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) Publication 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
Sensory–Motor Loop Adaptation in Boolean Network Robots
Abstract Recent technological advances have made it possible to produce tiny robots equipped with simple sensors and effectors. Micro-robots are particularly suitable for scenarios such as exploration of hostile environments, and emergency intervention, e.g., in areas subject to earthquakes or fires. A crucial desirable feature of such a robot is the capability of adapting to the specific environment in which it has to operate. Given the limited computational capabilities of a micro-robot, this property cannot be achieved by complicated software but it rather should come from the flexibility of simple control mechanisms, such as the sensory–motor loop. In this work, we explore the possibility of equipping simple robots controlled by Boolean networks with the capability of modulating their sensory–motor loop such that their behavior adapts to the incumbent environmental conditions. This study builds upon the cybernetic concept of homeostasis, which is the property of maintaining essential parameters inside vital ranges, and analyzes the performance of adaptive mechanisms intervening in the sensory–motor loop. In particular, we focus on the possibility of maneuvering the robot’s effectors such that both their connections to network nodes and environmental features can be adapted. As the actions the robot takes have a feedback effect to its sensors mediated by the environment, this mechanism makes it possible to tune the sensory–motor loop, which, in turn, determines the robot’s behavior. We study this general setting in simulation and assess to what extent this mechanism can sustain the homeostasis of the robot. Our results show that controllers made of random Boolean networks in critical and chaotic regimes can be tuned such that their homeostasis in different environments is kept. This outcome is a step towards the design and deployment of controllers for micro-robots able to adapt to different environments. Authors Michele Braccini, Yuri Gardinazzi, Andrea Roli, Marco Villani Journal Sensors (MDPI) Publication Date 24/04/2024
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
Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein
Abstract Louping ill virus (LIV) is a tick-borne flavivirus that predominantly causes disease in livestock, especially sheep in the British Isles. A preventive vaccine, previously approved for veterinary use but now discontinued, was based on an inactivated whole virion that likely provided protection by induction of neutralizing antibodies recognizing the viral envelope (E) protein. A major disadvantage of the inactivated vaccine was the need for high containment facilities for the propagation of infectious virus, as mandated by the hazard group 3 status of the virus. This study aimed to develop high-efficacy non-infectious protein-based vaccine candidates. Specifically, soluble envelope protein (sE), and virus-like particles (VLPs), comprised of the precursor of membrane and envelope proteins, were generated, characterized, and studied for their immunogenicity in mice. Results showed that the VLPs induced more potent virus neutralizing response compared to sE, even though the total anti-envelope IgG content induced by the two antigens was similar. Depletion of anti-monomeric E protein antibodies from mouse immune sera suggested that the neutralizing antibodies elicited by the VLPs targeted epitopes spanning the highly organized structure of multimer of the E protein, whereas the antibody response induced by sE focused on E monomers. Thus, our results indicate that VLPs represent a promising LIV vaccine candidate. Authors Rapeepat Tandavanitj, Chayanee Setthapramote, Giuditta De Lorenzo, Ricardo Sanchez-Velazquez, Jordan J Clark, Mara Rocchi, Colin McInnes, Alain Kohl, Arvind H Patel Journal Vaccine Publication Date 02/04/2024 Consult the publication
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
Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) human adaptation resulted in distinct lineages with enhanced transmissibility called variants of concern (VOCs). Omicron is the first VOC to evolve distinct globally dominant subvariants. Here we compared their replication in human cell lines and primary airway cultures and measured host responses to infection. We discovered that subvariants BA.4 and BA.5 have improved their suppression of innate immunity when compared with earlier subvariants BA.1 and BA.2. Similarly, more recent subvariants (BA.2.75 and XBB lineages) also triggered reduced innate immune activation. This correlated with increased expression of viral innate antagonists Orf6 and nucleocapsid, reminiscent of VOCs Alpha to Delta. Increased Orf6 levels suppressed host innate responses to infection by decreasing IRF3 and STAT1 signalling measured by transcription factor phosphorylation and nuclear translocation. Our data suggest that convergent evolution of enhanced innate immune antagonist expression is a common pathway of human adaptation and link Omicron subvariant dominance to improved innate immune evasion. Authors Ann-Kathrin Reuschl, Lucy G Thorne, Matthew VX Whelan, Roberta Ragazzini, Wilhelm Furnon, Vanessa M Cowton, Giuditta De Lorenzo, Dejan Mesner, Jane LE Turner, Giulia Dowgier, Nathasha Bogoda, Paola Bonfanti, Massimo Palmarini, Arvind H Patel, Clare Jolly, Greg J Towers Journal Nature microbiology Publication Date 16/02/2024 Consult the publication
What Is the Probability That a Random Symmetric Tensor Is Close to Rank-One?
Abstract We address the general problem of estimating the probability that a real symmetric tensor is close to rank-one tensors. Using Weyl’s tube formula, we turn this question into a differential geometric one involving the study of metric invariants of the real Veronese variety. More precisely, we give an explicit formula for its reach and curvature coefficients with respect to the Bombieri–Weyl metric. These results are obtained using techniques from random matrix theory and an explicit description of the second fundamental form of the Veronese variety in terms of Gaussian orthogonal ensemble matrices. Our findings give a complete solution to the original problem. In the case of rational normal curves it leads to a simple formula describing explicitly exponential decay with respect to the degree of the tensor. Authors Alberto Cazzaniga, Antonio Lerario, Andrea Rosana Journal SIAM Journal on Applied Algebra and Geometry Publication Date 01/02/2024 Consult the publication