Links between Immune Cells from the Periphery and the Brain in the Pathogenesis of Epilepsy: A Narrative Review

Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction. Peripheral immune cell invasion into the brain, along with these responses, is implicitly involved in epilepsy. This review explored the current literature on the association between the peripheral and central nervous systems in the pathogenesis of epilepsy, and highlights novel research directions for therapeutic interventions targeting these reactions. Previous experimental and human studies have demonstrated the activation of the innate and adaptive immune responses in the brain. The time required for monocytes (responsible for innate immunity) and T cells (involved in acquired immunity) to invade the central nervous system after a seizure varies. Moreover, the time between the leakage associated with blood–brain barrier (BBB) failure and the infiltration of these cells varies. This suggests that cell infiltration is not merely a secondary disruptive event associated with BBB failure, but also a non-disruptive event facilitated by various mediators produced by the neurovascular unit consisting of neurons, perivascular astrocytes, microglia, pericytes, and endothelial cells. Moreover, genetic manipulation has enabled the differentiation between peripheral monocytes and resident microglia, which was previously considered difficult. Thus, the evidence suggests that peripheral monocytes may contribute to the pathogenesis of seizures.     

Disambiguation of partial cognates

Partial cognates are pairs of words in two languages that have the same meaning in some, but not all contexts. Detecting the actual meaning of a partial cognate in context can be useful for Machine Translation tools and for Computer-Assisted Language Learning tools. We propose a supervised and a semi-supervised method to disambiguate partial cognates between two languages: French and English. The methods use only automatically-labeled data; therefore they can be applied to other pairs of languages as well. The aim of our work is to automatically detect the meaning of a French partial cognate word in a specific context.

The Predictive Role of Plasma Biomarkers in the Evolution of Aortopathies Associated with Congenital Heart Malformations

Dilatation of the aorta is a constantly evolving condition that can lead to the ultimate life-threatening event, acute aortic dissection. Recent research has tried to identify quantifiable biomarkers, with both diagnostic and prognostic roles in different aortopathies. Most studies have focused on the bicuspid aortic valve, the most frequent congenital heart disease (CHD), and majorly evolved around matrix metalloproteinases (MMPs). Other candidate biomarkers, such as asymmetric dimethylarginine, soluble receptor for advanced glycation end-products or transforming growth factor beta have also gained a lot of attention recently. Most of the aortic anomalies and dilatation-related studies have reported expression variation of tissular biomarkers. The ultimate goal remains, though, the identification of biomarkers among the serum plasma, with the upregulation of circulating MMP-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), asymmetric dimethylarginine (ADMA), soluble receptor for advanced glycation end-products (sRAGE) and transforming growth factor beta (TGF-β) being reported in association to several aortopathies and related complications in recent research. These molecules are apparently quantifiable from the early ages and have been linked to several CHDs and hereditary aortopathies. Pediatric data on the matter is still limited, and further studies are warranted to elucidate the role of plasmatic biomarkers in the long term follow-up of potentially evolving congenital aortopathies.     

Cytopathological Outcomes of Knocking down Expression of Mitochondrial Complex II Subunits in Dictyostelium discoideum

Mitochondrial Complex II is composed of four core subunits and mutations to any of the subunits result in lowered Complex II activity. Surprisingly, although mutations in any of the subunits can yield similar clinical outcomes, there are distinct differences in the patterns of clinical disease most commonly associated with mutations in different subunits. Thus, mutations to the SdhA subunit most often result in mitochondrial disease phenotypes, whilst mutations to the other subunits SdhB-D more commonly result in tumour formation. The reason the clinical outcomes are so different is unknown. Here, we individually antisense-inhibited three of the Complex II subunits, SdhA, SdhB or SdhC, in the simple model organism Dictyostelium discoideum. Whilst SdhB and SdhC knockdown resulted in growth defects on bacterial lawns, antisense inhibition of SdhA expression resulted in a different pattern of phenotypic defects, including impairments of growth in liquid medium, enhanced intracellular proliferation of the bacterial pathogen Legionella pneumophila and phagocytosis. Knockdown of the individual subunits also produced different abnormalities in mitochondrial function with only SdhA knockdown resulting in broad mitochondrial dysfunction. Furthermore, these defects were shown to be mediated by the chronic activation of the cellular energy sensor AMP-activated protein kinase. Our results are in agreement with a role for loss of function of SdhA but not the other Complex II subunits in impairing mitochondrial oxidative phosphorylation and they suggest a role for AMP-activated protein kinase in mediating the cytopathological outcomes.     

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism’s response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.     

Chalcogenide Thermoelectrics Empowered by an Unconventional Bonding Mechanism

Thermoelectric materials have attracted significant research interest in recent decades due to their promising application potential in interconverting heat and electricity. Unfortunately, the strong coupling between the material parameters that determine thermoelectric efficiency, i.e., the Seebeck coefficient, electrical conductivity, and thermal conductivity, complicates the optimization of thermoelectric energy converters. Main‐group chalcogenides provide a rich playground to alleviate the interdependence of these parameters. Interestingly, only a subgroup of octahedrally coordinated chalcogenides possesses good thermoelectric properties. This subgroup is also characterized by other outstanding characteristics suggestive of an exceptional bonding mechanism, which has been coined metavalent bonding. This conclusion is further supported by a map that separates different bonding mechanisms. In this map, all octahedrally coordinated chalcogenides with good performance as thermoelectrics are located in a well‐defined region, implying that the map can be utilized to identify novel thermoelectrics. To unravel the correlation between chemical bonding mechanism and good thermoelectric properties, the consequences of this unusual bonding mechanism on the band structure are analyzed. It is shown that features such as band degeneracy and band anisotropy are typical for this bonding mechanism, as is the low lattice thermal conductivity. This fundamental understanding, in turn, guides the rational materials design for improved thermoelectric performance by tailoring the chemical bonding mechanism.     

Morphology and surface properties of some siloxane–organic copolymers

BACKGROUND: It is well known that, due to their extremely low polarity, polysiloxanes are incompatible with almost any organic system. This incompatibility leads to phase separation in mixed siloxane–organic systems. RESULTS: Three siloxane–organic copolymers, poly[(5,5′‐methylene‐bis‐salicylaldehyde)‐imine‐(1,3‐bis(propylene)tetramethyldisiloxane)] (Paz1), poly[(2,5‐dihydroxy‐1,4‐benzoquinone)‐imine‐(1,3‐bis(propylene)tetramethyldisiloxane)] (Paz2) and poly[1,3‐bis(propylene)tetramethyldisiloxane diamide] (Pam), were prepared by the reaction of 1,3‐bis(3‐aminopropyl)tetramethyldisiloxane with appropriate organic partners (5,5′‐methylene‐bis‐salicylaldehyde, 2,5‐dihydroxy‐1,4‐benzoquinone and oxalyl chloride, respectively). The morphologies dictated by the incompatibility between siloxane and polar organic moieties were investigated using differential scanning calorimetry and scanning electron microscopy. The surface activity of the copolymers and water vapour sorption capacity were also measured. CONCLUSION: Even though the polar sequences are very short ones, the highly flexible siloxane‐containing sequence permits the self‐assembly of these into more or less polar domains. Such an organization influences the properties of the resulting materials, an important place being occupied by the surface properties. Copyright © 2009 Society of Chemical Industry     

Neural network modeling of the preparation process of a siloxane‐organic polyazomethine

Although apparently simple, the polycondensation reaction leading to polyazomethine is difficult to control because of its equilibrium character, the conversion degree being influenced by a series of parameters. The reaction between a siloxanediamine, 1,3‐bis(3‐aminopropyl)tetramethyldisiloxane, and terephthalaldehyde was performed here in solution (in tetrahydrofuran) without by‐products removal and in absence of any catalyst or pH modifier. Different conditions (co‐monomers ratio, dilution, and temperature), considered as input parameters for the process modeling, were varied according to a pre‐established experimental program. The viscosity of the reaction mixture was chosen as output parameter, being monitored with a Haake Viscotester 7 Plus‐L. The process modeling was performed using a hybrid combination of artificial neural networks and differential evolution algorithm, the last one having the role of developing the neural model in an optimal form. The simulation results showed that the methodology provides accurate results, the model predictions being in close correlation with the experimental data. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42552.