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1,346 results on '"Greco, D."'

1. An ancestral molecular response to nanomaterial particulates

Author

del Giudice, G., Serra, A., Saarimäki, L. A., Kotsis, K., Rouse, I., Colibaba, S. A., Jagiello, K., Mikolajczyk, A., Fratello, M., Papadiamantis, A. G., Sanabria, N., Annala, M. E., Morikka, J., Kinaret, P. A. S., Voyiatzis, E., Melagraki, G., Afantitis, A., Tämm, K., Puzyn, T., Gulumian, M., Lobaskin, V., Lynch, I., Federico, A., and Greco, D.

Published
2023
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3. Transcriptomic profiling reveals differential cellular response to copper oxide nanoparticles and polystyrene nanoplastics in perfused human placenta

Author

Chortarea S, Gupta G, Saarimäki LA, Netkueakul W, Manser P, Aengenheister L, Wichser A, Fortino V, Wick P, Greco D, and Buerki-Thurnherr T

Subjects
Nanoplastics, CuO nanoparticles, Placenta, Transcriptomic profiling, Developmental toxicity pathways, Environmental sciences, GE1-350
Abstract

The growing nanoparticulate pollution (e.g. engineered nanoparticles (NPs) or nanoplastics) has been shown to pose potential threats to human health. In particular, sensitive populations such as pregnant women and their unborn children need to be protected from harmful environmental exposures. However, developmental toxicity from prenatal exposure to pollution particles is not yet well studied despite evidence of particle accumulation in human placenta. Our study aimed to investigate how copper oxide NPs (CuO NPs; 10–20 nm) and polystyrene nanoplastics (PS NPs; 70 nm) impact on gene expression in ex vivo perfused human placental tissue. Whole genome microarray analysis revealed changes in global gene expression profile after 6 h of perfusion with sub-cytotoxic concentrations of CuO (10 µg/mL) and PS NPs (25 µg/mL). Pathway and gene ontology enrichment analysis of the differentially expressed genes suggested that CuO and PS NPs trigger distinct cellular response in placental tissue. While CuO NPs induced pathways related to angiogenesis, protein misfolding and heat shock responses, PS NPs affected the expression of genes related to inflammation and iron homeostasis. The observed effects on protein misfolding, cytokine signaling, and hormones were corroborated by western blot (accumulation of polyubiquitinated proteins) or qPCR analysis. Overall, the results of the present study revealed extensive and material-specific interference of CuO and PS NPs with placental gene expression from a single short-term exposure which deserves increasing attention. In addition, the placenta, which is often neglected in developmental toxicity studies, should be a key focus in the future safety assessment of NPs in pregnancy.

Published
2023
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4. Human Factors in Virtual Experiences: a Literature Overview

Author

Greco, D, Bani, M, Rampoldi, G, Ardenghi, S, Strepparava, M, Galli, P, Russo, S, Del Greco, Bani M., Rampoldi G., Ardenghi S., Strepparava M. G., Galli P., Russo S., Greco, D, Bani, M, Rampoldi, G, Ardenghi, S, Strepparava, M, Galli, P, Russo, S, Del Greco, Bani M., Rampoldi G., Ardenghi S., Strepparava M. G., Galli P., and Russo S.

Published
2024

5. L'arbitrabilità della lite tra richiamo e 'presa in considerazione' del diritto straniero

Author

Iovane, M, Palombino, FM, Zarra, G, Marotti, L, Pauciulo, D, Stiano, A, Greco, D., Benini, Caterina, Caterina Benini (ORCID:0000-0002-0587-217X), Iovane, M, Palombino, FM, Zarra, G, Marotti, L, Pauciulo, D, Stiano, A, Greco, D., Benini, Caterina, and Caterina Benini (ORCID:0000-0002-0587-217X)

Abstract

SOMMARIO: 1. Introduzione. – 2. L’arbitrabilità: nozione autonoma a contenuto nazionale. – 3. La legge applicabile all’arbitrabilità dinanzi alle corti statali e dinanzi agli arbitri. – 4. Il concorso di leggi applicabili all’arbitrabilità e l’impossibilità di risolverlo tramite le tecniche della prevalenza, della distribuzione e del cumulo. – 5. La tecnica della presa in considerazione di norme straniere. – 6. La tecnica della presa in considerazione applicata all'arbitrabilità. – 7. Conclusioni.

Published
2024

6. Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations

Author

Villa, R., Fergnani, V.G.C., Silipigni, R., Guerneri, S., Cinnante, C., Guala, A., Danesino, C., Scola, E., Conte, G., Fumagalli, M., Gangi, S., Colombo, L., Picciolini, O., Ajmone, P.F., Accogli, A., Madia, F., Tassano, E., Scala, M., Capra, V., Srour, M., Spaccini, L., Righini, A., Greco, D., Castiglia, L., Romano, C., and Bedeschi, M.F.

Published
2020
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7. Les Houches 2013: Physics at TeV Colliders: New Physics Working Group Report

Author

Brooijmans, G., Contino, R., Fuks, B., Moortgat, F., Richardson, P., Sekmen, S., Weiler, A., Alloul, A., Arbey, A., Baglio, J., Barducci, D., Barr, A. J., Basso, L., Battaglia, M., Bélanger, G., Belyaev, A., Bernon, J., Bharucha, A., Bondu, O., Boudjema, F., Boos, E., Buchkremer, M., Bunichev, V., Cacciapaglia, G., Chalons, G., Conte, E., Dolan, M. J., Deandrea, A., De Causmaecker, K., Djouadi, A., Dumont, B., Ellis, J., Englert, C., Falkowski, A., Fichet, S., Flacke, T., Gaz, A., Ghezzi, M., Godbole, R., Goudelis, A., Gouzevitch, M., Greco, D., Grober, R., Grojean, C., Guadagnoli, D., Gunion, J. F., Herrmann, B., Kalinowski, J., Kim, J. H., Kraml, S., Krauss, M. E., Kulkarni, S., Lee, S. J., Lim, S. H., Liu, D., Mahmoudi, F., Maravin, Y., Massironi, A., Mitzka, L., Mohan, K., Moreau, G., Mühlleitner, M. M., Nhung, D. T., O'Leary, B., Oliveira, A., Panizzi, L., Pappadopulo, D., Pataraia, S., Porod, W., Pukhov, A., Riva, F., Rojo, J., Rosenfeld, R., Ruiz-Álvarez, J., Rzehak, H., Sanz, V., Sengupta, D., Spannowsky, M., Spira, M., Streicher, J., Strobbe, N., Thamm, A., Thomas, M., Torre, R., Waltenberger, W., Walz, K., Wilcock, A., Wulzer, A., Würthwein, F., and Wymant, C.

Subjects
High Energy Physics - Phenomenology
Abstract

We present the activities of the "New Physics" working group for the "Physics at TeV Colliders" workshop (Les Houches, France, 3--21 June, 2013). Our report includes new computational tool developments, studies of the implications of the Higgs boson discovery on new physics, important signatures for searches for natural new physics at the LHC, new studies of flavour aspects of new physics, and assessments of the interplay between direct dark matter searches and the LHC., Comment: Proceedings of the New Physics Working Group of the 2013 Les Houches Workshop, Physics at TeV Colliders, Les Houches 3-21 June 2013. 201 pages

Published
2014

9. MicroRNA related polymorphisms and breast cancer risk

Author

Ashworth, Alan, Van 'T Veer, Laura, Khan, S, Greco, D, Michailidou, K, Milne, RL, Muranen, TA, Heikkinen, T, Aaltonen, K, Dennis, J, Bolla, MK, and Liu, J

Abstract

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may

Published
2014

10. Insufficient arterial driving pressure turns hypoxic microvascular remodeling into a catastrophe

Author

Korpisalo, P, primary, Tarvainen, S, additional, Wirth, G, additional, Juusola, G, additional, Happonen, K, additional, Frimodig, C, additional, Hytonen, J, additional, Taavitsainen, J, additional, Greco, D, additional, Knuuti, J, additional, Hartikainen, J, additional, Laitinen, T, additional, Yla-Herttuala, S, additional, Hakovirta, H, additional, and Makinen, K, additional

Published
2023
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12. Systems toxicology to advance human and environmental hazard assessment : A roadmap for advanced materials

Author

Amorim, M. J.B., Peijnenburg, W., Greco, D., Saarimäki, L. A., Dumit, V. I., Bahl, A., Haase, A., Tran, L., Hackermüller, J., Canzler, S., Scott-Fordsmand, J. J., Institute of Biotechnology, Division of Pharmaceutical Biosciences, Tampere University, and BioMediTech

Subjects
Adverse outcome pathways (AOP), New approach methodologies (NAMs), Smart materials, Omics, 1182 Biochemistry, cell and molecular biology, 3111 Biomedicine, Advanced materials (AdMa), Risk assessment
Abstract

Ideally, a Systems Toxicology (ST) approach is aimed at by (eco)toxicologists, i.e. a multidisciplinary area incorporating classical toxicological concepts with omics technologies, and the understanding of this through computational data sciences, chemistry, mathematics, and physics modelling. As outlined in sev-eral public reports (e.g. from ECHA-European Chemical Agency and EFSA-European Food Safety Authority), the way forward in the coming years in Europe is to integrate New Approach Methodologies (NAMs) (in-cluding omics technologies) into hazard and hence risk assessment (RA). Adverse Outcome Pathways (AOPs) describe a sequence of events in response to stress, from the molecular initiating event until an adverse outcome, which is relevant to RA or regulatory decision-making. AOPs are one of the facilitators to integrate mechanistic data into RA, but it is urgent to increase the inclusion of the vast mechanistic knowledge available, especially for the RA of novel smart and advanced materials (AdMa) with multi-functional characteristics. There are still many challenges to the routine usage of NAMs, e.g. omics-based information. Here, we summarise the current state of the art of ST, the benefits of human and environ-mental health cross knowledge and the available methods and output. The importance of this area has been highlighted for many years but is even more pressing in the context of AdMa. Furthermore, we outline the challenges and suggest recommendations for future implementation.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Published
2023

15. Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential

Author

Procaccini, C, Garavelli, S, Carbone, F, Di Silvestre, D, La Rocca, C, Greco, D, Colamatteo, A, Lepore, M, Russo, C, De Rosa, G, Faicchia, D, Prattichizzo, F, Grossi, S, Campomenosi, P, Buttari, F, Mauri, P, Uccelli, A, Salvetti, M, Brescia Morra, V, Vella, D, Galgani, M, Mottola, M, Zuccarelli, B, Lanzillo, R, Maniscalco, G, Centonze, D, de Candia, P, Matarese, G, Procaccini C., Garavelli S., Carbone F., Di Silvestre D., La Rocca C., Greco D., Colamatteo A., Lepore M. T., Russo C., De Rosa G., Faicchia D., Prattichizzo F., Grossi S., Campomenosi P., Buttari F., Mauri P., Uccelli A., Salvetti M., Brescia Morra V., Vella D., Galgani M., Mottola M., Zuccarelli B., Lanzillo R., Maniscalco G. T., Centonze D., de Candia P., Matarese G., Procaccini, C, Garavelli, S, Carbone, F, Di Silvestre, D, La Rocca, C, Greco, D, Colamatteo, A, Lepore, M, Russo, C, De Rosa, G, Faicchia, D, Prattichizzo, F, Grossi, S, Campomenosi, P, Buttari, F, Mauri, P, Uccelli, A, Salvetti, M, Brescia Morra, V, Vella, D, Galgani, M, Mottola, M, Zuccarelli, B, Lanzillo, R, Maniscalco, G, Centonze, D, de Candia, P, Matarese, G, Procaccini C., Garavelli S., Carbone F., Di Silvestre D., La Rocca C., Greco D., Colamatteo A., Lepore M. T., Russo C., De Rosa G., Faicchia D., Prattichizzo F., Grossi S., Campomenosi P., Buttari F., Mauri P., Uccelli A., Salvetti M., Brescia Morra V., Vella D., Galgani M., Mottola M., Zuccarelli B., Lanzillo R., Maniscalco G. T., Centonze D., de Candia P., and Matarese G.

Abstract

Human CD4+CD25hiFOXP3+ regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impaired in subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorder associated with reduced Treg cell proliferative capacity. Treatment of RRMS subjects with dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as major target for the rescue of Treg cell proliferation.

Published
2021

16. How has prostate cancer radiotherapy changed in Italy between 2004 and 2011? An analysis of the national patterns-of-practice (pop) database by the uro-oncology study group of the italian society of radiotherapy and clinical oncology (airo)

Author

Mazzeo, E, Triggiani, L, Frassinelli, L, Guarneri, A, Bartoncini, S, Antognoni, P, Gottardo, S, Greco, D, Borghesi, S, Nanni, S, Bruni, A, Ingrosso, G, D'Angelillo, R, Detti, B, Francolini, G, Magli, A, Guerini, A, Arcangeli, S, Spiazzi, L, Ricardi, U, Lohr, F, Magrini, S, Mazzeo E., Triggiani L., Frassinelli L., Guarneri A., Bartoncini S., Antognoni P., Gottardo S., Greco D., Borghesi S., Nanni S., Bruni A., Ingrosso G., D'angelillo R. M., Detti B., Francolini G., Magli A., Guerini A. E., Arcangeli S., Spiazzi L., Ricardi U., Lohr F., Magrini S. M., Mazzeo, E, Triggiani, L, Frassinelli, L, Guarneri, A, Bartoncini, S, Antognoni, P, Gottardo, S, Greco, D, Borghesi, S, Nanni, S, Bruni, A, Ingrosso, G, D'Angelillo, R, Detti, B, Francolini, G, Magli, A, Guerini, A, Arcangeli, S, Spiazzi, L, Ricardi, U, Lohr, F, Magrini, S, Mazzeo E., Triggiani L., Frassinelli L., Guarneri A., Bartoncini S., Antognoni P., Gottardo S., Greco D., Borghesi S., Nanni S., Bruni A., Ingrosso G., D'angelillo R. M., Detti B., Francolini G., Magli A., Guerini A. E., Arcangeli S., Spiazzi L., Ricardi U., Lohr F., and Magrini S. M.

Abstract

Background and purpose: Two previous “Patterns Of Practice” surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a “benchmark” Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. Methods: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. Results: More than 50% of POP III patients were classified as low or intermediate risk using D’Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate-and high-risk patients treated with ≥ 76 Gy. Conclusions: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004–2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT—allowing for ti

Published
2021

18. Governing the Access to COVID-19 Tools Accelerator: towards greater participation, transparency, and accountability

Author

Moon, S, Armstrong, J, Hutler, B, Upshur, R, Katz, R, Atuire, C, Bhan, A, Emanuel, E, Faden, R, Ghimire, P, Greco, D, Ho, CW, Kochhar, S, Schaefer, GO, Shamsi-Gooshki, E, Singh, JA, Smith, MJ, and Wolff, J

Subjects
International Cooperation, Health Policy, 05 social sciences, COVID-19, 06 humanities and the arts, General Medicine, 16. Peace & justice, 0603 philosophy, ethics and religion, Global Health, 3. Good health, 0506 political science, 050602 political science & public administration, Humans, 060301 applied ethics, Clinical Governance, Pandemics, Public Health Administration, Decision Making, Organizational
Abstract

The Access to COVID-19 Tools Accelerator (ACT-A) is a multistakeholder initiative quickly constructed in the early months of the COVID-19 pandemic to respond to a catastrophic breakdown in global cooperation. ACT-A is now the largest international effort to achieve equitable access to COVID-19 health technologies, and its governance is a matter of broad public importance. We traced the evolution of ACT-A's governance through publicly available documents and analysed it against three principles embedded in the founding mission statement of ACT-A: participation, transparency, and accountability. We found three challenges to realising these principles. First, the roles of the various organisations in ACT-A decision making are unclear, obscuring who might be accountable to whom and for what. Second, the absence of a clearly defined decision making body; ACT-A instead has multiple centres of legally binding decision making and uneven arrangements for information transparency, inhibiting meaningful participation. Third, the nearly indiscernible role of governments in ACT-A, raising key questions about political legitimacy and channels for public accountability. With global public health and billions in public funding at stake, short-term improvements to governance arrangements can and should now be made. Efforts to strengthen pandemic preparedness for the future require attention to ethical, legitimate arrangements for governance.

Published
2022

20. Lake salinization drives consistent losses of zooplankton abundance and diversity across coordinated mesocosm experiments

Author

Hébert, MP, Hébert, MP, Symons, CC, Cañedo-Argüelles, M, Arnott, SE, Derry, AM, Fugère, V, Hintz, WD, Melles, SJ, Astorg, L, Baker, HK, Brentrup, JA, Downing, AL, Ersoy, Z, Espinosa, C, Franceschini, JM, Giorgio, AT, Göbeler, N, Gray, DK, Greco, D, Hassal, E, Huynh, M, Hylander, S, Jonasen, KL, Kirkwood, A, Langenheder, S, Langvall, O, Laudon, H, Lind, L, Lundgren, M, McClymont, A, Proia, L, Relyea, RA, Rusak, JA, Schuler, MS, Searle, CL, Shurin, JB, Steiner, CF, Striebel, M, Thibodeau, S, Urrutia Cordero, P, Vendrell-Puigmitja, L, Weyhenmeyer, GA, Beisner, BE, Hébert, MP, Hébert, MP, Symons, CC, Cañedo-Argüelles, M, Arnott, SE, Derry, AM, Fugère, V, Hintz, WD, Melles, SJ, Astorg, L, Baker, HK, Brentrup, JA, Downing, AL, Ersoy, Z, Espinosa, C, Franceschini, JM, Giorgio, AT, Göbeler, N, Gray, DK, Greco, D, Hassal, E, Huynh, M, Hylander, S, Jonasen, KL, Kirkwood, A, Langenheder, S, Langvall, O, Laudon, H, Lind, L, Lundgren, M, McClymont, A, Proia, L, Relyea, RA, Rusak, JA, Schuler, MS, Searle, CL, Shurin, JB, Steiner, CF, Striebel, M, Thibodeau, S, Urrutia Cordero, P, Vendrell-Puigmitja, L, Weyhenmeyer, GA, and Beisner, BE

Abstract

Human-induced salinization increasingly threatens inland waters; yet we know little about the multifaceted response of lake communities to salt contamination. By conducting a coordinated mesocosm experiment of lake salinization across 16 sites in North America and Europe, we quantified the response of zooplankton abundance and (taxonomic and functional) community structure to a broad gradient of environmentally relevant chloride concentrations, ranging from 4 to ca. 1400 mg Cl− L−1. We found that crustaceans were distinctly more sensitive to elevated chloride than rotifers; yet, rotifers did not show compensatory abundance increases in response to crustacean declines. For crustaceans, our among-site comparisons indicate: (1) highly consistent decreases in abundance and taxon richness with salinity; (2) widespread chloride sensitivity across major taxonomic groups (Cladocera, Cyclopoida, and Calanoida); and (3) weaker loss of functional than taxonomic diversity. Overall, our study demonstrates that aggregate properties of zooplankton communities can be adversely affected at chloride concentrations relevant to anthropogenic salinization in lakes.

Published
2022

21. The integration of large-scale public data and network analysis uncovers molecular characteristics of psoriasis

Author

Federico, A., Pavel, Alisa, Mobus, Lena, McKean, David, Giudice, Giusy Del, Fortino, Vittorio, Niehues, H., Bogaard, E.H.J. van den, Rinaldis, Emanuele de, Greco, D., Federico, A., Pavel, Alisa, Mobus, Lena, McKean, David, Giudice, Giusy Del, Fortino, Vittorio, Niehues, H., Bogaard, E.H.J. van den, Rinaldis, Emanuele de, and Greco, D.

Abstract

Contains fulltext : 286078.pdf (Publisher’s version ) (Open Access)

Published
2022

22. Influence of FLG loss-of-function mutations in host-microbe interactions during atopic skin inflammation

Author

Oláh, P., Szlávicz, E., Kuchner, M., Nemmer, J., Zeeuwen, P.L.J.M., Lefèvre-Utile, A., Fyhrquist, N., Prast-Nielsen, S., Skoog, T., Serra, A., Rodríguez, E., Raap, U., Meller, S., Gyulai, R., Hupé, P., Kere, J., Levi-Schaffer, F., Tsoka, S., Alexander, H., Nestle, F.O., Schröder, J.M., Weidinger, S., Bogaard, E. van den, Soumelis, V., Greco, D., Barker, J., Lauerma, A., Ranki, A., Andersson, B., Alenius, H., Homey, B., Oláh, P., Szlávicz, E., Kuchner, M., Nemmer, J., Zeeuwen, P.L.J.M., Lefèvre-Utile, A., Fyhrquist, N., Prast-Nielsen, S., Skoog, T., Serra, A., Rodríguez, E., Raap, U., Meller, S., Gyulai, R., Hupé, P., Kere, J., Levi-Schaffer, F., Tsoka, S., Alexander, H., Nestle, F.O., Schröder, J.M., Weidinger, S., Bogaard, E. van den, Soumelis, V., Greco, D., Barker, J., Lauerma, A., Ranki, A., Andersson, B., Alenius, H., and Homey, B.

Abstract

Item does not contain fulltext, BACKGROUND: Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome and microbiome remain largely elusive. OBJECTIVE: In-depth analysis of FLG genotype-associated skin gene expression alterations and host-microbe interactions in AD. METHODS: Multi-omics characterization of a cohort of AD patients carrying heterozygous loss-of-function mutations in the FLG gene (AD(Mut)) (n = 15), along with matched wild-type (AD(Wt)) patients and healthy controls. Detailed clinical characterization, microarray gene expression and 16 S rRNA-based microbial marker gene data were generated and analyzed. RESULTS: In the context of filaggrin dysfunction, the transcriptome was characterized by dysregulation of barrier function and water homeostasis, while the lesional skin of AD(Wt) demonstrated the specific upregulation of pro-inflammatory cytokines and T-cell proliferation. S. aureus dominated the microbiome in both patient groups, however, shifting microbial communities could be observed when comparing healthy with non-lesional AD(Wt) or AD(Mut) skin, offering the opportunity to identify microbe-associated transcriptomic signatures. Moreover, an AD core signature with 28 genes, including CCL13, CCL18, BTC, SCIN, RAB31 and PCLO was identified. CONCLUSIONS: Our integrative approach provides molecular insights for the concept that FLG loss-of-function mutations are a genetic shortcut to atopic inflammation and unravels the complex interplay between genotype, transcriptome and microbiome in the human holobiont.

Published
2022

23. Requirements and expectations of high-quality biomarkers for atopic dermatitis and psoriasis in 2021-a two-round Delphi survey among international experts

Author

Ziehfreund, S., Tizek, L., Hangel, N., Fritzsche, M.C., Weidinger, S., Smith, C., Bryce, P.J., Greco, D., Bogaard, E.H.J. van den, Flohr, C., Rastrick Ucb, J., Eyerich, S., Buyx, A., Conrad, C., Eyerich, K., Zink, A., Ziehfreund, S., Tizek, L., Hangel, N., Fritzsche, M.C., Weidinger, S., Smith, C., Bryce, P.J., Greco, D., Bogaard, E.H.J. van den, Flohr, C., Rastrick Ucb, J., Eyerich, S., Buyx, A., Conrad, C., Eyerich, K., and Zink, A.

Abstract

Item does not contain fulltext, BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated. AIM: To identify the core elements of high-quality AD and PSO biomarkers to prepare recommendations for current biomarker research. METHOD: A cross-sectional two-round Delphi survey was conducted from August to October 2019 and October to November 2020. All participants were members of the BIOMAP project, an EU-funded consortium of clinicians, researchers, patient organizations and pharmaceutical industry partners. The first round consisted of three open-ended questions. Responses were qualitatively analysed, and 26 closed statements were developed. For the second round, 'agreement' was assumed when the responses of ≥70% of the participants were ≥5 points on a 7-point Likert scale for each statement. Priority classification was based on mean scores (<20th percentile = low, 20th to 60th percentile = medium, >60th percentile = high). RESULTS: Twenty-one and twenty-six individuals participated in rounds one and two, respectively. From 26 statements that were included in round 2, 18 achieved agreement (8 concerning the performance, 8 for the purpose and 2 on current obstacles). Seven statements were classified as high priority, e.g. those concerning reliability, clinical validity, a high positive predictive value, prediction of the therapeutic response and disease progression. Another seven statements were assigned medium priority, e.g. those about analytical validity, prediction of comorbidities and therapeutic algorithm. Low priority included four statements, like those concerning cost effectiveness and prediction of disease flares. CONCLUSION: Th

Published
2022

24. Exome sequencing in a child with neurodevelopmental disorder and epilepsy:variant analysis of the AHNAK2 gene

Author

Vinci, M. (Mirella), Kursula, P. (Petri), Greco, D. (Donatella), Elia, M. (Maurizio), Vetri, L. (Luigi), Schepis, C. (Carmelo), Chiavetta, V. (Valeria), Donadio, S. (Serena), Roccella, M. (Michele), Carotenuto, M. (Marco), Romano, V. (Valentino), Calì, F. (Francesco), Vinci, M. (Mirella), Kursula, P. (Petri), Greco, D. (Donatella), Elia, M. (Maurizio), Vetri, L. (Luigi), Schepis, C. (Carmelo), Chiavetta, V. (Valeria), Donadio, S. (Serena), Roccella, M. (Michele), Carotenuto, M. (Marco), Romano, V. (Valentino), and Calì, F. (Francesco)

Abstract

Background/Objectives: The AHNAK2 gene encodes a large nucleoprotein expressed in several tissues, including brain, squamous epithelia, smooth muscle, and neuropil. Its role in calcium signaling has been suggested and to date, clear evidence about its involvement in the pathogenesis of clinical disorders is still lacking. Methods: Here, we report a female 24-year-old patient diagnosed with a cardio-facio-cutaneous-like phenotype (CFC-like), characterized by epilepsy, psychomotor development delay, atopic dermatitis, congenital heart disease, hypotonia, and facial dysmorphism, who is compound heterozygote for two missense mutations in the AHNAK2 gene detected by exome sequencing. Results: This patient had no detectable variant in any of the genes known to be associated with the cardio-facio-cutaneous syndrome. Moreover, the mode of inheritance does not appear to be autosomal dominant, as it is in typical CFC syndrome. We have performed in silico assessment of mutation severity separately for each missense mutation, but this analysis excludes a severe effect on protein function. Protein structure predictions indicate the mutations are located in flexible regions possibly involved in molecular interactions. Conclusions: We discuss an alternative interpretation on the potential involvement of the two missense mutations in the AHNAK2 gene on the expression of CFC-like phenotype in this patient based on inter-allelic complementation.

Published
2022

25. Requirements and expectations of high‐quality biomarkers for atopic dermatitis and psoriasis in 2021—a two‐round Delphi survey among international experts

Author

Ziehfreund, S., primary, Tizek, L., additional, Hangel, N., additional, Fritzsche, M.‐C., additional, Weidinger, S., additional, Smith, C., additional, Bryce, P.J., additional, Greco, D., additional, van den Bogaard, E.H., additional, Flohr, C., additional, Rastrick (UCB), J., additional, Eyerich, S., additional, Buyx, A., additional, Conrad, C., additional, Eyerich, K., additional, and Zink, A., additional

Published
2022
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26. Experiences with HPF for scientific applications

Author

Cabitza, G., Nardone, C., Bagaini, C., Balzano, A., Bonomi, E., Brieger, L., Ennas, M., Garau, E., Greco, D., Lecca, G., Pieroni, E., Rossi, C., Goos, Gerhard, editor, Hartmanis, Juris, editor, van Leeuwen, Jan, editor, Liddell, Heather, editor, Colbrook, Adrian, editor, Hertzberger, Bob, editor, and Sloot, Peter, editor

Published
1996
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27. CpGmotifs: a tool to discover DNA motifs associated to CpG methylation events

Author

Scala G., Federico A., Greco D., Scala, G., Federico, A., and Greco, D.

Subjects
DNA methylation signature, DNA methylation, Nucleotide Motif, Genome, Human, R-Shiny, Transcription factor, CpG Island, DNA motif, Software, Human
Abstract

Background: The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena. Results: Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs. Conclusions: CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs.

Published
2021

28. Viral molecular mimicry influences the antitumor immune response in murine and human melanoma

Author

Chiaro J., Kasanen H. H. E., Whalley T., Capasso C., Gronholm M., Feola S., Peltonen K., Hamdan F., Hernberg M., Makela S., Karhapaa H., Brown P. E., Martins B., Fusciello M., Ylosmaki E. O., Greco D., Kreutzman A. S., Mustjoki S., Szomolay B., Cerullo V., Chiaro, J., Kasanen, H. H. E., Whalley, T., Capasso, C., Gronholm, M., Feola, S., Peltonen, K., Hamdan, F., Hernberg, M., Makela, S., Karhapaa, H., Brown, P. E., Martins, B., Fusciello, M., Ylosmaki, E. O., Greco, D., Kreutzman, A. S., Mustjoki, S., Szomolay, B., and Cerullo, V.

Subjects
Mice, Animal, Cell Line, Tumor, Molecular Mimicry, Immunity, Female, Immunotherapy, Melanoma, Human
Abstract

Molecular mimicry is one of the leading mechanisms by which infectious agents can induce autoimmunity. Whether a similar mechanism triggers an antitumor immune response is unexplored, and the role of antiviral T cells infiltrating the tumor has remained anecdotal. To address these questions, we first developed a bioinformatic tool to identify tumor peptides with high similarity to viral epitopes. Using peptides identified by this tool, we demonstrated that, in mice, preexisting immunity toward specific viral epitopes enhanced the efficacy of cancer immunotherapy via molecular mimicry in different settings. To understand whether this mechanism could partly explain immunotherapy responsiveness in humans, we analyzed a cohort of patients with melanoma undergoing anti-PD1 treatment who had a high IgG titer for cytomegalovirus (CMV). In this cohort of patients, we showed that high levels of CMV-specific antibodies were associated with prolonged progression-free survival and found that, in some cases, peripheral blood mononuclear cells (PBMC) could cross-react with both melanoma and CMV homologous peptides. Finally, T-cell receptor sequencing revealed expansion of the same CD8þ T-cell clones when PBMCs were expanded with tumor or homologous viral peptides. In conclusion, we have demonstrated that preexisting immunity and molecular mimicry could influence the response to immunotherapies. In addition, we have developed a free online tool that can identify tumor antigens and neoantigens highly similar to pathogen antigens to exploit molecular mimicry and cross-reactive T cells in cancer vaccine development.

Published
2021

30. Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders

Author

Wang T., Hoekzema K., Vecchio D., Wu H., Sulovari A., Coe B. P., Gillentine M. A., Wilfert A. B., Perez-Jurado L. A., Kvarnung M., Sleyp Y., Earl R. K., Rosenfeld J. A., Geisheker M. R., Han L., Du B., Barnett C., Thompson E., Shaw M., Carroll R., Friend K., Catford R., Palmer E. E., Zou X., Ou J., Li H., Guo H., Gerdts J., Avola E., Calabrese G., Elia M., Greco D., Lindstrand A., Nordgren A., Anderlid B. -M., Vandeweyer G., Van Dijck A., Van der Aa N., McKenna B., Hancarova M., Bendova S., Havlovicova M., Malerba G., Bernardina B. D., Muglia P., van Haeringen A., Hoffer M. J. V., Franke B., Cappuccio G., Delatycki M., Lockhart P. J., Manning M. A., Liu P., Scheffer I. E., Brunetti Pierri N., Rommelse N., Amaral D. G., Santen G. W. E., Trabetti E., Sedlacek Z., Michaelson J. J., Pierce K., Courchesne E., Kooy R. F., Acampado J., Ace A. J., Amatya A., Astrovskaya I., Bashar A., Brooks E., Butler M. E., Cartner L. A., Chin W., Chung W. K., Daniels A. M., Feliciano P., Fleisch C., Ganesan S., Jensen W., Lash A. E., Marini R., Myers V. J., O'Connor E., Rigby C., Robertson B. E., Shah N., Shah S., Singer E., Snyder L. A. G., Stephens A. N., Tjernagel J., Vernoia B. M., Volfovsky N., White L. C., Hsieh A., Shen Y., Zhou X., Turner T. N., Bahl E., Thomas T. R., Brueggeman L., Koomar T., Michael R. J., O'Roak B. J., Barnard R. A., Gibbs R. A., Muzny D., Sabo A., Ahmed K. L. B., Eichler E. E., Siegel M., Abbeduto L., Hilscher B. A., Li D., Smith K., Thompson S., Albright C., Butter E. M., Eldred S., Hanna N., Jones M., Coury D. L., Scherr J., Pifher T., Roby E., Dennis B., Higgins L., Brown M., Alessandri M., Gutierrez A., Hale M. N., Herbert L. M., Schneider H. L., David G., Annett R. D., Sarver D. E., Arriaga I., Camba A., Gulsrud A. C., Haley M., McCracken J. T., Sandhu S., Tafolla M., Yang W. S., Carpenter L. A., Bradley C. C., Gwynette F., Manning P., Shaffer R., Thomas C., Bernier R. A., Fox E. A., Gerdts J. A., Pepper M., Ho T., Cho D., Piven J., Lechniak H., Soorya L. V., Gordon R., Wainer A., Yeh L., Ochoa-Lubinoff C., Russo N., Berry-Kravis E., Booker S., Erickson C. A., Prock L. M., Pawlowski K. G., Matthews E. T., Brewster S. J., Hojlo M. A., Abada E., Lamarche E., Murali S. C., Harvey W. T., Kaplan H. E., Pierce K. L., DeMarco L., Horner S., Pandey J., Plate S., Sahin M., Riley K. D., Carmody E., Constantini J., Esler A., Fatemi A., Hutter H., Landa R. J., McKenzie A. P., Neely J., Singh V., Van Metre B., Wodka E. L., Fombonne E. J., Huang-Storms L. Y., Pacheco L. D., Mastel S. A., Coppola L. A., Francis S., Jarrett A., Jacob S., Lillie N., Gunderson J., Istephanous D., Simon L., Wasserberg O., Rachubinski A. L., Rosenberg C. R., Kanne S. M., Shocklee A. D., Takahashi N., Bridwell S. L., Klimczac R. L., Mahurin M. A., Cotrell H. E., Grant C. A., Hunter S. G., Martin C. L., Taylor C. M., Walsh L. K., Dent K. A., Mason A., Sziklay A., Smith C. J., Nordenskjold M., Romano C., Peeters H., Gecz J., Xia K., SPARK Consortium, Wang, T., Hoekzema, K., Vecchio, D., Wu, H., Sulovari, A., Coe, B. P., Gillentine, M. A., Wilfert, A. B., Perez-Jurado, L. A., Kvarnung, M., Sleyp, Y., Earl, R. K., Rosenfeld, J. A., Geisheker, M. R., Han, L., Du, B., Barnett, C., Thompson, E., Shaw, M., Carroll, R., Friend, K., Catford, R., Palmer, E. E., Zou, X., Ou, J., Li, H., Guo, H., Gerdts, J., Avola, E., Calabrese, G., Elia, M., Greco, D., Lindstrand, A., Nordgren, A., Anderlid, B. -M., Vandeweyer, G., Van Dijck, A., Van der Aa, N., Mckenna, B., Hancarova, M., Bendova, S., Havlovicova, M., Malerba, G., Bernardina, B. D., Muglia, P., van Haeringen, A., Hoffer, M. J. V., Franke, B., Cappuccio, G., Delatycki, M., Lockhart, P. J., Manning, M. A., Liu, P., Scheffer, I. E., Brunetti Pierri, N., Rommelse, N., Amaral, D. G., Santen, G. W. E., Trabetti, E., Sedlacek, Z., Michaelson, J. J., Pierce, K., Courchesne, E., Kooy, R. F., Acampado, J., Ace, A. J., Amatya, A., Astrovskaya, I., Bashar, A., Brooks, E., Butler, M. E., Cartner, L. A., Chin, W., Chung, W. K., Daniels, A. M., Feliciano, P., Fleisch, C., Ganesan, S., Jensen, W., Lash, A. E., Marini, R., Myers, V. J., O'Connor, E., Rigby, C., Robertson, B. E., Shah, N., Shah, S., Singer, E., Snyder, L. A. G., Stephens, A. N., Tjernagel, J., Vernoia, B. M., Volfovsky, N., White, L. C., Hsieh, A., Shen, Y., Zhou, X., Turner, T. N., Bahl, E., Thomas, T. R., Brueggeman, L., Koomar, T., Michael, R. J., O'Roak, B. J., Barnard, R. A., Gibbs, R. A., Muzny, D., Sabo, A., Ahmed, K. L. B., Eichler, E. E., Siegel, M., Abbeduto, L., Hilscher, B. A., Li, D., Smith, K., Thompson, S., Albright, C., Butter, E. M., Eldred, S., Hanna, N., Jones, M., Coury, D. L., Scherr, J., Pifher, T., Roby, E., Dennis, B., Higgins, L., Brown, M., Alessandri, M., Gutierrez, A., Hale, M. N., Herbert, L. M., Schneider, H. L., David, G., Annett, R. D., Sarver, D. E., Arriaga, I., Camba, A., Gulsrud, A. C., Haley, M., Mccracken, J. T., Sandhu, S., Tafolla, M., Yang, W. S., Carpenter, L. A., Bradley, C. C., Gwynette, F., Manning, P., Shaffer, R., Thomas, C., Bernier, R. A., Fox, E. A., Gerdts, J. A., Pepper, M., Ho, T., Cho, D., Piven, J., Lechniak, H., Soorya, L. V., Gordon, R., Wainer, A., Yeh, L., Ochoa-Lubinoff, C., Russo, N., Berry-Kravis, E., Booker, S., Erickson, C. A., Prock, L. M., Pawlowski, K. G., Matthews, E. T., Brewster, S. J., Hojlo, M. A., Abada, E., Lamarche, E., Murali, S. C., Harvey, W. T., Kaplan, H. E., Pierce, K. L., Demarco, L., Horner, S., Pandey, J., Plate, S., Sahin, M., Riley, K. D., Carmody, E., Constantini, J., Esler, A., Fatemi, A., Hutter, H., Landa, R. J., Mckenzie, A. P., Neely, J., Singh, V., Van Metre, B., Wodka, E. L., Fombonne, E. J., Huang-Storms, L. Y., Pacheco, L. D., Mastel, S. A., Coppola, L. A., Francis, S., Jarrett, A., Jacob, S., Lillie, N., Gunderson, J., Istephanous, D., Simon, L., Wasserberg, O., Rachubinski, A. L., Rosenberg, C. R., Kanne, S. M., Shocklee, A. D., Takahashi, N., Bridwell, S. L., Klimczac, R. L., Mahurin, M. A., Cotrell, H. E., Grant, C. A., Hunter, S. G., Martin, C. L., Taylor, C. M., Walsh, L. K., Dent, K. A., Mason, A., Sziklay, A., Smith, C. J., Nordenskjold, M., Romano, C., Peeters, H., Gecz, J., and Xia, K.

Subjects
0301 basic medicine, Male, CCCTC-Binding Factor, Transcription Factor, Basic Helix-Loop-Helix Transcription Factor, DNA Mutational Analysis, General Physics and Astronomy, RNA-Binding Protein, Heterogeneous-Nuclear Ribonucleoprotein U, VARIANTS, medicine.disease_cause, Cohort Studies, 0302 clinical medicine, Neurodevelopmental Disorder, Basic Helix-Loop-Helix Transcription Factors, SPARK Consortium, 2.1 Biological and endogenous factors, Copy-number variation, Aetiology, lcsh:Science, GABRG2, Genetics, Mutation, Multidisciplinary, biology, Neurodevelopmental disorders, RNA-Binding Proteins, High-Throughput Nucleotide Sequencing, Autism spectrum disorders, Multidisciplinary Sciences, DNA-Binding Proteins, Science & Technology - Other Topics, Female, Case-Control Studie, Engineering sciences. Technology, Human, Science, DNA-Binding Protein, Genetic Association Studie, COPY-NUMBER VARIATION, General Biochemistry, Genetics and Molecular Biology, DNA sequencing, Article, KCNQ3 Potassium Channel, DNA Mutational Analysi, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, AUTISM, Gene, Genetic Association Studies, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, DISABILITY, Prevention, Case-control study, General Chemistry, Repressor Protein, medicine.disease, FRAMEWORK, Repressor Proteins, DE-NOVO MUTATION, 030104 developmental biology, CTCF, Neurodevelopmental Disorders, Case-Control Studies, biology.protein, Next-generation sequencing, Autism, lcsh:Q, Cohort Studie, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF, For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

Published
2020

31. Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Author

Grapotte M., Saraswat M., Bessiere C., Menichelli C., Ramilowski J. A., Severin J., Hayashizaki Y., Itoh M., Tagami M., Murata M., Kojima-Ishiyama M., Noma S., Noguchi S., Kasukawa T., Hasegawa A., Suzuki H., Nishiyori-Sueki H., Frith M. C., Abugessaisa I., Aitken S., Aken B. L., Alam I., Alam T., Alasiri R., Alhendi A. M. N., Alinejad-Rokny H., Alvarez M. J., Andersson R., Arakawa T., Araki M., Arbel T., Archer J., Archibald A. L., Arner E., Arner P., Asai K., Ashoor H., Astrom G., Babina M., Baillie J. K., Bajic V. B., Bajpai A., Baker S., Baldarelli R. M., Balic A., Bansal M., Batagov A. O., Batzoglou S., Beckhouse A. G., Beltrami A. P., Beltrami C. A., Bertin N., Bhattacharya S., Bickel P. J., Blake J. A., Blanchette M., Bodega B., Bonetti A., Bono H., Bornholdt J., Bttcher M., Bougouffa S., Boyd M., Breda J., Brombacher F., Brown J. B., Bult C. J., Burroughs A. M., Burt D. W., Busch A., Caglio G., Califano A., Cameron C. J., Cannistraci C. V., Carbone A., Carlisle A. J., Carninci P., Carter K. W., Cesselli D., Chang J. -C., Chen J. C., Chen Y., Chierici M., Christodoulou J., Ciani Y., Clark E. L., Coskun M., Dalby M., Dalla E., Daub C. O., Davis C. A., de Hoon M. J. L., de Rie D., Denisenko E., Deplancke B., Detmar M., Deviatiiarov R., Di Bernardo D., Diehl A. D., Dieterich L. C., Dimont E., Djebali S., Dohi T., Dostie J., Drablos F., Edge A. S. B., Edinger M., Ehrlund A., Ekwall K., Elofsson A., Endoh M., Enomoto H., Enomoto S., Faghihi M., Fagiolini M., Farach-Carson M. C., Faulkner G. J., Favorov A., Fernandes A. M., Ferrai C., Forrest A. R. R., Forrester L. M., Forsberg M., Fort A., Francescatto M., Freeman T. C., Frith M., Fukuda S., Funayama M., Furlanello C., Furuno M., Furusawa C., Gao H., Gazova I., Gebhard C., Geier F., Geijtenbeek T. B. H., Ghosh S., Ghosheh Y., Gingeras T. R., Gojobori T., Goldberg T., Goldowitz D., Gough J., Greco D., Gruber A. J., Guhl S., Guigo R., Guler R., Gusev O., Gustincich S., Ha T. J., Haberle V., Hale P., Hallstrom B. M., Hamada M., Handoko L., Hara M., Harbers M., Harrow J., Harshbarger J., Hase T., Hashimoto K., Hatano T., Hattori N., Hayashi R., Herlyn M., Hettne K., Heutink P., Hide W., Hitchens K. J., Sui S. H., 't Hoen P. A. C., Hon C. C., Hori F., Horie M., Horimoto K., Horton P., Hou R., Huang E., Huang Y., Hugues R., Hume D., Ienasescu H., Iida K., Ikawa T., Ikemura T., Ikeo K., Inoue N., Ishizu Y., Ito Y., Ivshina A. V., Jankovic B. R., Jenjaroenpun P., Johnson R., Jorgensen M., Jorjani H., Joshi A., Jurman G., Kaczkowski B., Kai C., Kaida K., Kajiyama K., Kaliyaperumal R., Kaminuma E., Kanaya T., Kaneda H., Kapranov P., Kasianov A. S., Katayama T., Kato S., Kawaguchi S., Kawai J., Kawaji H., Kawamoto H., Kawamura Y. I., Kawasaki S., Kawashima T., Kempfle J. S., Kenna T. J., Kere J., Khachigian L., Kiryu H., Kishima M., Kitajima H., Kitamura T., Kitano H., Klaric E., Klepper K., Klinken S. P., Kloppmann E., Knox A. J., Kodama Y., Kogo Y., Kojima M., Kojima S., Komatsu N., Komiyama H., Kono T., Koseki H., Koyasu S., Kratz A., Kukalev A., Kulakovskiy I., Kundaje A., Kunikata H., Kuo R., Kuo T., Kuraku S., Kuznetsov V. A., Kwon T. J., Larouche M., Lassmann T., Law A., Le-Cao K. -A., Lecellier C. -H., Lee W., Lenhard B., Lennartsson A., Li K., Li R., Lilje B., Lipovich L., Lizio M., Lopez G., Magi S., Mak G. K., Makeev V., Manabe R., Mandai M., Mar J., Maruyama K., Maruyama T., Mason E., Mathelier A., Matsuda H., Medvedeva Y. A., Meehan T. F., Mejhert N., Meynert A., Mikami N., Minoda A., Miura H., Miyagi Y., Miyawaki A., Mizuno Y., Morikawa H., Morimoto M., Morioka M., Morishita S., Moro K., Motakis E., Motohashi H., Mukarram A. K., Mummery C. L., Mungall C. J., Murakawa Y., Muramatsu M., Nagasaka K., Nagase T., Nakachi Y., Nakahara F., Nakai K., Nakamura K., Nakamura Y., Nakazawa T., Nason G. P., Nepal C., Nguyen Q. H., Nielsen L. K., Nishida K., Nishiguchi K. M., Nishiyori H., Nitta K., Notredame C., Ogishima S., Ohkura N., Ohno H., Ohshima M., Ohtsu T., Okada Y., Okada-Hatakeyama M., Okazaki Y., Oksvold P., Orlando V., Ow G. S., Ozturk M., Pachkov M., Paparountas T., Parihar S. P., Park S. -J., Pascarella G., Passier R., Persson H., Philippens I. H., Piazza S., Plessy C., Pombo A., Ponten F., Poulain S., Poulsen T. M., Pradhan S., Prezioso C., Pridans C., Qin X. -Y., Quackenbush J., Rackham O., Ramilowski J., Ravasi T., Rehli M., Rennie S., Rito T., Rizzu P., Robert C., Roos M., Rost B., Roudnicky F., Roy R., Rye M. B., Sachenkova O., Saetrom P., Sai H., Saiki S., Saito M., Saito A., Sakaguchi S., Sakai M., Sakaue S., Sakaue-Sawano A., Sandelin A., Sano H., Sasamoto Y., Sato H., Saxena A., Saya H., Schafferhans A., Schmeier S., Schmidl C., Schmocker D., Schneider C., Schueler M., Schultes E. A., Schulze-Tanzil G., Semple C. A., Seno S., Seo W., Sese J., Sheng G., Shi J., Shimoni Y., Shin J. W., SimonSanchez J., Sivertsson A., Sjostedt E., Soderhall C., Laurent G. S., Stoiber M. H., Sugiyama D., Summers K. M., Suzuki A. M., Suzuki K., Suzuki M., Suzuki N., Suzuki T., Swanson D. J., Swoboda R. K., Taguchi A., Takahashi H., Takahashi M., Takamochi K., Takeda S., Takenaka Y., Tam K. T., Tanaka H., Tanaka R., Tanaka Y., Tang D., Taniuchi I., Tanzer A., Tarui H., Taylor M. S., Terada A., Terao Y., Testa A. C., Thomas M., Thongjuea S., Tomii K., Triglia E. T., Toyoda H., Tsang H. G., Tsujikawa M., Uhlen M., Valen E., van de Wetering M., van Nimwegen E., Velmeshev D., Verardo R., Vitezic M., Vitting-Seerup K., von Feilitzen K., Voolstra C. R., Vorontsov I. E., Wahlestedt C., Wasserman W. W., Watanabe K., Watanabe S., Wells C. A., Winteringham L. N., Wolvetang E., Yabukami H., Yagi K., Yamada T., Yamaguchi Y., Yamamoto M., Yamamoto Y., Yamanaka Y., Yano K., Yasuzawa K., Yatsuka Y., Yo M., Yokokura S., Yoneda M., Yoshida E., Yoshida Y., Yoshihara M., Young R., Young R. S., Yu N. Y., Yumoto N., Zabierowski S. E., Zhang P. G., Zucchelli S., Zwahlen M., Chatelain C., Brehelin L., Grapotte, M., Saraswat, M., Bessiere, C., Menichelli, C., Ramilowski, J. A., Severin, J., Hayashizaki, Y., Itoh, M., Tagami, M., Murata, M., Kojima-Ishiyama, M., Noma, S., Noguchi, S., Kasukawa, T., Hasegawa, A., Suzuki, H., Nishiyori-Sueki, H., Frith, M. C., Abugessaisa, I., Aitken, S., Aken, B. L., Alam, I., Alam, T., Alasiri, R., Alhendi, A. M. N., Alinejad-Rokny, H., Alvarez, M. J., Andersson, R., Arakawa, T., Araki, M., Arbel, T., Archer, J., Archibald, A. L., Arner, E., Arner, P., Asai, K., Ashoor, H., Astrom, G., Babina, M., Baillie, J. K., Bajic, V. B., Bajpai, A., Baker, S., Baldarelli, R. M., Balic, A., Bansal, M., Batagov, A. O., Batzoglou, S., Beckhouse, A. G., Beltrami, A. P., Beltrami, C. A., Bertin, N., Bhattacharya, S., Bickel, P. J., Blake, J. A., Blanchette, M., Bodega, B., Bonetti, A., Bono, H., Bornholdt, J., Bttcher, M., Bougouffa, S., Boyd, M., Breda, J., Brombacher, F., Brown, J. B., Bult, C. J., Burroughs, A. M., Burt, D. W., Busch, A., Caglio, G., Califano, A., Cameron, C. J., Cannistraci, C. V., Carbone, A., Carlisle, A. J., Carninci, P., Carter, K. W., Cesselli, D., Chang, J. -C., Chen, J. C., Chen, Y., Chierici, M., Christodoulou, J., Ciani, Y., Clark, E. L., Coskun, M., Dalby, M., Dalla, E., Daub, C. O., Davis, C. A., de Hoon, M. J. L., de Rie, D., Denisenko, E., Deplancke, B., Detmar, M., Deviatiiarov, R., Di Bernardo, D., Diehl, A. D., Dieterich, L. C., Dimont, E., Djebali, S., Dohi, T., Dostie, J., Drablos, F., Edge, A. S. B., Edinger, M., Ehrlund, A., Ekwall, K., Elofsson, A., Endoh, M., Enomoto, H., Enomoto, S., Faghihi, M., Fagiolini, M., Farach-Carson, M. C., Faulkner, G. J., Favorov, A., Fernandes, A. M., Ferrai, C., Forrest, A. R. R., Forrester, L. M., Forsberg, M., Fort, A., Francescatto, M., Freeman, T. C., Frith, M., Fukuda, S., Funayama, M., Furlanello, C., Furuno, M., Furusawa, C., Gao, H., Gazova, I., Gebhard, C., Geier, F., Geijtenbeek, T. B. H., Ghosh, S., Ghosheh, Y., Gingeras, T. R., Gojobori, T., Goldberg, T., Goldowitz, D., Gough, J., Greco, D., Gruber, A. J., Guhl, S., Guigo, R., Guler, R., Gusev, O., Gustincich, S., Ha, T. J., Haberle, V., Hale, P., Hallstrom, B. M., Hamada, M., Handoko, L., Hara, M., Harbers, M., Harrow, J., Harshbarger, J., Hase, T., Hashimoto, K., Hatano, T., Hattori, N., Hayashi, R., Herlyn, M., Hettne, K., Heutink, P., Hide, W., Hitchens, K. J., Sui, S. H., 't Hoen, P. A. C., Hon, C. C., Hori, F., Horie, M., Horimoto, K., Horton, P., Hou, R., Huang, E., Huang, Y., Hugues, R., Hume, D., Ienasescu, H., Iida, K., Ikawa, T., Ikemura, T., Ikeo, K., Inoue, N., Ishizu, Y., Ito, Y., Ivshina, A. V., Jankovic, B. R., Jenjaroenpun, P., Johnson, R., Jorgensen, M., Jorjani, H., Joshi, A., Jurman, G., Kaczkowski, B., Kai, C., Kaida, K., Kajiyama, K., Kaliyaperumal, R., Kaminuma, E., Kanaya, T., Kaneda, H., Kapranov, P., Kasianov, A. S., Katayama, T., Kato, S., Kawaguchi, S., Kawai, J., Kawaji, H., Kawamoto, H., Kawamura, Y. I., Kawasaki, S., Kawashima, T., Kempfle, J. S., Kenna, T. J., Kere, J., Khachigian, L., Kiryu, H., Kishima, M., Kitajima, H., Kitamura, T., Kitano, H., Klaric, E., Klepper, K., Klinken, S. P., Kloppmann, E., Knox, A. J., Kodama, Y., Kogo, Y., Kojima, M., Kojima, S., Komatsu, N., Komiyama, H., Kono, T., Koseki, H., Koyasu, S., Kratz, A., Kukalev, A., Kulakovskiy, I., Kundaje, A., Kunikata, H., Kuo, R., Kuo, T., Kuraku, S., Kuznetsov, V. A., Kwon, T. J., Larouche, M., Lassmann, T., Law, A., Le-Cao, K. -A., Lecellier, C. -H., Lee, W., Lenhard, B., Lennartsson, A., Li, K., Li, R., Lilje, B., Lipovich, L., Lizio, M., Lopez, G., Magi, S., Mak, G. K., Makeev, V., Manabe, R., Mandai, M., Mar, J., Maruyama, K., Maruyama, T., Mason, E., Mathelier, A., Matsuda, H., Medvedeva, Y. A., Meehan, T. F., Mejhert, N., Meynert, A., Mikami, N., Minoda, A., Miura, H., Miyagi, Y., Miyawaki, A., Mizuno, Y., Morikawa, H., Morimoto, M., Morioka, M., Morishita, S., Moro, K., Motakis, E., Motohashi, H., Mukarram, A. K., Mummery, C. L., Mungall, C. J., Murakawa, Y., Muramatsu, M., Nagasaka, K., Nagase, T., Nakachi, Y., Nakahara, F., Nakai, K., Nakamura, K., Nakamura, Y., Nakazawa, T., Nason, G. P., Nepal, C., Nguyen, Q. H., Nielsen, L. K., Nishida, K., Nishiguchi, K. M., Nishiyori, H., Nitta, K., Notredame, C., Ogishima, S., Ohkura, N., Ohno, H., Ohshima, M., Ohtsu, T., Okada, Y., Okada-Hatakeyama, M., Okazaki, Y., Oksvold, P., Orlando, V., Ow, G. S., Ozturk, M., Pachkov, M., Paparountas, T., Parihar, S. P., Park, S. -J., Pascarella, G., Passier, R., Persson, H., Philippens, I. H., Piazza, S., Plessy, C., Pombo, A., Ponten, F., Poulain, S., Poulsen, T. M., Pradhan, S., Prezioso, C., Pridans, C., Qin, X. -Y., Quackenbush, J., Rackham, O., Ramilowski, J., Ravasi, T., Rehli, M., Rennie, S., Rito, T., Rizzu, P., Robert, C., Roos, M., Rost, B., Roudnicky, F., Roy, R., Rye, M. B., Sachenkova, O., Saetrom, P., Sai, H., Saiki, S., Saito, M., Saito, A., Sakaguchi, S., Sakai, M., Sakaue, S., Sakaue-Sawano, A., Sandelin, A., Sano, H., Sasamoto, Y., Sato, H., Saxena, A., Saya, H., Schafferhans, A., Schmeier, S., Schmidl, C., Schmocker, D., Schneider, C., Schueler, M., Schultes, E. A., Schulze-Tanzil, G., Semple, C. A., Seno, S., Seo, W., Sese, J., Sheng, G., Shi, J., Shimoni, Y., Shin, J. W., Simonsanchez, J., Sivertsson, A., Sjostedt, E., Soderhall, C., Laurent, G. S., Stoiber, M. H., Sugiyama, D., Summers, K. M., Suzuki, A. M., Suzuki, K., Suzuki, M., Suzuki, N., Suzuki, T., Swanson, D. J., Swoboda, R. K., Taguchi, A., Takahashi, H., Takahashi, M., Takamochi, K., Takeda, S., Takenaka, Y., Tam, K. T., Tanaka, H., Tanaka, R., Tanaka, Y., Tang, D., Taniuchi, I., Tanzer, A., Tarui, H., Taylor, M. S., Terada, A., Terao, Y., Testa, A. C., Thomas, M., Thongjuea, S., Tomii, K., Triglia, E. T., Toyoda, H., Tsang, H. G., Tsujikawa, M., Uhlen, M., Valen, E., van de Wetering, M., van Nimwegen, E., Velmeshev, D., Verardo, R., Vitezic, M., Vitting-Seerup, K., von Feilitzen, K., Voolstra, C. R., Vorontsov, I. E., Wahlestedt, C., Wasserman, W. W., Watanabe, K., Watanabe, S., Wells, C. A., Winteringham, L. N., Wolvetang, E., Yabukami, H., Yagi, K., Yamada, T., Yamaguchi, Y., Yamamoto, M., Yamamoto, Y., Yamanaka, Y., Yano, K., Yasuzawa, K., Yatsuka, Y., Yo, M., Yokokura, S., Yoneda, M., Yoshida, E., Yoshida, Y., Yoshihara, M., Young, R., Young, R. S., Yu, N. Y., Yumoto, N., Zabierowski, S. E., Zhang, P. G., Zucchelli, S., Zwahlen, M., Chatelain, C., Brehelin, L., Institute of Biotechnology, Biosciences, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Computationnelle (IBC), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), National Institute of Advanced Industrial Science and Technology (AIST), SANOFI Recherche, University of British Columbia (UBC), Experimental Immunology, Infectious diseases, AII - Infectious diseases, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)

Subjects
0301 basic medicine, General Physics and Astronomy, Genome, Mice, 0302 clinical medicine, Transcription (biology), Promoter Regions, Genetic, Transcription Initiation, Genetic, 0303 health sciences, Multidisciplinary, 1184 Genetics, developmental biology, physiology, High-Throughput Nucleotide Sequencing, Neurodegenerative Diseases, 222 Other engineering and technologies, Genomics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], humanities, Enhancer Elements, Genetic, Microsatellite Repeat, Transcription Initiation Site, Sequence motif, Transcription Initiation, Human, Enhancer Elements, Neural Networks, Science, 610 Medicine & health, Computational biology, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Promoter Regions, 03 medical and health sciences, Computer, Deep Learning, Tandem repeat, Genetic, Clinical Research, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Machine learning, Genetics, Animals, Humans, Polymorphism, Enhancer, Transcriptomics, Gene, A549 Cell, 030304 developmental biology, Polymorphism, Genetic, Neurodegenerative Disease, Base Sequence, Animal, Genome, Human, Human Genome, Computational Biology, Promoter, General Chemistry, 113 Computer and information sciences, Cap analysis gene expression, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cardiovascular and Metabolic Diseases, A549 Cells, Minion, Generic health relevance, 3111 Biomedicine, Neural Networks, Computer, 610 Medizin und Gesundheit, 030217 neurology & neurosurgery, FANTOM consortium, Microsatellite Repeats
Abstract

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism., Nature Communications, 12 (1), ISSN:2041-1723

Published
2020

32. MaNGA: a novel multi-objective multi-niche genetic algorithm for QSAR modelling

Author

Serra A, Önlü S, Festa P., Fortino V, Greco D, Serra, A, Önlü, S, Festa, P., Fortino, V, and Greco, D

Subjects
QSAR modelling, Combinatorial Optimization, Genetic Algorithms
Abstract

Quantitative structure–activity relationship (QSAR) modelling is currently used in multiple fields to relate structural properties of compounds to their biological activities. This technique is also used for drug design purposes with the aim of predicting parameters that determine drug behaviour. To this end, a sophisticated process, involving various analytical steps concatenated in series, is employed to identify and fine-tune the optimal set of predictors from a large dataset of molecular descriptors (MDs). The search of the optimal model requires to optimize multiple objectives at the same time, as the aim is to obtain the minimal set of features that maximizes the goodness of fit and the applicability domain (AD). Hence, a multi-objective optimization strategy, improving multiple parameters in parallel, can be applied. Here we propose a new multi-niche multi-objective genetic algorithm that simultaneously enables stable feature selection as well as obtaining robust and validated regression models with maximized AD. We benchmarked our method on two simulated datasets. Moreover, we analyzed an aquatic acute toxicity dataset and compared the performances of single- and multi-objective fitness functions on different regression models. Our results show that our multi-objective algorithm is a valid alternative to classical QSAR modelling strategy, for continuous response values, since it automatically finds the model with the best compromise between statistical robustness, predictive performance, widest AD, and the smallest number of MDs

Published
2020

36. Topic: Rectum Diastasis

Author

Feleshtynsky, Y., Vatamanyuk, V. F., Dadayan, V. A., Smishchuk, V. V., Mbaye, P. A., Ndour, O., Fall, A. F., Ngom, G., Ndoye, M., Greco, D. P., Pradella, P., Bertoglio, C. L., Calabrese, F., Sanfilippo, F., Nounamo, F., Tang, J. X., Liang, C. H., Jang, J., Bowker, A., Panish, J., Chekan, E., Roy, S., Kim, A. L., Seo, K. W., Lee, S. H., Choi, S. H., Kamei, A., Kanehira, E., Nakagi, M., and Tanida, T.

Published
2015
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40. The Di Bella Multitherapy Trial

Author

Liberati, Alessandro, Magrini, Nicola, Patoia, Lucio, Pagliaro, Luigi, Raschetti, R., Greco, D., Menniti-Ippolito, F., Spila-Alegiani, S., Traversa, G., Benagiano, G., Bruzzi, P., Müllner, Marcus, and Evans, Stephen J. W.

Published
1999

45. PO-1347 Prostate cancer RT pattern of practice in Italy between 2004-2011: an analysis by the AIRO database

Author

Bruni, A., primary, Mazzeo, E., additional, Triggiani, L., additional, Frassinelli, L., additional, Guarneri, A., additional, Bartoncini, S., additional, Antognoni, P., additional, Gottardo, S., additional, Greco, D., additional, Borghesi, S., additional, Nanni, S., additional, Ingrosso, G., additional, D’Angelillo, R.M., additional, Detti, B., additional, Francolini, G., additional, Magli, A., additional, Guerini, A., additional, Arcangeli, S., additional, Spiazzi, L., additional, Ricardi, U., additional, Lohr, F., additional, and Magrini, S.M., additional

Published
2021
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47. Dna methylation levels in mononuclear leukocytes from the mother and her child are associated with ige sensitization to allergens in early life

Author

Acevedo, N., Scala, G., Merid, S.K., Frumento, P., Bruhn, S., Andersson, A., Ogris, C., Bottai, M., Pershagen, G., Koppelman, G.H., Melén, E., Sonnhammer, E., Alm, J., Söderhäll, C., Kere, J., Greco, D., Scheynius, A., STEMM - Stem Cells and Metabolism Research Program, Research Programs Unit, University of Helsinki, Institute of Biotechnology, Acevedo, Nathalie, Scala, Giovanni, Merid, Simon Kebede, Frumento, Paolo, Bruhn, Sören, Andersson, Anna, Ogris, Christoph, Bottai, Matteo, Pershagen, Göran, Koppelman, Gerard H, Melén, Erik, Sonnhammer, Erik, Alm, Johan, Söderhäll, Cilla, Kere, Juha, Greco, Dario, Scheynius, Annika, Groningen Research Institute for Asthma and COPD (GRIAC), Tampere University, and BioMediTech

Subjects
maternal effect, Adult, Male, Maternal effects, Cells, IgE sensitization, Mononuclear, Mothers, ALLADIN, Allergens, Atopy, BAMSE, DNA methylation, Epigenetics, Cells, Cultured, Child, Preschool, Cohort Studies, CpG Islands, Female, Fetal Blood, Genetic Predisposition to Disease, Humans, Hypersensitivity, Immunoglobulin E, Leukocytes, Mononuclear, Pregnancy, DNA Methylation, Article, lcsh:Chemistry, Leukocytes, Alladin, Bamse, Dna Methylation, Ige Sensitization, Maternal Effects, Child, Preschool, lcsh:QH301-705.5, Mother, Cultured, Allergen, lcsh:Biology (General), lcsh:QD1-999, 1182 Biochemistry, cell and molecular biology, 3111 Biomedicine, Cohort Studie, CpG Island, epigenetic, Human
Abstract

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition. publishedVersion

Published
2021

48. GEOLOGICAL ORIGIN OF BENTONITE: ITS ROLE IN THE SELECTION OF POTENTIAL BINDERS FOR AFLATOXIN ADSORPTION

Author

D'ASCANIO V., GRECO D., MENICAGLI E., LOGRIECO A.F., CATUCCI L., and AVANTAGGIATO G

Subjects
feed additives, bentonite, aflatoxin, clay, mycotoxin
Abstract

Since 2013, bentonite in the form of dioctahedral smectite is an additive authorised in the EU as a substance for the reduction of the contamination of feed by aflatoxins. Several studies indicate a big difference in the effectiveness of bentonites in sequestering aflatoxins. A clear correlation between mineralogical and physicochemical properties of bentonites and aflatoxin adsorption has not been well established. In this study, the most critical mineralogical, chemical, and physical properties that affect aflatoxin adsorption by bentonite were evaluated. Bentonite samples (29), mined from different locations around the world, were analyzed against the published selection criteria for aflatoxin adsorbents: mycotoxin adsorption parameters (maximum adsorption capacity and affinity) determined by the method of adsorption isotherms; pH; cation exchange capacity; particle size distribution; mineralogical/structural compositions; swell index and viscosity. A correlation between geological origin and AFB1 adsorption capacity was found (p

Published
2021
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49. LACTOBACILLUS ACIDOPHILUS CIP 76.13 AND L. DELBRUECKII SUBSP. BULGARICUS CIP 101027T AS PROMISING MYCOTOXIN DECONTAMINATING AGENTS

Author

RAGOUBI C., QUINTIERI L., GRECO D., MEHREZ A., MAATOUK I., D'ASCANIO V., LANDOULSI A., and AVANTAGGIATO G

Subjects
lactobacillus, feed additives, mycotoxins, food and beverages, decontamination
Abstract

Mycotoxins are harmful secondary metabolites produced by fungi which contaminate a wide range of food and feed. Lactic acid bacteria (LAB) show a promising potential to degrade or bind mycotoxins thus reducing their absorption at gastrointestinal level. This study was aimed to investigate the ability of Lactobacillus acidophilus CIP 76.13 and L. delbrueckii subsp. bulgaricus CIP 101027T in removing AFB1, OTA, ZEA and DON in culture media. Mycotoxin removal by viable and heat-inactivated cells was evaluated at pH7, 37°C and 24 h of incubation time, in PBS and MRS containing 1 ?g/mL of each mycotoxin. Residual mycotoxin content in supernatants and cell pellets was determined by UHPLC-FLD/PDA analytical methods. Mycotoxin reduction values differed depending on liquid media. In PBS, viable cells of these strains reduced, on average, ZEA and DON by 57.4 and 30.0%, respectively. AFB1 and OTA reductions in PBS were negligible, being lower than 15%. In MRS, mean values of ZEA and AFB1 reduction were 28.0 and 32.1%, respectively, while OTA and DON were not reduced. Mycotoxin reductions recorded using heat inactivated cells of each strain, tested in PBS or MRS, were significantly lower than those obtained with viable cells. These results suggests that mycotoxin reduction by bacterial strains may occur by a biotransformation process rather than a binding mechanism. In addition, both strains survived at pH 3, 5 and 7 for 24 h in PBS and exhibited lipolytic and proteolytic activities. This study suggests the potential use and broader application of LABs (CIP 76.13 and CIP 101027 T) for mycotoxin reduction in food and feed industry.

Published
2021

50. DEVELOPMENT OF A NEW BIO-ORGANOCLAY FOR MYCOTOXIN DECONTAMINATION: IN VITRO AND IN VIVO EVIDENCE

Author

D'ASCANIO V., GRECO D., CATTEUW A., CROUBELS S., DEVREESE M., SCALA R., MAQOUD F., TRICARICO D., MENICAGLI E., LOGRIECO A.F.1, and AVANTAGGIATO G.

Subjects
feed additives, food and beverages, bio-organoclay, decontamination, mycotoxin
Abstract

Bentonites adsorb preferably aflatoxins, with little adsorption efficacy towards other mycotoxins. To overcome this limitation a bio-organoclay, acting as a multimycotoxin adsorbent, was developed by functionalization of a Na-smectite with an organic, non-toxic modifier. The process was optimized at lab and industrial level. At low dosages (0.25-0.5% w/v), the bio-organoclay sequestered more than 95% of AFB1, FB1, OTA, and ZEA, in a large range of pH values (3-9). Mycotoxin adsorption occurred simultaneously with high capacity and affinity as determined by equilibrium isotherms. The efficacy of the bio-organoclay in reducing the systemic exposure to AFB1, FB1, OTA, and ZEA was further studied in rats and piglets, using the biomarker for exposure approach. Mycotoxins were administered by an intragastric oral bolus, singularly in rats and as a mixture in piglets. Control animals received the mycotoxins without the detoxifier, while treated animals received the mycotoxins with the bioorganoclay at 0.5% w/w of feed consumption. Samples of urine in rats and of blood in piglets were collected at different time points (4-72h), and then analysed for mycotoxin content by UPLC-FLD/PDA and UPLC-MS/MS methods, respectively. Toxicokinetic parameters, including area under the curve and maximal mycotoxin concentration, were calculated and used to compare control and treated groups. The bio-organoclay significantly reduced urinary excretion of AFM1, ZEA, FB1 and OTA in rats. In piglets, it was significantly effective in reducing systemic exposure to AFB1 and OTA, while the reduction of ZEA and FB1 exposure was not significant. In conclusion, the high efficacy of the bio-organoclay in sequestering AFB1, ZEA, OTA and FB1 measured by isothermal adsorption studies was fully and partially confirmed by rat and piglet studies, respectively.

Published
2021

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