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Di Cara, F.

Publications and source records attributed to Di Cara, F..

5 recordsLinked to original sources

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↗

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↗

Phage-displayed synthetic library and screening platform for nanobody discovery

Nanobodies, single-domain antibodies derived from camelid heavy-chain antibodies, are known for their high affinity, stability, and small size, which make them useful in biological research and therapeutic applications. However, traditional nanobody generation methods rely on camelid immunization, which can be costly and time-consuming, restricting their practical feasibility. In this study, we present a phage-displayed synthetic library for nanobody discovery. To validate this approach, we screened nanobodies targeting various Drosophila secreted proteins. The nanobodies identified were suitable for applications such as immunostaining and immunoblotting, supporting the phage-displayed synthetic library as a versatile platform for nanobody development. To address the challenge of limited accessibility to high-quality synthetic libraries, this library is openly available for non-profit use.

biochemistry↗

Impaired peroxisomal import in Drosophila hepatocyte-like cells induces cardiac dysfunction through the pro-inflammatory cytokine Upd3

Age is a major risk factor for cardiovascular diseases. Currently, the non-autonomous regulation of age-related cardiac dysfunction is poorly understood. In the present study, we discover that age-dependent induction of cytokine unpaired 3 (Upd3) in Drosophila oenocytes (hepatocyte-like cells), due to a dampened peroxisomal import function, is the primary non-autonomous mechanism for elevated arrhythmicity in old hearts. We show that Upd3 is significantly up-regulated (52-fold) in aged oenocytes. Oenocyte-specific knockdown of Upd3 is sufficient to block aging-induced cardiac arrhythmia. We further show that the age-dependent induction of Upd3 is triggered by impaired peroxisomal import and elevated JNK signaling in aged oenocytes. Intriguingly, oenocyte-specific over-expression of Pex5, the key peroxisomal import receptor, restores peroxisomal import, blocks age-related Upd3 induction, and alleviates aging- and paraquat-induced cardiac arrhythmicity. Thus, our studies identify an important role of the evolutionarily conserved pro-inflammatory cytokine signaling and hepatocyte-specific peroxisomal import in mediating non-autonomous regulation of cardiac aging.

physiology↗

Functional characterization of peroxisome biogenic proteins Pex5 and Pex7 of Drosophila

Peroxisomes are ubiquitous membrane-enclosed organelles involved in lipid processing and reactive oxygen detoxification. Mutations in human peroxisome biogenesis genes (Peroxin, PEX) cause progressive developmental disabilities and, in severe cases, early death. PEX5 and PEX7 are receptors that recognize different peroxisomal targeting signals called PTS1 and PTS2, respectively, and traffic proteins to the peroxisomal matrix. We characterized mutants of Drosophila melanogaster Pex5 and Pex7 and found that adult animals are affected in lipid processing. Moreover, Pex5 mutants exhibited severe developmental defects in the embryonic nervous system and muscle, similar to what is observed in humans with Pex5 mutations, while Pex7 fly mutants were weakly affected in brain development, suggesting different roles for Pex7 in fly and human. Of note, although no PTS2-containing protein has been identified in Drosophila, Pex7 from Drosophila can function as a bona fide PTS2 receptor because it can rescue targeting of the PTS2-containing protein Thiolase to peroxisomes in PEX7 mutant human fibroblasts.

cell biology↗