Control of neuronal ion channel function by glycogen synthase kinase-3: new prospective for an old kinase

Glycogen synthase kinase 3 (GSK-3) is an evolutionarily conserved multifaceted ubiquitous enzyme. In the central nervous system (CNS), GSK-3 acts through an intricate network of intracellular signaling pathways culminating in a highly divergent cascade of phosphorylations that control neuronal function during development and adulthood. Accumulated evidence indicates that altered levels of GSK-3 correlate with maladaptive plasticity of neuronal circuitries in psychiatric disorders, addictive behaviors, and neurodegenerative diseases, and pharmacological interventions known to limit GSK-3 can counteract some of these deficits. Thus, targeting the GSK-3 cascade for therapeutic interventions against this broad spectrum of brain diseases has raised a tremendous interest. Yet, the multitude of GSK-3 downstream effectors poses a substantial challenge in the development of selective and potent medications that could efficiently block or modulate the activity of this enzyme. Although the full range of GSK-3 molecular targets are far from resolved, exciting new evidence indicates that ion channels regulating excitability, neurotransmitter release, and synaptic transmission, which ultimately contribute to the mechanisms underling brain plasticity and higher level cognitive and emotional processing, are new promising targets of this enzyme. Here, we will revise this new emerging role of GSK-3 in controling the activity of voltage-gated Na(+), K(+), Ca(2+) channels and ligand-gated glutamate receptors with the goal of highlighting new relevant endpoints of the neuronal GSK-3 cascade that could provide a platform for a better understanding of the mechanisms underlying the dysfunction of this kinase in the CNS and serve as a guidance for medication development against the broad range of GSK-3-linked human diseases

The anandamide analog, Met-F-AEA, controls human breast cancer cell migration via the RHOA/RHO kinase signaling pathway

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Sulfur Starvation in Extremophilic Microalga Galdieria sulphuraria: Can Glutathione Contribute to Stress Tolerance?

This study reports the effects of sulfur (S) deprivation in cultures of Galdieria sulphuraria (Cyanidiophyceae). Galdieria is a unicellular red alga that usually grows, forming biomats on rocks, in S-rich environments. These are volcanic areas, where S is widespread since H2S is the prevalent form of gas. The glutathione content in Galdieria sulphuraria is much higher than that found in the green algae and even under conditions of S deprivation for 7 days, it remains high. On the other hand, the S deprivation causes a decrease in the total protein content and a significant increase in soluble protein fraction. This suggests that in the conditions of S starvation, the synthesis of enzy-matic proteins, that metabolically support the cell in the condition of nutritional stress, could be up regulated. Among these enzymatic proteins, those involved in cell detoxification, due to the accumulation of ROS species, have been counted

Seismic vulnerability assessment of existing Italian hospitals: The case study of the national cancer institute “G. Pascale foundation” of Naples

Introduction: A large portion of the Italian built heritage is characterized by a significant seismic vulnerability since many structures were designed with outdated criteria, i.e., without accounting for seismic actions. This aspect is particularly relevant for strategic structures and infrastructures, whose functionalities are crucial in case of seismic events. Objective: The main aim of the present paper is to share the key findings related to the seismic vulnerability assessment of the National Institute for the Study and Treatment of Cancer (IRCCS) “Giovanni Pascale Foundation” in Naples. In particular, the main evidences could be easily extended to existing hospitals realized in the last century, with the main reference to: construction techniques, quality of constructional material, overt and convert seismic vulnerabilities and possible intervention strategies for risk mitigation. Methods: In the present paper, the assessment methodologies adopted for such a strategic hospital complex are provided, focusing in particular on: i. preliminary research of original design documents and on-site investigation for determining constructional details; ii. material tests on structural elements; iii. vulnerability seismic assessment by means of non-linear FE analyses (push-over and capacity spectrum method); iv. recommendations on retrofitting measures and cost estimations. Results: The conducted study puts into clear evidence the inadequacy of the investigated buildings to face the design seismic actions provided by the current Italian code and thus showed the significant seismic vulnerabilities affecting the Institute “G. Pascale Foundation” of Naples. Among these, particular attention has also been focused on the so-called intrinsic vulnerabilities, namely the ones not measurable explicitly and interesting non-structural elements (e.g., connection of shelves, stained glass windows, facilities, etc.). Conclusion: The presented case study highlights the strong seismic vulnerability affecting structures realized in the past century, despite their strategic functions. On the whole, the examined structures can be considered as representative of this building typology, and the adopted calculation criteria, as well as the assumptions of the assessment process, could be easily extended to similar case studies

Domains 12 to 16 of tropoelastin promote cell attachment and spreading through interactions with glycosaminoglycan and integrins alphaV and alpha5beta1

Elastin is an extracellular matrix component with key structural and biological roles in elastic tissues. Interactions between resident cells and tropoelastin, the monomer of elastin, underpin elastin’s regulation of cellular processes. However, the nature of tropoelastin–cell interactions and the contributions of individual tropoelastin domains to these interactions are only partly elucidated. In this study, we identified and characterized novel cell-adhesive sites in the tropoelastin N-terminal region between domains 12 and 16. We found that this region interacts with aV and a5b1 integrin receptors, which mediate cell attachment and spreading. A peptide sequence from within this region, spanning domains 14 to mid-domain 16, binds heparan sulfate through electrostatic interactions with peptide lysine residues and induces conformational ordering of the peptide. We propose that domains 14–16 direct initial cell attachment through cell-surface heparan sulfate glycosaminoglycans, followed by aV and a5b1 integrin-promoted attachment and spreading on domains 12–16 of tropoelastin. These findings advance our mechanistic understanding of elastin matrix biology, with the potential to enhance tissue regenerative outcomes of elastin-based materials