A Single Episode of Cortical Spreading Depolarization Increases mRNA Levels of Proinflammatory Cytokines,Calcitonin Gene-Related Peptide and Pannexin-1 Channels in the Cerebral Cortex

Cortical spreading depolarization (CSD) is the neuronal correlate of migraine aura and the reliable consequence of acute brain injury. The role of CSD in triggering headaches that follow migraine aura and brain injury remains to be uncertain. We examined whether a single CSD occurring in awake animals modified the expression of proinflammatory cytokines (Il1b, TNF, and Il6) and endogenous mediators of nociception/neuroinflammation-pannexin 1 (Panx1) channel and calcitonin gene-related peptide (CGRP), transforming growth factor beta (TGFb) in the cortex. Unilateral microinjury of the somatosensory cortex triggering a single CSD was produced in awake Wistar rats. Three hours later, tissue samples from the lesioned cortex, intact ipsilesional cortex invaded by CSD, and homologous areas of the contralateral sham-treated cortex were harvested and analyzed using qPCR. Three hours post-injury, intact CSD-exposed cortexes increased TNF, Il1b, Panx1, and CGRP mRNA levels. The strongest upregulation of proinflammatory cytokines was observed at the injury site, while CGRP and Panx1 were upregulated more strongly in the intact cortexes invaded by CSD. A single CSD is sufficient to produce low-grade parenchymal neuroinflammation with simultaneous overexpression of Panx1 and CGRP. The CSD-induced molecular changes may contribute to pathogenic mechanisms of migraine pain and post-injury headache.     

Role of Nitric Oxide-Derived Metabolites in Reactions of Methylglyoxal with Lysine and Lysine-Rich Protein Leghemoglobin

Carbonyl stress occurs when reactive carbonyl compounds (RCC), such as reducing sugars, dicarbonyls etc., accumulate in the organism. The interaction of RCC carbonyl groups with amino groups of molecules is called the Maillard reaction. One of the most active RCCs is α-dicarbonyl methylglyoxal (MG) that modifies biomolecules forming non-enzymatic glycation products. Organic free radicals are formed in the reaction between MG and lysine or Nα-acetyllysine. S-nitrosothiols and nitric oxide (^•NO) donor PAPA NONOate increased the yield of organic free radical intermediates, while other ^•NO-derived metabolites, namely, nitroxyl anion and dinitrosyl iron complexes (DNICs) decreased it. At the late stages of the Maillard reaction, S-nitrosoglutathione (GSNO) also inhibited the formation of glycation end products (AGEs). The formation of a new type of DNICs, bound with Maillard reaction products, was found. The results obtained were used to explain the glycation features of legume hemoglobin—leghemoglobin (Lb), which is a lysine-rich protein. In Lb, lysine residues can form fluorescent cross-linked AGEs, and ^•NO-derived metabolites slow down their formation. The knowledge of these processes can be used to increase the stability of Lb. It can help in better understanding the impact of stress factors on legume plants and contribute to the production of recombinant Lb for biotechnology.     

Microsatellite Instability in Russian Patients with Colorectal Cancer

The aim of this study was to determine the characteristics of Russian patients with microsatellite instability (MSI) tumors. MSI in the tumor was determined in 514 patients with colon cancer using PCR and subsequent fragment analysis for five markers (NR21, NR24, BAT25, BAT26, and NR27). In the presence of microsatellite instability, the mismatch repair (MMR) system genes were examined using the NGS and MLPA methods to establish the diagnosis of Lynch syndrome. The overall frequency of MSI tumors was 15%: at stage I—19% (9/48), at stage II—21% (44/213), at stage III—16% (26/160), and at stage IV—2% (2/93). Patients with MSI tumors differed in the age of diagnosis, tumor localization, time of cancer recurrence, and stage of the disease. The overall and disease-free survival of patients whose tumors had MSI status was higher than that of patients with microsatellite-stable status, p = 0.04 and p = 0.02, respectively. Analysis of overall and disease-free survival of patients with Lynch syndrome and patients with sporadic colon cancer, but with MSI status, did not reveal significant differences, p = 0.52 and p = 0.24, respectively. The age of patients with Lynch syndrome was significantly younger than that of patients with sporadic colon cancer whose tumors had MSI status (p < 0.001).     

Asymptotic Stability Conditions and Estimates of Solutions for Nonlinear Multiconnected Time-Delay Systems

This paper examines certain classes of multiconnected (complex) systems with time-varying delay. Delay-independent stability conditions and estimates of the convergence rate of solutions to the origin for those systems are derived. It is shown that the exponents in the obtained estimates depend on the parameters of Lyapunov functions constructed for the corresponding isolated subsystems. The problem of computing parameter values that provide the most precise estimates is investigated. Some examples are presented to demonstrate the effectiveness of the proposed approaches.     

Using Ideas of Kolmogorov Complexity for Studying Biological Texts

Kolmogorov complexity furnishes many useful tools for studying different natural processes that can be expressed using sequences of symbols from a finite alphabet (texts), such as genetic texts, literary and music texts, animal communications, etc. Although Kolmogorov complexity is not algorithmically computable, in a certain sense it can be estimated by means of data compressors. Here we suggest a method of analysis of sequences based on ideas of Kolmogorov complexity and mathematical statistics, and apply this method to biological (ethological) ??texts.?? A distinction of the suggested method from other approaches to the analysis of sequential data by means of Kolmogorov complexity is that it belongs to the framework of mathematical statistics, more specifically, that of hypothesis testing. This makes it a promising candidate for being included in the toolbox of standard biological methods of analysis of different natural texts, from DNA sequences to animal behavioural patterns (ethological ??texts??). Two examples of analysis of ethological texts are considered in this paper. Theses examples show that the proposed method is a useful tool for distinguishing between stereotyped and flexible behaviours, which is important for behavioural and evolutionary studies.     

Contract-theoretic Approach for Delay Constrained Offloading in Vehicular Edge Computing Networks

Mobile Networks and Applications - Mobile Edge Computing (MEC) is a promising solution to improve vehicular services through offloading computation to cloud servers in close proximity to mobile...