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Treatment with biological products resulted in an increase in the area of the assimilation apparatus by 1.7 to 2.4 thousand m²/ha.The application of Bio-gel led to an increase in leaf surface by 1.7 thousand m2/ha or 5.3%, and the treatment with Helafit combi by 2.4 thousand m2/ha or 7.5%. The treatment with biological products contributed to an increase in photosynthetic potential by 5.1% compared to the treatment with Bio- gel and by 7.2% compared to the treatment with Helafit combi. It was found that the treatment of parental lines with Bio-gel and Helafit combi caused an increase in laboratory germination of seeds. When using Bio-gel, the laboratory germination rate increased by an average of 1.5%. The treatment with Helafit combi was more effective, as the germination rate in this experimental variant increased by 2.4%. The increase in laboratory germination was observed due to a decrease in the infection of seeds of the lines by Fusarium moniliforme Scheld. The maximum seed yield in the early maturing line - the parent component of DK 281 was recorded at a density of 90 thousand plants/ha and treatment with Helafit combi - 3.65 t/ha. The maximum yield in the line - the parent component of DK 247 was observed at a density of 80 thousand plants/ha and treatment with Helafit combi - 4.89 t/ha. The medium-late line - the parent component DK 411 showed the highest yield at a density of 70 thousand plants/ha and treatment with Helafit combi - 4.65 t/ha. The maximum yield in the experiment was observed in the line

Wastes from the coal industry, the oil and fat industry, and the processing of agricultural products can be turned into high-quality fuel raw materials. In this regard, research and development is underway in many countries, the results of which are new types of fuel. the results obtained, based on a scientifically based approach to the selection of effective compositions of organomineral components, made it possible to develop effective compositions of coal briquettes; Based on the research results, optimal compositions of effective coal briquettes based on organomineral ingredients from local raw materials and industrial wastes have been developed.

The main goal of this study was to characterize cancer/testis antigens (CTAs) as potential molecular markers of ovarian cancer. First, we gathered and analyzed a significantly large dataset of 21 selected CTAs that are encoded by 32 genes; the dataset consisted of the mutation data, expression data, and survival data of patients with ovarian cancer (n = 15,665). The 19 functionally significant missense mutations were identified in 9 CTA genes: ACRBP, CCT4, KDM5B, MAGEA1, MAGEA4, PIWIL1, PIWIL2, PRAME, and SPA17. The analysis of the mRNA expression levels of 21 CTAs in healthy and tumor ovarian tissue showed an up-regulation in the expression level of AKAP3, MAGEA4, PIWIL1, and PRAME in tumor samples and a down-regulation in the expression level of CTAG1A, CTAG1B, MAGEC1, and PIWIL2. The CCT4 up-regulation and PRAME mutations were correlated with a good prognosis for ovarian cancer, while higher levels of GAGE2A and CT45A1 mRNAs were correlated with a poor prognosis for ovarian cancer patients. Thus, GAGE2, CT45, CCT4, and PRAME cancer/testis antigens can be considered as potential prognostic markers for ovarian tumors, and GAGE2, CCT4, and PRAME were revealed to be correlated with the prognosis for ovarian cancer patients for the first time.

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted in silico, no direct experimental data are available for the orientation of NaPi2b extracellular domains in cancer cells. The presented results of antibody mapping of untagged NaPi2b in live ovarian carcinoma cells OVCAR-4 provide a platform for current and future epitope-based cancer therapies and serological diagnostics.

The sodium-dependent phosphate cotransporter NaPi2b encoded by the SLC34A2 gene is a transmembrane protein that belongs to the family of phosphate transporters SLC34 and is involved in maintaining phosphate homeostasis in the human body. The phosphate transporter NaPi2b is expressed in several normal tissues and body organs, as well as in malignant neoplasms of the ovary, lung, colorectal, and other types of cancer. The membrane protein NaPi2b is a target for therapeutic humanized antibodies Rebmab200, XMT-1535, and XMT-1536 in cancer cells. These antibodies were created based on MX35 antibodies and are directed against the large extracellular domain of the transporter NaPi2b. Since the location of the N-terminal domain of NaPi2b in the cell has not been experimentally confirmed, this work aimed to analyze the recognition of the phosphate transporter NaPi2b in ovarian cancer cells OVCAR-4 and OVCAR-8 by antibodies against the N-terminal domain of the transporter using Western blot analysis and confocal microscopy.

The high mortality rate from ovarian cancer is due to the asymptomatic nature of the course of the disease, which leads to the diagnosis of ovarian cancer in later stages. The sodium-dependent phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80–90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we aimed to evaluate NaPi2b as a molecular marker for diagnostics and predicting the course and outcome of ovarian cancer disease.Quantitative analysis of SLC34A2 gene expression in ovarian tumor tissue was performed at the level of transcription and translation using real-time PCR, droplet digital PCR and Western blot analysis respectively. Statistical analysis was performed taking into account various clinicopathological characteristics of the ovarian cancer patients, including the stage of the disease, the tumor grade, the applying of neoadjuvant chemotherapy and the presence of ascites. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer.

Pancreatic cancer is one of the most painful and aggressive types of cancer with high lethality rate. Early diagnosis of the disease is limited and antitumor therapy has low efficacy, because pancreatic cancer shows multiple drug resistance. It is still unclear how pancreatic tumor cells become resistant to chemotherapy and understanding of the resistance mechanisms and identification of their regulating genes is necessary to develop a new and more efficient pancreatic cancer therapy. One of the methods to identify such genes is CRISPR/Cas9 technology (clustered regularly interspaced short palindromic repeats) where Cas9 endonuclease is used to make double-strand DNA breaks in target genes. The aim of this work is modification of the pancreatic cancer cell line MIA PaCa-2 to express a doxycycline-inducible Cas9 endonuclease gene. Several plasmid vectors have been used to create a lentivirus containing the Cas9 endonuclease gene. The virus has been used for transduction of tumor cells to get doxycycline-inducible Cas9 expressing clones. Cas9 endonuclease expression has been detected by the western blot analysis with antibodies to FLAG epitope. Two tumor clones of the MIA Pa-Ca2/Cas9 cell line expressing Cas9 endonuclease have been generated. These cells can be used further to search genes related to regulation of the susceptibility to antitumor drugs.

The chemoresistance of tumor cells is one of the most urgent challenges in modern oncology and in pancreatic cancer, in which this problem is the most prominent. Therefore, the identification of new chemosensitizing co-targets may be a path toward increasing chemotherapy efficacy. In this work, we performed high-performance in vitro knockout CRISPR/Cas9 screening to find potential regulators of the sensitivity of pancreatic cancer. For this purpose, MIA PaCa-2 cells transduced with two sgRNA libraries (“cell cycle/nuclear proteins genes” and “genome-wide”) were screened by oxaliplatin and cisplatin. In total, 173 candidate genes were identified as potential regulators of pancreatic cancer cell sensitivity to oxaliplatin and/or cisplatin; among these, 25 genes have previously been reported, while 148 genes were identified for the first time as potential platinum drug sensitivity regulators. We found seven candidate genes involved in pancreatic cancer cell sensitivity to both cisplatin and oxaliplatin. Gene ontology enrichment analysis reveals the enrichment of single-stranded DNA binding, damaged DNA binding pathways, and four associated with NADH dehydrogenase activity. Further investigation and validation of the obtained results by in vitro, in vivo, and bioinformatics approaches, as well as literature analysis, will help to identify novel pancreatic cancer platinum sensitivity regulators.

The main goal of this study is to consider SLC34A2 as a potential prognostic marker of oncological diseases using the mutational, expression, and survival data of cancer studies which are publicly available online. We collected data from four databases (cBioPortal, The Cancer Genome Atlas; cBioPortal, Genie; International Cancer Genome Consortium; ArrayExpress). In total, 111,283 samples were categorized according to 27 tumor locations. Ninety-nine functionally significant missense mutations and twelve functionally significant indel mutations in SLC34A2 were found. The most frequent mutations were SLC34A2-ROS1, p.T154A, p.P506S/R/L, p.G257A/E/R, p.S318W, p.A396T, p.P410L/S/H, p.S461C, p.A473T/V, and p.Y503H/C/F. The upregulation of SLC34A2 was found in samples of myeloid, bowel, ovarian, and uterine tumors; downregulation was found in tumor samples of breast, liver, lung, and skin cancer tumors. It was found that the life expectancy of breast and thymus cancer patients with an SLC34A2 mutation is lower, and it was revealed that SLC34A2 overexpression reduced the life span of patients with brain, ovarian, and pancreatic tumors. Thereby, for these types of oncological diseases, the mutational profile of SLC34A2 can be a potential prognostic marker for breast and thymus cancers, and the upregulation of SLC34A2 can be a potential prognostic marker for brain, ovarian, and pancreatic cancers.

The research contains the analysis of the existing conceptions of the sense of humor, its psychological determinants and manifestations; this enables to justify the necessity of its study as a system personality trait from a position of structural-functional approach. The results of a comparative study of the sense of humor of the preadult and mature age representatives are analysed. The common links of the sense of humor components possessed by the preadult and mature age representatives with the choice of humor direction thematic constructs are examined and described. The specific links of the sense of humor components possessed by the pre - adult age representatives (such as socio-centricity, meaningfulness, awareness, subjectivity, vigor, inertia, sthenicity) with the choice of humor direction thematic constructs (such as gender interrelation, harmful habits, money, fashion, career, social woes, human stupidity) are described. The typical links of the sense of humor components possessed by the mature age representatives (such as egocentricity, subjectivity, vigor, externality) with the choice of humor direction thematic constructs (such as gender interrelation, fashion, family friction, social woes, lack of talent in art) are disclosed. In the end the article presents the findings, describing the psychological features of certain theme humor perception by the people of different ages.

The article considers the issue of variability among derivative preposition forms. It is stated that in the context of the suggested in the native linguistics criteria of qualification of a certain lexemes as a non-derivative or derivative preposition (such as derivative, syntactical and morphological features) the linguistic conditions of differentiation of variants of derivative prepositions haven't been fully investigated. The purpose of this article is to analyze and define the basic criteria of selection among the variants of derivative prepositions in the text of A.S. Pushkin. Reference to the language of this writer as the material of linguistic studies, on one hand, may be explained by recognition of the epoch of A.S. Pushkin to be the starting period in the establishment of the modern Russian literary language; on the other hand, the research opens an opportunity to trace vital changes in the language system within two centuries. The multiaspectual analysis helped to discover that the selection of a certain variant of prepositions pozadi / pozad', vperedi / vpredi, poseredi / posredi, vokrug / vkrug, vsled / vosled depends on the morphological, syntactical, semantic, stylistic, rhythmical criteria, namely the part of speech of the governed word, the syntactical structure and semantic construction into which a certain preposition is included, stylistic markedness of the context, and the poetic metre requirements.

Simple Summary: Acquired resistance of gastrointestinal stromal tumors (GISTs) to imatinib mesylate (IM) is one of the most critical challenges in GIST therapy. Here we show that a long-term culture of GIST T-1 cells with IM induces clonal heterogeneity resulting in the appearance of cancer cells exhibiting activation of the FGFR-signaling pathway which was associated with KIT loss. The first one was due to the overexpression of FGFR1/2 and increased production of FGF-2 ligand. These events maintained GIST resistance to IM and rendered these GIST cells highly sensitive to all types of pan-FGFR-inhibitors used in the current study. Knockout of FGFR2 in this GIST subclone significantly attenuated pro-apoptotic and anti-proliferative activities of infigratinib (BGJ 398) both in vitro and in vivo, thereby suggesting the activation of FGFR-signaling pathway via FGFR2-mediated axis as the predominant molecular mechanism in these GIST cells. Collectively, the extended inhibition of KIT-signaling in GISTs induces clonal heterogeneity of cancer cells and might change the tumor's sensitivity to FGFR-inhibitors due to selection of cancer cells with an FGFR-overactivated pathway. We showed previously that inhibition of KIT signaling in GISTs activates FGFR-signaling pathway rendering cancer cells resistant to receptor tyrosine kinase inhibitor (RTKi) imatinib mesylate (IM) (Gleevec) despite of absence of secondary KIT mutations and thereby illustrating a rationale for the combined (e.g., KIT- and FGFR-targeted) therapies. We show here that long-term culture of IM-resistant GISTs (GIST-R1) with IM substantially down-regulates KIT expression and induces activation of the FGFR-signaling cascade, evidenced by increased expression of total and phosphorylated forms of FGFR1 and 2, FGF-2, and FRS-2, the well-known adaptor protein of the FGF-signaling cascade. This resulted in activation of both AKT- and MAPK-signaling pathways shown on mRNA and protein levels, and rendered cancer cells highly sensitive to pan-FGFR-inhibitors (BGJ 398, AZD 4547, and TAS-120). Indeed, we observed a significant decrease of IC50 values for BGJ 398 in the GIST subclone (GIST-R2) derived from GIST-R1 cells continuously treated with IM for up to 12 months. An increased sensitivity of GIST-R2 cells to FGFR inhibition was also revealed on the xenograft models, illustrating a substantial (>70%) decrease in tumor size in BGJ 398-treated animals when treated with this pan-FGFR inhibitor. Similarly, an increased intra-tumoral apoptosis as detected by immunohistochemical (IHC)-staining for cleaved caspase-3 on day 5 of the treatment was found. As expected, both BGJ 398 and IM used alone lacked the pro-apoptotic and growth-inhibitory activities on GIST-R1 xenografts, thereby revealing their resistance to these TKis when used alone. Important, the knockdown of FGFR2, and, in much less content, FGF-2, abrogated BGJ 398′s activity against GIST-R2 cells both in vitro and in vivo, thereby illustrating the FGF-2/FGFR2-signaling axis in IM-resistant GISTs as a primary molecular target for this RTKi. Collectively, our data illustrates that continuous inhibition of KIT signaling in IM-resistant GISTs lacking secondary KIT mutations induced clonal heterogeneity of GISTs and resulted in accumulation of cancer cells with overexpressed FGF-2 and FGFR1/2, thereby leading to activation of FGFR-signaling. This in turn rendered these cells extremely sensitive to the pan-FGFR inhibitors used in combination with IM, or even alone, and suggests a rationale to re-evaluate the effectiveness of FGFR-inhibitors in order to improve the second-line therapeutic strategies for selected subgroups of GIST patients (e.g., IM-resistant GISTs lacking secondary KIT mutations and exhibiting the activation of the FGFR-signaling pathway). [ABSTRACT FROM AUTHOR]

The main goal of this study was to characterize cancer/testis antigens (CTAs) as potential molecular markers of ovarian cancer. First, we gathered and analyzed a significantly large dataset of 21 selected CTAs that are encoded by 32 genes; the dataset consisted of the mutation data, expression data, and survival data of patients with ovarian cancer (n = 15,665). The 19 functionally significant missense mutations were identified in 9 CTA genes: ACRBP, CCT4, KDM5B, MAGEA1, MAGEA4, PIWIL1, PIWIL2, PRAME, and SPA17. The analysis of the mRNA expression levels of 21 CTAs in healthy and tumor ovarian tissue showed an up-regulation in the expression level of AKAP3, MAGEA4, PIWIL1, and PRAME in tumor samples and a down-regulation in the expression level of CTAG1A, CTAG1B, MAGEC1, and PIWIL2. The CCT4 up-regulation and PRAME mutations were correlated with a good prognosis for ovarian cancer, while higher levels of GAGE2A and CT45A1 mRNAs were correlated with a poor prognosis for ovarian cancer patients. Thus, GAGE2, CT45, CCT4, and PRAME cancer/testis antigens can be considered as potential prognostic markers for ovarian tumors, and GAGE2, CCT4, and PRAME were revealed to be correlated with the prognosis for ovarian cancer patients for the first time. [ABSTRACT FROM AUTHOR]

One of the most perspective mechanisms for solving the problem of budget investments deficiency into Russian regions infrastructure is a state-private partnership (further SPP). This work states the main problems preventing the realization of the investment projects based on SPP principles of regional authorities and private business. The author proves that the efficiency of the system of business and state connection will become apparent when the state approach changes and it takes business owners' wishes into account. The ways of «dialogue statement» and setting of just «rules of play» between the projects participants are proposed.

Background: Immunoglobulin-E(IgE)-mediated hypersensitivity to cow's milk allergens is a frequent cause of severe and life-threatening anaphylactic reactions. Besides case histories and controlled food challenges, the detection of the IgE antibodies specific to cow's milk allergens is important for the diagnosis of cow-milk-specific IgE sensitization. Cow´s milk allergen molecules provide useful information for the refined detection of cow-milk-specific IgE sensitization. Methods: A micro-array based on ImmunoCAP ISAC technology was developed and designated milk allergen micro-array (MAMA), containing a complete panel of purified natural and recombinant cow's milk allergens (caseins, α-lactalbumin, β-lactoglobulin, bovine serum albumin-BSA and lactoferrin), recombinant BSA fragments, and α-casein-, α-lactalbumin- and β-lactoglobulin-derived synthetic peptides. Sera from 80 children with confirmed symptoms related to cow's milk intake (without anaphylaxis: n = 39; anaphylaxis with a Sampson grade of 1–3: n = 21; and anaphylaxis with a Sampson grade of 4–5: n = 20) were studied. The alterations in the specific IgE levels were analyzed in a subgroup of eleven patients, i.e., five who did not and six who did acquire natural tolerance. Results: The use of MAMA allowed a component-resolved diagnosis of IgE sensitization in each of the children suffering from cow's-milk-related anaphylaxis according to Sampson grades 1–5 requiring only 20–30 microliters of serum. IgE sensitization to caseins and casein-derived peptides was found in each of the children with Sampson grades of 4–5. Among the grade 1–3 patients, nine patients showed negative reactivity to caseins but showed IgE reactivity to alpha-lactalbumin (n = 7) or beta-lactoglobulin (n = 2). For certain children, an IgE sensitization to cryptic peptide epitopes without detectable allergen-specific IgE was found. Twenty-four children with cow-milk-specific anaphylaxis showed additional IgE sensitizations to BSA, but they were all sensitized to either caseins, alpha-lactalbumin, or beta-lactoglobulin. A total of 17 of the 39 children without anaphylaxis lacked specific IgE reactivity to any of the tested components. The children developing tolerance showed a reduction in allergen and/or peptide-specific IgE levels, whereas those remaining sensitive did not. Conclusions: The use of MAMA allows for the detection, using only a few microliters of serum, of IgE sensitization to multiple cow's milk allergens and allergen-derived peptides in cow-milk-allergic children with cow-milk-related anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) can be life-threatening and affects up to 3% of children. Hypoallergenic infant formulas based on hydrolyzed cow's milk protein are increasingly considered for therapy and prevention of cow's milk allergy. The aim of this study was to investigate the allergenic activity and ability to induce T cell and cytokine responses of an infant formula based on extensively hydrolyzed cow's milk protein (whey) (eHF, extensively hydrolyzed formula) supplemented with Galactooligosaccharides (GOS) and Limosilactobacillus fermentum CECT5716 (LF) to determine its suitability for treatment and prevention of CMA. Methods: eHF and standard protein formula based on intact cow's milk proteins (iPF) with or without Galactooligosaccharide (GOS) and Limosilactobacillus fermentum CECT5716 (LF) were investigated with allergen-specific antibodies and tested for IgE reactivity and allergenic activity in basophil degranulation assays with sera from cow's milk (CM)-allergic infants/children. Their ability to stimulate T cell proliferation and cytokine secretion in cultured peripheral blood mononuclear cells (PBMC) from CM-allergic infants and children was studied with a FACS-based carboxyfluorescein diacetate succinimidyl ester (CFSE) dilution assay and xMAP Luminex fluorescent bead-based technology, respectively. Results: An eHF supplemented with GOS and LF exhibiting almost no IgE reactivity and allergenic activity was identified. This eHF induced significantly lower inflammatory cytokine secretion as compared to an intact protein-based infant formula but retained T cell reactivity. Conclusions: Due to strongly reduced allergenic activity and induction of inflammatory cytokine secretion but retained T cell reactivity, the identified eHF may be used for treatment and prevention of CMA by induction of specific T cell tolerance. [ABSTRACT FROM AUTHOR]

Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five) was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892