المؤلفون: Gagliardi, F., Nardone, V., Grassi, R., Belfiore, M., Roccatagliata, P., Buono, M., Cimmino, G., Della Corte, C.M., Morgillo, F., Ciardiello, F., Reginelli, A., Cappabianca, S.

المصدر: ESMO Open ; volume 9, page 102737 ; ISSN 2059-7029

مصطلحات موضوعية: Cancer Research, Oncology

الإتاحة: https://doi.org/10.1016/j.esmoop.2024.102737Test
https://api.elsevier.com/content/article/PII:S2059702924005052?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2059702924005052?httpAccept=text/plainTest

المؤلفون: Comes, Maria Colomba, Fanizzi, Annarita, Bove, Samantha, Didonna, Vittorio, Diotiaiuti, Sergio, Fadda, Federico, La Forgia, Daniele, Giotta, Francesco, Latorre, Agnese, Nardone, Annalisa, Palmiotti, Gennaro, Ressa, Cosmo Maurizio, Rinaldi, Lucia, Rizzo, Alessandro, Talienti, Tiziana, Tamborra, Pasquale, Zito, Alfredo, Lorusso, Vito, Massafra, Raffaella

المساهمون: Ministero della Salute

المصدر: Computers in Biology and Medicine ; volume 172, page 108132 ; ISSN 0010-4825

مصطلحات موضوعية: Health Informatics, Computer Science Applications

الإتاحة: https://doi.org/10.1016/j.compbiomed.2024.108132Test
https://api.elsevier.com/content/article/PII:S0010482524002166?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0010482524002166?httpAccept=text/plainTest

المؤلفون: Moro, Francesca, Ianieri, Manuel Maria, De Cicco Nardone, Alessandra, Carfagna, Pietro, Mascilini, Floriana, Vizzielli, Giuseppe, Biasioli, Anna, Pontrelli, Giovanni, Virgilio, Bruna Anna, Ladisa, Irene, Carlea, Annunziata, Lo Turco, Alice, Beneduce, Giuliana, Arcieri, Martina, Scaglione, Giulia, Fanfani, Francesco, Scambia, Giovanni, Testa, Antonia Carla

المصدر: Reproductive BioMedicine Online ; volume 48, issue 4, page 103733 ; ISSN 1472-6483

مصطلحات موضوعية: Developmental Biology, Reproductive Medicine, Obstetrics and Gynecology

الإتاحة: https://doi.org/10.1016/j.rbmo.2023.103733Test
https://api.elsevier.com/content/article/PII:S1472648323008325?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1472648323008325?httpAccept=text/plainTest

المؤلفون: Perry, Morgan, McCall, Stephen, Nardone, Michael, Dorris, Joseph, Obbin, Samuel, Stanik, Christine

المساهمون: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services

المصدر: Journal of the American Medical Directors Association ; volume 25, issue 2, page 335-341.e4 ; ISSN 1525-8610

مصطلحات موضوعية: Health Policy, General Medicine, General Nursing, Geriatrics and Gerontology

الإتاحة: https://doi.org/10.1016/j.jamda.2023.11.019Test
https://api.elsevier.com/content/article/PII:S1525861023009817?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1525861023009817?httpAccept=text/plainTest

المؤلفون: Chen, Jiakun, Stork, Tobias, Kang, Yunsik, Nardone, Katherine A.M., Auer, Franziska, Farrell, Ryan J., Jay, Taylor R., Heo, Dongeun, Sheehan, Amy, Paton, Cameron, Nagel, Katherine I., Schoppik, David, Monk, Kelly R., Freeman, Marc R.

المساهمون: National Institutes of Health, Damon Runyon Cancer Research Foundation, Eunice Kennedy Shriver National Institute of Child Health and Human Development

المصدر: Neuron ; volume 112, issue 1, page 93-112.e10 ; ISSN 0896-6273

مصطلحات موضوعية: General Neuroscience

الإتاحة: https://doi.org/10.1016/j.neuron.2023.11.008Test
https://api.elsevier.com/content/article/PII:S0896627323008826?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0896627323008826?httpAccept=text/plainTest

المؤلفون: Iacucci, Marietta, Bonovas, Stefanos, Bazarova, Alina, Cannatelli, Rosanna, Ingram, Richard J.M., Labarile, Nunzia, Nardone, Olga Maria, Parigi, Tommaso Lorenzo, Piovani, Daniele, Siau, Keith, Smith, Samuel C.L., Zammarchi, Irene, Ferraz, Jose G.P., Fiorino, Gionata, Kiesslich, Ralph, Panaccione, Remo, Parra-Blanco, Adolfo, Principi, Mariabeatrice, Tontini, Gian Eugenio, Uraoka, Toshio, Ghosh, Subrata, Abbasi, Abdullah, Wargen, Adele, Feroz, Ahmed, Dell’Era, Alessandra, Piagnani, Alessandra, Rimondi, Alessandro, Chini, Alessia, Guarino, Alessia D., Todeschini, Alessia, Srinivasa, Amar, Sorge, Andrea, Toppeta, Angelica, Gabrielli, Anna M.C., Testa, Anna, MacLean, Anthony, Contaldo, Antonella, Churchhouse, Antonia, De Silva, Anupama, Marinoni, Beatrice, Lillo, Chiara, Andrews, Christopher N., Lentano, Ciro, Sgamato, Costantino, Gridavilla, Daniele, Noviello, Daniele, Cheung, Danny, Di Paolo, Dhanai, Novielli, Domenico, King, Dominic

المساهمون: Guts UK

المصدر: Gastrointestinal Endoscopy ; volume 99, issue 5, page 756-766.e4 ; ISSN 0016-5107

مصطلحات موضوعية: Gastroenterology, Radiology, Nuclear Medicine and imaging

الإتاحة: https://doi.org/10.1016/j.gie.2023.11.018Test
https://api.elsevier.com/content/article/PII:S0016510723030948?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0016510723030948?httpAccept=text/plainTest

المؤلفون: De Luca, Roberto, Nardone, Stefano, Grace, Kevin P, Venner, Anne, Cristofolini, Michela, Bandaru, Sathyajit S, Sohn, Lauren T, Kong, Dong, Mochizuki, Takatoshi, Viberti, Bianca, Zhu, Lin, Zito, Antonino, Scammell, Thomas E, Saper, Clifford B, Lowell, Bradford B, Fuller, Patrick M, Arrigoni, Elda

المصدر: Nature Communications. 13(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Basic Behavioral and Social Science, Behavioral and Social Science, Sleep Research, Animals, Arousal, Humans, Neurons, Orexins, Sleep, Wakefulness

الوصف: Humans and animals lacking orexin neurons exhibit daytime sleepiness, sleep attacks, and state instability. While the circuit basis by which orexin neurons contribute to consolidated wakefulness remains unclear, existing models posit that orexin neurons provide their wake-stabilizing influence by exerting excitatory tone on other brain arousal nodes. Here we show using in vivo optogenetics, in vitro optogenetic-based circuit mapping, and single-cell transcriptomics that orexin neurons also contribute to arousal maintenance through indirect inhibition of sleep-promoting neurons of the ventrolateral preoptic nucleus. Activation of this subcortical circuit rapidly drives wakefulness from sleep by differentially modulating the activity of ventrolateral preoptic neurons. We further identify and characterize a feedforward circuit through which orexin (and co-released glutamate) acts to indirectly target and inhibit sleep-promoting ventrolateral preoptic neurons to produce arousal. This revealed circuitry provides an alternate framework for understanding how orexin neurons contribute to the maintenance of consolidated wakefulness and stabilize behavioral state.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8jw3r30zTest

المؤلفون: Mikhail I. Dobrikov, Elena Y. Dobrikova, Dasean T. Nardone-White, Zachary P. McKay, Michael C. Brown, Matthias Gromeier

المصدر: mBio, Vol 14, Iss 6 (2023)

مصطلحات موضوعية: poliovirus, MDA5, interferon, IRF3, eIF4G, Microbiology, QR1-502

الوصف: ABSTRACTEnteroviruses (EVs)—positive-sense single-strand RNA viruses of Picornaviridae—are among the most common human viral pathogens. Unlike other cytoplasmic viral RNAs (vRNAs), which are detected by RIG-I, sensing of EV RNAs is mediated primarily by MDA5. EVs evolved with rapid, cytotoxic life cycles as a means of host cell interference, ostensibly to suppress MDA5-orchestrated antiviral type-I interferon (IFN) responses. At the core of this strategy are viral 2A protease (2Apro)-directed cleavage of the eukaryotic initiation factor (eIF)4G—the central translation initiation scaffold and ribosome adaptor—and degradation of nuclear pores. EV MDA5 agonism has an intriguing innate footprint, characterized by polar TBK1-IFN regulatory factor 3 (IRF3) signaling, which fuels sustained type-I IFN release to provide context for antitumor CD8+ T-cell priming after in situ cancer vaccination. Here we compared EV-host interactions between wild-type EVs and the highly attenuated recombinant polio:rhinovirus chimera and cancer immunotherapy agent (PVSRIPO) to test how targeted inhibition of discrete steps in the viral life cycle affects the innate antiviral response. Our investigations demonstrate that sustained MDA5-TBK1-IRF3 signaling elicited by PVSRIPO is the result of inefficient immediate 2Apro-directed eIF4G degradation, while wild-type EVs counter host innate type-I IFN defenses via rapid eIF4G cleavage. The MDA5-directed innate signature of profoundly attenuated EVs may provide efficient innate immune-stimulatory assets, for example, in in situ cancer vaccination strategies.IMPORTANCEMultiple pattern recognition receptors sense vRNAs and initiate downstream innate signaling: endosomal Toll-like receptors (TLRs) 3, 7, and 8 and cytoplasmic RIG-I-like receptors (RLRs) RIG-I, and MDA5. They engage distinct signaling scaffolds: mitochondrial antiviral signaling protein (RLR), MyD88, and TLR-adaptor interacting with SLC15A4 on the lysosome (TLR7 and TLR8) and toll/IL-1R domain-containing adaptor inducing IFN (TLR3). By virtue of their unusual vRNA structure and direct host cell entry path, the innate response to EVs uniquely is orchestrated by MDA5. We reported that PVSRIPO’s profound attenuation and loss of cytopathogenicity triggers MDA5-directed polar TBK1-IRF3 signaling that generates priming of polyfunctional antitumor CD8+ T-cell responses and durable antitumor surveillance in vivo. Here we unraveled EV-host relations that control suppression of host type-I IFN responses and show that PVSRIPO’s deficient immediate host eIF4G cleavage generates unopposed MDA5-directed downstream signaling cascades resulting in sustained type-I IFN release.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2150-7511Test

الوصول الحر: https://doaj.org/article/8dd642e7e9974b259b6880eaed7d2947Test

المؤلفون: Enrica Marchionni, Maria Rosaria D'Apice, Viviana Lupo, Giovanna Lattanzi, Elisabetta Mattioli, Gina Lisignoli, Elena Gabusi, Gerardo Pepe, Manuela Helmer Citterich, Elena Campione, Anna Maria Nardone, Paola Spitalieri, Noemi Pucci, Dario Cocciadiferro, Eliseo Picchi, Francesco Garaci, Antonio Novelli, Giuseppe Novelli

المصدر: Bone Reports, Vol 19, Iss , Pp 101728- (2023)

مصطلحات موضوعية: COL2A1, Type-II collagenopathies, Reverse-phenotyping, Exome sequencing, Functional characterization, Diseases of the musculoskeletal system, RC925-935

الوصف: COL2A1 gene encodes the alpha-1 chain of type-II procollagen. Heterozygous pathogenic variants are associated with the broad clinical spectrum of genetic diseases known as type-II collagenopathies. We aimed to characterize the NM_001844.5:c.1330G>A;p.Gly444Ser variant detected in the COL2A1 gene through trio-based prenatal exome sequencing in a fetus presenting a severe skeletal phenotype at 31 Gestational Weeks and in his previously undisclosed mild-affected father. Functional studies on father's cutaneous fibroblasts, along with in silico protein modeling and in vitro chondrocytes differentiation, showed intracellular accumulation of collagen-II, its localization in external Golgi vesicles and nuclear morphological alterations. Extracellular matrix showed a disorganized fibronectin network. These results showed that p.Gly444Ser variant alters procollagen molecules processing and the assembly of mature type-II collagen fibrils, according to COL2A1-chain disorganization, displayed by protein modeling. Clinical assessment at 38 y.o., through a reverse-phenotyping approach, revealed limp gait, short and stocky appearance. X-Ray and MRI showed pelvis asymmetry with severe morpho-structural alterations of the femoral heads bilaterally, consistent with a mild form of type-II collagenopathy. This study shows how the fusion of genomics and clinical expertise can drive a diagnosis supported by cellular and bioinformatics studies to effectively establish variants pathogenicity.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352187223000748Test; https://doaj.org/toc/2352-1872Test

الوصول الحر: https://doaj.org/article/7aab59cb6a3344baa1cce4c1308ebddcTest

المؤلفون: Anthony Nardone, Richard Pebody, Lorenzo Subissi, Isabel Bergeri, Aisling Vaughan, Erika Duffell, Gudrun S Freidl, Diogo Simão Lemos, M Valenciano, Eeva K Broberg, Pasi Penttinen, Maria Keramarou

المصدر: BMJ Open, Vol 13, Iss 11 (2023)

مصطلحات موضوعية: Medicine

الوصف: Objectives Systematic review of SARS-CoV-2 seroprevalence studies undertaken in the WHO European Region to measure pre-existing and cumulative seropositivity prior to the roll out of vaccination programmes.Design A systematic review of the literature.Data sources We searched MEDLINE, EMBASE and the preprint servers MedRxiv and BioRxiv in the WHO ‘COVID-19 Global literature on coronavirus disease’ database using a predefined search strategy. Articles were supplemented with unpublished WHO-supported Unity-aligned seroprevalence studies and other studies reported directly to WHO Regional Office for Europe and European Centre for Disease Prevention and Control.Eligibility criteria Studies published before the widespread implementation of COVID-19 vaccination programmes in January 2021 among the general population and blood donors, at national and regional levels.Data extraction and synthesis At least two independent researchers extracted the eligible studies; a third researcher resolved any disagreements. Study risk of bias was assessed using a quality scoring system based on sample size, sampling and testing methodologies.Results In total, 111 studies from 26 countries published or conducted between 1 January 2020 and 31 December 2020 across the WHO European Region were included. A significant heterogeneity in implementation was noted across the studies, with a paucity of studies from the east of the Region. Sixty-four (58%) studies were assessed to be of medium to high risk of bias. Overall, SARS-CoV-2 seropositivity prior to widespread community circulation was very low. National seroprevalence estimates after circulation started ranged from 0% to 51.3% (median 2.2% (IQR 0.7–5.2%); n=124), while subnational estimates ranged from 0% to 52% (median 5.8% (IQR 2.3%–12%); n=101), with the highest estimates in areas following widespread local transmission.Conclusions The low levels of SARS-CoV-2 antibody in most populations prior to the start of vaccine programmes underlines the critical importance of targeted vaccination of priority groups at risk of severe disease, while maintaining reduced levels of transmission to minimise population morbidity and mortality.

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/13/11/e064240.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/5f985260661f4f17b05d52cc72c7438eTest