Biology subjects

Kurant, E.

Publications and source records attributed to Kurant, E..

4 recordsLinked to original sources

bioRxiv2026

Masking phosphatidylserine prevents neuronal loss in two distinct Drosophila models of neurodegeneration

Neuronal loss is a hallmark of neurodegenerative diseases. Phosphatidylserine (PS), a key eat me signal, is exposed on stressed viable neurons, triggering their premature phagocytosis by activated glia. We investigated whether PS masking could serve as a universal strategy to prevent neuronal loss in two distinct Drosophila models of neurodegeneration: an adult-stage-specific knockdown of skpA and a Huntingtons disease model initiated during embryogenesis. Both models exhibit neuronal loss, motor dysfunction, and reduced lifespan. To mask PS, we used a truncated form of MFG-E8, a glycoprotein that binds PS without promoting engulfment. PS masking preserved two neuronal populations in both models, indicating that these neurons were eliminated alive via phagoptosis. Motor function and lifespan were improved to varying degrees, depending on the timing and severity of neuronal damage. These findings reveal that aberrant glial phagocytosis contributes to neuronal vulnerability and identify PS masking as a promising therapeutic approach for neurodegenerative diseases. Significance StatementNeuronal loss is a defining feature of neurodegenerative diseases, yet its underlying mechanisms remain incompletely understood. Here, we demonstrate in two Drosophila models of neurodegeneration that stressed but viable neurons are prematurely eliminated by glial phagocytosis through phosphatidylserine (PS) exposure. By masking PS with a truncated form of MFG-E8, we prevented neuronal loss, improved motor performance, and extended lifespan, highlighting PS-dependent removal of live neurons as a critical contributor to neurodegeneration. Our findings provide the first in vivo evidence that PS masking protects neurons in distinct neurodegenerative contexts, offering a broadly applicable strategy for therapeutic intervention. This work positions aberrant glial phagocytosis as a disease-driving mechanism and establishes Drosophila as a powerful model for dissecting neuron-glia interactions in neurodegeneration.

cell biology↗

bioRxiv2025

Reproducibility of Scientific Claims in Drosophila Immunity: A Retrospective Analysis of 400 Publications

Drosophila immunity has been the focus of intense study and has impacted other research fields including innate immunity and agriculturally or epidemiologically relevant investigations of insect pests and vectors. Unsurprisingly for such a large body of work, some published results were later found to be irreplicable. Although some results have been contradicted in the literature, many have no published follow-up, either due to a lack of research or low motivation to publish negative or contradictory results. We have addressed this by performing a reproducibility project that analyses the conceptual replicability of claims from articles published on Drosophila immunity before 2011. To assess replicability, we extracted claims from 400 articles on the Drosophila immune response to bacteria and fungi and performed preliminary verification by comparing these claims to other published literature in the field. Using alternative approaches, we also experimentally tested some unchallenged claims, with no published follow-up. The intent of this analysis was to centralize evidence on insights and findings to improve clarity for scientists that may base research programs on these data. Although the aim of the ReproSci project is to assess the replicability of claims made in articles published in the field of Drosophila immunity, it is in no way an assessment of the scientific value of the research. All our data are published on a publicly available website associated with this article (https://ReproSci.epfl.ch/) that encourages community participation. This article provides a short summary of claims that were found to have contradictory evidence, which may help the community to assess past findings on Drosophila immunity and improve clarity going forward. Statistical analysis of this reproducibility study and metascience insights obtained from this approach are discussed in a companion article.

genetics↗

bioRxiv2025

A retrospective analysis of 400 publications reveals patterns of irreproducibility across an entire life sciences research field

The ReproSci project retrospectively analyzed the conceptual replicability of 1006 claims from 400 papers published between 1959 and 2011 in the field of Drosophila immunity. This project attempts to provide a comprehensive assessment, 14 years later, of the replicability of nearly all publications across an entire scientific community in experimental life sciences. We found that 61% of claims were verified, while only 7% were directly challenged (not replicable), a replicability rate higher than previous assessments. Notably, 24% of claims had never been independently tested and remain unchallenged. We performed experimental validations of a selection of 45 unchallenged claim, that revealed that a significant fraction (38/45) of them is in fact non-replicable. We also found that high-impact journals and top-ranked institutions are more likely to publish challenged claims. In line with the reproducibility crisis narrative, the rates of both challenged and unchallenged claims increased over time, especially as the field gained popularity. We characterized the uneven distribution of irreplicability among first and last authors. Surprisingly, irreplicability rates were similar between PhD students and postdocs, and did not decrease with experience or publication count. However, group leaders, who had prior experience as first authors in another Drosophila immunity team, had lower irreplicability rates, underscoring the importance of early-career training. Finally, authors with a more exploratory, short-term engagement with the field exhibited slightly higher rates of challenged claims and a markedly higher proportion of unchallenged ones. While limited by its reliance on published literature, this systematic, field-wide retrospective study offers meaningful perspective into the ongoing discussion on reproducibility in experimental life sciences.

scientific communication and education↗

bioRxiv2025

The secreted Nimrod NimB1 negatively regulates early steps of apoptotic cell phagocytosis in Drosophila

Efferocytosis, the efficient clearance of apoptotic cells (ACs) by phagocytes, is vital for maintaining tissue homeostasis. Here, we reveal the role of the secreted protein NimB1 in reducing apoptotic cell recognition and binding in the early stages of efferocytosis. NimB1 is expressed in macrophages (also called plasmatocytes) and binds to ACs in a phosphatidylserine-dependent manner. Structural analysis shows that NimB1 shares striking similarities with the bridging molecule NimB4, and possesses two phosphatidylserine-binding motifs, supporting its role in efferocytosis. Larval macrophages of NimB1 null mutants display a hyper-phagocytic phenotype characterized by increased engulfment of ACs. Confocal imaging reveals that NimB1 specifically inhibits early steps in internalization of ACs, but does not impact phagosome maturation. We find that NimB1 is a secreted factor that negatively regulates efferocytosis, antagonizing the role of NimB4. Our study and the analogous opposing roles of Draper Isoforms II and I in efferocytosis suggest that a balance of negative and positive regulators allows optimization of the rate of apoptotic cell clearance by macrophages.

immunology↗