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Summary: Adult stem cells play a critical role in tissue repair and maintenance. In tissues with slow turnover, including skeletal muscle, these cells are maintained in a mitotically quiescent state yet remain poised to re-enter the cell cycle to replenish themselves and regenerate the tissue. Using a panomics approach we show that the PAX7/NEDD4L axis acts against muscle stem cell activation in homeostatic skeletal muscle. Our findings suggest that PAX7 transcriptionally activates the E3 ubiquitin ligase Nedd4L and that the conditional genetic deletion of Nedd4L impairs muscle stem cell quiescence, with an upregulation of cell cycle and myogenic differentiation genes. Loss of Nedd4L in muscle stem cells results in the expression of doublecortin (DCX), which is exclusively expressed during their in vivo activation. Together, these data establish that the ubiquitin proteasome system, mediated by Nedd4L, is a key contributor to the muscle stem cell quiescent state in adult mice.

Surveillance to better detect and respond to new pathogens remains a major challenge for global public health. The Pasteur Network recently held a brainstorming workshop located in Cameroon attended by Pasteur epidemiological teams from Niger, Central African Republic (CAR), Cameroon, Senegal, and Madagascar to discuss how the Pasteur Network in Africa could use the lessons of COVID-19 to set-up a pilot sentinel surveillance scheme given its expertise and involvement during the pandemic. The possibility of coupling sentinel syndromic and biological surveillance already implemented for influenza surveillance with the recent sequencing capacity put in place by the AFROSCREEN program prompted us to consider strengthening surveillance tools to target “Pathogen X” detection in Africa. The perspective project provided by the Pasteur Network teams and shared with other partners of the AFROSCREEN program will target strengthening of the diagnosis of severe acute respiratory infections (IRAS) and the surveillance of IRAS, the evaluation of the impact of SARS-CoV-2 on the epidemiology of IRAS, and the addition of the detection of new pathogens, called “Pathogen X,” based on sequencing capacity and epidemiological criteria from One Health approaches.

Respiratory interventions including noninvasive ventilation, continuous positive airway pressure and high-flow nasal oxygen generated infectious aerosols may increase risk of airborne disease (SARS-CoV-2, influenza virus) transmission to healthcare workers. We developed/tested a prototype portable UV-C 254 device to sterilize high flows of viral-contaminated air from a simulated patient source at airflow rates of up to 100 l/m. Our device consisted of a central quartz tube surrounded 6 high-output UV-C 254 lamps, within a larger cylinder allowing recirculation past the UV-C 254 lamps a second time before exiting the device. Testing was with nebulized A/PR/8/34 (H1N1) influenza virus. RNA extraction and qRT-PCR showed virus transited through the prototype. Turning on varying numbers of lamps controlled the dose of UVC. Viability experiments at low, medium and high (100 l/min) flows of contaminated gas were conducted with 6, 4, 2 and 1 lamp activated (single-pass and recirculation were tested). Our data show 5-log reduction in particle forming units from a single lamp (single- pass and recirculated conditions) at high and low flows. UVC dose at 100 l/m was calculated at 11.6 mJ/cm 2 single pass and 104 mJ/cm 2 recirculated. The protype device shows high efficacy in killing nebulized influenza virus in a high flow of contaminated air., Competing Interests: Competing Interests The A.G.-S laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. The MS laboratory received unrelated research support as sponsored research agreements from ArgenX BV, Phio Pharmaceuticals, 7Hills Pharma LLC and Moderna, Inc. All other authors did not have a competing interest.