c-Src non-receptor tyrosine kinase is an important component of the platelet-derived growth factor (PDGF) receptor signaling pathway. c-Src has been shown to mediate the mitogenic response to PDGF in fibroblasts. However, the exact components of PDGF receptor signaling pathway mediated by c-Src remain unclear. Here, we used stable isotope labeling with amino acids in cell culture (SILAC) coupled with mass spectrometry to identify Src family kinase substrates involved in PDGF signaling. Using SILAC, we were able to detect changes in tyrosine phosphorylation patterns of 43 potential c-Src kinase substrates in PDGF receptor signaling. This included 23 known c-Src kinase substrates, of which 16 proteins have known roles in PDGF signaling while the remaining 7 proteins have not previously been implicated in PDGF receptor signaling. Importantly, our analysis also led to identification of 20 novel Src family kinase substrates, of which 5 proteins were previously reported as PDGF receptor signaling pathway intermediates while the remaining 15 proteins represent novel signaling intermediates in PDGF receptor signaling. In validation experiments, we demonstrated that PDGF indeed induced the phosphorylation of a subset of candidate Src family kinase substrates – Calpain 2, Eps15 and Trim28 – in a c-Src-dependent fashion.
Introduction Polyvinylpyrrolidone–iodine (PVP-I) demonstrates broad-spectrum anti-infective activity and is available in different formulations for oral rinse and topical use in medical and personal care settings. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the need to supplement available preventive strategies. Methods We assessed virucidal activity of PVP-I formulations, including 0.5% (w/v) solution, 5.0% (w/v) solution, 7.5% (w/v) scrub, and 10.0% (w/v) solution, versus placebos when challenged with coronaviruses in two in vitro studies. Murine coronavirus strain A59 (American Type Culture Collection [ATCC] ® VR-764™), human coronavirus strain OC43 (ZeptoMetrix Corp. #0810024CF), human coronavirus strain NL63 (ZeptoMetrix Corp. #0810228CF), and human coronavirus strain 229E (ATCC ® VR-740™) were used as surrogates for SARS-CoV-2. Both studies used the American Society for Testing and Materials in vitro time-kill method. Results All active PVP-I formulations in study 1 demonstrated virucidal activity at 15 s, with mean log 10 reduction of greater than 4.56 or greater than 99.99% inactivation; a cytotoxic effect against the National Collection of Type Cultures clone 1469 host cells was observed with 5.0% (w/v) solution, 7.5% (w/v) scrub, and 10.0% (w/v) solution. Active PVP-I formulations in study 2 demonstrated effective virucidal activity against coronaviruses in less than 15 s; log 10 reduction in viral titer for each coronavirus strain was consistently higher for 10.0% (w/v) solution and 0.5% (w/v) solution versus 7.5% (w/v) scrub. Conclusion Both studies demonstrated in vitro virucidal activity of PVP-I formulations when challenged with SARS-CoV-2 surrogate coronaviruses . Although promising, further investigations are needed to evaluate SARS-CoV-2 inactivation.
Background Healthcare professionals, especially dentists and dental hygienists, are at increased risk for contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through air-borne particles and splatter. This study assessed the in vitro virucidal activity of 0.5% (w/v) povidone-iodine (PVP-I) oral rinse against SARS-CoV-2 to demonstrate its utility as a professional oral rinse. Methods A 0.5% (w/v) PVP-I oral rinse formulation, placebo oral rinse, and positive (70% [v/v] ethanol and water) and negative (water) controls were assessed using the time-kill method. SARS-CoV-2 was propagated in Vero 76 host cells. Following neutralization validation, triplicate tests were performed for each test formulation and virucidal activity measured at 15, 30, and 60 s and 5 min. Results The 0.5% (w/v) PVP-I oral rinse demonstrated effective in vitro virucidal activity against SARS-CoV-2 as early as 15 s after exposure; viral titer was reduced to < 0.67 log10 50% cell culture infectious dose (CCID50)/0.1 mL (log10 reduction of > 4.0) at 30 s, whereas the placebo oral rinse reduced the SARS-CoV-2 viral titer to 4.67 and 4.5 log10 CCID50/0.1 mL at the 15- and 30-s time points, with a log10 reduction of 0.63 and 0.17, respectively. No toxicity or cytotoxic effects against Vero 76 host cells were observed with the 0.5% (w/v) PVP-I oral rinse; positive and negative controls performed as expected. Conclusions In vitro virucidal activity of 0.5% (w/v) PVP-I oral rinse against SARS-CoV-2 was demonstrated. Rapid inactivation of SARS-CoV-2 was observed with 0.5% (w/v) formulation with a contact duration of 15 s. Clinical investigations are needed to assess the effectiveness of PVP-I oral rinse against SARS-CoV-2 in dental practice.
Dans cet article, nous présentons les fondements théoriques et pratiques d’un projet de plateforme interactive qui souhaite intégrer la maîtrise du logiciel Antidote au cœur d’une démarche pédagogique autonomisante. À l’aide de parcours d’apprentissage individualisés, nous espérons encourager les apprenant.e.s à adopter une attitude réflexive sur la langue qui leur permettra d’acquérir du métalangage et d’élaborer des stratégies interlinguistiques pour développer leurs compétences à l’écrit en français langue seconde. Notre plateforme souhaite répondre à des enjeux déjà prégnants dans l’enseignement/apprentissage d’une langue seconde dans une perspective plus équitable et inclusive pour atténuer les différences entre les apprenant.e.s dans le contexte de l’enseignement à distance que nous connaissons actuellement. Cette phase exploratoire a permis de développer la première étape du projet qui permettra, à terme, de mener de plus amples recherches sur des pratiques pédagogiques novatrices dans lesquelles langues et cultures sont utilisées comme un levier d’apprentissage de la langue cible.
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