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| 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 | |
| 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 | |
| 362421 | Poster | Caratterizzazione microbica mediante Next Generation Sequencing e analisi della frazione lipofila volatile e non volatile del formaggio Bitto storico in funzione dell'alpeggio | F. Turri, P. Cremonesi, G. Gandini, G. Battelli, M. Severgnini, F. Pizzi | Il Bitto Storico e un formaggio d'alpeggio a latte crudo, prodotto nei mesi estivi sulle Prealpi Orobie, in alpeggi che praticano il pascolo turnato. La produzione di questo formaggio e strettamente legata ad attivita tradizionali che valorizzano la biodiversita alpina delle zone di produzione. Il disciplinare di produzione prevede, infatti, l'utilizzo di Iatte crudo che deve essere lavorato a caldo entro 1 ora dal termine della mungitura e vieta di integrare l'alimentazione del bestiame con mangimi e insilati, e di utilizzare fermenti lattici durante il processo di caseificazione. Tali pratiche svolgono un ruolo basilare nella conservazione dell'ambiente e della biodiversita alpina garantendo una certa variabilita microbica e di conseguenza organolettica del formaggio, grazie alla flora batterica locale caratteristica di ogni produttore-alpeggio. Obiettivi del presente lavoro sono: 1) caratterizzare la variabilita microbica del formaggio Bitto Storico mediante tecnologia Next Generation Sequencing (NGS); 2) caratterizzare la frazione lipofila volatile (metaboloma volatile e composti terpenici) e non volatile (profilo acidico); 3) correlare quindi il microbiota alla frazione volatile del formaggio, e la componente terpenica e il profilo degli acidi grassi tenendo in considerazione il fattore produttore-alpeggio. Campioni di i formaggio sono stati prelevati da 54 forme di Bitto Storico prodotte in 6 diversi alpeggi in 3 zone geografiche lombarde (Val Gerola, Valli del Bitto, Valle Brembana), in tre periodi diversi (Giugno-Luglio-Agosto 2015). In ciascun periodo di lavorazione e per ciascun casaro sono state prelevate 3 repliche di formaggio nella stessa settimana di produzione. Per l'analisi metagenomica, il DNA batterico e stato estratto mediante un protocollo specifico ottimizzato in laboratorio ed utilizzato come templato per I'amplificazione del gene 16S rRNA (regione V3-V4 seguendo il protocollo standard 16S Metagenomic Sequencing Library Preparation e sequenziato su piattaforma Miseq (Illumina). La classificazione tassonomica dei microrganismi e stata effettuata utilizzando QllME (Caporaso et al., Nat Methods, 2010). La frazione lipofila volatile e stata caratterizzata mediante micro estrazione in fase solida-gascromatografia-spettrometria di massa (SPME-GC-MS) mentre il profilo in acidi grassi mediante gascromatografia ad alta risoluzione (HRGC). I risultati preliminari mostrano nei diversi campioni una comunita microbica dominata prevalentemente da Firmicutes con abbondanza di Streptococcaceae e Lactobacillaceae e una minor presenza di Enterococcaceae. Il metaboloma volatile mostra una variabilita coerente con una produzione casearia di montagna a latte crudo. | 11? Convegno Nazionale sulla Biodiversita, Matera, 9-10/06/2016 | 2016 | BATTELLI GIOVANNA, SEVERGNINI MARCO, CREMONESI PAOLA, TURRI FEDERICA, PIZZI FLAVIA | Alpeggio, Bitto Storico, biodiversita microbica, acidi grassi, terpeni | |
| 362816 | Poster | Studio della biodiversita del microbiota del latte bovino per la valorizzazione delle razze autoctone italiane | Paola CREMONESI1*, Federica RIVA2, Maria Filippa ADDIS3, Lauretta TURIN2, Claudia POLLERA2, Marco SEVERGNINI4, Joel FILIPE2, Dario CALONZI1, Giulio CURONE2, Daniele VIGO2, Paolo MORONI2, Valerio BRONZO2, Bianca CASTIGLIONI1 | Una migliore conoscenza della qualita e delle caratteristiche del latte prodotto da razze autoctone risulta necessaria ai fini della loro valorizzazione. In questi ultimi anni si e intensificato l'interesse per lo studio della composizione del microbiota del latte per l'impatto che i microrganismi presenti possono avere sia sulla salute dell'animale sia sulla qualita e la sicurezza dei prodotti lattiero caseari (Addis et al., Molecular Biosystem, 2016). Ricerche preliminari condotte sul microbiota mammario delle principali specie di ruminanti (bovina, ovina, bufalina) hanno messo in evidenza come nel latte crudo sia presente una comunita microbica complessa, la cui composizione e influenzata sia da fattori endogeni che esogeni (Quigley et al., FEMS Microbiol.Rev, 2013). Il presente studio mira quindi a comprendere le differenze nei meccanismi molecolari di interazione del microbiota del latte in bovine di razza Rendena rispetto alla Frisona. A tal fine e stata confrontata la composizione microbica del latte di tre bovine di razza Rendena con quella di tre bovine di razza Frisona Italiana, allevate in uno stesso allevamento e sottoposte allo stesso regime gestionale. Sono stati raccolti campioni di latte dai singoli quarti degli animali a quattro diversi tempi: alla messa in asciutta (T1), il giorno del parto (T2), 7-10 giorni dal parto (T3) e 30 giorni dal parto (T4). Per verificare lo stato di salute della ghiandola mammaria sui campioni di latte e stata eseguita la conta delle cellule somatiche e l'analisi batteriologica. Dopo aver estratto il DNA dai campioni di latte utilizzando un protocollo descritto in letteratura (Cremonesi et al., JDS, 2006), il gene 16S rRNA (regione V3-V4) e stato amplificato seguendo il protocollo standard di preparazione delle librerie Illumina e sequenziato mediante piattaforma Miseq (Illumina, San Diego, USA). L'analisi batteriologica ha mostrato l'assenza di microrganismi contagiosi nel latte di entrambe le razze analizzate. Nella razza Rendena il phylum predominante e risultato Firmicutes (94.3%), mentre nella razza Frisona Italiana il microbiota e risultato composto da Firmicutes (62.6%), Proteobacteria (19.2%), Bacteriodetes (7.5%) e Actinobacteria (6.8%). L'analisi condotta a livello di genere nella Rendena ha mostrato la netta prevalenza di Streptococcus (70.7%), seguita da Lactobacillus (10.4%) e Pediococcus (5.8%), mentre nella Frisona sono stati osservati come generi prevalenti Streptococcus (27.1%), Staphylococcus (5.5%) e Lactobacillus (4.5%). Per quanto riguarda le specie del genere Streptococcus presente, e stata osservata una differenza significativa fra la razza Rendena, dove il 51.6% degli streptococchi e costituito da Streptococcus thermophilus e la razza Frisona dove lo Streptococcus thermophilus rappresenta solo l'1.72% degli streptococchi totali osservati. Streptococcus thermophilus e un batterio lattico utilizzato nella produzione di latti fermentati, yogurt e moltissimi formaggi: la sua presenza in percentuali elevate nel latte della razza Rendena rende pertanto questo latte piu adatto alla trasformazione casearia (Quigley et al., FEMS Microbiol. Rev, 2013). Sono attualmente in corso analisi dell'espressione genica differenziale a livello della ghiandola mammaria di questi animali e lo studio delle proteine del latte mediante analisi con SDS-page e densitometria, allo scopo di acquisire maggiori conoscenze dei meccanismi molecolari, dei pathway cellulari e delle interazioni ospite-microbiota mammario. L'avvento di tecnologie high-troughput in grado di fornire un quadro completo della composizione microbica del latte consente una maggiore conoscenza delle caratteristiche di questi animali autoctoni promuovendone l'allevamento e salvaguardandone cosi la biodiversita. | 5? Congresso dell'Associazione Italiana dei tecnici del Latte (AITeL), LATTE E DERIVATI: RICERCA, INNOVAZIONE E VALORIZZAZIONE, Bari, 09/07/2016 | 2016 | CALONZI DARIO, CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA | Frisona, Rendena, latte, microbiota, next generation sequencing | |
| 363122 | Abstract in atti di convegno | STUDY OF BOVINE MILK MICROBIOTA BIODIVERSITY IN AUTOCTONOUS ITALIAN BREEDS | G. Curone1, P. Cremonesi2, F. Riva1, M.F. Addis3, L. Turin1, C. Pollera1, M. Severgnini4, J. Filipe1, D. Calonzi2, D. Vigo1, P. Moroni1, V. Bronzo1, B. Castiglioni2 | None | 4th World Congress on Targeting Microbiota, 17/10/2016, 19/10/2016 | 2016 | CASTIGLIONI BIANCA MARIA ELISABETTA, SEVERGNINI MARCO, CREMONESI PAOLA | Rendena, Holstein milk, microbiota, next generation sequencing | |
| 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 |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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 |
| 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 | |
| 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 | |
| 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 | |
| 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 |
| 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 | |
| 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 | |
| 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 |
| 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 | |
| 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 | |
| 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 | |
| 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 |
| 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 |
| 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 |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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. | Project report, Nestore, Deliverable D4.2, 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". | Project report, Nestore, Deliverable D6.3.2, 2019 | 2019 | PILLITTERI LOREDANA, RIZZO GIOVANNA, MIORI VITTORIO, PALUMBO FILIPPO, CRIVELLO ANTONINO | NESTORE Architecture, Shared Component, End User, API, Sensors, IOT, Platform, Cloud, Applications | |
| 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 | |
| 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 |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 447338 | Abstract in atti di convegno | Non-integrating Reprogramming of Mammalian Cells for Genome Resource Banking | Kehler J, Driscoll C, Roelke-Parker ME, Reinbold R, Zucchi I, Barr C. | Descrizione: The derivation of induced pluripotential cell (iPSC) lines from somatic cells undergoing Whole Genome Sequencing (WGS) provides a complementary resource for conservation and compar-ative genomic studies. Routine reprogramming of human patient cells is being used to capture the genetic diversity of individuals included in Genome Wide Association Studies (GWAS) to generate new cell models that can recapitulate developmental and disease processes in a dish. This strategy can be extended across genera to generate unlimited amounts of pluripotent cells from individual animals included in WGS projects. The conservation of identity of key transcription factors is sufficient that transduction with pseudo!typed retroviral vectors expressing the human Oct4, Sox2, Klf4 and c-Myc cDNAs can reprogram somatic cells from a wide range of mammals without the need to clone species specific genes. One concern of this retroviral approach is that the putative iPSC lines can become transformed, due to incomplete silencing of the integrated transgenic proto-oncogenes preventing differentiation, as well as promoting the accumulation of aneuploidies. To overcome these technical hurdles, non-integrating reprogramming methods including transduction with mRNA viral vectors and daily transfection with synthetic mRNAs were compared and have proven effective in reprogramming fibroblasts from a range of canine, feline and Non-Human Primate species. Of practical utility, these putative iPSC lines grow rapidly and can be cultured for over 15 passages, well beyond the point at which the parental fibroblast lines undergo senescence. The majority of putative iPSC lines derived by these non-integrating methods maintain a normal diploid karyotype by Giemsa banding. Standard in vitro and in vivo assays are underway to test the plurip!otency of these cell lines. In addition, WGS is being performed on select samples to compare the genomes before and after repro!gramming to make sure that no significant genetic drift has occurred in culture. RNA-based reprogramming provides a reproducible approach to generating viable cell models free of DNA-artifacts and can add value to current genome resource banking efforts. | BioGenomics2017 Global Biodiversity Genomics Conference, Washington, D.C., 21-23/02/ 2017 | 2017 | ZUCCHI ILEANA, REINBOLD ROLLAND ALVONS | reprograming, mammalian cells | |
| 447346 | Abstract in atti di convegno | Heparan Sulfate proteoglycans as regulators of cancer stem cell functions | Martin Gotte M, Sampath SK, Reinbold R, El-Ghomaimy, Zucchi I, Ibrahim SA, Ludwig Kiesel L, Greve B. | Syndecan-1 (CD138), a heparan sulfate proteoglycan, acts as a coreceptor for growth factors and chemokines and is a molecular marker associated with epithelial-mesenchymal transition during development and carcinogenesis. Resistance of Syndecan-1-deficient mice to experimentally-induced tumorigenesis has been linked to altered Wnt-responsive precursor cell pools, suggesting a potential role of Syndecan-1 in breast cancer cell stem function. Syndecan-1 knockdown in MDA-MB-231 cells significantly reduced putative cancer stem cell pools. Activation of STAT-3 and NFkB transcription factors and expression of a coreceptor for Wnt signaling, LRP-6, were reduced in Syndecan-1-depleted cells compared to controls Syndecan-1 siRNA reduced the formation of spheres and cysts in MCF-7 cells grown in suspension culture. Our study demonstrates the viability of flow cytometric approaches in analyzing cancer stem cell function. As Syndecan-1 modulates the cancer stem cell phenotype via regulation of the Wnt and IL-6/STAT3 signaling pathways, it emerges as a promising novel target for therapeutic approaches. | International Meeting: Glycans and Proteoglycans: The Sweet and Smart Molecules of the 21st century, Nancy, France, 18-19/10/ 2017 | 2017 | ZUCCHI ILEANA, REINBOLD ROLLAND ALVONS | syndecan, wnt, stemness | |
| 448121 | Monografia o trattato scientifico | Cucina Mediterranea Integrata e Terapie Oncologiche | G. Adolfo Sbisa, Maria Grazia Forte, Elisabetta Sbisa | Il volume vuole essere una guida pratica per pazienti e familiari, ma anche per tutti coloro che vogliano assumere sane abitudini alimentari, un supporto sui cibi da evitare e su quelli da prediligere. E quanto, del resto, si prefigge anche la scuola di nutrizione fondata da Adolfo Sbisa, coautore del libro. La Apulian Natural Cookery School, si occupa proprio di cucina mediterranea e di cibo per la salute, tanto e vero che una sezione e riservata alla nutrizione oncologica. Diversi gli alimenti che un paziente oncologico dovrebbe consumare con molta parsimonia, ancor piu quelli sconsigliati durante un regime di aggressione al cancro. Un adeguato stile alimentare, puo modulare gli effetti negativi delle terapie e, al tempo stesso, aiutare l'organismo ad essere piu ricettivo nei confronti delle cure medesime. Il libro non solo fornisce lo schema alimentare ma anche i mezzi per poterlo attuare senza rinunciare al piacere della buona tavola; ricette e consigli per i giorni no, la dieta che precede la somministrazione della chemioterapia e quella per i giorni seguenti. Un volume di grande spessore emotivo e culturale: fotografie accattivanti, ricette gustose e, nonostante l'argomento anche di natura medica, di facile lettura. | 2016 | 2016 | SBISA' ELISABETTA | Nutrizione paziente oncologico | |
| 448175 | Rapporto tecnico | Analisi di dati diagnostici di laboratorio e clinici tramite metodologie bioinformatiche e biostatistiche | M. Moscatelli, M. Gnocchi | La relazione descrive l'infrastruttura sviluppata che permette l'Integrazione di sorgenti multiple ed eterogenee di dati anonimizzati provenienti dalle differenti piattaforme cliniche utilizzate dal CDI. Descrive gli algoritmi implementati che consentono l'estrazione e l'utilizzo delle informazioni presenti anche all'interno di campi non strutturati (testo libero) o semi-strutturati, ottenendo un'analisi storica precisa delle attivita cliniche di uno o piu pazienti. Ed infine illustra come l'unione dei dati permette di porre le basi per una serie di valutazioni statistiche necessarie a rispondere a quesiti piu complessi utilizzabili in diversi ambiti come la medicina predittiva e di precisione. | Protocollo N 0001816 del 09/10/2017, 2017 | 2017 | GNOCCHI MATTEO, MOSCATELLI MARCO | Centro Diagnostico Italiano, Personal medicine, NoSQL Database | |
| 448182 | Rapporto tecnico | Dal web al desktop: come creare applicazioni ibride | Matteo Gnocchi e Marco Moscatelli | descrive come sviluppare, partendo da una applicazione web basata sul framework Angular, un eseguibile installabile ed utilizzabile sui maggiori sistemi operativi in commercio; in particolare: | Protocollo N 0002368 del 14/11/2019, 2019 | 2019 | GNOCCHI MATTEO, MOSCATELLI MARCO | Wen application, Desktop application | |
| 448179 | Rapporto tecnico | Nuova Directory Nazionale BBMRI.it | Matteo Gnocchi e Marco Moscatelli | Descrizione della nuova directory nazionale BBMRI.it sviluppata con il framework javascript Angular (prossima alla release 3.X) | Protocollo N 0002330 del 6/10/2018, 2018 | 2018 | GNOCCHI MATTEO, MOSCATELLI MARCO | BBMRI.it, Angular, Biobank directory | |
| 448169 | Rapporto tecnico | Realizzazione di una rete di sensori per il monitoraggio ambientale di un locale server | M. Gnocchi, M. Moscatelli | Scopo della relazione e quello di descrivere l'applicazione di tecnologie e metodiche per il monitoraggio ambientale del locale Server in uso presso la sede di Segrate del CNR-ITB. L'esigenza di integrare un sistema di questo tipo nasce dalle seguenti considerazioni: . Parametri di Monitoraggio Ambientali: Avere una visione globale della situazione ambientale all'interno e all'esterno del locale in tempo reale, consultabile remotamente. . Integrazione non invasiva L'infrastruttura non deve richiedere l'installazione di apparecchiature difficilmente collocabili ed utilizzabili . Risparmio Energetico Identificare eventuali problematiche ambientali nel locale in modo da migliorare l'efficienza energetica diminuendone i costi di mantenimento . Manutenzione predittiva Possibilita di intervenire in modo autonomo in caso di particolari eventi . Sicurezza Aumentare la sicurezza del locale dal punto di vista dei parametri ambientali | Protocollo N 0001808 del 05/10/2017, 2017 | 2017 | GNOCCHI MATTEO, MOSCATELLI MARCO | monitoraggio, sensori, edge node, risparmi energetico, sicurezza | |
| 448195 | Rapporto tecnico | Realizzazione di una piattaforma di High Performance Computing | M. Moscatelli, M. Gnocchi | L'infrastruttura descritta si basa sull'utilizzo di un sistema di provisioning per l'installazione dei diversi servizi. La piattaforma di High Performance Computing e composta principalmente da 3 Servizi: Identity Management, Storage e Job Scheduler system. L'identity Management consiste di un ambiente in cui vengono immagazzinate le informazioni relative agli utenti e ai servizi; per il corretto funzionamento del sistema, la sincronizzazione del timestamp e per l'autenticazione ai sistemi sono configurati anche i server NTP, DNS e Kerberos. Inoltre grazie al server Kerberos viene implementato il sistema di Single Sign On (SSO). Lo storage viene reso fruibile ai diversi server tramite l'esportazione di file system Lustre; per permettere un'alta disponibilita del sistema ed un'elevata efficienza di accesso ai dati vengono configurate due coppie di nodi. La prima coppia (MDS nodes) e responsabile dell'accesso ai metadati e quindi all'identificazione della posizione dei dati veri e propri; i dati sono provisionati dalla seconda coppia di nodi (ODS nodes) che rendono accessibili i dati ai client. Infine, il sistema di Scheduling viene gestito da un server Master affiancato da un sistema di Backup in caso di failure. I dati e l'accounting sono salvati su un apposito server con funzione di database. Al cluster e possibile accedere tramite appositi nodi di Login che permettono la sottomissione di job nel cluster. | Protocollo N 0 000924/2020 del 26/05/2020, 2020 | 2020 | GNOCCHI MATTEO, MOSCATELLI MARCO | Ansible, SSO, Kerberos, LDAP, HPC | |
| 448199 | Rapporto tecnico | Design E Prototipazione Di Una Piattaforma Per La Gestione Di Progetti Single Cell | M. Moscatelli, M. Gnocchi | Il prototipo descritto permette di centralizzare l'accesso ai principali servizi necessari alla gestione di un progetto di analisi "Single Cell". L'infrastruttura garantisce l'accesso ad un ampio spettro di risorse (dati, calcolo, applicazioni, etc ...) nascondendo all'utente la complessita dell'interazione con un ambiente eterogeneo. Tramite l'applicazione client l'utente puo accedere facilmente ed in modo ordinato ai dati suddivisi per progetto garantendo allo stesso tempo un pieno controllo di quel che succede agli amministratori di sistema. Le tecnologie implementate permettono di gestire una grande quantita di dati da qualsiasi dispositivo senza limitare le performance garantendo un accesso in mobilita. | Protocollo N 0000676/2020 del 01/04/2020, 2020 | 2020 | GNOCCHI MATTEO, MOSCATELLI MARCO | Single Cell, HPC, Web app | |
| 448378 | Rapporto di commissione | 2016 EMBnet Annual General Meeting - Executive Board Report | Domenica D'Elia1, Emiliano Barreto Hernandez2, Lubos Klucar3, Erik Bongcam-Rudloff4 | During the past year, the Executive Board (EB) held regular monthly meetings either via Skype or using Adobe Connect. These meetings were carried out with the Interim Board (IB), comprising members of the EB and Teresa Attwood and Etienne de Villiers. The IB was established during the 2015 Annual General Meeting (AGM) both to support the new EB in its first steps forward (as three of its members were new), and to help oversee implementation and delivery of the investment strategy. The EB also regularly invited Special Interest Group (SIG) Chairs to participate at EB-IB meetings. Additional monthly meetings open to the full EMBnet constituency were also convened. In this report, we provide a brief overview of activities and achievements from June 2015 to October 2016. | pp.e887-e887, 2017 | 2017 | D'ELIA DOMENICA | Activity Report, EMBnet, Executive Board, Bioinformatics | |
| 448496 | Presentazione | COST Action CHARME (CA15110) - Harmonising standardisation strategies to increase efficiency and competitiveness of European Life Science Research | Domenica D'Elia | The COST Action CHARME: a European initiative for the harmonisation of standards for life-science research Open Science (OS) describes the ongoing transitions in the way research is performed, i.e. researchers collaborate, knowledge is shared, and science is organised. OS is driven by digital technologies and by the growth of data, globalisation, enlargement of the scientific community and the need to address societal challenges. It has now widely been recognised that making research results more accessible contributes to more efficient science and innovation in the public and private sectors. To unlock that potential, data needs to be made computer readable and interoperable. Therefore, they must be generated, formatted and stored according to Standard Operating Procedures and Data Management Plans included as an integral part of any projects. Although several initiatives are actives in different life science research fields, they are still too much fragmented. A significant barrier hindering the implementation of FAIR (findable, accessible, interoperable and reusable) data principles is the lack of awareness and insufficient education of scientists and other stakeholders in the process of producing, handling, publishing and transferring knowledge to biotech applications. CHARME: "Harmonising standardisation strategies to increase the efficiency and competitiveness of European life-science research", is an Action funded through COST (European Cooperation in Science and Technology). CHARME aims to identify needs and gaps in standards, teaming up with other initiatives and organisations, and proposing new strategies for successful assimilation of standards into the daily work-flow of researchers. This presentation underlines the scenario in which CHARME moves and actions needed to increase the efficiency and competitiveness of life-science research. | ISCB-LA SOIBIO EMBnet 2018 Conference, Vina del Mar, Chile, Nov 5 - 9, 2018 | 2018 | D'ELIA DOMENICA | Standards, Standard Operating Procedure, Bioinformatics, Reproducibility, Open Access, Quality Control | |
| 448497 | Poster | The COST Action CHARME A European Initiative for the Harmonisation of Standards for Life Sciences Research (CA15110) | Domenica D'Elia | 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 modern research and bioinformatics. Only by the use of common standards life science research will improve its efficiency and competitiveness. CHARME aims to identify needs and gaps in standards, teaming up with other initiatives and organisations, and proposing new strategies for the successful assimilation of standards into the daily work-flow of researchers. Currently, 30 EU countries are involved in this initiative, which makes it one of the most widely recognised Actions among all COST initiatives. | ISCB-LA SOIBIO EMBnet 2018 Conference, pp. A17, Vina del Mar, Chile, 5-9 November, 2018 | 2018 | D'ELIA DOMENICA | Standards, COST Action, Standard Operating Procedure, Big Data Storage | |
| 448499 | Presentazione | Combined CHARME - EMBnet and NETTAB 2016 Workshop, October 25-26, 2016, Rome, Italy | Domenica D'Elia | Presentazione introduttiva al Congresso relativa alla COST Action CHARME - co-organizzatore el Congresso | Reproducibility, standards and SOP in bioinformatics - Combined CHARME - EMBnet and NETTAB 2016 Workshop, Rome, Italy, October 25-26, 2016 | 2016 | D'ELIA DOMENICA | Standards, Standard Operating Procedures, CHARME, COST Action, Reproducibility, Big Data | |
| 448502 | Poster | Multi-type clustering for the identification of lncRNA-disease relationships | Gianvito Pio1, Francesco Serafino1, Emanuele Pio Barracchia1, Domenica D'Elia2, Donato Malerba1, Michelangelo Ceci1 | High-throughput sequencing technology has been crucial for rapid advances in functional genomics. The most important result is the discovery of thousands of non-coding RNAs (ncRNAs) which are able to fine-tune the expression of many genes involved in cell development, differentiation, apoptosis and proliferation [1]. Among ncRNAs, the most investigated are the microRNAs (miRNAs), small molecules (20-22 nucleotide long) that play the role of post-transcriptional regulators [2]. Much less is known about the functional role of long non-coding RNAs (lncRNAs), RNA molecules longer than 200 nt, that have been recently discovered to have a plethora of regulatory functions spanning from epigenetics to post-transcriptional regulation [3]. However, the number of lncRNAs for which the functional characterisation is available is still quite poor. Most of existing approaches are based on expensive experimental evaluations or on computational methods that exploit known/verified relationships among the lncRNA and the disease [4]. Some recent works consider 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. To overcome these limitations we propose a computational method which is able to predict possible unknown relationships between lncRNA and diseases by exploiting different information 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. The proposed method is based on a clustering algorithm which is able to group objects of multiple types and to predict possible unknown relationships on the basis of the extracted clusters. Moreover, the proposed clustering algorithm is designed to identify highly cohesive, possibly overlapping and hierarchically organised clusters, since i) the same lncRNA/disease can be involved in multiple networks of relationships and ii) as shown in [5], clusters at different levels of the hierarchy can describe more specific or more general relationships and cooperation activities. | Reproducibility, standards and SOP in bioinformatics - Combined CHARME - EMBnet and NETTAB 2016 Workshop, Rome, Italy, October 25-26, 2016, Rome, Italy | 2016 | D'ELIA DOMENICA | Multi-Type Clustering, Bioinformatics, Machine Learning, Disease | |
| 448998 | Presentazione | Network diffusion-based analysis of genomic data. | Ettore Mosca | The information on direct and indirect molecular interactions can be modelleddefining genome-scale networks. The integrated analysis of "-omics" measurementsand molecular interactions, referred to as network-based analysis, provides severalopportunities for a better interpretation of omics data, which is often hindered bybiological complexity and experimental biases. In comparison to theindependentanalysis of every statistical unit, network-based quantities interpret omics data tak-ing into account the modular and functional architecture of cells. Network-basedapproaches have been proposed in relation to several problems, including gene mod-ule identification, pathway analysis and patient stratification, justto mention a few.Among network-based approaches, the principle of spreading information through-out a network - namely network diffusion - has been recently used in several applica-tions, mainly related to the "smoothing" of sparse input quantities and the prioritiza-tion of molecular entities in network proximity. Here, we describe a network-diffusionbased framework for -omics data analysis aimed at identifying gene modules [1]. Thisframework is based on indices that jointly quantify molecular measurements and net-work location. The resulting ranked gene list is then analysed to assess the presenceof significant subnetworks. After having introduced the method -implemented as anR package named dmfind - and its performance in a controlled scenario, we presentthe results obtained on prostate cancer molecular profiles (somatic mutations andgene expression) and multiple gene lists associated with autism spectrum disorders. | The 34th Leeds Annual Statistical Research Workshop, 26-28/06/2017 | 2017 | MOSCA ETTORE | Biological Networks, Genomics, Network Diffusion | |
| 449037 | Sito web | Sito Web EPICOViD19 | Matteo Gnocchi | Il progetto EPICOVID19 si propone di raggiungere ogni fascia adulta della popolazione, e stato approvato dal Comitato Etico dell'Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani I.R.C.C.S. | 2020 | 2020 | ADORNI FULVIO DANIELE, GNOCCHI MATTEO | COVID19, EPIDEMIOLOGIA | |
| 449179 | Rapporto tecnico | Using community events to increase quality and adoption of standards: the case of Bioschemas | Giuseppe Profiti, Rafael C. Jimenez, Federico Zambelli, Ivan Mi?eti?, Vito Flavio Licciulli, Matteo Chiara, Silvio Tosatto, Rita Casadio, Graziano Pesole | We present how a workshop for the local Italian ELIXIR community steered an improvement of the quality and adoption of Bioschemas, a series of semantic annotation templates for tools, data and samples developed by the ELIXIR Interoperability platform. Gathering a small number of different end-users and having them focus on applying Bioschemas specification to their tools and data resulted in recruitment of early adopters, eight annotated resources, Bioschemas examples for future users and more than ten suggestions for specification improvement. This approach could be applied to other open specifications, promoting a wider adoption and the integration of suggestions in a bottom-up fashion. | 2018 | 2018 | LICCIULLI VITO FLAVIO | Bioschemas, Elixir, schema.org | |
| 449317 | Recensione in rivista | recensione a S. Spinsanti, La medicina vestita di narrazione, Il Pensiero Scientifico, 2016 | Elena Mancini | | The Future of Science and Ethics (Online) 1 (2016): 193-193. | 2016 | MANCINI ELENA | medicina narrativa, malattie rare | |
| 449569 | Codici di condotta | Carta dei principi per la ricerca nelle scienze sociali e umane e codice di condotta | Filippo Giordano, Elena Mancini | orientamenti etici per la conduzione delle ricerche con i partecipanti, per la diffusione dei risultati e i rapporti con i committenti | 2017 | 2017 | MANCINI ELENA | etica della ricerca, scienze sociali e umane, codice di condotta | |
| 449571 | Codici di condotta | Child Protection Policy and Code of Conduct - Misure e strategie per la protezione dei minori nella ricerca scientifica e Codice di condotta | Cinzia Caporale, Elena Mancini | criteri per l'arruolamento e la formulazione del consenso, comunicazione e informazione, misure di prevenzione di possibili pregiudizi ai minori nella conduzione delle ricerche | 2017 | 2017 | CAPORALE CINZIA, MANCINI ELENA | diritti dei minori, misure di protezione, consenso, etica della ricerca | |
| 452134 | Materiale didattico | Quaderno delle sfide | Fabrizio Bianchi, Cinzia Caporale, Liliana Cori, Luana Gasparini, Pietro Greco, Carla Guerriero, Patrizia Lucialli, Elena Mancini, Federica Manzoli, Maria Grazia Petronio, Elisa Pollini, Meri Scaringi | Il quaderno si inserisce tra i risultati del progetto GOCONDA. I GIOVANI CONTANO NELLE DECISIONI su AMBIENTE e SALUTE, ed e dedicato ad una educazione ambientale innovativa e partecipata. | 2018 | 2018 | MANZOLI FEDERICA, CORI LILIANA, CAPORALE CINZIA, MANCINI ELENA, BIANCHI FABRIZIO | diritti ambientali, salute a ambiente, sviluppo sostenibile e cittadinanza | |
| 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 | |
| 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 | |
| 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 |
| 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 | |
| 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 | |
| 356380 | Comunicazione in rivista (Letter - Letter to editor) | Identification of a patient affected by "Juvenile-chronic" Tay Sachs disease in South Italy. | Liguori M., Tagarelli G., Romeo N., Bagala A., Spadafora P. | | Neurological sciences (Testo stamp.) 28 (2016): 1-3. | 2016 | ROMEO NELIDE, SPADAFORA PATRIZIA, LIGUORI MARIA, TAGARELLI GIUSEPPE, BAGALA' ANGELO | Ataxia; Hexa gene; Juvenile-chronic onset; Psychosis; TSD; Tay Sachs | 10.1007/s10072-016-2646-2 |
| 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 | |
| 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 | |
| 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 | |
| 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 | |
| 443504 | Abstract in rivista | DEVELOPMENT AND VALIDATION OF A NOVEL EPS-METABOLOMIC SIGNATURE FOR THE DIAGNOSIS OF CLINICALLY SIGNIFICANT PROSTATE CANCER. | Andolfo, Annapaola, Drago, Denise, Cucchiara, Vito, Nocera, Luigi, Mosca, Ettore, Orro, Alessandro, Bellone, Matteo, Montorsi, Francesco, Briganti, Alberto | None | The Journal of urology 201 (2019): E220-E220. | 2019 | ORRO ALESSANDRO, MOSCA ETTORE | metabolomics, prostate cancer, expressed prostatic secretion | |
| 443664 | Dataset | MIcrobial DIversity CHIP database | Lara, Y., Wilmotte, A., Boutte, C., Grubisic, S., Balthasart, P., De Bellis, G., Castiglioni, B., Rizzi, E., Frosini, A., Sivonen, K., Rajaniemi, P., Rantala, A., Kuuppo, P., Lepisto, L., Ventura, S., Mugnai, M.A., Turichia, S., Tedioli, G., Henderson, P., Seaby, R., Hoffmann, L., Willame, R., Komarek, J., Komarkova, J., Hrouzek, P., Zalewski, M., Tarczynska, M., Mankiewicz, J., Zydorczyk, K., Jurczak, T. | In order to be protected, biodiversity must be evaluated. For cyanobacteria, the traditional morphological measures of biodiversity are unsatisfactory. We utilize molecular markers (like SSU rRNA) to define taxa on the basis of phylogeny. In freshwater ecosystems huge populations of cyanobacteria can occur. These blooms may release toxins that make the water poisonous. A second part of the study is to compare the temporal dynamics of biodiversity in both natural and disturbed lakes. This comparative analysis requires the use of ecological indexes to summarise the diversity of the samples and allow inferences about the ecosystem to be made. | 2017 | 2017 | RIZZI ERMANNO, MUGNAI MARIA ANGELA, TURICCHIA SILVIA, DE BELLIS GIANLUCA, CASTIGLIONI BIANCA MARIA ELISABETTA, FROSINI ANDREA, VENTURA STEFANO | cyanobacteria, microcystins, bloom, toxicity, microarray | |
| 446930 | Abstract in atti di convegno | Characterization of mammary cells derived from single cells with stem cell properties and organoid formation capacity by cell lineage tracing and cell tracking | Piscitelli E, Karnavas T, Abeni E, Mosca E, Pelucchi P, Cocola C, Tria V, Moro M, Crosti MC, Zippo A, Milanesi L, Reinbold R, Bianchi M, Zucchi I. | Tissues and organs are generated during development and repaired over the lifetime by stem cells with extensive self-renewal and differentiation potential. The characteristics and the identity of the stem and differentiated cells are determined by specific transcription factors that act together with chromatin regulators to stabilize expression patterns that maintain the cell identities. Disruption of the chromatin state or changes in the expression levels of chromatin regulators is associated with cellular reprogramming, disease and oncogenesis. While a large number of chromatin regulators have been identified, the epigenomic processes by which stem cells differentiate remains largely unknown for some somatic stem cell types. Three dimensional organoid cultures generated from patient derived single cells with stem cells properties, allow for investigating regulators of the chromatin state and gene expression patterns in mammary gland normal or tumor development. In this work by using cell lineage tracing and cell tracking, I characterized homogenous populations of cells derived from single mammary cells with organoid formation capacity. My findings suggest that chromatin changes in the histone state of mammary cells both initiate and stabilize gene expression patterns before the establishment of lineage specifying transcription factors. | SIBBM Frontiers in Molecular Biology -From single cells to 3Dcell culture-, Milan, Italy, 14-16 /06/ 2017 | 2017 | PISCITELLI ELEONORA, COCOLA CINZIA, TRIA VALERIA, ABENI EDOARDO, ZUCCHI ILEANA, MILANESI LUCIANO, PELUCCHI PARIDE, MOSCA ETTORE, REINBOLD ROLLAND ALVONS | Stem cells, human mammary gland, lineage traking | |
| 446963 | Abstract in atti di convegno | MiRNA-A* contributes to the commitment of mammary epithelial cells to the EMT program during cancer development'. | V. Martino, V. Tria, P. Pelucchi, R. Reinbold, I. Zucchi. | Using our model of mammary carcinogenesis based on the rat epithelial cell line LA7 that recapitulates the entire process of tumor development including metastasis formation, we identified miRNA-a* upregulated during EMT occurring in vivo after the xenograft of a single LA7 cell in recipient mice. We show that cytokines known to induce EMT, trigger Twist1 dependent miRNA-a* up-regulation. We demonstrate that ectopic expression of miRNA-a* in LA7 recapitulates the mesenchymal-like phenotype. The down-regulation of miRNA-a* abrogates the invasion capacity of the LA7 in 3D in vitro cultures and the metastasis formation in vivo. Our study reveals a miRNA dependent mechanism for the commitment of mammary epithelial cells to the EMT program during cancer development. | International symposium Cancer as an evolving and systemic disease. Memorial Sloan Kettering Cancer Center, New York (USA), 12-15/03/2016 | 2016 | MARTINO VALENTINA, TRIA VALERIA, ZUCCHI ILEANA, PELUCCHI PARIDE, REINBOLD ROLLAND ALVONS | microRNA, EMT | |
| 448164 | Rapporto tecnico | Implementazione del Portale Collaborativo per il progetto Infrastrutturale Europeo BBMRI - Common Service For IT (BBMRI-CS) | M. Gnocchi, M. Moscatelli, L. Milanesi | Scopo del progetto BBMRI Common Service for IT e quello di accelerare lo sviluppo e la fruibilita di servizi e tools da utilizzare nell'ambito dell'infrastruttura Europea BBMRI-ERIC. Nella relazione viene descritta l'infrastruttura implementata per la gestione della community degli utenti dei diversi work packages | Protocollo N 0001572 del 13/07/2016, 2016 | 2016 | MILANESI LUCIANO, GNOCCHI MATTEO, MOSCATELLI MARCO | BBMRI-CS, Common Service IT, Portale | |
| 448167 | Rapporto tecnico | Aggiornamento del portale per il nodo nazionale BBMRI.IT | Matteo Gnocchi, Marco Moscatelli e Luciano Milanesi | Scopo della relazione e quello di descrivere la riorganizzazione a livello grafico e contenutistico del portale BBMRI.it nella sua seconda versione. | protocollo N 0000628 del 27/03/2017, 2017 | 2017 | MILANESI LUCIANO, GNOCCHI MATTEO, MOSCATELLI MARCO | BBMRI-ERIC, BBMRI.it, portale | |
| 448147 | Abstract in atti di convegno | An infrastructure for disease prevention and precision medicine | Moscatelli M., Manconi A., Gnocchi M., Milanesi L. | Precision medicine is an emerging and novel approach for both disease treatment and prevention. Precision medicine allows to classify individuals into subpopulations that differ in their susceptibility to a particular disease with the aim to tailor the medical treatment to the individual characteristics of each patient. To provide precision medicine to patients researchers needs to analyze huge amounts of heterogeneous data from both biomedical research and healthcare systems. The growing amount of these data gives rise to the need for new research methods and analysis techniques. In this paper we present a infrastructure that exploits new strategies aimed at storing, accessing, and analyzing efficiently these heterogeneous data. | KDWeb2016 - Knowledge Discovery on the We, 8-10 Settembre 2016 | 2016 | MILANESI LUCIANO, GNOCCHI MATTEO, MANCONI ANDREA, MOSCATELLI MARCO | precision medicine | |
| 448977 | Abstract in atti di convegno | Network diffusion for the integrative analysis of multiple "-omics": case studies on breast cancer | Di Nanni, N., Appierto, V., De Marco, C., Ortolan, E., Milanesi, L., Daidone, M., Mosca, E. | None | 51st European Society of Human Genetics Conference, pp. 570-570, 16-19/06/2018 | 2019 | DI NANNI NOEMI, MILANESI LUCIANO, MOSCA ETTORE | breast cancer, multiple omics, biological network | 10.1038/s41431-019-0404-7 |
| 448984 | Abstract in atti di convegno | Functional gene networks underlying somatic mutations in Breast Cancer Initiating Cells | Ettore Mosca1, Valentina Appierto2, Noemi Di Nanni1, 3, Cinzia De Marco2, Luciano Milanesi1, Maria Grazia Daidone2 | None | CSC 2018 - Cancer Stem Cells: impact on treatment, 11-15/12/2018 | 2018 | DI NANNI NOEMI, MILANESI LUCIANO, MOSCA ETTORE | Breast cancer initiating cells, somatic mutations, whole-exome sequencing, gene networks | |
| 448985 | Abstract in atti di convegno | An integrative analysis of genomic studies for the identification of the molecular network regions associated with autism spectrum disorders | E. Mosca1, M. Bersanelli2, R. Alfieri1, 3, M. Landini1, N. Galluccio1, M. E. Raggi4, L. Villa4, M. Moleteni4, A. Bonfanti4, S. Camposeo5, A. Massagli5, G. Castellani2, F. Ciceri4, A. Marabotti4, 6, L. Milanesi1, A. Mezzelani1 | None | European Human Genetics Conference 2016, 21-24/05/2016 | 2016 | MILANESI LUCIANO, MEZZELANI ALESSANDRA MARIA, MOSCA ETTORE, ALFIERI ROBERTA | Biological Networks, Autism Spectrum Disorders, Genomics | |
| 449026 | Abstract in atti di convegno | Whole-exome sequencing of breast cancer initiating cells and paired primary tumors: the impact of variant callers and filtering strategies. | Di Nanni N, Appierto V, De Marco C, Angeloni V, Daidone MG, Milanesi L, Mosca E | None | 14th Annual Meeting of the Bioinformatics Italian Society, 5-7/07/2017 | 2017 | DI NANNI NOEMI, MILANESI LUCIANO, MOSCA ETTORE | Genome Sequencing, Breast Cancer, Somatic Mutations, Breast Cancer Initiating Cells | |
| 449027 | Abstract in atti di convegno | Network diffusion-based gene prioritization integrating multiple omics and gene networks | Noemi Di Nanni1, 2, Luciano Milanesi1, Ettore Mosca1 | None | 15th Annual Meeting of the Bioinformatics Italian Society, 27-29/06/2018 | 2018 | DI NANNI NOEMI, MILANESI LUCIANO, MOSCA ETTORE | Data Integration, Molecular Networks, Multi-omics, Network Diffusion | |
| 449029 | Abstract in atti di convegno | Integrative analysis of multiple "-omics" with network diffusion | N. Di Nanni1, 2, M. Gnocchi1, M. Moscatelli1, L. Milanesi1, E. Mosca1 | None | VI National Congress of Bioengineering, 25-27/06/2018 | 2018 | DI NANNI NOEMI, MILANESI LUCIANO, GNOCCHI MATTEO, MOSCA ETTORE, MOSCATELLI MARCO | Integrative analysis, Breast Cancer, Omics data, Molecular networks | |
| 449032 | Software | isma - integrative somatic mutation analysis | Di Nanni, Noemi, Moscatelli, Marco, Gnocchi, Matteo, Milanesi, Luciano, Mosca, Ettore | We developed isma (integrative somatic mutation analysis), an R package for the integrative analysis of somatic mutations detected by multiple pipelines for matched tumor-normal samples. The package provides a series of functions to quantify the consensus, estimate the variability, underline outliers, integrate evidences from publicly available mutation catalogues and filter sites. | 2019 | 2019 | DI NANNI NOEMI, MILANESI LUCIANO, GNOCCHI MATTEO, MOSCA ETTORE, MOSCATELLI MARCO | Somatic mutations, Next-generation sequencing, Cancer, Data integration | |
| 449144 | Presentazione | A standard-based HPC platform for genome annotation, analysis and visualization | Manconi A, Moscatelli M, Gnocchi M, Milanesi L | Introduction Advances in next-generation sequencing technologies is facilitating the sequencing and de-novo assembly of genomes from different eukaryotic and prokaryotic species. The growing number of fully assembled sequences is providing new opportunities to study the genome of different species. In addition, the availability of genome sequences of related species provides valuable opportunities to compare them with the aim to study their evolution. In this context, researchers are increasingly relying on comparative genomics to explore the genomic signals that control gene function across many species with the aim to better understand the structure and function of genes. This information helps researchers to develop new approaches for treating of diseases. To perform these analyses researchers need to use a variety of tools to annotate, analyze, explore, and compare genome sequences. Specialized tools and with different features have been proposed to the scientific community. However, the use of these tools may be difficult for biologists. In general, to facilitate the work of researchers, these tools should adopt common standards to ensure interoperability among them [1]. However, tools and analytical methods do not always use common standards making difficult the interoperability. Moreover, researchers may need to replicate scientific analyses presented in a paper, as well as to apply modifications, and to update data according to their specific needs. This may involve the analysis of huge amount of data, posing new computational challenges. Another problem is related to the sharing of data. In fact, typically, each tool generates and stores data using formats that are incompatible with the other ones. To this end, researchers involved in these analyses should have access to a single platform designed with the aim to ensure direct interoperability among the tools while supporting automated computation. According to these considerations, we implemented a standard-based HPC platform aimed at providing support at researchers involved in the tasks of annotating, analyzing, and visualizing eukaryotic and prokaryotic genomes. Methods The platform has been conceived with the aim to provide support for storage, annotation and analysis of both eukaryotic and prokaryotic genomes. To this end, it has been built on a hardware infrastructure intended to enable big-data classes of applications which consists of a massive storage platform of 1.6 PB, 2040 CPU cores, 16 NVIDIA K20 GPUs, and 2 big memory nodes (i.e., 1 node equipped with 1TB and 1 node equipped with 512GB of memory). Most of the tools integrated in the platform are components of the Generic Model Organism Database (GMOD) project [2]. GMOD is a collection of interconnected tools and databases widely used by the scientific community that includes several components for managing, annotating and visualizing genomic data. Many of the GMOD components are mature tools with several years of development and testing driven by diverse groups of developers, scientists, and laboratories that use and/or improve these components every day. In particular, the platform supports the following GMOD components: Maker [3][4], Chado[5], WebApollo [6], Gbrowse [7][8], SynView [9], and Galaxy [10]. Moreover, the platform also provides support to the (not GMOD component) GA4GH API [11] released by the Global Alliance for Genomics and Health [12] to share genomic data. In the following of this section, the above tools are briefly described. ? Maker is an annotation pipeline that can be used for de-novo annotation of genomes as well as for updating of existing annotations with the aim to reflect new evidence. It should be pointed out that Maker is MPI-capable for rapid parallelization across computer clusters. This feature makes it also suitable to annotate large genomes. Its annotation pipeline identifies repeats, aligns ESTs and proteins to a genome, produces ab-initio gene predictions and automatically synthesizes these data into gene annotations with evidencebased quality values. Maker outputs annotations in the standard GFF3 format that can be directly loaded into relational databases as Chado and genome browsers that adhere to the GMOD standards. ? Chado is a relational database schema that underlies many GMOD installations. It is used to represent different type of biological data. It has been designed to handle biological knowledge related to sequence, sequence comparisons, phenotypes, genotypes, ontologies, publications, and phylogeny. ? WebApollo is a web-based manual annotation environment for distributed community. It allows multiple users to annotate parts of the same sequence concurrently. To this end, any change made by other users is notified in the user's browser window. WebApollo keeps tracks of all changes made that can be approved or rejected by an administrator. ? GBrowse is a powerful and mature genome browser. It supports most of genome browser features, including qualitative and quantitative tracks, track uploading, track sharing, track downloading, and interactive track configuration. ? SynView is a interactive and customizable comparative genomic visualization tool based on GBrowse. It is able to display both the genomes comparison and the associated functional annotations in the same working environment. ? Galaxy is an open web-based scientific workflow system for data intensive biomedical research easily accessible to researchers that do not have programming experience. It provides an environment that helps researchers to run bioinformatics analysis tools as well as ad-hoc defined workflows. ? GA4GH API have been defined with the aim to allow a interoperable exchange of genomic information among multiple organizations and on multiple platforms. This is a freely available open standard for interoperability, that uses common web protocols to support serving and sharing of data on DNA sequences, genomic annotations and genomic variations. The API allow to create a data source that can be easily integrated in genomic analysis pipeline as well as integrated into specialized genomics platforms. Results The above tools have been properly installed and configured to work in the platform. The platform provides different access points. Authorized users can access to Maker to annotate their sequences as well as for updating of existing ones. Annotation data obtained with Maker are loaded into a Chado database and integrated into both WebApollo and GBrowse. Users can access to WebApollo for manual annotation, and to GBrowse to explore the annotated sequences as well as to compare genome sequences with SynView. GBrowse has been configured to show different tracks to explore alignments, protein-coding genes, CDS, mRNA, and other regions, as well as the GC content of the analyzed sequences. Users can customize the tracks as well as download them or upload other tracks for visualization. Moreover, GBrowse has also been configured to send data to Galaxy. Using this feature, users can visualize selected tracks on a given part of a sequence, and with a single click can send these data to Galaxy for analysis. As for Galaxy, it has been configured to run jobs on the previously described hardware infrastructure and to provide support for both CPU- and GPU-based tools [13]. It should be pointed out that bioinformatics is exploring new computational approaches based on the use of hardware accelerators such as the GPUs. Use of GPUs over the last years has resulted in significant increases in the performance of certain applications. Despite GPUs are increasingly used most laboratories do not have access to a GPU cluster or server. In this context, it is very important to provide useful services to use these tools with the aim to ensure reproducibility of specific analyses. It should be observed that Galaxy supports different distributed resource managers with the aim to enable different clusters. In our opinion, SLURM [14] represents the most suitable workload manager to manage and control jobs. SLURM is a highly configurable workload and resource manager and it is currently used on six of the ten most powerful computers in the world including the Piz Daint, utilizing over 5000 NVIDIA Tesla K20 GPUs. Users can interactively perform and refine their analyses using Galaxy. In particular, users can send or upload data into Galaxy from the other access points of the platform, analyze them, and store the results ignoring the implementation details of the underlying computing infrastructure. A GA4GH server has also been installed with the aim to share and make easy to integrate annotation data into external genomic analysis pipelines. It should be pointed out that the GA4GH API allows to retrieve genomic data according to different criteria that can be combined to meet the needs of the researcher. Then, to facilitate the work of researchers, specialized tools have been added to Galaxy to retrieve annotation data from the GA4GH server. Currently, the platform is used to support some initiatives of the InterOmics Project [15] aimed at studying human cancer, microbiome, and some plant genomes. Conclusions We presented a dedicated platform for genome annotation and analysis. The platform has been implemented with the aim to help researchers to store, annotate, explore, and analyze genomic data. The main goal that has driven the design of the platform has been to facilitate analysis and computational reproducibility. To this end, the platform integrates interconnected tools that use common standards while ensuring automated computation on a robust hardware infrastructure that support both CPU- and GPU-based computation. The GA4Gh open standard has been used to share genomic data. The platform is intended to be dynamic, therefore it will be integrated with other specialized software solutions that will be useful for the genome analysis. Currently, we are working to integrate other specialized comparative genomics tools of the GMOD project as CMAP [16] and SynBrowse [17]. | NETTAB 2016, Roma, 25-26 Ottobre 2016 | 2016 | MILANESI LUCIANO, GNOCCHI MATTEO, MANCONI ANDREA, MOSCATELLI MARCO | genome annotation, genome visualization, genome analysis, hpc | |
| 449148 | Poster | Big Data for Disease Prevention and Precision Medicine | Moscatelli M, Gnocchi M, Manconi A, Milanesi L | Motivation Nowadays, advances in technology has arisen in a huge amount of data in both biomedical research and healthcare systems. This growing amount of data gives rise to the need for new research methods and analysis techniques. Analysis of these data offers new opportunities to define novel diagnostic processes. Therefore, a greater integration between healthcare and biomedical data is essential to devise novel predictive models in the field of biomedical diagnosis. In this context, the digitalization of clinical exams and medical records is becoming essential to collect heterogeneous information. Analysis of these data by means of big data technologies will allow a more in depth understanding of the mechanisms leading to diseases, and contextually it will facilitate the development of novel diagnostics and personalized therapeutics. The recent application of big data technologies in the medical fields will offer new opportunities to integrate enormous amount of medical and clinical information from population studies. Therefore, it is essential to devise new strategies aimed at storing and accessing the data in a standardized way. Moreover, it is important to provide suitable methods to manage these heterogeneous data. Methods In this work, we present a new information technology infrastructure devised to efficiently manage huge amounts of heterogeneous data for disease prevention and precision medicine. A test set based on data produced by a clinical and diagnostic laboratory has been built to set up the infrastructure. When working with clinical data is essential to ensure the confidentiality of sensitive patient data. Therefore, the set up phase has been carried out using "anonymous data". To this end, specific techniques have been adopted with the aim to ensure a high level of privacy in the correlation of the medical records with important secondary information (e.g., date of birth, place of residence). It should be noted that the rigidity of relational databases does not lend to the nature of these data. In our opinion, better results can be obtained using non-relational (NoSQL) databases. Starting from these considerations, the infrastructure has been developed on a NoSQL database with the aim to combine scalability and flexibility performances. In particular, MongoDB [1] has been used as it fits better to manage different types of data on large scale. In doing so, the infrastructure is able to provide an optimized management of huge amounts of heterogeneous data, while ensuring high speed of analysis. Results The presented infrastructure exploits big data technologies in order to overcome the limitations of relational databases when working with large and heterogeneous data. The infrastructure implements a set of interface procedures aimed at preparing the metadata for importing data in a NOSQL DB. Moreover, data can also be represented as a graph using Neo4j [2]; The Neo4J DB allows you to emphasize and enhance the connections between the data and facilitate the retrieve and navigation of data (Fig 1). Experimental tests on huge amount of data show that our infrastructure exhibits performances in terms of speed and scalability unachievable with relational databases. These performances are mainly related to ability of the infrastructure to index any type of field as well as to customize the queries. In particular, the high flexibility to customize the queries increases the search performance and specificity of the results. As for future work, we planned to implement new functions and operators to perform specialized statistics analysis on big data. References [1] http://www.mongodb.org [2] http://neo4j.com/ | 13th Annual Meeting of the Bioinformatics Italian Society, Fisciano (Salerno), 15-17 Giugno 2016 | 2016 | MILANESI LUCIANO, GNOCCHI MATTEO, MANCONI ANDREA, MOSCATELLI MARCO | big data, precision medicine | |
| 449157 | Poster | Web infrastructure for the management of the "bbmri.it" Italian Biobank Network | Gnocchi M, Moscatelli M, Manconi A, Milanesi L | Motivation BBMRI-ERIC mission is to construct a pan-European biobanking infrastructure, building on existing infrastructure, resources and technologies, specifically complemented with innovative components and properly embedded into European ethical, legal and societal frameworks. BBMRI.it is the national node member of the BBMRI-ERIC infrastructures involving the majority biobanks and biological resource centers located in Italy. The Italian node is actually composed by more than 18 universities, 23 IRCCS, 40 hospitals, associations of patients. The activities of BBMRI.it are aimed at harmonizing the standard operating procedures (SOPs) of biobanks, implementing the quality management system and encouraging public/private partnerships. For this purpose and in collaboration with the BBMRI.it partners we have developed a dedicated web portal (http://www.bbmri.it) to construct and operate a sustainable infrastructure for biological information in Italy to support biomedical research and its translation to medicine in Italy. Methods The BBMRI.it web portal [1] has been developed in order to collect the data and to ensure the easiest way to interact with the central node of BBMRI-ERIC infrastructures. For the development of this portal we have using the Liferay community Web Portal [2]. Based on the Liferay services, we have organized a public area of the portal for publishing all the information regarding the activities of the BBMRI.it node in Italy and Europe. The portal provide also a private area, only available via Login for the registered user in order to perform these specific services: A) To collect the initial information from the Biobank's we have developed the Survey for Biobank's accreditation using the Java Vaadin Framework [3] (Version 7.1.15). By means of this service users can add all Biobanks information online and submit to the evaluation committee the formal request to be accredited in the BBMRI.it network. All the information are stored into a specific database managed by a dedicate middleware developed with the Hibernate Framework [3]. B) The BBMRI.it Directory Service has been developed in order to allow the users to search on-line the public information regarding all the Biobanks in Italy and in Europe by the Directory 3.1 based on the MIABIS standard. This Service is realized using the Java PrimeFaces Framework [4] (Version 5.2). Thought this application is it possible to store and retrieve the information, based on the biobanks accepted in the Italian Network. This system is able to collect the data and to share the information with the BBMRI-ERIC Directory 3.1. This application is divided in 4 categories: Biobanks Networks, Biobanks, Collections and Contacts. A specific middleware for management of data has been implemented in order to manage the data with a RDBMS interconnection locally and with the BBMRI-ERIC Directory; this allow the utilization of multiple data connectors for sharing information with an unique user interface. C) The BBMRI.it Biobank Manager service, is available for the users administration in order to validate the submitted data; this operation consist in different steps: Step 1) The registered Biobank after the admission in BBMRI.it Network is granted with the permission for access to the BBMRI.it Directory Service in order to complete the information requested. Step 2) The data already present in the survey are automatically added into the BBMRI.it Directory Structure in order to simplify the process of share the information with the BBMRI-ERIC Directory. Step 3) Finally the biobanks owner is informed via email about the final acceptance in BBMRI.it. All the services described have been integrated into the portal as a portlets and can be utilized by the users in according with their role in the portal. Results We have developed the BBMRI.it Portal to facilitate the collection of data and the collaboration among the biobanks. This portal represent the centralize resource for the storage and the analysis of the information related the biobanks. By using the Directory application is possible to interact and share the information with the central European directory server. Actually the BBMRI.it Directory stores total information about more than 70 biobanks. Finally for the bioinformatics analysis of the Omics data generated from the Biobanks samples we have also developed a platform hosted on a computer cluster at the Institute of Biomedical Technologies (ITB/CNR) in Milan able to combines several Bioinformatics and Systems Biology tools. References [1] BBMRI.it Project web Site: http://www.bbmri.it [2] Liferay Portal Site: http://www.liferay.com [3] Vaadin Site: https://vaadin.com/home [3] Hibernate Site: http://www.hibernate.org [4] Primefaces: http://www.primefaces.org | 14th Annual Meeting of the Bioinformatics Italian Society, Cagliari, 5-7 Luglio 2017 | 2017 | MILANESI LUCIANO, GNOCCHI MATTEO, MANCONI ANDREA, MOSCATELLI MARCO | web infrastructure, biobanks | |
| 449152 | Poster | A GPU-based High Performance Computing Infrastructure for specialized NGS analyses | Manconi A, Moscatelli M, Gnocchi M, Armano G, Milanesi L | Motivation Recent advances in genome sequencing and biological data analysis technologies used in bioinformatics have led to a fast and continuous increase in biological data. The difficulty of managing the huge amounts of data currently available to researchers and the need to have results within a reasonable time have led to the use of distributed and parallel computing infrastructures for their analysis. Recently, bioinformatics is exploring new approaches based on the use of hardware accelerators as GPUs. From an architectural perspective, GPUs are very different from traditional CPUs. Indeed, the latter are devices composed of few cores with lots of cache memory able to handle a few software threads at a time. Conversely, the former are devices equipped with hundreds of cores able to handle thousands of threads simultaneously, so that a very high level of parallelism can be reached. Use of GPUs over the last years has resulted in significant increases in the performance of certain applications. Despite GPUs are increasingly used in bioinformatics most laboratories do not have access to a GPU cluster or server. In this context, it is very important to provide useful services to use these tools. Methods A web-based platform has been implemented with the aim to enable researchers to perform their analysis through dedicated GPU-based computing resources. To this end, a GPU cluster equipped with 16 NVIDIA Tesla k20c cards has been configured. The infrastructure has been built upon the Galaxy technology [1]. Galaxy is an open web-based scientific workflow system for data intensive biomedical research accessible to researchers that do not have programming experience. Let us recall that Galaxy provides a public server, but it does not provide support to GPU-computing. By default, Galaxy is designed to run jobs on local systems. However, it can also be configured to run jobs on a cluster. The front-end Galaxy application runs on a single server, but tools are run on cluster nodes instead. To this end, Galaxy supports different distributed resource managers with the aim to enable different clusters. For the specific case, in our opinion SLURM [2] represents the most suitable workload manager to manage and control jobs. SLURM is a highly configurable workload and resource manager and it is currently used on six of the ten most powerful computers in the world including the Piz Daint, utilizing over 5000 NVIDIA Tesla K20 GPUs. Results GPU-based tools [3] devised by our group for quality control of NGS data have been used to test the infrastructure. Initially, this activity required to make changes to the tools with the aim to optimize the parallelization on the cluster according to the adopted workload manager. Successively, the tools have been converted into web-based services accessible through the Galaxy portal. Currently, we are working to optimize the workload manager configuration. As for future work, we planned to share through Galaxy other GPU-based tools for NGS analyses released by our group [4][5] as well as specialized workflows created using these and other validated tools imported from the Galaxy ToolShed repository. These activities will be carried-out through the European ELIXIR project. 1. Goecks, J, Nekrutenko, A, Taylor, J and The Galaxy Team. "Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences". Genome Biol. 2010 Aug 25;11(8):R86. 2. http://slurm.schedmd.com/ 3. Manconi, A et al. "G-CNV: a GPU-based tool for preparing data to detect CNVs with readdepth methods". Frontiers in Bioengineering and Biotechnology, 2015, 3. 4. Manconi, A et al. "GPU-BSM: A GPU-based tool to map bisulfite-treated reads". PLoS ONE 9(5): e97277. doi:10.1371/journal.pone.0097277, 2014. 5. Manconi, A et al. "A tool for mapping single nucleotide polymorphisms using graphics processing units". BMC Bioinformatics, 15(Suppl 1), S10, 2014 | 13th Annual Meeting of the Bioinformatics Italian Society, Fisciano (Salerno), 15-17 Giugno 2016 | 2016 | MILANESI LUCIANO, GNOCCHI MATTEO, MANCONI ANDREA, MOSCATELLI MARCO | HPC, GPGPU, NGS | |
| 449170 | Poster | Pre-processing of high-throughput sequencing data | Manconi A, Moscatelli M, Gnocchi M, Milanesi L | Motivation NGS has revolutionized the genomic research. Technological advances have reduced the sequencing costs while have notably increased the sequence throughput. Typically, artifacts of different nature that arise during the sequencing process affect NGS data. As these artifacts may influence the downstream analyses, data quality control (QC) becomes mandatory. Different QC tools have been proposed. Without claiming to be exhaustive, let us cite some of the most popular tools, i.e., FASTQC [1], FASTX-Toolkit [2], NGS QC Toolkit [3], PRINSEQ [4]. FASTQC is a widely adopted tool for quality assessment. It provides a set of analyses to assess the raw data according to multiple aspects. It also provides a GUI to report all analyses highlighting problems in the data. FASTX-Toolkit is a collection of command line tools for FASTA/FASTQ file processing including some quality statistics. It also provides tools for quality filtering/trimming. NGS QC Toolkit is a standalone tool for QC that includes tools for sequence trimming and statistics calculation. It is also equipped with modules to generate statistics in graphical format. PRINSEQ is a web-based and standalone tool that can be used to generate summary statistics of sequence and quality data and to filter and trim sequences. It should be pointed out that the massive amounts of generated sequences make QC computationally intensive. Despite that, only some tools implement a multicore processing strategy to deal with that computational challenge. In our opinion, even though these tools implement very useful features, their implementation does not permit to efficiently analyze large amounts of NGS data. We deem that QC tasks can be efficiently parallelized on manycore architectures as GPUs. GPUs are devices equipped with hundreds of cores able to handle thousands of threads simultaneously, so that a very high level of parallelism can be reached. In this work, we present G-FastQC (GPU Fast Quality Control) a GPU-based tool for quality assessment, filtering, and trimming of NGS data. Methods G-FastQC has been devised to be massively parallelized on NVIDIA GPUs. It supports single- and paired-end libraries generated with Illumina platforms. G-FastQC implements a set of analyses to perform QC checks on raw data. These analyses allow to assess the data according to aspects related to the quality scores and content of the sequences. In particular, G-FastQC allows to calculate the: average quality values across all bases at each position; quality score distribution over all sequences; GC content across the whole length of each sequence; GC content across all bases; sequence content across all bases at each position.To help users to analyze the data quality, G-FastQC has been integrated with an interactive web-based interface built using Shiny[5] that allows to plot graphs of the performed analyses.G-FastQC also supports quality filtering and trimming. As for quality filtering, G-FastQC allows to filter sequences based on the amount of both low quality and N nucleotides as well as to filter sequences based on the GC content. It can also be used to mask the nucleotides with a quality score lower than a given threshold. As for trimming, G-FastQC implements an operator based on a sliding window approach. It analyzes the amount of low quality nucleotides in a sliding window. When the amount of these nucleotides is higher than a given threshold, G-FastQC trims all nucleotides from the start of the window to the 3'. Trimmed sequences with length lower than a given threshold can be automatically discarded. The same sliding window approach has been used to implement an operator aimed at masking these nucleotides rather than trimming them. It should be pointed out, that unlike the above-mentioned tools, G-FastQC has been designed to perform analysis of several datasets in a single run. Results Experiments carried out on a 12 cores Intel Xeon CPU E5-2667 2.90 GHz and an NVIDIA Tesla k20c show that G-FastQC outperforms notably the other tools in terms of computing time. For instance, in the task of filtering low-quality sequences, it has been 21.4x/28.3x faster than FASTX-Toolkit/NGS QC Toolkit analyzing a dataset consisting of 50M of 100 bp reads. Similar results have been obtained comparing the performance of G-FastQC with those of the other tools to generate the quality reports, and in the tasks of filtering/trimming the raw data. References 1. http://www.bioinformatics.abraham.ac.uk/projects/fastqc/ 2. http://hannonlab.cshl.edu/fastx_toolkit 3. Patel RK, Jain M (2012) NGS QC Toolkit: a toolkit for quality control of next generation sequencing data, PloS one, 7(2), e30619. 4. Schmieder R, Robert E (2011) Quality control and preprocessing of metagenomic datasets. Bioinformatics, 27(6), 863-864. 5. https://shiny.rstudio.com | 14th Annual Meeting of the Bioinformatics Italian Society -, Cagliari, 5-7 Luglio 2017 | 2017 | MILANESI LUCIANO, GNOCCHI MATTEO, MANCONI ANDREA, MOSCATELLI MARCO | NGS, GPGPU, HPC | |
| 449228 | Abstract in atti di convegno | MicroRNA and transcription factor co-regulatory network analysis: a combined bioinformatics and molecular strategy for uncovering genetic hub regulatory elements in multiple sclerosis pathogenesis | Nuzziello, N., Vilardo, L., Pelucchi, P., Consiglio, A., Trojano, M., Liguori, M. | Introduction: As the main regulators of gene expression, microRNAs (miRNAs) and transcription factors (TFs) play key roles in complex multifactorial diseases like Multiple Sclerosis (MS). Recently, miRNA/TF-based feed-forward loops (FFLs) have been identified as key elements of biological network motifs in MS. Objectives: Starting from preliminary results obtained by a High-Throughput Next-Generation Sequencing (HT-NGS) approach on an independent MS patients cohort, we aimed to search for miRNA-TF co-regulatory networks involved as hub genetic elements in MS pathogenesis. Methods: The study was performed on peripheral blood samples belonging to 58 MS patients and 20 healthy controls (HCs).To validate the differential expressed (DE) miRNAs resulted from HT-NGS analysis, total RNA extraction was followed by microfluidic qPCR. The subsequent analysis included: miRNA-target gene interaction evaluation using experimentally validated miRNA-target interaction databases (DIANA-Tarbase and miRTarBase) and the output of 5 algorithms (miRanda, DIANA-microT-CDS, RNA22, miRDB and TargetScan) for target genes prediction; miRNA-target experimentally validation using dual luciferase reporter assay; TF-miRNA co-regulatory network identification using miRNA-TF interaction tools (Harmonizome and TransmiR) and a gene-TF interaction database (TRRUST); pathway enrichment analysis using DAVID tool. Results: Microfluidic qPCR analysis revealed 6 significantly DE miRNAs (miR-320a, miR-125a-5p, miR-652-3p, miR-185-5p, miR-942-5p and miR-25-3p) in MS patients compared to HCs. The integrated analysis of miRNAs and computationally predicted mRNAs uncovered 638 miRNA-target pairs validated by reporter gene assays and/or predicted by at least 4 of the 5 interaction tools. Luciferase reporter assays indicated that miR-125a-5p was able to target and modulate DIP2A, ADD2 and E2F2 expression, thus confirming that the in silico predicted target were effectively subjected to miRNA-mediated post-transcriptional modulation. In addition, 409 TF-miRNA interactions were identified, including 198 miRNA-TF FFLs. Furthermore, the enrichment analysis categorized in functional pathways revealed significant representations of networks mostly related to neurotrophin signalling pathway, ErbB signalling pathway and axon guidance. Conclusions: These results uncovered several hub regulatory elements allowing to shed further lights in the gene regulation mechanisms that may underlie the pathogenesis of MS. | European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS 2018), pp. 593-593, Berlin, Germany, 10-12/10/2018 | 2018 | NUZZIELLO NICOLETTA, LIGUORI MARIA, PELUCCHI PARIDE, CONSIGLIO ARIANNA, VILARDO LAURA | microRNA, Multiple sclerosis, transcription factor | |
| 450046 | Toolkit metodologico | Incidental Findings nella ricerca scientifica. Criteri e indicazioni per le scienze e tecnologie -omiche | Giuseppe Testa, Cinzia Caporale, Elena Mancini, Marco Annoni, Luca Marelli | Ethical Toolkit per l'identificazione, analisi e comunicazione degli incidental findings nella ricerca | 2018 | 2018 | CAPORALE CINZIA, MANCINI ELENA, ANNONI MARCO ANGELO MARIA | incidental finding, etica della ricerca, consenso informato, diritto di non sapere | |
