• Rapid Colorimetric Determination of Methylglyoxal Equivalents for Manuka Honey

      Kwok, T. H.; Kirkpatrick, G.; Yusof, H. I. Mohd; Portokalakis, I; Nigam, Poonam S.; Owusu-Apenten, Richard K.; University of Chester, University of Ulster (Sciencedomain international, 2016-06-14)
      Aims: Realization of a rapid colorimetric assay for monitoring levels of methylglyoxal and other dicarbonyl compounds from Manuka honey. Methods: N-acetyl cysteine (NAC) and 2, 4-dinitrophenylhydrazine (DNPH) were adopted as reagents for methylglyoxal colorimetric analysis of honey at 288 or 525 nm, respectively. Results and Discussion: NAC and DNPH produced linear responses for methylglyoxal with:(i) regression coefficient (R2) equal to 0.99 or 0.97, (ii) molar absorptivity (measure of sensitivity) equal to 287±11 or 14189±498 M-1 cm-1, (iii) a minimum detectable concentration (MDC) of 0.18 mM vs 7.3 µM, (iv) upper linearity limit of linearity (ULL) equal to 4mM or 83 µM, and (v) a day-to-day precision of 16.0 and 18.3%, respectively. Low interferences occurred with reducing sugars, glyoxal or 3-deoxy-D-glucosone. For honey with a unique manuka factor (UMF) rating 5+ to UMF18+, the net concentration of dicarbonyl compounds ranged from 1069 mg-methylglyoxal equivalence per kg (mg MeGEq /kg) to 2208 (mg MeGEq /kg) using the NAC assay. For the DNPH assay, the apparent dicarbonyl concentration was 350 to 1009-mg MeGEq /kg honey. Measures of methylglyoxal equivalences were strongly correlated with the UMF rating for honeys (R2=0.98-0.99). Conclusion: The proposed colorimetric analysis of methylglyoxal equivalence in Manuka honey is feasible proposition. Further work is needed for method validation.
    • A re-appraisal of the reliability of the 20 m multi-stage shuttle run test

      Lamb, Kevin L.; Rogers, Louise; University of Chester (Springer-Verlag, 2007-03-07)
    • "Read with caution": A reply to Pickett et al

      Smith, Dave; Wright, Caroline J.; Bruce-Low, Stewart; Hale, Bruce; University College Chester ; University College Chester ; University College Chester ; Penn State University (British Association of Sport and Medicine, 2005-10-21)
      This article critiques a study by Pickett Lewis & Cash titled "Men, muscles, and body image: comparisons of competitive bodybuilders, weigh trainers, and athletically active controls" published in the British Journal of Sports Medicine in 2005.
    • Recapture rates and habitat associations of White-faced Darter Leucorhinnia dubia on Fenn's and Whixall Moss, Shropshire, UK

      Davies, Rachel; von Hardenberg, Achaz; Geary, Matthew; Conservation Biology Research Group, Department of Biological Sciences, University of Chester, CH1 4BJ (British Dragonfly Society, 2018-10-01)
      Land-use change and habitat loss are important drivers of biodiversity decline at both global and local scales. To protect species from the impacts of land-use change it is important to understand the population dynamics and habitat associations across these scales. Here we present an investigation into the survival and habitat preferences of Leucorrhinia dubia at the local scale at Fenn’s and Whixall Moss, Shropshire, UK. We used mark-release-recapture methods to investigate survival and used sightings of individual dragonflies along with habitat data to investigate habitat preference. We found that survival between capture-visits was very low and that L. dubia showed a clear preference for the open moss habitat on this site. In both cases, we found that the detectability, either through sightings or recaptures, was potentially very low and suggest that this should be taken into account in future analyses. We suggest that by encouraging recorders to submit complete lists and to repeat visits to sites detectability could be easily estimated for dragonfly species and incorporating this into analyses would improve estimates fo population trends and habitat associations.
    • Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells.

      Yacqub-Usman, Kiren; Pickard, Mark R.; Williams, Gwyn T.; Keele University (Wiley, 2015-02-03)
      BACKGROUND: New therapies are required for castrate-resistant prostate cancer (CRPC), and growth-arrest specific 5 (GAS5) lncRNA, which riborepresses androgen receptor action, may offer novel opportunities in this regard. This lncRNA promotes the apoptosis of prostate cancer cells and its levels decline as prostate cancer cells acquire castrate-resistance, so that enhancing GAS5 expression may improve the effectiveness of chemotherapies. Since GAS5 is a member of the 5' terminal oligopyrimidine gene family, we have examined mTOR inhibition as a strategy to increase GAS5 expression. Furthermore, we have determined if GAS5 itself mediates the action of mTOR inhibitors, as demonstrated for other chemotherapeutic agents in prostate cancer cells. METHODS: The effects of mTOR inhibitors on GAS5 lncRNA levels and cell growth were determined in a range of prostate cancer cell lines. Transfection of cells with GAS5 siRNAs and plasmid constructs was performed to determine the involvement of GAS5 lncRNA in mTOR inhibitor action. RESULTS: First generation mTORC1, combined mTORC1/mTORC2 and dual PI3K/mTOR inhibitors all increased cellular GAS5 levels and inhibited culture growth in androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU 145) cell lines. The latter exhibited low endogenous GAS5 expression, and GAS5 silencing in LNCaP and 22Rv1 cells decreased the sensitivity to mTOR inhibitors, whereas transfection of GAS5 lncRNA sensitized PC-3 and DU 145 cells to these agents. CONCLUSION: mTOR inhibition enhances GAS5 transcript levels in certain prostate cancer cell lines. This selectivity is likely to be related to endogenous GAS5 expression levels, since GAS5 lncRNA is itself required for mTOR inhibitor action in prostate cancer cells.
    • Recognising the potential role of native ponies in conservation management

      Stanley, Christina R.; Fraser, Marecia; Hegarty, Matt; University of Chester; Aberystwyth University (Elsevier, 2019-04-28)
      Population control of feral horses has been the subject of public debate in many parts of the world in recent years due to wide-reaching ecological and societal impacts. However, the feral populations in these high-profile cases are not ‘native’ but are instead descended from animals which escaped from or were released by settlers. This paper considers i) the potential role of indigenous equids as conservation grazers within native ecosystems currently in poor condition, and ii) the value of supporting semi-wild native ponies specifically. We argue that the high ecological overlap between ponies and cattle reported in a range of studies means that they should be considered as alternative tools for conservation management, particularly in scenarios where there is a need to reduce the dominance of plant species avoided by more-selective small ruminants such as sheep. Semi-wild ponies could be particularly suited to conservation grazing because their genomes have been predominately shaped by natural and not artificial selection, meaning they may have adaptations no longer present in domesticated equids. With agricultural and environmental policy in the EU and UK under major review, it is anticipated that the wider delivery of public goods, rather than primary production, will be prioritised under future subsidy payment schemes. Recognising the value of native ponies as conservation grazers would broaden the range of routes by which land managers could achieve biodiversity gain, while simultaneously supporting at-risk equine genotypes.
    • Recovery of high mountain Alpine lakes after the eradication of introduced brook trout Salvelinus fontinalis using non-chemical methods

      Tiberti, Rocco; Bogliani, Giuseppe; Brighenti, Stefano; Iacobuzio, Rocco; Liautaud, Kevin; Rolla, Matteo; von Hardenberg, Achaz; Bassano, Bruno; University of Pavia; Gran Paradiso National Park; University of Trento; Fondazione Edmund Mach; Swansea University; University of Chester (Springer, 2018-10-31)
      Fish stocking is a serious threat to originally fishless mountain lakes. We used non-chemical eradication methods (i.e. gillnetting and electrofishing) in four high mountain lakes in the Gran Paradiso National Park (Western Italian Alps) to eradicate alien brook trout Salvelinus fontinalis. Data of amphibians, macroinvertebrates, zooplankton, chlorophyll-a, nutrient concentrations, and water transparency were used as indicators of the recovery process. All treated lakes were returned to their original fishless condition in spite of their different sizes and habitat complexity, without permanent negative side-effects for native species. Several ecological indicators showed that many impacts of introduced fish can be reversed over a short time period following eradication. The present study adds to a still growing body of specialized literature on the recovery of habitats after the eradication of alien species and provides further evidence that physical eradication methods are effective and can be part of a more general strategy for the conservation of high mountain lake biota.
    • Rediscovering and conserving the Lower Palaeozoic 'treasures' of Ethel Woods (nee Skeat) and Margaret Crosfield in northeast Wales

      Burek, Cynthia V.; Malpas, Jacqui A.; University of Chester ; NEWRIGS, Millenium EcoCentre in Wrexham (2007-08-01)
      This book chapter explores, within a historical context, the importance of geoconservation of not only sitesbut also artefacts, collections and specimens as well as letters and original documents. It sets but the search and finding of sites in northeast Wales and materials thought lost then found and the subsequent nomination of Regionally Important Geological/Geomorphological Sites (RIGS) conservation status of the sites to safeguard them for the future. It is important to note that RIGS can be designated for their historical value alone, which is in contrast to Sites of Special Scientific Inleresi (SSSIs), which are protected solely for their national scientific and research value. The role of Ethel Woods (nee Skeat) and Margaret Crosfield in developing an understanding of the geological history of northeast Wales had been lost over time. This paper contains biographical sketches of the two women, followed by their Lower Palaeozoic lithological, structural and grap-tolite research and places it in an historical context. This case study illustrates how female curiosity, perseverance and attention to detail unearthed previously forgotten treasures. The importance of conserving their sites, specimens and sketch field notebooks in our electronic and throw-away age is vital. The role of the North East Wales Regionally Important Geological/ Geomorphological Sites (NEWRIGS) in conserving this information is put forward as an example of good practice.
    • Reduction in high intensity activity during senior elite rugby league matches

      Sykes, Dave; Twist, Craig; Lamb, Kevin L.; Nicholas, Ceri; University of Chester (2009-06)
    • A reflective account of a consultation in abortion care

      Astbury-Ward, Edna; Western Cheshire PCT (Scutari Projects, 2009-05-06)
      This article presents a reflective account of a consultation in a pre-assessment clinic for women requesting abortion. The reflection is based on Johns' model. Reflection enabled the author to address important issues that the consultation raised. These included the realisation that nurses do not always have to understand why patients make the choices they do, and the importance of allocating sufficient time for sensitive consultations.
    • Regional differences in mechanical and material properties of femoral head cancellous bone in health and osteoarthritis

      Brown, Sharon J.; Pollintine, Phillip; Powell, Diane E.; Davie, Michael W. J.; Sharp, Christopher A.; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry/Chester College of Higher Education ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry ; Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry (Springer, 2002-09)
      Osteoarthritis (OA) is a debilitating condition common among the aging population. In this study we have determined mechanical and material properties of cancellous bone cores from two differently loaded regions of femoral heads obtained from healthy subjects and those with end-stage osteoarthritis. Densitometric properties were determined prior to compression testing for Young's modulus (EC) and yield strength (sy), after which bones were powdered for analysis of collagen and mineral content. In both OA and normal cancellous bone, volumetric bone mineral density (BMDv), apparent density (rA), EC, and sy were systematically greater in the superior than in the inferior region (P<0.05). In the OA inferior region, median BMDv (0.434 g-cm-3) and rA (0.426 g-cm-3) were significantly greater than in normals (0.329 and 0.287 g-cm-3, respectively, both P<0.05) reflecting an increased amount of tissue. The mineral:collagen ratio was decreased in OA, but this was only significant in the superior region (P<0.008). Relationships between EC and both BMDv and rA were weaker in OA bone cores (r2 = 0.66 and r2 = 0.59) than in normals (r2 = 0.86 and r2 = 0.77, respectively). Likewise, sy and both BMDv and rA were weaker in OA (r2 = 0.74 and r2 = 0.70) than in normals (r2 = 0.83 and r2 = 0.77, respectively). For the same value of density measure, EC and sy tended to be lower in OA bone when compared with normal bone. In conclusion, femoral head cancellous bone mass in end-stage osteoarthritis is increased but undermineralized, and is neither stiffer nor stronger than normal cancellous bone.
    • Regulation and roles of Ca2+ stores in human sperm.

      Correia, Joao; Michelangeli, Francesco; Publicover, Stephen; University of Birmingham (Bioscientifica, 2015-05-11)
      [Ca(2)(+)]i signalling is a key regulatory mechanism in sperm function. In mammalian sperm the Ca(2)(+)-permeable plasma membrane ion channel CatSper is central to [Ca(2)(+)]i signalling, but there is good evidence that Ca(2)(+) stored in intracellular organelles is also functionally important. Here we briefly review the current understanding of the diversity of Ca(2)(+) stores and the mechanisms for the regulation of their activity. We then consider the evidence for the involvement of these stores in [Ca(2)(+)]i signalling in mammalian (primarily human) sperm, the agonists that may activate these stores and their role in control of sperm function. Finally we consider the evidence that membrane Ca(2)(+) channels and stored Ca(2)(+) may play discrete roles in the regulation of sperm activities and propose a mechanism by which these different components of the sperm Ca(2)(+)-signalling apparatus may interact to generate complex and spatially diverse [Ca(2)(+)]i signals.
    • Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy.

      Pickard, Mark R.; Williams, Gwyn T.; Keele University, United Kingdom (2014-05-01)
      The putative tumour suppressor and apoptosis-promoting gene, growth arrest-specific 5 (GAS5), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.
    • Regulation of Inducible Nitric Oxide Synthase by Arabinoxylans with molecular characterization from Wheat Flour in Cultured Human Monocytes

      Zhengxiao, Zhang; Christopher, Smith; Jason, Ashworth; Weili, Li; Manchester Metropolitan University; University of Chester (Wiley, 2018-01-08)
      The immunomodulatory activity of the arabinoxylans (AXs) extracts from cereal sources has been reported to impart health benefits in terms of immune enhancement. This study investigated the effect of enzymatic extraction on extraction yield and structure of AXs from wheat flour pentosan fraction. Under the optimised conditions, the extraction yield of AXs reached up to 81.25%. Furthermore, the study determined whether water-extracted AXs (WEAXs) and enzyme-extracted AXs (E-WEAXs) from wheat flour were able to differentially stimulate nitric oxide (NO) secretion through increased levels of inducible nitric oxide synthase (iNOS) in human U937 monocytes. The results indicated that AXs concomitantly induced (P < 0.05) both NO and iNOS productions in U937 monocytes compared to untreated cells. Compared with WEAXs, E-WEAXs resulted in a higher proportion of low Mw (1–10 KDa) AXs (49.51% vs. 19.11% in WEAXs), a higher A/X ratio (0.83 vs. 0.48 in WEAXs) and a higher yield (12.83 ± 0.35% vs. 7.54 ± 0.47% in WEAXs). Moreover, E-WEAXs induced significantly (P < 0.05) greater NO and iNOS production per million viable cells (61.8 ± 2.7 μm and 42.41 ± 3.83 ng respectively) than WEAXs (51.6 ± 2.6 μm and 33.46 ± 1.48 ng, respectively). The findings suggest AXs may heighten innate immune activity in the absence of infection or disease through an iNOS-mediated stimulation of NO production. The immunomodulatory activity of the wheat-derived AXs was enhanced by enzyme treatment, with low Mw and high A/X ratio associated with elevated NO/iNOS levels in human monocytes compared to water extraction.
    • Regulation of Nitric Oxide Synthase Expression by Structure Modified Arabinoxylans from Wheat Flour in Cultured Human Monocytes

      Zhang, Zhengxiao; Smith, Christopher J.; Ashworth, Jason J.; Li, Weili; Manchester Metropolitan University; University of Chester (Wiley, 2018-01-08)
      The immunomodulatory activity of the arabinoxylans (AXs) extracts from cereal sources has been reported to impart health benefits in terms of immune enhancement. This study investigated the effect of enzymatic extraction on extraction yield and structure of AXs from wheat flour pentosan fraction. Under the optimised conditions, the extraction yield of AXs reached up to 81.25%. Furthermore, the study determined whether water-extracted AXs (WEAXs) and enzyme-extracted AXs (E-WEAXs) from wheat flour were able to differentially stimulate nitric oxide (NO) secretion through increased levels of inducible nitric oxide synthase (iNOS) in human U937 monocytes. The results indicated that AXs concomitantly induced (P < 0.05) both NO and iNOS productions in U937 monocytes compared to untreated cells. Compared with WEAXs, E-WEAXs resulted in a higher proportion of low Mw (1–10 KDa) AXs (49.51% vs. 19.11% in WEAXs), a higher A/X ratio (0.83 vs. 0.48 in WEAXs) and a higher yield (12.83 ± 0.35% vs. 7.54 ± 0.47% in WEAXs). Moreover, E-WEAXs induced significantly (P < 0.05) greater NO and iNOS production per million viable cells (61.8 ± 2.7 μm and 42.41 ± 3.83 ng respectively) than WEAXs (51.6 ± 2.6 μm and 33.46 ± 1.48 ng, respectively). The findings suggest AXs may heighten innate immune activity in the absence of infection or disease through an iNOS-mediated stimulation of NO production. The immunomodulatory activity of the wheat-derived AXs was enhanced by enzyme treatment, with low Mw and high A/X ratio associated with elevated NO/iNOS levels in human monocytes compared to water extraction.
    • The regulation of osteoprotegerin and dickkopf-1 production in osteoblastic cells

      McCarthy, Helen S. (University of ChesterCharles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestry, 2011-06)
      Bone is a highly specialised living tissue and has both mechanical and metabolical functions. Remodelling of the bone ensures a healthy bone mass and is regulated by a trio of secreted proteins, namely receptor-activator of NFKB (RANK), receptor-activator of NFKB ligand (RANKL) and osteoprotegerin (OPG). OPG, a major regulator of osteoclastogenesis, bone resorption and vascular calcification, is produced by various cell types including mesenchymally derived cells, particularly osteoblastic cells. Wnt signalling also plays a role in maintaining healthy bone mass. Dickkopf- 1 (DKK-1) is a soluble inhibitor of Wnt signalling and its excessive expression contributes to bone loss in rheumatoid arthritis and multiple myeloma. Recently, NDKK-1 has been demonstrated to be over-produced in osteoblasts of patients with Paget's disease of bone (PDB). The osteoblastic cell lines MG63 and Saos-2 were subjected to a series of different growth factors, hormones and cytokines to investigate the production of OPG, DKK-1 and the expression of various Wnt proteins. These results demonstrate that during standard culture conditions, both OPG and DKK-1 production in osteoblastic cells depend on a factor present in serum. Serum deprivation resulted in the up-regulation of Wnt4 and Wnt11, while down-regulating the expression of Wnt7b. Serum-induced OPG and DKK-1 production and Wnt expression was found to be regulated via a number of different signalling pathways. OPG production and expression was stimulated by platelet-derived growth factor-AB (PDGF-AB) not only in MG63 and Saos-2 osteosarcoma cells, but also a mouse pre-osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (BMSC). PDGF-AB was shown to act through the PDGF receptor, PKC, PI3K, ERK and P38 and not via NFKB or JNK. PDGF isoforms AA, BB and AB demonstrated a similar stimulation of OPG production. The importance of PDGF in fracture healing suggests a role for OPG production in countering bone resorption during the early phase of this process. BIO, an inhibitor of canonical Wnt signalling resulted in the down-regulation of DKK-1 and the up-regulation of WntSa. Phorbol ester (PE), a known stimulator of PKC resulted in the up-regualtion of DKK-1, Wnt4, WntTa and Wnt16. The effects of PE were inhibited by bisindolymaleamide but not staurosporine. DKK-1 production, but not expression, was observed to be stimulated by calcium along with an up-regulation of WntTb and a down-regulation of WntWa and Wnt11. Incubation of pre-stimulated cells with Triton-X demonstrated the ability of calcium to increase DKK-1 secretion. DKK-1 was shown to be significantly elevated in the serum of PDB patients compared to healthy controls and did not correlate with ALP levels. Immunohistochemistry demonstrated that DKK-1 production is increased in both osteoblasts and fibrotic cells within the marrow cavity in PDB patients compared to fracture callus. B-catenin was found to be localised to intercellular membranes of plump osteoblasts, demonstrating its alternate role as a cell adhesion protein. DKK-1 therefore may be a useful biomarker of PDB and that Dkk-1 may play a central role in the aetiology of PDB. In summary, the results presented in this thesis have investigated the ways in which OPG and DKK-1 production in osteoblastic cells can be modulated with various effectors and the effect of Wnt signalling. These results may therefore be beneficial to increase the understanding of bone biology, improve fracture repair and generate further research into the role DKK-1 and the osteoblast in the aetiology of PDB to enable improved treatments to be developed.
    • Regulation of the cell cycle and cell death by protein phosphatase 4 in breast cancer cell lines

      Mohammed, Hiba N.; Pickard, Mark R.; Williams, Gwyn T.; Mourtada-Maarabouni, Mirna; Keele University, United Kingdom (NCRI Cancer Conference 2014 Abstracts, 2014)
      Background At the molecular level, cell death is often regulated by the level of phosphorylation of particular proteins, i.e. by the balance of between opposing kinase and phosphatase activities on those proteins. Protein phosphatase 4 (PP4) is a PP2A-related serine/threonine phosphatase. PP2A has already been implicated in the control of cell proliferation, cell cycle and tumorigenesis. Using a functional expression cloning strategy, we have previously identified the catalytic subunit of PP4 (PP4c) as an important gene influencing the regulation of both apoptosis and cell proliferation in human leukaemic cell lines and in normal lymphocytes. The aims of this study were to examine the effects of PP4c overexpression and silencing on the cell death and survival of breast cancer cell lines. Method MCF7 and MDA-MB-231 cells were transfected with pcDNA3.1 encoding PP4c (pcDNA3-PP4c) or siRNAs to different PP4c sequences. Cells transfected with scrambled siRNA or empty vector were considered as controls. Culture viability, apoptosis and cell cycle were assessed post transfection. Results In MCF7 and metastatic MDA-MB-231 cells, PP4c over-expression exerted an inhibitory effect on cell proliferation, enhanced spontaneous apoptosis and decreased their colony forming ability. Conversely, siRNA mediated silencing of PP4 enhanced the proliferation and survival of MCF7 and MDA-MB-231 cells, affected cell cycle kinetics by enhancing the proportion of cells in S and G2/M phases, increased the colony forming ability and stimulated the anchorage independent growth. Conclusion PP4c promotes cell death and inhibits proliferation in breast cells, suggestive of a role of PP4c as tumour suppressor gene. Down regulation of PP4c expression increases cell survival, proliferation and anchorage independent growth of breast cancer cells, indicating a potential link between the PP4c expression levels, tumorigenesis and metastasis.
    • ‘Regurgitation and reingestion’ (R/R) in great apes: A review of current knowledge

      Hill, Sonya, P.; University of Chester; University of Cambridge (Wiley, 2018-08-02)
      Research indicates that regurgitation and reingestion (R/R) is a relatively common behaviour in zoo-housed great apes, with most work to date carried out on Western lowland gorillas Gorilla gorilla gorilla and Chimpanzees Pan troglodytes. It is an abnormal behaviour because great apes are not anatomically adapted to regurgitate their food as part of their normal feeding processes, and because this behaviour is not seen in members of the species living freely in the wild, in conditions that would allow a full behavioural range. In this article, I give an overview of the published literature on R/R in great apes, which suggests that this behaviour is probably multifactorial and may be linked to inappropriate feeding environments (e.g. in terms of nutritional composition of the diet and/or presentation of food), and possibly also social and other factors as well. A similar behaviour to R/R, known as rumination disorder, can also occur in another great ape species, humans, in whom it is classified as a feeding and eating disorder, and there are potential consequences to people’s physical health as a result of oral acid. There have been no known studies to date to identify whether or not similar health consequences can occur in non-human great apes, but the regurgitant has been found to be significantly more acidic in gorillas than the food they ingested originally, meaning it is potentially injurious in non-human great apes. There is much that is not yet known about this behaviour and how to reduce or eliminate it when it does occur, as the research indicates that there are a range of factors involved, and these can vary by individual animal. More research into this behaviour is clearly needed to ensure that zoos and sanctuaries are providing the best possible care for these animals, and I make some suggestions for future research directions.
    • Related flavonoids cause cooperative inhibition of the sarcoplasmic reticulum Ca²⁺ ATPase by multimode mechanisms.

      Ogunbayo, Oluseye A.; Michelangeli, Francesco; University of Birmingham (Wiley, 2014-01-27)
      Flavonoids are group of plant-derived hydroxylated polycyclic molecules found in fruit and vegetables. They are known to bio-accumulate within humans and are considered to have beneficial health effects, including cancer chemoprotection. One mechanism proposed to explain this is that they are able to induce apoptosis in cancer cells by inhibiting a variety of kinases and also the Ca²⁺ ATPase. An investigation was undertaken with respect to the mechanism of inhibition for three flavonoids: quercetin, galangin and 3,6 dihydroxyflavone (3,6-DHF). Each inhibited the Ca²⁺ ATPase with K(i) values of 8.7, 10.3 and 5.4 μM, respectively, showing cooperative inhibition with n ~ 2. Given their similar structures, the flavonoids showed several differences in their mechanisms of inhibition. All three flavonoids stabilized the ATPase in the E₁ conformation and reduced [³²P]-ATP binding. However, both galangin and 3,6-DHF increased the affinity of Ca²⁺ for the ATPase by decreasing the Ca²⁺-dissociation rate constant, whereas quercetin had little effect. Ca²⁺-induced changes in tryptophan fluorescence levels were reduced in the presence of 3,6-DHF and galangin (but not with quercetin), indicating that Ca²⁺-associated changes within the transmembrane helices are altered. Both galangin and quercetin reduced the rates of ATP-dependent phosphorylation and dephosphorylation, whereas 3,6-DHF did not. Modelling studies suggest that flavonoids could potentially bind to two sites: one directly where nucleotides bind within ATP binding site and the other at a site close by. We hypothesize that interactions of these two neighbouring sites may account for both the cooperative inhibition and the multimode mechanisms of action seen with related flavonoids.
    • The Relationship Between Match-Play Characteristics of Elite Rugby League and Indirect Markers of Muscle Damage

      Oxendale, Chelsea; Twist, Craig; Daniels, Matthew; Highton, Jamie M.; University of Chester; St Helens Rugby League Club (Human Kinetics, 2016)
      Purpose: Whilst exercise-induced muscle damage (EIMD) after a rugby league match has been well documented, the specific match actions that contribute to EIMD are unclear. Accordingly, the purpose of this study was to examine the relationship between the physical demands of elite rugby league matches and subsequent EIMD. Methods: Twenty-eight performances were captured using 10 Hz global positioning systems. Upper and lower body neuromuscular fatigue, creatine kinase (CK) and perceived muscle soreness were assessed 24 h before and at 12, 36 and 60 h after a competitive match. Results: High-intensity running was moderately higher in backs (6.6 ± 2.6 m•min-1) compared to forwards (5.1 ± 1.6 m•min-1), whereas total collisions were moderately lower (31.1 ± 13.1 cf. 54.1 ± 37.0). Duration (r = 0.9, CI: 0.77 to 0.96), total distance covered (r = 0.86, CI: 0.7 to 0.95) and distance covered over 18 km•h-1 (r = 0.76, CI: 0.51 to 0.91) were associated with increased CK concentration post-match. Total collisions and repeated high-intensity efforts (RHIE) were associated with large decrements in upper body neuromuscular performance (r = -0.48, CI: -0.74 to 0.02 and r = -0.49, CI: -0.77 to 0.05, respectively), muscle soreness (r = -0.68, CI: -0.87 to -0.1 and r = -0.66, CI: -0.89 to 0.21, respectively), and CK concentration (r = 0.67, CI: 0.42 to 0.85 and r = 0.73, CI: 0.51 to 0.87, respectively). Conclusion: Match duration, high-intensity running and collisions were associated with variations in EIMD markers, suggesting recovery is dependent on individual match demands.