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Chronic fasudil treatment induces benzodiazepine-like tolerance via modulation of GABA-A receptor γ2 subunit expression and impairs contextual fear memory in mice
No full textBackground
Fasudil hydrochloride (FAS) is a selective Ras homologous (Rho) associated kinase (ROCK) inhibitor and vasodilator used to treat cerebral vasospasm. Owing to its neuroprotective effects in preclinical models of neurodegeneration, FAS is currently under clinical investigation for several neurological diseases. Although the precise mechanism of action of FAS remains unclear, some preclinical studies suggest that it may exert anxiolytic and anticonvulsant effects—pharmacological activities typically associated with positive allosteric modulators of the γ‐aminobutyric acid (GABA)-A receptor, such as benzodiazepines.
This study investigates whether FAS acts as a modulator of the GABA-A receptor and examines the effects of its chronic administration.
Methods
Protein comparative analyses and in silico docking assays were performed to assess the binding affinity of FAS for the GABA-A receptor. CD1 mice received daily oral administration of FAS for 12 weeks. One week after treatment cessation, behavioural tests and magnetic resonance (MR) analyses were conducted to evaluate brain function and metabolism. In addition, Rho guanosine triphosphatase activity, GABA-A receptor expression, and levels of postsynaptic density protein 95 (PSD‐95) were assessed.
Results
The computational analysis predicted a strong binding affinity of FAS for the GABA-A receptor. In vivo assays revealed that FAS impaired contextual fear memory without affecting anxiety-like behaviour, motor coordination, or recognition memory. These behavioural alterations were accompanied by a reduction in the γ2 subunit of the GABA-A receptor in both the hippocampus and the prefrontal cortex (PFC). Within the PFC, PSD‐95 expression was decreased, whereas the activity of Ras-related C3 botulinum toxin substrate 1 was increased. MR analyses showed elevated glutamate levels in the PFC, together with a general increase in total choline and a mild impairment of white matter integrity.
Conclusions
Our findings suggest that FAS influences GABA-A receptor expression and may act as an allosteric modulator. Chronic treatment in healthy mice appears to adversely affect the PFC, producing behavioural and molecular alterations resembling those observed following prolonged benzodiazepine exposure
La diffusione nell’accademia cinese dell’approccio storico-discorsivo (DHA): uno sguardo iniziale
No full textThis paper provides an overview of the application of the DiscourseHistorical Approach (DHA) in text analysis within Chinese academia. Drawing on publication data retrieved and processed from the China National Knowledge Infrastructure (CNKI), it offers a chronological account of the progressive adoption of this approach over the years and identifies the main research areas in which it has been employed. The analysis illustrates how the DHA has gained increasing prominence in Chinese scholarly production, demonstrating its versatility
across both linguistically oriented and politically informed studies. While this paper does not claim to present an exhaustive survey of the diffusion of the DHA in the People’s Republic of China academia, its main objective is to reconstruct its major developmental stages and to
contribute to a broader reflection on the reception and adaptation of Western methodological frameworks within the Chinese research context
Dhekalos Lab to Metaverse: Exploring XR Strategies for Digital Cultural Heritage
No full textThis chapter presents the design and implementation of Meta-Dhekalos, a digital twin of the Dhekalos Laboratory at the Università Politecnica delle Marche, developed within the Spatial platform. The project aims to transpose the physical lab into the Metaverse, enabling remote access, immersive interaction, and participatory dissemination of cultural heritage research. A curated selection of six XR-based digital experiences, spanning AR, VR, MR, and AI-enhanced environments, is also presented and integrated into the new Meta-space to reflect the lab’s evolving methodological and technological approaches. Each case was chosen for its ability to represent different stages and paradigms of immersive cultural storytelling. The chapter documents the criteria used in this selection and the design strategies adopted to translate them into a shared 3D environment. Finally, it presents the preliminary results of an evaluation test conducted with educators, offering early insights into presence, usability, and educational impact across the different experiences
Composite membranes added with graphene oxide and functionalized graphene oxide for anion and proton exchange membrane water electrolyzers
No full textIn recent years, interest in electrolysis for hydrogen production has increased, particularly as a means of utilizing surplus electricity from intermittent renewable sources. A promising approach to reduce CO2 emission is, in fact, the integration of hydrogen—produced using carbon-free electricity through advanced conversion technologies —into gas, chemicals, and fuels. Electrolysis, in particular, offers an environmentally friendly method of producing pure hydrogen as an energy carrier, utilizing electricity from renewable sources. In this regard Proton Exchange Membrane Water Electrolyzers (PEMWEs) and Anion Exchange Membrane Water Electrolyzers (AEMWEs) are among the most promising devices, but they still face some problems related to the stability and conductivity of the polymer electrolyte, that hinder their widespread use. Here in this thesis work we have focused on developing composite membranes in order to mitigate these problems. To do so, different amounts of Graphene Oxide (GO) and functionalized GO were added to the commercial Fumion ionomer (for AEMWE) and Nafion ionomer (for PEMWE) to obtain composites membranes with increased stability and conductivity. In the case of Anion Exchange Membranes (AEMs), bare GO, synthesized using the Modified Hummers Method, was first investigated to have information about the effect of the additive inside the polymeric matrix. Then GO was functionalized with quaternary ammonium groups using three different innovative and simple syntheses and the resulting composite AEMs were studied to investigate the effect of the GO quaternization. In the case of Proton Exchange Membranes (PEMs), GO was functionalized with phosphonate groups using the Arbuzov reaction. The composite PEMs prepared with this additive were characterized and the effect of the functionalization and quantity of the additive was studied. All the additives were characterized using different techniques like TGA, SEM, ATR-FTIR, Raman Spectroscopy, XRD and XPS in order to obtain information on the morphology, structure and the chemical nature of the samples. In the same way all the Ionic Exchange Membranes were characterized both at a fundamental and applicative level, using TGA, SEM, ATR-FTIR, Ionic Exchange Capacity (I.E.C.), Water Uptake (W.U.), alkaline stability (for Fumion-GO), stress-strain curves and conductivity, as well as electrolysis cell tests to evaluate the materials performances and stability. The first chapter of the thesis is dedicated to the scientific context (Chapter 1), in which significant attention is given to the explanation of the degradation phenomena, since these studies have been explored in depth and are included in a review that is currently under publication. The following chapter focuses on the materials and experimental methods (Chapter 2) and is followed by three chapters dedicated to the different types of composite membranes, namely AEMs added with Graphene Oxide (Chapter 3), AEMs added with Quaternized Graphene Oxide (Chapter 4), and PEMs added with Phosphonated Graphene Oxide (Chapter 5). Finally, the last chapter (Chapter 6) presents the conclusions and possible future perspectives
Gillian Rose, interpreter of Walter Benjamin: the ‘unintended consequences’ of asceticism
No full textThe focus of this text is Rose's interpretazione of Walter Benjamin's work. Rose takes two approaches
to Benjamin: one based on Derrida’s interpretation and the other in opposition to it. Both are important. The former is particu-larly interesting when it comes to exploring the critical issues of postmodern analyses, which encounter many difficulties when it
comes to accepting and elaborating on the potential and limits of modernity
Data-driven modeling of the flame composition space of an intrinsically unstable lean premixed ammonia/hydrogen/air flame
No full textThis study investigates the capability of different data-driven methodologies of achieving dimensionality reduction
of the flame composition space in a large-scale lean premixed, intrinsically unstable ammonia/hydrogen/air
flame, while accurately representing key chemical species. Two data-driven techniques, one consisting of a combination
of Singular Value Decomposition and Artificial Neural Network (SVD+ANN) and a second consisting of a
Linear-Nonlinear Autoencoder (LNAE), were employed to model three relevant species. The models were trained
on three different datasets: a small-scale DNS dataset, unstretched 1D flamelets, and a combination of stretched
and unstretched flamelets. Error analyses demonstrate that both techniques effectively capture the species behavior
using at least two (or three, depending on the behavior of specific species) independent variables, when
trained on the small-scale DNS dataset. The models trained on the unstretched flamelet dataset show worse testing
performance with both techniques, while the LNAE models trained on the stretched flamelet dataset can
accurately reproduce the pollutant concentrations when three or more predictors are used. The results highlight
the potential of the LNAE data-driven approach to accurately model key chemical species belonging to a DNS
dataset of an intrinsically unstable ammonia/hydrogen flames using strained flamelet data, while highlighting
the generalization capabilities of the different training datasets
Minority languages and intergroup communication: the case of Siwi (Amazigh) in Egypt
No full textMinority or minoritized languages are often restricted to ingroup use by their own speakers and indexically related to them. Nevertheless, minority languages and their speakers are never isolated; they are part of a multilingual ecology and included in local language hierarchies. In this paper, I focus on the occurrence and role of Siwi in the interaction between Siwi and Arabic speakers in the Siwa Oasis. In this multilingual space, a national minority language, Siwi Amazigh, is spoken by the majority of the population, and different varieties of the dominant language, Arabic, are spoken as L1 by a smaller portion of the population and as L2 by virtually everyone. Data from mixed-group conversations show that although Arabic varieties far outscore Siwi, as one would expect, everyday practices are characterized by the hybridity and heterogeneity typical of multilingual ecologies. This paper provides an accurate portrait of conversational habits in Siwa and depicts Siwi fluctuating between an identity marker value, due to its vitality, and an identity maker value, which builds on it
Pneumatic retinopexy (pnR) and Scleral Buckle (Sb) in primary rhegmatogenous retinal detachment: two procedures - same reattachment modalities? Proposal for a multicenter pilot study and review of the Literature
No full textPurpose: to report our recent work on PnR highlighting outcomes,indications, and eventually limitation of this procedure and to suggest a multicenter pilot study designed to study SB compared to PnR using harmonized inclusion criteria, surgical protocols, and outcome definitions, with a focus on reattachment mechanisms, prognostic factors, and postoperative recovery profiles.
Methods: starting from our recent published work on pnr, we retrospectively review the most recent Literature on pnR and reattachment modalities after rhegmatogenous retinal detachment surgical repair and set up a proposal for a multicenter pilot study focusing on scleral buckle surgery
Conclusion: PnR and Sb share same more “ natural” reattachment modalities compared to PPV, offering better visual acuity and quality of vision and could be the first choice of treatment in routinely less complex retinal detachments , aimimg to refine surgical decision-making and optimize patient outcomes across diverse clinical settings
Heritage Value and Short-Term Rentals: Spatial Dynamics of Airbnb Prices in Rome
No full textThe intangible accessibility of real estate markets via platforms like Airbnb profoundly influences the urban development industry, propelled by the dynamics of short- to medium-term rentals for tourists. The suggested study aims to examine the association between the prices of listed properties and the influence of proximity to tourist attractions on location-driven pricing. The city of Rome acts as a case study from which to derive pertinent conclusions and proof on the phenomena intended for exploration. The methodological approach relies on a comprehensive classification of locations recognized as tourist attractions, drawn from public resources, travel guides, search engines, and online trends. The identified attractionswere subsequently classified to analyze how spatial proximity influences price formation. Data on short-term rental listings were obtained from the Inside Airbnb platform. The results enable the characterization of Rome as a polycentric urban system, composed of multiple tourism hubs whose spatial interactions are closely associated with prevailing hotel pricing patterns. This study emphasizes the influence of tourist demand on land values, a phenomenon intricately connected to urban gentrification and the capitalization of the real estate market. These findings enhance comprehension of tourism’s impact on the geographical and economic structure of cities
Mental simulation(s) and memory: cognitive and sensorimotor mechanisms underlying embodied memory processes
No full textMental simulation is a widely investigated construct within the embodied cognition literature, and has been applied to a diverse range of cognitive processes and outcomes. However, there remains a lack of research systematically examining the distinct characteristics of these simulations and their implications for cognition, particularly memory. Across seven studies, the present work aims at addressing this gap by disentangling different types of mental simulation, ranging from action observation, language comprehension, to mental imagery, identifying specific modulatory factors and illustrating their complex role in different memory processes. In Study 1, we review the literature on mental simulation, delineate key distinctions among different types of simulations and propose a taxonomy positioning them along a continuum. Study 2 then provides empirical evidence for their differential effects on episodic memory enhancement. Subsequently, we investigate various cognitive factors underlying sensorimotor simulations. Specifically, we examine the role of predictability, both from a linguistic (Study 3) and contextual versus motor (Study 4) point of view, in the creation of false memories for actions. Study 5 further explores the role of linguistic and sensorimotor context, applied to the QWERTY-keyboard paradigm, investigating both implicit and explicit memory. Finally, Studies 6 and 7, also employing the QWERTY paradigm, investigate a distinct form of implicit motor memory, namely motor fluency, showing that this type of sensorimotor simulation is modulated not only by motor expertise but also suggesting it has considerably changed over the past decade. Overall, our findings underscore the conceptual complexity of “mental simulation”, suggesting that it may be differentially modulated by several cognitive and sensorimotor mechanisms with relevant implications for different types of memory processes. These results emphasize the need for analytically differentiated approaches in future research on “embodied memory”