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2. Caught in the act: Excited-state Proton Transfer to the solvent followed in real time by non-linear THz spectroscopy

Author

Hoberg, C, Ockelmann, T, Shee, J, Balzerowski, P, DasMahanta, D, Novelli, F, Head-Gordon, M, and Havenith, M

Subjects
Bioengineering
Abstract

We have investigated the solvent response after photoexcitation using Optical Pump THz Probe (OPTP) spectroscopy with sub-ps time resolution in combination with quantum-chemical modeling. Excited State Proton Transfer (ESPT) is found to be facilitated by excitation of an intermolecular stretch (Hpyranine-Owater) triggered by an instantaneous (< 100 fs) redistribution of charge density. Initiation of proton transfer is observed on a time scale of 0.4 ps, i.e. on a much shorter time scale than anticipated before. Our results demonstrate the exceptional sensitivity of OPTP, which enables us to follow the proton motion into the hydrogen bond network of water exploring charge transport in transient solvent configurations in real time.

Published
2020

3. Liquid crystal wave plate operating close to 18 THz

Author

Novelli, F., Friebel, P., Murillo-Sanchez, M. L., (0000-0002-3431-6666) Klopf, J. M., Cattaneo, L., Novelli, F., Friebel, P., Murillo-Sanchez, M. L., (0000-0002-3431-6666) Klopf, J. M., and Cattaneo, L.

Abstract

Controlling the properties of mid- and far-infrared radiation can provide a means to transiently alter the properties of materials for novel applications. However, a limited number of optical elements are available to control its polarization state. Here we show that a 15-µm thick liquid crystal cell containing 8CB (4-octyl-4′-cyanobiphenyl) in the ordered, smectic A phase can be used as a phase retarder or wave plate. This was tested using the bright, short-pulsed (∼1 ps) radiation centered at 16.5 µm (18.15 THz) that is emitted by a free electron laser at high repetition rate (13 MHz). These results demonstrate a possible tool for the exploration of the mid- and far-infrared range and could be used to develop novel metamaterials or extend multidimensional spectroscopy to this portion of the electromagnetic spectrum.

Published
2024

8. RItA: The Italian severe/uncontrolled asthma registry

Author

Maio, S., Baldacci, S., Bresciani, M., Simoni, M., Latorre, M., Murgia, N., Spinozzi, F., Braschi, M., Antonicelli, L., Brunetto, B., Iacovacci, P., Roazzi, P., Pini, C., Pata, M., La Grasta, L., Paggiaro, P., Viegi, G., Angino, A., Carrozzi, L., Cerrai, S., Di Pede, F., Martini, F., Pala, A.P., Pistelli, F., Sarno, G., Silvi, P., Novelli, F., Ferri, M., Bonifazi, F., and Viegi, G.

Published
2018
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10. Persistence of both reversible airway obstruction and higher blood eosinophils may predict lung function decline in severe asthma

Author

Sposato B., Scalese M., Ricci A., Rogliani P., Paggiaro P., Migliorini M. G., Di Tomassi M., Olivieri C., Perrella A., Camiciottoli G., Maselli R., Pelaia G., Busceti M. T., Sabato E., Cagnazzo M. G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M. F., Berra A., Calabrese C., Stanziola A. A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E. A., Scibilia G., Vianello A., Marchi M. R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Scichilone N., Novelli F., Latorre M., Vergura L., Masieri S., Rosati Y., Milanese M., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G. E., Foschino Barbaro M. P., Sposato B., Scalese M., Ricci A., Rogliani P., Paggiaro P., Migliorini M.G., Di Tomassi M., Olivieri C., Perrella A., Camiciottoli G., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M.F., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E.A., Scibilia G., Vianello A., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Scichilone N., Novelli F., Latorre M., Vergura L., Masieri S., Rosati Y., Milanese M., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G.E., Foschino Barbaro M.P., Sposato, B., Scalese, M., Ricci, A., Rogliani, P., Paggiaro, P., Migliorini, M. G., Di Tomassi, M., Olivieri, C., Perrella, A., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Novelli, F., Latorre, M., Vergura, L., Masieri, S., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulera, N., Carpagnano, G. E., Foschino Barbaro, M. P., and Et, Al

Subjects
Pulmonary and Respiratory Medicine, severe asthma, medicine.medical_specialty, medicine.drug_class, Severe asthma, Eosinophil, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Gastroenterology, Persistence (computer science), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Bronchodilator, allergic asthma, blood eosinophil, bronchodilator reversibility, lung function decline, severe asthma, salbutamol, Forced Expiratory Volume, medicine, Settore MED/10, Immunology and Allergy, Humans, 030212 general & internal medicine, Blood eosinophil, Lung, Genetics (clinical), Lung function, Bronchodilator Agent, allergic asthma, blood eosinophil, bronchodilator reversibility, lung function decline, salbutamol, bronchodilator agents, eosinophils, forced expiratory volume, humans, lung, airway obstruction, asthma, business.industry, Airway obstruction, medicine.disease, Asthma, Bronchodilator Agents, Airway Obstruction, Eosinophils, 030228 respiratory system, Salbutamol, Blood eosinophils, business, medicine.drug, Human
Abstract

Objective: This study analysed whether the persistence of both reversible airway obstruction (RAO) and elevated BE counts was associated to reduced asthma control and accelerated lung function decline in treated severe asthmatics. Methods: About 202 severe asthmatics were studied after 12–120months of step-5 treatment associated to anti-IgE therapy. Following treatments, reversibility tests, after inhaling 400 mcg of Salbutamol, were performed. FEV1>12% or ≤12% changes differentiated RAO+ from RAO− subjects. Blood eosinophil (BE) counts after treatment were considered. Results: Pre-/post-treatment bronchodilator FEV1% and ACT were lower (61% [50–71], 74.4% [62.5–83.7] and 20[18–22]), whereas BE were higher (380 cells/µl [170–590]) in RAO+ compared to RAO− subjects (77% [64–88], p=0.0001, 81.8% [66.1–94.3], p=0.0001, 21[18–23], p=0.045 and 230 cells/µl [80–360], p=0.003). A negative relationship between SABA-induced FEV1% changes and pre-bronchodilator FEV1% (β=−0.551%; p=0.0001) and ACT (β=−0.059; p=0.038) was found. Conversely, post-treatment BE levels were positively related (β=145.565 cells/µl; p=0.003) to FEV1>12% increases. A rising trend of pre-/post-bronchodilator FEV1% in time was observed in RAO− subjects with BE300 cells/µl reaching lower values after more than 36months of step-5 treatment (59.6% [39.9–72.1] vs 74[66.5–89.2] of RAO+ individuals with BE300 cells/µl [p=0.009]). Conclusion: Persistent SABA-induced FEV1>12%, especially when associated to BE>300 cells/ml, may be a marker of accelerated lung function decline in severe asthmatics despite maximal step-5 treatment. The highest bronchodilation associated to the lowest BE levels should be the main goal of asthma treatment to prevent such decline.

Published
2020

11. Terahertz pump-probe of liquid water at 12.3 THz

Author

Novelli, F., Hoberg, C., Adams, E. M., (0000-0002-3431-6666) Klopf, J. M., Havenith, M., Novelli, F., Hoberg, C., Adams, E. M., (0000-0002-3431-6666) Klopf, J. M., and Havenith, M.

Abstract

The dynamical complexity of the hydrogen-bonded water network can be investigated with intense Terahertz (THz) spectroscopy, which can drive the liquid into the nonlinear response regime and probe anharmonicity effects. Here we report single-color and polarization-dependent pump-probe experiments at 12.3 THz on liquid water, exciting the librational mode. By comparing results obtained on a static sample and a free-flowing water jet, we are able to disentangle the distinct contributions by thermal, acoustic, and nonlinear optical effects. We show that the transient transmission by the static water layer on a time scale of hundreds of microseconds can be described by thermal (slow) and acoustic (temperature-dependent) effects. In addition, during pump probe overlap we observe an anisotropic nonlinear optical response. This nonlinear signal is more prominent in the liquid jet than in the static cell, where temperature and density perturbations are more pronounced. Our measurements confirm that the THz excitation resonates with the rotationally-damped motion of water molecules, resulting in enhanced transient anisotropy. This model can be used to explain the non-linear response of water in the frequency range between about 1 and 20 THz.

Published
2022

12. Discovery of Targets for Cancer Immunoprevention

Author

Cappello, P., Bulfamante, S., Mandili, G., and Novelli, F.

Subjects
Vaccines, T-cells, Neoplasms, Tumor-associated antigen, SERPA, Neoplasm, Humans, Immunotherapy, Antigens, Immunoprevention, Antigens, Neoplasm, Gene Library, Cancer Vaccines
Published
2022

14. Higher blood eosinophil levels after omalizumab treatment may be associated with poorer asthma outcomes

Author

Sposato, B, Scalese, M, Milanese, M, Masieri, S, Cavaliere, C, Latorre, M, Scichilone, N, Ricci, A, Cresti, A, Santus, P, Olivieri, C, Perrella, A, Rogliani, P, Paggiaro, P, Migliorini, M. G, Di Tomassi, M, Camiciottoli, G, Maselli, R, Pelaia, G, Busceti, M. T, Sabato, E, Cagnazzo, M. G, Colombo, F, Palumbo, L, Ravazzi, A, Bucca, C, Caiaffa, M. F, Berra, A, Calabrese, C, Stanziola, A. A, Schino, P, Di Gioacchino, M, Cazzola, M, Segreti, A, Pastorello, E. A, Scibilia, G, Vianello, A, Marchi, M. R, Paladini, L, Baglioni, S, Abbritti, M, Almerigogna, F, Matucci, A, Vultaggio, A, Maggi, E, Maestrelli, P, Guarnieri, G, Steinhilber, G, Bonavia, M, Rottoli, P, Bargagli, E, Senna, G, Caminati, M, Macchia, L, Bellia, V, Novelli, F, Vergura, L, Rosati, Y, Folletti, I, Pio, R, Pio, A, Maccari, U, Maggiorelli, C, Scala, R, Vignale, L, Pulerà, N, Carpagnano, G. E, Foschino Barbaro, M. P, The Omalizumab Italian Study Group, Sposato, B, Scalese, M, Milanese, M, Masieri, S., Cavaliere, C, Latorre, M., Scichilone, N., Ricci, A., Cresti, A., Santus, P., Olivieri, C., Perrella, A., Rogliani, P., Paggiaro, P., Sposato, B., Migliorini, M. G., Di Tomassi, M., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Novelli, F., Vergura, L., Scalese, M., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulera, N., Carpagnano, G. E., Foschino Barbaro, M. P., Cavaliere, C., Sposato B., Scalese M., Milanese M., Masieri S., Cavaliere C., Latorre M., Scichilone N., Ricci A., Cresti A., Santus P., Olivieri C., Perrella A., Rogliani P., Paggiaro P., Migliorini M.G., Di Tomassi M., Camiciottoli G., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Caiaffa M.F., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Cazzola M., Segreti A., Pastorello E.A., Scibilia G., Vianello A., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Matucci A., Vultaggio A., Maggi E., Maestrelli P., Guarnieri G., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Macchia L., Bellia V., Novelli F., Vergura L., Rosati Y., Folletti I., Pio R., Pio A., Maccari U., Maggiorelli C., Scala R., Vignale L., Pulera N., Carpagnano G.E., and Foschino Barbaro M.P.

Subjects
Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Treatment outcome, MEDLINE, Omalizumab, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Immunoglobulin E, eosinophil, Omalizumab, anti-IgE, asthma, Leukocyte Count, Text mining, Forced Expiratory Volume, Internal medicine, Eosinophilia, medicine, Humans, Immunology and Allergy, Anti-Asthmatic Agents, Blood eosinophil, Aged, Retrospective Studies, Asthma, biology, business.industry, Retrospective cohort study, Middle Aged, asthma, Prognosis, medicine.disease, Eosinophils, Treatment Outcome, inflammation, biology.protein, Female, business, medicine.drug
Published
2019

22. Soluble stroma-related biomarkers of pancreatic cancer

Author

Resovi, A, Bani, M, Porcu, L, Anastasia, A, Minoli, L, Allavena, P, Cappello, P, Novelli, F, Scarpa, A, Morandi, E, Falanga, A, Torri, V, Taraboletti, G, Belotti, D, Giavazzi, R, Resovi A, Bani MR, Porcu L, Anastasia A, Minoli L, Allavena P, Cappello P, Novelli F, Scarpa A, Morandi E, Falanga A, Torri V, Taraboletti G, Belotti D, Giavazzi R, Resovi, A, Bani, M, Porcu, L, Anastasia, A, Minoli, L, Allavena, P, Cappello, P, Novelli, F, Scarpa, A, Morandi, E, Falanga, A, Torri, V, Taraboletti, G, Belotti, D, Giavazzi, R, Resovi A, Bani MR, Porcu L, Anastasia A, Minoli L, Allavena P, Cappello P, Novelli F, Scarpa A, Morandi E, Falanga A, Torri V, Taraboletti G, Belotti D, and Giavazzi R

Abstract

The clinical management of pancreatic ductal adenocarcinoma (PDAC) is hampered by the lack of reliable biomarkers. This study investigated the value of soluble stroma-related molecules as PDAC biomarkers. In the first exploratory phase, 12 out of 38 molecules were associated with PDAC in a cohort of 25 PDAC patients and 16 healthy subjects. A second confirmatory phase on an independent cohort of 131 PDAC patients, 30 chronic pancreatitis patients, and 131 healthy subjects confirmed the PDAC association for MMP7, CCN2, IGFBP2, TSP2, sICAM1, TIMP1, and PLG Multivariable logistic regression model identified biomarker panels discriminating respectively PDAC versus healthy subjects (MMP7 + CA19.9, AUC = 0.99, 99% CI = 0.98-1.00) (CCN2 + CA19.9, AUC = 0.96, 99% CI = 0.92-0.99) and PDAC versus chronic pancreatitis (CCN2 + PLG+FN+Col4 + CA19.9, AUC = 0.94, 99% CI = 0.88-0.99). Five molecules were associated with PanIN development in two GEM models of PDAC (PdxCre/LSL-KrasG12D and PdxCre/LSL-KrasG12D/+/LSL-Trp53R172H/+), suggesting their potential for detecting early disease. These markers were also elevated in patient-derived orthotopic PDAC xenografts and associated with response to chemotherapy. The identified stroma-related soluble biomarkers represent potential tools for PDAC diagnosis and for monitoring treatment response of PDAC patients

Published
2018

23. Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential

Author

Valfre di Bonzo, L., Ferrero, I., Cravanzola, C., Mareschi, K., Rustichel, D., Novo, E., Sanavio, F., Cannito, S., Zamara, E., Bertero, M., Davit, A., Francica, S., Novelli, F., Colombatto, S., Fagioli, F., and Parola, M.

Subjects
Liver cells -- Physiological aspects, Cell differentiation -- Research, Stem cells -- Transplantation, Stem cells -- Patient outcomes, Stem cells -- Physiological aspects, Stem cells -- Research, Liver -- Transplantation, Liver -- Patient outcomes, Liver -- Physiological aspects, Liver -- Research, Health
Published
2008

25. Higher blood eosinophil levels after omalizumab treatment may be associated with poorer asthma outcomes

Author

Sposato, B., Migliorini, M.G., Di Tomassi, M., Olivieri, C., Perrella, A., Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M.T., Sabato, E., Cagnazzo, M.G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Caiaffa, M.F., Berra, A., Calabrese, C., Stanziola, A.A., Schino, P., Di Gioacchino, M., Rogliani, P., Cazzola, M., Segreti, A., Pastorello, E.A., Scibilia, G., Vianello, A., Marchi, M.R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Paggiaro, P., Novelli, F., Latorre, M., Vergura, L., Masieri, S., Scalese, M., Rosati, Y., Milanese, M., Folletti, I., Pio, R., Pio, A., Maccari, U., Maggiorelli, C., Scala, R., Vignale, L., Pulerà, N., Carpagnano, G.E., Foschino Barbaro, M.P., Sposato, Bruno, Scalese, Marco, Milanese, Manlio, Masieri, Simonetta, Cavaliere, Carlo, Latorre, Manuela, Scichilone, Nicola, Ricci, Alberto, Cresti, Alberto, Santus, Pierachille, Olivieri, Carmela, Perrella, Antonio, Rogliani, Paola, and Paggiaro, Pierluigi

Published
2019
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27. RItA: The Italian severe/uncontrolled asthma registry

Author

Maio, S., Baldacci, S., Bresciani, M., Simoni, M., Latorre, M., Murgia, N., Spinozzi, F., Braschi, M., Antonicelli, L., Brunetto, B., Iacovacci, P., Roazzi, P., Pini, C., Pata, M., La Grasta, L., Paggiaro, P., Viegi, G., Angino, A., Carrozzi, L., Cerrai, S., Di Pede, F., Martini, F., Pala, A. P., Pistelli, F., Sarno, G., Silvi, P., Novelli, F., Ferri, M., and Bonifazi, F.

Subjects
Adult, Male, severe/uncontrolled asthma, medicine.medical_specialty, Exacerbation, Immunology, NO, 03 medical and health sciences, 0302 clinical medicine, exacerbations, pharmacological treatment, Internal medicine, eosinophilic inflammation, medicine, Humans, Immunology and Allergy, Nasal polyps, Registries, 030212 general & internal medicine, Sinusitis, Aged, Asthma, business.industry, Comorbidity, Eosinophilic inflammation, Exacerbations, Pharmacological treatment, Severe/uncontrolled asthma, Emergency department, Middle Aged, medicine.disease, Obesity, Allergic conjunctivitis, comorbidity, Italy, 030228 respiratory system, comorbidity, eosinophilic inflammation, exacerbations, pharmacological treatment, severe/uncontrolled asthma, Physical therapy, Female, business
Abstract

Background The Italian severe/uncontrolled asthma (SUA) web-based registry encompasses demographic, clinical, functional, inflammatory data; it aims to raise SUA awareness, identifying specific phenotypes and promoting optimal care. Methods 493 adult patients from 27 Italian centres (recruited in 2011-2014) were analyzed. Results Mean age was 53.8yrs. SUA patients were more frequently female (60.6%), with allergic asthma (83.1%). About 30% showed late onset of asthma diagnosis/symptoms (>40yrs); the mean age for asthma symptoms onset was 30.2yrs and for asthma diagnosis 34.4yrs. 97.1% used ICS (dose 2000 BDP), 93.6% LABA in association with ICS, 53.3% LTRAs, 64.1% anti-IgE, 10.7% theophylline, 16.0% oral corticosteroids. Mean FEV1% pred of 75.1%, median values of 300/mm3 of blood eosinophil count, 323 kU/l of serum total IgE, 24 ppb of FENO were shown. Most common comorbidities were allergic rhinitis (62.4%), gastroesophageal reflux (42.1%), sinusitis (37.9%), nasal polyposis (30.2%), allergic conjunctivitis (30.2%). 55.7% of SUA patients had exacerbations in the last 12 months, 9.7% emergency department visits, 7.3% hospitalizations. Factors associated with exacerbation risk were: obesity (OR, 95%CI 2.46, 1.11-5.41), psychic disorders (2.87, 0.89-9.30 - borderline), nasal polyps (1.86, 0.88-3.89 - borderline), partial/poor asthma treatment adherence (2.54, 0.97-6.67 - borderline), anti-IgE use in a protective way (0.26, 0.12-0.53). Comparisons to severe asthma multicentre studies and available registries showed data consistency across European and American populations. Conclusions An international effort in the implementation of SUA patients registries could help to better understand the clinical features and to manage severe asthma, representing a non negligible socio-economic burden for health services. This article is protected by copyright. All rights reserved.

Published
2017

28. Contribution of Genetic Background to the Radiation Risk for Cancer and Non-Cancer Diseases in Ptch1+/– Mice.

Author

De Stefano, I., Leonardi, S., Casciati, A., Pasquali, E., Giardullo, P., Antonelli, F., Novelli, F., Babini, G., Tanori, M., Tanno, B., Saran, A., Mancusoa, M., and Pazzaglia, S.

Subjects
BACKGROUND radiation, DISEASE risk factors, RADIATION tolerance, DENTATE gyrus, CRYSTALLINE lens, RADIATION exposure
Abstract

Experimental mouse studies are important to gain a comprehensive, quantitative and mechanistic understanding of the biological factors that modify individual risk of radiation-induced health effects, including age at exposure, dose, dose rate, organ/tissue specificity and genetic factors. In this study, neonatal Ptch1+/– mice bred on CD1 and C57Bl/6 background received whole-body irradiation at postnatal day 2. This time point represents a critical phase in the development of the eye lens, cerebellum and dentate gyrus (DG), when they are also particularly susceptible to radiation effects. Irradiation was performed with γ rays (60Co) at doses of 0.5, 1 and 2 Gy, delivered at 0.3 Gy/min or 0.063 Gy/min. Wild-type and mutant mice were monitored for survival, lens opacity, medulloblastoma (MB) and neurogenesis defects. We identified an inverse genetic background-driven relationship between the radiosensitivity to induction of lens opacity and MB and that to neurogenesis deficit in Ptch1+/– mutants. In fact, high incidence of radiation-induced cataract and MB were observed in Ptch1+/–/CD1 mutants that instead showed no consequence of radiation exposure on neurogenesis. On the contrary, no induction of radiogenic cataract and MB was reported in Ptch1+/–/C57Bl/6 mice that were instead susceptible to induction of neurogenesis defects. Compared to Ptch1+/–/CD1, the cerebellum of Ptch1+/–/C57Bl/6 mice showed increased radiosensitivity to apoptosis, suggesting that differences in processing radiation-induced DNA damage may underlie the opposite strain-related radiosensitivity to cancer and non-cancer pathologies. Altogether, our results showed lack of dose-rate-related effects and marked influence of genetic background on the radiosensitivity of Ptch1+/–mice, supporting a major contribution of individual sensitivity to radiation risk in the population. [ABSTRACT FROM AUTHOR]

Published
2022
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29. miRNA-Signature of Irradiated Ptch1+/– Mouse Lens is Dependent on Genetic Background.

Author

Tanno, B., Babini, G., Leonardi, S., De Stefano, I., Merla, C., Novelli, F., Antonelli, F., Casciati, A., Tanori, M., Pasquali, E., Giardullo, P., Pazzaglia, S., and Mancuso, M.

Subjects
MICE, IONIZING radiation, EPITHELIAL-mesenchymal transition, TOLL-like receptors, NUCLEOTIDE sequencing
Abstract

One harmful long-term effect of ionizing radiation is cataract development. Recent studies have been focused on elucidating the mechanistic pathways involved in this pathogenesis. Since accumulating evidence has established a role of microRNAs in ocular diseases, including cataract, the goal of this work was to determine the microRNA signature of the mouse lens, at short time periods postirradiation, to understand the mechanisms related to radio-induced cataractogenesis. To evaluate the differences in the microRNA profiles, 10-week-old Patched1 heterozygous (Ptch1+/–) mice, bred onto two different genetic backgrounds (CD1 and C57Bl/6J), received whole-body 2 Gy γ-ray irradiation, and 24 h later lenses were collected. Next-generation sequencing and bioinformatics analysis revealed that genetic background markedly influenced the list of the deregulated microRNAs and the mainly predicted perturbed biological functions of 2 Gy irradiated Ptch1+/– mouse lenses. We identified a subset of microRNAs with a contra-regulated expression between strains, with a key role in regulating Toll-like receptor (TLR)-signaling pathways. Furthermore, a detailed analysis of miRNome data showed a completely different DNA damage response in mouse lenses 24 h postirradiation, mainly mediated by a marked upregulation of p53 signaling in Ptch1+/–/C57Bl/6J lenses that was not detected on a CD1 background. We propose a strict interplay between p53 and TLR signaling in Ptch1+/–/C57Bl/6J lenses shortly after irradiation that could explain both the resistance of this strain to developing lens opacities and the susceptibility of CD1 background to radiation-induced cataractogenesis through activation of epithelial-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Published
2022
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31. Trasversalità nel paesaggio/ Crossing landscape

Author

Mellano, P., Bartolozzi, C., Berta, M., Crotti, M., Novelli, F., Roggero, M., Romeo, E., and Joao Ferreira Nunes

Subjects
Buffer Zone Unesco, Villa Adriana, Paesaggio Culturale, Paesaggio Archeologico, Progetto Sostenibile, Restauro, Villa Adriana, Paesaggio Archeologico, Paesaggio Culturale, Restauro, Progetto Sostenibile, Buffer Zone Unesco
Published
2019

33. Pancreatic cancer vaccine: a unique potential therapy

Author

Cappello P, Principe M, and Novelli F

Subjects
antibody, pancreatic cancer, T cells, lcsh:Diseases of the digestive system. Gastroenterology, immunotherapy, vaccines, lcsh:RC799-869, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282
Abstract

Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA) is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological checkpoints. Keywords: pancreatic cancer, vaccines, T-cells, antibody, immunotherapy

Published
2015

35. Asthma control in severe asthmatics under treatment with omalizumab: A cross-sectional observational study in Italy

Author

Novelli, Federica, Latorre, Matteo, Vergura, Letizia, Caiaffa, Maria Filomena, Camiciottoli, Gianna, Guarnieri, Gabriella, Matucci, Andrea, Macchia, Luigi, Vianello, Andrea, Vultaggio, Alessandra, Celi, Alessandro, Cazzola, Mario, Paggiaro, Pierluigi, Camiciottoli, G., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, Laura, Ravazzi, Aldo, Bucca, C., Caiaffa, M. F., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Cazzola, M., Segreti, A., Pastorello, E. A., Scibilia, G., Vianello, A., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Matucci, A., Vultaggio, A., Maggi, E., Maestrelli, P., Guarnieri, G., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Macchia, L., Bellia, V., Scichilone, N., Paggiaro, P., Novelli, F., Vergura, L., Novelli F., Latorre M., Vergura L., Caiaffa M.F., Camiciottoli G., Guarnieri G., Matucci A., Macchia L., Vianello A., Vultaggio A., Celi A., Cazzola M., Paggiaro P., Maselli R., Pelaia G., Busceti M.T., Sabato E., Cagnazzo M.G., Colombo F., Palumbo L., Ravazzi A., Bucca C., Berra A., Calabrese C., Stanziola A.A., Schino P., Di Gioacchino M., Segreti A., Pastorello E.A., Scibilia G., Marchi M.R., Paladini L., Baglioni S., Abbritti M., Almerigogna F., Maggi E., Maestrelli P., Steinhilber G., Bonavia M., Rottoli P., Bargagli E., Senna G., Caminati M., Bellia V., Scichilone N., Novelli, F., Latorre, M., Vergura, L., Caiaffa, M. F., Camiciottoli, G., Guarnieri, G., Matucci, A., Macchia, L., Vianello, A., Vultaggio, A., Celi, A., Cazzola, M., Paggiaro, P., Maselli, R., Pelaia, G., Busceti, M. T., Sabato, E., Cagnazzo, M. G., Colombo, F., Palumbo, L., Ravazzi, A., Bucca, C., Berra, A., Calabrese, C., Stanziola, A. A., Schino, P., Di Gioacchino, M., Segreti, A., Pastorello, E. A., Scibilia, G., Marchi, M. R., Paladini, L., Baglioni, S., Abbritti, M., Almerigogna, F., Maggi, E., Maestrelli, P., Steinhilber, G., Bonavia, M., Rottoli, P., Bargagli, E., Senna, G., Caminati, M., Bellia, V., and Scichilone, N.

Subjects
Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Exacerbation, Cross-sectional study, Omalizumab, Comorbidity, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Exhaled nitric oxide, Exacerbations, Comorbidities, Asthma, Control, Severity of Illness Index, Internal medicine, Severity of illness, Medicine, Anti-Asthmatic Agent, Humans, Pharmacology (medical), Anti-Asthmatic Agents, Inflammation Mediator, Respiratory Function Test, Aged, Cross-Sectional Studie, business.industry, Biochemistry (medical), Middle Aged, medicine.disease, Respiratory Function Tests, Cross-Sectional Studies, Italy, Physical therapy, Observational study, Female, Inflammation Mediators, Comorbiditie, business, medicine.drug, Human
Abstract

Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between poorly controlled and partially or well controlled asthmatics showed a statistically significant higher prevalence of some comorbidities in the first group, namely obesity, gastro-oesophageal reflux disease (GORD), aspirin intolerance and mental disorders (all p

Published
2015

37. Silk: Optical properties over 12.6 octaves THz-IR-visible-UV range

Author

Balčytis, A, Ryu, M, Wang, X, Novelli, F, Seniutinas, G, Du, S, Li, J, Davis, J, Appadoo, D, Morikawa, J, and Juodkazis, S

Abstract

Domestic (Bombyx mori) and wild (Antheraea pernyi) silk fibers were characterised over a wide spectral range from THz 8 cm-1 (λ = 1.25 mm, f = 0.24 THz) to deep-UV 50 × 103 cm-1 (λ = 200 nm, f = 1500 THz) wavelengths or over a 12.6 octave frequency range. Spectral features at β-sheet, α-coil and amorphous fibroin were analysed at different spectral ranges. Single fiber cross sections at mid-IR were used to determine spatial distribution of different silk constituents and revealed an α-coil rich core and more broadly spread β-sheets in natural silk fibers obtained from wild Antheraea pernyi moths. Low energy T-ray bands at 243 and 229 cm-1 were observed in crystalline fibers of domestic and wild silk fibers, respectively, and showed no spectral shift down to 78 K temperature. A distinct 20 ± 4 cm-1 band was observed in the crystalline Antheraea pernyi silk fibers. Systematic analysis and assignment of the observed spectral bands is presented. Water solubility and biodegradability of silk, required for bio-medical and sensor applications, are directly inferred from specific spectral bands.

Published
2017

38. Localized vibrations in superconducting YB a2 C u3 O7 revealed by ultrafast optical coherent spectroscopy

Author

Novelli F., Giovannetti G., Avella A., Cilento F., Patthey L., Radovic M., Capone M., Parmigiani F., and Fausti D.

Subjects
Condensed Matter::Superconductivity
Abstract

The interaction between phonons and high-energy excitations of electronic origin in cuprates and their role in the superconducting mechanisms is still controversial. Here we use coherent vibrational time-domain spectroscopy together with density functional and dynamical mean-field theory calculations to establish a direct link between the c-axis phonon modes and the in-plane electronic charge excitations in optimally doped YBa2Cu3O7. The nonequilibrium Raman tensor is measured by means of the broadband "coherent-phonon" response in pump-probe experiments and is qualitatively described by our model using density functional theory in the frozen-phonon approximation plus single-band dynamical mean-field theory to account for the electronic correlations. The major outcome of our experimental and theoretical study is to establish the link between out-of-plane copper ion displacements and the in-plane electronic correlations, and to estimate at a few unit cells the correlation length of the associated phonon mode. The approach introduced here could help in revealing the complex interplay between fluctuations of different nature and spatial correlation in several strongly correlated materials.

Published
2017

39. Prefazione

Author

Piccoli, E. and Novelli, F.

Published
2017

42. PI3Kγ inhibition protects from anthracycline-induced heart failure and reduces tumor growth

Author

Li, M., primary, Sala, V., additional, De Santis, M.C., additional, Cimino, J., additional, Cappello, P., additional, Pianca, N., additional, Martini, M., additional, Lazzarini, E., additional, Pirozzi, F., additional, Tocchetti, C.G., additional, Sandri, M., additional, Ameri, P., additional, Sciarretta, S., additional, Mongillo, M., additional, Zaglia, T., additional, Morello, F., additional, Novelli, F., additional, Hirsch, E., additional, and Ghigo, A., additional

Published
2018
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43. Macrophage PI3K gamma Drives Pancreatic Ductal Adenocarcinoma Progression

Author

Kaneda, MM, Cappello, P, Nguyen, AV, Ralainirina, N, Hardamon, CR, Foubert, P, Schmid, MC, Sun, P, Mose, E, Bouvet, M, Lowy, AM, Valasek, MA, Sasik, R, Novelli, F, Hirsch, E, and Varner, JA

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a low 5-year survival rate, yet new immunotherapeutic modalities may offer hope for this and other intractable cancers. Here, we report that inhibitory targeting of PI3Kγ, a key macrophage lipid kinase, stimulates antitumor immune responses, leading to improved survival and responsiveness to standard-of-care chemotherapy in animal models of PDAC. PI3Kγ selectively drives immunosuppressive transcriptional programming in macrophages that inhibits adaptive immune responses and promotes tumor cell invasion and desmoplasia in PDAC. Blockade of PI3Kγ in PDAC-bearing mice reprograms tumor-associated macrophages to stimulate CD8(+) T-cell-mediated tumor suppression and to inhibit tumor cell invasion, metastasis, and desmoplasia. These data indicate the central role that macrophage PI3Kγ plays in PDAC progression and demonstrate that pharmacologic inhibition of PI3Kγ represents a new therapeutic modality for this devastating tumor type.We report here that PI3Kγ regulates macrophage transcriptional programming, leading to T-cell suppression, desmoplasia, and metastasis in pancreas adenocarcinoma. Genetic or pharmacologic inhibition of PI3Kγ restores antitumor immune responses and improves responsiveness to standard-of-care chemotherapy. PI3Kγ represents a new therapeutic immune target for pancreas cancer. Cancer Discov; 6(8); 870-85. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 803.

Published
2016

44. Th22 cells are expanded in multiple sclerosisand are resistant to IFN-alpha

Author

Rolla, S, Bardina, V, De Mercanti, S, Quaglino, P, DE PALMA, Raffaele, Gned, D, Brusa, D, Durelli, L, Novelli, F, Clerico, M., Rolla, S, Bardina, V, De Mercanti, S, Quaglino, P, DE PALMA, Raffaele, Gned, D, Brusa, D, Durelli, L, Novelli, F, and Clerico, M.

Subjects
Multiple Sclerosis, Interpheron, Multiple Sclerosi, T cells, T cell
Published
2014

46. FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis

Author

Chattaragada, M S, primary, Riganti, C, additional, Sassoe, M, additional, Principe, M, additional, Santamorena, M M, additional, Roux, C, additional, Curcio, C, additional, Evangelista, A, additional, Allavena, P, additional, Salvia, R, additional, Rusev, B, additional, Scarpa, A, additional, Cappello, P, additional, and Novelli, F, additional

Published
2017
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48. Phase separation in the nonequilibrium Verwey transition in magnetite

Author

Randi, F., Vergara, I., Novelli, F., Esposito, M., Dell'Angela, M., Brabers, V. A. M., Metcalf, P., Kukreja, R., Duerr, H. A., Fausti, D., Grueninger, M., Parmigiani, F., Randi, F., Vergara, I., Novelli, F., Esposito, M., Dell'Angela, M., Brabers, V. A. M., Metcalf, P., Kukreja, R., Duerr, H. A., Fausti, D., Grueninger, M., and Parmigiani, F.

Abstract

We present equilibrium and out-of-equilibrium studies of the Verwey transition in magnetite. In the equilibrium optical conductivity, we find a steplike change at the phase transition for photon energies below about 2 eV. The possibility of triggering a nonequilibrium transient metallic state in insulating magnetite by photo excitation was recently demonstrated by an x-ray study. Here we report a full characterization of the optical properties in the visible frequency range across the nonequilibrium phase transition. Our analysis of the spectral features is based on a detailed description of the equilibrium properties. The out-of-equilibrium optical data bear the initial electronic response associated to localized photoexcitation, the occurrence of phase separation, and the transition to a transient metallic phase for excitation density larger than a critical value. This allows us to identify the electronic nature of the transient state, to unveil the phase transition dynamics, and to study the consequences of phase separation on the reflectivity, suggesting a spectroscopic feature that may be generally linked to out-of-equilibrium phase separation.

Published
2016

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