Positive Selection Drives the Evolution of the Structural Maintenance of Chromosomes (SMC) Complexes.

Structural Maintenance of Chromosomes (SMC) complexes are an evolutionary conserved protein family. In most eukaryotes, three SMC complexes have been characterized, as follows: cohesin, condensin, and SMC5/6 complexes. These complexes are involved in a plethora of functions, and defects in SMC genes can lead to an increased risk of chromosomal abnormalities, infertility, and cancer.

Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes.

Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through -1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features.

Depletion of CpG dinucleotides in bacterial genomes may represent an adaptation to high temperatures.

Dinucleotide biases have been widely investigated in the genomes of eukaryotes and viruses, but not in bacteria. We assembled a dataset of bacterial genomes (>15 000), which are representative of the genetic diversity in the kingdom Eubacteria, and we analyzed dinucleotide biases in relation to different traits. We found that TpA dinucleotides are the most depleted and that CpG dinucleotides show the widest dispersion.

SARS-CoV-2 ORF3c impairs mitochondrial respiratory metabolism, oxidative stress, and autophagic flux.

Coronaviruses encode a variable number of accessory proteins that are involved in host-virus interaction, suppression of immune responses, or immune evasion. SARS-CoV-2 encodes at least twelve accessory proteins, whose roles during infection have been studied. Nevertheless, the role of the ORF3c accessory protein, an alternative open reading frame of ORF3a, has remained elusive.

Whole-genome sequencing of hMPXV1 in five Italian cases confirms the occurrence of the predominant epidemic lineage.

The ongoing outbreak of monkeypox virus (hMPXV1) is the largest recorded in historically nonendemic countries. Genomic surveillance has emerged as a pivotal tool to track the spread and monitor the evolution of viral pathogens. Therefore, to assess the genetic diversity of circulating hMPXV1 in northern Italy in June to July 2022, we sequenced and analyzed five complete genomes of viruses sampled from patients presenting with a typical course of hMPXV1 infection.

Evolution of the orthopoxvirus core genome.

Orthopoxviruses comprise several relevant pathogens, including the causative agent of smallpox and monkeypox virus. Analysis of orthopoxvirus genome evolution mainly focused on gene gains/losses. We instead analyzed core genes, which are conserved in all orthopoxviruses.

Simplexviruses Successfully Adapt to Their Host by Fine-Tuning Immune Responses.

Primate herpes simplex viruses are species-specific and relatively harmless to their natural hosts. However, cross-species transmission is often associated with severe disease, as exemplified by the virulence of macacine herpesvirus 1 (B virus) in humans. We performed a genome-wide scan for signals of adaptation of simplexviruses to their hominin hosts.

Dating the Emergence of Human Endemic Coronaviruses.

Four endemic coronaviruses infect humans and cause mild symptoms. Because previous analyses were based on a limited number of sequences and did not control for effects that affect molecular dating, we re-assessed the timing of endemic coronavirus emergence. After controlling for recombination, selective pressure, and molecular clock model, we obtained similar tMRCA (time to the most recent common ancestor) estimates for the four coronaviruses, ranging from 72 (HCoV-229E) to 54 (HCoV-NL63) years ago.

Homology-based classification of accessory proteins in coronavirus genomes uncovers extremely dynamic evolution of gene content.

Coronaviruses (CoVs) have complex genomes that encode a fixed array of structural and nonstructural components, as well as a variety of accessory proteins that differ even among closely related viruses. Accessory proteins often play a role in the suppression of immune responses and may represent virulence factors. Despite their relevance for CoV phenotypic variability, information on accessory proteins is fragmentary.

Adaptation of the endemic coronaviruses HCoV-OC43 and HCoV-229E to the human host.

Four coronaviruses (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E) are endemic in human populations. All these viruses are seasonal and generate short-term immunity. Like the highly pathogenic coronaviruses, the endemic coronaviruses have zoonotic origins.

Antigenic variation of SARS-CoV-2 in response to immune pressure.

Analysis of the bat viruses most closely related to SARS-CoV-2 indicated that the virus probably required limited adaptation to spread in humans. Nonetheless, since its introduction in human populations, SARS-CoV-2 must have been subject to the selective pressure imposed by the human immune system. We exploited the availability of a large number of high-quality SARS-CoV-2 genomes, as well as of validated epitope predictions, to show that B cell epitopes in the spike glycoprotein (S) and in the nucleocapsid protein (N) have higher diversity than nonepitope positions.

Role of NEU3 Overexpression in the Prediction of Efficacy of EGFR-Targeted Therapies in Colon Cancer Cell Lines.

The epidermal growth factor receptor (EGFR), through the MAP kinase and PI3K-Akt-mTOR axis, plays a pivotal role in colorectal cancer (CRC) pathogenesis. The membrane-associated NEU3 sialidase interacts with and desialylates EGFR by promoting its dimerization and downstream effectors' activation. Among the targeted therapies against EGFR, the monoclonal antibody cetuximab is active only in a subgroup of patients not carrying mutations in the MAP kinase pathway.

Intrinsically disordered regions are abundant in simplexvirus proteomes and display signatures of positive selection.

Whereas the majority of herpesviruses co-speciated with their mammalian hosts, human herpes simplex virus 2 (HSV-2, genus ) most likely originated from the cross-species transmission of chimpanzee herpesvirus 1 to an ancestor of modern humans We exploited the peculiar evolutionary history of HSV-2 to investigate the selective events that drove herpesvirus adaptation to a new host. We show that HSV-2 intrinsically disordered regions (IDRs)-that is, protein domains that do not adopt compact three-dimensional structures-are strongly enriched in positive selection signals. Analysis of viral proteomes indicated that a significantly higher portion of simplexvirus proteins is disordered compared with the proteins of other human herpesviruses.

Past and ongoing adaptation of human cytomegalovirus to its host.

Cytomegaloviruses (order Herpesvirales) display remarkable species-specificity as a result of long-term co-evolution with their mammalian hosts. Human cytomegalovirus (HCMV) is exquisitely adapted to our species and displays high genetic diversity. We leveraged information on inter-species divergence of primate-infecting cytomegaloviruses and intra-species diversity of clinical isolates to provide a genome-wide picture of HCMV adaptation across different time-frames.

Evolution and Genetic Diversity of Primate Cytomegaloviruses.

Cytomegaloviruses (CMVs) infect many mammals, including humans and non-human primates (NHPs). Human cytomegalovirus (HCMV) is an important opportunistic pathogen among immunocompromised patients and represents the most common infectious cause of birth defects. HCMV possesses a large genome and very high genetic diversity.

The Diversity of Mammalian Hemoproteins and Microbial Heme Scavengers Is Shaped by an Arms Race for Iron Piracy.

Iron is an essential micronutrient for most living species. In mammals, hemoglobin (Hb) stores more than two thirds of the body's iron content. In the bloodstream, haptoglobin (Hp) and hemopexin (Hpx) sequester free Hb or heme.

The influence of DCDC2 risk genetic variants on reading: Testing main and haplotypic effects.

Developmental dyslexia (DD) is a complex neurodevelopmental heritable disorder. Among DD candidate genes, DCDC2 is one of the most replicated, with rs793862, READ1 and rs793842 likely contribute to phenotypic variability in reading (dis)ability. In this study, we tested the effects of these genetic variants on DD as a categorical trait and on quantitative reading-related measures in a sample of 555 Italian nuclear families with 930 offspring, of which 687 were diagnosed with DD.

Deregulation of sialidases in human normal and tumor tissues.

Background: Aberrant sialylation is a characteristic feature associated with cancer. The four types of mammalian sialidases identified to date have been shown to behave in different manners during carcinogenesis. While NEU1, NEU2 and NEU4 have been observed to oppose malignant phenotypes, the membrane-bound sialidase NEU3 was revealed to promote cancer progression.

Genetic susceptibility to infectious diseases: Current status and future perspectives from genome-wide approaches.

Genome-wide association studies (GWASs) have been widely applied to identify genetic factors that affect complex diseases or traits. Presently, the GWAS Catalog includes >2800 human studies. Of these, only a minority have investigated the susceptibility to infectious diseases or the response to therapies for the treatment or prevention of infections.

REST, a master regulator of neurogenesis, evolved under strong positive selection in humans and in non human primates.

The transcriptional repressor REST regulates many neuronal genes by binding RE1 motifs. About one third of human RE1s are recently evolved and specific to primates. As changes in the activity of a transcription factor reverberate on its downstream targets, we assessed whether REST displays fast evolutionary rates in primates.

Distinct selective forces and Neanderthal introgression shaped genetic diversity at genes involved in neurodevelopmental disorders.

In addition to high intelligence, humans evolved specialized social-cognitive skills, which are specifically affected in children with autism spectrum disorder (ASD). Genes affected in ASD represent suitable candidates to study the evolution of human social cognition. We performed an evolutionary analysis on 68 genes associated to neurodevelopmental disorders; our data indicate that genetic diversity was shaped by distinct selective forces, including natural selection and introgression from archaic hominins.

An LC-MS Assay with Isocratic Separation and On-line Solid Phase Extraction to Improve the Routine Therapeutic Drug Monitoring of Busulfan in Plasma.

Background: Busulfan (Bu) requires therapeutic drug monitoring (TDM) in subjects undergoing a conditioning regimen for hematopoietic stem cell transplantation (HSCT). To speed up the procedure and increase reproducibility, we improved our routine LC-MS/MS assay using the on-line solid-phase extraction (SPE) of samples.

Methods: A protein precipitation (PP) step was performed before the on-line SPE of Bu from 200 µL of plasma spiked with octa-deuterated Bu (D8-Bu) as the internal standard.

A common genetic variant in FOXP2 is associated with language-based learning (dis)abilities: Evidence from two Italian independent samples.

Language-based Learning Disabilities (LLDs) encompass a group of complex, comorbid, and developmentally associated deficits in communication. Language impairment and developmental dyslexia (DD) represent the most recognized forms of LLDs. Substantial genetic correlations exist between language and reading (dis)abilities.

A comparison of EuroQol 5-Dimension health-related utilities using Italian, UK, and US preference weights in a patient sample.

Weights associated with the EuroQol 5-Dimension 3-Level (EQ-5D-3L) instrument represent preferences for health states elicited from general population's samples. Weights have not been calculated for every country; however, empirical research shows that cross-country differences exist. This empirical study aims at investigating the impact of recently developed Italian weights in comparison with UK and US scores on health-related utility calculation using a sample of patients with Crohn's disease.