Pubblicazioni scientifiche
Universality in the Structure and Dynamics of Water under Lipidic Mesophase Soft Nanoconfinement
Abstract Water under soft nanoconfinement features physical and chemical properties fundamentally different from bulk water; yet, the multitude and specificity of confining systems and geometries mask any of its potentially universal traits. Here, we advance in this quest by resorting to lipidic mesophases as an ideal nanoconfinement system, allowing inspecting the behavior of water under systematic changes in the topological and geometrical properties of the confining medium, without altering the chemical nature of the interfaces. By combining Terahertz absorption spectroscopy experiments and molecular dynamics simulations, we unveil the presence of universal laws governing the physics of nanoconfined water, recapitulating the data collected at varying levels of hydration and nanoconfinement topologies. This geometry-independent universality is evidenced by the existence of master curves characterizing both the structure and dynamics of simulated water as a function of the distance from the lipid–water interface. Based on our theoretical findings, we predict a parameter-free law describing the amount of interfacial water against the structural dimension of the system (i.e., the lattice parameter), which captures both the experimental and numerical results within the same curve, without any fitting. Our results offer insight into the fundamental physics of water under soft nanoconfinement and provide a practical tool for accurately estimating the amount of nonbulk water based on structural experimental data. Autori Eva Zunzunegui-Bru, Serena Rosa Alfarano, Patrick Zueblin, Hendrik Vondracek, Federica Piccirilli, Lisa Vaccari, Salvatore Assenza, Raffaele Mezzenga Rivista ACS Nano Data di pubblicazione 01/08/2024 Consulta la pubblicazione
Competition of Mechanisms: Tracing How Language Models Handle Facts and Counterfactuals
Abstract Interpretability research aims to bridge the gap between empirical success and our scientific understanding of the inner workings of large language models (LLMs). However, most existing research focuses on analyzing a single mechanism, such as how models copy or recall factual knowledge. In this work, we propose a formulation of competition of mechanisms, which focuses on the interplay of multiple mechanisms instead of individual mechanisms and traces how one of them becomes dominant in the final prediction. We uncover how and where mechanisms compete within LLMs using two interpretability methods: logit inspection and attention modification. Our findings show traces of the mechanisms and their competition across various model components and reveal attention positions that effectively control the strength of certain mechanisms. Autori Francesco Ortu, Zhijing Jin, Diego Doimo, Mrinmaya Schaan, Alberto Cazzaniga, Bernhard Scholkopf Rivista Accepted at the Annual Meeting of the Association for Computational Linquistics (ACL), Arxiv preprint: 2402.11655 Data di pubblicazione 06/06/2024 Consulta la pubblicazione
Emergent representations in networks trained with the Forward-Forward algorithm
Abstract The Backpropagation algorithm has often been criticised for its lack of biological realism. In an attempt to find a more biologically plausible alternative, the recently introduced Forward-Forward algorithm replaces the forward and backward passes of Backpropagation with two forward passes. In this work, we show that the internal representations obtained by the Forward-Forward algorithm can organise into category-specific ensembles exhibiting high sparsity – composed of a low number of active units. This situation is reminiscent of what has been observed in cortical sensory areas, where neuronal ensembles are suggested to serve as the functional building blocks for perception and action. Interestingly, while this sparse pattern does not typically arise in models trained with standard Backpropagation, it can emerge in networks trained with Backpropagation on the same objective proposed for the Forward-Forward algorithm. These results suggest that the learning procedure proposed by Forward-Forward may be superior to Backpropagation in modelling learning in the cortex, even when a backward pass is used. Autori Niccolò Tosato, Lorenzo Basile, Emanuele Ballarin, Giuseppe de Alteriis, Alberto Cazzaniga, Alessio Ansuini Rivista Submitted at Advances in Neural Information Processing Systems 37 (NEURIPS 2024) Main Conference Track. Arxiv preprint: 2305.18353 Data di pubblicazione 19/06/2024 Consulta la pubblicazione
Enhancing Multi-Tip Artifact Detection in STM Images Using Fourier Transform and Vision Transformers
Abstract We address the issue of multi-tip artifacts in Scanning Tunneling Microscopy (STM) images by applying the fast Fourier transform (FFT) as a feature engineering method. We fine-tune various neural network architectures using a synthetic dataset, including Vision Transformers (ViT). The FFT-based preprocessing significantly improves the performance of ViT models compared to using only the grayscale channel. Ablation experiments highlight the optimal conditions for synthetic dataset generation. Unlike traditional methods that are challenging to implement for large datasets and used offline, our method enables on-the-fly classification at scale. Our findings demonstrate the efficacy of combining the Fourier transform with deep learning for enhanced artifact detection in STM images, contributing to more accurate analysis in material science research. Autori Tommaso Rodani, Alessio Ansuini, Alberto Cazzaniga Rivista ICML ’24 Workshop ML for Life and Material Science: From Theory to Industry Applications Data di pubblicazione 17/07/2024 Consulta la pubblicazione
Enhancing predictions of protein stability changes induced by single mutations using MSA-based language models
Abstract Protein language models offer a new perspective for addressing challenges in structural biology, while relying solely on sequence information. Recent studies have investigated their effectiveness in forecasting shifts in thermodynamic stability caused by single amino acid mutations, a task known for its complexity due to the sparse availability of data, constrained by experimental limitations. To tackle this problem, we introduce two key novelties: leveraging a protein language model that incorporates Multiple Sequence Alignments to capture evolutionary information, and using a recently released mega-scale dataset with rigorous data preprocessing to mitigate overfitting. Autori Francesca Cuturello, Marco Celoria, Alessio Ansuini, Alberto Cazzaniga Rivista Bioinformatics, 2024, 40 (7) Consulta la pubblicazione
Operando Soft X-ray Absorption of LaMn1–xCoxO3 Perovskites for CO Oxidation
Abstract We employed operando soft X-ray absorption spectroscopy (XAS) to monitor the changes in the valence states and spin properties of LaMn1–xCoxO3 catalysts subjected to a mixture of CO and O2 at ambient pressure. Guided by simulations based on charge transfer multiplet theory, we quantitatively analyze the Mn and Co 2p XAS as well as the oxygen K-edge XAS spectra during the reaction process. The Mn sites are particularly sensitive to the catalytic reaction, displaying dynamics in their oxidation state. When Co doping is introduced (x ≤ 0.5), Mn oxidizes from Mn2+ to Mn3+ and Mn4+, while Co largely maintains a valence state of Co2+. In the case of LaCoO3, we identify high-spin and low-spin Co3+ species combined with Co2+. Our investigation underscores the importance to consider the spin and valence states of catalyst materials under operando conditions. Autori Qijun Che, Mahnaz Ghiasi, Luca Braglia, Matt LJ Peerlings, Silvia Mauri, Piero Torelli, Petra de Jongh, Frank MF de Groot Rivista ACS Catalysis Data di pubblicazione 12/07/2024 Consulta la pubblicazione
Dimeric and monomeric conformation of SARS-CoV-2 main protease: New technical approaches based on IR radiation
Abstract The main proteases M are a group of highly conserved cysteine hydrolases in -coronaviruses. They have been demonstrated to play an unavoidable role in viral replication, and consequently they have been suggested as key targets for treating coronavirus-caused infectious diseases, mainly from the COVID-19 epidemic. Since the most functional form for M enzymatic activity is associated to its homodimer, compounds inhibiting dimerization should also inhibit catalytic activity. We show how PIR-SEIRA (Plasmonic Internal Reflection-Surface Enhanced InfraRed Absorption) spectroscopy can be a noteworthy technique to study proteins subtle structural variations associated to inhibitor binding. Nanoantennas arrays can selectively confine and enhance electromagnetic field via localized plasmonic resonances, thus promoting ultrasensitive detection of biomolecules in close proximity of nanoantenna arrays and enabling the effective investigation of protein monolayers. By adopting this approach, reflection measurements conducted under back illumination of nanoantennas allow to probe anchored protein monolayers, with minimum contribution of environmental buffer molecules. PIR-SEIRA spectroscopy on M was carried out by ad hoc designed devices, resonating in the spectral region of Amide I and Amide II bands. We evaluated here the structure of anchored monomers and dimers in different buffered environment and in presence of a newly designed M inhibitor. Experimental results show that dimerization is not associated to relevant backbone rearrangements of the protein at secondary structure level, and even if the compound inhibits the dimerization, it is not effective at breaking preformed dimers. Autori Federica Piccirilli, Hendrik Vondracek, Lucia Silvestrini, Pietro Parisse, Francesco Spinozzi, Lisa Vaccari, Andrea Toma, Vincenzo Aglieri, Loredana Casalis, Antonio Palumbo Piccionello, Paolo Mariani, Giovanni Birarda, Maria Grazia Ortore Rivista Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy Data di pubblicazione 6/7/2024 Consulta la pubblicazione
Molecular detection of transcriptionally active ovine papillomaviruses in commercial equine semen
Abstract Virological evaluation was performed on equine semen to detect the presence of papillomaviruses (PVs) using droplet digital polymerase chain reaction (ddPCR) as the aim of this study was to investigate whether the sperm from asymptomatic stallions harbors ovine papillomaviruses (OaPVs). Twenty-seven semen samples were analyzed, 18 of which were commercially acquired. The remaining nine samples comprising semen and peripheral blood, were collected from nine stallions with no apparent signs of PV-related diseases during clinical examination at the Didactic Veterinary University Hospital (DVUH) of Naples. OaPV was detected in 26 semen samples. OaPV1 was the most prevalent virus infecting equine semen. OaPV1 infected 21 semen samples (~80.8%) and showed a high number of DNA and RNA copies per microliter. qPCR was used to detect OaPV1 DNA in the 18 semen samples. ddPCR was used to detect and quantify the expression of OaPV2, OaPV3, and OaPV4. qPCR failed to detect DNA for these genotypes. Additionally, ddPCR was used to detect the transcriptionally active OaPV1 in six blood and semen samples from the same stallion. ddPCR failed to detect any nucleic acids in OaPVs in peripheral blood samples from the three stallions. In one semen sample, ddPCR detected OaPV1 DNA but failed to detect any nucleic acid in the remaining two semen samples, and peripheral blood from the same animals of the remaining 18 semen samples was not available, OaPV1 and OaPV4 were responsible for nine and five single infections, respectively. No single infections with either OaPV3 or OaPV4 were seen. Autori Anna Cutarelli, Francesca De Falco, Roberta Brunetti, Michele Napoletano, Giovanna Fusco, Sante Roperto Rivista Frontiers in Veterinary Science Data di pubblicazione 03/07/2024 Consulta la pubblicazione
Genome-wide DNA methylation and transcriptomic analysis of liver tissues subjected to early ischemia/reperfusion injury upon human liver transplantation
Abstract Introduction and Objectives Epigenetic changes represent a mechanism connecting external stresses with long-term modifications of gene expression programs. In solid organ transplantation, ischemia-reperfusion injury (IRI) appears to induce epigenomic changes in the graft, although the currently available data are extremely limited. The present study aimed to characterize variations in DNA methylation and their effects on the transcriptome in liver transplantation from brain-dead donors. Patients and Methods 12 liver grafts were evaluated through serial biopsies at different timings in the procurement-transplantation process: T0 (warm procurement, in donor), T1 (bench surgery), and T2 (after reperfusion, in recipient). DNA methylation (DNAm) and transcriptome profiles of biopsies were analyzed using microarrays and RNAseq. Results Significant variations in DNAm were identified, particularly between T2 and T0. Functional enrichment of the best 1000 ranked differentially methylated promoters demonstrated that 387 hypermethylated and 613 hypomethylated promoters were involved in spliceosomal assembly and response to biotic stimuli, and inflammatory immune responses, respectively. At the transcriptome level, T2 vs. T0 showed an upregulation of 337 and downregulation of 61 genes, collectively involved in TNF-α, NFKB, and interleukin signaling. Cell enrichment analysis individuates macrophages, monocytes, and neutrophils as the most significant tissue-cell type in the response. Conclusions In the process of liver graft procurement-transplantation, IRI induces significant epigenetic changes that primarily act on the signaling pathways of inflammatory responses dependent on TNF-α, NFKB, and interleukins. Our DNAm datasets are the early IRI methylome literature and will serve as a launch point for studying the impact of epigenetic modification in IRI. Autori Giraudi PJ, Laraño AA, Monego SD, Pravisani R, Bonazza D, Gondolesi G, Tiribelli C, Baralle F, Baccarani U, Licastro D. Rivista Ann Hepatol. Data di pubblicazione 01/07/2024 Consulta la pubblicazione
Low-Temperature Methane Activation Reaction Pathways over Mechanochemically-Generated Ce4+/Cu+ Interfacial Sites
Abstract Methane is a valuable resource and its valorization is an important challenge in heterogeneous catalysis. Here it is shown that CeO2/CuO composite prepared by ball milling activates methane at a temperature as low as 250 °C. In contrast to conventionally prepared catalysts, the formation of partial oxidation products such as methanol and formaldehyde is also observed. Through an in situ Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) and operando Near Edge X-Ray Absorption Fine Structure Spectroscopy (NEXAFS) approach, it can be established that this unusual reactivity can be attributed to the presence of Ce4+/Cu+ interfaces generated through a redox exchange between Ce3+ and Cu2+ atoms facilitated by the mechanical energy supplied during milling. DFT modeling of the electronic properties confirms the existence of a charge transfer mechanism. These results demonstrate the effectiveness and distinctiveness of the mechanical approach in creating unique and resilient interfaces thereby enabling the optimization and refining of CeO2/CuO catalysts in methane activation reactions. Autori Silvia Mauri, Rudy Calligaro, Carlo Federico Pauletti, Matteo Farnesi Camellone, Marta Boaro, Luca Braglia, Stefano Fabris, Simone Piccinin, Piero Torelli, Alessandro Trovarelli Rivista Small Data di pubblicazione 11/06/2024 Consulta la pubblicazione
Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure
Abstract Familial Dysautonomia (FD) is a rare disease caused by ELP1 exon 20 skipping. Here we clarify the role of RNA Polymerase II (RNAPII) and chromatin on this splicing event. A slow RNAPII mutant and chromatin-modifying chemicals that reduce the rate of RNAPII elongation induce exon skipping whereas chemicals that create a more relaxed chromatin exon inclusion. In the brain of a mouse transgenic for the human FD-ELP1 we observed on this gene an age-dependent decrease in the RNAPII density profile that was most pronounced on the alternative exon, a robust increase in the repressive marks H3K27me3 and H3K9me3 and a decrease of H3K27Ac, together with a progressive reduction in ELP1 exon 20 inclusion level. In HEK 293T cells, selective drug-induced demethylation of H3K27 increased RNAPII elongation on ELP1 and SMN2, promoted the inclusion of the corresponding alternative exons, and, by RNA-sequencing analysis, induced changes in several alternative splicing events. These data suggest a co-transcriptional model of splicing regulation in which age-dependent changes in H3K27me3/Ac modify the rate of RNAPII elongation and affect processing of ELP1 alternative exon 20. Autori Riccardi F, Romano G, Licastro D, Pagani F. Rivista PLoS One Data di pubblicazione 03/06/2024 Consulta la pubblicazione
Protein family annotation for the Unified Human Gastrointestinal Proteome by DPCfam clustering
Abstract Technological advances in massively parallel sequencing have led to an exponential growth in the number of known protein sequences. Much of this growth originates from metagenomic projects producing new sequences from environmental and clinical samples. The Unified Human Gastrointestinal Proteome (UHGP) catalogue is one of the most relevant metagenomic datasets with applications ranging from medicine to biology. However, the low levels of sequence annotation may impair its usability. This work aims to produce a family classification of UHGP sequences to facilitate downstream structural and functional annotation. This is achieved through the release of the DPCfam-UHGP50 dataset containing 10,778 putative protein families generated using DPCfam clustering, an unsupervised pipeline grouping sequences into single or multi-domain architectures. DPCfam-UHGP50 considerably improves family coverage at protein and residue levels compared to the manually curated repository Pfam. In the hope that DPCfam-UHGP50 will foster future discoveries in the field of metagenomics of the human gut, we release a FAIR-compliant database of our results that is easily accessible via a searchable web server and Zenodo repository. Autori Federico Barone, Elena Tea Russo, Edith Natalia Villegas Garcia, Marco Punta, Stefano Cozzini, Alessio Ansuini, Alberto Cazzaniga Rivista Scientific Data 11, 568 (2024) Data di pubblicazione 01/06/2024 Consulta la pubblicazione