Biology subjects

Dufour, N.

Publications and source records attributed to Dufour, N..

4 recordsLinked to original sources

bioRxiv2026

In vivo real-time elastography with unmodified commercial endoscopes using noise-correlation-inspired method and laser speckle imaging

AO_SCPLOWBSTRACTC_SCPLOWEarly tumor detection is critical for improving patient survival and recovery. Clinically, tissue palpation is routinely used to identify regions of abnormal stiffness, a hallmark of many pathological conditions. However, palpation is restricted to anatomically accessible sites and remains highly operator dependent. Here, we introduce a method for real-time quantitative stiffness mapping using an unmodified commercial endoscope, with the goal of enhancing diagnostic capabilities and restoring mechanical feedback during endoscopic procedures. Our approach combines shear wave elastography with speckle imaging and an innovative synchronization strategy that enables the measurement of shear wave propagation using an unmodified commercial endoscope. The resulting wave fields are analyzed with the noise-correlation-inspired (NCI) method[1], providing pixel-wise estimates of shear wave velocity and, consequently, quantitative maps of local tissue stiffness. The method demonstrated robust performance in both benchtop and endoscopic configurations. Validation was achieved on polymer phantoms as well as on ex vivo and in vivo biological tissues, highlighting its potential for minimally invasive biomechanical imaging and real-time tissue characterization.

biophysics↗

bioRxiv2024

Amyloid signaling in antiphage defense

Immune regulated cell death (RCD) is a defense strategy common to different domains of life involving purposeful sacrifice of infected cells. In animals and fungi, functional amyloids play a role in the control of RCD as molecular switches activating key cell death effectors, rather than causing direct toxicity as seen with pathological amyloids. Here, we describe a novel amyloid-based signal transduction mechanism in an antiphage defense system in Escherichia coli. This antiphage abortive infection (Abi) system is mediated by two proteins, Bab and Agp which share a common amyloid motif and are encoded by adjacent genes. Upon phage infection, Agp activates Bab through amyloid signaling, leading to cell death. We determined the structure of the Bab cell death execution domain, which is distantly related to pore-forming domains present in fungi, animals and plants. We show that Bab and the fungal HET-S amyloid-controlled cell death execution protein are functionally interchangeable in their respective roles in antiphage defense and allorecognition. These findings add antiphage defense to the functional repertoire of amyloids.

microbiology↗

bioRxiv2021

The JAK2-STAT3 pathway controls a beneficial proteostasis response of reactive astrocytes in Huntington disease

Huntingtons disease is a fatal neurodegenerative disease characterized by striatal neurodegeneration, aggregation of mutant Huntingtin and the presence of reactive astrocytes. Astrocytes are important partners for neurons and engage in a specific reactive response in Huntingtons disease that involves morphological, molecular and functional changes. How reactive astrocytes contribute to Huntingtons disease is still an open question, especially because their reactive state is poorly reproduced in experimental mouse models. Here, we show that the JAK2-STAT3 pathway, a central cascade controlling astrocyte reactive response, is activated in the putamen of Huntingtons disease patients. Selective activation of this cascade in astrocytes through viral gene transfer reduces the number and size of mutant Huntingtin aggregates in neurons and improves neuronal defects in two complementary mouse models of Huntingtons disease. It also reduces striatal atrophy and increases glutamate levels, two central clinical outcomes measured by non-invasive magnetic resonance imaging. Moreover, astrocyte-specific transcriptomic analysis shows that activation of the JAK2-STAT3 pathway in astrocytes coordinates a transcriptional program that increases their intrinsic proteolytic capacity, through the lysosomal and ubiquitin-proteasome degradation systems. This pathway also enhances their production and exosomal release of the co-chaperone DNAJB1, which contributes to mutant Huntingtin clearance in neurons. Together, our results show that the JAK2-STAT3 pathway controls a beneficial proteostasis response in reactive astrocytes in Huntingtons disease, which involves bi-directional signalling with neurons to reduce mutant Huntingtin aggregation, eventually improving disease outcomes.

neuroscience↗

bioRxiv2021

Combination of in vivo phage therapy data with in silico model highlights key parameters for treatment efficacy

The clinical (re)development of phage therapy to treat antibiotic resistant infections requires grasping specific biological properties of bacteriophages (phages) as antibacterial. However, identification of optimal dosing regimens is hampered by the poor understanding of phage-bacteria interactions in vivo. Here we developed a general strategy coupling in vitro and in vivo experiments with a mathematical model to characterize the interplay between phage and bacterial dynamics during pneumonia induced by a pathogenic strain of Escherichia coli. The model estimates some key parameters for phage therapeutic efficacy, in particular the impact of dose and route of administration on phage dynamics and the synergism of phage and the innate immune response on the bacterial clearance rate. Simulations predict a low impact of the intrinsic phage characteristics in agreement with the current semi-empirical choices of phages for compassionate treatments. Model-based approaches will foster the deployment of future phage therapy clinical trials.

microbiology↗