The Glacier Complexes of the Mountain Massifs of the North-West of Inner Asia and their Dynamics

The subject of this paper is the glaciation of the mountain massifs Mongun-Taiga, Tavan-Boghd-Ola, Turgeni- Nuru, and Harhira-Nuru. The glaciation is represented mostly by small forms that sometimes form a single complex of domeshaped peaks. According to the authors, the modern glaciated area of the mountain massifs is 21.2 km2 (Tavan-Boghd-Ola), 20.3 km2 (Mongun-Taiga), 42 km2 (Turgeni- Nuru), and 33.1 km2 (Harhira-Nuru). The area of the glaciers has been shrinking since the mid 1960’s. In 1995–2008, the rate of reduction of the glaciers’ area has grown considerably: valley glaciers were rapidly degrading and splitting; accumulation of morainic material in the lower parts of the glaciers accelerated. Small glaciers transformed into snowfields and rock glaciers. There has been also a degradation of the highest parts of the glaciers and the collapse of the glacial complexes with a single zone of accumulation into isolated from each other glaciers. Reduced snow cover area has led to a rise in the firn line and the disintegration of a common accumulation area of the glacial complex. In the of the Mongun-Taiga massif, in 1995– 2008, the firn line rose by 200–300 m. The reduction of the glaciers significantly lagged behind the change in the position of the accumulation area boundary. In the past two years, there has been a significant recovery of the glaciers that could eventually lead to their slower degradation or stabilization of the glaciers in the study area

QCL active region overheat in pulsed mode: effects of non-equilibrium heat dissipation on laser performance

Quantum cascade lasers are of high interest in the scientific community due to unique applications utilizing the emission in mid-IR range. The possible designs of QCL are quite limited and require careful engineering to overcome some crucial disadvantages. One of them is an active region (ARn) overheat, that significantly affects the laser characteristics in the pulsed operation mode. In this work we consider the effects related to the non-equilibrium temperature distribution, when thermal resistance formalism is irrelevant. We employ the heat equation and discuss the possible limitations and structural features stemming from the chemical composition of the AR. We show that the presence of alloys in the ARn structure fundamentally limits the heat dissipation in pulsed and CW regimes due to their low thermal conductivity. Also the QCL post-growths affects the thermal properties of a device only in (near)CW mode while it is absolutely invaluable in the pulsed mod

Trends in the epidemiology of diabetic retinopathy in Russian Federation according to the Federal Diabetes Register (2013–2016)

Background: Diabetic retinopathy (DR) is one of the most common causes of blindness in patients with diabetes mellitus (DM) that is why its necessary to study the epidemiological characteristics of this complication. Aims: The aim of the study was to evaluate the epidemiological characteristics of DR and blindness in adult patients with type 1 (T1) and 2 (T2) diabetes in Russian Federation (RF) for period 201316years. Materials and methods: Database of Federal Diabetes register, 81st regions included in the online register. Indicators were estimated per 10,000 adult DM patients (18years). Results: In 2016 the DR prevalence in RF was T1 38,3%, T2 15,0%, with marked interregional differences: 2,666,1%, 1,146,4%, respectively. The DR prevalence within 20132016 years was: T1 3830,93805,6; T2 1586,01497,0. Trend of new DR cases/per year increased: T1 153,2187,8; T2 99,7114,9. The structure of new cases of DR in 2016: non-proliferative stage (T1 71,4%, T2 80,3%), pre-proliferative stage 16,4%, 13,8%, proliferative 12,1%, 5,8%, terminal 0,2%, 0,1%, respectively, these data indicated the earlier detection of DR. The mean age of DR diagnosis increased: T1 by 1,2 years, T2 by 2,6. The average DM duration of DR determine increased T1 9,613,1 years, T2 6,09,1. The prevalence of blindness tends to decrease: T1 92,390,8; T2 15,415,2/10.000 DM adults. The amount of new cases of blindness/per year increased: T1 4,34,6; T2 1,21,4. The mean age of blindness increased: T1 39,141,6 years, T2 64,467,4; the mean duration of diabetes before blindness occur (from the time of DM diagnosis) increased: T1 20,221,2 years, in T2 10,711,3. We observed growth of DR treatment (laser surgery, vitrectomy, anti-VEGF medication) but the frequency of use in T2 patients is about 2 times less than in T1. Conclusions: There was a decrease in the overall incidence of eye damage in diabetes (DR and blindness) in the analyzed period in RF. DR and blindness develops at advanced age and with a longer duration of diabetes. As the main directions of eye care development in diabetes it is necessary to standardize primary care in the regions, to unify the examination algorithms and methods of early diagnostic, to increase the continuity and interaction of endocrinologists and ophthalmologists in managing patients with diabetes in order to prevent the development of new cases of vision loss

High and Low Molecular Weight Hyaluronic Acid Differentially Influences Oxylipins Synthesis in Course of Neuroinflammation

Hyaluronic acid (HA), a major glycosaminoglycan of the extracellular matrix, has cell signaling functions that are dependent on its molecular weight. Anti-inflammatory effects for high-molecular-weight (HMW) HA and pro-inflammatory effects for low-molecular-weight (LMW) HA effects were found for various myeloid cells, including microglia. Astrocytes are cells of ectodermal origin that play a pivotal role in brain inflammation, but the link between HA with different molecular weights and an inflammatory response in these cells is not clear. We tested the effects of LMW and HMW HA in rat primary astrocytes, stimulated with Poly:IC (PIC, TLR3 agonist) and lipopolysaccharide (LPS, TLR4 agonist). Oxylipin profiles were measured by the UPLC-MS/MS analysis and metabolites HDoHEs (from docosahexaenoic acid), -HETEs, prostaglandins (from arachidonic acid), DiHOMEs and HODEs (from linoleic acid) were detected. Both, HMW and LMW HA downregulated the cyclooxygenase-mediated polyunsaturated fatty acids metabolism, LMW also reduced lipoxygenase-mediated fatty acid metabolism. Taken together, the data show that both LMW and HMW (i) influence themselves on cytokines (TNFα, IL-6, IL-10), enzymes iNOS, COX-2, and oxylipin levels in extracellular medium of cultured astrocytes, (ii) induced cellular adaptations in long-term applications, (iii) modulate TLR4- and TLR3-signaling pathways. The effects of HMW and LMW HA are predominantly revealed in TLR4– and TLR3- mediated responses, respectively

Multi-Omics Approach Points to the Importance of Oxylipins Metabolism in Early-Stage Breast Cancer

The involvement of oxylipins, metabolites of polyunsaturated fatty acids, in cancer pathogenesis was known long ago, but only the development of the high-throughput methods get the opportunity to study oxylipins on a system level. The study aimed to elucidate alterations in oxylipin metabolism as characteristics of breast cancer patients. We compared the ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) oxylipin profile signatures in the blood plasma of 152 healthy volunteers (HC) and 169 patients with different stages of breast cancer (BC). To integrate lipidomics, transcriptomics, and genomics data, we analyzed a transcriptome of 10 open database datasets obtained from tissues and blood cells of BC patients and SNP data for 33 genes related to oxylipin metabolism. We identified 18 oxylipins, metabolites of omega-3 or omega-6 polyunsaturated fatty acids, that were differentially expressed between BCvsHC patients, including anandamide, prostaglandins and hydroxydocosahexaenoic acids. DEGs analysis of tissue and blood samples from BC patients revealed that 19 genes for oxylipin biosynthesis change their expression level, with CYP2C19, PTGS2, HPGD, and FAAH included in the list of DEGs in the analysis of transcriptomes and the list of SNPs associated with BC. Results allow us to suppose that oxylipin signatures reflect the organism’s level of response to the disease. Our data regarding changes in oxylipins at the system level show that oxylipin profiles can be used to evaluate the early stages of breast cancer

Sex-Mediated Differences in LPS Induced Alterations of TNFα, IL-10 Expression, and Prostaglandin Synthesis in Primary Astrocytes

Although many neurological and psychiatric disorders reveal clear sex-dependent variations, the molecular mechanism of this process is not clear enough. Astrocytes are involved in the response of neural tissue to injury and inflammation, produce steroid hormones, and sense steroid presence. To explore the hypothesis that astrocytes may participate in sex-mediated differences of inflammatory responses, we have examined whether male and female primary rat astrocytes show different responses to lipopolysaccharide (LPS) as a toll-like receptor 4 (TLR4) agonist. Levels of mRNA and proteins of tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and cyclooxygenase (COX)-2 were assessed using qPCR, immunoblotting, and ELISA. UPLC-MS/MS was used to detect prostaglandins (PGs). LPS stimulation resulted in different levels of cytokine production; more TNFα and less IL-10 were produced in female cells compared with male astrocytes. Although the levels of the COX-2 expression were not altered, LPS significantly induced the synthesis of PGs with notable sex-related differences. PGE2 and PGD2 were less and 6-keto-PGF1α was more upregulated in female astrocytes, and TXB2 had similar levels in cells obtained from males and females. Trilostane, an inhibitor of 3β-Hydroxysteroid dehydrogenase (3β-HSD), inhibited the LPS-induced TNFα production and the release of PGE2, PGD2, and 6-keto-PGF1α in female astrocytes. Thus, male and female astrocytes differentially respond to inflammatory challenges on the level of production of cytokines and steroid hormones. Sex-mediated differences in pro- and anti-inflammatory responses should be taken into consideration for the effective treatment of disorders with neuroinflammation

Cellular Model of Endotoxin Tolerance in Astrocytes: Role of Interleukin 10 and Oxylipins

A phenomenon of endotoxin tolerance where prior exposure of cells to minute amounts of lipopolysaccharide (LPS) causes them to become refractory to a subsequent high-amount endotoxin challenge is well described for innate immune cells such as monocytes/macrophages, but it is still obscure for brain cells. We exposed primary rat cortical astrocytes to a long-term low-grade concentration of LPS, followed by stimulation with a middle-grade concentration of LPS. Inflammatory markers, i.e., pro-inflammatory cytokine TNFα, inducible enzymes COX-2 and iNOS, anti-inflammatory cytokine interleukin 10 (IL-10) detected at the mRNA and protein levels reveal similarities between astrocytes and macrophages in the model, i.e., tolerance in pro-inflammatory markers and priming in IL-10. Long-term or short-term treatment with IL-10 does not change cell sensitivity for LPS, which makes doubtful its involvement in the mechanisms of cell tolerance development. Significant changes occur in the oxylipin profiles measured by UPLC-MS/MS analysis. The priming occurs in the following compounds: 11-HETE, PGD2, PGE2, cyclopentenone prostaglandins, and TXB2. Tolerance is observed for 12-HHT, PGF2α, and 6-keto-PGF1α. As far as we know, this is the first report on changes in oxylipin profiles in the endotoxin tolerance model. The data can greatly improve the understanding of oxylipins’ role in inflammatory and resolution processes in the brain and mechanisms of astrocyte involvement in neuroinflammation

ARGEOS: A New Bioinformatic Tool for Detailed Systematics Search in GEO and ArrayExpress

Conduct a reanalysis of transcriptome data for studying intracellular signaling or solving other experimental problems is becoming increasingly popular. Gene expression data are archived as microarray or RNA-seq datasets mainly in two public databases: Gene Expression Omnibus (GEO) and ArrayExpress (AE). These databases were not initially intended to systematically search datasets, making it challenging to conduct a secondary study. Therefore, we have created the ARGEOS service, which has the following advantages that facilitate the search: (1) Users can simultaneously send several requests that are supposed to be used for systematic searches, and it is possible to correct the requests; (2) advanced analysis of information about the dataset is available. The service collects detailed protocols, information on the number of datasets, analyzes the availability of raw data, and provides other reference information. All this contributes to both rapid data analysis with the search for the most relevant datasets and to the systematic search with detailed analysis of the information of the datasets. The efficiency of the service is shown in the example of analyzing transcriptome data of activated (polarized) cells. We have performed a systematic search of studies of cell polarization (when cells are exposed to different immune stimuli). The web interface for ARGEOS is user-friendly and straightforward. It can be used by a person who is not familiar with database searching