Biology subjects

De Simone, G.

Publications and source records attributed to De Simone, G..

5 recordsLinked to original sources

bioRxiv2026

Virtual Brain Modelling Reveals Altered Network Dynamics and Predicts Symptom Severity in Schizophrenia: Relevance to Antipsychotic Treatment Response and Resistance.

Background: Schizophrenia (SZ) is a heterogeneous disorder characterized by positive, negative, cognitive and disorganisation symptoms, with pleomorphic phenotype and poorly understood aetiology. Dopamine dysregulation represents the most replicated in vivo pathophysiology finding. However, accumulating evidence suggests altered large-scale brain connectivity and excitation/inhibition balance disruption. While quantifying these alterations would help clarify SZ neurophysiology and guide therapy, single-patient identification remains impractical. This is particularly relevant for treatment-resistant SZ (TRS) whose pathophysiology remains unclear. Methods: Using virtual brain modelling, we simulated large-scale brain dynamics from functional and structural MRI data in 43 healthy controls and 33 SZ patients, stratified into TRS and non-TRS. We used the Wong-Wang model to derive four network parameters reflecting GABAergic and NMDA receptor-mediated glutamatergic transmission: global coupling (G), local inhibitory (Ji) and excitatory (JNMDA) coupling, and recurrent excitation (w+). We performed simulations in the whole brain and in resting-state networks, compared model parameters between groups and tested their association with Positive and Negative Syndrome Scale (PANSS) scores. Results: Compared to non-TRS, TRS patients showed increased JNMDA and decreased w+ at the whole-brain level, increased JNMDA and G in the dorsal attention network, lower G in the limbic network and increased w+ in the visual network. Moreover, Ji in the default mode network predicted negative symptom severity while JNMDA in the limbic and ventral attention networks predicted total PANSS scores and disorganisation. Conclusions: These findings suggest that TRS is characterized by network-specific alterations in excitation/inhibition profiles and support the use of personalised multiscale modelling to identify symptom biomarkers.

neuroscience↗

bioRxiv2024

AGAPE (computAtional G-quadruplex Affinitiy PrEdiction): The first AI In-silico workflow for G-quadruplex binding affinity prediction.

AGAPE (computational G-quadruplex Affinity Prediction) is a novel machine learning (ML)-based tool designed to predict the binding and stabilizing potential of small molecules targeting G-quadruplexes (G4s). G4s, prevalent in telomeres and oncogene promoters, are promising therapeutic targets, but designing selective binders remains challenging. Building upon a curated dataset of 1217 compounds labelled through Forster Resonance Energy Transfer (FRET) melting assays, AGAPE integrates 5666 molecular descriptors, both classical and quantum chemical. It captures features relevant to G4 recognition, driving researcher to predict the potential G4 stabilization of small molecules, including both organic ligands and metal complexes. Among the trained ML models, XGBoost achieved the best performance with an accuracy of nearly 91%, using 489 selected features. SHAP analysis highlighted descriptors related to molecular topology, polarizability, and electrostatic potential as key contributors to the classification. AGAPE is deployed through a user-friendly web interface supporting batch prediction and secure data handling and provides a robust and interpretable tool to accelerate the discovery of G4-stabilizing compounds, integrating quantum chemical information within an ML-driven cheminformatics framework.

bioinformatics↗

bioRxiv2024

Co-Metabolic Growth and Microbial Diversity: Keys for the depletion of the α, δ, β and γ-HCH isomers.

The objective of this study was to select and enhance microbiomes capable of degrading the , {delta}, {beta} and {gamma}-HCH isomers. These microbiomes were isolated and enriched from an HCH-contaminated dumpsite in Italy, both in the presence of HCH isomers (1:1:1:1) as the sole carbon sources and under co-metabolic growth conditions in presence of glucose (0.1%). Four microbiomes were assessed for their relevant metabolic capabilities. A quantitative metabarcoding approach was employed to analyze the compositional evolution of the four microbiomes during the enrichment phase and the phase of tsting of the HCH isomers degradation kinetics. The use of a co-metabolic substrate during enrichment process was essential for selecting microbiomes with higher biodiversity. All microbiomes efficiently degraded the , {delta}, and {gamma}-HCH isomers. The highest efficiency in the {beta}-HCH degradation capacity was associated to the highest biodiversity of the microbiome, and the involvement of Chryseobacterium and Asinibacterium sps. has been proposed for a recorded increment in bacterial load during the HCH degradation process. Statement of environmental implicationsSoil contaminated with hexachlorocyclohexane (HCH), including all four isomers, poses a significant risk to environmental and public health. This study isolates and selects microbiomes capable of degrading HCH, demonstrating their degradation efficiency using GC-MS analysis, and studies the microbial communities through metabarcoding of both the initial soils and the selected microbiomes. The contaminated soil originates from the historically polluted area of Italy known as SIN-Valle del Sacco. Developing and optimizing microbiome selection techniques for application on contaminated sites can significantly enhance soil bioremediation, thereby reducing contamination and protecting the environment.

microbiology↗

bioRxiv2023

Bio-based decontamination and detoxification of total petroleum hydrocarbon contaminated dredged sediments: perspectives to produce constructed technosols in the frame of the circular economy.

To accelerate the depletion of total petroleum hydrocarbons, a hydrocarburoclastic ascomycetes, Lambertella sp. MUT 5852, was bioaugmented to dredged sediments co-composting with a lignocellulosic matrix. After only 28 days of incubation, a complete depletion of the contamination was observed. The 16S rDNA metabarcoding of the bacterial community and a predictive functional metagenomic analysis was adopted to evaluate potential bacterial degrading and detoxifying functions. A combination of toxicological assays on two eukaryotic models, the root tips of Vicia faba and the human intestinal epithelial Caco-2 cells, was adopted to assess the robustness of the process not only for the decontamination but also for the detoxification of the dredged sediments. Bacterial taxa, such as Kocuria and Sphingobacterium sps. resulted to be involved in both the decontamination and detoxification of the co-composting dredged sediments by potential activation of diverse oxidative processes. At the same time, the Kocuria sp. showed plant growth promoting activity by the potential expression of the 1-aminocyclopropane-1-carboxylate deaminase activity, providing functional traits of interest for a technosol in terms of sustaining primary producer growth and development.

microbiology↗

bioRxiv2020

PBAP chromatin remodeler mediates enhancer-driven transcription inDrosophila

Chromatin remodeler SWI/SNF is an important participant of gene activation acting predominantly by opening chromatin structure on promoters and enhancers. Here we describe its novel mode of action by mediating targeted action of enhancer. We studied functions of two signature subunits of PBAP subfamily, BAP170 and SAYP, in Drosophila. These subunits were stably tethered onto transgene reporter carrying hsp70 core promoter. Tethered subunits mediate transcription of reporter in a pattern prescribed by nearby enhancer in multiple loci throughout the genome, where the reporter construct was located. Both tethered SAYP and BAP170 recruit the whole PBAP complex onto reporter promoter. Studying difference between these subunits, we found that BAP170-dependent transcription is more resistant to depletion of other PBAP subunits, what may imply the principal role of BAP170 in establishing enhancer-dependent transcription. Author SummaryChromatin remodelers are key molecular machines that are responsible for local changes in chromatin structure in the nucleus. However, their functions in gene expression regulation seem to be broader. We describe the involvement of the SWI/SNF family of remodelers in establishing enhancer-promoter communication, which is apparently independent of its local remodeling activity. Using an artificial tethering of a remodeler on a promoter, we demonstrated that promoters of a certain type become responsive to activation by a nearby enhancer only in the presence of the remodeler, while a remodeler tethering itself is insufficient for gene activation. Thus, our approach helps to uncover novel aspects of molecular interplay on regulatory elements during the gene activation process.

genetics↗