Protein kinase WNK2 as a tumour suppressor gene in malignant gliomas

Malignant glioblastomas are the most common and lethal adult brain tumours, with patients dying within two years from diagnosis. Little is known about the molecular mechanisms underlying the formation and/or development of these tumours, which present a very invasive phenotype within the brain and are genetically heterogeneous and highly resistant to both chemo- and radio-therapies. Recently, the promoter region of the protein kinase WNK2 gene was found to be hypermethylated in 29 of 31 infiltrative gliomas and about 80% of meningiomas. We have previously described that the experimental depletion of WNK2 expression decreases RhoA activity whilst leading to increased Rac1 activity. Because RhoA/Rac1 activities are important for cell migration and glioblastomas are very invasive tumours, we tested the effects of WNK2 on wound-healing assays in glioma cell lines SW1088 and A172. SW1088 cells express endogenous WNK2 and we observed that wound closure was increased upon experimental depletion of endogenous WNK2. In contrast, A172 cells display complete promoter region methylation and WNK2 re-expression was found to decrease migration. Consistently, we observed an increase in Rac1 activity in SW1088 cells upon WNK2 down-regulation, but lower levels of active Rac1 in A172 cells stably expressing WNK2 cDNA when compared with an equivalent cell line stably transfected with the same empty vector. Our studies indicate that loss of WNK2 expression promotes Rac1 activation and may contribute to the highly invasive phenotype that glioblastomas present. We also observed that, in a panel of glioblastoma cell lines, WNK2 promoter methylation correlates with a marked deregulation in Akt, MEK1/2 and ERK1/2 activities, suggesting WNK2 may also be important for tumour cell survival and cell cycle progression.FC

Environmental baseline monitoring - Vale of Pickering: Phase I - final report (2015/16)

This report presents the collated results from the BGS-led project Science-based environmental baseline monitoring associated with shale gas development in the Vale of Pickering (including supplementary air quality monitoring in Lancashire). The project has been funded by a grant awarded by DECC for the period August 2015 – 31st March 2016. It complements (and extends to air quality) an on-going project, funded by BGS and the other project partners, in which similar activities are being carried out in the Fylde area of Lancashire. The project has initiated a wide-ranging environmental baseline monitoring programme that includes water quality (groundwater and surface water), seismicity, ground motion, atmospheric composition (greenhouse gases and air quality), soil gas and radon in air (indoors and outdoors). The motivation behind the project(s) was to establish independent monitoring in the area around the proposed shale gas hydraulic fracturing sites in the Vale of Pickering, North Yorkshire (Third Energy) and in Lancashire (Cuadrilla) before any shale gas operations take place. As part of the project, instrumentation has been deployed to measure, in real-time or near real-time, a range of environmental variables (water quality, seismicity, atmospheric composition). These data are being displayed on the project’s web site (www.bgs.ac.uk/Valeofpickering). Additional survey, sampling and monitoring has also been carried out through a co-ordinated programme of fieldwork and laboratory analysis, which has included installation of new monitoring infrastructure, to allow compilation of one of the most comprehensive environmental datasets in the UK. It is generally recognised that at least 12 months of baseline data are required. The duration of the grant award (7 months) has meant that this has not yet been possible. However there are already some very important findings emerging from the limited datasets which need be taken in to account when developing future monitoring strategy, policy and regulation. The information is not only relevant to the Vale of Pickering and Lancashire but will be more widely applicable in the UK and internationally. Although shale gas operations in other parts of the world are well-established there is a paucity of good baseline data and effective guidance on monitoring. It is hoped that the monitoring project will continue to allow at least 12 months of data for each of the work packages to be compiled and analysed. It will also allow the experience gained and the scientifically-robust findings to be used to develop and establish effective environmental monitoring strategies for shale gas and similar industrial activities

Improving sheep feedlot management

This paper summarise six studies undertaken by the Sheep CRC to elucidate certain aspects of confinement feeding of sheep. A review of confinement feeding highlighted the variability of growth rate and feed conversion of sheep and revealed that little is known about the use of sorghum for feeding sheep. The review indicated that the main factors responsible for variation of growth rate and feed conversion were adaptation to grain and feeding system, including the preparation and presentation of feed. The importance of social and physiological adaptation to grain feeding was confirmed. Factors identified as responsible for safe induction and uniform growth rates included prior exposure to grain as lambs, gradual introduction of grain and, when concentrate was provided ad libitum from the first day, the use of either virginiamycin, a pelleted feed, a total mixed ration or a step-wise increase of high-starch grain components. Separate feeding of hay and grain resulted in performance comparable with that of a pelleted diet and that of a total mixed ration. Sorghum-based concentrate diets resulted in growth rates and carcase weights similar to that for winter cereal grains or pellets. Steam flaking or expanding of sorghum had no significant effect on growth rates or carcase weights. These results can be used to determine the profitability of various feedlotting options

Dvoretzky type theorems for multivariate polynomials and sections of convex bodies

In this paper we prove the Gromov--Milman conjecture (the Dvoretzky type theorem) for homogeneous polynomials on $\mathbb R^n$, and improve bounds on the number $n(d,k)$ in the analogous conjecture for odd degrees $d$ (this case is known as the Birch theorem) and complex polynomials. We also consider a stronger conjecture on the homogeneous polynomial fields in the canonical bundle over real and complex Grassmannians. This conjecture is much stronger and false in general, but it is proved in the cases of $d=2$ (for $k$'s of certain type), odd $d$, and the complex Grassmannian (for odd and even $d$ and any $k$). Corollaries for the John ellipsoid of projections or sections of a convex body are deduced from the case $d=2$ of the polynomial field conjecture

<i>Sneathiella chinensis</i> gen. nov., sp. nov., a novel marine alphaproteobacterium isolated from coastal sediment in Qingdao, China

The taxonomic position of strain LMG 23452T, which was isolated from coastal sediment from an aquaculture site near Qingdao, China, in 2000, was determined. Strain LMG 23452T comprised Gram-negative, non-spore-forming, motile rods and was found to be a halotolerant, aerobic, chemoheterotroph that produces catalase and oxidase. Comparative 16S rRNA gene sequence analysis revealed that strain LMG 23452T shared approximately 89 % sequence similarity with members of the genera Devosia, Hyphomonas, Ensifer and Chelatococcus, which belong to two different orders within the Alphaproteobacteria. Further phylogenetic analysis of the 16S rRNA gene sequence showed that strain LMG 23452T formed a separate branch within the order Rhizobiales, falling between the genera Devosia and Ensifer of the families Hyphomicrobiaceae and Rhizobiaceae, respectively. Strain LMG 23452T could be differentiated from its closest phylogenetic neighbours on the basis of several phenotypic features, including hydrolysis of the substrates starch and casein and assimilation of the carbohydrates d-glucose, d-mannose, mannitol, maltose and l-arabinose, and chemotaxonomically by the presence of the fatty acids C14 : 0 3-OH, C16 : 1ω11c, C16 : 1 ω5c and C18 : 1ω5c. The major fatty acids detected in strain LMG 23452T were C18 : 1 ω7c, C16 : 0, C19 : 0 cyclo ω8c, C16 : 1 ω7c and C17 : 1ω6c and the G+C content of the genomic DNA was 57.1 mol%. Therefore, the polyphasic data support the placement of strain LMG 23452T within a novel genus and species, for which the name Sneathiella chinensis gen. nov., sp. nov. is proposed. The type strain is LMG 23452T (=CBMAI 737T)

Improving sheep feedlot management

This paper summarise six studies undertaken by the Sheep CRC to elucidate certain aspects of confinement feeding of sheep. A review of confinement feeding highlighted the variability of growth rate and feed conversion of sheep and revealed that little is known about the use of sorghum for feeding sheep. The review indicated that the main factors responsible for variation of growth rate and feed conversion were adaptation to grain and feeding system, including the preparation and presentation of feed. The importance of social and physiological adaptation to grain feeding was confirmed. Factors identified as responsible for safe induction and uniform growth rates included prior exposure to grain as lambs, gradual introduction of grain and, when concentrate was provided ad libitum from the first day, the use of either virginiamycin, a pelleted feed, a total mixed ration or a step-wise increase of high-starch grain components. Separate feeding of hay and grain resulted in performance comparable with that of a pelleted diet and that of a total mixed ration. Sorghum-based concentrate diets resulted in growth rates and carcase weights similar to that for winter cereal grains or pellets. Steam flaking or expanding of sorghum had no significant effect on growth rates or carcase weights. These results can be used to determine the profitability of various feedlotting options

Three Decades of Minnesota Lamb Feeding Research.

This archival publication may not reflect current scientific knowledge or recommendations. Current information available from University of Minnesota Agricultural Experiment Station: http://www.maes.umn.edu

Environmental Baseline Monitoring Project. Phase II, final report

This report is submitted in compliance with the conditions set out in the grant awarded to the British Geological Survey (BGS), for the period April 2016 – March 2017, to support the jointly-funded project "Science-based environmental baseline monitoring". It presents the results of monitoring and/or measurement and preliminary interpretation of these data to characterise the baseline environmental conditions in the Vale of Pickering, North Yorkshire and for air quality, the Fylde in Lancashire ahead of any shale gas development. The two areas where the monitoring is taking place have seen, during the project, planning applications approved for the exploration for shale gas and hydraulic fracturing. It is widely recognised that there is a need for good environmental baseline data and establishment of effective monitoring protocols ahead of any shale gas/oil development. This monitoring will enable future changes that may occur as a result of industrial activity to be identified and differentiated from other natural and man-made changes that are influencing the baseline. Continued monitoring will then enable any deviations from the baseline, should they occur, to be identified and investigated independently to determine the possible causes, sources and significance to the environment and public health. The absence of such data in the United States has undermined public confidence, led to major controversy and inability to identify and effectively deal with impact/contamination where it has occurred. A key aim of this work is to avoid a similar situation and the independent monitoring being carried out as part of this project provides an opportunity to develop robust environmental baseline for the two study areas and monitoring procedures, and share experience that is applicable to the wider UK situation. This work is internationally unique and comprises an inter-disciplinary researcher-led programme that is developing, testing and implementing monitoring methodologies to enable future environmental changes to be detected at a local scale (individual site) as well as across a wider area, e.g. ‘shale gas play’ where cumulative impacts may be significant. The monitoring includes: water quality (groundwater and surface water), seismicity, ground motion, soil gas, atmospheric composition (greenhouse gases and air quality) and radon in air. Recent scientific and other commissioned studies have highlighted that credible and transparent monitoring is key to gaining public acceptance and providing the evidence base to demonstrate the industry’s impact on the environment and importantly on public health. As a result, BGS and its partners initiated in early 2015, a co-ordinated programme of environmental monitoring in Lancashire that was then extended to the Vale of Pickering in North Yorkshire after the Secretary of State for Energy and Climate Change (BEIS) awarded a grant to the British Geological Survey (BGS). The current duration of the grant award is to 31st March 2018. It has so far enabled baseline environmental monitoring for a period of more than 12 months. With hydraulic fracturing of shale gas likely to take place during late 2017/early 2018, the current funding will allow the environmental monitoring to continue during the transition from baseline to monitoring during shale gas operations. This report presents the monitoring results to April 2017 and a preliminary interpretation. A full interpretation is not presented in this report as monitoring is continuing and it is expected that there will be at least six months of additional baseline data before hydraulic fracturing takes place. This represents up to 50% more data for some components of the montoring, and when included in the analysis will significantly improve the characterisation and interpretation of the baseline. In addition to this report, the BGS web site contains further information on the project, near real-time data for some components of the monitoring and links to other projects outputs, e.g. reports and videos (www.bgs.ac.uk/research/groundwater/shaleGas/monitoring/home.html)

UK Public Sector Information and Re-use Policy – A 2008 Analysis

INTRODUCTION: Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. METHODS: We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. RESULTS: The prevalence of TDR is predicted to rise from 6.7$1612 to $2234 (IQR$450-dominated) per QALY gained. CONCLUSIONS: While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost-effective approach to reduce TDR. Improving access to second-line ART is therefore a major priority