• LDL-C levels in older people: Cholesterol Homeostasis and the Free Radical Theory of Ageing Converge

      Mc Auley, Mark T.; Mooney, Kathleen M.; Univeristy of Chester; Edge Hill University (Elsevier, 2017-05-17)
      The cardiovascular disease (CVD) risk factor, low density lipoprotein cholesterol (LDL-C) increases with age, up until the midpoint of life in males and females. However, LDL-C can decrease with age in older men and women. Intriguingly, a recent systematic review also revealed an inverse association between LDL-C levels and cardiovascular mortality in older people; low levels of LDL-C were associated with reduced risk of mortality. Such findings are puzzling and require a biological explanation. In this paper a hypothesis is proposed to explain these observations. We hypothesize that the free radical theory of ageing (FRTA) together with disrupted cholesterol homeostasis can account for these observations. Based on this hypothesis, dysregulated hepatic cholesterol homeostasis in older people is characterised by two distinct metabolic states. The first state accounts for an older person who has elevated plasma LDL-C. This state is underpinned by the FRTA which suggests there is a decrease in cellular antioxidant capacity with age. This deficiency enables hepatic reactive oxidative species (ROS) to induce the total activation of HMG-CoA reductase, the key rate limiting enzyme in cholesterol biosynthesis. An increase in cholesterol synthesis elicits a corresponding rise in LDL-C, due to the downregulation of LDL receptor synthesis, and increased production of very low density lipoprotein cholesterol (VLDL-C). In the second state of dysregulation, ROS also trigger the total activation of HMG-CoA reductase. However, due to an age associated decrease in the activity of cholesterol-esterifying enzyme, acyl CoA: cholesterol acyltransferase, there is restricted conversion of excess free cholesterol (FC) to cholesterol esters. Consequently, the secretion of VLDL-C drops, and there is a corresponding decrease in LDL-C. As intracellular levels of FC accumulate, this state progresses to a pathophysiological condition akin to nonalcoholic fatty liver disease. It is our conjecture this deleterious state has the potential to account for the inverse association between LDL-C level and CVD risk observed in older people.
    • Lipid metabolism and hormonal interactions: Impact on cardiovascular disease and healthy aging

      Mc Auley, Mark T.; Mooney, Kathleen M.; University of Chester ; Edge Hill University (informa health care, 2014-07)
      Populations in developed nations are aging gradually; it is predicted that by 2050 almost a quarter of the world’s population will be over 60 years old, more than twice the figure at the turn of the 20th century. Although we are living longer, this does not mean the extra years will be spent in good health. Cardiovascular diseases are the primary cause of ill health and their prevalence increases with age. Traditionally, lipid biomarkers have been utilized to stratify disease risk and predict the onset of cardiovascular events. However, recent evidence suggests that hormonal interplay with lipid metabolism could have a significant role to play in modulating cardiovascular disease risk. This review will explore recent findings which have investigated the role hormones have on the dynamics of lipid metabolism. The aim is to offer an insight into potential avenues for therapeutic intervention.
    • A mathematical model of microbial folate biosynthesis and utilisation: implications for antifolate development

      Salcedo-Sora, J. Enrique; Mc Auley, Mark T.; Liverpool Hope University, University of Chester (Royal Society of Chemistry, 2016-01-15)
      The metabolic biochemistry of folate biosynthesis and utilisation has evolved into a complex network of reactions. Although this complexity represents challenges to the field of folate research it has also provided a renewed source for antimetabolite targets. A range of improved folate chemotherapy continues to be developed and applied particularly to cancer and chronic inflammatory diseases. However, new or better antifolates against infectious diseases remain much more elusive. In this paper we describe the assembly of a generic deterministic mathematical model of microbial folate metabolism. Our aim is to explore how a mathematical model could be used to explore the dynamics of this inherently complex set of biochemical reactions. Using the model it was found that: (1) a particular small set of folate intermediates are overrepresented, (2) inhibitory profiles can be quantified by the level of key folate products, (3) using the model to scan for the most effective combinatorial inhibitions of folate enzymes we identified specific targets which could complement current antifolates, and (4) the model substantiates the case for a substrate cycle in the folinic acid biosynthesis reaction. Our model is coded in the systems biology markup language and has been deposited in the BioModels Database (MODEL1511020000), this makes it accessible to the community as a whole.
    • Mathematical modelling of metabolic regulation in aging

      Mc Auley, Mark T.; Mooney, Kathleen M.; Angell, Peter J.; Wilkinson, Stephen J.; University of Chester ; Liverpool Hope University ; Edge Hill University ; University of Chester (MDPI, 2015-04-27)
      The underlying cellular mechanisms that characterize aging are complex and multifaceted. However, it is emerging that aging could be regulated by two distinct metabolic hubs. These hubs are the pathway defined by the mammalian target of rapamycin (mTOR) and that defined by the NAD+-dependent deacetylase enzyme, SIRT1. Recent experimental evidence suggests that there is crosstalk between these two important pathways; however, the mechanisms underpinning their interaction(s) remains poorly understood. In this review, we propose using computational modelling in tandem with experimentation to delineate the mechanism(s). We briefly discuss the main modelling frameworks that could be used to disentangle this relationship and present a reduced reaction pathway that could be modelled. We conclude by outlining the limitations of computational modelling and by discussing opportunities for future progress in this area.
    • Mathematically modelling the dynamics of cholesterol metabolism and ageing

      Morgan, Amy; Mooney, Kathleen M.; Wilkinson, Stephen J.; Pickles, Neil; Mc Auley, Mark T.; University of Chester, Edgehill University (Elsevier, 2016-07-30)
      Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This conditionbecomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism isinextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol(LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. Theaim of this work was to use mathematical modelling to explore how cholesterol metabolism is affectedby the ageing process. To do this we updated a previously published whole-body mathematical model ofcholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biologicalsystem. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reversecholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of themodel was explored by the use of both local and global parameter scans. In addition, acute cholesterolfeeding was used to explore the effectiveness of the regulatory mechanisms which are responsible formaintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responderto cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly.The model was also used to explore the effects of ageing in tandem with three different cholesterolester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype,conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotypereflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated theimportance of CETP genotypes such as I405V, and their potential role in healthy ageing.
    • Methods for the Treatment of Cattle Manure—A Review

      Font Palma, Carolina (MDPI, 2019-05-15)
      Environmental concerns, caused by greenhouse gases released to the atmosphere and overrunning of nutrients and pathogens to water bodies, have led to reducing direct spread onto the land of cattle manure. In addition, this practice can be a source of water and air pollution and toxicity to life by the release of undesirable heavy metals. Looking at the current practices, it is evident that most farms separate solids for recycling purposes, store slurries in large lagoons or use anaerobic digestion to produce biogas. The review explores the potential for cattle manure as an energy source due to its relatively large calorific value (HHV of 8.7–18.7 MJ/kg dry basis). This property is beneficial for thermochemical conversion processes, such as gasification and pyrolysis. This study also reviews the potential for upgrading biogas for transportation and heating use. This review discusses current cattle manure management technologies—biological treatment and thermochemical conversion processes—and the diverse physical and chemical properties due to the differences in farm practices.
    • Model-directed engineering of “difficult-to-express” monoclonal antibody production by Chinese hamster ovary cells

      Pybus, Leon P.; Dean, Greg; West, Nathan R.; Smith, Andrew; Daramola, Olalekan; Field, Ray; Wilkinson, Stephen J.; James, David C.; University of Sheffield ; BioPharmaceutical Development ; University of Sheffield ; BioPharmaceutical Development ; BioPharmaceutical Development ; BioPharmaceutical Development ; University of Sheffield ; University of Sheffield; ChELSI Institute; Department of Chemical and Biological Engineering; University of Sheffield; Mappin Street Sheffield S1 3JD UK; et al. (Wiley, 2013-11-14)
      Despite improvements in volumetric titer for monoclonal antibody (MAb) production processes using Chinese hamster ovary (CHO) cells, some “difficult-to-express” (DTE) MAbs inexplicably reach much lower process titers.
    • Modelling the molecular mechanisms of ageing

      Mc Auley, Mark T.; Martinez Guimera, Alvaro; Hodgson, David; McDonald, Neil; Mooney, Kathleen M.; Morgan, Amy; Proctor, Carole; University of Chester; Edgehill University; Newcastle University (Portland Press, 2017-02-23)
      The ageing process is driven at the cellular level by random molecular damage which slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the ageing process. The complexity of the ageing process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards, and discusses many specific examples of models which have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field.
    • Obesity and the Dysregulation of Fatty Acid Metabolism: Implications for Healthy Aging

      Morgan, Amy; Mooney, Kathleen M.; Mc Auley, Mark T.; University of Chester; Edge Hill University (Taylor & Francis, 2016-10-17)
      The population of the world is aging. In 2010, an estimated 524 million people were aged 65 years or older presenting eight percent of the global population. By 2050, this number is expected to nearly triple to approximately 1.5 billion, 16 percent of the world’s population. Although people are living longer, the quality of their lives are often compromised due to ill-health. Areas covered. Of the conditions which compromise health as we age, obesity is at the forefront. Over half of the global older population were overweight or obese in 2010, significantly increasing the risk of a range of metabolic diseases. Although, it is well recognised excessive calorie intake is a fundamental driver of adipose tissue dysfunction, the relationship between obesity; intrinsic aging; and fat metabolism is less understood. In this review we discuss the intersection between obesity, aging and the factors which contribute to the dysregulation of whole-body fat metabolism. Expert Commentary. Being obese disrupts an array of physiological systems and there is significant crosstalk among these. Moreover it is imperative to acknowledge the contribution intrinsic aging makes to the dysregulation of these systems and the onset of disease.
    • Oxyfuel power plant with novel CO2 separation and compression technology

      Font Palma, Carolina; University of Leeds (2014-04-03)
    • Part-load performance of direct-firing and co-firing of coal and biomass in a power generation system integrated with a CO2 capture and compression system

      Ali, Usman; Akram, Muhammad; Font Palma, Carolina; Ingham, Derek B.; Pourkashanian, Mohamed; University of Sheffield; University of Chester; University of Engineering and Technology (Elsevier, 2017-09-18)
      Bioenergy with Carbon Capture and Storage (BECCS) is recognised as a key technology to mitigate CO2 emissions and achieve stringent climate targets due to its potential for negative emissions. However, the cost for its deployment is expected to be higher than for fossil-based power plants with CCS. To help in the transition to fully replace fossil fuels, co-firing of coal and biomass provide a less expensive means. Therefore, this work examines the co-firing at various levels in a pulverised supercritical power plant with post-combustion CO2 capture, using a fully integrated model developed in Aspen Plus. Co-firing offers flexibility in terms of the biomass resources needed. This work also investigates flexibility within operation. As a result, the performance of the power plant at various part-loads (40%, 60% and 80%) is studied and compared to the baseline at 100%, using a constant fuel flowrate. It was found that the net power output and net efficiency decrease when the biomass fraction increases for constant heat input and constant fuel flow rate cases. At constant heat input, more fuel is required as the biomass fraction is increased; whilst at constant fuel input, derating occurs, e.g. 30% derating of the power output capacity at firing 100% biomass compared to 100% coal. Co-firing of coal and biomass resulted in substantial power derating at each part-load operation.
    • Prenatal exposures and exposomics of asthma

      Choi, Hyunok; Mc Auley, Mark T.; Lawrence, David A.; University at Albany ; University of Chester ; Center for Medical Sciences, Albany, NY (AIMS Press, 2015-02-19)
      This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental media
    • Process simulation and thermodynamic analysis of a micro turbine with post-combustion CO2 capture and exhaust gas recirculation

      Ali, Usman; Best, Thom; Finney, Karen N.; Font Palma, Carolina; Hughes, Kevin J.; Ingham, Derek B.; Pourkashanian, Mohamed; University of Leeds (Elsevier, 2014-12-31)
      With the effects of the emissions from power plants causing global climate change, the trend towards lower emission systems such as natural gas power plant is increasing. In this paper a Turbec T100 micro gas turbine is studied. The system is assessed thermodynamically using a steady-state model; model results of its alteration with exhaust gas recirculation (EGR) are presented in this paper. The process simulation with EGR offers a useful assessment when integrated with post-combustion CO2 capture. The EGR model results in the enrichment of the CO2 which decrease the energy demand of the CO2 capture system.
    • Production of Biomethane from Agricultural Waste Using a Cryogenic Carbon Capture Process

      Font Palma, Carolina; Lychnos, George; Willson, Paul; University of Chester; PMW Technology Limited (Energy Proceedings, 2019)
      This paper evaluates a novel cryogenic carbon capture process to upgrade biogas produced from agricultural waste. The A3C cryogenic process offers simplicity and compactness with lower capital and operating costs compared to many alternative processes. The work addresses potential technical issues presented by trace contaminants in the raw biogas including hydrogen sulphide, organics and siloxanes. It is found that the A3C process offers high CO2 removal with minimal biomethane losses while requiring simple raw gas treatment.
    • Promises and Challenges of Growing Microalgae in Wastewater

      Osundeko, Olumayowa; Ansolia, Preeti; Kumar Gupta, Sanjay; Bag, Pushan; Bajhaiya, Amit K.; University of Manchester (Springer, 2019-01-22)
      Microalgae have been theoretically described as a sustainable feedstock for biofuel production. However, there are still some concerns and obstacles that need to be overcome in order to translate the theoretical promise into commercial and economic success. These obstacles include a high requirement for nutrients and sustainable water source and the identification of affordable cultivation conditions. It has been suggested that growing microalgae in wastewater can potentially offset some of these obstacles. Microalgae can perform a dual role for remediation of nutrient pollutants and biomass production when grown in wastewater. However, there are huge challenges to overcome before this route can be exploited in an economically and environmentally sustainable manner. In the present chapter, the potentials and challenges of growing microalgae in wastewater and its future implications are discussed in detail.
    • Prospects for petcoke utilization with CO 2 capture in Mexico

      Font Palma, Carolina; Gonzalez Diaz, Abigail; University of Chester; Instituto Nacional de Electricidad y Energías Limpias (INEEL) (Elsevier, 2018-01-31)
      This paper evaluates the introduction of carbon capture and storage (CCS) to Mexico. The gasification technology is presented as a potential alternative to be applied into refinery plants due to high petcoke production. Although economic aspects, such as fuel price and selling CO2, are important in the selection of CCS alternatives, there are other limitations, i.e. water availability and space. In March 2014, Mexico launched its CCS technological roadmap. However, an evaluation of the installation of new CO2-capture ready power plants was not considered. For that reason, this study could be useful to create a technology roadmap that includes the design of CO2 capture plants into refineries and how they will have to operate for CO2 emissions reduction, and taking advantage that most of refineries and petrochemical plants are close to oil fields for enhanced oil recovery (EOR). Integrated gasification combined cycle (IGCC) with CCS was chosen in this paper for power generation using petcoke as feedstock. The emissions of CO2 in kg/kWh could be reduced by 68%.
    • A review of organic waste enrichment for inducing palatability of black soldier fly larvae: Wastes to valuable resources

      Raksasat, Ratchaprapa; Lim, Jun Wei; Kiatkittipong, Worapon; Kiatkittipong, Kunlanan; Ho, Yeek Chia; Lam, Man Kee; Font Palma, Carolina; Zaid, Hayyiratul Fatimah Mohd; Cheng, Chin Kui; Universiti Teknologi PETRONAS; Silpakorn University; King Mongkut's Institute of Technology Ladkrabang; University of Chester; Khalifa University
      The increase of annual organic wastes generated worldwide has become a major problem for many countries since the mismanagement could bring about negative effects on the environment besides, being costly for an innocuous disposal. Recently, insect larvae have been investigated to valorize organic wastes. This entomoremediation approach is rising from the ability of the insect larvae to convert organic wastes into its biomass via assimilation process as catapulted by the natural demand to complete its lifecycle. Among the insect species, black soldier fly or Hermetia illucens is widely researched since the larvae can grow in various environments while being saprophagous in nature. Even though black soldier fly larvae (BSFL) can ingest various decay materials, some organic wastes such as sewage sludge or lignocellulosic wastes such as waste coconut endosperm are destitute of decent nutrients that could retard the BSFL growth. Hence, blending with nutrient-rich low-cost substrates such as palm kernel expeller, soybean curd residue, etc. is employed to fortify the nutritional contents of larval feeding substrates prior to administering to the BSFL. Alternatively, microbial fermentation can be adopted to breakdown the lignocellulosic wastes, exuding essential nutrients for growing BSFL. Upon reaching maturity, the BSFL can be harvested to serve as the protein and lipid feedstock. The larval protein can be made into insect meal for farmed animals, whilst the lipid source could be extracted and transesterified into larval biodiesel to cushion the global energy demands. Henceforth, this review presents the influence of various organic wastes introduced to feed BSFL, targeting to reduce wastes and producing biochemicals from mature larvae through entomoremediation. Modification of recalcitrant organic wastes via fermentation processes is also unveiled to ameliorate the BSFL growth. Lastly, the sustainable applications of harvested BSFL biomass are as well covered together with the immediate shortcomings that entail further researches.
    • The role of DNA methylation in ageing and cancer

      Morgan, Amy; Davies, Trevor J.; Mc Auley, Mark T.; University of Chester (Cambridge University Press, 2018-04-30)
      The aim of the present review paper is to survey the literature related to DNA methylation, and its association with cancer and ageing. The review will outline the key factors, including diet, which modulate DNA methylation. Our rationale for conducting this review is that ageing and diseases, including cancer, are often accompanied by aberrant DNA methylation, a key epigenetic process, which is crucial to the regulation of gene expression. Significantly, it has been observed that with age and certain disease states, DNA methylation status can become disrupted. For instance, a broad array of cancers are associated with promoter-specific hypermethylation and concomitant gene silencing. This review highlights that hypermethylation, and gene silencing, of the EN1 gene promoter, a crucial homeobox gene, has been detected in various forms of cancer. This has led to this region being proposed as a potential biomarker for diseases such as cancer. We conclude the review by describing a recently developed novel electrochemical method that can be used to quantify the level of methylation within the EN1 promoter and emphasise the growing trend in the use of electrochemical techniques for the detection of aberrant DNA methylation.
    • The role of Mathematical Modelling in understanding Aging

      Mc Auley, Mark T.; Morgan, Amy; Mooney, Kathleen M.; University of Chester, Edgehill University (CRC Press, 2017-10-25)
      Mathematical models have played key roles in developing our understanding of aging. The first pioneering mathematical models evaluated aging from an evolutionary perspective, generating meaningful insights into why aging occurs and laid the foundations for our current understanding of aging. More recently mathematical models have been used to gain a deeper understanding of the intracellular mechanisms associated with intrinsic aging. This chapter will outline what mathematical modelling is, and the advantages it has over more conventional approaches used in biogerontology. The steps involved in assembling a model will also be described and the leading theoretical frameworks underpinning them will be outlined. Moreover, we discuss in detail a variety of aging focused mechanistic mathematical models which have been developed in recent years. The chapter concludes by challenging the community to develop a unified mechanistic mathematical model which can be used to examine aging in a more integrated fashion.
    • Scaling-up ultrasound standing wave enhanced sedimentation filters

      Prest, Jeff E.; Treves Brown, Bernard J.; Fielden, Peter R.; Wilkinson, Stephen J.; Hawkes, Jeremy J.; Lancaster University ; University of Manchester ; Lancaster University ; University of Chester ; University of Manchester (Elsevier, 2014-08-21)
      Particle concentration and filtration is a key stage in a wide range of processing industries and also one that can be present challenges for high throughput, continuous operation. Here we demonstrate some features which increase the efficiency of ultrasound enhanced sedimentation and could enable the technology the potential to be scaled up. In this work, 20 mm piezoelectric plates were used to drive 100 mm high chambers formed from single structural elements. The coherent structural resonances were able to drive particles (yeast cells) in the water to nodes throughout the chamber. Ultrasound enhanced sedimentation was used to demonstrate the efficiency of the system (>99% particle clearance). Sub-wavelength pin protrusions were used for the contacts between the resonant chamber and other elements. The pins provided support and transferred power, replacing glue which is inefficient for power transfer. Filtration energies of ∼4 J/ml of suspension were measured. A calculation of thermal convection indicates that the circulation could disrupt cell alignment in ducts >35 mm high when a 1K temperature gradient is present; we predict higher efficiencies when this maximum height is observed. For the acoustic design, although modelling was minimal before construction, the very simple construction allowed us to form 3D models of the nodal patterns in the fluid and the duct structure. The models were compared with visual observations of particle movement, Chladni figures and scanning laser vibrometer mapping. This demonstrates that nodal planes in the fluid can be controlled by the position of clamping points and that the contacts could be positioned to increase the efficiency and reliability of particle manipulations in standing waves.