Etude structurale des protéines SNAREs dans le complexe protéine-lipide impliqué dans la fusion membranaire lors du processus d'exocytose

La structure des protéines SNAREs (VAMP1 et Syntaxine1A) et de leur domaines trans- et juxtamembranaires (VAMP22, Syn23 et Syn27 respectivement) a été étudiée dans des membranes lipidiques modèles. Nous avons fait varier la concentration peptidique et la composition lipidique afin de déterminer les paramètres contrôlant l activité de ces molécules dans la membrane durant la fusion. L étude tructurale (IR et CD) des peptides VAMP22 et Syn23 ont montré une transition structurale dépendante de la concentration, entre un feuillet béta à forte concentration et une hélice alpha à faible concentration. Cette transition était réversible pour le peptide VAMP22 uniquement. Des perturbations de la membrane lipidique ont été observées suite à ce changement de structure. Les analyses structurales en PM-IRRAS de la protéine VAMP1 seule ou dans un film lipidique neutre (DMPC) a montré une transition structurale réversible entre une hélice alpha et un feuillet béta en fonction de la compression. Dans un film lipidique chargé du DMPG, cette transition n a pas été observée. Cela laisse suggérer une influence des charges membranaires sur l organisation de cette protéine. En parallèle, la protéine Syntaxine1A a montré une structure secondaire stable en hélice alpha, indépendamment de la composition lipidique de la membrane. L addition de quatre résidus juxtamembranaires au peptide Syn23 était associée à une nouvelle organisation structurale du domaine transmembranaire. L étude structurale associée à l étude cinétique de fusion ou d agrégation des peptido-liposomes du peptide Syn 27, permettent de suggérer un éventuel lien entre la structure et la fonction de ce peptide dans la membrane.The structure of SNARE proteins (VAMP1 & Syntaxine1A) and of their trans- and juxtamembrane domains (respectively VAMP22, Syn23 & Syn27) was investigated in synthetic lipid membranes. Different protein concentrations and lipid compositions were used in this study. VAMP22 and Syn23 peptides were studied in IR and CD. A structural transition between an alpha helix and a beta sheet was observed depending on peptide concentration. This transition was reversible only for VAMP22. Membrane Lipid phase was disturbed upon this structural evolution. PM-IRRAS data of pure full length VAMP1 protein film and mixed DMPC/VAMP1 film showed a dynamic behavior of this protein on the interface with a reversible structural transition upon surface compression/decompression cycles. Negatively charged lipid membranes (DMPG, DMPG/DMPC) prohibited this protein from changing structure under same conditions. Syntaxine1A protein subjected to a similar analysis showed no consequences of lipid composition or surface pressure on the structure of the originally alpha helix structured protein. Addition of four juxtamembrane residues to the Syn23 peptide produced modifications within the structural organization of this transmembrane peptide in model membranes. This larger peptide facilitated vesicles membranes fusion when organized as beta sheet.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Testing the correlation between indoor environmental quality and productive time

Indoor Environmental Quality (IEQ), being one of the main pillars of sustainability, stretches its effect far beyond ensuring a pleasant environment for the occupants to live in. In fact, IEQ plays a major role in defining the level of productivity within organizations. Recent studies acknowledge the link between IEQ and employees’ overall satisfaction at work, and in turn, productivity. The ultimate goal of an ongoing research project is to propose and validate a decision making tool that optimizes office buildings renovation projects based on maximizing occupants’ satisfaction with the IEQ conditions at their workplace, and in turn, maximizing their productive time. The first step in this direction requires an understanding of the relationship between IEQ and productivity. This is achieved in this paper through a survey of corporate employees, which provides a correlation between the level of IEQ in an office setting and the overall level of satisfaction with the workplace. The latter is, in turn, correlated with the level of occupant productivity at work, as measured by the amount of productive time. The paper concludes with an empirical model based on statistical regression analysis, depicting the relationship between IEQ satisfaction and productive time.Non UBCUnreviewedFacultyOthe

Left Lung Torsion: Complication of Lobar Resection for an Early Stage Lung Adenocarcinoma

Lobar torsion is a fatal but fortunately rare occurrence following lung resection. Early clinical signs and radiographic features may be nonspecific resulting in diagnostic delay. A high index of suspicion is vital for early diagnosis and intervention to avoid further parenchymal necrosis and deadly gangrene. We report a case of left lower lobe torsion in a 76-year-old female following elective upper lobectomy for underlying lung adenocarcinoma. Diagnosis was made following highly suggestive radiographic findings prompting bronchoscopy and revision thoracotomy. An emergency detorsion failed to restore lung viability and was followed by completion pneumonectomy. The patient recovered and was discharged on the seventh postoperative day

Survival of Campylobacter jejuni Co-Cultured with Salmonella spp. in Aerobic Conditions

Campylobacter and Salmonella are responsible for the two major foodborne zoonotic diseases in Europe; poultry is the main infection source. Campylobacter cannot grow under aerobic conditions, but can show aerobic survival when co-cultured with other microorganisms; however, its interaction with Salmonella has not been studied yet. In this study, these two bacteria were co-cultured under controlled aerobic conditions. Different concentrations and strains of C. jejuni were incubated with or without different Salmonella serotypes (10 CFU) at 37 °C for 16 h. C. jejuni did not grow after incubation with or without Salmonella. The survival of C. jejuni was observed only for the highest initial concentration of 6 log CFU/mL with or without Salmonella. However, its survival was significantly higher when co-cultured with Salmonella. No survival was observed at lower concentrations. C. jejuni survival was positively affected by the presence of Salmonella but depended on the Salmonella serotype, the C. jejuni strain and the initial concentration. On the other hand, the Salmonella enumerations were not affected by C. jejuni. Our results suggest potential interactions between Salmonella and C. jejuni that require further investigations for a clearer understanding of their behavior in natural habitats

TWO WEEKS OF CHRONIC UNPREDICTABLE STRESS ARE SUFFICIENT TO PRODUCE ORAL CANDIDIASIS IN BALB/C MICE

International audienceThe incidence of oral infections caused by Candida species with diverse virulence and susceptibility profiles has increased in recent years. Due to scarce clinical and experimental data on the ability of stress to induce oral candidiasis, the aim of this study was to assess the impact of stress on oral candidiasis in healthy BALB/c mice and compare its effect to other predisposing factors of oral candidiasis. Immunocompetent and immunocompromised BALB/c female mice were orally infected with C. albicans. A total of four groups of mice each receiving a different treatment were screened. Treatments included antibiotics, corticosteroids and chronic unpredictable stress. Oral tissue colonization and infection was inspected and evaluated comparatively in each group. Tissue burden on day 14 post challenge was measured and mice tongues were inspected for white patches and studied histo-pathologically for evidence of colonization or infection. The induced stress model was able to result in oral colonization and infection without the use of antibiotics or immuno-suppressants. Moreover, the fungal burden was significantly greater in stressed group than that in groups receiving antibiotics treatment or control group. Histopathological examination revealed the abundant presence of C. albicans cells with pseudo-hyphae and in the yeast form, in all tongue tissue samples of treated mice. Tissues were intact in the control group and Candida cells count was significantly lower in the treated unstressed group. White patches were significantly more dominant in stressed group than non-stressed and control group. In conclusion, stress maybe a more potent predisposing factor than the use of antibiotics in inducing oral candidiasis, although being a weaker factor than the combined use of antibiotics and corticosteroids together

In Vitro Cellular and Molecular Interplay between Human Foreskin-Derived Mesenchymal Stromal/Stem Cells and the Th17 Cell Pathway

Foreskin, considered a biological waste material, has been shown to be a reservoir of therapeutic cells. The immunomodulatory properties of mesenchymal stromal/stem cells (MSCs) from the foreskin (FSK-MSCs) are being evaluated in cell-based therapy for degenerative, inflammatory and autoimmune disorders. Within the injured/inflamed tissue, proinflammatory lymphocytes such as IL-17-producing T helper cells (Th17) may interact with the stromal microenvironment, including MSCs. In this context, MSCs may encounter different levels of T cells as well as specific inflammatory signals. Uncovering the cellular and molecular changes during this interplay is central for developing an efficient and safe immunotherapeutic tool. To this end, an in vitro human model of cocultures of FSK-MSCs and T cells was established. These cocultures were performed at different cell ratios in the presence of an inflammatory setting. After confirming that FSK-MSCs respond to ISCT criteria by showing a typical phenotype and multilineage potential, we evaluated by flow cytometry the expression of Th17 cell markers IL-17A, IL23 receptor and RORγt within the lymphocyte population. We also measured 15 human Th17 pathway-related cytokines. Regardless of the T cell/MSC ratio, we observed a significant increase in IL-17A expression associated with an increase in IL-23 receptor expression. Furthermore, we observed substantial modulation of IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, INF-γ, sCD40, and TNF-α secretion. These findings suggest that FSK-MSCs are receptive to their environment and modulate the T cell response accordingly. The changes within the secretome of the stromal and immune environment are likely relevant for the therapeutic effect of MSCs. FSK-MSCs represent a valuable cellular product for immunotherapeutic purposes that needs to be further clarified and developed