Збройні сили Королівства Данії у військовій структурі Північноатлантичного Альянсу

Пугачова Д. В. Збройні сили Королівства Данії у військовій структурі Північноатлантичного Альянсу / Д. В. Пугачова // Людина, суспільство, політика: актуальні виклики сучасності: матеріали ІІ Міжнародної науково-практичної конференції (м. Одеса, 13-14 лютого 2015 р.) / НУ «ОЮА», Одеське відділення Міжнародної асоціації студентів політологічної науки, за заг. ред. Д. В. Яковлева – Одеса : НУ «ОЮА», 2015. – С. 137-139

Collective and single cell behavior in epithelial contact inhibition

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition". The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured MDCK cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition

Slater-Pauling Behavior of the Half-Ferromagnetic Full-Heusler Alloys

Using the full-potential screened Korringa-Kohn-Rostoker method we study the full-Heusler alloys based on Co, Fe, Rh and Ru. We show that many of these compounds show a half-metallic behavior, however in contrast to the half-Heusler alloys the energy gap in the minority band is extremely small. These full-Heusler compounds show a Slater-Pauling behavior and the total spin-magnetic moment per unit cell (M_t) scales with the total number of valence electrons (Z_t) following the rule: M_t=Z_t-24. We explain why the spin-down band contains exactly 12 electrons using arguments based on the group theory and show that this rule holds also for compounds with less than 24 valence electrons. Finally we discuss the deviations from this rule and the differences compared to the half-Heusler alloys.Comment: 10 pages, 8 figures, revised figure 3, new text adde

Interleukin-1β sequesters hypoxia inducible factor 2α to the primary cilium.

BACKGROUND: The primary cilium coordinates signalling in development, health and disease. Previously we have shown that the cilium is essential for the anabolic response to loading and the inflammatory response to interleukin-1β (IL-1β). We have also shown the primary cilium elongates in response to IL-1β exposure. Both anabolic phenotype and inflammatory pathology are proposed to be dependent on hypoxia-inducible factor 2 alpha (HIF-2α). The present study tests the hypothesis that an association exists between the primary cilium and HIFs in inflammatory signalling. RESULTS: Here we show, in articular chondrocytes, that IL-1β-induces primary cilia elongation with alterations to cilia trafficking of arl13b. This elongation is associated with a transient increase in HIF-2α expression and accumulation in the primary cilium. Prolyl hydroxylase inhibition results in primary cilia elongation also associated with accumulation of HIF-2α in the ciliary base and axoneme. This recruitment and the associated cilia elongation is not inhibited by blockade of HIFα transcription activity or rescue of basal HIF-2α expression. Hypomorphic mutation to intraflagellar transport protein IFT88 results in limited ciliogenesis. This is associated with increased HIF-2α expression and inhibited response to prolyl hydroxylase inhibition. CONCLUSIONS: These findings suggest that ciliary sequestration of HIF-2α provides negative regulation of HIF-2α expression and potentially activity. This study indicates, for the first time, that the primary cilium regulates HIF signalling during inflammation

Resting cells rely on the DNA helicase component MCM2 to build cilia

Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues

The use of intermediate inserts for CO 2 laser welding of steel AISI 321 and a Grade 2 titanium alloy

The paper studies the structure, chemical and phase compositions, hardness and strength of welded joints obtained in AISI 321 steel and Grade 2 titanium alloy sheets by CO 2 continuous laser with the use of intermediate Cu, Ni and Ag-Cu-Zn alloy inserts. It is demonstrated that the maximum strength of welded joints is achieved by the welding conditions enabling one to form multiphase structures with intermetallics in the material of a weld, rather than only those based on solid solutions. © 2018 Author(s)

ON THE EXPANSION OF THE WAREHOUSE BASE IN THE CONSIDERED ECONOMIC AREA WITH PARALLEL DETERMINATION OF THE OPTIMAL LOGISTICS WORK

This article proposes a comprehensive solution of three linear programming problems: Transport problem (logistics problem), Maximum flow problem, Center allocation problem. Similar tasks in the proposed complex formulation often arise at enterprises in the process of making decisions on expanding the warehouse base with the subsequent determination of the optimal process for the operation of warehouses as points of shipment to the consumer. The basic algorithms for finding optimal solutions are considered, a complex task is formulated, a model is built and a solution algorithm is implemented, and comparison of the existing method and author's method is carried out. The proposed model can be used in any enterprise where it is necessary to find the best combinatory variantfor delivery in order to minimize the cost of transporting of the finished product. Such a task corresponds exactly to the economic situations when an enterprise will have to deliver products using a known transport infrastructure, taking into account the cost of transportation. The task that we have solved appearedfor the first time at a timber processing enterprise. Such a problem is non-trivial combinatorial

Regulation of the apoptotic genes in breast cancer cells by the transcription factor CTCF

CTCF is a highly conserved and ubiquitous transcription factor with versatile functions. We previously demonstrated that elevated protein levels of CTCF in breast cancer cells were associated with the specific anti-apoptotic function of CTCF. We used proteomics and microarray approaches to identify regulatory targets of CTCF specific for breast cancer cells. Among the CTCF identified targets were proteins involved in the control of apoptosis. A proapoptotic protein, Bax, negatively regulated by CTCF, was chosen for further investigation. Repression of the human Bax gene at the transcriptional level by CTCF in breast cancer cells was confirmed by real-time PCR. Two CTCF binding sites within the Bax promoter were identified by electrophoretic mobility shift assay and footprinting. In reporter assays, the Bax-luciferase reporter construct, containing CTCF-binding sites, was negatively regulated by CTCF. In vivo, CTCF occupied its binding sites in breast cancer cells and tissues, as confirmed by chromatin immunoprecipitation assay. Our findings suggest a possible mechanism of the specific CTCF anti-apoptotic function in breast cancer cells whereby CTCF is bound to the Bax promoter, resulting in repression of Bax and inhibition of apoptosis; depletion of CTCF leads to activation of Bax and apoptotic death. CTCF binding sites in the Bax promoter are unmethylated in all cells and tissues inspected. Therefore, specific CTCF interaction with the Bax promoter in breast cancer cells, and the functional outcome, may depend on a combination of epigenetic factors characteristic for these cells. Interestingly, CTCF appears to be a negative regulator of other proapoptotic genes (for example, Fas, Apaf-1, TP531NP1). Conversely, stimulating effects of CTCF on the anti-apoptotic genes (Bcl-2, Bag-3) have been observed. Taken together, these findings suggest that specific mechanisms have evolved in breast cancer cells to protect them from apoptosis; regulation of apoptotic genes by CTCF appears to be one of the resistance strategies

Kruppel-like factor 4 signals through microRNA-206 to promote tumor initiation and cell survival

Tumor cell heterogeneity poses a major hurdle in the treatment of cancer. Mammary cancer stem-like cells (MaCSCs), or tumor-initiating cells, are highly tumorigenic sub-populations that have the potential to self-renew and to differentiate. These cells are clinically important, as they display therapeutic resistance and may contribute to treatment failure and recurrence, but the signaling axes relevant to the tumorigenic phenotype are poorly defined. The zinc-finger transcription factor Kruppel-like factor 4 (KLF4) is a pluripotency mediator that is enriched in MaCSCs. KLF4 promotes RAS-extracellular signal-regulated kinase pathway activity and tumor cell survival in triple-negative breast cancer (TNBC) cells. In this study, we found that both KLF4and a downstream effector, microRNA-206 (miR-206), are selectively enriched in the MaCSC fractions of cultured human TNBC cell lines, as well as in the aldehyde dehydrogenase-high MaCSC sub-population of cells derived from xenografted human mammary carcinomas. The suppression of endogenous KLF4 or miR-206 activities abrogated cell survival and in vivo tumor initiation, despite having only subtle effects on MaCSC abundance. Using a combinatorial approach that included in silico as well as loss- and gain-of-function in vitro assays, we identified miR-206-mediated repression of the pro-apoptotic molecules programmed cell death 4 (PDCD4) and connexin 43 (CX43/GJA1). Depletion of either of these two miR-206-regulated transcripts promoted resistance to anoikis, a prominent feature of CSCs, but did not consistently alter MaCSC abundance. Consistent with increased levels of miR-206 in MaCSCs, the expression of both PDCD4 and CX43 was suppressed in these cells relative to control cells. These results identify miR-206 as an effector of KLF4-mediated prosurvival signaling in MaCSCs through repression of PDCD4 and CX43. Consequently, our study suggests that a pluripotency factor exerts prosurvival signaling in MaCSCs, and that antagonism of KLF4-miR-206 signaling may selectively target the MaCSC niche in TNBC