Free association experiment in determining the gender characteristics in the understanding of the concept "мong" by the speakers of Tatar linguistic culture

The relevance stated in the article the problem is due to the fact that the study of key concepts of the cultures is in recent times one of the dominant positions within the framework of the problem of interaction and mutual influence of language and cultureand the results of mass association experiment ongender-specificby the speakers of Tatar Linguistic Culture. The article includes the study of main characteristics of the concept "Моң" [moŋ] (lyrical sadness, melody) as an emotional concept in the Tatar language picture of the world and its derivations. The purpose of the study is to examine the representation of linguistic-cultural concept in the Tatar national-cultural picture of the world by means of mass associative experiment that extends the knowledge about the specifics of the Tatar mentality. The choice of methods of linguoculturological analysis, including the observation of language material and the description of linguistic facts, the method of analysis of dictionary definitions, etymological, contextual and interpretative analyses, structural-semantic modeling of lexical units, statistical method for processing language material, the associative interrogation of informants, due to the specifics of the studied material,that allow us to thoroughly review and analyze the studied concept. The analysis of the linguistic-cultural concept allows revealing the peculiarities of development of national and linguistic consciousness, to fix the reflection on the verbal level of cogitative activity of the Tatar people, the specifics of his mental world. The results of mass associative experiment can contribute to further study of the culturally significant concepts of the Tatar language picture of the world.Keywords and phrases: education, student. Concept, linguoculturological field, Linguisticculturology, language picture of the world, the association, a mass association experimen

Age-dependent action of reactive oxygen species on transmitter release in mammalian neuromuscular junctions

© 2016 Elsevier Inc.Reactive oxygen species (ROS) are implicated in aging, but the neurobiological mechanisms of ROS action are not fully understood. Using electrophysiological techniques and biochemical assays, we studied the age-dependent effect of hydrogen peroxide (H2O2) on acetylcholine release in rat diaphragm neuromuscular junctions. H2O2 significantly inhibited both spontaneous (measured as frequency of miniature end-plate potentials) and evoked (amplitude of end-plate potentials) transmitter release in adult rats. The inhibitory effect of H2O2 was much stronger in old rats, whereas in newborns tested during the first postnatal week, H2O2 did not affect spontaneous release from nerve endings and potentiated end-plate potentials. Proteinkinase C activation or intracellular Ca2+ elevation restored redox sensitivity of miniature end-plate potentials in newborns. The resistance of neonates to H2O2 inhibition was associated with higher catalase and glutathione peroxidase activities in skeletal muscle. In contrast, the activities of these enzymes were downregulated in old rats. Our data indicate that the vulnerability of transmitter release to oxidative damage strongly correlates with aging and might be used as an early indicator of senescence

Evaluation of the significance of early ultrasound diagnostics in children with congenital hydronephosis

The article assesses the results of a screening and control ultrasound study of full-term and premature newborns with a diagnosis of hydronephrosis, born between 2015 and 2018, who were treated at the Regional Children's Clinical Hospital.В статье дана оценка результатов скринингового и контрольного УЗИ-исследования доношенных и недоношенных новорожденных детей с диагнозом «Гидронефроз», рожденных в период с 2015 по 2018 годы, находившихся на лечении в ГАУЗ СО «Областная детская клиническая больница»

Estimation of efficiency of early identification and correction of hydronephrosis in newborns

In this article we present the results of ultrasound monitoring of newborn children diagnosed with hydronephrosis, born in the period from 2015 to 2018 under observation in clinic ODKB, Ekaterinburg, Sverdlovsk region.В статье представлены данные УЗИ мониторинга новорожденных детей с диагнозом гидронефроз, рожденных в период с 2015 по 2018 годы, находившихся на лечении в ОДКБ г. Екатеринбург, Свердловской области

Perioperative analysis of hematological features in patients with rheumatoid arthritis

The article presents the results of a retrospective comparative study of the hematological parameters of patients with rheumatoid arthritis and deforming arthrosis. Patients underwent hip replacement in the Sverdlovsk regional hospital in Yekaterinburg in 2017.В статье представлены результаты ретроспективного сравнительного исследования гематологических показателей пациентов с ревматоидным артритом и деформирующим артрозом, которым было выполнено эндопротезирование тазобедренного сустава в травматологическом отделении Свердловской областной больнице №1 г. Екатеринбурга в 2017 году

Microglial amyloid beta clearance is driven by PIEZO1 channels

Background Microglia are the endogenous immune cells of the brain and act as sensors of pathology to maintain brain homeostasis and eliminate potential threats. In Alzheimer's disease (AD), toxic amyloid beta (A beta) accumulates in the brain and forms stiff plaques. In late-onset AD accounting for 95% of all cases, this is thought to be due to reduced clearance of A beta. Human genome-wide association studies and animal models suggest that reduced clearance results from aberrant function of microglia. While the impact of neurochemical pathways on microglia had been broadly studied, mechanical receptors regulating microglial functions remain largely unexplored. Methods Here we showed that a mechanotransduction ion channel, PIEZO1, is expressed and functional in human and mouse microglia. We used a small molecule agonist, Yoda1, to study how activation of PIEZO1 affects AD-related functions in human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGL) under controlled laboratory experiments. Cell survival, metabolism, phagocytosis and lysosomal activity were assessed using real-time functional assays. To evaluate the effect of activation of PIEZO1 in vivo, 5-month-old 5xFAD male mice were infused daily with Yoda1 for two weeks through intracranial cannulas. Microglial Iba1 expression and A beta pathology were quantified with immunohistochemistry and confocal microscopy. Published human and mouse AD datasets were used for in-depth analysis of PIEZO1 gene expression and related pathways in microglial subpopulations. Results We show that PIEZO1 orchestrates A beta clearance by enhancing microglial survival, phagocytosis, and lysosomal activity. A beta inhibited PIEZO1-mediated calcium transients, whereas activation of PIEZO1 with a selective agonist, Yoda1, improved microglial phagocytosis resulting in A beta clearance both in human and mouse models of AD. Moreover, PIEZO1 expression was associated with a unique microglial transcriptional phenotype in AD as indicated by assessment of cellular metabolism, and human and mouse single-cell datasets. Conclusion These results indicate that the compromised function of microglia in AD could be improved by controlled activation of PIEZO1 channels resulting in alleviated A beta burden. Pharmacological regulation of these mechanoreceptors in microglia could represent a novel therapeutic paradigm for AD.Peer reviewe

PSEN1 Mutant iPSC-Derived Model Reveals Severe Astrocyte Pathology in Alzheimer's Disease

Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology. We describe here the generation of functional astrocytes from induced pluripotent stem cells (iPSCs) derived from AD patients with PSEN1 Delta E9 mutation, as well as healthy and gene-corrected isogenic controls. AD astrocytes manifest hallmarks of disease pathology, including increased beta-amyloid production, altered cytokine release, and dysregulated Ca2+ homeostasis. Furthermore, due to altered metabolism, AD astrocytes show increased oxidative stress and reduced lactate secretion, as well as compromised neuronal supportive function, as evidenced by altering Ca2+ transients in healthy neurons. Our results reveal an important role for astrocytes in AD pathology and highlight the strength of iPSC-derived models for brain diseases

Collagen XIII secures pre- and postsynaptic integrity of the neuromuscular synapse

© The Author 2017. Published by Oxford University Press. All rights reserved. Both transmembrane and extracellular cues, one of which is collagen XIII, regulate the formation and function of the neuromuscular synapse, and their absence results in myasthenia. We show that the phenotypical changes in collagen XIII knock-out mice are milder than symptoms in human patients, but the Col13a1 -/- mice recapitulate major muscle findings of congenital myasthenic syndrome type 19 and serve as a disease model. In the lack of collagen XIII neuromuscular synapses do not reach full size, alignment, complexity and function resulting in reduced muscle strength. Collagen XIII is particularly important for the preterminal integrity, and when absent, destabilization of the motor nerves results in muscle regeneration and in atrophy especially in the case of slow muscle fibers. Collagen XIII was found to affect synaptic integrity through binding the ColQ tail of acetylcholine esterase. Although collagen XIII is a muscle-bound transmembrane molecule, it also undergoes ectodomain shedding to become a synaptic basal lamina component. We investigated the two forms' roles by novel Col13a1 tm/tm mice in which ectodomain shedding is impaired. While postsynaptic maturation, terminal branching and neurotransmission was exaggerated in the Col13a1 tm/tm mice, the transmembrane form's presence sufficed to prevent defects in transsynaptic adhesion, Schwann cell invagination/retraction, vesicle accumulation and acetylcholine receptor clustering and acetylcholinesterase dispersion seen in the Col13a1 -/- mice, pointing to the transmembrane form as the major conductor of collagen XIII effects. Altogether, collagen XIII secures postsynaptic, synaptic and presynaptic integrity, and it is required for gaining and maintaining normal size, complexity and functional capacity of the neuromuscular synapse

PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia

Summary Here we elucidate the effect of Alzheimer disease (AD)-predisposing genetic backgrounds, APOE4, PSEN1ΔE9, and APPswe, on functionality of human microglia-like cells (iMGLs). We present a physiologically relevant high-yield protocol for producing iMGLs from induced pluripotent stem cells. Differentiation is directed with small molecules through primitive erythromyeloid progenitors to re-create microglial ontogeny from yolk sac. The iMGLs express microglial signature genes and respond to ADP with intracellular Ca2+ release distinguishing them from macrophages. Using 16 iPSC lines from healthy donors, AD patients and isogenic controls, we reveal that the APOE4 genotype has a profound impact on several aspects of microglial functionality, whereas PSEN1ΔE9 and APPswe mutations trigger minor alterations. The APOE4 genotype impairs phagocytosis, migration, and metabolic activity of iMGLs but exacerbates their cytokine secretion. This indicates that APOE4 iMGLs are fundamentally unable to mount normal microglial functionality in AD.Peer reviewe

Adoption of an “Open” Envelope Conformation Facilitating CD4 Binding and Structural Remodeling Precedes Coreceptor Switch in R5 SHIV-Infected Macaques

A change in coreceptor preference from CCR5 to CXCR4 towards the end stage disease in some HIV-1 infected individuals has been well documented, but the reasons and mechanisms for this tropism switch remain elusive. It has been suggested that envelope structural constraints in accommodating amino acid changes required for CXCR4 usage is an obstacle to tropism switch, limiting the rate and pathways available for HIV-1 coreceptor switching. The present study was initiated in two R5 SHIVSF162P3N-infected rapid progressor macaques with coreceptor switch to test the hypothesis that an early step in the evolution of tropism switch is the adoption of a less constrained and more “open” envelope conformation for better CD4 usage, allowing greater structural flexibility to accommodate further mutational changes that confer CXCR4 utilization. We show that, prior to the time of coreceptor switch, R5 viruses in both macaques evolved to become increasingly sCD4-sensitive, suggestive of enhanced exposure of the CD4 binding site and an “open” envelope conformation, and this correlated with better gp120 binding to CD4 and with more efficient infection of CD4low cells such as primary macrophages. Moreover, significant changes in neutralization sensitivity to agents and antibodies directed against functional domains of gp120 and gp41 were seen for R5 viruses close to the time of X4 emergence, consistent with global changes in envelope configuration and structural plasticity. These observations in a simian model of R5-to-X4 evolution provide a mechanistic basis for the HIV-1 coreceptor switch