Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

First attempt to evaluate PBDEs in skin biopsies of striped dolphins from the Mediterranean Sea

Many cetacean species, in particular odontocetes, are top predators in the marine food chain and therefore accumulate high levelsof lipophilic compounds such as halogenated hydrocarbons. Many studies indicate the possibility of using these animals as bioindicators of environmental contamination of relatively limited areas. Today there is a growing concern about the accumulation of brominated organic compounds in the marine food web. Polybrominated diphenyl ethers (PBDEs) are a major family of brominated flame retardants which are lipophilic, persistent, and toxic to both fauna and humans. The highest levels of PBDEs have been found in the top of the marine food chain. The aim of this study was to investigate the levels of PBDEs in specimens of striped dolphin (Stenella coeruleoalba) sampled with the non-lethal method of biopsy in the Mediterranean Sea and contiguous Atlantic areas with different anthropogenic impacts: the Gibraltar Straits, the Pelagos Sanctuary (Ligurian Sea) and the west Ionian Sea (Sicily). The levels of individual PBDEs were determined by GC/MS. Negative chemical ionisation (NCI-MS) using methane as reagent gas, was the operating mode. Results obtained indicated the presence of BDE-99, BDE-153, BDE- 154, BDE-100, and BDE-47 as the most abundant. Total PBDEs found in this study were in the range 8–25ppm (ug/g fresh weight), being samples from the Ligurian sea, the highest contaminated compared to specimens from the Straits of Gibraltar. In addition it should be remarked that total PBDE levels found in this study are similar to total PCB levels found in the same specimens

Use of immunofluorescence technique in cultured fibroblasts from Mediterranean cetaceans as new “in vitro” tool to investigate effects of environmental contaminants

International audienc

Use of immunofluorescence technique in cultured fibroblasts from Mediterranean cetaceans as new “in vitro” tool to investigate effects of environmental contaminants

6noreservedThe aim of the present study was to propose the immunofluorescence technique in cultured fibroblasts from Mediterranean cetaceans as a new “in vitro” tool to explore the susceptibility of these marine mammals to different xenobiotic compounds. The cell lines were cultured from integument biopsies of free-ranging and stranded cetaceans (dead within 12 h). Using the indirect immunofluorescence assay, we detected endogenous proteins induced by different contaminants. Here we present the method used for qualitative and quantitative evaluation of cytochromes P450 (CYP1A1 and CYP2B) induced by some POPs (DDTs and PCBs) and emerging contaminants (PBDEs) in fibroblast cell cultures of striped dolphin (Stenella coeruleoalba) and bottlenose dolphin (Tursiops truncatus). Immunofluorescence was quantified with a specially designed Olympus macro, DetectIntZ. A major result was the possibility of using this “in vitro” assay to quantify induction of endogenous proteins.mixedMarsili, L.; Casini, S.; Bucalossi, D.; Porcelloni, S.; Maltese, S.; Fossi, M.C.Marsili, L.; Casini, S.; Bucalossi, D.; Porcelloni, S.; Maltese, S.; Fossi, M. C

Biomarker responses in European sea bass (Dicentrarchus labrax) and gilthead sea bream (Sparus aurata) from a highly populated Mediterranean coastal area: The Gulf of La Spezia

The aim of this study, conducted as collaboration between the Department of Environmental Sciences (Siena University) and ICRAM (Rome), was to validate an integrated methodology to evaluate the ecotoxicological hazard in the gulf of La Spezia (Ligurian sea), a Mediterranean coastal area with high anthropogenic impact. The methodology was based on the application of a set of biomarkers (etoxyresorufin-o-deethylase (EROD), porphyrins, PAH bile metabolites) and chemical analysis (organochlorines (OCs), polycyclic aromatic hydrocarbons (PAHs), heavy metals) on two teleostean species with high commercial interest: the European sea bass (Dicentrarchus labrax) and the gilthead sea bream (Sparus aurata). The coastline offshore the village of Lavagna, 50km west of La Spezia, was selected as reference site. Seasonal samplings were carried out; fish were obtained from sea-caged farms at both sites. Statistical analyses indicated the induction of CYP1A (EROD activity) and naphthalene metabolites in bile as the most sensitive biomarkers, showing a significant induction in La Spezia in comparison with the control site. No significant differences in porphyrin concentrations were found between the sites. PAHs and OCs levels in liver and muscle showed a general agreement with biomarker responses. In conclusion, the integrated use of biomarkers and chemical analysis in sea bass and sea bream can be considered a powerful tool in evaluating the impact of pollutants that can be applied within the framework of marine coastal environmental monitoring programs. This study was supported by La Spezia Port Autority with the supervision of ICRAM institute within the research program related to the monitoring activities for the remediation and dredging activities of La Spezia Harbour area

Real-Time Characterization of Neutron-induced SEUs in Fusion Experiment at WEST Tokamak during D-D Plasma Operation

International audienceWe conducted a real-time SER characterization of CMOS bulk 65nm SRAMs subjected to fusion neutrons during deuterium-deuterium plasma operation at WEST tokamak. Neutron spectrometry and numerical simulation have been also performed to analyze experimental results

Real-Time Characterization of Neutron-induced SEUs in Fusion Experiment at WEST Tokamak during D-D Plasma Operation

International audienceWe conducted a real-time SER characterization of CMOS bulk 65nm SRAMs subjected to fusion neutrons during deuterium-deuterium plasma operation at WEST tokamak. Neutron spectrometry and numerical simulation have been also performed to analyze experimental results

Real-Time Characterization of Neutron-Induced SEUs in Fusion Experiments at WEST Tokamak during D-D Plasma Operation

International audienceWe conducted a real-time soft-error rate characterization of CMOS bulk 65 nm SRAMs subjected to fusion neutrons during deuterium-deuterium (D-D) plasma operation at WEST tokamak. The test equipment, installed in the experimental hall at several locations of the tokamak, was irradiated during machine shots by a flux of particles dominated by primary 2.45 MeV neutrons. Real-time neutron metrology, neutron spectrometry, complementary characterization with monoenergetic neutrons and Monte Carlo numerical simulations at both material and circuit levels have been also performed to analyze experimental data. Our results suggest that higher energy neutrons, simultaneously produced by deuterium-tritium (D-T) reactions due to triton burn up in the D-D plasma, play a significant role in the radiation response of the SRAMs for which multiple cell upsets are detected and cannot be attributed to D-D neutrons