Analisi neurocomputazionale dell'integrazione multisensoriale in soggetti neurotipici e sofferenti di disturbi dello spettro autistico

L'obiettivo prefissato è quello di sviluppare una rete neurale modificando un modello preesistente che permetta di analizzare e comprendere in termini matematici i processi neurali alla base dell'integrazione multisensoriale in soggetti sofferenti di disturbo dello spettro autistico confrontandoli con soggetti neurotipici, concentrandosi sul ruolo delle sinapsi feedforward (dirette dalle aree unisensoriali alla multisensoriale)

Isolation and characterization of two newly established thymoma PDXs from two relapses of the same patient: a new tool to investigate thymic malignancies

Background: Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies. Main body: Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin. Short conclusion: The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Towards an Integrated Platform for Adaptive Socio-Technical Systems for Smart Spaces

The widespread availability of mobile devices equipped with sensors on board is strongly pushing towards the development of smart spaces\u2014offices, streets, hospital, airports, homes and shops equipped with sensing systems to help people find relevant information quickly and use services comfortably, often in a collaborative way. A common aspect in these scenarios is that the technology complexity is amplified by the organisational and procedural complexity of the application domain: this is in fact typical of socio-technical systems\u2014kinds of systems that inherently need to be conceived, designed and developed taking into account both the technological and the human/organisational aspects from the earliest stages. In this paper, we select and discuss some challenges in the definition and development of adaptive socio-technical systems for smart spaces; the selected challenges aim at focusing in particular on (i) a socio-technical model and process, (ii) a multi-level integration framework, and (iii) methods and system analysis techniques for runtime adaptation. In fact, designing such systems requires the suitable combination of enabling technologies into an operational framework, integrating and coordinating a multiplicity of processes managed by complex organisations, each made up of independent and autonomous units

L-Methionine Protects against Oxidative Stress and Mitochondrial Dysfunction in an In Vitro Model of Parkinson’s Disease

Methionine is an aliphatic, sulfur-containing, essential amino acid that has been demonstrated to have crucial roles in metabolism, innate immunity, and activation of endogenous antioxidant enzymes, including methionine sulfoxide reductase A/B and the biosynthesis of glutathione to counteract oxidative stress. Still, methionine restriction avoids altered methionine/transmethylation metabolism, thus reducing DNA damage and possibly avoiding neurodegenerative processes. In this study, we wanted to study the preventive effects of methionine in counteracting 6-hydroxydopamine (6-OHDA)-induced injury. In particular, we analyzed the protective effects of the amino acid L-methionine in an in vitro model of Parkinson’s disease and dissected the underlying mechanisms compared to the known antioxidant taurine to gain insights into the potential of methionine treatment in slowing the progression of the disease by maintaining mitochondrial functionality. In addition, to ascribe the effects of methionine on mitochondria and oxidative stress, methionine sulfoxide was used in place of methionine. The data obtained suggested that an L-methionine-enriched diet could be beneficial during aging to protect neurons from oxidative imbalance and mitochondrial dysfunction, thus preventing the progression of neurodegenerative processes

L-Methionine Protects against Oxidative Stress and Mitochondrial Dysfunction in an In Vitro Model of Parkinson’s Disease

Methionine is an aliphatic, sulfur-containing, essential amino acid that has been demonstrated to have crucial roles in metabolism, innate immunity, and activation of endogenous antioxidant enzymes, including methionine sulfoxide reductase A/B and the biosynthesis of glutathione to counteract oxidative stress. Still, methionine restriction avoids altered methionine/transmethylation metabolism, thus reducing DNA damage and possibly avoiding neurodegenerative processes. In this study, we wanted to study the preventive effects of methionine in counteracting 6-hydroxydopamine (6-OHDA)-induced injury. In particular, we analyzed the protective effects of the amino acid L-methionine in an in vitro model of Parkinson’s disease and dissected the underlying mechanisms compared to the known antioxidant taurine to gain insights into the potential of methionine treatment in slowing the progression of the disease by maintaining mitochondrial functionality. In addition, to ascribe the effects of methionine on mitochondria and oxidative stress, methionine sulfoxide was used in place of methionine. The data obtained suggested that an L-methionine-enriched diet could be beneficial during aging to protect neurons from oxidative imbalance and mitochondrial dysfunction, thus preventing the progression of neurodegenerative processes.</jats:p