by language-related concepts like zero or negation. Whether non-linguistic creatures encode similar thoughts is an open question, as everyday behavior marked by absence (of food, of social partners) can be explained solely by expecting presence somewhere else. We investigated 8-day-old chicks looking behavior in response to events violating expectations about the presence or absence of an object. We found different behavioral responses to violations of presence and absence, suggesting distinct underlying mechanisms. Importantly, chicks displayed an avian signature of novelty detection to violations of absence, namely a sex-dependent left-eye-bias. Follow-up experiments excluded accounts that would explain this bias by perceptual mismatch or by representing the object at different locations. These results suggest that the ability to spontaneously form thoughts about the absence of objects likely belongs to the initial cognitive repertoire of vertebrate species.

animal behavior and cognition↗

bioRxiv2020

Host protection to intestinal worm infections: the importance of activated and armed innate effector cells at the host parasite interface.

The intestinal roundworm Heligmosomoides bakeri causes chronic infection in susceptible (C57Bl/6) mice; however, repeat (trickle) infection confers immunity and facilitates worm clearance. We previously showed that this acquired immunity is associated with a strong Th2 response, notably the enhanced production of intestinal granulomas. Here we demonstrate that elevated proportions of IgG1-bound eosinophils and macrophages are observed around the developing tissue worms of trickle-infected female C57Bl/6 mice compared to bolus infected animals. Levels of IgG2c, IgA or IgE were not detected in the granulomas. Increased proportions of SiglecF+ and CD206+ cells, but not Ly6G+ and/or NK1.1+ cells, were also found in the granulomas of trickle-infected mice. However, in the natural world rather than the laboratory setting, immune environments are more nuanced. We examined the impact of a mixed immune environment on trickle infection-induced immunity, using a pre-infection with Toxoplasma gondii. The mixed immune environment resulted in fewer and smaller granulomas with a lack of IgG -bound cells as well as reduced proportions of SiglecF+ and CD206+ cells, measured by immunofluorescence and flow cytometry. This was associated with a higher worm burden in the co-infected animals. Our data confirm the importance of intestinal granulomas and parasite-specific antibody for parasite clearance. They highlight why it may be more difficult to clear worms in the field than in the laboratory. AUTHORS SUMMARYDespite decades of research on intestinal parasitic worms, we are still unable to clearly point to why so many people (approximately 1.8 billion) and most livestock/wild animals are infected with these parasites. We have made progress in understanding how the immune system responds to parasitic worms, and how these parasites manipulate our immune system. However, identifying effective clearance mechanisms is complex and context dependent. We have used models of trickle infection (multiple low doses of parasites) and co-infection (two intestinal parasites) to simulate how people/animals get infected in the real world. Using these models, we have confirmed the host/parasite interface (the granuloma) within the intestinal tissue to be key in determining the hosts ability to clear worms. The lack of specific immune cells and antibodies within the granuloma was associated with chronic infection. Our results help explain why intestinal parasitic worms are so prevalent and why it may be difficult to clear worms in natural settings.

immunology↗

bioRxiv2020

Interactions of anti-COVID-19 drug candidates with multispecific ABC and OATP drug transporters

In the COVID-19 epidemic, several repurposed drugs have been proposed to alleviate the major health effects of the disease. These drugs are often applied together with analgesics or non-steroid anti-inflammatory compounds, and co-morbid patients may also be treated with anticancer, cholesterol-lowering or antidiabetic agents. Since drug ADME-tox properties may be significantly affected by multispecific transporters, here we examined the interactions of the repurposed drugs with the key human multidrug transporters, present in the major tissue barriers and strongly affecting pharmacokinetics. Our in vitro studies, using a variety of model systems, explored the interactions of the antimalarial agents chloroquine and hydroxychloroquine, the antihelmintic ivermectin, and the proposed antiviral compounds, ritonavir, lopinavir, favipiravir and remdesivir with the ABCB1/Pgp, ABCG2/BCRP and ABCC1/MRP1 exporters, as well as the OATP2B1 and OATP1A2 uptake transporters. The results presented here show numerous pharmacologically relevant transporter interactions and may provide a warning for the potential toxicities of these repurposed drugs, especially in drug combinations at the clinic.

pharmacology and toxicology↗

bioRxiv2018

Deterministic and stochastic processes influence the reproducibility of microbial community assembly during aerobic granulation

Aerobic granular sludge is an energy efficient and compact biofilm process for wastewater treatment which has received much attention during the last decades and is now being implemented in full-scale. However, the factors involved in microbial community assembly during formation of granules are poorly understood and little is known about the reproducibility in treatment performance and community structure. Here we show that both deterministic and stochastic factors exert a dynamic influence during microbial community assembly into granular sludge. During granulation, the microbial communities in three replicate sequencing batch reactors followed similar successional trajectories of the most abundant taxa and showed similar dynamics in diversity. Deterministic factors dominated the assembly of the most abundant community members as the microbial community transitioned from floccular to granular form. Stochastic factors mostly affected rare members of the communities and caused the microbial community structure to diverge in one of the reactors; however, this did not have an impact on the treatment performance. This demonstrates that the reactor function and the dynamics of the most abundant community members are in fact reproducible during the formation of aerobic granules.

microbiology↗