47,224 research outputs found

    Virtual libraries of tissue and clinical samples: potential role of a 3-D microscope.

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    Our international innovative teaching group from different European Universities (De Montfort University, DMU, UK; and the Spanish University of Alcalá, University Miguel Hernández and University of San Pablo CEU), in conjunction with practicing biomedical scientists in the National Health Service (UK) and biomedical researchers, are developing two complete e-learning packages for teaching and learning medical parasitology, named DMU e-Parasitology (accessible at: http://parasitology.dmu.ac.uk), and biology and chemistry, named DMU e-Biology (accessible at: http://parasitology.dmu.ac.uk/ebiology/index.htm), respectively. Both packages will include a virtual microscope with a complete library of digitised tissue images, clinical slides and cell culture slides/mini-videos for enhancing the teaching and learning of a myriad of techniques applicable to health science undergraduate and postgraduate students. Thus, these packages include detecting human parasites, by becoming familiar with their infective structures and/or organs (e.g. eggs, cysts) and/or explore pathogenic tissues stained with traditional (e.g. haematoxylin & eosin) or more modern (e.g. immunohistochemistry) techniques. The Virtual Microscope (VM) module in the DMU e-Parasitology package is almost completed (accessible at: http://parasitology.dmu.ac.uk/learn/microscope.htm) and contains a section for the three major groups of human-pathogenic parasites (Peña-Fernández et al., 2018) [1]. Digitised slides are provided with the functionality of a microscope by using the gadget Zoomify®, and we consider that they can enhance learning, as previous studies reported in the literature have reported similar sensitivity and specificity rates for identification of parasites for both digitised and real slides. The DMU e-Biology’s VM, currently in development, will provide healthy and pathological tissue samples from a range of mammalian tissues and organs. This communication will provide a description of both virtual libraries and the process of developing them. In conjunction, we will use a three-dimensional (3D) super-resolution microscopy, 3D Cell Explorer (Nanolive, Lausanne, Switzerland), to incorporate potential 3D microscopic photographs/short videos of cells to provide students with information about the spatial arrangement and morphologies of cells that are essential for life

    Molecular Docking and NMR Binding Studies to Identify Novel Inhibitors of Human Phosphomevalonate Kinase

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    Phosphomevalonate kinase (PMK) phosphorylates mevalonate-5-phosphate (M5P) in the mevalonate pathway, which is the sole source of isoprenoids and steroids in humans. We have identified new PMK inhibitors with virtual screening, using autodock. Promising hits were verified and their affinity measured using NMR-based 1H–15N heteronuclear single quantum coherence (HSQC) chemical shift perturbation and fluorescence titrations. Chemical shift changes were monitored, plotted, and fitted to obtain dissociation constants (Kd). Tight binding compounds with Kd’s ranging from 6–60 μM were identified. These compounds tended to have significant polarity and negative charge, similar to the natural substrates (M5P and ATP). HSQC cross peak changes suggest that binding induces a global conformational change, such as domain closure. Compounds identified in this study serve as chemical genetic probes of human PMK, to explore pharmacology of the mevalonate pathway, as well as starting points for further drug development

    Towards a virtual research environment for paediatric endocrinology across Europe

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    Paediatric endocrinology is a medical specialty dealing with variations of physical growth and sexual development in childhood. Genetic anomalies that can cause disorders of sexual development in children are rare. Given this, sharing and collaboration on the small number of cases that occur is needed by clinical experts in the field. The EU-funded EuroDSD project (www.eurodsd.eu) is one such collaboration involving clinical centres and clinical and genetic experts across Europe. Through the establishment of a virtual research environment (VRE) supporting sharing of data and a variety of clinical and bioinformatics analysis tools, EuroDSD aims to provide a research infrastructure for research into disorders of sex development. Security, ethics and information governance are at the heart of this infrastructure. This paper describes the infrastructure that is being built and the inherent challenges in security, availability and dependability that must be overcome for the enterprise to succeed

    A double-deletion method to quantifying incremental binding energies in proteins from experiment. Example of a destabilizing hydrogen bonding pair

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    The contribution of a specific hydrogen bond in apoflavodoxin to protein stability is investigated by combining theory, experiment and simulation. Although hydrogen bonds are major determinants of protein structure and function, their contribution to protein stability is still unclear and widely debated. The best method so far devised to estimate the contribution of side-chain interactions to protein stability is double-mutant-cycle analysis, but the interaction energies so derived are not identical to incremental binding energies (the energies quantifying net contributions of two interacting groups to protein stability). Here we introduce double-deletion analysis of isolated residue pairs as a means to precisely quantify incremental binding. The method is exemplified by studying a surface-exposed hydrogen bond in a model protein (Asp96/Asn128 in apoflavodoxin). Combined substitution of these residues by alanines slightly destabilizes the protein, due to a decrease in hydrophobic surface burial. Subtraction of this effect, however, clearly indicates that the hydrogen-bonded groups in fact destabilize the native conformation. In addition, Molecular Dynamics simulations and classic double-mutant-cycle analysis explain quantitatively that, due to frustration, the hydrogen bond must form in the native structure because, when the two groups get approximated upon folding their binding becomes favorable. We would like to remark two facts: that this is the first time the contribution of a specific hydrogen bond to protein stability has been measured from experiment, and that more hydrogen bonds need to be analyzed in order to draw general conclusions on protein hydrogen bonds energetics. To that end, the double deletion method should be of help.Comment: 41 pages, To appear in Biophysical Journal (in press

    Non-bisphosphonate inhibitors of isoprenoid biosynthesis identified via computer-aided drug design.

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    The relaxed complex scheme, a virtual-screening methodology that accounts for protein receptor flexibility, was used to identify a low-micromolar, non-bisphosphonate inhibitor of farnesyl diphosphate synthase. Serendipitously, we also found that several predicted farnesyl diphosphate synthase inhibitors were low-micromolar inhibitors of undecaprenyl diphosphate synthase. These results are of interest because farnesyl diphosphate synthase inhibitors are being pursued as both anti-infective and anticancer agents, and undecaprenyl diphosphate synthase inhibitors are antibacterial drug leads

    Sensing array for coherence analysis of modulated aquatic chemical plumes

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    An electrochemical sensor array can provide information about the spatial and temporal distribution of chemicals in liquid turbulent plumes. Planar laser induced fluorescence (PLIF) and amperometric sensor arrays were used to record signals from modulated chemical plumes released into a recirculating aquatic flume. Coherence analysis was applied to extract the frequency components contained in the sensor response. Effects due to release distance, modulation frequency, and array orientation were investigated. This study has demonstrated that frequency encoded information can be extracted from a turbulent chemical plume using an array of amperometric sensors with optimized three-dimensional geometry and tuning.M.S.Committee Chair: Janata, Jiri; Committee Member: Lyon, Andrew; Committee Member: Weissburg, Mar

    Evaluation of World Wide Web-based Lessons for a First Year Dental Biochemistry Course

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    First year dental students at The University of Texas Dental Branch at Houston (Dental Branch) are required to take a basic biochemistry course. To facilitate learning and allow student self-assessment of their progress, WWW-based lessons covering intermediary metabolism were developed as a supplement to traditional lectures. Lesson design combined text, graphics, and animations and included learner control, links to other learning resources, and practice exercises and exams with immediate feedback. Results from an on-line questionnaire completed by students in two different classes showed that they completed 50% of the lessons and spent an average of 4 hrs. on-line. A majority of the students either agreed or strongly agreed that practice exercises were helpful, that the ability to control the pace of the lessons was important, that the lesson structure and presentation was easy to follow, that the illustrations, animations, and hyperlinks were helpful, and that the lessons were effective as a review. The very positive response to the WWW-based lessons indicates the usefulness of this approach as a study aid for dental students

    11th German Conference on Chemoinformatics (GCC 2015) : Fulda, Germany. 8-10 November 2015.

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