The Spatiotemporal Coupling: Regional Energy Failure and Aberrant Proteins in Neurodegenerative Diseases

The spatial and temporal coordination of each element is a pivotal characteristic of systems, and the central nervous system (CNS) is not an exception. Glial elements and the vascular interface have been considered more recently, together with the extracellular matrix and the immune system. However, the knowledge of the single-element configuration is not sufficient to predict physiological or pathological long-lasting changes. Ionic currents, complex molecular cascades, genomic rearrangement, and the regional energy demand can be different even in neighboring cells of the same phenotype, and their differential expression could explain the region-specific progression of the most studied neurodegenerative diseases. We here reviewed the main nodes and edges of the system, which could be studied to develop a comprehensive knowledge of CNS plasticity from the neurovascular unit to the synaptic cleft. The future goal is to redefine the modeling of synaptic plasticity and achieve a better understanding of neurological diseases, pointing out cellular, subcellular, and molecular components that couple in specific neuroanatomical and functional regions.     

Low Ozone Concentrations Differentially Affect the Structural and Functional Features of Non-Activated and Activated Fibroblasts In Vitro

Oxygen–ozone (O₂–O₃) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O₃ concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O₂–O₃ gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O₃ stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-β1 secretion, while in LPS-activated fibroblasts, O₃ stimulated only antioxidant response and cytokines secretion. Therefore, the low O₃ concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated.     

A parallel block row-action method for solving large sparse linear systems on distributed memory multiprocessors

Recently developed block-iterative versions of some row-action algorithms for solving general systems of sparse linear equations allow parallelism in the computations when the underlying problem is appropriately decomposed. However, problems associated with the parallel implementation of these algorithms have to be addressed. In this paper we present an implementation on distributed memory multiprocessors of a block version of the Kaczmarz row-action method. One of the main issues related to the efficient implementation of this method on a concurrent environment is to develop suitable communication schemes in order to reduce the amount of communication needed at each iteration. We propose two data distribution strategies which lead to different computation and communication schemes. To verify and compare the effectiveness of the proposed strategies, numerical experiments have been carried out on a Symult S2010 and a Meiko Computing Surface. The performance evaluation has been done using a scaled efficiency model.     

Coupling of Carbon Dioxide with Epoxides Efficiently Catalyzed by Thioether‐Triphenolate Bimetallic Iron(III) Complexes: Catalyst Structure–Reactivity Relationship and Mechanistic DFT Study

A series of dinuclear iron(III)^I complexes supported by thioether‐triphenolate ligands have been prepared to attain highly Lewis acidic catalysts. In combination with tetrabutylammonium bromide (TBAB) they are highly active catalysts in the synthesis of cyclic organic carbonates through the coupling of carbon dioxide to epoxides with the highest initial turnover frequencies reported to date for the conversion of propylene oxide to propylene carbonate for iron‐based catalysts (5200 h⁻¹; 120 °C, 2 MPa, 1 h). In particular, these complexes are shown to be highly selective catalysts for the coupling of carbon dioxide to internal oxiranes affording the corresponding cyclic carbonates in good yield and with retention of the initial stereochemical configuration. A density functional theory (DFT) investigation provides a rational for the relative high activity found for these Fe(III) complexes, showing the fundamental role of the hemilabile sulfur atom in the ligand skeleton to promote reactivity. Notably, in spite of the dinuclear nature of the catalyst precursor only one metal center is involved in the catalytic cycle.

     

Diagnostic and Prognostic Role of Extracellular Vesicles in Pancreatic Cancer: Current Evidence and Future Perspectives

Pancreatic cancer is one of the most aggressive tumors, with a dismal prognosis due to poor detection rates at early stages, rapid progression, post-surgical complications, and limited effectiveness of conventional oncologic therapies. There are no consistently reliable biomarkers or imaging modalities to accurately diagnose, classify, and predict the biological behavior of this tumor. Therefore, it is imperative to develop new and improved strategies to detect pancreatic lesions in the early stages of cancerization with greater sensitivity and specificity. Extracellular vesicles, including exosome and microvesicles, are membrane-coated cellular products that are released in the outer environment. All cells produce extracellular vesicles; however, this process is enhanced by inflammation and tumorigenesis. Based on accumulating evidence, extracellular vesicles play a crucial role in pancreatic cancer progression and chemoresistance. Moreover, they may represent potential biomarkers and promising therapy targets. The aim of the present review is to review the current evidence on the role of extracellular vesicles in pancreatic cancer.     

The impact of chaotic advection on the microstructure of polymer‐modified bitumen

Owing to the high viscosity of the materials involved, mixing is often a critical step when processing polymer‐modified bitumen (PMB), directly influencing the microstructure and the stability of final products. We provide experimental evidence suggesting that laminar chaotic advection may prove a valuable strategy for obtaining a homogeneous and finely interdispersed polymer‐bitumen mixture in affordable time. As a case study, we investigate the mixing performance of a lab‐scale flat‐bottomed cylindrical vessel stirred by a radial impeller, either located symmetrically or eccentrically with respect to the vessel axis. The same geometries with a flat‐disk impeller are also considered for comparison. The Mix‐Norm is used in combination with image analysis as an objective measure of mixing performance. Results of mixing performance are independently validated by rheological tests. The experiments pinpoint kinematic chaos as the fundamental transport mechanism enhancing both the dispersion process and the microstructural quality of the resulting PMBs mixture. © 2014 American Institute of Chemical Engineers AIChE J, 60: 1870–1879, 2014