Experiencia de implementación del laboratorio remoto VISIR con estudiantes de ingeniería

Se presentan los resultados de la implementación de una experiencia didáctica utilizando el laboratorio remoto VISIR, con estudiantes de Ingeniería que cursaron Física II. Los estudiantes realizaron un pre test y un post test sobre el tema circuitos eléctricos, y un grupo realizó además una experiencia con el laboratorio remoto. Los resultados estadísticos reflejan que no hay diferencia estadística en los rendimientos, entre los estudiantes que realizaron el laboratorio remoto respecto de aquellos que no lo hicieron. Desde el punto de vista cualitativo no se observaron diferencias en el desempeño en general de los estudiantes, excepto en el aspecto procedimental de conexión y reconocimiento de instrumentos. Se resalta la valoración de los estudiantes del recurso, y también la capacidad del laboratorio para propiciar la resolución de problemas de manera colaborativa, aspecto esencial en la formación de profesionales. Si bien la experiencia se realizó en 2019, aportó insumos valiosos para abordar la Enseñanza Remota de Emergencia (ERE) en el ciclo lectivo 2020 en contexto de pandemia por COVID 19.Red de Universidades con Carreras en Informátic

Trust, Cooperation, and Self-Efficacy. A Research with Sicilian Entrepreneurs

Investigating the relationship between self-concept and potential territory was the aim of our research.  Particularly, we have provided if the self-concept, self-efficacy and metacognitive ability of Sicilian entrepreneurs correlate with trust in Sicily Region institution. Moreover, if there was a positive correlation between high levels in these constructs and trust in another Sicilian firms.  In the end, we provided if entrepreneurs, which have high levels in self-concept, self-efficacy and metacognitive ability, were good at seeing and understanding Sicily. Seeing the Sicily as potential territory to protective and to get reality.

CAP2 dimerization regulates cofilin in synaptic plasticity and Alzheimer's disease

Abstract Regulation of actin cytoskeleton dynamics in dendritic spines is crucial for learning and memory formation. Hence, defects in the actin cytoskeleton pathways are a biological trait of several brain diseases, including Alzheimer's Disease. Here, we describe a novel synaptic mechanism governed by the cyclase-associated protein 2 (CAP2), which is required for structural plasticity phenomena and completely disrupted in Alzheimer's Disease. We report that the formation of CAP2 dimers through its Cys32 is important for CAP2 binding to cofilin and for actin turnover. The Cys32-dependent CAP2 homodimerization and association to cofilin are triggered by long-term potentiation and are required for long-term potentiation-induced cofilin translocation into spines, spine remodelling and the potentiation of synaptic transmission. This mechanism is specifically affected in the hippocampus, but not in the superior frontal gyrus, of both Alzheimer's Disease patients and APP/PS1 mice, where CAP2 is down-regulated and CAP2 dimer synaptic levels are reduced. Notably, CAP2 levels in the cerebrospinal fluid are significantly increased in Alzheimer's Disease patients but not in subjects affected by frontotemporal dementia. In Alzheimer's Disease hippocampi, cofilin association to CAP2 dimer/monomer is altered and cofilin is aberrantly localized in spines. Taken together, these results provide novel insights into structural plasticity mechanisms that are defective in Alzheimer's Disease

Polynomial growth and identities of superalgebras and star-algebras

We study associative algebras with 1 endowed with an automorphism or antiautomor- phism ' of order 2, i.e., superalgebras and algebras with involution. For any fixed k >=1, we construct associative '-algebras whose '-codimension sequence is given asymptoti- cally by a polynomial of degree k whose leading coefficient is the largest or smallest possi- ble

Rabphilin-3A Drives Structural Modifications of Dendritic Spines Induced by Long-Term Potentiation

The interaction of Rabphilin-3A (Rph3A) with the NMDA receptor (NMDAR) in hippocampal neurons plays a pivotal role in the synaptic retention of this receptor. The formation of a Rph3A/NMDAR complex is needed for the induction of long-term potentiation and NMDAR-dependent hippocampal behaviors, such as spatial learning. Moreover, Rph3A can also interact with AMPA receptors (AMPARs) through the formation of a complex with myosin Va. Here, we used a confocal imaging approach to show that Rph3A overexpression in primary hippocampal neuronal cultures is sufficient to promote increased dendritic spine density. This morphological event is correlated with an increase in GluN2A-containing NMDARs at synaptic membranes and a decrease in the surface levels of GluA1-containing AMPARs. These molecular and morphological modifications of dendritic spines are sufficient to occlude the spine formation induced by long-term potentiation, but do not prevent the spine loss induced by long-term depression. Overall, our results demonstrate a key role for Rph3A in the modulation of structural synaptic plasticity at hippocampal synapses that correlates with its interactions with both NMDARs and AMPARs

Novel therapeutic approaches to target neurodegeneration

Ageing is the main risk factor common to most primary neurodegenerative disorders. Indeed, age-related brain alterations have been long considered to predispose to neurodegeneration. Although protein misfolding and the accumulation of toxic protein aggregates have been considered as causative events in neurodegeneration, several other biological pathways affected by brain ageing also contribute to pathogenesis. Here, we discuss the evidence showing the involvement of the mechanisms controlling neuronal structure, gene expression, autophagy, cell metabolism and neuroinflammation in the onset and progression of neurodegenerative disorders. Furthermore, we review the therapeutic strategies currently under development or as future approaches designed to normalize these pathways, which may then increase brain resilience to cope with toxic protein species. In addition to therapies targeting the insoluble protein aggregates specifically associated with each neurodegenerative disorder, these novel pharmacological approaches may be part of combined therapies designed to rescue brain function.We acknowledge funding from the Italian Ministry of University and Research (Ministero dell'Università e della Ricerca) (PRIN 202039WMFP to E.M. and 20202THZAW to M.D.L.); from Fondazione Cariplo (Grant No. 2018-0511) to E.M.; from Alzheimer Forschung Initiative (Grant No. 21019) and the Chica and Heinz Schaller Foundation (Chica and Heinz Schaller-Stiftung) to D.M.; from Instituto de Salud Carlos III (CP21/0032) and Spanish Science State Agency (PID2021-124465OA-I00) to A.G.d.l.F.; and from the BrightFocus Foundation (Grant A2019562S), the European Union (H2020 European Research Council Grants ERC-STG-2019-852086 and H2020-MSCA-IF-2017-797205), the Austrian Science Fund (Grant FWF-I5057), Clene Nanomedicine, the U.S. National Academy of Medicine (NAM), the Michael J. Fox Foundation for Parkinson's Research (MJFF), the Alzheimer’s Association (AARG-22-972303) and the NIH National Institute on Aging (Grant AG056306 and AG062429) to J.M.Open Access Funding provided by Universita degli Studi di Milano within the CRUI-CARE Agreement.Peer reviewe

Dysregulation of Immune Response Mediators and Pain-Related Ion Channels Is Associated with Pain-like Behavior in the GLA KO Mouse Model of Fabry Disease

Fabry disease (FD) is a rare life-threatening disorder caused by deficiency of the alpha-galactosidase A (GLA) enzyme with a characteristic pain phenotype. Impaired GLA production or function leads to the accumulation of the cell membrane compound globotriaosylceramide (Gb3) in the neurons of the dorsal root ganglia (DRG) of FD patients. Applying immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT PCR) analysis on DRG tissue of the GLA knockout (KO) mouse model of FD, we address the question of how Gb3 accumulation may contribute to FD pain and focus on the immune system and pain-associated ion channel gene expression. We show a higher Gb3 load in the DRG of young (<6 months) (p < 0.01) and old (≥12 months) (p < 0.001) GLA KO mice compared to old wildtype (WT) littermates, and an overall suppressed immune response in the DRG of old GLA KO mice, represented by a reduced number of CD206+ macrophages (p < 0.01) and lower gene expression levels of the inflammation-associated targets interleukin(IL)1b (p < 0.05), IL10 (p < 0.001), glial fibrillary acidic protein (GFAP) (p < 0.05), and leucine rich alpha-2-glycoprotein 1 (LRG1) (p < 0.01) in the DRG of old GLA KO mice compared to old WT. Dysregulation of immune-related genes may be linked to lower gene expression levels of the pain-associated ion channels calcium-activated potassium channel 3.1 (KCa3.1) and transient receptor potential ankyrin 1 channel (TRPA1). Ion channel expression might further be disturbed by impaired sphingolipid recruitment mediated via the lipid raft marker flotillin-1 (FLOT1). This impairment is represented by an increased number of FLOT1+ DRG neurons with a membranous expression pattern in old GLA KO mice compared to young GLA KO, young WT, and old WT mice (p < 0.001 each). Further, we provide evidence for aberrant behavior of GLA KO mice, which might be linked to dysregulated ion channel gene expression levels and disturbed FLOT1 distribution patterns. Behavioral testing revealed mechanical hypersensitivity in young (p < 0.01) and old (p < 0.001) GLA KO mice compared to WT, heat hypersensitivity in young GLA KO mice (p < 0.001) compared to WT, age-dependent heat hyposensitivity in old GLA KO mice (p < 0.001) compared to young GLA KO mice, and cold hyposensitivity in young (p < 0.001) and old (p < 0.001) GLA KO mice compared to WT, which well reflects the clinical phenotype observed in FD patients

Nuclear calcium signaling in spinal neurons drives a genomic program required for persistent inflammatory pain

Persistent pain induced by noxious stimuli is characterized by the transition from normosensitivity to hypersensitivity. Underlying mechanisms are not well understood, although gene expression is considered important. Here we show that persistent nociceptive-like activity triggers calcium transients in neuronal nuclei within the superficial spinal dorsal horn, and that nuclear calcium is necessary for the development of long-term inflammatory hypersensitivity. Using a nucleusspecific calcium signal perturbation strategy in vivo complemented by gene profiling, bioinformatics and functional analyses, we discovered a pain-associated, nuclear calciumregulated gene program in spinal excitatory neurons. This includes C1q, a novel modulator of synaptic spine morphogenesis, which we found to contribute to activity-dependent spine remodelling on spinal neurons in a manner functionally associated with inflammatory hypersensitivity. Thus, nuclear calcium integrates synapse-to-nucleus communication following noxious stimulation and controls a spinal genomic response that mediates the transition between acute and long-term nociceptive sensitization by modulating functional and structural plasticity

Colorectal Cancer after Kidney Transplantation: A Screening Colonoscopy Case-Control Study

The incidence of colorectal cancer in kidney transplant recipients has been previously reported with conflicting results. In this study, we investigated if the incidence of colorectal advanced neoplasms in kidney transplant recipients, evaluated with screening colonoscopy, was higher than in healthy individuals. One-hundred sixty kidney transplant recipients undergoing screening colonoscopy were compared with 594 age- and sex-matched healthy individuals. Advanced colorectal neoplasia was found in 22 patients (13.7%), including four patients (2.5%) with colorectal cancer. Compared with the healthy population, kidney transplant recipients did not have an increased risk of developing a colorectal cancer (OR 0.69; 95% CI 0.236–2.063, p = 0.688) although it developed at a younger age. In contrast, kidney transplant recipients had a higher risk of developing an advanced adenoma compared with the control group (OR 1.65; 95% CI 0.930–2.981, p = 0.04). In conclusion, kidney transplant recipients did not have an increased incidence of colorectal cancer compared with healthy population. However, transplant patients displayed a higher incidence of colorectal adenomas, suggesting that screening colonoscopy in kidney transplant recipients should be expanded to include even younger recipients (<50 years old)