Structure-based predictions broadly link transcription factor mutations to gene expression changes in cancers

© 2014 The Author(s). Thousands of unique mutations in transcription factors (TFs) arise in cancers, and the functional and biological roles of relatively few of these have been characterized. Here, we used structure-based methods developed specifically for DNA-binding proteins to systematically predict the consequences of mutations in several TFs that are frequently mutated in cancers. The explicit consideration of protein-DNA interactions was crucial to explain the roles and prevalence of mutations in TP53 and RUNX1 in cancers, and resulted in a higher specificity of detection for known p53-regulated genes among genetic associations between TP53 genotypes and genome-wide expression in The Cancer Genome Atlas, compared to existing methods of mutation assessment. Biophysical predictions also indicated that the relative prevalence of TP53 missense mutations in cancer is proportional to their thermodynamic impacts on protein stability and DNA binding, which is consistent with the selection for the loss of p53 transcriptional function in cancers. Structure and thermodynamics-based predictions of the impacts of missense mutations that focus on specific molecular functions may be increasingly useful for the precise and large-scale inference of aberrant molecular phenotypes in cancer and other complex diseases

Existence de la Leptospirose bovine en Algérie

Donatien André-Louis, Bernard Cl., Gayot G. Existence de la Leptospirose bovine en Algérie. In: Bulletin de l'Académie Vétérinaire de France tome 103 n°7, 1950. pp. 363-364

Application de Techniques de fluorescence et d'immunofluorescence a l'étude morphologique et immunologique de quelques souches de « virus » de l’avortement de la brebis (Rakeia ovis)

Faye P., Charton André, Le Layec Cl., Bernard C. Application de techniques de fluorescence et d’immunofluorescence à l’étude morphologique et immunologique de quelques souches de «Virus» de l’avortement de la Brebis (Rakeia ovis ). In: Bulletin de l'Académie Vétérinaire de France tome 121 n°9, 1968. pp. 363-371

Hypotrichose congénitale en race bovine normande. I. – Étude descriptive

International audienc

Etude préliminaire d’un enterovirus isolé d’une lésion de balano-posthite bovine

Un entérovirus bovin, appartenant au groupe sérologique I de La Placa, est isolé du fourreau d’un taureau d’insémination artificielle atteint de balano-posthite. Son rôle étiologique dans ce cas, bien que probable, n’est pas fermement établi

Fréquence relative des isolements de virus de diverses familles chez des veaux malades ou apparemment sains, dans le département de l’Aube

Au cours d’une enquête consacrée, dans le département de l’Aube, à la « mortalité des veaux », plusieurs centaines de prélèvements sont effectués, sur 243 sujets sains ou malades. Vingt trois souches de virus, parmi lesquels Picornavirus, Paramyxovirus, Herpes virus, virus de la « maladie des muqueuses » sont isolées. La fré quence relative des isolements, en fonction des observations épizootiologiques et cliniques correspondantes, de l’âge des sujets, de la nature des prélèvements effectués, le rôle étiologique éventuel de ces divers virus, sont analysés et discutés

Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong

Importance Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted. Objective This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes. Design, Setting, and Participants This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics. Exposures Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator). Main Outcomes and Measures The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022. Results This study included 30 385 patients. The propensity score–matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis. Conclusions and Relevance The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted

Rhinotrachéite infectieuse bovine : isolement du virus à l’occasion d’une enzootie observée dans le département de l’Aube

Charton André, Berkaloff A., Faye P., Lecoanet Jean, Le Layec Cl., Bernard C. Rhinotrachéite infectieuse bovine : Isolement du virus à l’occasion d’une enzootie observée dans le département de l’Aube. In: Bulletin de l'Académie Vétérinaire de France tome 123 n°3, 1970. pp. 123-129