Scientific Publications
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. Authors Riccardi F, Romano G, Licastro D, Pagani F. Journal PLoS One Date 03/06/2024 Consult the paper
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. Authors Federico Barone, Elena Tea Russo, Edith Natalia Villegas Garcia, Marco Punta, Stefano Cozzini, Alessio Ansuini, Alberto Cazzaniga Journal Scientific Data 11, 568 (2024) Date 01/06/2024 Consult the paper
Vertical Intrauterine Bovine and Ovine Papillomavirus Coinfection in Pregnant Cows.
Abstract There is very little information available about transplacental infections by the papillomavirus in ruminants. However, recent evidence has emerged of the first report of vertical infections of bovine papillomavirus (BPV) in fetuses from naturally infected, pregnant cows. This study reports the coinfection of BPV and ovine papillomavirus (OaPV) in bovine fetuses from infected pregnant cows suffering from bladder tumors caused by simultaneous, persistent viral infections. Some molecular mechanisms involving the binary complex composed of Eras and platelet-derived growth factor β receptor (PDGFβR), by which BPVs and OaPVs contribute to reproductive disorders, have been investigated. A droplet digital polymerase chain reaction (ddPCR) was used to detect and quantify the nucleic acids of the BPVs of the Deltapapillomavirus genus (BPV1, BPV2, BPV13, and BPV14) and OaPVs belonging to the Deltapapillomavirus (OaPV1, OaPV2, and OaPV4) and Dyokappapapillomavirus (OaPV3) genera in the placenta and fetal organs (heart, lung, liver, and kidneys) of four bovine fetuses from four pregnant cows with neoplasia of the urinary bladder. A papillomaviral evaluation was also performed on the bladder tumors and peripheral blood of these pregnant cows. In all fetal and maternal samples, the genotype distribution of BPVs and OaPVs were evaluated using both their DNA and RNA. A BPV and OaPV coinfection was seen in bladder tumors, whereas only BPV infection was found in peripheral blood. The genotype distribution of both the BPVs and OaPVs detected in placentas and fetal organs indicated a stronger concordance with the viral genotypes detected in bladder tumors rather than in peripheral blood. This suggests that the viruses found in placentas and fetuses may have originated from infected bladders. Our study highlights the likelihood of vertical infections with BPVs and OaPVs and emphasizes the importance of gaining further insights into the mechanisms and consequences of this exposure. This study warrants further research as adverse pregnancy outcomes are a major source of economic losses in cattle breeding. Authors Francesca De Falco, Anna Cutarelli, Leonardo Leonardi, Ioan Marcus, Sante Roperto Journal Pathogens Publication date 26/05/2024 Consult the publication
On the origin of the improved hydrogen evolution reaction in Mn-and Co-doped MoS 2
Abstract In the field of hydrogen production, MoS2 demonstrates good catalytic properties for the hydrogen evolution reaction (HER) which improve when doped with metal cations. However, while the role of sulfur atoms as active sites in the HER is largely reported, the role of metal atoms (i.e. molybdenum or the dopant cations) has yet to be studied in depth. To understand the role of the metal dopant, we study MoS2 thin films doped with Co and Mn ions. We identify the contribution of the electronic bands of the Mn and Co dopants to the integral valence band of the material using in situ resonant photoemission measurements. We demonstrate that Mn and Co dopants act differently: Mn doping favors the shift of the S–Mo hybridized band towards the Fermi level, while in the case of Co doping it is the less hybridized Co band that shifts closer to the Fermi level. Doping with Mn increases the effectiveness of S as the active site, thus improving the HER, while doping with Co introduces the metallic site of Co as the active site, which is less effective in improving HER properties. We therefore clarify the role of the dopant cation in the electronic structure determining the active site for hydrogen adsorption/desorption. Our results pave the way for the design of efficient materials for hydrogen production via the doping route, which can be extended to different catalytic reactions in the field of energy applications. Authors Pasquale Orgiani, Luca Braglia, Vincent Polewczyk, Zhiwei Nie, Francesco Lavini, Shyni Punathum Chalil, Sandeep Kumar Chaluvadi, Piu Rajak, Floriana Morabito, Edvard Dobovičnik, Vittorio Foglietti, Piero Torelli, Elisa Riedo, Regina Ciancio, Nan Yang, Carmela Aruta Journal Nanoscale Date 25/05/2024 Consult the ppaer
Advanced Electrode Materials Based on Brownmillerite Calcium Ferrite for Li-Ion Batteries
Abstract Iron-based materials are considered potential anode materials for lithium-ion batteries thanks to their low cost, abundancy, non-flammability, good safety, environmental benignity, and high specific capacity. Here, a series of calcium iron oxides materials having brownmillerite structure (i. e., Ca2Fe2-xMxO5, where M=Mn, Ni and Cu and x=0 and 0.1) has been extensively studied for their use as conversion anodes in lithium cell. In particular, a mechanochemical approach has been used either to synthesize the samples and to prepare electrodes for the tests in lithium cell. Ca2Fe2O5 based electrodes proved excellent performance in lithium cell, approaching the theoretical capacity and being stable upon prolonged cycling (529 mAh g−1 at C/10 and a capacity retention of 81 % after 100 cycles). Through the use of ex-situ diffraction measurements, we have analyzed the conversion mechanism and proved the partial reversibility of its electrochemical reaction. Also, the incorporation of dopants into the structure of calcium iron oxide resulted in further improvement of its electrochemical performance as is the case of Mn doped sample that show a considerable specific capacity of 567 mAh g−1 and the capacity retention is almost 99 % after 100 cycles. Authors Guido Spanu, Arcangelo Celeste, Francesco Bozza, Emanuele Serra, Piero Torelli, Luca Braglia, Sergio Brutti, Priscilla Reale, Laura Silvestri Journal Batteries & Supercaps Date 18/05/2024 Consult the paper
The Deep Proteomics Approach Identified Extracellular Vesicular Proteins Correlated to Extracellular Matrix in Type One and Two Endometrial Cancer
Abstract Among gynecological cancers, endometrial cancer is the most common in developed countries. Extracellular vesicles (EVs) are cell-derived membrane-surrounded vesicles that contain proteins involved in immune response and apoptosis. A deep proteomic approach can help to identify dysregulated extracellular matrix (ECM) proteins in EVs correlated to key pathways for tumor development. In this study, we used a proteomics approach correlating the two acquisitions—data-dependent acquisition (DDA) and data-independent acquisition (DIA)—on EVs from the conditioned medium of four cell lines identifying 428 ECM proteins. After protein quantification and statistical analysis, we found significant changes in the abundance (p < 0.05) of 67 proteins. Our bioinformatic analysis identified 26 pathways associated with the ECM. Western blotting analysis on 13 patients with type 1 and type 2 EC and 13 endometrial samples confirmed an altered abundance of MMP2. Our proteomics analysis identified the dysregulated ECM proteins involved in cancer growth. Our data can open the path to other studies for understanding the interaction among cancer cells and the rearrangement of the ECM. Authors Capaci V, Kharrat F, Conti A, Salviati E, Basilicata MG, Campiglia P, Balasan N, Licastro D, Caponnetto F, Beltrami AP, Monasta L, Romano F, Di Lorenzo G, Ricci G, Ura B. Journal Int J Mol Sci. Date 24/04/2024 Consult the paper
Pulsed Laser Deposition using high-power Nd:YAG laser source operating at its first harmonics: recent approaches and advances
Abstract We report on the progress of Pulsed Laser Deposition growth of thin films by using a high-power Nd:YAG laser source. We demonstrate that by using the fundamental wavelength at 1064 nm, the congruent ablation of a large number of materials can be successfully achieved. Even if the infra-red radiation of the fundamental harmonics of Nd:YAG lasers – corresponding to impinging photons with energy of about 1.16 eV – is unexpectedly proved to be also absorbed by insulating materials characterized by a large value of the band-gap (e.g. 3.0 eV for rutile TiO2). Combined investigation of structural properties by transmission electron microscopy and scanning electron microscopy provides evidence of the very high-quality thin films grown by Nd:YAG lasers with no trace of precipitates and droplets over a scale of tens of micrometers. Authors S. K. Chaluvadi, S. Punathum Chalil, F. Mazzola, P. Rajak, P. Banerjee, D. Knez, R. Ciancio, G. Rossi, P. Orgiani Journal Proceedings of SPIE – The International Society for Optical Engineering Date 11/04/2024 Consult the paper
Adipose-derived stem cell exosomes act as delivery vehicles of microRNAs in a dog model of chronic hepatitis
Abstract Exosomes are nanosized extracellular vesicles secreted by all cell types, including canine adipose-derived stem cells (cADSCs). By mediating intercellular communication, exosomes modulate the biology of adjacent and distant cells by transferring their cargo. In the present work after isolation and characterization of exosomes derived from canine adipose tissue, we treated the same canine donors affected by hepatopathies with the previously isolated exosomes. We hypothesize that cADSC-sourced miRNAs are among the factors responsible for a regenerative and anti-inflammatory effect in the treatment of hepatopathies in dogs, providing the clinical veterinary field with an effective and innovative cell-free therapy. Exosomes were isolated and characterized for size, distribution, surface markers, and for their miRNomic cargo by microRNA sequencing. 295 dogs affected with hepatopathies were treated and followed up for 6 months to keep track of their biochemical marker levels. Results confirmed that exosomes derived from cADSCs exhibited an average diameter of 91 nm, and positivity to 8 known exosome markers. The administration of exosomes to dogs affected by liver-associated inflammatory pathologies resulted in the recovery of the animal alongside the normalization of biochemical parameters of kidney function. In conclusion, cADSCs-derived exosomes are a promising therapeutic tool for treating inflammatory disorders in animal companions. Authors Zanolla I, Trentini M, Tiengo E, Zanotti F, Pusceddu T, Rubini A, Rubini G, Brugnoli F, Licastro D, Debortoli M, Delogu LG, Ferroni L, Lovatti L, Zavan B. Journal Nanotheranostics Date 09/03/2024 Consult the paper
Nickel-and/or iron-based ceria-supported catalysts for CO oxidation in combustion exhaust gases
Abstract We present a series of Ni, Fe, and mixed NiFe-based catalysts, deposited onto ceria prepared with either soft templated (with CTAB) or hard templated (with SBA-15) syntheses. The prepared materials were thoroughly characterized with SEM, HRTEM, EDX, ICP-MS, PXRD, and N2 adsorption techniques, to fully comprehend their physicochemical properties. All catalysts were then tested for carbon monoxide oxidation reaction at different temperatures, aiming to reach temperature and feed composition conditions typical of combustion exhausts from industrial and power plants (350–400 °C, in the presence of competitive species such as CO2 and H2O in the feed). Advanced reaction tests highlighted outstanding materials (especially NiFe catalyst deposited onto hard-templated ceria), displaying catalytic performances able to compete with those typical of noble metal–based catalysts. Such catalysts were further investigated by means of Raman, NEXAFS, H2–TPR, and CO@FT-IR, unraveling their surface and reduction properties, which make them excellent candidates for replacing more costly noble metal-based catalysts currently employed for CO oxidation reaction. Authors Andrea Lazzarini, Luciano Atzori, Matteo Signorile, Luca Braglia, Francesco Ferella, Maria Giorgia Cutrufello, Elisabetta Rombi, Marcello Crucianelli Journal Journal of Catalysis Date 24/01/2024 Consult the paper
Successful treatment of life-threatening mycobacteriosis using adjunctive gamma-interferon therapy with genetic analysis.
Abstract No abstract Authors Confalonieri P, Maiocchi S, Salton F, Ruaro B, Rizzardi C, Volpe MC, Licastro D, Braga L, Confalonieri M Journal IJTLD Open Date 01/01/2024 Consult the paper
Synthesis, characterization, functional testing and ageing analysis of bifunctional Zn-air battery GDEs, based on α-MnO2 nanowires and Ni/NiO nanoparticle electrocatalysts
Abstract Electrically rechargeable alkaline zinc air batteries (RZAB) – currently still at the R&D stage –, have great potential for stationary, as well as prospectively mobile, electrochemical energy storage applications. Their chief appeal is that they are made of abundant, environmentally friendly, intrinsically safe, and cheap materials, with established recycling concepts and auspicious life-cycle costs. One of the key weak points of present-generation RZAB programs is the air gas-diffusion electrode (GDE). In fact, on the one hand, GDE fabrication and testing are generally based on poorly understood protocols, and, on the other hand, performance is challenged by efficiency and durability issues. This work is centred on the fabrication of a novel bifunctional GDE for the air side of RZABs, on the assessment of its electrochemical performance and on the identification of factors impacting its efficiency and durability. The electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are α-MnO2 nanowires and Ni/NiO nanoparticles, respectively. The composition of the active layer was optimized with rotating ring-disc electrode (RRDE) electrocatalysts tests. The GDEs were fabricated by spray-coating an ink, formulated with the electrocatalysts and the PTFE binder in an aqueous matrix. Fabrication and functional performance of GDEs – in pristine form and after ageing under realistic RZAB conditions – are rationalized on the basis of Scanning Electron Microscopy (SEM), Scanning Transmission X-ray SpectroMicroscopy (STXSM) at the Mn l-edge and Transmission Electron Microscopy (TEM) analyses. Imaging and spectral imaging disclosed the morphological and chemical-state evolution, brought about by electrochemical cycling. Special attention was devoted to the understanding of the role played by the presence of zincate in the electrolyte on the performance and ageing of the reversible air electrodes. Authors Salman Y., Waseem S., Alleva A., Banerjee P., Bonanni V., Emanuele E., Ciancio R., Gianoncelli A., Kourousias G., Li Bassi A., Macrelli A, Marini E., Rajak P., Bozzini B., Journal Electrochimica Acta Date 20/11/2023 Consult the paper
The geometry of hidden representations of large transformer models
Abstract Large transformers are powerful architectures used for self-supervised data analysis across various data types, including protein sequences, images, and text. In these models, the semantic structure of the dataset emerges from a sequence of transformations between one representation and the next. We characterize the geometric and statistical properties of these representations and how they change as we move through the layers.By analyzing the intrinsic dimension (ID) and neighbor composition, we find that the representations evolve similarly in transformers trained on protein language taskand image reconstruction tasks. In the first layers, the data manifold expands, becoming high-dimensional, and then contracts significantly in the intermediate layers. In the last part of the model, the ID remains approximately constant or forms a second shallow peak. We show that the semantic information of the dataset is better expressed at the end of the first peak, and this phenomenon can be observed across many models trained on diverse datasets.Based on our findings, we point out an explicit strategy to identify, without supervision, the layers that maximize semantic content: representations at intermediate layers corresponding to a relative minimum of the ID profile are more suitable for downstream learning tasks. Authors Lucrezia Valeriani, Diego Doimo, Francesca Cuturello, Alessandro Laio, Alessio Ansuini, Alberto Cazzaniga Journal Advances in Neural Information Processing Systems 36 (NEURIPS 2023) Main Conference Track Date 21/09/2023 Consult the paper