• Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression.

      Zatyka, Malgorzatta; Xavier, Gabriela Da Silva; Bellomo, Elisa A.; Leadbeater, Wendy; Astuti, Dewi; Smith, Joel; Michelangeli, Francesco; Rutter, Guy A.; Barrett, Timothy G.; University of Birmingham, Imperial College London, (Oxford University Press, 2015-02-01)
      Wolfram syndrome is an autosomal recessive disorder characterized by neurodegeneration and diabetes mellitus. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER)-resident transmembrane protein that is involved in the regulation of the unfolded protein response (UPR), intracellular ion homeostasis, cyclic adenosine monophosphate production and regulation of insulin biosynthesis and secretion. In this study, single cell Ca(2+) imaging with fura-2 and direct measurements of free cytosolic ATP concentration ([ATP]CYT) with adenovirally expressed luciferase confirmed a reduced and delayed rise in cytosolic free Ca(2+) concentration ([Ca(2+)]CYT), and additionally, diminished [ATP]CYT rises in response to elevated glucose concentrations in WFS1-depleted MIN6 cells. We also observed that sarco(endo)plasmic reticulum ATPase (SERCA) expression was elevated in several WFS1-depleted cell models and primary islets. We demonstrated a novel interaction between WFS1 and SERCA by co-immunoprecipitation in Cos7 cells and with endogenous proteins in human neuroblastoma cells. This interaction was reduced when cells were treated with the ER stress inducer dithiothreitol. Treatment of WFS1-depleted neuroblastoma cells with the proteasome inhibitor MG132 resulted in reduced accumulation of SERCA levels compared with wild-type cells. Together these results reveal a role for WFS1 in the negative regulation of SERCA and provide further insights into the function of WFS1 in calcium homeostasis.
    • The sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD).

      Al-Mousa, Fawaz; Michelangeli, Francesco; University of Birmingham, UK (Elsevier, 2014-01-01)
      Hexabromocyclododecane (HBCD) is a widely utilised brominated flame retardant (BFR). It has been shown to bio-accumulate within organisms, including man, and possibly cause neurological disorders. The acute neurotoxicity of HBCD, and six other unrelated BFRs, were assessed in SH-SY5Y human neuroblastoma cells by 24h viability assays and HBCD proved to be the most lethal (LC50, 3μM). In addition, the effects of these BFRs were also assessed for their potency at inhibiting the sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) derived from the SH-SY5Y cells and again HBCD was the most potent (IC50, 2.7μM). The data for the other BFRs tested showed a direct correlation (coefficient 0.94) between the potencies of inducing cell death and inhibiting the Ca(2+) ATPase, indicating that SERCA is likely to be the molecular target for acute toxicity. Mechanistic studies of HBCD on the Ca(2+) ATPase suggest that it affects ATP binding, phosphorylation as well as the E2 to E1 transition step.
    • Scenario-Led Habitat Modelling of Land Use Change Impacts on Key Species

      Geary, Matthew; Fielding, Alan H.; McGowan, Philip J. K.; Marsden, Stuart J.; University of Chester, Manchester Metropolitan University; Newcastle University (PLOS, 2015-11-16)
      Accurate predictions of the impacts of future land use change on species of conservation concern can help to inform policy-makers and improve conservation measures. If predictions are spatially explicit, predicted consequences of likely land use changes could be accessible to land managers at a scale relevant to their working landscape. We introduce a method, based on open source software, which integrates habitat suitability modelling with scenario-building, and illustrate its use by investigating the effects of alternative land use change scenarios on landscape suitability for black grouse Tetrao tetrix. Expert opinion was used to construct five near-future (twenty years) scenarios for the 800 km2 study site in upland Scotland. For each scenario, the cover of different land use types was altered by 5–30% from 20 random starting locations and changes in habitat suitability assessed by projecting a MaxEnt suitability model onto each simulated landscape. A scenario converting grazed land to moorland and open forestry was the most beneficial for black grouse, and ‘increased grazing’ (the opposite conversion) the most detrimental. Positioning of new landscape blocks was shown to be important in some situations. Increasing the area of open-canopy forestry caused a proportional decrease in suitability, but suitability gains for the ‘reduced grazing’ scenario were nonlinear. ‘Scenario-led’ landscape simulation models can be applied in assessments of the impacts of land use change both on individual species and also on diversity and community measures, or ecosystem services. A next step would be to include landscape configuration more explicitly in the simulation models, both to make them more realistic, and to examine the effects of habitat placement more thoroughly. In this example, the recommended policy would be incentives on grazing reduction to benefit black grouse.
    • Seascape genomics reveals population isolation in the reef-building honeycomb worm, Sabellaria alveolata (L.)

      Dubois, Stanislas; Muir, Anna P; orcid: 0000-0002-6896-6915; Ross, Rebecca; Firth, Louise; Knights, Antony; Lima, Fernando; Seabra, Rui; Corre, Erwan; Le Corguillé, Gildas; Nunes, Flavia; et al.
      Background: Under the threat of climate change populations can disperse, acclimatise or evolve in order to avoid fitness loss. In light of this, it is important to understand neutral gene flow patterns as a measure of dispersal potential, but also adaptive genetic variation as a measure of evolutionary potential. In order to assess genetic variation and how this relates to environment in the honeycomb worm (Sabellaria alveolata (L.)), a reef-building polychaete that supports high biodiversity, we carried out RAD sequencing using individuals from along its complete latitudinal range. Patterns of neutral population genetic structure were compared to larval dispersal as predicted by ocean circulation modelling, and outlier analyses and genotype-environment association tests were used to attempt to identify loci under selection in relation to local temperature data. Results: We genotyped 482 filtered SNPs, from 68 individuals across nine sites, 27 of which were identified as outliers using BAYESCAN and ARLEQUIN. All outlier loci were potentially under balancing selection, despite previous evidence of local adaptation in the system. Limited gene flow was observed among reef-sites (FST = 0.28 ± 0.10), in line with the low dispersal potential identified by the larval dispersal models. The North Atlantic reef emerged as a distinct population and this was linked to high local larval retention and the effect of the North Atlantic Current on dispersal. Conclusions: As an isolated population, with limited potential for natural genetic or demographic augmentation from other reefs, the North Atlantic site warrants conservation attention in order to preserve not only this species, but above all the crucial functional ecological roles that are associated with their bioconstructions. Our study highlights the utility of using seascape genomics to identify populations of conservation concern.
    • Seasonality in birth rate in two 19th century North Wales parishes

      Lewis, Stephen J.; Glenn, Janine; Chester College of Higher Education (2000)
      An understanding of the basic patterns in the seasonality of birth rate may be useful in certain fertility techniques. The use of artificial birth control, however, has had the effect of masking the influence of underlying biometeriological factors. To elucidate trends in birth seasonality in the absence of current social factors, a study useing nineteenth-century parish records was undertaken. Analysis of 5,905 births recorded in the baptismal records of the parishes of Hawarden and Northop between the years 1837 and 1886 revealed significant seasonal trend with a peak occuring in the spring. Further analysis showed a significant positive correlation occuring between the (standardized) numbers of births in each month and the mean day length (hours between sunrise and sunset) of the pulative month of conception.
    • Seasonality of Plasmodium falciparum transmission: a systematic review

      Reiner, Robert C.; Geary, Matthew; Atkinson, Peter M.; Smith, David L.; Gething, Peter W.; 1 Fogarty International Center, National Institutes of Health, Bethesda, MD, USA 2 Department of Epidemiology and Biostatistics, Indiana University School of Public Health, Bloomington, IN, USA 3 Department of Entomology, University of California, Davis, CA, USA 4 Department of Biological Sciences, University of Chester, Chester, UK 5 Faculty of Science and Technology, Engineering Building, Lancaster University, Lancaster LA1 4YR, UK 6 Faculty of Geosciences, University of Utrecht, Heidelberglaan 2, Utrecht, 3584 CS, The Netherlands 7 School of Geography, Archaeology and Palaeoecology, Queen’s University Belfast, Belfast BT7 1NN, Northern Ireland, UK 8 Geography and Environment, University of Southampton, Highfield, Southampton SO17 1BJ, UK 9 Center for Disease Dynamics, Economics and Policy, Washington, DC, USA 10 Spatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, UK (BioMed Central, 2015-09-15)
      Background Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has “strongly seasonal” transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized. Methods The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts. Results and discussion 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both). Discussion Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location. Conclusions The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales. Keywords: Plasmodium falciparum ; Seasonality; Climatic drivers
    • A simple procedure for investigating differences in sexual dimorphism between populations

      Lewis, Stephen J.; Chester College of Higher Education (Oxbow Books (for The Osteoarchaeological Research Group), 1997-12-01)
      Although sexual dimorphism has a strong genetic component in many animals, external factors may alter its expression - enhancing or diminishing it depending on the parameter measured and the type of influence experienced. A measure of sexual dimorphism may be used, therefore, to characterise a whole population and the factors acting upon it. Differences between populations for such factors may then be investigated by comparing sexual dimorphisms and may be more informative than merely comparing population means. A quick and relatively simple technique which provides a coefficient of the relationship between a continuous variable and another which is dichotomous, such as sex, is the point biserial correlation. This is a less frequently described extension of the commonly used Pearson product-moment correlation. The point-biserial correlation coefficients can be calculated for a given parameter and compared to determine whether the same sexual dimorphism is evident in different samples. If it is not, some factor influencing one or other population, as a whole, may require further investigation. The full procedure, which can be performed without the need for statistical tables, and the necessary formulae are described. This method, in its generalised form, may also be applied to the study of bilateral asymmetry.
    • A simple procedure for testing for differences in sexual dimorphism between populations

      Lewis, Stephen J.; Chester College of Higher Education (InterStat, 2004)
      Using point bi-serial correlation, an approach to the biological problem of comparing differences in sexual dimorphism between populations is presented. In particular, a way of deriving the point bi-serial correlation coefficient from summary statistics (means, standard deviations and sample sizes) is given. This bypasses the need for access to raw data.
    • Skeletal changes during catch-up growth - suggestions from a rat model

      Lewis, Stephen J.; Chester College of Higher Education (2001)
      The removal of a growth limiting influence, such as undernutrition, is frequently followed by a period of growth at a rate greater than normally expected for chronological age. This, so called 'catch-up growth', tends to return affected individuals to their original growth trajectory. How catch-up growth is controlled or regulated remains unclear. Histological studies of the proximal tibial growth plate in rats which had been undernourished by half-feeding between the 56th and 70th days (post partum) showed them to be thinner than those of controls. Upon inspection, the chondrocytes also appeared to be flatter in profile and less numerous. However, during the catch-up period, when food was again allowed ad libitum, previously undernourished rats showed wider growth plates with rounder and more numerous chondrocytes than controls. It was noted that such changes were similar to those that accompany sectioning of the periosteum and the release of growth restraint that results. A study of the flexibility of the sacro-iliac joint in the same animals suggested that it was less flexible following undernutrition but more so during the catch-up period, by comparison with controls. This was in contrast to a progressive loss of flexibility shown by controls during the same period and would appear to result from changes in the characteristics of the fibrous connective tissues associated with the joint. If this reflects a more generalized change in such connective tissues, but particularly the periosteum, ligaments and joint capsules, this may represent a means whereby skeletal growth rate during the catch-up period may be influenced in a co-ordinated manner.
    • Social Experience of Captive Livingstone’s Fruit Bats (Pteropus livingstonii)

      Stanley, Christina R; Smith, Tessa; Welch, Morgan J; Hosie, Charlotte; Wormell, Dominic; Price, Eluned; University of Chester; Jersey Zoo
      Social network analysis has been highlighted as a powerful tool to enhance the evidence-based management of captive-housed species through its ability to quantify the social experience of individuals. We apply this technique to explore the social structure and social roles of 50 Livingstone’s fruit bats (Pteropus livingstonii) housed at Jersey Zoo, Channel Islands, through the observation of associative, affiliative, and aggressive interactions over two data collection periods. We implement binomial mixture modelling and characteristic-based assortment quantification to describe the complexity and organisation of social networks, as well as a multiple regression quadratic assignment procedural (MRQAP) test to analyse the relationship between network types. We examine the effects of individual characteristics (i.e., sex, age, and dominance rank) on social role by fitting models to explain the magnitude of node metrics. Additionally, we utilize a quadratic assignment procedural (QAP) test to assess the temporal stability of social roles over two seasons. Our results indicate that P. livingstonii display a non-random network structure. Observed social networks are positively assorted by age, as well as dominance rank. The frequency of association between individuals correlates with a higher frequency of behavioural interactions, both affiliative and aggressive. Individual social roles remain consistent over ten months. We recommend that, to improve welfare and captive breeding success, relationships between individuals of similar ages and dominance levels should be allowed to persist in this group where possible, and separating individuals that interact frequently in an affiliative context should be avoided.
    • Social stability in semiferal ponies: networks show interannual stability alongside seasonal flexibility

      Stanley, Christina R.; Mettke-Hofmann, Claudia; Hager, Reinmar; Shultz, Susanne; University of Chester; University of Manchester; Liverpool John Moores University (Elsevier, 2017-06-23)
      Long-term relationships that underlie many stable mammalian groups often occur between philopatric kin. Although stable groups of nonrelatives appear to be less common, there is increasing evidence that social bonds between nonkin may confer sufficient intrinsic fitness benefits for these groups to persist. Here we evaluate whether social stability occurs in a bisexually dispersing species where social bonds have been shown to have reproductive benefits: the feral horse, Equus caballus. First, we quantified female social stability by applying a three-level framework to a 3-year data set of associations in semiferal ponies; this tested for stability at the individual, dyadic and subpopulation levels. Despite the relative weakness of these female bonds, we found significant social stability across all levels, as shown by stable association preferences, social networks and individual network positions. Second, we investigated how seasonality impacts on social bond strength and grouping patterns. We found seasonal fluctuations in female gregariousness, with a peak during the mating season. We therefore propose that significant social stability in female horses is coupled with a degree of flexibility that allows for effects of ecological fluctuations. Although social network analysis is widely used in behavioural ecological research, this is one of only a handful of studies to assess the temporal dynamics of networks over a significant timescale. Temporal stability in female relationships suggests that equid social structures are multifaceted: although bonds between stallions and mares are clearly strong, long-term relationships between mares underpin the social network structure. We suggest this framework could be used to assess social stability in other group-living species in order to improve our understanding of the nature of social bonds.
    • Solving the conundrum of health and disease

      Lewis, Stephen J.; Chester College of Higher Education (1997)
    • Some notes on crucifixion

      Lewis, Stephen J.; Chester College of Higher Education (1995)
      This article discusses the injuries caused by crucifixion, based on an adult male skeleton found in ossuary I:4 in north-east Jerusalem in 1968.
    • Some research possibilities in diagnostic radiography

      Lewis, Stephen J.; University College Chester (Elsevier, 1998)
      Although scientific method is usually viewed as starting with hypotheses which must then be exposed to experimental test, there are situations where this rigid scenario is inappropriate. Fortunately, the alternatives provide avenues for valuable investigative work in radiographic research. Research questions may be addressed by collecting data from existing sources in a way that not only provides fundamental information about human biology, but may improve the efficacy of radiographic practice while avoiding ethical problems about the use of patients. Among those involved in osteology, it is radiographers who see and store the most bone images. Subsequently, they have access to more osteological information than anyone else. All that remains is for this information to be extracted and put into a more accessible form. Since they are closely involved with the patients from whom their radiographs stem, there are research questions which radiographers are uniquely situated to raise.
    • Some summary data from the N.W. Wales hand osteological database

      Lewis, Stephen J.; Chester College of Higher Education (Oxbow Books (for the Osteoarchaeological Research Group), 1999-12-01)
      Probably the richest store of osteological information lies in the radiographic images stored in X-ray departments. These have been greatly under-used. As an example of the sort of data available, some summary statistics from the N.W. Wales Hand Osteological Database are given. This data may be compared with historic or extant populations. Further data is available to colleagues on request.
    • Spatial and temporal changes in the distribution of salt marsh vegetation communities in the Dee estuary, NW England, determinded from aerial photographs

      Huckle, Jonathan M.; Potter, Jacqueline; Marrs, Robert H.; University College Chester (Potter) (Springer, 2004)
    • Spatial variation in species composition of Saprolegnia, a parasitic oomycete of amphibian eggs, in Scotland

      Muir, Anna P.; Kilbride, Elizabeth; Mable, Barbara K.; University of Chester; University of Glasgow (The British Herpetological Society, 2015-10-01)
      Parasitic water moulds in the genus Saprolegnia cause mortality of amphibian embryos and reduced size at metamorphosis, leading to increased adult mortality. Most studies of virulence have focused on only a single Saprolegnia species, but the Saprolegnia species associated with amphibian eggs and their distributions are not well known. This study aimed to investigate the distribution of amphibian-associated water moulds in Scotland. In particular, we asked the questions: i) Does Saprolegnia species composition vary between sites?; and ii) Is presence of Saprolegnia related to environmental parameters? Common frog (Rana temporaria) eggs with evidence of Saprolegnia infection were sampled from ten sites, cultured, and the 28S region of the rDNA array sequenced. Thirteen samples isolated from four sites were identified as members of the Saprolegniaceae and the ITS region of these samples were subsequently sequenced to further resolve species identification. Four species of Saprolegnia were found in total, with one or two species of Saprolegnia present in each of four sites. S. diclina was the most common species identified and was found at three of the four sites. Acidity was significantly lower and altitude significantly higher at sites where Saprolegniaceae were present. Therefore, R. temporaria eggs in different pools are subject to infection by different, and in some instances more than one, species of Saprolegnia. Overall, our findings suggest that future studies of virulence need to consider the effect of multiple Saprolegnia species within a site as well as the population of origin of the amphibian host
    • The sportization of swimming: A sociological examination of the development of swimming as a modern competitive sport, c.1595-1908

      Bloyce, Daniel; Cock, Steven (University of Chester, 2012-04)
      Modern competitive swimming is a highly structured, organized, codified and regulated sport. This has not always been the case. The aim of this thesis has been to examine the long-term development of competitive forms of swimming throughout the periods between the late sixteenth and early twentieth centuries. Despite some recent historical analyses, the emergence of swimming as a modern competitive sport is an under-researched topic. There are no sociological analyses relating to the development of competitive swimming and significant gaps within much historical research. This thesis has been conducted from a sociological perspective in order to test the relative adequacy of Norbert Elias’s concept of sportization. Figurational sociologists have often examined the concept of sportization in relation to the development of contact sports such as boxing and rugby. Some authors have sought to criticize figurational sociologists for over-emphasizing issues relating to the increasing control of violence when examining the development of such activities. In this manner, there is scope to contribute to existing empirical and theoretical knowledge by testing the relative adequacy of the concept of sportization in relation to the long-term development of the predominantly non-contact sport of competitive swimming. To this end, data have been examined from a range of documentary sources. Various swimming-based texts, treatises, periodicals and magazines were examined at the British Library and Colindale Newspaper Library in London. The original minute books of the Amateur Swimming Association and its predecessor bodies have also been analyzed. In addition, a range of digitized source material has been examined from several electronic databases. It has been argued that the development of modern competitive swimming was an unplanned and unintended outcome resulting from the complex interweaving of wider social processes in England throughout the periods between the Middle-Ages and the early twentieth century. The earliest reported swimming contests took place in the eighteenth and early nineteenth centuries in the form of a cash wager between two or more individuals. These events were less structured and regulated than modern forms of competitive swimming. Betting upon the outcome of such events was deemed to be an appropriate means to experience heightened levels of tension-excitement within the context of an emerging society in which people were increasingly expected to demonstrate greater self-control over their behaviour and emotions. More organized forms of competitive swimming gradually emerged during the nineteenth and early twentieth centuries. The emergence of an increasingly complex network of clubs, societies and associations at local, county, district and national levels facilitated such developments and contributed to the emergence of standardized rules and regulations within the emerging sport of swimming. Such developments have been explained in relation to ongoing processes of state-formation, pacification, lengthening chains of interdependence and a gradual lowering in the threshold of repugnance within England in the period between the Middle-Ages and the early twentieth century. In this manner, it has been argued that the concept of sportization is an appropriate theoretical framework for explaining the long-term development of the modern non-contact sport of competitive swimming.
    • Statins increase osteoprotegerin production and apoptosis in osteoblastic cells

      Smith, Heather L.; Buck, I.; Williams, John H. H.; Marshall, Michael J. (American Society for Bone and Mineral Research, 2005)
    • Stereoselective uptake of cell-penetrating peptides is conserved in antisense oligonucleotide polyplexes

      Favretto, Marco E.; Brock, Roland; Radboud University Medical Center (Wiley-VCH Verlag, 2014-11-10)
      Stereochemistry matters. A significant conceptual advancement is presented toward the understanding of how functional characteristics of delivery peptides can translate into functional characteristics of peptide-based oligoplexes