COVID-19-related persistent olfactory dysfunction (OD) presents remarkable interindividual differences, and little is known about the host genetic factors that are involved in its etiopathogenesis. The goal of this study was to explore the genetic factors underpinning COVID-19-related OD through the analysis of Whole Genome Sequencing data of 153 affected subjects, focusing on genes involved in antiviral response regulation. An innovative approach was developed, namely the assessment of the association between a “gene score”, defined as the ratio of the number of homozygous alternative variants within the gene to its length, and participants’ olfactory function. The analysis highlighted how an increased gene score in the ACE2 gene is associated with a worse olfactory performance, while an increased gene score in the IFI44 and NDUFAF4 genes is associated with a better olfactory function. Considering the physiological role of the proteins encoded by these genes, it can be hypothesized that a reduced expression of ACE2 may be associated with a protracted and severe inflammatory response in the olfactory epithelium, thus worsening patients’ smell abilities. Conversely, an increased gene score in IFI44 and NDUFAF4 might be associated with a decreased inflammatory response, thus correlating with a better olfactory performance. Overall, this study identified new host genetic factors that may play a pivotal role in determining COVID-19-related OD heterogeneity, possibly enabling more personalized and effective clinical management for affected individuals.

Background/Objectives: In recent years, short DNA duplexes have been studied as promising self-assembling systems and versatile building blocks for DNA-based nanotechnologies. Numerical simulations of colloidal systems incorporating such components require, as an input ingredient, reliable yet simplified force-fields capable of capturing the essential features of duplex-duplex interactions. Methods: We employed the coarse-grained SIRAH force field under an implicit solvent approximation to investigate the interactions between a pair of short, rigid double-stranded DNA (dsDNA) duplexes. We investigated the effect of duplex size by employing duplexes of 8 and 20 base pairs. Results: Using this realistic coarse-grained model, we obtained detailed insights into how the interaction force depends on the relative positions and orientations of the duplexes, as well as on salt concentration. Conclusions: Our findings provide a foundational step toward the systematic development of simplified, yet qualitatively accurate model potentials for DNA-based colloidal systems. Beyond nanotechnology, the short-range interaction features captured here are also relevant to biological contexts, including chromatin compaction, homologous recombination, and DNA repair.

Primary ciliary dyskinesia (PCD) is a congenital motile ciliopathy causing impaired mucociliary clearance and characterized by recurrent respiratory infections affecting both the upper and lower airways. Several genes involved in taste perception pathways are expressed in extraoral tissues and have recently emerged as regulators of airway immune responses. This study aimed to (1) analyze potential correlations between PCD clinical manifestations and (2) investigate whether genetic variants within sweet signaling genes (SweetG) could be associated with PCD features. A total of 17 SNPs in nine SweetG were tested for differences in allele frequency between patients and the gnomAD European reference population using a binomial test. Regression models were used to evaluate associations between SweetG-SNPs and clinical features of patients. A cohort of 34 patients (10–69 years, 44.1% male) was included in the study. Regarding (1), a moderate/high correlation was identified among the clinical manifestations of the pathologies. Regarding (2), the minor alleles of rs5415 (SLC2A4 gene) and rs838133 (FGF21 gene) were less frequent in patients than in the reference population (p < 0.05). In addition, rs5415 and rs838133 were associated with the presence of chronic rhinosinusitis and situs inversus, respectively (p < 0.05). This study reveals associations between SweetG-SNPs and PCD as well as its specific clinical features, suggesting a potential link between sweet signaling pathways and PCD clinical variability. Although larger multicenter studies are warranted to validate these findings, they represent a promising area of research that can enhance our understanding of PCD and elucidate the genetic basis of clinical manifestations associated with the disease.

The CYP2D6 gene is a highly polymorphic pharmacogene involved in the metabolism of 25% of commonly used drugs. We aim to assess the feasibility of extracting relevant pharmacogenomic information from Whole Genome Sequencing (WGS) data and to highlight any difference in CYP2D6 allele frequencies between the northeastern Italian and European populations. To achieve this aim, WGS was performed on two cohorts: 664 individuals from six different isolated communities (FIC) and 123 outbred Italian individuals (FOP). In silico CYP2D6 genotyping was performed and allele frequencies from the FIC cohort were compared to those of FOP and European individuals from 1000 Genomes. Interestingly, 18 alleles identified in FIC were absent in the control cohorts. In particular, 13 individuals carried the extremely rare CYP2D6*28x2 allele, whose activity is unknown. Moreover, we identified a carrier of the CYP2D6*34x2 allele, which has never been described before. The population structure and genetic differentiation of the cohorts were investigated, revealing that the genetic isolates differ only slightly from the outbred and the European populations, but still offer new insight into CYP2D6 heterogeneity. The findings described here will be relevant to tailoring the treatments in the northeastern Italian population.

Background/Objectives: In recent years, short DNA duplexes have been studied as promising self-assembling systems and versatile building blocks for DNA-based nanotechnologies. Numerical simulations of colloidal systems incorporating such components require, as an input ingredient, simplified but reliable force-fields that capture the essential features of duplex-duplex interactions. Methods: We employed the coarse-grained SIRAH force field under an implicit solvent approximation to in-vestigate the interactions between two short, rigid double-stranded DNA (dsDNA) duplexes. Results: Using this realistic coarse-grained model, we obtained detailed in-sights into how the force field depends on the relative positions, orientations and salt concentration. Calculations were performed for duplexes of 8 and 20 base pairs in length. Conclusions: Our findings represent a foundational step toward the systematic development of simplified, yet qualitatively accurate, model potentials for DNA-based colloidal systems. Beyond nanotechnology, the short-range interaction features cap-tured here are also relevant to biological contexts, including chromatin compaction, homologous recombination, and DNA repair.