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Collet, M.

Publications and source records attributed to Collet, M..

5 recordsLinked to original sources

Safety profiling of CAR-T cells using an organotypic human tissue platform

CAR-T-cell-associated on-target off-tumor (OTOT) toxicity represents a major safety concern, as recognition of target antigens on healthy tissues can trigger severe and potentially life-threatening complications. Predicting OTOT toxicity remains a challenge because current preclinical models fail to capture the complexity of native human tissues. Here, we developed a human organotypic tissue platform that enables functional assessment of CAR-T-cell activity in intact human tissues across organ-specific and inflammatory contexts. Using a panel of clinically relevant CAR-T-cell products with known OTOT toxicities, we demonstrate that the platform faithfully recapitulates clinically observed tissue-specific toxicity profiles. CAR-T cells targeting EGFR, HER2, and mesothelin induced inflammatory and cytotoxic responses in healthy human lung tissue, whereas CD19 CAR-T cells remained inactive. We further show that OTOT toxicity cannot be reliably predicted from antigen abundance alone but instead results from the integration of multiple target-dependent determinants, including CAR affinity, inflammatory context, antigen accessibility, and effector-cell dose. The platform also enables quantitative assessment of inflammatory and cytotoxic responses and supports evaluation of pharmacological and CAR design-based strategies to mitigate toxicity. Together, this work establishes the first human organotypic platform for functional modeling of CAR-T-cell-associated OTOT toxicity, providing a clinically relevant framework for preclinical safety evaluation and the rational development of safer engineered cell therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/740527v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@12c8addorg.highwire.dtl.DTLVardef@150d392org.highwire.dtl.DTLVardef@17218f7org.highwire.dtl.DTLVardef@1c54078_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

High Impact: Wikipedia sources and edit history document two decades of the climate change field

Since being founded in 2001, Wikipedia has grown into a trusted source of knowledge online, feeding Google search results and serving as training data for ChatGPT. Understanding the accuracy of its information, the sources behind its articles and their role in the transference of knowledge to the public are becoming increasingly important questions. Meanwhile, climate change has moved to the forefront of scientific and public discourse after years of warnings from the scientific community. Therefore, to understand how it was represented on English Wikipedia, we deployed a mixed-method approach on the article for "Effects of climate change" (ECC), its edit history and references, as well as hundreds of associated articles dealing with climate change in different ways. Using automated tools to scrape data from Wikipedia, we saw new articles were created as climatology-related knowledge grew and permeated into other fields, reflecting a growing body of climate research and growing public interest. Our qualitative textual analysis shows how specific descriptions of climatic phenomena became less hypothetical, reflecting the real-world public debate. The Intergovernmental Panel on Climate Change (IPCC) had a big impact on content and structure, we found using a bibliometric analysis, and what made this possible, we also discovered through a historical analysis, was the impactful work of just a few editors. This research suggests Wikipedias articles documented the real-world events around climate change and its wider acceptance - initially a hypothesis that soon became a regretful reality. Overall, our findings highlight the unique role IPCC reports play in making scientific knowledge about climate change actionable to the public, and underscore Wikipedias ability to facilitate access to research. This work demonstrates Wikipedia can be researched using both computational and qualitative methods to better understand transference of scientific information to the public and the history of contemporary science.

scientific communication and education↗

Wikipedia as a tool for contemporary history of science: A case study on CRISPR

Rapid developments and methodological divides hinder the study of how scientific knowledge accumulates, consolidates and transfers to the public sphere. Our work proposes using Wikipedia, the online encyclopedia, as a historiographical source for contemporary science. We chose the high-profile field of gene editing as our test case, performing a historical analysis of the English-language Wikipedia articles on CRISPR. Using a mixed method approach, we qualitatively and quantitatively analyzed its text, sections and references, alongside 50 affiliated articles. These, we found, documented CRISPRs maturation from a fundamental scientific discovery to a biotechnological revolution with vast social and cultural implications. We developed automated tools to support such research generically and demonstrated its applicability on two other scientific fields we have previously studied - COVID-19 and Circadian clocks. This method makes use of Wikipedia as a digital and free archive, documenting the incremental growth of knowledge and the manner scientific research accumulates and translates into public discourse. Using Wikipedia in this manner compliments and overcomes some issues with contemporary histories and can also augment existing bibliometric research.

scientific communication and education↗

Automated flight interception traps for interval sampling of insects

Recent debates on insect decline require sound assessments on the relative drivers that may negatively impact insect populations. Often, baseline data rely on insect monitorings that integrates catches over long time periods. If, however, effects of time-critical environmental factors (e.g., light pollution) are of interest, higher temporal resolution of insect observations during specific time intervals are required (e.g., between dusk and dawn). Conventional time-critical insect trapping is labour-intensive (manual activation/deactivation) and temporally inaccurate as not all traps can be serviced synchronically at different sites. Also, temporal shifts of environmental conditions (e.g., sunset/sunrise) are not accounted for. We provide a battery-driven automated insect flight-interception trap which samples insects during seven user-defined time intervals. A commercially available flight-interception trap is fitted to a rotating platform containing seven flasks and a passage hole. The passage hole avoids unwanted sampling during time-intervals not of interest. Comparisons between two manual and two automated traps during 71 nights in 2018 showed no difference in caught insects. An experiment using 20 automated traps during 104 nights in 2019 proved that the automated flight interception traps is reliable. The automated trap opens new research possibilities as any insect-sampling interval can be defined. It is efficient and saves manpower and associated costs as activation/deactivation is required only every seven sampling intervals. Also, the traps are accurate because all traps sample exactly the same intervals. The trap is low maintenance and robust due to straightforward technical design. It can be controlled manually or via Bluetooth and smartphone.

ecology↗

Insects and incest: field evidence for dangerous liaisons in a parasitoid wasp

O_LISib mating avoidance is a pervasive behaviour, which likely evolves in species that sare subject to inbreeding depression. Laboratory studies have provided elegant demonstrations, but small-scale bioassays often minimize the costs associated with mate finding and mate-choice and may for this reason produce spurious findings.\nC_LIO_LIWe inferred the mating behaviour of the parasitoid wasp Venturia canescens from the genetic analyses of natural populations. We used V. canescens as a model organism because in this species, laboratory experiments have shown that sib mating yields a 25% decrease in fertile offspring, and congruently, sib mating is partially avoided.\nC_LIO_LIOur study consisted in genotyping 86 wild-caught males, 155 wild-caught-females and their 226 daughters at eighteen microsatellite loci. With these data, we were able to reconstruct the genotype of females mate and estimate the relatedness of each mating pairs.\nC_LIO_LIWe found that the effective rate of sib mating does not differ from the probability that sibs encounter one another at random, which suggest a sib mating tolerance in this species. However, complementary lab experiments confirmed that kin discrimination exist in this species, with related pairs having a lower mating latency.\nC_LIO_LIThese results suggest that V. canescens tolerate sib mating in the field despite kin discrimination, and therefore call into question the common beliefs on inbreeding depression in species with single-locus complementary sex determination. This inbreeding tolerance also opens up the question of the maintenance of the kin discrimination in this species.\nC_LI

animal behavior and cognition↗