• Lipid remodelling in the reef-building honeycomb worm, Sabellaria alveolata, reflects acclimation and local adaptation to temperature

      Muir, Anna P.; Nunes, Flavia L. D.; Dubois, Stanislas F.; Pernet, Fabrice; University of Chester; Ifremer Centre Bretagne; Ifremer Centre Bretagne; Ifremer Centre Bretagne (Nature Publishing Group, 2016-10-20)
      Acclimation and adaptation, which are key to species survival in a changing climate, can be observed in terms of membrane lipid composition. Remodelling membrane lipids, via homeoviscous adaptation (HVA), counteracts membrane dysfunction due to temperature in poikilotherms. In order to assess the potential for acclimation and adaptation in the honeycomb worm, Sabellaria alveolata, a reefbuilding polychaete that supports high biodiversity, we carried out common-garden experiments using individuals from along its latitudinal range. Individuals were exposed to a stepwise temperature increase from 15 °C to 25 °C and membrane lipid composition assessed. Our results suggest that S. alveolata was able to acclimate to higher temperatures, as observed by a decrease in unsaturation index and 20:5n-3. However, over the long-term at 25 °C, lipid composition patterns are not consistent with HVA expectations and suggest a stress response. Furthermore, unsaturation index of individuals from the two coldest sites were higher than those from the two warmest sites, with individuals from the thermally intermediate site being in-between, likely reflecting local adaptation to temperature. Therefore, lipid remodelling appears limited at the highest temperatures in S. alveolata, suggesting that individuals inhabiting warm environments may be close to their upper thermal tolerance limits and at risk in a changing climate.
    • Literature and science: Social impact and interaction

      Cartwright, John H.; Baker, Brian; University of Chester (ABC-CLIO, 2005-07-31)
      This book discusses the complex relationship between science and literature from Dante and Chaucer through to the twenty-first century. It focuses on science and literature in medieval times, the Elizabethan Renaissance, the seventeenth and eighteenth centuries, nineteenth-century British and American literature and science, themes in science fiction, and the twentieth-century.
    • Llandudno trail questionnaire and workshop

      Tilson, Elaine; Burek, Cynthia V.; Underwood, John; Legg, Colin; University College Chester (Association of UK RIGS Groups, 2004)
      This book chapter discusses the development and production of a geologically focused brochure based on Llandudno.
    • Local adaptation with high gene flow: temperature parameters drive adaptation to altitude in the common frog (Rana temporaria)

      Muir, Anna P.; Biek, Roman; Thomas, R.; Mable, Barbara K.; University of Chester; University of Glasgow; Royal Zoological Society of Scotland (Wiley, 2014-01-20)
      Both environmental and genetic influences can result in phenotypic variation. Quantifying the relative contributions of local adaptation and phenotypic plasticity to phenotypes is key to understanding the effect of environmental variation on populations. Identifying the selective pressures that drive divergence is an important, but often lacking, next step. High gene flow between high- and low-altitude common frog (Rana temporaria) breeding sites has previously been demonstrated in Scotland. The aim of this study was to assess whether local adaptation occurs in the face of high gene flow and to identify potential environmental selection pressures that drive adaptation. Phenotypic variation in larval traits was quantified in R. temporaria from paired high- and low-altitude sites using three common temperature treatments. Local adaptation was assessed using QST -FST analyses, and quantitative phenotypic divergence was related to environmental parameters using Mantel tests. Although evidence of local adaptation was found for all traits measured, only variation in larval period and growth rate was consistent with adaptation to altitude. Moreover, this was only evident in the three mountains with the highest high-altitude sites. This variation was correlated with mean summer and winter temperatures, suggesting that temperature parameters are potentially strong selective pressures maintaining local adaptation, despite high gene flow.
    • The local evaluation of Halton's Healthy Living programme annual reach report, August 2004 - July 2005

      Alford, Simon; Samuels, Tanya; Perry, Catherine (Centre for Public Health Research, University of Chester, 2005-10)
      This project report discusses an evaluation of the services of Halton's Healthy Living Centre, which aims to promote good health, reduce health inequalities, and improve the health of the most disadvantaged in Halton.
    • The local evaluation of Halton's Healthy Living Programme annual reach report, August 2005 - July 2006

      Alford, Simon; Perry, Catherine (Centre for Public Health Research, University of Chester, 2006-11)
      This project report evaluates the Halton Healthy Living Programme, of which there are four key strands - arts, complementary therapy, food and physical activity.
    • The local evaluation of Knutsford’s Healthy Living Network: January 2006 – December 2006

      Alford, Simon; Perry, Catherine (Centre for Public Health Research, University of Chester, 2007-06-01)
      This was an exploratory study designed to evaluate the Knutsford Healthy Living Network (KHLN), one of many Healthy Living Centres (HLC) in the UK. The HLC initiative aims to ensure people can achieve their optimum state of health and well-being. The project report aims to establish the reach of KHLN services by monitoring the level of service usage using a database designed to capture service activity.
    • Local geodiversity action plans (LGAPs) and the community – The Cheshire region LGAP

      Potter, Jacqueline; University of Chester (English Nature, 2005)
    • Local geodiversity action plans - setting to context for geological conservation

      Burek, Cynthia V.; Potter, Jacqueline; University of Chester (English Nature, 2006)
      This booklet discusses local geodiversity action plans (LGAPs) can be established to safeguard and manage the geological resources. A number of case studies are included and recommendations are made.
    • Local geodiversity action plans - sharing good practice workshop, Peterborough, 3 December 2003

      Burek, Cynthia V.; Potter, Jacqueline; Chester College of Higher Education (English Nature, 2004)
      This booklet discusses a workshop held in Peterborough in 2003 to examine good practice in the development of local geodiversity action plans (LGAPs). Six cases studies from Cheshire, County Durham and North Pennines, Leicestershire and Rutland, Staffordshire, Tees Valley, and Warwickshire.
    • Local status and power in area-based health improvement partnerships

      Powell, Katie; Thurston, Miranda; Bloyce, Daniel; University of Sheffield ; Hedmark University College, Norway ; University of Chester (SAGE, 2014-04-01)
      Area-based initiatives (ABIs) have formed an important part of public policy towards more socio-economically deprived areas in many countries. Co-ordinating service provision within and across sectors has been a common feature of these initiatives. Despite sustained policy interest in ABIs, little empirical work has explored relations between ABI providers and partnership development within this context remains under-theorised. This paper addresses both of these gaps by exploring partnerships as a social and developmental process, drawing on concepts from figurational sociology to explain how provider relations develop within an ABI. Qualitative methods were used to explore, prospectively, the development of an ABI targeted at a town in the north west of England. A central finding was that, although effective delivery of ABIs is premised on a high level of coordination between service providers, the pattern of interdependencies between providers limits the frequency and effectiveness of cooperation. In particular, the interdependency of ABI providers with others in their organisation (what is termed here ‘organisational pull’) constrained the ways in which they worked with providers outside of their own organisations. ‘Local’ status, which could be earned over time, enabled some providers to exert greater control over the way in which provider relations developed during the course of the initiative. These findings demonstrate how historically constituted social networks, within which all providers are embedded, shape partnership development. The theoretical insight developed here suggests a need for more realistic expectations among policy makers about how and to what extent provider partnerships can be managed. Keywords: partnership, collaboration, community services, area-based initiatives, organisational pull, figurational sociology
    • Localisation of heat shock proteins in haematological malignancies

      Williams, John H. H.; Hoyle, Christine; Dempsey, Nina C. (University of Liverpool (University of Chester), 2009-08)
      Although a number of HSPs have been shown to be up-regulated in a wide range of human cancers, the full significance of this remains to be determined. The localisation of HSPs seems to be critical in determining their role in cancer cell survival; High intracellular levels (iHsp) appear to be advantageous to the tumour cell, inhibiting key steps in apoptosis, while in some circumstances, surface expression (sHsp) appears to be detrimental to the cell, aiding immune recognition by various effector cells. Consequently, clarifying the importance of HSP cellular location in the cancer setting may lead to the development of novel therapies based upon manipulation of HSP localisation. This thesis had two major aims; (1) to investigate the cellular localisation of HSPs in leukocytes from patients with both myelocytic and lymphocytic malignancies in order to establish relationships between apoptosis and stage of disease (2) to study the synergistic effect of four chemotherapeutic drugs with membrane fluidising agents, compounds which have the potential to modulate HSP localisation. Hsp90 and Hsp27 expression was shown to be restricted to the inside of peripheral blood leukocytes, while Hsp72 was localised both intracellularly and on the cell surface. In CLL, iHsp90 and iHsp27 levels were found to be significantly higher than in control subjects, while surface and intracellular Hsp72 was shown to be expressed either at very high levels or at very low levels. Furthermore, iHsp90 levels were found to be associated with stage of disease, while iHsp27 levels were shown to negatively correlate with levels of apoptosis. CLL patients with stable disease were found to express higher levels of iHsp72 than patients with progressive disease. However, in AML and MDS, levels of all HSPs in peripheral blood were found to be similar to those seen in control subjects, but disease patients showed a much wider range of expression. In AML, levels of sHsp72 positively correlated in all cell types, an observation not made in MDS patients or control subjects. HSP localisation was shown to be affected by membrane fluidising agents, with a movement of Hsp72 and Hsp60 to the cell surface. This effect was not due to proteotoxicity and supports data implicating the cell membrane in the regulation of HSP responses. This manipulation of HSP localisation and the increase in membrane fluidity resulted in increased sensitivity of CLL cells to three chemotherapeutic agents and points to the possibility that manipulation of membrane fluidity, may have significant value in the development of new treatment regimes.
    • The long non-coding RNA NEAT1 regulates cell survival in breast cancer cell lines

      Almnaseer, Zainab; Pickard, Mark R.; Mourtada-Maarabouni, Mirna; Keele University, United Kingdom (NCRI Cancer Conference 2015 Abstracts, 2015)
      Background Nuclear long non-coding RNAs (LncRNAs) regulate various cellular processes including the organization of nuclear sub-structures, the alteration of chromatin state, and the regulation of gene expression. Nuclear Enriched Abundant Transcript 1 (NEAT1) is a nuclear lncRNA transcribed from chromosome 11q13. Two transcripts are produced from the NEAT1 gene, 3.7-kb NEAT1_v1 and 23-kb NEAT1_v2. Both isoforms participate in the formation of the nuclear paraspeckles . NEAT1 is reported to be overexpressed in prostate cancer and a direct transcriptional target of hypoxia-inducible factor in many breast cancer cell lines. The aims of this study were to determine the effects of silencing NEAT1 on breast cancer cell survival. Method MCF7 and MDA-MB 231 cells were transfected with siRNAs to different NEAT1 sequences or NEAT1 antisense oligonucleotides (ASO). Controls received scrambled siRNA or scrambled oligonucleotide, as appropriate. In some experiments, cells were exposed to ultraviolet-C (UV-C) light post-transfection to induce apoptosis, and then culture viability and apoptosis were assessed. NEAT1 expression was evaluated by qRT-PCR TaqMan® analysis. Results In MCF7 and MDA-MB-231 cells, siRNA-mediated silencing of NEAT1 reduced basal survival and after UV-C irradiation and decreased their colony forming ability. NEAT1 ASOs were more effective in silencing NEAT1 and caused a greater reduction in cell viability. NEAT1 silencing also affected cell cycle profile by enhancing the proportion of cells in G0/G1 phase. Conclusion NEAT1 regulates the survival of Breast cells. Down regulation of NEAT1 expression decreased cell survival, proliferation and modulated cell cycle progression of breast cancer cells, indicating a link between the NEAT1 expression levels and carcinogenesis of breast cancer.
    • Long non-coding RNAs: new opportunities and old challenges in cancer therapy

      Williams, Gwyn T.; Pickard, Mark R.; Keele University; University of Chester (AME Publishing Company, 2016-09)
      No abstract - invited commentary
    • Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle

      Nye, Gareth; Sakellariou, Giorgos; Lightfoot, Adam; Pearson, Timothy; Wells, Nicola; McArdle, Anne; Jackson, Malcolm; Giakoumaki, Ifigeneia; Griffiths, Richard; University of Liverpool (Faseb Journal, 2016-08-22)
      Age-related skeletal muscle dysfunction is the underlying cause of morbidity that affects up to half the population aged 80 and over. Considerable evidence indicates that oxidative damage and mitochondrial dysfunction contribute to the sarcopenic phenotype that occurs with aging. To examine this, we administered the mitochondria-targeted antioxidant mitoquinone mesylate {[10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cyclohexadien-1-yl)decyl] triphenylphosphonium; 100 μM} to wild-type C57BL/6 mice for 15 wk (from 24 to 28 mo of age) and investigated the effects on age-related loss of muscle mass and function, changes in redox homeostasis, and mitochondrial organelle integrity and function. We found that mitoquinone mesylate treatment failed to prevent age-dependent loss of skeletal muscle mass associated with myofiber atrophy or alter a variety of in situ and ex vivo muscle function analyses, including maximum isometric tetanic force, decline in force after a tetanic fatiguing protocol, and single-fiber-specific force. We also found evidence that long-term mitoquinone mesylate administration did not reduce mitochondrial reactive oxygen species or induce significant changes in muscle redox homeostasis, as assessed by changes in 4-hydroxynonenal protein adducts, protein carbonyl content, protein nitration, and DNA damage determined by the content of 8-hydroxydeoxyguanosine. Mitochondrial membrane potential, abundance, and respiration assessed in permeabilized myofibers were not significantly altered in response to mitoquinone mesylate treatment. Collectively, these findings demonstrate that long-term mitochondria-targeted mitoquinone mesylate administration failed to attenuate age-related oxidative damage in skeletal muscle of old mice or provide any protective effect in the context of muscle aging
    • A longitudinal analysis of performance, growth and maturation in youth rugby league players: Implications for talent identification and development

      Worsfold, Paul R.; Twist, Craig; Lamb, Kevin L.; Waldron, Mark (University of Chester, 2013)
      This study monitored a cohort of youth rugby league players from one professional club in England, across three competitive seasons (under-15 to under-17 age group). The aims were to establish which dimensions of growth and performance characterized players who were either coach-selected or unselected each season and to evaluate annual developments in growth and performance. It was also necessary to establish the credibility of various measurement techniques that are implicated in the talent identification process. In the assessment of sprint performance, GPS measurements systematically underestimated both distance and timing gate speed but can be used to reliably evaluate sprint performance, particularly for measurements of peak speed (95% Limits of Agreement (LoA) = 0.00 ± 0.8 km·h-1; CV = 0.78%). Using a larger sample of youth team sport players (n = 60), multiple linear regression analysis, incorporating mean and peak GPS speeds as predictors of timing gate speed, yielded a prediction model that was able to provide a valid alternative to timing gates in the assessment of sprint performance over 30 m. With regards to the reliability of assessments of sport-specific skill in youth rugby league players, no comparisons met the pre-determined analytical goal of ‘perfect agreement’, meaning that up to 56% of players’ skill could be misinterpreted. The credibility of such assessments should be questioned and alternative tests considered. In the period between the under-15 and under-16 group, there were large annual increments in speed (5.02 Δ%), force (13.82 Δ%) and power (19.85 Δ%) generated over 10 m sprint intervals and predicted vertical jumping power (13.02 Δ%), with concomitant developments in body mass (5.14 Δ%), lean body mass (3.20 Δ%) and predicted muscle of the quadriceps (10.12 Δ%). A discriminant function analysis also highlighted 30 m force and 10 m acceleration as significant predictors of selected players in the under-15 group and under-16 group, explaining 47.3% and 40.7% of the between-group variance, respectively – which was the case independent of age at peak maturity. However, there were 5 no differences between selected and unselected players in the under-17 group. During match time, there were differences between selected (57.1 ± 11.9 min) and unselected (44.1 ± 12.3 min) players for average playing interval in the under-16 group. In turn, selected players covered more total distance (5181.0 ± 1063.5 m c.f. 3942.6 ± 1108.6 m, respectively; P = 0.012) and high intensity distance (1808.8 ± 369.3 m c.f. 1380.5 ± 367.7 m, respectively; P = 0.011) than unselected players. When age at peak height velocity (PHV) was statistically controlled, only distance in zone 3 and summated-HR remained higher in the selected players of the under-16 group. Conversely, higher values amongst the unselected under-16 players for total and relative distance in zone 4, 5 and high intensity were revealed. There was a relationship in the under-15 group (R = 0.702, P < 0.001), under-16 group (R = 0.607, P < 0.001) and under-17 group (R = 0.671, P < 0.006) between the number of successful ball carries and 10 m sprinting force, thus supporting the use of 10 m sprinting force as a predictor of match performance. The relationship (r = 0.51, P = 0.044) between aerobic capacity and HIT·min-1 in the under-17 group also provides preliminary evidence of aerobic endurance as a potential predictor of match running intensity. It was concluded that players who are coach-selected are not characterized by match related performance variables but are offered greater match exposure during the under-16 age group, resulting in larger running distances. Unselected players are unrewarded for higher intensity running during matches when maturational age is statistically controlled and are also equally effective in regard to tackling and ball carrying outcomes. These results collectively indicate the inability of match performance measurements to contribute to talent identification processes in players of this type. The changes in growth and performance should be used to guide talent development practices of rugby league coaches. In particular, the assessment of force (i.e. the product of acceleration and body mass) should be considered as an important factor in differentiating between higher and lower ability players, as well as relating to match performance.
    • A look at life

      Lewis, Stephen J.; Chester College of Higher Education (1996-11-14)
    • Low leukotriene B4 receptor 1 leads to ALOX5 downregulation at diagnosis of chronic myeloid leukemia

      Lucas, Claire; Harris, Robert; McDonald, Elizabeth; Giannoudis, Athina; Clark, Richard; University of Liverpool, Royal Liverpool University hospital, (Ferrata Storti Foundation, 2014-11-01)
      ALOX5 is implicated in chronic myeloid leukemia development in mouse leukemic stem cells, but its importance in human chronic myeloid leukemia is unknown. Functional ALOX5 was assessed using an LTB4 ELISA and ALOX5, and LTB4R1 mRNA expression was determined via a TaqMan gene expression assay. LTB4R1 and 5-LOX protein levels were assessed by cell surface flow cytometry analysis. At diagnosis ALOX5 was below normal in both blood and CD34(+) stem cells in all patients. On treatment initiation, ALOX5 levels increased in all patients except those who were destined to progress subsequently to blast crisis. LTB4 levels were increased despite low ALOX5 expression, suggesting that the arachidonic acid pathway is functioning normally up to the point of LTB4 production. However, the LTB4 receptor (BLT1) protein in newly diagnosed patients was significantly lower than after a period of treatment (P<0.0001). The low level of LTB4R1 at diagnosis explains the downregulation of ALOX5. In the absence of LTB4R1, the arachidonic acid pathway intermediates (5-HEPTE and LTA4) negatively regulate ALOX5. ALOX5 regulation is aberrant in chronic myeloid leukemia patients and may not be important for the development of the disease. Our data suggest caution when extrapolating mouse model data into human chronic myeloid leukemia.
    • Low pulse pressure does not reduce the efficacy of a heart failure exercise programme

      Leslie, Rosalind; Buckley, John P. (New Cross Hospital, Wolverhampton ; University of Chester, 2012-03)
      Patients with chronic heart failure (CHF) may have low pulse pressures (PP). This retrospective study was undertaken to analyse the relationship between PP and outcomes of a 12-week exercise training programme. Data analysed from 86 patients (69 male) aged 40 to 86 years, included: PP, functional capacity (metabolic equivalents [METS]) and quality of life (QoL) using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Median pre-training PP was 54 ± 19 mmHg. Functional capacity for the same heart rate (estimated 60% heart rate reserve) and Borg rating of 13 increased from 3.6 ± 1.1 to 4.0 ± 1.2 METS (p=0.0005); MLHFQ scores improved from 26 ± 19 to 22 ± 20 (p=0.0005). There was a high correlation between PP and systolic blood pressure pre- and post-training (pre: r=0.77, p=0.0005; post: r=0.80, p=0.0005). Changes in all the above outcomes were independent of pre-training PP. In conclusion, low PP did not reduce the efficacy of an exercise training programme, indicating that CHF patients with low PP can benefit similarly to those with normal/raised PP.
    • The low-risk perception of developing type 2 diabetes among women with a previous history of gestational diabetes

      Sharma, Manisha; Purewal, Tejpal Singh; Fallows, Stephen; Kennedy, Lynne; Edge Hill University; Royal Liverpool Hospital; University of Chester (Wiley, 2019-02-12)
      We conducted a qualitative study to explore the risk perceptions, health beliefs and behaviours of women with a previous history of gestational diabetes mellitus (GDM). Women aged between 18 to 40 years (at the time of pregnancy) with a previous history of GDM, registered at The Royal Liverpool University Hospital, United Kingdom, participated in individual, semi-structured, face-to-face interviews. Qualitative data from seven participants were collected until data saturation and were analysed by thematic analysis. Participants had a low-risk perception of the future risk of developing diabetes. Some believed that their risk was the same as that of any other woman without a history of GDM, and some other participants were not aware of the risk at all and perceived GDM as a temporary health condition with no long-term risks. Participants showed some understanding of a healthy lifestyle in general. However, most of the information was self-acquired by participants and not linked to the future risk of developing diabetes. The findings of this research also indicated a contrast between the high perception of the immediate risks of complications during the pregnancy and low long-term risk of developing diabetes after pregnancy associated with GDM. Participants received healthy lifestyle advice during their pregnancy, but none of them reported involvement in any postnatal health education, intervention or counselling as recommended by 2008 and 2014 NICE guidelines. The low-risk perception impedes positive health behaviour required to overcome the barriers against a healthy lifestyle. This was a small research project but the findings warrant scope for more research in this field. A larger study might promote the development of a well-structured, long-term follow-up health intervention programme, incorporating a reminder system for annual diabetes screenings to improve the risk perception and reduce the risk for the development of type 2 diabetes in this population.