Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Highly monodispersed palladium-ruthenium alloy nanoparticles assembled on poly(N-vinyl-pyrrolidone) for dehydrocoupling of dimethylamine–borane: An experimental and density functional theory study

PubMed: 30903812This study reports on one of the best heterogeneous catalysts for the dehydrogenation of dimethylamine–borane (DMAB). This new catalytic system consists of highly monodisperse Pd and Ru alloy nanoparticles supported by poly(N-vinyl-pyrrolidone) (PdRu@PVP). The prepared heterogeneous catalyst can be reproducibly formed using an ultrasonic reduction technique for DMAB dehydrogenation under mild conditions. For the characterization of PdRu@PVP nanomaterials, several spectroscopic and microscopic techniques were used. The prepared PdRu@PVP nanomaterials with an average particle size of 3.82 ± 1.10 nm provided an 808.03 h-1 turnover frequency (TOF) in the dehydrogenation of DMAB and yielded 100% of the cyclic product (Me2NBH2)2 under mild conditions. Furthermore, the activities of catalysts were investigated theoretically using DFT-B3LYP calculations. The theoretical results based on density functional theory were in favorable agreement with the experimental data. © 2019 Elsevier Inc.2014-05The authors thank Dumlupinar University BAP , Turkey ( 2014-05 ) for the financial support. Appendix

Toxicological effects of some antiparasitic drugs on equine liver glutathione S-Transferase enzyme activity

PubMed: 31887670Benzimidazoles are antiparasitic drugs having an extensive application field like agriculture, medicine, and especially in veterinary medicine. In this study, we report the effect of some benzimidazole drugs such as ricobendazole (RBZ), thiabendazole (TBZ), albendazole (ALBA) and oxfendazole (OFZ) on glutathione s-transferase (GST) enzyme activity. The kinetics studies, IC50 and Ki values of the tested drugs on GSTs enzyme activity were investigated. The obtained ranking of IC50 values were found to be approximately RBZ (53.31 µM, r2: 0.9778) < OFZ (57.75 µM, r2: 0.9630) < ALBA (63.00 µM, r2: 0.9443) < TBZ (69.30 µM, r2: 0.9491). And the obtained ranking of Ki values of the tested drugs (RBZ, TBZ, ALBA, and OFZ) for GSTs enzyme activity was found to be approximately 26.37 ± 2.96, 44.01 ± 5.74, 39.82 ± 3.98 and 30.14 ± 3.03 µM, respectively. Experimental results showed that tested the benzimidazoles drugs have some significant inhibitory effect on GSTs enzyme activity. And also, it was determined that RBZ, ALBA, OFZ are competitive inhibition, but TBZ is non-competitive inhibitors on GSTs enzyme activity. RBZ drug showed the best inhibitory effect with the lowest Ki value. © 2019 Elsevier B.V

AN INTERACTIVE GIS-BASED SOFTWARE FOR DYNAMIC MONITORING OF RIVERS

WOS: 000348254600027Water quality research and development attempts have been the most valuable resources in the sense of model calibration and verification techniques. Due to the fact that current degree of pollution in rivers and importance of the sustainable water resources management, the interactive river monitoring becomes inevitable. Within the scope of river water quality monitoring, Geographical Information Systems (GIS) are gaining widespread acceptance besides this fast and reliable water quality models and parameter estimation techniques are becoming available. However, integrating water quality models with GIS is limited in literature. This study presents an integrated platform on which ArcMap as a GIS and a water quality model in MATLAB are brought together in an interactive and user friendly manner. The software provides a considerable developments in future real time river monitoring and environmental pollution assessment

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Afegiu 653 1_Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

International audienceInterindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection