PECULIAR FEATURES OF TEACHING HISTORY TO ECONOMIST STUDENTS IN RUSSIAN UNIVERSITIES

The purpose of the article: The article is aimed at studying of key issues of the set of methods and methodology of teaching history to students of the direction "Economics"; identifying of key aspects of the history course, competent understanding whereof is important for development of professional competencies of future economists, is of special attention.Materials and methods: The leading approach to the study of this problem is the analysis of key problem issues of the history course, a competent understanding of which is important for the formation of professional competencies of economists.Results of the research: The article shows that in the history of economics there are a lot of controversial, controversial issues on which quite superficial, subjective judgments and conclusions can occur in the journalistic, and sometimes academic literature. A number of similar questions are considered, the features of their study with students are revealed. The work identifies key aspects of the course of history, a competent understanding of which is important for the formation of professional competencies of future economists. The recommendations of the methodological and methodological plan for their study are proposed to increase the effectiveness of training future economists. Applications: This research can be used for the universities, teachers, and students. Novelty/Originality: In this research, the model of peculiar features of teaching history to economist students in Russian universities is presented in a comprehensive and complete manner

Deletions of multidrug resistance gene loci in breast cancer leads to the down-regulation of its expression and predict tumor response to neoadjuvant chemotherapy

Neoadjuvant chemotherapy (NAC) is intensively used for the treatment of primary breast cancer. In our previous studies, we reported that clinical tumor response to NAC is associated with the change of multidrug resistance (MDR) gene expression in tumors after chemotherapy. In this study we performed a combined analysis of MDR gene locus deletions in tumor DNA, MDR gene expression and clinical response to NAC in 73 BC patients. Copy number variations (CNVs) in biopsy specimens were tested using high-density microarray platform CytoScanTM HD Array (Affymetrix, USA). 75%-100% persons having deletions of MDR gene loci demonstrated the down-regulation of MDR gene expression. Expression of MDR genes was 2-8 times lower in patients with deletion than in patients having no deletion only in post-NAC tumors samples but not in tumor tissue before chemotherapy. All patients with deletions of ABCB1 ABCB 3 ABCC5 gene loci--7q21.1, 6p21.32, 3q27 correspondingly, and most patients having deletions in ABCC1 (16p13.1), ABCC2 (10q24), ABCG1 (21q22.3), ABCG2 (4q22.1), responded favorably to NAC. The analysis of all CNVs, including both amplification and deletion showed that the frequency of 13q14.2 deletion was 85% among patients bearing tumor with the deletion at least in one MDR gene locus versus 9% in patients with no deletions. Differences in the frequency of 13q14.2 deletions between the two groups were statistically significant (p = 2.03 × 10(-11), Fisher test, Bonferroni-adjusted p = 1.73 × 10(-8)). In conclusion, our study for the first time demonstrates that deletion MDR gene loci can be used as predictive marker for tumor response to NAC

Δ133p53β isoform pro-invasive activity is regulated through an aggregation-dependent mechanism in cancer cells

International audienceAbstract The p53 isoform, Δ133p53β, is critical in promoting cancer. Here we report that Δ133p53β activity is regulated through an aggregation-dependent mechanism. Δ133p53β aggregates were observed in cancer cells and tumour biopsies. The Δ133p53β aggregation depends on association with interacting partners including p63 family members or the CCT chaperone complex. Depletion of the CCT complex promotes accumulation of Δ133p53β aggregates and loss of Δ133p53β dependent cancer cell invasion. In contrast, association with p63 family members recruits Δ133p53β from aggregates increasing its intracellular mobility. Our study reveals novel mechanisms of cancer progression for p53 isoforms which are regulated through sequestration in aggregates and recruitment upon association with specific partners like p63 isoforms or CCT chaperone complex, that critically influence cancer cell features like EMT, migration and invasion

Deformation Behavior of Wrought and EBAM Ti-6Al-4V under Scratch Testing

The microstructure, mechanical properties, and deformation behavior of wrought and electron beam additive manufactured (EBAM) Ti-6Al-4V samples under scratching were studied. As-received wrought Ti-6Al-4V was subjected to thermal treatment to obtain the samples with microstructure and mechanical characteristics similar to those of the EBAM samples. As a result, both alloys consisted of colonies of [alpha] phase laths within prior [beta] phase grains and were characterized by close values of hardness. At the same time, the Young's modulus of the EBAM samples determined by nanoindentation was lower compared with the wrought samples. It was found that despite the same hardness, the scratch depth of the EBAM samples under loading was substantially smaller than that of the wrought alloy. A mechanism was proposed, which associated the smaller scratch depth of EBAM Ti-6Al-4V with [alpha]′→[alpha]″ phase transformations that occurred in the contact area during scratching. Ab initio calculations of the atomic structure of V-doped Ti crystallites containing [alpha] or [alpha]″ phases of titanium were carried out to support the proposed mechanism

Effects of Water Cooling on the Microstructure of Electron Beam Additive-Manufactured Ti-6Al-4V

The inferior mechanical properties of EBAM Ti-6Al-4V samples are due to the coarse columnar grains containing coarse lamellar structures. One can expect that water cooling of the build platform will increase the cooling rate of the molten pool during the build-up process, causing microstructure refinement. In the present work, the substrate cooling effects on the microstructure and phase composition of EBAM Ti-6Al-4V samples are studied using optical, scanning electron, and scanning transmission microscopy, as well as X-ray diffraction analysis. It is shown that the microstructure of the EBAM Ti-6Al-4V samples built on the substrate without water cooling consists predominantly of columnar prior beta grains with lateral sizes ranging up to 2000 [mu]m, while cooling of the build platform causes the appearance of equiaxed prior beta grains measuring 1000 [mu]m. Moreover, the refinement of the martensite structure and the precipitation of alpha′′ martensite platelets within alpha laths occur in the EBAM Ti-6Al-4V samples built on the water-cooled build platform. An explanation of the mechanisms underlying the alpha′→alpha+beta and alpha′→alpha+alpha′′+beta transformations during the building process is provided based upon ab initio calculations. The fragmentation of the α laths under the residual compressive stresses is discussed

Smoking, genes and inflammation

Rheumatoid arthritis (RA) is an, autoimmune disease where genetic predisposition and environmental factors increase the risk of developing RA and the severity of the disease. Cigarette smoking is the major recognised environmental risk factor, and there is a combined effect from smoking and the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype on the risk of developing RA. This study sought to establish any direct effect of smoking and/or the genetic predisposition on the inflammation driving RA and to identify biological mechanism(s) that might explain epidemiological data linking smoking, genetics and RA. The aim of initial work was to establish any involvement of aryl hydrocarbon receptor (AHR)-mediated mechanisms within inflamed rheumatoid tissues. The expression of AHR, CYP1A1 and AHRR genes were quantified by real-time PCR in twenty synovial and eighteen subcutaneous nodule tissues. Patient’s smoking status was established at the time tissue was obtained. The results show smoking causes significant AHR activation in joint synovial tissue, but not in rheumatoid nodule tissues. A subset of synovial DCs show activated AHR in smokers, consistent with the sensitivity of human mo-DCs stimulated with the AHR agonist, benzo(a)pyrene (BaP) in vitro. It is concluded that DCs within the joint synovium are the principal immune cells that respond to cigarette smoke exposure. Microarray analysis revealed that the expression of 547 synovial genes was up-regulated by smoking, including folate receptor 1 (FOLR1), matrix metalloproteinases (MMP)9, MMP11 and MMP14, TNF-superfamily members, TNFSF10/TRAIL and TNFRSF10B/TRAILR2 and transcription factors, RUNX1 and RUNX2. Cell motility and adhesion were the biological processes in synovium most affected by smoking. The expression of 307 synovial genes was down-regulated by smoking, including the vascular “protective” genes, KLF2 and eNOS, suggesting that endothelial function is affected by smoking with implications for vasculitis and the development of rheumatoid nodules associated with severe RA. Any effect of smoking and SE copy number on genes associated with AHR signalling and other immune-inflammatory genes was established. Results suggest there are solitary, reciprocal or synergistic effects from smoking and the SE in rheumatoid inflammation, which are gene dependent. Thus, smoking increases AHR activation in synovium; the SE has no effect. Furthermore, while smoking reduces IL17A expression in synovial tissue, indications are that SE copy number increases IL17A expression. In combination, smoking and the SE increase synovial MMP9 gene expression. Human promonocytic U937 cells were used to model the effect of BaP exposure on MMP9 expression. PMA-activated U937 cells acquire an ability to respond to BaP, including with increased MMP9 gene expression. AHR-specific siRNA, confirmed that AHR regulates MMP9 gene expression. Further data implicate different MMPs in rheumatoid tissue destruction. High MMP7 expression by macrophages occurs in a subset of nodule tissues. This high MMP7 expression is associated with a -181G/G polymorphism within the MMP7 gene promoter but is reliant on the nodule environment for effect. Overall, the data presented in this thesis shows that smoking has a direct effect on rheumatoid synovial tissue. Gene-environment interactions are likely to determine the overall outcome for the inflammatory process in patients with RA

Smoking, genes and inflammation

Rheumatoid arthritis (RA) is an, autoimmune disease where genetic predisposition and environmental factors increase the risk of developing RA and the severity of the disease. Cigarette smoking is the major recognised environmental risk factor, and there is a combined effect from smoking and the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype on the risk of developing RA. This study sought to establish any direct effect of smoking and/or the genetic predisposition on the inflammation driving RA and to identify biological mechanism(s) that might explain epidemiological data linking smoking, genetics and RA. The aim of initial work was to establish any involvement of aryl hydrocarbon receptor (AHR)-mediated mechanisms within inflamed rheumatoid tissues. The expression of AHR, CYP1A1 and AHRR genes were quantified by real-time PCR in twenty synovial and eighteen subcutaneous nodule tissues. Patient’s smoking status was established at the time tissue was obtained. The results show smoking causes significant AHR activation in joint synovial tissue, but not in rheumatoid nodule tissues. A subset of synovial DCs show activated AHR in smokers, consistent with the sensitivity of human mo-DCs stimulated with the AHR agonist, benzo(a)pyrene (BaP) in vitro. It is concluded that DCs within the joint synovium are the principal immune cells that respond to cigarette smoke exposure. Microarray analysis revealed that the expression of 547 synovial genes was up-regulated by smoking, including folate receptor 1 (FOLR1), matrix metalloproteinases (MMP)9, MMP11 and MMP14, TNF-superfamily members, TNFSF10/TRAIL and TNFRSF10B/TRAILR2 and transcription factors, RUNX1 and RUNX2. Cell motility and adhesion were the biological processes in synovium most affected by smoking. The expression of 307 synovial genes was down-regulated by smoking, including the vascular “protective” genes, KLF2 and eNOS, suggesting that endothelial function is affected by smoking with implications for vasculitis and the development of rheumatoid nodules associated with severe RA. Any effect of smoking and SE copy number on genes associated with AHR signalling and other immune-inflammatory genes was established. Results suggest there are solitary, reciprocal or synergistic effects from smoking and the SE in rheumatoid inflammation, which are gene dependent. Thus, smoking increases AHR activation in synovium; the SE has no effect. Furthermore, while smoking reduces IL17A expression in synovial tissue, indications are that SE copy number increases IL17A expression. In combination, smoking and the SE increase synovial MMP9 gene expression. Human promonocytic U937 cells were used to model the effect of BaP exposure on MMP9 expression. PMA-activated U937 cells acquire an ability to respond to BaP, including with increased MMP9 gene expression. AHR-specific siRNA, confirmed that AHR regulates MMP9 gene expression. Further data implicate different MMPs in rheumatoid tissue destruction. High MMP7 expression by macrophages occurs in a subset of nodule tissues. This high MMP7 expression is associated with a -181G/G polymorphism within the MMP7 gene promoter but is reliant on the nodule environment for effect. Overall, the data presented in this thesis shows that smoking has a direct effect on rheumatoid synovial tissue. Gene-environment interactions are likely to determine the overall outcome for the inflammatory process in patients with RA