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Gauthier, D.

Publications and source records attributed to Gauthier, D..

3 recordsLinked to original sources

Integrating multi-host modelling with empirical wildlife-livestock contacts reveals an essential population in a pathogen reservoir

Infections at the animal-human or wildlife-livestock interfaces have severe health and socio-economic consequences. Combined with empirical data, mathematical models can contribute to a better understanding of the reservoirs of these infections, which is a priority for mitigating their impact by using appropriate management interventions. Taking brucellosis in the Bargy massif (French Alps) as an example of a zoonosis at the wildlife-livestock interface, we developed and calibrated a multi-host model integrating data on direct and environment-mediated cross-species contacts from field observations. Estimates of the basic reproduction number (R0) allowed to identify the population of Alpine ibex (Capra ibex) and its environment as an essential host in the reservoir, driving both pathogen maintenance (within-species R0[≥]1: 1.66, 95% credible interval: 1.42-2.03) and its transmission to livestock (between-species R0>0: 0.035, 0.01-0.05). Our approach can be adapted to other multi-host pathogens, which will contribute to improve the understanding and management of these complex systems.

ecology↗

Development and Characterization of Self-Tracing Neural Progenitor Cells for Mapping Their Synaptic Integration into Endogenous Neural Networks

Neural progenitor cell (NPC) transplantation holds immense promise for neurodegenerative and traumatic central nervous system (CNS) pathologies. However, it is crucial to define which neural circuits and pathways are targeted with transplanted NPCs under different conditions. A major roadblock lies in the limited ability to accurately trace integration of grafted cells into the host neural network. Conventional tracers suffer from drawbacks like low trans-synaptic efficiency, toxicity, and difficulty in efficiently and specifically targeting transplanted cells. To address these critical limitations, we have developed self-tracing NPCs genetically engineered to express both anterograde (WGA-mCherry) and retrograde (GFP-TTC) trans-synaptic tracers. These self-tracing NPCs maintain their intrinsic properties, differentiate into electrically active neurons, and integrate into host circuitry in vitro. Importantly, co-culture with primary rat neurons revealed successful trans-synaptic tracing of grafted human neurons, evidenced by single-positive WGA+ or TTC+ rat cells. In vivo, NPCs transplanted into a rodent spinal cord injury model retained tracer expression for 12 weeks, enabling visualization of grafted cells within the spinal cord. Co-labeling with WGA and TTC provided evidence that these NPCs forms neurons which integrated into local circuits. Our novel self-tracing NPC platform offers a powerful tool to overcome trans-synaptic tracing challenges. This approach provides the opportunity to gain critical insights into graft integration and neural circuit remodeling, paving the way for better-designed transplantation strategies and improved therapeutic outcomes in a broad spectrum of CNS disorders.

neuroscience↗

What challenges remain in harmonizing cytomegalovirus viral load quantification across laboratories?

Cytomegalovirus (CMV) infection monitoring is a key element in the management of immunocompromised patients. CMV DNA quantification in plasma or whole blood is the best indicator for clinicians to adjust immunosuppressive or antiviral therapies. Despite the availability of internationally standardized material, the commutability of CMV quantification results across laboratories remains inadequate. To assess inter-laboratory variability in CMV DNA quantification, we conducted a blinded study in seven independent laboratories. Each participant received a panel of 92 specimens for CMV quantification using their routinely used standard platform. While quantifications were highly correlated and reproducible, large discrepancies were observed with differences up to 1.45 log10 IU/mL between techniques for identical specimens. However, quantification scattering was lower for the WHO international standard or a commercially tested control (IQR=0.129) than for clinical specimens (0.469; p=0.0142). Blind quantification of the WHO or the commercial standard indicated that all techniques, except for fully integrated platforms, did not align well with the expected values and most platforms tended to quantify specimens and standards differently. Recalibration of all platforms against the same standard improved the spread of results, but differences of up to 1.19 log10 IU/mL remained for the same specimens. Achieving commutability in CMV quantification remains an elusive goal. Efforts should focus on improving both the assay calibrators and the run controls, which currently do not appear to simulate the unique characteristics of circulating CMV in patients. Until this is resolved, each transplanted patient should be consistently monitored by the same laboratory on the same platform.

microbiology↗