• GAS5 lncRNA Modulates the Action of mTOR Inhibitors in Prostate Cancer Cells

      Yacqub-Usman, Kiren; Pickard, Mark R.; Williams, Gwyn T.; Keele University, United Kingdom (NCRI Cancer Conference 2014 Abstracts, 2014)
      Background There is a need to develop new therapies for castrate-resistant prostate cancer (CRPC) and growth arrest-specific 5 (GAS5) long non-coding RNA (lncRNA), which riborepresses androgen receptor action, may offer novel opportunities in this regard. GAS5 lncRNA expression declines as prostate cancer cells acquire castrate-resistance, and decreased GAS5 expression attenuates the responses of prostate cancer cells to apoptotic stimuli. Enhancing GAS5 lncRNA expression may therefore offer a strategy to improve the effectiveness of chemotherapeutic agents. GAS5 is a member of the 5' terminal oligopyrimidine gene family, and we have therefore examined if mTOR inhibition can enhance cellular GAS5 levels in prostate cancer cells. In addition, we have determined if GAS5 lncRNA itself is required for mTOR inhibitor action in prostate cancer cells, as recently demonstrated in lymphoid cells. Method The effects of mTOR inhibitors on GAS5 lncRNA expression and cell proliferation were determined in a range of prostate cancer cell lines. Transfection of cells with GAS5 siRNA and plasmid constructs was performed to determine the involvement of GAS5 lncRNA in mTOR inhibitor action. Results Treatment with rapamycin and rapalogues increased cellular GAS5 levels and inhibited culture growth in both androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU145) cells. GAS5 silencing in both LNCaP and 22Rv1 cells decreased their sensitivity to growth inhibition by mTOR inhibitors. Moreover, transfection of GAS5 lncRNA sensitized PC-3 and DU145 cells to mTOR inhibitors, resulting in inhibition of culture growth. Conclusion mTOR inhibition enhances GAS5 transcript levels in some, but not all, prostate cancer cell lines. This may in part be related to endogenous levels of GAS5 expression, which tend to be lower in prostate cancer cells representative of advanced disease, particularly since current findings demonstrate a role for GAS5 lncRNA in mTOR inhibitor action in prostate cancer cells.
    • Genetic analysis of the critically endangered Trinidad Piping guan (Pipile pipile): Implications for phylogenetic placement and conservation strategies

      McDowall, Ian; Hosie, Charlotte A.; Robinson, Louise A. (University of Chester, 2011-11)
      Classified as critically endangered since 1994, the Trinidad Piping guan (Pipile pipile) is an endemic species estimated to number less than 200 individuals. Known to locals of Trinidad as the ‘Pawi’ this bird has been the subject of substantial hunting pressures and much of the species habitat has been destroyed through deforestation. Although officially protected since 1958, occasional recreational hunting of this elusive species still occurs. Due to difficulties locating and capturing the species, no genetic research has previously been performed using samples obtained from Trinidad. All previous research studies have been conducted using biological materials obtained from captive birds outside Trinidad and island data has never been obtained or compared. The genetic diversity of the remaining population was therefore examined through the investigation of mitochondrial haplotypes, pairwise comparison and SNP analysis. With the intention of assisting the protection of this endangered species by the location of remaining areas of habitation, methods of genetic identification were established for the Trinidad Piping guan utilising non-invasive feather samples. Species specific primers were created in the regions of the ND2 and cyt b genes of the mitochondrial genome to identify Pipile pipile. Species detection was further verified with the use of PCR-RFLP of the same gene regions digested with BsaXI, EcoRV and BsrDI. This combined approach allowed the separation of closely related taxa based on single inter-species SNPs. Confirmation of species identification was subsequently performed through the use of forensically informative nucleotide sequencing. The established methodologies were used in the current study to correct the classification of a UK breeding population of Piping guans thought to be Pipile pipile and to identify Trinidad field samples. These detection methods have implications for ecological studies through the location of populations from trace evidence collected in the field. In addition this method could be used to assist Trinidadian police forces in the identification of bushmeats or simply act as a deterrent to hunters. The sequence data obtained in the present study were also used to re-assess the phylogeny of Piping guans. As genetic sequence from a true island bird was previously unstudied, differences between phylogenies created using non-island and island bird data sets were examined. Combined analysis was performed on 1884bp of the ND2 and cyt b genes and placement of Trinidad Piping guan was found to differ from that which has been previously published.
    • The genetics and evolution of the critically endangered Trinidad Piping Guan Pipile pipile, synonym Aburria pipile.

      McDowall, Ian; Hosie, Charlotte A.; Grass, Amelia (University of Chester, 2018-02)
      The Trinidad Piping Guan, Pipile pipile synonym Aburria pipile (Jaquin, 1784) is the only endemic Cracid on the island of Trinidad. The species is currently listed as Critically Endangered and is considered to be in ‘on-going decline’ by the IUCN, BirdLife International and Cracid Specialist Group. This study aims to examine aspects of genetic variation and the evolution of the mitochondrial genome in the Trinidad Piping Guan utilising, for the first time, samples collected from individuals in the wild and reference specimens of the genus Pipile sourced from museum collections. In this study the complete mitochondrial genome of the Trinidad Piping Guan was sequenced for the first time. Analysis of intra-specific variation of wild Trinidad Piping Guan individuals using single nucleotide polymorphisms demonstrates extremely limited variation within the genes of the mitochondrial genome and nuclear gene intron sequences. Limited variation within this population is consistent with both historical and contemporary contractions of populations within a restricted island system, which may have serious implications for the future of this species in terms of both genetic diversity and conservation management. Phylogenetic analysis of the complete mitochondrial genome of the Trinidad Piping Guan enabled placement of the genus Pipile within the Galliforme evolutionary tree for the first time, and subsequently places the genus within the broader context of the Aves class. Mito-genomic analysis confirms that the Cracids are one of the basal Galliforme clades, and sister taxa to the Megapodidae. Phylogenetic placement of the Pipile genus is basal to that of the Crax species within the Cracidae family, indicative of an earlier evolutionary origin of the Piping Guans. The inclusion of the Trinidad Piping Guan, in the avian evolutionary tree using the whole mitochondrial genomes expands the current genetic phylogeny of the Cracid family, yielding a better understanding of evolutionary relationships among the Galliforme order and the diversification of modern avian lineages. This study has established novel molecular techniques for the analysis of mitochondrial DNA in historical specimens of the genus Pipile from museum reference collections. The analysis of inter-specific relationships within the genus Pipile has clarified the evolutionary and biogeographic relationships between the Piping Guan species. Additionally, the Trinidad Piping Guan is genetically defined for the first time as an evolutionarily significant unit, which represents a unique evolutionary pathway within this important genus in a closed island system on the island of Trinidad.
    • Geoconservation and geodiversity: What? Who? Where? - and why should I care?

      Nicholls, Keith H.; Burek, Cynthia V.; University of Chester (Institute of Civil Engineering Publishing, 2015-08-31)
      Whilst "geoconservation" is a relatively new sub-discipline in academic geology and earth science departments, this presentation argues that an appreciation of our 'geodiversity' is an important but often overlooked element of the background to development work. For practising engineering geologists or geotechnical engineers, taking up a role in one of the formal geoconservation bodies (be it a local geoconservation group, a Trust or a Geopark) can be a useful networking tool, can offer increased geological awareness and be a source of beneficial continuing Professional development (CPD)). However, the value of geoconservation needs to be brought to a wider audience, since at the moment threats to elements of geological natural heritage are only addressed when important geological landscapes are threatened by development (such as have been seen at Siccar Point and at Wenlock Edge in recent months). Because geodiversity is only rarely fully considered in the planning process, it can be difficult to differentiate between genuine local concern, and irrational "Nimbyism". It is time that those of us working in the geotechnical industry who have backgrounds in geology, drive forward an agenda that establishes our geological heritage as a cause for consern alongside ecology and archaeology. Failure to do so reflects badly on us as individuals and as an industry.
    • Geodiversity Action Plans – A method to facilitate, structure, inform and record action for geodiversity.

      Burek, Cynthia V.; Dunlop, Lesley; Larwood, Jonathan G.; University of Chester; Northumbria University, Natural England (Elsevier, 2017-12-15)
      Geodiversity Action Plans are used widely within the United Kingdom to inform and record action for geodiversity and geoconservation. They encompass both site-based audit and conservation with a wider perspective on geodiversity resources available in an agreed area (such as geological sites, museum collections and building stones) with ambitions to present and communicate, influence policy and practice, and to secure resources in relation to geodiversity. Geodiversity Action Plans (GAPs) are used particularly at local and company level to focus and highlight the work needed to be carried out and a as key mechanism to facilitate and support the delivery of the overarching UK Geodiversity Action Plan (UKGAP). Importantly, GAPs cross cut interests and are multidisciplinary. Although they are mainly a UK tool for geoconservation the principles and approach are easily transferred and could be duplicated in other countries.
    • Geodiversity trail: Walking through the past on the university's Chester campus

      Stillwell, Nicholas; Burek, Cynthia V.; University of Chester (University of Chester, 2007)
      This book illustrates the geodiversity trail on the University of Chester's Chester campus.
    • Girls, young women and sport in Norway: A case study of sporting convergence amid favourable socio-economic conditions

      Green, Ken; Thurston, Miranda; Vaage, Odd; Mordal-Moen, Kjersti; University of Chester; Hedmark University (Taylor & Francis, 2015-04-14)
      Based primarily on quantitative data from the Norwegian Statistisk Sentralbyrå (Statistics Norway) study of Mosjon, Friluftsliv og Kulturaktiviteter, this paper explores sports participation among females – and girls and young women, in particular – in Norway in the early years of the twenty-first century. In line with the observation that sport can be considered epiphenomenal, the paper argues that the comparatively high levels and marked increases in sports participation among young women are likely to have a great deal to do with their socio-economic status and, in particular, the diminishing gender gap over the past two decades. In short, the paper argues that trends in sports participation between 1997 and 2007 suggest that while young women in Norway may not be self-described feminists, they are heirs to the culture fostered by second-wave feminism: they have taken advantage of growing up in a country where standards of living are particularly high and at a time of greater equality between the sexes in order, among other things, to exploit the sporting opportunities increasingly available to them. In terms of the policy implications, the most salient lesson to be learned from the Norwegian situation – by countries keen to promote sports participation among girls and young women – is that instead of individually oriented approaches, sports policies need first and foremost to adopt society-level perspectives that address socio-economic gender disparities.
    • Glutamine supplementation reduces markers of intestinal permeability during running in the heat in a dose-dependent manner

      Pugh, Jamie N.; Sage, Stephen; Hutson, Mark; Doran, Dominic A.; Fleming, Simon C.; Highton, Jamie; Morton, James P.; Close, Graeme L.; email: g.l.close@ljmu.ac.uk (Springer Berlin Heidelberg, 2017-10-20)
      AbstractPurposeTo examine the dose–response effects of acute glutamine supplementation on markers of gastrointestinal (GI) permeability, damage and, secondary, subjective symptoms of GI discomfort in response to running in the heat.MethodsTen recreationally active males completed a total of four exercise trials; a placebo trial and three glutamine trials at 0.25, 0.5 and 0.9 g kg−1 of fat-free mass (FFM) consumed 2 h before exercise. Each exercise trial consisted of a 60-min treadmill run at 70% of V˙O2max in an environmental chamber set at 30 °C. GI permeability was measured using ratio of lactulose to rhamnose (L:R) in serum. Plasma glutamine and intestinal fatty acid binding protein (I-FABP) concentrations were determined pre and post exercise. Subjective GI symptoms were assessed 45 min and 24 h post-exercise.ResultsRelative to placebo, L:R was likely lower following 0.25 g kg−1 (mean difference: − 0.023; ± 0.021) and 0.5 g kg−1 (− 0.019; ± 0.019) and very likely following 0.9 g kg− 1 (− 0.034; ± 0.024). GI symptoms were typically low and there was no effect of supplementation.DiscussionAcute oral glutamine consumption attenuates GI permeability relative to placebo even at lower doses of 0.25 g kg−1, although larger doses may be more effective. It remains unclear if this will lead to reductions in GI symptoms. Athletes competing in the heat may, therefore, benefit from acute glutamine supplementation prior to exercise in order to maintain gastrointestinal integrity.
    • GORDON, Maria Matilda (nee Ogilvie: 1846-1939)

      Burek, Cynthia V.; University College Chester (Thoemmes Continuum, 2004)
      This dictionary entry discusses the life and work of Dame Maria Matilda Ogilvie Gordon (1864-1939).
    • Gorillas continue to thrive

      Fletcher, Alison W.; Uwingeli, Prosper; Fawcett, Katie; University College Chester (Dian Fossey Gorilla Fund International, 2005)
    • Grike-roclimates

      Burek, Cynthia V.; Legg, Colin; Chester College of Higher Education (English Nature, 1999-07)
      This journal article discusses data collected at two north Wales sites that demonstrates that the direction of grikes makes a significant difference on the biodiversity of limestone pavements.
    • Head imaging and craniometry: A historical note on a base line error

      Lewis, Stephen J.; Chester College of Higher Education (College of Radiographers, 1995-07)
      This journal article discusses the work of Lysholm, Reid, and von Ihering in standarding patient positioning during radiological examination of the skull.
    • Health benefits of Tai Chi exercise: Improved balance and blood pressure in middle-aged women

      Thornton, Everard W.; Sykes, Kevin; Tang, Wai K.; University of Liverpool ; University College Chester ; University College Chester (Oxford University Press, 2004-03)
      Tai Chi has been widely practiced as a Chinese martial art that focuses on slow sequential movements, providing a smooth, continuous and low intensity activity. It has been promoted to improve balance and strength and to reduce falls in the elderly, especially those 'at risk'. The potential benefits in healthy younger age cohorts and for wider aspects of health have received less attention. The present study documented prospective changes in balance and vascular responses for a community sample of middle-aged women. Seventeen relatively sedentary but healthy normotensive women aged 33-55 years were recruited into a three times per week, 12-week Tai Chi exercise programme. A further 17 sedentary subjects matched for age and body size were recruited as a control group. Dynamic balance measured by the Functional Reach Test was significantly improved following Tai Chi, with significant decreases in both mean systolic (9.71 mmHg) and diastolic (7.53 mmHg) blood pressure. The data confirm that Tai Chi exercise can be a good choice of exercise for middle-aged adults, with potential benefits for ageing as well as the aged.
    • Health-related effects and improving extractability of cereal arabinoxylans

      Fadel, Abdulmannan; Mahmoud, Ayman M.; Ashworth, Jason J.; Li, Weili; Ng, Yu L.; Plunkett, Andrew; Manchester Metropolitan University; Beni-Suef University; Charité-University Medicine; University of Chester (Elsevier, 2017-11-11)
      Arabinoxylans (AXs) are major dietary fibers. They are composed of backbone chains of -(1–4)- linked xylose residues to which -l-arabinose are linked in the second and/or third carbon positions. Recently, AXs have attracted a great deal of attention because of their biological activities such as their immunomodulatory potential. Extraction of AXs has some difficulties; therefore, various methods have beenusedto increase the extractability ofAXs withvaryingdegrees of success, suchas alkaline, enzymatic, mechanical extraction. However, some of these treatments have been reported to be either expensive, such as enzymatic treatments, or produce hazardous wastes and are non-environmentally friendly, such as alkaline treatments. On the other hand, mechanical assisted extraction, especially extrusion cooking, is an innovative pre-treatment that has been used to increase the solubility of AXs. The aim of the current review article is to point out the health-related effects and to discuss the current research on the extraction methods of AXs.
    • Heat shock proteins form part of a danger signal cascade in response to lipopolysaccharide and GroEL

      Davies, Emma L.; Bacelar, Maria M. F. V. G.; Marshall, Michael J.; Johnson, E.; Wardle, T. D.; Andrew, Sarah M.; Williams, John H. H.; University of Chester ; University of Chester ; Charles Salt Centre, The Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry ; Spinal Studies, The Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry ; Countess of Chester Hospital ; University of Chester ; University of Chester (Wiley, 2006-04)
      An increasing number of cell types, including peripheral blood mononuclear cells (PBMCs), have been demonstrated to release heat shock proteins (Hsps). This paper investigates further the hypothesis that Hsps are danger signals. PBMCs and Jurkat cells released Hsp70 (0·22 and 0·7 ng/106 cells, respectively) into medium over 24 h at 37°C. Release of Hsp70 was stimulated 10-fold by GroEL (P < 0·001) and more than threefold by lipopolysaccharide (LPS) (P < 0·001). Although Hsp60 could be detected in the medium of cells cultured at 37°C for 24 h, the low rates of release were due probably to cell damage. Significant release of Hsp60 was observed when Jurkat cells were exposed to GroEL (2·88 ng/106 cells) or LPS (1·40 ng/106 cells). The data are consistent with the hypothesis that Hsp70 and Hsp60 are part of a danger signalling cascade in response to bacterial infection.
    • Heat shock proteins: Interactions with bone and immune cells

      Williams, John H. H.; Davies, Emma L. (University of Liverpool (Chester College of Higher Education), 2004-09)
      Heat shock proteins (Hsps) are increasingly being seen as having roles other than those of intracellular molecular chaperones, particularly with regard to their potential to act as cytokines, and to stimulate the innate immune system. Hsps have also been found to promote bone resorption and osteoclast formation in vitro, although the mechanism has not been previously identified. The overall aims of this thesis were to determine whether Hsps could stimulate bone resorption by affecting the RANKL/OPG pathway, and to address the hypothesis that Hsps can act as a danger signal to the innate immune system. In order for Hsps to affect either the RANKL/OPG system of bone resorption or act as danger signals they would need to be actively released from cells, ideally in a controlled manner following exposure to the source of stress. Hsp60 and Hsp70 were found to be released from a range of immune cells including the cell lines Jurkat and U937, and also PBMCs, T-cells and B-cells. This release was not due to cell damage. The release of Hsp60 and Hsp70 were downregulated by inhibitors of protein secretion, in particular Hsp70 release was reduced by compounds that inhibited lysosomal pathways and Hsp60 release by classical secretion inhibitors. Hsp60, Hsp70, GroEL and LPS all affected the RANKL/OPG system of bone regulation; OPG production and release was down-regulated in the MG63 and GCT osteoblast-like cell lines following treatment with Hsp60, Hsp70 and LPS, and RANKL expression was upregulated following treatment with Hsp60, Hsp70, GroEL and LPS. This effect on the RANKL/OPG system was found to translate into an effect on osteoclast formation when conditioned media from treated osteoblasts was added to osteoclast precursors in the presence of M-CSF. A range of different factors that affected Hsp release were identified; PHA activation of PBMCs was found to upregulate Hsp60 release from PBMCs. GroEL and LPS caused an upregulation in Hsp70 release from PBMCs and GCT osteoblast like cells, and Hsp70 was found to stimulate Hsp60 release from PBMCs and GCT cells. These responses of Hsp release were used to form a theory of a cascade-like danger signal that may occur when cells are exposed to bacterial infection and which would result in activation of antigen presenting cells via previously identified receptors for Hsps such as CD14/TLR4 or by unidentified pathways. The elevated release of Hsps in response to GroEL and LPS was also identified as a mechanism that could stimulate bone loss during infection or autoimmuniry by affecting the RANKL/OPG system. hi conclusion, Hsp60 and Hsp70 can be released from immune cells under normal conditions, and from both immune and osteoblast-like cells following stimulation with LPS and other Hsps. The observed release responses provide a mechanism through which Hsps can act as danger signals to the innate immune system, and also as promoters of bone resorption via the RANKL/OPG system.
    • Helpers influence on territory use and maintenance in Alpine marmot groups

      Pasquaretta, Cristian; Busia, Laura; Ferrari, Caterina; Bogliani, Giuseppe; Reale, Denis; von Hardenberg, Achaz; University of Pavia, Universiteé du Quebec a Montreal, Gran Paradiso National Park (2015-04-22)
      In social mammals, territory size and shape vary according to the number and strength of neighbour individuals competing for resources. Two main theories have been proposed to explain this variability: the Group Augmentation (GA) and the realized Resource Holding Potential (rRHP) hypotheses. The first states that the outcome of the interactions among groups depends on the total number of individuals in the group while the second states that only the number of animals directly involved in intergroup competition determines this outcome. We collected data on space use of individually tagged Alpine marmots ( Marmota marmota), a cooperative breeding species that overlaps part of its territory with neighbouring groups. In accordance with the rRHP hypothesis, we found that groups having higher proportion of helpers, rather than higher total number of individuals, had lower percentage of the territory overlapping with neighbouring groups and a larger area available for individual exclusive use.
    • Hen Harrier Circus cyaneus nest sites on the Isle of Mull are associated with habitat mosaics and constrained by topography

      Geary, Matthew; Haworth, Paul F.; Fielding, Alan H.; University of Chester; Haworth Conservation Ltd. (Taylor & Francis, 2018-02-07)
      Capsule: Hen Harrier on the Isle of Mull, UK, are associated with habitat mosaics consisting of moorland, scrub and forestry but avoid grazed land, suggesting that forested habitats could be managed sympathetically for Hen Harrier in the future should the current UK population increase. Aims: To use distribution modelling to investigate nesting habitat associations using a long term dataset for Hen Harrier on Mull. Methods: We develop area-interaction models using a LASSO penalty to explore the distribution of 102 Hen Harrier nest sites in relation to habitat and topography. Our model is then successfully validated in tests using data for 70 nest sites from subsequent years. Results: Our model is effective in predicting suitable areas for Hen Harrier nest sites and indicates that Hen Harriers on Mull are found in habitat mosaics below 200 m asl. Hen Harrier nest intensity is positively associated with increasing proportions of moorland and scrub, open canopy forestry and closed canopy forestry. Nest intensity is negatively associated with increasing proportions of grazed land. Conclusion: Hen Harrier avoid grazed areas but are relatively tolerant of other habitat combinations. These findings are supported by previous observations of Hen Harrier habitat use and have implications for the recovery of some Hen Harrier SPA populations and future forest management. Open canopy forest and forest mosaics could potentially be incorporated into landscape-scale conservation plans for Hen Harriers using the population in Mull as an example.
    • Higher risk of gastrointestinal parasite infection at lower elevation suggests possible constraints in the distributional niche of Alpine marmots

      Zanet, Stefania; Miglio, Giacomo; Ferrari, Caterina; Bassano, Bruno; Ferroglio, Ezio; von Hardenberg, Achaz; Università di Torino; Gran Paradiso National Park; University of Chester (Public Library of Science, 2017-08-01)
      Alpine marmots Marmota marmota occupy a narrow altitudinal niche within high elevation alpine environments. For animals living at such high elevations where resources are limited, parasitism represents a potential major cost in life history. Using occupancy models, we tested if marmots living at higher elevation have a reduced risk of being infected with gastrointestinal helminths, possibly compensating the lower availability of resources (shorter feeding season, longer snow cover and lower temperature) than marmots inhabiting lower elevations. Detection probability of eggs and oncospheres of two gastro-intestinal helminthic parasites, Ascaris laevis and Ctenotaenia marmotae, sampled in marmot feces, was used as a proxy of parasite abundance. As predicted, the models showed a negative relationship between elevation and parasite detectability (i.e. abundance) for both species, while there appeared to be a negative effect of solar radiance only for C. marmotae. Site-occupancy models are used here for the first time to model the constrains of gastrointestinal parasitism on a wild species and the relationship existing between endoparasites and environmental factors in a population of free-living animals. The results of this study suggest the future use of site-occupancy models as a viable tool to account for parasite imperfect detection in ecoparasitological studies, and give useful insights to further investigate the hypothesis of the contribution of parasite infection in constraining the altitudinal niche of Alpine marmots.
    • Higher satiety ratings following yogurt consumption relative to fruit drink or dairy fruit drink

      Tsuchiya, Ami; Almiron-Roig, Eva; Lluch, Anne; Guyonnet, Denis; Drewnowski, Adam; University of Washington ; University of Washington ; Danone Research Centre, France ; Danone Research Centre, France ; University of Washington (Elsevier, 2006-04)
      This article compares the satiating power of semisolid and liquid yogurts with fruit beverages and dairy fruit drinks using 32 volunteers.