Expression of hypoxia-inducible factor 1α in thyroid carcinomas

Hypoxia-inducible factor 1α (HIF-1α) is upregulated by hypoxia and oncogenic signalling in many solid tumours. Its regulation and function in thyroid carcinomas are unknown. We evaluated the regulation of HIF-1α and target gene expression in primary thyroid carcinomas and thyroid carcinoma cell lines (BcPAP, WRO, FTC-133 and 8505c). HIF-1α was not detectable in normal tissue but was expressed in thyroid carcinomas. Dedifferentiated anaplastic tumours (ATCs) exhibited high levels of nuclear HIF-1α staining. The HIF-1 target glucose transporter 1 was expressed to a similar level in all tumour types, whereas carbonic anhydrase-9 was significantly elevated in ATCs. In vitro studies revealed a functionally active HIF-1α pathway in thyroid cells with transcriptional activation observed after graded hypoxia (1% O2, anoxia) or treatment with a hypoxia mimetic cobalt chloride. High basal and hypoxia-induced expression of HIF-1α in FTC-133 cells that harbour a phosphatase and tensin homologue (PTEN) mutation was reduced by introduction of wild-type PTEN. Similarly, pharmacological inhibition of the phosphoinositide 3-kinase (PI3K) pathway using LY294002 inhibited HIF-1α and HIF-1α targets in all cell lines, including those with B-RAF mutations (BcPAP and 8505c). In contrast, the effects of inhibition of the RAF/MEK/extracellular signal-regulated kinase pathway were restricted by environmental condition and B-RAF mutation status. HIF-1 is functionally expressed in thyroid carcinomas and is regulated not only by hypoxia but also via growth factor signalling pathways and, in particular, the PI3K pathway. Given the strong association of HIF-1α with an aggressive disease phenotype and therapeutic resistance, this pathway may be an attractive target for improved therapy in thyroid carcinomas

Aerial Measurement of Radioxenon Concentration off the West Coast of Vancouver Island following the Fukushima Reactor Accident

In response to the Fukushima nuclear reactor accident, on March 20th, 2011, Natural Resources Canada conducted aerial radiation surveys over water just off of the west coast of Vancouver Island. Dose-rate levels were found to be consistent with background radiation, however a clear signal due to Xe-133 was observed. Methods to extract Xe-133 count rates from the measured spectra, and to determine the corresponding Xe-133 volumetric concentration, were developed. The measurements indicate that Xe-133 concentrations on average lie in the range of 30 to 70 Bq/m3.Comment: 14 pages, 5 figures, accepted for publication in Journal of Environmental Radioactivit

The ecology of infrastructure decommissioning in the North Sea: what we need to know and how to achieve it

As decommissioning of oil and gas (O&G) installations intensifies in the North Sea, and worldwide, debate rages regarding the fate of these novel habitats and their associated biota—a debate that has important implications for future decommissioning of offshore wind farms (OWFs). Calls to relax complete removal requirements in some circumstances and allow part of an O&G installation to be left in the marine environment are increasing. Yet knowledge regarding the biological communities that develop on these structures and their ecological role in the North Sea is currently insufficient to inform such decommissioning decisions. To focus debate regarding decommissioning policy and guide ecological research, we review environmental policy objectives in the region, summarize existing knowledge regarding ecological aspects of decommissioning for both O&G and OWF installations, and identify approaches to address knowledge gaps through science–industry collaboration. We find that in some cases complete removal will conflict with other policies regarding protection and restoration of reefs, as well as the conservation of species within the region. Key ecological considerations that are rarely considered during decommissioning decisions are: (i) provision of reef habitat, (ii) productivity of offshore ecosystems, (iii) enhancement of biodiversity, (iv) protection of the seabed from trawling, and (v) enhancement of connectivity. Knowledge gaps within these areas will best be addressed using industry infrastructure and vessels for scientific investigations, re-analysis of historical data held by industry, scientific training of industry personnel, joint research funding opportunities, and trial decommissioning projects

Spatial and temporal occurrence of bats in the southern North Sea area

Since a few years it is known that bats migrate over sea on a regular basis. As numerous land-based studies have shown that wind turbines can cause high fatality rates amongst bats Rijkswaterstaat started a bat monitoring programme for 2015 and 2016 in order to reduce uncertainties about possible impacts. At the same time Eneco commissioned a bat monitoring programme for 2015 and 2016 as part of the Monitoring and Evaluation Programme (MEP) for the offshore windfarm Luchterduinen. In 2016 Gemini conducted a bat monitoring campaign in windfarm Buitengaats and Wageningen Marine Research executed a bat monitoring programme at Wintershall platform P6-A and offshore research station FINO3 in the same year. The joint monitoring effort included 12 different offshore locations and 5 locations at the coast. The specific aims of these monitoring programmes are an assessment of : 1. The species composition at sea and at the coast. 2. The spatiotemporal pattern of occurrence, including the flight height. 3. The relation between environmental conditions and the occurrence of bats. 4. The function of the Dutch Territorial Sea for bats. The monitoring results at the coast showed that Nathusius’ pipistrelle is very common during both spring and autumn migration, but is also regular throughout the summer. It is also the most frequently recorded species at sea, albeit much less frequently recorded in comparison to the coast. At sea it was recorded from late August until late October (and one observation in November), and –to a lesser extent- from early April until the end of June. There were no records in July until mid-August. The observed pattern of occurrence matches previous offshore monitoring studies in the German and Dutch North Sea

Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas.

Anaplastic (ATC) and certain follicular thyroid-carcinomas (FTCs) are radioresistant. The Phosphatidylinositide 3-kinase (PI3K) pathway is commonly hyperactivated in thyroid-carcinomas. PI3K can modify the PI3K-related kinases (PIKKs) in response to radiation: How PIKKs interact with PI3K and contribute to radioresistance in thyroid-carcinomas is unknown. Further uncertainties exist in how these interactions function under the radioresistant hypoxic microenvironment. Under normoxia/anoxia, ATC (8505c) and FTC (FTC-133) cells were irradiated, with PI3K-inhibition (via GDC-0941 and PTEN-reconstitution into PTEN-null FTC-133s) and effects on PIKK-activation, DNA-damage, clonogenic-survival and cell cycle, assessed. FTC-xenografts were treated with 5 × 2 Gy, ± 50 mg/kg GDC-0941 (twice-daily; orally) for 14 days and PIKK-activation and tumour-growth assessed. PIKK-expression was additionally assessed in 12 human papillary thyroid-carcinomas, 13 FTCs and 12 ATCs. GDC-0941 inhibited radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inhibition of ATM and DNA-PKcs was PI3K-dependent, since activation was reduced in PTEN-reconstituted FTC-133s. Inhibition of PIKK-activation was greater under anoxia: Consequently, whilst DNA-damage was increased and prolonged under both normoxia and anoxia, PI3K-inhibition only reduced clonogenic-survival under anoxia. GDC-0941 abrogated radiation-induced cell cycle arrest, an effect most likely linked to the marked inhibition of ATR-activation. Importantly, GDC-0941 inhibited radiation-induced PIKK-activation in FTC-xenografts leading to a significant increase in time taken for tumours to triple in size: 26.5 ± 5 days (radiation-alone) versus 31.5 ± 5 days (dual-treatment). PIKKs were highly expressed across human thyroid-carcinoma classifications, with ATM scoring consistently lower. Interestingly, some loss of ATM and DNA-PKcs was observed. These data provide new insight into the mechanisms of hypoxia-associated radioresistance in thyroid-carcinoma

Correlated /\c-/\cbar production in e+e- annihilations at sqrt{s}~10.5 GeV

Using 13.6/fb of continuum two-jet e+e- -> ccbar events collected with the CLEO detector, we have searched for baryon number correlations at the primary quark level. We have measured the likelihood for a /\c+ charmed baryon to be produced in the hemisphere opposite a /\c- relative to the likelihood for a /\c+ charmed baryon to be produced opposite an anticharmed meson Dbar; in all cases, the reconstructed hadrons must have momentum greater than 2.3 GeV/c. We find that, given a /\c- (reconstructed in five different decay modes), a /\c+ is observed in the opposite hemisphere (0.72+/-0.11)% of the time (not corrected for efficiency). By contrast, given a Dbar in one hemisphere, a /\c+ is observed in the opposite hemisphere only (0.21+/-0.02)% of the time. Normalized to the total number of either /\c- or Dbar ``tags'', it is therefore 3.52+/-0.45+/-0.42 times more likely to find a /\c+ opposite a /\c- than a Dbar meson. This enhancement is not observed in the JETSET 7.3 e+e- -> ccbar Monte Carlo simulation.Comment: 19 pages, Latex, one figure separat