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| 326838 | Abstract in atti di convegno | The protective and toxic role of neuromelanins in brain aging and Parkinson's disease | Zecca L., Bellei C., Mauri P., Casella L., Cebrian C., Sulzer D., Zucca F.A. | None | European Society for Neurochemistry's Conference Molecular Mechanisms of Regulation in the Nervous System, Tartu, Estonia, June 14-17, 2015 | 2015 | ZUCCA FABIO ANDREA, BELLEI CHIARA, ZECCA LUIGI, MAURI PIETRO LUIGI | | |
| 331974 | Abstract in atti di convegno | EFFECTS OF LINSEED AND HEMP SEEDS DIET SUPPLEMENTATION ON CAPRINE RUMEN BACTERIAL DIVERSITY | P. Cremonesi1, E. Capra1, F. Turri1, M. Severgnini2, G. Conte3, L. Rapetti4, S. Chessa1, B. Castiglioni1 | None | 6th Congress of European Microbiologists, Maastricht, The Nederlands, 7-11 June 2015 | 2015 | CAPRA EMANUELE, CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA, CHESSA STEFANIA, TURRI FEDERICA | caprine, metagenome, diet, rumen | |
| 337828 | Abstract in rivista | Evaluation of the effects of different diets on bacterial diversity and on fatty acid composition in goat rumen. | Paola Cremonesi, 1, Giuseppe Conte, 2 Emanuele Capra, 1 Federica Turri, 1 Marco Severgnini, 3 Luca Rapetti, 4 Stefania Colombini, 4 Stefania Chessa, 1 Marcello Mele, 2 Bianca Castiglioni.1 | None | Italian Journal of Animal Science (Testo stamp.) (2015). | 2015 | CAPRA EMANUELE, CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA, CHESSA STEFANIA, TURRI FEDERICA | metagenome, fatty acids, goat, diet | |
| 337901 | Abstract in atti di convegno | Milk's microbiota during the periparturient period in holstein cows: possible implication on animal health and milk quality | Paola Cremonesi1, Federica Riva2, Emanuele Capra1, Vittorio Tedde3, Maria Filippa Addis3, Lauretta Turin2, Claudia Pollera2, Marco Severgnini4, Joel Felipe Soares2, Giulio Curone2, Noemi Visconti2, Daniele Vigo2, Bianca Castiglioni1 | Dairy cattle are exposed to a high risk for disease during periparturient period and this period is often associated with the peak incidence of production problems, metabolic disorders, infectious diseases, metritis and mastitis. The aim of this study was to compare the milk's microbiota during the periparturient period in order to assess the possible implication on animal health and milk quality. Milk samples were collected from each quarters of six pluriparous Holstein cows at 340 ? 60 days of lactation (T1), at the day after calving (T2) and between 7 to 10 days after calving (T3). To determine the udder health status, a standard bacteriological analysis on milk samples were performed; moreover, SCC was obtained by an automated fluorescent microscopic somatic cell counter. For the microbiome analysis, the bacterial DNA was extracted from the pool of the quarters for each animal using a protocol previously described (Cremonesi et al., 2005) with some modifications and the 16S rRNA gene (V3-V4 region) was analyzed by Miseq (Illumina). Milk proteins were evaluated by SDS-PAGE and by densitometric analysis for assessment of total protein profiles. In addition, the presence of the inflammation markers cathelicidin and S100A9 was estimated by western immunoblotting. Tests were done for all quarters and for the three lactation stages. Moreover, the expression of CD45 and KRT5 messengers in the isolated milk cells was analyzed in order to assess the modification of leukocyte/exfoliated epithelial cell ratio during peripartum, while the expression of IL-1b and TNFa mRNA in the isolated milk cells was studied for their capability to produce cytokines. Finally, the expression of PTX3 transcript in the milk fat globules was analyzed in order to evaluate its modulation and to check the activation of the mammary epithelial cells. Bacteriological analysis showed the absence of contagious bacteria such as Staph. aureus and S. agalactiae. An interesting modification of the leukocyte/exfoliated epithelial cell ratio during peripartum was observed with an up-regulation of PTX3 in the colostrum. Moreover, this study describes the relative changes in milk protein abundance along lactation and according to composition of the microbial flora. These data have also been integrated with information on protein markers of inflammation. To our knowledge, this is the first time that mammary gland metagenome was studied during the periparturient period. | 6th International Symposium on Animal Functional Genomics, Piacenza, 27-29 Luglio 2015 | 2015 | CAPRA EMANUELE, CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA | microbiome, milk, periparturient period | |
| 338763 | Poster | NonCode aReNA DB: a non-redundant and integrated collection of non-coding RNAs | Giorgio De Caro1, Arianna Consiglio1, Domenica D'Elia1, Andreas Gisel1, Giorgio Grillo1, Sabino Liuni1, Angelica Tulipano1, Flavio Licciulli1 | MOTIVATION: The recent availability of next generation sequencing (NGS) technologies, has provided the scientific community with an unprecedented opportunity for large-scale analysis of genome in a large number of organisms. One of the most challenging task for bioinformaticians is to develop tools that provide biologists with an easy access to curated and non-redundant collections of sequence data. Non-coding RNAs, for a long time believed to be not-functional, are emerging as the most large and important family of gene regulators. METHODS: NonCode aReNA DataBase is a comprehensive and non-redundant source of manually curated and automatically annotated ncRNA transcripts collected from major public resources. The database is built through a set of ETL (Extraction Transformation Loading) automated processes which extracts and collects data from VEGA, ENSEMBL, RefSeq, miRBase, GtRNAdb and piRNABank. The automatic process guarantees also recurring updates. The identification of redundant sequences is made by analyzing both cross-link references and sequence similarity. Furthermore non-coding RNA sequences have been classified in diverse biotypes and associated to Sequence Ontology terms. NonCode aReNA DataBase is originally developed as a component of a bigger project, represented by a datawarehouse and an analysis workflow, for the functional annotation of ncRNAs from NGS data. RESULTS: NonCode aReNA Database is currently available as a web-resource at http://ncrnadb.ba.itb.cnr.it/. The database can be queried by using multi-criteria and ontological search, through an easy-to-use web interface. Query results can be exported as non-redundant collections of ncRNA transcripts. Currently NonCode aReNA DataBase contains 134,908 human ncRNAs classified in 24 biotypes, and next updates will include transcripts of Mus musculus and Arabidopsis thaliana | BITS 2015 Twelfth Annual Meeting of the Bioinformatics Italian Society, Milan, 3-5 Giugno 2015 | 2015 | TULIPANO ANGELICA, CONSIGLIO ARIANNA, DE CARO GIORGIO, D'ELIA DOMENICA, LICCIULLI VITO FLAVIO, GRILLO GIORGIO, GISEL ANDREAS, LIUNI SABINO | non-coding RNA, database | |
| 344188 | Annual report | ITB TR-052015 | Matteo Gnocchi | Report Annuale per il 2015 delle attivita -- Protocollo CNR N?0002278 del 18/11/2015 | 2015 | 2015 | GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay | |
| 344182 | Sito web | cs.bbmri.it | Matteo Gnocchi | Portale per il progetto europeo BBMRI-CS | 2015 | 2015 | GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay, Biobanks | |
| 354942 | Rapporto di progetto (Project report) | With CHARME towardsstandardisation in life sciences | Domenica D'Elia 1, Babette Regierer 2, Susanne Hollmann 3 | On March 21st, representatives from 26 countries met in Brussels to execute the kick-off meeting of the new COST Action (Cooperation in Science and Technology) CA15110: "Harmonising standardisation strategies to increase efficiency and competitiveness of European lifescience research (CHARME)". The participants exchanged information about the need for understanding formats and standards for biological data and computer models in systems biology research, and elected Chair, Vice Chair and working group leaders. | pp.2-2, 2016 | 2016 | D'ELIA DOMENICA | standards, Standard-Operating-Procedures, SOP, life sciences, bioinformatics, systems biology | |
| 368286 | Poster | Integrating bioinformatics resources for modelling Human non-coding RNA networks | Vincenzo Bonnici1*, Giorgio De Caro2*, Sabino Liuni2, Domenica D'Elia2, Nicola Bombieri1, Rosalba Giugno1*, Flavio Licciulli2* | Introduction Non-coding RNAs (ncRNAs) serve as regulatory molecules for a variety of biological processes. They are roughly classified into two major categories, small non-coding RNAs (sncRNAs), such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) according to their size. The lncRNAs have a broader spectrum of functions and are, therefore, a potential new class of cancer therapeutic target [1,2]. In addition there are other different types of ncRNAs whose role is not yet clear: circular-RNA, lincRNA, scRNA, sense-intronic and vault-RNA. New advances in translational research will require an accurate understanding of the functional relationships between protein- coding and ncRNA categories, as well as sponge regulatory networks [3,4]. To achieve this goal, we have built an integrated bioinformatics knowledge base, collecting non-redundant annotations of human ncRNAs, sequences and interactors, which provides a comprehensive access to all the knowledge available concerning ncRNAs, their interaction with other molecules and associated diseases. As key characteristics, the database overcomes the problem of different nomenclatures used by different sources and provides new clues about ncRNA functions throughout interactions inferred by network reconstruction [5]. Methods ncRNA interactions include physical (i.e. molecular bindings between ncRNAs and DNA, RNAs or proteins) and functional relationships (i.e., co-expression, regulation, associated diseases, statistical and functional associations). Interactions stored in the database are in the form 'ncRNAs-mate', where the mate entity belongs to one of the following types: ncRNA, protein coding RNA (pcRNA), gene, protein, pseudogene and phenotype. In order to ensure the data quality of our interaction database we have developed a series of Extraction Transformation and Loading (ETL) modules able to extract, collect and integrate primary annotations, sequences and interactions from different public biological resources. The biological extracted entities and their relations are modelled as a network, a mathematical object composed by nodes (entities) and edges (relations) [5]. Entities redundancy has been identified by cross-link references and sequence similarity using the Cleanup software [6]. Non- coding RNAs are classified in biotypes, associated to Sequence Ontology terms [7] and integrated with data of protein coding RNAs (pcRNAs), gene, protein, pseudogene and phenotype. Furthermore, we extended the cross-reference network with data provided by Ensembl [8], using the biomaRt library of BioConductor [9]. Results Total amount of different entities collected in our interaction database are: 168.058 ncRNA , 5.009 pcRNA, 52.811 genes, 1.999 proteins, 15.940 pseudogenes and 849 phenotype. Moreover, total amount of interactions, based on mate type cardinalities, include: 130.383 ncRNA- ncRNA, 55.048 ncRNA-pcRNA, 1.458.925 ncRNA-gene, 99.653 ncRNA-protein, 70.482 ncRNA-phenotype, 17.217 ncRNA-pseudogene. Conclusions An increasing huge amount of information is spread along existing scope-specific resources, and up to date, the integration of knowledges for relatively new discovered type of biological molecules suffers the lack of nomenclature standards and unified classifications. To show the potentialities offered by our interaction database, we related a subnet known tumour gene circuit of E2F6, EZH1, EZH2, and ARAF [10], by means of the ncRNA-gene interaction database. Among the retrieved interactions, we analyzed those involving one long non-coding RNA (HOTAIR) and one miRNA (miR-148b-3p). HOTAIR up-regulation may be a critical element in metastatic progression [11], whereas the over-expression of miR-148b-3p could inhibit cell proliferation in vitro and suppress tumorigenicity in vivo [12]. A possible mechanism of tumorigenesis, in colorectal cancer and other cancers, could operate in a circuit that involves the up-regulation of proteins aforementioned, and the down-regulation of miR-148b-3p, mediated by HOTAIR. Indeed, HOTAIR may function as competing endogenous RNAs (ceRNAs) to sponge miR-148b-3p, thus modulating the de-repression of its targets, such as ARAF, a proto-oncogene that may be involved in cell proliferation. This example demonstrate the utility of our interaction database for the discovery of ncRNAs regulatory networks. References 1.Qureshi et.al. (2010) "Long non-coding RNAs in nervous system function and diseases, Barin Res. 1338, 20-35. 2.Prenser, J.R et.al (2011)," The emergence of lncRNAs in cancer biology", Cancer Discov. 1, 391- 407. 3.Ebert, M.S. et al. (2010) "Emerging roles for natural microRNA sponges", Cur. Biol. 20, R858-R861. 4.Ebert, M.S, et.al. "MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells", Nat. Methods, 4 , 721-726. 5.Bonnici V, Russo F, Bombieri N, Pulvirenti A and Giugno R (2014) Comprehensive reconstruction and visualization of non-coding regulatory networks in human. Front. Bioeng. Biotechnol. 2:69. doi: 10.3389/fbioe.2014.00069 6.G.Grillo, M.Attimonelli, S.Liuni and G.Pesole, CLEANUP: a fast computer program for removing redundancies from nucleotide sequence databases, Comput Appl Biosci. 1996;12:1-8 7.The Sequence Ontology: A tool for the unification of genome annotations. Eilbeck K., Lewis S.E., Mungall C.J. et al., Genome Biology (2005) 6:R44 8.Hubbard, T., Barker, D., Birney, E., Cameron, G., Chen, Y., Clark, L., ... & Durbin, R. (2002). The Ensembl genome database project. Nucleic acids research, 30(1), 38-41. 9.Durinck, S., Moreau, Y., Kasprzyk, A., Davis, S., De Moor, B., Brazma, A., & Huber, W. (2005). BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis. Bioinformatics, 21(16), 3439-3440. 10.C. Attwooll et al. A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner. In: Journal of Biological Chemistry 280.2 (2005), pp. 1199-1208. 11.R. A. Gupta et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. In: Nature 464.7291 (2010), pp. 1071-1076. 12.Y. Song et al. MicroRNA-148b suppresses cell growth by targeting cholecystokinin-2 receptor in colorectal cancer. In: International Journal of Cancer 131.5 (2012), pp. 1042-1051. | Joint CHARME-EMBnet-NETTAB 2016 Workshop Reproducibility, standards and SOP in Bioinformatics, pp. 67-69, CNR, Piazzale Aldo Moro, 7, Roma, 25/10/2016, 26/10/2016 | 2016 | DE CARO GIORGIO, D'ELIA DOMENICA, LICCIULLI VITO FLAVIO, LIUNI SABINO | non-coding RNA, bioinformatics, interactions network, database | |
| 344176 | Abstract in atti di convegno | HIRMA: WEB PORTAL FOR THE MANAGEMENT OF HEPATOCARCINOMA CLINICAL DATA | Gnocchi M.(1), Moscatelli M.(1), Alfieri R.(1), Manconi A.(1), Milanesi L.(1) | The HIRMA project (Hepatocarcinoma Innovative Research Markers) aims at identifying and characterizing innovative markers related to the biological role of hepatotropic viruses (HBC, HBV and HDV) in the development of hepatocellular carcinoma, which is the third leading cause of cancer death worldwide. To achieve this result 30 research and hospital centres were involved to create an Italian collaborative network able to share and manage the information regarding a population of patients and their biological samples stored in biobanks. In order to allow the collection, the management and the search of the clinical data a dedicated centralized web portal (http://www.hirma.it) has been developed | BITS 2015, 03/06/2015 | 2015 | GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay | |
| 344185 | Rapporto tecnico | ITB TR-012015 | Matteo Gnocchi Marco Moscatelli | Implementazione di un portale per la gestione di dati clinici di pazienti affetti da virus epatitici -- Protocollo CNR N? 001380 del 26/06/2016 | 2015 | 2015 | MOSCATELLI MARCO, GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay | |
| 344183 | Rapporto tecnico | ITB TR-022015 | Matteo Gnocchi Marco Moscatelli | Implementazione del Portale per il nodo Nazionale BBMRI.IT -- Protocollo CNR N? 0001381 del 26/06/2015 | 2015 | 2015 | MOSCATELLI MARCO, GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay, Biobanks | |
| 344186 | Rapporto tecnico | ITB TR-032015 | Marco Moscatelli Matteo Gnocchi | Realizzazione di uno storage ad elevate prestazioni ed affidabilita a supporto dei progetti di ricerca bioinformatici -- Protocollo CNR N?0001864 del 25/09/2015 | 2015 | 2015 | MOSCATELLI MARCO, GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay | |
| 344187 | Rapporto tecnico | ITB TR-042015 | Matteo Gnocchi Marco Moscatelli | Realizzazione di un portale per la gestione di dataset multiomici --- protocollo CNR N? 0001863 del 25/09/2015 | 2015 | 2015 | MOSCATELLI MARCO, GNOCCHI MATTEO | Bioinformatics, Portal, Java, Liferay | |
| 338143 | Poster | Study of the effects of diet supplementation on milk fatty acids composition, rumen bacterial diversity and mammary gland transcriptome in Alpine lactating goats | S.Chessa1, P.Cremonesi1, E.Capra1, F.Turri1, B.Lazzari1, L.Rapetti2, S.Colombini2, G.Battelli3, M.Severgnini4, B.Castiglioni1 | Aim of this study was to evaluate the effects of diets enriched with polyunsaturated fatty acids (PUFAs), using flax (F) and hempseed (H) supplementation, on milk fatty acid composition, on bacterial diversity in rumen and mammary gene expression of 18 Alpine lactating goats divided into three groups (F, Hand control group C).For this study two time-points were taken into account: at the first time-point(T0), at about 40 DIM, all the goats were fed the same diet; after a week, the diets were differentiated and a second time-point (T1) was fixed at about 150 DIM. At T0 and T1, milk traits were recorded and fatty acid (FA) composition was determined. The concentration of milk fat at T1 increased of almost one percentage point between the animals of F and H groups with respect to C group. Contemporary, RNA-seq was used to study the caprine mammary gland stranscriptome. In total, 12.436 mRNA transcripts, across all the samples, were obtained. Among the three dietary treatment groups, 133 and 491 genes resulted differentially expressed (P<0.05, FDR<0.05) in T1 with respect to T0 in the F and Hgroup, respectively. At these two time points, ruminal fluid samples were also collected and the bacterial DNA extracted analyzed by a metagenomic approach. In the three dietary treatment groups, bacterial community was dominated by Bacteroidetes and Firmicutes. Further integrated analysis of differential gene expression and rumen metagenomics will help identifying the key mechanisms underlying milk composition traits in goat. | L'innovazione scientifica per la nutrizione, Lodi, 16 Ottobre 2015 | 2015 | CAPRA EMANUELE, BATTELLI GIOVANNA, LAZZARI BARBARA, CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA, CHESSA STEFANIA, TURRI FEDERICA | milk fatty acids, rumen bacterial diversity, mammary gland trascriptome, goat | |
| 380737 | Abstract in atti di convegno | Microbiota characterization and volatile and non-volatile lipophilic fraction analysis of Bitto Storico cheese produced in six different Alpine pastures. | Paola Cremonesi1, Federica Turri1, Gustavo Gandini2, Giovanna Battelli3, Marco Severgnini4, Flavia Pizzi1 | The Bitto Storico is an alpine heritage cheese made with raw milk and produced during the summer season in the Orobic Alps (Central Alps, Northern Italy). The cheese-making process depends on local traditions: freshly milked cow's milk is added to fresh goat's milk (10-20%), then production starts immediately in the "calecc" (itinerant dairy). The use of feeds and silage for animal feeding and the use of probiotics during curdling are prohibited thus the organoleptic variability of the cheese depends on local bacteria that change according to pastures and environment. These conditions guarantee a variability of organoleptic characteristics, probably associated to different microbial communities, highly appreciated by consumers. The objectives were (i) the characterization of the microbial variability of the Bitto Storico cheese by Next Generation Sequencing, and (ii) the analysis of the volatile and non-volatile lipophilic fractions. Samples were collected from 54 Bitto Storico cheeses produced in six different Alpine pastures, in three geographical areas (Val Gerola, Valli del Bitto, Valle Brembana), during 2015 summer season. Bacterial DNA was extracted using an optimized protocol and 16S rRNA gene amplicons on V3-V4 region analyzed by Miseq (Illumina). The lipophilic fraction was characterized by means of Solid Phase Extraction-Gas Chromatography-Mass Spectrometry (SPME-GC-MS), the fatty acid profile by the High Resolution Gas Chromatography (HRGC). Preliminary results showed a microbial community mainly dominated by Firmicutes with a high abundance of Streptococcaceae and Lactobacillaceae and low presence of Entrococcaceae. The volatile metabolome displayed a variability consistent with the dairy products of raw milk. | FEMS 7th Congress of European Microbiologist, Valencia, 9-13/07/2017 | 2017 | BATTELLI GIOVANNA, SEVERGNINI MARCO, CREMONESI PAOLA, TURRI FEDERICA, PIZZI FLAVIA | microbiota, cheese, alpine pasture | |
| 388705 | Poster | Effect of the use of chlorine usage in milking equipment cleaning procedures on raw milk microbiota | Cremonesi P., Ceccarani C., Cologna N., Goss A., Severgnini M., Mazzucchi M., Partel E., Morandi S., Castiglioni B., Tamburini A., Zanini L., Brasca M. | Aim Proper milking machine cleaning and disinfection procedures are essential to ensure milk hygienic quality, and sodium hypochlorite is generally present in commercially available products (Gleeson et al. 2012), but it has been previously demonstrated that nonchlorine detergent products give satisfactory results when used with sufficiently hot water (Teagasc et al. 2012). In addition, some studies highlighted the effect of chlorine on milk bacterial count, encouraging a deeper comprehension of the relationship between the use of chlorine products and milk microbiota, which represents a key point for raw milk cheese production (Gleeson et al. 2013). The aim of the study was to evaluate the influence of chlorine products usage for cleaning and sanitizing the milking equipment on raw milk and the deriving whey-starter microbiota in Trentingrana production. Trentingrana is a Protected Designation of Origin (PDO) hard cheese manufactured in the valleys of Trento province (eastern Italian Alps) by several small cooperative dairies linked in a consortium (Bittante et al. 2011). Materials and Methods Three farms (here named as F1, F2 and F3) located in Trentino and associated to a factory producing Trentingrana cheese, were involved in the study. The herds were composed by 55, 48 and 91 lactating cows (Italian Holstein-Friesian, Brown and Italian Simmental in different ratios). The farms were free stall barns with cubicles with mattress covered with sawdust and lactating cows were fed hay associated with concentrate. The herds were milked twice a day in DeLaval herringbone milking plants (F1 (5+5), F2 (4+4), F3 (6+6). The cleaning routine practices and products usage rates were those recommended by the producers and the water temperatures appropriate. Milk was collected thrice weekly during the sodium hypoclorite detergent usage (six-weeks period, C) and in a subsequent, analogous, nonchlorine detergent period (period NC); a 4-weeks interval was established between the two experimental periods in order to allow bacterial population adaptation to the new detergent. In the last three days of each experimental week, bulk milk was sampled from tank. The whey-starter used that day for cheese-making was sampled too. Within 12 h from collection, samples were submitted to microbiological analyses (Standard Plate Count SPC, coliforms, staphylococci coagulase positive, lactic acid bacteria LAB). For microbiome analysis, bacterial DNA was extracted from 5 ml of milk or whey-starter samples using a protocol previously described (Cremonesi et al. 2006) with some modifications. 16S rRNA gene (V3-V4 region) was amplified following standard 16S Metagenomic Sequencing Library Preparation and sequenced on a paired 2x250 bp run on Illumina MiSeq platform. Data analyses (alpha and beta diversity, taxonomical abundances) were performed using the QIIME pipeline (release 1.8.0; (Kuczynski et al., 2011). Results and Discussion Even if no microbiological significant differences were observed, higher levels of SPC and LAB in bulk milk were recorded going from period C to period NC (4,06 +-0,16 vs 4,10 +-0,20 log cfu/mL), while coliforms and staphylococci tended to be lower in NC period (1,97+-1,02 vs 1,60+-0,68 log ufc/mL and 2,17+-0,48 vs 2,07+-0,57 log cfu/mL respectively). An increase in LAB count, although not significant, was observed in LAB content in whey-starter (8,11+-0,43 log ufc/mL in period N vs 8,66 +-0,45 log cfu/mL in period NC). The microbiota composition was quite peculiar in the three farms analysed, and between C and NC periods. Alpha- and beta-diversity analyses revealed significant differences among farms (p values: 0.003 and 0.001, respectively): in fact, farm F1 and F2 microbial taxonomic composition was dominated by Firmicutes (rel. ab. respectively 60.5% and 42.8% in period C; 57.5% and 52.1% in period NC), while farm F3 showed a microbial composition dominated by Bacteriodetes (47.4% period C; 52.1% period NC). Differences in the microbiota profile (beta-diversity) between C and NC periods within each farm were found to be significant (p < 0.05). Relative abundances analysis revealed that farm F1 and F2 had a significant change in Oscillospira genus and, respectively, in Chryseobacterium and Clostridium genera; farm F3 showed Acinetobacter and Trichococcus genera significantly decreased. Though raw milk microbiota varied among farms, whey-starter bacterial composition consisted mainly of Lactobacillus genus. At a species-level, Lb. helveticus was predominant during period C (62.9% rel. ab.) and significantly reduced during period NC (31.8%), whereas Lb. delbrueckii had the exact opposite trend (28.1% period C; 58.6% period NC). Conclusion Our preliminary results report that is reasonable to further study chlorine influence on milk microbiota, in order to better understand the changes in its composition and, consequently, the possible effect on raw milk cheese production performances and overall quality. | International Bovine Mastitis Conference., Milano, 11-13/06/2018 | 2018 | CECCARANI CAMILLA, CASTIGLIONI BIANCA MARIA ELISABETTA, BRASCA MILENA, SEVERGNINI MARCO, MORANDI STEFANO, CREMONESI PAOLA | chlorine, milking equipment, cleaning procedures, raw milk microbiota | |
| 388694 | Software | ChromStruct v4.2 - Reconstruction of 3D chromatin structure from chromosome conformation capture data | Salerno E., Caudai C. | This Python (v.2.7.10) code provides an estimate of the 3D structure of the chromatin fibre in cell nuclei from the contact frequency data produced by a 'Chromosome conformation capture' experiment. The only input required is a text file containing a general real matrix of contact frequencies. The code features a GUI where all the tuneable parameters are made available to the user. The fibre is divided in independent segments whose structures are first estimated separately and then modelled as single elements of a lower-resolution fibre, which is treated iteratively in the same way until it cannot be divided anymore into independent segments. The full-resolution chain is then reconstructed by another iterative procedure. See the Readme file and the cited references for more detail. | 2018 | 2018 | CAUDAI CLAUDIA, SALERNO EMANUELE | Chromosome Conformation Capture, Chromatin Structure Estimation | |
| 390841 | Presentazione | Ripensare la poliarchia. Il pensiero di Dahl come antidoto al malessere della democrazia | ANTONUCCI, MARIA CRISTINA | Le democrazie contemporanee appaiono oggetto di disfunzioni tanto in termini procedurali, con la difficolta di tradurre gli orientamenti elettorali espressi dai cittadini nella fase elettorale in concrete pratiche di rappresentanza politica e in politiche di governo, quanto in termini sostanziali, in ragione della generalizzata disaffezione dei cittadini alla politica e ai suoi attori, prima ancora che all'astensionismo elettorale. Le difficolta dei regimi politici democratici sono radicate dentro un contesto sociale e politico dominato da fenomeni di una complessita non prevedibile nella genesi della democrazia rappresentativa: gli effetti dei media digitali e sociali sulla formazione dell'opinione pubblica, la nuova percezione del rapporto tra cittadini, politica e istituzioni, la percezione della inefficacia dei comportamenti elettorali a fronte di forti vincoli esterni (globalizzazione economica, partecipazione ad istituzioni politiche sovranazionali cui e demandato il processo decisionale) ed interni (governance multilivello, sussidiarieta) condizionano sempre di piu spazi, orientamenti e ambiti di azione e partecipazione nelle democrazie contemporanee, ritenute, a torto o a ragione, sempre piu foriere di promesse non mantenute nei confronti dei cittadini. La formulazione di preferenze, la capacita di rendere le preferenze espresse significative nel quadro del contesto istituzionale e la possibilita che queste preferenze vengano concretamente considerate nell'ambito della formazione di politiche di governo sono i fattori di sistema che vengono posti in questione dall'attuale crisi di partecipazione politico-elettorale, dal ridotto grado di accountability politico-istituzionale, dalla rottura delle premesse ideali e fiduciarie, fondate su classe, ceto, ideologia, nei confronti degli attori partitici, transitati da un modello organizzativo di massa consolidato e diffusivo alla galassia post-ideologica di cartel party e catch all party. Nel presente contributo, si intende riportare i termini del dibattito sul malessere della democrazia alla concezione di Robert Dahl espressa nel volume Poliarchia, cercando di porre in luce i fattori istituzionali, di sviluppo socio-economico e di natura propriamente politica in grado di favorire la realizzazione di un modello poliarchico all'interno di un determinato regime politico. In particolare, appare utile ancorare ogni ragionamento sulla crisi della democrazia rappresentativa all'idea sviluppata dallo studioso statunitense di poliarchia: se la concezione di democrazia appare legata alla dimensione puramente ideale di indagine, appare piu significativo impostare l'analisi sul concetto di poliarchia, intesa come regime politico relativamente, ma incompiutamente, democratizzato. Lo scarto tra idealizzazione democratica e concretezza delle esperienze poliarchiche realizzatesi nei regimi politici indagate da Dahl, porta alla riformulazione della valutazione dei regimi politici alla luce delle condizioni che ne aumentano gli ambiti di democratizzazione: 1.livello di liberalizzazione e margine di inclusione dei cittadini; 2. ammissibilita di spazi per la contestazione delle politiche poste in essere dal governo; 3. relazione tra ordine sociale pluralista e livello di sviluppo economico atto alla diversificazione sociale; 4. capacita del sistema di produrre eguaglianza nella distribuzione di risorse politiche ed economiche; 5. possibilita di tratteggiare uno spazio specifico per le sottoculture sub-nazionali, 6. costruzione di elementi a sostegno della legittimazione istituzionale dei sistemi poliarchici. Con particolare riferimento all'ultimo tema, per la legittimazione dei sistemi poliarchici un ruolo particolare sembra affidato all'autorita dei governi, alla efficienza delle politiche, intesa come capacita di un regime di risolvere le questioni critiche, alla fiducia riposta dai cittadini nei confronti del sistema politico e dei suoi attori, alla volonta di cooperazione dei diversi soggetti sociali, economici, istituzionali e politici, all'interno del regime politico poliarchico. Nell'analisi dei problemi di salute delle poliarchie contemporanee, grande spazio appare occupato dalla inefficacia delle politiche, dalla crisi di fiducia nei confronti delle istituzioni, dalla mancanza di cooperazione e dal limitato accesso, su base di pari opportunita tra i cittadini, alle risorse politiche. Riprendere in considerazione i fattori socio-economici che determinano le condizioni politiche dei regimi poliarchici e la principale indicazione che una rilettura odierna dal pensiero di Dahl puo offrire alla odierna crisi della democrazia, specialmente in un contesto di teoria politica piu concentrato sulle cause tecnico-procedurali del malessere democratico che sulle determinanti politiche, sociali e culturali dell'inefficacia dei regimi democratici. | SOCIETA' ITALIANA DI SCIENZA POLITICA, CONVEGNO ANNUALE 2018 - Democrazia e ri-definizioni. La teoria politica e il <> della teoria democratica, pp. 1-10, TORINO - UNIVERSITA' DEGLI STUDI, 06-08/09/2018 | 2018 | ANTONUCCI MARIA CRISTINA | DEMOCRAZIA, DAHL, POLIARCHIA, TEORIA POLITICA | |
| 337307 | Poster | Effects of edible plant microRNAs on cancer cell proliferation: a beneficial cross-kingdom interaction | Flaviana Marzano1, Mariano Caratozzolo1, Sabino Liuni1, Elisabetta Sbisa, Domenica D'Elia1, Apollonia Tullo1, Domenico Catalano2 | Diet in human health is no longer simple nutrition but, in the light of recent findings, it might play a pivotal role on cell health status by modulating apoptosis, detoxification, and appropriate gene response to environmental stresses. Epidemiological studies suggest a role of fruits and vegetables in protection against several diseases, and nutrients have been demonstrated to alter gene expression by DNA methylation and histone modifications [1-2]. Diet has also been found to modulate micro RNA (miRNA) expression, leading to a subsequent regulation of the effectors genes [3]. Furthermore, recent studies demonstrate that some plant/food-derived microRNAs (miRNAs) regulate gene expression in a sequence specific manner [4]. On the basis of all these findings, we have carried out a pilot study, using a combined "in-silico and wet" approach, to investigate the potential effects, and elucidate the molecular mechanisms, of edible plant miRNAs on the expression of human genes involved in cancer onset and progression. In the present paper we report the results obtained by transfecting 2 colon cancer cell lines, p53 wild type and p53 knock-out, with selected miRNAs of G. max, Z. mais and M. truncatula, which we found, by in silico analysis, to have a putative targeting activity on human oncogenes and tumor suppressor genes. | NETTAB 2015 & Integrative Bioinformatics 2015, pp. 136-139, Bari, 14-16 October 2015 | 2015 | CARATOZZOLO MARIANO FRANCESCO, MARZANO FLAVIANA, TULLO APOLLONIA, D'ELIA DOMENICA, CATALANO DOMENICO, LIUNI SABINO, SBISA' ELISABETTA | micro RNA, plants, human cancer | |
| 337311 | Poster | Comparison of co-regulation of DNA methylation and smallRNA expression between Arabidopsis infected with RNA and DNA virus | Angelica Tulipano1, Anna Vittoria Carluccio2, Giorgio De Caro1, Domenica D'Elia1, Fabrizio Cillo2, Flavio Liciulli1, Livia Stavolone2, 3, Andreas Gisel1, 3 | In plants, which are particularly sensitive to changes of environmental conditions, modulation of DNA methylation is a crucial mechanism of regulation of gene expression in response to abiotic and biotic stresses. Monitoring plant's immune system in response to bacterial pathogen infection demonstrated that also dynamic DNA methylation changes, and not only gene imprinting, have regulatory effect in plant pathogen defense. Critical elements for epigenetic modifications of plant genomes are non-coding smallRNA e same RNA family is also a hallmark of plant reaction to virus infection. Interestingly, sRNA have a central role in both plant genome methylation and resistance upon virus infection, however, the interaction between sRNA expression and DNA methylation regulating the immune system in response to virus infection has not been investigated so far. To correlate dynamic DNA methylation and differential sRNA expression in response to virus infection, we have performed genome-wide methylation and sRNA expression profiling on Arabidopsis leaves systemically infected with either the DNA-genome virus Caulifower mosaic virus or the RNA virus Cucumber mosaic virus. We developed a software package to analyze the sRNA expression and the DNA methylation profile and deploy a genome wide comparison of control and infected samples to search regions significantly different either in the methylation profile or in the sRNA expression, or in both. In the regions where we observe significant correlation of methylation (mainly CHH methylation) and sRNA expression modifications, we found that both hypo- and hypermethylation correlated with downregulation of 21/24nt sRNAs. These regions mostly comprised transposons and few of them contained promoter or coding sequences of genes involved, according to gene ontology, in DNA-binding and DNA-dependent regulation of transcription and response to abiotic or biotic stimulus. This confirms virus-induced infection regulation of sRNA and DNA methylation. We are presently still in the process of data analysis and more details about correlation of virus-induced modification of sRNA and DNA methylation levelswill be reported. | KEYSTONE SYMPOSIA ON MOLECULAR AND CELLULAR BIOLOGY - DNA Methylation (Z1) - Joint Meeting: Epigenomics (Z2), Keystone Resort o Keystone, Colorado USA, 29-31 March-1-2 April 2015 | 2015 | TULIPANO ANGELICA, CARLUCCIO ANNA VITTORIA, DE CARO GIORGIO, D'ELIA DOMENICA, LICCIULLI VITO FLAVIO, CILLO FABRIZIO, STAVOLONE LIVIA, GISEL ANDREAS | plant viruses, virus infection, DNA methylation | |
| 392376 | Presentazione | Effetto dell'impiego di cloro nella pulizia dell'impianto di mungitura sul microbiota del latte crudo | Morandi S., Cremonesi P., Ceccarani C., Cologna N., Goss A., Severgnini M., Mazzucchi M., Partel E., Castiglioni B., Tamburini A., Zanini L., Brasca M. | Lo scopo dello studio e stato quello di valutare l'influenza dell'uso di prodotti a base di cloro per la pulizia e la sanificazione delle attrezzature di mungitura sul latte crudo e del microbiota derivante dal siero nella produzione di Trentingrana. Trentingrana e un formaggio a pasta dura a denominazione di origine protetta (DOP) prodotto nelle valli della provincia di Trento (Alpi italiane orientali) da alcune piccole latterie cooperative collegate in un consorzio | 6? Congresso lattiero-caseario Aitel. Latte e derivati: ricerca, innovazione e valorizzazione, Trento, 20/09/2018 | 2018 | CECCARANI CAMILLA, CASTIGLIONI BIANCA MARIA ELISABETTA, BRASCA MILENA, SEVERGNINI MARCO, MORANDI STEFANO, CREMONESI PAOLA | Cloro, siero-innesto, metagenomica | |
| 400549 | Monografia o trattato scientifico | ARE THEY WORTH A SHOT? | Andrea Grignolio | The dangerous decline in vaccinations in many developed countries is at the heart of a lively debate that confirms how important the subject is today. Vaccinations are among mankind's most important scientific discoveries, yet they continue to be viewed with suspicion by part of the public - the victims of disinformation campaigns, instrumentalization and unfounded fears. There is, however, also an evolutionary explanation for these irrational beliefs, and countering the growing social opposition will be extremely difficult without grasping it. This book, which sheds new light on the safety and importance of vaccinations, is intended both for parents and those readers who want to understand the role of vaccinations in contemporary society, where the ease of access to knowledge is both a great opportunity and a great responsibility. The chapters follow a historical progression and conclude with a discussion of the most recent cognitive theories on how to overcome this opposition to vaccinations. | Basel: Springer Nature Switzerland, 2018 | 2018 | GRIGNOLIO ANDREA | Vaccini | |
| 400553 | Postfazione | "INTRODUZIONE". VOLUME DEDICATO A GIUSEPPE LEVI | Andrea Grignolio | Introduzione al Volume dedicato a Giuseppe Levi | GIUSEPPE LEVI: A BIBLIOGRAPHY, edited by Grignolio Andrea, pp. 9-14, 2018 | 2018 | GRIGNOLIO ANDREA | Giuseppe Levi | |
| 400596 | Postfazione | Why does medicine need rhetoric? Introduction to the issue on "Argumentation and Medicine" | Zagarella, Roberta Martina | Introduction to the issue on "Argumentation and Medicine" | "Argumentation and Medicine", pp. 1-4, 2018 | 2018 | ZAGARELLA ROBERTA MARTINA | Argumentation, Medicine | 10.4396/20180600 |
| 400604 | Curatela di numero monografico (di rivista o di collana) | Argumentation and medicine | Roberta Martina Zagarella | Argumentation theory, or "new rhetoric", focuses on our uses of language when a decision with an action in sight is at stake. Today, argumentation theory has proven particularly pertinent to the analysis of the role language plays in clinical practice and more generally in biomedicine - areas that increasingly involve individual choices regarding health and the body. The combination of rhetoric and medicine, however, is not a new one. The methodological affinities of the two disciplines constituted, in fact, a topos of ancient Greek thought, especially with regards to the ability of the rhetor and the physician to make good decisions; the constitutive possibility of deviating from pre-established, fixed paths by elaborating new hypotheses; as well as the importance of the individual case in both practices. The objective of this journal issue is to thematise the relationship between argumentation/rhetoric and medicine, by putting ancient tradition and the contemporary debate into dialogue. We hope to gather contributions from a variety of disciplines which will emphasise the key elements of this relationship. The interconnections between argumentation and medicine merit scrutiny from points of view that are diverse and complementary. On the one hand, this interdisciplinary approach will allow us to test a number of theoretical models of argumentation on an area of application that is less common than politics or law. Medicine entails ethically complex and continuously shifting individual situations, not least due to biomedical innovations. Furthermore, a juxtaposition of the two disciplines enables us to linger on some of their common epistemological traits, as well as on the status of proof; on the notions of credibility, trust, truth, and liberty; and finally on bioethical principles such as self-determination and autonomy. On the other hand, argumentation studies can offer tools for reflection on the era of post-paternalistic medicine, from a bioethical as well as biopolitical point of view. Moreover, a rhetorical or argumentative perspective can contribute to the contemporary need for what is called "high-quality communication" in the field of health. Finally, argumentation allows us to tackle - not only from a political, but also from a theoretical point of view - the issue of science's loss of credibility in the eyes of citizens, as seen, for instance, in the controversy over the safety and efficacy of vaccines; as well as to dissect the debate over fake news, post-truth and science communication. We welcome contributions that focus on: historical as well as theoretical reconstructions of the relationship between rhetoric and medicine; the role of persuasive language in contemporary medicine; the bioethical and biopolitical issues that underlie it; the discursive and decision-making processes that involve physicians and patients, including securing informed consent; the relationship between the word and the cure, or between discourse and biopower; the divulgation of science; the ways in which citizens understand, evaluate, and discuss medical information; the impact of fake news and the notion of post-truth. We will consider contributions which analyse the relationship between argumentation and medicine from diverse theoretical standpoints and disciplines, such as, but not limited to: argumentation theory; rhetoric; philosophy of language; linguistics; semiotics; history of ideas; bioethics; moral philosophy; philosophy of law; philosophy of science; medicine; psychoanalysis; psychology; neuroscience; sociology. | 2018 | 2018 | ZAGARELLA ROBERTA MARTINA | argumentation theory, rhetoric, medicine, bioethics | |
| 400608 | Rapporto tecnico | R1 - rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo, Cinzia Caporale | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n: 0032254/2018, 2018 | 2018 | CAPORALE CINZIA, ADAMO GIORGIA | Research integrity | |
| 400609 | Rapporto tecnico | R11 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0061896/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400610 | Rapporto tecnico | R12 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0016955/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400612 | Annual report | R13 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0016960/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400614 | Rapporto tecnico | R14 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0039081/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400615 | Rapporto tecnico | R15 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400616 | Rapporto tecnico | R23 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo, Cinzia Caporale | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0028546/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400617 | Rapporto tecnico | R36 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Adamo Giorgia | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0062334/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400618 | Rapporto tecnico | R37 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0039080/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400619 | Rapporto tecnico | R39 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0062341/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400620 | Rapporto tecnico | R40 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0062345/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400621 | Rapporto tecnico | R41 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0032907/2018, 2018 | 2018 | ADAMO GIORGIA | Research Integrity | |
| 400659 | Rapporto tecnico | R2 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0080220/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400660 | Rapporto tecnico | R3 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0080226/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400661 | Rapporto tecnico | R4 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0080229/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400663 | Rapporto tecnico | R5 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0080227/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400664 | Rapporto tecnico | R6 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0080222/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400665 | Rapporto tecnico | R7 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081631/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400666 | Rapporto tecnico | R8 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081022/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400667 | Rapporto tecnico | R9 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081025/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400668 | Rapporto tecnico | R10 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081030/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400669 | Rapporto tecnico | R16 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081044/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400670 | Rapporto tecnico | R17 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081063/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400671 | Rapporto tecnico | R18 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079146/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400672 | Rapporto tecnico | R19 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079196/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400673 | Rapporto tecnico | R20 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081067/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400674 | Rapporto tecnico | R21 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081060/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400675 | Rapporto tecnico | R22 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079192/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400676 | Rapporto tecnico | R24 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400677 | Rapporto tecnico | R25 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081052/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400678 | Rapporto tecnico | R26 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081058/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400679 | Rapporto tecnico | R27 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079181/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400680 | Rapporto tecnico | R28 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081040/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400681 | Rapporto tecnico | R29 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081628/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400682 | Rapporto tecnico | R30 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079177/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400683 | Rapporto tecnico | R31 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079186/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400684 | Rapporto tecnico | R34 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0079172/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400685 | Rapporto tecnico | R35 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0080218/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400686 | Rapporto tecnico | R38 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Giorgia Adamo | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0081038/2017, 2017 | 2017 | ADAMO GIORGIA | Research Integrity, Research Misconduct | |
| 400688 | Rapporto tecnico | R32 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Paola Grisanti | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0077229/2018, 2018 | 2018 | GRISANTI PAOLA | Research Integrity, Research Misconduct | |
| 400690 | Rapporto tecnico | R33 - Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Paola Grisanti | Rapporto tecnico relativo alla verifica di fabbricazione/falsificazione e/o plagio di dati, immagini e testi | Prot. n. 0077231/2018, 2018 | 2018 | GRISANTI PAOLA | Research Integrity, Research Misconduct | |
| 400881 | Recensione in rivista | Book Review "Capitali regionali" on Contemporary Italian Politics | ANTONUCCI M | | Bulletin of Italian politics 11 (2019): 104-105. | 2019 | ANTONUCCI MARIA CRISTINA | italian politics, regions, elections, political subcultures | 10.1080/23248823.2019.1577002 |
| 401902 | Monografia o trattato scientifico | Verita e cura. Dalla diagnosi al placebo, l'etica dell'inganno in medicina | Marco Annoni | Deve il medico dire sempre la verita ai pazienti? Oppure il dovere di veridicita dei medici puo essere sospeso quando la differenza tra bugia e verita equivale alla differenza tra la vita e la morte? E mai permissibile mentire in ambito clinico per compassione o per sfruttare i benefici dell'effetto placebo? E se si, come distinguere i casi in cui e moralmente giustificabile ingannare un paziente "a fin di bene" - e cioe, per ragioni paternalistiche - da quei casi in cui, invece, occorre essere onesti? Queste domande sono fondamentali per chiunque si trovi a prestare o ricevere delle cure perche "la verita" puo a volte segnare in modo indelebile il destino di una persona e di chi la assiste. Eppure, l'etica medica contemporanea ha finora dedicato scarsa attenzione a questa problematica cosi centrale. Se a cio si aggiunge che la formazione etica degli operatori sanitari e spesso inadeguata, e che i nostri giudizi morali tendono a essere intrinsecamente sbilanciati, esistono inoltre fondate ragioni per ritenere che ancora oggi i medici omettano e distorcano la verita ai pazienti molto piu di quanto essi stessi siano portati a credere e, sfortunatamente, anche piu di quanto sia eticamente giustificabile. In tale contesto, questo saggio propone e difende la teoria secondo cui il dovere di veridicita dei medici deve essere concepito come prima facie, e cioe come un dovere che occorre sempre rispettare a meno che cio non contrasti con il piu generale obbligo di prendersi cura del bene dei pazienti e a patto che si segua un processo di deliberazione morale adeguato. Perche la verita e sempre importante, ma non tutte le verita sono buone ai fini della cura, cosi come non tutti gli inganni sono necessariamente contrari al bene dei pazienti. | Pisa: Edizioni ETS, 2019 | 2019 | ANNONI MARCO ANGELO MARIA | Etica medica, Placebo, Bioetica | |
| 409080 | Sito web | www.gemma-project.eu | Matteo Gnocchi, Marco Moscatelli, Alessandra Mezzelani | Portale Scientifico del Progetto Europeo Gemma | 2019 | 2019 | MEZZELANI ALESSANDRA MARIA, GNOCCHI MATTEO, MOSCATELLI MARCO | Portale, Unione Europea, wordpress, Gemma-Project | |
| 409083 | Rapporto tecnico | GEMMA EU PROJECT INFRASTRUCTURE | Matteo Gnocchi, Marco Moscatelli, Alessandra Mezzelani | Descrizione della infrastruttura IT implementata nell'ambito del progetto europeo GEMMA | 2019 | 2019 | MEZZELANI ALESSANDRA MARIA, GNOCCHI MATTEO, MOSCATELLI MARCO | gemma-project | |
| 416885 | Editoriale in rivista | Latest advances in parallel, distributed, and network-based processing | I. Merelli, P. Lio, I. Kotenko, D. D'Agostino | | Concurrency and computation (Online) 32 (2020): e5683. | 2020 | D'AGOSTINO DANIELE, MERELLI IVAN | parallel computing, distributed computing, network-based computing | 10.1002/cpe.5683 |
| 323507 | Presentazione | Slow HCV kinetics following Sofosbuvir + Ribavirin administration in real-life setting of liver transplant recipients with severe recurrent hepatitis C | V. Cento, M.F. Donato, I. Lenci, M. Rendina, V.C. Di Maio, M. Milana, S. Monico, M. Aragri, R. Alfieri, A. Abedrabbo, D. Sforza, M. Manuelli, L. Mameli, M.C. Sorbo, R. Canu, M.L. Ponti, C. Chiala, F. Malinverno, S. Marenco, L. Milanesi, A. Picciotto, G. Rossi, A. Di Leo, G. Tisone, F. Zamboni, R. Ganga, M. Colombo, C.F. Perno1, M. Angelico, F. Ceccherini-Silberstein | None | Workshop on Innovation in HIV and Viral Hepatitis - Beyond viral undetectability: new frontiers and strategies, Milano, 26-27 gennaio 2013 | 2015 | ALFIERI ROBERTA, MILANESI LUCIANO | | |
| 344271 | Monografia o trattato scientifico | Detection of Foodborne Pathogens Using DNA Arrays | C. Consolandi, P. Cremonesi, M. Severgnini, B. Castiglioni | In this chapter, we report the main applications involving the use of DNA microarrays as detection tools for foodborne pathogen identification in food matrices. At first, we describe the most recent applications of microarray technology in foodborne detection, focusing on the experimental results obtained. Then, emerging platforms for the miniaturized detection of pathogens are discussed with the description of some interesting assays and innovative applications. A final paragraph will be dedicated to the latest developments and trends in the "omics" field applied to foodborne pathogen detection. | Amsterdam: Elsevier, 2015 | 2015 | CASTIGLIONI BIANCA MARIA ELISABETTA, CONSOLANDI CLARISSA, SEVERGNINI MARCO, CREMONESI PAOLA | Foodborne Pathogens, molecular diagnostics, array | |
| 348274 | Presentazione | Network analysis of genetic variations in Autism Spectrum Disorders | Ettore Mosca, Alessandra Mezzelani, Luciano Milanesi | Autism Spectrum Disorders (ASDs) are a group of neurodevelopmental disorders with a marked genetic heterogeneity [1]. Despite it is well established that ASDs have a strong genetic component, the underlying genetic cause is unknown in the majority of cases [2]. The use of genotyping and genome-sequencing technologies lead to the identification of hundreds of candidate genes, harbouring single nucleotide variations (SNVs) and copy number variations (CNVs). More recently, the integration of genetic data with molecular pathways and molecular interactions helped to propose hypotheses concerning the molecular circuits that have a key role in the pathogenesis [1-3]. The prediction of the effects of the perturbation of some elements in a complex system like the molecular interaction network is hard. However, several works have shown that genes in network proximity regulate similar biological functions and constitute disease modules, gene neighbourhoods associated with diseases [4]. In this study, we characterize the disease modules emerging from a network analysis of ASD associated genes. We collected gene evidences from several studies available in the literature and used network propagation, which simulates the diffusion of information throughout an interactome [5], to highlight the regions of the human protein-protein interaction network that are more strongly influenced by the genetic variations. Our approach provides a framework that will underline the functional relation between novel candidate genes and those "hot" network regions (modules of interacting genes) densely populated by ASD associated genes. References 1. A.S. Cristino, et al. Molecular Psychiatry (2014), 19, 294-301. 2. D. Pinto, et al. Nature (2010), 466, 368-372. 3. B.J. O'Roak, et al. Nature (2012), 485, 246-250. 4. S.D. Ghiassan, et al. PLOS Comput. Bio. (2015), 11 (4). 5. E. Mosca, et al., PLOS One (2014), 9 (12). | Bringing Maths to Life, 19-21/10/2015 | 2015 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, MOSCA ETTORE | Molecular Interaction Networks, Genetic Variations, Autism Spectrum Disorders | |
| 348287 | Poster | Propagation of hepatitis C virus effects throughout the host interactome reveals liver expression variations in the network proximity to Hepatitis C virus targets. | Roberta Alfieri, Ettore Mosca, Luciano Milanesi | Motivation Hepatitis C virus infection is one of the most common and chronic in the world, and hepatitis associated with HCV infection is a major risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). Known data on virus-host and host protein interactions enable network-based analyses of viral infection supported by omics data. The study of molecular interaction networks helps to elucidate the mechanistic pathways linking HCV molecular activities and the host response that modulates the stepwise hepatocarcinogenic process from preneoplastic lesions (cirrhosis and dysplasia) to HCC. Several studies have shown that network-based approaches lead to the identification of more robust markers and better stratifications of samples. However, it is still not clear whether acute and chronic effects of HCV activity can be explained according to a local impact hypothesis, i.e. in network proximity to host proteins targeted by viral proteins (HCV targets). We developed a computational approach to examine the relation between HCV targets, host protein-protein interaction (PPI) topology, pathways that regulate HCV response and the expression variations observed in preneoplastic and neoplastic lesions of liver cell samples from HCV-infected patients [1]. Methods We used the PPIs available in the STRING database v9.0 with score greater than 0.7, designated as ''high confidence''.We obtained a PPI network composed of a total of 14,116 unique human proteins involved in 223,088 PPIs. We used the viral-host interactions collected from De Chassey et al. (2008) [2], Kwofie et al. (2011) [3], Dolan et al. (2013) [4], HPIDB [5], Intact [6], VirHostNet [7] and defined 591 unique human proteins that interact directly with HCV proteins, 517 of which appear in the PPI network. We used network propagation algorithm [8] to smooth the HCV interaction information over the PPI network and to rank all the other proteins in relation to their network proximity to HCV targets in the PPI network. This method simulates a random walk on a graph with restarts. Two gene expression datasets collected from the Gene Expression Omnibus (GEO) database that are comparable in terms of histological characteristics (normal, cirrhotic and neoplastic tissues), viral infections (HCV) and microarray platform were used. The dataset GSE6764 [9] includes 75 samples from cirrhotic and neoplastic livers of 38 HCV-infected patients and healthy livers of 10 patients. The dataset GSE14323 [10] includes 108 samples from cirrhotic, neoplastic and normal tissues from 88 HCV-infected patients and 19 HCV seronegative patients. The raw data of the two datasets were separately processed and analyzed using the statistical software R. We considered as differentially expressed the genes with p-value < 0.05. The statistical significance of the overlap between each pair of protein lists was calculated using the hypergeometric distribution. The GSEA (Gene Set Enrichment Analysis) of HCV targets and differentially expressed genes was carried out using the R package HTSanalyzeR. The search of PPIs subnetworks in (i) network proximity to HCV targets and (ii) differentially expressed was formulated as the multi-objective optimization problem of minimizing two objective functions. We solved this problem using an evolutionary algorithm that creates a population of subnetworks extracted from the whole PPI network and, then, iteration by iteration, modifies the subnetworks (adding and removing vertexes) in order to minimize simultaneously the objective functions. Results In this work we ranked the host proteins in relation to their network proximity to viral targets by simulating the impact of HCV-host molecular interactions throughout the host protein-protein interaction (PPI) network. We observed that the set of proteins in the neighborhood of HCV targets in the host interactome is enriched in key players of the host response to HCV infection. We described the use of network propagation for predicting the host proteins that are in a relevant position of the PPI network on the basis of HCV-host interactions and show that network propagation successfully prioritizes proteins that are involved in the host response to HCV. Subsequently, we showed that networks of proteins "guilt-by-association" with HCV are significantly enriched in genes differentially expressed in cirrhotic samples compared to normal samples and in hepatocellular carcinoma compared to cirrhosis. These subnetworks contain established, recently proposed and novel candidate proteins for the regulation of the mechanisms of host response to acute and chronic HCV infection. REFS [1] Mosca E, Alfieri R, Milanesi L (2014) Diffusion of Information throughout the Host Interactome Reveals Gene Expression Variations in Network Proximity to Target Proteins of Hepatitis C Virus. PLoS ONE 9(12): e113660. [2] de Chassey B, Navratil V, Tafforeau L, Hiet MS, Aublin-Gex A, et al. (2008) Hepatitis C virus infection protein network. Mol Syst Biol 4: 230. [3] Dolan PT, Zhang C, Khadka S, Arumugaswami V, Vangeloff AD, et al. (2013) Identification and comparative analysis of hepatitis C virus-host cell protein interactions.t. Mol Biosys 9: 3199-3209. [4] Kwofie SK, Schaefer U, Sundararajan VS, Bajic VB, Christoffels A (2011) HCVpro: hepatitis C virus protein interaction database. Infect Genet Evol 11: 1971-1977. [5] Kumar R, Nanduri B (2010) HPIDB-a unified resource for host-pathogen interactions. BMC Bioinformatics. Suppl 6: S16. [6] Hermjakob H, Montecchi-Palazzi L, Lewington C, Mudali S, Kerrien S, et al. (2004) IntAct: an open source molecular interaction database. Nucleic Acids Res 32: D452-D455. [7] Navratil V, de Chassey B, Meyniel L, Delmotte S, Gautier C, et al. (2009) VirHostNet: a knowledge base for the management and the analysis of proteome-wide virus-host interaction networks. Nucleic Acids Res 37: D661-D668. [8] Vanunu O, Magger O, Ruppin E, Shlomi T, Sharan R (2010) Associating genes and protein complexes with disease via network propagation. PLoS Comput Biol 6: e1000641 [9] Wurmbach E, Chen YB, Khitrov G, Zhang W, Roayaie S, et al. (2007) Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology 45: 938-947. [10] Mas VR, Maluf DG, Archer KJ, Yanek K, Kong X, et al. (2009) Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med 15: 85-94. | Twelfth Annual Meeting of the Bioinformatics Italian Society, 3-5/06/ 2015 | 2015 | ALFIERI ROBERTA, MILANESI LUCIANO, MOSCA ETTORE | Molecular Interaction Networks, Gene Expression, Hepatitis Virus C, Hepatocellular Carcinoma | |
| 348292 | Poster | Identification of disease modules through network diffusion and integration of genome-wide datasets. | Ettore Mosca (1), Matteo Bersanelli (2), Gastone Castellani(2), Luciano Milanesi(1) | MOTIVATION. Integrative analyses of multi-layer datasets are required to draw a more comprehensive view of biological processes and the development of tools for the integration of different layers of biological information is one of the major challenges for computational scientists. Molecular interactions data, even if are still incomplete, provide a useful framework for integrative analysis of genome-wide data, and precious insights on molecular mechanisms that can be modulated by therapeutic strategies [Berger et al. 2013]. We describe a computational approach that take advantage of diffusion processes on networks in order to highlight disease modules from the integrative analysis of multiple omics datasets. METHODS. We use the network propagation (NP) algorithm [Vanunu et al. 2010] for smoothing genome-wide data of each sample. NP simulates a random walk with restarts on a network and can be seen as the discrete form of an open "source-sink" dynamical system in which particles of fluid diffuse throughout the network. After convergence, the stationary distribution of fluid remaining on the network depends mainly on initial distribution and network topology. We define pathway scores as the sum of the smoothed information detected in pathway components and scale pathway scores through a robust standardization that enables the direct comparison among pathways of different size (from 5 to 500 elements). We calculate two-classes statistics for genes and pathways using SAM (significance analysis of microarrays) [Tusher et al. 2001]. We use the Jaccard coefficient to define the similarity between pathways. We extract significant subnetworks from a graph (weighted with statistics) using search heuristics based on the calculation of the minimum-spanning-tree and genetic algorithms [Mosca et al. 2013]. We use the collection of pathways provided by the NCBI Biosystems database and protein interaction data from STRING, NCBI Interactions, the human interactome project and predictions by FPCLASS. RESULTS. We used network propagation to diffuse genome-wide information on the basis of the protein interaction network. This analysis redefines genome-wide statistics on the basis of the considered topology and calculates the regions of the network highly influenced by the most significant variations. We used a simulated dataset to study the possible initial distributions of information on nodes of a scale-free graph that lead to network smoothed statistics well separated from what is expected from random initial distributions. Initial conditions enriched with hubs and neighbouring proteins lead to significant steady states that enables the identification of disease modules. We used network smoothed scores, obtained from network smoothing of single nucleotide variations and differential expression, to calculate gene-wise and pathway-based differential scores between two classes of samples. We extracted the sub-network of genes and sub-network of pathways with the highest scoring statistics. The former summarizes the module of genes that represent the region of the interactome that is highly affected by molecular variations, while the latter provides a "higher-level" view of the relations among the biological processes regulated by the gene module. Lastly, we defined an integrative disease module that combines the finding in each of the two omics layers, mapping each module on the same protein interaction network. We repeated the network-based analysis using four protein interaction networks. We found genes and pathways shared by multiple interactomes, but also interactome-specific results, which reflect the significant differences among the available protein interaction networks. Preliminary results show that our network-based strategy identified a module of genes involved in biological processes that regulate lipid metabolism, when applied for studying the genetic variations and gene expression differences in obese and normal individuals. REFERENCES. Berger B, Peng J, Singh M. Computational solutions for omics data. Nature reviews Genetics. 2013;14(5):333-346. doi:10.1038/nrg3433. Mosca E, Milanesi L (2013) Network-based analysis of omics with multi-objective optimization. Molecular BioSystems 9, 2971-2980. Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response. PNAS 98 (9) 5116-5121. Vanunu O, Magger O, Ruppin E, Shlomi T, Sharan R (2010) Associating Genes and Protein Complexes with Disease via Network Propagation. PLoS Comput Biol 6(1): e1000641. | Twelfth Annual Meeting of the Bioinformatics Italian Society, 03-05/06/2015 | 2015 | MILANESI LUCIANO, MOSCA ETTORE | Molecular Interaction Networks, Network diffusion, Omics, Disease Module | |
| 356204 | Rapporto di ricerca (Research report) | Relazione Scientifica Progetto Invecchiamento - Sotto-progetto GOJI - periodo 01/04/2014 - 31/12 2014 | ITIA: M. Sacco, L. Greci, C. Redaelli, , A. Zangiacomi, S. Arlati, L. Fontana, ITB: M. Musicco, F. Adorni, F. Prinelli, S. Di Santo, IBFM: M. Marzorati, A. Vezzoli, G. Rizzo, IMM: A. Leone, A. Caroppo. | Relazione scientifica Progetto Invecchiamento - Sottoprogetto GOJI - periodo 1 | 2015 | 2015 | DI SANTO SIMONA GABRIELLA, PRINELLI FEDERICA, CAROPPO ANDREA, ARLATI SARA, SACCO MARCO, VEZZOLI ALESSANDRA, ZANGIACOMI ANDREA, RIZZO GIOVANNA, MARZORATI MAURO, GRECI LUCA, LEONE ALESSANDRO, REDAELLI CLAUDIA, ADORNI FULVIO DANIELE, MUSICCO MASSIMO | demenza, training, virtuale | |
| 356213 | Rapporto di ricerca (Research report) | Relazione Scientifica Progetto Invecchiamento - Sotto-progetto GOJI - periodo 01/01/2015 - 30/09/2015 | ITIA: M. Sacco, L. Greci, C. Redaelli, , A. Zangiacomi, S. Arlati, L. Fontana, ITB: M. Musicco, F. Adorni, F. Prinelli, S. Di Santo, N. Jesuthasan, IBFM: M. Marzorati, A. Vezzoli, G. Rizzo, IMM: A. Leone, A. Caroppo | Il progetto mira a definire un programma di prevenzione per l'insorgere della demenza negli anziani con lievi disordini cognitivi probabilmente dovuti a malattie neurodegenerative. E stata arruolata una coorte di persone di 65 anni o piu con iniziale decadimento cognitivo lieve; questa coorte e stata indagata in relazione alla presenza di caratteristiche identificate come possibili fattori di rischio di progressione verso la demenza, sulla cui base e stato sviluppato il programma di prevenzione mirata globale, sviluppando due ambiente virtuale (VE) collegati (un ambiente per la navigazione attraverso cicloergometro e un supermercato virtuale) come strumento finalizzato alla stimolazione fisica e cognitiva e di attivita da realizzare all'interno di un ampio programma di prevenzione della demenza nelle persone con disturbi cognitivi lievi. In attesa dell'approvazione del comitato etico per la partenza della sperimentazione con la popolazione campione prescelta si e provveduto alla validazione degli ambienti dal punto di vista funzionale e delle interfacce. | 2015 | 2015 | DI SANTO SIMONA GABRIELLA, PRINELLI FEDERICA, CAROPPO ANDREA, JESUTHASAN NITHIYA, ARLATI SARA, SACCO MARCO, VEZZOLI ALESSANDRA, ZANGIACOMI ANDREA, RIZZO GIOVANNA, MARZORATI MAURO, GRECI LUCA, LEONE ALESSANDRO, REDAELLI CLAUDIA, ADORNI FULVIO DANIELE, MUSICCO MASSIMO | demenza, training, virtuale | |
| 358534 | Monografia o trattato scientifico | Da advocacy a trasparenza. Glossario sulla rappresentanza e la partecipazione del terzo settore | ANTONUCCI M | Glossario ragionato di 24 voci sui temi della partecipazione e della rappresentanza degli enti di terzo settore, alla luce delle recenti trasformazioni apportate dalla L. 106 del 2016 (cd "riforma terzo settore"). | 2016 | 2016 | ANTONUCCI MARIA CRISTINA | terzo settore, partecipazione, rappresentanza, lobbying | |
| 359631 | Poster | Visualization and data exploration of Community Biodiversity in a phylo-geospatial context | Saverio Vicario, Francesco Paolo Lovergine, Giacinto Donvito, Bachir Balech, Anna Sandionigi, Palma Blonda | The study of biodiversity requires the ability to explores a plurality of genomic and/or observational data under a geospatial, phylogenetic and temporal frameworks. Diversity expressed as the exponential of Shannon Entropy the selected measure unit for this exploration. Building on Chao et al. 2010 entropy was generalized to take in account that entity are differently different following a rooted phylogenetic structure and the contribution to alpha and beta diversity of each node was estimated (Sandionigi et al. 2014). Alpha and Beta diversity contribution was parsed also by sampling locations and exposed in a GEO compliant web services (WPS 1.0 ) that expose GEO compliant file format. The tool presented is a synthesis from previous work on biodiversity analysis services in FP7 project BioVeL by CNR-ITB, IBBE and INFN and word done in the Group of Earth Observation done by CNR-ISSIA and algorithm development by CNR-ITB and ZooPlant lab. | NETTAB & IB, Bari, 2015 | 2015 | VICARIO SAVERIO, BALECH BACHIR, LOVERGINE FRANCESCO, BLONDA PALMA NICOLETTA | biodiversity, geospatial | |
| 359842 | Abstract in atti di convegno | The structure, synthesis and role of neuromelanins in brain aging and neurodegeneration | Zecca L., Cebrian C., Mauri P., Isaias I., Casella L., Zucca F.A., Sulzer D. | None | PanAmerican Society for Pigment Cell Research - PASPCR Conference 2015, Orange, California, USA, 27-30/09/2015. | 2015 | ZUCCA FABIO ANDREA, ZECCA LUIGI, MAURI PIETRO LUIGI | neuromelanin, synthesis | |
| 359843 | Abstract in atti di convegno | Protective and toxic role of neuromelanin in brain aging and Parkinson's disease | Zecca L., Isaias I.U., Casella L., Sulzer D., Zucca F.A. | None | Dopamine 2016, Campus of the University of Vienna, Vienna, Austria, 5-8/09/2016 | 2016 | ZECCA LUIGI, ZUCCA FABIO ANDREA | neuromelanin, parkinson disease | |
| 359848 | Poster | Neuromelanin-sensitive MRI as a proxy-measure of dopamine function in neuropsychiatric illness. | Cassidy C., Zecca L., Ferrari E., Zucca F.A., Weinstein J., Baker S., Benavides C., Kang U., Sulzer D., Abi-Dargham A., Horga G. | Neuromelanin-sensitive MRI as a proxy-measure of dopamine function in neuropsychiatric illness. | Dopamine 2016, Campus of the University of Vienna, Vienna, Austria, 5-8/09/2016 | 2016 | FERRARI EMANUELE, ZECCA LUIGI, ZUCCA FABIO ANDREA | neuromelanin, MRI, dopamine, neuropsychiatric illness | |
| 359850 | Poster | Application of Pump-Probe Imaging Towards Chemical and Structural Characterization of Neuromelanin. | Deb S., Ferrari E., Zucca F.A., Zecca L., Warren W.S. | Application of Pump-Probe Imaging Towards Chemical and Structural Characterization of Neuromelanin. | World Molecular Imaging Congress (WMIC) 2016, New York, NY, USA, 7-10/09/2016 | 2016 | FERRARI EMANUELE, ZECCA LUIGI, ZUCCA FABIO ANDREA | Pump-Probe Imaging, neuromelanin | |
| 359856 | Poster | The role of neuromelanins in the oxidative stress of Parkinson's disease. | Zecca L, Isaias I, Casella L, Capucciati A, Ferrari E, Horga G, Cassidy C, Sulzer D, Zucca FA | The role of neuromelanins in the oxidative stress of Parkinson's disease. | Xth International Workshop on EPR in Biology and Medicine, Krakow, Poland, 2-6/10/2016 | 2016 | FERRARI EMANUELE, ZECCA LUIGI, ZUCCA FABIO ANDREA | neuromelanin, oxidative stress, parkinson disease | |
| 368915 | Presentazione | Macronutrients intake in adulthood and risk of dementia in old age: a 20-years follow-up Italian study | Prinelli, F., Adorni, F., Leite, L. Correa, Musicco, M. | Objectives: A high caloric intake has been associated with an increased risk of cognitive decline. Macronutrients are the main determinants of total caloric intake, thus aim of this study was to investigate the association between daily energy intake derived from carbohydrates, proteins and fats in relation to the risk of dementia. Materials and Methods: This is a prospective cohort study on a population of residents (n = 1604) in two districts of Northern Italy aged 40-74 years old who were examined about dietary habits and other lifestyles during the period 1991-5. Dietary habits were assessed by means of a 158-item food frequency questionnaire at baseline. Occurrence of Alzheimer' Disease (AD) and Vascular/other forms of Dementia (VaOD) were ascertained using Regional Health Registries. The proportion of daily energy intake (calories) derived from carbohydrates (%), proteins (%) and fats (%) was calculated and participants were ranked as "low" and "high" intake. Cox models were used to assess the associations between % macronutrients and incident AD and VaOD adjusting for potential confounders. Results: During a median of 18.6 years of followup, 73 incident dementia cases had occurred (39 AD and 34 VaOD). In the fully adjusted models the risk of AD was signifi cantly increased in people with high % carbohydrates (HR 2.45, 95%CI 1.08-5.57) but was reduced in those with high % fats (HR 0.34, 95%CI 0.16-0.71) and high % proteins (HR 0.78, 95%CI 0.38-1.60). The risk of VaOD was elevated in subjects with high % fats (HR 1.77, 0.79-3.95) but was decreased in persons with high % protein intake (HR 0.49, 95%CI 0.22-1.08) even though the estimates did not reach the signifi cance. No association with % carbohydrates was observed. Discussion: High % carbohydrates and low % proteins and fats were associated with an increased risk of AD whereas low % proteins and high % fats increased the risk of VaOD in our cohort. A possible explanation might reside in the food sources. Olive oil, rich in monounsaturated fatty acids, was the main source of fats in AD subjects. Persons who developed VaOD had a high intake of lard and margarine, rich in saturated and trans-unsaturated fatty acids. Regarding carbohydrates, subjects with AD had a higher intake of foods with high glycemic index than individuals with VaOD. Conclusion: Our data suggest that certain dietary choices and habits in adulthood can play a key role in the prevention of AD and dementia in old age. | XI CONVEGNO NAZIONALE SINDEM SOCIETA ITALIANA DEMENZE, pp. S7-S8, Firenze, 17-19/03/2016 | 2016 | PRINELLI FEDERICA, ADORNI FULVIO DANIELE, CORREA LEITE MARIA LEA, MUSICCO MASSIMO | Dementia, epidemiology, prevention, alimentary habits | |
| 380163 | Poster | Identification of incident dementia with a case passive follow-up in a cohort of 1693 subjects in Northern Italy: reliability of a classification algorithm querying the health information system | Adorni, F., Prinelli, F., Musicco, M. | Health Informative Systems constitute a powerful resource to produce epidemiological results from large scale population-based studies. Scientifi c literature reports an increasing number of studies investigating through their use different health outcomes. Aim of this study was to evaluate the reliability of an algorithm in identifying Dementia cases from Health Information System of ASLMi1 (HIS-Mi1) by comparing the observed incidence with the expected in the general European population (EuroDem) | XI Convegno Nazionale SINDEM, pp. S33-S33, Firenze (Italy), 17-19/03/2016 | 2016 | ADORNI FULVIO DANIELE, PRINELLI FEDERICA, MUSICCO MASSIMO | Classification Algorithm, Dementia, Health Information System | |
| 409554 | Poster | Raw milk microbiota modifications as affected by different cleaning procedures: the Trentingrana case. Interbational Conference on raw milk. | Battelli G., Cremonesi P., Ceccarani C., Cologna N., Goss A., Severgnini M., Mazzucchi M., Partel E., Morandi S., Castiglioni B., Tamburini A., Zanini L., Brasca M. | x | International conference on raw milk., Valencia, Spain, 24-25/10/2019 | 2019 | CECCARANI CAMILLA, BATTELLI GIOVANNA, CASTIGLIONI BIANCA MARIA ELISABETTA, BRASCA MILENA, SEVERGNINI MARCO, MORANDI STEFANO, CREMONESI PAOLA | raw milk, cheese, microbiome, sanitizing products | |
| 396211 | Poster | Confronto tra la biodiversita del microbioma del latte delle razze Frisona Italiana e Rendena | Paola Cremonesi1, Camilla Ceccarani2, 3, Giulio Curone4, Marco Severgnini2, Claudia Pollera4, Valerio Bronzo4, Federica Riva4, Maria Filippa Addis4, Joel Filipe4, Massimo Amadori5, Erminio Trevisi6, Daniele Vigo4, Paolo Moroni4, 7, Bianca Castiglioni1 | Il periodo del periparto rappresenta una delle fasi piu critiche per la salute delle mammelle nei bovini, specialmente nelle razze altamente produttive, come la Frisona Italiana, mentre alcune razze autoctone, come la Rendena (REN), attualmente diffusa maggiormente nelle province di Padova, Trento, Vicenza e Verona, hanno una prevalenza inferiore di mastite o di altre malattie. In questo studio abbiamo pertanto confrontato il microbiota del latte di 6 vacche di razza Frisona Italiana con quello di 3 animali di razza Rendena, allevati tutti nello stesso luogo e con le stesse condizioni, allo scopo di definire la prevalenza d quei gruppi batterici che potrebbero avere un effetto sulla salute della ghiandola mammaria. Sono stati considerati quattro punti temporali (asciutta, 1 giorno dopo il parto, 7-10 giorni dopo il parto e 30 giorni dopo il parto). Abbiamo caratterizzato, attraverso il sequenziamento del gene rRNA 16S, il microbioma di 117 campioni di latte raccolti durante il periodo sperimentale soltanto dai quarti sani con una conta delle cellule somatiche (SCC) inferiore a 200.000 cellule / ml. Le popolazioni microbiche presenti nel latte delle due razze sono risultate profondamente diverse in tutto il periodo, con il latte della razza Rendena che mostrava una biodiversita microbica significativamente piu bassa. I profili tassonomici di entrambe le razze cosmopolite e locali erano dominati dai Firmicutes, per lo piu rappresentati dal genere Streptococcus, sebbene in proporzioni molto diverse (27,5 nella razza Frisona, 68,6% nella razza Rendena). Infine, solo il latte delle bovine di razza Frisona ha mostrato cambiamenti significativi nella composizione microbica durante il periodo di transizione, mentre il latte della razza Rendena ha mantenuto un microbiota piu stabile. In conclusione, le significative differenze riscontrate nel microbioma del latte delle due razze potrebbero anche avere un impatto sulla salute della ghiandola mammaria, oltre ad un'influenza sulle caratteristiche finali dei prodotti caseari delle due razze. | 6? Congresso lattiero-caseario Aitel. Latte e derivati: ricerca, innovazione e valorizzazione, Trento, 20/09/2018 | 2018 | CECCARANI CAMILLA, CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA | microbioma, latte, bovina | |
| 368017 | Software | dmfind - Network diffusion-based analysis of omics for the identifcation of differentially enriched modules. | Ettore Mosca, Matteo Bersanelli, Luciano Milanesi | The software implements the methods described in Bersanelli M*, Mosca E*, Remondini D, Castellani G, Milanesi L, Sci Rep. 2016 Oct 12;6:34841. doi: 10.1038/srep34841. | 2016 | 2016 | MILANESI LUCIANO, MOSCA ETTORE | Biological Networks, omics technologies, network medicine, gene module | |
| 400632 | Traduzione in rivista | Early gut microbiota signature of aGvHD in children given allogeneic hematopoietic cell transplantation for hematological disorders | Elena Biagi 1, Daniele Zama 2, Simone Rampelli 1, Silvia Turroni 1, Patrizia Brigidi 1, Clarissa Consolandi 3, Marco Severgnini 3, Eleonora Picotti 2, Pietro Gasperini 2, Pietro Merli 4, Nunzia Decembrino 5, Marco Zecca 5, Simone Cesaro 6, Maura Faraci 7, Arcangelo Prete 2, Franco Locatelli 4, Andrea Pession 2, Marco Candela 1, Riccardo Masetti 2 | Background The onset of acute Graft-versus-Host Disease (aGvHD) has been correlated with the gut microbiota (GM) composition, but experimental observations are still few, mainly involving cohorts of adult patients. In the current scenario where fecal microbiota transplantation has been used as a pioneer therapeutic approach to treat steroid-refractory aGvHD, there is an urgent need to expand existing observational studies of the GM dynamics in Hematopoietic Stem Cell Transplantation (HSCT). Aim of the present study is to explore the GM trajectory in 36 pediatric HSCT recipients in relation to aGvHD onset. Methods Thirty-six pediatric patients, from four transplantation centers, undergoing HSCT were enrolled in the study. Stools were collected at three time points: before HSCT, at time of engraftment and > 30 days following HSCT. Changes in the GM phylogenetic structure were studied by 16S rRNA gene Illumina sequencing and phylogenetic assignation. Results Children developing gut aGvHD had a dysbiotic GM layout before HSCT occurred. This putative aGvHD-predisposing ecosystem state was characterized by (i) reduced diversity, (ii) lower Blautia content, (iii) increase in Fusobacterium abundance. At time of engraftment, the GM structure underwent a deep rearrangement in all patients but, regardless of the occurrence of aGvHD and its treatment, it reacquired a eubiotic configuration from day 30. Conclusions We found a specific GM signature before HSCT predictive of subsequent gut aGvHD occurrence. Our data may open the way to a GM-based stratification of the risk of developing aGvHD in children undergoing HSCT, potentially useful also to identify patients benefiting from prophylactic fecal transplantation. | BMC medical genomics (2019). | 2019 | CONSOLANDI CLARISSA, SEVERGNINI MARCO | Gut microbiota Hematopoietic stem cell transplantation Acute graft-versus-host disease Alloreactivity 16S rRNA gene sequencing Pediatric patients | |
| 402332 | Editoriale in rivista | The 2017 Network Tools and Applications in Biology (NETTAB) workshop: aims, topics and outcomes | P. Romano, A. Ceol, A. Drager, A. Fiannaca, R. Giugno, M. La Rosa, L. Milanesi, U. Pfeffer, R. Rizzo, S.Y. Shin, J. Xia, A. Urso | | BMC bioinformatics 20 (2019). | 2019 | RIZZO RICCARDO, URSO ALFONSO, MILANESI LUCIANO, FIANNACA ANTONINO, LA ROSA MASSIMO | NETTAB 2017 | 10.1186/s12859-019-2681-0 |
| 389321 | Abstract in rivista | Feasibility of shotgun urinary proteomics for investigating prematurely born preschoolers (PBP) | Pierluigi Mauri, Rossana Rossi, Antonella De Palma, Rosalia Paola Gagliardo, Velia Malizia, Giovanna Cilluffo, Giuliana Ferrante, Sabrina D'Arpa, Stefania La Grutta | None | European respiratory journal (Online) (2016). | 2016 | MALIZIA VELIA, CILLUFFO GIOVANNA, GAGLIARDO ROSALIA PAOLA, LA GRUTTA STEFANIA, MAURI PIETRO LUIGI | Proteomics, Preterm | |
| 405968 | Poster | Effect of the use of chlorine usage in milking equipment cleaning procedures on raw milk microbiota | Cremonesi P, Morandi S, Ceccarani C, Cologna N, Goss A, Severgnini M, Mazzucchi M, Partel E, Castiglioni B, Tamburini A, Zanini L, Brasca M | Background: Sodium hypochlorite (NaClO) is generally used for disinfection of milking equipment ensuring milk hygienic quality. Different studies showed that the chlorine can affect milk microbial population, encouraging the comprehension of the relationship between the use of chlorine products and milk microbiota, which represents a key point for raw milk cheese production. Objectives: The aim of the study was to evaluate the influence of NaClO on raw milk microbiota and the deriving whey-starter bacterial composition in Trentingrana PDO cheese production. Methods: Three farms were involved in the study. Milk was collected thrice weekly during the NaClO usage (six-weeks period, C) and in a subsequent, analogous, nonchlorine detergent period (NC). Fourweeks interval was established between the two experimental periods. The deriving whey-starter was sampled too. Samples were submitted to microbiological analyses (Standard Plate Count, coliforms, staphylococci, Lactic Acid Bacteria) and to metagenomic analysis. To this aim, 16S rRNA gene (V3-V4 region) was sequenced by Illumina MiSeq platform. Data analyses were performed with QIIME pipeline. Results: No significant differences were observed but higher SPC and LAB counts were recorded in milk going from period C to period NC. The metagenomic analysis of milk showed a distinctive microbiota composition for the three farms during the whole experimental period, moreover we evidenced a significant difference in microbial population related to chlorine use. The use of chlorine was found to affect the whey-starter population; Lactobacillus helveticus was predominant during period C and significantly reduced during period NC, whereas Lb. delbrueckii had the exact opposite trend. | 8th Congress of European Microbiologist (FEMS), pp. 1569-1569, Glasgow (UK), 7-11/07/2019 | 2019 | CECCARANI CAMILLA, CASTIGLIONI BIANCA MARIA ELISABETTA, BRASCA MILENA, SEVERGNINI MARCO, MORANDI STEFANO, CREMONESI PAOLA | Chlorine, Raw milk, Whey culture, milking equipment, Trentingrana | |
| 406069 | Abstract in atti di convegno | Comparison among four different bacterial DNA extraction protocols for analysing milk metagenomics | Paola Cremonesi1, Marco Severgnini2, Alicia Romano3, 4, Mario Luini3, Bianca Castiglioni1 | Bovine udder is colonized by a huge number of microorganisms that constitute the intramammary ecosystem, with a specific role in modulating not only the udder homeostasis and mastitis susceptibility but also the quality of the dairy products. Therefore, information on milk microbiota composition will facilitate the dairy industry in the production of safe and high-quality products. However, generating high-quality bacterial DNA could be critical. In the present study, bacterial DNA from healthy milk samples was isolated by four different protocols to evaluate the effect of the extraction procedures on milk microbiota composition. For the characterization of the milk microbiota by 16S deep sequencing, 500 ml of bulk tank milk samples were aseptically collected from three different farms and bacterial DNA was extracted by using an internal laboratory protocol and three commercial kits. Bacterial DNA was then amplified using the primers for the V3-V4 hypervariable regions and sequenced in one MiSeq (Illumina) run with 2x250-base paired-end reads. Data analysis was performed by using QIIME suite and SILVA 132 as reference database for taxonomy. The results showed that the four extraction kits performed very differently and showed a significant separation on both microbial richness (alpha-diversity) and composition (beta-diversity). In particular, the relative abundance of some genera (e.g.: Lactobacillus, Acinetobacter and Microbacterium) were consistently altered by the extraction method. Based on these data, then, particular attention must be kept in choosing the proper extraction method, for example, carefully evaluating eventual biases towards or against bacterial genera of interest. Moreover, we believe that, in order to define which kit best resembles the original bacterial community, an additional set of experiments with a mock community with known composition should be performed. | 23? Congresso dell'Associazione per la Scienza e le Produzioni Animali (ASPA), Sorrento, Italy, 11/06/2019, 14/06/2019 | 2019 | CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA | bovine milk, DNA extraction, milk microbiome | 10.1080/1828051X.2019.1622269 |
| 406138 | Abstract in atti di convegno | NeoHiC: a web application for the analysis of Hi-C data | D. D'Agostino, I. Merelli, M. Aldinucci, P. Lio | High-throughput sequencing Chromosome Conformation Capture (Hi-C) allows the study of chromatin interactions and 3D chromosome folding on a larger scale. A graph-based representation of Hi-C data is very important for a proper visualization of the spatial pattern they represent, in particular for comparing different experiments or for re-mapping omics-data in a space-aware context. But the size of these graphs can be very large, and this prevents the straightforward use of current available graph visualization tools and libraries. In this paper, we present the first version of NeoHIC, a web application for the progressive graph visualization of Hi-C data based on the use of the Neo4j graph database. | Computational Intelligence methods for Bioinformatics and Biostatistics (CIBB 2019), pp. 29-32, Bergamo, Italy, 4-6/9/2019 | 2019 | D'AGOSTINO DANIELE, MERELLI IVAN | Hi-C, graph databases, web application, graph visualization | |
| 411298 | Poster | Dual Therapy with Darunavir/rtv Plus Rilpivirine QD versus Triple Therapy in Patients with Suppressed Viraemia: Evaluation of Virological Efficacy and Non-HIV Related Morbidity at 48 Weeks | S. Rusconi, V. Di Cristo, F. Adorni, R. Maserati, M. Annovazzi Lodi, N. Ladisa, P. Maggi, A. Volpe, P. Vitiello, C. Abeli, S. Bonora, M. Ferrara, M.V. Cossu, E. Colella, M. Galli | Objectives: The DUAL study is a phase III, randomized, open-label, multicenter, 96 weeks-long pilot study in virologically suppressed HIV-1+ patients with the aim of evaluating the efficacy and the impact on non-HIV related morbidity of switching to a dual therapy with darunavir-ritonavir (DRV/r) and rilpivirine (RPV). Methods: We recruited patients who received a PI/r-containing HAART for >=6 months, HIV-RNA< 50 cp/mL for >=3 months, eGFR>60 mL/min/1,73m2, without DRV or RPV RAMs. We randomized patients in arm A: RPV+DRV/r QD or arm B: triple therapy. Primary endpoint: percentage of patients with HIV-RNA< 50 cp/mL at week 48 (ITT). VACS index, Framingham CVD risk (FRS) and urinary RBP were calculated. We used Chi-square or Fisher statistics for categorical variables and Mann-Whitney U for continuous ones. Results: Forty-two patients were enrolled (23 in arm A, 14 in arm B, plus 5 screening failures): 26 patients reached 48 weeks: 17/17 had HIV-RNA< 50 cp/mL in arm A versus 8/9 in arm B (Figure). One patient in arm A showed detectable HIV-RNA at baseline (955 cp/mL), reported scarce adherence and was discontinued at week 4. Similar changes were observed in median CD4/mL between baseline and week 48 (-14 versus -116, p n.s.). Thirty-one in arm A and 20 in arm B adverse events took place, whereas only 1 serious (arm A, unrelated to HAART). Among the 7 discontinuations (4 in A, 3 in B), only 1 was related to adverse event (arm A: G3 depression, insomnia, weakness). The tolerability parameters (FRS, VACS index, uRBP) did not vary from baseline to week 48. | 16th European AIDS Conference, Milan, Italy, 25-27 October 2017 | 2017 | ADORNI FULVIO DANIELE | Antiretroviral therapy, HIV, Clinical trial, Efficacy, Safety | |
| 412873 | Abstract in atti di convegno | Biotic stress trigger plant endogenous short non-coding RNAs that regulate components of photosynthetic machinery | Leonetti P., Gazemzadeh A., Gursinsky T., Consiglio A., Behrens S.E., Pantaleo V. | A massive and diverse population of short non-coding (s)RNAs accumulates in plant tissues. sRNAs drive RNA silencing-based gene repression. Besides their role in tissue and organ development, differentiation and in the maintenance of genome integrity, sRNA play crucial roles in host response to a wide range of environmental conditions, including biotic stresses. By image data augmentation technique, we have selected Brassica rapa (turnip) and B. napus (canola) plant tissues infected by cauliflower mosaic virus (CaMV) showing mosaic and yellowing symptoms. sRNA populations associated to CaMV-infected tissues of the two crops were characterized by sequencing and bioinformatics and compared with those from the model pathosystem CaMV-Arabidopsis. We revealed orthologues genes producing endogenous sRNAs shared out among turnip, canola and Arabidopsis. In the three plant species, the majority of these siRNAs were from protein coding genes encoding components of the photosynthetic machinery, such as LHCB1.3, LHCB1.4, LHCA1, and FBA1. By quantitative real time PCR we revealed a significant down-regulation of transcripts generating the endogenous RNA in the two crops. Moreover, by in vitro assays we have proved the functionality of selected sRNAs in cleaving the corresponding RNA targets upon incorporation into specific core proteins of the class of "Argonautes". The results herein suggested that the generation of sRNA regulators from specific gene clusters of the photosynthetic machinery is an unifying qualitative feature among plant species of the Brassicaceae family under biotic stress. | Biophysics-of-Phenosynthesis from molecules to the field, pp. 115-115, Accademia dei Lincei, Roma, 2-4/10/2019 | 2019 | PANTALEO VITANTONIO, LEONETTI PAOLA, CONSIGLIO ARIANNA | sRNA, biotic stress, photosynthesis | |
| 416339 | Rapporto di progetto (Project report) | Nestore - D4.2 - First prototype of the DSS | Orte S., Subias P., Dauwalder S., Roecke C., Guye S., Palumbo F., Rizzo G. | The D4.2 is the software that conforms the first prototype of the Decision Support System. As the DSS is merely designed and implemented in form of a Software as a Service platform, and it does not have any graphical user interface, this document is intended to report a description of the DSS first prototype main features with a particular focus on the architecture, functionalities and technical implementation. Therefore, the aim of this document is to provide a picture of the actual development of the DSS starting from the scientific background from which it is grounded and going through the different elements that form the DSS. The DSS main objective is to help users in selecting coaching plans by proposing personalised recommendations based on users' behaviours and preferences. Recognising such behaviours and their evolution over time is therefore a crucial element for tailoring the interaction of the system with the user. A three-layer system composed of pathways, coaching activity plans, and coaching events, constitutes the so-called coaching timeline on which the analysis is grounded. Various techniques are used to model and personalise the recommendations and feedback. Firstly, the indicators are extracted from disparate data sources, then these are modelled through a profiling system and, finally, recommendations on the pathways and coaching plans are performed through a tagging system. With the aim of developing and testing the models and workflow prior to the pilot starting date, two simulators are also being implemented and reported in this document. | 2019 | 2019 | RIZZO GIOVANNA, PALUMBO FILIPPO | Decision Support System, Architecture, Functionalities, Data Processing, Data Sources, Scoring System, Tagging System, Scheduler, Pathway, Coaching Activity Plan, Coaching Event, API Services, Data Simulators | |
| 416345 | Rapporto di progetto (Project report) | D6.3.2 - NESTORE Platform Shared components & Architecture | Candea C., Staicu M., Candea G., Zgripcea C., Orte S., Kniestedt I., Segato D., Radeva P, Crivello A., Palumbo F., Pillitteri L., Miori V., Rizzo G., Rocke C. | Present document aims to describe in detail the NESTORE ecosystem architecture and explains its technical specifications on both the implementation criteria and the requirements. NESTORE adopt an evolutionary architecture approach: "An evolutionary architecture designs for incremental change in an architecture as a first principle. Evolutionary architectures are appealing because change has historically been difficult to anticipate and expensive to retrofit. If evolutionary change is built into the architecture, change becomes easier and cheaper, allowing changes to development practices, release practices, and overall agility". | 2019 | 2019 | PILLITTERI LOREDANA, RIZZO GIOVANNA, MIORI VITTORIO, PALUMBO FILIPPO, CRIVELLO ANTONINO | NESTORE Architecture, Shared Component, End User, API, Sensors, IOT, Platform, Cloud, Applications | |
| 408133 | Rassegna della letteratura scientifica in rivista (Literature review) | The MicroRNA Centrism in the Orchestration of Neuroinflammation in Neurodegenerative Diseases. | Nicoletta Nuzziello and Maria Liguori | MicroRNAs (miRNAs) are small non-coding RNAs with a unique ability to regulate the transcriptomic profile by binding to complementary regulatory RNA sequences. The ability of miRNAs to enhance (proinflammatory miRNAs) or restrict (anti-inflammatory miRNAs) inflammatory signalling within the central nervous system is an area of ongoing research, particularly in the context of disorders that feature neuroinflammation, including neurodegenerative diseases (NDDs). Furthermore, the discovery of competing endogenous RNAs (ceRNAs) has led to an increase in the complexity of miRNA-mediated gene regulation, with a paradigm shift from a unidirectional to a bidirectional regulation, where miRNA acts as both a regulator and is regulated by ceRNAs. Increasing evidence has revealed that ceRNAs, including long non-coding RNAs, circular RNAs, and pseudogenes, can act as miRNA sponges to regulate neuroinflammation in NDDs within complex cross-talk regulatory machinery, which is referred to as ceRNA network (ceRNET). In this review, we discuss the role of miRNAs in neuroinflammatory regulation and the manner in which cellular and vesicular ceRNETs could influence neuroinflammatory dynamics in complex multifactorial diseases, such as NDDs. | Cells (2019). | 2019 | NUZZIELLO NICOLETTA, LIGUORI MARIA | EVs; NDDs; ceRNAs; competing endogenous RNAs; extracellular vesicles; miRNA; microRNA; neurodegenerative diseases; neuroinflammation | 10.3390/cells8101193 |
| 414907 | Rassegna della letteratura scientifica in rivista (Literature review) | Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs' World. | Nuzziello N, Ciaccia L, Liguori M. | Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and efficacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine. | Cells (2019). | 2019 | NUZZIELLO NICOLETTA, LIGUORI MARIA | drug response; epidrug; microRNA; neurodegenerative diseases; pharmacoepigenomic; precision medicine | 10.3390/cells9010075 |
| 401232 | Comunicazione in rivista (Letter - Letter to editor) | Seeking a standardized normalization method for the quantification of microRNA expression | Nuzziello N., Liguori M. | | Muscle & nerve (Print) (2019). | 2019 | NUZZIELLO NICOLETTA, LIGUORI MARIA | microRNA, HT-NGS, qPCR, standardization | 10.1002/mus.26455 |
| 421744 | Presentazione | Presentation of National Research Council (CNR) Institute for Biomedical Technologies (ITB) as LifeTime Associated Partner | Alessandra Mezzelani | CNR-ITB is the largest public institute of its kind in Italy It pioneers new types of cross-disciplinary biomedical research by bringing biology, engineering, medicine, and the basic sciences together. It counts on collaborations between industry and basic scientists and clinicians from a broad range of disciplines. CNR-ITB: Platforms, Infrastructures and Units related to LifeTime Bioinformatics, Stem Cell - 3D Organoid Technologies Unit, BMI1 is studied at the SC-transcriptomics level as novel therapeutic targetin lung cancer, Clinical Proteomics Laboratory, Epigenetics, Genomics, Research ethics, Bioethics and Biolaw UNIT, Proposed involvement and expertise CNR-ITB is the largest public institute of its kind in Italy It pioneers new types of cross-disciplinary biomedical research by bringing biology, engineering, medicine, and the basic sciences together. It counts on collaborations between industry and basic scientists and clinicians from a broad range of disciplines. | LifeTime UnConference: Single-cell Multi-omics and Imaging and Data Science, Artificial Intelligence and Machine Learning., Barcellona, 22- 23 July 2019. | 2019 | MEZZELANI ALESSANDRA MARIA | single cell analysis, LifeTime, European initiative | |
| 425410 | Poster | GOBLET: fostering international collaboration for advanced Learning, Education and Training in Computational Biology and Bioinformatics | Javier De Las Rivas (1), Domenica D'Elia (2), Eija Korpelainen (3), Annette McGrath (4), Asif M. Khan (5), Michelle D. Brazas (6), Teresa K. Attwood (7), Celia Van Gelder (8) | In the current era of Big Data production and Artificial Intelligence development, one of the fastest growing scientific and professional areas that is generating petabytes of data is Life Sciences. In this context, many scientific and educational institutions recognize that it is no longer possible to carry out adequate studies and research in this area without well-trained computational biologists and bioinformaticians. GOBLET is an international organization, established in 2012, with the mission to cultivate a global community of bioinformatics trainers who support learning, education and training. GOBLET's mission was defined under the vision that there is a clear worldwide need to harmonize bioinformatics training activities and to unite, inspire and equip bioinformatics trainers. This can only be achieved by developing active linkages and collaborations with many national and international institutions that work in the field of Life Sciences. Relevant activities conducted last year by GOBLET members, together with other international experts, include the initiation of a series of assets, standards and guidelines, to define competencies, promote best practices and provide high-quality resources for learning, education and training in bioinformatics and computational biology, worldwide. GOBLET's new website offers a comprehensive portal, providing many materials and resources for the international bioinformatics community. | ISMB 2020 - 28th Conference on Intelligent Systems for Molecular Biology, Virtual - Montreal (Canada), 13-16 July, 2020 | 2020 | D'ELIA DOMENICA | Education, Bioinformatics | |
| 425411 | Presentazione | GOBLET- The Global Organisation for Bioinformatics Learning, Education & Training | Domenica D'Elia | GOBLET, the Global Organisation for Bioinformatics Learning, Education and Training, is a legally registered foundation whose mission is to cultivate the global bioinformatics trainer community, set standards and provide high-quality resources to support learning, education and training. GOBLET main objectives are: for the training portal to become both a pull mechanism and repository; to offer training for trainers and end-users; to develop training material and course standards; to provide training resources (surveys, best-practice guidelines, etc.); to raise funds to be able to meet our objectives; to offer a network/community forum; to give further consideration to mechanisms for trainer recognition. | ISCB 2020 - 28th Conference on Intelligent Systems for Molecular Biology, Virtual - Montreal (Canada), 13/07/2020, 16/07/2020 | 2020 | D'ELIA DOMENICA | Education, Training, Learning, Bioinformatics | |
| 426212 | Poster | Linked-read whole genome sequencing reveals undetected variants in autism spectrum disorder | F.A. Cupaioli1, E Mosca1, N. Di Nanni1, P. Pelucchi1, L. Milanesi1, M.E. Raggi2, M.L. Villa2, A. Mezzelani1 | Abstract Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition with complex etiology. Although genetics play a key role in ASD, causative or predisposing genetic variants have been detected only in 30% of patients. Here, for the first time, linked-read whole genome sequencing of ASD patients is used to access disease associated regions unmappable by short-reads NGS. Materials and Methods: 10 children with ASD, including 3 couples of affected siblings, were enrolled and HMW DNA isolated from peripheral blood. DNA was submitted to 10Xgenomics microfluidics partitioning and barcoding, library preparation and Illumina WG-NGS. Data were analyzed through 10x Long Ranger pipelines to find SNVs, in/dels and larger structural variants in comparison to 1000 genomes, genome aggregation database and NHLBI-ESP populations. Genes affected by variants were compared with those already known to be associated with ASD (SFARI database, large-scale sequencing studies, bioinformatics predictions). Results: this approach successfully produced sequences up to 9mln bp in length. Among the detected variants, 405 were listed in SFARI, 43 confirmed bioinformatics predictions and 3,210 were new. Among the latter variants, 22 were homozygous in all the 3 couples of siblings. Conclusion: this powerful approach deciphered underlying genomic heterogeneity and missing variations in ASD. Further studies will be performed to validate the new ASD variants in a large size of samples and in public data. Data integration will be also performed to identify pathways and gene networks involved in the disorder to understand disease mechanisms and design target-driven treatment. Acknowledgements: EU project GEMMA (grant agreement No 825033). | European Human Genetics Virtual Conference ESHG 2020.2, JUNE 6-9, 2020 | 2020 | DI NANNI NOEMI, MEZZELANI ALESSANDRA MARIA, PELUCCHI PARIDE, MOSCA ETTORE, CUPAIOLI FRANCESCA ANNA | whole genome sequencing, autism spectrum disorder, linked read | |
| 406463 | Poster | Antarctic Dry Valleys melt water systems analogues of Martian gullies: characterization of microbial communities and soil properties | Fabiana Canini 1, 2, Laura Zucconi 1, Jozsef Geml 2, 3, Luigi Paolo D'Acqui 4, Marco Severgnini 5, Giacomo Mele 6, Valentina Raimondi 7, Lorenzo Palombi 7, Clarissa Consolandi 5, Tania Camboni 5, Silvano Onofri 1, Laura Selbmann 1, 8, Alessia Cassaro 1, Claudia Pacelli 1, 9, Stefano Ventura 4, 10 | Antarctic McMurdo Dry Valleys (MDVs) are characterized by extremely low temperatures, strong desiccating winds, very low precipitation, aridity, high solar irradiation, and locally high salt concentrations. The majority of the MDVs surface is unconsolidated sediment, with an ice-cemented permafrost with neither wet nor dry active layers, as soil temperature generally never rises above 0 ?C. For these characteristics, these soils are regarded as one of the closest terrestrial analogues of the cold arid Martian regolith. Despite cold and dry conditions, gullies and streams occur in a broad zone distal to the ephemeral streams, as dark bands, commonly on north-facing slopes, from surface top-down melting of snow and ice, due to enhanced summer solar insolation. They host a biological activity that can persist even after surface water flow in the channel has ceased, surviving long periods of desiccation and extreme cold in a cryptobiotic state. MDVs hydrological system may provide important insights into the potential configuration of Mars climate, in which MDV-like ephemeral streams and rivers could have originated through processes related to the presence of liquid water in the recent geological past and could have hosted life forms remained trapped within the gully (Levy et al., 2012). NASA has chosen Jezero Crater as the landing site for Mars 2020 rover mission, as it is located on the western edge of Isidis Planitia, a giant basin, once home of a river delta. This area could have preserved organic molecules and other potential signs of a hypothetical microbial life from the water and sediments that flowed into the crater billions of years ago. During the XXXI (2015/16) Italian Antarctic expedition, soil samples have been collected in MDVs, in the areas surrounding three Antarctic lakes, namely Lake Fryxell, Lake Hoare and Lake Joyce. Although soil communities of these areas have already been deeply studied, here we propose a new multidisciplinary approach that could lead to characterize the microbiota and the environmental conditions determining the colonization in such limiting environment, and to provide parameters that could be uniquely descriptive of the presence and the type of colonization. To achieve these goals, both fungal and bacterial diversity have been characterized via metabarcoding next-generation sequencing. In these samples, we found 21987 and 292 OTUs for Bacteria and Fungi, respectively, with richness ranging from 2962 to 4859 OTUs and from 7 and 122 OTUs, respectively. Main bacterial phyla within Lake Hoare and Lake Joyce communities were Bacteroidetes and Firmicutes (accounting for >80% of the relative abundance), whereas, Lake Fryxell samples showed 27% Cyanobacteria and 3% Deinococcus-Thermus, that were nearly absent in the other two sites. Instead for fungal communities, we highlighted a dominance of saprotrophic and lichen forming organisms in all the samples. Soil edaphic parameters (pH, relative moisture, C, N, P, Na, K, Mg and Ca content and cation exchange capacity) and granulometry have been characterized, to relate communities diversity and composition to soil characteristics. Laser induced fluorescence spectra were also acquired in situ by using an in-house developed instrument to detect accessory pigments and contribute to the characterization of soil communities. Additionally, the DRIFT (Diffuse Reflectance Infrared Spectroscopy) spectra and colorimetric data have been recorded for soil samples, in order to be associated to specific communities and edaphic characteristics. In this view, our data could be of interest for future Martian explorations, focused on the search of signs of past or present life forms, as they could describe composition, soil parameters or specific color spectra that could be descriptive of living or extinct biological colonization. Levy, J. (2012). Icarus, 219(1), 1-4. | EANA 2019: 19th EANA Astrobiology Conference, Orleans, France, 3rd-6th September 2019 | 2019 | CAMBONI TANIA, D'ACQUI LUIGI PAOLO, MELE GIACOMO, RAIMONDI VALENTINA, CONSOLANDI CLARISSA, SEVERGNINI MARCO, PALOMBI LORENZO, VENTURA STEFANO | Astrobiology, Antarctica, bacteria, fungi, soil | |
| 426366 | Presentazione | Bioinformatic Integration of "Omics" Data to Evaluate and Improve Laser Induced Neuroregeneration after SCI: an Overview | Mezzelani A, Cupaioli F, Sicurello F, Milanesi L. | Spinal cord injury (SCI) counts about 17,000 new cases each year in the United States. Since axons lose the competence to regenerate in adult mammals, SCI can lead to permanent neurological damages with dramatic personal, social and economic impacts. The long-term deficit of SCI results first from the type of insult and then from the secondary phase that includes many pathophysiological events. Among these, inflammation and epigenetic factors play a crucial role in the recovery of neuron connections. Variations in epigenetic and immune contribution, in turn, depend on age and health status as well as to microbiota profile of individuals at the time of, or consequent to SCI. Indeed, gut microorganisms, highly influence the immune system, but also produce bioactive substances such as folates, butyrate and acetate that participate to the epigenetic processes. Interestingly, variations in the profile of microbiota and bioactive substances have been described in patients with neurologic intestine because of SCI. Recently, different approaches, including stem cell therapy, use of biomaterial and laser therapy, have been proposed for neuronal regeneration after SCI but they are still far from resolutive interventions. As the complexity of pathophysiological processes of the secondary phase can deeply condition the success of regeneration, we provide a landscape of microbiota-epigenetic-immune modulation of neurological recovery predisposition or prevention. We discuss most of data about epigenetics (microRNAs, circulating microRNAs and chromatin remodelling) after SCI in animal models as well as microbiome profile of patients with SCI. We also propose a bioinformatics approach to compare "comics" data (gut microbiome, circulating microRNAs and inflammatory profiles) of patiens with SCI before and after laser therapy to evaluate and improve laser induced neuroregeneration. Acknowledgements: Flagship InterOmics (PB05). | 29th international medical congress, Laser Florence 2017, Firenze, 9/11/2017-11/11/2017 | 2017 | CUPAIOLI FRANCESCA ANNA, MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO | Spinal cord inury, gut microbiome, microRNA, Inflammation, data integration, personalized medicine | |
| 426380 | Presentazione | Neurotossicita dell'ocratossina A: effetti epigenetici e di accumulo | Mezzelani A, Cupaioli FA, Raggi ME, Brera C, De Santis B, Milanesi L. | L'ocratossina A (OTA) e una micotossina prodotta da funghi ubiquitari dei generi Aspergillus e Penicillium che contamina i prodotti alimentari e i mangimi in tutto il mondo. In un recente studio pilota, l'OTA e risultata associata all'autismo, un disturbo del neurosviluppo che colpisce prevalentemente i soggetti di sesso maschile caratterizzato da difficolta nell'interazione sociale, interessi ristretti e comportamenti ripetitivi. L'autismo e quasi sempre associato ad altri disturbi come l'aumento dei livelli di infiammazione e dello stress ossidativo. L'OTA e nefrotossica, epatotossica e neurotossica soprattutto nei maschi che sono carenti dell'enzima CYP4A3 che la metabolizza. Essa esercita la sua tossicita inducendo stress ossidativo, infiammazione e fibrosi attraverso meccanismi epigenetici e aumentando il rapporto fenilalanina (phe)/tirosina. L'OTA e infatti composta da una molecola di isocumarina e da una di phe. Quest'ultima compete nella sintesi di neurotrasmettitori con la phe libera come substrato per la phe idrossilasi (che idrolizza la phe in tirosina, precursore della L-DOPA) con conseguente accumulo di phe e riduzione di L-DOPA e dei neurotrasmettitori che ne derivano. Inoltre, un accumulo di phe nel cervello forma fibrille simil-amilode. A livello epigenetico, l'OTA modula l'espressione di alcuni microRNA: diminuisce il mir-29b, inibitore della produzione del collagene, che si traduce in un aumento di quest'ultimo, alterazione fibrotica e nefropatia. Una diminuzione del mir-29b inoltre aumenta l'espressione della alpha-secretase (BACE1), l'enzima coinvolto nella produzione di beta-amiloide, il cui accumulo causa amiloidosi tra cui l'Alzheimer. L'OTA stimola anche la sintesi di mir-132 come si verifica in alcune condizioni neuro-psichiatriche e nello stress ossidativo. Il mir-132 agisce nella regolazione reciproca dei geni correlati all'autismo MEeCP2 e PTEN e diminuisce l'antiossidante Nrf2 aumentando i livelli di ossidanti (ROS). I ROS, a loro volta, aumentano l'espressione del mir-200c che altera ulteriormente i meccanismi antiossidativi e la plasticita sinaptica attraverso la inibizone dell'eme ossigenasi e della neuroligina4X (NLGN4X). Sia MECP2 che NLGN4X sono coinvolti in disordini dello sviluppo neurologico, incluso l'autismo, e sono mappati sul cromosoma X cosa che potrebbe spiegare la prevalenza maschile di questo disturbo. Sono necessari ulteriori studi in vitro e in vivo, da condurre separatamente nei due sessi, per ottenere un quadro completo degli effetti epigenetici dell'OTA e per prevenirli o contrastarli. Fondi: Interomix-OTANEXT-AUT. | Nutrigenomica e alimentazione, Bari, 12/10/2018 - 13/10/2018 | 2018 | CUPAIOLI FRANCESCA ANNA, MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO | Autism, ocratoxin, inflammation, microRNA, oxidative stress | |
| 426464 | Poster | Linked read sequencing reveals new genetic variants in autism | Cupaioli FA, Di Nanni N, Pelucchi P, Cifola I, Villa L, Raggi ME, Milanesi L, Mosca M, Mezzelani A | Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, prevalence is 1:68. Although genetics plays a key role in ASD etiology, only 30% of patients exhibit ASD associated genetic variants that are detectable by CGH, GWAS and/or exome NGS approach and hundreds of genes have been involved. Here, we tested the hypothesis that variants in non-coding and/or NGS unmappable regions could be involved in ASD and detected by long-reads whole-genome sequencing (LR-WGS). This approach allows to probe previously unreadable genomic tracts and discover disease-associated phased loci across very long haplotype blocks. Thus, we performed LR-WGS, by 10XGenomics technology, on genomic DNA isolated from 10 children with ASD (7 males and 3 females, including 2 couples of male siblings and 1 couple of male-female siblings) followed by bioinformatics analysis performed by 10X-Long Ranger pipeline. All the sequences passed the QC test, and the longest phase block reached 9M bp in length. We first looked at large structural variants (SVs) detectable only by long-read approach. We found a total of 204 hetero- or homo-zygous large SVs (deletions, duplications, inversions and breakends), up to 30 per subject and affecting 52 distinct genomic regions of 10^5 bp in average within almost all chromosomes. Interestingly, each SV affected from 1 up to 10 subjects and 51 out of 53 SVs involved genes that have never been associated with autism (not listed in SFARI database). All genes were submitted to DAVID 6.8 and METASCAPE gene enrichment tools evidencing some pathways including that of immune response and olfactory transduction. These SVs will be validated on an independent set of DNA samples previously collected from children with ASD and healthy controls. Resulting data will be integrated with clinical data to find genotype-phenotype associations. Small variants will be analyzed and validated, too. In conclusion, LR-WGS successfully discovered 51 new gene variants in 10 patients with ASD that, if confirmed, could explain some pathogenetic mechanisms of the disorder and represent possible diagnostic biomarkers for patient stratification and personalized medicine approaches. | Neurogenetics, Nature Conferences, Virtual (Covid19), 29/07/2020 | 2020 | DI NANNI NOEMI, MEZZELANI ALESSANDRA MARIA, CIFOLA INGRID, PELUCCHI PARIDE, MILANESI LUCIANO, MOSCA ETTORE, CUPAIOLI FRANCESCA ANNA | linked reads, autism, whole genome sequencing, large structural variants | |
| 426691 | Poster | Epigenetic-immune-microbiota contribution to neural regeneration after spinal cord injury: an overview | Mezzelani A, Cupaioli F, Sicurello F, Milanesi L. | Spinal cord injury (SCI) counts about 12,000 new cases each year in the United States. Since axons lose the competence to regenerate in adult mammals, SCI can lead to permanent neurological damages with dramatic personal, social and economic impacts. The long-term deficit of SCI results first from the type of insult and then from the secondary phase that includes many pathophysiological events. Among these, inflammation and epigenetic factors play a crucial role in the recovery of neuron connections. Indeed, variations in epigenetic and immune contribution can be associated to injury and, at systemic level, to age and health status as well as to microbiota profile of individuals at the time of, or consequent to SCI. Indeed, gut microorganisms, highly influence the immune system, but also produce bioactive substances such as folates, butyrate and acetate that participate to the epigenetic processes. Interestingly, variations in the profile of microbiota and bioactive substances have been described in patients with neurologic intestine because of SCI. Recently, advances in SCI regenerative medicine, such as stem cell therapy, biomaterial approach and laser therapy, have been obtained but they are still far from resolutive interventions. As the complexity of pathophysiological processes of the secondary phase can deeply condition the success of regeneration, here we provide a landscape of epigenetic-immune biomarkers of neurological recovery predisposition or prevention. We discuss most of data about epigenetics (microRNAs, circulating microRNAs and chromatin remodeling) after SCI in animal models. We also stress the microbiota epigenetic-immune modulation since controlling its composition and function is of therapeutic potential in regenerative medicine. Acknowledgements: Flagship InterOmics (PB05). | International Spinal Cord Repair - ISCORE 2017, Barcellona, Spagna, 03/11/2017 - 04/11/2017 | 2017 | CUPAIOLI FRANCESCA ANNA, MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO | spinal cord injury, microRNA, microbiota, microRNA-based therapy, nutraceuticals | |
| 426696 | Poster | Epigenetic-immune-microbiota contribution to neural regeneration after spinal cord injury: an overview. | Mezzelani A, Cupaioli F, Sicurello F, Milanesi L. | Objectives: spinal cord injury (SCI) triggers a cascade of intrinsic pathophysiological events that influence the SCI long-term deficit and that should be therapeutically modulated. The aim is to identify biomarkers to favour neuronal recovery after SCI. Material and Methods: we reviewed the literature indexed in PubMed about SCI, SCI epigenetics, SCI microbiota and novel therapeutic strategies for SCI repair. Results: inflammation-epigenetics-microbiota vicious cycle affects recovery after SCI. The dysregulation of specific microRNAs and circulating microRNAs was found in spinal cord and in serum, respectively, after SCI thus circulating microRNAs are promising biomarkers for evaluating the severity of SCI, as demonstrated in animal models. SCI patients often display neurogenic intestine dysfunction including changes in gut microbiome composition with a significant reduction in butyrate producing bacteria. Butyrate is a potent anti-inflammatory agent, a histone deacetylase inhibitor and suppresses inflammation in the CNS probably reducing microglia-mediated neurotoxicity. In mice, induced gut dysbiosis exacerbates neurologic damage impairing recovery after SCI. To date, there is not a cure for SCI, however new regenerative approaches are recently suggested. In rats, valproic acid administration after SCI protects motoneurons through modulation of apoptotic pathways. The microRNA-based therapy, manipulating the expression of specific microRNAs can activate or block target genes involved in neuro-regeneration; advances in CNS microRNA delivery technologies able to cross the spinal cord blood barrier have been reached. In SC injured rats, passive cycling exercises modulated microRNAs and gene transcription favouring biochemical and cellular restore, and potentially damage recovery. Then again, regarding microbiota, probiotic-induced eubiosis improves loco-motor recovery in mice. New nutraceuticals have also been demonstrated to help in neuro-regeneration and SCI recovery. This is the case of Naringin, curcumin epigallocathechin-3-gallate, omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) that play anti-oxidant, anti-inflammatory and anti-apoptotic rules. | SRSI - Nature Conference "Regeneration", Milano, Italia, 16/11/2017 - 18/11/2017 | 2017 | CUPAIOLI FRANCESCA ANNA, MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO | Spinal cord injury, microRNA, Inflammation, microbiota, nutraceuticals, microRNA-based therapy | |
| 426699 | Abstract in rivista | Association of Haptoglobin-1 allele with Autism | Mezzelani, A., Cupaioli, F. A., Mosca, E., Magri, C., Gennarelli, M., Raggi, M. E., Landini, M., Galluccio, N., Chiappori, F., Moscatelli, M., Gnocchi, M., Villa, C., Molteni, M., Bonfanti, A., Ciceri, F., Marabotti, A., Milanesi, L. | Gene-environment interaction, through abnormal intestinal adsorption, has been proposed as possible mechanism for autism pathogenesis in those patients lacking of causative genetic variants. Haptoglobin (HP) is a haemoglobin binding and acute-phase plasma protein, encoded by two co-dominant alleles, HP-1 and HP-2, producing pre-HP-1 and pre-HP-2 proteins that mature in HP-1 and HP-2, respectively. Due to a 1.7Kb copy number variation in the HP gene, the HP-2 allele has two extra exons with respect to HP-1. Thus the HP protein is a dimer in homozygous subjects for HP-1 allele and is multimer in homozygous HP-2. Endogenous pre-HP-2 protein deregulates intestinal tight-junctions through EGFR and PAR2 activation, increases intestinal permeability and has been associated with autoimmune and inflammatory diseases as well as with psychiatric conditions (Fasano, 2011; Sturgeon and Fasano, 2016). Since the association between HP alleles and autism has just been investigated in a very small sample size of patients and controls (Rose et al., 2018), we genotyped, by PCR analysis, HP in a cohort of Italian patients with autism (n=406) and in controls (n=367). The aim was to evaluate the possible association of HP-2 and autism spectrum disorder (ASD). Contrary to what we expected, HP-1 allele distribution was different between patients and controls (36.3% and 29.4%, respectively) and significantly associated with autism (P=0.0041). Since a subgroup of patients and controls have already been genotyped by Illumina Human Omni-15-8 v.1.0 and Affy-6.0 chips, respectively, we are trying to impute HP alleles from flanking SNP haplotypes. HP alleles will therefore be predicted in publicly available large cohorts of patients with autism. | European journal of human genetics 27 (2019): 280-281. | 2019 | CHIAPPORI FEDERICA, CUPAIOLI FRANCESCA ANNA, LANDINI MARTINA, GALLUCCIO NADIA, MOSCATELLI MARCO, MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, GNOCCHI MATTEO, MOSCA ETTORE | Autism spectrum disorders, Haptoglobin, intestinal permeability | 10.1038/s41431-019-0404-7 |
| 426706 | Poster | Association of Haptoglobin-1 allele with Autism. | Mezzelani A, Cupaioli F, Mosca E, Magri C, Gennarelli M, Raggi ME, Landini M, Galluccio N, Chiappori F, Moscatelli M, Gnocchi M, Villa CL, Molteni M, Bonfanti A, Ciceri F, Marabotti A, Milanesi L. | Gene-environment interaction, through abnormal intestinal adsorption, has been proposed as possible mechanism for autism pathogenesis in those patients lacking of causative genetic variants. Haptoglobin (HP) is a haemoglobin binding and acute-phase plasma protein, encoded by two co-dominant alleles, HP-1 and HP-2, producing pre-HP-1 and pre-HP-2 proteins that mature in HP-1 and HP-2, respectively. Due to a 1.7Kb copy number variation in the HP gene, the HP-2 allele has two extra exons with respect to HP-1 (Fig. 1). Thus the HP protein is a dimer in homozygous subjects for HP-1 allele and is multimer in homozygous HP-2. Endogenous pre-HP-2 protein deregulates intestinal tight-junctions through EGFR and PAR2 activation, increases intestinal permeability and has been associated with autoimmune and inflammatory diseases as well as with psychiatric conditions (Fasano, 2011; Sturgeon and Fasano, 2016). Since the association between HP alleles and autism has just been investigated in a very small sample size of patients and controls (Rose et al., 2018), we genotyped, by PCR analysis, HP in a cohort of Italian patients with autism (n=406) and in controls (n=367). The aim was to evaluate the possible association of HP-2 and autism spectrum disorder (ASD). Contrary to what we expected, HP-1 allele distribution was different between patients and controls (36.3% and 29.4%, respectively) and significantly associated with autism (P=0.0041). Since a subgroup of patients and controls have already been genotyped by Illumina Human Omni-15-8 v.1.0 and Affy-6.0 chips, respectively, we are trying to impute HP alleles from flanking SNP haplotypes. HP alleles will therefore be predicted in publicly available large cohorts of patients with autism. | European Conference of Human Genetics 2018, Milano, Italy, 16/06/2018 - 19/06/2018 | 2018 | CHIAPPORI FEDERICA, CUPAIOLI FRANCESCA ANNA, LANDINI MARTINA, GALLUCCIO NADIA, MOSCATELLI MARCO, MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, GNOCCHI MATTEO | Autism spectrum disorders, Haptoglobin, Zonulin, intestinal permeability | |
| 426789 | Poster | Microbiota Profile in Autism Spectrum Disorder: Different Metagenomics Approaches to analyze 16S and 18S rRNA | Chiappori F, Cupaioli F.A., Milanesi L., Raggi M.E., Mezzelani A. | Abstract Introduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by communication impairments, limited social interaction, restricted interests, repetitive behaviors and stereotypies. It manifests within the first 3 years of age and lasts for a lifetime with dramatic personal, familial and social consequences. ASD affects much more males than females (male:female=5:1) and its prevalence, that is continuously increasing, interests 2.24% of children and 1% of the general population [1,3]. Although genetics play a key role in ASD, its etiology is complex. Since most of individuals with ASD suffer from additional comorbidities including gastrointestinal disorders, intestinal permeability, inflammation and allergies, a gene-environment interaction has been proposed as ASD triggering [3]. Dysbiosis has been frequently associated with many neurological disorders including ASD. Thanks to the last advances in metagenomics, much progress has been made in the knowledge of gut microbiota profile and role, especially the prokaryotic one, but literature lacks of studies about eukaryotic colonizer of human intestine and their role in human health. Aims Here, employing different bioinformatics tools, we propose a metagenomics pilot study to define the prokaryotic and eukaryotic gut microbiota of children with ASD and neurotypical controls. The aims are to test different metagenomics pipelines and set up the more performing bioinformatics conditions to identify ASD microbial biomarkers useful for patient stratification and personalized treatments. Materials and Methods: We isolated DNA from stools collected from 6 children with ASD (5 males and 1 female) and 6 neurotypical controls matching for age and sex. Both 16S and 18S were amplified for each DNA and Illumina libraries prepared. NGS was performed by Illunima MiSeq platform coupled with Flowcell V3 2X300 and forward and reverse reading, reaching about 22Milion of sequences. As for bioinformatics analysis, three different software with several pipelines were applied: the automatic pipeline of SILVAngs analysis platform (https://ngs.arb-silva.de/silvangs/) [4], the MiSeq SOP pipeline of Mothur (https://mothur.org/) [5], and two pipelines of Qiime2 (https://qiime2.org/) [6]. The latter includes the Dada2 pipeline and the Deblur one. All the analyses were performed against SILVAv132 database [7], the only one that includes both 16s and 18S reference database. Results: The results obtained from the four tools are superimposable, also at different level of taxonomy detail. Restricting to Bacteria results, the identified genera are comparable with literature data [8]. As for Fungi, this first round of analysis doesn't return relevant differences between patients and controls. Further studies are needed to set up a pipeline specifically for the 18S datasets. Acknowledgements: EU project GEMMA (grant agreement No 825033), EPTRI and CNRBiOmics. Istituto San Vincenzo Erba and Albese, Italy | EPTRI open meeting 2020, virtuale (causa Covid19), April 2-3, 2020 | 2020 | CUPAIOLI FRANCESCA ANNA, MEZZELANI ALESSANDRA MARIA, CHIAPPORI FEDERICA CATERINA | microbiota, metagenomics, gene-environment interaction, autism | |
| 426810 | Presentazione | Autism Spectrum Disorder: Linked-Read Sequencing Reveals New and Undetected Variants | F.A. Cupaioli, E. Mosca, N. Di Nanni, P. Pelucchi, L. Milanesi, M.E. Raggi, L. Villa, A. Mezzelani | Introduction Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by limited social interaction, communication impairments, restricted interests and repetitive behaviors. It occurs in pediatric age, within the first 3 years of life, and lasts for a lifetime with severe consequences for the individual and his/her family and with very high social costs. In the last decades, ASD has increased dramatically reaching the prevalence of 1:68. Although genetics play a key role in ASD, its etiology is complex and recent studies hypothesize a gene-environment interaction. Indeed, causative or predisposing genetic variants have been detected only in 30% of patients and thousands of genes are involved. Here, for the first time, linked-read whole genome sequencing of ASD patients is used to access disease associated regions unmappable by short-reads NGS. Materials and Methods Ten children suffering from ASD (diagnosed by ADOS 2 and ADI-R), including 3 couples of affected siblings, were enrolled, peripheral blood collected and HMW DNA isolated. All the procedures had been approved by Ethical Committee as well as clinical data collected according to current privacy laws. HMW DNA, 50 kb in size or greater, was submitted to 10Xgenomics microfluidics partitioning and barcoding and then to Illumina library preparation and whole genome-next generation sequencing. Data were analyzed through 10x Long Ranger pipelines to find SNVs, in/del and larger structural variants in comparison to 1,000 genomes, genome aggregation database and NHLBI-ESP populations. Genes affected by variants were compared with those already associated with ASD: SFARI database, large-scale sequencing studies, bioinformatics predictions. Results The linked-read sequencing approach successfully produced sequences up to 9mln bps in length haplo-blocks. This technique allowed to detect variants in whole genome of ASD patients. We found genes affected by mutations already listed in SFARI and previously predicted by bioinformatics analysis and discovered hundreds of new variants. Among these latter, we focused on those homozygous in the 3 couples of siblings and found that some of them are related to neuro-development and -physiology or to xenobiotic metabolism. Conclusion For the first time, we applied the linked-read sequencing technology for studying ASD genomics. This powerful approach allowed us deciphering the genomics heterogeneity in ADS and highlighting variations otherwise undetectable by classic NGS. Indeed, we identified homozygous variants within genes or regulatory regions common to 3 couples of affected siblings. Further studies will be performed to validate the new ASD variations by PCR amplification and Sanger sequencing in a large size of ASD samples and in public data; then, the new biomarkers will be used to stratify ASD patients population. Data integration will be also performed to identify pathways and gene networks involved in the disorder to understand disease mechanisms and design target-driven personalized treatment. Acknowledgements: EU project GEMMA (grant agreement No 825033), EPTRI and CNRBiOmics. | EPTRI (European Paediatric Translational Research Infrastructure) open meeting 2020, virtual meeting, 02/04/2020 - 03/04/2020 | 2020 | DI NANNI NOEMI, MEZZELANI ALESSANDRA MARIA, PELUCCHI PARIDE, MILANESI LUCIANO, MOSCA ETTORE, CUPAIOLI FRANCESCA ANNA | Autism Spectrum Disorder, linked reads, whole genome sequencing, biomarkers, patients stratification | |
| 421675 | Altro prodotto | Autismo: il coordinatore del progetto GEMMA alla conferenza internazionale "Dr. Roger's Prize" | Alessandra Mezzelani | comunicato stampa inerente il progetto europeo GEMMA, di cui il CNR e partner, attraverso le news CNR | 2019 | 2019 | MEZZELANI ALESSANDRA MARIA | GEMMA, Dr. Roger's Prize | |
| 421672 | Altro prodotto | GEMMA, progetto europeo per identificare i biomarcatori dell'autismo | Alessandra Mezzelani | Comunicato stampa pubblicato sulla pagina News del sito web CNR: presentazione del progetto europeo GEMMA | 2019 | 2019 | MEZZELANI ALESSANDRA MARIA | GEMMA, progetto europeo, autismo multi-omics | |
| 421673 | Altro prodotto | Il progetto europeo GEMMA continua il reclutamento dei bambini a rischio di sviluppare autismo | Alessandra Mezzelani | Comunicato stampa pubblicato sulle News del sito web CNR inerente il progetto europeo GEMMA, di cui sono responsabile per il CNR, | 2019 | 2019 | MEZZELANI ALESSANDRA MARIA | peogetto europeo GEMMA, autismo, reclutamento | |
| 426825 | Rassegna della letteratura scientifica in rivista (Literature review) | Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics | Dragani, Tommaso A., Matarese, Valerie, Colombo, Francesca | Thousands of candidate cancer biomarkers have been proposed, but so far, few are used in cancer screening. Failure to implement these biomarkers is attributed to technical and design flaws in the discovery and validation phases, but a major obstacle stems from cancer biology itself. Oncogenomics has revealed broad genetic heterogeneity among tumors of the same histology and same tissue (or organ) from different patients, while tumors of different tissue origins also share common genetic mutations. Moreover, there is wide intratumor genetic heterogeneity among cells within any single neoplasm. These findings seriously limit the prospects of finding a single biomarker with high specificity for early cancer detection. Current research focuses on developing biomarker panels, with data assessment by machine-learning algorithms. Whether such approaches will overcome the inherent limitations posed by tumor biology and lead to tests with true clinical value remains to be seen. | BioEssays 42 (2020). | 2020 | COLOMBO FRANCESCA | biomarkers, clinical validation, discovery pipeline, early diagnosis, genetic heterogeneity, genome sequencing, oncogenomics, screening | 10.1002/bies.201900122 |
| 426848 | Poster | Proteins and miRNA in feline renal amyloid deposits | Genova F, Nonnis S, Maffioli E, Grassi Scalvini, Di Nanni N, Cupaioli F, Mosca E, Mezzelani A, Sironi G, Lyons LA, Tedeschi G, Longeri M. | Amyloidosis is a group of diseases occurring in humans and animals, due to the deposition of misfolding proteins in different organs. In humans, deposits were characterized using proteomics and more recently the role of miRNAs in the pathogenesis was proposed. In Abyssinian cat the main target is the kidney. Little is known on the mechanisms underlying the disease. The aim of this study is to profile proteins and miRNAs in healthy and affected Abyssinian cats, to evaluate their differential expression and clarify the pathogenesis mechanisms. Formalin-fixed paraffin-embedded kidney slices were collected from 7 affected and 5 healthy Abyssinians and used for proteomic and miRNAs analyzes. Peptides were analyzed with an LTQ-Orbitrap Velos mass spectrometer (MS). MS spectra were searched against the F.catus NCBI sequence database (release31.01.2017) by MaxQuant. Bioinformatic analysis was performed with DAVID and Panther softwares. MiRNAs were sequenced on the Illumina NextSeq500 platform. MiRDeep2 was used to map reads on the genome vs9.0, identify putative miRNAs, quantify their expression and identify homologous. Filtered proteins and miRNs statistically different were identified using a student t-test and a moderate t-test respectively (p- value<=.05). Part of the proteins was exclusively detected in the affected (n.175), part in the healthy (n.47) and part were common to the two groups (n.160). A fraction of the latter resulted upregulated (n.16) or down regulated (n.18) in affected compared to the healthy cats (p-value<=.05). Annotation and functional grouping suggested an effect on extracellular matrix and macromolecular complex subunit organization. MiRNA analysis detected 341 representatives, 22 differentially expressed between affected and healthy (p<.05). Six miRNAs out of 22 (four with a P-value<.009) are known to be involved in Alzheimer Disease. Interestingly, miR-26a-5p (P-value 0.120) is involved in the human immunoglobulin light chain amyloidosis onset. This study identified different miRNA and protein renal compositions in Abyssinian affected and healthy cats. The pathways involving these molecules are under investigation, providing new insights for the pathogenesis understanding. | ISAG 2019 - 37th International Society for Animal Genetics Conference, Lleida, Spain, 07/07/2019 - 12/07/2019 | 2019 | CUPAIOLI FRANCESCA ANNA, DI NANNI NOEMI, MEZZELANI ALESSANDRA MARIA, MOSCA ETTORE | Amyloidosis, MiRNA, protein, Transcriptomics, Proteomics | |
| 426853 | Poster | Identification of miRNAs and evaluation of their differential expression in Abyssinian cat amyloidosis | Genova F 1, Mosca E 2, Di Nanni N 2, Cupaioli F 2, Mezzelani A 2, Longeri M. 1 | Introduction: Domestic felids represent one of the main species in which amyloidosis occurs. The disease is caused by the presence of protein complexes, known as amyloids, which form insoluble deposits in different organs. However, little is known about the pathogenic pathway and the genetic of the disease is still under exploration. Among cat breeds, amyloidosis particularly affects Abyssinian/Somali and Siamese/Oriental cats, where the main target organs for the deposit are kidneys and liver, respectively. Objective: The aim of this study is i) to detect miRNAs expressed in amyloidosis affected and healthy Abyssinian kidneys ii) to evaluate their possible differential expression iii) to identify miRNAs potentially involved in the disease onset or in the regulation of its pathogenesis. Materials & Methods: miRNAs were extracted from Formalin Fixed Paraffin Embedded (FFPE) kidney slides collected from 6 affected and 4 healthy Abyssinians using the miRNeasy Mini Kit (Qiagen). The sequencing of miRNAs was carried out by smallRNA-seq kit (Illumina) and Illumina NextSeq500 platform, and its quality was assessed with FastQC. Cutadapter was used to remove the adapter sequences from the high-throughput sequencing reads. MiRDeep2 was then used to map reads against the cat reference genome (Felis catus, genome assembly version 9.0), identify putative miRNAs, quantify their expression and identify homologous human miRNAs. MiRNAs with less than 10 reads for each sample were filtered out. Raw counts were normalized with TMM method (Trimmed mean of M values) and expressed as log2 CPM (counts per million). Differential expression was assessed with a moderated t test (limma) and nominal p values were adjusted by Benjamini-Hochberg method. Results: A total of 854 miRNAs were detected, and 341 miRNAs were selected as representative after filtering. A total of 22 miRNAs showed significant expression difference between affected and healthy Abyssinians (p<0.05), but none of this was significant after p-value correction for multiple hypotheses. A total of 6 (out of 22) are known to be involved in the development of Alzheimer Disease (AD), four of which with a P-value < 0.009. Suggestively, within the not significantly associated to amyloidosis miRNAs (p>0.05), miR- 26a-5p (P-value 0.120) is one of the main miRNAs involved in the human immunoglobulin light chain (AL) amyloidosis onset. Conclusions: recent studies in humans have been focusing on disclosing the potential role of miRNAs in the accumulation of amyloid fibrils, especially in AD. It was shown that miRNAs dysregulation plays an important role in the disease alterations, although it cannot be considered the main trigger of the AD itself. Some of the identified miRNAs in the present study were already known to be associated with human AD. These results are encouraging and will help understanding the pathogenesis of feline amyloidosis. The genes directly regulated and involved in these pathways are under investigation and further evidences will be obtained with an integrative approach through a proteomic analysis. | 10th Conference of canine and feline genetics and genomics 2019, Kursaal, Bern, Switzerland, 26/05/2019 - 29/05/2019 | 2019 | CUPAIOLI FRANCESCA ANNA, DI NANNI NOEMI, MEZZELANI ALESSANDRA MARIA, MOSCA ETTORE | Amyloidosis, miRNA, Transcriptomics | |
| 426874 | Comunicazione in rivista (Letter - Letter to editor) | Differential lung tissue gene expression in males and females: implications for the susceptibility to develop COPD | van den Berge, Maarten, Brandsma, Corry Anke, Faiz, Alen, de Vries, Maaike, Rathnayake, Senani N.H., Pare, Peter D., Sin, Don D., Bosse, Yohan, Laviolette, Michel, Nickle, David C., Hao, Ke, Obeidat, Ma'en, Dragani, Tommaso A., Colombo, Francesca, Timens, Wim, Postma, Dirkje S. | | The European respiratory journal 54 (2019). | 2019 | COLOMBO FRANCESCA | transcriptome, lung parenchyma, chronic obstructive pulmonary disease, sex differences | 10.1183/13993003.02567-2017 |
| 426880 | Comunicazione in rivista (Letter - Letter to editor) | Response to comments on 'Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure' by Farioli et al. and Oddone et al. | Dragani, Tommaso A., Colombo, Francesca, Pavlisko, Elizabeth N., Roggli, Victor L. | | Carcinogenesis (N.Y., Print) 40 (2019): 490-491. | 2019 | COLOMBO FRANCESCA | pleural malignant mesothelioma, age at diagnosis, asbestos exposure | 10.1093/carcin/bgy145 |
| 426882 | Comunicazione in rivista (Letter - Letter to editor) | Corrigendum: Malignant mesothelioma diagnosed at a younger age is associated with heavier asbestos exposure (Carcinogenesis (bgy145) DOI: 10.1093/carcin/bgy145) | Dragani, Tommaso A., Colombo, Francesca, Pavlisko, Elizabeth N., Roggli, Victor L. | | Carcinogenesis (N.Y., Print) 40 (2019): 492. | 2019 | COLOMBO FRANCESCA | age at diagnosis, pleural malignant mesothelioma, asbestos exposure | 10.1093/carcin/bgz037 |
| 426884 | Rassegna della letteratura scientifica in rivista (Literature review) | Prolonged activity and toxicity of sirolimus in a patient with metastatic renal perivascular epithelioid cell tumor: A case report and literature review | Raimondi, Alessandra, Colombo, Francesca, Pintarelli, Giulia, Morosi, Carlo, Renne, Salvatore L., Frezza, Anna M., Saponara, Maristella, Dei Tos, Angelo P., Mazzocchi, Arabella, Provenzano, Salvatore, Casali, Paolo G., Stacchiotti, Silvia | Perivascular epithelioid cell tumor (PEComa) is a family of mesenchymal tumors. Conventional chemotherapy has little activity in this disease, but case reports are available on the activity of mammalian target of rapamycin inhibitors (e.g. sirolimus and temsirolimus). Pharmacokinetic assays of sirolimus are available as this drug has a precise therapeutic window and blood levels might be influenced by CYP3A4 polymorphisms and drug interactions. We report on a case of a patient with metastatic, progressive PEComa who started sirolimus at a dose of 5 mg/day with evidence of grade (G) 3 mucositis, G2 thrombocytopenia, and G1 leucopenia 10 days after the treatment started, in absence of concomitant medications or prohibited food assumption. Elevated sirolimus blood levels were detected (156.8 ng/ml). Sirolimus was stopped, and toxicity resolved in 5 weeks. Computed tomography scan 2 months after the treatment started showed a partial response (RECIST). After toxicity resolution, the patient restarted sirolimus at a dose of 1 mg/day, with blood levels in the range of 10-20 ng/ml. Tumor response was confirmed and maintained, and the patient is still under treatment 18 months later, with no additional adverse effects. Genetic analysis of five selected polymorphisms (rs2740574, rs776746, rs1128503, rs2032582, and rs1045642) in drug metabolism enzymes and transporters did not provide a clear explanation of the observed unusual pharmacokinetic. This case confirms the activity of mammalian target of rapamycin inhibitors in PEComa and strengthens the importance of pharmacokinetic drug blood levels monitoring in patients treated with sirolimus. In our patient, after dose adjustment, sirolimus could be restarted with a prolonged clinical benefit and no additional toxicity. | Anti-cancer drugs 29 (2018): 589-595. | 2018 | COLOMBO FRANCESCA | chemotherapy, drug metabolizing enzyme, drug monitoring, mammalian target of rapamycin inhibitor, perivascular epithelioid cell tumor, pharmacokinetics, polymorphism, sarcoma, sirolimus, toxicity | 10.1097/CAD.0000000000000634 |
| 427919 | Altro prodotto | New methods and agent for cellular reprogamming | Zucchi I, Tria V, Reinbold RA. | The present invention relates to a new transcript referred to here as INT6- 5a, which is an isoform of the human tran - script, known in the literature, INT6 full length (INT6-FL) encoded by the gene EIF3E (gene ID 3646, mRNA NM_001568.2), the use thereof in cellular reprogramming methods for the production of induced pluripotent stem cells or somatic stem cells, the cells obtained from such methods, and use thereof. | 2019 | 2019 | TRIA VALERIA, REINBOLD ROLLAND ALVONS, ZUCCHI ILEANA | cellular reprogramming, induced pluripotent stem cells, epigenetics | |
| 401625 | Abstract in atti di convegno | Molecular signatures associated with cognitive dysfunctions in pediatric multiple sclerosis | Liguori, M., Nuzziello, N., Simone, M., Licciulli, V. F., Viterbo, R. G., Ancona, N., Consiglio, A., Creanza, T., De Caro, G., Liuni, S., Margari, L., Trojano, M. | None | Congresso annuale dello European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), pp. 270-270, Londra, 14-17/09/2016 | 2016 | ANCONA NICOLA, LICCIULLI VITO FLAVIO, LIGUORI MARIA, LIUNI SABINO, CREANZA TERESA MARIA, CONSIGLIO ARIANNA | Cognitive Impairment, Multiple Sclerosis | |
| 396715 | Abstract in rivista | Induced pluripotent stem cells-derived extracellular vesicles shuttle bioactive molecules with anti-fibrotic potential in vitro and in vivo | Povero, D., Pinatel, E. M., Kim, J., Goyal, N., Johnson, C. D., Kneiber, D., Feldstein, A. E. | None | Journal of hepatology (Print) 66 (2017): S649-S650. | 2017 | PINATEL EVA MARIA | miRNA, Vesicles, Pluripotent cells, Fibrosis | 10.1016/S0168-8278(17)31760-9 |
| 432991 | Poster | CXCL10 binding mode to CXCR3 isoforms: different behaviors | Carisetti M, Moscatelli M, Milanesi L, Mezzelani A, Chiappori F | CXCR3 is a G-protein coupled receptor expressed principally on leukocytes, monocytes and epithelial cells; it is involved in leukocyte traffic, integrin activation, cytoskeletal changes and chemotactic migration, by binding to its classical ligands, CXCL-9/10/11 (1). Three splicing variants of CXCR3 are known: CXCR3a, the most common isoform, consisting of 368 amino acid residues; CXCR3b resulting from an alternative splicing of the CXCR3 mRNA with a 52 aa extended N-terminal domain when compared to the isoform a, while CXCR3-alt is a significantly truncated variant not involved in classical ligand binding (1). CXCL10, the interferon-?-inducible protein (IP-10) belongs to the CXC family of chemokines and acts as an immunoinflammatory mediator, inhibits angiogenesis and displays antitumor properties (2). Several studies indicated that the CXCR3 N-terminal domain plays a key role in determining binding affinity, receptor selectivity, and also in regulating allosteric signalling through the receptor (3). Moreover, tyrosine sulfation in chemokine receptors is emerging as a post-translational modification that contributes substantially to ligand binding (2). Tyr 27 and 29, two of the N- terminal tyrosine can be sulfonated. Finally, Kleist and co-workers hypothesize a "two-step" model, where receptor binding and activation can be dissociated (4). In the first step, the chemokine binds to the N-term domain of the receptor. In the second, residues on IP10 N-terminal bind to the binding cavity on the TM domain of the receptor and induce the allosteric communication to the cytosol. In this work, we analyse by a supervised molecular dynamics (SuMD) (5) simulation, the binding mechanism of IP10 on CXCR3. We explored the binding site in order to evaluate the residue- residue interactions between the chemockine and its receptor. Starting from the same equilibrated system, 3 runs of supervised MD were performed using the same conditions. A residue selection from the CXCR3 N-term domain and all the Extra-Cellular Loop (ECL) were considered for the binding interface, instead the entire chemokine was treated as ligand in order to perform the supervision on the distance between the receptor (CXCR3) and the ligand (CXCL10). They resulted with consistent similarity in both ligand-receptor contacts and interaction energies. Simulations didn't had identical durations (30.8 ns for simulation 1, 31.2 ns for simulation 2 and 36.6 ns for simulation 3), but all of them reached the ligand correctly positioned in the binding site in 15ns. Simulations 2 and 3 presented overlapping situations of decreasing energies related to minor R-L distances and of contacts, involving both residues from the CXCR3-N- term and the Extra-cellular ?-sheet, which has been described as an important player for the receptor activation. The next step will be the evaluation of the effect of tyrosine sulfation (Y27 and Y29) on binding mode and affinity. | CDDD 2019, Roma, 28-29/03/2019 | 2019 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, MOSCATELLI MARCO, CHIAPPORI FEDERICA CATERINA | CXCR3, IP10, supervised molecular dynamics, protein-protein interaction, post-translational modifications | |
| 432983 | Poster | Thermal and ionic effect on Euplotes focardii superoxide dismutase structure | Chiappori F1, Pucciarelli S2, Priyan K2, Miceli C2, Milanesi L1 | Superoxide dismutases (SODs) are ubiquitous enzymes, which catalyse the dismutation of superoxide to molecular oxygen and peroxide. Generally, cold adapted enzymes are characterized by an increased flexibility related to a low stability at higher temperature and an improved catalytic efficiency in the cold; these modifications involve the structural stability of psychrophilic enzymes. Euplotes focardii is an Antarctic marine ciliate. The optimal temperature for growth and reproduction is 4?C. It has two Cu/Zn - SODs isoforms which display about 40% of sequence identity. MD simulations were performed with the GPU implementation of the pmemd code, from AMBER14. The calculations employed the ff99SSBildn forcefield. Results are interpreted in comparison with E. crassus SODs, a congeneric mesophilic marine species. At the respective phisiological living temperatures SOD1 displays greater difference between rmsd values of simulations with and without ions -> more evident ionic effect SOD2 is more flexible than SOD1, it displays a reduced difference between rmsd values of simulations with and without ions -> lower influence of temperature and ionic presence Both ions presence and temperature changes mainly influence the loops forming the ions binding site. | BITS 2015, Milano, 03-05/06/2015 | 2015 | MILANESI LUCIANO, CHIAPPORI FEDERICA CATERINA | thermal adaptation, SOD, ions effect, protein structure | |
| 432985 | Poster | Effect of serine phosphorylation on aB-Crystallin interface multimeric form | Federica CHIAPPORI1, Luca MATTIAZZI1, 2, Luciano MILANESI1, Ivan MERELLI1 | ?B-Crystallin is a member of the small Heat Shock Protein (HSP) family. ?B-Crystallin simpler multimeric form is an homodimer, while more complex structures can be hollow globes composed from up to 40 monomers (the greatest homooligomer validated atomic model obtained is a 24-mer, Fig. 1a). This HSP is modulated by a trade-off between its different multimeric conformations: in particular, the active units are small complexes, like the hexamers (Fig. 1b), which are torus-like structures composed by 3 dimers connected via an interdimeric interface, while larger conformations are almost inactive. The multimerization of ?B-Crystallin, and thus its function, is controlled by the phosphorylation of two serine residues, Ser45 and Ser59 (Fig. 1c). They localize near the interdimeric interface, which supports the idea that phosphorylations influence the aggregation of dimers in higher structures. With the aim of studying the ?B-Crystallin multimerization, in this work we evaluate the phosphorylation effect on protein structures by molecular dynamics (MD). In particular, our purpose was to link different phosphorylation patterns to the diverse behaviours of the ?B-Crystallin in the 24meric state, using data collected from MD simulations of different multimeric structures. A previous analysis based on dimers II and hexamers MD simulations, identified 5 phosphorilation clusters (Fig2.): the first include phosphorylation patterns comparable to dimers with all P-ser, while the fifth includes pattern comparable to the non-P dimers. Dimers and hexamers structures were undergone to 30 ns of MD simulation at 300 K with Gromacs 4.5, employing the amber99sbP force field, which includes an energy model for phosphoserines. Moreover, three MD simulations of 100ns were obtained for the 24-mer: the first one without phosphorilation and the other two with a combination of promising phosphorylation patterns identified in the analysis of the phosphorylated dimer II. | EMBO course "Molecular chaperones: From molecules to cells and misfolding diseases", Crete, 08-13/05/2015 | 2016 | MERELLI IVAN, MILANESI LUCIANO, CHIAPPORI FEDERICA CATERINA | ?B-Crystallin, HSP, post-translational modifications, molecular dynamics | |
| 432986 | Poster | Autism and intestinal permeability: bioinformatics selection of candidate genes target | Federica CHIAPPORI, Matteo GNOCCHI, Luciano MILANESI, Alessandra MEZZELANI | AUTISM is considered a complex multifactorial disorder with genetic base, but causative genetic variations involve only a limited number of patients (15-40%), also evidenced by the risk familiarity. As hundreds of gene variants were found in only a subset of patients, the best model for ASD etiology would be OLIGOGENIC (HEREDITY + DE NOVO MUTATIONS) with an ENVIRONMENTAL contribution indeed a large number of genes confer risk to ASD as well as a large number of environmental factors have been proposed to interact with these genes. Moreover autistic patients often suffer from several comorbidities, among which, GASTROINTESTINAL (GI) DISORDERS with intestinal pathogen overgrowth and gut permeability have 60% prevalence and correlates with autistic symptom severity. These evidences have suggested that GI disorders alter the so called "GUT-BRAIN AXIS", or even MICROBIOTA-GUT- BRAIN EQUILIBRIUM and trigger the disease in genetically predisposed children. Perturbations of the gut microbiota alter the INTESTINAL PERMEABILITY and INFLAMMATORY SYSTEM thus playing a deleterious role IN NEURODEVELOPMENT as evidenced by inflammation condition in severe ASD patients with GI disorders and dysbiosis. Our aim was to identify the GENETIC PREDISPOSITION TO GUT PERMEABILITY leading to ABSORPTION OF ENVIRONMENTAL RISK FACTORS that, in turn, trigger the disease. Starting from these findings we will focus on the four underlined proteins among the 17 selected, involved in intestinal permeability in order to define the role of the relative mutations on the protein function and in ASD pathogenesis | BITS 2016, Salerno, 15-17/06/2016 | 2016 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, GNOCCHI MATTEO, CHIAPPORI FEDERICA CATERINA | autism, gut-brain axis, microbiota, gut permeability, genetic predisposition, environmental risk factors | |
| 432987 | Poster | Effect of gliadin modification on CXCR3 binding | Carisetti M, Moscatelli M, Milanesi L, Mezzelani A, Chiappori F | Gluten, the protein of wheat, is a complex molecule made of gliadin and glutenins; it is considered as "the environmental component" triggering Celiac disease (CD) since its components are both toxic for CD patients. During digestion, gliadin is reduced into small peptides of about 20 amino acids enriched in glutamine and prolines. These peptides can be deamidated by transglutaminase, converting specific glutamine (Q) residues into glutamic acid (E). In the intestinal epithelium the isoforms A and B of CX-Chemokine Receptor Type 3 (CXCR3), a G-Protein Coupled Receptor, specifically binds two of the gliadin peptides (111-130 and 151-170). Both gliadin and CXCR3 involved in CD onset. Evaluate the differential binding of the two-gliadin peptides. Evaluate differences between deamidated peptides and normal while binding the two CXCR3 isoforms (A and B). HADDOCK run returned up to 14 clusters for each peptide- protein docking simulation. The model with the lowest score and/or the lowest binding energy (VdW, Electrostatic and Desolvation) from each run was selected for MD simulation. They display different scores between deamidated and normal peptides. Among the resulting conformations from the Autodock CG simulations, the selected one correspond to the complexes with the lowest binding energy if considering peptide 111-130; instead, for peptide 151-170, the chosen conformation results the second in terms of binding energy but the first in terms of cluster numerosity, since the lowest binding energy conformation displays a backward orientation of the peptide. Haddock docking simulations suggested a higher affinity for normal peptides than for deamidated ones. Autodock CG application display a preference for A or B isoforms by deamidated peptides 111-130 and 151-170, respectively; on the contrary, normal peptides show an inverted preference for Cxcr3 isoforms. Given that our aim is to evaluate the effects of deamidation on the binding mode and affinity between CXCR3 isoforms, the MD simulations of CXCR3-gliadin are on-going. | CDDD 2017, IFOM, Milano, 16-17/11/2017 | 2017 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, MOSCATELLI MARCO, CHIAPPORI FEDERICA CATERINA | cxcr3, gliadin, celiac disease, protein-peptide docking | |
| 432989 | Poster | Gliadin peptide deamidation: effects on CXCR3 binding and signal transmission | Carisetti M, Moscatelli M, Milanesi L, Mezzelani A, Chiappori F | Gluten is a complex molecule made of gliadin and glutenins. During digestion, gliadin is reduced into small peptides of about 20 amino acids enriched in glutamine and prolines. In the intestinal epithelium the CXCR3 (CX-Chemokine Receptor Type 3, a G-Protein Coupled Receptor - GPCR) binds two of the gliadin peptides (pep 111-130 QQQQQQQQQQQQILQQILQQ and pep 151-170 QVLQQSTYQLLQELCCQHLW). Moreover, it is involved in celiac disease (CD) development inducing an increase of intestinal permeability, resulting in zonulin release, which is induced and activated through the MyD88-pathway. Two of the three splicing variants of CXCR3 are involved in CD: CXCR3-A and CXCR3-B. Furthermore, it is known that gliadin peptides are modified by tissue transglutaminase (tTG) converting specific glutamine (Q) residues into glutamic acid (E): pep 111-130E QQQQQQQQQQQQILQQILQE and pep 151-170E QVLQESTYQLLQELCCQHLW. Evaluate differences between deamidated and non-modified gliadin peptides bound to both CXCR3 a and b isoforms The selected conformations resulting from the Autodock CG simulations (Table 1) correspond to the complexes with the lowest binding energy if considering peptide 111-130; instead, for peptide 151-170, the chosen conformations result the second in terms of binding energy and the first in terms of cluster numerosity, since the lowest binding energy conformation displays a backward orientation of the peptide. HADDOCK run (Table 2) returned up to 14 clusters for each protein-peptide docking simulation, displaying different score ranges between deamidated and normal peptides. Instead, regarding energy values they display overlapping results except for Cxcr3b-pep111 complexes. The model with the lowest score and/or the lowest binding energy (VdW, Electrostatic and Desolvation) from each run was selected for MD simulations. MD trajectories analysis suggested either a change in CXCR3 TM-helices or in C- ter flexibility when comparing non-modified peptides to deamidated ones. Therefore, what we expect to understand is the effect of the gliadin deamidation, first on binding to CXCR3, secondly on the signal transmission to the cytoplasmic domain. Accordingly, an H-bond analysis was performed on MD trajectories. Results displayed an uninterrupted H-bond network from the binding cavity to the C-ter helix in the CXCR3a/111-130 (Fig. 2a) and CXCR3b/111-130E (Fig. 2b) complexes. But, the two complexes differ for the receptor residues involved in peptide binding (in blue in Fig.2), since the deamidated peptide binds charged residues, while the non-modified interacts with non-charged residues. Likewise, also the resulting Hbond networks involve different residues. The other CXCR3 complexes display several H-bond network stops before the C-ter. Haddock docking simulations did not allow a discrimination between non-modified and deamidated peptides while Autodock CG application displays a preference for CXCR3 a or b isoforms by deamidated peptides 111-130 and 151-170, respectively. H-bond analysis let us evaluate the effects of deamidation on the binding mode and on the affinity with CXCR3 isoforms, concluding that deamidation actively influences the binding to the receptor. Furthermore, we did not observe any substantial differences in signal transduction for peptide 151-170 (Fig. 2c), while peptide 111-130 displayed two distinct networks for each isoform (Fig. 2a and 2b). Given that CXCR3 is a GPCR, so the C-ter is involved in the activation of the G-coupled protein, these results suggest pep 111-130 as favoured ligand than pep 151-170, both for CXCR3 a and b. | BITS 2018, Torino, 27-29/06/2018 | 2018 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, MOSCATELLI MARCO, CHIAPPORI FEDERICA CATERINA | CXCR3, gliadin, protein/peptide modeling, protein-peptide docking | |
| 432994 | Presentazione | Psychrophilic protein modeling | Chiappori Federica | Tubulin dimers of psychrophilic eukaryotes can polymerize into microtubules at 4?C, a temperature at which microtubules from mesophiles disassemble. This unique capability requires changes in the primary structure and/or in post-translational modifications of the tubulin subunits. To contribute to the understanding of mechanisms responsible for microtubule cold stability, here we present a computational structural analysis based on molecular dynamics (MD) and experimental data of three ?-tubulin isotypes, named EFBT2, EFBT3, and EFBT4, from the Antarctic protozoon Euplotes focardii that optimal temperature for growth and reproduction is 4?C. The unique characteristics of the primary and tertiary structures of psychrophilic ?-tubulin isotypes seem responsible for the formation of microtubules with distinct dynamic and functional properties. Folding assistance is a fundamental requirement for tubulin. Here, we report a pilot folding analysis of a divergent beta- tubulin isotype, named EFBT3, from the Antarctic psychrophilic ciliate Euplotes focardii. To attain its native monomeric structure, beta-tubulin needs the assistance of the eukaryotic class II chaperonin CCT and cofactor A (CofA). We demonstrated that the rare Cys281 of EFBT3 is critical for the folding reaction. Model predictions indicate that EFBT3 binds to CofA differently from yeast beta-tubulin, suggesting a diverse folding mechanism that may be correlated with microtubule cold adaptation. Superoxide dismutases (SODs) are ubiquitous enzymes, which catalyse the disproportion of superoxide to molecular oxygen and peroxide. This reaction preempts the oxidizing chain reaction, preventing several cell damage caused by reactive oxygen species. E. focardii has two Cu/Zn - SODs isoforms which display about 40% of sequence identity. In order to investigate the structural adaptation and the effect of ions at living low temperature and at mesophilic temperature, we performed a computational structural analysis based on molecular dynamics (MD) at 4?C and 27?C, and complexed or un-complexed with Cu and Zn ions, for comparing the ions effect on protein structure and the structure flexibility at different temperature. | CIBB 2015, Napoli, 10-12/09/2015 | 2015 | CHIAPPORI FEDERICA CATERINA | tubulin, SOD, psycrophilic adaptation, protein modeling | |
| 432998 | Presentazione | Allosteric modulation: the Hsp70 case study | Federica Chiappori, Ivan Merelli, Luciano Milanesi | Allostery is a long-range macromolecular mechanism of internal regulation, in which the binding of a ligand in an allosteric site induces distant conformational changes in a distant portion of the protein, modifying its activity. From the drug design viewpoint, this mechanism can be exploited to achieve therapeutic effects; since allosteric ligands are able to regulate target proteins reducing side effects. Computational tools are a valid support in this sense, since they allow the characterization of allosteric communications within proteins, which are essential to design modulator ligands. We will discuss in silico approaches to characterize allosteric modulations, describing the Heat Shock Proteins family Hsp70, which is involved in many cancers, neurodegenerative diseases and plays an important role in pathogens survival under stress conditions. We apply an all-atom MD approach, in order to elucidate the molecular determinants underlying the allosteric inter-domain communication from the NBD to the SBD and back. In detail, a comparative analysis of an allosteric (Hsp70-DnaK) and a non-allosteric structural homolog (Hsp110-Sse1) of the Hsp70 family is carried out, starting from different conformations and ligand-states. Besides, Hsp70 complexes with a different ligand combination bound to the two Hsp70 binding sites, the nucleotide-binding site and the substrate-binding site, are simulated to analyze the allostery from the SBD to the NBD. Moreover, we performed a differential analysis of DnaK and human_Hsp70 to identify hot spots in the bacterial protein that are not present in the human homolog, with the aim of characterizing the key pharmacological features necessary to design selective inhibitors for DnaK | Proteomics, Roma, 24-26/10/2016 | 2016 | MERELLI IVAN, MILANESI LUCIANO, CHIAPPORI FEDERICA CATERINA | allostery, HSP, HPS70, DnaK | |
| 433000 | Presentazione | Identification of molecular determinants of CXCR3-gliadin-mediated triggering of intestinal permeability | Carisetti M(1, 2), Moscatelli M(2), Longeri M(1), Milanesi L(2), Mezzelani A(2), Chiappori F(2) | CXCR3 is a G-protein coupled receptor expressed principally on leukocytes, monocytes and epithelial cells; it is involved in leukocyte traffic, integrin activation, cytoskeletal changes and chemotactic migration by binding to its classical ligands, CXCL-9/10/11. Moreover, it is involved in celiac disease by binding of 2 peptides produced from gliadin digestion (111-130 and 151-170). This interaction induces an increase of intestinal permeability in a zonulin dependent way: the cytosolic adapter protein MyD88, crucial for the maintenance of gut homeostasis, is recruited and activates zonulin release. The latter, in turn, transactivates epidermal growth factor receptor (EGFr) through proteinase activated receptor 2 (PAR2) leading to tight junctions disassembly by the combination of TJ protein phosphorylation and actin polymerization. This causes the rearrangement of the filaments of actin and the subsequent displacement of proteins from the junctional complex. Three splicing variants of CXCR3 are known: CXCR3-A, the most common isoform, consists of 368 amino acid residues and is the most frequently expressed on immune cells; it couples to a G-protein which mediates pro-migratory and proliferative signalling and increases intracellular calcium levels; CXCR3-B, which can bind CXCL4 in addition to classical CXCL, results from an alternative splicing of the CXCR3 mRNA with a 52 aa extended NH2-terminal domain when compared to the isoform A, while CXCR3-alt is a significantly truncated variant activated only by CXCL11 and not involved in celiac disease. Recently it has been demonstrated that isoform A is more abundantly expressed in the intestinal mucosa of celiac patients, while the B isoform in gluten sensitive, non-celiac patients suggesting that both isoforms are involved in gliadin binding. Our goal is to evaluate the differential binding of the natural ligand, CXCL10 (or IP-10), and of the two gliadin peptides, on the two CXCR3 isoforms (-A and -B) involved in intestinal permeability. The 3D model of both isoforms, CXCR3-A (UNIPROT-id: P49682-1) and CXCR3-B (UNIPROT-id: P49682-2) were obtained from GPCR-I-TASSER [1]. Models were included in a membrane system with CHARMM-GUI server [2]. The obtained complexes were refined by MD simulation in agreement with CHARMM-GUI suggested protocol for Gromacs. X-ray structure of IP-10 was obtained from PDB (PDB ID: 1LV9), while gliadin peptides were predicted using different de novo peptide structure modeling servers: PEP-FOLD 3 [3] , PEPstrMOD [4] and QUARK [5]. Overall, 4 conformers were obtained for peptide 111-130 and 5 for 151-170. Protein-protein docking of CXCR3(A/B)-IP10 was performed with Haddock [6] and ZDOCK [7] servers, as well as protein-peptide docking of CXCR3(A/B)-gliadin(111-130/151-170) was performed with Z-DOCK, Haddock, and a coarse grained (CG) application of AutoDock. CXCR3(A/B)-IP10 docking outputs from ZDOCK have been discarded as the ligand did not interact with the binding cavity of the receptor, while Haddock results have been evaluated through structural analysis (FCC, i-RMSD and l-RMSD) and the HADDOCK model with the lowest score has been selected for further simulations. Docking complexes of CXCR3(A/B)-gliadin peptides obtained from ZDOCK have been clustered by chimera clustering tool and 1 conformer for each complex has been achieved; Moreover, HADDOCK run returned 1 or 2 clusters for each peptide-protein docking simulation. The AutoDock CG simulation on CXCR3(A/B)-gliadin peptides is ongoing. Outputs will be processed in order to compare the different docking algorithms employed. Given that our aim is to identify the molecular determinants of peptide binding instead of the natural ligand and the different binding mode and affinity between CXCR3 isoforms, complexes will undergo MD simulations. Moreover an MMPBSA analysis on the trajectories will be performed in order to determine the binding affinity. | BITS 2017, Cagliari, 05-07/7/2017 | 2017 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, MOSCATELLI MARCO, CHIAPPORI FEDERICA CATERINA | gliadin peptides, CXCR3, intestinal permeability, protein-peptide docking | |
| 433002 | Presentazione | CXCL10-CXCR3 complex formation, different isoforms result in different binding modes | M. Carisetti, M. Moscatelli, L. Milanesi, A. Mezzelani, F. Chiappori | CXCR3 is a G-protein coupled receptor expressed principally on leukocytes, monocytes and epithelial cells; it is involved in leukocyte traffic, integrin activation, cytoskeletal changes and chemotactic migration, by binding to its classical ligands, CXCL-9/10/11 (1). Three splicing variants of CXCR3 are known: CXCR3a, the most common isoform, consisting of 368 amino acid residues; CXCR3b resulting from an alternative splicing of the CXCR3 mRNA with a 52 aa extended N-terminal domain when compared to the isoform a, instead CXCR3-alt is a significantly truncated variant not involved in classical ligand binding (1). CXCL10, the interferon-?-inducible protein (IP-10) belongs to the CXC family of chemokines and acts as an immunoinflammatory mediator, inhibits angiogenesis and displays antitumor properties (2). Several studies indicated that the CXCR3 N-terminal domain plays a key role in determining binding affinity, receptor selectivity, and also in regulating allosteric signaling through the receptor (3). Moreover, sulfation of tyrosine in chemokine receptors is emerging as a post-translational modification that substantially contributes to ligand binding (2). Tyr 27 and 29, two of the N-terminal tyrosine can be sulfonated. Additionally, CXCR3b displays two other potential sulfonable tyrosines in the extended N-term domain, at position 6 and 40; these differences may affect the binding mechanism and the receptor activation of CXCR3b rather than CXCR3a (4). Finally, Kleist and co-workers hypothesize a "two-step" model, where receptor binding and activation can be dissociated (5). In the first step, the chemokine binds to the N-term domain of the receptor. In the second, residues on IP10 N-terminal bind to the binding cavity on the transmembrane domain of the receptor and induce the allosteric communication to the cytosol. In this work, we analyse by molecular dynamics (MD) simulation the binding mechanism of CXCL10 on CXCR3, evaluating the effect of tyrosine sulfonation and taking into account different sulfotyrosine combinations, on binding mode and affinity. In parallel, we analyse variations between CXCR3 isoforms a and b to highlight the different allosteric communication toward the cytoplasmic C-term domain, responsible of G-protein binding. We modelled CXCR3a and b isoforms, both were included in a double layer membrane with CHARMM-GUI server (http://www.charmm-gui.org/) and through the MD we optimized the structure conformation. The binding between CXCL10 and CXCR3 representative conformation was simulated employing a supervised MD approach (6). Several simulations were collected for each complex, in order to obtain a consistent result. In particular, the supervised MD was performed in 3 runs, using the same conditions, starting from the same equilibrated system. A list of selected residues from the N-term of CXCR3 and all the extra-cellular loop were adopted for the computation of the binding site instead the entire chemokine was considered as ligand in order to perform the supervision on the distance between the receptor (CXCR3) and the ligand (CXCL10). All simulations return the CXCL10 correctly positioned in CXCR3a binding site within the first 15ns (fig 1a). While, CXCR3b simulations doesn't reach the complex formation due to the closing up of the N-term domain, and interrupt at 9 A of ligand-receptor distance (fig 1b). CXCR3a complex simulations resulted consistent in both ligand-receptor decreasing energies, related to minor R-L distances and similarities in pattern of contacts, involving both residues from the CXCR3 N-terminal and the extra-cellular ?-sheet, which has been described as an important player for the receptor activation. A second round of supervised MD will be performed to evaluate the second step of the "two-step" model. The next step will be the evaluation of the effect of tyrosine sulfation (Y27, Y29 for both receptors and Y6, Y40 only for CXCR3b) (fig 1c) on binding mode and affinity. | BITS 2019, Palermo, 26-28/06/2019 | 2019 | MEZZELANI ALESSANDRA MARIA, MILANESI LUCIANO, MOSCATELLI MARCO, CHIAPPORI FEDERICA CATERINA | CXCR3, CXCL10, IP10, protein-protein binding, supervised molecular dynamics | |
| 433003 | Presentazione | Neuromics | Chiappori Federica | presentazione sull'applicazione delle omiche in ambito neuro | Neuroinformatica, CNR, Area Milano 1, 30/09/2015 | 2015 | CHIAPPORI FEDERICA CATERINA | omiche, neuroinformatica | |
| 433252 | Comunicazione in rivista (Letter - Letter to editor) | Standards Make The World Go Round | Domenica D'Elia1, Chris Evelo2, 3, Babette Regierer 4, 5, Susanne Hollmann 4, 6 | | EMBnet journal 25 (2020): 1-2. | 2020 | D'ELIA DOMENICA | standard, standard operating procedure, life science, omics, NGS | 10.14806/ej.25.0.931 |
| 434840 | Abstract in rivista | Analysis of cortical gene expression variability in a mouse model of X-linked Infantile spsms syndrome | Verrillo L, Tuccillo M, Drongitis D, Mangano E, Franco C, Terrone G, Canzoniero MT, Del Giudice E, Bordoni R, Poeta L, Miano MG. | None | Translational medicine @ UniSa (2019). | 2019 | DRONGITIS DENISE, TUCCILLO MARIACARMINE, VERRILLO LUCIA, BORDONI ROBERTA, MIANO MARIA GIUSEPPINA, MANGANO ELEONORA | Single-cell RNAseq, primary cells, embryonic brain | |
| 434884 | Poster | Analysis of transcriptome landscapes in the epileptogenic cortex of the Arx(GCG)7/Y mouse | Tuccillo M, Verrillo L, Drongitis D, Mangano E, Consolandi C, Franco C, Mallardo M, Cankaya I, M. T. Canzoniero, Poeta L, Bordoni R, Miano MG. | The X-linked Aristaless-related homeobox gene (ARX) encodes an interneuron-specific transcription factor (TF) with a key role in mammalian corticogenesis and GABAergic sub-type specification. Elongations in two of its four polyalanine (PolyA) tracts have been found in incurable neurodevelopmental disorders (NDDs), such as intellectual disability (XLID) and infantile spasms, a catastrophic chronic epilepsy resistant to standard cures. Here we report on a single-cell RNA sequencing (scRNA-Seq) study aimed to identify transcriptome landscapes in an epileptogenic niche of the Arx(GCG)7/Y mouse compared to the Wild Type (WT) one. Understanding all these aspects may help us to identify cell-specific epileptic-biomarkers linked to the disease-response that could be used as druggable molecules in anti-epileptic drug discovery research. | 19th International Workshop on Fragile X and other Neurodevelopmental Disorders, Sorrento, Naples, Italy, 18-21 September 2019 | 2019 | POETA LOREDANA, DRONGITIS DENISE, MALLARDO MARIO, TUCCILLO MARIACARMINE, VERRILLO LUCIA, BORDONI ROBERTA, MIANO MARIA GIUSEPPINA, CONSOLANDI CLARISSA, MANGANO ELEONORA | ARX, corticogenesis, scRNA-Seq, 10x Genomics | |
| 434897 | Poster | Exploring transcriptional single-cell signatures in a mouse model of epilepsy caused by a polyalanine expansion mutation in Aristaless-related homeobox gene. | Tuccillo M, Mangano E, Verrillo L, Poeta L, Consolandi C, Padula A, Franco C, Drongitis D, Mallardo M, Cervicato G, Canzoniero L M T, Bordoni R, Miano MG. | The X-linked Aristaless-related homeobox gene (ARX) encodes an interneuron-specific transcription factor (TF) with a key role in mammalian corticogenesis and GABAergic sub-type specification. Elongations in two of its four polyalanine (PolyA) tracts have been found in incurable neurodevelopmental disorders (NDDs), such as intellectual disability (XLID) and infantile spasms, a catastrophic chronic epilepsy resistant to standard cures. Our main objective is to disclose cell-to-cell expression variability, in terms of transcriptomic dynamics, underlying cellular heterogeneity and cell populations that bulk the Arx polyA epileptic brain. Understanding all these aspects may help us to identify cell-specific epileptic-biomarkers linked to the disease-response that could be used as druggable molecules in anti-epileptic drug discovery research. | EMBO Workshop- From epigenome towards epitranscriptome in cell fate choice, Capri, Nplaes, Italy, 14 -17 October 2018 | 2018 | POETA LOREDANA, PADULA AGNESE, CERVICATO GIUSEPPE, DRONGITIS DENISE, MALLARDO MARIO, TUCCILLO MARIACARMINE, VERRILLO LUCIA, BORDONI ROBERTA, MIANO MARIA GIUSEPPINA, CONSOLANDI CLARISSA, MANGANO ELEONORA | ARX, single-cell signatures, polialanine expansion mutation | |
| 435608 | Poster | Evaluation of the effectiveness of a preventive program focused on cognitive stimulation and physical exercise in virtual reality in people with mild cognitive impairment or subjective cognitive decline | Flaminia Franchini, Beatrice Filipputti, Federica Ratto, Matilde Luchi, Sara Arlati, Sarah Tabbozzi, C Caltagirone, Massimo Musicco, Simona Gabriella di Santo | TARGETS: An association exists between vascular and lifestyle modifiable risk factors and incident dementia. Many clinical trials have been started to provide evidence of the effectiveness of interventions aimed at these risk factors in preventing or postponing dementia onset, and multidomain approaches seem to be more effective than single-factor strategies. Virtual Reality (VR) is an innovative approach in neuroscience, that could be feasible and effective for intervention. GR-2013-02356043 is a RCT with 2X2 factorial design, to evaluate the separate and combined effect of cognitive stimulation (CS) and physical exercise (PE) in VR in delaying dementia onset or reduce cognitive and functional progression in 320 people with MCI OR SCD. METHODS: Here we present the results of analyses that compared the sub-samples subjected to training in VR and the outpatient control group (80 participants aged a?JPY 60 yrs). Each subject was twice randomized to receive CS/NO CS and PE/NO PE. The training provided twice-weekly sessions of CS and/or PE for 12 weeks. A complete neuropsychological and functional evaluation was performed at baseline (t0), post-training (t1) and 4 months after (t2). Mixed factor ANOVA (4 groups, 3 times) on ITT-LOCF data were conducted, corrected for demographics and baseline MMSE scores. RESULTS: 59 (73.8%) and 44 (55,0%) participants underwent t1 and t2 evaluations. Analyses showed significant group differences in Immediate and delayed recall of a short story (IR and DR: F3,74 = 2.94; p = 0.04 and F 3,74 = 3.11; p = 0.03) scores. Planned contrasts revealed significant differences at t2 between controls and CS+PE groups in IR (T(38) = 2,76; p < 0,01) and DR scores (t(38) = 2.00; p = 00.45) and between controls and CS groups in DR (T(38) = 2.15; p = 0.03). CONCLUSIONS: CS and CS+PE seem to exert mild effects ON memory performances that appear after a time from treatment. Caution in the interpretation is required due to high drop-out rates; however, the conservativeness of statistical analyses it presumably implies an underestimation of these effects, compared to their real extent. | XV Convegno Nazionale Sindem, Siena (Virtual Conference), 5-7/11/2020 | 2020 | DI SANTO SIMONA GABRIELLA, TABOZZI SARAH ANTONELLA, ARLATI SARA, MUSICCO MASSIMO | cognitive training, physical exercise, virtual reality, mild cognitive impairment | |
| 368284 | Abstract in atti di convegno | Modern research requires the use of standards: the CHARME project and its aims | Domenica D'Elia1, Babette Regierer2, Teresa K. Attwood3, Erik Bongcam-Rudloff4, Susanne Holmann5 | Introduction One of the most pressing need of modern research is efficient data sharing and integration, but tools and legislation about standards and Standard Operating Procedures (SOPs) that scientists can currently use are still not enough comprehensive, efficient and well harmonised. The production of omics data, by the use of High Throughput Next Generation Sequencing Technologies (HT-NGS), is providing incredible amounts of data at a rate much higher than the one taken to the scientists for to analyse and interpret them. This unbalanced situation prevents the scientific community to exploit the full potential that this "data production revolution" provides. The use of standards for the production and publication of research data is essential to maximize the results of research efforts and technology transfer because only standards can assure and ensure quality, efficient sharing and data interoperability. Reproducibility is essential for good research practices and reproducibility of data and experimental procedures can be obtained only if research data are produced and published by adhering to well established quality standards. Standards and SOPs must be key elements of any research project and be adopted in lab procedure as well as for in silico data production, storage and analysis. The CHARME project: "Harmonising standardisation strategies to increase efficiency and competitiveness of European life-science research", is a COST Action (CA 15110) whose main goal is to unite experts from all areas of scientific research and strategic development (academia, industry, policy, legal, ethical, etc.), joining their expertise to address needs and challenges along the value chain for life sciences research across Europe. The objectives are to address main gaps in standards and SOPs in different research domains, co-ordinate current research efforts in this field, integrate different stakeholder groups in CHARME's activities, co-develop a common research roadmap on quality management and standardization to provide the European Commission the support for the positioning of Europe as a "leading partner" in international standardisation and standardisation activities in life sciences, including input for technology transfer and cooperation with private enterprises. Methods To achieve the CHARME's 4-year vision, an integrated project strategy has been designed to ensure de-centralised decision-making and enhanced cooperation between the different stakeholders and partners. The leverage of the COST Action CHARME relates to four pillars: 1) the creation of a network of all relevant stakeholder groups involved in standardisation, to exchange and harmonise activities; 2) the development of a cross-cutting education and training strategy to raise awareness and facilitate the implementation of standards and SOPs; 3) strengthening of innovation creation and technology transfer; 4) strategy development to urge the implementation of standards and SOPs. This will be achieved via conferences and thematic workshops, short-term scientific missions, training schools and symposia, and deployment of standards optimising the transfer from basic research into innovation. Conferences and thematic workshops will be essential for to involve as many as possible experts from pan-European standardisation projects and initiatives, and attract as many as possible stakeholders, to present and discuss the state of the art in their specific research domain, to address current challenges and to collaborate with CHARME in finding and develop new effective solutions. Results On March 21st, representatives from 26 countries met in Brussels to execute the kick-off meeting. The participants exchanged information about the need for understanding formats and standards for biological data and computer models in systems biology research, and elected Chair, Vice Chair and working group leaders. During this meeting the action plan for the 1st Grant Period (01/05/2016 - 30/04/2017) was agreed among members and the Science and Administrative Officers of the Action. This plan include different events and Short Term Scientific Missions (STMS). A first step forward was the CHARME kick off Conference, which was held on June 21-22, 2016 in Warsaw. The conference: "The CHARME of standardistaion in life science", was designed to promote CHARME's efforts about standardisation to the broader scientific public, to merge the content with existing initiatives and finally to bring the experts together for information exchange. Representatives from academia, industry and standardisation bodies who have been making exceptional contributions to develop and disseminate standards were invited. The conference attracted more than 70 researchers from different European countries. Among the resources and initiatives that were presented there were: the "BioSharing Information Resources" (http://www.biosharing.org), a curated, web-based, searchable portal of three linked registries of content standards, databases, and data policies in the life sciences, broadly encompassing the biological, natural and biomedical sciences; COMBINE, a grass-roots standardisation initiative to coordinate the development of various community standards and formats for computational models; FAIRDOM (http://www.fair-dom.org), an initiative, funded by ERANet ERASysAPP and EU Research Infrastructure ISBE, to enable the systems biology community to produce and publish FAIR Data, Operating procedures and Models; the Big Data Reference Architecture (BDRA), whose development has been committed to "The International Standards Organisation (ISO)"; The Human Proteome Organization (HUPO) Proteomics Standards Initiative (PSI), whose mandate is to define community standards for data representation in proteomics to facilitate data comparison, exchange and verification; and many others. Another step forward is represented by the thematic workshop in Rome (IT), 25-26 October 2016, on 'Reproducibility, standards and SOP in bioinformatics' co-organised by CHARME, EMBnet (The Global Bioinformatics Network) and NETTAB (International Workshop Series on Network Tools and Applications for Biology) and hosted by the ELIXIR-IIB (ELIXIR Italian Node) at the Italian National Research Council head-quarter. This workshop will primarily involve bioinformaticians and computer scientists presenting and discussing methods, theoretical approaches, algorithms, tools, platforms, practical applications and experiences on the focus theme. Conclusions Since March 2016 CHARME has attracted 3 additional partners from different countries and others are willing to join. A survey among stakeholder that participated at the CHARME Conference in Warsaw has been an important resource to address stakeholder needs and the way CHARME is perceived (benefits it can provide). Main issues raised were the current lack of proper tools, the need for linking among different initiatives and of compatible/convertible standards. Solutions for metadata curation and for software availability were also requested as well as initiatives for to address and solve gaps in knowledge and communication. CHARME web site: http://www.cost-charme.eu/ Management Committee Members: http://www.cost-charme.eu/the-action/members Contacts: http://www.cost-charme.eu/contact | Combined CHARME - EMBnet and NETTAB 2016 Workshop on Reproducibility, standards and SOP in bioinformatics, pp. 188-190, CNR, Piazza Aldo Moro, 7, Roma, 25/10/2016, 26/10/2016 | 2016 | D'ELIA DOMENICA | Standards, SOP, COST Action, CHARME | |
| 368285 | Presentazione | Multi-type clustering for the identification of lncRNA-disease relationships | Gianvito Pio1, Francesco Serafino1, Emanuele Barracchia1, Domenica D'Elia2, Michelangelo Ceci1 | Introduction High-throughput sequencing technology, alongside new or improved computational methods, have been crucial for rapid advances in functional genomics. Among the most important results obtained thanks to the introduction of these new technologies, there is the discovery of thousands of non-coding RNAs (ncRNAs) whose function is pivotal for the fine-tuning of the expression of many genes that guide cell development, differentiation, apoptosis and proliferation [2]. Therefore, in the last decade, the number of papers reporting evidences about ncRNAs involvement in human complex diseases, such as cancer, is grown at an exponential rate. Among the different classes of ncRNAs, the most investigated one is that of microRNAs (miRNAs), which are small molecules (20-22nt long) that regulate the expression of genes through the modulation of the translation of their transcripts [4]. Much less is known about the functional involvement of long non-coding RNAs (lncRNAs), represented by RNA molecules longer than 200 nt, that have been recently discovered to have a plethora of regulatory functions spanning from chromatin modifications to post-transcriptional regulation [8]. However, the number of lncRNAs for which the functional characterization is available is still quite poor. Assessing the role and, especially, the molecular mechanisms underlining the involvement of lncRNAs in human diseases, is not a trivial task. Most of existing approaches are based on expensive experimental evaluations or on computational methods which exploit known/verified relationships among the lncRNA and the disease [6]. However, because of the complex functional interactions that lncRNAs can establish with other regulatory RNAs (i.e., miRNAs) or proteins, considering only the evidences of a direct relationship between lncRNAs and diseases may be very limiting. Some recent works started to consider further related information, but they do not consider possible dependencies among the relationships, but analyze single relationships independently. This corresponds to the assumption that all the instances follow the same probability distribution and that are independent to each other. In this case such assumption is easily violated, since different lncRNAs can be involved in the development of the same disease, as well as different diseases can be related to each other on the basis of the involvement of common lncRNAs or other regulatory entities such as miRNAs. To overcome these limitations we propose a computational method which is able to predict possibly unknown relationships between lncRNA and diseases by exploiting different in- formation about an heterogeneous set of (related) biological entities. In particular, we focus on lncRNAs, miRNAs, target genes and diseases, as well as on known relationships among these entities (see Figure 1). The proposed method is based on a clustering algorithm which is able to group objects of multiple types and to predict possibly unknown relationships on the basis of the extracted clusters. Moreover, the proposed algorithm is designed to identify highly cohesive, possibly overlapping and hierarchically orga- nized clusters, since i) the same lncRNA/disease can be involved in multiple networks of relationships and ii) as shown in [9], clusters at different levels of the hierarchy can describe more specific or more general relationships and cooperation activities. Methods In this section, we describe the solution we propose, which is based on three main steps: i) estimation of the strength of the relationships between lncRNAs and diseases; ii) identification of a hierarchy of possibly overlapping and hierarchically organized clusters of lncRNAs and diseases; iii) identification of possibly unknown lcRNA-disease relationships. In the following, we briefly describe each single step. Estimation of the strength of the relationships. The first step of the method consists in the iden- tification of the strength of the relationship for each lncRNA-disease pair. Such strength is represented by a score, which is computed as: s(li, dj ) = 1, if there exists a direct known relationship between the lncRNA li and the disease dj in the data, i.e. if there exists the relationship in the table disease_lcrna (see Figure 1). Otherwise s(li, dj ) = scoreP aths(li, dj ), where scorePaths(li, dj ) computes such score by considering all the alternative paths in the scheme, that are: olncrna - lncrna_target - target - disease_target - disease olncrna - lncrna_mirna - mirna - mirna_target - target - disease olncrna - lncrna_mirna - mirna - disease_mirna - disease In particular, scoreP aths(li, dj ) is computed as the maximum score obtained over all the paths. For each path P , the score is the cosine similarity computed over all the attributes of the entities involved in the path connecting li and dj . It is noteworthy that this score already gives an idea of the possibility that such relationships exist. However, we exploit them to build the hierarchy of clusters which is able to estimate the score more reliably, since based on the whole set of relationships. Construction of the hierarchy of clusters. Once each pair has been associated with a score, we build a cluster for each pair having a score greater than a given threshold ?. The goal is to identify the first level of the hierarchy consisting of clusters in form of cliques, where each lncRNA is associated to each disease in the cluster, with a score greater than ?. At this aim, we apply an iterative process which: sorts the clusters according to a quality criterion; for each cluster, finds the first cluster which can be merged with it preserving the clique constraint. The process stops when no further merging is possible, forming the first level of the hierarchy. The quality criterion we use, inspired by [9], is the cluster cohesiveness, which is the average score of the all the pairs that can be identified from the cluster. In order to build further hierarchical levels, we repeat the same process, by relaxing the clique constraint and by introducing a quality threshold ? on the cohesiveness of the cluster after merging. In details, the iterative process stops (and return a new hierarchical level), when no merging leading to a cluster with a cohesiveness greater than ? can be performed. Prediction of the relationships. Once we obtain the hierarchy of clusters, we identify possibly un- known relationships for each level of the hierarchy. In particular, the prediction is performed by assigning to each possible lncRNA-disease pair the score computed as the cohesiveness of the cluster in which it falls. When a lncRNA-disease pair appears in multiple clusters, we combine the cohesiveness of the set of clusters to obtain the final score. Baseline combination strategies can be the maximum, the minimum and the average. In this work, we propose a different combination function, which rewards those cases in which the pair appears in several highly cohesive clusters (indicating a higher probability of existence). Formally, given Cij = [C1, C2, . . . , Cn], the list of the clusters in which the lcRNA li and the disease dj appear, sorted in descending order with respect to their cohesiveness values w1, w2, . . . , wn, the score of the pair li, dj is computed as G(Cn), where: G(C1) = w1 G(Ck ) = G(Ck-1) + (1 - G(Ck-1) . wk In the experiments, we call this combination function custom and also evaluate its effectiveness with respect to the baseline combination approaches. Results The proposed method has been implemented in the system LP-MTRCLUS Figure 1. Relational schema of the database considered in the analysis and the results of the preliminary experiments, at three different levels of the hierarchy. A point in the graphs repre- sents the percentage of true relationships discovered (Y-axis) when we take a given number of returned interactions (X-axis). (Link Prediction through Multi-Type CLUStering). The dataset considered in this preliminary experiment (showed in Figure 1 as a relational database) has been built by integrating several existing biological datasets: interaction between lncRNAs and diseases and between lncRNAs and their target genes from [3]; interactions between miR- NAs and lncRNAs from [5]; interactions between diseases and genes from DisGeNET [1]; interactions between miRNAs and genes and interactions between miRNAs and diseases from miR2Disease [7]. The obtained relational database consists of 7.050 diseases, 507 lncRNAs, 508 miRNAs, 94.527 genes, 953 interactions between diseases and lncRNAs, 2.877 interactions between diseases and miRNAs, 26.522 interactions between diseases and genes, 70 interactions between lncRNAs and miRNAs, 252 interactions between lncRNAs and genes, and 803 interactions between miRNAs and genes. In this preliminary experiment, we performed a comparison between LP-MTRCLUS and HOCCLUS2 [9] which is a biclustering algorithm that also builds a hierarchy of clusters. The evaluation has been performed by applying the 10-fold cross validation on the set of known lncRNA-disease relationships. We averaged the results obtained according to the true positive rate measure, which is defined as TP R = TP where TP is the number of lncRNA-disease relationships that have been discovered and that have also been validated in literature, whereas FN is the number of known lncRNA-disease relationships that the considered system was not able to predict. Both TP and FN have been computed according to a threshold on the relationship score. By moving such threshold we obtain a curve where a point represents the percentage of true relationships discov- ered when we take a given number of returned interactions (see Figure 1). Following the results in [9], for both systems (LP-MTRCLUS and HOCCLUS2) we set the value of ? to 0.2 and ? = ? - 0.2. For space constraints, we limit the results to the first three levels of the hierarchical clustering. In Figure 1 it is possible to observe that LP-MTRCLUS is able to outperform HOCCLUS2 in all the hierarchical levels when we use the custom combination function. Such combination function is also able to outperform the other combination strategies whose performances are often worse than HOCCLUS2. As expected, the min strategy is the most conservative, whereas the max strategy shows a trend which is similar to HOCCLUS2. avg strategy is always in the middle between MIN and MAX strategies. As a final remark, it is noteworthy that HOCCLUS2 was able to obtain comparable performances because we provided it with set of lncRNA-disease scores computed by our system, since, in its original form, it is not able to analyze a complex relational database. For this reason, we are currently performing further experiments with other competitors to evaluate the effect of the integrated information on the results. Conclusions In this work, we focused on the recognized role of lncRNAs in human diseases. In particular, we pro- posed a computational method which is able to predict possibly unknown lncRNA-disease relationships by exploiting a clustering algorithm which work on multiple types of objects. Preliminary experiments showed that the proposed method, especially when adopting the proposed combination strategy, is able to outperform the algorithm HOCCLUS2. Currently we are performing additional experiments with other competitor approaches to deeply evaluate the effectiveness of the clustering-based method for this pur- pose as well as the effect of the exploitation of information about related biological entities, such as miRNAs, genes and their relationships with diseases and lncRNAs. References 1.A. Bauer-Mehren, M. Rautschka, F. Sanz, and L. I. Furlong. DisGeNET: a Cytoscape plugin to visualize, integrate, search and analyze gene-disease networks. Bioinformatics, 26(22):2924-2926, 2010. 2.T. Cech and J. Steitz. The Noncoding {RNA} Revolution--Trashing Old Rules to Forge New Ones. Cell, 157(1):77 - 94, 2014. 3.G. Chen, Z. Wang, D. Wang, C. Qiu, M. Liu, X. Chen, Q. Zhang, G. Yan, and Q. Cui. LncRNADisease: a database for long-non-coding RNA-associated diseases. Nucleic acids research, 41(D1):D983-D986, 2013. 4.J. Hayes, P. P. Peruzzi, and S. Lawler. MicroRNAs in cancer: biomarkers, functions and therapy. Trends in Molecular Medicine, 20(8):460 - 469, 2014. 5.A. Helwak, G. Kudla, T. Dudnakova, and D. Tollervey. Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell, 153(3):654-665, 2013. 6.S. Jalali, S. Kapoor, A. Sivadas, D. Bhartiya, and V. Scaria. Computational approaches towards understanding human long noncoding rna biology. Bioinformatics, 2015. 7.Q. Jiang, Y. Wang, Y. Hao, L. Juan, M. Teng, X. Zhang, M. Li, G. Wang, and Y. Liu. miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic acids research, 37(suppl 1):D98-D104, 2009. 8.M.-T. Melissari and P. Grote. Roles for long non-coding RNAs in physiology and disease. Pflugers Archiv - European Journal of Physiology, 468(6):945-958, 2016. 9.G. Pio, M. Ceci, D. D'Elia, C. Loglisci, and D. Malerba. A Novel Biclustering Algorithm for the Discovery of Meaningful Biological Correlations between microRNAs and their Target Genes. BMC Bioinformatics, 14(S- 7):S8, 2013. | Joint CHARME-EMBnet-NETTAB 2016 Workshop Reproducibility, standards and SOP in Bioinformatics, pp. 119-124, CNR, Piazzale Aldo More, 7, Roma, 25/10/2016, 26/10/2016 | 2016 | D'ELIA DOMENICA | Multi-type clustering, data mining, bioinformatics, long non-coding RNAs | |
| 368287 | Key note o lezione magistrale | 2016 Big Data Forum for Life and Health Sciences | Domenica D'Elia | The discovery of the pivotal roles of non-coding RNAs (ncRNAs) on gene expression and genome maintenance represents one of the most significant revolution of the last decades in life science research. Some ncRNA classes, such as ribosomal RNAs and transfer RNAs, have been known for a very long time, others, such as micro RNAs (miRNAs), Piwi interacting RNAs (piRNAs), and long non-coding RNAs (lnRNAs) were discovered in more recent years. However, the discovery of the great diversity and magnitude of this family of regulators is a recent achievement. Indeed, it is only in the last decade that, thanks to the advent of next generation sequencing technologies, large-scale sequencing studies have allowed scientists to systematically analyse ncRNAs for their real size and functional activities. These studies have identified a surprisingly large number of new and diverse ncRNA genes that are emerging to be central to many aspects of plant and animal gene regulation. Domenica D'Elia will expose some of the most relevant and recent results in this fascinating research domain, highlighting her research and recent achievements. | 2016 Big Data Forum for Life and Health Sciences, Beijing Institute of Genomics, Chinese Academy of Sciences No.1 Beichen West Road, Chaoyang District Beijing 100101, China, 05/12/2016, 08/12/2016 | 2016 | D'ELIA DOMENICA | non-coding RNA, genome, functional genomics | |
| 368288 | Poster | Standardisation in Life Sciences - with CHARME towards a unified standardisation European strategy | D'Elia D(1), Regierer B(2), Hollmann S(3) | Motivation Standardisation and quality management are important drivers in the life sciences and biotechnology, as only data generated with minimum quality assurance can be easily implemented into industrial applications. Standards assure and ensure that data become easily accessible, shareable and comparable along the value chain. Reproducibility, standards and standard operating procedures (SOPs) in data generation and analysis are challenging topics of the modern research and bioinformatics. Only by the use of common standards European life science research will improve its efficiency and competitiveness. In the past years several initiatives have been launched to develop and implement standards in life science research. Unfortunately, these efforts remain fragmented and largely disconnected. The Cost Action CHARME (CA15110) is designed as a central interface between existing standardisation initiatives, and as an intermediary between existing parallel efforts. The goals of CHARME are: 1) to develop a framework for standardisation of standards and formats in life sciences; 2) community building/networking of scientific standardisation initiatives; 3) development of a common understanding/definition of the subject matter; 4) to create a common platform for all stakeholders, for sustainable and efficient cooperation on standardisation and standardisation; 5) mediation between the scientific standardisation initiatives and the competent standardisation bodies and standards committees' activities (including input from stakeholders, e.g. standardisation bodies, policy makers, regulators, users); 6) the analysis and classification of existing (or developing) community standards in the field of systems biology and computational modelling (and beyond); 7) to support the positioning of Europe as a "leading partner" in international standardisation and standardisation activities in the life sciences (including input for future market applications and cooperation with private enterprises). Methods CHARME's pan-European network unites experts from all areas of scientific research and strategic development (academia, industry, policy, legal, ethical, etc.), joining their expertise to address needs and challenges along the value chain for life sciences across Europe. To achieve the Action's 4-year vision, an integrated project strategy has been designed to ensure de-centralised decision-making and enhanced cooperation between the different stakeholders and partners. The leverage of the COST Action CHARME relates to four pillars: 1) the creation of a network of all relevant stakeholder groups involved in standardisation, to exchange and harmonise activities; 2) the development of a cross-cutting education and training strategy to raise awareness and facilitate the implementation of standards and SOPs; 3) strengthening of innovation creation and technology transfer; 4) strategy development to urge the implementation of standards and SOPs. This will be achieved via workshops, short-term scientific missions, training schools and symposia, and deployment of standards optimising the transfer from basic research into innovation. Results On March 21st, representatives from 26 countries met in Brussels to execute the kick-off meeting. The participants exchanged information about the need for understanding formats and standards for biological data and computer models in systems biology research, and elected Chair, Vice Chair and working group leaders. During this meeting the action plan for the 1st Grant Period (01/05/2016 - 30/04/2017) was agreed among members and the Science and Administrative Officers of the Action. This plan include different events and Short Term Scientific Missions (STMS). The CHARME kick off conference will be held on June 21-22, 2016 in Warsaw. The conference "The CHARME of standardistaion in life science" is designed to promote 2016 in Warsaw. The conference "The CHARME of standardistaion in life science" is designed to promote our efforts about standardisation to the broader scientific public, to merge the content with existing initiatives and finally to bring the experts together for information exchange. Representatives from academia, industry and standardisation bodies who have been making exceptional contributions to develop and disseminate standards have been invited. Another step forward is represented by the workshop that will be held in Rome (IT), October 25-26, 2016 on 'Reproducibility, standards and SOP in bioinformatics'. This workshop is coorganised by CHARME, EMBnet (The Global Bioinformatics Network) and NETTAB (International Workshop Series on Network Tools and Applications for Biology) and it is hosted by the ELIXIR-ITA Node. This workshop will primarily involve bioinformaticians and computer scientists presenting and discussing methods, theoretical approaches, algorithms, tools, platforms, practical applications and experiences on the focus theme. Info CHARME Representatives: http://www.cost-charme.eu/the-action/members - Upcoming events: 1st CHARME Conference - "The CHARME of standardisation in life sciences", 21-22 June 2016, Warsaw, polland (http://www.cost-charme.eu/events/the-charme-of-standardisation-in-life-sciences-21-22-june-2016-inwarsaw- poland) Combined CHARME, EMBnet and NETTAB 2016 Workshop - "Reproducibility, standards and SOP in bioinformatics, October 25-26, 2016, Rome, Italy (http://www.igst.it/nettab/2016/) - For information on how to join CHARME: http://www.cost-charme.eu/training/how-to-join - For further information, please feel free to send an e-mail to info@cost-charme.eu. | 13th Annual Meeting of the Bioinformatics Italian Society, University of Salerno, Italy, 15/06/2016, 17/06/2016 | 2016 | D'ELIA DOMENICA | Standards, SOP, bioinformatics, system biology, COST Action, CHARME | |
| 376715 | Rapporto di ricerca (Research report) | Governance urbana e partecipazione dei cittadini. Aree di policy, formati di cooperazione e ruolo dei Sindaci nella gestione dei processi | AAVV | formati, pratiche e processi di governance urbana e partecipazione civica. | pp.30-46, 2017 | 2017 | ANTONUCCI MARIA CRISTINA | governance urbana, partecipazione civica, cittadinanza attiva, politiche locali, sindaci | |
| 380119 | Presentazione | PROMOTING HEALTHY TEENAGE BEHAVIOUR THROUGH THE USE OF A NOVEL MHEALTH TECHNOLOGY PLATFORM: PEGASO, DEVELOPED WITH AND FOR TEENAGERS | Lang, Alexandra Rosewall, Martin, Anne, Condon, Laura, McKinstry, Brian, Atkinson, Sarah, Gomez, Santiago, Puigdomenech, Elisa, Adorni, Fulvio, Rashid, Rajeeb | Mobile technology is ubiquitous in teenagers' lives, providing an opportunity for health behavior monitoring support and education (Ferrer-Roca 2012) to tackle the increasing prevalence of obesity in young people (WHO 2013). The mHealth based PEGASO project utilizes a user-centred design (UCD) approach integrating teenage and scientific requirements with a framework of behavior change (Michie et al. 2011) for real-time behavior detection and evaluation using an innovative technology platform to target obesity-related behaviors in teenagers (Pate et al. 2013). An evaluation of the multi-technology system (mobile applications, wearable sensors and serious game) is being undertaken to understand; - the impact on teenage lifestyle awareness and motivation for healthier behaviors - teenage experience of longitudinal system interaction and perspectives on health information technologies. | SAHM 2017 Annual Meeting, pp. S65-S66, New Orleans, March 8-11, 2017 | 2017 | ADORNI FULVIO DANIELE | Obesity prevention, mhealth, adolescents, lifestyles | 10.1016/j.jadohealth.2016.10.313 |