The role of environmental and endogenous AHR ligands in estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2-negative (ER-/PR-/HER2-) breast cancer progression

Recent studies indicate that endogenously ligand-activated Aryl Hydrocarbon Receptor (AHR) plays an important role in normal and pathological processes, including the induction and progression of breast cancer. As the known number of AHR-mediated processes grows, so too does the importance of identifying endogenous AHR ligands that influence breast cancer progression. The following studies focus on two tryptophan metabolism pathway branches, the kynurenine (KYN) branch and the indoxyl sulfate (IS) branch, to determine if ER-/PR-/HER2- breast cancer cells can produce, or are exposed to, AHR ligands from these branches, how these ligands affect cell migration and, if produced, how their production is controlled. It is hypothesized that: 1) malignant cells produce, or derive from their microenvironment, AHR ligands through the KYN and/or IS pathways, 2) these metabolites drive AHR-dependent breast cancer migration, 3) environmental AHR ligands mimic the effects of endogenous ligands, 4) rate-limiting kynurenine pathway enzymes are responsible for endogenous AHR ligand production and their downstream effects, and 5) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a positive feedback loop. ER-/PR-/HER2- mammary epithelial cells were assayed for production of AHR-activating tryptophan metabolites and for the kynurenine pathway enzymes tryptophan 2,3-dioxygenase (TDO) and indolamine 2,3-dioxygenase (IDO). The relationship between kynurenine and IS pathways, AHR activity, cell migration, and aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker associated with poor prognosis, was investigated using tryptophan metabolites, enzyme-specific gene knockdown or over-expression, qPCR, cell migration assays and ALDH1 activity assay. ER-/PR-/HER2- tumor cells produce KYN and its downstream metabolite xanthurenic acid (XA), at levels sufficient to activate the AHR. KYN, XA, and IS significantly accelerate migration in an AHR-dependent fashion, and at physiological doses, while environmental AHR ligands 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and benzo[a]pyrene (B[a]P) mimic this effect. IS induces ALDH1 activity. AHR knockdown or inhibition significantly reduces Tdo2 expression. Finally, gene expression dataset analyses reveal high Tdo2 levels in primary breast tumors, with the highest levels in ER-/PR-/Her2- and stage 4 tumors. These studies identify three tryptophan-derived AHR ligands that contribute to breast cancer progression and demonstrate a positive feedback loop, where AHR activity up-regulates Tdo2, which drives endogenous AHR ligand production

Assessment and ways to increase the rate of return in the Russian medium-sized agricultural enterprises

The rate of return (profitability) is the category that allows evaluation of financial, production and other costs of the enterprise. The detailed analysis of return ratios enables to regulate the enterprise financial system and has a positive effect on its financial performance. The article considers the method of the rate of return assessment and suggests the ways to increase it. The case of the medium-sized agro-industrial company was used. Based on the financial performance of the enterprise, the range of the rate of return indicators was calculated, such as fixed assets, rate of return on current assets and on equity capital, gross profit margin, operating and net profit margin. Based on the calculations, the authors show that the rate of return of the enterprise increased, and a high efficiency of operations was observed. However, at the same time, there are tasks to be solved. One of them is to introduce a payment schedule. The analysis of the financial effect of the payment schedule introduction showed that it increased the current rate of return of the enterprise by 10%

Evolutionary History of LTR Retrotransposon Chromodomains in Plants

Chromodomain-containing LTR retrotransposons are one of the most successful groups of mobile elements in plant genomes. Previously, we demonstrated that two types of chromodomains (CHDs) are carried by plant LTR retrotransposons. Chromodomains from group I (CHD_I) were detected only in Tcn1-like LTR retrotransposons from nonseed plants such as mosses (including the model moss species Physcomitrella) and lycophytes (the Selaginella species). LTR retrotransposon chromodomains from group II (CHD_II) have been described from a wide range of higher plants. In the present study, we performed computer-based mining of plant LTR retrotransposon CHDs from diverse plants with an emphasis on spike-moss Selaginella. Our extended comparative and phylogenetic analysis demonstrated that two types of CHDs are present only in the Selaginella genome, which puts this species in a unique position among plants. It appears that a transition from CHD_I to CHD_II and further diversification occurred in the evolutionary history of plant LTR retrotransposons at approximately 400 MYA and most probably was associated with the evolution of chromatin organization

The main provisions of the evolutionary doctrine in economics

Today, in the economic theory, the mainstream is the following areas: neoclassical economic theory, neo-Keynesianism, monetarism, institutionalism. The basis of these areas is the principle of economic equilibrium. However, more and more economists see the economy not as an equilibrium, but, on the contrary, as a non-equilibrium system. In the framework of this study, the evolutionary economic theory is studied, which can become the theoretical basis for studying economics from the point of view of disequilibrium. For this purpose, the paper reveals the main provisions of evolutionary doctrine in economics, describes the evolutionary mechanisms of development in the economy (variability, heredity, selection, competition), defines the main elements of evolution in the economy (economic feasibility, levels of evolutionary transformation, evolutionary material in the economy, elementary evolutionary factors). This paper is part of a series that reveals the hypothesis that the evolutionary economic theory is a more general economic theory, from the position of which it is possible to more fully reveal the principles of behavior of individuals and institutions to maximize the satisfaction of material needs and on this basis to formulate an effective economic policy of individuals and institutions, including the state

Creation of a homogeneous plasma column by means of hohlraum radiation for ion-stopping measurements

In this work, we present the results of two-dimensional radiation-hydrodynamics simulations of a hohlraum target whose outgoing radiation is used to produce a homogeneously ionized carbon plasma for ion-beam stopping measurements. The cylindrical hohlraum with gold walls is heated by a frequency-doubled ($\lambda_l = 526.5$ $\mu m$) $1.4$ $ns$ long laser pulse with the total energy of $E_l = 180$ $J$. At the laser spot, the peak matter and radiation temperatures of, respectively, $T \approx 380$ $eV$ and $T_r \approx 120$ $eV$ are observed. X-rays from the hohlraum heat the attached carbon foam with a mean density of $\rho_C = 2$ $mg/cm^3$ to a temperature of $T \approx 25$ $eV$. The simulation shows that the carbon ionization degree ($Z \approx 3.75$) and its column density stay relatively stable (within variations of about $\pm7\%$) long enough to conduct the ion-stopping measurements. Also, it is found that a special attention should be paid to the shock wave, emerging from the X-ray heated copper support plate, which at later times may significantly distort the carbon column density traversed by the fast ions.Comment: 12 pages, 12 figure

The construction of the digital organizational, social and economic production mechanism in the agro-industry

The article represents the construction of the digital organizational, social and economic production mechanism in the agro-industry. The following main conclusions were obtained based on the exposition of the article materials: The development and reformation of the organizational, social and economic mechanism can have a positive impact on the development of agriculture. The definition of “digital organizational, social and economic production mechanism” is given. The article proposes a functional target scheme for the construction of the digital organizational, social and economic mechanism to produce agro-industrial products. This functional target scheme is a set of institutional approach elements in the market economy aimed at institutional provision of relatively favorable business conditions for all participants in the digital economy of the agro-industrial products output.peer-reviewe

STUDENT ATTITUDE TO ETHICAL CONSUMPTION AS NEW ECOLOGICAL PRACTICE

Purpose of the study: The aim of this article is to analyze the attitude of students to ethical consumption as a new environmental practice; to explore current research on ethical consumption. Methodology: The leading methods for the study of this problem are the methods of questioning and testing, allowing to make a qualitative analysis of the students' attitude to the new environmental practice – ethical consumption and contributing to a more detailed identification of such issues as: knowledge of students about ethical consumption; students' attitude to separate waste disposal; students' attitude to the use of environmental packaging products; identification of students' practices of secondary consumption. Results: The article deals with the theoretical and methodological foundations of the analysis of students' attitudes to ethical consumption as a new environmental practice. It is established that the level of students' awareness of ethical consumption is low. The proportion of informed students among social and humanities specialties is twice more than high as students of technical specialties. It is revealed that more than a third of respondents do not know about the production of environmentally friendly goods.  Almost all students are aware of the separate disposal of garbage and believe that it is necessary to install the appropriate bins. More than half of students are ready to sort garbage in the presence of such containers, and the readiness of humanitarians is 1.5 times higher than that of students of technical specialties. The main reasons why respondents would not buy goods in eco-friendly packaging are the lack of funds and the lack of sense for students. The majority of students believe the practice of secondary consumption to be popular one.  Applications of this study: The data obtained in the work can be used in environmental psychology, social psychology, pedagogy, the psychology of education, age psychology, sociology, as well as for further theoretical development of this issue. Novelty/Originality of this study: The originality of this article lies in the analysis of the social phenomenon of ethical consumption, which implies that only purchase and consumption of those goods, the production of which does not cause great harm to the environment, those goods in the production of which are not infringed the rights of the worker and moreover child labor is not used, and most importantly the recycling of waste after consumption of the product will not harm nature is ethical one