Biology subjects

Dilucca, M.

Publications and source records attributed to Dilucca, M..

10 recordsLinked to original sources

bioRxiv2025

An inherited mtDNA mutation remodels inflammatory cytokine responses in macrophages and in vivo

Impaired mitochondrial bioenergetics in macrophages can drive hyperinflammatory cytokine responses1-6, but whether this may also be caused by inherited mtDNA mutations is unknown. Here, we address this question using a multi-omic approach that integrates super-resolution imaging and metabolic analyses to profile macrophages from a mouse model of mitochondrial disease arising from a heteroplasmic mutation (m.5019A>G) in the mitochondrial tRNA for alanine7. These m.5019A>G macrophages exhibit defects in respiratory chain complexes and oxidative phosphorylation (OxPhos) due to decreased intra-mitochondrial translation. To adapt to this metabolic stress, mitochondrial fusion, reductive glutamine metabolism, and aerobic glycolysis are all increased. Upon inflammatory activation, type I interferon (IFN-I) release is enhanced, while the production of pro-inflammatory cytokines and oxylipins are restrained in m.5019A>G macrophages. Finally, an in vivo endotoxemia model using m.5019A>G mice reveal elevated IFN-I levels and sickness behaviour. In conclusion, our study identifies an unexpected imbalance in innate immune signalling in response to a pathogenic mtDNA mutation, with important implications for the progression of pathology in patients with mtDNA diseases8.

immunology↗

bioRxiv2020

Temporal evolution and adaptation of SARS-COV 2 codon usage

The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 134,905 SARS-CoV-2 genomes isolated from all affected countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan, China to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns of SARS-CoV-2 genes encoding the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), RNA-dependent RNA polymerase (RdRp). The polyproteins ORF1a and ORF1b were examined separately. We found that SARS-CoV-2 tends to diverge over time by accumulating mutations on its genome and, specifically, on the sequences encoding proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S and N tend to use a narrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use the broader set of synonymous codons, which does not vary in respect to the reference genome. CAI and SiD time evolutions show a tendency to decrease that emerge for most genes. Forsdyke plots are used to study the nature of mutations and they show a rapid evolutionary divergence of each gene, due to the low values of x-intercepets.

genomics↗

bioRxiv2020

Identification of conserved epitopes in SARS-CoV-2 spike and nucleocapsid protein.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December 2019, is a novel virus that causes a severe acute respiratory disease. The virus spike glycoproteins and nucleocapsid proteins are the main targets for the development of vaccines and antiviral drugs, to control the disease spread. We herein study the structural order-disorder propensity and the rates of evolution of these two proteins to characterize their B cell and T cell epitopes, previously suggested to contribute to immune response caused by SARS-CoV-2 infections. We first analyzed the rates of evolution along the sequences of spike and nucleocapsid proteins in relation to the spatial locations of their epitopes. For this purpose, we compared orthologs from seven human coronaviruses: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1. We then focus on the local, structural order-disorder propensities of the protein regions where the SARS-CoV-2 epitopes are located. We show that the vast majority of nucleocapsid protein epitopes overlap the RNA-binding and dimerization domains and some of them are characterized by low rates of evolutions. Similarly, spike protein epitopes are preferentially located in regions that are predicted to be ordered and well-conserved, in correspondence of the heptad repeats 1 and 2. Interestingly, both the receptor-binding motif to ACE2 and the fusion peptide of spike protein are characterized by high rates of evolution, probably to overcome host immunity. In conclusion, our results provide evidence for conserved epitopes that may help to develop long-lasting, broad-spectrum SARS-CoV-2 vaccines.

bioinformatics↗

bioRxiv2020

Knowledge, attitude and practice of secondary school students toward COVID-19 epidemic in Italy: a cross selectional study

The coronavirus disease (COVID-19) is a highly transmittable and pathogenic viral infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which emerges in December 2019 in Wuhan, China and spreads around the world at the beginning of 2020. The World Health Organization declares the outbreak a Public Health Emergency of International Concern on the 30th of January, and a pandemic on the 11th of March. On the 4th of March, the Italian government orders the full closure of all schools and universities nationwide.The aim of this study is to investigate the knowledge, practice and attitudes (KAP) of secondary school at the time of COVID-19 pandemic in Italy. In this cross-sectional, web-based survey, conducted among the high school student population with age ranging from 14 to 19 years old, a questionnaire with 19 items regarding the KAP toward COVID-19 is asked. Study participants are recruited from several secondary schools of different areas. Frequencies and histograms are computed for descriptive purposes. Statistical analysis is computed with Chi square test, utilized to depict relevant difference between geender. Among a total of 2380 students who answers the questionnaire, 40.7% are male and 59.3% are female.Level of knowledge about generical characteristics of COVID-19 is quite similar among gender. Students present a good level of knowledge about the clinical presentation of the disease, the basic hygiene principles, the modes of transmission and the method of protection against virus transmission. The knowledge about number of this pandemia and easy scientific correlation with COVID-19 is quite confused. The most frequently reported source of knowledge about COVID-19 is television, whereas the less is the school. Our findings suggest that student population shows appropriate practice, and positive attitude towards COVID-19 at the time of its outbreak.More emphasis should be placed on education of the student partecipants about biological meaning of this infection and relative preventive or future measures.Competing Interest StatementThe authors have declared no competing interest.View Full Text

scientific communication and education↗

bioRxiv2020

Bacterial protein interaction networks: connectivityis ruled by gene conservation, essentiality andfunction

Protein-protein interaction (PPI) networks are the backbone of all processes in living cells. In this work we relate conservation, essentiality and functional repertoire of a gene to the connectivity k of the corresponding protein in the PPI networks. Focusing on a set of 42 bacterial species with reasonably separated evolutionary trajectories, we investigate three issues: i) whether the distribution of connectivity values changes between PPI subnetworks of essential and nonessential genes; ii) how gene conservation, measured both by the evolutionary retention index (ERI) and by evolutionary pressures (evaluated through the ratio Ka/Ks and ENC plots) is related to the the connectivity of the corresponding protein; iii) how PPI connectivities are modulated by evolutionary and functional relationships, as represented by the Clusters of Orthologous Proteins (COGs). We show that conservation, essentiality and functional specialization of genes control in a quite universal way the topology of the emerging bacterial PPI networks. Noteworthy, a structural transition in the network is observed such that, for connectivities k [≥] 40, bacterial PPI networks are mostly populated by genes that are conserved, essential and which, in most cases, belong to the COG cluster J, related to ribosomal functions and to the processing of genetic information.

genomics↗

bioRxiv2020

Codon usage bias in prokaryotic genomes and environmental adaptation

In each genome synonymous codons are used with different frequencies; this phenomenon is known as codon usage bias. The preferred codons tend to correspond to the most highly expressed tRNAs. It had been known that codon usage bias can influence the cellular fitness and that might be associated with the lifestyle of the organism. To test the impact of environments on genome evolution we studied the relationship between codon usage bias and the phenotypic traits of 615 prokaryotic organisms. Principal component analysis revealed that prokaryotes with a specific phenotypic characteristic and living in similar environmental conditions have similar codon preferences, accessed by the Relative Synonymous Codon Usage (RSCU), and a similar tRNA availability gauged by the tRNA gene copy number (tGCN). In addition, by measuring the average tRNA adaptation index (tAI) for each genome, we discovered that organisms able to live in multiple habitats, including facultative organisms, mesophiles and pathogenic bacteria, exhibit lower extents of translational efficiency, consistent with their need to adapt to different environments. This is the first large-scale study that examines the role of translational efficiency in the environmental adaptation of prokaryotes. Our results show that synonymous codon choices might be under strong translational selection, adapting the codons to the tRNA pool to different extents depending on the organisms lifestyle needs.

bioinformatics↗

bioRxiv2020

Co-evolution between codon usage and Protein-Protein Interaction Networks in Bacterial genomes

In this work, we study the correlation between codon usage and the network features of the PPI in bacteria genomes. We want to extend the information by Dilucca et al. (2015) about E.Colis genome for a set of other 34 bacteria. We use PCA techniques in the space of codon bias indices (compAI, compAI_w, tAI, NC) and GC content to show that genes with similar patterns of codon usage feature have a significantly higher probability that their encoded proteins interact within the PPI. And vice-versa, we show that interacting in the PPI have a coherent codon usage. This work could allow for future investigations into the possible effects that codon bias signal can have on the topology of protein interaction network and, as such, to improve existing bioinformatics methods for predicting protein interactions.

genomics↗

bioRxiv2020

Analysis of codon usage and evolutionary rates of the 2019-nCoV genes

Severe acute respiratory syndrome coronavirus 2 (2019-nCoV), which first broke out in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a mortality ranging from 3% to 6%. To better understand the evolution of the newly emerging 2019-nCoV, in this paper, we analyze the codon usage pattern of 2019-nCoV. For this purpose, we compare the codon usage of 2019-nCoV with that of other 30 viruses belonging to the subfamily of orthocoronavirinae. We found that 2019-nCoV shows a rich composition of AT nucleotides that strongly influences its codon usage, which appears to be not optimized to human host. Then, we study the evolutionary pressures influencing the codon usage and evolutionary rates of the sequences of five conserved genes that encode the corresponding proteins (viral replicase, spike, envelope, membrane and nucleocapsid) characteristic of coronaviruses. We found different patterns of both mutational bias and nature selection that affect the codon usage of these genes at different extents. Moreover, we show that the two integral membrane proteins proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins are important targets for the development of vaccines and antiviral drugs, tend to evolve faster as compared to other ones. Taken together, our results suggest that the higher evolutionary rate observed for these two genes could represent a major barrier in the development of antiviral therapeutics 2019-nCoV.

genomics↗

bioRxiv2020

Codon usage bias in radioresistant bacteria

The relationship between patterns of codon usage bias (CUB), the preferential usage of synonimous nucleotide triplets encoding the same amino acid, and radioresistance was investigated int he genomes of 16 taxonomically distinct radioresistant prokaryotic organisms and in a control set of 11 non-radioresistant bacteria. The radioresistant species were found to be strongly biased towards G and C in the third synonimous codon position. ENC and neutrality plots also sugest that CUB in radioresistant bacteria is mainly affected by mutational bias. Furthermore, the availability of tRNA gene copy number was analyzed and it was found that nine radioresistant species have the sam number of tRNA gene copies for each codon. This suggests that tRNA gene copies and codon bias co-evolved in a specific way in radioresistant species.

molecular biology↗

bioRxiv2019

Bacterial protein interaction networks: connectivity is ruled by gene conservation, essentiality and function

Protein-protein interaction (PPI) networks are the backbone of all processes in living cells. In this work we study how conservation, essentiality and functional repertoire of a gene relate to the connectivity k of the corresponding protein in the PPI networks. Focusing on a set of 42 mostly distantly related bacterial species, we investigate three issues: i) whether the distribution of connectivity values changes between PPI subnetworks of essential and nonessential genes; ii) how gene conservation, measured both by the evolutionary retention index (ERI) and by evolutionary pressure (as represented by the ratio Ka/Ks) is related to the the connectivity of the corresponding protein; iii) how PPI connectivities are modulated by evolutionary and functionaly relationships, as represented by the Clusters of Orthologous Proteins (COGs). We show that conservation, essentiality and functional specialization of genes control in a universal way the topology of the emerging bacterial PPI networks. Noteworthy, a structural transition in the network is observed such that, for connectivities k [≥] 40, bacterial PPI networks are mostly populated by genes that are conserved, essential and which, in most cases, belong to the COG cluster J, related to ribosomal functions and to the processing of genetic information.

systems biology↗