Links between soil microbial communities and plant traits in a species-rich grassland under long-term climate change

Climate change can influence soil microorganisms directly by altering their growth and activity but also indirectly via effects on the vegetation, which modifies the availability of resources. Direct impacts of climate change on soil microorganisms can occur rapidly, whereas indirect effects mediated by shifts in plant community composition are not immediately apparent and likely to increase over time. We used molecular fingerprinting of bacterial and fungal communities in the soil to investigate the effects of 17 years of temperature and rainfall manipulations in a species‐rich grassland near Buxton, UK. We compared shifts in microbial community structure to changes in plant species composition and key plant traits across 78 microsites within plots subjected to winter heating, rainfall supplementation, or summer drought. We observed marked shifts in soil fungal and bacterial community structure in response to chronic summer drought. Importantly, although dominant microbial taxa were largely unaffected by drought, there were substantial changes in the abundances of subordinate fungal and bacterial taxa. In contrast to short‐term studies that report high resistance of soil fungi to drought, we observed substantial losses of fungal taxa in the summer drought treatments. There was moderate concordance between soil microbial communities and plant species composition within microsites. Vector fitting of community‐weighted mean plant traits to ordinations of soil bacterial and fungal communities showed that shifts in soil microbial community structure were related to plant traits representing the quality of resources available to soil microorganisms: the construction cost of leaf material, foliar carbon‐to‐nitrogen ratios, and leaf dry matter content. Thus, our study provides evidence that climate change could affect soil microbial communities indirectly via changes in plant inputs and highlights the importance of considering long‐term climate change effects, especially in nutrient‐poor systems with slow‐growing vegetation

JULES-BE:Representation of bioenergy crops and harvesting in the Joint UK Land Environment Simulator vn5.1

We describe developments to the land surface model JULES, allowing for flexible user-prescribed harvest regimes of various perennial bioenergy crops or natural vegetation types. Our aim is to integrate the most useful aspects of dedicated bioenergy models into dynamic global vegetation models, in order that assessment of bioenergy options can benefit from state-of-the-art Earth system modelling. A new plant functional type (PFT) representing Miscanthus is also presented. The Miscanthus PFT fits well with growth parameters observed at a site in Lincolnshire, UK; however, global observed yields of Miscanthus are far more variable than is captured by the model, primarily owing to the model's lack of representation of crop age and establishment time. Global expansion of bioenergy crop areas under a 2 ?C emissions scenario and balanced greenhouse gas mitigation strategy from the IMAGE integrated assessment model (RCP2.6- SSP2) achieves a mean yield of 4.3 billion tonnes of dry matter per year over 2040-2099, around 30 % higher than the biomass availability projected by IMAGE. In addition to perennial grasses, JULES-BE can also be used to represent short-rotation coppicing, residue harvesting from cropland or forestry and rotation forestry

Hedgehog Signalling in Androgen Independent Prostate Cancer

Objectives: Androgen-deprivation therapy effectively shrinks hormone-naïve prostate cancer, both in the prostate and at sites of distant metastasis. However prolonged androgen deprivation generally results in relapse and androgen-independent tumour growth, which is inevitably fatal. The molecular events that enable prostate cancer cells to proliferate in reduced androgen conditions are poorly understood. Here we investigate the role of Hedgehog signalling in androgen-independent prostate cancer (AIPC). Methods: Activity of the Hedgehog signalling pathway was analysed in cultured prostate cancer cells, and circulating prostate tumour cells were isolated from blood samples of patients with AIPC. Results: AIPC cells were derived through prolonged culture in reduced androgen conditions, modelling hormone therapy in patients, and expressed increased levels of Hedgehog signalling proteins. Exposure of cultured AIPC cells to cyclopamine, which inhibits Hedgehog signalling, resulted in inhibition of cancer cell growth. The expression of the Hedgehog receptor PTCH and the highly prostate cancer-specific gene DD3PCA3 was significantly higher in circulating prostate cancer cells isolated from patients with AIPC compared with samples prepared from normal individuals. There was an association between PTCH and DD3PCA3 expression and the length of androgen-ablation therapy. Conclusions: Our data are consistent with reports implicating overactivity of Hedgehog signalling in prostate cancer and suggest that Hedgehog signalling contributes to the androgen-independent growth of prostate cancer cells. As systemic anti-Hedgehog medicines are developed, the Hedgehog pathway will become a potential new therapeutic target in advanced prostate cancer.Peer reviewedFinal Accepted Versio

Public understandings of potential policy responses to health inequalities:Evidence from a UK national survey and citizens’ juries in three UK cities

A substantial body of research describes the distribution, causes and potential reduction of health inequalities, yet little scholarship examines public understandings of these inequalities. Existing work is dominated by small-scale, qualitative studies of the experiences of specific communities. As a result, we know very little about what broader publics think about health inequalities; and even less about public views of potential policy responses. This is an important gap since previous research shows many researchers and policymakers believe proposals for ‘upstream’ policies are unlikely to attract sufficient public support to be viable. This mixed methods study combined a nationally representative survey with three two-day citizens' juries exploring public views of health inequalities and potential policy responses in three UK cities (Glasgow, Manchester and Liverpool) in July 2016. Comparing public opinion elicited via a survey to public reasoning generated through deliberative processes offers insight into the formation of public views. The results challenge perceptions that there is a lack of public support for upstream, macro-level policy proposals and instead demonstrate support for proposals aiming to tackle health inequalities via improvements to living and working conditions, with more limited support for proposals targeting individual behavioural change. At the same time, some macro-economic proposals, notably those involving tax increases, proved controversial among study participants and results varied markedly by data source. Our analysis suggests that this results from three intersecting factors: a resistance to ideas viewed as disempowering (which include, fundamentally, the idea that health inequalities exist); the prevalence of individualising and fatalistic discourses, which inform resistance to diverse policy proposals (but especially those that are more ‘upstream’, macro-level proposals); and a lack of trust in (local and national) government. This suggests that efforts to enhance public support for evidence-informed policy responses to health inequalities may struggle unless these broader challenges are also addressed

The spatial organization and microbial community structure of an epilithic biofilm.

Microbial biofilms are common on lithic surfaces, including stone buildings. However, the ecology of these communities is poorly understood. Few studies have focused on the spatial characteristics of lithobiontic biofilms, despite the fact that spatial structure has been demonstrated to influence ecosystem function (and hence biodegradation) and community diversity. Furthermore, relatively few studies have utilized molecular techniques to characterize these communities, even though molecular methods have revealed unexpected microbial diversity in other habitats. This study investigated (1) the spatial structure and (2) the taxonomic composition of an epilithic biofilm using molecular techniques, namely amplicon pyrosequencing and terminal restriction fragment length polymorphism. Dispersion indices and Mantel correlograms were used to test for the presence of spatial structure in the biofilm. Diversity metrics and rank-abundance distributions (RADs) were also generated. The study revealed spatial structure on a centimetre scale in eukaryotic microbes (fungi and algae), but not the bacteria. Fungal and bacterial communities were highly diverse; algal communities much less so. The RADs were characterized by a distinctive 'hollow' (concave up) profile and long tails of rare taxa. These findings have implications for understanding the ecology of epilithic biofilms and the spatial heterogeneity of stone biodeterioration.This work was supported by the Engineering and Physical Sciences Research Council (grant no. EP/G011338/1).This is the author accepted manuscript. The final version is available from OUP at http://femsec.oxfordjournals.org/content/91/3/fiu027

How Do Countries' Health Information Systems Perform in Assessing Asylum Seekers' Health Situation? Developing a Health Information Assessment Tool on Asylum Seekers (HIATUS) and Piloting It in Two European Countries

Bozorgmehr K, Goosen S, Mohsenpour A, Kuehne A, Razum O, Kunst AE. How Do Countries' Health Information Systems Perform in Assessing Asylum Seekers' Health Situation? Developing a Health Information Assessment Tool on Asylum Seekers (HIATUS) and Piloting It in Two European Countries. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH. 2017;14(8): 894.Background: Accurate data on the health status, health behaviour and access to health care of asylum seekers is essential, but such data is lacking in many European countries. We hence aimed to: (a) develop and pilot-test an instrument that can be used to compare and benchmark the country health information systems (HIS) with respect to the ability to assess the health status and health care situation of asylum seekers and (b) present the results of that pilot for The Netherlands (NL) and Germany (DE). Materials and Methods: Reviewing and adapting existing tools, we developed a Health Information Assessment Tool on Asylum Seekers (HIATUS) with 50 items to assess HIS performance across three dimensions: (1) availability and detail of data across potential data sources; (2) HIS resources and monitoring capacity; (3) general coverage and timeliness of publications on selected indicators. We piloted HIATUS by applying the tool to the HIS in DE and NL. Two raters per country independently assessed the performance of country HIS and the inter-rater reliability was analysed by Pearson's rho and the intra-class correlation (ICC). We then applied a consensus-based group rating to obtain the final ratings which were transformed into a weighted summary score (range: 0-97). We assessed HIS performance by calculating total and domain-specific HIATUS scores by country as well as absolute and relative gaps in scores within and between countries. Results: In the independent rating, Pearson's rho was 0.14 (NL) and 0.30 (DE), the ICC yielded an estimated reliability of 0.29 (NL) and 0.83 (DE) respectively. In the final consensus-based rating, the total HIATUS score was 47 in NL and 15 in DE, translating into a relative gap in HIS capacity of 52% (NL) and 85% (DE) respectively. Shortfalls in HIS capacity in both countries relate to the areas of HIS coordination, planning and policies, and to limited coverage of specific indicators such as self-reported health, mental health, socio-economic status and health behaviour. The relative gap in the HIATUS component "data sources and availability" was much higher in Germany (92%) than in NL (28%). Conclusions: The standardised tool (HIATUS) proved useful for assessment of country HIS performance in two countries by consensus-based rating. HIATUS revealed substantial limitations in HIS capacity to assess the health situation of asylum seekers in both countries. The tool allowed for between-country comparisons, revealing that capacities were lower in DE relative to NL. Monitoring and benchmarking gaps in HIS capacity in further European countries can help to strengthen HIS in the future

AKT regulates NPM dependent ARF localization and p53mut stability in tumors

Nucleophosmin (NPM) is known to regulate ARF subcellular localization and MDM2 activity in response to oncogenic stress, though the precise mechanism has remained elusive. Here we describe how NPM and ARF associate in the nucleoplasm to form a MDM2 inhibitory complex. We find that oligomerization of NPM drives nucleolar accumulation of ARF. Moreover, the formation of NPM and ARF oligomers antagonizes MDM2 association with the inhibitory complex, leading to activation of MDM2 E3-ligase activity and targeting of p53. We find that AKT phosphorylation of NPM-Ser48 prevents oligomerization that results in nucleoplasmic localization of ARF, constitutive MDM2 inhibition and stabilization of p53. We also show that ARF promotes p53 mutant stability in tumors and suppresses p73 mediated p21 expression and senescence. We demonstrate that AKT and PI3K inhibitors may be effective in treatment of therapeutically resistant tumors with elevated AKT and carrying gain of function mutations in p53. Our results show that the clinical candidate AKT inhibitor MK-2206 promotes ARF nucleolar localization, reduced p53(mut) stability and increased sensitivity to ionizing radiation in a xenograft model of pancreatic cancer. Analysis of human tumors indicates that phospho-S48-NPM may be a useful biomarker for monitoring AKT activity and in vivo efficacy of AKT inhibitor treatment. Critically, we propose that combination therapy involving PI3K-AKT inhibitors would benefit from a patient stratification rationale based on ARF and p53(mut) status

Hedonic shopping motivations in collectivistic and individualistic consumer cultures

We reinvestigate what constitutes hedonic customer experiences in collectivistic versus individualistic cultures using four country samples (N=2,336) in Germany and the U.S. as well as Oman and India. Across country samples, intrinsically enjoyable customer experiences are associated with the same underlying hedonic shopping motivations as shown in the original U.S. context. In comparison with individualistic cultures, we find that a hedonic shopping experience in collectivistic cultures is less strongly associated with selforiented gratification shopping, yet more strongly associated with others-oriented role shopping