175 research outputs found
Deformation uniformity of additively manufactured materials on the example of austenitic stainless steel 321 and copper C11000
Structural studies and mechanical tests of additively manufactured samples from AISI 321 steel copper C110000 have been carried out. Mechanical tensile tests of 321 steel show slight differences in the ultimate tensile strength (up to 3-4%) and ductility (up to 10%) of test coupons tested along the material growth direction and along the layer deposition direction. The strength of C11000 copper samples is 9.4% higher in the layer deposition direction, but their ductility is 15.4% lower than that of samples deformed in the growth direction. The strain relief on the surface of the polished gage section of the steel test coupons demonstrates changes in the material structure with small elongated grains along the growth direction of the sample. The deformation relief of copper samples is mainly related to the deformation of large columnar grains stretched in the growth direction
Structure formation features of large block-shaped samples from the copper and aluminum alloy produced by the wire-feed electron-beam additive technology
In this work the study of the structure of samples made by the wire-feed electronbeam 3D printing from copper C11000 and aluminum alloy AA5056 was carried out. The presence of a dendritic structure typical of this method was revealed, as well as the presence of pores, cracks and other defects that occurred during printing. Mechanical properties of samples cut in the planar section are at a rather low level. The ultimate tensile strength of copper block samples varies between 165 and 187 MPa. The relative elongation of samples without pores is at 18%, but with the presence of pores it decreases sharply to 7%, while the strength is practically not decreased. The samples of alloy AA5056 demonstrate slightly higher mechanical properties: the strength is at the level of 190-192 MPa and the relative elongation is about 16-18%. In samples with defects such as large pores or discontinuities, the strength drops to almost zero
From Barbie to the oligarchs wife: Reading fantasy femininity and globalisation in post-Soviet Russian womens magazines
This article shows how an analysis of fantasy femininity sheds light on how norms of gender, class and national identity reflect global and local cross-cultural currents in post-Soviet Russia. Drawing on a discourse analysis of womenβs magazines and in-depth interviews with readers, it shows how, in the globalized post-Soviet cultural landscape, fantasy femininity represents both change and continuity. Feminine archetypes in womenβs magazines, from fairytale princesses to Barbie dolls, reflect a wider post-Soviet cultural hybridisation, and show how Western womenβs magazines have adapted to the Russian context. Furthermore, the article highlights readersβ ambiguous attitudes towards post-Soviet cultural trends linked to perceived Westernisation or globalisation, such as individualism, conspicuous consumption, and glamour
Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis
The Forkhead Box m1 (Foxm1) protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1β/β mice) prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT). Decreased lung tumorigenesis in epFoxm1β/β mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2Ξ± (TOPO-2Ξ±), a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2Ξ± mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2Ξ± promoter region, indicating that TOPO-2Ξ± is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2Ξ± expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy
Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice
<p>Abstract</p> <p>Background</p> <p>Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression <it>in vivo.</it></p> <p>Methods</p> <p>Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated.</p> <p>Results</p> <p>We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression <it>in vitro</it>, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na<sup>+</sup>-K<sup>+ </sup>ATPase Ξ±1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1Ξ± and HIF2Ξ±) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na<sup>+</sup>-K<sup>+ </sup>ATPase Ξ±1, c) increased HIF1Ξ± expression (no HIF2Ξ± was detected) and d) increased microvessel density in the tumor tissues.</p> <p>Conclusions</p> <p>This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na<sup>+</sup>-K<sup>+ </sup>ATPase was involved in hypoxic inhibition of tumor progression. The results from this study provide new insights into the role of hypoxia in tumor progression and therapeutic strategies for cancer treatment.</p
Peroxiredoxin 3 Is a Redox-Dependent Target of Thiostrepton in Malignant Mesothelioma Cells
Thiostrepton (TS) is a thiazole antibiotic that inhibits expression of FOXM1, an oncogenic transcription factor required for cell cycle progression and resistance to oncogene-induced oxidative stress. The mechanism of action of TS is unclear and strategies that enhance TS activity will improve its therapeutic potential. Analysis of human tumor specimens showed FOXM1 is broadly expressed in malignant mesothelioma (MM), an intractable tumor associated with asbestos exposure. The mechanism of action of TS was investigated in a cell culture model of human MM. As for other tumor cell types, TS inhibited expression of FOXM1 in MM cells in a dose-dependent manner. Suppression of FOXM1 expression and coincidental activation of ERK1/2 by TS were abrogated by pre-incubation of cells with the antioxidant N-acetyl-L-cysteine (NAC), indicating its mechanism of action in MM cells is redox-dependent. Examination of the mitochondrial thioredoxin reductase 2 (TR2)-thioredoxin 2 (TRX2)-peroxiredoxin 3 (PRX3) antioxidant network revealed that TS modifies the electrophoretic mobility of PRX3. Incubation of recombinant human PRX3 with TS in vitro also resulted in PRX3 with altered electrophoretic mobility. The cellular and recombinant species of modified PRX3 were resistant to dithiothreitol and SDS and suppressed by NAC, indicating that TS covalently adducts cysteine residues in PRX3. Reduction of endogenous mitochondrial TRX2 levels by the cationic triphenylmethane gentian violet (GV) promoted modification of PRX3 by TS and significantly enhanced its cytotoxic activity. Our results indicate TS covalently adducts PRX3, thereby disabling a major mitochondrial antioxidant network that counters chronic mitochondrial oxidative stress. Redox-active compounds like GV that modify the TR2/TRX2 network may significantly enhance the efficacy of TS, thereby providing a combinatorial approach for exploiting redox-dependent perturbations in mitochondrial function as a therapeutic approach in mesothelioma
Π‘ΠΠ£Π§ΠΠ ΠΠΠ’Π―ΠΠΠΠΠΠ Π’ΠΠ§ΠΠΠΠ― ΠΠ ΠΠΠΠΠΠΠΠΠ ΠΠΠ€Π ΠΠ’ΠΠ§ΠΠ‘ΠΠΠΠ Π‘ΠΠΠΠ ΠΠΠ
Nephrotic syndrome is a severe renal disease that may result in the end-stage renal failure despite the extent of proteinuria. Prognosis and tactics of therapy of nephrotic syndrome depend both on the morphological diagnosis and on the cause of the disease. It ought to be considered that congenital nephrotic syndrome is resistant to immunosuppressive therapy. However, several foreign authors demonstrate cases of immunosuppressive therapy effectiveness (steroids and cyclosporine A) in a range of familial cases of nephroticsyndrome. Timely detection of children with genetically caused nephrotic syndrome allows to define the patient management tactics in each case on time. This clinical case represents non-severe course of congenital nephrotic syndrome caused by an NPHS2 gene mutation, which had not before been described neither in Russian nor in foreign literature. The authors deem introduction of the molecular genetic analysis to the routine clinical practice for all cases of congenital nephrotic syndrome and steroid-resistant nephrotic syndrome reasonable.Β ΠΠ΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌ β ΡΠ΅ΡΡΠ΅Π·Π½ΠΎΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠ΅ ΠΏΠΎΡΠ΅ΠΊ, ΠΈΡΡ
ΠΎΠ΄ΠΎΠΌ ΠΊΠΎΡΠΎΡΠΎΠ³ΠΎ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎ ΠΎΡ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΠΏΡΠΎΡΠ΅ΠΈΠ½ΡΡΠΈΠΈ ΠΌΠΎΠΆΠ΅Ρ ΡΡΠ°ΡΡ ΡΠ΅ΡΠΌΠΈΠ½Π°Π»ΡΠ½Π°Ρ ΡΡΠ°Π΄ΠΈΡ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈ. ΠΡΠΎΠ³Π½ΠΎΠ· ΠΈ ΡΠ°ΠΊΡΠΈΠΊΠ° ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Π·Π°Π²ΠΈΡΡΡ ΠΊΠ°ΠΊ ΠΎΡ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄ΠΈΠ°Π³Π½ΠΎΠ·Π°, ΡΠ°ΠΊ ΠΈ ΠΎΡ ΠΏΡΠΈΡΠΈΠ½Ρ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. Π‘Π»Π΅Π΄ΡΠ΅Ρ ΡΡΠΈΡΡΠ²Π°ΡΡ ΡΠΎΡ ΡΠ°ΠΊΡ, ΡΡΠΎ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΡΠΉ Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠΈΠ½Π΄ΡΠΎΠΌ ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΠΌ ΠΊ ΠΈΠΌΠΌΡΠ½ΠΎΡΡΠΏΡΠ΅ΡΡΠΈΠ²Π½ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ. ΠΠ΄Π½Π°ΠΊΠΎ, ΡΡΠ΄ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΡΡ
Π°Π²ΡΠΎΡΠΎΠ² Π΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΡΠ΅Ρ ΠΏΡΠΈΠΌΠ΅ΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΈΠΌΠΌΡΠ½ΠΎΡΡΠΏΡΠ΅ΡΡΠΈΠ²Π½ΡΡ
ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ² (ΡΡΠ΅ΡΠΎΠΈΠ΄Ρ ΠΈ ΡΠΈΠΊΠ»ΠΎΡΠΏΠΎΡΠΈΠ½ Π) ΠΏΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΡΠ΅ΠΌΠ΅ΠΉΠ½ΡΡ
ΡΠ»ΡΡΠ°ΡΡ
Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ°. Π‘Π²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠ΅ Π²ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ Π΄Π΅ΡΠ΅ΠΉ Ρ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π²ΠΎΠ²ΡΠ΅ΠΌΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡΡΡ Ρ ΡΠ°ΠΊΡΠΈΠΊΠΎΠΉ Π²Π΅Π΄Π΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° Π² ΠΊΠ°ΠΆΠ΄ΠΎΠΌ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅. ΠΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π½ΡΠΉ Π² ΡΡΠ°ΡΡΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΡΠΈΠΌΠ΅Ρ ΠΎΠΏΠΈΡΡΠ²Π°Π΅Ρ Π½Π΅ΡΡΠΆΠ΅Π»ΠΎΠ΅ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠ³ΠΎ Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ°, ΠΏΡΠΈΡΠΈΠ½ΠΎΠΉ ΠΊΠΎΡΠΎΡΠΎΠ³ΠΎ ΡΡΠ°Π»Π° ΡΠ°Π½Π΅Π΅ Π½Π΅ ΠΎΠΏΠΈΡΠ°Π½Π½Π°Ρ Π² ΠΎΡΠ΅ΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΈ Π·Π°ΡΡΠ±Π΅ΠΆΠ½ΠΎΠΉ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅ ΠΌΡΡΠ°ΡΠΈΡ Π³Π΅Π½Π° NPHS2. ΠΠ²ΡΠΎΡΡ ΡΡΠΈΡΠ°ΡΡ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΡΠΌ Π²Π²Π΅Π΄Π΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Π² ΠΏΠΎΠ²ΡΠ΅Π΄Π½Π΅Π²Π½ΡΡ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΡΡ ΠΏΡΠ°ΠΊΡΠΈΠΊΡ ΠΏΡΠΈ Π²ΡΠ΅Ρ
ΡΠ»ΡΡΠ°ΡΡ
Π²ΡΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠ³ΠΎ Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ°, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΏΡΠΈ ΡΡΠ΅ΡΠΎΠΈΠ΄ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΠΌ Π²Π°ΡΠΈΠ°Π½ΡΠ΅ Π½Π΅ΡΡΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ°.
2-Deoxy-D-Glucose Treatment of Endothelial Cells Induces Autophagy by Reactive Oxygen Species-Mediated Activation of the AMP-Activated Protein Kinase
Autophagy is a cellular self-digestion process activated in response to stresses such as energy deprivation and oxidative stress. However, the mechanisms by which energy deprivation and oxidative stress trigger autophagy remain undefined. Here, we report that activation of AMP-activated protein kinase (AMPK) by mitochondria-derived reactive oxygen species (ROS) is required for autophagy in cultured endothelial cells. AMPK activity, ROS levels, and the markers of autophagy were monitored in confluent bovine aortic endothelial cells (BAEC) treated with the glycolysis blocker 2-deoxy-D-glucose (2-DG). Treatment of BAEC with 2-DG (5 mM) for 24 hours or with low concentrations of H2O2 (100 Β΅M) induced autophagy, including increased conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles, and increased fusion of autophagosomes with lysosomes. 2-DG-treatment also induced AMPK phosphorylation, which was blocked by either co-administration of two potent anti-oxidants (Tempol and N-Acetyl-L-cysteine) or overexpression of superoxide dismutase 1 or catalase in BAEC. Further, 2-DG-induced autophagy in BAEC was blocked by overexpressing catalase or siRNA-mediated knockdown of AMPK. Finally, pretreatment of BAEC with 2-DG increased endothelial cell viability after exposure to hypoxic stress. Thus, AMPK is required for ROS-triggered autophagy in endothelial cells, which increases endothelial cell survival in response to cell stress
Symbiotic Associations in the Phenotypically-Diverse Brown Alga Saccharina japonica
The brown alga Saccharina japonica (Areschoug) Lane, Mayes, Druehl et Saunders is a highly polymorphic representative of the family Laminariaceae, inhabiting the northwest Pacific region. We have obtained 16S rRNA sequence data in symbiont microorganisms of the typical form (TYP) of S. japonica and its common morphological varieties, known as βlongipesβ (LON) and βshallow-waterβ (SHA), which show contrasting bathymetric distribution and sharp morphological, life history traits, and ecological differences. Phylogenetic analysis of the 16S rRNA sequences shows that the microbial communities are significantly different in the three forms studied and consist of mosaic sets of common and form-specific bacterial lineages. The divergence in bacterial composition is substantial between the TYP and LON forms in spite of their high genetic similarity. The symbiont distribution in the S. japonica forms and in three other laminarialean species is not related to the depth or locality of the algae settlements. Combined with our previous results on symbiont associations in sea urchins and taking into account the highly specific character of bacteria-algae associations, we propose that the TYP and LON forms may represent incipient species passing through initial steps of reproductive isolation. We suggest that phenotype differences between genetically similar forms may be caused by host-symbiont interactions that may be a general feature of evolution in algae and other eukaryote organisms. Bacterial symbionts could serve as sensitive markers to distinguish genetically similar algae forms and also as possible growth-promoting inductors to increase algae productivity
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