Recent Submissions

  • High speed running and repeated sprinting in male academy football players

    Twist, Craig; Gibson, Neil V (University of Chester, 2019-08)
    High speed running and repeated sprinting are component parts of training and match play among academy football players. Despite players having to self-pace running speed and the intervening recovery periods during match play, the way these qualities are trained and tested are often externally regulated with specific work-to-rest ratios and prescribed intensities. The aims of this thesis were to investigate high speed running separated by externally regulated and self-selected recovery periods under conditions that replicate training and testing practices analogous with football. Under controlled conditions replicating training practices common amongst academy players, Chapter 4 showed that high speed running and repeated sprinting separated by externally regulated recovery periods resulted in running speeds that differed by a smaller magnitude than those used in their prescription. These data question the fidelity of this approach and the ability of players to replicate prescribed running speeds in the field. Data from Chapter 4 also demonstrated that neuromuscular function was likely reduced 14 hours after high speed running (-5.6%; ES –0.44 ± 0.32; P = 0.01) and combination running (-6.8%; ES -0.53 ± 0.47; P = 0.07) . During 10 x 30 m repeated sprints there was a most likely higher percentage decrement (65%; 0.36 ± 0.21; P = 0.12) and most likely increased physiological load evidenced by between sprint heart rate recovery (-58.9%; ES -1.10 ± 0.72; P = 0.05) when sprints were interspersed by self-selected compared to externally regulated recovery periods (Chapter 5). Performance decrements were, however, attenuated in more mature players (Chapter 6). When considering biological maturity, prePHV players displayed a lower percentage decrement (2.1 ± 1.1%) than post-PHV (3.2 ± 2.1%) players across all sprints when recovery periods were externally regulated (37%; ES 0.41 ± 0.51; P = 0.03). When self-selected recovery periods were used, percentage decrement was lower in the post-PHV group. In Chapter 7, ratings of perceived exertion were used to guide 4 running speed and recovery distribution during a high speed running test performed to volitional exhaustion. Peak running speed in the self-paced (21.8 ± 1.4 km·h-1 ) was likely (4.1%: ES 0.63 ± 0.43; P = 0.03) higher than in the externally regulated YYIRT1 (20.9 ± 1.1 km·h-1); however, average running speed in the self-paced (13.5 ± 1.2 km·h-1) was likely (6.5%; ES 0.67 ± 0.51; P = 0.05) slower (12.7 ± 1.6 km·h-1). There was a moderate difference in total between shuttle recovery periods (13.3%; ES 0.58 ± 0.81; P = 0.16) in the self-paced (552 ± 132 s) compared to externally regulated versions (634 ± 125 s) of the YYIRT1. When exposed to running drills separated by self-selected and externally regulated recovery periods, academy footballers allocate insufficient recovery to preserve running performance and are unable to differentiate between sprinting and high speed running when prescribed according to specific speeds (Chapter 4) and subjective ratings of exertion (Chapter 7). Prescribing self-paced high intensity running interspersed with self-selected recovery periods results in higher physiological loads when compared to externally regulated recovery intermissions and therefore should be considered during training programmes that target adaptations in aerobic capacity. Despite this, where coaches are using high speed running programmes to improve speed and/or speed endurance, externally regulated recoveries are likely to result in the preservation of performance across the repetition range and, as such, are more beneficial to the intended adaptation.
  • Perceptions and experiences of occupational sedentary behaviour and cardiometabolic responses to reducing sitting time at work

    Deery, Elizabeth C. (University of Chester, 2020-09-10)
    Sedentary behaviour is linked to cardiometabolic health, independent of physical activity (PA), in a majority of the UK population. The workplace accounts for around 70% of daily sitting time, thus making it a popular domain for intervention. This thesis included a critical review and four studies which evaluated the use of sit-stand desks in relation to; perceptions and experiences; acute blood glucose responses; longerterm cardiometabolic health changes and self-reported use and finally the vascular health changes. Within this thesis a review of the literature was carried out, and examined evidence relating to occupational sedentary behaviour and its impact on health amongst adults, as well as the effectiveness of interventions to reduce occupational sitting time. The review highlighted that whilst many sit-stand desk interventions effectively reduced occupational sitting time, findings regarding both acute and chronic cardiometabolic responses to such interventions were equivocal. The review also highlighted that perceptions of sit-stand desk use are underinvestigated, particularly in the UK context. Study one used focus groups to examine the perceptions and experiences of sit-stand desk work amongst UK based officeworkers. Expected health beliefs and personal health history were important drivers of behaviour change whilst experienced benefits, organisational culture and peers were important in maintaining behaviour change. Study two examined the acute bloodglucose responses to sit-stand desk work using continuous glucose monitoring (CGM) and assessed changes to workplace sitting, standing and stepping time. Objectively measured workplace sitting time decreased by ~50% and total daily sitting percentage reduced from 70% to 45%. However there were no significant differences in postprandial blood glucose excursion between conditions. Occupational sitting time of this sample was much lower than that previously reported within the literature and may explain differences in findings. Study three examined a longer-term (6 and 12 month) intervention, assessing self-reported sitting time, self-reported physical activity and cardiometabolic health markers including anthropometric measurements, predicted aerobic capacity, blood pressure and blood profiles. Self-reported sitting time significantly decreased over 6 and 12 month interventions. A decrease was also seen in the control group prior to the intervention period suggesting a possible trial effect. Despite this change to self-reported sitting, there was no significant impact on cardiometabolic health markers. Study four explored the impact of an 8-week sit-stand desk intervention on flow-mediated dilation (FMD), blood pressure and blood profile whilst measuring fidelity to the intervention using both self-report and objective measures of PA and sitting time. There was a significant decrease in self-report total daily sitting time however, objectively measured sitting time and cardiometabolic health markers did not significantly differ over the intervention period. Moreover, a significant difference was observed between self-report and objectively measured sitting time at midpoint, in the intervention group only. To conclude, whilst sit-stand desks are an attractive means to work, which participants perceive to be of benefit physically, mentally and in their work performance, the installation of sit-stand desks in isolation does not appear to be a sufficient means by which to impact on longerterm occupational sitting time. Additionally, self-report methods may not be a suitable means to measure changes to sitting time during an intervention. Future research should aim to explore the behaviour change techniques effective in reducing occupational sitting time, whether interventions which successfully decrease occupational sitting time bring about cardiometabolic benefits and disparities between perceived and measured outcomes of sit-stand desk interventions on activity levels, health markers, and performance markers.
  • An investigation of canine mesenchymal stem cells and their secretome in the context of spinal cord injury

    Johnson, Eustace; Wood, Chelsea R (University of Chester, 2020-05-26)
    Spinal cord injury (SCI) is a condition that has devastating effects on both humans and animals alike. Damage inflicted causes loss of neural tissue and secondary inflammatory mechanisms produce an inhibitory environment that results in partial or complete loss of motor and sensory functions. Additionally, SCI can cause multisystem issues such as organ failures, infections, muscle atrophy and decrease in mental health. Coupled with emotional and financial burdens, these effects can reduce quality of life. Mesenchymal Stem Cells (MSC) are known to have immunomodulatory, angiogenic and paracrine activity, all of which are beneficial to wound healing following SCI. Pre-clinical studies have shown encouraging results of MSC therapy for SCI, however replication of results has been difficult to achieve in the clinic. Dogs also suffer from SCI and show the same heterogenous nature and pathophysiology of SCI as humans. This provides a good potential clinical model for MSC therapies for SCI, as well as providing benefit in the veterinary clinic. Therefore, the overall aim of this study was to assess if canine MSC (cMSC) and cMSC secretome (conditioned medium; CM) could potentially be used for treatment of SCI in veterinary clinics, simultaneously providing model data that could be translated into the human clinic. It was first required to confirm efficacy of cMSC when used to treat other conditions in dogs, such as arthritis, along with safety of autologous transplantation. Characterisation of both cMSC phenotype and paracrine (angiogenic and neurogenic) activity was confirmed using ISCT criteria and the established cell lines EA.hy926 and SH-SY5Y. Further examination showed that exposure to certain elements of the injured spinal cord, such as CSPG which are found within the inhibitory glial scar, exerted some effects on cMSC and cMSC angiogenic and neurogenic paracrine activity. To finish, the study aimed to assess the effect of cMSC CM on an ex vivo model of the spinal cord, a multicellular environment and it was found that cMSC CM increased astrocyte reactivity but reduced neuronal maturation and growth, suggesting that cMSC paracrine activity depends in part on the spinal cord microenvironment. Overall, this study has shown that cMSC, in particular cMSC CM, could be used as complete or partial treatment for SCI in dogs.
  • Investigating morphometrics, movement and oviposition in the Lissotriton and Triturus newts

    Johnson, Lisa (University of Chester, 2015-09)
    This thesis focuses on the UK pond newts, the smaller bodied species known as Lissotriton newts and the larger Triturus. The primary aims were to identify and address gaps in the current Tritus/Lissotriton literature; to provide a more complete understanding of this group as many assumptions about morphology and physiology exist untested, for example that larger/fatter females will lay more eggs. Specifically for Lissotriton helveticus, many assumptions are based on the similarly sized Lissotriton vulgaris, potentially missing any species specific differences. A further focus of the work was to provide a clearer view over the whole breeding season; using measures of condition over a season and egg-laying.
  • A multidisciplinary approach to structuring in reduced triacylglycerol based systems

    Bonwick, Graham A.; Young, Niall; Wassell, Paul (University of Chester, 2013-05)
    This study (Wassell & Young 2007; Wassell et al., 2010a) shows that behenic (C22:0) fatty acid rich Monoacylglycerol (MAG), or its significant inclusion, has a pronounced effect on crystallisation (Wassell et al., 2010b; 2012; Young et al., 2008) and interfacial kinetics (3.0; 4.0). New interfacial measurements demonstrate an unusual surface-interactive relationship of long chain MAG compositions, with and without Polyglycerol Polyricinoleate (PGPR). A novel MAG synthesised from Moringa oleifera Triacylglycerol (TAG) influenced textural behaviour of water-in-oil (W/O) emulsions and anhydrous TAG systems (4.0: 5.0; 6.0). Emulsifier mixtures of PGPR and MAG rich in C18:1 / 18:2 and C16:0 / C18:0 do not decrease interfacial tension compared with PGPR alone. Only those containing MAG with significant proportion of C22:0 impacted interfacial behaviour. A mixture of C22:0 based MAG and PGPR results with decreasing tension from ~20°C and is initially dominated by PGPR, then through rearrangement, the surface is rapidly dominated by C22:0 fatty acids. A Moringa oleifera based MAG showed unusual decreased interfacial behaviour not dissimilar to PGPR. All other tested MAG (excluding a C22:0 based MAG), irrespective of fatty acid composition resulted with high interfacial tension values across the measured temperature spectrum (50°C to 5°C). A relative decrease of interfacial tension, with decreased temperature, was greater, the longer the chain length (Krog & Larsson 1992). Moreover, results from bulk and interfacial rheology showed that the presence of C22:0 based MAG has a pronounced effect on both elastic modulus (G’) and viscous modulus (G’’). Through a multidisciplinary approach, results were verified in relevant product applications. By means of ultrasonic velocity profiling with pressure difference (UVP-PD) technique, it was possible to examine the effect of a C22:0 based MAG in an anhydrous TAG system whilst in a dynamic non-isothermal condition (3.0). The non-invasive UVP-PD technique conclusively validated structural events. The application of a Moringa oleifera based MAG in low TAG (35% - 41%), W/O emulsions, results in high emulsion stability without a co-surfactant (PGPR). The bi-functional behaviour of Moringa oleifera based MAG is probably attributed to miscibility (Ueno et al., 1994) of its fatty acids, ranging ~30% of saturated fatty acids (SAFA), with ~70% of C18:1 (5.0). It is concluded that the surface-interactive behaviour of Moringa oleifera based MAG, is attributed to approximately 10% of its SAFA commencing from C20:0. When examined separately and compared, results showed that physical effect of a Moringa oleifera based MAG was not dissimilar to PGPR, influencing the crystallisation kinetics of the particular anhydrous TAG system. When either was combined with a C22:0 rich MAG, enhanced gelation onset and strong propensity to form dendrite structure occurred (5.0). Macrobeam and synchrotron radiation microbeam small angle x-ray diffraction (SR-μ-SAXD) was utilized (6.0) to assess behavior of C22:0 rich MAG, with and without PGPR (Wassell et al., 2012). The C22:0 based MAG combined with PGPR promoted TAG crystallisation as observed by differential scanning calorimetry (DSC). Polarised optical microscopy (POM) observations indicated that C22:0 based MAG eliminates formation of large crystal aggregates, resulting in the likely formation of tiny Pickering TAG / MAG crystals (6.0). It is concluded that the presence and interactive behaviour of Pickering surface-active MAG, is strongly linked to increased fatty acid chain length, which induce increased textural resilience owing to viscoelasticity (4.0; 5.0). A multidisciplinary approach was able to verify structuring behaviour (4.0; 5.0), using multiple analyses (Wassell et al., 2010b; 2012; Young et al., 2008). Novel structuring solutions in reduced TAG based systems have been provided (4.0; 5.0). This study both enhances current understanding of structuring in low TAG W/O emulsions and has led to novel MAG compositions, which address emulsification, structuring and texture in TAG based food systems (Wassell et al., 2010a; 2012a; 2012b; 2012c; 2012d; 2012e; Bech et al., 2013).
  • Delivery and engagement in public health nutrition: The use of ethnographic fiction to examine the socio-cultural experiences of food and health among mothers of young children in Skelmersdale, Lancashire

    Ellahi, Basma; Cox, Peter; Gregg, Rebecca A. (University of Liverpool (University of Chester), 2013-04)
    Encouraging good nutrition is particularly important in the early years of life for the development of appropriate food habits and healthy adults in later life. These are governed by many contending and conflicting influences. Objective: This research examines the food choice influences for mothers of young children in Skelmersdale, West Lancashire (UK). Participants were recruited from a large community food intervention (clients) and were compared with those not involved in the initiative (non-clients). This enabled the reflection of the broader socio-cultural experiences of food and the influence of “structure” and “agency” on food choices. The research adopted a phenomenological approach using ethnographic recording techniques (interview and observation). The research findings are presented as ethnographic fictions. These short fictional stories provide a “thick” description of the participant’s lifeworld. They locate these choices in the person and the place. A hierarchy of food choice influences emerged from the data, with three main findings. Most prominently, the influence of individual capacity on the food choices made. Secondly, the influence of place, town planning and the geography of an area on food choices. Thirdly, the influence of gender, relationships and social networks. Central to the thesis of this research is the use of ethnographic fiction to enable a better understanding of the complexity involved in food choice and community development approaches to nutritional change. The use of ethnographic fiction conveyed a better understanding of people and of the role and impact of an intervention upon the wider processes involved in food choice. Ethnographic fiction was used here for the first time in public health nutrition to explain the complex picture of food choice for mothers of young children in Skelmersdale, and to convey new insight on food choice and the complexity of food choice influence.
  • Conflict management in wild spider monkeys (Ateles geoffroyi yucatanensis)

    Schaffner, Colleen; Rebecchini, Luisa (University of Liverpool (University of Chester), 2010-05)
    Animals living in groups are frequently exposed to conflicts of interest which can escalate into aggression. Aggressive interactions may be a means to resolve incompatibility among objectives. Nevertheless, aggression may undermine the benefits of group living by disrupting the relationships between opponents. Thus, conflict management mechanisms have evolved to cope with the potential damage brought about by aggressive interactions. The aim of my thesis was to investigate the mechanisms to prevent aggressive escalation and to mitigate its negative consequences in 2 communities of wild spider monkeys (Ateles geoffroyi yucanensis). I also examined the factors, such as relationship characteristics, affecting the occurrence of these mechanisms. Spider monkeys live in communities with a high degree of fission fusion dynamics in which individuals frequently split and merge into subgroups of variable composition. The implications of this social system for conflict management were also explored. To characterise spider monkeys’ social relationships, two components were identified and labelled compatibility and risk. These components were further related to relationship characteristics, such as kinship, sex combinations, and tenure in the community. Kin had more compatible relationships than non kin, but there was no difference for risk. Male-male dyads were characterised as being significantly more compatible and riskier than either female-female dyads or male-female dyads. Furthermore, individuals with longer tenure had riskier relationships than individuals with shorter tenure. Among the post-conflict management mechanisms spider monkeys did not engage in reconciliation, redirected aggression, or bystander affiliation. However, an option afforded by their high degree of fission fusion dynamics was used in the aftermath of aggression. Fission from former aggressors was more likely to occur within one hour of the aggressive conflicts than in control periods. Furthermore, individuals sharing riskier and less compatible relationships had significantly shorter latencies to fission compared to those with less risky and more compatible relationships. These patterns suggest that fission may function to reduce the possibility of renewed aggression and cope with increased post-conflict anxiety. Indeed, anxiety levels were higher in the recipients of aggression during the first 5 post-conflict minutes compared to baseline levels. Whereas fission may be a mechanism to cope with the negative consequences of aggressive escalation, fusion of subgroups could lead to uncertainty and hostility. Indeed, aggression increased in the first five post-fusion minutes compared to baseline levels. There was also an increase in post-fusion friendly behaviours, which may function as signals of good intentions. This view was confirmed as post-fusion aggression was reduced when friendly behaviours took place. In addition, shorter latencies of post-fusion aggression and friendly behaviours were found between individuals with riskier relationships compared to those with less risky relationships. Prevention of aggressive conflicts may also be achieved by adjusting subgroup size to the availability of feeding resources thereby reducing competition. The effectiveness of this flexible adjustment was demonstrated during a period of drastic reduction in food sources caused by two consecutive hurricanes at the field site. Mean subgroup size and fusion rates were significantly reduced in the post-hurricane compared to pre-hurricane periods. Hence, my thesis adds to the study of social relationships and conflict management in non-human animals by making several contributions. I provided the first evidence of relationship components in new world monkeys. I then examined the potential of fission-fusion dynamics as a means to manage conflicts among community members. I was the first demonstrating that fission is a post-conflict mechanism. Fission from the former aggressor was especially used by individuals with riskier and less compatible relationships. Subgroup fusion increased aggressive conflicts, especially between individuals with riskier relationships, but post-fusion friendly behaviours reduced them. The effectiveness of fission-fusion dynamics in conflict management was further demonstrated by how the spider monkeys coped with the potential increase in conflict among community members due to a dramatic reduction in food supplies due to two hurricanes. Overall, spider monkeys appear to deal with conflicts using the full range of the flexible social options afforded by their social system.
  • Extra-curricular education for sustainable development interventions in higher education

    Degg, Martin; Burek, Cynthia V.; Ribchester, Chris; Potter, Jacqueline; Lipscombe, Bryan P. (University of Liverpool (University of Chester), 2009-12)
    Universities are seen to have a central role in the UN Decade of Education for Sustainable Development (ESD), partly through their teaching and research activities. However, the critique of Higher Education's (HE) contribution to sustainable development thus far points to the limitations of a discipline driven, curriculum content and solely student focused response. Within this context, extra-curricular interventions, for example, running awareness campaigns, creating groups and organising events, appear to have potential to advance ESD in HE. However, there has been little investigation or published work in this area. Ideas of non formal and informal education; constructivist theories of learning; concepts of free choice, tacit and social learning, and the notions of whole systems thinking and sustainable education all point to roles for interventions in the extra-curricular sphere. This thesis explores the use of extra-curricular interventions in HE through an empirical investigation in the UK. A 2006 postal survey of Higher Education Institutions (HEIs) records the extent and type of interventions in use and opinions about their utility. A case study, developed through action research, reports the use and impact of extra-curricular ESD-related interventions at one HEI over an academic year (2006-07). In this case study, regular contact with a group of staff and students over the year is used to map changes in their thoughts and actions relating to sustainable development, and to record the influences attributed to these changes. Importantly, extra-curricular ESD-related interventions are found to be commonly used in UK HE, and to have a prominent position in ESD work despite their limited visibility in the literature. Their utility is confirmed as they are seen to provide experiences that contribute to student and staff learning, as well as institutional change. The evidence collected supports their roles as: disciplinary bridge', community bridge; socialisation scaffold, and social learning arena. They appear to have a useful developmental role in mobilising and motivating members of the campus community. As peripheral activities, however, extra-curricular interventions may be prone to erratic implementation through being under-resourced. They can extend participation in BSD although will not reach everyone. They are best viewed as a complementary part of BSD and linked to a process of curricular and pedagogic renewal. In addition to confirming the extent, utility and limitations of extra-curricular ESD practice, the research contributes a model to map understandings of sustainable development. This model points to a core environmental understanding to which extra layers and strands of thinking can be added. It also confirms the importance of non formal and informal influences in shaping people's conceptions of sustainable development.
  • Hsp72 translocation and secretion in in vivo and in vitro models

    Williams, John H. H.; Andrew, Sarah M.; Leoni, Francesca (University of Liverpool (Chester College of Higher Education), 2009-03)
    Evidence suggesting that Hsp72 is actively participating in cellular signalling as well interacting with immune system dynamics has been increasing. This is true in healthy, stressed and diseased cells but to different degrees. Modulation of the plasma membrane association and secretion in the extracellular environment by different types of stressors is the key event that leads to different degrees of immune system activation. Hence a better understanding of the mechanisms of Hsp72 secretion and association with plasma membrane is crucial. This thesis investigated the tissue source and mechanism of Hsp72 surface presentation to plasma membrane structures and release in relation with different cellular and physiological stressors. In vivo models confirmed that different tissue types determine specific Hsp72 responses following the same stress and increase serum Hsp72 dependant on intensity and duration of the stress. Diseases models confirm that Hsp72 responses in specific cell populations is related to disease progression, while in vitro models clearly showed that there are multiple mechanisms of secretion and surface presentation, dependent on the nature of the stressor as well as the intensity and duration. This observations clearly change the view of extracellular Hsp72 as a danger signal and lead to a revision of the original danger model. It also suggests that manipulation of Hsp72 translocation through the different pathways involved may prove effective therapeutically.
  • Severe acute malnutrition and HIV in children in Malawi

    Fergusson, Pamela L. (University of Liverpool (University of Chester), 2009-07)
    Sub-Saharan Africa is more affected by the HIV epidemic than any other region of the world. At the same time, malnutrition remains a major public health concern. HIV and malnutrition are interlinked, both epidemiologically and physiologically, contributing to high mortality and poor growth and development of children in sub-Saharan Africa. This thesis aims to explore the impact of HIV on the treatment and care of children with severe acute malnutrition in Malawi. The thesis will investigate mortality and nutritional recovery in HIV-infected and uninfected children with SAM; HIV infection and nutritional status in carers of children with SAM; and caregiver perspectives on quality of care for children with SAM. The study is based on a prospective cohort study of 454 children with SAM and meta-analysis of 17 relevant studies; a cross sectional study of 322 carer-child pairs; and a qualitative study using a grounded theory approach.
  • 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.
  • Behavioural development in wild Western lowland gorillas (gorilla gorilla gorilla)

    Fletcher, Alison W.; Nowell, Angela A. (University of Liverpool (University of Chester), 2005-02)
    Behavioural development has received little attention in primates, despite having important influences on infant mortality, interbirth intervals, and therefore, growth of populations. Gorillas have long developmental periods, exhibit strong maternal bonds and integrate into intricate social systems, making them an ideal species in which to investigate non-human primate development. Gorillas exist across a range of habitats, and differences in behaviour, both within and between species reflect socioecological differences, for example, in the availability and distribution of food. Consequently, by using gorillas as a model, opportunities also exist to investigate environmental constraints on the development of independence. This study provides the first detailed analysis, with reference to ecological factors, of the development of behavioural skills and relationships in wild western lowland gorillas (Gorilla gorilla gorilla). Behavioural development of western lowland gorillas is then compared with published accounts of development in mountain gorillas (Gorilla beringei beringei) to determine the extent to which differing ecology influences behaviour. The study was conducted at Mbeli Bai in the Republic of Congo, a large, marshy clearing, visited by gorillas predominantly for feeding purposes. Data were collected using scan, focal, all-occurrence and ad libitum sampling methods from 58 gorillas below 8 years of age. Spatial relationships, suckling, and the nature of interactions involving immature individuals were analysed. The distribution of time between different behaviours by immatures, and the development of independent feeding and travelling behaviour was also investigated, and all were tested for differences as a result of immature age, sex and social group, or the mother's parity. Towards the end of infancy, individuals showed competent feeding behaviour in the bai. However, western lowland gorillas were not weaned until the juvenile period, and until this time, close association was common between mothers and offspring. With increasing independence from the mother there was limited investment in relationships with other individuals, and instead, a greater emphasis was placed on developing skills through play, alloparenting and agonistic interactions. When results were compared with those of mountain gorillas, there was evidence of increased investment in relationships, particularly with the silverback, by immature mountain gorillas, which was assumed to reflect lower rates of natal dispersal by mountain gorillas, and the greater likelihood that relationships with individuals in the natal group could prove useful in the future. Suckling and close proximity to the mother continued until later ages in western lowland gorillas, resulting in clear differences between them mountain gorillas in the duration of investment by mothers. More frugivorous western lowland gorillas required increased levels of investment by the mother before independence could be achieved, demonstrating the effect that resource availability can have on behavioural development in species where resources are widely and unpredictably dispersed.
  • The effect of bone matrix extract on bone cell activity

    Williams, John H. H.; Powell, Diane E. (University of Liverpool (University of Chester), 2006-10)
    Bone remodelling is a complex process, which involves the coupling of bone formation to completed foci of bone resorption, the balance between these 2 processes determines if bone is lost or gained at a particular site. During bone resorption osteoclasts release growth factors sequestered in bone matrix, which are thought to initiate new bone formation. On the other hand, osteoblasts can regulate osteoclast activity through the expression of the counter-acting cytokines, RANKL and OPG. The aim of this project was to determine if factors released during bone resorption impact on the RANKL/OPG system or on osteoclasts directly to regulate bone remodelling. OPG secretion was characterized in a number of osteoblast-like cells and the osteosarcoma cell line MG-63 was chosen as a model for osteoblastic cell behaviour in vitro. EDTA bone extracts prepared from normal human cortical bone powder were used to treat MG-63 cells in vitro. The response to the extract was dependent on the purification procedure used. OPG production was inhibited by partially purified extracts prepared using hydrophobic interaction chromatography, C18 SPE. In comparison extracts prepared using size exclusion centrifugal filters stimulated OPG secretion in confluent MG-63 cells. Therefore bone matrix constituents were able to influence osteoclast activity directly and indirectly through the osteoblastic cells to produce the same response. The simplest mechanism for this co-ordinated response would be the presence of one factor in the extract that is able to influence both osteoblasts and osteoclasts. The identity of the factor responsible for the opposing effects seen in the bone matrix extracts is at the moment unknown. The work presented in this thesis clearly demonstrated that unknown growth factors present in bone matrix influence bone remodelling.
  • Hsp72 modulation of inflammatory immune responses

    Williams, John H. H.; Ireland, H. Elyse (University of Liverpool (University of Chester), 2009-03)
    The body initiates an immune response to danger signals. The Danger model of the immune system postulates that danger signals are produced by exogenous molecules from foreign invaders, such as bacteria, and endogenous molecules released from damaged or injured cells. The response involves antigen recognition leading to up-regulation of cytokines and cell surface markers, followed by the recruitment of antigen presenting cells and T-helper cells which determine how the immune system responds. Endogenous danger signals include Hsp72 and HMGB-1. This thesis describes the development of specific antibodies and ELISAs for use in the quantification and detection of intra-cellular Hsp72 from cell extracts, and released Hsp72 from cell cultures which enabled the confirmation of physiological levels of Hsp72 from model systems. The ability of endogenous Hsp72 to stimulate an immune response was demonstrated and this response was not solely due to LPS contamination of recombinant protein preparations. Hsp72 was able to augment the response to LPS. In the presence of another endogenous danger signal, HMGB-1, relative amounts of Hsp72 were shown to augment a pro-inflammatory response whilst being able to maintain an anti-inflammatory response demonstrating Hsp72 has the ability to modulate the immune response. Hsp72 was also shown to be able to stimulate an immune response by binding to cell surface receptors, which could be blocked by specific peptides corresponding to known receptors. These include some receptors not utilised by LPS. The proportion of these different danger signals has consequences for the progression and outcome of an immune response and this may well be modulated by imposition of a supplemental or future stress at different points. In the most severe case, this can lead to death through sepsis following trauma.