31 results on '"Meli, G."'
Search Results
2. Cyclic Lateral Load Test of a Wall with Timber Frame Structure and Lightearth Envelope
- Author
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Becerra, G., primary, Onnis, S., additional, Meli, G., additional, Wieser, M., additional, and Vargas-Neumann, J., additional
- Published
- 2023
- Full Text
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3. Characterization of a Low Noise and Low Background Charge Sensitive Amplifier for the Readout of Germanium Detectors
- Author
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Butta, D., primary, Meli, G., additional, Bosio, F., additional, Carminati, M., additional, Borghi, G., additional, Henkes, F., additional, Willers, M., additional, Mertens, S., additional, Riboldi, S., additional, and Fiorini, C. E., additional
- Published
- 2023
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4. Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?
- Author
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Boglione, L, primary, Meli, G, additional, Poletti, F, additional, Rostagno, R, additional, Moglia, R, additional, Cantone, M, additional, Esposito, M, additional, Scianguetta, C, additional, Domenicale, B, additional, Di Pasquale, F, additional, and Borrè, S, additional
- Published
- 2021
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5. NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimerʼs disease
- Author
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Corsetti, V., Florenzano, F., Atlante, A., Bobba, A., Ciotti, M.T., Natale, F., Della Valle, F., Borreca, A., Manca, A., Meli, G., Ferraina, C., Feligioni, M., DʼAguanno, S., Bussani, R., Ammassari-Teule, M., Nicolin, V., Calissano, P., and Amadoro, G.
- Published
- 2015
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6. Imerys technical mineral fillers for reduced environmental impact in rubber applications
- Author
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Cauchy J., e-Rubbercon 2020, Association Francaise des Ingenieurs et Cadres du Caoutchouc et des Polymeres (AFICEP), Paris, France, 11-12/02/2021, Meli G., Cauchy J., e-Rubbercon 2020, Association Francaise des Ingenieurs et Cadres du Caoutchouc et des Polymeres (AFICEP), Paris, France, 11-12/02/2021, and Meli G.
- Published
- 2021
7. Correction to: Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular A? oligomers (Cell Death & Differentiation, (2020), 27, 3, (934-948), 10.1038/s41418-019-0409-3)
- Author
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Scopa C., Marrocco F., Latina V., Ruggeri F., Corvaglia V., La Regina F., Ammassari-Teule M., Middei S., Amadoro G., Meli G., Scardigli R., and Cattaneo A.
- Subjects
amyloid beta ,neurogenesis ,tau ,Alzheimer's Disease - Abstract
Since the publication of the original article, the authors have noticed that in "Acknowledgements" section the following funding Statement was erroneously missing: "CS was recipient of a MIUR fellowship for the PhD program in Molecular, Cellular and Environmental Biology at the Department of Science, University Roma Tre (Supervisor Prof. Sandra Moreno)". This has now been corrected in both the PDF and HTML versions of the paper. The authors apologize for any inconvenience this may have caused.
- Published
- 2020
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8. Catania e Living Lab di Cultura e Tecnologia. Quando la ricerca scientifica incontra il pubblico
- Author
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Malfitana, D., Arena, L., Cutroni, L., Iachello, S., Meli, G., and Pantellaro, C.
- Published
- 2017
9. Nanoscale electrical characteristics of metal (Au, Pd)–graphene–metal (Cu) contacts
- Author
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Ruffino, F., Meli, G., and Grimaldi, M.G.
- Published
- 2016
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10. Effectiveness of long-acting aripiprazole in schizoaffective disorders: A naturalistic longitudinal study
- Author
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Nivoli, A., primary, Antonioli, M., additional, Folini, L., additional, Floris, L., additional, Meli, G., additional, Paolo, M., additional, and Lorettu, L., additional
- Published
- 2017
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11. The Spectre of Death in the Physician-patient Relationship. the Psychiatrist's Point of View
- Author
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Meli, G., primary, Nieddu, G., additional, Milia, P., additional, and Lorettu, L., additional
- Published
- 2015
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12. NH2-truncated human tau induces deregulated mitophagy in neurons by aberrant recruitment of Parkin and UCHL-1: implications in Alzheimer's disease.
- Author
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Corsetti, V., Florenzano, F., Atlante, A., Bobba, A., Ciotti, M. T., Natale, F., Valle, F. Della, Borreca, A., Manca, A., Meli, G., Ferraina, C., Feligioni, M., D'Aguanno, S., Bussani, R., Ammassari-Teule, M., Nicolin, V., Calissano, P., and Amadoro, G.
- Published
- 2015
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13. A General Framework for Hierarchical Redundancy Resolution Under Arbitrary Constraints
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Mario Daniele Fiore, Gaetano Meli, Anton Ziese, Bruno Siciliano, Ciro Natale, Fiore, M. D., Meli, G., Ziese, A., Siciliano, B., and Natale, C.
- Subjects
FOS: Computer and information sciences ,Hierarchical control ,optimization and optimal control ,Robot ,Service robot ,motion control ,Kinematic ,Robot kinematic ,Computer Science Applications ,Computer Science::Robotics ,Computer Science - Robotics ,Mathematical model ,Redundancy ,Control and Systems Engineering ,Task analysis ,Electrical and Electronic Engineering ,Robotics (cs.RO) ,redundancy resolution ,redundant robot - Abstract
The increasing interest in autonomous robots with a high number of degrees of freedom for industrial applications and service robotics demands control algorithms to handle multiple tasks as well as hard constraints efficiently. This paper presents a general framework in which both kinematic (velocity- or acceleration-based) and dynamic (torque-based) control of redundant robots are handled in a unified fashion. The framework allows for the specification of redundancy resolution problems featuring a hierarchy of arbitrary (equality and inequality) constraints, arbitrary weighting of the control effort in the cost function and an additional input used to optimize possibly remaining redundancy. To solve such problems, a generalization of the Saturation in the Null Space (SNS) algorithm is introduced, which extends the original method according to the features required by our general control framework. Variants of the developed algorithm are presented, which ensure both efficient computation and optimality of the solution. Experiments on a KUKA LBRiiwa robotic arm, as well as simulations with a highly redundant mobile manipulator are reported., Accepted to Transactions on Robotics (T-RO). Final version in preparaton. 20 pages, 19 figures
- Published
- 2022
14. Il progetto di rilievo Antonio Zanca (1861/1958) ed il nuovo progetto di rilievo
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Milone Manuela, Verro,G, Rotolo, M, Panasci, F, Antonini, C, Carlea,D., Bellanca,L. G, Sarullo, F, Bucaro, G, Di Paola, M, Buscemi, F, Meli, G, Infurna,M, Agnello, F, Milone, M, Peri, E, Esposito, G, Marino, S, Oddo, S, Monorchio, G, MILONE, Manuela, Verro, G, Carlea, D, Bellanca, LG, Infurna, M, and Milone Manuela
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Cattedrale ,Cattedrale Palermo, Santa vergine Maria Assunta, Rilievo ,topografia ,rilievo ,Settore ICAR/17 - Disegno ,Palermo - Abstract
Historical path and state of the art reliefs on the cathedral of Palermo. Particular attention to the important work carried out by the architect Zanca and then to analyze the work I did on the survey project using a topographic station.
- Published
- 2019
15. Nel serra serra dei capelli. L'amore in un manipolo di odii
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GERBINO, Aldo, SANTANGELO, Giovanni Saverio, Santangelo, GS, Gerbino, A, and Meli, G
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Amore ,Lingua siciliana ,Lirica - Abstract
Viene ricordato dopo i duecento anni della morte, il poeta Giovanni Meli. Sono messe in evidenza le anacreontiche che raccontano dell'amore, della bellezza femminile in una nota cornice arcadica.
- Published
- 2016
16. Retinal pathological features and proteome signatures of Alzheimer's disease.
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Koronyo Y, Rentsendorj A, Mirzaei N, Regis GC, Sheyn J, Shi H, Barron E, Cook-Wiens G, Rodriguez AR, Medeiros R, Paulo JA, Gupta VB, Kramerov AA, Ljubimov AV, Van Eyk JE, Graham SL, Gupta VK, Ringman JM, Hinton DR, Miller CA, Black KL, Cattaneo A, Meli G, Mirzaei M, Fuchs DT, and Koronyo-Hamaoui M
- Subjects
- Male, Humans, Female, Amyloid beta-Peptides metabolism, Proteome metabolism, Proteomics, Retina pathology, Atrophy pathology, Biomarkers metabolism, Alzheimer Disease pathology
- Abstract
Alzheimer's disease (AD) pathologies were discovered in the accessible neurosensory retina. However, their exact nature and topographical distribution, particularly in the early stages of functional impairment, and how they relate to disease progression in the brain remain largely unknown. To better understand the pathological features of AD in the retina, we conducted an extensive histopathological and biochemical investigation of postmortem retina and brain tissues from 86 human donors. Quantitative examination of superior and inferior temporal retinas from mild cognitive impairment (MCI) and AD patients compared to those with normal cognition (NC) revealed significant increases in amyloid β-protein (Aβ
42 ) forms and novel intraneuronal Aβ oligomers (AβOi), which were closely associated with exacerbated retinal macrogliosis, microgliosis, and tissue atrophy. These pathologies were unevenly distributed across retinal layers and geometrical areas, with the inner layers and peripheral subregions exhibiting most pronounced accumulations in the MCI and AD versus NC retinas. While microgliosis was increased in the retina of these patients, the proportion of microglial cells engaging in Aβ uptake was reduced. Female AD patients exhibited higher levels of retinal microgliosis than males. Notably, retinal Aβ42 , S100 calcium-binding protein B+ macrogliosis, and atrophy correlated with severity of brain Aβ pathology, tauopathy, and atrophy, and most retinal pathologies reflected Braak staging. All retinal biomarkers correlated with the cognitive scores, with retinal Aβ42 , far-peripheral AβOi and microgliosis displaying the strongest correlations. Proteomic analysis of AD retinas revealed activation of specific inflammatory and neurodegenerative processes and inhibition of oxidative phosphorylation/mitochondrial, and photoreceptor-related pathways. This study identifies and maps retinopathy in MCI and AD patients, demonstrating the quantitative relationship with brain pathology and cognition, and may lead to reliable retinal biomarkers for noninvasive retinal screening and monitoring of AD., (© 2023. The Author(s).)- Published
- 2023
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17. The Evolving Need for Neuropsychology in Neurosurgical Settings: Challenges Facing Transformative Care.
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Koay JM, Spat-Lemus J, Cornwell MA, Sacks-Zimmerman A, Mandelbaum S, Kohn A, McLean E, Meli G, and Bender HA
- Subjects
- Humans, Reproducibility of Results, Neuropsychological Tests, Neuropsychology methods, Brain
- Abstract
Clinical neuropsychology has been a valuable asset to neurologic surgery, contributing to lateralization and localization of pathologic brain tissue, identification of eloquent cortex, and evaluation of postoperative neuropsychological functioning. Moreover, neuropsychologists provide empirically driven interventions aimed at supporting preparation and/or recovery of neurosurgery patients. Nonetheless, several challenges may limit the reliability, validity, and generalizability of the assessment data obtained and reduce the usefulness of other neuropsychological services provided. Specifically, linguistic, cultural, educational, and other biases associated with demographic characteristics can lead to a narrowed view of an individual's life experiences, which must be confronted to fulfill the mission of ensuring that all patients have access to care that is appropriate to their needs. Instead of perceiving these challenges as insurmountable barriers, such issues can be viewed as opportunities to catalyze change and foster innovation for the future of neuropsychological care in neurosurgical settings. In addition to reviewing the possible mechanisms of these obstacles, the current article offers tangible solutions at both a macro level (e.g., discipline-wide transformations) and micro level (e.g., individualized patient-centric approaches). Outlined are practical techniques to potentially improve consensus and standardization of methods, advance and globalize research, expand representativeness of measures and practices to serve diverse individuals, and increase treatment adherence through engagement of patients and their families., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2023
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18. Innovations in Neuropsychology: Future Applications in Neurosurgical Patient Care.
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McLean E, Cornwell MA, Bender HA, Sacks-Zimmerman A, Mandelbaum S, Koay JM, Raja N, Kohn A, Meli G, and Spat-Lemus J
- Subjects
- Humans, Neurosurgical Procedures, Patient Care, Computers, Neuropsychology history
- Abstract
Over the last century, collaboration between clinical neuropsychologists and neurosurgeons has advanced the state of the science in both disciplines. These advances have provided the field of neuropsychology with many opportunities for innovation in the care of patients prior to, during, and following neurosurgical intervention. Beyond giving a general overview of how present-day advances in technology are being applied in the practice of neuropsychology within a neurological surgery department, this article outlines new developments that are currently unfolding. Improvements in remote platform, computer interface, "real-time" analytics, mobile devices, and immersive virtual reality have the capacity to increase the customization, precision, and accessibility of neuropsychological services. In doing so, such innovations have the potential to improve outcomes and ameliorate health care disparities., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2023
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19. Remdesivir treatment in hospitalized patients affected by COVID-19 pneumonia: A case-control study.
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Boglione L, Dodaro V, Meli G, Rostagno R, Poletti F, Moglia R, Bianchi B, Esposito M, and Borrè S
- Subjects
- Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Alanine therapeutic use, Antiviral Agents therapeutic use, Case-Control Studies, Humans, SARS-CoV-2, Treatment Outcome, COVID-19 Drug Treatment
- Abstract
To date the optimal antiviral treatment against severe coronavirus disease 2019 (COVID-19) has not been proven; remdesivir is a promising drug with in vitro activity against several viruses, but in COVID-19 the clinical results are currently not definitive. In this retrospective observational study, we analyzed the clinical outcomes (survival analysis, efficacy, and safety) in a group of hospitalized patients with COVID-19 treated with remdesivir in comparison with a control group of patients treated with other antiviral or supportive therapies. We included 163 patients treated with remdesivir and 403 subjects in the control group; the baseline characteristics were similar in the two groups; the mortality rate was higher in the control group (24.8% vs. 2.4%, p < 0.001), the risk of intensive care unit (ICU) admission was higher in the control group (17.8% vs. 9.8%, p = 0.008); hospitalization time was significantly lower in patients treated with remdesivir (9.5 vs. 12.5 days, p < 0.001). The safety of remdesivir was good and no significant adverse events were reported. In multivariate analysis, the remdesivir treatment was independently associated with a 34% lower mortality rate (odds ratio = 0.669; p = 0.014). In this analysis, the treatment with remdesivir was associated with lower mortality, lower rate of ICU admission, and shorter time of hospitalization. No adverse events were observed. This promising antiviral treatment should also be confirmed by other studies., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
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- 2022
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20. The development of ADAM10 endocytosis inhibitors for the treatment of Alzheimer's disease.
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Musardo S, Therin S, Pelucchi S, D'Andrea L, Stringhi R, Ribeiro A, Manca A, Balducci C, Pagano J, Sala C, Verpelli C, Grieco V, Edefonti V, Forloni G, Gardoni F, Meli G, Di Marino D, Di Luca M, and Marcello E
- Subjects
- ADAM10 Protein genetics, ADAM10 Protein metabolism, Amyloid Precursor Protein Secretases genetics, Amyloid beta-Protein Precursor metabolism, Animals, Disease Models, Animal, Endocytosis, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Mice, Transgenic, Synapses metabolism, Alzheimer Disease drug therapy, Alzheimer Disease metabolism
- Abstract
The development of new therapeutic avenues that target the early stages of Alzheimer's disease (AD) is urgently necessary. A disintegrin and metalloproteinase domain 10 (ADAM10) is a sheddase that is involved in dendritic spine shaping and limits the generation of amyloid-β. ADAM10 endocytosis increases in the hippocampus of AD patients, resulting in the decreased postsynaptic localization of the enzyme. To restore this altered pathway, we developed a cell-permeable peptide (PEP3) with a strong safety profile that is able to interfere with ADAM10 endocytosis, upregulating the postsynaptic localization and activity of ADAM10. After extensive validation, experiments in a relevant animal model clarified the optimal timing of the treatment window. PEP3 administration was effective for the rescue of cognitive defects in APP/PS1 mice only if administered at an early disease stage. Increased ADAM10 activity promoted synaptic plasticity, as revealed by changes in the molecular compositions of synapses and the spine morphology. Even though further studies are required to evaluate efficacy and safety issues of long-term administration of PEP3, these results provide preclinical evidence to support the therapeutic potential of PEP3 in AD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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21. Risk factors and incidence of long-COVID syndrome in hospitalized patients: does remdesivir have a protective effect?
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Boglione L, Meli G, Poletti F, Rostagno R, Moglia R, Cantone M, Esposito M, Scianguetta C, Domenicale B, Di Pasquale F, and Borrè S
- Subjects
- Adenosine Monophosphate analogs & derivatives, Alanine analogs & derivatives, Hospitalization, Humans, Incidence, Intensive Care Units, Prospective Studies, Risk Factors, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Adenosine Monophosphate therapeutic use, Alanine therapeutic use, COVID-19 complications, COVID-19 Drug Treatment
- Abstract
Background: The definition of 'long-COVID syndrome' (LCS) is still debated and describes the persistence of symptoms after viral clearance in hospitalized or non-hospitalized patients affected by coronavirus disease 2019 (COVID-19)., Aim: In this study, we examined the prevalence and the risk factors of LCS in a cohort of patients with previous COVID-19 and followed for at least 6 months of follow-up., Design: We conducted a prospective study including all hospitalized patients affected by COVID-19 at our center of Infectious Diseases (Vercelli, Italy) admitted between 10 March 2020 and 15 January 2021 for at least 6 months after discharge. Two follow-up visits were performed: after 1 and 6 months after hospital discharge. Clinical, laboratory and radiological data were recorded at each visit., Results: A total of 449 patients were included in the analysis. The LCS was diagnosed in 322 subjects at Visit 1 (71.7%) and in 206 at Visit 2 (45.9); according to the post-COVID-19 functional status scale we observed 147 patients with values 2-3 and 175 with values >3 at Visit 1; at Visit 2, 133 subjects had the score between 2-3 and 73 > 3. In multivariate analysis, intensive care unit (ICU) admission (OR = 2.551; 95% CI = 1.998-6.819; P = 0.019), time of hospitalization (OR = 2.255; 95% CI = 1.018-6.992; P = 0.016) and treatment with remdesivir (OR = 0.641; 95% CI = 0.413-0.782; P < 0.001) were independent predictors of LCS., Conclusions: Treatment with remdesivir leads to a 35.9% reduction in LCS rate in follow-up. Severity of illness, need of ICU admission and length of hospital stay were factor associated with the persistence of PCS at 6 months of follow-up., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
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22. Amyloid Β-Peptide Increases Mitochondria-Endoplasmic Reticulum Contact Altering Mitochondrial Function and Autophagosome Formation in Alzheimer's Disease-Related Models.
- Author
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Leal NS, Dentoni G, Schreiner B, Naia L, Piras A, Graff C, Cattaneo A, Meli G, Hamasaki M, Nilsson P, and Ankarcrona M
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- Aged, Aged, 80 and over, Alzheimer Disease physiopathology, Animals, Autophagosomes physiology, Brain metabolism, Brain physiopathology, Disease Models, Animal, Endoplasmic Reticulum physiology, Female, Homeostasis physiology, Humans, Male, Mice, Mice, Transgenic, Middle Aged, Mitochondrial Membrane Transport Proteins metabolism, Mitochondrial Membranes metabolism, Neurons metabolism, Neurons physiology, Up-Regulation physiology, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Autophagosomes metabolism, Endoplasmic Reticulum metabolism, Mitochondria metabolism, Mitochondria physiology
- Abstract
Recent findings have shown that the connectivity and crosstalk between mitochondria and the endoplasmic reticulum (ER) at mitochondria-ER contact sites (MERCS) are altered in Alzheimer's disease (AD) and in AD-related models. MERCS have been related to the initial steps of autophagosome formation as well as regulation of mitochondrial function. Here, the interplay between MERCS, mitochondria ultrastructure and function and autophagy were evaluated in different AD animal models with increased levels of Aβ as well as in primary neurons derived from these animals. We start by showing that the levels of Mitofusin 1, Mitofusin 2 and mitochondrial import receptor subunit TOM70 are decreased in post-mortem brain tissue derived from familial AD. We also show that Aβ increases the juxtaposition between ER and mitochondria both in adult brain of different AD mouse models as well as in primary cultures derived from these animals. In addition, the connectivity between ER and mitochondria are also increased in wild-type neurons exposed to Aβ. This alteration in MERCS affects autophagosome formation, mitochondrial function and ATP formation during starvation. Interestingly, the increment in ER-mitochondria connectivity occurs simultaneously with an increase in mitochondrial activity and is followed by upregulation of autophagosome formation in a clear chronological sequence of events. In summary, we report that Aβ can affect cell homeostasis by modulating MERCS and, consequently, altering mitochondrial activity and autophagosome formation. Our data suggests that MERCS is a potential target for drug discovery in AD.
- Published
- 2020
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23. Computational Modeling of Inhibitory Transsynaptic Signaling in Hippocampal and Cortical Neurons Expressing Intrabodies Against Gephyrin.
- Author
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Lupascu CA, Morabito A, Ruggeri F, Parisi C, Pimpinella D, Pizzarelli R, Meli G, Marinelli S, Cherubini E, Cattaneo A, and Migliore M
- Abstract
GABAergic transmission regulates neuronal excitability, dendritic integration of synaptic signals and oscillatory activity, thought to be involved in high cognitive functions. By anchoring synaptic receptors just opposite to release sites, the scaffold protein gephyrin plays a key role in these tasks. In addition, by regulating GABA
A receptor trafficking, gephyrin contributes to maintain, at the network level, an appropriate balance between Excitation (E) and Inhibition (I), crucial for information processing. An E/I imbalance leads to neuropsychiatric disorders such as epilepsy, schizophrenia and autism. In this article, we exploit a previously published computational method to fit spontaneous synaptic events, using a simplified model of the subcellular pathways involving gephyrin at inhibitory synapses. The model was used to analyze experimental data recorded under different conditions, with the main goal to gain insights on the possible consequences of gephyrin block on IPSCs. The same approach can be useful, in general, to analyze experiments designed to block a single protein. The results suggested possible ways to correlate the changes observed in the amplitude and time course of individual events recorded after different experimental protocols with the changes that may occur in the main subcellular pathways involved in gephyrin-dependent transsynaptic signaling., (Copyright © 2020 Lupascu, Morabito, Ruggeri, Parisi, Pimpinella, Pizzarelli, Meli, Marinelli, Cherubini, Cattaneo and Migliore.)- Published
- 2020
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24. Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers.
- Author
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Scopa C, Marrocco F, Latina V, Ruggeri F, Corvaglia V, La Regina F, Ammassari-Teule M, Middei S, Amadoro G, Meli G, Scardigli R, and Cattaneo A
- Subjects
- Animals, Cell Differentiation, Cell Proliferation, Humans, Mice, Transgenic, Microtubules metabolism, Neural Stem Cells metabolism, Neurons pathology, Olfactory Bulb metabolism, Protein Conformation, Alzheimer Disease complications, Amyloid beta-Peptides chemistry, Amyloid beta-Peptides metabolism, Intracellular Space metabolism, Nerve Degeneration complications, Neurogenesis, Protein Multimerization
- Abstract
Alterations of adult neurogenesis have been reported in several Alzheimer's disease (AD) animal models and human brains, while defects in this process at presymptomatic/early stages of AD have not been explored yet. To address this, we investigated potential neurogenesis defects in Tg2576 transgenic mice at 1.5 months of age, a prodromal asymptomatic age in terms of Aβ accumulation and neurodegeneration. We observe that Tg2576 resident and SVZ-derived adult neural stem cells (aNSCs) proliferate significantly less. Further, they fail to terminally differentiate into mature neurons due to pathological, tau-mediated, and microtubule hyperstabilization. Olfactory bulb neurogenesis is also strongly reduced, confirming the neurogenic defect in vivo. We find that this phenotype depends on the formation and accumulation of intracellular A-beta oligomers (AβOs) in aNSCs. Indeed, impaired neurogenesis of Tg2576 progenitors is remarkably rescued both in vitro and in vivo by the expression of a conformation-specific anti-AβOs intrabody (scFvA13-KDEL), which selectively interferes with the intracellular generation of AβOs in the endoplasmic reticulum (ER). Altogether, our results demonstrate that SVZ neurogenesis is impaired already at a presymptomatic stage of AD and is caused by endogenously generated intracellular AβOs in the ER of aNSCs. From a translational point of view, impaired SVZ neurogenesis may represent a novel biomarker for AD early diagnosis, in association to other biomarkers. Further, this study validates intracellular Aβ oligomers as a promising therapeutic target and prospects anti-AβOs scFvA13-KDEL intrabody as an effective tool for AD treatment.
- Published
- 2020
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25. Breast implant-associated anaplastic large cell lymphoma with lymph node localization: case report and review of literature.
- Author
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Broggi G, Motta F, Angilello A, Bortolussi C, Meli G, Magro G, and Vecchio GM
- Subjects
- Adult, Breast Neoplasms surgery, Female, Humans, Lymphoma, Large-Cell, Anaplastic surgery, Breast Implantation adverse effects, Breast Implants adverse effects, Breast Neoplasms etiology, Breast Neoplasms pathology, Lymphoma, Large-Cell, Anaplastic etiology, Lymphoma, Large-Cell, Anaplastic pathology
- Published
- 2019
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26. Activity-Induced Amyloid-β Oligomers Drive Compensatory Synaptic Rearrangements in Brain Circuits Controlling Memory of Presymptomatic Alzheimer's Disease Mice.
- Author
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Pignataro A, Meli G, Pagano R, Fontebasso V, Battistella R, Conforto G, Ammassari-Teule M, and Middei S
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- Animals, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neuronal Plasticity, Alzheimer Disease physiopathology, Brain physiopathology, Dendritic Spines physiology, Fear physiology, Memory, Neural Pathways physiopathology
- Abstract
Background: A consistent proportion of individuals at risk for Alzheimer's disease show intact cognition regardless of the extensive accumulation of amyloid-β (Aβ) peptide in their brain. Several pieces of evidence indicate that overactivation of brain regions negative for Aβ can compensate for the underactivation of Aβ-positive ones to preserve cognition, but the underlying synaptic changes are still unexplored., Methods: Using Golgi staining, we investigate how dendritic spines rearrange following contextual fear conditioning (CFC) in the hippocampus and amygdala of presymptomatic Tg2576 mice, a genetic model for Aβ accumulation. A molecular biology approach combined with intrahippocampal injection of a γ-secretase inhibitor evaluates the impact of Aβ fluctuations on spine rearrangements., Results: Encoding of CFC increases Aβ oligomerization in the hippocampus but not in the amygdala of Tg2576 mice. The presence of Aβ oligomers predicts vulnerability to network dysfunctions, as low c-Fos activation and spine maturation are detected in the hippocampus of Tg2576 mice upon recall of CFC memory. Rather, enhanced c-Fos activation and new spines are evident in the amygdala of Tg2576 mice compared with wild-type control mice. Preventing Aβ increase in the hippocampus of Tg2576 mice restores CFC-associated spine changes to wild-type levels in both the hippocampus and amygdala., Conclusions: Our study provides the first evidence of neural compensation consisting of enhanced synaptic activity in brain regions spared by Aβ load. Furthermore, it unravels an activity-mediated feedback loop through which neuronal activation during CFC encoding favors Aβ oligomerization in the hippocampus and prevents synaptic rearrangements in this region., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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27. Sample path properties of the average generation of a Bellman-Harris process.
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Meli G, Weber TS, and Duffy KR
- Subjects
- Algorithms, Cell Culture Techniques, Cell Death genetics, Cell Proliferation genetics, Computer Simulation, Intravital Microscopy, Telomere Homeostasis genetics, Time-Lapse Imaging, Cell Differentiation genetics, DNA Replication, Models, Genetic
- Abstract
Motivated by a recently proposed design for a DNA coded randomised algorithm that enables inference of the average generation of a collection of cells descendent from a common progenitor, here we establish strong convergence properties for the average generation of a super-critical Bellman-Harris process. We further extend those results to a two-type Bellman-Harris process where one type can give rise to the other, but not vice versa. These results further affirm the estimation method's potential utility by establishing its long run accuracy on individual sample-paths, and significantly expanding its remit to encompass cellular development that gives rise to differentiated offspring with distinct population dynamics.
- Published
- 2019
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28. NGF steers microglia toward a neuroprotective phenotype.
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Rizzi C, Tiberi A, Giustizieri M, Marrone MC, Gobbo F, Carucci NM, Meli G, Arisi I, D'Onofrio M, Marinelli S, Capsoni S, and Cattaneo A
- Subjects
- Amyloid beta-Peptides metabolism, Animals, Brain cytology, Brain metabolism, CX3C Chemokine Receptor 1 genetics, CX3C Chemokine Receptor 1 metabolism, Cells, Cultured, Coculture Techniques, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Male, Mice, Inbred C57BL, Mice, Transgenic, Microglia cytology, Nerve Growth Factor administration & dosage, Neurons cytology, Neurons metabolism, Phagocytosis physiology, Receptors, Nerve Growth Factor antagonists & inhibitors, Synaptic Transmission physiology, Tissue Culture Techniques, Transcriptome, Microglia metabolism, Nerve Growth Factor metabolism, Neuroprotection physiology, Receptors, Nerve Growth Factor metabolism
- Abstract
Microglia are the sentinels of the brain but a clear understanding of the factors that modulate their activation in physiological and pathological conditions is still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on microglia by steering them toward a neuroprotective and anti-inflammatory phenotype. We show that microglial cells express functional NGF receptors in vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia, NGF treatment leads to a modulation of motility, phagocytosis and degradation pathways. At the functional level, NGF induces an increase in membrane dynamics and macropinocytosis and, in vivo, it activates an outward rectifying current that appears to modulate glutamatergic neurotransmission in nearby neurons. Since microglia are supposed to be a major player in Aβ peptide clearance in the brain, we tested the effects of NGF on its phagocytosis. NGF was shown to promote TrkA-mediated engulfment of Aβ by microglia, and to enhance its degradation. Additionally, the proinflammatory activation induced by Aβ treatment is counteracted by the concomitant administration of NGF. Moreover, by acting specifically on microglia, NGF protects neurons from the Aβ-induced loss of dendritic spines and inhibition of long term potentiation. Finally, in an ex-vivo setup of acute brain slices, we observed a similar increase in Aβ engulfment by microglial cells under the influence of NGF. Our work substantiates a role for NGF in the regulation of microglial homeostatic activities and points toward this neurotrophin as a neuroprotective agent in Aβ accumulation pathologies, via its anti-inflammatory activity on microglia., (© 2018 The Authors GLIA Published by Wiley Periodicals, Inc.)
- Published
- 2018
- Full Text
- View/download PDF
29. [Trazodone prolonged release in bipolar disorder II-obsessive-compulsive disorder comorbidity: a case report].
- Author
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Lorettu L, Meli G, Antonioli E, Zeppa A, Milia P, and Nivoli A
- Subjects
- Adult, Bipolar Disorder complications, Bipolar Disorder diagnosis, Comorbidity, Humans, Obsessive-Compulsive Disorder complications, Obsessive-Compulsive Disorder diagnosis, Treatment Outcome, Anti-Anxiety Agents therapeutic use, Bipolar Disorder drug therapy, Obsessive-Compulsive Disorder drug therapy, Trazodone therapeutic use
- Abstract
Approximately 21% of patients with bipolar disorder (BD) also have an additional diagnosis of obsessive-compulsive disorder (OCD). This condition is associated with a more severe prognosis and complicates the treatment of BD. In our case report we provide documentary evidence of our experience with trazodone prolonged release in the treatment of depressive phase in a patient with BD II-OCD comorbidity. Rationality in the choise of treatment was based on the need to manage depressive and obsessive symptoms without facilitating hypomania switches.
- Published
- 2017
- Full Text
- View/download PDF
30. The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.
- Author
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Capsoni S, Malerba F, Carucci NM, Rizzi C, Criscuolo C, Origlia N, Calvello M, Viegi A, Meli G, and Cattaneo A
- Subjects
- Administration, Intranasal, Animals, Behavior, Animal, Cerebral Cortex drug effects, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Nerve Growth Factor administration & dosage, Nerve Growth Factor adverse effects, Receptors, CXCR4 antagonists & inhibitors, Alzheimer Disease drug therapy, Cerebral Cortex metabolism, Chemokine CXCL12 metabolism, Memory Disorders drug therapy, Nerve Growth Factor pharmacology, Neuronal Plasticity drug effects, Pain chemically induced, Plaque, Amyloid drug therapy
- Abstract
Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)
- Published
- 2017
- Full Text
- View/download PDF
31. An unusual cause of anemia in cirrhosis: spur cell anemia, a case report with review of literature.
- Author
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Privitera G and Meli G
- Abstract
Chronic anemia is common in liver cirrhosis. In this setting, the pathogenesis of anemia is complex and multifactorial. Spur cell anemia is a serious disorder in cirrhotic patients and is associated with poor prognosis. Liver transplantation constitutes the only therapeutic tool. We report a case with severe spur cell anemia in alcoholic liver cirrhosis. In the attempt to investigate the origin of the disorder, we have evaluated the lipoprotein profile and found a significant reduction of apolipoprotein AI and HDL
3 subclass as a possible cause of the disease.- Published
- 2016
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