P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the <it>P53 </it>tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of <it>P53 </it>in melanoma is uncommon; however, its function often appears abnormal.</p> <p>Methods</p> <p>In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts.</p> <p>Results</p> <p>The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant <it>P53 </it>compared to those with wild-type <it>P53</it>, suggesting that altered expression in melanoma was not related to <it>P53 </it>status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation.</p> <p>Conclusions</p> <p>These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.</p

Comparison of the impacts of elevated CO₂ soil gas concentrations on selected European terrestrial environments

Selected European studies have illustrated the impacts of elevated CO₂ concentrations in shallow soils on pasture. For the first time, general unified conclusions can be made, providing CO₂ thresholds where effects on plants and soil microbiology are observed and making recommendations on how this information can be used when planning projects for CO₂ storage. The sites include those where CO₂ is being naturally released to the atmosphere from deep geological formations; and a non-adapted site, with no previous history of CO₂ seepage, where CO₂ has been injected into the unsaturated soil horizon. Whilst soil gas concentrations will be influenced by flux rates and other factors, the results suggest that a concentration of between 10% and 15% CO₂ soil gas at 20 cm depth, which is within the root zone, is an important threshold level for observing changes in plant coverage. Site-specific plant ‘indicators’ are also observed for CO₂ concentrations at ≥35%. Microbiological changes are seen where CO₂ soil gas concentrations are between 15% and 40%. As part of site characterisation, an evaluation of the risks of leakage and their potential environmental impacts should be undertaken

A new study programme in spatial management at the Institute of Geography and Spatial Management, Jagiellonian University

Ważnym wyzwaniem stojącym przed instytucjami odpowiedzialnymi za wdrażanie infrastruktur informacji przestrzennej (IIP) jest zwiększanie stopnia wykorzystania zasobów IIP w różnych dziedzinach, np. w planowaniu przestrzennym, ochronie środowiska, nauce. W tym celu niezbędne jest nowe podejście do kształcenia na poziomie wyższym, w którym na pierwszy plan wysuwają się wiedza i umiejętności właściwego stosowania danych przestrzennych w różnego typu zagadnieniach środowiskowych i społecznych, wymagające łączenia treści tradycyjnie przypisywanych do odrębnych dyscyplin akademickich i przekraczania barier dziedzinowych. Próbą takiego nowego podejścia jest opracowany w Instytucie Geografii i Gospodarki Przestrzennej Uniwersytetu Jagiellońskiego nowy kierunek studiów magisterskich: "e–gospodarka przestrzenna", który został zainaugurowany w październiku 2015 r. Celem kształcenia na tym kierunku jest zintegrowane rozwijanie wiedzy i umiejętności studentów z zakresu gospodarki przestrzennej i geoinformatyki. Nacisk położony został na zajęcia specjalistyczne, prezentujące metody wykorzystywania nowoczesnych narzędzi geoinformatycznych i zasobów danych przestrzennych w praktycznych działaniach na rzecz społeczeństwa i środowiska przyrodniczego. Zakłada się, że tego typu wiedza i umiejętności zwiększą szanse absolwentów tego kierunku na rynku pracy, który obejmować będzie instytucje, przedsiębiorstwa i jednostki administracji państwowej zajmujące się gospodarką przestrzenną, planowaniem przestrzennym, rozwojem lokalnym i regionalnym, przedsięwzięciami rewitalizacyjnymi, ochroną przyrody oraz analizą przyrodniczych i społeczno-ekonomicznych danych przestrzennych. W artykule omówiona zostanie szczegółowo koncepcja studiów, sposób budowania programu oraz napotkane w czasie prac problemy.For all institutions responsible for the implementation of spatial information infrastructures (SII) it is important to maximize the use of SII resources in various domains, like spatial planning, nature conservation, science. One of necessary actions to meet this goal is to develop new approaches in higher education that integrate traditionally distinct disciplines, and in which knowledge and skills in proper use of spatial information in environmental and socio-economic problems are at the core. A new study programme “e-spatial management”, initiated in October 2015 at the Institute of Geography and Spatial Management, Jagiellonian University in Kraków, Poland, is such an attempt. An overall learning goal for this study programme is the integration of knowledge and skills in geographic information science and technology (GIS&T), and spatial management. We have emphasized classes that present how GI tools and new spatial data resources may be used in practical actions for society and environment. We assume that knowledge and skills of this type may increase chances of the alumni for the employment in institutions, companies and governmental entities that work in the field of spatial management, spatial planning, local and regional development, revitalisation, nature conservation and analysis of environmental and socio-economic spatial data. The paper presents a detailed overview of the study programme, its development and problems encountered in the conceptual and preparatory phases