Electroencephalographic Intercentral Interaction as a Reflection of Normal and Pathological Human Brain Activity

The authors summarized EEG findings and defined the nature of the intercentral EEG relationships in different functional states in healthy subjects and patients with organic cerebral pathology, based on a coherence analysis. Similar EEG characteristics in healthy individuals were identified: an anterior-posterior gradient of average coherence levels, the type of cortical-subcortical relationships in anterior cerebral structures. Right- and left-handed individuals showed frequent and regional differences in EEG coherence, which mainly reflected specificity of intracortical relationships. Development and regression of pathology in right-and left-handed individuals with organic brain lesions were thought to be caused by these differences. Lesions of regulatory structures (diencephalic, brain stem and limbic structures) provoked a more diffused kind of changes of intercentral relationships, in contrast to cortical pathology. These changes tended to reciprocate. The dynamic nature of intercentral relationships and their interhemispheric differences was revealed when changing functional states of the brain (increase and decrease of functional level) in healthy individuals and patients with organic cerebral pathology in the process of conscious and psychic activity restoration. Changing activity predominance of certain regulatory structures was considered one of the most important factors determining the dynamic nature of EEG coherenceLos autores resumen los resultados de las investigaciones de las relaciones intercentrales de EEG de personas sanas en distintos estados funcionales y de enfermos con lesiones orgánicas del SNC, mediante análisis de coherencia. Se revelan características semejantes de la estructura de relaciones de EEG de personas sanas: la gradiente anterior-posterior de niveles medios de coherencia, el carácter de la interacción cortical-subcortical de las secciones anteriores de los hemisferios. A su vez, se detectan diferencias de frecuencia y regionales en la coherencia de EEG en diestros y zurdos, que reflejan mayoritariamente la especificidad de la interacción intracortical. Se cree que estas diferencias causan la especificidad del desarrollo y la regresión de los estados patológicos de diestros y zurdos en lesiones cerebrales orgánicas. Se señala que en las lesiones de formaciones reguladoras (diencefálicas, troncales, límbicas) Provocan unos cambios de las relaciones intercentrales más difusos que en casos de patología cortical. Estos cambios tienden a la reciprocidad. Se revela el carácter dinámico de las relaciones intercentrales y sus diferencias interhemisféricas en los cambios de los estados funcionales del cerebro (incremento, disminución del nivel de funcionamiento) en personas sanas así como en la recuperación de la conciencia y la actividad psíquica en enfermos con patología cerebral orgánica. Uno de los factores que determina el carácter dinámico del cambio de la coherencia del EEG es el cambio del predominio de la actividad de ciertas estructuras reguladoras

State regulation of supply chains through the introduction of goods marking

Among the most acute problems of the modern economy is not only reducing the cost and improving the efficiency of supply chains, but also their protection from the influence of the shadow economy. In this case, the greatest threat is the illicit trafficking of industrial products. Authors analyze state regulation of supply chains in Russia and abroad, consider the prospects for the development of digital marking and traceability of goods as a method of state regulation of supply chains. The article emphasizes that the existing marking system contains a number of shortcomings. The authors propose mechanisms to improve state regulation of supply chains in modern conditions

Estrogen Receptors and Ubiquitin Proteasome System: Mutual Regulation

This review provides information on the structure of estrogen receptors (ERs), their localization and functions in mammalian cells. Additionally, the structure of proteasomes and mechanisms of protein ubiquitination and cleavage are described. According to the modern concept, the ubiquitin proteasome system (UPS) is involved in the regulation of the activity of ERs in several ways. First, UPS performs the ubiquitination of ERs with a change in their functional activity. Second, UPS degrades ERs and their transcriptional regulators. Third, UPS affects the expression of ER genes. In addition, the opportunity of the regulation of proteasome functioning by ERs—in particular, the expression of immune proteasomes—is discussed. Understanding the complex mechanisms underlying the regulation of ERs and proteasomes has great prospects for the development of new therapeutic agents that can make a significant contribution to the treatment of diseases associated with the impaired function of these biomolecules

Влияние длительного воздействия субингибирующих доз антибиотиков и наночастиц серебра на уропатогенные бактерии

Relevance.Although the primary purpose of using antibiotics is to treat infectious diseases, their misuse gradually leads to loss of their effectiveness. The aim of the current investigation was to explore the changes that occur in uropathogenic bacteria after long exposure to antimicrobials. Materials and Methods. We compared the effects of long-term exposure to ampicillin, cefazoline, kanamycin and silver nanoparticles (AgNPs) on susceptibility, biofilm formation and planktonic bacteria in 4 clinical uropathogenic strains namely Escherichia coli (UPEC), Staphylococcus aureus(S. aureus),Enterococcus faecalis (E. faecalis) and Streptococcus agalactiae(St. agalactiae). The minimum inhibitory concentrations (MIC) were determined using the microplate mircodilution method and bacteria were exposed to increasing concentrations of each antimicrobial (from MIC/2 to MIC) prepared in the brain heart infusion broth for 8 days. The susceptibility of bacteria to antibiotics was assessed using the Kirby Bauer disc diffusion method and the biofilm formation was assessed using crystal violet bacterial attachment assay. Results and Discussion. The data in this investigation highlight that long-term exposure to antimicrobials may induce changes in susceptibility to other antibiotics and biofilm formation in Uropathogenic strains. Indeed, exposure to ampicillin made E. faecalis resistant to ceftazidime and St agalactiae resistant to tetracycline, ceftazidime/clavulanate and ceftazidime. Following exposure to cefazolin, a significant decrease in susceptibility was observed in E. coli to ceftazidime/clavulanate and ceftazidime while S. aureus became resistant to ceftazidime/clavulanate, ceftazidime and to ceftriaxone. Similar variations were observed on St agalactiae and E. faecalis, which in addition to the 3 antibiotics above- mentioned, have become resistant to tetracycline. The most significant variations in susceptibility to antibiotics were observed following exposure to kanamycin: E. coli developed resistance to ceftazidime and a decrease in sensitivity was noted on ceftazidime/clavulanate while S. aureus, E. faecalis and St. agalactiae all 3 became resistant to ceftazidime/clavulanate and ceftazidime. In addition, except for E. coli all the bacteria in this investigation which had undergone successive passages in AgNPs developed resistance to ceftazidime/ clavulanate and ceftazidime. Bacteria exposed to ampicillin and cefazolin produced more biofilms than their respective controls. Conclusion.Long term exposure of uropathogens to antibiotics and AgNPs induces significant changes in susceptibility to other antibiotics and biofilm formation and antibiotics should therefore only be used when necessary.Актуальность. В последние годы все более нерациональное использование антибиотиков привело к потере их эффективности. Цель исследования. Настоящее исследование было направлено на изучение изменений, происходящих у уропатогенных бактерий после длительного воздействия противомикробных препаратов. Материалы и методы. Мы оценили влияние длительного воздействия ампициллина, цефазолина, канамицина и наночастиц серебра (AgNP) на чувствительность к другим антибиотикам, образование биопленок и планктонные бактерии у 4 клинических уропатогенных штаммов, а именно Escherichia coli (UPEC), Staphylococcus aureus, Enterococcus faecalis и Streptococcus agalactiae. Минимальные ингибирующие концентрации (МИК) определяли с использованием метода микроразведений на микропланшетах, и бактерии подвергали воздействию увеличивающихся концентраций каждого противомикробного препарата (от МИК/2 до МИК) в течение 8 дней. Чувствительность бактерий к антибиотикам оценивали с использованием метода дисковой диффузии Кирби-Бауэра, а образование биопленки оценивали с помощью анализа прикрепления бактерий кристаллическим фиолетовым. Результаты и обсуждение. В результате воздействие ампициллина сделало E. faecalis устойчивым к цефтазидиму, а St agalactiae - к тетрациклину, цефтазидиму/клавуланату и цефтазидиму. После воздействия цефазолином наблюдалось значительное снижение чувствительности E. coli к цефтазидиму/клавуланату и цефтазидиму, в то время как S. aureus приобретала устойчивость к цефтазидиму/клавуланату, цефтазидиму и цефтриаксону. Аналогичные вариации наблюдались у St. agalactiae и E. faecalis, которые в дополнение к трем вышеупомянутым антибиотикам стали устойчивыми к тетрациклину. Наиболее значительные изменения в чувствительности к антибиотикам наблюдались после воздействия канамицина: у E. coli развилась устойчивость к цефтазидиму и снижение чувствительности было отмечено к цефтазидиму/клавуланату, в то время как S. aureus, E. faecalis и St agalactiae все 3 стали устойчивыми к цефтазидиму/клавуланат и цефтазидим. Кроме того, за исключением E. coli, все бактерии в этом исследовании, подвергшиеся последовательным пассажам в AgNP, выработали устойчивость к цефтазидиму/клавуланату и цефтазидиму. Бактерии, подвергшиеся воздействию ампициллина и цефазолина, продуцировали больше биопленок, чем их соответствующие контроли. Выводы. Длительное воздействие антибиотиков и AgNP на уропатогены вызывает значительные изменения в чувствительности к другим антибиотикам и образование биопленок

Proteasome functioning in breast cancer: connection with clinical-pathological factors.

Breast cancer is one of four oncology diseases that are most widespread in the world. Moreover, breast cancer is one of leading causes of cancer-related deaths in female population within economically developed regions of the world. So far, detection of new mechanisms of breast cancer development is very important for discovery of novel areas in which therapy approaches may be elaborated. The objective of the present study is to investigate involvement of proteasomes, which cleave up to 90% of cellular proteins and regulate numerous cellular processes, in mechanisms of breast cancer development. Proteasome characteristics in 106 patient breast carcinomas and adjacent tissues, as well as relationships of detected proteasome parameters with clinical-pathological factors, were investigated. Proteasome chymotrypsin-like activity was evaluated by hydrolysis of fluorogenic peptide Suc-LLVY-AMC. The expression of proteasome subunits was studied by Western-blotting and immunohistochemistry. The wide range of chymotrypsin-like activity in tumors was detected. Activity in tumors was higher if compared to adjacent tissues in 76 from 106 patients. Multiple analysis of generalized linear models discovered that in estrogen α-receptor absence, tumor growth was connected with the enhanced expression of proteasome immune subunit LMP2 and proteasome activator PA700 in tumor (at 95% confidence interval). Besides, by this analysis we detected some phenomena in adjacent tissue, which are important for tumor growth and progression of lymph node metastasis in estrogen α-receptor absence. These phenomena are related to the enhanced expression of activator PA700 and immune subunit LMP7. Thus, breast cancer development is connected with functioning of immune proteasome forms and activator PA700 in patients without estrogen α-receptors in tumor cells. These results could indicate a field for search of new therapy approaches for this category of patients, which has the worst prognosis of health recovery

Gene Expression Profile and Functionality of ESC-Derived Lin-ckit+Sca-1+ Cells Are Distinct from Lin-ckit+Sca-1+ Cells Isolated from Fetal Liver or Bone Marrow

In vitro bioreactor-based cultures are being extensively investigated for large-scale production of differentiated cells from embryonic stem cells (ESCs). However, it is unclear whether in vitro ESC-derived progenitors have similar gene expression profiles and functionalities as their in vivo counterparts. This is crucial in establishing the validity of ESC-derived cells as replacements for adult-isolated cells for clinical therapies. In this study, we compared the gene expression profiles of Lin-ckit+Sca-1+ (LKS) cells generated in vitro from mouse ESCs using either static or bioreactor-based cultures, with that of native LKS cells isolated from mouse fetal liver (FL) or bone marrow (BM). We found that in vitro-generated LKS cells were more similar to FL- than to BM LKS cells in gene expression. Further, when compared to cells derived from bioreactor cultures, static culture-derived LKS cells showed fewer differentially expressed genes relative to both in vivo LKS populations. Overall, the expression of hematopoietic genes was lower in ESC-derived LKS cells compared to cells from BM and FL, while the levels of non-hematopoietic genes were up-regulated. In order to determine if these molecular profiles correlated with functionality, we evaluated ESC-derived LKS cells for in vitro hematopoietic-differentiation and colony formation (CFU assay). Although static culture-generated cells failed to form any colonies, they did differentiate into CD11c+ and B220+ cells indicating some hematopoietic potential. In contrast, bioreactor-derived LKS cells, when differentiated under the same conditions failed to produce any B220+ or CD11c+ cells and did not form colonies, indicating that these cells are not hematopoietic progenitors. We conclude that in vitro culture conditions significantly affect the transcriptome and functionality of ESC-derived LKS cells and although in vitro differentiated LKS cells were lineage negative and expressed both ckit and Sca-1, these cells, especially those obtained from dynamic cultures, are significantly different from native cells of the same phenotype.This work was partially supported through National Institutes of Health grant number EB005026 to KR and PWT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding received for this study.Biomedical Engineerin

Statistical indicators for revealed dependence of the proteasome parameters in breast samples on simultaneous effect of clinical-pathological factors.^1.

1<p>Multiple GLM (generalized linear models) analysis was applied;</p>2<p>F (DF), F-test value for indicated pair of interacting signs (Degrees of Freedom);</p>3<p><i>p</i>, statistical significance of observed effects.</p><p>Statistical indicators for revealed dependence of the proteasome parameters in breast samples on simultaneous effect of clinical-pathological factors.^1.</p