One-step immortalization of primary human airway epithelial cells capable of oncogenic transformation

BACKGROUND: The ability to transform normal human cells into cancer cells with the introduction of defined genetic alterations is a valuable method for understanding the mechanisms of oncogenesis. Easy establishment of immortalized but non-transformed human cells from various tissues would facilitate these genetic analyses. RESULTS: We report here a simple, one-step immortalization method that involves retroviral vector mediated co-expression of the human telomerase protein and a shRNA targeting the CDKN2A gene locus. We demonstrate that this method could successfully immortalize human small airway epithelial cells while maintaining their chromosomal stability. We further showed that these cells retain p53 activity and can be transformed by the KRAS oncogene. CONCLUSIONS: Our method simplifies the immortalization process and is broadly applicable for establishing immortalized epithelial cell lines from primary human tissues for cancer research

The effect of medications which cause inflammation of the gastro-oesophageal tract on cancer risk : a nested case–control study of routine Scottish data

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Subtractive CRISPR screen identifies the ATG16L1/vacuolar ATPase axis as required for non-canonical LC3 lipidation

Although commonly associated with autophagosomes, LC3 can also be recruited to membranes by covalent lipidation in a variety of non-canonical contexts. These include responses to ionophores such as the M2 proton channel of influenza A virus. We report a subtractive CRISPR screen that identifies factors required for non-canonical LC3 lipidation. As well as the enzyme complexes directly responsible for LC3 lipidation in all contexts, we show the RALGAP complex is important for M2-induced, but not ionophore drug-induced, LC3 lipidation. In contrast, ATG4D is responsible for LC3 recycling in M2-induced and basal LC3 lipidation. Identification of a vacuolar ATPase subunit in the screen suggests a common mechanism for non-canonical LC3 recruitment. Influenza-induced and ionophore drug-induced LC3 lipidation lead to association of the vacuolar ATPase and ATG16L1 and can be antagonized by Salmonella SopF. LC3 recruitment to erroneously neutral compartments may therefore represent a response to damage caused by diverse invasive pathogens

South Korea's automotive labour regime, Hyundai Motors’ global production network and trade‐based integration with the European Union

This article explores the interrelationship between global production networks(GPNs) and free trade agreements (FTAs) in the South Korean auto industry and its employment relations. It focuses on the production network of the Hyundai Motor Group (HMG) — the third biggest automobile manufacturer in the world — and the FTA between the EU and South Korea. This was the first of the EU’s ‘new generation’ FTAs, which among other things contained provisions designed to protect and promote labour standards. The article’s argument is twofold. First, that HMG’s production network and Korea’s political economy (of which HMG is a crucial part) limited the possibilities for the FTA’s labour provisions to take effect. Second, that the commercial provisions in this same FTA simultaneously eroded HMG’s domestic market and corporate profitability, leading to adverse consequences for auto workers in the more insecure and low-paid jobs. In making this argument, the article advances a multiscalar conceptualization of the labour regime as an analytical intermediary between GPNs and FTAs. It also provides one of the first empirical studies of the EU–South Korea FTA in terms of employment relations, drawing on 105 interviews with trade unions, employer associations, automobile companies and state officials across both parties

Climatic and Resource Determinants of Forest Elephant Movements

As a keystone megafaunal species, African forest elephants (Loxodonta cyclotis) influence the structure and composition of tropical forests. Determining the links between food resources, environmental conditions and elephant movement behavior is crucial to understanding their habitat requirements and their effects on the ecosystem, particularly in the face of poaching and global change. We investigate whether fruit abundance or climate most strongly influence forest elephant movement behavior at the landscape scale in Gabon. Trained teams of “elephant trackers” performed daily fruit availability and dietary composition surveys over a year within two relatively pristine and intact protected areas. With data from 100 in-depth field follows of 28 satellite-collared elephants and remotely sensed environmental layers, we use linear mixed-effects models to assess the effects of sites, seasons, focal elephant identification, elephant diet, and fruit availability on elephant movement behavior at monthly and 3-day time scales. At the month-level, rainfall, and to a lesser extent fruit availability, most strongly predicted the proportion of time elephants spent in long, directionally persistent movements. Thus, even elephants in moist tropical rainforests show seasonal behavioral phenotypes linked to rainfall. At the follow-level (2–4 day intervals), relative support for both rainfall and fruit availability decreased markedly, suggesting that at finer spatial scales forest elephants make foraging decisions largely based on other factors not directly assessed here. Focal elephant identity explained the majority of the variance in the data, and there was strong support for interindividual variation in behavioral responses to rainfall. Taken together, this highlights the importance of approaches which follow individuals through space and time. The links between climate, resource availability and movement behavior provide important insights into the behavioral ecology of forest elephants that can contribute to understanding their role as seed dispersers, improving management of populations, and informing development of solutions to human-elephant conflict

Tele-Operated Lunar Rover Navigation Using Lidar

Near real-time tele-operated driving on the lunar surface remains constrained by bandwidth and signal latency despite the Moon s relative proximity. As part of our work within NASA s Human-Robotic Systems Project (HRS), we have developed a stand-alone modular LIDAR based safeguarded tele-operation system of hardware, middleware, navigation software and user interface. The system has been installed and tested on two distinct NASA rovers-JSC s Centaur2 lunar rover prototype and ARC s KRex research rover- and tested over several kilometers of tele-operated driving at average sustained speeds of 0.15 - 0.25 m/s around rocks, slopes and simulated lunar craters using a deliberately constrained telemetry link. The navigation system builds onboard terrain and hazard maps, returning highest priority sections to the off-board operator as permitted by bandwidth availability. It also analyzes hazard maps onboard and can stop the vehicle prior to contacting hazards. It is robust to severe pose errors and uses a novel scan alignment algorithm to compensate for attitude and elevation errors

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer : An analysis of two independent population-based databases

Acknowledgements We acknowledge collaboration with the Research Applications and Data Management Team lead by Ms Katie Wilde, University of Aberdeen in conducting our study. This research has been conducted using the UK Bio-bank Resource under application number 34374.Peer reviewedPostprin

The Angular Correlation Function of Galaxies from Early SDSS Data

The Sloan Digital Sky Survey is one of the first multicolor photometric and spectroscopic surveys designed to measure the statistical properties of galaxies within the local Universe. In this Letter we present some of the initial results on the angular 2-point correlation function measured from the early SDSS galaxy data. The form of the correlation function, over the magnitude interval 18<r*<22, is shown to be consistent with results from existing wide-field, photographic-based surveys and narrower CCD galaxy surveys. On scales between 1 arcminute and 1 degree the correlation function is well described by a power-law with an exponent of ~ -0.7. The amplitude of the correlation function, within this angular interval, decreases with fainter magnitudes in good agreement with analyses from existing galaxy surveys. There is a characteristic break in the correlation function on scales of approximately 1-2 degrees. On small scales, < 1', the SDSS correlation function does not appear to be consistent with the power-law form fitted to the 1'< theta <0.5 deg data. With a data set that is less than 2% of the full SDSS survey area, we have obtained high precision measurements of the power-law angular correlation function on angular scales 1' < theta < 1 deg, which are robust to systematic uncertainties. Because of the limited area and the highly correlated nature of the error covariance matrix, these initial results do not yet provide a definitive characterization of departures from the power-law form at smaller and larger angles. In the near future, however, the area of the SDSS imaging survey will be sufficient to allow detailed analysis of the small and large scale regimes, measurements of higher-order correlations, and studies of angular clustering as a function of redshift and galaxy type