Dr. Ahmed Ouali, 1948–2020

International audienceAhmed Ouali was born on October 4, 1948 in Tigzirt, Tizi-Ouzou, Algeria. In 1952, he moved with his parents to Montluçon, France. In 1974, he was trained and graduated with a bachelor's degree in Biochemistry at the University of Lyon. He then, in 1976, earned a joint Ph.D. in Animal Science at the University of Blaise Pascal (Clermont-Ferrand) where he studied at the National Institute of Agricultural Research (INRA, Theix). The title of his doctorate thesis was “The role of muscle proteases on meat tenderization”. Subsequently, he was employed in a private laboratory for medical analysis from 1976 to 1978 and thereafter at the Meat Research Laboratory group at INRA, Theix as a permanent researcher. In 1990, he was appointed as a research director and led the “Biochemistry and Functions of Muscle Proteins” unit for 8 years. The Meat Research Station focused their research on many topics including colour and protein oxidation; enzymology and tenderness; and muscle protein functionalities. During his entire scientific career at INRA, but before his retirement on October 2013, Ahmed was living in Clermont-Ferrand, the city of the famous volcanic chain of the Puy-de-Dôme, with his wife Anne-Marie with whom he had two lovely children: Armelle (41 years) and Gäel (38 years). In 2019, they moved to their new house in Montpellier in the South of France

Dephosphorylation of tyrosine 393 in argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence.

Oncogenic RAS (H-RAS(V12)) induces premature senescence in primary cells by triggering production of reactive oxygen species (ROS), but the molecular role of ROS in senescence remains elusive. We investigated whether inhibition of protein tyrosine phosphatases by ROS contributed to H-RAS(V12)-induced senescence. We identified protein tyrosine phosphatase 1B (PTP1B) as a major target of H-RAS(V12)-induced ROS. Inactivation of PTP1B was necessary and sufficient to induce premature senescence in H-RAS(V12)-expressing IMR90 fibroblasts. We identified phospho-Tyr 393 of argonaute 2 (AGO2) as a direct substrate of PTP1B. Phosphorylation of AGO2 at Tyr 393 inhibited loading with microRNAs (miRNAs) and thus miRNA-mediated gene silencing, which counteracted the function of H-RAS(V12)-induced oncogenic miRNAs. Overall, our data illustrate that premature senescence in H-RAS(V12)-transformed primary cells is a consequence of oxidative inactivation of PTP1B and inhibition of miRNA-mediated gene silencing

Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells

Background and objectivesTo evaluate the therapeutic potential of targeting highly differentiated T cells in patients with inclusion body myositis (IBM) by establishing high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1+) within the T and natural killer (NK) cell compartments.MethodsBlood was collected from 51 patients with IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naive T cells (Tn), central memory T cells (Tcm), 4 stages of effector memory differentiation T cells (Tem 1-4), and effector memory re-expressing CD45RA T cells (TemRA), as well as total and subpopulations of NK cells based on the differential expression of CD16 and C56.ResultsWe found that a population of KLRG1+ Tem and TemRA were expanded in both the CD4+ and CD8+ T-cell subpopulations in patients with IBM. KLRG1 expression in CD8+ T cells increased with T-cell differentiation with the lowest levels of expression in Tn and highest in highly differentiated TemRA and CD56+CD8+ T cells. The frequency of KLRG1+ total NK cells and subpopulations did not differ between patients with IBM and healthy donors. IBM disease duration correlated with increased CD8+ T-cell differentiation.DiscussionOur findings reveal that the selective expansion of blood KLRG1+ T cells in patients with IBM is confined to the TemRA and Tem cellular compartments