Supporting information for "Bis-michael acceptors as novel probes to study the Keap1/Nrf2/ARE pathway"

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator that promotes the transcription of cytoprotective genes in response to oxidative/electrophilic stress. Various Michael-type compounds were designed and synthesized, and their potency to activate the Keap1/Nrf2/ARE pathway was evaluated. Compounds bearing two Michael-type acceptors proved to be the most active. Tether length and rigidity between the acceptors was crucial. This study will help to understand how this feature disrupts the interaction between Keap1 and Nrf2

Herpetic Pneumonitis Following Posterior Fossa Surgery

Reactivation of Herpes simplex virus (HSV) following manipulation of the trigeminal nerve root. has been reported in a substantial number of immunocompetent patients. Usually it was manifest as an oral mucocutaneous lesion and considered a benign postoperative complication. In the case described here, however, severe respiratory distress due to herpetic pneumonia developed following a pontocerebellar angle surgery complicated by an orolabial herpetic lesion. The delays necessary to confirm HSV diagnosis prior to initiating treatment are discussed, considering the rarity of this complication following neurosurgery

Staphylococcus aureus sigma B-dependent emergence of small-colony variants and biofilm production following exposure to Pseudomonas aeruginosa 4-hydroxy-2-heptylquinoline-N-oxide

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>and <it>Pseudomonas aeruginosa </it>are often found together in the airways of cystic fibrosis (CF) patients. It was previously shown that the <it>P. aeruginosa </it>exoproduct 4-hydroxy-2-heptylquinoline-<it>N-</it>oxide (HQNO) suppresses the growth of <it>S. aureus </it>and provokes the emergence of small-colony variants (SCVs). The presence of <it>S. aureus </it>SCVs as well as biofilms have both been associated with chronic infections in CF.</p> <p>Results</p> <p>We demonstrated that HQNO stimulates <it>S. aureus </it>to form a biofilm in association with the formation of SCVs. The emergence of SCVs and biofilm production under HQNO exposure was shown to be dependent on the activity of the stress- and colonization-related alternative sigma factor B (SigB). Analysis of gene expression revealed that exposure of a prototypical <it>S. aureus </it>strain to HQNO activates SigB, which was leading to an increase in the expression of the fibronectin-binding protein A and the biofilm-associated <it>sarA </it>genes. Conversely, the quorum sensing accessory gene regulator (<it>agr</it>) system and the α-hemolysin gene were repressed by HQNO. Experiments using culture supernatants from <it>P. aeruginosa </it>PAO1 and a double chamber co-culture model confirmed that <it>P. aeruginosa </it>stimulates biofilm formation and activates SigB in a <it>S. aureus </it>strain isolated from a CF patient. Furthermore, the supernatant from <it>P. aeruginosa </it>mutants unable to produce HQNO induced the production of biofilms by <it>S. aureus </it>to a lesser extent than the wild-type strain only in a <it>S. aureus </it>SigB-functional background.</p> <p>Conclusions</p> <p>These results suggest that <it>S. aureus </it>responds to HQNO from <it>P. aeruginosa </it>by forming SCVs and biofilms through SigB activation, a phenomenon that may contribute to the establishment of chronic infections in CF patients.</p

The Prostanoid 15-Deoxy-D 12,14 -Prostaglangin-J 2 Reduces Lung Inflammation and Protects Mice Against Lethal Influenza Infection

Background. Growing evidence indicates that influenza pathogenicity relates to altered immune responses and hypercytokinemia. Therefore, dampening the excessive inflammatory response induced after infection might reduce influenza morbidity and mortality. Methods. Considering this, we investigated the effect of the anti-inflammatory molecule 15-deoxy-D 12,14 -prostaglandin J 2 (15d-PGJ 2 ) in a mouse model of lethal influenza infection. Results. Administration of 15d-PGJ 2 on day 1 after infection, but not on day 0, protected 79% of mice against lethal influenza infection. In addition, this treatment considerably reduced the morbidity associated with severe influenza infection. Our results also showed that treatment with 15d-PGJ 2 decreased influenza-induced lung inflammation, as shown by the diminished gene expression of several proinflammatory cytokines and chemokines. Unexpectedly, 15d-PGJ 2 also markedly reduced the viral load in the lungs of infected mice. This could be attributed to maintained type I interferon gene expression levels after treatment. Interestingly, pretreatment of mice with a peroxisome proliferator-activated receptor gamma (PPARc) antagonist before 15d-PGJ 2 administration completely abrogated its protective effect against influenza infection. Conclusions. Our results demonstrate for the first time that treatment of mice with 15d-PGJ 2 reduces influenza morbidity and mortality through activation of the PPARc pathway. PPARc agonists could thus represent a potential therapeutic avenue for influenza infections

Bactericidal Effect of Tomatidine-Tobramycin Combination against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa Is Enhanced by Interspecific Small-Molecule Interactions.

This study investigated the antibacterial activity of the plant alkaloid tomatidine (TO) against Staphylococcus aureus grown in presence of Pseudomonas aeruginosa. Since the P. aeruginosa exoproduct 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) is known to cause respiratory deficiency in S. aureus and that respiratory-deficient S. aureus are known to be hypersensitive to TO, we performed kill kinetics of TO (8 mug/ml) against S. aureus in co-culture with P. aeruginosa. Kill kinetics were also carried out using P. aeruginosa mutants deficient in the production of different exoproducts and quorum sensing-related compounds. After 24h in co-culture, TO increased the killing of S. aureus by 3.4 log10 CFU/ml in comparison to that observed in a co-culture without TO. The effect of TO was abolished when S. aureus was in co-culture with the lasR-/rhlR-, pqsA-, pqsL- or lasA- mutant of P. aeruginosa. The bactericidal effect of TO against S. aureus in co-culture with the pqsL- mutant was restored by supplemental HQNO. In a S. aureus mono-culture, the combination of HQNO and TO was bacteriostatic, indicating that the pqsL- mutant produced an additional factor required for the bactericidal effect. The bactericidal activity of TO was also observed against a tobramycin-resistant methicillin-resistant S. aureus (MRSA) in co-culture with P. aeruginosa and addition of tobramycin significantly suppressed the growth of both microorganisms. TO shows a strong bactericidal effect against S. aureus when co-cultured with P. aeruginosa. The combination of TO and tobramycin may represent a new treatment approach for cystic fibrosis patients frequently co-colonized by MRSA and P. aeruginosa

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

Background Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. Methods The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. Results The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. Conclusions The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition

BackgroundFollowing SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.MethodsThe study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.ResultsThe frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.ConclusionsThe antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens

Saint Pierre Damien. La vie du B. Romuald. Bruno de Querfurt. La vie des cinq frères.

Cantin André. Saint Pierre Damien. La vie du B. Romuald. Bruno de Querfurt. La vie des cinq frères.. In: Cahiers de civilisation médiévale, 7e année (n°27), Juillet-septembre 1964. pp. 343-344

Arts libéraux et philosophie au moyen âge. Actes du IVe Congrès international de Philosophie médiévale (Université de Montréal, 27 août-2 sept. 1967)

Cantin André. Arts libéraux et philosophie au moyen âge. Actes du IVe Congrès international de Philosophie médiévale (Université de Montréal, 27 août-2 sept. 1967). In: Cahiers de civilisation médiévale, 15e année (n°59), Juillet-septembre 1972. pp. 223-226

Pierre Damien. Vita beati Romualdi

Cantin André. Pierre Damien. Vita beati Romualdi. In: Cahiers de civilisation médiévale, 3e année (n°12), Octobre-décembre 1960. pp. 520-523