IMT Institutional Repository: No conditions. Results ordered -Date Deposited. 2024-03-28T22:24:03ZEPrintshttp://eprints.imtlucca.it/images/logowhite.pnghttp://eprints.imtlucca.it/2018-03-09T13:10:49Z2018-03-09T13:10:49Zhttp://eprints.imtlucca.it/id/eprint/3996This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/39962018-03-09T13:10:49ZComplexity in Neural and Financial Systems: From Time-Series to Networks (editorial)Tiziano Squartinitiziano.squartini@imtlucca.itAndrea GabrielliDiego Garlaschellidiego.garlaschelli@imtlucca.itTommaso GiliAngelo BifoneFabio Caccioli2017-01-16T08:16:29Z2017-01-16T08:16:29Zhttp://eprints.imtlucca.it/id/eprint/3627This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/36272017-01-16T08:16:29ZMolecularly Imprinted Biodegradable NanoparticlesBiodegradable polymer nanoparticles are promising carriers for targeted drug delivery in nanomedicine applications. Molecu- lar imprinting is a potential strategy to target polymer nanoparticles through binding of endogenous ligands that may promote recognition and active transport into specific cells and tissues. However, the lock-and-key mechanism of molecular imprinting requires relatively rigid cross-linked structures, unlike those of many biodegradable polymers. To date, no fully biodegradable molecularly imprinted particles have been reported in the literature. This paper reports the synthesis of a novel molecularly- imprinted nanocarrier, based on poly(lactide-co-glycolide) (PLGA) and acrylic acid, that combines biodegradability and molec- ular recognition properties. A novel three-arm biodegradable cross-linker was synthesized by ring-opening polymerization of glycolide and lactide initiated by glycerol. The resulting macromer was functionalized by introduction of end-functions through reaction with acryloyl chloride. Macromer and acrylic acid were used for the synthesis of narrowly-dispersed nanoparticles by radical polymerization in diluted conditions in the presence of biotin as template molecule. The binding capacity of the imprinted nanoparticles towards biotin and biotinylated bovine serum albumin was twentyfold that of non-imprinted nanoparti- cles. Degradation rates and functional performances were assessed in in vitro tests and cell cultures, demonstrating effective biotin-mediated cell internalization.Mariacristina Gagliardimariacristina.gagliardi@imtlucca.itAlice BerteroAngelo Bifone2016-10-04T11:13:27Z2016-10-04T11:13:27Zhttp://eprints.imtlucca.it/id/eprint/3553This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/35532016-10-04T11:13:27ZHierarchical organization of functional connectivity in the mouse brain: a complex network approachThis paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.Giampiero BardellaAngelo BifoneAndrea GabrielliAlessandro GozziTiziano Squartinitiziano.squartini@imtlucca.it2016-03-21T09:44:02Z2016-03-21T09:44:02Zhttp://eprints.imtlucca.it/id/eprint/3252This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/32522016-03-21T09:44:02ZPolymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNSPolymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modified for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood–brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications.Mariacristina Gagliardimariacristina.gagliardi@imtlucca.itGiuseppe BardiAngelo Bifone2016-03-21T09:38:57Z2016-03-21T09:38:57Zhttp://eprints.imtlucca.it/id/eprint/3251This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/32512016-03-21T09:38:57ZSurface functionalisation regulates polyamidoamine dendrimer toxicity on blood–brain barrier cells and the modulation of key inflammatory receptors on microgliaAbstractDendrimers are branched polymers with spherical morphology. Their tuneable chemistry and surface modification make them valuable nanomaterials for biomedical applications. In view of possible dendrimer uses as brain-aimed nanocarriers, the authors studied amine- and lipid-functionalised (G4) polyamidoamine (PAMAM) biocompatibility with cell population forming the blood–brain barrier (BBB). Both amine-PAMAM and lipid-PAMAM dendrimers were able to enter endothelial and primary neural cells. However, only amine-PAMAM damaged cell membranes in a dose-dependent manner. Transmission electron microscopy evidenced the ability of dendrimers to precipitate salts and serum components present in culture medium that slightly increased toxicity of the amine-PAMAM. Amine- and lipid-PAMAM were both able to cross the BBB and differently induced CD11b and CCR2 overexpression on primary CX3CR1-GFP murine microglia in vitro. These data emphasise the role of dendrimer surface functionalisation in toxicity and neural immune cell activation, raising concerns about possible neuroinflammatory reactions.Alice BerteroAdriano BoniMauro GemmiMariacristina Gagliardimariacristina.gagliardi@imtlucca.itAngelo BifoneGiuseppe Bardi2016-03-21T09:18:54Z2016-03-21T09:20:12Zhttp://eprints.imtlucca.it/id/eprint/3246This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/32462016-03-21T09:18:54ZChemical synthesis of a biodegradable PEGylated copolymer from ε-caprolactone and γ-valerolactone: evaluation of reaction and functional propertiesThis paper reports the chemical synthesis of methoxy poly(ethyleneglycol)-block-poly(ε-caprolactone-co-4-hydroxyvalerate) from ε-caprolactone and γ-valerolactone, a five-membered ring rarely used in chemical synthesis due to its low reactivity. This procedure enabled production of copolymers with controlled ratios of repeating units and molecular weights, as demonstrated by GPC, FT-IR and NMR characterization. Copolymer degradation rate was found to depend on macromolecular composition, and finely tuneable in a wide range of values. Similarly, hydrophilicity was dependent on γ-valerolactone content, and could be accurately controlled by varying the composition of the reaction feed. Importantly, this copolymer showed lower levels of acidic degradation products than other biodegradable polymers, thus resulting in improved biocompatibility. These encouraging results demonstrate the feasibility of the chemical synthesis of a novel and versatile material with interesting properties that fill a gap in the range of commercially available biodegradable polymers.Mariacristina Gagliardimariacristina.gagliardi@imtlucca.itFederica MicheleBarbara MazzolaiAngelo Bifone2016-03-21T09:02:41Z2016-03-21T09:19:23Zhttp://eprints.imtlucca.it/id/eprint/3243This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/32432016-03-21T09:02:41ZA poly(ether-ester) copolymer for the preparation of nanocarriers with improved degradation and drug delivery kineticsAbstract This paper reports the synthesis and the physicochemical, functional and biological characterisations of nanocarriers made of a novel di-block biodegradable poly(ether-ester) copolymer. This material presents tunable, fast biodegradation rates, but its products are less acidic than those of other biosorbable polymers like PLGA, thus presenting a better biocompatibility profile and the possibility to carry pH-sensitive payloads. A method for the production of monodisperse and spherical nanoparticles is proposed; drug delivery kinetics and blood protein adsorption were measured to evaluate the functional properties of these nanoparticles as drug carriers. The copolymer was labelled with a fluorescent dye for internalisation tests, and rhodamine B was used as a model cargo to study transport and release inside cultured cells. Biological tests demonstrated good cytocompatibility, significant cell internalisation and the possibility to vehiculate non-cell penetrating moieties into endothelial cells. Taken together, these results support the potential use of this nanoparticulate system for systemic administration of drugs.Mariacristina Gagliardimariacristina.gagliardi@imtlucca.itAlice BerteroGiuseppe BardiAngelo Bifone2016-02-11T15:16:10Z2016-04-06T10:06:34Zhttp://eprints.imtlucca.it/id/eprint/3055This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/30552016-02-11T15:16:10ZLarge-scale analysis of neuroimaging data on commercial clouds with content-aware resource allocation strategieThe combined use of mice that have genetic mutations (transgenic mouse models) of human pathology and advanced neuroimaging methods (such as magnetic resonance imaging) has the potential to radically change how we approach disease understanding, diagnosis and treatment. Morphological changes occurring in the brain of transgenic animals as a result of the interaction between environment and genotype can be assessed using advanced image analysis methods, an effort described as ‘mouse brain phenotyping’. However, the computational methods involved in the analysis of high-resolution brain images are demanding. While running such analysis on local clusters is possible, not all users have access to such infrastructure and even for those that do, having additional computational capacity can be beneficial (e.g. to meet sudden high throughput demands). In this paper we use a commercial cloud platform for brain neuroimaging and analysis. We achieve a registration-based multi-atlas, multi-template anatomical segmentation, normally a lengthy-in-time effort, within a few hours. Naturally, performing such analyses on the cloud entails a monetary cost, and it is worthwhile identifying strategies that can allocate resources intelligently. In our context a critical aspect is the identification of how long each job will take. We propose a method that estimates the complexity of an image-processing task, a registration, using statistical moments and shape descriptors of the image content. We use this information to learn and predict the completion time of a registration. The proposed approach is easy to deploy, and could serve as an alternative for laboratories that may require instant access to large high-performance-computing infrastructures. To facilitate adoption from the community we publicly release the source code.Massimo Minervinimassimo.minervini@imtlucca.itCristian RusuMario DamianoValter TucciAngelo BifoneAlessandro GozziSotirios A. Tsaftarissotirios.tsaftaris@imtlucca.it2014-03-27T09:30:26Z2016-04-05T12:01:10Zhttp://eprints.imtlucca.it/id/eprint/2182This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/21822014-03-27T09:30:26ZCOMT Genetic Reduction Produces Sexually Divergent Effects on Cortical Anatomy and Working Memory in Mice and HumansGenetic variations in catechol-O-methyltransferase (COMT) that modulate cortical dopamine have been associated with pleiotropic behavioral effects in humans and mice. Recent data suggest that some of these effects may vary among sexes. However, the specific brain substrates underlying COMT sexual dimorphisms remain unknown. Here, we report that genetically driven reduction in COMT enzyme activity increased cortical thickness in the prefrontal cortex (PFC) and postero-parieto-temporal cortex of male, but not female adult mice and humans. Dichotomous changes in PFC cytoarchitecture were also observed: reduced COMT increased a measure of neuronal density in males, while reducing it in female mice. Consistent with the neuroanatomical findings, COMT-dependent sex-specific morphological brain changes were paralleled by divergent effects on PFC-dependent working memory in both mice and humans. These findings emphasize a specific sex–gene interaction that can modulate brain morphological substrates with influence on behavioral outcomes in healthy subjects and, potentially, in neuropsychiatric populations. Sara SanninoAlessandro GozziAntonio CerasaFabrizio PirasDiego ScheggiaFrancesca ManagoMario DamianoAlberto GalbuseraLucy C. EricksonDavide De Pietri TonelliAngelo BifoneSotirios A. Tsaftarissotirios.tsaftaris@imtlucca.itCarlo CaltagironeDaniel R. WeinbergerGianfranco SpallettaFrancesco Papaleo2013-11-20T11:52:55Z2014-12-11T13:31:29Zhttp://eprints.imtlucca.it/id/eprint/1919This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/19192013-11-20T11:52:55ZNeuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of AutismBTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations.Luca DoderoMario DamianoAlberto GalbuseraAngelo BifoneSotirios A. Tsaftarissotirios.tsaftaris@imtlucca.itMaria Luisa ScattoniAlessandro Gozzi2013-03-06T10:07:58Z2013-03-12T09:32:21Zhttp://eprints.imtlucca.it/id/eprint/1515This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/15152013-03-06T10:07:58ZMouse neuroimaging phenotyping in the cloudThe combined use of mice that have genetic mutations (transgenic mouse models) of human pathology and advanced neuroimaging methods (such as MRI) has the potential to radically change how we approach disease understanding, diagnosis and treatment. Morphological changes occurring in the brain of transgenic animals as a result of the interaction between environment and genotype, can be assessed using advanced image analysis methods, an effort described as “mouse brain phenotyping”. However, the computational methods required for the analysis of high-resolution brain images are demanding. In this paper, we propose a computationally effective cloud-based implementation of morphometric analysis of high-resolution mouse brain datasets. We show that the proposed approach is highly scalable and suited for a variety of methods for MR-based brain phenotyping. The proposed approach is easy to deploy, and could become an alternative for laboratories that may require instant access to large high performance computing infrastructure.Massimo Minervinimassimo.minervini@imtlucca.itMario DamianoValter TucciAngelo BifoneAlessandro GozziSotirios A. Tsaftarissotirios.tsaftaris@imtlucca.it2013-03-06T09:58:23Z2016-04-05T12:10:18Zhttp://eprints.imtlucca.it/id/eprint/1514This item is in the repository with the URL: http://eprints.imtlucca.it/id/eprint/15142013-03-06T09:58:23ZNeuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of AutismLuca DoderoFrancesco SforazziniAlberto GalbuseraMario DamianoSotirios A. Tsaftarissotirios.tsaftaris@imtlucca.itAngelo BifoneMaria Luisa ScattoniAlessandro Gozzi