• Ibuprofen Nanoparticles and its cytotoxicity on A549 and HaCaT cell lines

      Graham, Stan; Phillip, Roy; Zahid, Myra; Bano, Nadia; Iqbal, Qasim; Mahboob, Fidaa; Chen, Xianfeng; Shang, Lijun (2016)
      Ibuprofen (IBF) is an outstanding non-steroidal drug for analgesic and anti-inflammatory therapies but it exhibits poor solubility in water [1, 2]. Increased dosage administration has been linked to gastrointestinal and cardiovascular complications [3]. Many techniques have been employed to improve the solubility of NSAIDs [4]. In this study, the anti-solvent precipitation method was used to make Ibuprofen nanoparticles (IBF NPs). Optimised preparation parameters such as solvent (ethanol), raw drug concentration (400 mg), solvent/anti-solvent ratio (1:50) and surfactant concentration (0.25 mg/ml) have been studied to yield nanoparticles with a mean size of 58.8 nm, which is confirmed by dynamic light scattering and transmission electron microscopy. These IBF NPs posess increased aqueous solubility compared to the micro counterpart and maintain with chemical integrity indicated by high performance liquid chromatography and Fourier transform infrared spectroscopy. In addition, in vitro cytotoxicity of IBF NPs has been studied on A549 and HaCat cell lines using MTT and LDH assays. Both cells were obtained from ATCC. The A549 cells were grown in a modification of Ham’s F-12, containing L-glutamine, called F-12K. The HaCaT cells were grown in DMEM containing sodium pyruvate (110 mg/l). Normal cell culture and sub-culture were applied and the cells were used after around 45 passages [5]. The cell culture media containing 105cells/ml were placed in a 96-well plate with addition of IBF NPs and Micro form at concentrations in the range of between 6 and 500 ug/ml by diluting them with DMEM and F-12K for use with the HaCaT and A549 cells respectively. After 24, 48 and 72h exposure, the MTT and LDH cytotoxicity assay were performed in triplicates and on three separate experiment cultures and the absorbance was recorded at 570 nm and 492nm respectively with Elisa micro plate reader. The cell viability (%) related to control (cells in culture medium without NPs) was calculated. A very good cytotoxicity profile was observed, indicating an in vitro cytocompatibility of the IBF NPs in these cell culture systems and no significant changes in cytotoxicity compared with Micro IBF. We conclude that our IBF NPs have increased solubility, same chemical integrity and unchanged cytotoxicity compared to IBF Micro drug. Further work will concentrate on optimising more rigorous parameter to produce excellent quality NPs. More detailed characterisation of IBF NPs is to be tested, such as using PXRD and SEM to further corroborate particle shape and size. The range of no toxic in vitro concentrations is also to be further confirmed. Eventually scaled up preparation of IBF NPs will be developed without relinquishing NPs quality. This would improve the potential for in vitro/ in vivo applications and clinical use of IBF NPs and NSAIDs in general.
    • Identification and characterisation of two extracellular proteases of Streptococcus mutans

      Harrington, Dean J.; Russell, R.R.B. (1994-08)
      Streptococcus mutans was shown to produce two extracellular proteases capable of degrading both gelatin and collagen-like substrates. These enzymes have molecular masses of 52 and 50 kDa when analysed by SDS-PAGE. Both enzymes were inhibited by EDTA, but not by a range of other inhibitors with different specificities, indicating that they are metalloproteases. The activity of EDTA-inactivated enzymes could be restored by the addition of manganese and zinc. The identical inhibition and restoration profiles of the two enzymes suggest that one of the proteases may be a degradation product of the other.
    • Identification and Genetic Characterisation of Melibiose-Negative Isolates of Streptococcus mutans

      Colby, S.M.; Harrington, Dean J.; Russell, R.R.B. (1995)
      Streptococcus mutans is frequently identified on the basis of phenotypic characteristics such as the ability to ferment carbohydrates. The usefulness of some of these identification tests may be limited in the case of isolates which are atypical with regard to their fermentation properties. We previously identified isolates of S. mutans which were unable to ferment melibiose, a characteristic which is included in some typing schemes. In all of these isolates there was a large chromosomal deletion which included the multiple sugar metabolism (msm) operon which encodes several genes involved in the uptake and metabolism of a number of sugars including melibiose. In the present study, sugar fermentation tests, ribotyping, colony hybridisation with DNA probes and polymerase chain reaction (PCR) were used to investigate the relatedness of these atypical isolates. The PCR and colony hybridisation procedures were based on amplification and detection of two genes: the wapA gene which encodes a surface protein found in all S. mutans strains and the gtfA gene which lies within the msm operon. The colony hybridisation and PCR results confirmed loss of the gtfA gene in the melibiose-negative isolates. Three new melibiose-negative isolates were also identified, but in only 2 of these was the gtfA gene absent, the third did not appear to have lost this region of the chromosome. Biotyping, as well as ribotyping based on an EcoRl digest of chromosomal DNA, revealed that the melibiose-negative isolates fell into a number of distinct groups. The identification of an isolate which is unable to ferment melibiose but does not appear to have lost the msm operon indicates that the melibiose-negative phenotype can arise from more than one type of genetic event.
    • Identification of an acetyl disulfide derivative in the synthesis of thiosialosides

      Ribeiro Morais, Goreti; Oliveira, Inês P.F.; Humphrey, Andrew J.; Falconer, Robert A. (2009)
      The first report of the formation of an acetyl disulfide sialoside during the synthesis of thioglycosides is described. This compound is a by-product in the synthesis of the 2-thioacetyl sialoside commonly used in thioglycoside preparation. Our investigations into the identification of this novel disulfide are described.
    • Identification of compounds with cytotoxic activity from the leaf of the Nigerian medicinal plant, Anacardium occidentale L. (Anacardiaceae)

      Taiwo, Bamigboye J.; Fatokun, Amos A.; Olubiyi, O.O.; Bamigboye-Taiwo, O.T.; van Heerden, F.R.; Wright, Colin W. (2017-04-15)
      Cancer is now the second-leading cause of mortality and morbidity, behind only heart disease, necessitating urgent development of (chemo)therapeutic interventions to stem the growing burden of cancer cases and cancer death. Plants represent a credible source of promising drug leads in this regard, with a long history of proven use in the indigenous treatment of cancer. This study therefore investigated Anacardium occidentale, one of the plants in a Nigerian Traditional Medicine formulation commonly used to manage cancerous diseases, for cytotoxic activity. Bioassay-guided fractionation, spectroscopy, Alamar blue fluorescence-based viability assay in cultured HeLa cells and microscopy were used. Four compounds: zoapatanolide A (1), agathisflavone (2), 1, 2-bis (2,6-dimethoxy-4-methoxybenzoyl) ethane (Anacardicin, 3) and methyl gallate (4) were isolated, with the most potent being zoapatanolide A with an IC50 value of 36.2 ± 9.8 μM in the viability assay. To gain an insight into the likely molecular basis of their observed cytotoxic effects, Autodock Vina binding free energies of each of the isolated compounds with seven molecular targets implicated in cancer development (MAPK8, MAPK10, MAP3K12, MAPK3, MAPK1, MAPK7 and VEGF), were calculated. Pearson correlation coefficients were obtained with experimentally-determined IC50 in the Alamar blue viability assay. While these compounds were not as potent as a standard anti-cancer compound, doxorubicin, the results provide reasonable evidence that the plant species contains compounds with cytotoxic activity. This study provides some evidence of why this plant is used ethnobotanically in anti-cancer herbal formulations and justifies investigating Nigerian medicinal plants highlighted in recent ethno-botanical surveys.
    • Identification of cryptolepine metabolites in rat and human hepatocytes and metabolism and pharmacokinetics of cryptolepine in Sprague Dawley rats

      Forkuo, A.D.; Ansah, C.; Pearson, D.; Gertsch, W.; Cirello, A.; Amaral, A.; Spear, J.; Wright, Colin W.; Rynn, C. (2017-12)
      Background: This study aims at characterizing the in vitro metabolism of cryptolepine using human and rat hepatocytes, identifying metabolites in rat plasma and urine after a single cryptolepine dose, and evaluating the single-dose oral and intravenous pharmacokinetics of cryptolepine in male Sprague Dawley (SD) rats. Methods: The in vitro metabolic profiles of cryptolepine were determined by LC-MS/MS following incubation with rat and human hepatocytes. The in vivo metabolic profile of cryptolepine was determined in plasma and urine samples from Sprague Dawley rats following single-dose oral administration of cryptolepine. Pharmacokinetic parameters of cryptolepine were determined in plasma and urine from Sprague Dawley rats after single-dose intravenous and oral administration. Results: Nine metabolites were identified in human and rat hepatocytes, resulting from metabolic pathways involving oxidation (M2-M9) and glucuronidation (M1, M2, M4, M8, M9). All human metabolites were found in rat hepatocyte incubations except glucuronide M1. Several metabolites (M2, M6, M9) were also identified in the urine and plasma of rats following oral administration of cryptolepine. Unchanged cryptolepine detected in urine was negligible. The Pharmacokinetic profile of cryptolepine showed a very high plasma clearance and volume of distribution (Vss) resulting in a moderate average plasma half-life of 4.5 h. Oral absorption was fast and plasma exposure and oral bioavailability were low. Conclusions: Cryptolepine metabolism is similar in rat and human in vitro with the exception of direct glucuronidation in human. Clearance in rat and human is likely to include a significant metabolic contribution, with proposed primary human metabolism pathways hydroxylation, dihydrodiol formation and glucuronidation. Cryptolepine showed extensive distribution with a moderate half-life.
    • Identification of LDH-A as a therapeutic target for cancer cell killing via (i) p53.NAD(H)-dependent and (ii) p53-independent pathways

      Allison, Simon J.; Knight, J.R.P.; Granchi, C.; Rani, R.; Minutolo, F.; Milner, J.; Phillips, Roger M. (2014)
      Most cancer cells use aerobic glycolysis to fuel their growth. The enzyme lactate dehydrogenase-A (LDH-A) is key to cancer’s glycolytic phenotype, catalysing the regeneration of nicotinamide adenine dinucleotide (NAD+) from reduced nicotinamide adenine dinucleotide (NADH) necessary to sustain glycolysis. As such, LDH-A is a promising target for anticancer therapy. Here we ask if the tumour suppressor p53, a major regulator of cellular metabolism, influences the response of cancer cells to LDH-A suppression. LDH-A knockdown by RNA interference (RNAi) induced cancer cell death in p53 wild-type, mutant and p53-null human cancer cell lines, indicating that endogenous LDH-A promotes cancer cell survival irrespective of cancer cell p53 status. Unexpectedly, however, we uncovered a novel role for p53 in the regulation of cancer cell NAD+ and its reduced form NADH. Thus, LDH-A silencing by RNAi, or its inhibition using a small-molecule inhibitor, resulted in a p53-dependent increase in the cancer cell ratio of NADH:NAD+. This effect was specific for p53+/+ cancer cells and correlated with (i) reduced activity of NAD+-dependent deacetylase sirtuin 1 (SIRT1) and (ii) an increase in acetylated p53, a known target of SIRT1 deacetylation activity. In addition, activation of the redox-sensitive anticancer drug EO9 was enhanced selectively in p53+/+ cancer cells, attributable to increased activity of NAD(P)H-dependent oxidoreductase NQO1 (NAD(P)H quinone oxidoreductase 1). Suppressing LDH-A increased EO9-induced DNA damage in p53+/+ cancer cells, but importantly had no additive effect in non-cancer cells. Our results identify a unique strategy by which the NADH/NAD+ cellular redox status can be modulated in a cancer-specific, p53-dependent manner and we show that this can impact upon the activity of important NAD(H)-dependent enzymes. To summarise, this work indicates two distinct mechanisms by which suppressing LDH-A could potentially be used to kill cancer cells selectively, (i) through induction of apoptosis, irrespective of cancer cell p53 status and (ii) as a part of a combinatorial approach with redox-sensitive anticancer drugs via a novel p53/NAD(H)-dependent mechanism.
    • Identification of lipoprotein homologues of pneumococcal PsaA in the equine pathogens Streptococcus equi and Streptococcus zooepidemicus

      Harrington, Dean J.; Greated, J.S.; Chanter, N.; Sutcliffe, I.C. (2000-10)
      Streptococcus equi and Streptococcus zooepidemicus are major etiological agents of upper and lower airway disease in horses. Despite the considerable animal suffering and economic burden associated with these diseases, the factors that contribute to the virulence of these equine pathogens have not been extensively investigated. Here we demonstrate the presence of a homologue of the Streptococcus pneumoniae PsaA protein in both of these equine pathogens. Inhibition of signal peptide processing by the antibiotic globomycin confirmed the lipoprotein nature of the mature proteins, and surface exposure was confirmed by their release from intact cells by mild trypsinolysis.
    • Identification of methionine-processed HPr in the equine pathogen Streptococcus equi

      Sutcliffe, I.C.; Trigg, J.; Harrington, Dean J. (2000-10)
      Using preparative electrophoresis, a low molecular weight protein has been partially purified from a cell extract of the equine pathogen Streptococcus equi susp. equi. N-terminal sequence analysis and Western blotting revealed the protein to be HPr, a central component of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). Interestingly, the only form of the HPr protein detected in S. equi was one with the amino-terminal methionine removed, a modification that has previously been associated with surface localization of streptococcal HPr proteins.
    • Identification of Stage-Specific Breast Markers using Quantitative Proteomics

      Shaheed, Sadr-ul; Rustogi, Nitin; Scally, Andy J.; Wilson, J.; Thygesen, H.; Loizidou, M.A.; Hadjisavvas, A.; Hanby, A.; Speirs, V.; Loadman, Paul M.; et al. (2013)
      Matched healthy and diseased tissues from breast cancer patients were analyzed by quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive ductal carcinoma (four patients), we identified protein alterations that correlated with breast cancer progression. Three 8-plex iTRAQ experiments generated an average of 826 protein identifications, of which 402 were common. After excluding those originating from blood, 59 proteins were significantly changed in tumor compared with normal tissues, with the majority associated with invasive carcinomas. Bioinformatics analysis identified relationships between proteins in this subset including roles in redox regulation, lipid transport, protein folding, and proteasomal degradation, with a substantial number increased in expression due to Myc oncogene activation. Three target proteins, cofilin-1 and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3 (decreased in invasive carcinoma), were subjected to further validation. All three were observed in phenotype-specific breast cancer cell lines, normal (nontransformed) breast cell lines, and primary breast epithelial cells by Western blotting, but only cofilin-1 and p23 were detected by multiple reaction monitoring mass spectrometry analysis. All three proteins were detected by both analytical approaches in matched tissue biopsies emulating the response observed with proteomics analysis. Tissue microarray analysis (361 patients) indicated cofilin-1 staining positively correlating with tumor grade and p23 staining with ER positive status; both therefore merit further investigation as potential biomarkers.
    • Identifying active vascular microcalcification by 18F-sodium fluoride positron emission tomography

      Irkle, A.; Vesey, A.T.; Lewis, D.Y.; Skepper, J.N.; Bird, Joseph; Dweck, M.R.; Joshi, F.R.; Gallagher, F.A.; Warburton, E.A.; Bennett, M.R.; et al. (2015)
      Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of highrisk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of 18F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse 18F-NaF binding. We show that 18F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. 18F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of 18F-NaF may foster new approaches to developing treatments for vascular calcification.
    • Identifying active vascular micro‐calcification by 18F‐sodium fluoride positron emission tomography

      Vesey, A.T.; Irkle, A.; Skepper, J.N.; Bird, Joseph; Dweck, M.R.; Joshi, F.J.; Gallagher, F.A.; Warburton, E.A.; Bennett, M.R.; Brindle, K.M.; et al. (2015-07)
      Background: Vascular calcification is an active cell-mediated process that is a hallmark of atherosclerosis. Whilst macro-calcification confers stability to plaque, micro-calcification is a key feature of high-risk atheroma associated with major adverse cardiovascular events. Positron emission tomography combined with computed tomography (PET/CT) imaging of atherosclerosis using 18F-sodium fluoride (18F-NaF) has the potential to identify active micro-calcification and thus high-risk plaque. The precise molecular mechanism of 18F-NaF binding has however not been validated. The aim of this study was to provide a comprehensive model describing the binding characteristics, pharmacodynamics and pharmacokinetics of 18F-NaF. Methods: Patients undergoing carotid endarterectomy were studied. 18F-NaF binding was analysed using a combination of electron microscopy, autoradiography, gamma scintigraphy, histology and immunohistochemistry, pre-clinical microPET/microCT and dynamic clinical PET/CT. Results: 18F-NaF was shown to bind to calcium within plaque with high affinity. Binding was selective and specific. 18F-NaF PET was able to identify on-going nascent micro-calcification far beyond the resolution of clinical and pre-clinical CT systems. Furthermore, 18F-NaF was able to distinguish between areas of macro and micro-calcification. Conclusions: 18F-NaF PET/CT is the only currently available clinical imaging platform that can detect micro-calcification in active unstable atherosclerosis. The use of 18F-NaF will foster new approaches to developing treatments targeting unstable plaque and vascular calcification.
    • Identifying Archaeological Bone via Non-Destructive ZooMS and the Materiality of Symbolic Expression: Examples from Iroquoian Bone Points

      McGrath, K.; Rowsell, K.; Gates St-Pierre, C.; Tedder, Andrew; Foody, G.; Roberts, C.; Speller, C.; Collins, M. (2019-07-30)
      Today, practical, functional and symbolic choices inform the selection of raw materials for worked objects. In cases where we can discern the origin of worked bone, tooth, ivory and antler objects in the past, we assume that similar choices are being made. However, morphological species identification of worked objects is often impossible due to the loss of identifying characteristics during manufacture. Here, we describe a novel non-destructive ZooMS (Zooarchaeology by Mass Spectrometry) method which was applied to bone points from Pre-Contact St. Lawrence Iroquoian village sites in southern Quebec, Canada. The traditional ZooMS technique requires destructive analysis of a sample, which can be problematic when dealing with artefacts. Here we instead extracted proteins from the plastic bags in which the points had been stored. ZooMS analysis revealed hitherto unexpected species, notably black bear (Ursus americanus) and human (Homo sapiens sapiens), used in point manufacture. These surprising results (confirmed through genomic sequencing) highlight the importance of advancing biomolecular research in artefact studies. Furthermore, they unexpectedly and exceptionally allow us to identify and explore the tangible, material traces of the symbolic relationship between bears and humans, central to past and present Iroquoian cosmology and mythology.
    • Identifying green logistics best practices leading to the effective usage of pharmaceuticals: a case study of Thailand’s Public Hospitals

      Bandoophanit, Thianthip; Breen, Liz; Barber, Kevin D. (2017-09)
      Purpose Pharmaceuticals are a key input into healthcare operations and so their effective management is vital. This issue is of key importance in Thailand and is aligned with the Thailand’s 2nd National Logistics and Supply Chain Research Strategies (2012-2016) focusing on healthcare green logistics. Pharmaceuticals in hospitals account for more than 50% of the total hospital purchasing budget. Moreover, the overuse of medicine was generally found to be prevalent in Thai hospitals despite serious financial concerns. The aim of this study was twofold: Phase (i) to investigate the movement and lifecycle of pharmaceuticals within Thai hospital sites and Phase (ii) identify the GL practices that effectively control/minimize the use of pharmaceuticals. Research Approach Using a case research method six hospitals were examined, to give coverage of the different types/sizes, locations and a range of environmental performance issues. Hospital visits were undertaken during January to July 2014, to obtain data by using a multi-method approach: interviews, documentation reviews and in situ observation. Purposive respondent sampling was undertaken to ensure that data was collected from staff with experience of pharmaceutical management and a bespoke form of content analysis used for the data review before further cross-case analysis. Findings and Originality The result of Phase (i) revealed that pharmaceutical flows appeared to be sophisticated and problematic, caused by issues such as limited budget allocation, ineffective governmental processes, and the over-prescribing of medicine for chronic patients. The findings also identified effective GL practices such as: (i) prescribing medicines for only 1-2 months for some patient conditions/drug types and increasing the frequency of follow-up reviews, (ii) conducting a medicines return programme and (iii) having a clearly defined system of pharmaceutical product review. The outcomes of the study proposed key practices to support a Sustainable Health System at both policy and hospital levels. Within this were: (i) a representation of stakeholder views, (ii) the provision of healthcare education and communication, (iii) addressing self-health management issues and (iv) planned system review and improvement. The design and execution of such a system should be grounded in Thailand’s Sufficiency Economy Philosophy (SEP) concept. Research Impacts In the GL research paradigm public healthcare, developing nations, human elements and life-cycle products have received limited attention; this study therefore contributes to the reduction of these gaps. The SEP concept was highly recommended by the United Nations, instead of Sustainable Development, in addressing GL practices in Thai culture to promote sustainable health standards and this underpins the focus and the originality/impact of this study. Practical Impacts This study recommends that staff in Thai hospitals focus on effective pharmaceutical management to contribute to the sustainability of good GL practices (as identified) and to the design and delivery of a Sustainable Health System in Thailand. The study presents guidance and support to do this.
    • Identifying green logistics best practices: a case study of Thailand's public hospitals

      Bandoophanit, T.; Breen, Liz; Barber, Kevin D. (2018-09)
      Purpose Previous research (Bandoophanit et al, 2017) has shown that pharmaceuticals are a key input into effective healthcare operations but other equally important inputs are medical supplies, food, utilities, equipment and linen. As stated by the Twelfth National Economic and Social Development Plan (2017-2021) of Thailand, to attempt to deliver national Sustainable Development Goals (SDGs) organisations should preserve resources and minimize waste-generation in all aspects. The principal aim of this research project was to identify green practices and develop a model which supported and promoted healthcare efficiencies. Research Approach This was a mixed methods multi-site study using both qualitative and quantitative data collection and analysis methods. Six public hospitals were selected as case organizations, covering different types/sizes, locations, and environmental performance expertise. The data collection methods included interviews, documentation reviews and in situ observations. Respondents’ selection was purposive and a bespoke form of content analysis was used for the data review before further cross-case analysis, resulting in the identification of best practices using key indicators. Findings and Originality In spite of facing financial crisis, by reviewing key logistical processes and lifecycle, the overuse of healthcare resources and the poor management of waste, were clearly identified within in this study. This had a negative effect on personnel and patient hygiene. The result of identifying effective GL practices were reported as: (i) promoting the usage of multiple-use medical devices that can minimize inputs, waste, and cost, and (ii) producing/selecting organic food materials and fruits and reusing these waste byproducts to create secondary products e.g. fertilizer, biogas and electricity and cleaning/sterilizing liquid. The results also indicated that there was a drive from leaders to introduce green and efficient systems to improve staff personnel awareness and engagement in this area. The output of this study presents a model for GL implementation guidance, grounded in Thailand’s Sufficiency Economy Philosophy (SEP) concept. Research Impacts Currently, healthcare green logistics has received limited attention in developing nations and this study contributes to the reduction of these gaps. The SEP concept promotes sustainable health standards and underpins the focus and the originality/impact of this study. Practical Impacts This study recommends that staff in Thai hospitals focus on effective resource and waste management to contribute to sustainable sufficiency. This allows Thailand to offer an effective healthcare service to its patients. The study presents guidance and support to do this.
    • Identifying reverse exchange practices: a comparative study of laundry logistics in public hospitals (Thailand)

      Bandoophanit, T.; Breen, Liz (2018-09-07)
      The effective reverse exchange of healthcare products such as laundry within a hospital environment can support the health system, for achieving the highest goal: ‘to provide regular and timely supply of clean linen to the satisfaction of patients and staff’ (Srikar et al., 2015, p. 593). Previous studies by Bandoophanit et al. (2015, 2017) assert there are constant shortages of linen availability in many Thai public hospitals which can undermine the efficacy of laundry management and quality of medical treatment. This study investigates the practices, culture, and operational performance of three large-sized public hospitals (700-2,000 beds) located in Thailand reflecting on the application of Reverse Exchanges (R/E) theory. This study contributes to the Thai healthcare agenda, a core mission of which is to “Develop the health system with quality, efficiency and equality; with participation of the people, communities and all sectors for good health of all Thai people in order to achieve a good and sustainable society following the King’s Sufficiency Economy philosophy” (Ministry of Public Health, 2018).
    • Identity of Streptococcus mutans Surface Protein Antigen III and Wall-Associated Protein Antigen A of Streptococcus mutans

      Russell, M.W.; Harrington, Dean J.; Russell, R.R.B. (1995-02)
      Preparations of Streptococcus mutans surface proteins AgIII and antigen A from different laboratories were compared with regard to amino acid composition, N-terminal amino acid sequence, electrophoretic mobility, and antigenic similarity. Despite previous observations of differences in physical properties, data indicate that these two preparations represent the same protein.
    • The Identity of the St Bees Lady, Cumbria: An Osteobiographical Approach

      Knüsel, Christopher J.; Batt, Catherine M.; Cook, G.; Montgomery, Janet; Müldner, G.; Ogden, Alan R.; Palmer, C.; Stern, Ben; Todd, J.; Wilson, Andrew S. (2010)
      Using an Osteobiographical approach, this contribution considers the identity of the woman found alongside the St Bees Man, one of the best-preserved archaeological bodies ever discovered. Osteological, isotopic and radiocarbon analyses, combined with the archaeological context of the burial and documented social history, provide the basis for the identification of a late 14th-century heiress whose activities were at the heart of medieval northern English geopolitics.
    • IFNλ stimulates MxA production in human dermal fibroblasts via a MAPK-dependent STAT1-independent mechanism

      Alase, Adewonuola A.; El-Sherbiny, Y.; Vital, E.; Tobin, Desmond J.; Turner, N.A.; Wittmann, Miriam (2015-08)
      Interferon lambda (IFNλ) is important for epidermal defence against viruses. It is produced by, and acts on, keratinocytes, whereas fibroblasts were previously considered to be unresponsive to this type III IFN. Herein we report findings revealing cell type-specific differences in IFNλ signalling and function in skin resident cells. In dermal fibroblasts, IFNλ induced the expression of MxA, a potent antiviral factor, but not other IFN signature genes as it does in primary keratinocytes. In contrast to its effect on keratinocytes, IFNλ did not phosphorylate STAT1 in fibroblasts, but instead activated MAPKs. Accordingly, inhibition of MAPK activation (p38 and p42/44) blocked the expression of MxA protein in fibroblasts but not in keratinocytes. Functionally, IFNλ inhibited proliferation in keratinocytes but not in fibroblasts. Moreover, IFNλ upregulated the expression of TGFβ1-induced collagens in fibroblasts. Taken together, our findings identify primary human dermal fibroblasts as responder cells to IFNλ. Our study shows cutaneous cell type-specific IFN signalling and suggests that IFNλ, whilst important for epidermal anti-viral competence, may also have a regulatory role in the dermal compartment balancing type I IFN-induced inhibition of tissue repair processes.
    • IL-17A RNA aptamer: possible therapeutic potential in some cells, more than we bargained for in others?

      Doble, R.; McDermott, M.F.; Cesur, O.; Stonehouse, N.J.; Wittmann, Miriam (2014)