Self Protection from Anti-Viral Responses – Ro52 Promotes Degradation of the Transcription Factor IRF7 Downstream of the Viral Toll-Like Receptors

Ro52 is a member of the TRIM family of single-protein E3 ligases and is also a target for autoantibody production in systemic lupus erythematosus and Sjögren's syndrome. We previously demonstrated a novel function of Ro52 in the ubiquitination and proteasomal degradation of IRF3 following TLR3/4 stimulation. We now present evidence that Ro52 has a similar role in regulating the stability and activity of IRF7. Endogenous immunoprecipitation of Ro52-bound proteins revealed that IRF7 associates with Ro52, an effect which increases following TLR7 and TLR9 stimulation, suggesting that Ro52 interacts with IRF7 post-pathogen recognition. Furthermore, we show that Ro52 ubiquitinates IRF7 in a dose-dependent manner, resulting in a decrease in total IRF7 expression and a subsequent decrease in IFN-α production. IRF7 stability was increased in bone marrow-derived macrophages from Ro52-deficient mice stimulated with imiquimod or CpG-B, consistent with a role for Ro52 in the negative regulation of IRF7 signalling. Taken together, these results suggest that Ro52-mediated ubiquitination promotes the degradation of IRF7 following TLR7 and TLR9 stimulation. As Ro52 is known to be IFN-inducible, this system constitutes a negative-feedback loop that acts to protect the host from the prolonged activation of the immune response

La proteine C3 du complement humain: etude de sa fixation sur les lymphocytes T Jurkat et de son role fonctionnel dans l'activation T

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 84794 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Discordant D-dimer results of two rapid quantitative automated assays are related to age.

International audienceNo abstract is availabl

Should plasma homocysteine be used as a biomarker of venous thromboembolism? A case-control study.

International audienceMild or moderate hyperhomocysteinemia as a risk factor for venous thrombosis is still a matter of debate. The strength of this study is to bring a body of elements to evaluate whether hyperhomocysteinemia should be used as a biomarker for venous thromboembolism (VTE). These elements consist of a biological evaluation of several hematological risk factors, and an original control group made of patients with a negative Doppler ultrasonography. A total of 151 cases and 155 controls were included. Total plasma homocysteine level, MTHFR C677T polymorphism, inherited abnormalities of the natural anticoagulant system as well as plasma folate and cobalamin levels were determined. A total of 41 (27.2 %) of cases and only 9 (5.8%) of controls had at least one of the coagulation defects studied. No significant difference was observed for total homocysteine levels between the 2 groups: median (interquartile range) = 8.3 (7.2-10.8) micromol/L for cases and 8.4 (7-10.9) micromol/L for controls. We found significantly more plasma folates and/or cobalamin deficiencies in controls (18.3%) than in cases (8.6%). After adjustment for several variables significantly related to risk factors of VTE, hyperhomocysteinemia (>13.2 micromol/L) was not found statistically associated with VTE: odds ratio 1.36 (95% confidence interval, 0.52-3.54). The prevalence of the homozygous 677TT polymorphism in the MTHFR gene was not increased in cases compared with controls. Mild or moderate hyperhomocysteinemia does not seem to be a strong determinant in VTE not only when the control group does not exclusively include healthy persons but also in investigated disease-free (thromboembolic disease) controls

Interactive Natural Language Technology for Explainable Artificial Intelligence

We have defined an interdisciplinary program for training a new generation of researchers who will be ready to leverage the use of Artificial Intelligence (AI)-based models and techniques even by non-expert users. The final goal is to make AI self-explaining and thus contribute to translating knowledge into products and services for economic and social benefit, with the support of Explainable AI systems. Moreover, our focus is on the automatic generation of interactive explanations in natural language, the preferred modality among humans, with visualization as a complementary modality.Accepted Author ManuscriptWeb Information System