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Search Results: 1 - 10 of 6861 matches for " Paolo Livrea "
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CDK5 Is Essential for Soluble Amyloid β-Induced Degradation of GKAP and Remodeling of the Synaptic Actin Cytoskeleton
Francesco Roselli, Paolo Livrea, Osborne F. X. Almeida
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023097
Abstract: The early stages of Alzheimer's disease are marked by synaptic dysfunction and loss. This process results from the disassembly and degradation of synaptic components, in particular of scaffolding proteins that compose the post-synaptic density (PSD), namely PSD95, Homer and Shank. Here we investigated in rat frontal cortex dissociated culture the mechanisms involved in the downregulation of GKAP (SAPAP1), which links the PSD95 complex to the Shank complex and cytoskeletal structures within the PSD. We show that Aβ causes the rapid loss of GKAP from synapses through a pathway that critically requires cdk5 activity, and is set in motion by NMDAR activity and Ca2+ influx. We show that GKAP is a direct substrate of cdk5 and that its phosphorylation results in polyubiquitination and proteasomal degradation of GKAP and remodeling (collapse) of the synaptic actin cytoskeleton; the latter effect is abolished in neurons expressing GKAP mutants that are resistant to phosphorylation by cdk5. Given that cdk5 also regulates degradation of PSD95, these results underscore the central position of cdk5 in mediating Aβ-induced PSD disassembly and synapse loss.
Disassembly of Shank and Homer Synaptic Clusters Is Driven by Soluble β-Amyloid1-40 through Divergent NMDAR-Dependent Signalling Pathways
Francesco Roselli, Peter Hutzler, Yvonne Wegerich, Paolo Livrea, Osborne F. X. Almeida
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006011
Abstract: Disruption of the postsynaptic density (PSD), a network of scaffold proteins located in dendritic spines, is thought to be responsible for synaptic dysfunction and loss in early-stage Alzheimer's disease (AD). Extending our previous demonstration that derangement of the PSD by soluble amyloid-β (Aβ) involves proteasomal degradation of PSD-95, a protein important for ionotropic glutamate receptor trafficking, we now show that Aβ also disrupts two other scaffold proteins, Homer1b and Shank1, that couple PSD-95 with ionotropic and metabotropic glutamate receptors. Treatment of fronto-cortical neurons with soluble Aβ results in rapid (within 1 h) and significant thinning of the PSD, decreased synaptic levels of Homer1b and Shank1, and reduced synaptic mGluR1 levels. We show that de novo protein synthesis is required for the declustering effects of Aβ on Homer1b (but not Shank1) and that, in contrast to PSD-95, Aβ-induced Homer1b and Shank1 cluster disassembly does not depend on proteasome activity. The regulation of Homer1b and Shank1 by Aβ diverges in two other respects: i) whereas the activity of both NMDAR and VDCC is required for Aβ-induced declustering of Homer1b, Aβ-induced declustering of Shank1 only requires NMDAR activity; and ii) whereas the effects of Aβ on Homer1b involve engagement of the PI-3K pathway and calcineurin phosphatase (PP2B) activity, those on Shank1 involve activation of the ERK pathway. In summary, soluble Aβ recruits discrete signalling pathways to rapidly reduce the synaptic localization of major components of the PSD and to regulate the availability of mGluR1 in the synapse.
Virtual Visual Effect of Hospital Waiting Room on Pain Modulation in Healthy Subjects and Patients with Chronic Migraine
Marina de Tommaso,Katia Ricci,Luigi Laneve,Nicola Savino,Vincenzo Antonaci,Paolo Livrea
Pain Research and Treatment , 2013, DOI: 10.1155/2013/515730
Abstract: Environmental context has an important impact on health and well being. We aimed to test the effects of a visual distraction induced by classical hospital waiting room (RH) versus an ideal room with a sea view (IH), both represented in virtual reality (VR), on subjective sensation and cortical responses induced by painful laser stimuli (LEPs) in healthy volunteers and patients with chronic migraine (CM). Sixteen CM and 16 controls underwent 62 channels LEPs from the right hand, during a fully immersive VR experience, where two types of waiting rooms were simulated. The RH simulated a classical hospital waiting room while the IH represented a room with sea viewing. CM patients showed a reduction of laser pain rating and vertex LEPs during the IH vision. The sLORETA analysis confirmed that in CM patients the two VR simulations induced a different modulation of bilateral parietal cortical areas (precuneus and superior parietal lobe), and superior frontal and cingulate girus, in respect to controls. The architectural context may interfere with pain perception, depending upon the status of subject. Many variables may change patients’ outcome and support the use of VR technology to test the best conditions for their management. 1. Introduction Pain is a complex function of the human brain, involving attention and emotions [1, 2]. The process of distraction appears to involve competition for attention between a highly salient sensation (pain) and consciously directed focus on some other information processing activity. In fact, the neuronal network, devoted to painful inputs elaboration, is not nociceptive specific, similar activations being produced by relevant tactile, auditory, and visual stimuli [3, 4]. The multisensory nature of this network makes it a likely candidate for cross-modal modulation of pain [5]. In this sense, growing interest exists toward virtual reality (VR) technology, which is based on integrating multimodal (visual, auditory, tactile, and olfactory) sensory distractions [6]. Virtual reality (VR) is as effective in inducing emotional responses as reality and its application is extremely valuable in exposure treatment [7]. In fact, in virtual environments, the patients experience similar physiological symptoms as they do in real life situations, so virtual models can be employed to test how the ambient of real life could possibly interfere with pain modulation. Presently there is a growing body of evidence on the impact of the environment on health and well-being, and some aspects of hospital rooms have been studied as “positive
Intra-oral orthosis vs amitriptyline in chronic tension-type headache: a clinical and laser evoked potentials study
Marina de Tommaso, Elliott Shevel, Carla Pecoraro, Michele Sardaro, Daniela Divenere, Olimpia Di fruscolo, Paolo Lamberti, Paolo Livrea
Head & Face Medicine , 2006, DOI: 10.1186/1746-160x-2-15
Abstract: Eighteen patients with diagnosed CTTH participated in this open label, controlled study. A baseline evaluation was performed for clinical features, Total Tenderness Score (TTS) and a topographic analysis of LEPs obtained manually and the pericranial points stimulation in all patients vs. healthy subjects. Thereafter, patients were randomly assigned to a two-month treatment by either amitriptyline or intra-oral appliance.Both the intra-oral appliance and amitriptyline significantly reduced headache frequency. The TTS was significantly reduced in the group treated with the appliance. The amplitude of P2 response elicited by stimulation of pericranial zones showed a reduction after amitriptyline treatment.Both therapies were effective in reducing headache severity, the appliance with a prevalent action on the pericranial muscular tenderness, amitriptyline reducing the activity of the central cortical structures subtending pain elaborationThe results of this study may suggest that in CTTH both the interventions at the peripheral and central levels improve the outcome of headache.Although tension-type headache is the most common type of primary headache, its pathophysiology is poorly understood. The best documented abnormality in patients with tension type headache is increased pericranial myofascial tenderness [1,2]. Pericranial tenderness has been shown to be positively associated with both the intensity and the frequency of tension type headache [2,3]. It is generally accepted that myofascial tenderness probably plays a key role in the pathophysiology of tension type headache. Recently, a pathophysiological model for tension type headache has been proposed. Accordingly, the main problem is central sensitization at the level of the spinal dorsal horn/trigeminal nucleus, resulting from prolonged nociceptive inputs from pericranial myofascial tissues. This central sensitization is posited to cause supraspinal sensitization and central neuroplastic changes, that possibly
Low Serum Urate Levels Are Associated to Female Gender in Multiple Sclerosis Patients
Stefano Zoccolella, Carla Tortorella, Pietro Iaffaldano, Vita Direnzo, Mariangela D’Onghia, Elena Luciannatelli, Damiano Paolicelli, Paolo Livrea, Maria Trojano
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040608
Abstract: Background Urate is a natural antioxidant and may prevent CNS tissue damage and the clinical manifestations of experimental autoimmune encephalitis. Results from clinical studies are conflicting and the contribution of urate to the pathogenesis of Multiple Sclerosis (MS) remains uncertain. Objective To evaluate serum urate levels in MS patients and their relationships with clinical, demographic and MRI variables. Methods Levels of non-fasting serum uric acid and creatinine were determined by an automated enzymatic assay and glomerular filtration rate was assessed in 245 MS patients, in 252 age/sex-matched neurological controls (NC) and in 59 Healthy controls (HC). Results Median serum urate levels did not differ between MS patients (3.8 mg/dL), HC (4.0 mg/dl) and NC (4.0 mg/dL). Serum urate levels were lower in females than in males in all groups (p = <0.0001). In female-MS, serum urate levels (3.2 mg/dL) were lower compared to those in female HC (3.8; p = 0.01) and NC (3.5 mg/dL; p = 0.02), whereas in male-MS they(4.8 mg/dL) did not differ from those in male HC (4.5 mg/dl) and NC (4.8 mg/dL). Urate concentrations trended to be lower in Clinically isolated syndromes suggestive of MS (3.7 mg/dL) and in relapsing MS (3.7 mg/dL), compared to patients with progressive MS (4.4 mg/dL; p = 0.06), and in patients with an annual relapse rate (ARR) >2 (3.3 mg/dL) than in those with an ARR ≤2: 3.9 mg/dL; p = 0.05). Significant lower serum urate levels were found in females than in males in all clinical MS subtypes (p<0.01), separately evaluated. Female sex (beta: ?0.53; p<0.00001) was the most significant determinant of serum urate concentrations in MS patients on multivariate regression analysis. Conclusions Our findings suggest that low urate levels could be of significance in predominantly inflammatory phases of MS even at the early stage and mainly in females.
Existence of three periodic solutions for a non-autonomous second order system
Giuseppina Barletta,Roberto Livrea
Le Matematiche , 2002,
Abstract: The purpose of the present paper is to establish a multiplicity result for some differencial system.
Periodic solutions for a class of second-order Hamiltonian systems
Gabriele Bonanno,Roberto Livrea
Electronic Journal of Differential Equations , 2005,
Abstract: Multiplicity results for an eigenvalue second-order Hamiltonian system are investigated. Using suitable critical points arguments, the existence of an exactly determined open interval of positive eigenvalues for which the system admits at least three distinct periodic solutions is established. Moreover, when the energy functional related to the Hamiltonian system is not coercive, an existence result of two distinct periodic solutions is given.
Influence of Interferon beta treatment on quality of life in multiple sclerosis patients
Isabella Simone, Antonia Ceccarelli, Carla Tortorella, Alessandra Bellacosa, Fabio Pellegrini, Immacolata Plasmati, Maria De Caro, Mariangela Lopez, Francesco Girolamo, Paolo Livrea
Health and Quality of Life Outcomes , 2006, DOI: 10.1186/1477-7525-4-96
Abstract: Seventy-seven disease modifying treatment (DMT) free and 41 IFN-β treated MS patients were evaluated. QoL, assessed by MSQoL-54, was related to IFN-β treatment and to clinical and demographic parameters at baseline and after two years. Multivariate hierarchical linear model for repeated measurements was used.Treated patients showed a younger age, a lower disease duration and a higher relapse rate in the two years preceding study entry. At inclusion time treated and untreated patients did not differ in relapse rate, expanded disability status scale (EDSS), fatigue, depression, physical and mental QoL. IFN-β did not influence QoL at inclusion time, but when QoL was evaluated after two years, treatment negatively affected mental QoL. Depression and fatigue negatively influenced physical and mental QoL both at baseline and after two years. EDSS correlated with a poor physical QoL only at baseline.IFN-β had a negative impact on QoL over the time in MS patients, influencing mainly mental QoL. The impairment of QoL in MS was strongly associated with increasing fatigue and depression, whereas clinical disability had a minor unfavourable role.In the last years increasing interest focused on QoL instrument as a broader measure of the burden of MS. Recent studies reported that QoL assessment may provide unique information often underestimated by the EDSS [1-3], which remains to date the primary clinical outcome measure for MS related disability [4]. Several factors may influence the QoL in MS patients. Previous studies showed varying results on the relationship between neurological disability and impaired QoL, suggesting only a partial contribute of disability on QoL. On the contrary fatigue and depression are highly associated to a poor QoL [5-11].Although the QoL instrument is recommended as an outcome measure of therapeutic choices and treatment effectiveness, its use is still limited in the routine clinical approaches [12]. Patient's perspectives derived from lifelong trea
Periodic solutions for second order Hamiltonian systems
Giuseppina D'Aguì,Roberto Livrea
Le Matematiche , 2011,
Abstract: In this paper we present some recent multiplicity results for a class of second order Hamiltonian systems. Exploiting the variational structure of the problem, it will be shown how the existence of multiple, even infinitely many, periodic solutions can be assured.
A Field Experiment on the Recurrence of Large Waves in Wind Seas  [PDF]
Paolo Boccotti
Open Journal of Marine Science (OJMS) , 2011, DOI: 10.4236/ojms.2011.13007
Abstract: Wind generated sea waves are generally regarded as an example of pure randomness in nature. Here we give a proof that the matter is not exactly so: some identical sequences of relatively large waves were found many hours apart from one another. This finding supports the theory of quasi determinism of sea waves.
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