Immortalization of T-cells is accompanied by gradual changes in CpG methylation resulting in a profile resembling a subset of T-cell leukemias

We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis

5th International Conference on Future-Oriented Technology Analysis (FTA) - Engage today to shape tomorrow

The practice-oriented paper reflects on the results of a strategic technology roadmapping project realised in the Green Triangle region of South Australia. The project integrated different methods in order to provide policy recommendations for the renewal of the forest industry in the region. Firstly, the project created a multi-criteria assessment framework for the evaluation of the present state of local companies. Secondly, the project made three value chain depictions: one that described the present value chain based on physical, monetary and information flows, and two so-called ‘potential’ value chain descriptions. Thirdly, the projectformulated technology roadmaps and assessed the potential for forest industry renewal. Fourthly, the project provided detailed policy recommendations based on the findings in the project.The integrated methodological approach of the project provided a robust basis for construction of policy recommendations. The company assessment grouped the local companies in four categories for comparative assessment purposes: forest owners, harvesters and hauliers, sawmills, and specialised suppliers. For the roadmap construction, the main information categories were drivers, markets, regulation, customer needs, solutions, and enabling technologies, and the specific dynamics connected to all these categories. This information was structured into three temporal spans: present, short term (ca. 3-5 years)and long term (ca. 5-10 years).There are, at least, three novel aspects of the project. Firstly, the integration of multi-criteria evaluation, value chain analysis and roadmapping creates new opportunities, but also new challenges. Secondly, the future-oriented view of the Australian forest industry is a new aspect. Thirdly, the project also had a strong regional policy perspective, especially connected with the discussions on path dependency and path creation in the regional development context.The project had both practical and managerial implications. Firstly, the company assessment identified the domains where each individual firm had weaknesses as well as where the group as a whole lagged global best practice. Secondly, the value chain analysis showed strengths and weaknesses of the present structure, but also delineated the necessary components to be developed in order to move towards higher value added production. Thirdly, the roadmaps showed the frontiers of research and business in advanced cellulose fibre-based industries, and made possible the positioning of the Green Triangle region.The project had two wider implications for policy. Firstly, the integrated methodological approach of the foresight exercise enabled the production of detailed policy recommendations that were embedded in the local industrial context. Secondly, the project open a window of opportunity to consider so-called platform policies, that is, policies that aim to develop the fragmented regional structure of the Green Triangle’s forest industry towards an integrated cluster-based platform, which would enable the region to benefit from agglomeration economics through a collaborative strategy.</p

Transit in Regional Economic Development: The Case of the Kaliningrad Exclave

The study analyses the role of the transit function in the development of a regional transport system drawing on the example of the Kaliningrad exclave region (Russia). The article studies the role and extent of the impact of changes in the volume and structure of transit operations on the value-added creation in the regional economy. The assessment of the transit function was conducted using analytical software for strategizing and situational forecasting of the socio-economic development of the Kaliningrad region, the analogue of which is the CGE-model. The article describes the results of the regional value-added modelling based on the integrated index of gross regional product (GRP) and the changing volume and structure of transit cargo. The article explores the transit specialisation options for the Kaliningrad region based on different scenarios of its social and economic development and the changes in external factors. The results can be applied to similar studies on assessing the transit potential of a particular territory and developing measures to support the transportation system development in other regions

Influence of the medium length on high-order harmonic generation

We study high-order harmonic generation using a 110 fs Ti:sapphire laser loosely focused into a variable-length gas cell filled with neon or argon at 5 mbar pressure. The harmonic intensity is recorded as a function of the medium length, varying between 2 and 21 mm. Several cases are examined, the 17th and the 29th harmonic in argon, and the 29th and 51st harmonic in neon, at the same intensity 4 x 10(14) W cm(-2). We find that the length which maximizes the harmonic yield varies from 10 mm to more than 20 mm. We discuss the different effects affecting the photon yield of the high-order harmonics

Разработка инвестиционного проекта «Пасека» в развитии агротуризма

Материалы V Междунар. науч. конф. студентов, аспирантов и молодых ученых, Гомель, 24 мая 2012

Longer Leukocyte Telomere Length Is Associated with Smaller Hippocampal Volume among Non-Demented APOE ε3/ε3 Subjects

Telomere length shortens with cellular division, and leukocyte telomere length is used as a marker for systemic telomere length. The hippocampus hosts adult neurogenesis and is an important structure for episodic memory, and carriers of the apolipoprotein E ε4 allele exhibit higher hippocampal atrophy rates and differing telomere dynamics compared with non-carriers. The authors investigated whether leukocyte telomere length was associated with hippocampal volume in 57 cognitively intact subjects (29 ε3/ε3 carriers; 28 ε4 carriers) aged 49–79 yr. Leukocyte telomere length correlated inversely with left (rs = −0.465; p = 0.011), right (rs = −0.414; p = 0.025), and total hippocampus volume (rs = −0.519; p = 0.004) among APOE ε3/ε3 carriers, but not among ε4 carriers. However, the ε4 carriers fit with the general correlation pattern exhibited by the ε3/ε3 carriers, as ε4 carriers on average had longer telomeres and smaller hippocampi compared with ε3/ε3 carriers. The relationship observed can be interpreted as long telomeres representing a history of relatively low cellular proliferation, reflected in smaller hippocampal volumes. The results support the potential of leukocyte telomere length being used as a biomarker for tapping functional and structural processes of the aging brain

The Individual Blood Cell Telomere Attrition Rate Is Telomere Length Dependent

Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at ∼10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = –0.164, P<0.001, n = 959). However, approximately one-third of the individuals exhibited a stable or increased TL over a decade. The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = –0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline. In accordance, the age-associated telomere attrition rate was more prominent in families with members displaying longer telomeres at a young age (r = –0.691, P<0.001). Abnormal blood TL has been reported at diagnosis of various malignancies, but in the present study there was no association between individual telomere attrition rate or prediagnostic TL and later tumor development. The collected data strongly suggest a TL maintenance mechanism acting in vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development

Cell Recovery in Bronchoalveolar Lavage Fluid in Smokers Is Dependent on Cumulative Smoking History

Background: Smoking is a risk factor for various lung diseases in which BAL may be used as a part of a clinical investigation. Interpretation of BAL fluid cellularity is however difficult due to high variability, in particular among smokers. In this study we aimed to evaluate the effect of smoking on BAL cellular components in asymptomatic smokers. The effects of smoking cessation, age and gender were also investigated in groups of smokers and exsmokers. Methods: We performed a retrospective review of BAL findings, to our knowledge the largest single center investigation, in our department from 1999 to 2009. One hundred thirty two current smokers (48 males and 84 females) and 44 ex-smokers (16 males and 28 females) were included. A group of 295 (132 males and 163 females) never-smokers served as reference. Result: The median [5–95 pctl] total number of cells and cell concentration in current smokers were 63.4 [28.6–132.1]610 6 and 382.1 [189.7–864.3]610 6 /L respectively and correlated positively to the cumulative smoking history. Macrophages were the predominant cell type (96.7 % [90.4–99.0]) followed by lymphocytes (2 % [0.8–7.7]) and neutrophils (0.6 % [0–2.9]). The concentration of all inflammatory cells was increased in smokers compared to never smokers and ex-smokers. BAL fluid recovery was negatively correlated with age (p,0.001). Smoking men had a lower BAL fluid recovery than smoking women. Conclusion: Smoking has a profound effect on BAL fluid cellularity, which is dependent on smoking history. Our results performed on a large group of current smokers and ex-smokers in a well standardized way, can contribute to bette

A sub-national economic complexity analysis of Australia’s states and territories

© 2017 Regional Studies AssociationA sub-national economic complexity analysis of Australia’s states and territories. Regional Studies. This paper applies economic complexity analysis to the Australian sub-national economy (nine regions with 506 exported goods and services). Using a 2009 Australian multi-regional input–output table for base data, we determine the number of export goods or services in which each state and territory has a revealed comparative advantage, and visualize the complexity of Australia’s interstate and international exports. We find that small differences in industrial capability and knowledge are crucial to relative complexity. The majority of states (especially Western Australia) export primarily resource-intensive goods, yet interstate trade has many complex products that are not currently internationally exported

Shortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis

BACKGROUND: Telomeres play a key role in the maintenance of chromosome integrity and stability, and telomere shortening is involved in initiation and progression of malignancies. A series of epidemiological studies have examined the association between shortened telomeres and risk of cancers, but the findings remain conflicting. METHODS: A dataset composed of 11,255 cases and 13,101 controls from 21 publications was included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and the relative telomere length. Heterogeneity among studies and their publication bias were further assessed by the χ(2)-based Q statistic test and Egger's test, respectively. RESULTS: The results showed that shorter telomeres were significantly associated with cancer risk (OR = 1.35, 95% CI = 1.14-1.60), compared with longer telomeres. In the stratified analysis by tumor type, the association remained significant in subgroups of bladder cancer (OR = 1.84, 95% CI = 1.38-2.44), lung cancer (OR = 2.39, 95% CI = 1.18-4.88), smoking-related cancers (OR = 2.25, 95% CI = 1.83-2.78), cancers in the digestive system (OR = 1.69, 95% CI = 1.53-1.87) and the urogenital system (OR = 1.73, 95% CI = 1.12-2.67). Furthermore, the results also indicated that the association between the relative telomere length and overall cancer risk was statistically significant in studies of Caucasian subjects, Asian subjects, retrospective designs, hospital-based controls and smaller sample sizes. Funnel plot and Egger's test suggested that there was no publication bias in the current meta-analysis (P = 0.532). CONCLUSIONS: The results of this meta-analysis suggest that the presence of shortened telomeres may be a marker for susceptibility to human cancer, but single larger, well-design prospective studies are warranted to confirm these findings