Humán papillomavírus onkoproteinek hatása celluláris gének expressziójára = Effects of human papillomavirus oncoproteins on the expression of cellular genes

A genitális humán papillomavírusok (HPV) a méhnyakrák (cervix carcinoma) kialakulásának legfontosabb kockázati tényezői. A survivin fehérje az apoptózis gátlása mellett a sejtosztódás szabályozásában is részt vesz. Tranziens transzfekciós kísérleteinkben, a HPV 16 E6 szignifikánsan aktiválta a survivin gén promóterét. Úgy találtuk, hogy az E6 survivin promoterre gyakorolt hatását nagymértékben a p53 tumorszuppresszor fehérje közvetíti. Kimutattuk, hogy a HPV 16 E6 és E7 is képes az endogén survivin mRNS szintjét növelni humán embrionális fibroblaszt sejtekben. Különböző populációk összehasonlításával azt találtuk, hogy a survivin promóter (-31 G/C) polimorfizmusa nem befolyásolja jelentősen a méhnyakrák kialakulását. Az E-cadherin tumorszuppresszor gén promóter (-160 C/A) polimorfizmusának szerepét méhnyakrákos és laryngeális daganatok kialakulásában vizsgáltuk. Eredményeink szerint, az említett polimorfizmusnak sem a cervix carcinoma, sem a laryngealis carcinoma kialakulásában nincs lényeges szerepe. Primer humán keratinocytákban, a HPV 16 E6 csökkentette az involukrin és a transzglutamináz 1 expresszióját is. Tranziens transzfekciós kísérletekben, a HPV 16 E6 csökkentette az involukrin és a transzglutamináz 1 promóterek transzkripciós aktivitását. Eredményeink szerint tehát a HPV 16 E6 onkogén mindkét, a celluláris differenciálódás folyamatában alapvető fontosságú gén promóterét képes gátolni, ily módon befolyásolva a gazdasejt differenciálódási folyamatait. | Genital human papillomaviruses (HPV) are the main risk factors in the development of the cancer of the uterine cervix. Survivin protein has a major role both in the inhibition of apoptosis and in the regulation of the cell cycle. In our transient transfection experiments, HPV 16 E6 significantly activated the survivin gene promoter. We found that the effect of E6 on the survivin promoter is largely mediated by the p53 tumor suppressor protein. Both E6 and E7 were able to increase the level of endogenous survivin mRNA in human embryonic fibroblast cells. By analysing different patient populations, we found that the survivin promoter (-31 G/C) polymorphism has no significant role in the development of cervical cancer. We studied the E-cadherin tumor suppressor gene promoter (-160 C/A) polymorphism in cervical and laryngeal cancer samples. Our results suggest that this polymorphism has no major role in the development of cervical cancer or laryngeal cancer. In primary human keratinocytes, HPV 16 E6 decreased the expression of involucrin and transglutaminase 1. In transient transfection experiments, HPV 16 E6 decreased the transcriptional activity of involucrin and transglutaminase 1 promoters. Our results suggest that HPV 16 E6 is modulating the differentiation processes of its host cell by inhibiting the promoters of genes with essential roles in cellular differentiation

The Possible Causes of and Means of Avoiding External Financial Vulnerability – Hungary versus Singapore

Difficulties in external debt-financing in the period since the financial crisis of 2008 have shed light on the financial vulnerability of the Hungarian economy. In this study our aim is to reveal the causes of external financial vulnerability, which can be incorporated into economic policy choices. We analyse the case of Singapore to demonstrate an example of those policies which can help avoid unnecessary financial vulnerability. External financial vulnerability is related to the quality of foreign accounts liberalisation, deregulation and privatisation, but in a wider context the direct and indirect public financing means which determine the global competitiveness of a national economy (educational policy, cluster management etc.) can be linked to it as well. Based on the analysis of Singapore’s related policies, the theoretical advantages of economic openness (such as export expansion, employment, management expertise, know-how and technology acquisition) can be achieved at a much lower lever of external financial vulnerability than what was experienced in Hungary. Singapore and Hungary are excellent for such a comparison as small, economically open countries which are among the most globalised ones based on globalisation indices

Introduction of a Cost Effective Method for Analysing Engine Intake Ice Removal Device for Small Aircraft

As the need for personal air transport increases significantly, new aircraft and/or its components are required to be designed and developed together with expectations for guarantying the high level flight safety. Since smaller aircraft manufacturers don’t have the infrastructural and experimental resources for complex investigations, analysis of engine components with especial care for the behaviour of particle separation components in the inlet air duct for example, smarter, more efficient solutions have to be developed. CFD software gives an opportunity to simulate the trajectories of different type of particles, such as hailstones, dust, or even liquid water droplets. Hence, in this study an upper-wing type, two engines thrusted, small turboprop aircraft’s integrated engine air intake device has been analysed, to prove the effectivity of the aircraft performance in the considered raining and icing conditions. The flow field has been discretized with a detailed, hybrid mesh using hexa elements at the simpler parts, and tetra elements, where the geometry is more complex. Inflation layers have been inserted on the wall-type surfaces, with especial care to the problematic parts, where the y+ number is predictably higher. The inlet boundary conditions of the model have been extracted from a larger, complex pre-simulation, performed in a previous study. Standard Reynolds Averaged Navier-Stokes equations have been considered with Shear Stress Transport turbulence model. Solid (ice) and liquid particles have been defined, and their trajectories are investigated by using fully coupled model. The interaction of the wall-fluid particle has been taken into consideration

2010 utáni magyar gazdaságpolitikai modell

A tanulmány célja bemutatni a 2010 utáni magyar gazdaságpolitika stratégiai változásait. A magyar gazdaságot jellemző magas külső eladósodás és belső egyensúlytalanság tette szükségszerűvé a 2010 utáni stratégiai irányváltást. A stratégiai változtatásoknak köszönhetően a következő eredményeket tudja felmutatni a magyar gazdaságpolitika. A belső egyensúlytalanság csökkentése: a foglalkoztatási ráta 9 százalékponttal nőtt; a kkv-k teljes adóterhelése 9,1 százalékponttal csökkent; a bérhányad növekedett a szektorális adók terhére végrehajtott béradókedvezmények következtében; részben az adószerkezeti átalakításnak köszönhetően a nettó bérek és a nettó minimálbér 10 és 14 százalékkal növekedtek 2010–2015 között. A külső sebezhetőség csökkenése: a nettó külső tartozásállomány 40 százalékkal csökkent GDP arányosan 2010–2015 között; az államadósság külföldi fizetőeszközben denominált aránya 49 százalékról 30 százalékra mérséklődött; az állam részesedése a működő vagyonból a GDP mintegy 5 százalékával növekedett 2010 és 2014 között, többnyire közművek és a kritikus infrastruktúrához tartozó oligopol és monopol piaci vállalkozások megvásárlásával. A tanulmány diagnózisát követve a 2010 utáni gazdaságpolitikai intézkedések koherens stratégiává állnak össze. A tanulmány amellett érvel, hogy a magyar gazdaság jelenlegi kihívásai a múlt hibás stratégiai döntéseiben gyökereznek, valamint hogy a 2010 utáni gazdaságpolitika ezen kihívások kezelésére irányul

Humán papillomavírus fertőzések = Human papillomavirus infections

A survivin kifejeződése fontos lehet a méhnyakrák kialakulásában. A survivin és a HPV (human papillomavírus) közötti kapcsolatot vizsgálva megállapították, hogy a survivin promóter polimorfizmus nem jelent kockázati tényezőt a cervix carcinoma kialakulásában. Megállapították, hogy a HPV 16 E7 fehérjéje gátolja a TGF-?2 promóter transzkripciós aktivitását az E2F1 Rb/E2F komplexből történő felszabadítása révén. A gége laphámsejtes karcinomás betegekben, ha az 1. genocsoportú TTV (human circovírus)-fertőzés HPV fertőzéssel társul, szignifikánsan romlik a betegek tumorprogresszió-mentes túlélése. Az E cadherin ? 160 C/A polimorfizmusának megléte és a HPV jelenléte között nincs összefüggés a cervix carcinomás és a laryngeális carcinoma planocellulare daganatokból származó mintákban. A laryngeális papilloma planocellulare mintákban viszont szignifikánsan nagyobb volt a polimorf A allél frekvenciája, mint a kontroll populációban. Cidofovir terápiára a rekurrens respiratory papillomatosis (RRP) az első kéthetes kezelés alatt jelentősen javult, s a mindig kimutatható HPV-11 genom kópiaszám jelentősen lecsökkent. | Expression of survivin may play an important role in development of cervical carcinoma. Studying the interaction between survivin and HPV (human papillomavirus) it was suggested that promoter polymorphism of survivin gene is not a risk factor in cervical carcinoma. It was suggested that E7 protein of HPV 16 inhibits the transcriptional activity of TGF-?2 promoter by releasing E2F1 from Rb/E2F complex. If TTV (human circovirus) genogroup 1 infection is accompanied by HPV infection in patients with squamous cell carcinoma of the larynx progression free survival of patients are significantly decreased. Correlation between ? 160 C/A polymorphism of E cadherin and presence of HPV in samples originated from cervical cancer and carcinoma planocellulare of larynx was not detected. In case of laryngeal papilloma planocellulare the frequency of polymorph A allel was found significantly higher than in the control population. Owing to the cidofovir therapy recurrent respiratory papillomatosis (RRP) shows remarkable improvement, and the copy number of HPV 11 detected every time decreased considerably

Effects of human papillomavirus (HPV) type 16 oncoproteins on the expression of involucrin in human keratinocytes

<p>Abstract</p> <p>Background</p> <p>The human papillomavirus (HPV) life cycle is closely linked to keratinocyte differentiation. Oncogenic HPV infection has been shown to hamper the normal differentiation of keratinocytes; however, the underlying mechanisms responsible for this phenomenon are yet to be clarified. Here, we aimed to study the effects of HPV16 E6 and E7 oncogenes on the expression of involucrin (IVL), an established marker of keratinocyte differentiation, in human foreskin keratinocyte (HFK) cells.</p> <p>Results</p> <p>The differentiation of HFK cells by serum and high calcium significantly increased both the mRNA and the protein levels of IVL. The E6 and E7 oncoproteins of HPV16 together caused strong down-regulation of IVL mRNA and protein both in proliferating and in differentiating HFK cells. To study the effects of HPV oncogenes on the <it>IVL </it>promoter, we made transient transfection assays and luciferase tests and found that HPV 16 E6 but not E7 repressed <it>IVL </it>promoter activity in proliferating HFK cells. The inhibitory effect of HPV 16 E6 on the human <it>IVL </it>promoter could be localised to the proximal regulatory region (PRR) of the gene.</p> <p>Conclusions</p> <p>These results suggest that the down-regulation of <it>IVL </it>promoter activity by HPV 16 E6 significantly contribute to the inhibition of endogenous <it>IVL </it>expression by the HPV 16 oncoproteins. In contrast, the down-regulation of endogenous IVL expression by HPV16 E7 is probably not caused by a direct and specific effect of E7 on the <it>IVL </it>promoter.</p

Development of microsatellite markers for Rhodiola rosea

Rhodiola rosea L. is an important adaptogen medicinal plant. In this study two new microsatellite markers were developed. The assessment of the genetic diversity of R. rosea has recently started with molecular markers, but only a few species-specific microsatellite markers have been published so far. However the small number of markers allows only a limited insight into the genetic variability of the species therefore the aim of our work was to develop new microsatellite markers for R. rosea with a microsatellite enrichment library technique. Genomic DNA was cleaved with an endonuclease enzyme followed by adaptor ligation and PCR amplification. DNA fragments that contained microsatellites were first isolated using a biotin-streptavidin linkage based magnetic selection and then cloned into plasmids. Out of forty-three sequenced clones three contained&nbsp; microsatellites, in these cases primers were designed for the amplification of the microsatellite repeats. The newly developed primer pairs were tested on individuals from distant R. rosea populations and the variability of the amplified fragments was estimated by fragment-length analysis. The locus RhpB14a was found to be monomorphic while RhpB14b and RhpB13 were polymorphic. As a result of the present study, two novel variable microsatellite loci were identified in the genome of R. rosea