Regulatory Noncoding and Predicted Pathogenic Coding Variants of CCR5 Predispose to Severe COVID-19

Genome-wide association studies (GWAS) found locus 3p21.31 associated with severe COVID-19. CCR5 resides at the same locus and, given its known biological role in other infection diseases, we investigated if common noncoding and rare coding variants, affecting CCR5, can predispose to severe COVID-19. We combined single nucleotide polymorphisms (SNPs) that met the suggestive significance level (P ≤ 1 × 10⁻⁵) at the 3p21.31 locus in public GWAS datasets (6406 COVID-19 hospitalized patients and 902,088 controls) with gene expression data from 208 lung tissues, Hi-C, and Chip-seq data. Through whole exome sequencing (WES), we explored rare coding variants in 147 severe COVID-19 patients. We identified three SNPs (rs9845542, rs12639314, and rs35951367) associated with severe COVID-19 whose risk alleles correlated with low CCR5 expression in lung tissues. The rs35951367 resided in a CTFC binding site that interacts with CCR5 gene in lung tissues and was confirmed to be associated with severe COVID-19 in two independent datasets. We also identified a rare coding variant (rs34418657) associated with the risk of developing severe COVID-19. Our results suggest a biological role of CCR5 in the progression of COVID-19 as common and rare genetic variants can increase the risk of developing severe COVID-19 by affecting the functions of CCR5.     

Study of the natural occurrence of T-2 and HT-2 toxins and their glucosyl derivatives from field barley to malt by high-resolution Orbitrap mass spectrometry

This paper reports a new method for the determination of T-2 and HT-2 toxins and their glucosylated derivatives in cereals, and some survey data aimed at obtaining more comprehensive information on the co-occurrence of T-2 and HT-2 toxins and their glucosylated derivatives in naturally contaminated cereal samples. For these purposes, barley samples originating from a Northern Italian area were analysed by LC-HRMS for the presence of T-2, HT-2 and relevant glucosyl derivatives. Quantitative analysis of T-2 and HT-2 glucosides was performed for the first time using a recently made available standard of T-2 glucoside. The glucosyl derivative of HT-2 was detected at levels up to 163 µg kg^–1 in 17 of the 18 analysed unprocessed barley grains, whereas the monoglucosyl derivative of T-2 toxin was detected in only a few samples and at low µg kg^–1 levels. The ratio between glucosylated toxins (sum of T-2 and HT-2 glucosides) and native toxins (sum of T-2 and HT-2) ranged from 2% to 283%. Moreover, taking advantage of the possibility of retrospective analysis of full-scan HRMS chromatograms, samples were also screened for the presence of other type-A trichothecenes, namely neosolaniol, diacetoxyscirpenol and their monoglucosyl derivatives, which were detected at trace levels. A subset of nine different samples was subjected to micro-maltation in order to carry out a preliminary investigation on the fate of T-2, HT-2 and relevant glucosides along the malting process. Mycotoxin reduction from cleaned barley to malt was observed at rates ranging from 4% to 87%.     

A satellite snow depth multi-year average derived from SSM/I for the high latitude regions

The hydrological cycle for high latitude regions is inherently linked with the seasonal snowpack. Thus, accurately monitoring the snow depth and the associated aerial coverage are critical issues for monitoring the global climate system. Passive microwave satellite measurements provide an optimal means to monitor the snowpack over the arctic region. While the temporal evolution of snow extent can be observed globally from microwave radiometers, the determination of the corresponding snow depth is more difficult. A dynamic algorithm that accounts for the dependence of the microwave scattering on the snow grain size has been developed to estimate snow depth from Special Sensor Microwave/Imager (SSM/I) brightness temperatures and was validated over the U.S. Great Plains and Western Siberia.

The purpose of this study is to assess the dynamic algorithm performance over the entire high latitude (land) region by computing a snow depth multi-year field for the time period 1987–1995. This multi-year average is compared to the Global Soil Wetness Project-Phase2 (GSWP2) snow depth computed from several state-of-the-art land surface schemes and averaged over the same time period. The multi-year average obtained by the dynamic algorithm is in good agreement with the GSWP2 snow depth field (the correlation coefficient for January is 0.55). The static algorithm, which assumes a constant snow grain size in space and time does not correlate with the GSWP2 snow depth field (the correlation coefficient with GSWP2 data for January is − 0.03), but exhibits a very high anti-correlation with the NCEP average January air temperature field (correlation coefficient − 0.77), the deepest satellite snow pack being located in the coldest regions, where the snow grain size may be significantly larger than the average value used in the static algorithm. The dynamic algorithm performs better over Eurasia (with a correlation coefficient with GSWP2 snow depth equal to 0.65) than over North America (where the correlation coefficient decreases to 0.29).     

Uptake of Escherichia coli, Vibrio cholerae non-O1 and Enterococcus durans by, and depuration of mussels (Mytilus galloprovincialis)

The uptakes of Escherichia coli, Vibrio cholerae non-O1 and Enterococcus durans by mussels (Mytilus galloprovincialis) and the times for depuration were investigated in order to determine the most useful indicator of vibrio contamination. The mussels were maintained in tanks of static seawater contaminated with bacteria at 5 log10 CFU/ml for bioaccumulation. Depuration was carried out by circulating fresh seawater through the tanks. Each organism was presented alone and with others to mussels, at temperatures of 14 and 21 degrees C. In water contaminated with either single or mixed organisms, the bacteria accumulated rapidly in the mussels reaching high concentrations after 1 h. With both single and mixed organisms, the maximum numbers of E. coli in mussels were 6.6 log10 CFU/g at 14 degrees C and 5.4 log10 CFU/g at 21 degrees C. Both V. cholerae non-O1 and E. durans alone or with other organisms reached a number ranging from 6.5 to 7 log10 CFU/g at both temperatures. During depuration the numbers of all the organisms slowly decreased, with E. coli alone, numbers ranged from 2.8 to 2 log10 CFU/g after 72 h at both 14 and 21 degrees C, and the organisms were undetectable after 144 h. With mixed organisms at 14 degrees C E. coli became undetectable after 168 h but at 21 degrees C no E. coli were recovered after 72 h. At 14 degrees C V. cholerae non-O1 alone also was undetectable after 168 h, but at 21 degrees C and with mixed organisms at both temperatures. V. cholerae was recovered after 168 h at numbers about 1 log10 CFU/g. After 168 h numbers of E. durans alone ranged from 2.6 log10 CFU/g at 14 degrees C to 1.5 log10 CFU/g at 21 degrees C, and with mixed organisms the numbers ranged from 2.3 to 2.0 log10 CFU/g at both temperatures. Of the three bacteria of faecal origin, E. durans is quickly acquired by mussels and released more slowly than the others, while E. coli quickly becomes undetectable. The results suggest that, for this kind of seafood, enterococci may be a more appropriate indicator than E. coli of risks to consumers from vibrios.     

Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis

Myasthenia gravis with antibodies (Abs) against the muscle-specific tyrosine kinase (MuSK) is a rare autoimmune disorder (AD) of the neuromuscular junction (NMJ) and represents a prototype of AD with proven IgG4-mediated pathogenicity. Thanks to the mechanism of Fab-arm exchange (FAE) occurring in vivo, resulting MuSK IgG4 k/λ Abs increase their interference on NMJ and pathogenicity. The characterization of hybrid MuSK IgG4 as a biomarker for MG management is poorly investigated. Here, we evaluated total IgG4, hybrid IgG4 k/λ, and the hybrid/total ratio in 14 MuSK-MG sera in comparison with 24 from MG with Abs against acetylcholine receptor (AChR) that represents the not IgG4-mediated MG form. In both subtypes of MG, we found that the hybrid/total ratio reflects distribution reported in normal individuals; instead, when we correlated the hybrid/total ratio with specific immune-reactivity we found a positive correlation only with anti-MuSK titer, with a progressive increase of hybrid/total mean values with increasing disease severity, indirectly confirming that most part of hybrid IgG4 molecules are engaged in the anti-MuSK pathogenetic immune-reactivity. Further analysis is necessary to strengthen the significance of this less unknown biomarker, but we retain it is full of a diagnostic-prognostic powerful potential for the management of MuSK-MG.     

Assimilation of virtual wide swath altimetry to improve Arctic river modeling

Global surface water variations are still difficult to monitor with current satellite measurements. The future Surface Water and Ocean Topography (SWOT) mission is designed to address this issue. Its main payload will be a wide swath altimeter which will provide maps of water surface elevations between 78°S and 78°N over a 120 km swath. This study aims to combine coupled hydrologic/hydraulic modeling of an Arctic river with virtual SWOT observations using a local ensemble Kalman smoother to characterize river water depth variations. We assumed that modeling errors are only due to uncertainties in atmospheric forcing fields (precipitation and air temperature) and different SWOT orbits were tested. First, we tested orbits that all have a three day repeat period but differ in terms of their spatial coverage of the study reach; these orbits correspond to the first three months of the mission, which will be dedicated to calibration and validation experiments. For these orbits, the mean spatial Root Mean Square Error (RMSE) in modeled channel water depth decreased by between 29% and 79% compared to the modeled RMSE with no assimilation, depending on the spatial coverage. The corresponding mean temporal RMSE decrease was between 54% and 91%. We then tested the nominal orbit with a twenty two day repeat period which will be used during the remaining lifetime of the mission. Unlike the three day repeat orbits, this orbit will observe all continental surfaces (except Antartica and the northern part of Greenland) during one repeat period. The assimilation of SWOT observations computed with this nominal orbit into the hydraulic model leads to a decrease of 59% and 66% in the mean spatial and temporal RMSE in modeled channel water depth, respectively. These results show the huge potential of the future SWOT mission for land surface hydrology, especially at high latitudes which will be very well sampled during one orbit repeat period. Still, further work is needed to reduce current modeling uncertainties and to better characterize SWOT measurement errors.     

Photopolymerization of biomaterials: issues and potentialities in drug delivery,tissue engineering,and cell encapsulation applications

Photopolymerization is a widely explored technology that has recently been recognized to have also great potentialities in the biomedical field. This paper aims to provide a general overview of this technology by briefly describing materials and methods used to produce linear or crosslinked polymer networks for drug delivery, tissue engineering and cell encapsulation. In addition, potentialities and areas of investigation that are not fully explored but that could provide solutions for better control over the technology when applied to the biomedical field will be indicated as well. Copyright © 2006 Society of Chemical Industry