Biology subjects

Clement, S.

Publications and source records attributed to Clement, S..

5 recordsLinked to original sources

bioRxiv2026

Ex vivo human airway epithelia modelling reveals specific alterations in lung and hematopoietic stem cell transplant recipients

Deterioration of lung function is a major cause of long-term morbidity after hematopoietic stem cell transplantation (HSCT) and lung transplantation (LT). In both settings, obliterative bronchiolitis represents the most common final pathway, with bronchiolitis obliterans syndrome (BOS), representing its clinical correlate. Understanding of the pathophysiological mechanisms leading to BOS is limited by restricted access to human lung tissue and the imperfect relevance of animal models. We hypothesize that transplantation procedures cause bronchial epithelial damage that promotes the development of BOS. To investigate this, we established ex vivo human airway epithelia (HAE) cultures from bronchial biopsies of HSCT and LT recipients, collected prior to the development of BOS, and compared them with non-transplant controls. HAE from HSCT recipients exhibited reduced tissue differentiation ability, associated with defect in mucociliary clearance and impaired barrier integrity, most markedly in one patient who subsequently developed BOS. In contrast, LT-derived HAE showed normal mucociliary clearance and barrier integrity but displayed increased mucin secretion. Donor and recipient-derived cells were detected in both paraffin-embedded biopsies and reconstructed HAE derived from transplant recipients, demonstrating epithelial chimerism. Our data highlight specific modifications of the airway epithelium after LT and HSCT that may represent a first trigger for subsequent BOS development.

Molecular Biology↗

bioRxiv2026

Human airway organoids as a high-throughput screening platform for antiviral natural products discovery

Antiviral drug discovery for respiratory viruses is hindered by the lack of scalable physiologically relevant systems. Here, we report the first high-throughput screen of 764 natural plant extracts against respiratory syncytial virus (RSV) using human primary airway organoids as a relevant model. A parallel screen conducted in A549 cells allowed the identification of 70 extracts with organoid-specific antiviral activity from which 45 active phytocompounds were purified. We identified early- and late-acting antiviral compounds and demonstrated a polarization-dependent activity for some of them. Collectively, our results establish the use of airway organoids as a scalable first-line platform for high-throughput antiviral discovery and exploit the plant-derived chemical space as an underexplored source of RSV inhibitors.

microbiology↗

bioRxiv2025

Pathway diversity: a resilience metric sensitive to agency applied to a lake eutrophication problem

Measuring resilience has been a longstanding challenge in social-ecological research. While there are established resilience metrics, they often do not account for agency, which is crucial in social-ecological systems. Pathway diversity is a recent approach to measuring resilience that integrates systems thinking with individual-based elements, such as agency. According to this approach, resilience is larger if actors have more decision pathways and can maintain them over time. Here we measure resilience using pathway diversity within a lake eutrophication model to analyse (a) the extent to which it is sensitive to changes in agency and (b) its compatibility with more established resilience metrics. Our findings reveal that pathway diversity is sensitive to regime shifts and can provide early warnings of them. Through five policy decision-making scenarios, we then show how pathway diversity can capture constraints on decision makers capability and agency that affect the systems resilience. We find that higher pathway diversity is associated with greater capability of decision-makers to influence the system. Pathway diversity addresses a critical gap by incorporating agency into a resilience metric while remaining compatible with established metrics. This work shows the potential of pathway diversity to identify resilience-based policy implications.

ecology↗

bioRxiv2024

Enterovirus A71 adaptation to heparan sulfate comes with capsid stability tradeoff

Because of high mutation rates, viruses constantly adapt to new environments. When propagated in cell lines, certain viruses acquire positively charged amino acids on their surface proteins, enabling them to utilize negatively charged heparan sulfate (HS) as an attachment receptor. In this study, we used enterovirus A71 (EV-A71) as model and demonstrated that unlike the parental MP4 variant, the cell-adapted strong HS-binder MP4-97R/167G does not require acidification for uncoating and releases its genome in the neutral or weakly acidic environment of early endosomes. We experimentally confirmed that this pH-independent entry is not associated with the use of HS as an attachment receptor but rather with compromised capsid stability. We then extended these findings to another HS-dependent strain, suggesting that adaptation to HS generally modifies capsid stability and alters entry mechanism. Our data show EV-A71 pH-independent entry for the first time and, more importantly, highlight the intricate interplay between HS-binding, capsid stability, and viral fitness, wherein enhanced multiplication in cell lines leads to attenuation in hostile in vivo environments such as the gastrointestinal tract.

microbiology↗

bioRxiv2019

The fungal sesquiterpenoid pyrenophoric acid B uses the plant ABA biosynthetic pathway to inhibit seed germination.

HighlightThe fungus Pyrenophora semeniperda produces pyrenophoric acid B, a small molecule that exploits the plant ABA biosynthetic pathway to reduce seed germination, increasing its reproductive success.\n\nAbstractPyrenophoric acid (P-Acid), P-Acid B and P-Acid C are three phytotoxic sesquiterpenoids produced by the ascomycete seed pathogen Pyrenophora semeniperda, a fungus proposed as a mycoherbicide for biocontrol of cheatgrass, an extremely invasive weed. When tested in cheatgrass bioassays these metabolites were able to delay seed germination, with P-Acid B being the most active compound. Here, we have investigated the cross-kingdom activity of P-Acid B and its mode of action and found that it activates the ABA signaling pathway in order to inhibit seedling establishment. P-Acid B inhibits seedling establishment in wild-type Arabidopsis thaliana while several mutants affected in the early perception as well as in downstream ABA signaling components were insensitive to the fungal compound. However, in spite of structural similarities between ABA and P-Acid B, the latter is not able to activate the PYR/PYL family of ABA receptors. Instead, we have found that P-Acid B uses the ABA biosynthesis pathway at the level of alcohol dehydrogenase ABA2 to reduce seedling establishment. We propose that the fungus Pyrenophora semeniperda manipulates plant ABA biosynthesis as a strategy to reduce seed germination, increasing its ability to cause seed mortality and thereby increase its fitness through higher reproductive success.

plant biology↗