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Humor y disolución de lo real en Los traidores (1956) de Rodolfo Wilcock y Silvina Ocampo
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Trimetazidine stimulates intracellular Ca2+ transients and zebrafish locomotor activity in spinal neurons
No full textThe metabolic modulator trimetazidine (TMZ) is an antianginal recently found to improve skeletal muscle performance in mice models of sarcopenia and of amyotrophic lateral sclerosis (ALS). The mechanism underlying the effect of TMZ on locomotor activity has been proposed to rely on its ability to enhance metabolic efficiency with a consequent improvement of myogenesis and of neuromuscular junction (NMJ) and muscle function. However, although promising and therefore under clinical trials, the mechanism of action of TMZ has not been clearly disclosed; here we hypothesized that it might involve the modulation of neuronal Ca2+ flows. We studied the effect of TMZ on Ca2+ dynamics in vivo, by using the transgenic zebrafish line Tg(neurod1:GCaMP6f) in which the neuronal expression of the Ca2+ indicator GCaMP allows to visualize Ca2+ dynamics in neurons of zebrafish larvae. By this elegant tool, we demonstrated, for the first time, that TMZ promotes an increase of intracellular Ca2+ transients in zebrafish spinal neurons likely enhancing motor neuron firing, which correlates with enhanced motor performance induced by this drug. Even though elevated intracellular Ca2+ levels have often been associated to neurotoxicity, it is unclear if the neuronal excitability features in some neuro-muscular disorders are compensatory or pathological. Therefore, this newly reported effect of TMZ which transiently and selectively enhances spinal neuron firing deserves to be further detailed and taken into account when the possible repurposing of this drug is proposed for the treatment of neuro-muscular disorders
Acute Hyperglycemia-Induced Inflammation in MIO-M1 Cells: The Role of Aldose Reductase
No full text: Diabetic retinopathy (DR), traditionally considered a microvascular complication, is now recognized as a neuroinflammatory disorder involving retinal glial cells. Aldose reductase (AKR1B1), a key enzyme in the polyol pathway, has been implicated in the hyperglycemia-induced inflammatory response in various cell types, although its role in retinal Müller glial cells under acute glucose stress remains unclear. This study investigates AKR1B1 activity and its contribution to inflammatory signaling in MIO-M1 human Müller cells exposed to acute hyperglycemia. AKR1B1 expression and activity, as well as NF-κB activation and COX-2 expression, were evaluated. Sorbinil, a specific AKR1B1 inhibitor, was used to determine the enzyme's contribution to acute hyperglycemia-induced inflammation. Acute high-glucose treatment significantly increased AKR1B1 activity and sorbitol accumulation without affecting cell viability. In addition, activation of NF-κB and increased expression of cyclooxygenase-2 (COX-2) were observed, both of which were significantly reduced by Sorbinil. Our findings highlight the role of macroglia as active contributors to early inflammatory events in DR and suggest that transient hyperglycemic spikes are sufficient to trigger AKR1B1-dependent glial activation
Environmental Risks and Toxicity of Fipronil and Imidacloprid Used in Pets Ectoparasiticides
No full text: Fipronil (FIP) and imidacloprid (IMID) are two of the most commonly used ectoparasiticides to control parasites in pets. Compared with those of farm animals, their environmental risks have generally been considered low because of their limited use; however, the growing pet population and evolving treatment practices make this assumption challenging. To assess these risks, water samples were collected at an animal shelter in Italy to monitor the abundance of ectoparasiticides in aquatic environments. Additionally, laboratory-based ecotoxicological assays were carried out on a range of marine non-target species across different trophic levels (algae, copepods, and mussels). In vitro toxicity tests on human epithelial cell cultures were also implemented to examine potential cytotoxic effects at the levels of human exposure detectable in a domestic setting after pet treatment. Wastewater samples from the shelter contained 0.18 μg L-1 of IMID, 0.50 μg L-1 of FIP, and 0.20 μg L-1 of FIP-sulfone, with these concentrations remaining stable for 60 days. Chronic exposure to FIP and IMID at 30.0 μg L-1 impaired the mobility of the copepods. The EC10 and EC20 values were determined to be 1.7 (0.06-6.59) μg L-1 and 2.8 (0.436-8.51) μg L-1 for FIP and 2.6 (0.80-6.33) μg L-1 and 7.6 (3.12-15.8) μg L-1 for IMID, respectively. FIP and IMID exposure led to lipid peroxidation in the digestive glands and gills of mussels, whereas only IMID exposure increased acetylcholinesterase activity in the digestive glands at concentrations between 0.5 and 5.0 μg L-1. Additionally, both fipronil and imidacloprid triggered the production of reactive oxygen species and lipid peroxidation and decreased the viability of human keratinocyte cells in a concentration-dependent manner. These findings highlight the persistence and potential risks of FIP and IMID, stressing the need for stricter regulations and further research on chronic environmental exposure to safeguard ecosystems and public health
Learning-Based Foot-Shape-Aware Foothold Selection for Quadrupedal Robots
No full textMastering rough terrain locomotion is a tough challenge for robots due to its dynamic, unpredictable nature and frequent physical contact. Traditionally, robots rely on carefully planned foot placements to maintain grip and stability. Recent advancements in quadruped robot feet offer diverse shapes and high grip for various terrains. However, control systems and planners often struggle to leverage these varied capabilities, relying instead on simplified foot models e.g., ball-like, flat. The simplified feet models committed to the single shape of the foot can not be used on robots equipped with diverse feet or modern adaptive feet. This work proposes a novel foothold optimization method that efficiently searches for optimal contact points for different foot shapes using a polynomial approximation. The system leverages a Convolutional Neural Network (CNN) trained on simulated data to predict a cost for each candidate foothold. We show that a single neural network can work with different and new foot mechanical designs without retraining the system. We experimentally validate our system on the ANYmal robot using both ball feet and adaptive soft feet, in indoor and outdoor environments, finding that our system improves stability, in terms of pitch and roll angles of the base, with respect to a state-of-the-art method
β-Cyclodextrin nanosponges for the ocular delivery of therapeutic Micro-RNA in a Mouse model of retinitis Pigmentosa: A proof of concept study
No full textThe exploitation of micro-RNA (miR) sequences as therapeutics has become highly attractive for the treatment of several diseases, including those still lacking effective cures such as retinitis pigmentosa (RP). Interestingly, miR-155-5p plays a role in photo-oxidative inflammation in wild-type mice and is up-regulated in rd10 mice showing peak rod degeneration, suggesting its inhibition by the corresponding anti-miR as a viable therapeutic strategy for RP. However, biomedical application of (anti-)miRs is limited by their oligonucleotide nature, suffering from low solubility and bioavailability along with a very low half-life in vivo due to enzymatic degradation. Thereby, the need for suitable delivery systems led to the development of various nanocarriers, including oligosaccharide-based polymers. In this context, we designed and prepared an innovative nanosponge (NS) with a β-cyclodextrin (β-CD) motif payload with a bridge-like molecule, the amphipathic adamantane derivative (ADM), able to establish strong interactions with both NS and the therapeutic miR, thereby delivering and eventually releasing it close to the active site. Through an in vivo study, we both validated the NS system as a useful tool for miR topical administration by eye drop formulation and the functional activity of anti-miR-155-5p in RP
L’Unione europea sulla scena internazionale. Sfide e trasformazioni sul piano interno ed esterno. Atti del Convegno Nazionale AISDUE, Università di Pisa, 25-26 ottobre 2024
No full textIl Volume raccoglie gli atti del Convegno annuale dell'Associazione Italiana degli Studiosi di Diritto dell'Unione europea (AISDUE) organizzato dai due curatori presso l'Università di Pisa il 25 ed il 26 ottobre 2024
Improved bounds for randomized Schatten norm estimation of numerically low-rank matrices
No full textIn this work, we analyze the variance of a stochastic estimator for computing Schatten norms of matrices. The estimator extracts information from a single sketch of the matrix, that is, the product of the matrix with a few standard Gaussian random vectors. While this estimator has been proposed and used in the literature before, the existing variance bounds are often pessimistic. Our work provides a new upper bound and estimates of the variance of this estimator. These theoretical findings are supported by numerical experiments, demonstrating that the new bounds are significantly tighter than the existing ones in the case of numerically low-rank matrices
