Biology subjects

Chillemi, G.

Publications and source records attributed to Chillemi, G..

6 recordsLinked to original sources

bioRxiv2024

Building a model of sepsis: data integration unravels pathogenic mechanisms in severe P. aeruginosa infections.

Understanding host-pathogen interactions is crucial for explaining the variability in sepsis outcomes, with Pseudomonas aeruginosa (PA) remaining a significant public health concern. In this work, we explored PA-human host interaction mechanisms through a data integration workflow, focusing on protein-protein and metabolite-protein interactions, along with pathway modulation in affected organs during severe infections. A scoping literature review enabled us to construct a domain-based infection network encompassing pathogenesis concepts, molecular interactions, and host response signatures, providing a wide view of the relevant mechanisms involved in severe bacterial infections. Our analysis yielded a literature-based comprehensive description of PA infection mechanisms and an annotated dataset of 189 PA-human interactions involving 152 proteins/molecules (109 human proteins, 3 human molecules, 34 PA proteins, and 5 PA molecules). This dataset was complemented with gene expression analysis from in vivo PA-infected lung samples. The results indicated a notable overexpression of proinflammatory pathways and PA-mediated modulation of host lung responses. Our comprehensive molecular network of PA infection represents a valuable tool for the understanding of severe bacterial infections and offers potential applications in predicting clinical phenotypes. Through this approach combining omics data, clinical information, and pathogen characteristics, we have provided a foundation for future research in host-pathogen interactions and the mechanistic grounds to build dynamic computational models for clinical phenotype predictions.

systems biology↗

bioRxiv2022

Dynamic involvement of premotor and supplementary motor areas in bimanual pinch force control

Many bimanual activities of daily living require quick shifts between symmetric and asymmetric motor output generated by the right and left hand. Bimanual motor control has been mostly studied during continuous repetitive tasks, while little research has been carried out in experimental settings requiring dynamic changes in motor output generated by both hands. Here, we performed functional magnetic resonance imaging (MRI) while healthy volunteers performed a visually guided, bimanual pinch force task. This enabled us to map functional activity and connectivity of premotor and motor areas during bimanual pinch force control in different task contexts, requiring mirror-symmetric or inverse-asymmetric changes in discrete pinch force exerted with the right and left hand. The bilateral dorsal premotor cortex showed increased activity and effective coupling to the ipsilateral supplementary motor area (SMA) in the inverse-asymmetric context compared to the mirror-symmetric context of bimanual pitch force control. Compared to unilateral pinches, all bimanual pinch force conditions were characterized by an increased level of activation in the bilateral primary motor hand area (M1-HAND) and stronger coupling from SMA to the ipsilateral M1-HAND. Task-related activity of a cluster in the left caudal SMA scaled positively with the degree of synchronous initiation of bilateral pinch force adjustments, irrespectively of the task context. The results suggest that the dorsal premotor cortex mediates increasing complexity of bimanual coordination by increasing coupling to the SMA-M1 network.

neuroscience↗

bioRxiv2022

The SARS-CoV-2 spike protein binds and modulates estrogen receptors

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein binds angiotensin-converting enzyme 2 (ACE2) at the cell surface, which constitutes the primary mechanism driving SARS-CoV-2 infection. Molecular interactions between the transduced S and endogenous proteins likely occur post-infection, but such interactions are not well understood. We used an unbiased primary screen to profile the binding of full-length S against >9,000 human proteins and found significant S-host protein interactions, including one between S and human estrogen receptor alpha (ER). After confirming this interaction in a secondary assay, we used bioinformatics, supercomputing, and experimental assays to identify a highly conserved and functional nuclear receptor coregulator (NRC) LXD-like motif on the S2 subunit and an S-ER binding mode. In cultured cells, S DNA transfection increased ER cytoplasmic accumulation, and S treatment induced ER-dependent biological effects and ACE2 expression. Noninvasive multimodal PET/CT imaging in SARS-CoV-2-infected hamsters using [18F]fluoroestradiol (FES) localized lung pathology with increased ER lung levels. Postmortem experiments in lung tissues from SARS-CoV-2-infected hamsters and humans confirmed an increase in cytoplasmic ER expression and its colocalization with S protein in alveolar macrophages. These findings describe the discovery and characterization of a novel S-ER interaction, imply a role for S as an NRC, and are poised to advance knowledge of SARS-CoV-2 biology, COVID-19 pathology, and mechanisms of sex differences in the pathology of infectious disease.

immunology↗

bioRxiv2020

HPC-REDItools: a Novel HPC-aware Tool for Improved Large Scale RNA-editing Analysis

BackgroundRNA editing is a widespread co-/post-transcriptional mechanism that alters primary RNA sequences through the modification of specific nucleotides and it can increase both the transcriptome and proteome diversity. The automatic detection of RNA-editing from RNA-seq data is computational intensive and limited to small data sets, thus preventing a reliable genome-wide characterisation of such process. ResultsIn this work we introduce HPC-REDItools, an upgraded tool for accurate RNA-editing events discovery from large dataset repositories. Availability: https://github.com/BioinfoUNIBA/REDItools2. ConclusionsHPC-REDItools is dramatically faster than the previous version, REDItools, enabling big-data analysis by means of a MPI-based implementation and scaling almost linearly with the number of available cores.

bioinformatics↗

bioRxiv2020

New Insights Into the Effect of Residue Mutation on the Rotavirus VP1 Function Using Molecular Dynamic Simulations

Rotavirus group A remains a major cause of diarrhea in infants and young children worldwide. The permanently emergence of new genotypes puts the potential effectiveness of vaccines under serious question. Thirteen VP1 mutants were analyzed using molecular dynamic simulations and the results were combined with the experimental findings, reported previously. The results revealed structural fluctuations and secondary structure change of VP1 protein that may alter its function during viral replication/transcription. Altogether, the structural analysis of VP1 may boost efforts to develop antivirals, as they might complement the available vaccines.

bioinformatics↗

bioRxiv2020

Re-insights into origin and adaptation of SARS-CoV-2

In depth evolutionary and structural analyses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from bats, pangolins, and humans are necessary to assess the role of natural selection and recombination in the emergence of the current pandemic strain. The SARS-CoV-2 S glycoprotein unique features have been associated with efficient viral spread in the human population. Phylogeny-based and genetic algorithm methods clearly show that recombination events between viral progenitors infecting animal hosts led to a mosaic structure in the S gene. We identified recombination coldspots in the S glycoprotein and strong purifying selection. Moreover, although there is little evidence of diversifying positive selection during host-switching, structural analysis suggests that some of the residues emerged along the ancestral lineage of current pandemic strains may contribute to enhanced ability to infect human cells. Interestingly, recombination did not affect the long-range covariant movements of SARS-CoV-2 S glycoprotein monomer in pre-fusion conformation but, on the contrary, could contribute to the observed overall viral efficiency. Our dynamic simulations revealed that the movements between the host cell receptor binding domain (RBD) and the novel furin-like cleavage site are correlated. We identified threonine 333 (under purifying selection), at the beginning of the RBD, as the hinge of the opening/closing mechanism of the SARS-CoV-2 S glycoprotein monomer functional to hACE2 binding. Our findings support a scenario where ancestral recombination and fixation of amino acid residues in the RBD of the S glycoprotein generated a virus with unique features, capable of extremely efficient infection of the human host.

evolutionary biology↗