68 results on '"Chiara Romualdi"'
Search Results
2. Interactomic exploration of LRRC8A in volume-regulated anion channels
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Veronica Carpanese, Margherita Festa, Elena Prosdocimi, Magdalena Bachmann, Soha Sadeghi, Sara Bertelli, Frank Stein, Angelo Velle, Mostafa A. L. Abdel-Salam, Chiara Romualdi, Michael Pusch, and Vanessa Checchetto
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 ,Cytology ,QH573-671 - Abstract
Abstract Ion channels are critical in enabling ion movement into and within cells and are important targets for pharmacological interventions in different human diseases. In addition to their ion transport abilities, ion channels interact with signalling and scaffolding proteins, which affects their function, cellular positioning, and links to intracellular signalling pathways. The study of “channelosomes” within cells has the potential to uncover their involvement in human diseases, although this field of research is still emerging. LRRC8A is the gene that encodes a crucial protein involved in the formation of volume-regulated anion channels (VRACs). Some studies suggest that LRRC8A could be a valuable prognostic tool in different types of cancer, serving as a biomarker for predicting patients’ outcomes. LRRC8A expression levels might be linked to tumour progression, metastasis, and treatment response, although its implications in different cancer types can be varied. Here, publicly accessible databases of cancer patients were systematically analysed to determine if a correlation between VRAC channel expression and survival rate exists across distinct cancer types. Moreover, we re-evaluated the impact of LRRC8A on cellular proliferation and migration in colon cancer via HCT116 LRRC8A-KO cells, which is a current topic of debate in the literature. In addition, to investigate the role of LRRC8A in cellular signalling, we conducted biotin proximity-dependent identification (BioID) analysis, revealing a correlation between VRAC channels and cell-cell junctions, mechanisms that govern cellular calcium homeostasis, kinases, and GTPase signalling. Overall, this dataset improves our understanding of LRRC8A/VRAC and explores new research avenues while identifying promising therapeutic targets and promoting inventive methods for disease treatment.
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- 2024
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3. Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma
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Silvia Muccioli, Valentina Brillo, Tatiana Varanita, Federica Rossin, Elisabetta Zaltron, Angelo Velle, Giorgia Alessio, Beatrice Angi, Filippo Severin, Anna Tosi, Manuela D’Eletto, Luca Occhigrossi, Laura Falasca, Vanessa Checchetto, Roberto Ciaccio, Amelia Fascì, Leonardo Chieregato, Ana Paula Rebelo, Marta Giacomello, Antonio Rosato, Ildikò Szabò, Chiara Romualdi, Mauro Piacentini, and Luigi Leanza
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Cytology ,QH573-671 - Abstract
Abstract Skin cutaneous melanoma (SKCM) is the deadliest form of skin cancer due to its high heterogeneity that drives tumor aggressiveness. Melanoma plasticity consists of two distinct phenotypic states that co-exist in the tumor niche, the proliferative and the invasive, respectively associated with a high and low expression of MITF, the master regulator of melanocyte lineage. However, despite efforts, melanoma research is still far from exhaustively dissecting this phenomenon. Here, we discovered a key function of Transglutaminase Type-2 (TG2) in regulating melanogenesis by modulating MITF transcription factor expression and its transcriptional activity. Importantly, we demonstrated that TG2 expression affects melanoma invasiveness, highlighting its positive value in SKCM. These results suggest that TG2 may have implications in the regulation of the phenotype switching by promoting melanoma differentiation and impairing its metastatic potential. Our findings offer potential perspectives to unravel melanoma vulnerabilities via tuning intra-tumor heterogeneity.
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- 2023
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4. Defective excitation-contraction coupling and mitochondrial respiration precede mitochondrial Ca2+ accumulation in spinobulbar muscular atrophy skeletal muscle
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Caterina Marchioretti, Giulia Zanetti, Marco Pirazzini, Gaia Gherardi, Leonardo Nogara, Roberta Andreotti, Paolo Martini, Lorenzo Marcucci, Marta Canato, Samir R. Nath, Emanuela Zuccaro, Mathilde Chivet, Cristina Mammucari, Marco Pacifici, Anna Raffaello, Rosario Rizzuto, Andrea Mattarei, Maria A. Desbats, Leonardo Salviati, Aram Megighian, Gianni Sorarù, Elena Pegoraro, Elisa Belluzzi, Assunta Pozzuoli, Carlo Biz, Pietro Ruggieri, Chiara Romualdi, Andrew P. Lieberman, Gopal J. Babu, Marco Sandri, Bert Blaauw, Manuela Basso, and Maria Pennuto
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Science - Abstract
Marchioretti and colleagues show that in the skeletal muscle of SBMA mice and patients there is an early, but reversible alteration of expression of genes involved in muscle contraction and of mitochondrial respiration, followed by accumulation of calcium inside the mitochondria, which is concomitant with the onset of motor dysfunction, and late alteration of muscle structure.
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- 2023
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5. Hydrogen peroxide induced by nerve injury promotes axon regeneration via connective tissue growth factor
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Samuele Negro, Fabio Lauria, Marco Stazi, Toma Tebaldi, Giorgia D’Este, Marco Pirazzini, Aram Megighian, Francesca Lessi, Chiara M. Mazzanti, Gabriele Sales, Chiara Romualdi, Silvia Fillo, Florigio Lista, James N. Sleigh, Andrew P. Tosolini, Giampietro Schiavo, Gabriella Viero, and Michela Rigoni
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Connective tissue growth factor ,Hydrogen peroxide ,Nerve regeneration ,Neuromuscular junction ,Schwann cells ,Yes-associated protein ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Regeneration of the neuromuscular junction (NMJ) leverages on extensive exchange of factors released from motor axon terminals (MATs), muscle fibers and perisynaptic Schwann cells (PSCs), among which hydrogen peroxide (H2O2) is a major pro-regenerative signal. To identify critical determinants of NMJ remodeling in response to injury, we performed temporal transcriptional profiling of NMJs from 2 month-old mice during MAT degeneration/regeneration, and cross-referenced the differentially expressed genes with those elicited by H2O2 in SCs. We identified an enrichment in extracellular matrix (ECM) transcripts, including Connective Tissue Growth Factor (Ctgf), which is usually expressed during development. We discovered that Ctgf levels are increased in a Yes-associated protein (YAP)-dependent fashion in response to rapid, local H2O2 signaling generated by stressed mitochondria in the injured sciatic nerve, a finding highlighting the importance of signals triggered by mechanical force to motor nerve repair. Through sequestration of Ctgf or inactivation of H2O2, we delayed the recovery of neuromuscular function by impairing SC migration and, in turn, axon-oriented re-growth. These data indicate that H2O2 and its downstream effector Ctgf are pro-regenerative factors that enable axonal growth, and reveal a striking ECM remodeling process during nerve regeneration upon local H2O2 signaling. Our study identifies key transcriptomic changes at the regenerating NMJ, providing a rich source of pro-regenerative factors with potential for alleviating the consequences of peripheral nerve injuries.
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- 2022
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6. A thorough annotation of the krill transcriptome offers new insights for the study of physiological processes
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Ilenia Urso, Alberto Biscontin, Davide Corso, Cristiano Bertolucci, Chiara Romualdi, Cristiano De Pittà, Bettina Meyer, and Gabriele Sales
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Medicine ,Science - Abstract
Abstract The krill species Euphausia superba plays a critical role in the food chain of the Antarctic ecosystem. Significant changes in climate conditions observed in the Antarctic Peninsula region in the last decades have already altered the distribution of krill and its reproductive dynamics. A deeper understanding of the adaptation capabilities of this species is urgently needed. The availability of a large body of RNA-seq assays allowed us to extend the current knowledge of the krill transcriptome. Our study covered the entire developmental process providing information of central relevance for ecological studies. Here we identified a series of genes involved in different steps of the krill moulting cycle, in the reproductive process and in sexual maturation in accordance with what was already described in previous works. Furthermore, the new transcriptome highlighted the presence of differentially expressed genes previously unknown, playing important roles in cuticle development as well as in energy storage during the krill life cycle. The discovery of new opsin sequences, specifically rhabdomeric opsins, one onychopsin, and one non-visual arthropsin, expands our knowledge of the krill opsin repertoire. We have collected all these results into the KrillDB2 database, a resource combining the latest annotation of the krill transcriptome with a series of analyses targeting genes relevant to krill physiology. KrillDB2 provides in a single resource a comprehensive catalog of krill genes; an atlas of their expression profiles over all RNA-seq datasets publicly available; a study of differential expression across multiple conditions. Finally, it provides initial indications about the expression of microRNA precursors, whose contribution to krill physiology has never been reported before.
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- 2022
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7. Spatial compartmentalization of signaling imparts source-specific functions on secreted factors
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Elena Groppa, Paolo Martini, Nima Derakhshan, Marine Theret, Morten Ritso, Lin Wei Tung, Yu Xin Wang, Hesham Soliman, Mark Stephen Hamer, Laura Stankiewicz, Christine Eisner, Le Nevé Erwan, Chihkai Chang, Lin Yi, Jack H. Yuan, Sunny Kong, Curtis Weng, Josephine Adams, Lucas Chang, Anne Peng, Helen M. Blau, Chiara Romualdi, and Fabio M.V. Rossi
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CP: Stem cell research ,Biology (General) ,QH301-705.5 - Abstract
Summary: Efficient regeneration requires multiple cell types acting in coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profile the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. We generate a time-resolved computational model of interactions and identify VEGFA-driven endothelial engagement as a key differentiating feature in models of successful and failed regeneration. In addition, the analysis highlights that the majority of secreted signals, including VEGFA, are simultaneously produced by multiple cell types. To test whether the cellular source of a factor determines its function, we delete VEGFA from two cell types residing in close proximity: stromal and myogenic progenitors. By comparing responses to different types of damage, we find that myogenic and stromal VEGFA have distinct functions in regeneration. This suggests that spatial compartmentalization of signaling plays a key role in intercellular communication networks.
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- 2023
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8. BrewerIX enables allelic expression analysis of imprinted and X-linked genes from bulk and single-cell transcriptomes
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Paolo Martini, Gabriele Sales, Linda Diamante, Valentina Perrera, Chiara Colantuono, Sara Riccardo, Davide Cacchiarelli, Chiara Romualdi, and Graziano Martello
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Biology (General) ,QH301-705.5 - Abstract
BrewerIX is an easy-to-use computational tool that can assess bi-allelic expression of imprinted and X-linked genes from RNA-seq data.
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- 2022
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9. Detecting differentially expressed circular RNAs from multiple quantification methods using a generalized linear mixed model
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Alessia Buratin, Chiara Romualdi, Stefania Bortoluzzi, and Enrico Gaffo
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Circular RNAs ,circRNAs ,Differential expression ,Generalized linear mixed models ,RNA-seq ,Biotechnology ,TP248.13-248.65 - Abstract
Finding differentially expressed circular RNAs (circRNAs) is instrumental to understanding the molecular basis of phenotypic variation between conditions linked to circRNA-involving mechanisms. To date, several methods have been developed to identify circRNAs, and combining multiple tools is becoming an established approach to improve the detection rate and robustness of results in circRNA studies. However, when using a consensus strategy, it is unclear how circRNA expression estimates should be considered and integrated into downstream analysis, such as differential expression assessment. This work presents a novel solution to test circRNA differential expression using quantifications of multiple algorithms simultaneously. Our approach analyzes multiple tools’ circRNA abundance count data within a single framework by leveraging generalized linear mixed models (GLMM), which account for the sample correlation structure within and between the quantification tools. We compared the GLMM approach with three widely used differential expression models, showing its higher sensitivity in detecting and efficiently ranking significant differentially expressed circRNAs. Our strategy is the first to consider combined estimates of multiple circRNA quantification methods, and we propose it as a powerful model to improve circRNA differential expression analysis.
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- 2022
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10. MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary
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Noemi Laprovitera, Mattia Riefolo, Elisa Porcellini, Giorgio Durante, Ingrid Garajova, Francesco Vasuri, Ariane Aigelsreiter, Nadia Dandachi, Giuseppe Benvenuto, Federico Agostinis, Silvia Sabbioni, Ioana Berindan Neagoe, Chiara Romualdi, Andrea Ardizzoni, Davide Trerè, Martin Pichler, Antonietta D'Errico, and Manuela Ferracin
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cancer of unknown primary ,droplet digital PCR ,metastasis ,microRNAs ,molecular diagnostics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Metastasis is responsible for the majority of cancer‐related deaths. Particularly, challenging is the management of metastatic cancer of unknown primary site (CUP), whose tissue of origin (TOO) remains undetermined even after extensive investigations and whose therapy is rather unspecific and poorly effective. Molecular approaches to identify the most probable TOO of CUPs can overcome some of these issues. In this study, we applied a predetermined set of 89 microRNAs (miRNAs) to infer the TOO of 53 metastatic cancers of unknown or uncertain origin. The miRNA expression was assessed with droplet digital PCR in 159 samples, including primary tumors from 17 tumor classes (reference set) and metastases of known and unknown origin (test set). We combined two different statistical models for class prediction to obtain the most probable TOOs: the nearest shrunken centroids approach of Prediction Analysis of Microarrays (PAMR) and the least absolute shrinkage and selection operator (LASSO) models. The molecular test was successful for all formalin‐fixed paraffin‐embedded samples and provided a TOO identification within 1 week from the biopsy procedure. The most frequently predicted origins were gastrointestinal, pancreas, breast, lung, and bile duct. The assay was applied also to multiple metastases from the same CUP, collected from different metastatic sites: The predictions showed a strong agreement, intrinsically validating our assay. The final CUPs' TOO prediction was compared with the clinicopathological hypothesis of primary site. Moreover, a panel of 13 miRNAs proved to have prognostic value and be associated with overall survival in CUP patients. Our study demonstrated that miRNA expression profiling in CUP samples could be employed as diagnostic and prognostic test. Our molecular analysis can be performed on request, concomitantly with standard diagnostic workup and in association with genetic profiling, to offer valuable indications about the possible primary site, thereby supporting treatment decisions.
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- 2021
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11. MyoData: An expression knowledgebase at single cell/nucleus level for the discovery of coding-noncoding RNA functional interactions in skeletal muscle
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Davide Corso, Francesco Chemello, Enrico Alessio, Ilenia Urso, Giulia Ferrarese, Martina Bazzega, Chiara Romualdi, Gerolamo Lanfranchi, Gabriele Sales, and Stefano Cagnin
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Single myofiber ,Single nucleus ,Non-coding RNAs ,Database ,Networks ,Pathways ,Biotechnology ,TP248.13-248.65 - Abstract
Non-coding RNAs represent the largest part of transcribed mammalian genomes and prevalently exert regulatory functions. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) can modulate the activity of each other. Skeletal muscle is the most abundant tissue in mammals. It is composed of different cell types with myofibers that represent the smallest complete contractile system. Considering that lncRNAs and miRNAs are more cell type-specific than coding RNAs, to understand their function it is imperative to evaluate their expression and action within single myofibers. In this database, we collected gene expression data for coding and non-coding genes in single myofibers and used them to produce interaction networks based on expression correlations. Since biological pathways are more informative than networks based on gene expression correlation, to understand how altered genes participate in the studied phenotype, we integrated KEGG pathways with miRNAs and lncRNAs. The database also integrates single nucleus gene expression data on skeletal muscle in different patho-physiological conditions. We demonstrated that these networks can serve as a framework from which to dissect new miRNA and lncRNA functions to experimentally validate. Some interactions included in the database have been previously experimentally validated using high throughput methods. These can be the basis for further functional studies. Using database information, we demonstrate the involvement of miR-149, -214 and let-7e in mitochondria shaping; the ability of the lncRNA Pvt1 to mitigate the action of miR-27a via sponging; and the regulatory activity of miR-214 on Sox6 and Slc16a3. The MyoData is available at https://myodata.bio.unipd.it.
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- 2021
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12. Assessment of statistical methods from single cell, bulk RNA-seq, and metagenomics applied to microbiome data
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Matteo Calgaro, Chiara Romualdi, Levi Waldron, Davide Risso, and Nicola Vitulo
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Microbiome ,Benchmark ,Single-cell ,Metagenomics ,Differential abundance ,Biology (General) ,QH301-705.5 ,Genetics ,QH426-470 - Abstract
Abstract Background The correct identification of differentially abundant microbial taxa between experimental conditions is a methodological and computational challenge. Recent work has produced methods to deal with the high sparsity and compositionality characteristic of microbiome data, but independent benchmarks comparing these to alternatives developed for RNA-seq data analysis are lacking. Results We compare methods developed for single-cell and bulk RNA-seq, and specifically for microbiome data, in terms of suitability of distributional assumptions, ability to control false discoveries, concordance, power, and correct identification of differentially abundant genera. We benchmark these methods using 100 manually curated datasets from 16S and whole metagenome shotgun sequencing. Conclusions The multivariate and compositional methods developed specifically for microbiome analysis did not outperform univariate methods developed for differential expression analysis of RNA-seq data. We recommend a careful exploratory data analysis prior to application of any inferential model and we present a framework to help scientists make an informed choice of analysis methods in a dataset-specific manner.
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- 2020
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13. Targeting p53 and histone methyltransferases restores exhausted CD8+ T cells in HCV infection
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Valeria Barili, Paola Fisicaro, Barbara Montanini, Greta Acerbi, Anita Filippi, Giovanna Forleo, Chiara Romualdi, Manuela Ferracin, Francesca Guerrieri, Giuseppe Pedrazzi, Carolina Boni, Marzia Rossi, Andrea Vecchi, Amalia Penna, Alessandra Zecca, Cristina Mori, Alessandra Orlandini, Elisa Negri, Marco Pesci, Marco Massari, Gabriele Missale, Massimo Levrero, Simone Ottonello, and Carlo Ferrari
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Science - Abstract
Here, the authors report that exhausted HCV-specific CD8+ T cells are marked by upregulation of p53 signaling already detectable in an early phase of chronic HCV infection and by a later development of a repressive chromatin state, and show that chemical targeting of these pathways improves CD8+ T cell metabolism and antiviral function.
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- 2020
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14. Zebrafish Mutant Lines Reveal the Interplay between nr3c1 and nr3c2 in the GC-Dependent Regulation of Gene Transcription
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Alberto Dinarello, Annachiara Tesoriere, Paolo Martini, Camilla Maria Fontana, Davide Volpato, Lorenzo Badenetti, Francesca Terrin, Nicola Facchinello, Chiara Romualdi, Oliana Carnevali, Luisa Dalla Valle, and Francesco Argenton
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glucocorticoid receptor ,mineralocorticoid receptor ,zebrafish ,CRISPR/Cas9 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Glucocorticoids mainly exert their biological functions through their cognate receptor, encoded by the nr3c1 gene. Here, we analysed the glucocorticoids mechanism of action taking advantage of the availability of different zebrafish mutant lines for their receptor. The differences in gene expression patterns between the zebrafish gr knock-out and the grs357 mutant line, in which a point mutation prevents binding of the receptor to the hormone-responsive elements, reveal an intricate network of GC-dependent transcription. Particularly, we show that Stat3 transcriptional activity mainly relies on glucocorticoid receptor GR tethering activity: several Stat3 target genes are induced upon glucocorticoid GC exposure both in wild type and in grs357/s357 larvae, but not in gr knock-out zebrafish. To understand the interplay between GC, their receptor, and the mineralocorticoid receptor, which is evolutionarily and structurally related to the GR, we generated an mr knock-out line and observed that several GC-target genes also need a functional mineralocorticoid receptor MR to be correctly transcribed. All in all, zebrafish mutants and transgenic models allow in vivo analysis of GR transcriptional activities and interactions with other transcription factors such as MR and Stat3 in an in-depth and rapid way.
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- 2022
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15. Editorial: Multi-omic Data Integration in Oncology
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Francesca Finotello, Enrica Calura, Davide Risso, Sampsa Hautaniemi, and Chiara Romualdi
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multi-omic ,single-cell ,transcriptomics ,pathways ,cancer ,data integration ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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16. SourceSet: A graphical model approach to identify primary genes in perturbed biological pathways.
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Elisa Salviato, Vera Djordjilović, Monica Chiogna, and Chiara Romualdi
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Biology (General) ,QH301-705.5 - Abstract
Topological gene-set analysis has emerged as a powerful means for omic data interpretation. Although numerous methods for identifying dysregulated genes have been proposed, few of them aim to distinguish genes that are the real source of perturbation from those that merely respond to the signal dysregulation. Here, we propose a new method, called SourceSet, able to distinguish between the primary and the secondary dysregulation within a Gaussian graphical model context. The proposed method compares gene expression profiles in the control and in the perturbed condition and detects the differences in both the mean and the covariance parameters with a series of likelihood ratio tests. The resulting evidence is used to infer the primary and the secondary set, i.e. the genes responsible for the primary dysregulation, and the genes affected by the perturbation through network propagation. The proposed method demonstrates high specificity and sensitivity in different simulated scenarios and on several real biological case studies. In order to fit into the more traditional pathway analysis framework, SourceSet R package also extends the analysis from a single to multiple pathways and provides several graphical outputs, including Cytoscape visualization to browse the results.
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- 2019
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17. Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features
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Elisa Palumbo, Celeste Piotto, Enrica Calura, Elena Fasanaro, Elena Groff, Fabio Busato, Badr El Khouzai, Michele Rigo, Laura Baggio, Chiara Romualdi, Demetre Zafiropoulos, Antonella Russo, Maddalena Mognato, and Luigi Corti
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radiotherapy ,adverse effects ,chromosomal radiosensitivity ,gene expression ,association analysis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity.Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G2-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes.Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX).Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues.
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- 2019
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18. Circulating miR-185-5p as a Potential Biomarker for Arrhythmogenic Right Ventricular Cardiomyopathy
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Claudia Sacchetto, Zenab Mohseni, Robin M. W. Colpaert, Libero Vitiello, Marzia De Bortoli, Indira G. C. Vonhögen, Ke Xiao, Giulia Poloni, Alessandra Lorenzon, Chiara Romualdi, Riccardo Bariani, Elisa Mazzotti, Luciano Daliento, Barbara Bauce, Domenico Corrado, Thomas Thum, Alessandra Rampazzo, Leon J. de Windt, and Martina Calore
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arrhythmogenic right ventricular cardiomyopathy ,MicroRNAs ,circulating microRNAs ,heart failure ,biomarkers ,genetics ,Cytology ,QH573-671 - Abstract
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease characterized by progressive myocardial fibro-fatty replacement, arrhythmias and risk of sudden death. Its diagnosis is challenging and often it is achieved after disease onset or postmortem. In this study, we sought to identify circulating microRNAs (miRNAs) differentially expressed in ARVC patients compared to healthy controls. In the pilot study, we screened the expression of 754 miRNAs from 21 ARVC patients and 20 healthy controls. After filtering the miRNAs considering a log fold-change cut-off of ±1, p-value < 0.05, we selected five candidate miRNAs for a subsequent validation study in which we used TaqMan-based real-time PCR to analyse samples from 37 ARVC patients and 30 healthy controls. We found miR-185-5p significantly upregulated in ARVC patients. Receiver operating characteristic analysis indicated an area under the curve of 0.854, corroborating the link of this miRNA and ARVC pathophysiology.
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- 2021
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19. Comprehensive Profiling of Hypoxia-Related miRNAs Identifies miR-23a-3p Overexpression as a Marker of Platinum Resistance and Poor Prognosis in High-Grade Serous Ovarian Cancer
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Paola Todeschini, Elisa Salviato, Chiara Romani, Vittoria Raimondi, Francesco Ciccarese, Federico Ferrari, Germana Tognon, Sergio Marchini, Maurizio D’Incalci, Laura Zanotti, Antonella Ravaggi, Franco Odicino, Enrico Sartori, Donna M. D’Agostino, Michele Samaja, Chiara Romualdi, and Eliana Bignotti
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miRNA ,hypoxia ,ovarian cancer ,platinum response ,prognostic marker ,miR-23a-3p ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The onset of chemo-resistant recurrence represents the principal cause of high-grade serous ovarian carcinoma (HGSOC) death. HGSOC masses are characterized by a hypoxic microenvironment, which contributes to the development of this chemo-resistant phenotype. Hypoxia regulated-miRNAs (HRMs) represent a molecular response of cancer cells to hypoxia and are involved in tumor progression. We investigated the expression of HRMs using miRNA expression data from a total of 273 advanced-stage HGSOC samples. The miRNAs associated with chemoresistance and survival were validated by RT-qPCR and target prediction, and comparative pathway analysis was conducted for target gene identification. Analysis of miRNA expression profiles indicated miR-23a-3p and miR-181c-5p over-expression as associated with chemoresistance and poor PFS. RT-qPCR data confirmed upregulation of miR-23a-3p in tumors from chemoresistant HGSOC patients and its significant association with shorter PFS. In silico miR-23a-3p target prediction and comparative pathway analysis identified platinum drug resistance as the pathway with the highest number of miR-23a-3p target genes. Among them, APAF-1 emerged as the most promising, being downregulated in platinum-resistant patients and in HGSOC chemo-resistant cells. These results highlight miR-23a-3p as a potential biomarker for HGSOC platinum response and prognosis and the miR23a-3p/APAF1 axis as a possible target to overcome platinum-resistance.
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- 2021
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20. Increased NK Cell Count in Multiple Sclerosis Patients Treated With Dimethyl Fumarate: A 2-Year Longitudinal Study
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Damiano Marastoni, Alessandro Buriani, Anna Isabella Pisani, Francesco Crescenzo, Carmela Zuco, Stefano Fortinguerra, Vincenzo Sorrenti, Bruno Marenda, Chiara Romualdi, Roberta Magliozzi, Salvatore Monaco, and Massimiliano Calabrese
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multiple sclerosis ,dimethyl fumarate ,lymphopenia ,natural killer cells ,cell count ,lymphocyte subsets ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Dimethyl fumarate (DMF) is a disease-modifying drug for relapsing-remitting multiple sclerosis. Among others, DMF impedes immune activation by shifting the balance between inflammatory and regulatory cell types and by inducing apoptosis-triggered lymphopenia. Although the decrease in lymphocyte count is an early effect of the drug in several patients, the long-term impact on lymphocyte subsets is largely unknown.Methods: We performed a 2-years observational study on total lymphocyte count and subsets thereof by flow cytometry of peripheral blood of 38 multiple sclerosis patients in treatment with DMF. Data were collected at the beginning and after 3, 6, 12, and 24 months of therapy.Results: Total lymphocyte count decreased in relation to time of exposure to DMF. Mean absolute B cell count decreased by 34.1% (p < 0.001) within the first 3 months of therapy and then remained stable over time. Mean absolute CD3+ T cells count decrement reached 47.5% after 12 months of treatment (p < 0.001). NK cells count showed a heterogeneous trend, increasing by 85.9% (p < 0.001) after 2 years of treatment. CD4+ T cells and CD8+ T cells substantially decreased, with a significant increase of CD4+/CD8+ ratio during the first year of therapy.Conclusions: NK cells showed a heterogeneous behavior during DMF treatment with a significant increase over time. Since NK cells may also have a regulatory effect on immune system modulation, their increase during DMF treatment might play a role in the efficacy and safety of the drug.
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- 2019
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21. Transcriptomic Analysis of Single Isolated Myofibers Identifies miR-27a-3p and miR-142-3p as Regulators of Metabolism in Skeletal Muscle
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Francesco Chemello, Francesca Grespi, Alessandra Zulian, Pasqua Cancellara, Etienne Hebert-Chatelain, Paolo Martini, Camilla Bean, Enrico Alessio, Lisa Buson, Martina Bazzega, Andrea Armani, Marco Sandri, Ruggero Ferrazza, Paolo Laveder, Graziano Guella, Carlo Reggiani, Chiara Romualdi, Paolo Bernardi, Luca Scorrano, Stefano Cagnin, and Gerolamo Lanfranchi
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Biology (General) ,QH301-705.5 - Abstract
Summary: Skeletal muscle is composed of different myofiber types that preferentially use glucose or lipids for ATP production. How fuel preference is regulated in these post-mitotic cells is largely unknown, making this issue a key question in the fields of muscle and whole-body metabolism. Here, we show that microRNAs (miRNAs) play a role in defining myofiber metabolic profiles. mRNA and miRNA signatures of all myofiber types obtained at the single-cell level unveiled fiber-specific regulatory networks and identified two master miRNAs that coordinately control myofiber fuel preference and mitochondrial morphology. Our work provides a complete and integrated mouse myofiber type-specific catalog of gene and miRNA expression and establishes miR-27a-3p and miR-142-3p as regulators of lipid use in skeletal muscle. : Chemello et al. characterize coding mRNAs and non-coding microRNAs expressed by myofibers of hindlimb mouse muscles, identifying complex interactions between these molecules that modulate mitochondrial functions and muscle metabolism. They demonstrate that specific short non-coding RNAs influence the contractile fiber composition of skeletal muscles by modulating muscle metabolism. Keywords: single myofiber, skeletal muscle metabolism, mitochondria, miRNAs, lipids
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- 2019
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22. Transcriptome Profiles of Human Visceral Adipocytes in Obesity and Colorectal Cancer Unravel the Effects of Body Mass Index and Polyunsaturated Fatty Acids on Genes and Biological Processes Related to Tumorigenesis
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Manuela Del Cornò, Antonella Baldassarre, Enrica Calura, Lucia Conti, Paolo Martini, Chiara Romualdi, Rosaria Varì, Beatrice Scazzocchio, Massimo D'Archivio, Andrea Masotti, and Sandra Gessani
- Subjects
obesity ,body mass index ,colorectal cancer ,adipocyte ,fatty acid ,transcriptome ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Obesity, a low-grade inflammatory condition, represents a major risk factor for the development of several pathologies including colorectal cancer (CRC). Although the adipose tissue inflammatory state is now recognized as a key player in obesity-associated morbidities, the underlying biological processes are complex and not yet precisely defined. To this end, we analyzed transcriptome profiles of human visceral adipocytes from lean and obese subjects affected or not by CRC by RNA sequencing (n = 6 subjects/category), and validated selected modulated genes by real-time qPCR. We report that obesity and CRC, conditions characterized by the common denominator of inflammation, promote changes in the transcriptional program of adipocytes mostly involving pathways and biological processes linked to extracellular matrix remodeling, and metabolism of pyruvate, lipids and glucose. Interestingly, although the transcriptome of adipocytes shows several alterations that are common to both disorders, some modifications are unique under obesity (e.g., pathways associated with inflammation) and CRC (e.g., TGFβ signaling and extracellular matrix remodeling) and are influenced by the body mass index (e.g., processes related to cell adhesion, angiogenesis, as well as metabolism). Indeed, cancer-induced transcriptional program is deeply affected by obesity, with adipocytes from obese individuals exhibiting a more complex response to the tumor. We also report that in vitro exposure of adipocytes to ω3 and ω6 polyunsaturated fatty acids (PUFA) endowed with either anti- or pro-inflammatory properties, respectively, modulates the expression of genes involved in processes potentially relevant to carcinogenesis, as assessed by real-time qPCR. All together our results suggest that genes involved in pyruvate, glucose and lipid metabolism, fibrosis and inflammation are central in the transcriptional reprogramming of adipocytes occurring in obese and CRC-affected individuals, as well as in their response to PUFA exposure. Moreover, our results indicate that the transcriptional program of adipocytes is strongly influenced by the BMI status in CRC subjects. The dysregulation of these interrelated processes relevant for adipocyte functions may contribute to create more favorable conditions to tumor establishment or favor tumor progression, thus linking obesity and colorectal cancer.
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- 2019
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23. Microbiota of the Therapeutic Euganean Thermal Muds with a Focus on the Main Cyanobacteria Species
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Barbara Gris, Laura Treu, Raffaella Margherita Zampieri, Fabrizio Caldara, Chiara Romualdi, Stefano Campanaro, and Nicoletta La Rocca
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peloids ,microbial community ,cyanobacteria ,Phormidium ETS-05 ,Euganean district ,therapeutic thermal muds ,Biology (General) ,QH301-705.5 - Abstract
The Euganean Thermal District has been known since Roman times for the therapeutic properties of peloids, obtained from natural clays that have undergone a traditional maturation process. This leads to the growth of a green microbial biofilm with Cyanobacteria and the target species Phormidium sp. ETS-05 as fundamental components for their ability to synthetize anti-inflammatory molecules. Currently, in-depth studies on the microbiota colonizing Euganean peloids, as in general on peloids utilized worldwide, are missing. This is the first characterization of the microbial community of Euganean thermal muds, also investigating the effects of environmental factors on its composition. We analysed 53 muds from 29 sites (Spas) using a polyphasic approach, finding a stable microbiota peculiar to the area. Differences among mud samples mainly depended on two parameters: water temperature and shading of mud maturation plants. In the range 37–47 °C and in the case of irradiance attenuation due to the presence of protective roofs, a statistically significant higher mud Chl a content was detected. Moreover, in these conditions, a characteristic microbial and Cyanobacteria population composition dominated by Phormidium sp. ETS-05 was observed. We also obtained the complete genome sequence of this target species using a mixed sequencing approach based on Illumina and Nanopore sequencing.
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- 2020
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24. Circulating Cell-Free DNA in Dogs with Mammary Tumors: Short and Long Fragments and Integrity Index.
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Giorgia Beffagna, Alessandro Sammarco, Chiara Bedin, Chiara Romualdi, Marta Mainenti, Antonio Mollo, Laura Cavicchioli, Silvia Ferro, Davide Trez, Raffaella De Maria, Donato Nitti, Andrea Saccani, Michelangelo Campanella, Marco Agostini, and Valentina Zappulli
- Subjects
Medicine ,Science - Abstract
Circulating cell-free DNA (cfDNA) has been considered an interesting diagnostic/prognostic plasma biomarker in tumor-bearing subjects. In cancer patients, cfDNA can hypothetically derive from tumor necrosis/apoptosis, lysed circulating cells, and some yet unrevealed mechanisms of active release. This study aimed to preliminarily analyze cfDNA in dogs with canine mammary tumors (CMTs). Forty-four neoplastic, 17 non-neoplastic disease-bearing, and 15 healthy dogs were recruited. Necrosis and apoptosis were also assessed as potential source of cfDNA on 78 CMTs diagnosed from the 44 dogs. The cfDNA fragments and integrity index significantly differentiated neoplastic versus non-neoplastic dogs (P
- Published
- 2017
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25. KrillDB: A de novo transcriptome database for the Antarctic krill (Euphausia superba).
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Gabriele Sales, Bruce E Deagle, Enrica Calura, Paolo Martini, Alberto Biscontin, Cristiano De Pittà, So Kawaguchi, Chiara Romualdi, Bettina Meyer, Rodolfo Costa, and Simon Jarman
- Subjects
Medicine ,Science - Abstract
Antarctic krill (Euphausia superba) is a key species in the Southern Ocean with an estimated biomass between 100 and 500 million tonnes. Changes in krill population viability would have catastrophic effect on the Antarctic ecosystem. One looming threat due to elevated levels of anthropogenic atmospheric carbon dioxide (CO2) is ocean acidification (lowering of sea water pH by CO2 dissolving into the oceans). The genetics of Antarctic krill has long been of scientific interest for both for the analysis of population structure and analysis of functional genetics. However, the genetic resources available for the species are relatively modest. We have developed the most advanced genetic database on Euphausia superba, KrillDB, which includes comprehensive data sets of former and present transcriptome projects. In particular, we have built a de novo transcriptome assembly using more than 360 million Illumina sequence reads generated from larval krill including individuals subjected to different CO2 levels. The database gives access to: 1) the full list of assembled genes and transcripts; 2) their level of similarity to transcripts and proteins from other species; 3) the predicted protein domains contained within each transcript; 4) their predicted GO terms; 5) the level of expression of each transcript in the different larval stages and CO2 treatments. All references to external entities (sequences, domains, GO terms) are equipped with a link to the appropriate source database. Moreover, the software implements a full-text search engine that makes it possible to submit free-form queries. KrillDB represents the first large-scale attempt at classifying and annotating the full krill transcriptome. For this reason, we believe it will constitute a cornerstone of future approaches devoted to physiological and molecular study of this key species in the Southern Ocean food web.
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- 2017
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26. rs4143815-PDL1, a New Potential Immunogenetic Biomarker of Biochemical Recurrence in Locally Advanced Prostate Cancer after Radiotherapy
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Chiara Zanusso, Eva Dreussi, Roberto Bortolus, Chiara Romualdi, Sara Gagno, Elena De Mattia, Loredana Romanato, Franca Sartor, Luca Quartuccio, Erika Cecchin, and Giuseppe Toffoli
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prostate cancer ,immunogenetics ,biomarker ,radiotherapy ,biochemical recurrence ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Up to 30−50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients’ treatment. The aim of this study is to define the immunogenetic biomarkers of 10 year BCR (primary aim), 10 year overall survival (OS) and 5 year BCR (secondary aims). In this mono-institutional retrospective study, 549 Caucasian patients (a discovery set n = 418; a replication set n = 131) were affected by locally advanced PCa and homogeneously treated with RT. In the training set, associations were made between 447 SNPs in 77 genes of the immune system; and 10 year BCR and 10 year OS were tested through a multivariate Cox proportional hazard model. Significant SNPs (p-value < 0.05, q-value < 0.15) were analyzed in the replication set. Replicated SNPs were tested for 5 year BCR in both sets of patients. A polymorphism in the PDL1 gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set: p = 0.003, HR (95% CI) = 0.58 (0.41−0.83); replication set: p = 0.063, HR (95% CI) = 0.52 (0.26−1.04)) that was significantly associated with 5 year BCR (training set: p = 0.009, HR (95% CI) = 0.59 (0.40−0.88); replication set: p = 0.036, HR (95% CI) = 0.39 (0.16−0.94)). No biomarkers of OS were replicated. rs4143815-PDL1 arose as a new immunogenetic biomarker of BCR in PCa, giving new insights into the RT/immune system interaction, which could be potentially useful in new approaches using anti-PDL1 therapies for PCa.
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- 2019
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27. Systems Biology Approach to the Dissection of the Complexity of Regulatory Networks in the S. scrofa Cardiocirculatory System
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Paolo Martini, Gabriele Sales, Enrica Calura, Mattia Brugiolo, Gerolamo Lanfranchi, Chiara Romualdi, and Stefano Cagnin
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pathway analysis ,miRNA ,cardiocirculatory ,network reconstruction ,integrative analysis ,pig ,artery ,vein ,vessel ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.
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- 2013
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28. Regional Distribution and Evolution of Gray Matter Damage in Different Populations of Multiple Sclerosis Patients.
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Massimiliano Calabrese, Richard Reynolds, Roberta Magliozzi, Marco Castellaro, Aldo Morra, Antonio Scalfari, Gabriele Farina, Chiara Romualdi, Alberto Gajofatto, Marco Pitteri, Maria Donata Benedetti, and Salvatore Monaco
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Medicine ,Science - Abstract
Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients.We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration
- Published
- 2015
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29. Beneficial Bacteria Isolated from Grapevine Inner Tissues Shape Arabidopsis thaliana Roots.
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Enrico Baldan, Sebastiano Nigris, Chiara Romualdi, Stefano D'Alessandro, Anna Clocchiatti, Michela Zottini, Piergiorgio Stevanato, Andrea Squartini, and Barbara Baldan
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Medicine ,Science - Abstract
We investigated the potential plant growth-promoting traits of 377 culturable endophytic bacteria, isolated from Vitis vinifera cv. Glera, as good biofertilizer candidates in vineyard management. Endophyte ability in promoting plant growth was assessed in vitro by testing ammonia production, phosphate solubilization, indole-3-acetic acid (IAA) and IAA-like molecule biosynthesis, siderophore and lytic enzyme secretion. Many of the isolates were able to mobilize phosphate (33%), release ammonium (39%), secrete siderophores (38%) and a limited part of them synthetized IAA and IAA-like molecules (5%). Effects of each of the 377 grapevine beneficial bacteria on Arabidopsis thaliana root development were also analyzed to discern plant growth-promoting abilities (PGP) of the different strains, that often exhibit more than one PGP trait. A supervised model-based clustering analysis highlighted six different classes of PGP effects on root architecture. A. thaliana DR5::GUS plantlets, inoculated with IAA-producing endophytes, resulted in altered root growth and enhanced auxin response. Overall, the results indicate that the Glera PGP endospheric culturable microbiome could contribute, by structural root changes, to obtain water and nutrients increasing plant adaptation and survival. From the complete cultivable collection, twelve promising endophytes mainly belonging to the Bacillus but also to Micrococcus and Pantoea genera, were selected for further investigations in the grapevine host plants towards future application in sustainable management of vineyards.
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- 2015
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30. Tissue-specific expression and regulatory networks of pig microRNAome.
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Paolo Martini, Gabriele Sales, Mattia Brugiolo, Alessandro Gandaglia, Filippo Naso, Cristiano De Pittà, Michele Spina, Gino Gerosa, Francesco Chemello, Chiara Romualdi, Stefano Cagnin, and Gerolamo Lanfranchi
- Subjects
Medicine ,Science - Abstract
BackgroundDespite the economic and medical importance of the pig, knowledge about its genome organization, gene expression regulation, and molecular mechanisms involved in physiological processes is far from that achieved for mouse and rat, the two most used model organisms in biomedical research. MicroRNAs (miRNAs) are a wide class of molecules that exert a recognized role in gene expression modulation, but only 280 miRNAs in pig have been characterized to date.ResultsWe applied a novel computational approach to predict species-specific and conserved miRNAs in the pig genome, which were then subjected to experimental validation. We experimentally identified candidate miRNAs sequences grouped in high-confidence (424) and medium-confidence (353) miRNAs according to RNA-seq results. A group of miRNAs was also validated by PCR experiments. We established the subtle variability in expression of isomiRs and miRNA-miRNA star couples supporting a biological function for these molecules. Finally, miRNA and mRNA expression profiles produced from the same sample of 20 different tissue of the animal were combined, using a correlation threshold to filter miRNA-target predictions, to identify tissue-specific regulatory networks.ConclusionsOur data represent a significant progress in the current understanding of miRNAome in pig. The identification of miRNAs, their target mRNAs, and the construction of regulatory circuits will provide new insights into the complex biological networks in several tissues of this important animal model.
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- 2014
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31. Revertant fibers in the mdx murine model of Duchenne muscular dystrophy: an age- and muscle-related reappraisal.
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Sarah R Pigozzo, Lorena Da Re, Chiara Romualdi, Pietro G Mazzara, Eva Galletta, Sue Fletcher, Stephen D Wilton, and Libero Vitiello
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Medicine ,Science - Abstract
Muscles in Duchenne dystrophy patients are characterized by the absence of dystrophin, yet transverse sections show a small percentage of fibers (termed "revertant fibers") positive for dystrophin expression. This phenomenon, whose biological bases have not been fully elucidated, is present also in the murine and canine models of DMD and can confound the evaluation of therapeutic approaches. We analyzed 11 different muscles in a cohort of 40 mdx mice, the most commonly model used in pre-clinical studies, belonging to four age groups; such number of animals allowed us to perform solid ANOVA statistical analysis. We assessed the average number of dystrophin-positive fibers, both absolute and normalized for muscle size, and the correlation between their formation and the ageing process. Our results indicate that various muscles develop different numbers of revertant fibers, with different time trends; besides, they suggest that the biological mechanism(s) behind dystrophin re-expression might not be limited to the early development phases but could actually continue during adulthood. Importantly, such finding was seen also in cardiac muscle, a fact that does not fit into the current hypothesis of the clonal origin of "revertant" myonuclei from satellite cells. This work represents the largest, statistically significant analysis of revertant fibers in mdx mice so far, which can now be used as a reference point for improving the evaluation of therapeutic approaches for DMD. At the same time, it provides new clues about the formation of revertant fibers/cardiomyocytes in dystrophic skeletal and cardiac muscle.
- Published
- 2013
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32. A systems biology approach to characterize the regulatory networks leading to trabectedin resistance in an in vitro model of myxoid liposarcoma.
- Author
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Sarah Uboldi, Enrica Calura, Luca Beltrame, Ilaria Fuso Nerini, Sergio Marchini, Duccio Cavalieri, Eugenio Erba, Giovanna Chiorino, Paola Ostano, Daniela D'Angelo, Maurizio D'Incalci, and Chiara Romualdi
- Subjects
Medicine ,Science - Abstract
Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parental 402-91 cell line to stepwise increases in drug concentration. The aim of this study was to compare mRNAs, miRNAs and proteins profiles of 402-91 and 402-91/ET cells through a systems biology approach. We identified 3,083 genes, 47 miRNAs and 336 proteins differentially expressed between 402-91 and 402-91/ET cell lines. Interestingly three miRNAs among those differentially expressed, miR-130a, miR-21 and miR-7, harbored CHOP binding sites in their promoter region. We used computational approaches to integrate the three regulatory layers and to generate a molecular map describing the altered circuits in sensitive and resistant cell lines. By combining transcriptomic and proteomic data, we reconstructed two different networks, i.e. apoptosis and cell cycle regulation, that could play a key role in modulating trabectedin resistance. This approach highlights the central role of genes such as CCDN1, RB1, E2F4, TNF, CDKN1C and ABL1 in both pre- and post-transcriptional regulatory network. The validation of these results in in vivo models might be clinically relevant to stratify myxoid liposarcoma patients with different sensitivity to trabectedin treatment.
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- 2012
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33. Impact of host genes and strand selection on miRNA and miRNA* expression.
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Marta Biasiolo, Gabriele Sales, Marta Lionetti, Luca Agnelli, Katia Todoerti, Andrea Bisognin, Alessandro Coppe, Chiara Romualdi, Antonino Neri, and Stefania Bortoluzzi
- Subjects
Medicine ,Science - Abstract
Dysregulation of miRNAs expression plays a critical role in the pathogenesis of genetic, multifactorial disorders and in human cancers. We exploited sequence, genomic and expression information to investigate two main aspects of post-transcriptional regulation in miRNA biogenesis, namely strand selection regulation and expression relationships between intragenic miRNAs and host genes. We considered miRNAs expression profiles, measured in five sizeable microarray datasets, including samples from different normal cell types and tissues, as well as different tumours and disease states. First, the study of expression profiles of "sister" miRNA pairs (miRNA/miRNA*, 5' and 3' strands of the same hairpin precursor) showed that the strand selection is highly regulated since it shows tissue-/cell-/condition-specific modulation. We used information about the direction and the strength of the strand selection bias to perform an unsupervised cluster analysis for the sample classification evidencing that is able to distinguish among different tissues, and sometimes between normal and malignant cells. Then, considering a minimum expression threshold, in few miRNA pairs only one mature miRNA is always present in all considered cell types, whereas the majority of pairs were concurrently expressed in some cell types and alternatively in others. In a significant fraction of concurrently expressed pairs, the major and the minor forms found at comparable levels may contribute to post-transcriptional gene silencing, possibly in a coordinate way. In the second part of the study, the behaved tendency to co-expression of intragenic miRNAs and their "host" mRNA genes was confuted by expression profiles examination, suggesting that the expression profile of a given host gene can hardly be a good estimator of co-transcribed miRNA(s) for post-transcriptional regulatory networks inference. Our results point out the regulatory importance of post-transcriptional phases of miRNAs biogenesis, reinforcing the role of such layer of miRNA biogenesis in miRNA-based regulation of cell activities.
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- 2011
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34. benchdamic: benchmarking of differential abundance methods for microbiome data.
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Matteo Calgaro, Chiara Romualdi, Davide Risso, and Nicola Vitulo
- Published
- 2023
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35. The power of word-frequency-based alignment-free functions: a comprehensive large-scale experimental analysis.
- Author
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Giuseppe Cattaneo, Umberto Ferraro Petrillo, Raffaele Giancarlo, Francesco Palini, and Chiara Romualdi
- Published
- 2022
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36. PsiNorm: a scalable normalization for single-cell RNA-seq data.
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Matteo Borella, Graziano Martello, Davide Risso, and Chiara Romualdi
- Published
- 2021
- Full Text
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37. A pan-cancer landscape of pathogenic somatic copy number variations.
- Author
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Tommaso Becchi, Luca Beltrame, Laura Mannarino, Enrica Calura, Sergio Marchini, and Chiara Romualdi
- Published
- 2023
- Full Text
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38. The Power of Alignment-Free Histogram-based Functions: a Comprehensive Genome Scale Experimental Analysis - Version 1.
- Author
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Giuseppe Cattaneo, Umberto Ferraro Petrillo, Raffaele Giancarlo, Francesco Palini, and Chiara Romualdi
- Published
- 2021
39. metaGraphite-a new layer of pathway annotation to get metabolite networks.
- Author
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Gabriele Sales, Enrica Calura, and Chiara Romualdi
- Published
- 2019
- Full Text
- View/download PDF
40. Similarity Measures Based on the Overlap of Ranked Genes Are Effective for Comparison and Classification of Microarray Data.
- Author
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Fabrizio Serra, Chiara Romualdi, and Federico Fogolari
- Published
- 2016
- Full Text
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41. COLOMBOS v3.0: leveraging gene expression compendia for cross-species analyses.
- Author
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Marco Moretto, Paolo Sonego, Nicolas Dierckxsens, Matteo Brilli, Luca Bianco, Daniela Ledezma-Tejeida, Socorro Gama-Castro, Marco Galardini, Chiara Romualdi, Kris Laukens, Julio Collado-Vides, Pieter Meysman, and Kristof Engelen
- Published
- 2016
- Full Text
- View/download PDF
42. Graphite Web: web tool for gene set analysis exploiting pathway topology.
- Author
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Gabriele Sales, Enrica Calura, Paolo G. V. Martini, and Chiara Romualdi
- Published
- 2013
- Full Text
- View/download PDF
43. MAGIA2: from miRNA and genes expression data integrative analysis to microRNA-transcription factor mixed regulatory circuits (2012 update).
- Author
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Andrea Bisognin, Gabriele Sales, Alessandro Coppe, Stefania Bortoluzzi, and Chiara Romualdi
- Published
- 2012
- Full Text
- View/download PDF
44. simPATHy: a new method for simulating data from perturbed biological PATHways.
- Author
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Elisa Salviato, Vera Djordjilovic, Monica Chiogna, and Chiara Romualdi
- Published
- 2017
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45. The Biological Connection Markup Language: a SBGN-compliant format for visualization, filtering and analysis of biological pathways.
- Author
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Luca Beltrame, Enrica Calura, Razvan R. Popovici, Lisa Rizzetto, Damariz Rivero Guedez, Michele Donato, Chiara Romualdi, Sorin Draghici, and Duccio Cavalieri
- Published
- 2011
- Full Text
- View/download PDF
46. MAGIA, a web-based tool for miRNA and Genes Integrated Analysis.
- Author
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Gabriele Sales, Alessandro Coppe, Andrea Bisognin, Marta Biasiolo, Stefania Bortoluzzi, and Chiara Romualdi
- Published
- 2010
- Full Text
- View/download PDF
47. A modified LOESS normalization applied to microRNA arrays: a comparative evaluation.
- Author
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Davide Risso, Maria Sofia Massa, Monica Chiogna, and Chiara Romualdi
- Published
- 2009
- Full Text
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48. Morphology and evolution of cortical lesions in multiple sclerosis. A longitudinal MRI study.
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Massimiliano Calabrese, Massimo Filippi, Marco Rovaris, Irene Mattisi, Valentina Bernardi, Matteo Atzori, Alice Favaretto, Luigi Barachino, Luciano Rinaldi, Chiara Romualdi, Paola Perini, and Paolo Gallo
- Published
- 2008
- Full Text
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49. RAP: a new computer program for de novo identification of repeated sequences in whole genomes.
- Author
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Davide Campagna, Chiara Romualdi, Nicola Vitulo, Micky Del Favero, Matej Lexa, Nicola Cannata, and Giorgio Valle
- Published
- 2005
- Full Text
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50. MIDAW: a web tool for statistical analysis of microarray data.
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Chiara Romualdi, Nicola Vitulo, Micky Del Favero, and Gerolamo Lanfranchi
- Published
- 2005
- Full Text
- View/download PDF
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