129 research outputs found
The role of the S1P3 receptor in inflammation-associated proliferative disorders
No full textInflammation is involved in the pathogenesis of many different disorders,
including glomerulonephritis, fibrosis and cancer. Unraveling the regulatory
mechanisms underlying the molecular processes of inflammation remains
crucial for the development of novel therapeutics for future treatment of
inflammatory disorders.
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid molecule,
which likely plays an important role in inflammation. However, the molecular
mechanisms involved in S1P-mediated inflammation are still not completely
understood. This work aimed to unravel the interconnection between S1P and
other molecular players implicated in inflammatory response, as well as to
indicate the S1P receptor subtype the activation of which contributes to
proliferation and migration of non-cancerous cells and to metastatic progression
of breast cancer. In addition, the therapeutic potential of drugs targeting early
steps of the inflammatory response was assessed.
As model systems for the non-cancerous studies we used renal mesangial
cells (rMC) and mouse embryonic fibroblasts (MEF), and for the cancer studies
the breast cancer cell line MDA-MB-231 and two metastatic sublines derived
from lung (4175) and bone (1833).
Our data demonstrate that the S1P3 receptor is strongly upregulated in
lung and bone metastatic cell lines compared to the parental MDA-MB-231
cells, and its activation by S1P has pro-inflammatory, pro-migratory and pro
invasive potential by inducing COX-2 expression and PGE2 signaling via EP2
and EP4. These data were confirmed in non-cancerous studies, where we found
that S1P3 receptor is upregulated in mMC and MEFs upon the loss of SphK2.
Our results show that the deficiency of SphK2 in these cells correlates with an
enhanced proliferative and migratory capacity, indicating that SphK2 exerts
suppressive effects on cell growth and migration. This finding is likely to be due
8
to the enhanced expression of S1P3, as its depletion in mesangial cells reduced
their proliferation and migration rate.
Our next study revealed that the novel cPLA2 inhibitors AVX001 and
AVX002 have an anti-inflammatory potential in cultures of rMC by reducing the pro-inflammatory mediator PGE2 through the inhibitory effect on NFκB
activation. Thus, they represent promising novel drugs for the treatment of
inflammatory disorders.
Altogether, our data demonstrate for the first time a critical role of the
S1P3 receptor in S1P-mediated proliferative and inflammatory responses, and
identify S1P3 as a potential target for therapeutic intervention to treat
inflammation-associated proliferative disorders
Child soldiers and military actors: a variation in detention policies across liberal democracies
No full textThe professional militaries of Canada, the United States, and the United Kingdom have increasingly recognized that children can become part of opposing forces and face the operational and policy decisions regarding their detention. These Anglo-Saxon, consolidated, liberal democracies demonstrate a high level of similarity, in terms of their shared norms and values, and common security practices. Nonetheless, these three countries have developed distinct policies on the detention of child soldiers. This dissertation addressed the question: what explains the cross-national variation in the development of policies on the detention of child soldiers in Canada, the United Kingdom, and the United States?In order to answer this research question, I proposed a series of hypotheses to examine the role of three strategic actors in the policy process: military lawyers, government officials, and representatives from non-governmental organizations. I analyzed data that required both quantitative and qualitative methods to test these hypotheses. Specifically, qualitatively, I performed a content analysis of a total of 69 semi-structured interviews; and, quantitatively, I used NVivo 11 coding query tools to generate numerical data to present aggregate results. These methods allowed for comparing the roles of these three actors in each national context. I utilized the comparative case study method to identify causal patterns across these three countries to offer a second test of these hypotheses. My dissertation suggested an explanatory relationship between NGOs’ choice of strategies and the policy outcomes in each of these three countries. First, the NGOs’ choice between different types of framing and how to engage in framing contests, during the agenda-setting stage, had far-reaching implications for the policy-making process. It defined the key terms and demarcated boundaries of the issue in a policy domain that abounds with contested elements. Second, the selection of strategies and decision-making venues simultaneously influenced the NGOs’ ability to shape policy outcomes during the policy formulation stage. Third, the application of the strategy of ‘naming and shaming’ during the policy implementation stage remained effective only if the NGOs applied it in combination with other policy instruments, such as the use of domestic litigation. This dissertation hopes to make an empirical contribution to the debate on how policy actors engage and shape outcomes in contested policy domains, which require balancing national security and human rights agendas.Ph.D.Includes bibliographical referencesby Iuliia Hoba
Проблемы национального брендинга современной Испании
No full textВ данной работе рассматриваются теоретические аспекты территориального брендинга, комплексно проанализирована история развития брендинговой стратегии Испании, брендинговый потенциал и основные инструменты формирования имиджа данной страны. Отдельное внимание уделено роли брендинга испанских городов в национальном бренде на примере Барселоны. Автор также определяет проблемы и вызовы, с которыми сталкивается брендинг Испании в настоящее время, на основе чего предлагает практические рекомендации для разработки дальнейшей брендинговой стратегии южноевропейской страны. Также оценена возможность применения испанского опыта в российской действительности.This study presents the basic theory of territory branding as well as a comprehensive analysis of the history of national branding of Spain, its branding capacity, and the main tools of image making of the country. Separate attention is given to the role of branding of Spanish cities, Barcelona in particular. The author determines the problems and challenges that Spanish branding faces nowadays, and offers practical recommendations for further branding of the South European country. The possibility of applying the Spanish experience to national branding of Russian Federation is examined
The ω3-polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells
No full textω3-polyunsaturated fatty acids (ω3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized
Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
No full textBoth of the sphingosine kinase (SK) subtypes SK-1 and SK-2 catalyze the production of the bioactive lipid molecule sphingosine 1-phosphate (S1P). However, the subtype-specific cellular functions are largely unknown. In this study, we investigated the cellular function of SK-2 in primary mouse renal mesangial cells (mMC) and embryonic fibroblasts (MEF) from wild-type C57BL/6 or SK-2 knockout (SK2ko) mice. We found that SK2ko cells displayed a significantly higher proliferative and migratory activity when compared to wild-type cells, with concomitant increased cellular activities of the classical extracellular signal regulated kinase (ERK) and PI3K/Akt cascades, and of the small G protein RhoA. Furthermore, we detected an upregulation of SK-1 protein and S1P3 receptor mRNA expression in SK-2ko cells. The MEK inhibitor U0126 and the S1P1/3 receptor antagonist VPC23019 blocked the increased migration of SK-2ko cells. Additionally, S1P3ko mesangial cells showed a reduced proliferative behavior and reduced migration rate upon S1P stimulation, suggesting a crucial involvement of the S1P3 receptor. In summary, our data demonstrate that SK-2 exerts suppressive effects on cell growth and migration in renal mesangial cells and fibroblasts, and that therapeutic targeting of SKs for treating proliferative diseases requires subtype-selective inhibitors
PECULIARITIES OF TRANSLATION OF PHRASEOLOGICAL UNITS MEANING THE ENVIRONMENTAL REALITIES
No full textThe author considers the role of phraseological units in the language picture of the world, as well as peculiarities of translation of phraseological units denoting the environmental realities
Upregulation of the S1P3 receptor in metastatic breast cancer cells increases migration and invasion by induction of PGE2 and EP2/EP4 activation.
No full textBreast cancer is one of the most common and devastating malignancies among women worldwide. Recent evidence suggests that malignant progression is also driven by processes involving the sphingolipid molecule sphingosine 1-phosphate (S1P) and its binding to cognate receptor subtypes on the cell surface. To investigate the effect of this interaction on the metastatic phenotype, we used the breast cancer cell line MDA-MB-231 and the sublines 4175 and 1833 derived from lung and bone metastases in nude mice, respectively. In both metastatic cell lines expression of the S1P3 receptor was strongly upregulated compared to the parental cells and correlated with higher S1P-induced intracellular calcium ([Ca(2+)]i), higher cyclooxygenase (COX)-2 and microsomal prostaglandin (PG) E2 synthase expression, and consequently with increased PGE2 synthesis. PGE2 synthesis was decreased by antagonists and siRNA against S1P3 and S1P2. Moreover, in parental MDA-MB-231 cells overexpression of S1P3 by cDNA transfection also increased PGE2 synthesis, but only after treatment with the DNA methyltransferase inhibitor 5-aza-2-deoxycytidine, indicating reversible silencing of the COX-2 promoter. Functionally, the metastatic sublines showed enhanced migration and Matrigel invasion in adapted Boyden chamber assays, which further increased by S1P stimulation. This response was abrogated by either S1P3 antagonism, COX-2 inhibition or PGE2 receptor 2 (EP2) and 4 (EP4) antagonism, but not by S1P2 antagonism. Our data demonstrate that in breast cancer cells overexpression of S1P3 and its activation by S1P has pro-inflammatory and pro-metastatic potential by inducing COX-2 expression and PGE2 signaling via EP2 and EP4
Negotiations and diplomatic protocol as a mean of political conflicts resolution
No full textThe author of the article made an attempt to prove the relevance and importance of such topic
as negotiations and diplomatic protocol as a mean of conflicts resolution. Bases of negotiations
were determined; etymology of word “protocol”, the role and importance of diplomatic protocol
for the development of modern international politics was described
"Not a man - but a cloud in trousers!" : two translations of Vladimir Mayakovsky's futuristic poem "A cloud in trousers" in comparison
No full textZu Beginn des zwanzigsten Jahrhunderts gewann in der Kunst in Russland eine neue Strömung namens Futurismus an Bedeutung. Dessen Ziel war, alte Traditionen zu zerstören und eine neue Ästhetik zu schaffen. Werke dieser Richtung sind gekennzeichnet durch Neologismen, Metaphern, Jargon, falsche Zeichensetzung und Lautspiele. Majakowski verfasste 1915 das Werk “Облако в штанах/Wolke in Hosen”, das neben den oben genannten Merkmalen zahlreiche Anspielungen auf die damalige Ideologie und Politik enthält. Übersetzungen ins Deutsche wurden unter anderem von Karl Dedecius und Alexander Nitzberg angefertigt und werden in dieser Masterarbeit untersucht. Da zwischen den Übersetzungen etwa 26 Jahre liegen und die Übersetzer in ihren Übertragungen Tendenzen ihrer Zeit, Kultur, Übersetzungstraditionen und Ideologie widerspiegeln, unterscheiden sich diese. Um die Übersetzungen zu vergleichen, die Unterschiede zu identifizieren und zu erklären, wurde zunächst eine Analyse der Übersetzungsstrategien für Neologismen und Metaphern nach dem für diese Masterarbeit entwickelten Modell vorgenommen, wobei die bestehenden Modelle von Newmark, Schüler und Aixela als Grundlage dienten. Außerdem wurden die die Übersetzungen begleitenden Paratexte mit den später erschienenen Rezensionen sowie die unterschiedlichen Umfeldbedingungen beschrieben und miteinander verglichen. Im theoretischen Teil der Arbeit wurden drei große Themenbereiche erläutert: Lyrikübersetzungen, Neuübersetzungen und Paratexte, wobei letztere wichtig bei der Interpretation der Wahl der Übersetzungsstrategien sind. So konnten dank dem analysierten Material Unterschiede in der Wahl der Übersetzungsstrategien sowie in Stil, Rhythmus, Nähe zur:zum Autor:in und in der Rolle der:des Übersetzer:in festgestellt werden. All das kann dadurch erklärt kann, dass alle Übersetzungen einen „Handabdruck“ der:des Übersetzers:in tragen, die:der ein:e Träger:in einer bestimmten Zeit und Natur ist.At the beginning of the twentieth century, a new movement called Futurism gained importance in Russian art. Its aim was to destroy old traditions and create a new aesthetic. Works belonging to this trend are characterised by the usage of neologisms, metaphors, jargon, false punctuation, and sound plays. Mayakovsky wrote the work “Облако в штанах/A Cloud in Trousers” in 1915, which contains numerous allusions to the ideology and politics of that time in addition to the above-mentioned characteristics. Translations into German were made by Karl Dedecius and Alexander Nitzberg, among others, and are examined in this master's thesis. The translations differ as there is a gap of about 26 years between them, and the translators reflect trends of their time, culture, translation traditions, and ideology in their translations. In order to compare the translations, identify and explain the differences, first an analysis of the translation strategies of neologisms and metaphors was carried out using an adapted model, based on existing models of Newmark, Schüler and Aixela. In addition, the paratexts accompanying the translations were described and compared with the later published reviews, as well as with various framework conditions. In the theoretical part of the thesis three major topics were explored: poetry translations, retranslations, and paratexts, the latter being important in interpreting the choice of translation strategies. Thus, thanks to the analysed material, differences in the choice of translation strategies as well as in style, rhythm, proximity to the author, and in the role of the translator could be identified. All this can be explained by the fact that all translations contain a “handprint“ of the translator, who is a bearer of a certain time and nature.vorgelegt von Iuliia FörsterAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinMasterarbeit Universität Graz 2023Text überwiegend Deutsch, Textbeispiele teilweise Englisch, teilweise Russisch Teilweise in kyrillischer Schrif
"Not a man - but a cloud in trousers!" : two translations of Vladimir Mayakovsky's futuristic poem "A cloud in trousers" in comparison
No full textZu Beginn des zwanzigsten Jahrhunderts gewann in der Kunst in Russland eine neue Strömung namens Futurismus an Bedeutung. Dessen Ziel war, alte Traditionen zu zerstören und eine neue Ästhetik zu schaffen. Werke dieser Richtung sind gekennzeichnet durch Neologismen, Metaphern, Jargon, falsche Zeichensetzung und Lautspiele. Majakowski verfasste 1915 das Werk “Облако в штанах/Wolke in Hosen”, das neben den oben genannten Merkmalen zahlreiche Anspielungen auf die damalige Ideologie und Politik enthält. Übersetzungen ins Deutsche wurden unter anderem von Karl Dedecius und Alexander Nitzberg angefertigt und werden in dieser Masterarbeit untersucht. Da zwischen den Übersetzungen etwa 26 Jahre liegen und die Übersetzer in ihren Übertragungen Tendenzen ihrer Zeit, Kultur, Übersetzungstraditionen und Ideologie widerspiegeln, unterscheiden sich diese. Um die Übersetzungen zu vergleichen, die Unterschiede zu identifizieren und zu erklären, wurde zunächst eine Analyse der Übersetzungsstrategien für Neologismen und Metaphern nach dem für diese Masterarbeit entwickelten Modell vorgenommen, wobei die bestehenden Modelle von Newmark, Schüler und Aixela als Grundlage dienten. Außerdem wurden die die Übersetzungen begleitenden Paratexte mit den später erschienenen Rezensionen sowie die unterschiedlichen Umfeldbedingungen beschrieben und miteinander verglichen. Im theoretischen Teil der Arbeit wurden drei große Themenbereiche erläutert: Lyrikübersetzungen, Neuübersetzungen und Paratexte, wobei letztere wichtig bei der Interpretation der Wahl der Übersetzungsstrategien sind. So konnten dank dem analysierten Material Unterschiede in der Wahl der Übersetzungsstrategien sowie in Stil, Rhythmus, Nähe zur:zum Autor:in und in der Rolle der:des Übersetzer:in festgestellt werden. All das kann dadurch erklärt kann, dass alle Übersetzungen einen „Handabdruck“ der:des Übersetzers:in tragen, die:der ein:e Träger:in einer bestimmten Zeit und Natur ist.At the beginning of the twentieth century, a new movement called Futurism gained importance in Russian art. Its aim was to destroy old traditions and create a new aesthetic. Works belonging to this trend are characterised by the usage of neologisms, metaphors, jargon, false punctuation, and sound plays. Mayakovsky wrote the work “Облако в штанах/A Cloud in Trousers” in 1915, which contains numerous allusions to the ideology and politics of that time in addition to the above-mentioned characteristics. Translations into German were made by Karl Dedecius and Alexander Nitzberg, among others, and are examined in this master's thesis. The translations differ as there is a gap of about 26 years between them, and the translators reflect trends of their time, culture, translation traditions, and ideology in their translations. In order to compare the translations, identify and explain the differences, first an analysis of the translation strategies of neologisms and metaphors was carried out using an adapted model, based on existing models of Newmark, Schüler and Aixela. In addition, the paratexts accompanying the translations were described and compared with the later published reviews, as well as with various framework conditions. In the theoretical part of the thesis three major topics were explored: poetry translations, retranslations, and paratexts, the latter being important in interpreting the choice of translation strategies. Thus, thanks to the analysed material, differences in the choice of translation strategies as well as in style, rhythm, proximity to the author, and in the role of the translator could be identified. All this can be explained by the fact that all translations contain a “handprint“ of the translator, who is a bearer of a certain time and nature.vorgelegt von Iuliia FörsterAbweichender Titel laut Übersetzung des Verfassers/der VerfasserinMasterarbeit Universität Graz 2023Text überwiegend Deutsch, Textbeispiele teilweise Englisch, teilweise Russisch Teilweise in kyrillischer Schrif
- …
