Organización en clúster de industrias extractivas en las regiones del norte: un método de evaluación integral

La organización espacial de las fuerzas productivas, el uso eficiente de las instalaciones disponibles y la evaluación del potencial productivo de los sectores económicos de una región determinada son temas de actualidad. La República de Sakha (Yakutia) es una gran región de Rusia dependiente de los recursos, notable por la dispersión geográfica de los depósitos en un vasto territorio y las complejas infraestructuras de transporte y suministro de energía. Este documento presenta una evaluación integral de la viabilidad de la organización de clusters en el sector de uso del subsuelo en la República de Sakha (Yakutia), Federación de Rusia, teniendo en cuenta la zonificación económica existente y prospectiva y el potencial existente. La república se dividió en zonas basadas en un marco de clúster de los usuarios del subsuelo. El estudio utilizó datos estadísticos de los distritos municipales e indicadores financieros de las empresas de la industria extractiva. En la evaluación se aplicó el método integrado y se calculó el índice de desempeño de los territorios del clúster identificados en una escala de diez puntos. Las zonas identificadas se clasificaron por recursos y potencial de producción. Se calculó el índice de rendimiento general de la zona de conglomerados. Pareció factible agrupar la industria extractiva en la región estudiada, ya que puede aumentar la competitividad de las empresas locales y contribuir al desarrollo socioeconómico de sus distritos municipales. El método propuesto se puede aplicar para una evaluación integral del sector de uso del subsuelo en los territorios del nort

Прогнозирование локализации отдаленных метастазов при раке молочной железы

Background. Distant organ tumor dissemination is a major cause of breast cancer-related deaths. Breast cancer can metastasize to several organs, and the most frequent metastatic sites include the bones, lungs and liver. There is a question what factors can influence the direction of spread of tumor cells to a particular organ.Material and Methods. We summarized the data available in the world literature on methods for prediction of the localization of distant metastases in breast cancer patients.Results. We divided the factors associated with the localization of distant metastases into two main groups: clinicopathological parameters of breast cancer patients and molecular features of tumor microenvironment and tumor cells (primary tumor and circulating tumor cells) or its derivates – exosomes. From our point of view, the most powerful clinicopathological factor predicting the distant metastasis site is a molecular subtype of primary tumor. We can conclude that luminal (HR+/HER2-) tumors are often characterized by single metastases and bones are the most common metastatic site, while TNBC and HER2-enriched tumors often metastasize to multiple sites, most commonly brain and liver. However, several authors did not reveal these associations in their studies. It likely indicates the existence of other factors that significantly affect the organotropism of metastasis. Numerous studies demonstrate the association of different molecules expressed on tumor cells with organotropic metastasis. However, these data are very fragmentary and rather contradictory.Conclusion. The found associations are common to all participants of metastatic cascade, but remains unclear which factors are essential and crucial in determining the direction of metastasis.Введение. Метастазирование опухоли в отдаленные органы является основной причиной смерти при раке молочной железы. Преимущественная локализация отдаленных метастазов при раке молочной железы – кости, легкие и печень. Возникает вопрос, какие факторы могут влиять на направление распространения опухолевых клеток в тот или иной орган.Материал и методы. Мы обобщили имеющиеся в мировой литературе данные о методах прогнозирования локализации отдаленных метастазов у больных раком молочной железы.Результаты. Факторы, связанные с локализацией отдаленных метастазов, мы разделили на две основные группы: клинико-патологические параметры больных раком молочной железы и молекулярные особенности микроокружения опухоли и опухолевых клеток (первичных опухолевых и циркулирующих опухолевых клеток) или их производных – экзосом. Представляется, что молекулярный подтип первичной опухоли является наиболее перспективным предиктором, предсказывающим место отдаленного метастазирования. Люминальные опухоли (HR+/ HER2-) чаще характеризуются единичными метастазами, с преимущественной локализацией в костях, в то время как трижды негативные и HER2-обогащенные опухоли чаще образуют множественные метастазы, которые чаще локализуются в головном мозге и печени. Однако некоторые авторы не обнаруживают в своих исследованиях таких закономерностей, что, вероятно, свидетельствует о наличии других факторов, существенно влияющих на органотропность метастазирования. Многочисленные исследования демонстрируют ассоциацию различных молекул, экспрессируемых на опухолевых клетках, с органотропным метастазированием. Однако эти данные весьма фрагментарны и иногда весьма противоречивы.Заключение. Обнаруженные ассоциации относятся ко всем участникам метастатического каскада, но остается неясным, какие факторы являются существенными и решающими в определении направления метастазирования

Smoking-related DNA adducts as potential diagnostic markers of lung cancer: new perspectives

In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers)

Search for potential gastric cancer markers using miRNA databases and gene expression analysis

Aim: The aim of this study was to identify genes that are differentially expressed in gastric tumors and to analyze the association of their expression level with tumor clinicopathologic features. Methods: In the present research, we used bioinformatic-driven search to identify miRNA that are down-regulated in gastric tumors and to find their potential targets. Then, the expression levels of some of the target mRNAs were investigated using reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: As a result of the bioinformatics analysis, fifteen genes were found to be potentially differentially expressed between the tumors and normal gastric tissue. Five of them were chosen for the further analysis (WNT4, FGF12, EFEMP1, CTGF, and HSPG2) due to their important role in cell proliferation and differentiation. Expression levels of these genes were evaluated in our collection of frozen tissue samples of gastric tumor and paired normal stomach epithelia. Increased FGF12 expression was observed in diffuse type of gastric cancer while WNT4 mRNA was found to be down-regulated in intestinal type of gastric cancer. Besides, CTGF gene overexpression was revealed in diffuse type of stomach cancer in comparison with that in intestinal type. Up-regulation of CTGF was also associated with lymph node metastasis. Conclusions: The findings show its expedient to perform further investigations in order to clarify diagnostic and prognostic value of CTGF, FGF12, and WNT4’s in stomach cancer as well as the role of these genes in carcinogenesis

Fungal and bacterial successions in the process of co-composting of organic wastes as revealed by 454 pyrosequencing

© 2017 Galitskaya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Composting is viewed as one of the primary methods to treat organic wastes. Co-composting may improve the efficiency of this treatment by establishing the most suitable conditions for decomposers than those present in the individual wastes. Given that bacteria and fungi are the driving agents of composting, information about the composition of their communities and dynamics during composting may improve reproducibility, performance and quality of the final compost as well as help to evaluate the potential human health risk and the choice of the most appropriate application procedure. In this study, the co-composting of mixtures containing two similar components (organic fraction of municipal solid waste and sawdust polluted by oil) and one discriminate component (sewage sludges of different origin) were investigated. Bacterial and fungal community successions in the two mixtures were analyzed during the composting process by determining the change in their structural dynamics using qPCR and 454 pyrosequencing methods in a lab experiment for a period of 270 days. During the initial composting stage, the number of 16S bacterial copies was (3.0 ±0.2) × 10 6 and (0.4±0.0) × 10 7 g -1 , and the Rhodospiralles and Lactobacialles orders dominated. Fungal communities had (2.9±0.0) ×10 5 and (6.1±0.2) ×10 5 ITS copies g -1 , and the Saccharomycetales order dominated. At the end of the thermophilic stage on the 30 th day of composting, bacterial and fungal communities underwent significant changes: dominants changed and their relative abundance decreased. Typical compost residents included Flavobacteriales, Chitinophagaceae and Bacterioidetes for bacteria and Microascaceae, Dothideomycetes, Eurotiomycetes, Sordariomycetes, and Agaricomycetes for fungi. During the later composting stages, the dominating taxa of both bacterial and fungal communities remained, while their relative abundance decreased. In accordance with the change in the dominating OTUs, it was concluded that the dynamics of the bacterial and fungal communities were not similar. Analysis by non-metric multidimensional scaling (NMDS) revealed that the bacterial communities of the two composts became progressively more similar; a similar trend was followed by the fungal community

Lessons from the Whole Exome Sequencing Effort in Populations of Russia and Tajikistan

© 2016, Springer Science+Business Media New York.In contrast with the traditional methods applied to assessment of population diversity, high-throughput sequencing technologies have a wider application in clinical practice with greater potential to find novel disease-causing variants for multifactorial disorders. Widely used test panels may not meet their goal to diagnose the patient’s condition with a full reliability since this method often does not take into account the population frequencies of analyzed genetic markers. Here, we analyzed 57 male individuals of five ethnic groups from Russia and Tajikistan using the whole exome sequencing technique (Ion AmpliSeq Exome), which resulted in detecting more than 299,000 single nucleotide polymorphisms. Samples formed clusters on the PCA plot according to the geographical location of the corresponding populations. Thereby, the methodology of whole-exome sequencing, in general, and the Ion AmpliSeq Exome panel, in particular, could be positively applied for the purposes of population genetics and for detection of the novel clinically relevant variants

Shotgun metagenomic data on the human stool samples to characterize shifts of the gut microbial profile after the Helicobacter pylori eradication therapy

© 2017 The Authors The shotgun sequencing data presented in this report are related to the research article named “Gut microbiome shotgun sequencing in assessment of microbial community changes associated with H. pylori eradication therapy” (Khusnutdinova et al., 2016) [1]. Typically, the H. pylori eradication protocol includes a prolonged two-week use of the broad-spectrum antibiotics. The presented data on the whole-genome sequencing of the total DNA from stool samples of patients before the start of the eradication, immediately after eradication and several weeks after the end of treatment could help to profile the gut microbiota both taxonomically and functionally. The presented data together with those described in Glushchenko et al. (2017) [2] allow researchers to characterize the metagenomic profiles in which the use of antibiotics could result in dramatic changes in the intestinal microbiota composition. We perform 15 gut metagenomes from 5 patients with H. pylori infection, obtained through the shotgun sequencing on the SOLiD 5500 W platform. Raw reads are deposited in the ENA under project ID PRJEB21338

Cytokine profile in hospitalized patients with COVID-19 of different severity

Analysis of cytokine profile markers in conjunction with the clinical manifestations of coronavirus disease 2019 (COVID-19) can provide valuable information about the pathogenetic manifestations of the disease, and therefore, in the future, determine drugs that affect the cytokine storm and have an anti-inflammatory effect.Aim. To identify correlations between the parameters of the developed cytokine profile and the clinical course in hospitalized patients with COVID-19 of different severity.Material and methods. The study included 70 hospitalized patients with a confirmed diagnosis of COVID-19, with a mean age of 58 [50;69] years, including 40 men (57%) and 30 women (43%). The average lung involvement according to computed tomography (CT) at admission was CT-2 [1;3]. Peripheral venous blood was taken at admission, which averaged 7 [6; 8] days from the symptom onset. Standard biochemical parameters were studied, as well as 47 cytokines and chemokines using the Multiplex system (Merck KGaA, Darmstadt, Germany).Results. Correlations was found between the lung involvement degree and the level of IL-8 (r=0,31, p<0,05), IL-15 (r=0,35, p<0,05), IL-18 (r=0,31, p<0,05), MCP-1 (r=0,36, p<0,05), MIG (r=0,50, p<0,05), TNF-α (r=0,41, p<0,05). An inverse correlation was also found in the level of blood oxygen saturation with the same indicators as follows: IL-8 (r=-0,27, p<0,05), IL-15 (r=-0,34, p<0,05), IL-18 (r=-0,31, p<0,05), MCP-1 (r=-0,40, p<0,05), MIG (r=-0,56, p<0,05), TNF-α (r=-0,45, p<0,05). IL-6 levels were significantly elevated in patients with severe COVID-19 (CT3, CT4), while no increase in IL-6 was observed in patients with moderate disease (CT1, CT2). It is noteworthy that in patients with diabetes, the highest values of IL-12, IL-9 were recorded.Conclusion. Hyperinflammatory syndrome in severe COVID-19 is manifested by high levels of IL-6, MIG, MDC, MCP-1, M-CSF, TNF-α, β, IL-8, IL-18, IL-15. With the CT-1 and CT-2, an increase in only the level of IL-18, IL-8 is noted. The identified patterns prove and make it possible to explain a number of systemic inflammatory changes that occur with COVID-19

LC-MS Method Development for Simultaneous Determination of Trans-3′-hydroxycotinine and Three Mercapturic Acids in Urine

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The negative impact of tobacco smoke on the human body is due to a wide range of harmful substances including volatile organic compounds (VOCs). Some VOCs of tobacco smoke metabolize in human organism into mercapturic acids (MAs). The determination of the amount of MAs in readily available biological fluids, for example in urine, allows to assess the level of exposure of these VOCs in a particular person. It is useful to assess the impact of individual VOCs on the body together with the assessment of the intake of nicotine. The intake of nicotine can be determined by the content of its metabolites in the urine, in particular by the content of trans-3′-hydroxycotinine (tH-Cot). A joint assessment of the concentrations of trans-3′-hydroxycotinine and MAs in urine allows obtaining selective information about effects of different VOCs and nicotine on the smoker’s body. We have developed a liquid chromatography–mass spectrometry (LC-MS) method for simultaneous quantifying of tH-Cot and three MAs: N-Acetyl-S-(3-hydroxypropyl)cysteine (HPMA), N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HMPMA), N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA). We used this method to quantify the levels of MAs and tH-Cot in the urine of a group of 15 smokers just before and 5 days after smoking cessation. For all studied compounds, we have found statistically significant changes in concentration on the fifth day of smoking cessation. The method developed can be used to jointly assess the levels of exposure to nicotine and VOCs in the study of various tobacco products

First Results from the AMoRE-Pilot neutrinoless double beta decay experiment

The Advanced Molybdenum-based Rare process Experiment (AMoRE) aims to search for neutrinoless double beta decay (0$\nu\beta\beta$) of $^{100}$Mo with $\sim$100 kg of $^{100}$Mo-enriched molybdenum embedded in cryogenic detectors with a dual heat and light readout. At the current, pilot stage of the AMoRE project we employ six calcium molybdate crystals with a total mass of 1.9 kg, produced from $^{48}$Ca-depleted calcium and $^{100}$Mo-enriched molybdenum ($^{48\textrm{depl}}$Ca$^{100}$MoO$_4$). The simultaneous detection of heat(phonon) and scintillation (photon) signals is realized with high resolution metallic magnetic calorimeter sensors that operate at milli-Kelvin temperatures. This stage of the project is carried out in the Yangyang underground laboratory at a depth of 700 m. We report first results from the AMoRE-Pilot $0\nu\beta\beta$ search with a 111 kg$\cdot$d live exposure of $^{48\textrm{depl}}$Ca$^{100}$MoO$_4$ crystals. No evidence for $0\nu\beta\beta$ decay of $^{100}$Mo is found, and a upper limit is set for the half-life of 0$\nu\beta\beta$ of $^{100}$Mo of $T^{0\nu}_{1/2} > 9.5\times10^{22}$ y at 90% C.L.. This limit corresponds to an effective Majorana neutrino mass limit in the range $\langle m_{\beta\beta}\rangle\le(1.2-2.1)$ eV