Prove di campo e analisi degli effetti del compost sulla coltura di frumento tenero e sul microbioma rizosferico ad essa associata

Il presente volume presenta le attività e i risultati ottenuti dal Gruppo Operativo “ABRIOPACK”, nato dalla collaborazione tra aziende agricole marchigiane, imprese agroindustriali, università, enti di ricerca pubblici, consulenti ed aziende private leader nel settore della produzione di bioplastiche. Grazie ad una sperimentazione durata quattro anni, il gruppo ha sviluppato protocolli di allevamento avicolo che non prevedono l’uso di antibiotici ed un imballaggio alimentare biodegradabile e compostabile, riciclabile interamente (vaschetta, pellicola, etichetta e scarto organico avicolo) insieme ai rifiuti organici. Queste innovazioni consentono di far fronte a problemi estremamente sentiti in ambito zootecnico ed agroalimentare, quali quello dell’antibiotico resistenza e dell’eccessivo uso di plastica tradizionale, riducendo la produzione di rifiuti indifferenziati ed incrementando il recupero di rifiuti organici attraverso un fine vita virtuoso (compostaggio). I risultati ottenuti e presentati attraverso la presente pubblicazione sono utili alla filiera avicola, ma replicabili anche ad altre filiere agroalimentari

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

Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Image_4_An integrated genomic and biochemical approach to investigate the potentiality of heirloom tomatoes: Breeding resources for food quality and sustainable agriculture.tif

A revival of interest in traditional varieties reflects the change in consumer preferences and the greater awareness of the quality of locally grown products. As ancient cultivars, heirlooms have been selected for decades in specific habitats and represent nowadays potential germplasm sources to consider for breeding high-quality products and cultivation in sustainable agriculture. In this study, 60 heirloom tomato (Solanum lycopersicum L.) accessions, including diverse varietal types (beefsteak, globe, oxheart, plum, and cherry), were profiled over two seasons for the main chemical and biochemical fruit traits. A medium–high level of heritability was found for all traits ranging from 0.52 for soluble solids to 0.99 for fruit weight. The average content of ascorbic acid was ~31 mg 100 g−1 of fw in both seasons, while the greatest variability was found for carotenoids with peaks of 245.65 μg g−1 of fw for total lycopene and 32.29 μg g−1 of fw for β-carotene. Dissection of genotypic (G) and seasonal (Y) factors highlighted genotype as the main source of variation for all traits. No significant effect of Y and G × Y was found for ascorbic acid and fruit weight, respectively, whereas a high influence of Y was found on the variation of lycopene. Molecular fingerprinting was performed using the 10K SolCAP array, yielding a total of 7,591 SNPs. Population structure, phylogenetic relationships, and principal components analysis highlighted a differentiation of plum and cherry genotypes with respect to the beefsteak and globe types. These results were confirmed by multivariate analysis of phenotypic traits, shedding light on how breeding and selection focused on fruit characteristics have influenced the genetic and phenotypic makeup of heirlooms. Marker–trait association showed 11 significantly associated loci for β-carotene and fruit weight. For β-carotene, a single variant on chromosome 8 was found at 12 kb to CCD8, a cleavage dioxygenase playing a key role in the biosynthesis of apocarotenoids. For fruit weight, a single association was located at less than 3 Mbp from SLSUN31 and fw11.3, two candidates involved in the increasing of fruit mass. These results highlight the potentiality of heirlooms for genetic improvement and candidate gene identification.</p

Image_3_An integrated genomic and biochemical approach to investigate the potentiality of heirloom tomatoes: Breeding resources for food quality and sustainable agriculture.tif

A revival of interest in traditional varieties reflects the change in consumer preferences and the greater awareness of the quality of locally grown products. As ancient cultivars, heirlooms have been selected for decades in specific habitats and represent nowadays potential germplasm sources to consider for breeding high-quality products and cultivation in sustainable agriculture. In this study, 60 heirloom tomato (Solanum lycopersicum L.) accessions, including diverse varietal types (beefsteak, globe, oxheart, plum, and cherry), were profiled over two seasons for the main chemical and biochemical fruit traits. A medium–high level of heritability was found for all traits ranging from 0.52 for soluble solids to 0.99 for fruit weight. The average content of ascorbic acid was ~31 mg 100 g−1 of fw in both seasons, while the greatest variability was found for carotenoids with peaks of 245.65 μg g−1 of fw for total lycopene and 32.29 μg g−1 of fw for β-carotene. Dissection of genotypic (G) and seasonal (Y) factors highlighted genotype as the main source of variation for all traits. No significant effect of Y and G × Y was found for ascorbic acid and fruit weight, respectively, whereas a high influence of Y was found on the variation of lycopene. Molecular fingerprinting was performed using the 10K SolCAP array, yielding a total of 7,591 SNPs. Population structure, phylogenetic relationships, and principal components analysis highlighted a differentiation of plum and cherry genotypes with respect to the beefsteak and globe types. These results were confirmed by multivariate analysis of phenotypic traits, shedding light on how breeding and selection focused on fruit characteristics have influenced the genetic and phenotypic makeup of heirlooms. Marker–trait association showed 11 significantly associated loci for β-carotene and fruit weight. For β-carotene, a single variant on chromosome 8 was found at 12 kb to CCD8, a cleavage dioxygenase playing a key role in the biosynthesis of apocarotenoids. For fruit weight, a single association was located at less than 3 Mbp from SLSUN31 and fw11.3, two candidates involved in the increasing of fruit mass. These results highlight the potentiality of heirlooms for genetic improvement and candidate gene identification.</p