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The Bacterial Skin Microbiome In Psoriatic Arthritis, An Unexplored Link In Pathogenesis: Challenges And Opportunities Offered By Recent Technological Advances., Madhura Castelino, Stephen Eyre, Mathew Upton, Pauline Ho, Anne Barton

School of Biomedical Sciences

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both …

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Implementation Of Fourier Transform Infrared Spectroscopy For The Rapid Typing Of Uropathogenic Escherichia Coli., S. E. Dawson, T. Gibreel, N. Nicolaou, H. Alrabiah, Y. Xu, R. Goodacre, M. Upton

School of Biomedical Sciences

In this paper, we demonstrate that Fourier transform infrared (FT-IR) spectroscopy is able to discriminate rapidly between uropathogenic Escherichia coli (UPEC) of key lineages with only relatively simple sample preparation. A total of 95 bacteria from six different epidemiologically important multilocus sequence types (ST10, ST69, ST95, ST73, ST127 and ST131) were used in this project and principal component-discriminant function analysis (PC-DFA) of these samples produced clear separate clustering of isolates, based on the ST. Analysis of data using partial least squares-discriminant analysis (PLS-DA), incorporating cross-validation, indicated a high prediction accuracy of 91.19% for ST131. These results suggest that FT-IR spectroscopy …

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Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

Galleria mellonella larvae are an alternative in vivo model for investigating bacterial pathogenicity. Here, we examined the pathogenicity of 71 isolates from five leading uropathogenic E. coli (UPEC) lineages using G. mellonella larvae. Larvae were challenged with a range of inoculum doses to determine the 50% lethal dose (LD50) and for analysis of survival outcome using Kaplan-Meier plots. Virulence was correlated with carriage of a panel of 29 virulence factors (VF). Larvae inoculated with ST69 and ST127 isolates (10(4) colony-forming units/larvae) showed significantly higher mortality rates than those infected with ST73, ST95 and ST131 isolates, killing 50% of the larvae …

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A Workflow For Bacterial Metabolic Fingerprinting And Lipid Profiling: Application To Ciprofloxacin Challenged Escherichia Coli, J. William Allwood, Haitham Alrabiah, Elon Correa, Andrew Vaughan, Yun Xu, Mathew Upton, Royston Goodacre

School of Biomedical Sciences

No abstract provided.

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A Novel Phosphatidylinositol 3-Kinase (Pi3k) Inhibitor Directs A Potent Foxo-Dependent, P53-Independent Cell Cycle Arrest Phenotype Characterized By The Differential Induction Of A Subset Of Foxo-Regulated Genes, Richard Hill, Ravi Kiran Reddy Kalathur, Sergio Callejas, Laura Colaço, Ricardo Brandão, Beatriz Serelde, Antonio Cebriá, Carmen Blanco-Aparicio, Joaquín Pastor, Matthias Futschik, Ana Dopazo, Wolfgang Link

School of Biomedical Sciences

No abstract provided.

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Differentially Expressed Micrornas In Maternal Plasma For The Noninvasive Prenatal Diagnosis Of Down Syndrome (Trisomy 21), J Kamhieh-Milz, Reham Fadl Hassan Moftah, Gürkan Bal, Matthias Futschik, Viktor Sterzer, Omid Khorramshahi, Martin Burow, Gundula Thiel, Annegret Stuke-Sontheimer, Rabih Chaoui, S Kamhieh-Milz, Abdulgabar Salama

School of Biomedical Sciences

Objectives. Most developmental processes are under the control of small regulatory RNAs called microRNAs (miRNAs). We hypothesize that different fetal developmental processes might be reflected by extracellular miRNAs in maternal plasma and may be utilized as biomarkers for the noninvasive prenatal diagnosis of chromosomal aneuploidies. In this proof-of-concept study, we report on the identification of extracellular miRNAs in maternal plasma of Down syndrome (DS) pregnancies.Methods. Using high-throughput quantitative PCR (HT-qPCR), 1043 miRNAs were investigated in maternal plasma via comparison of seven DS pregnancies with age and fetal sex matched controls.Results. Six hundred and ninety-five miRNAs were identified. Thirty-six significantly differentially …

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Nuclear Her4 Mediates Acquired Resistance To Trastuzumab And Is Associated With Poor Outcome In Her2 Positive Breast Cancer, Snm Nafi, D Generali, G Kramer-Marek, M Gijsen, Et Al

School of Biomedical Sciences

The role of HER4 in breast cancer is controversial and its role in relation to trastuzumab resistance remains unclear. We showed that trastuzumab treatment and its acquired resistance induced HER4 upregulation, cleavage and nuclear translocation. However, knockdown of HER4 by specific siRNAs increased trastuzumab sensitivity and reversed its resistance in HER2 positive breast cancer cells. Preventing HER4 cleavage by a γ-secretase inhibitor and inhibiting HER4 tyrosine kinase activity by neratinib decreased trastuzumab-induced HER4 nuclear translocation and enhanced trastuzumab response. There was also increased nuclear HER4 staining in the tumours from BT474 xenograft mice and human patients treated with trastuzumab. Furthermore, …

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Evidence That Duplications Of 22q11.2 Protect Against Schizophrenia, E Rees, G Kirov, Mc O'Donovan, Wellcome Trust Case Control Consortium, Et Al

School of Biomedical Sciences

A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2--the reciprocal of the well-known, risk-inducing deletion of this locus--are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia.

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Exploring Perceived Barriers, Drivers, Impacts And The Need For Evaluation Of Public Involvement In Health And Social Care Research: A Modified Delphi Study, D. Snape, J. Kirkham, N. Britten, K. Froggatt, F. Gradinger, F. Lobban, Jennie Popay, K. Wyatt, Ann Jacoby

Peninsula Medical School

ObjectiveTo explore areas of consensus and conflict in relation to perceived public involvement (PI) barriers and drivers, perceived impacts of PI and ways of evaluating PI approaches in health and social care research.BackgroundInternationally and within the UK the recognition of potential benefits of PI in health and social care research is gathering momentum and PI is increasingly identified by organisations as a prerequisite for funding. However, there is relatively little examination of the impacts of PI and how those impacts might be measured.DesignMixed method, three-phase, modified Delphi technique, conducted as part of a larger MRC multiphase project.SampleClinical and non-clinical academics, …

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Qualified Doctor And Medical Students' Use Of Resources For Accessing Information: What Is Used And Why?, Nicola Brennan, Sarah Edwards, Narcie Kelly, Alice Miller, Lucy Harrower, Karen Mattick

Peninsula Medical School

BACKGROUND: Learning to access information using resources such as books and search engines is an important and fast changing challenge for doctors and medical students. Many resources exist to support evidence-based clinical decision-making, but a wide range of factors influences their use. OBJECTIVE: To explore qualified doctor and medical students' use of resources for accessing information and to determine what is used and why. METHODS: A stratified sample of 46 participants was recruited in Devon, UK. Participants kept a self-report diary of resources used over a week. The diaries were then used to stimulate recall within a semi-structured interview. Diary …

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Deficiency Of Sphingosine-1-Phosphate Lyase Impairs Lysosomal Metabolism Of The Amyloid Precursor Protein, I Karaca, Iy Tamboli, K Glebov, J Richter, Lh Fell, Mo Grimm, Vj Haupenthal, T Hartmann, Mh Gräler, Echten-Deckert G Van, J Walter

Peninsula Medical School

No abstract provided.

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Longitudinal Evaluation Of Quality Of Life In 288 Patients With Neurofibromatosis 2, Rosalie E. Ferner, Adam Shaw, D. Gareth Evans, Dympna Mcaleer, Dorothy Halliday, Allyson Parry, F. Lucy Raymond, Juliette Durie-Gair, C. Oliver Hanemann, Rachel Hornigold, Patrick Axon, John F. Golding

Peninsula Medical School

No abstract provided.

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Full-Text Articles in Entire DC Network

The Bacterial Skin Microbiome In Psoriatic Arthritis, An Unexplored Link In Pathogenesis: Challenges And Opportunities Offered By Recent Technological Advances., Madhura Castelino, Stephen Eyre, Mathew Upton, Pauline Ho, Anne Barton

School of Biomedical Sciences

Implementation Of Fourier Transform Infrared Spectroscopy For The Rapid Typing Of Uropathogenic Escherichia Coli., S. E. Dawson, T. Gibreel, N. Nicolaou, H. Alrabiah, Y. Xu, R. Goodacre, M. Upton

School of Biomedical Sciences

Galleria Mellonella Infection Model Demonstrates High Lethality Of St69 And St127 Uropathogenic E. Coli., Majed F. Alghoribi, Tarek M. Gibreel, Andrew R. Dodgson, Scott A. Beatson, Mathew Upton

School of Biomedical Sciences

A Workflow For Bacterial Metabolic Fingerprinting And Lipid Profiling: Application To Ciprofloxacin Challenged Escherichia Coli, J. William Allwood, Haitham Alrabiah, Elon Correa, Andrew Vaughan, Yun Xu, Mathew Upton, Royston Goodacre

School of Biomedical Sciences

School of Biomedical Sciences

School of Biomedical Sciences

Nuclear Her4 Mediates Acquired Resistance To Trastuzumab And Is Associated With Poor Outcome In Her2 Positive Breast Cancer, Snm Nafi, D Generali, G Kramer-Marek, M Gijsen, Et Al

School of Biomedical Sciences

Evidence That Duplications Of 22q11.2 Protect Against Schizophrenia, E Rees, G Kirov, Mc O'Donovan, Wellcome Trust Case Control Consortium, Et Al

School of Biomedical Sciences

Exploring Perceived Barriers, Drivers, Impacts And The Need For Evaluation Of Public Involvement In Health And Social Care Research: A Modified Delphi Study, D. Snape, J. Kirkham, N. Britten, K. Froggatt, F. Gradinger, F. Lobban, Jennie Popay, K. Wyatt, Ann Jacoby

Peninsula Medical School

Qualified Doctor And Medical Students' Use Of Resources For Accessing Information: What Is Used And Why?, Nicola Brennan, Sarah Edwards, Narcie Kelly, Alice Miller, Lucy Harrower, Karen Mattick

Peninsula Medical School

Deficiency Of Sphingosine-1-Phosphate Lyase Impairs Lysosomal Metabolism Of The Amyloid Precursor Protein, I Karaca, Iy Tamboli, K Glebov, J Richter, Lh Fell, Mo Grimm, Vj Haupenthal, T Hartmann, Mh Gräler, Echten-Deckert G Van, J Walter

Peninsula Medical School

Longitudinal Evaluation Of Quality Of Life In 288 Patients With Neurofibromatosis 2, Rosalie E. Ferner, Adam Shaw, D. Gareth Evans, Dympna Mcaleer, Dorothy Halliday, Allyson Parry, F. Lucy Raymond, Juliette Durie-Gair, C. Oliver Hanemann, Rachel Hornigold, Patrick Axon, John F. Golding

Peninsula Medical School