Mechano-Transduction Boosts the Aging Effects in Human Erythrocytes Submitted to Mechanical Stimulation

Erythrocytes’ aging and mechano-transduction are fundamental cellular pathways that determine the red blood cells’ (RBCs) behavior and function. The aging pattern can be influenced, in morphological, biochemical, and metabolic terms by the environmental conditions. In this paper, we studied the effect of a moderate mechanical stimulation applied through external shaking during the RBCs aging and revealed a strong acceleration of the aging pattern induced by such stimulation. Moreover, we evaluated the behavior of the main cellular effectors and resources in the presence of drugs (diamide) or of specific inhibitors of the mechano-transduction (probenecid, carbenoxolone, and glibenclamide). This approach provided the first evidence of a direct cross-correlation between aging and mechano-transduction and permitted an evaluation of the overall metabolic regulation and of the insurgence of specific morphological features, such as micro-vesicles and roughness alterations. Overall, for the first time the present data provided a schematic to understand the integration of distinct complex patterns in a comprehensive view of the cell and of its interactions with the environment. Mechano-transduction produces structural effects that are correlated with the stimulation and the strength of the environmental stimulation is paramount to effectively activate and trigger the biological cascades initiated by the mechano-sensing.     

Gain-of-Function Dynamin-2 Mutations Linked to Centronuclear Myopathy Impair Ca2+-Induced Exocytosis in Human Myoblasts

Gain-of-function mutations of dynamin-2, a mechano-GTPase that remodels membrane and actin filaments, cause centronuclear myopathy (CNM), a congenital disease that mainly affects skeletal muscle tissue. Among these mutations, the variants p.A618T and p.S619L lead to a gain of function and cause a severe neonatal phenotype. By using total internal reflection fluorescence microscopy (TIRFM) in immortalized human myoblasts expressing the pH-sensitive fluorescent protein (pHluorin) fused to the insulin-responsive aminopeptidase IRAP as a reporter of the GLUT4 vesicle trafficking, we measured single pHluorin signals to investigate how p.A618T and p.S619L mutations influence exocytosis. We show here that both dynamin-2 mutations significantly reduced the number and durations of pHluorin signals induced by 10 μM ionomycin, indicating that in addition to impairing exocytosis, they also affect the fusion pore dynamics. These mutations also disrupt the formation of actin filaments, a process that reportedly favors exocytosis. This altered exocytosis might importantly disturb the plasmalemma expression of functional proteins such as the glucose transporter GLUT4 in skeletal muscle cells, impacting the physiology of the skeletal muscle tissue and contributing to the CNM disease.     

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body’s own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016–2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.     

Effect of RF magnetron sputtering parameters on the optimization of the discharge capacity of ternary lithium oxide thin films

Journal of Materials Science: Materials in Electronics - The increasing demand for lithium-ion batteries has stimulated the investigation of new compounds in order to reduce the costs and the...     

A new experimental approach to the investigation of contact forces at an interface

The piezoelectric films recently developed permit the design of very efficient thin sensors which are suited to interesting applications in contact problems, not only in industrial robotics but also in experimental research. After a brief introduction exemplifying the electrical principles, the primary aspects of the technique are presented and discussed with reference to possible structural engineering applications. A rather simple example regarding the interaction between a steel bar and a block of concrete is also presented. The bar is excited by dynamic cyclic loads having variable frequency. The reliability of forces detected via a PVDF sensor is evaluated by comparing the results with those obtained in parallel by means of a dynamometer strain-gauge. The comparison is promising, even if some technological problems must be resolved before this experimental technique may be applied extensively.

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Resume L'étude expérimentale des forces qui se manifestent à une interface équivaut souvent à un problème technique insoluble car chaque appareillage influe de manière significative sur le comportement mécanique. En outre, si l'interface se situe dans un continuum, l'utilisation de transducteurs ou d'extensomètres devient aussi plus complexe. Dans tous les cas, les mesures peuvent se faire éventuellement à proximité de l'interface, mais non à l'interface. Des améliorations techniques récentes dans le domaine de la robotique permettent d'utiliser des films de polymères piézoélectriques (fluoride de polyvinylidène, PVDF). En raison de l'épaisseur de ce capteur qui ne dépasse pas quelques micromètres, le comportement mécanique n'est pas perturbé. Le principle électrique est typique du transducteur piézoélectrique: les charges crées par le film piézoélectrique sollicité sont concentrées sur les surfaces métallisées qui le recouvrent. Cette technique permet d'étudier de nombreux problèmes structurels. S'il s'agit de béton armé, par exemple, il est intéressant d'examiner la répartition de la pression sur un appui de poutre ou bien à la surface d'un boulon d'ancrage, les contraintes interfaciales aussi bien d'une barre d'armature chargée axialement et transversalement, que de goujons dans des structures composites. Un exemple simple montre la fiabilité de la nouvelle technique: une haute barre d'adhérence enrobée dans un bloc de béton est mise sous charge dynamique. On compare la force détectée par le capteur PVDF placé à l'interface barre d'acier-barre d'enrobage avec celle qui est mesurée au moyen du dynamomètre traditionnel placé parallèlement au support. La comparaison, établie à différentes fréquences, est satisfaisante. Cependant, pour utiliser cette nouvelle technique sur une grande échelle, il convient de résoudre quelques problèmes techniques: l'améioration de la conductivité électrique des connexions entre les surfaces métallisées de la couche sensible et les fils d'entrée et de sortie la prévention d'une éventuelle perforation du film par des particules de granulats siliceux qui sont un des constituants de base des mortiers et bétons; l'évaluation de la sensibilité d'un capteur multicouches à l'écrasement inévitable du matériau à proximité d'une barre d'acier, avec une microfissuration locale et un glissement limité. La recherche se poursuit tant au niveau technologique qu'électronique.

     

Use of compatible blends to fabricate carbon black composite vapor detectors

The aim of this work was the development of materials to be used in the field of gas sensing for the detection of organic vapors. Conductive sensors were prepared with carbon black filled blends of poly(vinyl chloride) and diol‐terminated poly(?‐caprolactone), an oligomeric plasticizer. For comparison, blends with di(2‐ethylhexyl)phthalate, a traditional low‐molecular‐weight plasticizer, were also prepared. All sensors were tested upon exposure to different organic vapors. In general, the plasticizer content affected the response rates of the sensors, and a linear variation of the relative resistance with the analyte concentration was observed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1816–1821, 2004     

Mathematical model for the unidirectional solidification of metals: I. cooled molds

This paper presents a new mathematical model that can be used to predict the solidification rate and the temperature distribution during the unidirectional solidification of metals n molds cooled by fluids such as air and water. The model differs from other analytical methods presented in the literature in the sense that it is more general in application and easier to manipulate, while retaining the advantage of convenience over numerical techniques. The proposed model permits the measurement of the Newtonian heat transfer coefficient at the metal/mold interface. In order to verify the applicability to air cooled molds, the model is compared with experimental results in the literature for the cases of lead, tin and lead-tin eutectic. Finally, the case of water cooled molds is examined, the model being compared with experimental results obtained in this work for lead and aluminum.     

Multivariate data analysis of some xenobiotic trace metals in mussels from the Gulf of Trieste

Summary The concentration of Cd, Hg and Pb in the soft part of mussels has been studied by means of bi-and multi-variate statistical approaches. In particular, the principal component analysis has been applied to study the association among these toxic metals in mussels sampled from the gulf of Trieste, which is a critical area as far as mercury pollution is concerned.

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Mehrdimensionale Analyse der Daten einiger xenobiotischer Spurenmetalle in Miesmuscheln aus dem Golf von Triest

Zusammenfassung Der Gehalt von Cd, Hg und Pb in Miesmuschelfleisch wurde nach einer statistischen mehrdimensionalen Analyse untersucht. Besonders wurde die Hauptkomponentenanalyse zum Studium der Assoziationen dieser toxischen Metalle in Miesmuscheln angewandt. Die Miesmuschelproben stammten aus dem Golf von Triest, ein kritisches Gebiet für Quecksilberverunreinigungen.

     

Differential roles of IRS-1 and SHC signaling pathways in breast cancer cells

Several polypeptide growth factors stimulate breast cancer growth and may be involved in tumor progression. However, the relative importance of diverse growth factor signaling pathways in the development and maintenance of the neoplastic phenotype is largely unknown. The activation of such growth factor receptors as the insulin-like growth factor I receptor (IGF-I R), erbB-type receptors (erbB Rs) and FGF receptors (FGF Rs) controls the phenotype of a model breast cancer cell line MCF-7. To evaluate the function of 2 post-receptor signaling molecules, insulin receptor substrate-1 (IRS-1) (a major substrate of the IGF-IR) and SHC (a common substrate of tyrosine kinase receptors), we developed several MCF-7-derived cell clones in which the synthesis of either IRS-1 or SHC was blocked by antisense RNA. In MCF-7 cells, down-regulation of IRS-1 by 80-85% strongly suppressed anchorage-dependent and -independent growth and induced apoptotic cell death under growth factor- and estrogen-reduced conditions. The reduction of SHC levels by approximately 50% resulted in the inhibition of monolayer and anchorage-independent growth but did not decrease cell survival. Importantly, cell aggregation and the ability of cells to survive on the extracellular matrix were inhibited in MCF-7/anti-SHC clones, but not in MCF-7/anti-IRS-1 clones. Cell motility toward IGF was not attenuated in any of the tested cell lines, but motility toward EGF was decreased in MCF-7/anti-SHC clones. Our results suggest that in MCF-7 cells: 1) both IRS-1 and SHC are implicated in the control of monolayer and anchorage-independent growth; 2) IRS-1 is critical to support cell survival; 3) SHC is involved in EGF-dependent motility; and 4) normal levels of SHC, but not IRS-1, are necessary for the formation and maintenance of cell-cell interactions.