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126 results on '"Fanucchi, S."'

1. A snapshot of emergency neurology management in the Lombardy Region, Italy

Author

Zanferrari, C, Salmaggi, A, Belcastro, V, Domina, E, Beretta, S, Braga, M, Bonato, S, Ghione, I, Caputi, L, Brusaferri, F, Cavallini, A, Persico, A, Ciccone, A, Silvestrelli, G, Clerici, R, De Piazza, C, Conti, G, Cotelli, M, Turla, M, Dallocchio, C, Mazza, S, Ferrarese, C, Piatti, M, Ferraro, B, Carpo, M, Fanucchi, S, Fiacco, F, Maggio, P, Frediani, F, Tonietti, S, Grampa, G, Russo, L, Savio, F, Magni, E, Palmerini, F, Magoni, M, Marcheselli, S, Corato, M, Mattioli, M, Padovani, A, Pantoni, L, Baso, G, Prelle, A, Muscia, F, Priori, A, Tancredi, L, Santilli, I, Scaccabarozzi, C, Sessa, M, Gioia, S, Zanferrari C., Salmaggi A., Belcastro V., Domina E., Beretta S., Braga M., Bonato S., Ghione I., Caputi L., Brusaferri F., Cavallini A., Persico A., Ciccone A., Silvestrelli G., Clerici R., De Piazza C., Conti G., Cotelli M. S., Turla M., Dallocchio C., Mazza S., Ferrarese C., Piatti M. L., Ferraro B., Carpo M., Fanucchi S., Fiacco F., Maggio P., Frediani F., Tonietti S., Grampa G., Russo L. L., Savio F. L., Magni E., Palmerini F., Magoni M., Marcheselli S., Corato M., Mattioli M., Padovani A., Pantoni L., Baso G., Prelle A., Muscia F., Priori A., Tancredi L., Santilli I., Scaccabarozzi C., Sessa M., Gioia S. L., Zanferrari, C, Salmaggi, A, Belcastro, V, Domina, E, Beretta, S, Braga, M, Bonato, S, Ghione, I, Caputi, L, Brusaferri, F, Cavallini, A, Persico, A, Ciccone, A, Silvestrelli, G, Clerici, R, De Piazza, C, Conti, G, Cotelli, M, Turla, M, Dallocchio, C, Mazza, S, Ferrarese, C, Piatti, M, Ferraro, B, Carpo, M, Fanucchi, S, Fiacco, F, Maggio, P, Frediani, F, Tonietti, S, Grampa, G, Russo, L, Savio, F, Magni, E, Palmerini, F, Magoni, M, Marcheselli, S, Corato, M, Mattioli, M, Padovani, A, Pantoni, L, Baso, G, Prelle, A, Muscia, F, Priori, A, Tancredi, L, Santilli, I, Scaccabarozzi, C, Sessa, M, Gioia, S, Zanferrari C., Salmaggi A., Belcastro V., Domina E., Beretta S., Braga M., Bonato S., Ghione I., Caputi L., Brusaferri F., Cavallini A., Persico A., Ciccone A., Silvestrelli G., Clerici R., De Piazza C., Conti G., Cotelli M. S., Turla M., Dallocchio C., Mazza S., Ferrarese C., Piatti M. L., Ferraro B., Carpo M., Fanucchi S., Fiacco F., Maggio P., Frediani F., Tonietti S., Grampa G., Russo L. L., Savio F. L., Magni E., Palmerini F., Magoni M., Marcheselli S., Corato M., Mattioli M., Padovani A., Pantoni L., Baso G., Prelle A., Muscia F., Priori A., Tancredi L., Santilli I., Scaccabarozzi C., Sessa M., and Gioia S. L.

Abstract

Background: The assessment of human and diagnostic resources is a prerequisite to improving the management of emergency neurology. Objective: To provide a landscape on the organization of the Lombardy Region hospitals for emergency neurological care management. Methods: We designed an anonymized questionnaire including 6 sections with 21 questions on facilities, human and diagnostic resources, and intra- and between-hospital connections. The time needed to fill the questionnaire was estimated not to exceed 6 min. Results: The questionnaire was returned by 33/41 (80.5%) hospitals, 22 classified as level 1 (spoke), and 11 as level 2 (hub). Five of 33 (15%) did not have a neurology unit. The mean annual rate of neurological consultations accounted for 5–6% of all admissions (range 2–8%) and did not differ between levels 1 and 2 hospitals. Neurologists were 24-h available in 21/33 (64%) hospitals, 12-h and on call at night in 6 (18%), less than 12 h without nocturnal availability in 5 (15%), and neither present nor available in 1 (3%). Brain CT and CSF examinations were 24-h universally available, whereas EEG and neurosonology were not in most hospitals. Despite angio-CT was 24-h available in more than 75% of the hospitals, only 45% of them had 24-h availability of diffusion/perfusion imaging, and 43% were not available at any time. Only 12% of the hospitals had 24-h availability of neuroradiologists and 6% of interventional neuroradiologists. Conclusion: Our data, while emphasizing current critical issues, offer clues for identifying priorities and improving the management of emergency and time-dependent neurological diseases.

Published
2022

2. Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa

Author

Boahen, C.K., Moorlag, S.J.C.F.M., Jensen, K.J., Matzaraki, V., Fanucchi, S., Monteiro, I., Bree, Charlotte de, Fok, E.T., Mhlanga, M.M.K., Joosten, L.A., Aaby, P., Benn, C.S., Netea, M.G., Kumar, V., Boahen, C.K., Moorlag, S.J.C.F.M., Jensen, K.J., Matzaraki, V., Fanucchi, S., Monteiro, I., Bree, Charlotte de, Fok, E.T., Mhlanga, M.M.K., Joosten, L.A., Aaby, P., Benn, C.S., Netea, M.G., and Kumar, V.

Abstract

Item does not contain fulltext

Published
2023

3. Long noncoding RNA CHROMR regulates antiviral immunity in humans

Author

Solingen, C. van, Cyr, Y., Scacalossi, K.R., Vries, Maren de, Barrett, T.J., Jong, A. de, Gourvest, M., Zhang, T., Peled, D., Kher, R., Cornwell, M., Gildea, M.A., Brown, E.J., Fanucchi, S., Mhlanga, M.M.K., Berger, J.S., Dittmann, M., Moore, K.J., Solingen, C. van, Cyr, Y., Scacalossi, K.R., Vries, Maren de, Barrett, T.J., Jong, A. de, Gourvest, M., Zhang, T., Peled, D., Kher, R., Cornwell, M., Gildea, M.A., Brown, E.J., Fanucchi, S., Mhlanga, M.M.K., Berger, J.S., Dittmann, M., and Moore, K.J.

Abstract

Contains fulltext : 284073.pdf (Publisher’s version ) (Open Access), Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.

Published
2022

5. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Divangahi, M., Aaby, P., Khader, S.A., Barreiro, L.B., Bekkering, S., Chavakis, T., Crevel, R. van, Curtis, N., DiNardo, A.R., Dominguez Andres, J., Duivenvoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K.L., Khan, N., Joosten, L.A.B., Kaufmann, E., Latz, E., Matarese, G., Meer, J.W.M. van der, Mhlanga, M.M.K., Moorlag, S.J.C.F.M., Mulder, W.J.M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N.P., Sauerwein, R.W., Sherwood, E.R., Schlitzer, A., Schultze, J.L., Sieweke, M.H., Benn, C.S., Stunnenberg, H., Sun, J, Veerdonk, F.L. van de, Weis, S., Williams, D.L., Xavier, R., Netea, M.G., Divangahi, M., Aaby, P., Khader, S.A., Barreiro, L.B., Bekkering, S., Chavakis, T., Crevel, R. van, Curtis, N., DiNardo, A.R., Dominguez Andres, J., Duivenvoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K.L., Khan, N., Joosten, L.A.B., Kaufmann, E., Latz, E., Matarese, G., Meer, J.W.M. van der, Mhlanga, M.M.K., Moorlag, S.J.C.F.M., Mulder, W.J.M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N.P., Sauerwein, R.W., Sherwood, E.R., Schlitzer, A., Schultze, J.L., Sieweke, M.H., Benn, C.S., Stunnenberg, H., Sun, J, Veerdonk, F.L. van de, Weis, S., Williams, D.L., Xavier, R., and Netea, M.G.

Abstract

Contains fulltext : 232545.pdf (Publisher’s version ) (Open Access)

Published
2021

8. Advances in understanding molecular regulation of innate immune memory

Author

Dominguez Andres, J., Fanucchi, S., Joosten, L.A.B., Mhlanga, M.M., Netea, M.G., Dominguez Andres, J., Fanucchi, S., Joosten, L.A.B., Mhlanga, M.M., and Netea, M.G.

Abstract

Contains fulltext : 220529.pdf (Publisher’s version ) (Open Access), The epigenetic and functional reprogramming of immune genes during induction of trained immunity is accompanied by the metabolic rewiring of cellular state. This memory is induced in the hematopoietic niche and propagated to daughter cells, generating epigenetically and metabolically reprogrammed innate immune cells that are greatly enhanced in their capacity to resolve inflammation. In particular, these cells show accumulation of H3K4me3 and H3K27Ac epigenetic marks on multiple immune gene promoters and associated enhancers. However, the mechanism governing how these epigenetic marks accumulate at discrete immune gene loci has been poorly understood, until now. Here, we discuss some recent advances in the regulation of trained immunity, with a particular focus on the mechanistic role of a novel class of long non-coding RNAs in the establishment of epigenetic marks on trained immune gene promoters.

Published
2020

15. The Italian multicenter observational study on post-stroke depression (DESTRO)

Author

Paolucci, S. T., Gandolfo, C., Provinciali, L., Torta, R., TOSO AND ON THE BEHALF OF THE DESTRO STUDY GROUP, V., Lagalla, THE DESTRO STUDY GROUP INCLUDES G., Manicone, M. G., Del, M., Gobbo, Paolini, S., Ancona, Bottacchi, E., Corso, G., Aosta, Federico, F., Martino, D, Bari, Salsa, F., Turinese, E., BASSANO DEL GRAPPA VI, Gentile, M., Bogo, S., Belluno, Crisci, M., Sacquegna, T., Bologna, Santamato, V., Pietrarossa, G., Carbonara, Ba, Coppola, G., Toni, V., Trianni, G., Casarano, Le, Pennisi, Giovanni, Bella, Rita, Catania, Ricci, S., Amantini, K., Città, DELLA PIEVE PG, Buzzelli, S., DI FRANCESCO, L., ANGELO PE, CITTÀ S., Antonelli, B, Pelliccia, G., Fermo, Ap, Paolino, E., Iezzi, E., Ferrara, P, Nencini, Sarti, C., Florence, Neri, W., Galletti, G., Forli, Pretta, S., Sette, Genoa, Giaccaglini, E., Sconocchini, C., Iesi, An, Carolei, A., Capannolo, C, Laquila, Musolino, R., Gangemi, S., Vita, G., DI LEO, R., Messina, Comola, M., Mammi, S., Zamperetti, M. A., Defanti, C. A., Milan, DE FALCO, F. A., Santangelo, R., Scarano, V., Naples, M. T, Giordana, Sciolla, R., Orbassano, To, Meneghetti, G., Ottina, M., Padua, Ponari, A., Castiglia, R., Palermo, Mancia, D., Zanferrari, C., Parma, Micieli, G., Zambrelli, E., Pavia, Cardaioli, G., Gallai, V., Perugia, Badino, R., Tassinari, T., PIETRA LIGURE SV, Orlandi, G., Fanucchi, S., Pisa, Ciucci, G., Padoan, G., Ravenna, Gasparini, F., Guidetti, D., Reggio, Emilia, DE ANGELIS, D., Amabile, G. A., Fiermonte, G., Rome, Roberti, C., Foti, A., Roma, Cainelli, L., Chiusole, M., Rovereto, Tn, Pasqualino, S., Intiso, D., GIOVANNI ROTONDO FG, S., Tonizzo, M., Basile, A., VITO AL, S., Tagliamento, Pn, Viviani, P., SANT ARSENIO SA, Stromillo, M. L., Federico, A, Siena, Liboni, W., Pavanelli, E., Bergamasco, B., Cerrato, P., Boghi, A, Cicolin, A., Berra, C., Turin, Zorzon, M., Tommasi, M. A., Chiodo, F., Grandi, Koscica, N., Trieste, Micoli, B., Lorio, R., Venice, Bovi, P., Trabucco, G., Verona, Consoli, D., Galati, F., and Vibo, Valentia

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Time Factors, Adolescent, Personality Inventory, Physical examination, Observation, Disability Evaluation, Quality of life, medicine, History of depression, Post-stroke depression, Humans, Psychiatry, Stroke, Depression (differential diagnoses), Aged, Retrospective Studies, Aged, 80 and over, Psychiatric Status Rating Scales, Chi-Square Distribution, medicine.diagnostic_test, Depression, Beck Depression Inventory, Retrospective cohort study, Middle Aged, medicine.disease, Neurology, Italy, Female, Neurology (clinical), Psychology
Abstract

Despite growing information, questions still surround various aspects of post-stroke depression (PSD). The Italian multicenter observational study Destro was designed to help clarify in a large sample the frequency and clinical impact of PSD. A total of 53 centers consecutively admitted 1064 patients with ischemic or hemorrhagic stroke, assessing them periodically in the first 9 months after the event. Patients with depression were followed for two years. Depression was diagnosed on clinical examination, verbal (Beck Depression Inventory) and non-verbal rating systems (Visual Analog Mood Scale), identifying the nosographic condition attributable to the mental state. The patient's clinical history, residual independence, and post-ictus quality of life were also taken into account. PSD was detected in 383 patients (36 %), most of whom had minor depression (80.17 %), with dysthymia, rather than major depression and adaptation disorder. About 80% developed depression within three months of the stroke. Cases with later onset tended to have less severe symptoms. Risk factors were a history of depression, severe disability, previous stroke and female sex, but not the type and site of the vascular lesion. PSD was not correlated with any increase in mortality or cerebrovascular recurrences, but these patients had lower autonomy and quality of life ratings. In conclusion, patients should be close observed in the first few weeks after a stroke in order to check for depression,which is more likely in those with clear risk factors and may spoil their quality of life.

Published
2006

16. The Italian multicenter observational study on post-stroke depression (DESTRO)

Author

Paolucci, S, Gandolfo, C, Provinciali, L, Torta, R, Toso, V, Lagalla, G., Manicone, M. G., Del Gobbo, M., Paolini, S., Bottacchi, E., Corso, G., Federico, F., Martino, D., Salsa, F., Turinese, E., Gentile, M., Bogo, S., Crisci, M., Sacquegna, T., Santamato, V., Pietrarossa, G., Coppola, G., Toni, V., Trianni, G., Pennisi, G., Bella, R., Ricci, S., Amantini, K., Buzzelli, S., Di Francesco, L., Antonelli, B., Pelliccia, G., Paolino, E., Iezzi, E., Nencini, P., Sarti, C., Neri, W., Galletti, G., Pretta, S., Del Sette, M., Giaccaglini, E., Sconocchini, C., Carolei, A., Capannolo, C., Musolino, Rosa Fortunata, Gangemi, S., Vita, Giuseppe, Di Leo, R., Comola, M., Mammi, S., Zamperetti, M. A., Defanti, C. A., De Falco, F. A., Santangelo, R., Scarano, . V., Giordana, M. T., Sciolla, R., Meneghetti, G., Ottina, M., Ponari, A., Castiglia, R., Mancia, D., Zanferrari, C., Micieli, G., Zambrelli, E., Cardaioli, G., Gallai, . V., Badino, R., Tassinari, T., Orlandi, G., Fanucchi, S., Ciucci, G., Padoan, G., Gasparini, F., Guidetti, D., De Angelis, D., Amabile, G. A., Fiermonte, G., Roberti, C., Foti, A., Cainelli, L., Chiusole, M., Pasqualino, S., Intiso, D., Tonizzo, M., Basile, A., Viviani, P., Stromillo, M. L., Federico, A., Liboni, W., Pavanelli, E., Bergamasco, B., Cerrato, P., Boghi, A., Cicolin, A., Berra, C., Zorzon, M., Tommasi, M. A., Chiodo Grandi, F., Koscica, N., Micoli, B., Lorio, R., Bovi, P., Trabucco, G., Consoli, D., Galati, F., Bortolon, F., Morra, M., Crespi, . V., and Braga, M.

Published
2006

18. Quantification of the risk of post-stroke depression: the Italian multicenter observational study (DESTRO)

Author

Paolucci, S, Gandolfo, C, Provinciali, L, Torta, R, Sommacal, S, Toso, V, Lagalla, G., Manicone, M. G., Del Gobbo, M., Paolini, S., Bottacchi, E., Corso, G., Federico, F., Martino, D., Salsa, F., Turinese, E., Gentile, M., Bogo, S., Crisci, M., Sacquegna, T., Santamato, V., Pietrarossa, G., Coppola, G., Toni, V., Trianni, G., Pennisi, G., Bella, R., Ricci, S., Amantini, K., Buzzelli, S., Di Francesco, L., Antonelli, B., Pelliccia, G., Paolino, E., Iezzi, E., Nencini, P., Sarti, C., Neri, W., Galletti, G., Pretta, S., Del Sette, M., Giaccaglini, E., Sconocchini, C., Carolei, A., Capannolo, C., Musolino, Rosa Fortunata, Gangemi, S., Vita, Giuseppe, Di Leo, R., Comola, M., Mammi, S., Zamperetti, M. A., Defanti, C. A., Grassivaro, N., Rudelli, G., De Falco, F. A., Santangelo, R., Scarano, V., Giordana, M. T., Sciolla, R., Meneghetti, G., Ottina, M., Ponari, A., Castiglia, R., Mancia, D., Zanferrari, C., Micieli, G., Zambrelli, E., Cardaioli, G., Gallai, V., Badino, R., Tassinari, T., Orlandi, G., Fanucchi, S., Ciucci, G., Padoan, G., Gasparini, F., Guidetti, D., De Angelis, D., Amabile, G. A., Roberti, G. Fiermonte C., Foti, A., Cainelli, L., Chiusole, M., Pasqualino, S., Intiso, D., Tonizzo, M., Basile, A., Viviani, P., Stromillo, M. L., Federico, A., Liboni, W., Pavanelli, E., Bergamasco, B., Cerrato, P., Boghi, A., Cicolin, A., Berra, C., Zorzon, M., Tommasi, M. A., Chiodo Grandi, F., Koscica, N., Micoli, B., Lorio, R., Bovi, P., Trabucco, G., Consoli, D., Galati, F., Bortolon, F., Morra, M., Crespi, V., and Braga, M.

Published
2005

19. Quantification of the risk of post stroke depression : the Italian multicenter observational study DESTRO

Author

Paolucci, S., Gandolfo, C., Provinciali, L., Torta, R., SOMMACAL ON BEHALF OF, S., DESTRO STUDY GROUP AND, Lagalla, V. TOSOPARTICIPANTS IN THE DESTRO STUDY INCLUDE G., M. G, Manicone, DEL GOBBO, M., Paolini, S., Ancona, Bottacchi, E., Corso, G., Aosta, Federico, F., Martino, D., Bari, Salsa, F., Turinese, E, BASSANO DEL GRAPPA VI, Gentile, M., Bogo, S., Belluno, Crisci, M., Sacquegna, T., Bologna, Santamato, V., Pietrarossa, G, Carbonara, Ba, Coppola, G., Toni, V., Trianni, G, Casarano, Le, Pennisi, Giovanni, Bella, Rita, Catania, S, Ricci, Amantini, K., CITTA DELLA PIEVE PG, Buzzelli, S., Di, L., Francesco, ANGELO PE, CITTA S., Antonelli, B., Pelliccia, G., Fermo, Ap, Paolino, E., Iezzi, E., Ferrara, Nencini, P., Sarti, C., Florence, Neri, W., Galletti, G., Forli, Pretta, S., DEL SETTE, M., Genoa, Giaccaglini, E., Sconocchini, C., Iesi, An, Carolei, A., Capannolo, C., Laquila, Musolino, R., Gangemi, S., Vita, G., DI LEO, R., Messina, Comola, M., Mammi, S., Zamperetti, M. A., Defanti, C. A., Grassivaro, N., Rudelli, G., Milan, F. A., De, Falco, Santangelo, R., Scarano, V., Naples, M. T, Giordana, Sciolla, R., Orbassano, To, Meneghetti, G., Ottina, M, Padua, Ponari, A., Castiglia, R., Palermo, Mancia, D., Zanferrari, C, Parma, Micieli, G., Zambrelli, E., Pavia, Cardaioli, G., Gallai, V., Perugia, Badino, R., Tassinari, T., Pietra, Ligure, Orlandi, G., Fanucchi, S., Pisa, Ciucci, G., Padoan, G., Ravenna, Gasparini, F., Guidetti, D., Reggio, Emilia, De, D., Angelis, Amabile, G. A., FIERMONTE ROME, G., Roberti, C., Foti, A, Roma, Cainelli, L., Chiusole, M., Rovereto, Tn, Pasqualino, S, Intiso, D., GIOVANNI ROTONDO FG, S., Tonizzo, M., Basile, A., VITO AL TAGLIAMENTO PN, S., Viviani, P., Santarsenio, Sa, Stromillo, M. L., Federico, A., Siena, W, Liboni, Pavanelli, E., Bergamasco, B., Cerrato, P., Boghi, A., Cicolin, A, Berra, C., Turin, Zorzon, M., Tommasi, M. A., F, Chiodo, Grandi, Koscica, N., Trieste, Micoli, B., Lorio, R., Venice, Bovi, P., Trabucco, G., Verona, Consoli, D., Galati, F., Vibo, Valentia, Bortolon, F., Morra, M., Vicenza, and Crespi, V.

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, Adolescent, Sex Factors, Risk Factors, mental disorders, medicine, Humans, Disabled Persons, Risk factor, Stroke, Depression (differential diagnoses), Aged, Aged, 80 and over, Psychiatric Status Rating Scales, Depression, business.industry, Beck Depression Inventory, Middle Aged, medicine.disease, Psychiatry and Mental health, Mood, Italy, Relative risk, Physical therapy, Female, Observational study, business, Follow-Up Studies
Abstract

Objective: The Italian multicenter observational study depression in stroke (DESTRO) aimed to identify risk factors for poststroke depression (PSD) and quantify the likelihood of it arising in various categories of patients. Method: Mood evaluation was performed in 1064 consecutive stroke patients by means of Beck Depression Inventory and Visual Analog Mood Scale. Depressive symptoms were classified using the DSM-IV and revised WHO criteria for depression in the course of a neurological disorder. Results: Poststroke depression was seen in 36% of the survivors, with dysthymia by far the predominant form (80.7%). Female sex, disability, previous cerebrovascular or depressive episodes were significantly associated with an increased risk of depression. Combinations of these factors raised the risk of PSD exponentially, from 24.3 to 89.1%. The site of the stroke did not come into the uni- or multivariate analysis. Conclusion.: At admission, it is possible to predict the likelihood of PSD and quantify the relative risk.

Published
2005

20. Post-stroke depression: research methodology of a large multicentre observational study (DESTRO)

Author

Toso, V, Gandolfo, C, Paolucci, S, Provinciali, L, Torta, R, Grassivaro, N, Lagalla, G., Manicone, M. G., Del Gobbo, M., Paolini, S., Bottacchi, E., Corso, G., Federico, F., Martino, D., Salsa, F., Turinese, E., Gentile, M., Bogo, S., Crisci, M., Sacquegna, T., Santamato, V., Pietrarossa, G., Coppola, G., Pennisi, G. T. r. i. a. n. n. i. G., Bella, R., Ricci, S., Amantini, K., Buzzelli, S., Di Francesco, L., Antonelli, B., Pelliccia, G., Paolino, E., Iezzi, E., Nencini, P., Sarti, C., Neri, W., Galletti, G., Pretta, S., Del Sette, M., Giaccaglini, E., Sconocchini, C., Carolei, A., Capannolo, C., De Falco, F. A., Santangelo, R., Musolino, Rosa Fortunata, Gangemi, S., Vita, Giuseppe, Di Leo, R., Comola, M., Mammi, S., Zamperetti, M. A., Defanti, C. A., Sommacal, S., Rudelli, G., Scarano, V., Giordana, M. T., Sciolla, R., Meneghetti, G., Ottina, M., Ponari, A., Castiglia, R., Mancia, D., Zanferrari, C., Micieli, G., Zambrelli, E., Cardaioli, G., Gallai, V., Badino, R., Tassinari, T., Orlandi, G., Fanucchi, S., Ciucci, G., Padoan, G., Gasparini, F., Guidetti, D., De Angelis, D., Amabile, G. A., Fiermonte, G., Roberti, C., Foti, A., Cainelli, L., Chiusole, M., Viviani, P., Stromillo, M. L., Federico, A., Liboni, W., Pavanelli, E., Bergamasco, B., Cerrato, P., Boghi, A., Cicolin, A., Berra, C., Zorzon, M., Tommasi, M. A., Chiodo Grandi, F., Koscica, N., Micoli, B., Lorio, R., Bovi, P., Trabucco, G., Consoli, D., Galati, F., Bortolon, F., Morra, M., Crespi, V., and Braga, M.

Published
2004

41. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Boris Novakovic, Andreas Schlitzer, Giuseppe Matarese, Zahi A. Fayad, Willem J. M. Mulder, Henk Stunnenberg, Andrew R. DiNardo, Niels P. Riksen, Joachim L. Schultze, Christine Stabell Benn, Joseph C. Sun, Eva Kaufmann, Shabaana A. Khader, Michael H. Sieweke, Siroon Bekkering, Stephanie Fanucchi, Luis B. Barreiro, Maziar Divangahi, Mihai G. Netea, Reinout van Crevel, Jordi Ochando, Peter Aaby, Shruti Naik, Leo A. B. Joosten, Triantafyllos Chavakis, Musa M. Mhlanga, Eicke Latz, David L. Williams, Jos W. M. van der Meer, Luke A. J. O'Neill, Ramnik J. Xavier, Nigel Curtis, Robert W. Sauerwein, Kate L. Jeffrey, Edward R. Sherwood, Elaine Fuchs, Sebastian Weis, Nargis Khan, Melanie Hamon, Raphael Duivenwoorden, Keiko Ozato, Simone J.C.F.M. Moorlag, Jorge Domínguez-Andrés, Frank L. van de Veerdonk, Precision Medicine, ICMS Core, McGill University Health Center [Montreal] (MUHC), Bandim Health Project, International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH Network), Washington University in Saint Louis (WUSTL), The University of Chicago Medicine [Chicago], Radboud University Medical Center [Nijmegen], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Melbourne, Baylor College of Medicine (BCM), Baylor University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Eindhoven University of Technology [Eindhoven] (TU/e), University of Cape Town, Rockefeller University [New York], Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), Harvard Medical School [Boston] (HMS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Trinity Biomedical Sciences Institute, School of Biochemistry & Immunology, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Universität Bonn = University of Bonn, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology Center, and Center for Regenerative Therapies Dresden (CRTD), Max Delbrück Centrum für Molekulare Medizin (MDC), University of Southern Denmark (SDU), Radboud University [Nijmegen], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Jena University Hospital [Jena], East Tennessee State University (ETSU), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts Institute of Technology (MIT), Divangahi, M., Aaby, P., Khader, S. A., Barreiro, L. B., Bekkering, S., Chavakis, T., van Crevel, R., Curtis, N., Dinardo, A. R., Dominguez-Andres, J., Duivenwoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K. L., Khan, N., Joosten, L. A. B., Kaufmann, E., Latz, E., Matarese, G., van der Meer, J. W. M., Mhlanga, M., Moorlag, S. J. C. F. M., Mulder, W. J. M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N. P., Sauerwein, R., Sherwood, E. R., Schlitzer, A., Schultze, J. L., Sieweke, M. H., Benn, C. S., Stunnenberg, H., Sun, J., van de Veerdonk, F. L., Weis, S., Williams, D. L., Xavier, R., Netea, M. G., Institut Pasteur [Paris], Consiglio Nazionale delle Ricerche (CNR), University of Bonn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, Radboud university [Nijmegen], Hamon, Melanie, and ACS - Atherosclerosis & ischemic syndromes

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], animal diseases, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Priming (immunology), Adaptive Immunity, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, ComputingMilieux_MISCELLANEOUS, immunology [BCG Vaccine], Vaccination, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Cell Differentiation, Common framework, [SDV] Life Sciences [q-bio], MESH: BCG Vaccine, BCG Vaccine, MESH: Immunologic Memory, MESH: Immunity, Innate, MESH: Cell Differentiation, MESH: Immune Tolerance, Immunology, education, immunology [Adaptive Immunity], chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, Immunity, Immune Tolerance, Animals, Humans, ddc:610, Molecular Biology, MESH: Humans, immunology [Immune Tolerance], Cell Biology, MESH: Vaccination, biochemical phenomena, metabolism, and nutrition, Immunity, Innate, immunology [Immunologic Memory], immunology [Immunity, Innate], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030104 developmental biology, bacteria, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Neuroscience, Immunologic Memory, MESH: Adaptive Immunity, 030215 immunology
Abstract

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Published
2021

42. Unraveling the interplay between the leucine zipper and forkhead domains of FOXP2: Implications for DNA binding, stability and dynamics.

Author

Perumal CM, Thulo M, Buthelezi S, Naicker P, Stoychev S, Lakhi A, and Fanucchi S

Subjects
Humans, Protein Multimerization, Protein Stability, Binding Sites, Protein Domains, Models, Molecular, Protein Interaction Domains and Motifs, Forkhead Transcription Factors chemistry, Forkhead Transcription Factors metabolism, Forkhead Transcription Factors genetics, Leucine Zippers, Protein Binding, DNA metabolism, DNA chemistry
Abstract

FOXP2 is a transcription factor associated with speech and language. Like other FOX transcription factors, it has a DNA binding region called the forkhead domain (FHD). This domain can exist as a monomer or a domain swapped dimer. In addition to the FHD, the leucine zipper region (LZ) of FOXP2 is also believed to be associated with both DNA binding and oligomerization. To better understand the relationship between DNA binding and oligomerization of FOXP2, we investigated its structure, stability and dynamics, focusing specifically on the FHD and the LZ. We did this by using two constructs: one containing the isolated FHD and one containing both the LZ and the FHD (LZ-END). We demonstrate in this work, that while the FHD maintains a monomeric form that is capable of binding DNA, the LZ-END undergoes a dynamic transition between oligomeric states in the presence of DNA. Our findings suggest that FOXP2's LZ domain influences DNA binding affinity through a change in oligomeric state. We show through hydrogen exchange mass spectroscopy that certain parts of the FHD and interlinking region become less dynamic when in the presence of DNA, confirming DNA binding and oligomerization in these regions. Moreover, the detection of a stable equilibrium intermediate state during LZ-END unfolding supports the idea of cooperation between these two domains. Overall, our study sheds light on the interplay between two FOXP2 domains, providing insight into the protein's ability to respond dynamically to DNA, and enriching our understanding of FOXP2's role in gene regulation., (© 2024 The Author(s). Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

Published
2024
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43. Identification and characterisation of a novel interaction between oestrogen receptor alpha and FOXP2.

Author

Lakhi A and Fanucchi S

Subjects
Humans, Protein Domains, DNA metabolism, Forkhead Transcription Factors metabolism, Forkhead Transcription Factors genetics, Estrogen Receptor alpha metabolism, Estrogen Receptor alpha genetics, Estrogen Receptor alpha chemistry, Protein Binding
Abstract

Forkhead box P2 (FOXP2) regulates expression of various genes and is associated with language, speech and neural development as well as cancer. Since there may be a putative link between sex and language and because transcription factors rarely function in isolation, this study aims to investigate whether FOXP2 directly associates with oestrogen receptor α (ER1), a nuclear receptor responsible for sexual differentiation that is also associated with cancer. Isothermal titration calorimetry and fluorescence anisotropy were used to investigate the interaction between the DNA-binding forkhead domain (FHD) of FOXP2, the N-terminal region (NT) of FOXP2, and the ligand-binding domain (LBD) of ER1. ER1 LBD does not interact with FOXP2 NT but associates with apo-FOXP2 FHD in an enthalpically favourable manner. The affinity of this interaction is inversely correlated to the salt concentration. Additionally, FOXP2 FHD that is bound to ER1 LBD, has reduced ability to interact with its cognate DNA. This research identifies a novel interaction between ER1 LBD and FOXP2 FHD and shows that the interaction is regulated by salt. Moreover, FOXP2 FHD cannot bind to both ER1 LBD and DNA simultaneously, suggesting that this interaction could be involved in regulating the transcriptional pathway of FOXP2 should the interaction be found in vivo. This study could serve as a foundation for uncovering the basis of sexual dimorphism in speech and language development and related disorders and potentially offers an alternate for targeted cancer therapies., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Published
2024
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44. A chromatin-regulated biphasic circuit coordinates IL-1β-mediated inflammation.

Author

Fok ET, Moorlag SJCFM, Negishi Y, Groh LA, Dos Santos JC, Gräwe C, Monge VV, Craenmehr DDD, van Roosmalen M, da Cunha Jolvino DP, Migliorini LB, Neto AS, Severino P, Vermeulen M, Joosten LAB, Netea MG, Fanucchi S, and Mhlanga MM

Subjects
Humans, Interleukin-1beta genetics, Interleukin-1beta metabolism, Interleukin-1beta pharmacology, Cytokines, Anti-Inflammatory Agents, Interleukin-1 metabolism, Chromatin genetics, Inflammation genetics, Inflammation metabolism
Abstract

Inflammation is characterized by a biphasic cycle consisting initially of a proinflammatory phase that is subsequently resolved by anti-inflammatory processes. Interleukin-1β (IL-1β) is a master regulator of proinflammation and is encoded within the same topologically associating domain (TAD) as IL-37, which is an anti-inflammatory cytokine that opposes the function of IL-1β. Within this TAD, we identified a long noncoding RNA called AMANZI, which negatively regulates IL-1β expression and trained immunity through the induction of IL37 transcription. We found that the activation of IL37 occurs through the formation of a dynamic long-range chromatin contact that leads to the temporal delay of anti-inflammatory responses. The common variant rs16944 present in AMANZI augments this regulatory circuit, predisposing individuals to enhanced proinflammation or immunosuppression. Our work illuminates a chromatin-mediated biphasic circuit coordinating expression of IL-1β and IL-37, thereby regulating two functionally opposed states of inflammation from within a single TAD., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2024
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45. Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1.

Author

Donald H, Blane A, Buthelezi S, Naicker P, Stoychev S, Majakwara J, and Fanucchi S

Subjects
YY1 Transcription Factor genetics, YY1 Transcription Factor metabolism, DNA metabolism, Gene Expression Regulation, Intrinsically Disordered Proteins genetics, Intrinsically Disordered Proteins metabolism
Abstract

YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These structural changes may alter its DNA binding ability and hence its transcriptional activity. Just as YY1's oligomeric state can impact its role in transcription, so does its interaction with other proteins such as FOXP2. The aim of this work is to study the structure and dynamics of YY1 so as to determine the influence of oligomerisation and associations with FOXP2 on its DNA binding mechanism. The results confirm that YY1 is primarily a disordered protein, but it does consist of certain specific structured regions. We observed that YY1 quaternary structure is a heterogenous mixture of oligomers, the overall size of which is dependent on ionic strength. Both YY1 oligomerisation and its dynamic behaviour are further subject to changes upon DNA binding, whereby increases in DNA concentration result in a decrease in the size of YY1 oligomers. YY1 and the FOXP2 forkhead domain were found to interact with each other both in isolation and in the presence of YY1-specific DNA. The heterogeneous, dynamic multimerisation of YY1 identified in this work is, therefore likely to be important for its ability to make heterologous associations with other proteins such as FOXP2. The interactions that YY1 makes with itself, FOXP2 and DNA form part of an intricate mechanism of transcriptional regulation by YY1, which is vital for appropriate neural development., (© 2023 The Author(s).)

Published
2023
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46. Genetic regulators of cytokine responses upon BCG vaccination in children from West Africa.

Author

Boahen CK, Moorlag SJCFM, Jensen KJ, Matzaraki V, Fanucchi S, Monteiro I, de Bree C, Fok ET, Mhlanga M, Joosten LAB, Aaby P, Benn CS, Netea MG, and Kumar V

Subjects
Infant, Newborn, Infant, Humans, Child, Africa, Western, Vaccination, BCG Vaccine genetics, Cytokines genetics
Abstract

Genetic variation is a key factor influencing cytokine production capacity, but which genetic loci regulate cytokine production before and after vaccination, particularly in African population is unknown. Here, we aimed to identify single-nucleotide polymorphisms (SNPs) controlling cytokine responses after microbial stimulation in infants of West-African ancestry, comprising of low-birth-weight neonates randomized to bacillus Calmette-Guérin (BCG) vaccine-at-birth or to the usual delayed BCG. Genome-wide cytokine cytokine quantitative trait loci (cQTL) mapping revealed 12 independent loci, of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed. Furthermore, nine distinct cQTLs were found among infants randomized to BCG. Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination. We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals. These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations., Competing Interests: Conflict of interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2023
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47. The Unusual Architecture of RNA-Dependent RNA Polymerase (RdRp)'s Catalytic Chamber Provides a Potential Strategy for Combination Therapy against COVID-19.

Author

Metwally K, Abo-Dya NE, Alahmdi MI, Albalawi MZ, Yahya G, Aljoundi A, Salifu EY, Elamin G, Ibrahim MAA, Sayed Y, Fanucchi S, and Soliman MES

Subjects
Humans, RNA-Dependent RNA Polymerase metabolism, SARS-CoV-2 metabolism, RNA, Viral, Suramin, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Antiviral Agents chemistry, Molecular Docking Simulation, COVID-19
Abstract

The unusual and interesting architecture of the catalytic chamber of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) was recently explored using Cryogenic Electron Microscopy (Cryo-EM), which revealed the presence of two distinctive binding cavities within the catalytic chamber. In this report, first, we mapped out and fully characterized the variations between the two binding sites, BS1 and BS2, for significant differences in their amino acid architecture, size, volume, and hydrophobicity. This was followed by investigating the preferential binding of eight antiviral agents to each of the two binding sites, BS1 and BS2, to understand the fundamental factors that govern the preferential binding of each drug to each binding site. Results showed that, in general, hydrophobic drugs, such as remdesivir and sofosbuvir, bind better to both binding sites than relatively less hydrophobic drugs, such as alovudine, molnupiravir, zidovudine, favilavir, and ribavirin. However, suramin, which is a highly hydrophobic drug, unexpectedly showed overall weaker binding affinities in both binding sites when compared to other drugs. This unexpected observation may be attributed to its high binding solvation energy, which disfavors overall binding of suramin in both binding sites. On the other hand, hydrophobic drugs displayed higher binding affinities towards BS1 due to its higher hydrophobic architecture when compared to BS2, while less hydrophobic drugs did not show a significant difference in binding affinities in both binding sites. Analysis of binding energy contributions revealed that the most favorable components are the ΔE ele , ΔE vdw , and ΔG gas , whereas ΔG sol was unfavorable. The ΔE ele and ΔG gas for hydrophobic drugs were enough to balance the unfavorable ΔG sol , leaving the ΔE vdw to be the most determining factor of the total binding energy. The information presented in this report will provide guidelines for tailoring SARS-CoV-2 inhibitors with enhanced binding profiles.

Published
2023
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48. Long noncoding RNA CHROMR regulates antiviral immunity in humans.

Author

van Solingen C, Cyr Y, Scacalossi KR, de Vries M, Barrett TJ, de Jong A, Gourvest M, Zhang T, Peled D, Kher R, Cornwell M, Gildea MA, Brown EJ, Fanucchi S, Mhlanga MM, Berger JS, Dittmann M, and Moore KJ

Subjects
Humans, Interferon Regulatory Factors genetics, Interferon Regulatory Factors metabolism, COVID-19 genetics, COVID-19 immunology, DNA-Binding Proteins metabolism, Immunity, Innate genetics, Influenza A virus immunology, Influenza, Human genetics, Influenza, Human immunology, RNA, Long Noncoding genetics, RNA, Long Noncoding physiology, SARS-CoV-2 immunology, Transcription Factors metabolism
Abstract

Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.

Published
2022
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49. Focal Cerebral Arteriopathy in a Young Adult Following SARS-CoV2 Reinfection.

Author

Zanferrari C, Fanucchi S, Sollazzo MT, Ranieri M, Volterra D, and Valvassori L

Subjects
Adult, COVID-19 diagnosis, COVID-19 virology, Cerebral Angiography, Cerebral Arterial Diseases diagnostic imaging, Cerebral Arterial Diseases drug therapy, Diffusion Magnetic Resonance Imaging, Dual Anti-Platelet Therapy, Female, Humans, Ischemic Stroke diagnostic imaging, Ischemic Stroke drug therapy, Magnetic Resonance Angiography, Platelet Aggregation Inhibitors administration & dosage, Tomography, X-Ray Computed, Treatment Outcome, COVID-19 complications, Cerebral Arterial Diseases etiology, Ischemic Stroke etiology, Reinfection
Abstract

Ten days after SARS-Cov2 reinfection with mild gastrointestinal symptoms and headache that occurred 2 months after an initial infection, a previously healthy 37-year-old woman developed fluctuating facial and upper limb paresthesia and weakness. Diffusion-weighted magnetic resonance imaging revealed ischemic lesions in the right parietal region of different stages within the same vascular territory. A cerebral angiography demonstrated an isolated focal arteriopathy with no other arterial involvement. Focal cerebral arteriopathy is exceedingly rare among adults and most commonly triggered by varicella-zoster virus reactivation. We present a case of focal cerebral arteriopathy in a patient with a recent reinfection with SARS-CoV-2., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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50. Author Correction: Trained immunity, tolerance, priming and differentiation: distinct immunological processes.

Author

Divangahi M, Aaby P, Khader SA, Barreiro LB, Bekkering S, Chavakis T, van Crevel R, Curtis N, DiNardo AR, Dominguez-Andres J, Duivenvoorden R, Fanucchi S, Fayad Z, Fuchs E, Hamon M, Jeffrey KL, Khan N, Joosten LAB, Kaufmann E, Latz E, Matarese G, van der Meer JWM, Mhlanga M, Moorlag SJCFM, Mulder WJM, Naik S, Novakovic B, O'Neill L, Ochando J, Ozato K, Riksen NP, Sauerwein R, Sherwood ER, Schlitzer A, Schultze JL, Sieweke MH, Benn CS, Stunnenberg H, Sun J, van de Veerdonk FL, Weis S, Williams DL, Xavier R, and Netea MG

Published
2021
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