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Fabrication and characterisation of random and aligned electrospun scaffolds to investigate hypothalamic stem/progenitor cell behaviour

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Engineered Regeneration

Engineered Regeneration 2024年第1期5卷 11-20页

作者： Selina Beal iain Stewart Paul Hatton Marysia Placzek Ilida Ortega School of clinical Dentistry and Insigneo Institute Claremont CrescentUniversity of SheffieldSheffield S102TAUK School of Biosciences University of SheffieldEnglandUK National Heart and Lung Institute Imperial CollegeLondon SW36LYUK

Tanycytes are stem/progenitor cells that reside in the hypothalamus of the adult vertebrate *** can be cultured as free-floating neurospheres in vitro but tend to spontaneously differentiate over *** we asked whether morphological cues provided by engineered polymer scaffolds can modify spontaneous ***-derived neurospheres were cultured on electrospun scaffolds,prepared with either random or aligned fiber *** dispersed widely on the scaffolds,and-on aligned scaffolds-were highly organized,orientated parallel to the *** analysis showed that cells cultured on aligned scaffolds showed significantly greater expression of the neural stem/progenitor cell marker,NrcAM and reduced expres-sion of differentiated cell markers in comparison to those cultured on random *** this shows that tanycytes respond to local engineered cues,and that a morphologically constrained environment can better main-tain tanycytes as stem *** aligned scaffold culture system provides a powerful tool to better investigate this novel stem/progenitor cell population.

关键词： Scaffold Tanycytes Neural stem/progenitor cells Fiber alignment Electrospinning

Activation of mitochondrial ATP-sensitive potassium channels delays ischemia-induced cellular uncoupling in rat heart

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Acta Pharmacologica Sinica 2004年第1期 24-30页

作者： iain c BRUcE china Department of Physiology Faculty of Medicine The University of Hong Kong

AIM: To test the hypothesis that cellular uncoupling induced by myocardial ischemia is mediated by activation of cmitochondrial ATP-sensitive potassium channels (mitoKATP). METHODS: Rat hearts were perfused on a Langendorff apparatus and subjected to 40-min ischemia followed by 30-min reperfusion (I/R). changes in cellular coupling were monitored by measuring whole-tissue resistance. RESULTS: (1) In hearts subjected to I/R, the onset of uncoupling started at (13.3±1.0) mm of ischemia; (2) Ischemic preconditioning (IPc) delayed the onset of uncoupling until (22.7±1.3) min. Blocking mitoKATP channels with 5-

关键词： heart mitochondria potassium channels adenosine ttiphosphate ischemic preconditioning uncoupling

New synthetic methodology paves the way to prepare electron deficient semiconducting mesopolymers with very high performance

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Science china chemistry 2019年第7期62卷 885-886页

作者： iain Mcculloch Department of chemistry Imperial College London King Abdullah University of Science and Technology (KAUST) Physical Sciences and Engineering Division KAUST Solar Center(KSC)

Organic electronic applications require a combination of low-cost fabrication methods and features such as mechanical flexibility that are not achievable with inorganic materials. Both organic small molecule and polymer semiconductors offer the potential to deliver a new range of consumer applications, enabled by the unique benefits of these classes of materials [1]. Polymers in particular are attractive materials, offering potentially low cost synthesis and

关键词： New synthetic methodology paves the way to prepare electron deficient semiconducting mesopolymers with very high performance

A phylum level analysis reveals lipoprotein biosynthesis to be a fundamental property of bacteria

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Protein & cell 2012年第3期3卷 163-170页

作者： iain c.Sutcliffe Dean J.Harrington Matthew I.Hutchings School of Life Sciences University of Northumbria at NewcastleNewcastle upon TyneNE18STUK Division of Biomedical Science School of Life SciencesUniversity of BradfordWest YorkshireBD71DPUK School of Biological Sciences University of East AngliaNorwich Research ParkNorwichNR47TJUK

Bacterial lipoproteins are proteins that are post-trans-lationally modified with a diacylglyceride at an N-terminal cysteine,which serves to tether these proteins to the outer face of the plasma membrane or to the outer *** paper reviews recent insights into the enzymology of bacterial lipoprotein biosynthe-sis and ***,we use bioinformatic analyses of bacterial lipoprotein signal peptide features and of the key biosynthetic enzymes to consider the distribution of lipoprotein biosynthesis at the phylum level.

关键词： level. outer property

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Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA

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Genomics, Proteomics & Bioinformatics 2017年第3期15卷 177-186页

作者： iain M.Dykes costanza Emanueli School of clinical Sciences University of Bristol National Heart and Lung Institute Imperial College London

Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA （lncRNA）, a heteroge- neous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA （miRNA） pathways, lncRNA has been shown to act as both a source and an inhi- bitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying com- plexes by directing them to specific loci.

关键词： Long non-coding RNA MicroRNA Transcriptional regulation Epigenetics Post-transcriptionalregulation

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A sting in the tail： the N-terminal domain of the androgen receptor as a drug target

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Asian Journal of Andrology 2016年第5期18卷 687-694页

作者： Amy E Monaghan iain J McEwan School of Medicine Medical Sciences and Nutrition Institute of Medical Sciences University of Aberdeen Foresterhill Aberdeen AB25 2ZD United Kingdom.

The role of androgen receptor （AR） in the initiation and progression of prostate cancer （Pca） is well established. competitive inhibition of the AR ligand-binding domain （LBD） has been the staple of antiandrogen therapies employed to combat the disease in recent years. However, their efficacy has often been limited by the emergence of resistance, mediated through point mutations, and receptor truncations. As a result, the prognosis for patients with malignant castrate resistant disease remains poor. The amino-terminal domain （NTD） of the AR has been shown to be critical for AR function. Its modular activation function （AF-1） is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been dismissed in the past. The recent emergence of the small molecule EPI-O01 has provided evidence that AR-NTD can be targeted therapeutically, independent of the LBD. Targeting of AR-NTD has the potential to disrupt multiple intermolecular interactions between AR and its coregulatory binding partners, in addition to intramolecular cross-talk between the domains of the AR. Therapeutics targeting these protein-protein interactions or NTD directly should also have efficacy against emerging AR splice variants which may play a role in Pca progression. This review will discuss the role of intrinsic disorder in AR function and illustrate how emerging therapies might target NTD in Pca.

关键词： androgen receptor inhibitor intrinsically disordered structure N-terminal domain prostate cancer small molecules

A machine learning approach for regional geochemical data:Platinum-group element geochemistry vs geodynamic settings of the North Atlantic Igneous Province

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Geoscience Frontiers 2021年第3期12卷 42-59页

作者： Jordan J.Lindsay Hannah S.R.Hughes christopher M.Yeomans Jens c.Ø.Andersen iain McDonald camborne School of Mines University of ExeterPenryn CampusPenrynCornwall TR109FEUnited Kingdom School of Earth and Ocean Sciences Main CollegeCardiff UniversityPark PlaceCardiff CF103ATUnited Kingdom

Whilst traditional approaches to geochemistry provide valuable insights into magmatic processes such as melting and element fractionation,by considering entire regional data sets on an objective basis using machine learning algorithms(MLAs),we can highlight new facets within the broader data structure and significantly enhance previous geochemical *** platinum-group element(PGE)budget of lavas in the North Atlantic Igneous Province(NAIP)has been shown to vary systematically according to age,geographic location and geodynamic *** the large multi-element geochemical data set available for the region,MLAs were employed to explore the magmatic controls on these shifting *** key advantage of using machine learning in analysis is its ability to cluster samples across multi-dimensional(i.e.,multi-element)*** NAIP data set is manipulated using Principal component Analysis(PcA)and t-Distributed Stochastic Neighbour Embedding(t-SNE)techniques to increase separability in the data alongside clustering using the k-means *** new multi-element classification is compared to the original geographic classification to assess the performance of both *** workflow provides a means for creating an objective high-dimensional investigation on a geochemical data set and particularly enhances the identification of metallogenic anomalies across the *** techniques used highlight three distinct multi-element end-members which successfully capture the variability of the majority of elements included as input *** end-members are seen to fluctuate in prominence throughout the NAIP,which we propose reflects the changing geodynamic environment and melting ***,the variability of Pt and Pd are not reflected in MLA-based clustering trends,suggesting that they vary independently through controls not readily demonstrated by the NAIP major or trace element data structure(i.e.,other proxies for magmatic differe

关键词： Platinum-group elements Machine learning Plume Geochemistry Metallogenesis Mantle

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Predictive value of symptoms and demographics in diagnosing malignancy or peptic stricture

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World Journal of Gastroenterology 2012年第32期18卷 4357-4362页

作者： iain A Murray Joanne Palmer carolyn Waters Harry R Dalton Department of Gastroenterology Royal Cornwall HospitalTruroCornwall TR1 3LJUnited Kingdom Research and Development Knowledge SpaRoyal Cornwall HospitalTruroCornwall TR1 3LJUnited Kingdom

AIM:To determine which features of history and demographics predict a diagnosis of malignancy or peptic stricture in patients presenting with ***:A prospective case-control study of 2000 consecutive referrals(1031 female,age range:17-103 years) to a rapid access service for dysphagia,based in a teaching hospital within the United Kingdom,over 7 *** service consists of a nurse-led telephone triage followed by investigation(barium swallow or gastroscopy),if appropriate,within 2 *** regression analysis of demographic and clinical variables was *** includes age,sex,duration of dysphagia,whether to liquids or solids,and whether there are associated features(reflux,odynophagia,weight loss,regurgitation).We determined odds ratio(OR) for these variables for the diagnoses of malignancy and peptic *** determined the value of the Edinburgh Dysphagia Score(EDS) in predicting cancer in our *** logistic regression was performed and P considered *** local ethics committee confirmed ethics approval was not required(audit).RESULTS:The commonest diagnosis is gastro-esophageal reflux disease(41.3%).Malignancy(11.0%) and peptic stricture(10.0%) were also relatively *** were diagnosed by histology(97%) or on radiological criteria,either sequential barium swallows showing progression of disease or unequivocal evidence of malignancy on computed *** majority of malignancies were esophago-gastric in origin but ear,nose and throat tumors,pancreatic cancer and extrinsic compression from lung or mediastinal metastatic cancer were also *** was statistically more frequent in older patients(aged >73 years,OR 1.1-3.3,age 73 years 11.8%,P 26 wk 2.5%,P < 0.0005),progressive symptoms(OR 1.3-2.6:progressive 14.8%,int

关键词： Dysphagia Deglutition disorders Esophageal neoplasms Esophageal stenosis Gastroscopy Barium swallow Predictive value of tests

Targeting collagen expression in alcoholic liver disease

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World Journal of Gastroenterology 2011年第20期17卷 2473-2481页

作者： Kyle J Thompson iain H McKillop Laura W Schrum Department of General Sur gery Carolinas Medical Center Liver Digestive and Metabolic Disorder LaboratoryCarolinas Medical Center

Alcoholic liver disease （ALD） is a leading cause of liver disease and liver-related deaths globally, particularly in developed nations. Liver fibrosis is a consequence of ALD and other chronic liver insults, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Liver fibrosis is characterized by accumulation of excess extracellular matrix components, including type I collagen, which disrupts liver microcirculation and leads to injury. To date, there is no therapy for the treatment of liver fibrosis; thus treatments that either prevent the accumulation of type I collagen or hasten its degradation are desirable. The focus of this review is to examine the regulation of type I collagen in fibrogenic cells of the liver and to discuss current advances in therapeutics to eliminate excessive collagen deposition.

关键词： Type I collagen Fibrosis Extracellular matrix Hepatic stellate cell Alcohol Antioxidants Endoplasmic reticulum chaperones Matrix metalloproteinase microRNA