T-cadherin upregulation correlates with cell-cycle progression and promotes proliferation of vascular cells

Objective: In vascular tissue, T-cadherin (T-cad) levels correlate with the progression of atherosclerosis, restenosis and tumour neovascularization. This study investigates whether T-cad influences proliferation of vascular cells. Methods and Results: Cultures of human umbilical vein endothelial cells (HUVEC) and rat and human aortic smooth muscle cells (rSMC, hSMC) were used. T-cad was overexpressed in HUVEC and hSMC using an adenoviral expression system. In cultures released from G1/G0 synchrony parallel immunoblot analysis of T-cad and cell cycle phase specific markers (p27Kip1, cyclin D1, E2F1, PCNA, cyclin B) showed increased T-cad protein levels subsequent to entry into early S-phase with sustained elevation through S-and M-phases. T-cad was increased in G2/M-phase (colchicine) synchronized cultures. In FACS-sorted cell populations, expression of T-cad in S-and G2/M-phase was higher than G1/G0-phase. Compared with empty-and LacZ-vector infected controls, HUVEC and hSMC overexpressing T-cad exhibited increased proliferation as assessed in enumeration and DNA synthesis assays. Additionally, following release from G1/G0 synchrony, HUVEC and hSMC overexpressing T-cad enter S-phase more rapidly. Flow cytometry after BrdU/propidium labelling confirmed increased cell cycle progression in T-cad overexpressing cells. Conclusion: In vascular cells, T-cad is dynamically regulated during the cell cycle and its expression functions in the promotion of proliferation. T-cad may facilitate progression of proliferative vascular disorders such as atherosclerosis, restenosis and tumour angiogenesi

Polarisation of T-cadherin to the leading edge of migrating vascular cells in vitro: a function in vascular cell motility?

Both histological and in vitro studies indicate a relationship between T-cadherin levels and acquisition of a modulated, migratory phenotype by vascular cells. This study further examines a role for T-cadherin in relation to cell migration and adhesion. Fluorescence microscopic examination of T-cadherin localisation in confluent cultures of human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells and the human carcinoma cell line ECV-304 revealed global distribution over the entire cell body, and with only slight enrichment at cell borders. This contrasts with restricted cell-cell junction localisation of classical cadherin (for example, VE-cadherin in HUVEC). In wounded cultures, T-cadherin polarised to the leading edge of cells migrating into the wound area, again contrasting with classical VE-cadherin, which was undetectable in this region. Confocal microscopy demonstrated that potential signalling functions of T-cadherin at the leading edge are unrelated to physical interactions with caveolin. Adherence of HUVEC onto a monolayer of T-cadherin-transfected L929 cells is significantly reduced compared with adhesion onto control (T-cadherin-negative) L929. Thus T-cadherin is not required for maintenance of intercellular adhesion, but may rather function as a signalling molecule involved in cell-cell recognition and sensing of the environment in processes where cell detachment occur

Nominal tone in isiNdebele

Peer reviewe

Click variation and reacquisition in two South African Ndebele varieties

Peer reviewe

Modernization reflected creatively: Central European capitals in the mirror of horror movies

The article deals with the creative interpretations of Central Europe by means of cinematography in the context of discussions about whether modernization means Westernization. The position is asserted that within Europe the ideal type of modernization is persistently associated with the West. The constructed in horror films images of Central European capitals are analyzed, with the example of such films as Short Night of Glass Dolls (La Corta notte delle bambole di vetro, 1971), The Spider Labyrinth (Il nido del ragno, 1988) and Hostel (2005). Prague (Chech Republic), Budapest (Hungary) and Bratislava (Slovakia), represented in these films, are marked with features of pseudo-modernity, which destroys the representatives of Western civilization or forces them to degenerate into monsters. Santrauka Straipsnyje nagrinėjamos kūrybinės Vidurio Europos interpretacijos, pasitelkiant kinematografijos priemones diskusijų, ar modernizacija reiškia vesternizaciją, kontekste. Tvirtinama, kad Europoje idealus modernizacijos tipas yra nuolat siejamas su Vakarais. Analizuojami siaubo filmuose konstruojami Vidurio Europos sostinių įvaizdžiai, pasitelkiant tokius filmų pavyzdžius, kaip Trumpa stiklo lėlių naktis (La Corta notte delle bambole di vetro, 1971), Voro labirintas (Il nido del ragno, 1988) ir Nakvynės namai (Hostel, 2005). Šiuose filmuose vaizduojamus Prahą (Čekija), Budapeštą (Vengrija) ir Bratislavą (Slovakija) ženklina pseudomodernybės, griaunančios Vakarų civilizacijos reprezentantus arba priverčiančios juos išsigimti į pabaisas, bruožai. Reikšminiai žodžiai: Vidurio Europos sostinės, kinas, kūrybinė refleksija, siaubo filmai, modernizacija, orientalizacija, stereotipai.

Social equity : a route to progressive taxation of individuals

Most countries of the world use a progressive scale to tax individuals. However, the level of tax progression decreased a lot thanks to a lower number of rates and their fall in the first two decades of the XXI-st century as liberal ideas had spread in the middle of the XX-th century. Individuals’ income can be taxed either at a progressive or a flat scale of rates. At the same time, there is no straightforward position, which scale to choose in the economic theory. Tying the personal income tax rate not to the absolute figures of income, but to such categories as a household’s subsistence level, a budget of a household in comfortable circumstances would be reasonable in conditions of a dynamic Russian market environment burdened with inflationary phenomena. This model of the personal income tax and the use of a progressive scale in a city with population numbers of up to 20 million people shows that the tax will rise by a mere US $4.7 compared with the current 13the income tax for medium paid workers will rise by US$ 57.8. At the same time the figure rose by US$ 372.9 for highly paid employees. The use of this model ensures a significant increase of budget income of a region and closure of the gap between wages of highly and low paid workers employed in the economy.peer-reviewe

T-cadherin attenuates insulin-dependent signalling, eNOS activation, and angiogenesis in vascular endothelial cells

Aims T-cadherin (T-cad) is a glycosylphosphatidylinositol-anchored cadherin family member. Experimental, clinical, and genomic studies suggest a role for T-cad in vascular disorders such as atherosclerosis and hypertension, which are associated with endothelial dysfunction and insulin resistance (InsRes). In endothelial cells (EC), T-cad and insulin activate similar signalling pathways [e.g. PI3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)] and processes (e.g. angiogenesis). We hypothesize that T-cad is a regulatory component of insulin signalling in EC and therefore a determinant of the development of endothelial InsRes. Methods and results We investigated T-cad-dependent effects on insulin sensitivity using human EC stably transduced with respect to T-cad overexpression or T-cad silencing. Responsiveness to insulin was examined at the level of effectors of the insulin signalling cascade, EC nitric oxide synthase (eNOS) activation, and angiogenic behaviour. Overexpression and ligation of T-cad on EC attenuates insulin-dependent activation of the PI3K/Akt/mTOR signalling axis, eNOS, EC migration, and angiogenesis. Conversely, T-cad silencing enhances these actions of insulin. Attenuation of EC responsiveness to insulin results from T-cad-mediated chronic activation of the Akt/mTOR-dependent negative feedback loop of the insulin cascade and enhanced degradation of the insulin receptor (IR) substrate. Co-immunoprecipitation experiments revealed an association between T-cad and IR. Filipin abrogated inhibitory effects of T-cad on insulin signalling, demonstrating localization of T-cad-insulin cross-talk to lipid raft plasma membrane domains. Hyperinsulinaemia up-regulates T-cad mRNA and protein levels in EC. Conclusion T-cad expression modulates signalling and functional responses of EC to insulin. We have identified a novel signalling mechanism regulating insulin function in the endothelium and attribute a role for T-cad up-regulation in the pathogenesis of endothelial InsRe

Macroeconomic indicators and their impact on the foreign debt burden : the case of BRICS countries

The main aim of this article is to analyse the macro indicators affecting the foreign debt burden of BRICS. It has been proven that it is required to design development scenarios in mid-term planning via forming a numerical estimate plane, taking into account expectations of economic variables’ behavior and other factors, which would stabilize the debt burden and other indicators at sensible levels. Using the elimination approach towards the impact of all factors on the amount on the end result except one, the article formulates and proves the hypothesis that market indicators in relation to GDP influence the size of the country’s debt.peer-reviewe

ТРАНСПОРТНЫЕ ПОТОКИ АМЕРИКАНСКОЙ АДМИНИСТРАЦИИ ПОМОЩИ (АРА) НА ПРИМЕРЕ ПЕТРОГРАДА (1921-1923 ГГ.)

Purpose. The American Relief Administration (ARA) provided the great humanitarian mission in Russia during the famine in 1921–1923. Wherein the problem of suppling food from the United States to starving people in the vast territories of Russia was successfully fulfiled. The ARA practice remains interesting for modern humanitarian organizations.Methodology. The history of the ARA in Russia is being investigated now, but its work in Petrograd has been almost unexplored. Our paper used the documents from the Russian central and regional archives such as the Central State Archives of St. Petersburg, the The State Archive of the Russian Federation (GARF, Moscow) and published studies.Results. This aspect of aid was studied on the example of Petrograd as the place of first unloading of foreign aid delivered by sea and rail transport, its reloading onto the railroad for transportation to the ARA aid regions. The scheme of food delivery from the ARA to the starving people of Petrograd is considered for the first time.Petrograd received 53,111.8 tons of cargo on 30 ships both directly from the United States and after transshipment in Hamburg. By rail, ARA cargoes arrived in Petrograd from Tallinn, by the way Petrograd recieved some ARA cargoes from Moscow. Deliveries from Petrograd was sent by rail through Moscow and Vologda to the Volga region, the destination stations were Rybinsk and Nizhny Novgorod.The ARA’s relief to the starving population of Petrograd itself was also significant, its total weight was 2947.335 tons, and the cost was $282,210.61.The main places associated with the transportation of goods and food points for the starving population of the city have been identified and shown on the map of Petrograd. Horse-drawn and road transport was used within the city.Practical implications. The materials can be useful for scientific development in the subject of relief of the ARA, in preparation of educational works on Russian history. The results may be of interest to local historians.Цель. Американская администрация помощи (АРА) оказала масштабную гуманитарную помощь России во время голода в 1921–1923 гг. При этом была успешна решена проблема доставки продовольствия из США к голодающим людям на огромных пространствах России. Практика АРА остается актуальной для современных гуманитарных организаций.Метод проведения работы. Деятельность АРА в Петрограде практически не исследована. В статье использованы документы из Центрального государственного архива Санкт-Петербурга, Государственного архива Российской Федерации (Москва) и опубликованные исследования.Результаты. Транспортный аспект помощи АРА изучен на примере Петрограда как места первой разгрузки иностранной помощи, доставленной морским и железнодорожным транспортом, ее перегрузки на железную дорогу для транспортировки к районам оказания помощи АРА. Впервые рассмотрена схема доставки продовольствия от АРА голодающим людям Петрограда.В Петроград поступило 53111,8 т грузов на 30 пароходах как прямо из США, так и после перегрузки в Гамбурге. По Северо-Западным железным дорогам грузы АРА поступали в Петроград из Таллина, некоторые грузы АРА в Петроград доставлялись по железной дороге через Москву. Помощь из Петрограда отправляли по железной дороге через Москву и Вологду в Волжский регион, станциями назначения были Рыбинск и Нижний Новгород.Помощь АРА голодающему населению самого Петрограда также была значительной, ее общий вес составил 2947,335 т, а стоимость – 282210,61$.Установлены и показаны на карте Петрограде основные места, связанные с транспортировкой грузов, и пункты питания для голодающего населения города. Для доставки помощи внутри города использовали гужевой и автомобильный транспорт.Область применения результатов. Материалы работы могут быть использованы для научных обобщений в теме помощи АРА, при подготовке учебных материалов по отечественной истории. Результаты могут заинтересовать краеведов

Language as means of mutual integration in multicultural university environment

Considering openness of modern Russian education to international students from all over the world the university has been undergoing a huge transformation into a multicultural and multilingual space that provokes new challenges for both administration and students. Addressing these challenges requires a common starting point for adaptation, socialization and further integration. And that common substance is neither more nor less than the language (both native and foreign) that proved to be the best facilitator. Any language (Russian, English and national languages of all students) has an endless capacity to create an international student-friendly environment within the campus and foster mutual integration of students from various cultural backgrounds. Authors come up with the model of deep integration based on building shared lingual environment, seen as a task for University administrators