Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

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

Laser ablation of GaAs in liquid: the role of laser pulse duration

The synthesis of gallium arsenide (GaAs) nanoparticles has attracted wide scientific and technological interest due to the possibility of tuning the GaAs NP (nanoparticle) band gap across the visible spectrum and their consequent use in optoelectronic devices. In recent years, laser ablation in liquid (LAL) has been widely used for the preparation of colloidal solutions of semiconducting and metallic nanoparticles, thanks to its flexibility. With the aim of highlighting the key role played by laser pulse duration on the ablation mechanism and on the properties of the obtained materials, laser ablation of a gallium arsenide target in acetone was performed using laser sources operating in two different temporal regimes: Nd:glass laser (l = 527 nm, pulse duration of 250 fs and frequency repetition rate of 10 Hz) and Nd:YAG laser (l = 532 nm, pulse duration of 7 ns and frequency repetition rate of 10 Hz). The ablation process was studied following the dynamics of the laser induced shock waves (SWs) and cavitation bubbles (CBs) by fast shadowgraphy, showing that CB dimension and lifetime is related to the laser pulse length. A characterization of the obtained materials by TEM (transmission electron microscopy) and microRaman spectroscopy have shown that quite spherical gallium oxide/GaAs nanoparticles can be obtained by nanosecond laser ablation. On the other hand, pure polycrystalline GaAs nanoparticles can be produced by using an ultrashort laser source

Ultrashort Pulsed Laser Ablation of Magnesium Diboride: Plasma Characterization and Thin Films Deposition

A MgB2 target has been ablated by Nd:glass laser with a pulse duration of 250 fs. The plasma produced by the laser-target interaction, showing two temporal separated emissions, has been characterized by time and space resolved optical emission spectroscopy and ICCD fast imaging. The films, deposited on silicon substrates and formed by the coalescence of particles with nanometric size, have been analyzed by scanning electron microscopy, atomic force microscopy, X-ray photoelectron spectroscopy, micro-Raman spectroscopy, and X-ray diffraction. The first steps of the films growth have been studied by Transmission Electron Microscopy. The films deposition has been studied by varying the substrate temperature from 25 to 500°C and the best results have been obtained at room temperature

Iron and Iron Oxide nanoparticles obtained by ultra-short laser ablation in liquid

Laser ablation of an iron target in water and acetone has been carried out using a frequency doubled Nd:glass laser source (pulse duration of 250fs and frequency repetition rate of 10 Hz). The observation of the nanostructures formed in the laser irradiated region of the metallic target and fast shadowgraphic analysis of the laser induced cavitation bubble have been performed in order to correlate the size distribution of the obtained nanoparticles to the dynamics of the ablation process. The composition, morphology and oxidation state of the synthesized nanoproducts have been investigated by XPS (X-ray Photoelectron Spectroscopy), TEM (Transmission Electron Microscopy) and microRaman spectroscopy. The experimental data support a relationship between the nanoparticles size distribution and the femtosecond laser ablation mechanism, while the chemical and structural characteristics of the nanoparticles can be tuned by varying the liquid medium

The role of the solvent in the ultrashort laser ablation of palladium target in liquid

In the present study, the pulsed laser ablation in liquid technique was used to produce palladium nanoparticles in acetone and in water. The composition, morphology and oxidation state of the obtained nanoparticles have been characterized by HR-TEM, XPS and XRD techniques. The results evidence that the nature of the solvent influences the physical–chemical properties of the products. In acetone non-aggregate metallic nanoparticles have been obtained, while in water the oxidation of the particles surface is present, as showed by the XPS analysis. Moreover, the particles obtained in water are aggregated and the coalescence effect is evident. The different size distributions of nanoparticles obtained in the two liquids have been interpreted considering the different cavitation bubble dynamics

Formation of Titanium Carbide (TiC) and TiC@C core-shell nanostructures by ultra-short laser ablation of titanium carbide and metallic titanium in liquid

Laser ablation of bulk target in liquid allows to obtain stable nanoparticles and nanostructures, also in metastable phases, limiting the use of hazardous reagents and extreme reaction conditions. Titanium carbide (TiC) is a ceramic compound with several technological applications ranging from biocompatible materials to wear resistant coatings. The possibility to obtain core/shell structures expands its range of application due to the ability of modify the surface properties of the core ceramic material. TiC and metallic titanium targets have been ablated by means of an ultra-short laser source in different liquid media (water, acetone, n-hexane and toluene). The obtained colloidal solutions have been characterized by TEM, XRD and micro-Raman analysis. In all the used experimental conditions TiC nanoparticles have been produced. During water and acetone mediated ablations, the oxidation of titanium has been observed, whereas by using oxygen free solvents, such as n-hexane and toluene, core/shell TiC nanoparticles embedded in amorphous and graphitic carbon shell, respectively, have been obtained

Transition metal carbide core/shell nanoparticles by ultra-short laser ablation in liquid

Transition metal carbide nanoparticles are a class of technological interesting materials with a wide range of applications. Among metal carbides, tantalum carbides have good compatibility with the biological environment while molybdenum carbides are used as catalyst in electrochemical reactions. Laser ablation of bulk transition metal targets in some liquids is here reported and laser ablation in organic solvents is used as simple synthetic strategy for the production of carbide nanostructures. Herein, the nanoparticles produced by ultra-short laser ablation of tantalum and molybdenum in water, acetone, ethanol and toluene have been characterized by TEM, XRD and XPS analysis. The combined effect of metal and solvent chemical and physical properties on the composition of the nanomaterials obtained has been pointed out. In particular, the different reactivity of Ta and Mo with respect to oxidizing species determines the composition of particles obtained in water, on the other hand the organic solvents decomposition allows to obtain transition metal carbide (TMC) nanoparticles. The observed carbonaceous shell formed on TMC allows to protect the particle’s carbidic core and to improve and tailor the applications of these nanomaterials