Protocetraric and Salazinic Acids as Potential Inhibitors of SARS-CoV-2 3CL Protease: Biochemical, Cytotoxic, and Computational Characterization of Depsidones as Slow-Binding Inactivators

The study investigated the inhibitory activity of protocetraric and salazinic acids against SARS-CoV-2 3CL(pro). The kinetic parameters were determined by microtiter plate-reading fluorimeter using a fluorogenic substrate. The cytotoxic activity was tested on murine Sertoli TM4 cells. In silico analysis was performed to ascertain the nature of the binding with the 3CL(pro). The compounds are slow-binding inactivators of 3CL(pro) with a K(i) of 3.95 μM and 3.77 μM for protocetraric and salazinic acid, respectively, and inhibitory efficiency k(inact)/K(i) at about 3 × 10(−5) s(−1)µM(−1). The mechanism of inhibition shows that both compounds act as competitive inhibitors with the formation of a stable covalent adduct. The viability assay on epithelial cells revealed that none of them shows cytotoxicity up to 80 μM, which is well below the K(i) values. By molecular modelling, we predicted that the catalytic Cys145 makes a nucleophilic attack on the carbonyl carbon of the cyclic ester common to both inhibitors, forming a stably acyl-enzyme complex. The computational and kinetic analyses confirm the formation of a stable acyl-enzyme complex with 3CL(pro). The results obtained enrich the knowledge of the already numerous biological activities exhibited by lichen secondary metabolites, paving the way for developing promising scaffolds for the design of cysteine enzyme inhibitors

Student Retention Issues in the TDSB French Immersion Programs

The Toronto District School Board (TDSB) is experiencing problems in retaining students in their French Immersion (FI) programs. This study aims to identify some of the strategies that French Immersion teachers are using to keep students in the program and to point to some of their perceived reasons for students choosing to leave. After reviewing literature on the benefits and barriers of second language immersion programs, special education in French Immersion, gender differences in language immersion programs and teacher strategies in the matter, three semi-structured interviews with FI teachers in the TDSB were conducted. The findings indicate that teachers perceive that: students experience behavioural or academic difficulties, there is a lack of French in-school support and atmosphere, and the motivations of parents and students differ, which all are perceived to contribute to retention issues. Also, FI teachers are using many in-class strategies such as kinesthetic learning and teaching on areas of student interest, and enacting vigorous processes in an attempt to retain their students

Imparare a 'leggere le sentenze' nell'età della giurisdizione

Le tracce, sia nel concorso in magistratura sia nell'esame di avvocato, sono modellate su casi e pronunce giurisprudenziali. Sicché imparare a leggere le sentenze non è soltanto professionalmente formativo ma è anche concretamente funzionale al superamento delle rispettive prove scritte. Il numero di sentenze da leggere e che è necessaria saper leggere si è moltiplicato nel corso degli ultimi decenni (Cassazione, Consiglio di Stato, Corti europee), tanto da accentuare il ruolo e la centralità della giurisdizione, connotando il passaggio della storia giuridica che stiamo vivendo, come età della giurisdizione

EZIOPATOGENESI, DIAGNOSI E TERAPIA DEL BRUCIORE ORALE

Il bruciore orale è un’ affezione diffusa soprattutto fra gli anziani; può essere secondario a varie patologie di carattere generale (infezioni del cavo orale, disordini endocrini, diabete, deficit di acido folico e ferro,allergie, gastriti ecc) o primitivo. In quest’ultimo caso si parla di Sindrome della Bocca Urente o BMS, caratterizzata dal fatto che colpisce soprattutto le donne in menopausa e spesso si accompagna a disgeusia e a xerostomia. Fra le varie possibili cause di tale patologia, si annoverano in letteratura fattori psicologici e fattori ormonali, ma ultimamente l’ipotesi eziologica che appare più accreditata è quella di una neuropatia che colpirebbe le vie nervose centrali o periferiche del trigemino. Sono tuttavia necessari ulteriori studi ed approfondimenti per confermare queste asserzioni

LINGUA A CARTA GEOGRAFICA IN UN PAZIENTE ANZIANO AFFETTO DA PSORIASI ED EPATITE C

Oral problems increases with age because of the modifications of oral mucose and the simultaneous presence of other diseases