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The E3-ligase Siah2 activates mitochondrial quality control in neurons to maintain energy metabolism during ischemic brain tolerance
No full textMitochondrial quality control is crucial for the homeostasis of the mitochondrial network. The balance between mitophagy and biogenesis is needed to reduce cerebral ischemia-induced cell death. Ischemic preconditioning (IPC) represents an adaptation mechanism of CNS that increases tolerance to lethal cerebral ischemia. It has been demonstrated that hypoxia-induced Seven in absentia Homolog 2 (Siah2) E3-ligase activation influences mitochondrial dynamics promoting the degradation of mitochondrial proteins. Therefore, in the present study, we investigated the role of Siah2 in the IPC-induced neuroprotection in in vitro and in vivo models of IPC. To this aim, cortical neurons were exposed to 30-min oxygen and glucose deprivation (OGD, sublethal insult) followed by 3 h OGD plus reoxygenation (lethal insult). Our results revealed that the mitochondrial depolarization induced by hypoxia activates Siah2 at the mitochondrial level and increases LC3-II protein expression, a marker of mitophagy, an effect counteracted by the reoxygenation phase. By contrast, hypoxia reduced the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a marker of mitochondrial biogenesis, whereas its expression was increased after reoxygenation thus improving mitochondrial membrane potential, mitochondrial calcium content, and mitochondrial morphology, hence leading to neuroprotection in IPC. Furthermore, Siah2 silencing confirmed these results. Collectively, these findings indicate that the balance between mitophagy and mitochondrial biogenesis, due to the activation of the Siah2-E3-ligase, might play a role in IPC-induced neuroprotection
Isotherm Modeling and Statistical Physics Interpretation of Dye and Pesticide Adsorption on Activated Carbons for Environmental Remediation
No full textA multilayer adsorption model was used to explain the adsorption mechanism of two toxic organic pollutants, methylene blue (MB) and 2,4-dichlorophenoxyacetic acid (2,4-D), on a commercial activated carbon (CPAC) and olive stone activated carbon prepared with ZnCl2 (ZnCl2 /OSAC). Statistical physics-based modeling showed that the adsorption of both pollutants on tested activated carbons was multimolecular where 2–4 layers can be formed on the adsorbent surface. The calculated saturation adsorption capacities of ZnCl2 /OSAC and CPAC for MB were 481–574 and 873–932 mg/g at 30–50 °C, respectively, while the saturation 2,4-D adsorption capacities were 392–607 and 526–675 mg/g for the same adsorbents. Endothermic adsorption was observed for MB, while 2,4-D removal was exothermic. It was found that the MB and 2,4-D removal implied an inclined adsorption geometry, where physical interaction forces contributed to separating these pollutants. Overall, this research provides new findings to explain the adsorption mechanism of these relevant water pollutants on carbonaceous-based materials
International Welcome day
No full textL'importanza della scelta dell'Università Federico II per la sua storia, le sue radici antichissime. Lictera generalis e il principio Ad scientiarum haustum et seminarium doctrinaru
La transizione digitale tra Parlamento e processi di governo interistituzionali
No full textLa relazione ha considerato stato di attuazione ed effetti della transizione digitale promossa dal PNRR sul Parlamento e sui processi di negoziazione interistituzionali
Ragione magica e razionalizzazione simbolica della magia nella stesura prebellica di Wirtschaft und Gesellschaft
No full textWeber’s ideal type of action guided by purposive rationality includes an important sub-type. It can be seen simply as an action orientated towards an end according to a subjectively purposive rationality, or also as an action that is determined by valid experience and thus by technically correct rationality. The essay explores the possible tensions between the two modes of zweckrationales Handeln, as well as their possible convergences and the urgency, which their contrasting relationships presuppose, of defining in each case what exactly is meant by “reason” and what is meant by “anti-reason”. The author’s argumentation is largely, though not exclusively, based on the pre-war draft of "Wirtschaft und Gesellschaft". It examines the passages in the first chapter of "Religiöse Gemeinschaften" (1913) where Weber deals with the original consistency of magical-religious action and the processes of the symbolic rationalisation of magic, and then turns to a few pages of "Die Entwicklungsbedingungen des Rechts" (1911-1914), where Weber discusses the complicated constellation from which the processes of the rationalization of law emerge
Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study
No full textObjective: Gain-of-function (GoF) variants in KCNT1 encoding for potassium channels are associated with different epilepsy phenotypes, including epilepsy of infancy with migrating focal seizures (EIMFS), other early infantile developmental and epileptic encephalopathies, and focal epilepsy. Fluoxetine blocks currents from both wild-type (WT) and mutant KCNT1 channels with GoF in vitro features. In this study, we tested the hypothesis that treatment with fluoxetine might improve clinical outcome in patients with EIMFS carrying GoF variants in KCNT1 channels showing in vitro sensitivity to fluoxetine blockade. Methods: We enrolled three pediatric patients carring de novo KCNT1 genetic variants linked to EIMFS. Functional and pharmacological studies to assess fluoxetine's ability to counteract in vitro variant-induced functional effects were performed with patch-clamp electrophysiology on heterologous channel expression in mammalian Chinese hamster ovary cells. Neuropsychological assessment, electroencephalogram and seizure diary were evaluated at baseline and every 3 months during the study. Electrocardiography and blood levels of medications were monitored for safety. Results: All 3 KCNT1 variants displayed GoF effects in vitro. Exposure to fluoxetine (10μM) blocked both WT and mutant KCNT1 channels, therefore, counteracting variant-induced functional effects. Treatment with fluoxetine caused a variable reduction of seizure frequency (25–75%). Improvement in visual attention, participation, and muscle tone was also reported. No adverse events were reported except for transient dyskinesia in 1 patient, which was probably related to an increase in fluoxetine plasma level. Interpretation: Fluoxetine may be a potential targeted medication in EIMFS caused by KCNT1 GoF variants. Further research is needed to assess its long-term efficacy and safety. ANN NEUROL 2025
On the Serrin problem for ring-shaped domains
No full textIn this paper, we deal with the open problem of characterising rotationally symmetric solutions to Δu=−2, when Dirichlet boundary conditions are imposed on a ring-shaped planar domain. In contrast with Serrin’s classical result, we show that the simplest possible set of overdetermining conditions, namely the prescription of locally constant Neumann boundary data, is not sufficient to obtain a complete characterisation of the solutions. A further requirement on the number of maximum points arises in our analysis as a necessary and sufficient condition for the rotational symmetry. Some new arguments are also introduced in the spirit of comparison geometry, that we believe of independent interest. In particular, the notion of expected core radius is defined and employed to achieve a qualitative description of the solutions, eventually leading to new classification results
Insights into the quasi-static mechanics of transversely isotropic polymer foams
No full textOwing to their favorable balance of mechanical performance, lightness, and cost-effectiveness, polymer foams are the material of choice in numerous structural applications, where knowledge of the relationship between their microstructure and mechanical behavior is needed for design purposes. This research investigates how microstructural anisotropy affects the quasi-static mechanics of transversely isotropic polymer foams. Such foams were designed and produced by expanding polystyrene preforms with different polydispersity indices in cylindrical molds via a batch-foaming method. Microstructural anisotropy was defined to include both the aspect ratio and orientation of the cell, allowing us to apply the well-known homogenized rectangular cell model by Gibson and Ashby (1997) and isolating the effect of microstructural anisotropy. We observed that Young's modulus increased more than threefold and non-linear properties more than twofold within a microstructural anisotropy range from 0.69 to 1.43. Additionally, it is shown that the rheology of the base polystyrene influenced anisotropy development. In conclusion, design maps for transversely isotropic foams are proposed. These findings improve our understanding of the process-structure-property relationship in anisotropic polymer foams, fostering a more effective and efficient use of such ubiquitous materials
Dedalo presso i re. Un esempio di produzione attached
No full textLa lezione seminariale ha avuto come oggetto il rapporto, nelle dinamiche di produzione, fra Dedalo e i suoi committenti, i due re Minosse e Cocalo
Microscopic structure and dynamics of shear-thinning suspensions of polydisperse, repulsive vesicles
No full textWe investigate the rheology, microscopic structure, and dynamics of an industrially relevant dispersion made of charged vesicles, from dilute to concentrated conditions. We find that these suspensions exhibit a shear-thinning behavior at relatively low volume fractions. At the microscale, this corresponds to a well-defined transition in both the structure, marked by a sudden increase of the scattered intensity, and the dynamics, which slow down and develop a two-step decay in the correlation functions. This low-concentration transition is particularly surprising in light of experiments showing that for surfactant vesicles of similar composition the interactions should be purely repulsive. This leads us to suggest that the observed structural and dynamic transition could arise, as an entropic effect, from the large sample polydispersity coupled to crowding. The shear-thinning behavior is thus interpreted as the nonlinear response of this transient structure to the imposed flow. Our work suggests that similar effects might be a generic feature of dense, highly polydisperse charged suspensions