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Sample records for membrane leaflet mimic

  1. A Coarse Grained Model for a Lipid Membrane with Physiological Composition and Leaflet Asymmetry.

    Directory of Open Access Journals (Sweden)

    Satyan Sharma

    Full Text Available The resemblance of lipid membrane models to physiological membranes determines how well molecular dynamics (MD simulations imitate the dynamic behavior of cell membranes and membrane proteins. Physiological lipid membranes are composed of multiple types of phospholipids, and the leaflet compositions are generally asymmetric. Here we describe an approach for self-assembly of a Coarse-Grained (CG membrane model with physiological composition and leaflet asymmetry using the MARTINI force field. An initial set-up of two boxes with different types of lipids according to the leaflet asymmetry of mammalian cell membranes stacked with 0.5 nm overlap, reliably resulted in the self-assembly of bilayer membranes with leaflet asymmetry resembling that of physiological mammalian cell membranes. Self-assembly in the presence of a fragment of the plasma membrane protein syntaxin 1A led to spontaneous specific positioning of phosphatidylionositol(4,5bisphosphate at a positively charged stretch of syntaxin consistent with experimental data. An analogous approach choosing an initial set-up with two concentric shells filled with different lipid types results in successful assembly of a spherical vesicle with asymmetric leaflet composition. Self-assembly of the vesicle in the presence of the synaptic vesicle protein synaptobrevin 2 revealed the correct position of the synaptobrevin transmembrane domain. This is the first CG MD method to form a membrane with physiological lipid composition as well as leaflet asymmetry by self-assembly and will enable unbiased studies of the incorporation and dynamics of membrane proteins in more realistic CG membrane models.

  2. Membrane-Mimic Nanoparticles for Drug and Gene Delivery

    KAUST Repository

    Alamoudi, Kholod

    2017-01-01

    -mimic nanoparticles are considered highly attractive materials for in vivo and in vitro applications. Synthetic membrane vesicles (liposomes) and nanoconstructs built with native cancer cellular membrane are excellent scaffolds to improve cellular delivery. Liposomes

  3. Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids.

    Science.gov (United States)

    Li, Guangtao; Kim, JiHyun; Huang, Zhen; St Clair, Johnna R; Brown, Deborah A; London, Erwin

    2016-12-06

    Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally replace the sphingolipids and phospholipids in the outer leaflet of the plasma membrane of living mammalian cells with exogenous lipids, including unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of metabolically active cells was similar to that previously defined for erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane outer leaflet phosphatidylcholine had a significantly lower level of unsaturation than phosphatidylcholine in the remainder of the cell. The data also provided a rough estimate for the total cellular lipids residing in the plasma membrane (about half). In addition to such lipidomics applications, the exchange method should have wide potential for investigations of lipid function and modification of cellular behavior by modification of lipids.

  4. Detection of cholesterol-rich microdomains in the inner leaflet of the plasma membrane

    International Nuclear Information System (INIS)

    Hayashi, Masami; Shimada, Yukiko; Inomata, Mitsushi; Ohno-Iwashita, Yoshiko

    2006-01-01

    The C-terminal domain (D4) of perfringolysin O binds selectively to cholesterol in cholesterol-rich microdomains. To address the issue of whether cholesterol-rich microdomains exist in the inner leaflet of the plasma membrane, we expressed D4 as a fusion protein with EGFP in MEF cells. More than half of the EGFP-D4 expressed in stable cell clones was bound to membranes in raft fractions. Depletion of membrane cholesterol with β-cyclodextrin reduced the amount of EGFP-D4 localized in raft fractions, confirming EGFP-D4 binding to cholesterol-rich microdomains. Subfractionation of the raft fractions showed most of the EGFP-D4 bound to the plasma membrane rather than to intracellular membranes. Taken together, these results strongly suggest the existence of cholesterol-rich microdomains in the inner leaflet of the plasma membrane

  5. Interdigitation of long-chain sphingomyelin induces coupling of membrane leaflets in a cholesterol dependent manner

    DEFF Research Database (Denmark)

    Róg, Tomasz; Orłowski, Adam; Llorente, Alicia

    2016-01-01

    It has been a long-standing question how the two leaflets in a lipid bilayer modulate each others' physical properties. In this paper, we discuss how this interaction may take place through interdigitation. We use atomistic molecular dynamics simulations to consider asymmetric lipid membrane mode...

  6. Transmembrane protein diffusion in gel-supported dual-leaflet membranes.

    Science.gov (United States)

    Wang, Chih-Ying; Hill, Reghan J

    2014-11-18

    Tools to measure transmembrane-protein diffusion in lipid bilayer membranes have advanced in recent decades, providing a need for predictive theoretical models that account for interleaflet leaflet friction on tracer mobility. Here we address the fully three-dimensional flows driven by a (nonprotruding) transmembrane protein embedded in a dual-leaflet membrane that is supported above and below by soft porous supports (e.g., hydrogel or extracellular matrix), each of which has a prescribed permeability and solvent viscosity. For asymmetric configurations, i.e., supports with contrasting permeability, as realized for cells in contact with hydrogel scaffolds or culture media, the diffusion coefficient can reflect interleaflet friction. Reasonable approximations, for sufficiently large tracers on low-permeability supports, are furnished by a recent phenomenological theory from the literature. Interpreting literature data, albeit for hard-supported membranes, provides a theoretical basis for the phenomenological Stokes drag law as well as strengthening assertions that nonhydrodynamic interactions are important in supported bilayer systems, possibly leading to overestimates of the membrane/leaflet viscosity. Our theory provides a theoretical foundation for future experimental studies of tracer diffusion in gel-supported membranes.

  7. Getting to the Outer Leaflet: Physiology of Phosphatidylserine Exposure at the Plasma Membrane.

    Science.gov (United States)

    Bevers, Edouard M; Williamson, Patrick L

    2016-04-01

    Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca(2+), and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure. Copyright © 2016 the American Physiological Society.

  8. Interleaflet Coupling, Pinning, and Leaflet Asymmetry—Major Players in Plasma Membrane Nanodomain Formation

    Science.gov (United States)

    Fujimoto, Toyoshi; Parmryd, Ingela

    2017-01-01

    The plasma membrane has a highly asymmetric distribution of lipids and contains dynamic nanodomains many of which are liquid entities surrounded by a second, slightly different, liquid environment. Contributing to the dynamics is a continuous repartitioning of components between the two types of liquids and transient links between lipids and proteins, both to extracellular matrix and cytoplasmic components, that temporarily pin membrane constituents. This make plasma membrane nanodomains exceptionally challenging to study and much of what is known about membrane domains has been deduced from studies on model membranes at equilibrium. However, living cells are by definition not at equilibrium and lipids are distributed asymmetrically with inositol phospholipids, phosphatidylethanolamines and phosphatidylserines confined mostly to the inner leaflet and glyco- and sphingolipids to the outer leaflet. Moreover, each phospholipid group encompasses a wealth of species with different acyl chain combinations whose lateral distribution is heterogeneous. It is becoming increasingly clear that asymmetry and pinning play important roles in plasma membrane nanodomain formation and coupling between the two lipid monolayers. How asymmetry, pinning, and interdigitation contribute to the plasma membrane organization is only beginning to be unraveled and here we discuss their roles and interdependence. PMID:28119914

  9. Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

    Science.gov (United States)

    Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

    2010-03-01

    Atomistic details of beta-amyloid (Aβ ) protein unfolding and lipid interaction kinetics mediated by the neuronal membrane surface are important for developing new therapeutic strategies to prevent and cure Alzheimer's disease. Using all-atom MD simulations, we explored the early unfolding and insertion kinetics of 40 and 42 residue long Aβ in binary lipid mixtures with and without cholesterol that mimic the cholesterol-depleted and cholesterol-enriched lipid nanodomains of neurons. The protein conformational transition kinetics was evaluated from the secondary structure profile versus simulation time plot. The extent of membrane disruption was examined by the calculated order parameters of lipid acyl chains and cholesterol fused rings as well as the density profiles of water and lipid headgroups at defined regions across the lipid bilayer from our simulations. Our results revealed that both the cholesterol content and the length of the protein affect the protein-insertion and membrane stability in our model lipid bilayer systems.

  10. Ergosterol is mainly located in the cytoplasmic leaflet of the yeast plasma membrane.

    Science.gov (United States)

    Solanko, Lukasz M; Sullivan, David P; Sere, Yves Y; Szomek, Maria; Lunding, Anita; Solanko, Katarzyna A; Pizovic, Azra; Stanchev, Lyubomir D; Pomorski, Thomas Günther; Menon, Anant K; Wüstner, Daniel

    2018-03-01

    Transbilayer lipid asymmetry is a fundamental characteristic of the eukaryotic cell plasma membrane (PM). While PM phospholipid asymmetry is well documented, the transbilayer distribution of PM sterols such as mammalian cholesterol and yeast ergosterol is not reliably known. We now report that sterols are asymmetrically distributed across the yeast PM, with the majority (~80%) located in the cytoplasmic leaflet. By exploiting the sterol-auxotrophic hem1Δ yeast strain we obtained cells in which endogenous ergosterol was quantitatively replaced with dehydroergosterol (DHE), a closely related fluorescent sterol that functionally and accurately substitutes for ergosterol in vivo. Using fluorescence spectrophotometry and microscopy we found that membrane-impermeant collisional quenchers (spin-labeled phosphatidylcholine and trinitrobenzene sulfonic acid). Efficient quenching was seen only after the cells were disrupted by glass-bead lysis or repeated freeze-thaw to allow quenchers access to the cell interior. The extent of quenching was unaffected by treatments that deplete cellular ATP levels, collapse the PM electrochemical gradient or affect the actin cytoskeleton. However, alterations in PM phospholipid asymmetry in cells lacking phospholipid flippases resulted in a more symmetric transbilayer distribution of sterol. Similarly, an increase in the quenchable pool of DHE was observed when PM sphingolipid levels were reduced by treating cells with myriocin. We deduce that sterols comprise up to ~45% of all inner leaflet lipids in the PM, a result that necessitates revision of current models of the architecture of the PM lipid bilayer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Membrane-Mimic Nanoparticles for Drug and Gene Delivery

    KAUST Repository

    Alamoudi, Kholod

    2017-12-01

    Nanoscale organic particles have gained a prominent role in drug and gene delivery field. As the nature of the nanoparticle’s (NPs) surface plays a major role in their targeting efficiency, bioavailability, and cytotoxicity, membrane-mimic nanoparticles are considered highly attractive materials for in vivo and in vitro applications. Synthetic membrane vesicles (liposomes) and nanoconstructs built with native cancer cellular membrane are excellent scaffolds to improve cellular delivery. Liposomes have been extensively used due to their high loading capacity, biocompatibility and biodegradability. However, modifications with stimuli responsive materials are highly needed to improve their stability and turn them active participants in controlled delivery. Towards a nature inspired approach, reconstructed bilayers from cell membrane are a good candidate to enhance NP’s targeting ability and biocompatibility. The primary focus of this research is to develop smart responsive (lipid) membrane coated NPs with surface modifications for controlled and targeted drug and/or gene delivery for application in cancer therapy. Three approaches have been developed, namely i) liposomes as thermoresponsive nanocarriers for the delivery of genetic material; ii) magnetically photosensitive liposome hybrids and iii) biomimetic periodic mesoporous organo silica engineered for better a biocompatibility and targeting capabilities. In the first project synthetic liposomes were loaded with ammonium bicarbonate salt (ABC) and siRNA. The combination of lipids chosen and the relative ratios allowed the rapid release of the genetic material to the multi drug resistant cancer cells studied, upon external heat trigger. This design has improved the gene silencing efficiency via successful endosomal escape. In the second project, SPIO@Au nanoparticles were imbedded in the lipid bilayer to produce a photo/thermal responsive carrier that could be also used in cell imaging besides gene transfection

  12. In Vivo Imaging of Diacylglycerol at the Cytoplasmic Leaflet of Plant Membranes.

    Science.gov (United States)

    Vermeer, Joop E M; van Wijk, Ringo; Goedhart, Joachim; Geldner, Niko; Chory, Joanne; Gadella, Theodorus W J; Munnik, Teun

    2017-07-01

    Diacylglycerol (DAG) is an important intermediate in lipid biosynthesis and plays key roles in cell signaling, either as a second messenger itself or as a precursor of phosphatidic acid. Methods to identify distinct DAG pools have proven difficult because biochemical fractionation affects the pools, and concentrations are limiting. Here, we validate the use of a genetically encoded DAG biosensor in living plant cells. The sensor is composed of a fusion between yellow fluorescent protein and the C1a domain of protein kinase C (YFP-C1aPKC) that specifically binds DAG, and was stably expressed in suspension-cultured tobacco BY-2 cells and whole Arabidopsis thaliana plants. Confocal imaging revealed that the majority of the YFP-C1aPKC fluorescence did not locate to membranes but was present in the cytosol and nucleus. Treatment with short-chain DAG or PMA (phorbol-12-myristate-13-acetate), a phorbol ester that binds the C1a domain of PKC, caused the recruitment of the biosensor to the plasma membrane. These results indicate that the biosensor works and that the basal DAG concentration in the cytoplasmic leaflet of membranes (i.e. accessible to the biosensor) is in general too low, and confirms that the known pools in plastids, the endoplasmic reticulum and mitochondria are located at the luminal face of these compartments (i.e. inaccessible to the biosensor). Nevertheless, detailed further analysis of different cells and tissues discovered four novel DAG pools, namely at: (i) the trans-Golgi network; (ii) the cell plate during cytokinesis; (iii) the plasma membrane of root epidermal cells in the transition zone, and (iv) the apex of growing root hairs. The results provide new insights into the spatiotemporal dynamics of DAG in plants and offer a new tool to monitor this in vivo. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. Lipid diffusion in the distal and proximal leaflets of supported lipid bilayer membranes studied by single particle tracking

    Science.gov (United States)

    Schoch, Rafael L.; Barel, Itay; Brown, Frank L. H.; Haran, Gilad

    2018-03-01

    Supported lipid bilayers (SLBs) have been studied extensively as simple but powerful models for cellular membranes. Yet, potential differences in the dynamics of the two leaflets of a SLB remain poorly understood. Here, using single particle tracking, we obtain a detailed picture of bilayer dynamics. We observe two clearly separate diffusing populations, fast and slow, that we associate with motion in the distal and proximal leaflets of the SLB, respectively, based on fluorescence quenching experiments. We estimate diffusion coefficients using standard techniques as well as a new method based on the blur of images due to motion. Fitting the observed diffusion coefficients to a two-leaflet membrane hydrodynamic model allows for the simultaneous determination of the intermonolayer friction coefficient and the substrate-membrane friction coefficient, without any prior assumptions on the strengths of the relevant interactions. Remarkably, our calculations suggest that the viscosity of the interfacial water confined between the membrane and the substrate is elevated by ˜104 as compared to bulk water. Using hidden Markov model analysis, we then obtain insight into the transbilayer movement of lipids. We find that lipid flip-flop dynamics are very fast, with half times in the range of seconds. Importantly, we find little evidence for membrane defect mediated lipid flip-flop for SLBs at temperatures well above the solid-to-liquid transition, though defects seem to be involved when the SLBs are cooled down. Our work thus shows that the combination of single particle tracking and advanced hydrodynamic modeling provides a powerful means to obtain insight into membrane dynamics.

  14. Bicelles and Other Membrane Mimics: Comparison of Structure, Properties, and Dynamics from MD Simulations

    DEFF Research Database (Denmark)

    Vestergaard, Mikkel; Kraft, Johan Frederik; Vosegaard, Thomas

    2015-01-01

    present molecular dynamics simulations to elucidate structural and dynamic properties of small bicelles and compare them to a large alignable bicelle, a small nanodisc, and a lipid bilayer. Properties such as lipid packing and properties related to embedding both an α-helical peptide and a transmembrane...... protein are investigated. The small bicelles are found to be very dynamic and mainly assume a prolate shape substantiating that small bicelles cannot be regarded as well-defined disclike structures. However, addition of a peptide results in an increased tendency to form disc-shaped bicelles. The small......The increased interest in studying membrane proteins has led to the development of new membrane mimics such as bicelles and nanodiscs. However, only limited knowledge is available of how these membrane mimics are affected by embedded proteins and how well they mimic a lipid bilayer. Herein, we...

  15. Understanding Peptide Dendrimer Interactions with Model Cell Membrane Mimics

    DEFF Research Database (Denmark)

    Lind, Tania Kjellerup

    few new drugs have been marketed over the last decades, making it impossible to keep pace with the disturbing levels of multi-drug resistant bacteria. Research in the area of novel drugs, which are less prone to induce resistance, and in-depth knowledge on their uptake mechanisms is thus of paramount...... fusion method, which presents improved means for studying drug-membrane interactions in the future. The interaction mechanism of a family of dendrimers was examined and in particular one dendrimer (BALY) was extensively studied by the combined use of quartz crystal microbalance, atomic force microscopy...

  16. Asymmetric Hybrid Polymer-Lipid Giant Vesicles as Cell Membrane Mimics.

    Science.gov (United States)

    Peyret, Ariane; Ibarboure, Emmanuel; Le Meins, Jean-François; Lecommandoux, Sebastien

    2018-01-01

    Lipid membrane asymmetry plays an important role in cell function and activity, being for instance a relevant signal of its integrity. The development of artificial asymmetric membranes thus represents a key challenge. In this context, an emulsion-centrifugation method is developed to prepare giant vesicles with an asymmetric membrane composed of an inner monolayer of poly(butadiene)- b -poly(ethylene oxide) (PBut- b -PEO) and outer monolayer of 1-palmitoyl-2-oleoyl- sn -glycero-3-phosphocholine (POPC). The formation of a complete membrane asymmetry is demonstrated and its stability with time is followed by measuring lipid transverse diffusion. From fluorescence spectroscopy measurements, the lipid half-life is estimated to be 7.5 h. Using fluorescence recovery after photobleaching technique, the diffusion coefficient of 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine- N -(lissamine rhodamine B sulfonyl) (DOPE-rhod, inserted into the POPC leaflet) is determined to be about D = 1.8 ± 0.50 μm 2 s -1 at 25 °C and D = 2.3 ± 0.7 μm 2 s -1 at 37 °C, between the characteristic values of pure POPC and pure polymer giant vesicles and in good agreement with the diffusion of lipids in a variety of biological membranes. These results demonstrate the ability to prepare a cell-like model system that displays an asymmetric membrane with transverse and translational diffusion properties similar to that of biological cells.

  17. Decoupling of bilayer leaflets under gas supersaturation: nitrogen nanobubbles in a membrane and their implication in decompression sickness

    Science.gov (United States)

    Li, Jing; Zhang, Xianren; Cao, Dapeng

    2018-05-01

    Decompression sickness (also known as diver’s sickness) is a disease that arises from the formation of a bubble inside the body caused by rapid decompression from high atmospheric pressures. However, the nature of pre-existing micronuclei that are proposed for interpreting the formation and growth of the bubble, as well as their very existence, is still highly controversial. In this work, atomistic molecular dynamics simulations are employed to investigate the nucleation of gas bubbles under the condition of nitrogen supersaturation, in the presence of a lipid bilayer and lipid micelle representing other macromolecules with a smaller hydrophobic region. Our simulation results demonstrate that by crossing a small energy barrier, excess nitrogen molecules can enter the lipid bilayer nearly spontaneously, for which the hydrophobic core serves as a potential well for gas enrichment. At a rather low nitrogen supersaturation, gas molecules in the membrane are dispersed in the hydrophobic region of the bilayer, with a slight increase in membrane thickness. But as the level of gas supersaturation reaches a threshold, the accumulation of N2 molecules in the bilayer center causes the two leaflets to be decoupled and the formation of nanobubbles. Therefore, we propose a nucleation mechanism for bubble formation in a supersaturated solution of inert gas: a cell membrane acts as a potential well for gas enrichment, being an ideal location for forming nanobubbles that induce membrane damage at a high level of gas supersaturation. As opposed to previous models, the new mechanism involves forming gas nuclei in a very low-tension hydrophobic environment, and thus a rather low energy barrier is required and pre-existing bubble micronuclei are not needed.

  18. Interaction of a peptide derived from C-terminus of human TRPA1 channel with model membranes mimicking the inner leaflet of the plasma membrane.

    Science.gov (United States)

    Witschas, Katja; Jobin, Marie-Lise; Korkut, Dursun Nizam; Vladan, Maria Magdalena; Salgado, Gilmar; Lecomte, Sophie; Vlachova, Viktorie; Alves, Isabel D

    2015-05-01

    The transient receptor potential ankyrin 1 channel (TRPA1) belongs to the TRP cation channel superfamily that responds to a panoply of stimuli such as changes in temperature, calcium levels, reactive oxygen and nitrogen species and lipid mediators among others. The TRP superfamily has been implicated in diverse pathological states including neurodegenerative disorders, kidney diseases, inflammation, pain and cancer. The intracellular C-terminus is an important regulator of TRP channel activity. Studies with this and other TRP superfamily members have shown that the C-terminus association with lipid bilayer alters channel sensitivity and activation, especially interactions occurring through basic residues. Nevertheless, it is not yet clear how this process takes place and which regions in the C-terminus would be responsible for such membrane recognition. With that in mind, herein the first putative membrane interacting region of the C-terminus of human TRPA1, (corresponding to a 29 residue peptide, IAEVQKHASLKRIAMQVELHTSLEKKLPL) named H1 due to its potential helical character was chosen for studies of membrane interaction. The affinity of H1 to lipid membranes, H1 structural changes occurring upon this interaction as well as effects of this interaction in lipid organization and integrity were investigated using a biophysical approach. Lipid models systems composed of zwitterionic and anionic lipids, namely those present in the lipid membrane inner leaflet, where H1 is prone to interact, where used. The study reveals a strong interaction and affinity of H1 as well as peptide structuration especially with membranes containing anionic lipids. Moreover, the interactions and peptide structure adoption are headgroup specific. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Reverse-Bumpy-Ball-Type-Nanoreactor-Loaded Nylon Membranes as Peroxidase-Mimic Membrane Reactors for a Colorimetric Assay for H₂O₂.

    Science.gov (United States)

    Tong, Ying; Jiao, Xiangyu; Yang, Hankun; Wen, Yongqiang; Su, Lei; Zhang, Xueji

    2016-04-01

    Herein we report for the first time fabrication of reverse bumpy ball (RBB)-type-nanoreactor-based flexible peroxidase-mimic membrane reactors (MRs). The RBB-type nanoreactors with gold nanoparticles embedded in the inner walls of carbon shells were loaded on nylon membranes through a facile filtration approach. The as-prepared flexible catalytic membrane was studied as a peroxidase-mimic MR. It was found that the obtained peroxidase-mimic MR could exhibit several advantages over natural enzymes, such as facile and good recyclability, long-term stability and easy storage. Moreover, the RBB NS-modified nylon MRs as a peroxidase mimic provide a useful colorimetric assay for H₂O₂.

  20. A bioartificial environment for kidney epithelial cells based on a supramolecular polymer basement membrane mimic and an organotypical culture system.

    Science.gov (United States)

    Mollet, Björne B; Bogaerts, Iven L J; van Almen, Geert C; Dankers, Patricia Y W

    2017-06-01

    Renal applications in healthcare, such as renal replacement therapies and nephrotoxicity tests, could potentially benefit from bioartificial kidney membranes with fully differentiated and functional human tubular epithelial cells. A replacement of the natural environment of these cells is required to maintain and study cell functionality cell differentiation in vitro. Our approach was based on synthetic supramolecular biomaterials to mimic the natural basement membrane (BM) on which these cells grow and a bioreactor to provide the desired organotypical culture parameters. The BM mimics were constructed from ureidopyrimidinone (UPy)-functionalized polymer and bioactive peptides by electrospinning. The resultant membranes were shown to have a hierarchical fibrous BM-like structure consisting of self-assembled nanofibres within the electrospun microfibres. Human kidney-2 (HK-2) epithelial cells were cultured on the BM mimics under organotypical conditions in a custom-built bioreactor. The bioreactor facilitated in situ monitoring and functionality testing of the cultures. Cell viability and the integrity of the epithelial cell barrier were demonstrated inside the bioreactor by microscopy and transmembrane leakage of fluorescently labelled inulin, respectively. Furthermore, HK-2 cells maintained a polarized cell layer and showed modulation of both gene expression of membrane transporter proteins and metabolic activity of brush border enzymes when subjected to a continuous flow of culture medium inside the new bioreactor for 21 days. These results demonstrated that both the culture and study of renal epithelial cells was facilitated by the bioartificial in vitro environment that is formed by synthetic supramolecular BM mimics in our custom-built bioreactor. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Fluorescence response of hypocrellin B to the environmental changes in a mimic biological membrane--liposome

    Institute of Scientific and Technical Information of China (English)

    JIN; Xuanye; ZHAO; Yuewei; XIE; Jie; ZHAO; Jingquan

    2004-01-01

    , Photochem.Photobiol., 2001, 73 (5): 482-488.[13]Mang, T. S., Dougherty, T. J., Potter, W. R. et al., Photobleaching of porphyrins used in photodynamic therapy and implications for therapy, Photochem. Photobiol., 1987, 45: 501-506.[14]Shoko, Y., Tadahiro, T., Masahiko, A., Preparation of ganglioside GM3 liposomes and their membrane properties, Colloid Surface B, 2002, 27: 181-187.[15]Murakami, S., Packer, L., The role of cations in the organization of chloroplast membranes, Arch. Biochem. Biophys., 1971, 146:337-347.[16]Angeli, N. G., Lagorio, M. G., San Román, E. et al., Meso-substituted cationic porphyrins of biological interest, Photophysical and physicochemical properties in solution and bound to liposomes,Photochem. Photobiol., 2000, 72(1 ): 49-56.

  2. Prosthetic Mitral Valve Leaflet Escape

    Science.gov (United States)

    Kim, Darae; Hun, Sin Sang; Cho, In-Jeong; Shim, Chi-Young; Ha, Jong-Won; Chung, Namsik; Ju, Hyun Chul; Sohn, Jang Won

    2013-01-01

    Leaflet escape of prosthetic valve is rare but potentially life threatening. It is essential to make timely diagnosis in order to avoid mortality. Transesophageal echocardiography and cinefluoroscopy is usually diagnostic and the location of the missing leaflet can be identified by computed tomography (CT). Emergent surgical correction is mandatory. We report a case of fractured escape of Edward-Duromedics mitral valve 27 years after the surgery. The patient presented with symptoms of acute decompensated heart failure and cardiogenic shock. She was instantly intubated and mechanically ventilated. After prompt evaluation including transthoracic echocardiography and CT, the escape of the leaflet was confirmed. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. Eleven days after the surgery, the dislodged leaflet in iliac artery was removed safely and the patient recovered well. PMID:23837121

  3. Vasculitis mimics.

    Science.gov (United States)

    Molloy, Eamonn S; Langford, Carol A

    2008-01-01

    There are many disorders that may closely resemble the clinical, radiologic and/or pathologic features of the primary vasculitides. In this review, we focus on recently described and under-recognized syndromes that may mimic vasculitis. Hereditary causes of large-artery aneurysms such as Marfan's syndrome have long been recognized; recent years have seen a greater understanding of the genetics of Marfan's and other such disorders, including Loeys-Dietz syndrome and Ehler-Danlos syndrome type IV. Under-recognized mimics of medium-vessel vasculitis include segmental arterial mediolysis and Grange syndrome. A large number of entities can mimic small-vessel vasculitis. Recent descriptions of antibodies to human neutrophil elastase have provided insight into the occurrence of antineutrophil cytoplasmic antibodies in cocaine-induced midline destructive lesions. The differential diagnosis of cerebral vasculitis can be particularly difficult. Reversible cerebral vasoconstriction syndromes represent an important class of entities that can readily mimic cerebral vasculitis but have a very different management approach and outcome. The diagnosis of vasculitis requires careful assessment of all available clinical, laboratory, radiologic and pathologic information, and consideration of many competing differential diagnoses. Awareness of noninflammatory mimics of vasculitis is essential to avoid unnecessary and potentially harmful treatment with immunosuppressive agents.

  4. Grape tannin catechin and ethanol fluidify oral membrane mimics containing moderate amounts of cholesterol: Implications on wine tasting?

    Science.gov (United States)

    Furlan, Aurélien L; Saad, Ahmad; Dufourc, Erick J; Géan, Julie

    2016-11-01

    Wine tasting results in interactions of tannin-ethanol solutions with proteins and lipids of the oral cavity. Among the various feelings perceived during tasting, astringency and bitterness most probably result in binding events with saliva proteins, lipids and receptors. In this work, we monitored the conjugated effect of the grape polyphenol catechin and ethanol on lipid membranes mimicking the different degrees of keratinization of oral cavity surfaces by varying the amount of cholesterol present in membranes. Both catechin and ethanol fluidify the membranes as evidenced by solid-state 2 H NMR of perdeuterated lipids. The effect is however depending on the cholesterol proportion and may be very important and cumulative in the absence of cholesterol or presence of 18 mol % cholesterol. For 40 mol % cholesterol, mimicking highly keratinized membranes, both ethanol and catechin can no longer affect membrane dynamics. These observations can be accounted for by phase diagrams of lipid-cholesterol mixtures and the role played by membrane defects for insertion of tannins and ethanol when several phases coexist. These findings suggest that the behavior of oral membranes in contact with wine should be different depending of their cholesterol content. Astringency and bitterness could be then affected; the former because of a potential competition between the tannin-lipid and the tannin-saliva protein interaction, and the latter because of a possible fluidity modification of membranes containing taste receptors. The lipids that have been up to now weakly considered in oenology may be become a new actor in the issue of wine tasting. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  5. Myositis Mimics.

    Science.gov (United States)

    Michelle, E Harlan; Mammen, Andrew L

    2015-10-01

    Patients with autoimmune myositis typically present with muscle weakness, elevated serum levels of muscle enzymes, and abnormal muscle biopsies. However, patients with other acquired myopathies or genetic muscle diseases may have remarkably similar presentations. Making the correct diagnosis of another muscle disease can prevent these patients from being exposed to the risks of immunosuppressive medications, which benefit those with myositis, but not those with other types of muscle disease. Here, we review some of the most common acquired and inherited muscle diseases that can mimic autoimmune myositis, including inclusion body myositis, limb girdle muscular dystrophies, metabolic myopathies, mitochondrial myopathies, and endocrine myopathies. We emphasize aspects of the medical history, physical exam, laboratory evaluation, and muscle biopsy analysis that can help clinicians distinguish myositis mimics from true autoimmune myositis.

  6. Document of the Month: German Propaganda Leaflets

    Science.gov (United States)

    Byers, CeCe; Alexander, Mary

    1978-01-01

    Excerpts from two propaganda leaflets distributed by Germany during World War I to demoralize American soldiers. Teaching suggestions encourage students to examine the leaflets' tone, guess who the authors might have been, and analyze the leaflets as examples of a propaganda technique. (AV)

  7. Membrane interactions of a self-assembling model peptide that mimics the self-association, structure and toxicity of Aβ(1-40)

    Science.gov (United States)

    Salay, Luiz C.; Qi, Wei; Keshet, Ben; Tamm, Lukas K.; Fernandez, Erik J.

    2013-01-01

    β-amyloid peptide (Aβ) is a primary protein component of senile plaques in Alzheimer’s disease (AD) and plays an important, but not fully understood role in neurotoxicity. Model peptides with the demonstrated ability to mimic the structural and toxicity behavior of Aβ could provide a means to evaluate the contributions to toxicity that are common to self–associating peptides from many disease states. In this work, we have studied the peptide-membrane interactions of a model β-sheet peptide, P11-2 (CH3CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Glu-Gln-Gln-NH2), by fluorescence, infrared spectroscopy, and hydrogen-deuterium exchange. Like Aβ(1-40), the peptide is toxic, and conditions which produce intermediate oligomers show higher toxicity against cells than either monomeric forms or higher aggregates of the peptide. Further, P11-2 also binds to both zwitterionic (POPC) and negatively charged (POPC:POPG) liposomes, acquires a partial β-sheet conformation in presence of lipid, and is protected against deuterium exchange in the presence of lipids. The results show that a simple rationally designed model β-sheet peptide recapitulates many important features of Aβ peptide structure and function, reinforcing the idea that toxicity arises, at least in part, from a common mode of action on membranes that is independent of specific aspects of the amino acid sequence. Further studies of such well-behaved model peptide systems will facilitate the investigation of the general principles that govern the molecular interactions of aggregation-prone disease-associated peptides with cell and/or membrane surfaces. PMID:19393615

  8. Lipid clustering correlates with membrane curvature as revealed by molecular simulations of complex lipid bilayers.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    2014-10-01

    Full Text Available Cell membranes are complex multicomponent systems, which are highly heterogeneous in the lipid distribution and composition. To date, most molecular simulations have focussed on relatively simple lipid compositions, helping to inform our understanding of in vitro experimental studies. Here we describe on simulations of complex asymmetric plasma membrane model, which contains seven different lipids species including the glycolipid GM3 in the outer leaflet and the anionic lipid, phosphatidylinositol 4,5-bisphophate (PIP2, in the inner leaflet. Plasma membrane models consisting of 1500 lipids and resembling the in vivo composition were constructed and simulations were run for 5 µs. In these simulations the most striking feature was the formation of nano-clusters of GM3 within the outer leaflet. In simulations of protein interactions within a plasma membrane model, GM3, PIP2, and cholesterol all formed favorable interactions with the model α-helical protein. A larger scale simulation of a model plasma membrane containing 6000 lipid molecules revealed correlations between curvature of the bilayer surface and clustering of lipid molecules. In particular, the concave (when viewed from the extracellular side regions of the bilayer surface were locally enriched in GM3. In summary, these simulations explore the nanoscale dynamics of model bilayers which mimic the in vivo lipid composition of mammalian plasma membranes, revealing emergent nanoscale membrane organization which may be coupled both to fluctuations in local membrane geometry and to interactions with proteins.

  9. Patients’ views on electronic patient information leaflets

    Directory of Open Access Journals (Sweden)

    Hammar T

    2016-06-01

    Full Text Available Background: Information in society and in health care is currently undergoing a transition from paper to digital formats, and the main source of information will probably be electronic in the future. Objective: To explore patients’ use and perceptions of the patient information leaflet included in the medication package, and their attitude towards a transition to an electronic version. Methods: The data was collected during October to November 2014 among individuals in South-Eastern Sweden, using a questionnaire (n=406, response rate 78% and interviews (n=15. Results: The questionnaire showed that the majority of the respondents (52% occasionally read the patient information leaflet, 37% always read it, and 11% never read it. Almost half of the patients (41% were positive towards reading the patient information leaflet electronically while 32% were hesitant and 26% neutral. A majority of the patients would request to get the patient information leaflet printed at the pharmacy if it was not included in the package. There were differences in attitude related to age and gender. The interviews showed that patients had mixed views on a transition to an electronic patient information leaflet. The patients perceived several positive aspects with an electronic patient information leaflet but were concerned about elderly patients. Conclusion: Although many were positive towards reading the patient information leaflet electronically, the majority prefer the patient information leaflet in paper form. Providing appropriate and useful eHealth services for patients to access the patient information leaflet electronically, along with education, could prepare patients for a transition to electronic patient information leaflet.

  10. [Evaluation of a self-care leaflet].

    Science.gov (United States)

    Lystad, N; Heian, F

    1989-01-20

    A self care leaflet of 50 pages was distributed in Tingvoll, a municipality with 3,500 inhabitants. The leaflet gives advice about self treatment and prevention of common health problems, and guidelines for contacting the health services. In surveys conducted just before and 10 months after the distribution, we documented -- how the leaflet was accepted and used --changes in knowledge about the health problems mentioned in the leaflet. The leaflet was well accepted. It was characterized as easy to read and to use. 10 months after distribution to read and to use. 10 months after distribution 90% found it within five minutes. 63% used the leaflet when they had a health problem. 90% of those using the leaflet felt more sure that they acted correctly after consulting it, and 60% changed their mind about consulting a general practitioner. We consider the level of knowledge about health problems to be low. The evaluation showed increased knowledge in all groups, except for persons "responsible for caring for elderly relatives". The increase was most marked for "men" and for "persons with health education".

  11. Consent information leaflets - readable or unreadable?

    Science.gov (United States)

    Graham, Caroline; Reynard, John M; Turney, Benjamin W

    2015-05-01

    The objective of this article is to assess the readability of leaflets about urological procedures provided by the British Association of Urological Surgeons (BAUS) to evaluate their suitability for providing information. Information leaflets were assessed using three measures of readability: Flesch Reading Ease, Flesch-Kincaid and Simple Measure of Gobbledygook (SMOG) grade formulae. The scores were compared with national literacy statistics. Relatively good readability was demonstrated using the Flesch Reading Ease (53.4-60.1) and Flesch-Kincaid Grade Level (6.5-7.6) methods. However, the average SMOG index (14.0-15.0) for each category suggests that the majority of the leaflets are written above the reading level of an 18-year-old. Using national literacy statistics, at least 43% of the population will have significant difficultly understanding the majority of these leaflets. The results suggest that comprehension of the leaflets provided by the BAUS is likely to be poor. These leaflets may be used as an adjunct to discussion but it is essential to ensure that all the information necessary to make an informed decision has been conveyed in a way that can be understood by the patient.

  12. Consent information leaflets – readable or unreadable?

    Science.gov (United States)

    Graham, Caroline; Reynard, John M; Turney, Benjamin W

    2016-01-01

    Objective The objective of this article is to assess the readability of leaflets about urological procedures provided by the British Association of Urological Surgeons (BAUS) to evaluate their suitability for providing information. Methods Information leaflets were assessed using three measures of readability: Flesch Reading Ease, Flesch-Kincaid and Simple Measure of Gobbledygook (SMOG) grade formulae. The scores were compared with national literacy statistics. Results Relatively good readability was demonstrated using the Flesch Reading Ease (53.4–60.1) and Flesch-Kincaid Grade Level (6.5–7.6) methods. However, the average SMOG index (14.0–15.0) for each category suggests that the majority of the leaflets are written above the reading level of an 18-year-old. Using national literacy statistics, at least 43% of the population will have significant difficultly understanding the majority of these leaflets. Conclusions The results suggest that comprehension of the leaflets provided by the BAUS is likely to be poor. These leaflets may be used as an adjunct to discussion but it is essential to ensure that all the information necessary to make an informed decision has been conveyed in a way that can be understood by the patient. PMID:27867520

  13. Vent-induced prosthetic leaflet thrombosis treated by open-heart valve-in-valve implantation.

    Science.gov (United States)

    Stamm, Christof; Pasic, Miralem; Buz, Semih; Hetzer, Roland

    2015-09-01

    A patient required emergency mitral valve replacement and extracorporeal membrane oxygenation (ECMO) support for acute biventricular failure. The left ventricular (LV) vent inserted via the left upper pulmonary vein induced thrombotic immobilization of a prosthetic valve leaflet, with significant intra-prosthesis regurgitation after ECMO explantation. Therefore, the left atrium was opened on the beating heart during conventional extracorporeal circulation, all prosthesis leaflets were excised and a 29-mm expandable Edwards Sapien prosthesis was inserted within the scaffold of the original prosthesis under direct vision. This case illustrates the benefits and potential problems of LV venting on ECMO support, and a rapid and safe way of replacing the prosthesis leaflets in a critical situation. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  14. Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets.

    Science.gov (United States)

    Courtman, D W; Pereira, C A; Omar, S; Langdon, S E; Lee, J M; Wilson, G J

    1995-12-01

    Heart valve substitutes of biological origin often fail by degenerative mechanisms. Many authors have hypothesized that mechanical fatigue and structural degradation are instrumental to in vivo failure. Since the properties of the structural matrix at implantation may predetermine failure, we have examined the ultrastructure, fracture, mechanics, and uniaxial high-strain-rate viscoelastic properties of: (1) fresh, (2) cryopreserved, and (3) cellular extracted porcine aortic valve leaflets. The cellular extraction process is being developed in order to reduce immunological attack and calcification. Cryopreservation causes cellular disruption and necrotic changes throughout the tissue, whereas extraction removes all cells and lipid membranes. Both processes leave an intact collagen and elastin structural matrix and preserve the high-strain-rate viscoelastic characteristics of the fresh leaflets. Extraction does cause a 20% reduction in the fracture tension and increases tissue extensibility, with the percent strain at fracture rising to 45.3 +/- 4 (mean +/- SEM) from 31.5 +/- 3 for fresh leaflets. However, extraction does preserve matrix structure and mechanics over the physiological loading range. Glutaraldehyde fixation produces increased extensibility, increased elastic behavior, and, when applied to extracted leaflets, it causes a marked drop in fracture tension, to 50% of that for fresh leaflets. The combination of extraction and fixation may lead to early degenerative failure. The cellular extraction technique alone may be a useful alternative to glutaraldehyde fixation in preparing bioprosthetic heart valves.

  15. The readability and suitability of sexual health promotion leaflets.

    Science.gov (United States)

    Corcoran, Nova; Ahmad, Fatuma

    2016-02-01

    To investigate the readability and suitability of sexual health promotion leaflets. Application of SMOG, FRY and SAM tests to assess the readability and suitability of a selection of sexual health leaflets. SMOG and FRY scores illustrate an average reading level of grade 9. SAM scores indicate that 59% of leaflets are superior in design and 41% are average in design. Leaflets generally perform well in the categories of content, literacy demand, typography and layout. They perform poorly in use of graphics, learning stimulation/motivation and cultural appropriateness. Sexual health leaflets have a reading level that is too high. Leaflets perform well on the suitability scores indicating they are reasonably suitable. There are a number of areas where sexual health leaflets could improve their design. Numerous practical techniques are suggested for improving the readability and suitability of sexual health leaflets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Optimal elastomeric scaffold leaflet shape for pulmonary heart valve leaflet replacement.

    Science.gov (United States)

    Fan, Rong; Bayoumi, Ahmed S; Chen, Peter; Hobson, Christopher M; Wagner, William R; Mayer, John E; Sacks, Michael S

    2013-02-22

    Surgical replacement of the pulmonary valve (PV) is a common treatment option for congenital pulmonary valve defects. Engineered tissue approaches to develop novel PV replacements are intrinsically complex, and will require methodical approaches for their development. Single leaflet replacement utilizing an ovine model is an attractive approach in that candidate materials can be evaluated under valve level stresses in blood contact without the confounding effects of a particular valve design. In the present study an approach for optimal leaflet shape design based on finite element (FE) simulation of a mechanically anisotropic, elastomeric scaffold for PV replacement is presented. The scaffold was modeled as an orthotropic hyperelastic material using a generalized Fung-type constitutive model. The optimal shape of the fully loaded PV replacement leaflet was systematically determined by minimizing the difference between the deformed shape obtained from FE simulation and an ex-vivo microCT scan of a native ovine PV leaflet. Effects of material anisotropy, dimensional changes of PV root, and fiber orientation on the resulting leaflet deformation were investigated. In-situ validation demonstrated that the approach could guide the design of the leaflet shape for PV replacement surgery. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Iodine leaflets in chapter D5 'Distribution of iodine pills'

    International Nuclear Information System (INIS)

    1981-01-01

    Jodine leaflet A will be distributed together with iodine pills in a nuclear disaster. Iodine leaflet B is suitable for informing the public in advance. Iodine leaflet C informs physicians in a scientific way on the benefits and risk of iodine pills. (orig./HP) [de

  18. Mimics of scleroderma

    Directory of Open Access Journals (Sweden)

    Kaveri K Nalianda

    2017-01-01

    Full Text Available Systemic sclerosis is a rare autoimmune connective tissue disorder characterised typically by tightening and tethering of skin. However, several other disorders are also characterised by hardening and thickening of skin. These mimics can be potentially confused with systemic sclerosis, leading to a misdiagnosis. This review describes the aetiopathogenesis, clinical features and treatment of Morphea (localised scleroderma, Scleredema, Scleromyxoedema, Eosinophilic fasciitis, Nephrogenic Systemic Fibrosis, Diabetic Cheiroarthropathy, chronic GVHD, POEMS syndrome and drug induced scleroderma like illness. A careful and thorough clinical assessment is essential in order to differentiate these mimics from each other and from systemic sclerosis, establish the diagnosis, and initiate appropriate treatment.

  19. Synthetic mimics of antimicrobial peptides.

    Science.gov (United States)

    Som, Abhigyan; Vemparala, Satyavani; Ivanov, Ivaylo; Tew, Gregory N

    2008-01-01

    Infectious diseases and antibiotic resistance are now considered the most imperative global healthcare problem. In the search for new treatments, host defense, or antimicrobial, peptides have attracted considerable attention due to their various unique properties; however, attempts to develop in vivo therapies have been severely limited. Efforts to develop synthetic mimics of antimicrobial peptides (SMAMPs) have increased significantly in the last decade, and this review will focus primarily on the structural evolution of SMAMPs and their membrane activity. This review will attempt to make a bridge between the design of SMAMPs and the fundamentals of SMAMP-membrane interactions. In discussions regarding the membrane interaction of SMAMPs, close attention will be paid to the lipid composition of the bilayer. Despite many years of study, the exact conformational aspects responsible for the high selectivity of these AMPs and SMAMPs toward bacterial cells over mammalian cells are still not fully understood. The ability to design SMAMPs that are potently antimicrobial, yet nontoxic to mammalian cells has been demonstrated with a variety of molecular scaffolds. Initial animal studies show very good tissue distribution along with more than a 4-log reduction in bacterial counts. The results on SMAMPs are not only extremely promising for novel antibiotics, but also provide an optimistic picture for the greater challenge of general proteomimetics.

  20. Promotion of family planning services in practice leaflets.

    Science.gov (United States)

    Marshall, M N; Gray, D J; Pearson, V; Phillips, D R; Owen, M

    1994-10-08

    Providing 75% of family planning services in the United Kingdom, general practitioners are required to produce leaflets which describe the contraceptive services they provide. The authors analyzed information about family planning provided to clients through practice leaflets. 88% of practice leaflets from the 198 practices in Devon were available from the Devon Family Health Services Authority for analysis. It was determined that the leaflets are not being best used to advertise the range and potential of family planning services. Although all practices in Devon offer contraceptive services, only 90% of leaflets mentioned that the services are available. Reference to postcoital contraception and information about services outside the practice for people who might not want to see their family doctor are also sorely lacking. A clear need exists to provide patients with more information. Finally, the authors found that group practices and those with female partners are most likely to give high priority to family planning issues in their leaflets.

  1. Readability of Malaria Medicine Information Leaflets in Nigeria ...

    African Journals Online (AJOL)

    Purpose: To assess the readability of malaria medicines information leaflets available in Nigeria. Methods: Fourty five leaflets were assessed using the Simplified Measure of Gobbledygook (SMOG) readability test and by examining them for paper type, font size type, use of symbols and pictograms, and bilingual information ...

  2. Quality assessment of patient leaflets on misoprostol-induced labour

    DEFF Research Database (Denmark)

    Clausen, Jette Aaroe; Juhl, Mette; Rydahl, Eva

    2016-01-01

    =13). Design: Patient leaflets were evaluated according to a validated scoring tool (International Patient Decision Aid Standards instrument, IPDAS), core elements in the Danish Health Act, and items regarding off-label use and non-registered medication. Two of the authors scored all leaflets...

  3. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves

    DEFF Research Database (Denmark)

    Makkar, Raj R; Fontana, Gregory; Jilaihawi, Hasan

    2015-01-01

    BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis...... patients and 1 of 115 patients, respectively; P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further...

  4. PIV validation of blood-heart valve leaflet interaction modelling.

    Science.gov (United States)

    Kaminsky, R; Dumont, K; Weber, H; Schroll, M; Verdonck, P

    2007-07-01

    The aim of this study was to validate the 2D computational fluid dynamics (CFD) results of a moving heart valve based on a fluid-structure interaction (FSI) algorithm with experimental measurements. Firstly, a pulsatile laminar flow through a monoleaflet valve model with a stiff leaflet was visualized by means of Particle Image Velocimetry (PIV). The inflow data sets were applied to a CFD simulation including blood-leaflet interaction. The measurement section with a fixed leaflet was enclosed into a standard mock loop in series with a Harvard Apparatus Pulsatile Blood Pump, a compliance chamber and a reservoir. Standard 2D PIV measurements were made at a frequency of 60 bpm. Average velocity magnitude results of 36 phase-locked measurements were evaluated at every 10 degrees of the pump cycle. For the CFD flow simulation, a commercially available package from Fluent Inc. was used in combination with inhouse developed FSI code based on the Arbitrary Lagrangian-Eulerian (ALE) method. Then the CFD code was applied to the leaflet to quantify the shear stress on it. Generally, the CFD results are in agreement with the PIV evaluated data in major flow regions, thereby validating the FSI simulation of a monoleaflet valve with a flexible leaflet. The applicability of the new CFD code for quantifying the shear stress on a flexible leaflet is thus demonstrated.

  5. Amyotrophic lateral sclerosis mimic syndromes.

    Science.gov (United States)

    Ghasemi, Majid

    2016-04-03

    Amyotrophic lateral sclerosis (ALS) misdiagnosis has many broad implications for the patient and the neurologist. Potentially curative treatments exist for certain ALS mimic syndromes, but delay in starting these therapies may have an unfavorable effect on outcome. Hence, it is important to exclude similar conditions. In this review, we discuss some of the important mimics of ALS.

  6. Enzyme Mimics: Advances and Applications.

    Science.gov (United States)

    Kuah, Evelyn; Toh, Seraphina; Yee, Jessica; Ma, Qian; Gao, Zhiqiang

    2016-06-13

    Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Leaflet escape in a new bileaflet mechanical valve: TRI technologies.

    Science.gov (United States)

    Bottio, Tomaso; Casarotto, Dino; Thiene, Gaetano; Caprili, Luca; Angelini, Annalisa; Gerosa, Gino

    2003-05-13

    Leaflet escape is a mode of structural valve failure for mechanical prostheses. This complication previously has been reported for both monoleaflet and bileaflet valve models. We report 2 leaflet escape occurrences observed in 2 patients who underwent valve replacement with a TRI Technologies valve prosthesis. At the University of Padua, between November 2000 and February 2002, 36 TRI Technologies valve prostheses (26 aortic and 10 mitral) were implanted in 34 patients (12 women and 22 men) with a mean age of 59.9+/-10.3 years (range, 30 to 75 years). There were 5 deaths: 3 in hospital, 1 early after discharge, and 1 late. Two patients experienced a catastrophic prosthetic leaflet escape; the first patient was a 52-year-old man who died 10 days after aortic valve and ascending aorta replacement, and the second was a 58-year-old man who underwent a successful emergency reoperation 20 months after mitral valve replacement. Examination of the explanted prostheses showed in both cases a leaflet escape caused by a leaflet's pivoting system fracture. Prophylactic replacement was then successfully accomplished so far in 12 patients, without evidence of structural valve failure in any of them. Among other significant postoperative complications, we observed 3 major thromboembolisms, 1 hemorrhage, and 1 paravalvular leak. These catastrophes prompted us to interrupt the implantation program, and they cast a shadow on the durability of the TRI Technologies valve prosthesis because of its high risk of structural failure.

  8. Late leaflet fracture and embolization of a Duromedics mitral prosthesis.

    Science.gov (United States)

    Sudo, K; Sasagawa, N; Ide, H; Nunokawa, M; Fujiki, T; Tonari, K

    2000-08-01

    A case of leaflet fracture and embolization of a mitral prosthetic valve is described. A 54-year-old man had received mitral valve replacement with an Edwards-Duromedics 29M prosthetic valve, at 10 years ago. Emergency mitral valve replacement was performed because the patient had severe congestive left heart failure with severe acute mitral regurgitation caused by a fracture in one of the mitral valve leaflets. The leaflet, which was fractured into 2 pieces, was removed from the right common iliac artery at 3 months after valve replacement. Visual inspection revealed that the leaflet contained a midline fracture. The fracture originated within a cavitary erosion pit near the major radius of the leaflet. The patient recovered from acute renal failure, requiring hemodialysis for 80 days, and is currently without complaints. We have used a Duromedics mitral valve in 11 patients, from April 1987 to April 1988. No subsequent valve failure has occurred. The diagnosis, treatment and cause of a mechanical valve fracture are discussed.

  9. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves

    DEFF Research Database (Denmark)

    Chakravarty, Tarun; Søndergaard, Lars; Friedman, John

    2017-01-01

    rates of transient ischaemic attacks (TIAs; 4·18 TIAs per 100 person-years vs 0·60 TIAs per 100 person-years; p=0·0005) and all strokes or TIAs (7·85 vs 2·36 per 100 person-years; p=0·001). INTERPRETATION: Subclinical leaflet thrombosis occurred frequently in bioprosthetic aortic valves, more commonly...... outcomes after TAVR with the new-generation valves, prevention and treatment of subclinical leaflet thrombosis might offer a potential opportunity for further improvement in valve haemodynamics and clinical outcomes. FUNDING: RESOLVE (Cedars-Sinai Heart Institute) and SAVORY (Rigshospitalet)....

  10. Information meeting on the AD leaflets of the HP series

    International Nuclear Information System (INIS)

    1976-05-01

    The present brochure contains discussions and summaries of papers from an information meeting on new leaflets issued by the Arbeitsgemeinschaft Druckbehaelter, Reihe Herstellung und Pruefung (task group pressure vessels, production and testing section), organized by the TUEV of Bavaria. (RW) [de

  11. The effectiveness of a pregnancy leaflet to promote health in ...

    African Journals Online (AJOL)

    2014-11-21

    Nov 21, 2014 ... Method: The research design used was a pre-test post-test design. Two samples of 30 ... Self-report data were gathered with a questionnaire based on the leaflet. ..... scenarios for young adults, whether or not they are infected.

  12. Including patients’ perspectives in patient information leaflets: A polyocular approach

    DEFF Research Database (Denmark)

    Fage-Butler, Antoinette Mary

    2013-01-01

    Existing research reveals that patients’ perspectives are missing from mandatory patient information leaflets (PILs). At the same time, there is overwhelming consensus that they should be included in this genre, and a corresponding need for potential approaches to tackle this problem. This paper ...

  13. Readability of Malaria Medicine Information Leaflets in Nigeria

    African Journals Online (AJOL)

    Erah

    2010-12-18

    Dec 18, 2010 ... for malaria medicines information leaflets available in Nigeria was 13.69 ± 1.70. This value is equivalent ... Health promotion and behaviour change communication ... their rational use at the community level. Readability is the ...

  14. Readability of medicinal package leaflets: a systematic review.

    Science.gov (United States)

    Pires, Carla; Vigário, Marina; Cavaco, Afonso

    2015-01-01

    OBJECTIVE To review studies on the readability of package leaflets of medicinal products for human use. METHODS We conducted a systematic literature review between 2008 and 2013 using the keywords "Readability and Package Leaflet" and "Readability and Package Insert" in the academic search engine Biblioteca do Conhecimento Online, comprising different bibliographic resources/databases. The preferred reporting items for systematic reviews and meta-analyses criteria were applied to prepare the draft of the report. Quantitative and qualitative original studies were included. Opinion or review studies not written in English, Portuguese, Italian, French, or Spanish were excluded. RESULTS We identified 202 studies, of which 180 were excluded and 22 were enrolled [two enrolling healthcare professionals, 10 enrolling other type of participants (including patients), three focused on adverse reactions, and 7 descriptive studies]. The package leaflets presented various readability problems, such as complex and difficult to understand texts, small font size, or few illustrations. The main methods to assess the readability of the package leaflet were usability tests or legibility formulae. Limitations with these methods included reduced number of participants; lack of readability formulas specifically validated for specific languages (e.g., Portuguese); and absence of an assessment on patients literacy, health knowledge, cognitive skills, levels of satisfaction, and opinions. CONCLUSIONS Overall, the package leaflets presented various readability problems. In this review, some methodological limitations were identified, including the participation of a limited number of patients and healthcare professionals, the absence of prior assessments of participant literacy, humor or sense of satisfaction, or the predominance of studies not based on role-plays about the use of medicines. These limitations should be avoided in future studies and be considered when interpreting the results.

  15. Mimic of OSU research reactor

    International Nuclear Information System (INIS)

    Lu, Hong; Miller, D.W.

    1991-01-01

    The Ohio State University research reactor (OSURR) is undergoing improvements in its research and educational capabilities. A computer-based digital data acquisition system, including a reactor system mimic, will be installed as part of these improvements. The system will monitor the reactor system parameters available to the reactor operator either in digital parameters available to the reactor operator either in digital or analog form. The system includes two computers. All the signals are sent to computer 1, which processes the data and sends the data through a serial port to computer 2 with a video graphics array VGA monitor, which is utilized to display the mimic system of the reactor

  16. Natural history of subclinical leaflet thrombosis affecting motion in bioprosthetic aortic valves

    DEFF Research Database (Denmark)

    Sondergaard, Lars; De Backer, Ole; Kofoed, Klaus F

    2017-01-01

    . No patients developed symptoms of valve dysfunction and leaflet thickening was not clearly associated with any clinical events. Conclusions: Subclinical leaflet thrombosis is a common finding after TAVI and SAVR, and may progress from normal leaflet over HALT to the more severe HAM. The phenomenon can develop...

  17. Crutches, confetti or useful tools? Professionals' views on and use of health education leaflets.

    Science.gov (United States)

    Murphy, S; Smith, C

    1993-06-01

    This paper examines the views on and use of health education leaflets by a number of professional groups: health visitors, midwives, occupational health workers, pharmacists and school health education co-ordinators. Eighty nine percent currently obtain leaflets from health promotion units, with the exception of health visitors, professionals are largely satisfied with the units' service. Seventy six percent use commercial or sponsored leaflets primarily because of the large numbers and topics that are available. The numbers and type of leaflets used were found to vary across the professions. All professionals see an increasingly important role for leaflets in their work. A number of them, pharmacists and occupational health workers in particular, saw the numbers they use rising. These views were accompanied by lower levels of belief in a leaflets ability to increase knowledge and behaviour as well as lower levels of satisfaction with current leaflet use and a concern over the public's reception of leaflets. Methods of leaflet distribution to the public largely reflect the professionals' work contexts. Most popular were handing out leaflets with advice, leaving them in a public place and using them as a back-up to a meeting. A number of contradictions emerge between distribution practices and perceived effectiveness. Few professionals thought leaving leaflets in a public place was effective, and few health visitors and midwives believed giving leaflets to the family of a client was effective despite large numbers doing so. The implications of these findings for health promotion policy and practice are discussed.

  18. Diet and Colorectal Cancer Risk: Evaluation of a Nutrition Education Leaflet

    Science.gov (United States)

    Dyer, K. J.; Fearon, K. C. H.; Buckner, K.; Richardson, R. A.

    2005-01-01

    Objective: To evaluate the effect of a needs-based, nutrition education leaflet on nutritional knowledge. Design: Comparison of nutritional knowledge levels before and after exposure to a nutrition education leaflet. Setting: A regional colorectal out-patient clinic in Edinburgh. Method: A nutrition education leaflet, based on an earlier…

  19. Movement influences carambola leaflet chlorophyll fluorescence and temperature under sunny conditions

    International Nuclear Information System (INIS)

    Marler, T.E.; Lawton, P.D.

    1995-01-01

    Leaflets of 'Arkin', 'B-10', 'Kary', and 'Sri Kembangan' carambola (Averrhoa carambola L.) trees were restrained in a horizontal position for 3.5 h during midday under full sun conditions to determine the influence of overriding natural leaflet movement on adaxial chlorophyll fluorescence and temperature. Induced chlorophyll fluorescence obtained after 30 minutes of dark adaptation following the period of full sun exposure was affected by leaflet movement. Restrained leaflets exhibited a variable fluorescence (Fv)/peak fluorescence (Fm) of 0.48, while that of unrestrained leaflets was 0.65. Adaxial leaflet temperature of restrained leaflets was 6C higher than that of leaflets that were allowed to move. The influence of leaflet movement on temperature or chlorophyll fluorescence was not different among the four cultivars. However, mean Fv/Fm of 'Kary' and 'Sri Kembangan' was lower than that of 'B-10'. Our results indicate that the ability of carambola to change leaflet angle leads to lower temperature and higher photochemical efficiency than occurs when leaflets are not allowed to move naturally (vertically orient) under full sun conditions

  20. The enigmatic fast leaflet rotation in Desmodium motorium

    Science.gov (United States)

    Lev-Yadun, Simcha

    2013-01-01

    I propose that the enigmatic leaflet movements in elliptical circles every few minutes of the Indian telegraph (semaphore) plant Desmodium motorium ( = D. gyrans = Hedysarum gyrans = Codariocalyx motorius), which has intrigued scientists for centuries, is a new type of butterfly or general winged arthropod mimicry by this plant. Such leaflet movement may deceive a passing butterfly searching for an un-occupied site suitable to deposit its eggs, that the plant is already occupied. It may also attract insectivorous birds, reptiles or arthropods to the plant because it looks as if it is harboring a potential prey and while they patrol there, they can find insects or other invertebrates that indeed attack the plant. The possibility that diurnal mammalian herbivores may also be deterred by these movements should not be dismissed. PMID:23603964

  1. Danglers in Patient Information Leaflets and Technical Manuals

    DEFF Research Database (Denmark)

    Køhler Simonsen, Henrik

    2014-01-01

    in fact been proved. The analysis and the discussion showed that dangling participles are not very frequent in PILs, but much more common in technical manuals. The data showed that there were no “ludicrous” danglers,(see Matthews and Matthews 2008:146), in PILcorp. However, the analysis showed that both......Dangling participles and other types of ambiguous or unclear sentence constructions in directive and informative medical and technical texts, such as patient information leaflets (PILs) and technical manuals, render instructions unclear and potentially dangerous for the layman reader, i......, and readability on the basis of two corpora: a corpus of PILs (PILcorp) and a corpus of technical manuals (TECHcorp). The hypothesis is that patient information leaflets will contain fewer dangling constructions than technical manuals because of the strict regulations on product information texts including PILs...

  2. A Structural Analysis of a Mechanical Heart Valve Prosthesis with Flat Leaflet

    Science.gov (United States)

    Kwon, Young Joo

    This paper addresses the basic concept of MDO methodology and the structural analysis that should be performed in the design process of a mechanical heart valve prosthesis with flat leaflet using MDO methodology. In the structural design of the mechanical heart valve (MHV) prosthesis, the fluid mechanics analysis is executed for the blood flow passing through the leaflets of a mechanical heart valve prosthesis. Thereafter, the rigid body dynamics analysis of the leaflet motion is performed to obtain the structural condition for the structural mechanics analysis of the deformed leaflet. Then the structural mechanics analysis of the deformed leaflet follows to confirm the minimum thickness of the leaflet for the structural durability of the mechanical heart valve prosthesis. This paper shows that the minimum leaflet thickness can be evaluated to be 0.6mm among the suggested thicknesses.

  3. [Micromorphology of pejibaye leaflets Bactris gasipaes (Arecaceae) var. diamonds-10].

    Science.gov (United States)

    Sánchez-Chacón, Ethel; Alvarado-Rodríguez, Olman; Rodríguez-Arrieta, Alexander; Gómez-Alpízar, Luis

    2016-09-01

    Bactris gasipaes is widely cultivated for the consumption of palm hearts and fruits. The present work describes the micro morphological characteristics of leaflets from adult plants of B. gasipaes, thornless variety Diamantes-10, collected in the Diamantes Experimental Station in Guápiles, Costa Rica. We collected 25 leaflets and analyses were performed with a combination of microscopy techniques: light microscopy, scanning electron microscopy and transmission electron microscopy to study their structure. Our results showed that leaflets have abundant epicuticular wax on adaxial and abaxial surfaces. Analyses from the epidermis indicated that it is composed of isodiametric cells, and it is also evident that hypodermis cells have rectangular shape and are larger than the other epidermal cells. We observed stomata on both surfaces, but they were more abundant in the abaxial surface. On the other hand, the epidermis showed the presence of trichomes with three different morphologies. In the parenchyma, cells are large and not well defined, and we observed the presence of astroesclereids, and compact groups of fiber bundles between parenchyma cells. The central vein has several vascular bundles, arranged in a continuous manner, and they are surrounded by sclerotic tissue; some of these fibers presented live protoplasts. All minor veins showed the same anatomy as the central vein. In these veins, the vessel elements of protoxylem and metaxylem showed scalariform ornaments on their walls. Phloem is located towards the adaxial surface of the vein and we observed sieve and companion cells surrounded by fibers and parenchyma cells. The companion cells presented branched plasmodesmata attached to a sieve element, and in these elements we found protein bodies called P-protein. The main anatomical difference in the leaflets of the var. Diamantes-10, compared to the other varieties of B. gasipaes K, is the lack of thorns; the other morphological features seem to be conserved.

  4. The Impact of Fluid Inertia on In Vivo Estimation of Mitral Valve Leaflet Constitutive Properties and Mechanics.

    Science.gov (United States)

    Bark, David L; Dasi, Lakshmi P

    2016-05-01

    We examine the influence of the added mass effect (fluid inertia) on mitral valve leaflet stress during isovolumetric phases. To study this effect, oscillating flow is applied to a flexible membrane at various frequencies to control inertia. Resulting membrane strain is calculated through a three-dimensional reconstruction of markers from stereo images. To investigate the effect in vivo, the analysis is repeated on a published dataset for an ovine mitral valve (Journal of Biomechanics 42(16): 2697-2701). The membrane experiment demonstrates that the relationship between pressure and strain must be corrected with a fluid inertia term if the ratio of inertia to pressure differential approaches 1. In the mitral valve, this ratio reaches 0.7 during isovolumetric contraction for an acceleration of 6 m/s(2). Acceleration is reduced by 72% during isovolumetric relaxation. Fluid acceleration also varies along the leaflet during isovolumetric phases, resulting in spatial variations in stress. These results demonstrate that fluid inertia may be the source of the temporally and spatially varying stiffness measurements previously seen through inverse finite element analysis of in vivo data during isovolumetric phases. This study demonstrates that there is a need to account for added mass effects when analyzing in vivo constitutive relationships of heart valves.

  5. Multiphoton microscopy of ECM proteins in baboon aortic leaflet

    Science.gov (United States)

    Gonzalez, Mariacarla; Saytashev, Ilyas; Luna, Camila; Gonzalez, Brittany; Pinero, Alejandro; Perez, Manuel; Ramaswamy, Sharan; Ramella-Roman, Jessica

    2018-02-01

    The extracellular matrix (ECM) plays crucial role in defining mechanical properties of a heart valve yet the mechanobiological role of the ECM proteins - collagen and elastin - in living heart valve leaflets is still poorly understood. In this study, non-linear microscopy was used to obtain three dimensional images of collagen and elastin arrangement in aortic leaflets under combined steady flow (850 ml/min) and cyclic flexure (1 Hz) mechanical (dynamic) training. A novel bioreactor capable of mimicking the flow conditions in a living heart was used in this study and was optimized for microscopic imagery. A custom made non-linear microscope was used in this study to provide Second Harmonic Generation (SHG) imaging of collagen arrangement and two-photon imaging of elastin. Two control and three trained leaflet samples from static and dynamic tissue culture were imaged to observe protein changes in the tissue for a period of seven days. Dynamic training led to a decrease in alignment index of the protein fibers compared to the static treatment.

  6. Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils.

    Science.gov (United States)

    Araman, Can; Thompson, Robert E; Wang, Siyao; Hackl, Stefanie; Payne, Richard J; Becker, Christian F W

    2017-09-01

    The prion protein (PrP) is an N -glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrP Sc ) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrP C ) into PrP Sc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179-231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics.

  7. Piezoelectric materials mimic the function of the cochlear sensory epithelium.

    Science.gov (United States)

    Inaoka, Takatoshi; Shintaku, Hirofumi; Nakagawa, Takayuki; Kawano, Satoyuki; Ogita, Hideaki; Sakamoto, Tatsunori; Hamanishi, Shinji; Wada, Hiroshi; Ito, Juichi

    2011-11-08

    Cochlear hair cells convert sound vibration into electrical potential, and loss of these cells diminishes auditory function. In response to mechanical stimuli, piezoelectric materials generate electricity, suggesting that they could be used in place of hair cells to create an artificial cochlear epithelium. Here, we report that a piezoelectric membrane generated electrical potentials in response to sound stimuli that were able to induce auditory brainstem responses in deafened guinea pigs, indicating its capacity to mimic basilar membrane function. In addition, sound stimuli were transmitted through the external auditory canal to a piezoelectric membrane implanted in the cochlea, inducing it to vibrate. The application of sound to the middle ear ossicle induced voltage output from the implanted piezoelectric membrane. These findings establish the fundamental principles for the development of hearing devices using piezoelectric materials, although there are many problems to be overcome before practical application.

  8. Energy consumption of small refrigerators - Information leaflet; Merkblatt Kleinkuehlschrank

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-07-01

    In this leaflet published by the Swiss Federal Office of Energy (SFOE), the energy consumption of small refrigerators with a capacity of less than 100 litres is reported on. Such small refrigerators are often used in hotel rooms or in campers. It is noted that, in comparison, a typical, 150 litre class A++ domestic refrigerator uses only a fraction of the amount of energy used by such small refrigerators. The results of measurements made according to EN 153 and ISO 15502 norms are discussed. Recommendations are made on the purchase and operation of these small refrigerators.

  9. Advertising, expectations and informed consent: the contents and functions of acupuncture leaflets.

    Science.gov (United States)

    Bishop, Felicity L; Salmon, Cathy

    2013-12-01

    To evaluate the content of patient information leaflets about acupuncture. 401 patient information leaflets were obtained from practising UK acupuncturists and subjected to content and thematic analysis. 59% of included leaflets were from NHS physiotherapists. Almost all the leaflets defined acupuncture and the majority explained how it might work, described the treatment process and placed it in a historical context. Most described possible benefits and risks of acupuncture and discussed contraindications and safety. Just under a third of leaflets (120, 30%) suggested conditions that might be helped by acupuncture, most commonly musculoskeletal pain, arthritis and injuries. By emphasising differences between individuals in acupuncture treatments and responsiveness, the leaflets fostered hope for positive effects without making any guarantees. Information leaflets are broadly consistent with the evidence for acupuncture, but some claims are inconsistent with official advice from advertising regulators. An ethically sound, scientifically grounded and psychologically effective leaflet should accurately convey both benefits and risks of treatment, optimise patients' expectations and allay concerns about needling. This study suggests that acupuncture leaflets might achieve these multiple functions but care should be taken to ensure adequate coverage of risks.

  10. Randomised trial of mitral valve repair with leaflet resection versus leaflet preservation on functional mitral stenosis (The CAMRA CardioLink-2 Trial).

    Science.gov (United States)

    Chan, Vincent; Chu, Michael W A; Leong-Poi, Howard; Latter, David A; Hall, Judith; Thorpe, Kevin E; de Varennes, Benoit E; Quan, Adrian; Tsang, Wendy; Dhingra, Natasha; Yared, Kibar; Teoh, Hwee; Chu, F Victor; Chan, Kwan-Leung; Mesana, Thierry G; Connelly, Kim A; Ruel, Marc; Jüni, Peter; Mazer, C David; Verma, Subodh

    2017-05-30

    The gold-standard treatment of severe mitral regurgitation (MR) due to degenerative disease is valve repair, which is surgically performed with either a leaflet resection or leaflet preservation approach. Recent data suggest that functional mitral stenosis (MS) may occur following valve repair using a leaflet resection strategy, which adversely affects patient prognosis. A randomised comparison of these two approaches to mitral repair on functional MS has not been conducted. This is a prospective, multicentre randomised controlled trial designed to test the hypothesis that leaflet preservation leads to better preservation of mitral valve geometry, and therefore, will be superior to leaflet resection for the primary outcome of functional MS as assessed by 12-month mean mitral valve gradient at peak exercise. Eighty-eight patients with posterior leaflet prolapse will be randomised intraoperatively once deemed by the operating surgeon to feasibly undergo mitral repair using either a leaflet resection or leaflet preservation approach. Secondary end points include comparison of repair strategies with regard to mitral valve orifice area, leaflet coaptation height, 6 min walk test and a composite major adverse event end point consisting of recurrent MR ≥2+, death or hospital readmission for congestive heart failure within 12 months of surgery. Institutional ethics approval has been obtained from all enrolling sites. Overall, there remains clinical equipoise regarding the mitral valve repair strategy that is associated with the least likelihood of functional MS. This trial hopes to introduce high-quality evidence to help surgical decision making in this context. NCT02552771. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  11. Cholesterol asymmetry in synaptic plasma membranes.

    Science.gov (United States)

    Wood, W Gibson; Igbavboa, Urule; Müller, Walter E; Eckert, Gunter P

    2011-03-01

    Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  12. [Communication prostheses and behavioral alignment in hospital leaflets].

    Science.gov (United States)

    Vasconcellos-Silva, Paulo Roberto; Rivera, Francisco Javier Uribe; Rozemberg, Brani

    2003-08-01

    Review was made of publications that describe experience with printed material distributed to the lay public in hospital institutions. From the 146 leaflets examined, those aimed at professionals or disabled people, thus leaving 75 papers that illustrate the present pattern for the rationality behind the production, use and evaluation of this type of resource. In a general manner, such leaflets invest in the power of "ideal printed information" to align behavior with the hospital's biomedical agenda. The underlying rationality that permeates them perceives the "perfect information package" as one that efficiently describes its technical content for the purpose of unidirectional persuasion, is up-to-date in relation to readability scales and embellished by graphic design, and emphasizes the priorities defined by the professionals. Such "communication prostheses" should be capable of electronic validation by means of software suitable for proportioning the "doses" to the subject matter. Information as a drug, cognitivism, the lack of research on message reception and the need for communicative action for the deconstruction of systems of closed thinking within the hospital environment have been discussed.

  13. Trans-membrane area asymmetry controls the shape of cellular organelles

    NARCIS (Netherlands)

    Beznoussenko, Galina V; Pilyugin, Sergei S; Geerts, Willie J C; Kozlov, Michael M; Burger, Koert N J; Luini, Alberto; Derganc, Jure; Mironov, Alexander A

    2015-01-01

    Membrane organelles often have complicated shapes and differ in their volume, surface area and membrane curvature. The ratio between the surface area of the cytosolic and luminal leaflets (trans-membrane area asymmetry (TAA)) determines the membrane curvature within different sites of the organelle.

  14. Membrane fusion and exocytosis.

    Science.gov (United States)

    Jahn, R; Südhof, T C

    1999-01-01

    Membrane fusion involves the merger of two phospholipid bilayers in an aqueous environment. In artificial lipid bilayers, fusion proceeds by means of defined transition states, including hourglass-shaped intermediates in which the proximal leaflets of the fusing membranes are merged whereas the distal leaflets are separate (fusion stalk), followed by the reversible opening of small aqueous fusion pores. Fusion of biological membranes requires the action of specific fusion proteins. Best understood are the viral fusion proteins that are responsible for merging the viral with the host cell membrane during infection. These proteins undergo spontaneous and dramatic conformational changes upon activation. In the case of the paradigmatic fusion proteins of the influenza virus and of the human immunodeficiency virus, an amphiphilic fusion peptide is inserted into the target membrane. The protein then reorients itself, thus forcing the fusing membranes together and inducing lipid mixing. Fusion of intracellular membranes in eukaryotic cells involves several protein families including SNAREs, Rab proteins, and Sec1/Munc-18 related proteins (SM-proteins). SNAREs form a novel superfamily of small and mostly membrane-anchored proteins that share a common motif of about 60 amino acids (SNARE motif). SNAREs reversibly assemble into tightly packed helical bundles, the core complexes. Assembly is thought to pull the fusing membranes closely together, thus inducing fusion. SM-proteins comprise a family of soluble proteins that bind to certain types of SNAREs and prevent the formation of core complexes. Rab proteins are GTPases that undergo highly regulated GTP-GDP cycles. In their GTP form, they interact with specific proteins, the effector proteins. Recent evidence suggests that Rab proteins function in the initial membrane contact connecting the fusing membranes but are not involved in the fusion reaction itself.

  15. Comparative study between CardiaMed valves (freely floating valve leaflets versus St. Jude Medical (fixed valve leaflets in mitral valve replacement surgery

    Directory of Open Access Journals (Sweden)

    Mostafa Ahmed

    2017-09-01

    Conclusions: CardiaMed freely floating leaflet prostheses showed good hemodynamic characteristics. The prosthesis adequately corrects hemodynamics and is safe and no worse than the St. Jude Medical valve in the mitral valve position.

  16. Readability Statistics of Patient Information Leaflets in a Speech and Language Therapy Department

    Science.gov (United States)

    Pothier, Louise; Day, Rachael; Harris, Catherine; Pothier, David D.

    2008-01-01

    Background: Information leaflets are commonly used in Speech and Language Therapy Departments. Despite widespread use, they can be of variable quality. Aims: To revise current departmental leaflets using the National Health Service (NHS) Toolkit for Producing Patient Information and to test the effect that this has on the readability scores of the…

  17. Effect of the Mitral Valve's Anterior Leaflet on Axisymmetry of Transmitral Vortex Ring.

    Science.gov (United States)

    Falahatpisheh, Ahmad; Pahlevan, Niema M; Kheradvar, Arash

    2015-10-01

    The shape and formation of transmitral vortex ring are shown to be associated with diastolic function of the left ventricle (LV). Transmitral vortex ring is a flow feature that is observed to be non-axisymmetric in a healthy heart and its inherent asymmetry in the LV assists in efficient ejection of the blood during systole. This study is a first step towards understanding the effects of the mitral valve's anterior leaflet on transmitral flow. We experimentally study a single-leaflet model of the mitral valve to investigate the effect of the anterior leaflet on the axisymmetry of the generated vortex ring based on the three-dimensional data acquired using defocusing digital particle image velocimetry. Vortex rings form downstream of a D-shaped orifice in presence or absence of the anterior leaflet in various physiological stroke ratios. The results of the statistical analysis indicate that the formed vortex ring downstream of a D-shaped orifice is markedly non-axisymmetric, and presence of the anterior leaflet improves the ring's axisymmetry. This study suggests that the improvement of axisymmetry in presence of the anterior leaflet might be due to coupled dynamic interaction between rolling-up of the shear layer at the edges of the D-shaped orifice and the borders of the anterior leaflet. This interaction can reduce the non-uniformity in vorticity generation, which results in more axisymmetric behavior compared to the D-shaped orifice without the anterior leaflet.

  18. Infective Endocarditis of the Aortic Valve with Anterior Mitral Valve Leaflet Aneurysm

    NARCIS (Netherlands)

    Tomsic, Anton; Li, Wilson W. L.; van Paridon, Marieke; Bindraban, Navin R.; de Mol, Bas A. J. M.

    2016-01-01

    Mitral valve leaflet aneurysm is a rare and potentially devastating complication of aortic valve endocarditis. We report the case of a 48-year-old man who had endocarditis of the native aortic valve and a concomitant aneurysm of the anterior mitral valve leaflet. Severe mitral regurgitation occurred

  19. Influence of Printed Leaflets on Consumer Purchase Behavior

    Directory of Open Access Journals (Sweden)

    Jan Huml

    2015-01-01

    Full Text Available This article deals with the way customers perceive individual non-direct response printed leaflets and it is simultaneously focused on the question whether this material has any importance in general for customers during their purchase realization. The research is further concerned with the issue of the differences between customers living in family built-up areas and those who are living in residential housing. The research explores the differences related to preferences of various target groups. It identifies whether customers wish to receive printed advertising material into their letter boxes, what sort of media they read and what kinds of assortment are most frequently requested to appear in this form of promotion by customers. Preferences are aggregated by means of data classification based on different criteria and they provide a clue for better orientation in customer thinking.

  20. Lay-friendliness in translated Patient Information Leaflets

    DEFF Research Database (Denmark)

    Jensen, Matilde Nisbeth; Zethsen, Karen Korning

    This paper seeks to empirically explore the claim that translated Danish Patient Information Leaflets (PILs) are less lay-friendly than their English source texts. The last two decades have seen an increased focus on providing patients with lay-friendly, easily understood information, enabling them...... to make informed decisions concerning their health. For this purpose, many new genres have been created, one such genre being the PIL, a mandatory text which in an EU context has to accompany all medication informing patients about dosage, side effects etc. Legally, the PIL genre is required to ensure lay......-friendly information as it must be “written and designed to be clear and understandable, enabling the users to act appropriately” (Article 63(2) of EU Directive 2001/83/EC). Despite the legal requirements and the intensified focus on lay-friendly health communication, many studies have shown that PILs are often...

  1. Introducing Membrane Charge and Membrane Potential to T Cell Signaling

    Directory of Open Access Journals (Sweden)

    Yuanqing Ma

    2017-11-01

    Full Text Available While membrane models now include the heterogeneous distribution of lipids, the impact of membrane charges on regulating the association of proteins with the plasma membrane is often overlooked. Charged lipids are asymmetrically distributed between the two leaflets of the plasma membrane, resulting in the inner leaflet being negatively charged and a surface potential that attracts and binds positively charged ions, proteins, and peptide motifs. These interactions not only create a transmembrane potential but they can also facilitate the formation of charged membrane domains. Here, we reference fields outside of immunology in which consequences of membrane charge are better characterized to highlight important mechanisms. We then focus on T cell receptor (TCR signaling, reviewing the evidence that membrane charges and membrane-associated calcium regulate phosphorylation of the TCR–CD3 complex and discuss how the immunological synapse exhibits distinct patterns of membrane charge distribution. We propose that charged lipids, ions in solution, and transient protein interactions form a dynamic equilibrium during T cell activation.

  2. Stress Analysis of Transcatheter Aortic Valve Leaflets Under Dynamic Loading: Effect of Reduced Tissue Thickness.

    Science.gov (United States)

    Abbasi, Mostafa; Azadani, Ali N

    2017-07-01

    In order to accommodate transcatheter valves to miniaturized catheters, the leaflet thickness must be reduced to a value which is typically less than that of surgical bioprostheses. The study aim was to use finite-element simulations to determine the impact of the thickness reduction on stress and strain distribution. A 23 mm transcatheter aortic valve (TAV) was modelled based on the Edwards SAPIEN XT (Edwards Lifesciences, Irvine, CA, USA). Finite-element (FE) analysis was performed using the ABAQUS/Explicit solver. An ensemble-averaged transvalvular pressure waveform measured from in-vitro tests conducted in a pulse duplicator was applied to the leaflets. Through a parametric study, uniform TAV leaflet thickness was reduced from 0.5 to 0.18 mm. By reducing leaflet thickness, significantly higher stress values were found in the leaflet's fixed edge during systole, and in the commissures during diastole. Through dynamic FE simulations, the highest stress values were found during systole in the leaflet fixed edge. In contrast, at the peak of diastole high-stress regions were mainly observed in the commissures. The peak stress was increased by 178% and 507% within the leaflets after reducing the thickness of 0.5 mm to 0.18 mm at the peak of systole and diastole, respectively. The study results indicated that, the smaller the leaflet thickness, the higher the maximum principal stress. Increased mechanical stress on TAV leaflets may lead to accelerated tissue degeneration. By using a thinner leaflet, TAV durability may not atch with that of surgical bioprostheses.

  3. Biomimetic membranes and methods of making biomimetic membranes

    Science.gov (United States)

    Rempe, Susan; Brinker, Jeffrey C.; Rogers, David Michael; Jiang, Ying-Bing; Yang, Shaorong

    2016-11-08

    The present disclosure is directed to biomimetic membranes and methods of manufacturing such membranes that include structural features that mimic the structures of cellular membrane channels and produce membrane designs capable of high selectivity and high permeability or adsorptivity. The membrane structure, material and chemistry can be selected to perform liquid separations, gas separation and capture, ion transport and adsorption for a variety of applications.

  4. Tiny plastic lung mimics human pulmonary function

    Science.gov (United States)

    Careers Inclusion & Diversity Work-Life Balance Career Resources Apply for a Job Postdocs Students Goals Recycling Green Purchasing Pollution Prevention Reusing Water Resources Environmental Management Releases - 2016 » April » Tiny plastic lung mimics human pulmonary function Tiny plastic lung mimics

  5. Preparation, validation and user-testing of pictogram-based patient information leaflets for hemodialysis patients.

    Science.gov (United States)

    Mateti, Uday Venkat; Nagappa, Anantha Naik; Attur, Ravindra Prabhu; Bairy, Manohar; Nagaraju, Shankar Prasad; Mallayasamy, Surulivelrajan; Vilakkathala, Rajesh; Guddattu, Vasudev; Balkrishnan, Rajesh

    2015-11-01

    Patient information leaflets are universally-accepted resources to educate the patients/users about their medications, disease and lifestyle modification. The objective of the study was to prepare, validate and perform user-testing of pictogram-based patient information leaflets (P-PILs) among hemodialysis (HD) patients. The P-PILs are prepared by referring to the primary, secondary and tertiary resources. The content and pictograms of the leaflet have been validated by an expert committee consisting of three nephrologists and two academic pharmacists. The Baker Able Leaflet Design has been applied to develop the layout and design of the P-PILs. Quasi-experimental pre- and post-test design without control group was conducted on 81 HD patients for user-testing of P-PILs. The mean Baker Able Leaflet Design assessment score for English version of the leaflet was 28, and 26 for Kannada version. The overall user-testing knowledge assessment mean scores were observed to have significantly improved from 44.25 to 69.62 with p value information leaflets can be considered an effective educational tool for HD patients.

  6. [Consensus on the legibility criteria of health education leaflets].

    Science.gov (United States)

    Barrio-Cantalejo, I; Simón-Lorda, P; Jiménez, M Melguizo; Ruiz, A Molina

    2011-01-01

    To identify the most relevant aspects that guarantee the readability, clarity and simplicity of written health education materials. Delphi methodology in order to reach a state of consensus among health education experts on criteria of legibility in the design and publication of informative material and literature. Seventeen experts reached agreement on the principal recommendations for ensuring the legibility of health education materials. They were as follows: a) text content and layout: to structure the text using a title or subtitle, message explanation and conclusion; b) text construction: to use simple and concise sentences, diagrams and examples, and graphically highlighting the principal ideas; c) lexical comprehension: to use simple words and avoid technical language and abbreviations; d) typography: to use an easy-to-read font. There is a high degree of consensus regarding the way health education materials should be drawn up. This list of recommendations could be used as an instrument for reviewing and improving the design of health education materials. In general, it is recommended to identify the users of the leaflets and involve them in the writing and design.

  7. [Instrumental, directive, and affective communication in hospital leaflets].

    Science.gov (United States)

    Vasconcellos-Silva, Paulo Roberto; Uribe Rivera, Francisco Javier; Castiel, Luis David

    2003-01-01

    This study focuses on the typical semantic systems extracted from hospital staff communicative resources which attempt to validate information as an "object" to be transferred to patients. We describe the models of textual communication in 58 patient information leaflets from five hospital units in Brazil, gathered from 1996 to 2002. Three categories were identified, based on the theory of speech acts (Austin, Searle, and Habermas): 1) cognitive-instrumental utterances: descriptions by means of technical terms validated by self-referred, incomplete, or inaccessible argumentation, with an implicit educational function; 2) technical-directive utterances: self-referred (to the context of the source domains), with a shifting of everyday acts to a technical terrain with a disciplinary function and impersonal features; and 3) expressive modulations: need for inter-subjective connections to strengthen bonds of trust and a tendency to use childish arguments. We conclude that the three categories displayed: fragmentary sources; assumption of univocal messages and invariable use of information (idealized motivations and interests, apart from individualized perspectives); and assumption of universal interests as generators of knowledge.

  8. How well does cholesteryl hemisuccinate mimic cholesterol in saturated phospholipid bilayers?

    DEFF Research Database (Denmark)

    Kulig, W.; Tynkkynen, J.; Javanainen, M.

    2014-01-01

    Cholesteryl hemisuccinate is a detergent that is often used to replace cholesterol in crystallization of membrane proteins. Here we employ atomistic molecular dynamics simulations to characterize how well the properties of cholesteryl hemisuccinate actually match those of cholesterol in saturated...... protein-free lipid membranes. We show that the protonated form of cholesteryl hemisuccinate mimics many of the membrane properties of cholesterol quite well, while the deprotonated form of cholesteryl hemisuccinate is less convincing in this respect. Based on the results, we suggest that cholesteryl...... hemisuccinate in its protonated form is a quite faithful mimic of cholesterol for membrane protein crystallization, if specific cholesterol-protein interactions (not investigated here) are not playing a crucial role....

  9. A new self-expandable aortic valved stent deployed above native leaflets for aortic insufficiency: an in vitro study.

    Science.gov (United States)

    Huang, H; Zhou, Y; Shao, J; Cai, J; Mei, Y; Wang, Y

    2012-12-01

    The aim of this paper was to develop a new self-expandable aortic valved stent following the shape of the sinus of Valsalva, which can be deployed above native leaflets for aortic regurgitation, and study it's effect on coronary artery flow when orthotopic implantation in and above native leaflets. New self-expandable aortic valved stent consist of nitinol stent and bovine pericardium, and was designed following the shape of the sinus of Valsalva, the bovine pericardium was tailed as native leaflet. Thirty-six swine hearts were divided into three equal groups of twelve. In Group A (N.=12), the new self-expandable aortic valved stents deployed in native leaflets. In Group B (N.=12), the new self-expandable aortic valved stents deployed above native leaflets. In Group C (N.=12), the cylinder-like valved stents deployed only in native leaflets. The measurements of each coronary flow rate and endoscopic inspections were repeated post-implantation. In Group A and C, valve implantation in native leaflets resulted in a significant decrease in both left and right coronary flows. In Group B, no significant change in either right or left coronary flow was found after new self-expandable aortic valved stent placement. Endoscopic inspections showed that in group A and C the native leaflets sandwiched between valved stent and aortic wall, whereas, in group B the native leaflets were under the artificial leaflets. Two kinds of stents deployed in native leaflets affect left and right coronary flows significantly. No significant effect was found when the new self-expandable aortic valved stent deployed above native leaflets. This new self-expandable aortic valved stent can be deployed above the native leaflets, which avoids the obstruction of native leaflets on coronary flow.

  10. Direct type gerbode defect with cleft in anterior mitral leaflet: A rarest of rare combination

    Directory of Open Access Journals (Sweden)

    Rakesh Jain

    2016-01-01

    Full Text Available A 15-year-old boy was evaluated for the new onset of dyspnea. He had no significant medical or surgical history. On echocardiography, he was found to have a direct communication between the left ventricle and the right atrium through the atrioventricular (AV septum (a rare type of Gerbode defect with an associated cleft in the anterior mitral leaflet. The combination of direct type Gerbode defect with the cleft of the anterior mitral leaflet is extremely rare.

  11. Acute Mitral Valve Dysfunction Due to Escape of Prosthetic Mechanical Leaflet and Peripheral Leaftlet Embolization.

    Science.gov (United States)

    Calik, Eyup Serhat; Limandal, Husnu Kamil; Arslan, Umit; Tort, Mehmet; Yildiz, Ziya; Bayram, Ednan; Dag, Ozgur; Kaygin, Mehmet Ali; Erkut, Bilgehan

    2015-12-14

    Leaflet escape of prosthetic valve is rare but potentially life threatening. Early diagnosis is essential on account of avoiding mortality, and emergency surgical correction is compulsory. This complication has previously been reported for both monoleaflet and bileaflet valve models. A 30-year-old man who had undergone mitral valve replacement with a bileaflet valve 8 years prior at another center was admitted with acute-onset with cardiogenic shock as an emergency case. Transthoracic echocardiograms showed acute-starting severe mitral regurgitation associated with prosthetic mitral valve. There was a suspicious finding of a single prosthetic mitral leaflet. But the problem related with the valve wasn't specifically determined. The patient underwent emergent surgery for replacement of the damaged prosthetic valves immediately. There was no tissue impingement and thrombosis, one of the two leaflets was absent, and there were no signs of endocarditis or pannus formation in the prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet during surgery. The damaged valve was removed and a replacement 29 mm bileaflet mechanical valve was inserted by right lateral thoracotomy. After post-operative week one, the abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the left femoral artery. Fifteen days after the surgery the escaped leaflet was removed safely from the left femoral artery and the patient made a complete recovery. The escaped leaflet showed a fracture of one of the pivot systems caused by structural failure. Early cardiac surgery should be applied because of life-threatening problems.

  12. Outlet strut fracture and leaflet escape of Bjork-Shiley convexo-concave valve.

    Science.gov (United States)

    Uchino, Gaku; Yoshida, Hideo; Sakoda, Naoya; Hattori, Shigeru; Kawabata, Takuya; Saiki, Munehiro; Fujita, Yasufumi; Yunoki, Keiji; Hisamochi, Kunikazu; Mine, Yoshinari

    2017-06-01

    Prosthetic valve fracture is a serious complication and may arise in patient post-valve replacement. We experienced an outlet strut fracture and leaflet escape of a Bjork-Shiley convexo-concave valve. We performed an emergency redo mitral valve replacement and successfully retrieved the fractured strut and escaped leaflet from superficial femoral artery and the abdominal aorta. The patient showed an uneventful postoperative recovery.

  13. Fluence of Product Leaflets on Purchasing Behaviour in Times of Crisis

    Directory of Open Access Journals (Sweden)

    Halina Starzyczná

    2015-01-01

    Full Text Available This paper presents partial results of primary research on consumer purchasing behaviour with regards to the utilization of product leaflets. It deals with the consumer reaction on the use of these leaflets. The main goal is to assess the impulse to purchase goods on the basis of promotional leaflets in mailboxes, depending on the personal characteristics of the consumer. Partial goals are a brief theoretical basis of the examined issues and selected results of secondary research on consumer behaviour based on available statistical data and information. Consumer behaviour changes drastically in times of crisis. Czech consumer is addressed daily by a specific communication media of store chains – the leaflets. These appear daily in mailboxes and are generally positively accepted. There are also negative opinions, both from consumers as well as the EU. Respondents were asked about their financial situation, to what extent they change their buying behaviour with respect to the income level of households. It turned out that the impulse to purchase goods on the basis of promotional leaflets in mailboxes does not depend on the age and sex of respondents, but depends on the income level and education. The largest proportion of respondents considers leaflets because of promotional discounts.

  14. Determination of correlation between backflow volume and mitral valve leaflet young modulus from two dimensional echocardiogram images

    Science.gov (United States)

    Jong, Rudiyanto P.; Osman, Kahar; Adib, M. Azrul Hisham M.

    2012-06-01

    Mitral valve prolapse without proper monitoring might lead to a severe mitral valve failure which eventually leads to a sudden death. Additional information on the mitral valve leaflet condition against the backflow volume would be an added advantage to the medical practitioner for their decision on the patients' treatment. A study on two dimensional echocardiography images has been conducted and the correlations between the backflow volume of the mitral regurgitation and mitral valve leaflet Young modulus have been obtained. Echocardiogram images were analyzed on the aspect of backflow volume percentage and mitral valve leaflet dimensions on different rates of backflow volume. Young modulus values for the mitral valve leaflet were obtained by using the principle of elastic deflection and deformation on the mitral valve leaflet. The results show that the backflow volume increased with the decrease of the mitral valve leaflet Young modulus which also indicate the condition of the mitral valve leaflet approaching failure at high backflow volumes. Mitral valve leaflet Young modulus values obtained in this study agreed with the healthy mitral valve leaflet Young modulus from the literature. This is an initial overview of the trend on the prediction of the behaviour between the fluid and the structure of the blood and the mitral valve which is extendable to a larger system of prediction on the mitral valve leaflet condition based on the available echocardiogram images.

  15. Membrane interaction of retroviral Gag proteins

    Directory of Open Access Journals (Sweden)

    Robert Alfred Dick

    2014-04-01

    Full Text Available Assembly of an infectious retroviral particle relies on multimerization of the Gag polyprotein at the inner leaflet of the plasma membrane. The three domains of Gag common to all retroviruses-- MA, CA, and NC-- provide the signals for membrane binding, assembly, and viral RNA packaging, respectively. These signals do not function independently of one another. For example, Gag multimerization enhances membrane binding and is more efficient when NC is interacting with RNA. MA binding to the plasma membrane is governed by several principles, including electrostatics, recognition of specific lipid head groups, hydrophobic interactions, and membrane order. HIV-1 uses many of these principles while Rous sarcoma virus (RSV appears to use fewer. This review describes the principles that govern Gag interactions with membranes, focusing on RSV and HIV-1 Gag. The review also defines lipid and membrane behavior, and discusses the complexities in determining how lipid and membrane behavior impact Gag membrane binding.

  16. Promoting chlamydia screening with posters and leaflets in general practice--a qualitative study.

    Science.gov (United States)

    Freeman, Elaine; Howell-Jones, Rebecca; Oliver, Isabel; Randall, Sarah; Ford-Young, William; Beckwith, Philippa; McNulty, Cliodna

    2009-10-12

    General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. The NCSP should consider developing a range of more discrete but eye

  17. Promoting chlamydia screening with posters and leaflets in general practice - a qualitative study

    Science.gov (United States)

    Freeman, Elaine; Howell-Jones, Rebecca; Oliver, Isabel; Randall, Sarah; Ford-Young, William; Beckwith, Philippa; McNulty, Cliodna

    2009-01-01

    Background General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Methods Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Results Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. Conclusion The NCSP should consider developing

  18. Promoting chlamydia screening with posters and leaflets in general practice - a qualitative study

    Directory of Open Access Journals (Sweden)

    Ford-Young William

    2009-10-01

    Full Text Available Abstract Background General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP, have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Methods Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Results Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. Conclusion The NCSP

  19. Serotonin receptor 2B signaling with interstitial cell activation and leaflet remodeling in degenerative mitral regurgitation.

    Science.gov (United States)

    Driesbaugh, Kathryn H; Branchetti, Emanuela; Grau, Juan B; Keeney, Samuel J; Glass, Kimberly; Oyama, Mark A; Rioux, Nancy; Ayoub, Salma; Sacks, Michael S; Quackenbush, John; Levy, Robert J; Ferrari, Giovanni

    2018-02-01

    Mitral valve interstitial cells (MVIC) play an important role in the pathogenesis of degenerative mitral regurgitation (MR) due to mitral valve prolapse (MVP). Numerous clinical studies have observed serotonin (5HT) dysregulation in cardiac valvulopathies; however, the impact of 5HT-mediated signaling on MVIC activation and leaflet remodeling in MVP have been investigated to a limited extent. Here we test the hypothesis that 5HT receptors (5HTRs) signaling contributes to MVP pathophysiology. Diseased human MV leaflets were obtained during cardiac surgery for MVP; normal MV leaflets were obtained from heart transplants. MV RNA was used for microarray analysis of MVP patients versus control, highlighting genes that indicate the involvement of 5HTR pathways and extracellular matrix remodeling in MVP. Human MV leaflets were also studied in vitro and ex vivo with biomechanical testing to assess remodeling in the presence of a 5HTR2B antagonist (LY272015). MVP leaflets from Cavalier King Charles Spaniels were used as a naturally acquired in vivo model of MVP. These canine MVP leaflets (N=5/group) showed 5HTR2B upregulation. This study also utilized CB57.1ML/6 mice in order to determine the effect of Angiotensin II infusion on MV remodeling. Histological analysis showed that MV thickening due to chronic Angiotensin II remodeling is mitigated by a 5HTR2B antagonist (LY272015) but not by 5HTR2A inhibitors. In humans, MVP is associated with an upregulation in 5HTR2B expression and increased 5HT receptor signaling in the leaflets. Antagonism of 5HTR2B mitigates MVIC activation in vitro and MV remodeling in vivo. These observations support the view that 5HTR signaling is involved not only in previously reported 5HT-related valvulopathies, but it is also involved in the pathological remodeling of MVP. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Constructing osteoarthritis through discourse – a qualitative analysis of six patient information leaflets on osteoarthritis

    Directory of Open Access Journals (Sweden)

    Ong Bie

    2007-04-01

    Full Text Available Abstract Background Health service policy in the United Kingdom emphasises the importance of self-care by patients with chronic conditions. Written information for patients about their condition is seen as an important aid to help patients look after themselves. From a discourse analysis perspective written texts such as patient information leaflets do not simply describe the reality of a medical condition and its management but by drawing on some sorts of knowledge and evidence rather than others help construct the reality of that condition. This study explored patient information leaflets on osteoarthritis (OA to see how OA was constructed and to consider the implications for self-care. Methods Systematic and repeated readings of six patient information leaflets on osteoarthritis to look for similarities and differences across leaflets, contradictions within leaflets and the resources called on to make claims about the nature of OA and its management. Results Biomedical discourse of OA as a joint disease dominated. Only one leaflet included an illness discourse albeit limited, and was also the only one to feature patient experiences of living with OA. The leaflets had different views on the causes of OA including the role of lifestyle and ageing. Most emphasised patient responsibility for preventing the progression of OA. Advice about changing behaviour such as diet and exercise was not grounded in lived experience. There were inconsistent messages about using painkillers, exercise and the need to involve professionals when making changes to lifestyle. Conclusion The nature of the discourse impacted on how OA and the respective roles of patients and professionals were depicted. Limited discourse on illness meant that the complexity of living with OA and its consequences was underestimated. Written information needs to shift from joint biology to helping patients live with osteoarthritis. Written information should incorporate patient

  1. The usefulness and scientific accuracy of private sector Arabic language patient drug information leaflets.

    Science.gov (United States)

    Sukkari, Sana R; Al Humaidan, Abdullah S; Sasich, Larry D

    2012-07-01

    Inadequate access to useful scientifically accurate patient information is a major cause of the inappropriate use of drugs resulting in serious personal injury and related costs to the health care system. The definition of useful scientifically accurate patient information for prescription drugs was accepted by the US Secretary of the Department of Health and Human Services in 1996 as that derived from or consistent with the US FDA approved professional product label for a drug. Previous quality content studies found that English language patient drug information leaflets distributed by US pharmacies failed to meet minimum criteria defining useful and scientifically accurate information. Evaluation forms containing the explicit elements that define useful scientifically accurate information for three drugs with known serious adverse drug reactions were created based on the current US FDA approved professional product labels. The Arabic language patient drug information leaflets for celecoxib, paroxetine, and lamotrigine were obtained locally and evaluated using a methodology similar to that used in previous quality content patient drug information studies in the US. The Arabic leaflets failed to meet the definition of useful scientifically accurate information. The celecoxib leaflet contained 30% of the required information and the paroxetine and lamotrigine leaflets contained 24% and 20%, respectively. There are several limitations to this study. The Arabic leaflets from only one commercial North American vendor were evaluated and the evaluation included a limited number of drugs. A larger study is necessary to be able to generalize these results. The study results are consistent with those of previous quality content studies of commercially available English patient drug information leaflets. The results have important implications for patients as access to a reliable source of drug information may prevent harm or limit the suffering from serious adverse drug

  2. Practitioner and lay perspectives of the service provision of nutrition information leaflets in primary care.

    Science.gov (United States)

    McClinchy, Jane; Dickinson, Angela; Barron, Duncan; Thomas, Hilary

    2011-12-01

    In primary care, leaflets are often used to communicate health information. Increasingly, primary healthcare practitioners need to provide dietary advice. There is limited research exploring how nutrition information leaflets are used in primary care. The present study explored practitioner and lay experiences with respect to providing and receiving nutrition information in primary care, focusing in particular on the use of leaflets for nutrition information. A qualitative design was used incorporating focus groups with 57 practitioners based at seven general practitioner practices and a purposive sample of 30 lay participants attending six Consumer Health Organisations within one primary care trust. Focus groups were taped and transcribed verbatim and data were analysed thematically, assisted by computer software n6® (QSR International Pty Ltd, Melbourne, Australia). Practitioners discussed barriers to giving nutritional advice, access to leaflets, lay receptiveness to advice and their perceptions about the value of leaflets to lay people. Food was not considered in terms of its nutritional components by lay participants and the need for nutritional information was not perceived to be relevant until they had received a medical diagnosis. Lay participants discussed the importance of receiving nutritional advice relating to their medical diagnosis and the altered status of written information that was delivered personally. Practitioner and lay groups suggested improvements to ensure that nutritional advice be supported by relevant and appropriate written information. This research has underlined the continuing importance of nutrition information leaflets and concludes that there is particular value in involving lay participants in the development of nutrition information leaflets. © 2011 The Authors. Journal of Human Nutrition and Dietetics © 2011 The British Dietetic Association Ltd.

  3. Carbocyclic Carbohydrate Mimics as Potential Glycosidase Inhibitors

    DEFF Research Database (Denmark)

    Fanefjord, Mette; Lundt, Inge

    It has been proven that aminocyclopentanols having the aminogroup adjacent to a carbon sidechain could be potential anomer-selective glycosidase inhibitors [1]. A successful pathway for synthesising mimics to L-carbohydrates 2, by introducing nitrogen to the C6 position in compound 1, has been...... developed in our group. A similar strategy has been used for synthesising mimics of D-carbohydrates. The α,β-unsaturated lactone 3 was cyclised to compound 4 which was further transformed into 5. The nitrogen functionality in compound 7 is introduced by an Overman rearrangement of 6 and the hydroxyl...... functionalities was introduced by either epoxidation or dihydroxylation of 7. Finally, reduction of the lactone ring led to the sugar mimics 8. The synthesis of several isomers of 8 will be presented. [1] a) Kleban, M. ; Hilgers, P. ; Greul, J.N. ; Kugler, R.D. ; Li, J. ; Picasso, S. ; Vogel, P. ; Jäger, V. Chem...

  4. Retrieval of a leaflet escaped in a Tri-technologies bileaflet mechanical prosthetic valve.

    Science.gov (United States)

    Cianciulli, Tomás F; Lax, Jorge A; Saccheri, María C; Guidoin, Robert; Salvado, César M; Fernández, Adrián J; Prezioso, Horacio A

    2008-01-01

    The escape of the prosthetic heart valve disc is one of the causes of prosthetic dysfunction that requires emergency surgery. The removal of the embolized disc should be carried out because of the risk of a progressive extrusion on the aortic wall. Several imaging techniques can be used for the detection of the missing disc localization. In this report we describe a 32-year-old man who underwent mitral valve replacement with a Tri-technologies bileaflet valve three years ago, and was admitted in cardiogenic shock. Transesophageal echocardiography showed acute-onset massive mitral regurgitation. The patient underwent emergency replacement of the prosthetic valve. Only one of the two leaflets remained in the removed prosthetic valve. The missing leaflet could not be found within the cardiac cavity. The abdominal fluoroscopic study and plain radiography were unable to detect the escaped leaflet. The abdominal computed tomography scan and the ultrasound showed the escaped leaflet in the terminal portion of the aortic bifurcation. To retrieve the embolized disc laparotomy and aortotomy were performed three months later. The escaped leaflet shows a fracture of one of the pivot systems caused by structural failure. This kind of failure mode is usually the result of high stress concentration.

  5. Creation New Patient Information Leaflets with Diabetes by Pharmacists and Assesment Conducted by Patients.

    Science.gov (United States)

    Arai, Motoharu; Maeda, Kazuto; Satoh, Hiroki; Miki, Akiko; Sawada, Yasufumi

    2016-10-01

    We created a draft of new patient information leaflets to ensure patients' proper use of drugs and to highlight safety issues and improvement plans extracted and proposed by small group discussions (SGD) with pharmacists. A total of 3 SGDs (participants: 15 pharmacists) were conducted with the aim of improving patient information leaflets for oral diabetes drugs. First, the disadvantages and advantages of the current instructions as well as requests for ideal patient information leaflets were obtained from participants. Conventional patient information leaflets that could be improved were useful to understand drug efficacy, adverse effects, and instructions for daily consumption of medicines, and to encourage patients to re-check drugs at home and inform their family of the measures to be taken in the case of adverse effects from the standpoint of patients. However, some disadvantages arose; for example, the instructions were difficult to read because of small lettering and illustrations and too much text. It was not tailored for individual patients, and descriptions about serious adverse effects caused patients much anxiety. Therefore, we have created a draft of new patient information leaflets with diabetes that are simpler and easier to understand and use concise wording and illustrations that are impactful.

  6. MIMIC Methods for Assessing Differential Item Functioning in Polytomous Items

    Science.gov (United States)

    Wang, Wen-Chung; Shih, Ching-Lin

    2010-01-01

    Three multiple indicators-multiple causes (MIMIC) methods, namely, the standard MIMIC method (M-ST), the MIMIC method with scale purification (M-SP), and the MIMIC method with a pure anchor (M-PA), were developed to assess differential item functioning (DIF) in polytomous items. In a series of simulations, it appeared that all three methods…

  7. Explosives mimic for testing, training, and monitoring

    Science.gov (United States)

    Reynolds, John G.; Durban, Matthew M.; Gash, Alexander E.; Grapes, Michael D.; Kelley, Ryan S.; Sullivan, Kyle T.

    2018-02-13

    Additive Manufacturing (AM) is used to make mimics for explosives. The process uses mixtures of explosives and matrices commonly used in AM. The explosives are formulated into a mixture with the matrix and printed using AM techniques and equipment. The explosive concentrations are kept less than 10% by wt. of the mixture to conform to requirements of shipping and handling.

  8. Hybrid mimics and hybrid vigor in Arabidopsis

    Science.gov (United States)

    Wang, Li; Greaves, Ian K.; Groszmann, Michael; Wu, Li Min; Dennis, Elizabeth S.; Peacock, W. James

    2015-01-01

    F1 hybrids can outperform their parents in yield and vegetative biomass, features of hybrid vigor that form the basis of the hybrid seed industry. The yield advantage of the F1 is lost in the F2 and subsequent generations. In Arabidopsis, from F2 plants that have a F1-like phenotype, we have by recurrent selection produced pure breeding F5/F6 lines, hybrid mimics, in which the characteristics of the F1 hybrid are stabilized. These hybrid mimic lines, like the F1 hybrid, have larger leaves than the parent plant, and the leaves have increased photosynthetic cell numbers, and in some lines, increased size of cells, suggesting an increased supply of photosynthate. A comparison of the differentially expressed genes in the F1 hybrid with those of eight hybrid mimic lines identified metabolic pathways altered in both; these pathways include down-regulation of defense response pathways and altered abiotic response pathways. F6 hybrid mimic lines are mostly homozygous at each locus in the genome and yet retain the large F1-like phenotype. Many alleles in the F6 plants, when they are homozygous, have expression levels different to the level in the parent. We consider this altered expression to be a consequence of transregulation of genes from one parent by genes from the other parent. Transregulation could also arise from epigenetic modifications in the F1. The pure breeding hybrid mimics have been valuable in probing the mechanisms of hybrid vigor and may also prove to be useful hybrid vigor equivalents in agriculture. PMID:26283378

  9. Comprehensive 4-stage categorization of bicuspid aortic valve leaflet morphology by cardiac MRI in 386 patients.

    Science.gov (United States)

    Murphy, I G; Collins, J; Powell, A; Markl, M; McCarthy, P; Malaisrie, S C; Carr, J C; Barker, A J

    2017-08-01

    Bicuspid aortic valve (BAV) disease is heterogeneous and related to valve dysfunction and aortopathy. Appropriate follow up and surveillance of patients with BAV may depend on correct phenotypic categorization. There are multiple classification schemes, however a need exists to comprehensively capture commissure fusion, leaflet asymmetry, and valve orifice orientation. Our aim was to develop a BAV classification scheme for use at MRI to ascertain the frequency of different phenotypes and the consistency of BAV classification. The BAV classification scheme builds on the Sievers surgical BAV classification, adding valve orifice orientation, partial leaflet fusion and leaflet asymmetry. A single observer successfully applied this classification to 386 of 398 Cardiac MRI studies. Repeatability of categorization was ascertained with intraobserver and interobserver kappa scores. Sensitivity and specificity of MRI findings was determined from operative reports, where available. Fusion of the right and left leaflets accounted for over half of all cases. Partial leaflet fusion was seen in 46% of patients. Good interobserver agreement was seen for orientation of the valve opening (κ = 0.90), type (κ = 0.72) and presence of partial fusion (κ = 0.83, p < 0.0001). Retrospective review of operative notes showed sensitivity and specificity for orientation (90, 93%) and for Sievers type (73, 87%). The proposed BAV classification schema was assessed by MRI for its reliability to classify valve morphology in addition to illustrating the wide heterogeneity of leaflet size, orifice orientation, and commissural fusion. The classification may be helpful in further understanding the relationship between valve morphology, flow derangement and aortopathy.

  10. Subclinical leaflet thickening and stent frame geometry in self-expanding transcatheter heart valves

    DEFF Research Database (Denmark)

    Fuchs, Andreas; De Backer, Ole; Brooks, Matthew

    2017-01-01

    AIMS: This study aimed to assess the potential relationship between subclinical leaflet thickening and stent frame geometry in patients who underwent aortic valve replacement with a self-expanding transcatheter heart valve (THV). METHODS AND RESULTS: Seventy-five patients with a self-expanding THV....... CONCLUSIONS: Regional THV stent frame underexpansion is associated with an increased risk of leaflet thickening. Post-dilatation of self-expanding THV as well as a supra-annular valve position seem to reduce the occurrence of this phenomenon....

  11. Catheter Entrapment During Posterior Mitral Leaflet Pushing Maneuver for MitraClip Implantation.

    Science.gov (United States)

    Castrodeza, Javier; Amat-Santos, Ignacio J; Tobar, Javier; Varela-Falcón, Luis H

    2016-06-01

    MitraClip (Abbott Vascular) therapy has been reported to be an effective procedure for mitral regurgitation, especially in high-risk patients. Recently, the novel pushing maneuver technique has been described for approaching restricted and short posterior leaflets with a pigtail catheter in order to facilitate grasping of the clip. However, complications or unexpected situations may occur. We report the case of an 84-year-old patient who underwent MitraClip implantation wherein the pushing maneuver was complicated by the clip accidentally gripping the pigtail catheter along with the two leaflets.

  12. Molecular aspects of GAPR-1 interactions with biological and model membranes

    NARCIS (Netherlands)

    van Galen, J.

    2008-01-01

    Golgi-Associated Plant Pathogenesis-Related protein 1 (GAPR-1) is a mammalian protein that belongs to the superfamily of plant pathogenesis related proteins group 1 (PR-1). It is a peripheral membrane protein that strongly associates with the cytosolic leaflet of Golgi membranes and is enriched in

  13. Histologic Mimics of Basal Cell Carcinoma.

    Science.gov (United States)

    Stanoszek, Lauren M; Wang, Grace Y; Harms, Paul W

    2017-11-01

    - Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment. - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction. - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis. - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

  14. Package leaflets of the most consumed medicines in Portugal: safety and regulatory compliance issues. A descriptive study

    Directory of Open Access Journals (Sweden)

    Carla Pires

    Full Text Available CONTEXT AND OBJECTIVES: Package leaflets are necessary for safe use of medicines. The aims of the present study were: 1 to assess the compliance between the content of the package leaflets and the specifications of the pharmaceutical regulations; and 2 to identify potential safety issues for patients. DESIGN AND SETTING: Qualitative descriptive study, involving all the package leaflets of branded medicines from the three most consumed therapeutic groups in Portugal, analyzed in the Department of Pharmacoepidemiology, School of Pharmacy, University of Lisbon. METHODS: A checklist validated through an expert consensus process was used to gather the data. The content of each package leaflet in the sample was classified as compliant or non-compliant with compulsory regulatory issues (i.e. stated dosage and descriptions of adverse reactions and optional regulatory issues (i.e. adverse reaction frequency, symptoms and procedures in cases of overdose. RESULTS: A total of 651 package leaflets were identified. Overall, the package leaflets were found to be compliant with the compulsory regulatory issues. However, the optional regulatory issues were only addressed in around half of the sample of package leaflets, which made it possible to identify some situations of potentially compromised drug safety. CONCLUSION: Ideally, the methodologies for package leaflet approval should be reviewed and optimized as a way of ensuring the inclusion of the minimum essential information for safe use of medicines.

  15. Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye.

    Science.gov (United States)

    Barba-Bon, Andrea; Costero, Ana M; Gil, Salvador; Martínez-Máñez, Ramón; Sancenón, Félix

    2014-11-21

    A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared. Probe P4 contains three reactive sites; i.e. (i) a nucleophilic phenol group able to undergo phosphorylation with nerve gases, (ii) a carbonyl group as a reactive site for cyanide; and (iii) a triisopropylsilyl (TIPS) protecting group that is known to react with fluoride. The reaction of P4 with DCNP in acetonitrile resulted in both the phosphorylation of the phenoxy group and the release of cyanide, which was able to react with the carbonyl group of P4 to produce a colour modulation from pink to orange. In contrast, phosphorylation of P4 with DFP in acetonitrile released fluoride that hydrolysed the TIPS group in P4 to yield a colour change from pink to blue. Probe P4 was able to discriminate between DFP and DCNP with remarkable sensitivity; limits of detection of 0.36 and 0.40 ppm for DCNP and DFP, respectively, were calculated. Besides, no interference from other organophosphorous derivatives or with presence of acid was observed. The sensing behaviour of P4 was also retained when incorporated into silica gel plates or onto polyethylene oxide membranes, which allowed the development of simple test strips for the colorimetric detection of DCNP and DFP in the vapour phase. P4 is the first probe capable of colorimetrically differentiating between a Tabun mimic (DCNP) and a Sarin and Soman mimic (DFP).

  16. Tetralogy of Fallot with restrictive ventricular septal defect by accessory tricuspid leaflet tissue

    OpenAIRE

    Mahipat Raj Soni; Deepak A. Bohara; Ajay U. Mahajan; Pratap J. Nathani

    2012-01-01

    In tetralogy of Fallot septal defect is usually large because of malalignment of outlet septum, restrictive defect has been reported rarely. We present a case of tetralogy of Fallot with accessory tricuspid leaflet tissue restricting ventricular septal defect. The report includes echocardiographic and catheter images of this rare presentation of tetralogy of Fallot.

  17. Morphological and mechanical properties of the posterior leaflet chordae tendineae in the mitral valve

    NARCIS (Netherlands)

    Lodder, J.; Verkerke, Gijsbertus Jacob; Delemarre, B.J.M.; Dodou, D.

    2016-01-01

    A number of studies have investigated the morphological and mechanical properties of the chordae tendineae of the mitral valve, providing comparisons between basal, marginal, and strut chordae and between chordae at the anterior and posterior leaflets. This study contributes to the literature by

  18. Morphological and mechanical properties of the posterior leaflet chordae tendineae in the mitral valve

    NARCIS (Netherlands)

    Lodder, Joost; Verkerke, Gijsbertus J.; Delemarre, Ben J. M.; Dodou, Dimitra

    A number of studies have investigated the morphological and mechanical properties of the chordae tendineae of the mitral valve, providing comparisons between basal, marginal, and strut chordae and between chordae at the anterior and posterior leaflets. This study contributes to the literature by

  19. A study of the pulsatile flow and its interaction with rectangular leaflets

    Science.gov (United States)

    Ledesma, Rene; Zenit, Roberto; Pulos, Guillermo

    2009-11-01

    To avoid the complexity and limited understanding of the 3D pulsatile flow field through heart valves, a cardiac-like flow circuit and a test channel were designed to study the behavior of bidimensional leaflets made of hyperelastic materials. We study a simple 2D arrangement to understand the basic physics of the flow-leaflet interaction. Creating a periodic pressure gradient, measurements of leaflet deflection were obtained for different flow conditions, geometries and materials. Using PIV and Phase Locking techniques, we have obtained the leaflet motion and the time-dependent flow velocity fields. The results show that two dimensionless parameters determine the performance of a simple bi-dimensional valve, in accordance with the flow conditions applied: π1=f(sw)^1/2(E/ρ)^1/2 and π2=V/(2slw), where f is the pulsation frequency, V is the stroke volume, s, w and l are the dimensions on the leaftlet and E and ρ are the elastic modulus and density of the material, respectively. Furthermore, we have identified the conditions for which the fluid stresses can be minimized. With these results we propose a new set of parameters to improve the performance of prosthetic heart valves and, in consequence, to reduce blood damage.

  20. Wikis to facilitate patient participation in developing information leaflets: first experiences

    NARCIS (Netherlands)

    Belt, T.H. van de; Faber, M.J.; Knijnenburg, J.M.; Duijnhoven, N.T.L. van; Nelen, W.L.D.M.; Kremer, J.A.M.

    2014-01-01

    OBJECTIVE: Although patients have gained a wealth of experienced based knowledge they are usually not involved in the development of patient information. We sought to determine the technical feasibility of wikis in generating dynamic patient information leaflets with participation from patients and

  1. Role of LLD, a new locus for leaflet/pinna morphogenesis in Pisum ...

    Indian Academy of Sciences (India)

    Opposite pinnae of rachis nodes often formed fused incompletely developed leaflets. The lld mutation was observed to abort pinna development at almost all morphogenetic stages. The lld mutation demonstrated high penetrance and low expressivity. The phenotypes of lld plants in tl, tac, tl tac, tl af and tl af tac backgrounds ...

  2. The value of an information leaflet for patients having nuclear medicine investigations

    International Nuclear Information System (INIS)

    Ahmed, Susan Mohamed; Mohammed, Nada Yousif; Elhasseen, Amna Elnour

    2001-01-01

    This research aimed at design an information leaflet about nuclear medicine investigations usually done at the radiation and isotopes centre of Khartoum (RICK). The objectives are: to confirm lack of knowledge among patients attending hospital, to find out kind of information required and to improve service quality

  3. Initial results of combined anterior mitral leaflet extension and myectomy in patients with obstructive hypertrophic cardiomyopathy

    NARCIS (Netherlands)

    M.J.M. Kofflard (Marcel); L.A. van Herwerden (Lex); D.J. Waldstein; P.N. Ruygrok (Peter); H. Boersma (Eric); M.A. Taams (Meindert); F.J. ten Cate (Folkert)

    1996-01-01

    textabstractObjectives. The purpose of this study was to describe the clinical and functional results of combined anterior mitral leaflet extension and myectomy in patients with hypertrophic obstructive cardiomyopathy. Background. Septal myectomy is the most commonly performed surgical procedure in

  4. PERAN PENYULUHAN DENGAN MENGGUNAKAN LEAFLET TERHADAP PERUBAHAN PENGETAHUAN DAN SIKAP IBU BALITA GIZI KURANG

    Directory of Open Access Journals (Sweden)

    Salimar Salimar

    2012-11-01

    Full Text Available ABSTRACT Background: Nutrition extension is one of the approach efforts to increase knowledge in order to gain good behavior. Through this extension, we expected mother of under five years child would understood and comprehended as well as had a willing and could implement what she was advised, so that she could took care of under five years child with underweight nutrition to become better nutrition. Purpose: To study about the changing of knowledge and attitude of mother with undernourished of under-five years child after got intervention of extension for 3 months of between two groups got leaflet and didn't get leaflet. Methods: This applied research applied quasi experiment research design. Population is mother having undernourished of under five years child and mother age ranges from 18-45 years, totally 176 samples. Group of treatment got extension package for 3 months and given leaflet to be studied in house. Group of control was participated extension package for 3 months, but they weren’t given leaflet, and leaflet was given after this research completed. Results: After followed extension package during 3 months, samples showed improvement for mother’s knowledge as 11.4% in group of treatment and 10.4% in group of control. Statististically by using Chi quadrate test, there were a significance difference (p=0.00 for mother’s knowledge before and after research in both group of research. There is a changing for mother’s attitude in group of treatment as 28.1% and 16.1% in group of control. By using chi square test we found significance difference (p=0,021 on mother’s attitude in group of treatment before and after extension for 3 month, while in group of control there was no significance difference ( p=0.187. Conclusions: Leaflet is one of the supporting facilities which applicable to change knowledge and attitude of mother. There is no difference of mother’s motivation in participating this research. The role of husband and

  5. Home delivery of medication - the role of a patient information leaflet on maximising service uptake.

    Science.gov (United States)

    Watson, L; Ahmed, N; Mccall, H; Minton, J; Benn, P; Edwards, S; Waters, L

    2014-12-01

    There are currently over 30,000 HIV-positive individuals in London and over 25,000 on anti-retroviral therapy. In 2009/2010, this equated to £170m spent by London's NHS on anti-retroviral drugs. Ways employed to reduce this cost include standardising the drugs patients are on and delivering medication to patients at home. Home delivery (HD) medication is exempt from value-added tax. The savings made from 10 patients using the home delivery service would free up resources to provide anti-retroviral therapy to one further patient. Studies have shown that concerns surrounding potential breaches of confidentiality are a potential barrier to some people using the home delivery service. In order to challenge these concerns, a leaflet was devised highlighting the major benefits to both the patient and the NHS of home delivery and addressing concerns over confidentiality. The leaflet was handed out to patients at the Mortimer Market Centre who were currently on anti-retroviral medication but not on home delivery. They were asked to complete a survey on their views of the service before and after reading the leaflet, whether they had been previously aware of the service and whether their concerns had been addressed. Some 79% felt that the patient information leaflet addressed all of their concerns, and it helped 11% decide whether to consider using home delivery. However, as more patients were opposed to the service after reading the patient information leaflet than those considering it, more work needs to be done to explore patients' concerns and other factors influencing home delivery service uptake. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  6. Posterior leaflet preservation during mitral valve replacement for rheumatic mitral stenosis.

    Science.gov (United States)

    Djukić, P L; Obrenović-Kirćanski, B B; Vranes, M R; Kocica, M J; Mikić, A Dj; Velinović, M M; Kacar, S M; Kovacević, N S; Parapid, B J

    2006-01-01

    Mitral valve replacement with posterior leaflet preservation was shown beneficial for postoperative left vetricular (LV) performance in patients with mitral regurgitation. Some authors find it beneficial even for the long term LV function. We investigated a long term effect of this technique in patients with rheumatic mitral stenosis. We studied 20 patents with mitral valve replacement due to rheumatic mitral stenosis, in the period from January 1988 to December 1989. In group A (10 patients) both leaflets and coresponding chordal excision was performed, while in group B (10 patients) the posterior leaflet was preserved. In all patients a Carbomedics valve was inserted. We compared clinical pre and postoperative status, as well as hemodynamic characteristics of the valve and left ventricle in both groups. Control echocardiographyc analysis included: maximal (PG) and mean (MG) gradients; effective valve area (AREA); telediastolic (TDV) and telesystolic (TSV) LV volume; stroke volume (SV); ejection fraction (EF); fractional shortening (FS) and segmental LV motion. The mean size of inserted valve was 26.6 in group A and 27.2 in group B. Hemodynamic data: PG (10.12 vs 11.1); MG (3.57 vs 3.87); AREA (2.35 vs 2.30); TDV 126.0 vs 114.5); TSV (42.2 vs 36.62); SV (83.7 vs 77.75); EF (63.66 vs 67.12); FS (32.66 vs 38.25). Diaphragmal segmental hypokinesis was evident in one patient from group A and in two patients from group B. In patients with rheumatic stenosis, posterior leaflet preservation did not have increased beneficial effect on left ventricular performance during long-term follow-up. An adequate posterior leaflet preservation does not change hemodynamic valvular characteristics even after long-term follow-up.

  7. Stereocontrolled Synthesis of Methyl Silanediol Peptide Mimics

    DEFF Research Database (Denmark)

    Nielsen, Lone; Lindsay, Karl; Faber, Jesper

    2007-01-01

     The treatment of chiral sulfinimines with (methyldiphenylsilyl)lithium gives R-(methyldiphenylsilyl)-sulfinamides with excellent diastereoselectivity, and in good yield. The presence of α-protons on the imines is also well tolerated. The sulfinamide auxiliary is easily removed via treatment with...... corresponding bis-TMS siloxane via protection with TMSCl, and converted back to the desired silanediol via hydrolysis with aqueous KOH. Efforts to apply this approach to biologically relevant silanediol peptide mimics, with a view to protease inhibition, are described....

  8. Two interdependent mechanisms of antimicrobial activity allow for efficient killing in nylon-3-based polymeric mimics of innate immunity peptides.

    Science.gov (United States)

    Lee, Michelle W; Chakraborty, Saswata; Schmidt, Nathan W; Murgai, Rajan; Gellman, Samuel H; Wong, Gerard C L

    2014-09-01

    Novel synthetic mimics of antimicrobial peptides have been developed to exhibit structural properties and antimicrobial activity similar to those of natural antimicrobial peptides (AMPs) of the innate immune system. These molecules have a number of potential advantages over conventional antibiotics, including reduced bacterial resistance, cost-effective preparation, and customizable designs. In this study, we investigate a family of nylon-3 polymer-based antimicrobials. By combining vesicle dye leakage, bacterial permeation, and bactericidal assays with small-angle X-ray scattering (SAXS), we find that these polymers are capable of two interdependent mechanisms of action: permeation of bacterial membranes and binding to intracellular targets such as DNA, with the latter necessarily dependent on the former. We systemically examine polymer-induced membrane deformation modes across a range of lipid compositions that mimic both bacteria and mammalian cell membranes. The results show that the polymers' ability to generate negative Gaussian curvature (NGC), a topological requirement for membrane permeation and cellular entry, in model Escherichia coli membranes correlates with their ability to permeate membranes without complete membrane disruption and kill E. coli cells. Our findings suggest that these polymers operate with a concentration-dependent mechanism of action: at low concentrations permeation and DNA binding occur without membrane disruption, while at high concentrations complete disruption of the membrane occurs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Supra-annular Valve-in-Valve implantation reduces blood stasis on the transcatheter aortic valve leaflets.

    Science.gov (United States)

    Vahidkhah, Koohyar; Azadani, Ali N

    2017-06-14

    Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and Valve-in-Valve (ViV) procedures has been increasingly recognized. This study aimed to investigate the effect of positioning of the transcatheter aortic valve (TAV) in ViV setting on the flow dynamics aspect of post-ViV thrombosis by quantifying the blood stasis in the intra-annular and supra-annular settings. To that end, two idealized computational models, representing ViV intra-annular and supra-annular positioning of a TAV were developed in a patient-specific geometry. Three-dimensional flow fields were then obtained via fluid-solid interaction modeling to study the difference in blood residence time (BRT) on the TAV leaflets in the two settings. At the end of diastole, a strip of high BRT (⩾1.2s) region was observed on the TAV leaflets in the ViV intra-annular positioning at the fixed boundary where the leaflets are attached to the frame. Such a high BRT region was absent on the TAV leaflets in the supra-annular positioning. The maximum value of BRT on the surface of non-, right, and left coronary leaflets of the TAV in the supra-annular positioning were 53%, 11%, and 27% smaller compared to the intra-annular positioning, respectively. It was concluded that the geometric confinement of TAV by the leaflets of the failed bioprosthetic valve in ViV intra-annular positioning increases the BRT on the leaflets and may act as a permissive factor in valvular thrombosis. The absence of such a geometric confinement in the ViV supra-annular positioning leads to smaller BRT and subsequently less likelihood of leaflet thrombosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Anionic lipids and the maintenance of membrane electrostatics in eukaryotes.

    Science.gov (United States)

    Platre, Matthieu Pierre; Jaillais, Yvon

    2017-02-01

    A wide range of signaling processes occurs at the cell surface through the reversible association of proteins from the cytosol to the plasma membrane. Some low abundant lipids are enriched at the membrane of specific compartments and thereby contribute to the identity of cell organelles by acting as biochemical landmarks. Lipids also influence membrane biophysical properties, which emerge as an important feature in specifying cellular territories. Such parameters are crucial for signal transduction and include lipid packing, membrane curvature and electrostatics. In particular, membrane electrostatics specifies the identity of the plasma membrane inner leaflet. Membrane surface charges are carried by anionic phospholipids, however the exact nature of the lipid(s) that powers the plasma membrane electrostatic field varies among eukaryotes and has been hotly debated during the last decade. Herein, we discuss the role of anionic lipids in setting up plasma membrane electrostatics and we compare similarities and differences that were found in different eukaryotic cells.

  11. DNA mimic proteins: functions, structures, and bioinformatic analysis.

    Science.gov (United States)

    Wang, Hao-Ching; Ho, Chun-Han; Hsu, Kai-Cheng; Yang, Jinn-Moon; Wang, Andrew H-J

    2014-05-13

    DNA mimic proteins have DNA-like negative surface charge distributions, and they function by occupying the DNA binding sites of DNA binding proteins to prevent these sites from being accessed by DNA. DNA mimic proteins control the activities of a variety of DNA binding proteins and are involved in a wide range of cellular mechanisms such as chromatin assembly, DNA repair, transcription regulation, and gene recombination. However, the sequences and structures of DNA mimic proteins are diverse, making them difficult to predict by bioinformatic search. To date, only a few DNA mimic proteins have been reported. These DNA mimics were not found by searching for functional motifs in their sequences but were revealed only by structural analysis of their charge distribution. This review highlights the biological roles and structures of 16 reported DNA mimic proteins. We also discuss approaches that might be used to discover new DNA mimic proteins.

  12. The enigmatic fast leaflet rotation in Desmodium motorium: butterfly mimicry for defense?

    Science.gov (United States)

    Lev-Yadun, Simcha

    2013-06-01

    I propose that the enigmatic leaflet movements in elliptical circles every few minutes of the Indian telegraph (semaphore) plant Desmodium motorium ( = D. gyrans = Hedysarum gyrans = Codariocalyx motorius), which has intrigued scientists for centuries, is a new type of butterfly or general winged arthropod mimicry by this plant. Such leaflet movement may deceive a passing butterfly searching for an un-occupied site suitable to deposit its eggs, that the plant is already occupied. It may also attract insectivorous birds, reptiles or arthropods to the plant because it looks as if it is harboring a potential prey and while they patrol there, they can find insects or other invertebrates that indeed attack the plant. The possibility that diurnal mammalian herbivores may also be deterred by these movements should not be dismissed.

  13. The surface microstructure of cusps and leaflets in rabbit and mouse heart valves

    Directory of Open Access Journals (Sweden)

    Xia Ye

    2014-05-01

    Full Text Available In this investigation, scanning electron microscopy was used to characterize the microstructure on the surfaces of animal heart valve cusps/leaflets. The results showed that though these surfaces appear smooth to the naked eye, they are actually comprised of a double hierarchical structure consisting of a cobblestone-like microstructure and nano-cilia along with mastoids with a directional arrangement. Such nanostructures could play a very important role in the hemocompatibility characteristics of heart valves. On this basis, the model of the microstructure was constructed and theoretical analysis was used to obtain optimal geometric parameters for the rough surface of artificial valve cusps/leaflets. This model may help improve reconstructive techniques and it may be beneficial in the design and fabrication of valve substitutes or partial substitutes. Namely, the model may help ameliorate heart valve replacement surgery.

  14. Introduction to forest diseases -- revised edition. Pest leaflet No. FPL 54

    Energy Technology Data Exchange (ETDEWEB)

    Callan, B.E.

    1994-12-31

    This leaflet provides a basic introduction to forest pathology. It includes descriptions of the common types of forest diseases and their causes as well as an outline of modern principles of disease control and investigation. It describes fungus classes associated with tree diseases, fungus anatomy, and examples of diseases caused by fungi; viruses, bacteria, and mycoplasma-like organisms; diseases caused by dwarf mistletoe; and non-infectious agents of disease. A glossary is included.

  15. Septal Leaflet versus Chordal Detachment in Closure of Hard-To-Expose Ventricular Septal Defects.

    Science.gov (United States)

    Pourmoghadam, Kamal K; Boron, Agnieszka; Ruzmetov, Mark; Narasimhulu, Sukumar Suguna; Kube, Alicia; O'Brien, Michael C; DeCampli, William M

    2018-04-04

    Different techniques have been used for exposure of ventricular septal defect (VSD) margins when there is crowding of the VSD anatomy by tricuspid valve (TV) subvalvar apparatus. The aim of this study was to compare surgical outcomes, for the two techniques of TV leaflet detachment and the rarely described TV chordal detachment for hard-to-expose VSDs. Patients undergoing transatrial VSD repair were identified from our institutional database. Follow-up echocardiography and patient data were obtained from medical records. Between 1/2005-8/2016, 130 isolated conoventricular VSDs were repaired. Among these, 26patients had leaflet detachment, while 15 underwent chordal detachment, and 89 had regular VSD repair (reference group). There was no significant difference between the groups in age, weight, postoperative length-of-stay, genetic/syndromic abnormalities, time-to-extubation, and left and right ventricular systolic function. The cardiopulmonary bypass and cross-clamp time were significantly higher in leaflet detachment group, when compared with reference group (118+28vs102+32, p=0.02; and 73+20vs61+23, p=0.01, respectively). Echocardiographic follow-up were available for 87patients at a mean of 2.6years (1month-11years). Tricuspid regurgitation was rated as none or trivial in 66(76%), mild in 20(23%) and moderate in one reference group patient. There was no difference in presence of residual VSD, or degree of tricuspid regurgitation amongst the three groups. There was no reoperation for tricuspid regurgitation. Tricuspid valve leaflet and chordal detachment techniques provide equally viable and safe alternative to closure of hard-to-expose VSDs while maintaining appropriate TV function. Their use in our series did not lead to increased TV dysfunction at early-to-midterm echocardiographic assessment. Copyright © 2018. Published by Elsevier Inc.

  16. Role of Information Anxiety and Information Load on Processing of Prescription Drug Information Leaflets.

    Science.gov (United States)

    Bapat, Shweta S; Patel, Harshali K; Sansgiry, Sujit S

    2017-10-16

    In this study, we evaluate the role of information anxiety and information load on the intention to read information from prescription drug information leaflets (PILs). These PILs were developed based on the principals of information load and consumer information processing. This was an experimental prospective repeated measures study conducted in the United States where 360 (62% response rate) university students (>18 years old) participated. Participants were presented with a scenario followed by exposure to the three drug product information sources used to operationalize information load. The three sources were: (i) current practice; (ii) pre-existing one-page text only; and (iii) interventional one-page prototype PILs designed for the study. Information anxiety was measured as anxiety experienced by the individual when encountering information. The outcome variable of intention to read PILs was defined as the likelihood that the patient will read the information provided in the leaflets. A survey questionnaire was used to capture the data and the objectives were analyzed by performing a repeated measures MANOVA using SAS version 9.3. When compared to current practice and one-page text only leaflets, one-page PILs had significantly lower scores on information anxiety ( p information load ( p Information anxiety and information load significantly impacted intention to read ( p < 0.001). Newly developed PILs increased patient's intention to read and can help in improving the counseling services provided by pharmacists.

  17. Relief of mitral leaflet tethering following chronic myocardial infarction by chordal cutting diminishes left ventricular remodeling.

    Science.gov (United States)

    Messas, Emmanuel; Bel, Alain; Szymanski, Catherine; Cohen, Iris; Touchot, Bernard; Handschumacher, Mark D; Desnos, Michel; Carpentier, Alain; Menasché, Philippe; Hagège, Albert A; Levine, Robert A

    2010-11-01

    one of the key targets in treating mitral regurgitation (MR) is reducing the otherwise progressive left ventricular (LV) remodeling that exacerbates MR and conveys adverse prognosis. We have previously demonstrated that severing 2 second-order chordae to the anterior mitral leaflet relieves tethering and ischemic MR acutely. The purpose of this study was to test whether this technique reduces the progression of LV remodeling in the chronic ischemic MR setting. a posterolateral MI was created in 18 sheep by obtuse marginal branch ligation. After chronic remodeling and MR development at 3 months, 6 sheep were randomized to sham surgery (control group) and 12 to second-order chordal cutting (6 each to anterior leaflet [AntL] and bileaflet [BiL] chordal cutting, techniques that are in clinical application). At baseline, chronic infarction (3 months), and follow-up at a mean of 6.6 months post-myocardial infarction (MI) (euthanasia), we measured LV end-diastolic (EDV) and end-systolic volume (ESV), ejection fraction, wall motion score index, and posterior leaflet (PL) restriction angle relative to the annulus by 2D and 3D echocardiography. All measurements were comparable among groups at baseline and chronic MI. At euthanasia, AntL and BiL chordal cutting limited the progressive remodeling seen in controls. LVESV increased relative to chronic MI by 109±8.7% in controls versus 30.5±6.1% with chordal cutting (Pbenefits have the potential to improve clinical outcomes.

  18. PENGGUNAAN LEAFLET DALAM PENDIDIKAN GIZI DAN PENGARUHNYA TERHADAP TINGKAT PENGETAHUAN IBU

    Directory of Open Access Journals (Sweden)

    Susilowati Herman

    2012-11-01

    Full Text Available Selama ini pendidikan gizi umumnya belum memanfaatkan alat bantu pendidikan gizi secara optimal. Selain itu pesan-pesan pendidikan gizi terkadang belum dirancang dengan seksama, sesuai dengan kebutuhan sasaran. Tidak jarang dijumpai pesan yang terlalu banyak, umum atau tidak terarah. Penyampaian pesan-pesan pendidikan gizi yang dilakukan secara berulang dan disertai penggunaan alat bantu pendidikan yang dirancang dengan baik, dapat mempermudah sasaran pendidikan menangkap dan mengerti isi pesan pendidikan. Penelitian ini bertujuan menilai perubahan tingkat pengetahuan gizi sebagai hasil dari paket pendidikan gizi yang terarah dengan menggunakan alat bantu pendidikan berupa leaflet yana dibawa pulang oleh sasaran pendidikan. Sasaran pendidikan adalah ibu-ibu dari anak Balita penderita gizi buruk (KKP berat pengunjung Klinik Gizi, Puslitbang Gizi, Bogor. Kelompok pembanding adalah juga ibu-ibu dari anak Balita penderita gizi buruk pengunjung Klinik Gizi yang sama dan kepadanya juga diberikan pendidikan gizi dengan isi pesan sama, tetapi tidak diberi alat bantu pendidikan berupa leaflet. Hasil penelitian menunjukkan babwa perubahan tingkat pengetahuan gizi ibu-ibu yang diberi leaflet, lebih baik daripada pengetahuan gizi ibu-ibu kelompok pembanding.

  19. [EFFECT OF EDUCATIONAL LEAFLETS ON KNOWLEDGE AND ATTITUDE TO TUBERCULOSIS AMONG HOMELESS PERSONS IN TOKYO, JAPAN].

    Science.gov (United States)

    Kawatsu, Lisa; Uchimura, Kazuhiro; Watabe, Hiroyuki; Kaguraoka, Sumi; Kubota, Yuka; Sakakibara, Marie; Ishikawa, Nobukatsu

    2015-08-01

    Delay in seeking care is one of the critical issues in tuberculosis (TB) control among homeless persons in Japan. Yet knowledge of and attitude towards TB among homeless persons have remained unclear and limited efforts have been made to disseminate information related to TB among homeless persons. To evaluate the effect of TB leaflets, produced and distributed to homeless persons by a group of ex-homeless TB patients, and to understand what homeless persons know about TB. Self-administered questionnaire was conducted among homeless persons before and after distribution of the TB leaflets. Changes in the responses to each question were also subjected to principal component analysis to group questions into types according to response patterns and identify constructs of TB-related knowledge. Results of 88 participants were analyzed. TB knowledge score related to risks and symptoms significantly improved after the intervention (from 54.3% to 70.6%, p < 0.05), while knowledge on treatment cost did not. Two components were identified, namely, the "improvement in TB impression" and "improvement in TB knowledge". TB leaflets were effective in improving certain aspects of TB knowledge. However, its effect on knowledge regarding treatment cost, which may be crucial in improving delay, was limited and thus the messages need to be revised.

  20. Simulation of Blood flow in Different Configurations Design of Bi-leaflet Mechanical Heart Valve

    Science.gov (United States)

    Hafizah Mokhtar, N.; Abas, Aizat

    2018-05-01

    In this work, two different designs of artificial heart valve were devised and then compared by considering the thrombosis, wear and valve orifice to anatomical orifice ratio of each mechanical heart valve. These different design configurations of bi-leaflet mechanical heart valves model are created through the use of Computer-aided design (CAD) modelling and simulated using Computational fluid dynamic (CFD) software. Design 1 is based on existing conventional bi-leaflet valve and design 2 based on modified bi-leaflet respectively. The flow pattern, velocity, vorticity and stress analysis have been done to justify the best design. Based on results, both of the designs show a Doppler velocity index of less than the allowable standard of 2.2 which is safe to be used as replacement of the human heart valve. However, design 2 shows that it has a lower possibility of cavitation issue which will lead to lower thrombosis and provide good central flow area of blood as compared to design 1.

  1. Recent developments in skin mimic systems to predict transdermal permeation.

    Science.gov (United States)

    Waters, Laura J

    2015-01-01

    In recent years there has been a drive to create experimental techniques that can facilitate the accurate and precise prediction of transdermal permeation without the use of in vivo studies. This review considers why permeation data is essential, provides a brief summary as to how skin acts as a natural barrier to permeation and discusses why in vivo studies are undesirable. This is followed by an in-depth discussion on the extensive range of alternative methods that have been developed in recent years. All of the major 'skin mimic systems' are considered including: in vitro models using synthetic membranes, mathematical models including quantitative structure-permeability relationships (QSPRs), human skin equivalents and chromatographic based methods. All of these model based systems are ideally trying to achieve the same end-point, namely a reliable in vitro-in vivo correlation, i.e. matching non-in vivo obtained data with that from human clinical trials. It is only by achieving this aim, that any new method of obtaining permeation data can be acknowledged as a potential replacement for animal studies, for the determination of transdermal permeation. In this review, the relevance and potential applicability of the various models systems will also be discussed.

  2. Layer-by-layer cell membrane assembly

    Science.gov (United States)

    Matosevic, Sandro; Paegel, Brian M.

    2013-11-01

    Eukaryotic subcellular membrane systems, such as the nuclear envelope or endoplasmic reticulum, present a rich array of architecturally and compositionally complex supramolecular targets that are as yet inaccessible. Here we describe layer-by-layer phospholipid membrane assembly on microfluidic droplets, a route to structures with defined compositional asymmetry and lamellarity. Starting with phospholipid-stabilized water-in-oil droplets trapped in a static droplet array, lipid monolayer deposition proceeds as oil/water-phase boundaries pass over the droplets. Unilamellar vesicles assembled layer-by-layer support functional insertion both of purified and of in situ expressed membrane proteins. Synthesis and chemical probing of asymmetric unilamellar and double-bilayer vesicles demonstrate the programmability of both membrane lamellarity and lipid-leaflet composition during assembly. The immobilized vesicle arrays are a pragmatic experimental platform for biophysical studies of membranes and their associated proteins, particularly complexes that assemble and function in multilamellar contexts in vivo.

  3. Tricuspid leaflet resection in an open beating heart for the creation of a canine tricuspid regurgitation model.

    Science.gov (United States)

    Xie, Xu-jing; Liao, Sheng-jie; Wu, Yue-heng; Lu, Cong; Zhu, Ping; Fei, Hong-wen; Xiao, Xue-jun; Huang, Huan-lei

    2016-02-01

    Outcomes of tricuspid valve replacement are poor, partly due to right heart remodelling. The research on its underlying mechanisms is hampered by a lack of animal models of tricuspid regurgitation (TR). Our objective was to create a reproducible and clinically compatible TR animal model to study right heart remodelling caused by TR. Fourteen juvenile male Beagle dogs were divided randomly into an intervention group (n = 11) and a sham-operated control group (n = 3). The intervention group underwent thoracotomy and right atrial incision following superior and inferior vena caval occlusion. The anterior leaflet, together with the chordae, of the tricuspid valve was resected in eight dogs ('one leaflet' group), whereas both anterior and posterior leaflets, together with the chordae, were resected in three dogs ('two leaflets' group). The right atrium and chest were then closed. The control group underwent the same procedure, except leaflet resection. One dog from the 'two leaflets' group and one control dog were sacrificed and autopsy was performed at 12 months post-surgery. All dogs survived over the 1-year observation period postoperatively. TR grade IV occurred immediately postoperatively in the 'one leaflet' group, and TR grade IV plus in the 'two leaflets' group. The overall procedure lasted 30-40 min, and the mean time of vena caval occlusion was 87 ± 10 s. Central venous pressure increased from 6 ± 1.2 at baseline to 13 ± 1.7 mmHg (P heart remodelling. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  4. Exergames versus self-regulated exercises with instruction leaflets to improve adherence during geriatric rehabilitation: a randomized controlled trial

    OpenAIRE

    Oesch, Peter; Kool, Jan; Fernandez-Luque, Luis; Brox, Ellen; Evertsen, Gunn; Civit, Anton; Hilfiker, Roger; Bachmann, Stefan

    2017-01-01

    Background Improving mobility in elderly persons is a primary goal in geriatric rehabilitation. Self-regulated exercises with instruction leaflets are used to increase training volume but adherence is often low. Exergames may improve adherence. This study therefore compared exergames with self-regulated exercise using instruction leaflets. The primary outcome was adherence. Secondary outcomes were enjoyment, motivation and balance during walking. Methods Design: single center parallel group n...

  5. Exergames versus self-regulated exercises with instruction leaflets to improve adherence during geriatric rehabilitation: a randomized controlled trial.

    OpenAIRE

    Oesch, Peter; Kool, Jan; Fernandez-Luque, Luis; Brox, Ellen; Evertsen, Gunn; Civit, Anton; Hilfiker, Roger; Bachmann, Stefan

    2017-01-01

    BACKGROUND Improving mobility in elderly persons is a primary goal in geriatric rehabilitation. Self-regulated exercises with instruction leaflets are used to increase training volume but adherence is often low. Exergames may improve adherence. This study therefore compared exergames with self-regulated exercise using instruction leaflets. The primary outcome was adherence. Secondary outcomes were enjoyment, motivation and balance during walking. METHODS Design: single center para...

  6. Penggunaan VCD dan Leaflet untuk Peningkatan Pengetahuan, Sikap, dan Perilaku Siswa dalam Pencegahan Kecelakaan Sepeda Motor

    Directory of Open Access Journals (Sweden)

    Mulyono Notosiswoyo

    2014-04-01

    Full Text Available Indonesia belum mempunyai kebijakan penyuluhan pencegahan kecelakaan sepeda motor yang efektif. Tujuan penelitian ini adalah menilai efektivitas penggunaan visual compact disk (VCD dan leaflet terhadap peningkatan pengetahuan, sikap dan perilaku siswa SLTA dalam pencegahan kecelakaan sepeda motor di Kota Bekasi pada tahun 2010. Desain penelitian yang digunakan quasi experiment dengan rancangan equivalent pretest and post-test with control group, dengan intervensi pemutaran VCD dan pemberian leaflet. Sampel dihitung berdasarkan uji 2 proporsi, diperoleh sampel minimal 211 untuk yang di intervensi dan 211 untuk kontrol. Mereka diambil dari siswa SLTA kelas I dan kelas II yang sering mengendarai sepeda motor. Evaluasi hasil intervensi dilakukan setelah tiga bulan. Alat pengumpul data adalah kuesioner yang telah diuji coba. Analisis data menggunakan uji Kolmogorov-Smirnov, uji-t berpasangan dan uji-t independen. Hasil penelitian menunjukan uji-t berpasangan pada kelompok yang di intervensi meningkatkan rerata skor pengetahuan, sikap, dan perilaku siswa SLTA sebelum dibandingkan sesudah pemutaran VCD dan pemberian leaflet bermakna (nilai p < 0,05, tetapi pada kelompok kontrol hanya terjadi peningkatan rerata skor perilaku sebelum dibandingkan sesudah adanya perlakukan. Sedangkan, hasil uji-t independen menunjukan hanya pada rerata skor variabel pengetahuan terdapat perbedaan peningkatan skor antara kelompok intervensi dan kelompok kontrol yang bermakna (nilai p < 0,05. Kesimpulannya, penyuluhan menggunakan VCD dan leaflet dapat meningkatkan pengetahuan siswa SLTA dalam pencegahan kecelakaan sepeda motor. Indonesia does not have a policy of promotion motorcycle accident prevention. The purpose of this study was to assess the effectiveness of the Visual Compact Disks and leaflets to increase in knowledge, attitudes and behavior of the motorcycle accident prevention on high school students in Bekasi City. The method used a non-randomized quasi

  7. Reexpression of Prior Stroke Symptoms in Adults: When is a Mimic a Mimic?

    Science.gov (United States)

    Siegler, James E; George, Alexander J; Martin-Schild, Sheryl

    2017-09-01

    A "stroke mimic" refers to any clinical condition that causes neurological symptoms clinically indistinguishable from a cerebral lesion that affects a vascular distribution, but is not caused by ischemia. One subtype of stroke mimic, termed stroke reexpression, is a form of mimicry in which previously recovered or improved stroke symptoms recur in the setting of a neurological disturbance (seizure, hypoperfusion state) or a systemic disturbance (toxic, metabolic, infectious). Many reports of stroke reexpression exist in the literature and are well known to clinicians, but there has been no consensus regarding terminology that has been published to date. The purpose of this review is to summarize several examples of stroke reexpression and propose simple, useful criteria for this clinical condition.

  8. Mycosis Fungoides mimic chronic eczema? Observation

    Directory of Open Access Journals (Sweden)

    Jacek Andruszkiewicz

    2013-07-01

    Full Text Available Mycosis fungoides (MF is the most common type of cutaneous T-cell lymphoma [1]. Because of its great variety of clinical features and nonspecific histological findings (especially in early stages has been named the "great imitator "and can induce many wrong diagnosis [2,3]. Mycosis fungoides (MF, is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known [4,5]. Therefore very often Mycosis fungoides is misdiagnosed as chronic eczema [6]. MF can also mimic: vitiligo [6], alopecia-Areata [7], ecchymosis [8].

  9. Sorting of bacterial lipoproteins to the outer membrane by the Lol system.

    Science.gov (United States)

    Narita, Shin-ichiro; Tokuda, Hajime

    2010-01-01

    Bacterial lipoproteins comprise a subset of membrane proteins with a lipid-modified cysteine residue at their amino termini through which they are anchored to the membrane. In Gram-negative bacteria, lipoproteins are localized on either the inner or the outer membrane. The Lol system is responsible for the transport of lipoproteins to the outer membrane.The Lol system comprises an inner-membrane ABC transporter LolCDE complex, a periplasmic carrier protein, LolA, and an outer membrane receptor protein, LolB. Lipoproteins are synthesized as precursors in the cytosol and then translocated across the inner membrane by the Sec translocon to the outer leaflet of the inner membrane, where lipoprotein precursors are processed to mature lipoproteins. The LolCDE complex then mediates the release of outer membrane-specific lipoproteins from the inner membrane while the inner membrane-specific lipoproteins possessing Asp at position 2 are not released by LolCDE because it functions as a LolCDE avoidance signal, causing the retention of these lipoproteins in the inner membrane. A water-soluble lipoprotein-LolA complex is formed as a result of the release reaction mediated by LolCDE. This complex traverses the hydrophilic periplasm to reach the outer membrane, where LolB accepts a lipoprotein from LolA and then catalyzes its incorporation into the inner leaflet of the outer membrane.

  10. Sensing Phosphatidylserine in Cellular Membranes

    Directory of Open Access Journals (Sweden)

    Jason G. Kay

    2011-01-01

    Full Text Available Phosphatidylserine, a phospholipid with a negatively charged head-group, is an important constituent of eukaryotic cellular membranes. On the plasma membrane, rather than being evenly distributed, phosphatidylserine is found preferentially in the inner leaflet. Disruption of this asymmetry, leading to the appearance of phosphatidylserine on the surface of the cell, is known to play a central role in both apoptosis and blood clotting. Despite its importance, comparatively little is known about phosphatidylserine in cells: its precise subcellular localization, transmembrane topology and intracellular dynamics are poorly characterized. The recent development of new, genetically-encoded probes able to detect phosphatidylserine within live cells, however, is leading to a more in-depth understanding of the biology of this phospholipid. This review aims to give an overview of the current methods for phosphatidylserine detection within cells, and some of the recent realizations derived from their use.

  11. Participants' preference for type of leaflet used to feed back the results of a randomised trial: a survey.

    Science.gov (United States)

    Brealey, Stephen; Andronis, Lazaros; Dennis, Laura; Atwell, Christine; Bryan, Stirling; Coulton, Simon; Cox, Helen; Cross, Ben; Fylan, Fiona; Garratt, Andrew; Gilbert, Fiona; Gillan, Maureen; Hendry, Maggie; Hood, Kerenza; Houston, Helen; King, David; Morton, Veronica; Robling, Michael; Russell, Ian; Wilkinson, Clare

    2010-12-01

    Hundreds of thousands of volunteers take part in medical research, but many will never hear from researchers about what the study revealed. There is a growing demand for the results of randomised trials to be fed back to research participants both for ethical research practice and for ensuring their co-operation in a trial. This study aims to determine participants' preferences for type of leaflet (short versus long) used to summarise the findings of a randomised trial; and to test whether certain characteristics explained participants' preferences. 553 participants in a randomised trial about General Practitioners' access to Magnetic Resonance Imaging for patients presenting with suspected internal derangement of the knee were asked in the final follow-up questionnaire whether they would like to be fed back the results of the trial. Participants who agreed to this were included in a postal questionnaire survey asking about their preference, if any, between a short and a long leaflet and what it was about the leaflet that they preferred. Multinomial logistic regression was used to test whether certain demographics of responding participants along with treatment group explained whether a participant had a preference for type of leaflet or no preference. Of the participants who returned the final follow-up questionnaire, 416 (88%) agreed to receive the results of the trial. Subsequently 132 (32%) participants responded to the survey. Most participants preferred the longer leaflet (55%) and the main reasons for this were the use of technical information (94%) and diagrams (89%). There was weak evidence to suggest that gender might explain whether participants have a preference for type of leaflet or not (P = 0.084). Trial participants want to receive feed back about the results and appear to prefer a longer leaflet. Males and females might require information to be communicated to them differently and should be the focus of further research. The trial is registered

  12. Restoration of Tricuspid Valve Mechanism at the Level of Displaced Septal and Posterior Leaflets in Ebstein's Anomaly.

    Science.gov (United States)

    Im, Yu-Mi; Park, Chun Soo; Park, Jeong-Jun; Yun, Tae-Jin

    2016-03-01

    Surgical techniques currently used for the repair of Ebstein's anomaly comprise reconstruction of the tricuspid valve mechanism at the level of the true annulus with or without plication of the atrialized right ventricle. However, performing this procedure for patients with a dysmorphic anterior leaflet (i.e., insufficient leaflet tissue and decreased mobility due to tethering) may necessitate technical modifications. A retrospective review was performed of 31 patients (seven males and 24 females, median age at operation 31 years) with Ebstein's anomaly, who underwent tricuspid valve repair between March 2002 and December 2014. The original Hetzer technique (annulus to annulus approximation) was employed for six patients with a well-formed anterior leaflet. In 25 patients, the tricuspid valve mechanism was restored at the displaced septal leaflet by approximating the anterior leaflet attachment in the true annulus to the displaced septal leaflet attachment in the mid-septum. A bidirectional superior cavopulmonary anastomosis was added in 27 of 31 (87%) patients. No early or late death occurred during the median follow-up of 66 months (1-138 months). Immediate postoperative tricuspid regurgitation was trivial to mild in 22 patients, and the median preoperative, immediate postoperative, and last follow-up tricuspid regurgitation jet areas in 21 adult patients were 23.3 cm2, 10.4 cm2, and 7.0 cm2, respectively. Two patients underwent reoperation at 81 and 119 months postoperatively. Five-year freedom from severe tricuspid regurgitation or reoperation was 93.2%. Restoration of the tricuspid valve mechanism at the level of displaced septal leaflet leads to excellent long-term outcomes. The addition of the bidirectional superior cavopulmonary anastomosis has contributed to the success of this technique. © 2016 Wiley Periodicals, Inc.

  13. Low literacy and written drug information: information-seeking, leaflet evaluation and preferences, and roles for images.

    Science.gov (United States)

    van Beusekom, Mara M; Grootens-Wiegers, Petronella; Bos, Mark J W; Guchelaar, Henk-Jan; van den Broek, Jos M

    2016-12-01

    Background Low-literate patients are at risk to misinterpret written drug information. For the (co-) design of targeted patient information, it is key to involve this group in determining their communication barriers and information needs. Objective To gain insight into how people with low literacy use and evaluate written drug information, and to identify ways in which they feel the patient leaflet can be improved, and in particular how images could be used. Setting Food banks and an education institution for Dutch language training in the Netherlands. Method Semi-structured focus groups and individual interviews were held with low-literate participants (n = 45). The thematic framework approach was used for analysis to identify themes in the data. Main outcome measure Low-literate people's experience with patient information leaflets, ideas for improvements, and perceptions on possible uses for visuals. Results Patient information leaflets were considered discouraging to use, and information difficult to find and understand. Many rely on alternative information sources. The leaflet should be shorter, and improved in terms of organisation, legibility and readability. Participants thought images could increase the leaflet's appeal, help ask questions, provide an overview, help understand textual information, aid recall, reassure, and even lead to increased confidence, empowerment and feeling of safety. Conclusion Already at the stages of paying attention to the leaflet and maintaining interest in the message, low-literate patients experience barriers in the communication process through written drug information. Short, structured, visual/textual explanations can lower the motivational threshold to use the leaflet, improve understanding, and empower the low-literate target group.

  14. Preparation, validation and user-testing of pictogram-based patient information leaflets for tuberculosis.

    Science.gov (United States)

    Shrestha, Anmol; Rajesh, V; Dessai, Sneha Shamrao; Stanly, Sharon Mary; Mateti, Uday Venkat

    2018-05-25

    Patient education is of paramount importance with regard to the condition of the disease and the treatment given besides lifestyle remodelling in order to get the desired therapeutic outcome. When verbal information is provided to the patients, they often tend to forget it. Pictorial aids or pictograms, as they are commonly known, are tools that are widely used for imparting knowledge to the patients. The aim of the study is to prepare and validate a Pictogram-based Patient Information Leaflet (P-PILs) on Tuberculosis (TB). P-PILs have been prepared from tertiary, secondary and primary sources. The knowledge-based questions are prepared with respect to the P-PILs. The baseline knowledge of the volunteers and patients have been analyzed before administering the P-PILs by using the validated questionnaire. The post-knowledge of the volunteers and patients has been analyzed after administering the P-PILs (20 min) by using the same questionnaire and the user-opinion has also been obtained at the end. The study results show that the mean scores of the overall user-testing knowledge assessment are found to have improved significantly from the pre-P-PILs administration score of 62.67 to the post-P-PILs administration score of 91. The overall user-opinion about the P-PILs has been found to be good (75%) followed by average (25%). The present study shows that there is significant improvement in the knowledge levels of the patients and volunteers after reading the validated leaflets. The Pictogram-based Patient Information Leaflets are found to be an effective educational tool for TB patients. Copyright © 2018. Published by Elsevier Ltd.

  15. Introduction of a paediatric anaesthesia comic information leaflet reduced preoperative anxiety in children.

    Science.gov (United States)

    Kassai, B; Rabilloud, M; Dantony, E; Grousson, S; Revol, O; Malik, S; Ginhoux, T; Touil, N; Chassard, D; Pereira de Souza Neto, E

    2016-07-01

    The aim of the study was to determine whether the introduction of a paediatric anaesthesia comic information leaflet reduced preoperative anxiety levels of children undergoing major surgery. Secondary objectives were to determine whether the level of understanding of participants and other risk factors influence STAIC-S (State-Trait Anxiety Inventory for Children-State subscale) score in children. We performed a randomized controlled parallel-group trial comparing preoperative anxiety between two groups of children aged >6 and comic information leaflet at home in addition to routine information given by the anaesthetist at least 1 day before surgery. The control group received the routine information only. The outcome measure was the difference between STAIC-S scores measured before any intervention and after the anaesthetist's visit. A multiple regression analysis was performed to explore the influence of the level of education, the anxiety of parents, and the childrens' intelligence quotient on STAIC-S scores. One hundred and fifteen children were randomized between April 2009 and April 2013. An intention-to-treat analysis on data from 111 patients showed a significant reduction (P=0.002) in STAIC-S in the intervention group (n=54, mean=-2.2) compared with the control group (n=57, mean=0.90). The multiple regression analysis did not show any influence on STAIC-S scores of the level of education, parental anxiety, or the intelligence quotient of the children. A paediatric anaesthesia comic information leaflet was a cheap and effective means of reducing preoperative anxiety, measured by STAIC-S, in children. NCT 00841022. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Membrane transport of anandamide through resealed human red blood cell membranes

    DEFF Research Database (Denmark)

    Bojesen, I.N.; Hansen, Harald S.

    2005-01-01

    The use of resealed red blood cell membranes (ghosts) allows the study of the transport of a compound in a nonmetabolizing system with a biological membrane. Transmembrane movements of anandamide (N-arachidonoylethanolamine, arachidonoylethanolamide) have been studied by exchange efflux experiments...... at 0°C and pH 7.3 with albumin-free and albumin-filled human red blood cell ghosts. The efflux kinetics is biexponential and is analyzed in terms of compartment models. The distribution of anandamide on the membrane inner to outer leaflet pools is determined to be 0.275 ± 0.023, and the rate constant...... of unidirectional flux from inside to outside is 0.361 ± 0.023 s. The rate constant of unidirectional flux from the membrane to BSA in the medium ([BSA]) increases with the square root of [BSA] in accordance with the theory of an unstirred layer around ghosts. Anandamide passed through the red blood cell membrane...

  17. Aggressiveness of Phytophthora infestans on detached potato leaflets in four Nordic countries

    DEFF Research Database (Denmark)

    Lehtinen, A; Andersson, B; Le, V H

    2009-01-01

    differences between the test laboratories for infection efficiency, lesion growth rate and sporulation capacity on detached leaflets. When the laboratory effect was taken into account, the differences in aggressiveness between the countries were generally small or inconsistent between the test cultivars...... and epidemiologically insignificant. By contrast, variation among isolates within countries was substantial. The magnitude of the variation depended on country and cultivar. Maximal variation for the means of the isolates was between 89 and 185 h for latent period, between 100 and 1297 sporangia mm-2 for sporulation...

  18. The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus.

    Science.gov (United States)

    Midha, Prem A; Raghav, Vrishank; Sharma, Rahul; Condado, Jose F; Okafor, Ikechukwu U; Rami, Tanya; Kumar, Gautam; Thourani, Vinod H; Jilaihawi, Hasan; Babaliaros, Vasilis; Makkar, Raj R; Yoganathan, Ajit P

    2017-10-24

    Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon. Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus). SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%; P <0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth ( R 2 =0.7, P <0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased. Although transcatheter aortic valve replacement thrombosis is a multifactorial process

  19. Posters y trípticos (Brochures) en LATEX con Beamer y Leaflet

    OpenAIRE

    Borbón, Alexánder

    2013-01-01

    Resumen. En este artículo se muestra la manera en que se puede realizar posters y trípticos (panfletos o brochures) con LATEX. Para realizar los posters se utiliza la clase beamer que usualmente se utiliza para hacer presentaciones, se utiliza el paquete beamerposter para poder utilizarla para posters. Los trípticos se realizan de dos formas, la primera utilizando la clase beamer con el paquete geometry y la segunda utilizando la clase leaflet que es una clase especializada para hacer este ti...

  20. Nanoscale Membrane Domain Formation Driven by Cholesterol

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

    2017-01-01

    Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

  1. Development of Prescription Drug Information Leaflets: Impact of Cognitive Effort and Patient Involvement on Prescription Medication Information Processing.

    Science.gov (United States)

    Patel, Harshali K; Bapat, Shweta S; Bhansali, Archita H; Sansgiry, Sujit S

    2018-01-01

    The objective of this study was to develop a one-page (1-page) prescription drug information leaflet (PILs) and assess their impact on the information processing variables, across 2 levels of patient involvement. One-page PILs were developed using cognitive principles to lower mental effort and improve comprehension. An experimental, 3 × 2 repeated measures study was conducted to determine the impact of cognitive effort, manipulated using leaflet type on comprehension across 2 levels (high/low) of patient involvement. Adults (≥18 years) in a university setting in Houston were recruited for the study. Each participant was exposed to 3 different types of prescription drug information leaflet (the current practice, preexisting 1-page text-only, and 1-page PILs) for the 3 drugs (Celebrex, Ventolin HFA, Prezista) for a given involvement scenario. A prevalidated survey instrument was used to measure product knowledge, attitude toward leaflet, and intention to read. Multivariate analysis of variance indicated significant positive effect of cognitive effort, involvement, and their interaction effect across all measured variables. Mean scores for product knowledge, attitude toward leaflet, and intention to read were highest for PILs ( P information processing for consumers by reducing their cognitive effort.

  2. Hydrothermal Pretreatment of Date Palm (Phoenix dactylifera L. Leaflets and Rachis to Enhance Enzymatic Digestibility and Bioethanol Potential

    Directory of Open Access Journals (Sweden)

    Chuanji Fang

    2015-01-01

    Full Text Available Date palm residues are one of the most promising lignocellulosic biomass for bioethanol production in the Middle East. In this study, leaflets and rachis were subjected to hydrothermal pretreatment to overcome the recalcitrance of the biomass for enzymatic conversion. Evident morphological, structural, and chemical changes were observed by scanning electron microscopy, X-ray diffraction, and infrared spectroscopy after pretreatment. High glucan (>90% for both leaflets and rachis and xylan (>75% for leaflets and >79% for rachis recovery were achieved. Under the optimal condition of hydrothermal pretreatment (210°C/10 min highly digestible (glucan convertibility, 100% to leaflets, 78% to rachis and fermentable (ethanol yield, 96% to leaflets, 80% to rachis solid fractions were obtained. Fermentability test of the liquid fractions proved that no considerable inhibitors to Saccharomyces cerevisiae were produced in hydrothermal pretreatment. Given the high sugar recovery, enzymatic digestibility, and ethanol yield, production of bioethanol by hydrothermal pretreatment could be a promising way of valorization of date palm residues in this region.

  3. Structure and physical properties of bio membranes and model membranes

    International Nuclear Information System (INIS)

    Tibor Hianik

    2006-01-01

    Bio membranes belong to the most important structures of the cell and the cell organelles. They play not only structural role of the barrier separating the external and internal part of the membrane but contain also various functional molecules, like receptors, ionic channels, carriers and enzymes. The cell membrane also preserves non-equilibrium state in a cell which is crucial for maintaining its excitability and other signaling functions. The growing interest to the bio membranes is also due to their unique physical properties. From physical point of view the bio membranes, that are composed of lipid bilayer into which are incorporated integral proteins and on their surface are anchored peripheral proteins and polysaccharides, represent liquid s crystal of smectic type. The bio membranes are characterized by anisotropy of structural and physical properties. The complex structure of bio membranes makes the study of their physical properties rather difficult. Therefore several model systems that mimic the structure of bio membranes were developed. Among them the lipid monolayers at an air-water interphase, bilayer lipid membranes, supported bilayer lipid membranes and liposomes are most known. This work is focused on the introduction into the physical word of the bio membranes and their models. After introduction to the membrane structure and the history of its establishment, the physical properties of the bio membranes and their models are stepwise presented. The most focus is on the properties of lipid monolayers, bilayer lipid membranes, supported bilayer lipid membranes and liposomes that were most detailed studied. This lecture has tutorial character that may be useful for undergraduate and graduate students in the area of biophysics, biochemistry, molecular biology and bioengineering, however it contains also original work of the author and his co-worker and PhD students, that may be useful also for specialists working in the field of bio membranes and model

  4. Mimic sensor to monitor condition of human health; Mimic sensor wo riyoshita taicho monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Y. [Mechanical Engineering Lab., Tokyo (Japan)

    2000-04-01

    In the aging society where the birth rate decreases and the number of nuclear families increases, it is very important to inquire after the aged or physically handicapped people, to monitor their physical conditions, and to take steps to keep them healthy. As for the in-home physical measurement for the aged or physically handicapped people and the work of health management for them based on such measurement, it is feared that under the present conditions the invalid themselves or their family members or nurses will inevitably have to bear the burden and that nobody can deny the difficulty of continuing such nursing care. If daily physical condition measurement and related data collection are automatically carried out, however, interested people' burden will lessen and in-home heath management will become actually feasible. In this paper, a mimic sensor for realizing such a situation is described, which will measure physical conditions without interfering with the daily life of interested people. Serving as the mimic sensor is a blood flow sensor embedded in a telephone receiver, and changes in the blood flow during telephone conversation and changes in the gaps between peeks will be monitored. The feasibility is shown of continual collection of information necessary for the measurement of physical conditions of the aged or physically handicapped persons. (NEDO)

  5. Surgically Confirmed Intra- and Extratesticular Hematoma Clinically Mimicing Epididymo-Orchitis and Radiologically Mimicing Traumatic Torsion

    International Nuclear Information System (INIS)

    Akay, Sinan; Kaygisiz, Mustafa; Oztas, Muharrem; Turgut, Mustafa Suphi

    2015-01-01

    Scrotal blunt trauma may result in injuries, such as testicular rupture, dislocation, torsion, hematoma, spermatic cord injury or contusion, and epididymal, scrotal, and urethral injuries. Ultrasonography (US) has a crucial role in the evaluation of those kinds of pathologies. Early diagnosis of testicular rupture may lead to the salvaging of the testicle by prompt surgical exploration within 72 h. A 21-year-old male with right scrotal swelling and pain complaints was admitted to another hospital one month ago. Epididymo-orchitis was diagnosed and the patient was given medical treatment. The patient was admitted to our emergency service with ongoing complaints. The patient stated that the pain and swelling suddenly developed after prolonged marching. On US, a large hematoma was detected between the leaves of the tunica vaginalis, and rupture from the lower pole was diagnosed. On color Doppler US, no vascularity was observed in the heterogeneous testicular parenchyma. Traumatic torsion was primarily suggested. Intraoperatively, an extratesticular hematoma, hematocele, and rupture were confirmed but torsion was not found. Because the hematoma entirely replaced the normal parenchyma, orchiectomy was performed. Testicular rupture may occur even after moderate sportive action such as prolonged marching. If any delay occurs in diagnosis and/or operation, the coagulum may replace the entire parenchyma. We think that US and clinical findings may sometimes mislead the physicians and cause misdiagnoses, such as inflammation or torsion. In this paper, we present a complex delayed diagnosed example case of testicular rupture clinically mimicing epididymo-orchitis and radiologically mimicing traumatic testicular torsion

  6. Evaluation of the Readability of Dermatological Postoperative Patient Information Leaflets Across England.

    Science.gov (United States)

    Hunt, William T N; McGrath, Emily J

    2016-06-01

    Postoperative patient information leaflets (PILs) provide important guidance to patients after skin surgery. Readability is a method of evaluating information for text comprehension. The recommended level for PIL readability is US grade ≤6. To evaluate the readability of public English dermatological postoperative PILs. All dermatology departments in England were requested to provide their postoperative PILs. Patient information leaflets were evaluated using Readability Studio (Oleander Software, Vandalia, OH). Two preselected parameters were also noted: whether the PIL was doctor or nurse-written, and whether the PIL was Information Standard hallmarked. Eighty-five of one hundred thirty (65.4%) of PILs were evaluated. Only 29.4% of the PILs were grade level ≤6 with Flesch-Kincaid. The mean readability levels were 7.8 for Flesch-Kincaid, 67 for Flesch reading ease, 10.5 for Simple Measure of Gobbledygook (SMOG), 9.4 for Gunning-Fog, 8 for Fry, and 9.8 for FORCAST. No instruments demonstrated a significant difference between doctor (6) and nurse-written (7) PILs. Two instruments found that the 3 Information Standard hallmarked PILs had a higher (harder) readability than ordinary PILs (n = 82) (Gunning-Fog, p = .029*; SMOG p = .049*). Most English postoperative dermatological PILs' readability levels exceed recommendations (US grade ≤6). Departmental PILs should be reviewed to ensure that they are comprehensible to their patients.

  7. Stroke mimic diagnoses presenting to a hyperacute stroke unit.

    Science.gov (United States)

    Dawson, Ang; Cloud, Geoffrey C; Pereira, Anthony C; Moynihan, Barry J

    2016-10-01

    Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered. © Royal College of Physicians 2016. All rights reserved.

  8. Intrinsic potential of cell membranes: opposite effects of lipid transmembrane asymmetry and asymmetric salt ion distribution

    DEFF Research Database (Denmark)

    Gurtovenko, Andrey A; Vattulainen, Ilpo

    2009-01-01

    Using atomic-scale molecular dynamics simulations, we consider the intrinsic cell membrane potential that is found to originate from a subtle interplay between lipid transmembrane asymmetry and the asymmetric distribution of monovalent salt ions on the two sides of the cell membrane. It turns out......Cl saline solution and the PE leaflet is exposed to KCl, the outcome is that the effects of asymmetric lipid and salt ion distributions essentially cancel one another almost completely. Overall, our study highlights the complex nature of the intrinsic potential of cell membranes under physiological...... that both the asymmetric distribution of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids across a membrane and the asymmetric distribution of NaCl and KCl induce nonzero drops in the transmembrane potential. However, these potential drops are opposite in sign. As the PC leaflet faces a Na...

  9. Molecular analysis of interactions between dendrimers and asymmetric membranes at different transport stages.

    Science.gov (United States)

    He, XiaoCong; Qu, ZhiGuo; Xu, Feng; Lin, Min; Wang, JiuLing; Shi, XingHua; Lu, TianJian

    2014-01-07

    Studying dendrimer-biomembrane interactions is important for understanding drug and gene delivery. In this study, coarse-grained molecular dynamics simulations were performed to investigate the behaviors of polyamidoamine (PAMAM) dendrimers (G4 and G5) as they interacted with asymmetric membranes from different sides of the bilayer, thus mimicking different dendrimer transport stages. The G4 dendrimer could insert into the membrane during an equilibrated state, and the G5 dendrimer could induce pore formation in the membrane when the dendrimers interacted with the outer side (outer interactions) of an asymmetric membrane [with 10% dipalmitoyl phosphatidylserine (DPPS) in the inner leaflet of the membrane]. During the interaction with the inner side of the asymmetric membrane (inner interactions), the G4 and G5 dendrimers only adsorbed onto the membrane. As the membrane asymmetry increased (e.g., increased DPPS percentage in the inner leaflet of the membrane), the G4 and G5 dendrimers penetrated deeper into the membrane during the outer interactions and the G4 and G5 dendrimers were adsorbed more tightly onto the membrane for the inner interactions. When the DPPS content reached 50%, the G4 dendrimer could completely penetrate through the membrane from the outer side to the inner side. Our study provides molecular understanding and reference information about different dendrimer transport stages during drug and gene delivery.

  10. Consumer’s Perception on Design and Layout of Consumer Medical Information Leaflets on Obesity and Lipid Lowering Drugs

    Science.gov (United States)

    Mathew, Elizabeth M.; Rajiah, Kingston; Sharma, Krishana Kumar

    2013-01-01

    Background: Printed education materials are often used to augment healthcare professional’s verbal information to consumers so it serves as an important component of symptom management. They also enhance the teaching process and can be used by consumers as a home reference. Objective: This study was aimed to interpret consumers’ perception on Consumer Medical Information Leaflets (CMILs) on obesity and lipid lowering drugs, on design and layout using the standard method such as Baker Able Leaflet Design (BALD). Material and Methods: Convenience sampling was done. The study was conducted over a period of 3 years in community pharmacy settings in Tamil Nadu, India. The Consumer Medical Information Leaflets (CMILs) were randomly collected from different community pharmacies. Total of 19 CMILs which are commonly used by the consumers were collected and CMILs were assessed using BALD assessment tool Results: According to BALD assessment (46.28%) leaflets were rated as ‘above standard’ and (53.72) leaflets were rated as ‘standard or poor’ in layout and design since their scores were less than 25. This shows that this issue may be important from the patient’s perspective, which may discourage patient from actually reading the CMILs. Conclusion: In India, generally CMILs are continued to be prepared in English and with higher proportion of consumers with English illiteracy. CMILs, which are prepared without taking consideration of reading level of consumers and proper layout and design, may not achieve the intended purpose. This is an important aspect that any company has to reckon while preparing leaflets and at least in some major local languages in which CMILs have to be prepared. PMID:24551641

  11. Consumer's Perception on Design and Layout of Consumer Medical Information Leaflets on Obesity and Lipid Lowering Drugs.

    Science.gov (United States)

    Mathew, Elizabeth M; Rajiah, Kingston; Sharma, Krishana Kumar

    2013-12-01

    Printed education materials are often used to augment healthcare professional's verbal information to consumers so it serves as an important component of symptom management. They also enhance the teaching process and can be used by consumers as a home reference. This study was aimed to interpret consumers' perception on Consumer Medical Information Leaflets (CMILs) on obesity and lipid lowering drugs, on design and layout using the standard method such as Baker Able Leaflet Design (BALD). Convenience sampling was done. The study was conducted over a period of 3 years in community pharmacy settings in Tamil Nadu, India. The Consumer Medical Information Leaflets (CMILs) were randomly collected from different community pharmacies. Total of 19 CMILs which are commonly used by the consumers were collected and CMILs were assessed using BALD assessment tool Results: According to BALD assessment (46.28%) leaflets were rated as 'above standard' and (53.72) leaflets were rated as 'standard or poor' in layout and design since their scores were less than 25. This shows that this issue may be important from the patient's perspective, which may discourage patient from actually reading the CMILs. In India, generally CMILs are continued to be prepared in English and with higher proportion of consumers with English illiteracy. CMILs, which are prepared without taking consideration of reading level of consumers and proper layout and design, may not achieve the intended purpose. This is an important aspect that any company has to reckon while preparing leaflets and at least in some major local languages in which CMILs have to be prepared.

  12. Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc02719b Click here for additional data file.

    Science.gov (United States)

    Araman, Can; Thompson, Robert E.; Wang, Siyao; Hackl, Stefanie; Payne, Richard J.

    2017-01-01

    The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrPSc) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrPC) into PrPSc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179–231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics. PMID:28989689

  13. Influence of the membrane environment on cholesterol transfer.

    Science.gov (United States)

    Breidigan, Jeffrey Michael; Krzyzanowski, Natalie; Liu, Yangmingyue; Porcar, Lionel; Perez-Salas, Ursula

    2017-12-01

    Cholesterol, an essential component in biological membranes, is highly unevenly distributed within the cell, with most localized in the plasma membrane while only a small fraction is found in the endoplasmic reticulum, where it is synthesized. Cellular membranes differ in lipid composition and protein content, and these differences can exist across their leaflets too. This thermodynamic landscape that cellular membranes impose on cholesterol is expected to modulate its transport. To uncover the role the membrane environment has on cholesterol inter- and intra-membrane movement, we used time-resolved small angle neutron scattering to study the passive movement of cholesterol between and within membranes with varying degrees of saturation content. We found that cholesterol moves systematically slower as the degree of saturation in the membranes increases, from a palmitoyl oleyl phosphotidylcholine membrane, which is unsaturated, to a dipalmitoylphosphatidylcholine (DPPC) membrane, which is fully saturated. Additionally, we found that the energetic barrier to move cholesterol in these phosphatidylcholine membranes is independent of their relative lipid composition and remains constant for both flip-flop and exchange at ∼100 kJ/mol. Further, by replacing DPPC with the saturated lipid palmitoylsphingomyelin, an abundant saturated lipid of the outer leaflet of the plasma membrane, we found the rates decreased by a factor of two. This finding is in stark contrast with recent molecular dynamic simulations that predict a dramatic slow-down of seven orders of magnitude for cholesterol flipping in membranes with a similar phosphocholine and SM lipid composition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  14. Overcoming the knowledge-behavior gap: The effect of evidence-based HPV vaccination leaflets on understanding, intention, and actual vaccination decision.

    Science.gov (United States)

    Wegwarth, O; Kurzenhäuser-Carstens, S; Gigerenzer, G

    2014-03-10

    Informed decision making requires transparent and evidence-based (=balanced) information on the potential benefit and harms of medical preventions. An analysis of German HPV vaccination leaflets revealed, however, that none met the standards of balanced risk communication. We surveyed a sample of 225 girl-parent pairs in a before-after design on the effects of balanced and unbalanced risk communication on participants' knowledge about cervical cancer and the HPV vaccination, their perceived risk, their intention to have the vaccine, and their actual vaccination decision. The balanced leaflet increased the number of participants who were correctly informed about cervical cancer and the HPV vaccine by 33 to 66 absolute percentage points. In contrast, the unbalanced leaflet decreased the number of participants who were correctly informed about these facts by 0 to 18 absolute percentage points. Whereas the actual uptake of the HPV vaccination 14 months after the initial study did not differ between the two groups (22% balanced leaflet vs. 23% unbalanced leaflet; p=.93, r=.01), the originally stated intention to have the vaccine reliably predicted the actual vaccination decision for the balanced leaflet group only (concordance between intention and actual uptake: 97% in the balanced leaflet group, rs=.92, p=.00; 60% in the unbalanced leaflet group, rs=.37, p=.08). In contrast to a unbalanced leaflet, a balanced leaflet increased people's knowledge of the HPV vaccination, improved perceived risk judgments, and led to an actual vaccination uptake, which first was robustly predicted by people's intention and second did not differ from the uptake in the unbalanced leaflet group. These findings suggest that balanced reporting about HPV vaccination increases informed decisions about whether to be vaccinated and does not undermine actual uptake. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Mitral valve stenosis caused by abnormal pannus extension over the prosthetic ring and leaflets after Duran ring mitral annuloplasty.

    Science.gov (United States)

    Yunoki, Junji; Minato, Naoki; Katayama, Yuji; Sato, Hisashi

    2009-01-01

    We treated a 61-year-old woman with mitral stenosis caused by pannus formation after Duran ring annuloplasty. Pannus overgrowth on the ring with extension onto both leaflets narrowed the mitral orifice and severely restricted the mobility of the valve leaflets. Mitral valve replacement with a St. Jude Medical mechanical heart valve prosthesis was successfully performed, and the postoperative course was uneventful. Patients undergoing Duran ring annuloplasty should be followed up with the consideration of possible mitral stenosis caused by pannus extension, as the cause for pannus formation remains unclear.

  16. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic

  17. Decontamination Of Bacterial Spores by a Peptide-Mimic

    National Research Council Canada - National Science Library

    Nagarajan, R; Muller, Wayne S; Ashley, Rebekah; Mello, Charlene M

    2006-01-01

    .... In this work, we demonstrate that a peptide-mimic (cationic, amphiphilic) chemical agent, dodecylamine is capable of performing the dual functions of germinating the dormant spore as well as deactivating...

  18. Sharp incision of the anterior mitral leaflet due to penetrating trauma - Report of a case and long-term follow-up

    NARCIS (Netherlands)

    de Boer, HD; Hamer, HPM; Ebels, T

    A case is described of sharp incision of the anterior leaflet of the mitral valve, due to penetrating trauma to the chest with a knife. The lesion of the mitral leaflet was diagnosed with echocardiography and successfully repaired with autologous pericardial tissue. Follow up after 15 years showed

  19. Process mining in oncology using the MIMIC-III dataset

    Science.gov (United States)

    Prima Kurniati, Angelina; Hall, Geoff; Hogg, David; Johnson, Owen

    2018-03-01

    Process mining is a data analytics approach to discover and analyse process models based on the real activities captured in information systems. There is a growing body of literature on process mining in healthcare, including oncology, the study of cancer. In earlier work we found 37 peer-reviewed papers describing process mining research in oncology with a regular complaint being the limited availability and accessibility of datasets with suitable information for process mining. Publicly available datasets are one option and this paper describes the potential to use MIMIC-III, for process mining in oncology. MIMIC-III is a large open access dataset of de-identified patient records. There are 134 publications listed as using the MIMIC dataset, but none of them have used process mining. The MIMIC-III dataset has 16 event tables which are potentially useful for process mining and this paper demonstrates the opportunities to use MIMIC-III for process mining in oncology. Our research applied the L* lifecycle method to provide a worked example showing how process mining can be used to analyse cancer pathways. The results and data quality limitations are discussed along with opportunities for further work and reflection on the value of MIMIC-III for reproducible process mining research.

  20. Peptide insertion, positioning, and stabilization in a membrane: insight from an all-atom molecular dynamics simulation.

    Science.gov (United States)

    Babakhani, Arneh; Gorfe, Alemayehu A; Gullingsrud, Justin; Kim, Judy E; Andrew McCammon, J

    Peptide insertion, positioning, and stabilization in a model membrane are probed via an all-atom molecular dynamics (MD) simulation. One peptide (WL5) is simulated in each leaflet of a solvated dimyristoylglycero-3-phosphate (DMPC) membrane. Within the first 5 ns, the peptides spontaneously insert into the membrane and then stabilize during the remaining 70 ns of simulation time. In both leaflets, the peptides localize to the membrane interface, and this localization is attributed to the formation of peptide-lipid hydrogen bonds. We show that the single tryptophan residue in each peptide contributes significantly to these hydrogen bonds; specifically, the nitrogen heteroatom of the indole ring plays a critical role. The tilt angles of the indole rings relative to the membrane normal in the upper and lower leaflets are approximately 26 degrees and 54 degrees , respectively. The tilt angles of the entire peptide chain are 62 degrees and 74 degrees . The membrane induces conformations of the peptide that are characteristic of beta-sheets, and the peptide enhances the lipid ordering in the membrane. Finally, the diffusion rate of the peptides in the membrane plane is calculated (based on experimental peptide concentrations) to be approximately 6 A(2)/ns, thus suggesting a 500 ns time scale for intermolecular interactions.

  1. Two interdependent mechanisms of antimicrobial activity allow for efficient killing in nylon-3-based polymeric mimics of innate immunity peptides ☆

    Science.gov (United States)

    Lee, Michelle W.; Chakraborty, Saswata; Schmidt, Nathan W.; Murgai, Rajan; Gellman, Samuel H.; Wong, Gerard C.L.

    2015-01-01

    Novel synthetic mimics of antimicrobial peptides have been developed to exhibit structural properties and antimicrobial activity similar to those of natural antimicrobial peptides (AMPs) of the innate immune system. These molecules have a number of potential advantages over conventional antibiotics, including reduced bacterial resistance, cost-effective preparation, and customizable designs. In this study, we investigate a family of nylon-3 polymer-based antimicrobials. By combining vesicle dye leakage, bacterial permeation, and bactericidal assays with small-angle X-ray scattering (SAXS), we find that these polymers are capable of two interdependent mechanisms of action: permeation of bacterial membranes and binding to intracellular targets such as DNA, with the latter necessarily dependent on the former. We systemically examine polymer-induced membrane deformation modes across a range of lipid compositions that mimic both bacteria and mammalian cell membranes. The results show that the polymers' ability to generate negative Gaussian curvature (NGC), a topological requirement for membrane permeation and cellular entry, in model Escherichia coli membranes correlates with their ability to permeate membranes without complete membrane disruption and kill E. coli cells. Our findings suggest that these polymers operate with a concentration dependent mechanism of action: at low concentrations permeation and DNA binding occur without membrane disruption, while at high concentrations complete disruption of the membrane occurs. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. PMID:24743021

  2. Comprehension and acceptability of a patient information leaflet (pil for antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Betty Mwingira

    2006-11-01

    Full Text Available The patient information leaflet (PIL is recognised as playing a key role in informing patients about their medicines. The objectives of this research were to evaluate the readability and understanding of a PIL for the first-line ARV (antiretroviral regimen available in the South African public health sector, and investigate its acceptability in the target Xhosa population. Opsomming Daar word algemeen aanvaar dat die pasiëntinligtingsblaadjie (PIB ‘n sleutelrol speel in die oordra van inligting ten opsigte van medikasie aan pasiënte. Die doelwitte van hierdie navorsing was om die leesbaarheid en begrip van ‘n PIB vir die eerste-linie antiretrovirale (ARV regimen wat in die Suid-Afrikaanse openbare gesondheidsektor beskikbaar is, te evalueer, en om die aanvaarbaarheid daarvan in ‘n teiken-Xhosabevolking te ondersoek. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

  3. Patient information leaflets: informing or frightening? A focus group study exploring patients' emotional reactions and subsequent behavior towards package leaflets of commonly prescribed medications in family practices.

    Science.gov (United States)

    Herber, Oliver Rudolf; Gies, Verena; Schwappach, David; Thürmann, Petra; Wilm, Stefan

    2014-10-02

    The purpose of patient information leaflets (PILs) is to inform patients about the administration, precautions and potential side effects of their prescribed medication. Despite European Commission guidelines aiming at increasing readability and comprehension of PILs little is known about the potential risk information has on patients. This article explores patients' reactions and subsequent behavior towards risk information conveyed in PILs of commonly prescribed drugs by general practitioners (GPs) for the treatment of Type 2 diabetes, hypertension or hypercholesterolemia; the most frequent cause for consultations in family practices in Germany. We conducted six focus groups comprising 35 patients which were recruited in GP practices. Transcripts were read and coded for themes; categories were created by abstracting data and further refined into a coding framework. Three interrelated categories are presented: (i) The vast amount of side effects and drug interactions commonly described in PILs provoke various emotional reactions in patients which (ii) lead to specific patient behavior of which (iii) consulting the GP for assistance is among the most common. Findings show that current description of potential risk information caused feelings of fear and anxiety in the reader resulting in undesirable behavioral reactions. Future PILs need to convey potential risk information in a language that is less frightening while retaining the information content required to make informed decisions about the prescribed medication. Thus, during the production process greater emphasis needs to be placed on testing the degree of emotional arousal provoked in patients when reading risk information to allow them to undertake a benefit-risk-assessment of their medication that is based on rational rather than emotional (fearful) reactions.

  4. Nanoscale domain formation of phosphatidylinositol 4-phosphate in the plasma and vacuolar membranes of living yeast cells.

    Science.gov (United States)

    Tomioku, Kan-Na; Shigekuni, Mikiko; Hayashi, Hiroki; Yoshida, Akane; Futagami, Taiki; Tamaki, Hisanori; Tanabe, Kenji; Fujita, Akikazu

    2018-05-01

    In budding yeast Saccharomyces cerevisiae, PtdIns(4)P serves as an essential signalling molecule in the Golgi complex, endosomal system, and plasma membrane, where it is involved in the control of multiple cellular functions via direct interactions with PtdIns(4)P-binding proteins. To analyse the distribution of PtdIns(4)P in yeast cells at a nanoscale level, we employed an electron microscopy technique that specifically labels PtdIns(4)P on the freeze-fracture replica of the yeast membrane. This method minimizes the possibility of artificial perturbation, because molecules in the membrane are physically immobilised in situ. We observed that PtdIns(4)P is localised on the cytoplasmic leaflet, but not the exoplasmic leaflet, of the plasma membrane, Golgi body, vacuole, and vesicular structure membranes. PtdIns(4)P labelling was not observed in the membrane of the endoplasmic reticulum, and in the outer and inner membranes of the nuclear envelope or mitochondria. PtdIns(4)P forms clusters of plasma membrane and vacuolar membrane according to point pattern analysis of immunogold labelling. There are three kinds of compartments in the cytoplasmic leaflet of the plasma membrane. In the present study, we showed that PtdIns(4)P is specifically localised in the flat undifferentiated plasma membrane compartment. In the vacuolar membrane, PtdIns(4)P was concentrated in intramembrane particle (IMP)-deficient raft-like domains, which are tightly bound to lipid droplets, but not surrounding IMP-rich non-raft domains in geometrical IMP-distributed patterns in the stationary phase. This is the first report showing microdomain formations of PtdIns(4)P in the plasma membrane and vacuolar membrane of budding yeast cells at a nanoscale level, which will illuminate the functionality of PtdIns(4)P in each membrane. Copyright © 2018 Elsevier GmbH. All rights reserved.

  5. Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke Mimics Evaluated Over Telestroke Networks.

    Science.gov (United States)

    Ali, Syed F; Hubert, Gordian J; Switzer, Jeffrey A; Majersik, Jennifer J; Backhaus, Roland; Shepard, L Wylie; Vedala, Kishore; Schwamm, Lee H

    2018-03-01

    Up to 30% of acute stroke evaluations are deemed stroke mimics, and these are common in telestroke as well. We recently published a risk prediction score for use during telestroke encounters to differentiate stroke mimics from ischemic cerebrovascular disease derived and validated in the Partners TeleStroke Network. Using data from 3 distinct US and European telestroke networks, we sought to externally validate the TeleStroke Mimic (TM) score in a broader population. We evaluated the TM score in 1930 telestroke consults from the University of Utah, Georgia Regents University, and the German TeleMedical Project for Integrative Stroke Care Network. We report the area under the curve in receiver-operating characteristic curve analysis with 95% confidence interval for our previously derived TM score in which lower TM scores correspond with a higher likelihood of being a stroke mimic. Based on final diagnosis at the end of the telestroke consultation, there were 630 of 1930 (32.6%) stroke mimics in the external validation cohort. All 6 variables included in the score were significantly different between patients with ischemic cerebrovascular disease versus stroke mimics. The TM score performed well (area under curve, 0.72; 95% confidence interval, 0.70-0.73; P mimic during telestroke consultation in these diverse cohorts was similar to its performance in our original cohort. Predictive decision-support tools like the TM score may help highlight key clinical differences between mimics and patients with stroke during complex, time-critical telestroke evaluations. © 2018 American Heart Association, Inc.

  6. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    Current topics include membrane-protein interactions with regard to membrane deformation or curvature sensing by BAR domains. Also, we study the dynamics of membrane tubes of both cells and simple model membrane tubes. Finally, we study membrane phase behavior which has important implications...... for the lateral organization of membranes as wells as for physical properties like bending, permeability and elasticity...

  7. Membranous Septal Aneurysm: An Unusual Case for Sub-Pulmonary Obstruction in cTGA

    Directory of Open Access Journals (Sweden)

    Onur Isik

    2013-10-01

    Full Text Available Aneurysm of the membranous portion of the interventricular septum is an uncommon congenital cardiac malformation that is rarely diagnosed during life. Perimembranous ventricular septal defects are the most common type of the ventricular septal defects and originates from morphologically membranous interventricular septum. Surgical exposure and accurate closure of a ventricular septal defect with a membranous septal aneurysm beneath the tricuspid septal leaflet carries a risk of tricuspid valve insufficiency and conduction disturbances. The current study presents a case with membranous septal aneursym with congenitally corrected transposition of the great arteries and sub-pulmonary obstruction, which was surgically corrected.

  8. Participants' preference for type of leaflet used to feed back the results of a randomised trial: a survey

    Directory of Open Access Journals (Sweden)

    Houston Helen

    2010-12-01

    Full Text Available Abstract Background Hundreds of thousands of volunteers take part in medical research, but many will never hear from researchers about what the study revealed. There is a growing demand for the results of randomised trials to be fed back to research participants both for ethical research practice and for ensuring their co-operation in a trial. This study aims to determine participants' preferences for type of leaflet (short versus long used to summarise the findings of a randomised trial; and to test whether certain characteristics explained participants' preferences. Methods 553 participants in a randomised trial about General Practitioners' access to Magnetic Resonance Imaging for patients presenting with suspected internal derangement of the knee were asked in the final follow-up questionnaire whether they would like to be fed back the results of the trial. Participants who agreed to this were included in a postal questionnaire survey asking about their preference, if any, between a short and a long leaflet and what it was about the leaflet that they preferred. Multinomial logistic regression was used to test whether certain demographics of responding participants along with treatment group explained whether a participant had a preference for type of leaflet or no preference. Results Of the participants who returned the final follow-up questionnaire, 416 (88% agreed to receive the results of the trial. Subsequently 132 (32% participants responded to the survey. Most participants preferred the longer leaflet (55% and the main reasons for this were the use of technical information (94% and diagrams (89%. There was weak evidence to suggest that gender might explain whether participants have a preference for type of leaflet or not (P = 0.084. Conclusions Trial participants want to receive feed back about the results and appear to prefer a longer leaflet. Males and females might require information to be communicated to them differently and should

  9. E-learning or educational leaflet: does it make a difference in oral health promotion? A clustered randomized trial.

    Science.gov (United States)

    Al Bardaweel, Susan; Dashash, Mayssoon

    2018-05-10

    The early recognition of technology together with great ability to use computers and smart systems have promoted researchers to investigate the possibilities of utilizing technology for improving health care in children. The aim of this study was to compare between the traditional educational leaflets and E-applications in improving oral health knowledge, oral hygiene and gingival health in schoolchildren of Damascus city, Syria. A clustered randomized controlled trial at two public primary schools was performed. About 220 schoolchildren aged 10-11 years were included in this study and grouped into two clusters. Children in Leaflet cluster received oral health education through leaflets, while children in E-learning cluster received oral health education through an E-learning program. A questionnaire was designed to register information related to oral health knowledge and to record Plaque and Gingival indices. Questionnaire administration and clinical assessment were undertaken at baseline, 6 and at 12 weeks of oral health education. Data was analysed using one way repeated measures ANOVA, post hoc Bonferroni test and independent samples t-test. Leaflet cluster (107 participants) had statistically significant better oral health knowledge than E-learning cluster (104 participants) at 6 weeks (P E-learning cluster:100 participants). The mean knowledge gain compared to baseline was higher in Leaflet cluster than in E-learning cluster. A significant reduction in the PI means at 6 weeks and 12 weeks was observed in both clusters (P E-learning cluster at 6 weeks (P E-learning cluster at 6 weeks (P < 0.05) and 12 weeks (P < 0.05). Traditional educational leaflets are an effective tool in the improvement of both oral health knowledge as well as clinical indices of oral hygiene and care among Syrian children. Leaflets can be used in school-based oral health education for a positive outcome. Australian New Zealand Clinical Trials Registry ( ACTRN

  10. Subaortic membrane mimicking hypertrophic cardiomyopathy.

    Science.gov (United States)

    Anderson, Mark Joseph; Arruda-Olson, Adelaide; Gersh, Bernard; Geske, Jeffrey

    2015-11-04

    A 34-year-old man was referred for progressive angina and exertional dyspnoea refractory to medical therapy, with a presumptive diagnosis of hypertrophic cardiomyopathy (HCM). Transthoracic echocardiography (TTE) revealed asymmetric septal hypertrophy without systolic anterior motion of the mitral valve leaflet and with no dynamic left ventricular outflow tract (LVOT) obstruction. However, the LVOT velocity was elevated at rest as well as with provocation, without the characteristic late peaking obstruction seen in HCM. Focused TTE to evaluate for suspected fixed obstruction demonstrated a subaortic membrane 2.2 cm below the aortic valve. Coronary CT angiography confirmed the presence of the subaortic membrane and was negative for concomitant coronary artery disease. Surgical resection of the subaortic membrane and septal myectomy resulted in significant symptomatic relief and lower LVOT velocities on postoperative TTE. This case reminds the clinician to carefully evaluate for alternative causes of LVOT obstruction, especially subaortic membrane, as a cause of symptoms mimicking HCM. 2015 BMJ Publishing Group Ltd.

  11. Identification of stroke mimics among clinically diagnosed acute strokes.

    Science.gov (United States)

    Tuntiyatorn, Lojana; Saksornchai, Pichaya; Tunlayadechanont, Supoch

    2013-09-01

    Stroke is a clinically syndrome of a sudden onset of neurological deficit in a vascular cause. Stroke mimics is the non-vascular disorders with stroke-like clinical symptoms. It is important to distinguish true stroke from mimics since treatment plan may differ To determine the incidence of the stroke mimics and identify their etiologies. All non-contrast head CT of the patients with clinically diagnosed stroke who immediately received imaging upon arrival at the emergency department of the university hospital were retrospectively reviewed in 12-month period between January 1 and December 31, 2008. Medical records, laboratory results, MRI, and 6-month clinical follow-up records were reviewed for final diagnosis. Seven hundred four patients were included in this study, including 363 (51.5%) men and 341 (48.5%) women with range in age from 24 to 108 years. Amongst those, 417 (59.2%) were ischemic stroke, 80 (11.40%) were hemorrhagic stroke, 186 (26.4%) were stroke-mimics, and 21 (3%) were inconclusive. The etiologies among stroke-mimics were metabolic/intoxication (35, 18.8%), sepsis (28, 15.0%), seizure (21, 11.3%), syncope (20, 10.8%), subdural hemorrhage (14, 7.5%), vertigo (11, 6.0%), brain tumor (10, 5.30%), central nervous system infection (5, 2.7%), others (26, 14.0%), and unspecified (16, 8.6%). Incidence rates and etiologies of the stroke mimics were similar to the western reports. However the frequency of each mimic was not.

  12. Proteomic analysis of GPI-anchored membrane proteins

    DEFF Research Database (Denmark)

    Jung, Hye Ryung; Jensen, Ole Nørregaard

    2006-01-01

    Glycosyl-phosphatidyl-inositol-anchored proteins (GPI-APs) represent a subset of post-translationally modified proteins that are tethered to the outer leaflet of the plasma membrane via a C-terminal GPI anchor. GPI-APs are found in a variety of eukaryote species, from pathogenic microorganisms...... to humans. GPI-APs confer important cellular functions as receptors, enzymes and scaffolding molecules. Specific enzymes and detergent extraction methods combined with separation technologies and mass spectrometry permit proteomic analysis of GPI-APs from plasma membrane preparations to reveal cell...

  13. Readability Analysis of the Package Leaflets for Biological Medicines Available on the Internet Between 2007 and 2013: An Analytical Longitudinal Study.

    Science.gov (United States)

    Piñero-López, María Ángeles; Modamio, Pilar; Lastra, Cecilia F; Mariño, Eduardo L

    2016-05-25

    The package leaflet included in the packaging of all medicinal products plays an important role in the transmission of medicine-related information to patients. Therefore, in 2009, the European Commission published readability guidelines to try to ensure that the information contained in the package leaflet is understood by patients. The main objective of this study was to calculate and compare the readability levels and length (number of words) of the package leaflets for biological medicines in 2007, 2010, and 2013. The sample of this study included 36 biological medicine package leaflets that were downloaded from the European Medicines Agency website in three different years: 2007, 2010, and 2013. The readability of the selected package leaflets was obtained using the following readability formulas: SMOG grade, Flesch-Kincaid grade level, and Szigriszt's perspicuity index. The length (number of words) of the package leaflets was also measured. Afterwards, the relationship between these quantitative variables (three readability indexes and length) and categorical (or qualitative) variables were analyzed. The categorical variables were the year when the package leaflet was downloaded, the package leaflet section, type of medicine, year of authorization of biological medicine, and marketing authorization holder. The readability values of all the package leaflets exceeded the sixth-grade reading level, which is the recommended value for health-related written materials. No statistically significant differences were found between the three years of study in the readability indexes, although differences were observed in the case of the length (P=.002), which increased over the study period. When the relationship between readability indexes and length and the other variables was analyzed, statistically significant differences were found between package leaflet sections (Preadability indexes (SMOG grade and Flesch-Kincaid grade level: r(2)=.92; SMOG grade and Szigriszt

  14. A scanning electron microscopy study of the invasion of leaflets of a bloat-safe and a bloat-causing legume by rumen microorganisms.

    Science.gov (United States)

    Fay, J P; Cheng, K J; Hanna, M R; Howarth, R E; Costerton, J W

    1981-04-01

    A newly developed technique using ruthenium red to detect foci of bacterial digestion in mounts of whole leaflets that had been incubated with rumen bacteria was used to compare the digestion of alfalfa, a bloat-causing legume, and sainfoin, a bloat-safe legume. When whole leaflets were suspended in an artificial rumen medium and inoculated with rumen bacteria, massive bacterial adhesion and proliferation were noted at the stomata of alfalfa leaflets after 6 h of incubation, whereas only a few isolated bacteria adhered near the stomata of sainfoin leaflets After 22 h of incubation, the epidermal layers of alfalfa leaflets had peeled away in many areas, revealing an extensive bacterial invasion of the underlying mesophyll tissue in which large bacterial microcolonies had formed in intercellular spaces, and in intracellular spaces in several areas where plant cell walls had broken down. After 22 h of incubation, the surface of sainfoin leaflets resembled that of alfalfa leaflets at 6 h, with bacterial microcolonies adhering to the area surrounding the stomata, but without sloughing of the epidermis. Uninoculated control leaflets of both species showed no surface alteration but part of their normal bacterial flora had proliferated to form microcolonies on the surface after 22 h incubation. Dry matter loss due to leaching or bacterial digestion when whole leaflets of legumes were suspended in an artificial rumen medium, alone or with rumen bacteria, was significantly higher in the bloat-causing group. Values of leaching and of bacterial digestion were positively correlated. We conclude that reported differences in plant anatomy, and in cell wall chemistry, produce distinct rates or organic nutrient release from legume leaflets, and that these same differences produce an equally distinct susceptibility of leaflets to bacterial invasion, plant cell rupture, and the consequent release of intracellular plant components. The rate of release of organic nutrients from legume

  15. Molecular mimics of the tumour antigen MUC1.

    Directory of Open Access Journals (Sweden)

    Tharappel C James

    Full Text Available A key requirement for the development of cancer immunotherapy is the identification of tumour-associated antigens that are differentially or exclusively expressed on the tumour and recognized by the host immune system. However, immune responses to such antigens are often muted or lacking due to the antigens being recognized as "self", and further complicated by the tumour environment and regulation of immune cells within. In an effort to circumvent the lack of immune responses to tumour antigens, we have devised a strategy to develop potential synthetic immunogens. The strategy, termed mirror image phage display, is based on the concept of molecular mimicry as demonstrated by the idiotype/anti-idiotype paradigm in the immune system. Here as 'proof of principle' we have selected molecular mimics of the well-characterised tumour associated antigen, the human mucin1 protein (MUC1 from two different peptide phage display libraries. The putative mimics were compared in structure and function to that of the native antigen. Our results demonstrate that several of the mimic peptides display T-cell stimulation activity in vitro when presented by matured dendritic cells. The mimic peptides and the native MUC1 antigenic epitopes can cross-stimulate T-cells. The data also indicate that sequence homology and/or chemical properties to the original epitope are not the sole determining factors for the observed immunostimulatory activity of the mimic peptides.

  16. Biogenesis and Membrane Targeting of Lipoproteins.

    Science.gov (United States)

    Narita, Shin-Ichiro; Tokuda, Hajime

    2010-09-01

    Bacterial lipoproteins represent a unique class of membrane proteins, which are anchored to membranes through triacyl chains attached to the amino-terminal cysteine. They are involved in various functions localized in cell envelope. Escherichia coli possesses more than 90 species of lipoproteins, most of which are localized in the outer membrane, with others being in the inner membrane. All lipoproteins are synthesized in the cytoplasm with an N-terminal signal peptide, translocated across the inner membrane by the Sec translocon to the periplasmic surface of the inner membrane, and converted to mature lipoproteins through sequential reactions catalyzed by three lipoprotein-processing enzymes: Lgt, LspA, and Lnt. The sorting of lipoproteins to the outer membrane requires a system comprising five Lol proteins. An ATP-binding cassette transporter, LolCDE, initiates the sorting by mediating the detachment of lipoproteins from the inner membrane. Formation of the LolA-lipoprotein complex is coupled to this LolCDE-dependent release reaction. LolA accommodates the amino-terminal acyl chain of lipoproteins in its hydrophobic cavity, thereby generating a hydrophilic complex that can traverse the periplasmic space by diffusion. Lipoproteins are then transferred to LolB on the outer membrane and anchored to the inner leaflet of the outer membrane by the action of LolB. In contrast, since LolCDE does not recognize lipoproteins possessing Asp at position +2, these lipoproteins remain anchored to the inner membrane. Genes for Lol proteins are widely conserved among gram-negative bacteria, and Lol-mediated outer membrane targeting of lipoproteins is considered to be the general lipoprotein localization mechanism.

  17. Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface.

    Science.gov (United States)

    Cheng, Sara Y; Chou, George; Buie, Creighton; Vaughn, Mark W; Compton, Campbell; Cheng, Kwan H

    2016-03-01

    We used molecular dynamics simulations to explore the effects of asymmetric transbilayer distribution of anionic phosphatidylserine (PS) lipids on the structure of a protein on the membrane surface and subsequent protein-lipid interactions. Our simulation systems consisted of an amyloidogenic, beta-sheet rich dimeric protein (D42) absorbed to the phosphatidylcholine (PC) leaflet, or protein-contact PC leaflet, of two membrane systems: a single-component PC bilayer and double PC/PS bilayers. The latter comprised of a stable but asymmetric transbilayer distribution of PS in the presence of counterions, with a 1-component PC leaflet coupled to a 1-component PS leaflet in each bilayer. The maximally asymmetric PC/PS bilayer had a non-zero transmembrane potential (TMP) difference and higher lipid order packing, whereas the symmetric PC bilayer had a zero TMP difference and lower lipid order packing under physiologically relevant conditions. Analysis of the adsorbed protein structures revealed weaker protein binding, more folding in the N-terminal domain, more aggregation of the N- and C-terminal domains and larger tilt angle of D42 on the PC leaflet surface of the PC/PS bilayer versus the PC bilayer. Also, analysis of protein-induced membrane structural disruption revealed more localized bilayer thinning in the PC/PS versus PC bilayer. Although the electric field profile in the non-protein-contact PS leaflet of the PC/PS bilayer differed significantly from that in the non-protein-contact PC leaflet of the PC bilayer, no significant difference in the electric field profile in the protein-contact PC leaflet of either bilayer was evident. We speculate that lipid packing has a larger effect on the surface adsorbed protein structure than the electric field for a maximally asymmetric PC/PS bilayer. Our results support the mechanism that the higher lipid packing in a lipid leaflet promotes stronger protein-protein but weaker protein-lipid interactions for a dimeric protein on

  18. Branchial cleft anomalies and their mimics: computed tomographic evaluation

    International Nuclear Information System (INIS)

    Harnsberger, H.R.; Mancuso, A.A.; Muraki, A.S.; Byrd, S.E.; Dillon, W.P.; Johnson, L.P.; Hanafee, W.N.

    1984-01-01

    A review was made of the clinical records and radiographic examinations of 38 patients with neck lesions clinically suspected of being branchial cleft anomalies. The impact of computed tomography in this sometimes confusing clinical picture was assessed and CT criteria for diagnosing branchial cleft anomalies (BCAs) and differentiating them from their mimics were identified. Seventeen branchial cleft anomalies and 21 BCA mimics were evaluated. A definitive CT diagnosis of second branchial cleft cysts based on characteristic morphology, location, and displacement of surrounding structures was possible in 80% of cases. CT was found to be the best radiographic examination in making a definitive diagnosis of BCA if a neck mass was present

  19. GLTP mediated non-vesicular GM1 transport between native membranes.

    Directory of Open Access Journals (Sweden)

    Ines Lauria

    Full Text Available Lipid transfer proteins (LTPs are emerging as key players in lipid homeostasis by mediating non-vesicular transport steps between two membrane surfaces. Little is known about the driving force that governs the direction of transport in cells. Using the soluble LTP glycolipid transfer protein (GLTP, we examined GM1 (monosialotetrahexosyl-ganglioside transfer to native membrane surfaces. With artificial GM1 donor liposomes, GLTP can be used to increase glycolipid levels over natural levels in either side of the membrane leaflet, i.e., external or cytosolic. In a system with native donor- and acceptor-membranes, we find that GLTP balances highly variable GM1 concentrations in a population of membranes from one cell type, and in addition, transfers lipids between membranes from different cell types. Glycolipid transport is highly efficient, independent of cofactors, solely driven by the chemical potential of GM1 and not discriminating between the extra- and intracellular membrane leaflet. We conclude that GLTP mediated non-vesicular lipid trafficking between native membranes is driven by simple thermodynamic principles and that for intracellular transport less than 1 µM GLTP would be required in the cytosol. Furthermore, the data demonstrates the suitability of GLTP as a tool for artificially increasing glycolipid levels in cellular membranes.

  20. Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging.

    Science.gov (United States)

    Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R

    2013-01-16

    Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

  1. Differentiation of meningiomas from histologic mimics via the use of claudin-1

    International Nuclear Information System (INIS)

    Shalaby, A.M.R.; Naquib, S.M.

    2006-01-01

    Meningiomas may be occasionally difficult to distinguish pathologically from other tumors of the central nervous system. Claudin-1 is a tight junction-associated protein recently shown to be expressed in anaplastic meningiomas. This study aimed at assessment whether immunohistochemical staining for claudin-1 could help distinguish meningiomas from histologic mimics, compared with commonly used markers. Tissue sections from 20 meningothelial meningiomas, 40 fibrous meningiomas, 20 atypical meningiomas, 14 solitary fibrous tumors of the meninges, 10 meningeal hemangiopericytomas, and 14 vestibular schwannomas were stained immunohistochemically for claudin-1, epithelial membrane antigen, S-100 protein, CD34, and glial fibrillary acidic protein. In total, 42(53%) of 80 meningiomas were immunoreactive for claudin-1, whereas none of the other tumors were positive. In contrast, there was considerable overlap in the distribution of the other antibodies evaluated. Claudin-1 seems to be a specific marker for meningiomas in this context. Although its sensitivity is relatively low, claudin-1 may be helpful in a panel of immunostains to distinguish meningiomas from histologic mimics. (author)

  2. Synthesis of aminocyclopentanols: a-D-galacto configured sugar mimics

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Lundt, Inge

    2005-01-01

    Four aminocyclopentanols, as mimics of putative intermediates in hydrolysis of a-D-galactosides, have been synthesized through a number of stereoselective transformations, using the cis-fused cyclopentane-1,4-lactone (1R, 5S, 7R, 8R)-7,8-dihydroxy-2-oxabicyclo[3.3.0]oct-3-one 1 as a chiral buildi...

  3. Gene-specific cell labeling using MiMIC transposons.

    Science.gov (United States)

    Gnerer, Joshua P; Venken, Koen J T; Dierick, Herman A

    2015-04-30

    Binary expression systems such as GAL4/UAS, LexA/LexAop and QF/QUAS have greatly enhanced the power of Drosophila as a model organism by allowing spatio-temporal manipulation of gene function as well as cell and neural circuit function. Tissue-specific expression of these heterologous transcription factors relies on random transposon integration near enhancers or promoters that drive the binary transcription factor embedded in the transposon. Alternatively, gene-specific promoter elements are directly fused to the binary factor within the transposon followed by random or site-specific integration. However, such insertions do not consistently recapitulate endogenous expression. We used Minos-Mediated Integration Cassette (MiMIC) transposons to convert host loci into reliable gene-specific binary effectors. MiMIC transposons allow recombinase-mediated cassette exchange to modify the transposon content. We developed novel exchange cassettes to convert coding intronic MiMIC insertions into gene-specific binary factor protein-traps. In addition, we expanded the set of binary factor exchange cassettes available for non-coding intronic MiMIC insertions. We show that binary factor conversions of different insertions in the same locus have indistinguishable expression patterns, suggesting that they reliably reflect endogenous gene expression. We show the efficacy and broad applicability of these new tools by dissecting the cellular expression patterns of the Drosophila serotonin receptor gene family. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Laser Doppler anemometry measurements of steady flow through two bi-leaflet prosthetic heart valves

    Directory of Open Access Journals (Sweden)

    Ovandir Bazan

    2013-12-01

    Full Text Available INTRODUCTION: In vitro hydrodynamic characterization of prosthetic heart valves provides important information regarding their operation, especially if performed by noninvasive techniques of anemometry. Once velocity profiles for each valve are provided, it is possible to compare them in terms of hydrodynamic performance. In this first experimental study using laser doppler anemometry with mechanical valves, the simulations were performed at a steady flow workbench. OBJECTIVE: To compare unidimensional velocity profiles at the central plane of two bi-leaflet aortic prosthesis from St. Jude (AGN 21 - 751 and 21 AJ - 501 models exposed to a steady flow regime, on four distinct sections, three downstream and one upstream. METHODS: To provide similar conditions for the flow through each prosthesis by a steady flow workbench (water, flow rate of 17L/min. and, for the same sections and sweeps, to obtain the velocity profiles of each heart valve by unidimensional measurements. RESULTS: It was found that higher velocities correspond to the prosthesis with smaller inner diameter and instabilities of flow are larger as the section of interest is closer to the valve. Regions of recirculation, stagnation of flow, low pressure, and flow peak velocities were also found. CONCLUSIONS: Considering the hydrodynamic aspect and for every section measured, it could be concluded that the prosthesis model AGN 21 - 751 (RegentTM is superior to the 21 AJ - 501 model (Master Series. Based on the results, future studies can choose to focus on specific regions of the these valves.

  5. Obstructed bi-leaflet prosthetic mitral valve imaging with real-time three-dimensional transesophageal echocardiography.

    Science.gov (United States)

    Shimbo, Mai; Watanabe, Hiroyuki; Kimura, Shunsuke; Terada, Mai; Iino, Takako; Iino, Kenji; Ito, Hiroshi

    2015-01-01

    Real-time three-dimensional transesophageal echocardiography (RT3D-TEE) can provide unique visualization and better understanding of the relationship among cardiac structures. Here, we report the case of an 85-year-old woman with an obstructed mitral prosthetic valve diagnosed promptly by RT3D-TEE, which clearly showed a leaflet stuck in the closed position. The opening and closing angles of the valve leaflets measured by RT3D-TEE were compatible with those measured by fluoroscopy. Moreover, RT3D-TEE revealed, in the ring of the prosthetic valve, thrombi that were not visible on fluoroscopy. RT3D-TEE might be a valuable diagnostic technique for prosthetic mitral valve thrombosis. © 2014 Wiley Periodicals, Inc.

  6. Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance

    Science.gov (United States)

    2013-01-01

    Background Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. Methods 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. Results Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). Conclusions Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria. PMID:23398958

  7. Contribution of mitral valve leaflet length and septal wall thickness to outflow tract obstruction in patients with hypertrophic cardiomyopathy.

    Science.gov (United States)

    Morant, Kareem; Mikami, Yoko; Nevis, Immaculate; McCarty, David; Stirrat, John; Scholl, David; Rajchl, Martin; Giannoccaro, Peter; Kolman, Louis; Heydari, Bobby; Lydell, Carmen; Howarth, Andrew; Grant, Andrew; White, James A

    2017-08-01

    We sought to examine whether elongation of the mitral valve leaflets in patients with hypertrophic cardiomyopathy (HCM) is synergistic to septal wall thickness (SWT) in the development of left ventricular outflow tract obstruction (LVOTO). HCM is a common genetic cardiac disease characterized by asymmetric septal hypertrophy and predisposition towards LVOTO. It has been reported that elongation of the mitral valve leaflets may be a primary phenotypic feature and contribute to LVOTO. However, the relative contribution of this finding versus SWT has not been studied. 152 patients (76 with HCM and 76 non-diseased age, race and BSA-matched controls) and 18 young, healthy volunteers were studied. SWT and the anterior mitral valve leaflet length (AMVLL) were measured using cine MRI. The combined contribution of these variables (SWT × AMVLL) was described as the Septal Anterior Leaflet Product (SALP). Peak LVOT pressure gradient was determined by Doppler interrogation and defined as "obstructive" if ≥ 30 mmHg. Patients with HCM were confirmed to have increased AMVLL compared with controls and volunteers (p SALP were significantly higher in patients with LVOTO (N = 17) versus without. SALP showed modest improvement in predictive accuracy for LVOTO (AUC = 0.81) among the HCM population versus SWT alone (AUC = 0.77). However, in isolated patients this variable identified patients with LVOTO despite modest SWT. Elongation of the AMVLL is a primary phenotypic feature of HCM. While incremental contributions to LVOTO appear modest at a population level, specific patients may have dominant contribution to LVOTO. The combined marker of SALP allows for maintained identification of such patients despite modest increases in SWT.

  8. Contribution of ankyrin-band 3 complexes to the organization and mechanical properties of the membrane skeleton of human erythrocyte

    Energy Technology Data Exchange (ETDEWEB)

    Shen, B.W. [Argonne National Lab., IL (United States). Biological and Medical Research Div.

    1995-02-01

    To understand the role of ankyrin-band 3 complexes in the organization of the spectrin-based membrane skeleton and its contribution to the mechanical properties of human erythrocytes, intact skeletons and single-layered skeleton leaflets were prepared from intact and physically sheared membrane ghosts, expanded in low salt buffer, and examined by transmission electron microscopy. While the structures of intact skeletons and single-layered skeleton leaflets shared many common features, including rigid junctional complexes of spectrin, actin, and band 4.1; short stretches ({approximately}50 {angstrom}) of flexible spectrin filaments; and globular masses of ankyrin-band 3 complexes situated close to the middle of the spectrin filaments, the definition of structural units in the intact skeleton is obscured by the superposition of the two layers. However, the spatial disposition of structural elements can be clearly defined in the images of the single-layered skeleton leaflets. Partially expanded skeletal leaflets contain conglomerates of ankyrin-band 3 complexes arranged in a circular or clove-leaf configuration that straddles multiple strands of thick spectrin cables, presumably reflecting the association of ankyrin-band 3 complexes on neighboring spectrin tetramers as well as the lateral association of the spectrin filaments. Hyperexpansion of the skeleton leaflets led to dissociation of the conglomerates of ankyrin-band 3 complexes, full-extension of the spectrin tetramers, and separation of the individual strands of spectrin tetramers. Clearly defined stands of spectrin tetramers in the hyperexpanded single-layered skeletal leaflets often contained two sets of globular protein masses that divided the spectrin tetramers into three segments of approximately equal length.

  9. Using routinely collected data to evaluate a leaflet campaign to increase the presentation of people with memory problems to general practice: a locality based controlled study

    Directory of Open Access Journals (Sweden)

    Tom Chan

    2010-09-01

    Conclusions During a leaflet campaign the recording and management ofmemory problems increased. However, there was greater improvement in the control locality. This study demonstrates the importance of including a control group and the strengths of routine primary care data.

  10. Membrane fluidity increases during apoptosis of sheep ileal Peyer's patch B cells

    International Nuclear Information System (INIS)

    Jourd'heuil, D.; Aspinall, A.; Reynolds, J.D.; Meddings, J.B.

    1996-01-01

    To investigate specific plasma membrane structural changes associated with apoptosis, whole cells and purified plasma membranes of apoptotic B cells from the ileal Peyer's patch of sheep were analyzed for their 'membrane fluidity'. The ileal Peyer's patch of sheep provided a large number of B cells required for plasma membrane isolation (>5 x 10 9 ). As the incidence of apoptosis increased with time of culture, the fluidity of purified plasma membranes, as measured with the fluorophore DPH (diphenylhexatriene), increased. To evaluate this phenomenon with intact cells, B cells at different apoptotic stages were fractionated on discontinuous Percoll gradients. Similar results were obtained using the fluorophore TMA-DPH (trimethylammoniumdiphenylhexatriene), which has been shown to localize specifically to the plasma membrane. Functionally, the increase in plasma membrane fluidity associated with apoptosis may represent either a mechanism to cycle phosphatidylserine to the outer leaflet, mediating phagocytic recognition of apoptotic cells, or a consequence of this event. (author). 20 refs., 1 tab., 4 figs

  11. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

    At Stanford University, Boxer lab, I worked on membrane fusion of small unilamellar lipid vesicles to flat membranes tethered to glass surfaces. This geometry closely resembles biological systems in which liposomes fuse to plasma membranes. The fusion mechanism was studied using DNA zippering...... between complementary strands linked to the two apposing membranes closely mimicking the zippering mechanism of SNARE fusion complexes....

  12. Comparative anatomy of leaflets of Zamia acuminata and Z. pseudomonticola (Zamiaceae in Costa Rica

    Directory of Open Access Journals (Sweden)

    Rafael Acuña-Castillo

    2013-06-01

    Full Text Available The genus Zamia is morphologically and ecologically the most diverse of the order Cycadales. Throughout its history this genus has been restricted to the New World and is presently almost entirely restricted to the Neotropics. Unusual anatomical traits of the leaflets, such as the sunken stomata and thick cuticle, are common in this and related genera. The objective of this research was to study and compare the leaflet anatomy of Zamia acuminata and Z. pseudomonticola and establish possible phylogenetic relationships between the anatomical traits and the near relatives of these species. The leaf material was obtained from living plants and then processed for electron microscopy study. We found that both species are very similar to each other and to Z. fairchildiana, and that they share several unusual traits with other species of the genus, such as the parenchyma morphology, the spatial distribution of tissues between the veins and the stomata morphology. The main differences between these species were seen in their fiber clusters and in the abundance of trichome basal cells on the epidermis. The anatomical similarities between the three species could be the result of their close phylogenetic relationship and the divergences between them could be the result of recent speciation during the Pleistocene, resulting from geological changes in Southern Costa Rica.Zamia es morfológica y ecológicamente el género más diverso del orden Cycadales. Este género siempre ha estado restringido a América, pero en la actualidad habita principalmente en la región neotropical. Características anatómicas inusuales en los foliolos como los estomas hundidos y las cutículas gruesas son comunes en Zamia y géneros afines. El objetivo de este trabajo consiste en comparar la anatomía de los foliolos de Zamia acuminata y Z. pseudomonticola y establecer posibles relaciones filogenéticas entre las características anatómicas y los parientes cercanos de esta

  13. Descending projections of the hamster intergeniculate leaflet: relationship to the sleep/arousal and visuomotor systems

    Science.gov (United States)

    Morin, Lawrence P.; Blanchard, Jane H.

    2005-01-01

    The intergeniculate leaflet (IGL), homolog of the primate pregeniculate nucleus, modulates circadian rhythms. However, its extensive anatomical connections suggest that it may regulate other systems, particularly those for visuomotor function and sleep/arousal. Here, descending IGL-efferent pathways are identified with the anterograde tracer, Phaseolus vulgaris leucoagglutinin, with projections to over 50 brain stem nuclei. Projections of the ventral lateral geniculate are similar, but more limited. Many of the nuclei with IGL afferents contribute to circuitry governing visuomotor function. These include the oculomotor, trochlear, anterior pretectal, Edinger-Westphal, and the terminal nuclei; all layers of the superior colliculus, interstitial nucleus of the medial longitudinal fasciculus, supraoculomotor periaqueductal gray, nucleus of the optic tract, the inferior olive, and raphe interpositus. Other target nuclei are known to be involved in the regulation of sleep, including the lateral dorsal and pedunculopontine tegmentum. The dorsal raphe also receives projections from the IGL and may contribute to both sleep/arousal and visuomotor function. However, the locus coeruleus and medial vestibular nucleus, which contribute to sleep and eye movement regulation and which send projections to the IGL, do not receive reciprocal projections from it. The potential involvement of the IGL with the sleep/arousal system is further buttressed by existing evidence showing IGL-efferent projections to the ventrolateral preoptic area, dorsomedial, and medial tuberal hypothalamus. In addition, the great majority of all regions receiving IGL projections also receive input from the orexin/hypocretin system, suggesting that this system contributes not only to the regulation of sleep, but to eye movement control as well.

  14. How sociodemographic features impact subjects' opinion on packages leaflets of medicines?

    Directory of Open Access Journals (Sweden)

    Carla Pires

    2017-09-01

    Full Text Available Background Packages leaflets (PLs are essential for the safe use and efficacy of medicines. Aims To quantify the opinion of users of medicines on PLs through the application of a self-administered Likert scale, taking into consideration subjects’ sociodemographic data. Methods Participants were enrolled from two Portuguese regions: urban/littoral (Lisbon and rural/interior (Centre. 503 participants were included: 53 per cent males, 45 per cent 12 years of schooling. A questionnaire was used to collect the sociodemographic data. A Likert scale was self-administered to rate the characteristics of 12 randomized PLs (6 from prescription medicines and 6 from over-the-counter medicines (August-December 2014. An invitation was send to several institutions (e.g., municipal councils. The inclusion criteria were: agreeing, be capable of reading/writing, and be more than 17 years old. Results In the Likert scores obtained, no significant differences were found related to region, sex, marital status, age group (≥65 years and other, and employment status of participants. By contrast, significant differences were found related to education (2=42.747; p 12 years of schooling, more regular reading habits (2 or more books/year, higher income and less frequent medicines use, showed a more negative global opinion on PLs. Conclusion Sociodemographic data are important to understand users’ opinion on PLs. It seems that more educated subjects are more demanding. A lower socio-economic status positively influenced the participants’ opinion, with subjects’ poorer education being a relevant factor in this population. A higher frequency of taking medicines also positively contributed to a better opinion, probably due to a greater familiarity with PLs.

  15. Sexual health-related information delivery - are patient information leaflets still relevant?

    Science.gov (United States)

    Varma, Rick; Chung, Charles; Townsend, Amanda; Power, Melissa

    2016-06-01

    Background Patient information leaflets (PILs) are widely utilised within publically funded sexual health clinics to deliver sexual health-related information (SHRI); however, their continued value to clients in the era of social media is unclear. This study aimed to evaluate clients' opinions on three newly developed PILs and examine client views on other forms of SHRI delivery. An anonymous self-administered questionnaire was completed by clients attending the Western Sydney Sexual Health Centre (WSSHC) in 2012. High-risk population (HRP) vs non-high-risk population (non-HRP) views on PILs vs alternative methods of SHRI delivery were analysed by using Mann-Whitney U, Wilcoxon, McNemar and χ(2) tests. Over half (210/315; (67%)) of the consecutive clients from a culturally diverse population completed the survey. Sex workers (SW) and young people (YP) were significantly likely to have a high school education than non-HRP (PInformation Link (SHIL), a state-wide website and telephone line, were ranked significantly higher as a means of SHRI delivery on a Likert scale than newer technologies including Facebook (P<0.001), email (P<0.001), mobile phone applications (P<0.001), TVs in waiting rooms (P<0.001) and business cards (P<0.001). There was no significant difference in opinion between HRP and non-HRP. This study provides evidence for the ongoing use of PILs to deliver SHRI to clinic attendees, in conjunction with other forms of SHRI delivery such as websites and SHIL. Novel methods may require additional consumer engagement and a greater understanding of specific population's needs.

  16. Mitral valve repair. Quadrangular resection of the posterior leaflet in patients with myxomatous degeneration

    Directory of Open Access Journals (Sweden)

    Pablo Maria Alberto Pomerantzeff

    1999-09-01

    Full Text Available OBJECTIVE - To analyze the immediate and late results of mitral valve repair with quadrangular resection of the posterior leaflet without the use of a prosthetic ring annuloplasty. METHODS - Using this technique, 118 patients with mitral valve prolapse who underwent mitral repair from January '84 through December '96 were studied. Age ranged from 30 to 86 (mean = 59.1±11.8 years and 62.7% were males. An associated surgery was performed in 22% of the patients, and coronary artery bypass graft was the most frequently performed surgery (15 patients - 12.7%. In 20 (16.9% patients other associated techniques of mitral valve repair were used and shortening of elongated chordae tendineae was the most frequent one (6 patients. RESULTS - Immediate mortality was 0.9% (one patient. Long-term rates for thromboembolism, endocarditis, re-operation and death in the late postoperative period were 0.4%, 0.4%, 1.7% and 2.2% patients/year, respectively. The actuarial curve of survival was 83.8±8.6% over 12 years; survival free from re-operation was 91.8±4.3%, free from endocarditis was 99.2±0.8% and free from thromboembolism was 99.2±0.8%. In the late postoperative period, 93.8% of the patients were in functional class 1 (NYHA, with a complete follow-up in 89.7% of the patients. CONCLUSION - Patients with mitral valve prolapse who undergo mitral valve repair using this technique have a satisfactory prognosis over 12 years.

  17. Spontaneous Spinal Epidural Hematoma as a Potentially Important Stroke Mimic

    Directory of Open Access Journals (Sweden)

    Tetsu Akimoto

    2014-01-01

    Full Text Available Hemiparesis develops in response to a wide range of neurological disorders, such as stroke, neoplasms and several inflammatory processes. Occasionally, it may also occur due to a lesion located in the high cervical spinal cord. In this concise review, we describe the features of spontaneous spinal epidural hematoma, which should be included in the large list of stroke mimics. Various concerns regarding the diagnostic and therapeutic conundrums relating to the condition are also discussed.

  18. Constraining cyclic peptides to mimic protein structure motifs

    DEFF Research Database (Denmark)

    Hill, Timothy A.; Shepherd, Nicholas E.; Diness, Frederik

    2014-01-01

    peptides can have protein-like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three-dimensional structures of strand, turn or helical segments of peptides...... and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic pepti-domimetics that refine peptide structure and confer biological properties....

  19. The ability of lizards to identify an artificial Batesian mimic.

    Science.gov (United States)

    Beneš, Josef; Veselý, Petr

    2017-08-01

    Birds are usually considered the main predators shaping the evolution of aposematic signals and mimicry. Nevertheless, some lizards also represent predominately visually oriented predators, so they may also play an important role in the evolution of aposematism. Despite this fact, experimental evidence regarding the responses of lizards to aposematic prey is very poor compared to such evidence in birds. Lizards possess very similar sensory and cognitive abilities to those of birds and their response to aposematic prey may thus be affected by very similar processes. We investigated the reactions of a lizard, the Gran Canaria skink (Chalcides sexlineatus), to an aposematic prey and its artificial Batesian mimic. Further, we attempted to ascertain whether the lizard's food experience has any effect on its ability to recognise an artificial Batesian mimic, by using two groups of predators differing in their prior experience with the prey from which the mimic was fabricated. The red firebug (Pyrrhocoris apterus) was used as an aposematic model, and the Guyana spotted roach (Blaptica dubia) as the palatable prey from which the mimic was fabricated. The appearance of the roach was modified by a paper sticker placed on its back. The skinks showed a strong aversion towards the model firebug. They also avoided attacking the cockroaches with the firebug pattern sticker. This suggests that a visual rather than a chemical signal is responsible for this aversion. The protection provided by the firebug sticker was even effective when the skinks were familiar with unmodified cockroaches (previous food experience). Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours.

    Science.gov (United States)

    Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack; Bortell, Rita; Greiner, Dale L; Shultz, Leonard D; Han, Gang; McCormick, Beth A

    2016-07-25

    Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.

  1. To die or not to die? Lessons from lesion mimic mutants

    KAUST Repository

    Bruggeman, Quentin

    2015-01-30

    Programmed cell death (PCD) is a ubiquitous genetically regulated process consisting in an activation of finely controlled signaling pathways that lead to cellular suicide. Although some aspects of PCD control appear evolutionary conserved between plants, animals and fungi, the extent of conservation remains controversial. Over the last decades, identification and characterization of several lesion mimic mutants (LMM) has been a powerful tool in the quest to unravel PCD pathways in plants. Thanks to progress in molecular genetics, mutations causing the phenotype of a large number of LMM and their related suppressors were mapped, and the identification of the mutated genes shed light on major pathways in the onset of plant PCD such as (i) the involvements of chloroplasts and light energy, (ii) the roles of sphingolipids and fatty acids, (iii) a signal perception at the plasma membrane that requires efficient membrane trafficking, (iv) secondary messengers such as ion fluxes and ROS and (v) the control of gene expression as the last integrator of the signaling pathways.

  2. To die or not to die? Lessons from lesion mimic mutants

    Directory of Open Access Journals (Sweden)

    Quentin eBruggeman

    2015-01-01

    Full Text Available Programmed cell death (PCD is a ubiquitous genetically regulated process consisting in an activation of finely controlled signaling pathways that lead to cellular suicide. Although some aspects of PCD control appear evolutionary conserved between plants, animals and fungi, the extent of conservation remains controversial. Over the last decades, identification and characterization of several lesion mimic mutants (LMM has been a powerful tool in the quest to unravel PCD pathways in plants. Thanks to progress in molecular genetics, mutations causing the phenotype of a large number of LMM and their related suppressors were mapped, and the identification of the mutated genes shed light on major pathways in the onset of plant PCD such as (i the involvements of chloroplasts and light energy, (ii the roles of sphingolipids and fatty acids, (iii a signal perception at the plasma membrane that requires efficient membrane trafficking, (iv secondary messengers such as ion fluxes and ROS and (v the control of gene expression as the last integrator of the signaling pathways.

  3. Platelet factor 4 activity against P. falciparum and its translation to nonpeptidic mimics as antimalarials.

    Science.gov (United States)

    Love, Melissa S; Millholland, Melanie G; Mishra, Satish; Kulkarni, Swapnil; Freeman, Katie B; Pan, Wenxi; Kavash, Robert W; Costanzo, Michael J; Jo, Hyunil; Daly, Thomas M; Williams, Dewight R; Kowalska, M Anna; Bergman, Lawrence W; Poncz, Mortimer; DeGrado, William F; Sinnis, Photini; Scott, Richard W; Greenbaum, Doron C

    2012-12-13

    Plasmodium falciparum pathogenesis is affected by various cell types in the blood, including platelets, which can kill intraerythrocytic malaria parasites. Platelets could mediate these antimalarial effects through human defense peptides (HDPs), which exert antimicrobial effects by permeabilizing membranes. Therefore, we screened a panel of HDPs and determined that human platelet factor 4 (hPF4) kills malaria parasites inside erythrocytes by selectively lysing the parasite digestive vacuole (DV). PF4 rapidly accumulates only within infected erythrocytes and is required for parasite killing in infected erythrocyte-platelet cocultures. To exploit this antimalarial mechanism, we tested a library of small, nonpeptidic mimics of HDPs (smHDPs) and identified compounds that kill P. falciparum by rapidly lysing the parasite DV while sparing the erythrocyte plasma membrane. Lead smHDPs also reduced parasitemia in a murine malaria model. Thus, identifying host molecules that control parasite growth can further the development of related molecules with therapeutic potential. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Engineering poly(hydroxy butyrate-co-hydroxy valerate) based vascular scaffolds to mimic native artery.

    Science.gov (United States)

    Deepthi, S; Nivedhitha Sundaram, M; Vijayan, Ponni; Nair, Shantikumar V; Jayakumar, R

    2018-04-01

    Electrospun tri-layered fibrous scaffold incorporating VEGF and Platelet Factor Concentrate (PFC) in multiple layers having different layer architectures was designed to mimic native artery. The scaffold consisted of longitudinally aligned poly(hydroxy butyrate-co-hydroxy valerate) (PHBV) and poly(vinyl alcohol) (PVA) nanofibers (inner layer), radially aligned PHBV-elastin nanofibers (middle layer) to provide the bi-directional alignment and combination of longitudinally aligned PHBV-elastin and random PHBV/PVA multiscale fibers (peripheral layer). Tubular constructs of diameter <6 mm were developed. The developed electrospun fibers were characterised by Scanning Electron Microscope (SEM), Fourier Transform Infrared Spectroscopy and Tensile tests. Further the burst strength, compliance and stiffness index of tri-layered tubular scaffold was evaluated. SEM images of fibrous layers showed the typical longitudinal and radial alignment of fibers in the tubular construct. SEM images showed that the prepared PHBV nanofibers were in the range of 500-800 nm and PHBV microfibers were of 1-2 μm in diameter in the tri-layered electrospun membrane. PVA nanofibers were of size 200-250 nm. The tensile strength, percentage compliance and stiffness index of tri-layered membrane was in accordance with that of native small blood vessels. The developed tri-layered membrane was blood compatible, with hemolysis degree 0.85 ± 0.21% and did not activate platelets. Controlled release of VEGF and PFC was observed from the scaffold. The biocompatibility of the tri-layered scaffold was evaluated using HUVECs, SMCs and MSCs and SMCs infiltration from the outer layer was also evaluated. Specific protein expression for the HUVECs and SMCs was evaluated by flow cytometry and immunocytochemistry. HUVECs and SMCs exhibited good elongation and alignment along the direction of fibers and was found to maintain its CD31, VE-Cadherin and αSMA expression respectively. The results

  5. Plasma Membrane ATPase Activity following Reversible and Irreversible Freezing Injury 1

    Science.gov (United States)

    Iswari, S.; Palta, Jiwan P.

    1989-01-01

    Plasma membrane ATPase has been proposed as a site of functional alteration during early stages of freezing injury. To test this, plasma membrane was purified from Solanum leaflets by a single step partitioning of microsomes in a dextran-polyethylene glycol two phase system. Addition of lysolecithin in the ATPase assay produced up to 10-fold increase in ATPase activity. ATPase activity was specific for ATP with a Km around 0.4 millimolar. Presence of the ATPase enzyme was identified by immunoblotting with oat ATPase antibodies. Using the phase partitioning method, plasma membrane was isolated from Solanum commersonii leaflets which had four different degrees of freezing damage, namely, slight (reversible), partial (partially reversible), substantial and total (irreversible). With slight (reversible) damage the plasma membrane ATPase specific activity increased 1.5- to 2-fold and its Km was decreased by about 3-fold, whereas the specific activity of cytochrome c reductase and cytochrome c oxidase in the microsomes were not different from the control. However, with substantial (lethal, irreversible) damage, there was a loss of membrane protein, decrease in plasma membrane ATPase specific activity and decrease in Km, while cytochrome c oxidase and cytochrome c reductase were unaffected. These results support the hypothesis that plasma membrane ATPase is altered by slight freeze-thaw stress. Images Figure 1 Figure 2 PMID:16666856

  6. A novel biotinylated lipid raft reporter for electron microscopic imaging of plasma membrane microdomains[S

    Science.gov (United States)

    Krager, Kimberly J.; Sarkar, Mitul; Twait, Erik C.; Lill, Nancy L.; Koland, John G.

    2012-01-01

    The submicroscopic spatial organization of cell surface receptors and plasma membrane signaling molecules is readily characterized by electron microscopy (EM) via immunogold labeling of plasma membrane sheets. Although various signaling molecules have been seen to segregate within plasma membrane microdomains, the biochemical identity of these microdomains and the factors affecting their formation are largely unknown. Lipid rafts are envisioned as submicron membrane subdomains of liquid ordered structure with differing lipid and protein constituents that define their specific varieties. To facilitate EM investigation of inner leaflet lipid rafts and the localization of membrane proteins therein, a unique genetically encoded reporter with the dually acylated raft-targeting motif of the Lck kinase was developed. This reporter, designated Lck-BAP-GFP, incorporates green fluorescent protein (GFP) and biotin acceptor peptide (BAP) modules, with the latter allowing its single-step labeling with streptavidin-gold. Lck-BAP-GFP was metabolically biotinylated in mammalian cells, distributed into low-density detergent-resistant membrane fractions, and was readily detected with avidin-based reagents. In EM images of plasma membrane sheets, the streptavidin-gold-labeled reporter was clustered in 20–50 nm microdomains, presumably representative of inner leaflet lipid rafts. The utility of the reporter was demonstrated in an investigation of the potential lipid raft localization of the epidermal growth factor receptor. PMID:22822037

  7. [Ultrastructural organization of cytoplasmatic membrane of Anaerobacter polyendosporus studied by electron microscopic cryofractography].

    Science.gov (United States)

    Duda, V I; Suzina, N E; Dmitriev, V V

    2001-01-01

    Anaerobacter polyendosporus cells do not have typical mesosomes. However, the analysis of this anaerobic multispore bacterium by electron microscopic cryofractography showed that its cytoplasmic membrane contains specific intramembrane structures in the form of flat lamellar inverted lipid membranes tenths of nanometers to several microns in size. It was found that these structures are located in the hydrophobic interior between the outer and inner leaflets of the cytoplasmic membrane and do not contain intramembrane particles that are commonly present on freeze-fracture replicas. The flat inverted lipid membranes were revealed in bacterial cells cultivated under normal growth conditions, indicating the existence of a complex-type compartmentalization in biological membranes, which manifests itself in the formation of intramembrane compartments having the appearance of vesicles and inverted lipid membranes.

  8. The frequency, characteristics and aetiology of stroke mimic presentations: a narrative review.

    Science.gov (United States)

    McClelland, Graham; Rodgers, Helen; Flynn, Darren; Price, Christopher I

    2018-05-01

    A significant proportion of patients with acute stroke symptoms have an alternative 'mimic' diagnosis. A narrative review was carried out to explore the frequency, characteristics and aetiology of stroke mimics. Prehospital and thrombolysis-treated patients were described separately. Overall, 9972 studies were identified from the initial search and 79 studies were included with a median stroke mimic rate of 19% (range: 1-64%). The prehospital median was 27% (range: 4-43%) and the thrombolysis median 10% (range: 1-25%). Seizures, migraines and psychiatric disorders are the most frequently reported causes of stroke mimics. Several characteristics are consistently associated with stroke mimics; however, they do not fully exclude the possibility of stroke. Nineteen per cent of suspected stroke patients had a mimic condition. Stroke mimics were more common with younger age and female sex. The range of mimic diagnoses, a lack of clear differentiating characteristics and the short treatment window for ischaemic stroke create challenges for early identification.

  9. Exergames versus self-regulated exercises with instruction leaflets to improve adherence during geriatric rehabilitation: a randomized controlled trial.

    Science.gov (United States)

    Oesch, Peter; Kool, Jan; Fernandez-Luque, Luis; Brox, Ellen; Evertsen, Gunn; Civit, Anton; Hilfiker, Roger; Bachmann, Stefan

    2017-03-23

    Improving mobility in elderly persons is a primary goal in geriatric rehabilitation. Self-regulated exercises with instruction leaflets are used to increase training volume but adherence is often low. Exergames may improve adherence. This study therefore compared exergames with self-regulated exercise using instruction leaflets. The primary outcome was adherence. Secondary outcomes were enjoyment, motivation and balance during walking. Design: single center parallel group non-blinded randomized controlled trial with central stratified randomization. center for geriatric inpatient rehabilitation. Included were patients over 65 with mobility restrictions who were able to perform self-regulated exercise. Patients were assigned to self-regulated exercise using a) exergames on Windows Kinect® (exergame group EG) or b) instruction leaflets (conventional group CG). During two 30 min sessions physical therapists instructed self-regulated exercise to be conducted twice daily during thirty minutes during ten working days. Patients reported adherence (primary outcome), enjoyment and motivation daily. Balance during walking was measured blind before and after the treatment phase with an accelerometer. Analysis was by intention to treat. Repeated measures mixed models and Cohen's d effect sizes (ES, moderate if >0.5, large if > 0.8) with 95% CIs were used to evaluate between-group effects over time. Alpha was set at 0.05. From June 2014 to December 2015 217 patients were evaluated and 54 included, 26 in the EG and 28 in the CG. Adverse effects were observed in two patients in the EG who stopped because of pain during exercising. Adherence was comparable at day one (38 min. in the EG and 42 min. in the CG) and significantly higher in the CG at day 10 (54 min. in the CG while decreasing to 28 min. in the EG, p = 0.007, ES 0.94, 0.39-0.151). Benefits favoring the CG were also observed for enjoyment (p = 0.001, ES 0.88, 0.32 - 1.44) and motivation (p = 0

  10. The MIMIC Method with Scale Purification for Detecting Differential Item Functioning

    Science.gov (United States)

    Wang, Wen-Chung; Shih, Ching-Lin; Yang, Chih-Chien

    2009-01-01

    This study implements a scale purification procedure onto the standard MIMIC method for differential item functioning (DIF) detection and assesses its performance through a series of simulations. It is found that the MIMIC method with scale purification (denoted as M-SP) outperforms the standard MIMIC method (denoted as M-ST) in controlling…

  11. The Mediated MIMIC Model for Understanding the Underlying Mechanism of DIF

    Science.gov (United States)

    Cheng, Ying; Shao, Can; Lathrop, Quinn N.

    2016-01-01

    Due to its flexibility, the multiple-indicator, multiple-causes (MIMIC) model has become an increasingly popular method for the detection of differential item functioning (DIF). In this article, we propose the mediated MIMIC model method to uncover the underlying mechanism of DIF. This method extends the usual MIMIC model by including one variable…

  12. The MIMIC Code Repository: enabling reproducibility in critical care research.

    Science.gov (United States)

    Johnson, Alistair Ew; Stone, David J; Celi, Leo A; Pollard, Tom J

    2018-01-01

    Lack of reproducibility in medical studies is a barrier to the generation of a robust knowledge base to support clinical decision-making. In this paper we outline the Medical Information Mart for Intensive Care (MIMIC) Code Repository, a centralized code base for generating reproducible studies on an openly available critical care dataset. Code is provided to load the data into a relational structure, create extractions of the data, and reproduce entire analysis plans including research studies. Concepts extracted include severity of illness scores, comorbid status, administrative definitions of sepsis, physiologic criteria for sepsis, organ failure scores, treatment administration, and more. Executable documents are used for tutorials and reproduce published studies end-to-end, providing a template for future researchers to replicate. The repository's issue tracker enables community discussion about the data and concepts, allowing users to collaboratively improve the resource. The centralized repository provides a platform for users of the data to interact directly with the data generators, facilitating greater understanding of the data. It also provides a location for the community to collaborate on necessary concepts for research progress and share them with a larger audience. Consistent application of the same code for underlying concepts is a key step in ensuring that research studies on the MIMIC database are comparable and reproducible. By providing open source code alongside the freely accessible MIMIC-III database, we enable end-to-end reproducible analysis of electronic health records. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  13. A Less Known Stroke Mimic: Posterior Reversible Encephalopathy Syndrome

    Directory of Open Access Journals (Sweden)

    Keneilwe Malomo

    2016-04-01

    Full Text Available Posterior reversible encephalopathy syndrome (PRES is a clinico-neuro-radiological diagnosis, which can complicate a wide range of conditions. Clinical features include generalised and/or focal neurological deficits. These features are also present in neurovascular disorders, such as stroke. Currently, emphasis in the management of hyperacute stroke is thrombolysis, and it is important to bear in mind stroke mimics as a possible cause of clinical features. The Authors present the case of a 66-year-old man, who presented with acute focal neurological deficit. His brain imaging and history were consistent with PRES.

  14. Approaches to mimic the metallic sheen in beetles

    DEFF Research Database (Denmark)

    Lenau, Torben Anker; Aggerbeck, Martin; Nielsen, Steffen

    2009-01-01

    layers have high and low refractive index. The other is the Bouligand structure where birefringent chiral nanofibres are organised in spiral structures. The paper describes work done to explore different approaches to mimic these structures using polymer based materials and production methods...... that are suitable for more complex double curved geometry. One approach is to use alternating layers of 2 different polymers applied by dipping and another is applying cholesteric liquid crystals in paint. However, none of them can yet make the desired metal-looking free-form surfaces....

  15. Posterior Reversible Encephalopathy Syndrome Presenting as Stroke Mimic

    Directory of Open Access Journals (Sweden)

    Daniel Frick

    2017-05-01

    Full Text Available We present the case of a 33-year-old male with end stage renal disease presenting to the emergency department (ED with headache, dizziness, and unilateral weakness. Initial concern was for ischemic or hemorrhagic stroke. Magnetic resonance imaging confirmed posterior reversible encephalopathy syndrome (PRES. The patient was treated appropriately and made a full neurologic recovery. PRES is an under-recognized diagnosis in the ED. As a stroke mimic, PRES can lead the clinician on an incorrect diagnostic pathway with potential for iatrogenic harm.

  16. Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins

    DEFF Research Database (Denmark)

    Elortza, Felix; Nühse, Thomas S; Foster, Leonard J

    2003-01-01

    Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a functionally and structurally diverse family of post-translationally modified membrane proteins found mostly in the outer leaflet of the plasma membrane in a variety of eukaryotic cells. Although the general role of GPI-APs remains...... unclear, they have attracted attention because they act as enzymes and receptors in cell adhesion, differentiation, and host-pathogen interactions. GPI-APs may represent potential diagnostic and therapeutic targets in humans and are interesting in plant biotechnology because of their key role in root...... and 44 GPI-APs in an Arabidopsis thaliana membrane preparation, representing the largest experimental dataset of GPI-anchored proteins to date....

  17. A numerical analysis on the curved bileaflet Mechanical Heart Valve (MHV) : leaflet motion and blood flow in an elastic blood vessel

    International Nuclear Information System (INIS)

    Bang, Jin Seok; Kim, Chang Nyung; Choi, Choeng Ryul

    2005-01-01

    In blood flow passing through the Mechanical Heart Valve (MHV) and elastic blood vessel, hemolysis and platelet activation causing thrombus formation can be seen owing to the shear stress in the blood. Also, fracture and deformation of leaflets can be observed depending on the shape and material properties of the leaflets which is opened and closed in a cycle. Hence, comprehensive study is needed on the hemodynamics which is associated with the motion of leaflet and elastic blood vessel in terms of fluid-structure interaction. In this paper, a numerical analysis has been performed for a three-dimensional pulsatile blood flow associated with the elastic blood vessel and curved bileaflet for multiple cycles in light of fluid-structure interaction. From this analysis fluttering phenomenon and rebound of the leaflet have been observed and recirculation and regurgitation have been found in the flow fields of the blood. Also, the pressure distribution and the radial displacement of the elastic blood vessel have been obtained. The motion of the leaflet and flow fields of the blood have shown similar tendency compared with the previous experiments carried out in other studies. The present study can contribute to the design methodology for the curved bileaflet mechanical heart valve. Furthermore, the proposed fluid-structure interaction method will be effectively used in various fields where the interaction between fluid flow and structure are involved

  18. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2013-01-01

    Physics, mathematics and chemistry all play a vital role in understanding the true nature and functioning of biological membranes, key elements of living processes. Besides simple spectroscopic observations and electrical measurements of membranes we address in this book the phenomena of coexistence and independent existence of different membrane components using various theoretical approaches. This treatment will be helpful for readers who want to understand biological processes by applying both simple observations and fundamental scientific analysis. It provides a deep understanding of the causes and effects of processes inside membranes, and will thus eventually open new doors for high-level pharmaceutical approaches towards fighting membrane- and cell-related diseases.

  19. Cholesterol, sphingolipids, and glycolipids: What do we know about their role in raft-like membranes?

    DEFF Research Database (Denmark)

    Rog, T.; Vattulainen, I.

    2014-01-01

    Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units with pote......Lipids rafts are considered to be functional nanoscale membrane domains enriched in cholesterol and sphingolipids, characteristic in particular of the external leaflet of cell membranes. Lipids, together with membrane-associated proteins, are therefore considered to form nanoscale units...... with potential specific functions. Although the understanding of the structure of rafts in living cells is quite limited, the possible functions of rafts are widely discussed in the literature, highlighting their importance in cellular functions. In this review, we discuss the understanding of rafts that has...... emerged based on recent atomistic and coarse-grained molecular dynamics simulation studies on the key lipid raft components, which include cholesterol, sphingolipids, glycolipids, and the proteins interacting with these classes of lipids. The simulation results are compared to experiments when possible...

  20. Genetic Analysis of the Mode of Interplay between an ATPase Subunit and Membrane Subunits of the Lipoprotein-Releasing ATP-Binding Cassette Transporter LolCDE†

    OpenAIRE

    Ito, Yasuko; Matsuzawa, Hitomi; Matsuyama, Shin-ichi; Narita, Shin-ichiro; Tokuda, Hajime

    2006-01-01

    The LolCDE complex, an ATP-binding cassette (ABC) transporter, releases lipoproteins from the inner membrane, thereby initiating lipoprotein sorting to the outer membrane of Escherichia coli. The LolCDE complex is composed of two copies of an ATPase subunit, LolD, and one copy each of integral membrane subunits LolC and LolE. LolD hydrolyzes ATP on the cytoplasmic side of the inner membrane, while LolC and/or LolE recognize and release lipoproteins anchored to the periplasmic leaflet of the i...

  1. Wolff-Parkinson-White Syndrome Mimics a Conduction Disease

    Directory of Open Access Journals (Sweden)

    S. Marrakchi

    2014-01-01

    Full Text Available Background. It is important to recognise Wolff-Parkinson-White (WPW syndrome in electrocardiograms (ECG, as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a “false positive” of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

  2. Wolff-Parkinson-white syndrome mimics a conduction disease.

    Science.gov (United States)

    Marrakchi, S; Kammoun, I; Kachboura, S

    2014-01-01

    Background. It is important to recognise Wolff-Parkinson-White (WPW) syndrome in electrocardiograms (ECG), as it may mimic ischaemic heart disease, ventricular hypertrophy, and bundle branch block. Recognising WPW syndrome allows for risk stratification, the identification of associated conditions, and the institution of appropriate management. Objective. The present case showed that electrophysiological study is indicated in patients with abnormal ECG and syncope. Case Report. A 40-year-old man with Wolff-Parkinson-White syndrome was presented to emergency with syncope. A baseline ECG was a complete right branch block and posterior left hemiblock. He was admitted to the cardiac care unit for pacemaker implantation. The atypical figure of complete right branch block and posterior left hemiblock was thought to be a "false positive" of conduction abnormality. But the long anterograde refractory period of the both accessory pathway and atrioventricular conduction may cause difficulty in diagnosing Wolff-Parkinson-White syndrome, Conclusion. A Wolff-Parkinson-White Syndrome may mimic a conduction disease. No reliable algorithm exists for making an ECG diagnosis of a preexcitation syndrome with conduction disorders. This can lead to diagnostic and therapeutic dilemmas in the context of syncope.

  3. Novel β-amyloid aggregation inhibitors possessing a turn mimic.

    Science.gov (United States)

    Hamada, Yoshio; Miyamoto, Naoko; Kiso, Yoshiaki

    2015-04-01

    Amyloid β peptide, the main component of senile plaques found in the brain of Alzheimer disease (AD) patients, is a molecular target for AD therapeutic intervention. A number of potential AD therapeutics have been reported, including inhibitors of β-secretase, γ-secretase, and Aβ aggregation, and anti-amyloid agents, such as neprilysin, insulin degrading enzyme (IDE), and Aβ antibodies. Recently, we reported potent small-sized β-secretase (BACE1) inhibitors, which could serve as anti-AD drugs. However AD is a progressive disorder, where dementia symptoms gradually worsen over several decades, and therefore may require many years to get cured. One possible way to achieve a greater therapeutic effect is through simultaneous administration of multiple drugs, similar to those used in Highly Active Anti-Retroviral Therapy (HAART) used to treat AIDS. In order to overcome AD, we took a drug discovery approach to evaluate, novel β-amyloid aggregation inhibitors. Previously, we reported that a tong-type compound possessing a turn mimic as the inhibitor of HIV-1 protease dimerization. Oligomerized amyloid β peptides contain a turn structure within the molecule. Here, we designed and synthesized novel β-amyloid aggregation inhibitors with a turn-mimic template, based on the turn conformer of the oligomerized amyloid β peptides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. [Effects of using an information leaflet in reducing perioperative anxiety and pain in patients undergoing urological surgery].

    Science.gov (United States)

    Miguel Romeo, M Carmen; Sagardoy Muniesa, Lorena

    2014-01-01

    The preoperative anxiety state is mainly caused by the fear of the circumstances surrounding the intervention. Anxiety causes increased postoperative pain, and a prolonged length of stay in hospital, which directly affect the cost of care. To evaluate the effects of providing an anaesthesia information leaflet on postoperative anxiety and pain in patients undergoing urological surgery in the Miguel Servet Hospital. A prospective quasi-experimental study of 100 cases, 51 of whom made up the intervention group who received the information leaflet, with the remaining 49 cases being in the control group. The Hospital Anxiety and Depression Scale and the visual analogue scale for pain were assessed in both groups, before and after surgery. Of the 100 patients, 72% were male and 28% female, with an average age of 67.3 years (standard deviation, 9.7). In the intervention group, 21.6% showed anxiety before surgery and 0% in the postoperative period. In the control group 30.6% presented anxiety during the preoperative period and 4% in the postoperative period (χ(2) Pearson 5.20, P=.023). The study showed a direct relationship between preoperative anxiety and postoperative pain (χ(2) Pearson 10.519, P=.001). Good information about the surgical process reduces anxiety levels in the postoperative period. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  5. Triple leaflet perforation due to endocarditis in aortic valve complicated by pneumonia and exacerbation of chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Elton Soydan

    2015-09-01

    Full Text Available Valve perforation complicating infective endocarditis has been for decades a bad sign leading to severe valve destruction, intractable heart failure and even death if surgical therapy is not administered in time. Here we present a 57 years old male patient inadvertently diagnosed with pneumonia and chronic obstructive pulmonary disease exacerbation in another hospital. After 20 days of broad spectrum antibiotics and bronchodilator therapy no improvement was achieved. During examination a severe aortic regurgitation was recognized. Immediately after, patient was transferred to our hospital for aortic valve surgery evaluation. Transthorasic echocardiography (TTE showed a severe aortic regurgitation and vegetation like echogenicity over the noncoronary leaflet. An aortic valve replacement surgical therapy was decided. During the aortic valve excision underneath the vegetations, multiple small perforations in all the three leaflets were noticed. The destructed valve was excised and a mechanical aortic prosthesis (St Jude No: 23, MN, USA was successfully replaced. After 14 days of treatment patient was healthily discharged.

  6. Perfringolysin O Theta Toxin as a Tool to Monitor the Distribution and Inhomogeneity of Cholesterol in Cellular Membranes.

    Science.gov (United States)

    Maekawa, Masashi; Yang, Yanbo; Fairn, Gregory D

    2016-03-08

    Cholesterol is an essential structural component of cellular membranes in eukaryotes. Cholesterol in the exofacial leaflet of the plasma membrane is thought to form membrane nanodomains with sphingolipids and specific proteins. Additionally, cholesterol is found in the intracellular membranes of endosomes and has crucial functions in membrane trafficking. Furthermore, cellular cholesterol homeostasis and regulation of de novo synthesis rely on transport via both vesicular and non-vesicular pathways. Thus, the ability to visualize and detect intracellular cholesterol, especially in the plasma membrane, is critical to understanding the complex biology associated with cholesterol and the nanodomains. Perfringolysin O (PFO) theta toxin is one of the toxins secreted by the anaerobic bacteria Clostridium perfringens and this toxin forms pores in the plasma membrane that causes cell lysis. It is well understood that PFO recognizes and binds to cholesterol in the exofacial leaflets of the plasma membrane, and domain 4 of PFO (D4) is sufficient for the binding of cholesterol. Recent studies have taken advantage of this high-affinity cholesterol-binding domain to create a variety of cholesterol biosensors by using a non-toxic PFO or the D4 in isolation. This review highlights the characteristics and usefulness of, and the principal findings related to, these PFO-derived cholesterol biosensors.

  7. Insertion of Neurotransmitters into a Lipid Bilayer Membrane and Its Implication on Membrane Stability: A Molecular Dynamics Study.

    Science.gov (United States)

    Shen, Chun; Xue, Minmin; Qiu, Hu; Guo, Wanlin

    2017-03-17

    The signaling molecules in neurons, called neurotransmitters, play an essential role in the transportation of neural signals, during which the neurotransmitters interact with not only specific receptors, but also cytomembranes, such as synaptic vesicle membranes and postsynaptic membranes. Through extensive molecular dynamics simulations, the atomic-scale insertion dynamics of typical neurotransmitters, including methionine enkephalin (ME), leucine enkephalin (LE), dopamine (DA), acetylcholine (ACh), and aspartic acid (ASP), into lipid bilayers is investigated. The results show that the first three neurotransmitters (ME, LE, and DA) are able to diffuse freely into both 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) membranes, and are guided by the aromatic residues Tyr and Phe. Only a limited number of these neurotransmitters are allowed to penetrate into the membrane, which suggests an intrinsic mechanism by which the membrane is protected from being destroyed by excessive inserted neurotransmitters. After spontaneous insertion, the neurotransmitters disturb the surrounding phospholipids in the membrane, as indicated by the altered distribution of components in lipid leaflets and the disordered lipid tails. In contrast, the last two neurotransmitters (ACh and ASP) cannot enter the membrane, but instead always diffuse freely in solution. These findings provide an understanding at the atomic level of how neurotransmitters interact with the surrounding cytomembrane, as well as their impact on membrane behavior. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Treatment of severe mitral regurgitation caused by lesions in both leaflets using multiple mitral valve plasty techniques in a small dog

    Directory of Open Access Journals (Sweden)

    Satoko Yokoyama

    2017-11-01

    Full Text Available Mitral valve plasty (MVP is preferred over mitral valve replacement (MVR for mitral regurgitation in humans because of its favorable effect on quality of life. In small dogs, it is difficult to repair multiple lesions in both leaflets using MVP. Herein, we report a case of severe mitral regurgitation caused by multiple severe lesions in the posterior leaflet (PL in a mixed Chihuahua. Initially, we had planned MVR with an artificial valve. However, MVP combined with artificial chordal reconstruction of both leaflets, semicircular suture annuloplasty, and valvuloplasty using a newly devised direct scallop suture for the PL was attempted in this dog. The dog recovered well and showed no adverse cardiac signs, surviving two major operations. The dog died 4 years and 10 months after the MVP due to non-cardiovascular disease. Our additional technique of using a direct scallop suture seemed useful for PL repair involving multiple scallops in a small dog.

  9. Surgical repair of tricuspid valve leaflet tear following percutaneous closure of perimembranous ventricular septal defect using Amplatzer duct occluder I: Report of two cases

    Directory of Open Access Journals (Sweden)

    Saatchi Mahesh Kuwelker

    2017-01-01

    Full Text Available Tricuspid valve (TV injury following transcatheter closure of perimembranous ventricular septal defect (PMVSD with Amplatzer ductal occluder I (ADO I, requiring surgical repair, is rare. We report two cases of TV tear involving the anterior and septal leaflets following PMVSD closure using ADO I. In both the patients, the subvalvular apparatus remained unaffected. The patients presented with severe tricuspid regurgitation (TR 6 weeks and 3 months following the device closure. They underwent surgical repair with patch augmentation of the TV leaflets. Postoperatively, both are asymptomatic with a mild residual TR.

  10. Colonoscopic tattoo dye spillage mimics endometriosis on laparoscopy.

    Science.gov (United States)

    Stemmer, Shlomo M; Shurshalina, Anna

    2014-01-01

    Rare adverse effects of India ink injection spillage during colonoscopy have been reported. We present a case report in which prior colonoscopic India ink tattooing was found to mimic intraperitoneal endometriosis in a 48 year-old woman undergoing laparoscopic sterilization. Multiple black lesions suspicious for endometriosis involving the anterior and posterior cul-de-sac, left ovary, and omentum were found. A pathological assessment showed peritoneal tissue with focal dark pigment associated with mild chronic inflammation and deposition of tattoo pigment; there was no evidence of endometriosis in the specimens. Surgical recognition of tattoo ink spillage in the peritoneum is very important to prevent misinterpretation of peritoneal findings. Copyright © 2014 AAGL. Published by Elsevier Inc. All rights reserved.

  11. [Granulomatous lobular mastitis: a benign abnormality that mimics malignancy].

    Science.gov (United States)

    Vingerhoedt, N M; Janssen, S; Mravunac, M; Wauters, C A P; Strobbe, L J A

    2008-05-03

    A palpable abnormality of the breast was found in three women, one aged 57 and two aged 41. The first two patients predominantly showed the characteristics of a purulent inflammation, and on mammogram the third patient appeared to have mastitis carcinomatosa. Histopathological investigation revealed a lobular, non-caseating granulomatous inflammation. They were treated with prednisone and the first and third patients also received azathioprine. After some time, the condition recurred in the contralateral breast in the second and third patients. Once again, medicinal treatment was given. When a palpable tumour of the breast is found the primary goal is to exclude malignancy. Granulomatous lobular mastitis is a rare and benign tumour of the breast that clinically mimics carcinoma. Often, conventional imaging does not lead to the diagnosis. A histological needle biopsy is the best way to reach a diagnosis. Immunosuppressive therapy is effective and is preferred over surgery.

  12. Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

    International Nuclear Information System (INIS)

    Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

    2008-01-01

    Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS

  13. Antiproliferative efficacy of curcumin mimics through microtubule destabilization.

    Science.gov (United States)

    Khwaja, Sadiya; Fatima, Kaneez; Hasanain, Mohammad; Behera, Chittaranjan; Kour, Avneet; Singh, Arjun; Luqman, Suaib; Sarkar, Jayanta; Chanda, Debabrata; Shanker, Karuna; Gupta, A K; Mondhe, D M; Negi, Arvind S

    2018-05-10

    Curcumin possesses an attractive chemical structure with highly conjugated diferuloylmethane core. Curcumin mimics have been designed and prepared with an additional bridged phenyl ring in conjugation. Fourteen diverse analogues were evaluated against a panel of human cancer cell lines. The best analogue of the series i.e. compound 6a exhibited potent cytotoxicity against A431, epidermoid carcinoma cell line (IC 50  = 1.5 μM) and DLD1, colorectal adenocarcinoma cell line (IC 50  = 6.9 μM). In tubulin kinetics experiment, compound 6a destabilized polymerisation process (IC 50  = 4.68 μM). In cell cycle analysis, compound 6a exerted G2/M phase arrest in A431 cells and induced apoptosis. In Ehrlich Ascites Carcinoma in Swiss-albino mice, compound 6a showed 78.6% tumour reduction at 80 mg/kg dose and 57% solid tumour reduction at 150 mg/kg dose. Further, in acute-oral toxicity experiment in rodent model, compound 6a was given in three different oral doses to Swiss albino mice. There were non-significant changes in various biochemical parameters and major body organs studied, including their absolute and relative weights. It was tolerable up to 300 mg/kg dose in Swiss-albino mice. The present study shows that the novel curcumin mimic 6a is a safe and efficacious anticancer compound. However, it needs to be optimized for better efficacy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Testing of Synthetic Biological Membranes for Forward Osmosis Applications

    Science.gov (United States)

    Parodi, Jurek; Mangado, Jaione Romero; Stefanson, Ofir; Flynn, Michael; Mancinelli, Rocco; Kawashima, Brian; Trieu, Serena; Brozell, Adrian; Rosenberg, Kevan

    2016-01-01

    Commercially available forward osmosis membranes have been extensively tested for human space flight wastewater treatment. Despite the improvements achieved in the last decades, there is still a challenge to produce reliable membranes with anti-fouling properties, chemical resistance, and high flux and selectivity. Synthetic biological membranes that mimic the ones present in nature, which underwent millions of years of evolution, represent a potential solution for further development and progress in membrane technology. Biomimetic forward osmosis membranes based on a polymeric support filter and coated with surfactant multilayers have been engineered to investigate how different manufacturing processes impact the performance and structure of the membrane. However, initial results of the first generation prototype membranes tests reveal a high scatter in the data, due to the current testing apparatus set up. The testing apparatus has been upgraded to improve data collection, reduce errors, and to allow higher control of the testing process.

  15. Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus.

    Science.gov (United States)

    Adu-Gyamfi, Emmanuel; Johnson, Kristen A; Fraser, Mark E; Scott, Jordan L; Soni, Smita P; Jones, Keaton R; Digman, Michelle A; Gratton, Enrico; Tessier, Charles R; Stahelin, Robert V

    2015-09-01

    Lipid-enveloped viruses replicate and bud from the host cell where they acquire their lipid coat. Ebola virus, which buds from the plasma membrane of the host cell, causes viral hemorrhagic fever and has a high fatality rate. To date, little has been known about how budding and egress of Ebola virus are mediated at the plasma membrane. We have found that the lipid phosphatidylserine (PS) regulates the assembly of Ebola virus matrix protein VP40. VP40 binds PS-containing membranes with nanomolar affinity, and binding of PS regulates VP40 localization and oligomerization on the plasma membrane inner leaflet. Further, alteration of PS levels in mammalian cells inhibits assembly and egress of VP40. Notably, interactions of VP40 with the plasma membrane induced exposure of PS on the outer leaflet of the plasma membrane at sites of egress, whereas PS is typically found only on the inner leaflet. Taking the data together, we present a model accounting for the role of plasma membrane PS in assembly of Ebola virus-like particles. The lipid-enveloped Ebola virus causes severe infection with a high mortality rate and currently lacks FDA-approved therapeutics or vaccines. Ebola virus harbors just seven genes in its genome, and there is a critical requirement for acquisition of its lipid envelope from the plasma membrane of the human cell that it infects during the replication process. There is, however, a dearth of information available on the required contents of this envelope for egress and subsequent attachment and entry. Here we demonstrate that plasma membrane phosphatidylserine is critical for Ebola virus budding from the host cell plasma membrane. This report, to our knowledge, is the first to highlight the role of lipids in human cell membranes in the Ebola virus replication cycle and draws a clear link between selective binding and transport of a lipid across the membrane of the human cell and use of that lipid for subsequent viral entry. Copyright © 2015, American

  16. Plasma membrane organization and dynamics is probe and cell line dependent.

    Science.gov (United States)

    Huang, Shuangru; Lim, Shi Ying; Gupta, Anjali; Bag, Nirmalya; Wohland, Thorsten

    2017-09-01

    The action and interaction of membrane receptor proteins take place within the plasma membrane. The plasma membrane, however, is not a passive matrix. It rather takes an active role and regulates receptor distribution and function by its composition and the interaction of its lipid components with embedded and surrounding proteins. Furthermore, it is not a homogenous fluid but contains lipid and protein domains of various sizes and characteristic lifetimes which are important in regulating receptor function and signaling. The precise lateral organization of the plasma membrane, the differences between the inner and outer leaflet, and the influence of the cytoskeleton are still debated. Furthermore, there is a lack of comparisons of the organization and dynamics of the plasma membrane of different cell types. Therefore, we used four different specific membrane markers to test the lateral organization, the differences between the inner and outer membrane leaflet, and the influence of the cytoskeleton of up to five different cell lines, including Chinese hamster ovary (CHO-K1), Human cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), fibroblast (WI-38) and rat basophilic leukemia (RBL-2H3) cells by Imaging Total Internal Reflection (ITIR)-Fluorescence Correlation Spectroscopy (FCS). We measure diffusion in the temperature range of 298-310K to measure the Arrhenius activation energy (E Arr ) of diffusion and apply the FCS diffusion law to obtain information on the spatial organization of the probe molecules on the various cell membranes. Our results show clear differences of the FCS diffusion law and E Arr for the different probes in dependence of their localization. These differences are similar in the outer and inner leaflet of the membrane. However, these values can differ significantly between different cell lines raising the question how molecular plasma membrane events measured in different cell lines can be compared. This article is part of a Special Issue

  17. Randomly organized lipids and marginally stable proteins: a coupling of weak interactions to optimize membrane signaling.

    Science.gov (United States)

    Rice, Anne M; Mahling, Ryan; Fealey, Michael E; Rannikko, Anika; Dunleavy, Katie; Hendrickson, Troy; Lohese, K Jean; Kruggel, Spencer; Heiling, Hillary; Harren, Daniel; Sutton, R Bryan; Pastor, John; Hinderliter, Anne

    2014-09-01

    Eukaryotic lipids in a bilayer are dominated by weak cooperative interactions. These interactions impart highly dynamic and pliable properties to the membrane. C2 domain-containing proteins in the membrane also interact weakly and cooperatively giving rise to a high degree of conformational plasticity. We propose that this feature of weak energetics and plasticity shared by lipids and C2 domain-containing proteins enhance a cell's ability to transduce information across the membrane. We explored this hypothesis using information theory to assess the information storage capacity of model and mast cell membranes, as well as differential scanning calorimetry, carboxyfluorescein release assays, and tryptophan fluorescence to assess protein and membrane stability. The distribution of lipids in mast cell membranes encoded 5.6-5.8bits of information. More information resided in the acyl chains than the head groups and in the inner leaflet of the plasma membrane than the outer leaflet. When the lipid composition and information content of model membranes were varied, the associated C2 domains underwent large changes in stability and denaturation profile. The C2 domain-containing proteins are therefore acutely sensitive to the composition and information content of their associated lipids. Together, these findings suggest that the maximum flow of signaling information through the membrane and into the cell is optimized by the cooperation of near-random distributions of membrane lipids and proteins. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

    Science.gov (United States)

    Kolb, Alexander L; Corridon, Peter R; Zhang, Shijun; Xu, Weimin; Witzmann, Frank A; Collett, Jason A; Rhodes, George J; Winfree, Seth; Bready, Devin; Pfeffenberger, Zechariah J; Pomerantz, Jeremy M; Hato, Takashi; Nagami, Glenn T; Molitoris, Bruce A; Basile, David P; Atkinson, Simon J; Bacallao, Robert L

    2018-04-01

    Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine ( P <0.05) observed in controls and increased the mitochondria membrane potential ( P <0.05), maximal respiratory capacity ( P <0.05), and intracellular ATP levels ( P <0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning. Copyright © 2018 by the American Society of Nephrology.

  19. Cultivation of Human Microvascular Endothelial Cells on Topographical Substrates to Mimic the Human Corneal Endothelium

    Directory of Open Access Journals (Sweden)

    Jie Shi Chua

    2013-03-01

    Full Text Available Human corneal endothelial cells have a limited ability to replicate in vivo and in vitro. Allograft transplantation becomes necessary when an accident or trauma results in excessive cell loss. The reconstruction of the cornea endothelium using autologous cell sources is a promising alternative option for therapeutic or in vitro drug testing applications. The native corneal endothelium rests on the Descemet’s membrane, which has nanotopographies of fibers and pores. The use of synthetic topographies mimics the native environment, and it is hypothesized that this can direct the behavior and growth of human microvascular endothelial cells (HMVECs to resemble the corneal endothelium. In this study, HMVECs are cultivated on substrates with micron and nano-scaled pillar and well topographies. Closely packed HMVEC monolayers with polygonal cells and well-developed tight junctions were formed on the topographical substrates. Sodium/potassium (Na+/K+ adenine triphosphatase (ATPase expression was enhanced on the microwells substrate, which also promotes microvilli formation, while more hexagonal-like cells are found on the micropillars samples. The data obtained suggests that the use of optimized surface patterning, in particular, the microtopographies, can induce HMVECs to adopt a more corneal endothelium-like morphology with similar barrier and pump functions. The mechanism involved in cell contact guidance by the specific topographical features will be of interest for future studies.

  20. Membrane Binding and Bending in Ebola VP40 Assembly and Egress

    Directory of Open Access Journals (Sweden)

    Robert V Stahelin

    2014-06-01

    Full Text Available Lipid-enveloped viruses contain a lipid bilayer coat that protects their genome and helps to facilitate entry into the host cell. Filoviruses are lipid-enveloped viruses that have up to 90% clinical fatality and include Marbug (MARV and Ebola (EBOV. These pleomorphic filamentous viruses enter the host cell through their membrane embedded glycoprotein and then replicate using just seven genes encoded in their negative sense RNA genome. EBOV budding occurs from the inner leaflet of the plasma membrane and is driven by the matrix protein VP40, which is the most abundantly expressed protein of the virus. VP40 expressed in mammalian cells alone can trigger budding of filamentous virus-like particles (VLPs that are nearly indistinguishable from authentic EBOV. VP40, like matrix proteins from other viruses, has been shown to bind anionic lipid membranes. However, how VP40 selectively interacts with the inner leaflet of the plasma membrane and assembles into a filamentous lipid enveloped particle is mostly unknown. This article describes what is known regarding VP40 membrane interactions and what answers will fill the gaps.

  1. Membrane paradigm

    International Nuclear Information System (INIS)

    Price, R.H.; Thorne, K.S.

    1986-01-01

    The membrane paradigm is a modified frozen star approach to modeling black holes, with particles and fields assuming a complex, static, boundary-layer type structure (membrane) near the event horizon. The membrane has no effects on the present or future evolution of particles and fields above itself. The mathematical representation is a combination of a formalism containing terms for the shear and bulk viscosity, surface pressure, momentum, temperature, entropy, etc., of the horizon and the 3+1 formalism. The latter model considers a family of three-dimensional spacelike hypersurfaces in one-dimensional time. The membrane model considers a magnetic field threading the hole and undergoing torque from the hole rotation. The field is cleaned by the horizon and distributed over the horizon so that ohmic dissipation is minimized. The membrane paradigm is invalid inside the horizon, but is useful for theoretically probing the properties of slowly evolving black holes

  2. Membrane processes

    Science.gov (United States)

    Staszak, Katarzyna

    2017-11-01

    The membrane processes have played important role in the industrial separation process. These technologies can be found in all industrial areas such as food, beverages, metallurgy, pulp and paper, textile, pharmaceutical, automotive, biotechnology and chemical industry, as well as in water treatment for domestic and industrial application. Although these processes are known since twentieth century, there are still many studies that focus on the testing of new membranes' materials and determining of conditions for optimal selectivity, i. e. the optimum transmembrane pressure (TMP) or permeate flux to minimize fouling. Moreover the researchers proposed some calculation methods to predict the membrane processes properties. In this article, the laboratory scale experiments of membrane separation techniques, as well their validation by calculation methods are presented. Because membrane is the "heart" of the process, experimental and computational methods for its characterization are also described.

  3. An Experimental Comparison of a Co-Design Visualizing Personal Drug Information and Patient Information Leaflets: Usability Aspects.

    Science.gov (United States)

    Khodambashi, Soudabeh; Haugland, Dagrun; Ellingsberg, Anette; Kottum, Hanne; Sund, Janne Kutschera; Nytrø, Øystein

    2017-01-01

    Providing patients with specific information about their own drugs can reduce unintentional misuse and improve compliance. Searching for information is time-consuming when information is not personalized and is written using medical vocabulary that is difficult for patients to understand. In this study we explored patient information needs regarding visualizing of drug information and interrelationships by conducting a total of four co-design workshops with patients, other users and pharmacists. We developed a prototype and drug ontology to support reasoning about drug interactions. We evaluated individual performance in finding information, understanding the drug interactions, and learning from the provided information in the prototype compared to using patient information leaflets (PILs). We concluded that interactive visualization of drug information helps individuals find information about drugs, their side effects and interactions more quickly and correctly compared to using PILs. Our study is limited to co-morbid patients with transient ischaemic attack with several chronic diseases.

  4. Impact of Mediterranean diet education versus posted leaflet on dietary habits and serum cholesterol in a high risk population for cardiovascular disease

    NARCIS (Netherlands)

    Bemelmans, Wanda J. E.; Broer, Jan; de Vries, Jeanne H. M.; Hulshof, Karin F. A. M.; May, Jo F.; Meyboom-de Jong, Betty

    Objective: To investigate the impact of intensive group education on the Mediterranean diet on dietary intake and serum total cholesterol after 16 and 52 weeks, compared to a posted leaflet with the Dutch nutritional guidelines, in the context of primary prevention of cardiovascular disease (CVD).

  5. Temperature shift experiments suggest that metabolic impairment and enhanced rates of photorespiration decrease organic acid levels in soybean leaflets exposed to supra-optimal growth temperatures

    Science.gov (United States)

    Citrate, malate, malonate, fumarate and succinate in soybean leaflets decreased 40 to 80% when plants were grown continuously in controlled environment chambers at 36/28 compared to 28/20 °C. Glycerate was not temperature responsive in this study. Temperature effects on the above mentioned organi...

  6. Flip-flop of phospholipids in proteoliposomes reconstituted from detergent extract of chloroplast membranes: kinetics and phospholipid specificity.

    Directory of Open Access Journals (Sweden)

    Archita Rajasekharan

    Full Text Available Eukaryotic cells are compartmentalized into distinct sub-cellular organelles by lipid bilayers, which are known to be involved in numerous cellular processes. The wide repertoire of lipids, synthesized in the biogenic membranes like the endoplasmic reticulum and bacterial cytoplasmic membranes are initially localized in the cytosolic leaflet and some of these lipids have to be translocated to the exoplasmic leaflet for membrane biogenesis and uniform growth. It is known that phospholipid (PL translocation in biogenic membranes is mediated by specific membrane proteins which occur in a rapid, bi-directional fashion without metabolic energy requirement and with no specificity to PL head group. A recent study reported the existence of biogenic membrane flippases in plants and that the mechanism of plant membrane biogenesis was similar to that found in animals. In this study, we demonstrate for the first time ATP independent and ATP dependent flippase activity in chloroplast membranes of plants. For this, we generated proteoliposomes from Triton X-100 extract of intact chloroplast, envelope membrane and thylakoid isolated from spinach leaves and assayed for flippase activity using fluorescent labeled phospholipids. Half-life time of flipping was found to be 6 ± 1 min. We also show that: (a intact chloroplast and envelope membrane reconstituted proteoliposomes can flip fluorescent labeled analogs of phosphatidylcholine in ATP independent manner, (b envelope membrane and thylakoid reconstituted proteoliposomes can flip phosphatidylglycerol in ATP dependent manner, (c Biogenic membrane ATP independent PC flipping activity is protein mediated and (d the kinetics of PC translocation gets affected differently upon treatment with protease and protein modifying reagents.

  7. Large screen mimic display design research for advanced main control room in nuclear power plant

    International Nuclear Information System (INIS)

    Zheng Mingguang; Yang Yanhua; Xu Jijun; Zhang Qinshun; Ning Zhonghe

    2002-01-01

    Firstly the evolution of mimic diagrams or displays used in the main control room of nuclear power plant was introduced. The active functions of mimic diagrams were analyzed on the release of operator psychological burden and pressure, the assistance of operator for the information searching, status understanding, manual actuation, correct decision making as well as the safe and reliable operation of the nuclear power plant. The importance and necessity to use the (large screen) mimic diagrams in advanced main control room of nuclear power plant, the design principle, design details and verification measures of large screen mimic display are also described

  8. Accessing the public MIMIC-II intensive care relational database for clinical research.

    Science.gov (United States)

    Scott, Daniel J; Lee, Joon; Silva, Ikaro; Park, Shinhyuk; Moody, George B; Celi, Leo A; Mark, Roger G

    2013-01-10

    The Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II) database is a free, public resource for intensive care research. The database was officially released in 2006, and has attracted a growing number of researchers in academia and industry. We present the two major software tools that facilitate accessing the relational database: the web-based QueryBuilder and a downloadable virtual machine (VM) image. QueryBuilder and the MIMIC-II VM have been developed successfully and are freely available to MIMIC-II users. Simple example SQL queries and the resulting data are presented. Clinical studies pertaining to acute kidney injury and prediction of fluid requirements in the intensive care unit are shown as typical examples of research performed with MIMIC-II. In addition, MIMIC-II has also provided data for annual PhysioNet/Computing in Cardiology Challenges, including the 2012 Challenge "Predicting mortality of ICU Patients". QueryBuilder is a web-based tool that provides easy access to MIMIC-II. For more computationally intensive queries, one can locally install a complete copy of MIMIC-II in a VM. Both publicly available tools provide the MIMIC-II research community with convenient querying interfaces and complement the value of the MIMIC-II relational database.

  9. Primordial membranes

    DEFF Research Database (Denmark)

    Hanczyc, Martin M; Monnard, Pierre-Alain

    2017-01-01

    Cellular membranes, which are self-assembled bilayer structures mainly composed of lipids, proteins and conjugated polysaccharides, are the defining feature of cell physiology. It is likely that the complexity of contemporary cells was preceded by simpler chemical systems or protocells during...... the various evolutionary stages that led from inanimate to living matter. It is also likely that primitive membranes played a similar role in protocell 'physiology'. The composition of such ancestral membranes has been proposed as mixtures of single hydrocarbon chain amphiphiles, which are simpler versions...

  10. WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Clark, Andrea J; Coury, Emma L; Meilhac, Alexandra M; Petty, Howard R

    2016-01-01

    To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO 3 /Pt nanoparticles that mimic a leukocyte’s functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO 3 /Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye’s anterior chamber, we show that WO 3 /Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer. (paper)

  11. WO3/Pt nanoparticles are NADPH oxidase biomimetics that mimic effector cells in vitro and in vivo

    Science.gov (United States)

    Clark, Andrea J.; Coury, Emma L.; Meilhac, Alexandra M.; Petty, Howard R.

    2016-02-01

    To provide a means of delivering an artificial immune effector cell-like attack on tumor cells, we report the tumoricidal ability of inorganic WO3/Pt nanoparticles that mimic a leukocyte’s functional abilities. These nanoparticles route electrons from organic structures and electron carriers to form hydroxyl radicals within tumor cells. During visible light exposure, WO3/Pt nanoparticles manufacture hydroxyl radicals, degrade organic compounds, use NADPH, trigger lipid peroxidation, promote lysosomal membrane disruption, promote the loss of reduced glutathione, and activate apoptosis. In a model of advanced breast cancer metastasis to the eye’s anterior chamber, we show that WO3/Pt nanoparticles prolong the survival of 4T1 tumor-bearing Balb/c mice. This new generation of inorganic photosensitizers do not photobleach, and therefore should provide an important therapeutic advance in photodynamic therapy. As biomimetic nanoparticles destroy targeted cells, they may be useful in treating ocular and other forms of cancer.

  12. Engineering monolayer poration for rapid exfoliation of microbial membranes.

    Science.gov (United States)

    Pyne, Alice; Pfeil, Marc-Philipp; Bennett, Isabel; Ravi, Jascindra; Iavicoli, Patrizia; Lamarre, Baptiste; Roethke, Anita; Ray, Santanu; Jiang, Haibo; Bella, Angelo; Reisinger, Bernd; Yin, Daniel; Little, Benjamin; Muñoz-García, Juan C; Cerasoli, Eleonora; Judge, Peter J; Faruqui, Nilofar; Calzolai, Luigi; Henrion, Andre; Martyna, Glenn J; Grovenor, Chris R M; Crain, Jason; Hoogenboom, Bart W; Watts, Anthony; Ryadnov, Maxim G

    2017-02-01

    The spread of bacterial resistance to traditional antibiotics continues to stimulate the search for alternative antimicrobial strategies. All forms of life, from bacteria to humans, are postulated to rely on a fundamental host defense mechanism, which exploits the formation of open pores in microbial phospholipid bilayers. Here we predict that transmembrane poration is not necessary for antimicrobial activity and reveal a distinct poration mechanism that targets the outer leaflet of phospholipid bilayers. Using a combination of molecular-scale and real-time imaging, spectroscopy and spectrometry approaches, we introduce a structural motif with a universal insertion mode in reconstituted membranes and live bacteria. We demonstrate that this motif rapidly assembles into monolayer pits that coalesce during progressive membrane exfoliation, leading to bacterial cell death within minutes. The findings offer a new physical basis for designing effective antibiotics.

  13. IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Zaydfudim, Victor M; Wang, Andrew Y; de Lange, Eduard E; Zhao, Zimin; Moskaluk, Christopher A; Bauer, Todd W; Adams, Reid B

    2015-07-01

    IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

  14. Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

    Directory of Open Access Journals (Sweden)

    Lukas P. Feilen

    2017-05-01

    Full Text Available Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs. The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

  15. Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

    Science.gov (United States)

    Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

    2017-01-01

    Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

  16. Nanorod mediated collagen scaffolds as extra cellular matrix mimics

    International Nuclear Information System (INIS)

    Vedhanayagam, Mohan; Nair, Balachandran Unni; Sreeram, Kalarical Janardhanan; Mohan, Ranganathan

    2015-01-01

    Creating collagen scaffolds that mimic extracellular matrices without using toxic exogenous materials remains a big challenge. A new strategy to create scaffolds through end-to-end crosslinking through functionalized nanorods leading to well-designed architecture is presented here. Self-assembled scaffolds with a denaturation temperature of 110 °C, porosity of 70%, pore size of 0.32 μm and Young’s modulus of 231 MPa were developed largely driven by imine bonding between 3-mercapto-1-propanal (MPA) functionalized ZnO nanorods and collagen. The mechanical properties obtained were much higher than that of native collagen, collagen—MPA, collagen—3-mercapto-1-propanol (3MPOH) or collagen- 3-MPOH-ZnO, clearly bringing out the relevance of nanorod mediated assembly of fibrous networks. This new strategy has led to scaffolds with mechanical properties much higher than earlier reports and can provide support for cell growth and facilitation of cell attachment. (paper)

  17. Chimpanzees and humans mimic pupil-size of conspecifics.

    Directory of Open Access Journals (Sweden)

    Mariska E Kret

    Full Text Available Group-living typically provides benefits to individual group members but also confers costs. To avoid incredulity and betrayal and allow trust and cooperation, individuals must understand the intentions and emotions of their group members. Humans attend to other's eyes and from gaze and pupil-size cues, infer information about the state of mind of the observed. In humans, pupil-size tends to mimic that of the observed. Here we tested whether pupil-mimicry exists in our closest relative, the chimpanzee (P. troglodytes. We conjectured that if pupil-mimicry has adaptive value, e.g. to promote swift communication of inner states and facilitate shared understanding and coordination, pupil-mimicry should emerge within but not across species. Pupillometry data was collected from human and chimpanzee subjects while they observed images of the eyes of both species with dilating/constricting pupils. Both species showed enhanced pupil-mimicry with members of their own species, with effects being strongest in humans and chimpanzee mothers. Pupil-mimicry may be deeply-rooted, but probably gained importance from the point in human evolution where the morphology of our eyes became more prominent. Humans' white sclera surrounding the iris, and the fine muscles around their eyes facilitate non-verbal communication via eye signals.

  18. Thrombolytic treatment to stroke mimic patients via telestroke.

    Science.gov (United States)

    Asaithambi, Ganesh; Castle, Amy L; Sperl, Michael A; Ravichandran, Jayashree; Gupta, Aditi; Ho, Bridget M; Hanson, Sandra K

    2017-02-01

    The safety and outcomes of intravenous thrombolysis (IVT) to stroke patients via telestroke (TS) is similar to those presenting to stroke centers. Little is known on the accuracy of TS diagnosis among those receiving IVT. We sought to compare the rate of patients receiving IVT with diagnosis of ischemic stroke as opposed to stroke mimic (SM) in our TS network to those who presented to our comprehensive stroke center (CSC). Consecutive patients receiving IVT between August 2014 and June 2015 were identified at our CSC and TS network. We compared rates of SM, post-IVT symptomatic intracerebral hemorrhage (sICH), in-hospital mortality, and discharge destination. We evaluated 131 receiving IVT were included in the analysis. Rates of SM receiving IVT were similar (CSC 12% versus 7% TS, p=0.33). Four stroke patients experienced sICH or in-hospital mortality; neither were found among SM patients. Discharge destination was similar between stroke and SM patients (p=0.9). SM patients had higher diagnoses of migraine (p=0.05) and psychiatric illness (p<0.01). The accuracy of diagnosing stroke in IVT-eligible patients evaluated via TS is similar to evaluations at our CSC. Continued efforts should be made to minimize exposure of SM patients to IVT in both settings. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. A MIMIC approach to modeling the underground economy in Taiwan

    Science.gov (United States)

    Wang, David Han-Min; Lin, Jer-Yan; Yu, Tiffany Hui-Kuang

    2006-11-01

    The size of underground economy (UE) expansion usually increases the tax gap, impose a burden on the economy, and results in tax distortions. This study uses the MIMIC approach to model the causal variables and indicating variables to estimate the UE in Taiwan. We also focus on testing the data for non-stationarity and perform diagnostic tests. By using annual time-series data for Taiwan from 1961 to 2003, it is found that the estimated size of the UE varies from 11.0% to 13.1% before 1988, and from 10.6% to 11.8% from 1989 onwards. That the size of the UE experienced a substantial downward shift in 1989 indicates that there was a structural break. The UE is significantly and positively affected by such casual variables as the logarithm of real government consumption and currency inflation, but is negatively affected by the tax burden at 5% significant level. Unemployment rate and crime rate are not significantly correlated with the UE in this study.

  20. Penerapan Model MIMIC untuk Menguji Konsistensi Hasil Pengukuran melalui Skala

    Directory of Open Access Journals (Sweden)

    Wahyu Widhiarso

    2012-04-01

    Full Text Available This study aimed to demonstrate the use of multiple indicators and multiple (MIMIC model in testing the consistency of the measurement results when it's applied to individuals with different characteristics. Self-Esteem and Student Motivation Scale were employed to measure participant attributes. Impact of three student characteristics (gender, intelligence and school location on both measurement model were examined. Total of 2981 students from 30 cities of 15 provinces were participated in this study. Data analysis was utilized using confirmatory factor analysis under structural equation modeling (SEM approach. Results showed that measuring self-esteem was prone to be contaminated by individual heterogeneity. However, contrary results was found on motivation measure. Excluding three student characteristics as covariance in the model have increased model fit indices in the self-esteem measurement model, but not in the self-esteem. The presence of susceptibility scale to different characteristics indicated that this scale needs to be further modified. Therefore, when it is applied to heterogeneous population, the measurement results will produce consistently results.

  1. Membranous nephropathy

    Science.gov (United States)

    ... skin-lightening creams Systemic lupus erythematosus , rheumatoid arthritis, Graves disease, and other autoimmune disorders The disorder occurs at ... diagnosis. The following tests can help determine the cause of membranous nephropathy: Antinuclear antibodies test Anti-double- ...

  2. A web-based data visualization tool for the MIMIC-II database.

    Science.gov (United States)

    Lee, Joon; Ribey, Evan; Wallace, James R

    2016-02-04

    Although MIMIC-II, a public intensive care database, has been recognized as an invaluable resource for many medical researchers worldwide, becoming a proficient MIMIC-II researcher requires knowledge of SQL programming and an understanding of the MIMIC-II database schema. These are challenging requirements especially for health researchers and clinicians who may have limited computer proficiency. In order to overcome this challenge, our objective was to create an interactive, web-based MIMIC-II data visualization tool that first-time MIMIC-II users can easily use to explore the database. The tool offers two main features: Explore and Compare. The Explore feature enables the user to select a patient cohort within MIMIC-II and visualize the distributions of various administrative, demographic, and clinical variables within the selected cohort. The Compare feature enables the user to select two patient cohorts and visually compare them with respect to a variety of variables. The tool is also helpful to experienced MIMIC-II researchers who can use it to substantially accelerate the cumbersome and time-consuming steps of writing SQL queries and manually visualizing extracted data. Any interested researcher can use the MIMIC-II data visualization tool for free to quickly and conveniently conduct a preliminary investigation on MIMIC-II with a few mouse clicks. Researchers can also use the tool to learn the characteristics of the MIMIC-II patients. Since it is still impossible to conduct multivariable regression inside the tool, future work includes adding analytics capabilities. Also, the next version of the tool will aim to utilize MIMIC-III which contains more data.

  3. Cationic Au Nanoparticle Binding with Plasma Membrane-like Lipid Bilayers: Potential Mechanism for Spontaneous Permeation to Cells Revealed by Atomistic Simulations

    DEFF Research Database (Denmark)

    Heikkila, E.; Martinez-Seara, H.; Gurtovenko, A. A.

    2014-01-01

    Despite being chemically inert as a bulk material, nanoscale gold can pose harmful side effects to living organisms. In particular, cationic Au nanoparticles (AuNP+) of 2 nm diameter or less permeate readily through plasma membranes and induce cell death. We report atomistic simulations of cationic...... to be governed by cooperative effects where AuNP+, counterions, water, and the two membrane leaflets all contribute. On the extracellular side, we find that the nanoparticle has to cross a free energy barrier of about 5 k(B)T prior forming a stable contact with the membrane. This results in a rearrangement...

  4. Interaction of monomeric Ebola VP40 protein with a plasma membrane: A coarse-grained molecular dynamics (CGMD) simulation study.

    Science.gov (United States)

    Mohamad Yusoff, Mohamad Ariff; Abdul Hamid, Azzmer Azzar; Mohammad Bunori, Noraslinda; Abd Halim, Khairul Bariyyah

    2018-06-01

    Ebola virus is a lipid-enveloped filamentous virus that affects human and non-human primates and consists of several types of protein: nucleoprotein, VP30, VP35, L protein, VP40, VP24, and transmembrane glycoprotein. Among the Ebola virus proteins, its matrix protein VP40 is abundantly expressed during infection and plays a number of critical roles in oligomerization, budding and egress from the host cell. VP40 exists predominantly as a monomer at the inner leaflet of the plasma membrane, and has been suggested to interact with negatively charged lipids such as phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and phosphatidylserine (PS) via its cationic patch. The hydrophobic loop at the C-terminal domain has also been shown to be important in the interaction between the VP40 and the membrane. However, details of the molecular mechanisms underpinning their interactions are not fully understood. This study aimed at investigating the effects of mutation in the cationic patch and hydrophobic loop on the interaction between the VP40 monomer and the plasma membrane using coarse-grained molecular dynamics simulation (CGMD). Our simulations revealed that the interaction between VP40 and the plasma membrane is mediated by the cationic patch residues. This led to the clustering of PIP 2 around the protein in the inner leaflet as a result of interactions between some cationic residues including R52, K127, K221, K224, K225, K256, K270, K274, K275 and K279 and PIP 2 lipids via electrostatic interactions. Mutation of the cationic patch or hydrophobic loop amino acids caused the protein to bind at the inner leaflet of the plasma membrane in a different orientation, where no significant clustering of PIP 2 was observed around the mutated protein. This study provides basic understanding of the interaction of the VP40 monomer and its mutants with the plasma membrane. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Field-effect detection using phospholipid membranes -Topical Review

    Directory of Open Access Journals (Sweden)

    Chiho Kataoka-Hamai and Yuji Miyahara

    2010-01-01

    Full Text Available The application of field-effect devices to biosensors has become an area of intense research interest. An attractive feature of field-effect sensing is that the binding or reaction of biomolecules can be directly detected from a change in electrical signals. The integration of such field-effect devices into cell membrane mimics may lead to the development of biosensors useful in clinical and biotechnological applications. This review summarizes recent studies on the fabrication and characterization of field-effect devices incorporating model membranes. The incorporation of black lipid membranes and supported lipid monolayers and bilayers into semiconductor devices is described.

  6. The asymmetrical structure of Golgi apparatus membranes revealed by in situ atomic force microscope.

    Directory of Open Access Journals (Sweden)

    Haijiao Xu

    Full Text Available The Golgi apparatus has attracted intense attentions due to its fascinating morphology and vital role as the pivot of cellular secretory pathway since its discovery. However, its complex structure at the molecular level remains elusive due to limited approaches. In this study, the structure of Golgi apparatus, including the Golgi stack, cisternal structure, relevant tubules and vesicles, were directly visualized by high-resolution atomic force microscope. We imaged both sides of Golgi apparatus membranes and revealed that the outer leaflet of Golgi membranes is relatively smooth while the inner membrane leaflet is rough and covered by dense proteins. With the treatment of methyl-β-cyclodextrin and Triton X-100, we confirmed the existence of lipid rafts in Golgi apparatus membrane, which are mostly in the size of 20 nm -200 nm and appear irregular in shape. Our results may be of significance to reveal the structure-function relationship of the Golgi complex and pave the way for visualizing the endomembrane system in mammalian cells at the molecular level.

  7. A lesion mimic phenotype in tomato obtained by isolating and silencing an Lls1 homologue

    NARCIS (Netherlands)

    Spassieva, S; Hille, J

    Lesion mimic phenotypes serve as a tool to study the regulation of cell death in plants. In order to obtain a tomato lesion mimic phenotype, we used the conservation of the lethal leaf spot 1 (Lls1) genes between plant species. The tomato Lls1 homologue was cloned, sequenced and analyzed. It showed

  8. Biological Mimics: A New Paradigm in the Detection of Toxic Compounds

    Science.gov (United States)

    Monty, Chelsea Nicole

    2009-01-01

    The purpose of this thesis is to introduce a new idea: using biological mimics in the detection of toxic compounds. Biological mimics imitate the active site of a given enzyme or have catalytic chemistry similar to enzymes and can be used in place of biological molecules to provide longer stability and simpler operation. In the following text the…

  9. Touch the Page and Mimic Me: Evaluation of a Talking-Pen Learning Tool

    Science.gov (United States)

    Odakura, Abigail

    2013-01-01

    The purpose of this paper is to evaluate the talking-pen device called the Mimic Me, an educational technology product of a large English conversation school in Japan, as an educational learning tool. The product will be reviewed in terms of its developmental appropriateness for the target audience based on current research. Although the Mimic Me…

  10. Inhibition of duck hepatitis B virus replication by mimic peptides in vitro.

    Science.gov (United States)

    Jia, Hongyu; Liu, Changhong; Yang, Ying; Zhu, Haihong; Chen, Feng; Liu, Jihong; Zhou, Linfu

    2015-11-01

    The aim of the present study was to investigate the inhibitory effect of specific mimic peptides targeting duck hepatitis B virus polymerase (DHBVP) on duck hepatitis B virus (DHBV) replication in primary duck hepatocytes. Phage display technology (PDT) was used to screen for mimic peptides specifically targeting DHBVP and the associated coding sequences were determined using DNA sequencing. The selected mimic peptides were then used to treat primary duck hepatocytes infected with DHBV in vitro. Infected hepatocytes expressing the mimic peptides intracellularly were also prepared. The cells were divided into mimic peptide groups (EXP groups), an entecavir-treated group (positive control) and a negative control group. The medium was changed every 48 h. Following a 10-day incubation, the cell supernatants were collected. DHBV-DNA in the cellular nucleus, cytoplasm and culture supernatant was analyzed by quantitative polymerase chain reaction (qPCR). Eight mimic peptides were selected following three PDT screening rounds for investigation in the DHBV-infected primary duck hepatocytes. The qPCR results showed that following direct treatment with mimic peptide 2 or 7, intracellular expression of mimic peptide 2 or 7, or treatment with entecavir, the DHBV-DNA levels in the culture supernatant and cytoplasm of duck hepatocytes were significantly lower than those in the negative control (Pmimic peptide 7 was lower than that in the other groups (Pmimic peptide 7 was significantly lower than that in the other groups (PMimic peptides specifically targeting DHBVP, administered directly or expressed intracellularly, can significantly inhibit DHBV replication in vitro .

  11. Primary study on lesion mimic mutants of rice (oryza sativa L.)

    International Nuclear Information System (INIS)

    Hao Zhongna; Zhang Hongzhi; Tao Rongixang

    2007-01-01

    Nineteen lesion mimic mutants (xsl1-19) of japonica rice Xiushui11 were obtained by γ-rays irradiation treatment. All mutants belonged to whole life lesion mimic. Lesion mimic of mutants didn't largen after tillering stage, leaves didn't wither, and no effect on the plants exsert spikes and seed. When the highest temperature in day exceeded 32 degree C in seedling stage, lesion mimic of all mutant expect xsl19 disappeared. Under 32 degree C, lesion mimic would appear gradually, and symptoms weren't inhibited by high temperature after 5 leaf stage. The plant heights of all lesion mimic mutants were 47.56-63.54 cm in the tillering stage, and that of CK was 83.75 cm; but the dwarf phenomenon of mutants only appeared before tillering stage, and didn't affect plant heights finally; the heading dates of mutants were the same to the CK, the ear length of all mutants were 9.43-15.19 cm, and that of CK was 16.41 cm; the total grain quantity per spike of all mutants were 88.17-165.33, and those of xsl19 and CK were 49.50 and 76.17. The results showed all lesion mimic mutants except xsl19 had short spikes and total grain quantity per spike increasing. All lesion mimic mutants were susceptible to Magnaporthe grisea, and they had no relationship with resistance. (authors)

  12. Testing Measurement Invariance Using MIMIC: Likelihood Ratio Test with a Critical Value Adjustment

    Science.gov (United States)

    Kim, Eun Sook; Yoon, Myeongsun; Lee, Taehun

    2012-01-01

    Multiple-indicators multiple-causes (MIMIC) modeling is often used to test a latent group mean difference while assuming the equivalence of factor loadings and intercepts over groups. However, this study demonstrated that MIMIC was insensitive to the presence of factor loading noninvariance, which implies that factor loading invariance should be…

  13. Nuclear power station: validation of a method for designing operation mimic diagrams

    International Nuclear Information System (INIS)

    Colard, M.I.; De Vlaminck, M.; Javaux, D.

    1995-01-01

    This is the first time in a Belgium nuclear power station that the design of mimic diagrams has involved biotechnologists. The methodology is based upon task analysis, the formalism of which has been evaluated. It is now integrated in the Dimos assisted supervision system to produce the final design of mimic diagram images. (authors). 3 figs., 3 refs

  14. Hyperechoic caudate nuclei: a potential mimic of germinal matrix hemorrhage

    International Nuclear Information System (INIS)

    Schlesinger, A.E.; Shackelford, G.D.; Adcock, L.M.

    1998-01-01

    Background. We have encountered bilateral hyperechoic foci in the region of the germinal matrix on cranial sonograms in neonates that have an appearance similar to germinal matrix hemorrhage (GMH), but are unusual either due to the age of the patient at presentation or to the evolution of the foci on follow-up. We believe that these findings represent hyperechoic caudate nuclei (HCN) rather than GMH. Objective. To demonstrate that bilateral HCN can be seen on cranial sonography in neonates and can mimic bilateral GMH. Materials and methods. The cranial sonograms were reviewed in nine neonates (three term and six premature) who had HCN identified on at least one sonographic examination. CT (two patients) and MR (one patient) studies were also reviewed, as well as the neuropathological examination in one patient who died and had an autopsy. The patients' medical records were reviewed to identify any clinical markers for significant risk of perinatal ischemia. Results. There was clinical evidence for risk of ischemia in five of the nine neonates. All nine patients had bilateral HCN on the initial or follow-up studies. Small cysts were seen sonographically in two patients. CT was normal in one patient and revealed a small unilateral focus of increased attenuation in one infant (very small compared to the bilateral HCN). MR was normal in one patient. Histopathological examination of the brain was normal in the one patient who died and had an autopsy. Conclusion. Hyperechoic caudate nuclei can occur in neonates either as a normal finding, or possibly related to ischemia, and should not always be attributed to GMH. (orig.)

  15. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of resistant pathogens.

  16. Adaptation of the European Commission-recommended user testing method to patient medication information leaflets in Japan

    Directory of Open Access Journals (Sweden)

    Yamamoto M

    2017-06-01

    Full Text Available Michiko Yamamoto,1 Hirohisa Doi,1 Ken Yamamoto,2 Kazuhiro Watanabe,2 Tsugumichi Sato,3 Machi Suka,4 Takeo Nakayama,5 Hiroki Sugimori6 1Department of Drug Informatics, Center for Education & Research on Clinical Pharmacy, Showa Pharmaceutical University, Tokyo, Japan; 2Department of Pharmacy Practice, Center for Education & Research on Clinical Pharmacy, Showa Pharmaceutical University, Tokyo, Japan; 3Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan; 4Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo, Japan; 5Department of Health Informatics, Kyoto University School of Public, Kyoto, Japan; 6Department of Preventive Medicine, Graduate School of Sports and Health Sciences, Daito Bunka University, Saitama, Japan Background: The safe use of drugs relies on providing accurate drug information to patients. In Japan, patient leaflets called Drug Guide for Patients are officially available; however, their utility has never been verified. This is the first attempt to improve Drug Guide for Patients via user testing in Japan.Purpose: To test and improve communication of drug information to minimize risk for patients via user testing of the current and revised versions of Drug Guide for Patients, and to demonstrate that this method is effective for improving Drug Guide for Patients in Japan.Method: We prepared current and revised versions of the Drug Guide for Patients and performed user testing via semi-structured interviews with consumers to compare these versions for two guides for Mercazole and Strattera. We evenly divided 54 participants into two groups with similar distributions of sex, age, and literacy level to test the differing versions of the Mercazole guide. Another group of 30 participants were divided evenly to test the versions of the Strattera guide. After completing user testing, the participants evaluated both guides in terms of amount of information

  17. Membrane-Assisted Growth of DNA Origami Nanostructure Arrays

    Science.gov (United States)

    2015-01-01

    Biological membranes fulfill many important tasks within living organisms. In addition to separating cellular volumes, membranes confine the space available to membrane-associated proteins to two dimensions (2D), which greatly increases their probability to interact with each other and assemble into multiprotein complexes. We here employed two DNA origami structures functionalized with cholesterol moieties as membrane anchors—a three-layered rectangular block and a Y-shaped DNA structure—to mimic membrane-assisted assembly into hierarchical superstructures on supported lipid bilayers and small unilamellar vesicles. As designed, the DNA constructs adhered to the lipid bilayers mediated by the cholesterol anchors and diffused freely in 2D with diffusion coefficients depending on their size and number of cholesterol modifications. Different sets of multimerization oligonucleotides added to bilayer-bound origami block structures induced the growth of either linear polymers or two-dimensional lattices on the membrane. Y-shaped DNA origami structures associated into triskelion homotrimers and further assembled into weakly ordered arrays of hexagons and pentagons, which resembled the geometry of clathrin-coated pits. Our results demonstrate the potential to realize artificial self-assembling systems that mimic the hierarchical formation of polyhedral lattices on cytoplasmic membranes. PMID:25734977

  18. Membrane-assisted growth of DNA origami nanostructure arrays.

    Science.gov (United States)

    Kocabey, Samet; Kempter, Susanne; List, Jonathan; Xing, Yongzheng; Bae, Wooli; Schiffels, Daniel; Shih, William M; Simmel, Friedrich C; Liedl, Tim

    2015-01-01

    Biological membranes fulfill many important tasks within living organisms. In addition to separating cellular volumes, membranes confine the space available to membrane-associated proteins to two dimensions (2D), which greatly increases their probability to interact with each other and assemble into multiprotein complexes. We here employed two DNA origami structures functionalized with cholesterol moieties as membrane anchors--a three-layered rectangular block and a Y-shaped DNA structure--to mimic membrane-assisted assembly into hierarchical superstructures on supported lipid bilayers and small unilamellar vesicles. As designed, the DNA constructs adhered to the lipid bilayers mediated by the cholesterol anchors and diffused freely in 2D with diffusion coefficients depending on their size and number of cholesterol modifications. Different sets of multimerization oligonucleotides added to bilayer-bound origami block structures induced the growth of either linear polymers or two-dimensional lattices on the membrane. Y-shaped DNA origami structures associated into triskelion homotrimers and further assembled into weakly ordered arrays of hexagons and pentagons, which resembled the geometry of clathrin-coated pits. Our results demonstrate the potential to realize artificial self-assembling systems that mimic the hierarchical formation of polyhedral lattices on cytoplasmic membranes.

  19. Axionic membranes

    International Nuclear Information System (INIS)

    Aurilia, A.; Spallucci, E.

    1992-01-01

    A metal ring removed from a soap-water solution encloses a film of soap which can be mathematically described as a minimal surface having the ring as its only boundary. This is known to everybody. In this letter we suggest a relativistic extension of the above fluidodynamic system where the soap film is replaced by a Kalb-Ramand gauge potential B μν (x) and the ring by a closed string. The interaction between the B μν field and the string current excites a new configuration of the system consisting of a relativistic membrane bounded by the string. We call such a classical solution of the equation of motion an axionic membrane. As a dynamical system, the axionic membrane admits a Hamilton-Jacobi formulation which is an extension of the HJ theory of electromagnetic strings. (orig.)

  20. Metamaterial membranes

    International Nuclear Information System (INIS)

    Restrepo-Flórez, Juan Manuel; Maldovan, Martin

    2017-01-01

    We introduce a new class of metamaterial device to achieve separation of compounds by using coordinate transformations and metamaterial theory. By rationally designing the spatial anisotropy for mass diffusion, we simultaneously concentrate different compounds in different spatial locations, leading to separation of mixtures across a metamaterial membrane. The separation of mixtures into their constituent compounds is critically important in biophysics, biomedical, and chemical applications. We present a practical case where a mixture of oxygen and nitrogen diffusing through a polymeric planar matrix is separated. This work opens doors to new paradigms in membrane separations via coordinate transformations and metamaterials by introducing novel properties and unconventional mass diffusion phenomena. (paper)

  1. Exclusive photorelease of signalling lipids at the plasma membrane.

    Science.gov (United States)

    Nadler, André; Yushchenko, Dmytro A; Müller, Rainer; Stein, Frank; Feng, Suihan; Mulle, Christophe; Carta, Mario; Schultz, Carsten

    2015-12-21

    Photoactivation of caged biomolecules has become a powerful approach to study cellular signalling events. Here we report a method for anchoring and uncaging biomolecules exclusively at the outer leaflet of the plasma membrane by employing a photocleavable, sulfonated coumarin derivative. The novel caging group allows quantifying the reaction progress and efficiency of uncaging reactions in a live-cell microscopy setup, thereby greatly improving the control of uncaging experiments. We synthesized arachidonic acid derivatives bearing the new negatively charged or a neutral, membrane-permeant coumarin caging group to locally induce signalling either at the plasma membrane or on internal membranes in β-cells and brain slices derived from C57B1/6 mice. Uncaging at the plasma membrane triggers a strong enhancement of calcium oscillations in β-cells and a pronounced potentiation of synaptic transmission while uncaging inside cells blocks calcium oscillations in β-cells and causes a more transient effect on neuronal transmission, respectively. The precise subcellular site of arachidonic acid release is therefore crucial for signalling outcome in two independent systems.

  2. Perforin rapidly induces plasma membrane phospholipid flip-flop.

    Directory of Open Access Journals (Sweden)

    Sunil S Metkar

    Full Text Available The cytotoxic cell granule secretory pathway is essential for host defense. This pathway is fundamentally a form of intracellular protein delivery where granule proteases (granzymes from cytotoxic lymphocytes are thought to diffuse through barrel stave pores generated in the plasma membrane of the target cell by the pore forming protein perforin (PFN and mediate apoptotic as well as additional biological effects. While recent electron microscopy and structural analyses indicate that recombinant PFN oligomerizes to form pores containing 20 monomers (20 nm when applied to liposomal membranes, these pores are not observed by propidium iodide uptake in target cells. Instead, concentrations of human PFN that encourage granzyme-mediated apoptosis are associated with pore structures that unexpectedly favor phosphatidylserine flip-flop measured by Annexin-V and Lactadherin. Efforts that reduce PFN mediated Ca influx in targets did not reduce Annexin-V reactivity. Antigen specific mouse CD8 cells initiate a similar rapid flip-flop in target cells. A lipid that augments plasma membrane curvature as well as cholesterol depletion in target cells enhance flip-flop. Annexin-V staining highly correlated with apoptosis after Granzyme B (GzmB treatment. We propose the structures that PFN oligomers form in the membrane bilayer may include arcs previously observed by electron microscopy and that these unusual structures represent an incomplete mixture of plasma membrane lipid and PFN oligomers that may act as a flexible gateway for GzmB to translocate across the bilayer to the cytosolic leaflet of target cells.

  3. Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.

    Science.gov (United States)

    Takechi-Haraya, Yuki; Saito, Hiroyuki

    2018-01-01

    Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. The homeodomain derived peptide Penetratin induces curvature of fluid membrane domains.

    Directory of Open Access Journals (Sweden)

    Antonin Lamazière

    Full Text Available BACKGROUND: Protein membrane transduction domains that are able to cross the plasma membrane are present in several transcription factors, such as the homeodomain proteins and the viral proteins such as Tat of HIV-1. Their discovery resulted in both new concepts on the cell communication during development, and the conception of cell penetrating peptide vectors for internalisation of active molecules into cells. A promising cell penetrating peptide is Penetratin, which crosses the cell membranes by a receptor and metabolic energy-independent mechanism. Recent works have claimed that Penetratin and similar peptides are internalized by endocytosis, but other endocytosis-independent mechanisms have been proposed. Endosomes or plasma membranes crossing mechanisms are not well understood. Previously, we have shown that basic peptides induce membrane invaginations suggesting a new mechanism for uptake, "physical endocytosis". METHODOLOGY/PRINCIPAL FINDINGS: Herein, we investigate the role of membrane lipid phases on Penetratin induced membrane deformations (liquid ordered such as in "raft" microdomains versus disordered fluid "non-raft" domains in membrane models. Experimental data show that zwitterionic lipid headgroups take part in the interaction with Penetratin suggesting that the external leaflet lipids of cells plasma membrane are competent for peptide interaction in the absence of net negative charges. NMR and X-ray diffraction data show that the membrane perturbations (tubulation and vesiculation are associated with an increase in membrane negative curvature. These effects on curvature were observed in the liquid disordered but not in the liquid ordered (raft-like membrane domains. CONCLUSIONS/SIGNIFICANCE: The better understanding of the internalisation mechanisms of protein transduction domains will help both the understanding of the mechanisms of cell communication and the development of potential therapeutic molecular vectors. Here we

  5. Stroke mimics under the drip-and-ship paradigm.

    Science.gov (United States)

    Mehta, Sonal; Vora, Nirav; Edgell, Randall C; Allam, Hesham; Alawi, Aws; Koehne, Jennifer; Kumar, Abhay; Feen, Eliahu; Cruz-Flores, Salvador; Alshekhlee, Amer

    2014-01-01

    Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). The drip-and-ship paradigm and any psychiatric history predict the diagnosis of

  6. Accumulation of murine amyloid-β mimics early Alzheimer's disease.

    Science.gov (United States)

    Krohn, Markus; Bracke, Alexander; Avchalumov, Yosef; Schumacher, Toni; Hofrichter, Jacqueline; Paarmann, Kristin; Fröhlich, Christina; Lange, Cathleen; Brüning, Thomas; von Bohlen Und Halbach, Oliver; Pahnke, Jens

    2015-08-01

    Amyloidosis mouse models of Alzheimer's disease are generally established by transgenic approaches leading to an overexpression of mutated human genes that are known to be involved in the generation of amyloid-β in Alzheimer's families. Although these models made substantial contributions to the current knowledge about the 'amyloid hypothesis' of Alzheimer's disease, the overproduction of amyloid-β peptides mimics only inherited (familiar) Alzheimer's disease, which accounts for patients with Alzheimer's disease. The inherited form is even regarded a 'rare' disease according to the regulations for funding of the European Union (www.erare.eu). Here, we show that mice that are double-deficient for neprilysin (encoded by Mme), one major amyloid-β-degrading enzyme, and the ABC transporter ABCC1, a major contributor to amyloid-β clearance from the brain, develop various aspects of sporadic Alzheimer's disease mimicking the clinical stage of mild cognitive impairment. Using behavioural tests, electrophysiology and morphological analyses, we compared different ABC transporter-deficient animals and found that alterations are most prominent in neprilysin × ABCC1 double-deficient mice. We show that these mice have a reduced probability to survive, show increased anxiety in new environments, and have a reduced working memory performance. Furthermore, we detected morphological changes in the hippocampus and amygdala, e.g. astrogliosis and reduced numbers of synapses, leading to defective long-term potentiation in functional measurements. Compared to human, murine amyloid-β is poorly aggregating, due to changes in three amino acids at N-terminal positions 5, 10, and 13. Interestingly, our findings account for the action of early occurring amyloid-β species/aggregates, i.e. monomers and small amyloid-β oligomers. Thus, neprilysin × ABCC1 double-deficient mice present a new model for early effects of amyloid-β-related mild cognitive impairment that allows investigations

  7. A quality assessment of patient leaflets on misoprostol induced labour – does written information adhere to international standards for patient involvement and informed consent?

    DEFF Research Database (Denmark)

    Clausen, Jette Aaroe; Juul, Mette; Rydahl, Eva

    Objectives: The need for thorough patient information is increasing as maternity care becomes more medicalised. The aim was to assess the quality of written patient information on labour induction. In most Danish hospitals misoprostol is the first-choice drug for induction in low-risk pregnancies......). Design: Patient leaflets were evaluated according to a validated scoring tool (IPDAS), core elements in The Danish Health Act, and items regarding off-label use and non-registered medication. Two of the authors scored all leaflets independently. Outcome measures: Women’s involvement in decision making......, and information on benefits and harms associated with the treatment, other justifiable treatment options, and non-registered treatment. Results: Generally, the hospitals scored low on the IPDAS checklist. No hospitals encouraged women to consider their preferences. Information on side-effects and adverse outcomes...

  8. Open-access MIMIC-II database for intensive care research.

    Science.gov (United States)

    Lee, Joon; Scott, Daniel J; Villarroel, Mauricio; Clifford, Gari D; Saeed, Mohammed; Mark, Roger G

    2011-01-01

    The critical state of intensive care unit (ICU) patients demands close monitoring, and as a result a large volume of multi-parameter data is collected continuously. This represents a unique opportunity for researchers interested in clinical data mining. We sought to foster a more transparent and efficient intensive care research community by building a publicly available ICU database, namely Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC-II). The data harnessed in MIMIC-II were collected from the ICUs of Beth Israel Deaconess Medical Center from 2001 to 2008 and represent 26,870 adult hospital admissions (version 2.6). MIMIC-II consists of two major components: clinical data and physiological waveforms. The clinical data, which include patient demographics, intravenous medication drip rates, and laboratory test results, were organized into a relational database. The physiological waveforms, including 125 Hz signals recorded at bedside and corresponding vital signs, were stored in an open-source format. MIMIC-II data were also deidentified in order to remove protected health information. Any interested researcher can gain access to MIMIC-II free of charge after signing a data use agreement and completing human subjects training. MIMIC-II can support a wide variety of research studies, ranging from the development of clinical decision support algorithms to retrospective clinical studies. We anticipate that MIMIC-II will be an invaluable resource for intensive care research by stimulating fair comparisons among different studies.

  9. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor; Villalobos Vazquez de la Parra, Luis Francisco; Hilke, Roland

    2015-01-01

    microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  10. Synthesis of Carbon Nanotube (CNT Composite Membranes

    Directory of Open Access Journals (Sweden)

    Dusan Losic

    2010-12-01

    Full Text Available Carbon nanotubes are attractive approach for designing of new membranes for advanced molecular separation because of their unique transport properties and ability to mimic biological protein channels. In this work the synthetic approach for fabrication of carbon nanotubes (CNTs composite membranes is presented. The method is based on growth of multi walled carbon nanotubes (MWCNT using chemical vapour deposition (CVD on the template of nanoporous alumina (PA membranes. The influence of experimental conditions including carbon precursor, temperature, deposition time, and PA template on CNT growth process and quality of fabricated membranes was investigated. The synthesis of CNT/PA composites with controllable nanotube dimensions such as diameters (30–150 nm, and thickness (5–100 µm, was demonstrated. The chemical composition and morphological characteristics of fabricated CNT/PA composite membranes were investigated by various characterisation techniques including scanning electron microscopy (SEM, energy-dispersive x-ray spectroscopy (EDXS, high resolution transmission electron microscopy (HRTEM and x-ray diffraction (XRD. Transport properties of prepared membranes were explored by diffusion of dye (Rose Bengal used as model of hydrophilic transport molecule.

  11. Cyclic stress-strain behavior of polymeric nonwoven structures for the use as artificial leaflet material for transcatheter heart valve prostheses

    Directory of Open Access Journals (Sweden)

    Arbeiter Daniela

    2017-09-01

    Full Text Available Xenogenic leaflet material, bovine and porcine pericardium, is widely used for the fabrication of surgically implanted and transcatheter heart valve prostheses. As a biological material, long term durability of pericardium is limited due to calcification, degeneration and homogeneity. Therefore, polymeric materials represent a promising approach for a next generation of artificial heart valve leaflets with improved durability. Within the current study we analyzed the mechanical performance of polymeric structures based on elastomeric materials. Polymeric cast films were prepared and nonwovens were manufactured in an electrospinning process. Analysis of cyclic stress-strain behavior was performed, using a universal testing machine. The uniaxial cyclic tensile experiments of the elastomeric samples yielded a non-linear elastic response due to viscoelastic behavior with hysteresis. Equilibrium of stress-strain curves was found after a specific number of cycles, for cast films and nonwovens, respectively. In conclusion, preconditioning was found obligatory for the evaluation of the mechanical performance of polymeric materials for the use as artificial leaflet material for heart valve prostheses.

  12. Communicating the benefits and harms of colorectal cancer screening needed for an informed choice: a systematic evaluation of leaflets and booklets.

    Science.gov (United States)

    Dreier, Maren; Borutta, Birgit; Seidel, Gabriele; Münch, Inga; Kramer, Silke; Töppich, Jürgen; Dierks, Marie-Luise; Walter, Ulla

    2014-01-01

    Evidence-based health information (EBHI) can support informed choice regarding whether or not to attend colorectal cancer (CRC) screening. The present study aimed to assess if German leaflets and booklets appropriately inform consumers on the benefits and harms of CRC screening. A systematic search for print media on CRC screening was performed via email enquiry and internet search. The identified documents were assessed for the presence and correctness of information on benefits and harms by two reviewers independently using a comprehensive list of criteria. Many of the 28 leaflets and 13 booklets identified presented unbalanced information on the benefits and harms of CRC screening: one-third did not provide any information on harms. Numeracy information was often lacking. Ten cross-language examples of common misinterpretations or basically false and misleading information were identified. Most of the CRC screening leaflets and booklets in Germany do not meet current EBHI standards. After the study, the publishers of the information materials were provided feedback, including a discussion of our findings. The results can be used to revise existing information materials or to develop new materials that provide correct, balanced, quantified, understandable and unbiased information on CRC screening.

  13. Communicating the benefits and harms of colorectal cancer screening needed for an informed choice: a systematic evaluation of leaflets and booklets.

    Directory of Open Access Journals (Sweden)

    Maren Dreier

    Full Text Available Evidence-based health information (EBHI can support informed choice regarding whether or not to attend colorectal cancer (CRC screening. The present study aimed to assess if German leaflets and booklets appropriately inform consumers on the benefits and harms of CRC screening.A systematic search for print media on CRC screening was performed via email enquiry and internet search. The identified documents were assessed for the presence and correctness of information on benefits and harms by two reviewers independently using a comprehensive list of criteria.Many of the 28 leaflets and 13 booklets identified presented unbalanced information on the benefits and harms of CRC screening: one-third did not provide any information on harms. Numeracy information was often lacking. Ten cross-language examples of common misinterpretations or basically false and misleading information were identified.Most of the CRC screening leaflets and booklets in Germany do not meet current EBHI standards. After the study, the publishers of the information materials were provided feedback, including a discussion of our findings. The results can be used to revise existing information materials or to develop new materials that provide correct, balanced, quantified, understandable and unbiased information on CRC screening.

  14. Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs

    DEFF Research Database (Denmark)

    Jensen, Marie; Schmidt, Steffen; Fedosova, Natalya

    2011-01-01

    recent years cardiac glycosides have furthermore been suggested to possess valuable anticancer activity. To mimic the labile trisaccharide of digitoxin with a stabile carbohydrate surrogate, we have used sulfur linked ethylene glycol moieties of varying length (mono-, di-, tri- or tetra-ethylene glycol...... the shortest mimics were found to have highest efficacy, with the best ligand having a monoethylene glycol unit (IC(50) 0.24 μM), which was slightly better than digitoxigenin (IC(50) 0.64 μM), while none of the novel cardiac glycoside mimics display an in vitro effect as high as digitoxin (IC(50) 0.02 μM)....

  15. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

    Science.gov (United States)

    Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2017-06-25

    Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Structural adaptations of proteins to different biological membranes

    Science.gov (United States)

    Pogozheva, Irina D.; Tristram-Nagle, Stephanie; Mosberg, Henry I.; Lomize, Andrei L.

    2013-01-01

    To gain insight into adaptations of proteins to their membranes, intrinsic hydrophobic thicknesses, distributions of different chemical groups and profiles of hydrogen-bonding capacities (α and β) and the dipolarity/polarizability parameter (π*) were calculated for lipid-facing surfaces of 460 integral α-helical, β-barrel and peripheral proteins from eight types of biomembranes. For comparison, polarity profiles were also calculated for ten artificial lipid bilayers that have been previously studied by neutron and X-ray scattering. Estimated hydrophobic thicknesses are 30-31 Å for proteins from endoplasmic reticulum, thylakoid, and various bacterial plasma membranes, but differ for proteins from outer bacterial, inner mitochondrial and eukaryotic plasma membranes (23.9, 28.6 and 33.5 Å, respectively). Protein and lipid polarity parameters abruptly change in the lipid carbonyl zone that matches the calculated hydrophobic boundaries. Maxima of positively charged protein groups correspond to the location of lipid phosphates at 20-22 Å distances from the membrane center. Locations of Tyr atoms coincide with hydrophobic boundaries, while distributions maxima of Trp rings are shifted by 3-4 Å toward the membrane center. Distributions of Trp atoms indicate the presence of two 5-8 Å-wide midpolar regions with intermediate π* values within the hydrocarbon core, whose size and symmetry depend on the lipid composition of membrane leaflets. Midpolar regions are especially asymmetric in outer bacterial membranes and cell membranes of mesophilic but not hyperthermophilic archaebacteria, indicating the larger width of the central nonpolar region in the later case. In artificial lipid bilayers, midpolar regions are observed up to the level of acyl chain double bonds. PMID:23811361

  17. Protection against Shiga-Toxigenic Escherichia coli by Non-Genetically Modified Organism Receptor Mimic Bacterial Ghosts.

    Science.gov (United States)

    Paton, Adrienne W; Chen, Austen Y; Wang, Hui; McAllister, Lauren J; Höggerl, Florian; Mayr, Ulrike Beate; Shewell, Lucy K; Jennings, Michael P; Morona, Renato; Lubitz, Werner; Paton, James C

    2015-09-01

    Shiga-toxigenic Escherichia coli (STEC) causes severe gastrointestinal infections in humans that may lead to life-threatening systemic sequelae, such as the hemolytic uremic syndrome (HUS). Rapid diagnosis of STEC infection early in the course of disease opens a window of opportunity for therapeutic intervention, for example, by administration of agents that neutralize Shiga toxin (Stx) in the gut lumen. We previously developed a recombinant bacterium that expresses a mimic of the Stx receptor globotriaosyl ceramide (Gb3) on its surface through modification of the lipopolysaccharide (A. W. Paton, R. Morona, and J. C. Paton, Nat Med 6:265-270, 2000, http://dx.doi.org/10.1038/73111). This construct was highly efficacious in vivo, protecting mice from otherwise fatal STEC disease, but the fact that it is a genetically modified organism (GMO) has been a barrier to clinical development. In the present study, we have overcome this issue by development of Gb3 receptor mimic bacterial ghosts (BGs) that are not classified as GMOs. Gb3-BGs neutralized Stx1 and Stx2 in vitro with high efficiency, whereas alternative Gb3-expressing non-GMO subbacterial particles (minicells and outer membrane blebs) were ineffective. Gb3-BGs were highly efficacious in a murine model of STEC disease. All mice (10/10) treated with Gb3-BGs survived challenge with a highly virulent O113:H21 STEC strain and showed no pathological signs of renal injury. In contrast, 6/10 mice treated with control BGs succumbed to STEC challenge, and survivors exhibited significant weight loss, neutrophilia, and histopathological evidence of renal damage. Thus, Gb3-BGs offer a non-GMO approach to treatment of STEC infection in humans, particularly in an outbreak setting. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. Carbon monoxide induced erythroid differentiation of K562 cells mimics the central macrophage milieu in erythroblastic islands.

    Directory of Open Access Journals (Sweden)

    Shlomi Toobiak

    Full Text Available Growing evidence supports the role of erythroblastic islands (EI as microenvironmental niches within bone marrow (BM, where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule--CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage.Based on the above, the study hypothesized CO to have a role in erythroid maturation. Thus, the effect of CO gas as a potential erythroid differentiation inducer on the common model for erythroid progenitors, K562 cells, was explored. Cells were kept under oxygen lacking environment to mimic BM conditions. Nitrogen anaerobic atmosphere (N₂A served as control for CO atmosphere (COA. Under both atmospheres cells proliferation ceased: in N₂A due to cell death, while in COA as a result of erythroid differentiation. Maturation was evaluated by increased glycophorin A expression and Hb concentration. Addition of 1%CO only to N₂A, was adequate for maintaining cell viability. Yet, the average Hb concentration was low as compared to COA. This was validated to be the outcome of diversified maturation stages of the progenitor's population.In fact, the above scenario mimics the in vivo EI conditions, where at any given moment only a minute portion of the progenitors proceeds into terminal differentiation. Hence, this model might provide a basis for further molecular investigations of the EI structure/function relationship.

  19. Developing Nanodiscs as a Tool for Low Resolution Studies of Membrane Proteins

    DEFF Research Database (Denmark)

    Skar-Gislinge, Nicholas

    studies of membrane proteins. So far most of the studies using nanodiscs have been concerning the function of the incorporated membrane protein. However, due to the good control of the size and lipid composition of the nanodisc system, they seem an ideal tool for expanding the use of small angle......Phospholipid nanodiscs are ⇠ 10 nm disc shaped particles consisting of about 150 phospholipids arranged in a central bilayer stabilized by two amphipathic protein ”belts” that wrap around the rim of the bilayer. Because they contain a small bilayer leaflet they can be used as a tool for solution......-assembly process in general, and in particular in relation to incorporation of membrane proteins. This was the aim of work done early in this thesis. Here a detailed model for the small angle x-ray and neutron scattering from the empty nanodisc system was derived and used to describe the nanodisc system with great...

  20. The membrane stress response buffers lethal effects of lipid disequilibrium by reprogramming the protein homeostasis network.

    Science.gov (United States)

    Thibault, Guillaume; Shui, Guanghou; Kim, Woong; McAlister, Graeme C; Ismail, Nurzian; Gygi, Steven P; Wenk, Markus R; Ng, Davis T W

    2012-10-12

    Lipid composition can differ widely among organelles and even between leaflets of a membrane. Lipid homeostasis is critical because disequilibrium can have disease outcomes. Despite their importance, mechanisms maintaining lipid homeostasis remain poorly understood. Here, we establish a model system to study the global effects of lipid imbalance. Quantitative lipid profiling was integral to monitor changes to lipid composition and for system validation. Applying global transcriptional and proteomic analyses, a dramatically altered biochemical landscape was revealed from adaptive cells. The resulting composite regulation we term the "membrane stress response" (MSR) confers compensation, not through restoration of lipid composition, but by remodeling the protein homeostasis network. To validate its physiological significance, we analyzed the unfolded protein response (UPR), one facet of the MSR and a key regulator of protein homeostasis. We demonstrate that the UPR maintains protein biogenesis, quality control, and membrane integrity-functions otherwise lethally compromised in lipid dysregulated cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Potential Therapeutic Uses of p19ARF Mimics in Mammary Tumorigenesis

    National Research Council Canada - National Science Library

    Hann, Stephen R

    2005-01-01

    Since many breast tumors have deregulated c-Myc we hypothesize that an ARF mimic would be a valuable therapeutic agent for breast cancer to inhibit c-Myc-induced transformation/tumorigenesis without...

  2. [Discussion of the implementation of MIMIC database in emergency medical study].

    Science.gov (United States)

    Li, Kaiyuan; Feng, Cong; Jia, Lijing; Chen, Li; Pan, Fei; Li, Tanshi

    2018-05-01

    To introduce Medical Information Mart for Intensive Care (MIMIC) database and elaborate the approach of critically emergent research with big data based on the feature of MIMIC and updated studies both domestic and overseas, we put forward the feasibility and necessity of introducing medical big data to research in emergency. Then we discuss the role of MIMIC database in emergency clinical study, as well as the principles and key notes of experimental design and implementation under the medical big data circumstance. The implementation of MIMIC database in emergency medical research provides a brand new field for the early diagnosis, risk warning and prognosis of critical illness, however there are also limitations. To meet the era of big data, emergency medical database which is in accordance with our national condition is needed, which will provide new energy to the development of emergency medicine.

  3. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders.

    Science.gov (United States)

    Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

    2016-04-05

    Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  4. MOCVD process technology for affordable, high-yield, high-performance MESFET structures. Phase 3: MIMIC

    Science.gov (United States)

    1993-01-01

    Under the MIMIC Program, Spire has pursued improvements in the manufacturing of low cost, high quality gallium arsenide MOCVD wafers for advanced MIMIC FET applications. As a demonstration of such improvements, Spire was tasked to supply MOCVD wafers for comparison to MBE wafers in the fabrication of millimeter and microwave integrated circuits. In this, the final technical report for Spire's two-year MIMIC contract, we report the results of our work. The main objectives of Spire's MIMIC Phase 3 Program, as outlined in the Statement of Work, were as follows: Optimize the MOCVD growth conditions for the best possible electrical and morphological gallium arsenide. Optimization should include substrate and source qualification as well as determination of the optimum reactor growth conditions; Perform all work on 75 millimeter diameter wafers, using a reactor capable of at least three wafers per run; and Evaluate epitaxial layers using electrical, optical, and morphological tests to obtain thickness, carrier concentration, and mobility data across wafers.

  5. An evaluation of the effects of long term cryopreservation, cause of death, and time between death and donation on heart valve leaflet viability

    International Nuclear Information System (INIS)

    Strachan, K.

    1999-01-01

    The protocol for cryopreservation of allograft heart valves at the Donor Tissue Bank of Victoria was based on validation studies on the viability of the heart valve leaflets at the time of processing. The heart block is removed within 24 hours of death and the aor-tic and pulmonary valves trimmed immediately following retrieval. Following this processing, the valves are incubated in antibiotics at 30 degree C for 6 to 8 hours before being frozen in 10% DMSO at a controlled rate. A sample of tricuspid valve leaflet is placed in Krebs solution at the time of trimfning and is used for viability studies. Leaflet viability studies have been perfon-ned on all heart valves retrieved from 1993 to the present day at the Donor Tissue Bank of Victoria. Viability involves a qualitative assessment of the cellular outgrowth by leaflet fibroblasts, this assessment ranging from '-' for no outgrowth to '++++' for maximum outgrowth. Surgeons do not request valves with any particular viability and will use them whether they are viable or not. This evaluation was to determine the effects of long-term cryopreservation, cause of death, and also time lapse of heart removal following death on the viability of the retrieved leaflets. The aim of investigating the effects of long-term cryopreservation was to determine whether there was any correlation between initial viability and viability following storage for several months to several years. It was also decided to investigate whether there was any correlation between time length between death and heart retrieval and the viability. It was also thought that the cause of death may have had an effect on the viability, for example, did death by carbon monoxide poisoning have an effect on the viability of heart valve cells. Heart valves, which had been cryopreserved but could not be transplanted for various reasons were used to study the effects of cryopreservation in this study. These were thawed according to protocol and a sample of the valve

  6. Analysis of the data on pregnancy and lactation provided by patient information leaflets of anti-rheumatic drugs in Argentina.

    Science.gov (United States)

    Sabando, Miguel Ormaza; Saavedra, Maira Arias; Sequeira, Gabriel; Kerzberg, Eduardo

    2018-04-01

    To analyse the level of consistency and updating of the information on pregnancy and lactation provided by patient information leaflets (PILs) of the antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR Task Force recommendations on the use of anti-rheumatic drugs during pregnancy and lactation and the information provided by PILs of the same drugs approved in Argentina were analysed along with inconsistencies within the PILs of different registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were analysed. Out of the 88 PILs, 50% presented information inconsistencies as to pregnancy. Medications comprised in this group were: hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As for lactation, 56% had information inconsistencies. Medications encompassed in this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone, colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered trademark, information inconsistencies on pregnancy were found in the PILs of sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning lactation, inconsistencies were present in the PILs of hydroxychloroquine, sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half of the PILs of anti-rheumatic drugs analysed in this study had information inconsistencies on pregnancy and lactation. This is a serious state of affairs because the consensual decision-making process between patient and professional may be compromised, which, in turn, may give rise to medical-legal issues.

  7. Exploring consumer opinions on the presentation of side-effects information in Australian Consumer Medicine Information leaflets.

    Science.gov (United States)

    Tong, Vivien; Raynor, David K; Blalock, Susan J; Aslani, Parisa

    2016-06-01

    Consumer Medicine Information (CMI) is a brand-specific and standardized source of written medicine information available in Australia for all prescription medicines. Side-effect information is poorly presented in CMI and may not adequately address consumer information needs. To explore consumer opinions on (i) the presentation of side-effect information in existing Australian CMI leaflets and alternative study-designed CMIs and (ii) side-effect risk information and its impact on treatment decision making. Fuzzy trace, affect heuristic, frequency hypothesis and cognitive-experiential theories were applied when revising existing CMI side-effects sections. Together with good information design, functional linguistics and medicine information expertise, alternative ramipril and clopidogrel CMI versions were proposed. Focus groups were then conducted to address the study objectives. Three focus groups (n = 18) were conducted in Sydney, Australia. Mean consumer age was 58 years (range 50-65 years), with equal number of males and females. All consumers preferred the alternative CMIs developed as part of the study, with unequivocal preference for the side-effects presented in a simple tabular format, as it allowed quick and easy access to information. Consumer misunderstandings reflected literacy and numeracy issues inherent in consumer risk appraisal. Many preferred no numerical information and a large proportion preferred natural frequencies. One single method of risk presentation in CMI is unable to cater for all consumers. Consumer misunderstandings are indicative of possible health literacy and numeracy factors that influence consumer risk appraisal, which should be explored further. © 2014 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  8. SV40 late protein VP4 forms toroidal pores to disrupt membranes for viral release.

    Science.gov (United States)

    Raghava, Smita; Giorda, Kristina M; Romano, Fabian B; Heuck, Alejandro P; Hebert, Daniel N

    2013-06-04

    Nonenveloped viruses are generally released from the cell by the timely lysis of host cell membranes. SV40 has been used as a model virus for the study of the lytic nonenveloped virus life cycle. The expression of SV40 VP4 at later times during infection is concomitant with cell lysis. To investigate the role of VP4 in viral release and its mechanism of action, VP4 was expressed and purified from bacteria as a fusion protein for use in membrane disruption assays. Purified VP4 perforated membranes as demonstrated by the release of fluorescent markers encapsulated within large unilamellar vesicles or liposomes. Dynamic light scattering results revealed that VP4 treatment did not cause membrane lysis or change the size of the liposomes. Liposomes encapsulated with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-3-indacene-labeled streptavidin were used to show that VP4 formed stable pores in membranes. These VP4 pores had an inner diameter of 1-5 nm. Asymmetrical liposomes containing pyrene-labeled lipids in the outer monolayer were employed to monitor transbilayer lipid diffusion. Consistent with VP4 forming toroidal pore structures in membranes, VP4 induced transbilayer lipid diffusion or lipid flip-flop. Altogether, these studies support a central role for VP4 acting as a viroporin in the disruption of cellular membranes to trigger SV40 viral release by forming toroidal pores that unite the outer and inner leaflets of membrane bilayers.

  9. Lipid self-assembly and lectin-induced reorganization of the plasma membrane.

    Science.gov (United States)

    Sych, Taras; Mély, Yves; Römer, Winfried

    2018-05-26

    The plasma membrane represents an outstanding example of self-organization in biology. It plays a vital role in protecting the integrity of the cell interior and regulates meticulously the import and export of diverse substances. Its major building blocks are proteins and lipids, which self-assemble to a fluid lipid bilayer driven mainly by hydrophobic forces. Even if the plasma membrane appears-globally speaking-homogeneous at physiological temperatures, the existence of specialized nano- to micrometre-sized domains of raft-type character within cellular and synthetic membrane systems has been reported. It is hypothesized that these domains are the origin of a plethora of cellular processes, such as signalling or vesicular trafficking. This review intends to highlight the driving forces of lipid self-assembly into a bilayer membrane and the formation of small, transient domains within the plasma membrane. The mechanisms of self-assembly depend on several factors, such as the lipid composition of the membrane and the geometry of lipids. Moreover, the dynamics and organization of glycosphingolipids into nanometre-sized clusters will be discussed, also in the context of multivalent lectins, which cluster several glycosphingolipid receptor molecules and thus create an asymmetric stress between the two membrane leaflets, leading to tubular plasma membrane invaginations.This article is part of the theme issue 'Self-organization in cell biology'. © 2018 The Author(s).

  10. In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a novel Mn porphyrin-based antioxidant enzyme mimic.

    Science.gov (United States)

    Li, Bao-qiu; Dong, Xin; Li, Na; Gao, Ji-you; Yuan, Qiang; Fang, Shi-hong; Gong, Xian-chang; Wang, Shu-juan; Wang, Feng-shan

    2014-10-01

    Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The aim of the present study was to investigate the enzyme-mimic activity and the therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on the decomposition of hydrogen peroxide. The antitumor, radioprotective and chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing Kunming mice. The anti-inflammatory and hepatoprotective effects were, respectively, evaluated in histamine-induced edema model and CCl4-induced hepatic damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001-10 µmol/L significantly inhibited the generation of superoxide anion. Significant hydrogen peroxide scavenging activity was observed when the concentration of HSJ-0017 was higher than 0.01 µmol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited significant antitumor effect on S180 tumor xenografts, whereas no significant antitumor effect was observed in H22 tumor xenografts. HSJ-0017 at a dose of 3.0 mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed significant anti-inflammatory and hepatoprotective effects. Our results demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory, radioprotective, chemoprotective, and hepatoprotective effects. It is a potent dual SOD/CAT mimic. © 2014 by the Society for Experimental Biology and Medicine.

  11. Structure and organization of nanosized-inclusion-containing bilayer membranes

    Science.gov (United States)

    Ren, Chun-Lai; Ma, Yu-Qiang

    2009-07-01

    Based on a considerable amount of experimental evidence for lateral organization of lipid membranes which share astonishingly similar features in the presence of different inclusions, we use a hybrid self-consistent field theory (SCFT)/density-functional theory (DFT) approach to deal with bilayer membranes embedded by nanosized inclusions and explain experimental findings. Here, the hydrophobic inclusions are simple models of hydrophobic drugs or other nanoparticles for biomedical applications. It is found that lipid/inclusion-rich domains are formed at moderate inclusion concentrations and disappear with the increase in the concentration of inclusions. At high inclusion content, chaining of inclusions occurs due to the effective depletion attraction between inclusions mediated by lipids. Meanwhile, the increase in the concentration of inclusions can also cause thickening of the membrane and the distribution of inclusions undergoes a layering transition from one-layer structure located in the bilayer midplane to two-layer structure arranged into the two leaflets of a bilayer. Our theoretical predictions address the complex interactions between membranes and inclusions suggesting a unifying mechanism which reflects the competition between the conformational entropy of lipids favoring the formation of lipid- and inclusion-rich domains in lipids and the steric repulsion of inclusions leading to the uniform dispersion.

  12. Solid-state nuclear magnetic resonance measurements of HIV fusion peptide 13CO to lipid 31P proximities support similar partially inserted membrane locations of the α helical and β sheet peptide structures.

    Science.gov (United States)

    Gabrys, Charles M; Qiang, Wei; Sun, Yan; Xie, Li; Schmick, Scott D; Weliky, David P

    2013-10-03

    infection. The present study shows that HFPmn_V2E induces much less vesicle fusion than HFPmn. "HFPtr" contained three strands with HFPmn sequence that were chemically cross-linked near their C-termini. HFPtr mimics the trimeric topology of gp41 and induces much more rapid and extensive vesicle fusion than HFPmn. For HFPmn and HFPtr, well-resolved α and β peaks were observed for A6-, L9-, and L12-labeled samples. For each of these samples, there were similar HFP (13)CO to lipid (31)P proximities in the α and β structures, which evidenced comparable membrane locations of the HFP in either structure including insertion into a single membrane leaflet. The data were also consistent with deeper insertion of HFPtr relative to HFPmn in both the α and β structures. The results supported a strong correlation between the membrane insertion depth of the HFP and its fusogenicity. More generally, the results supported membrane location of the HFP as an important determinant of its fusogenicity. The deep insertion of HFPtr in both the α and β structures provides the most relevant membrane location of the FP for HIV gp41-catalyzed membrane fusion because HIV gp41 is natively trimeric. Well-resolved α and β signals were observed in the HFPmn_V2E samples with L9- and L12- but not A6-labeling. The α signals were much more dominant for L9- and L12-labeled HFPmn_V2E than the corresponding HFPmn or HFPtr. The structural model for the less fusogenic HFPmn_V2E includes a shorter helix and less membrane insertion than either HFPmn or HFPtr. This greater helical population and different helical structure and membrane location could result in less membrane perturbation and lower fusogenicity of HFPmn_V2E and suggest that the β sheet fusion peptide is the most functionally relevant structure of HFPmn, HFPtr, and gp41.

  13. Formation of carrageenan-CaCO{sub 3} bioactive membranes

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Lucas F.B.; Maniglia, Bianca C.; Pereira, Lourivaldo S.; Tapia-Blácido, Delia R.; Ramos, Ana P., E-mail: anapr@ffclrp.usp.br

    2016-01-01

    The high biocompatibility and resorbability of polymeric membranes have encouraged their use to manufacture medical devices. Here, we report on the preparation of membranes consisting of carrageenan, a naturally occurring sulfated polysaccharide that forms helical structures in the presence of calcium ions. We incorporated CaCO{sub 3} particles into the membranes to enhance their bioactivity and mechanical properties. Infrared spectroscopy and X-ray diffraction data confirmed CaCO{sub 3} incorporation into the polymeric matrix. We tested the bioactivity of the samples by immersing them in a solution that mimics the ionic composition and pH of the human body fluid. The hybrid membranes generated hydroxyapatite, as attested by X-ray diffraction data. Scanning electron and atomic force microscopies aided investigation of membrane topography before and after CaCO{sub 3} deposition. The wettability and surface free energy, evaluated by contact angle measures, increased in the presence of CaCO{sub 3} particles. These parameters are important for membrane implantation in the body. Moreover, membrane stiffness was up to 110% higher in the presence of the inorganic particles, as revealed by Young's modulus. - Highlights: • Hybrid kappa and iota carrageenan-CaCO{sub 3} membranes were formed. • The hybrid membrane's origin hydroxyapatite after exposure to simulated body fluid • The carrageenan's specificity to bind Ca{sup 2+} ions tailors the surface properties.

  14. Imaging of Conductive Hearing Loss With a Normal Tympanic Membrane.

    Science.gov (United States)

    Curtin, Hugh D

    2016-01-01

    This article presents an approach to imaging conductive hearing loss in patients with normal tympanic membranes and discusses entities that should be checked as the radiologist evaluates this potentially complicated issue. Conductive hearing loss in a patient with a normal tympanic membrane is a complicated condition that requires a careful imaging approach. Imaging should focus on otosclerosis, and possible mimics and potential surgical considerations should be evaluated. The radiologist should examine the ossicular chain and the round window and keep in mind that a defect in the superior semicircular canal can disturb the hydraulic integrity of the labyrinth.

  15. Prediction of the ischemic origin of functional mitral regurgitation in patients with systolic heart failure through posterior mitral leaflet angle

    Directory of Open Access Journals (Sweden)

    Fereshteh Ghaderi

    2018-01-01

    Full Text Available BACKGROUND: Differentiating ischemic from non-ischemic functional mitral regurgitation‎ (FMR in patients with cardiomyopathy is important in terms of the therapeutic decision-making and prognosis, but might be clinically challenging. In this study, the deformation of mitral valve (MV indices in the prediction of the etiology of FMR was assessed using 2D transthoracic and tissue Doppler echocardiography.METHODS: This case-control study was conducted from April 2015 to January 2016 in Imam Reza Hospital in Mashhad, Iran. The participants consisted of 40 patients with ischemic cardiomyopathy (ICM and 22 with non-ischemic dilated cardiomyopathy (DCM who referred to the heart failure clinic. Transthoracic echocardiography was performed using the conventional 2D and tissue Doppler imaging (TDI. MV tenting area (TA, coaptation distance (CD, anterior and posterior mitral leaflet angles (AMLA and PMLA, and regional systolic myocardial velocity (Sm were measured.RESULTS: There were no significant differences in echocardiographic indices between the two groups, besides Sm and PMLA which were significantly lower and higher, respectively, in ICM subjects in comparison with DCM patients (P = 0.002. PMLA ≥ 40 degrees and Sm ≤ 4 cm/second have a relatively high value for discriminating the ischemic from non-ischemic origin of functional MR in subjects with systolic heart failure (sensitivity: 80.0% and 70.0%, specificity: 73.0% and 77.3%; P = 0.001 and P < 0.001; respectively. Multivariable logistic regression identified PMLA and anterior Sm as major determinants for ischemic MR {Odds ratio (OR [95% confidence interval (CI] = 0.89 (0.82-0.96, P = 0.003, OR (95% CI = 0.29 (0.14-0.60, P = 0.001, respectively}.CONCLUSION: The present study showed that PMLA and Sm had an independent significant association with the mechanism of FMR. These findings are suggestive of the predictive role of mitral deformation echocardiographic indices in the determination of the

  16. Systematic Assessment of Strategies for Lung-targeted Delivery of MicroRNA Mimics

    Science.gov (United States)

    Schlosser, Kenny; Taha, Mohamad; Stewart, Duncan J.

    2018-01-01

    There is considerable interest in the use of synthetic miRNA mimics (or inhibitors) as potential therapeutic agents in pulmonary vascular disease; however, the optimal delivery method to achieve high efficiency, selective lung targeting has not been determined. Here, we sought to investigate the relative merits of different lung-targeted strategies for delivering miRNA mimics in rats. Methods: Tissue levels of a synthetic miRNA mimic, cel-miR-39-3p (0.5 nmol in 50 µL invivofectamine/PBS vehicle) were compared in male rats (n=3 rats/method) after delivery by commonly used lung-targeting strategies including intratracheal liquid instillation (IT-L), intratracheal aerosolization with (IT-AV) or without ventilator assistance (IT-A), intranasal liquid instillation (IN-L) and intranasal aerosolization (IN-A). Intravenous (IV; via jugular vein), intraperitoneal (IP) and subcutaneous (SC) delivery served as controls. Relative levels of cel-miR-39 were quantified by RT-qPCR. Results: At 2 h post delivery, IT-L showed the highest lung mimic level, which was significantly higher than levels achieved by all other methods (from ~10- to 10,000-fold, pMimic levels remained detectable in the lung 24 h after delivery, but were 10- to 100-fold lower. The intrapulmonary distribution of cel-miR-39 was comparable when delivered as either a liquid or aerosol, with evidence of mimic distribution to both the left and right lung lobes and penetration to distal regions. All lung-targeted strategies showed lung-selective mimic uptake, with mimic levels 10- to 100-fold lower in heart and 100- to 10,000-fold lower in liver, kidney and spleen. In contrast, IV, SC and IP routes showed comparable or higher mimic levels in non-pulmonary tissues. Conclusions: miRNA uptake in the lungs differed markedly by up to 4 orders of magnitude, demonstrating that the choice of delivery strategy could have a significant impact on potential therapeutic outcomes in preclinical investigations of miRNA-based drug

  17. Dynamic nanoplatforms in biosensor and membrane constitutional systems.

    Science.gov (United States)

    Mahon, Eugene; Aastrup, Teodor; Barboiu, Mihail

    2012-01-01

    Molecular recognition in biological systems occurs mainly at interfacial environments such as membrane surfaces, enzyme active sites, or the interior of the DNA double helix. At the cell membrane surface, carbohydrate-protein recognition principles apply to a range of specific non-covalent interactions including immune response, cell proliferation, adhesion and death, cell-cell interaction and communication. Protein-protein recognition meanwhile accounts for signalling processes and ion channel structure. In this chapter we aim to describe such constitutional dynamic interfaces for biosensing and membrane transport applications. Constitutionally adaptive interfaces may mimic the recognition capabilities intrinsic to natural recognition processes. We present some recent examples of 2D and 3D constructed sensors and membranes of this type and describe their sensing and transport capabilities.

  18. Interaction of the amyloid β peptide with sodium dodecyl sulfate as a membrane-mimicking detergent.

    NARCIS (Netherlands)

    Hashemi, Shabestari M.; Meeuwenoord, N.J.; Filippov, D.V.; Huber, M.I.

    2016-01-01

    The amyloid β (A β) peptide is important in the context of Alzheimer's disease, since it is one of the major components of the fibrils that constitute amyloid plaques. Agents that can influence fibril formation are important, and of those, membrane mimics are particularly relevant, because the

  19. Monitoring HSVtk suicide gene therapy : the role of [F-18]FHPG membrane transport

    NARCIS (Netherlands)

    Buursma, AR; van Dillen, IJ; van Waarde, A; Vaalburg, W; Hospers, GAP; Mulder, NH; de Vries, EFJ

    2004-01-01

    Favourable pharmacokinetics of the prodrug are essential for successful HSVtk/ganciclovir (GCV) suicide gene therapy. [F-18] FHPG PET might be a suitable technique to assess the pharmacokinetics of the prodrug GCV noninvasively, provided that [F-18] FHPG mimics the behaviour of GCV. Since membrane

  20. A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing.

    Science.gov (United States)

    Ismail, Anisa S; Valastyan, Julie S; Bassler, Bonnie L

    2016-04-13

    Host-microbial symbioses are vital to health; nonetheless, little is known about the role crosskingdom signaling plays in these relationships. In a process called quorum sensing, bacteria communicate with one another using extracellular signal molecules called autoinducers. One autoinducer, AI-2, is proposed to promote interspecies bacterial communication, including in the mammalian gut. We show that mammalian epithelia produce an AI-2 mimic activity in response to bacteria or tight-junction disruption. This AI-2 mimic is detected by the bacterial AI-2 receptor, LuxP/LsrB, and can activate quorum-sensing-controlled gene expression, including in the enteric pathogen Salmonella typhimurium. AI-2 mimic activity is induced when epithelia are directly or indirectly exposed to bacteria, suggesting that a secreted bacterial component(s) stimulates its production. Mutagenesis revealed genes required for bacteria to both detect and stimulate production of the AI-2 mimic. These findings uncover a potential role for the mammalian AI-2 mimic in fostering crosskingdom signaling and host-bacterial symbioses. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. MIMIC II: a massive temporal ICU patient database to support research in intelligent patient monitoring

    Science.gov (United States)

    Saeed, M.; Lieu, C.; Raber, G.; Mark, R. G.

    2002-01-01

    Development and evaluation of Intensive Care Unit (ICU) decision-support systems would be greatly facilitated by the availability of a large-scale ICU patient database. Following our previous efforts with the MIMIC (Multi-parameter Intelligent Monitoring for Intensive Care) Database, we have leveraged advances in networking and storage technologies to develop a far more massive temporal database, MIMIC II. MIMIC II is an ongoing effort: data is continuously and prospectively archived from all ICU patients in our hospital. MIMIC II now consists of over 800 ICU patient records including over 120 gigabytes of data and is growing. A customized archiving system was used to store continuously up to four waveforms and 30 different parameters from ICU patient monitors. An integrated user-friendly relational database was developed for browsing of patients' clinical information (lab results, fluid balance, medications, nurses' progress notes). Based upon its unprecedented size and scope, MIMIC II will prove to be an important resource for intelligent patient monitoring research, and will support efforts in medical data mining and knowledge-discovery.

  2. Enzyme-Triggered Defined Protein Nanoarrays: Efficient Light-Harvesting Systems to Mimic Chloroplasts.

    Science.gov (United States)

    Zhao, Linlu; Zou, Haoyang; Zhang, Hao; Sun, Hongcheng; Wang, Tingting; Pan, Tiezheng; Li, Xiumei; Bai, Yushi; Qiao, Shanpeng; Luo, Quan; Xu, Jiayun; Hou, Chunxi; Liu, Junqiu

    2017-01-24

    The elegance and efficiency by which chloroplasts harvest solar energy and conduct energy transfer have been a source of inspiration for chemists to mimic such process. However, precise manipulation to obtain orderly arranged antenna chromophores in constructing artificial chloroplast mimics was a great challenge, especially from the structural similarity and bioaffinity standpoints. Here we reported a design strategy that combined covalent and noncovalent interactions to prepare a protein-based light-harvesting system to mimic chloroplasts. Cricoid stable protein one (SP1) was utilized as a building block model. Under enzyme-triggered covalent protein assembly, mutant SP1 with tyrosine (Tyr) residues at the designated sites can couple together to form nanostructures. Through controlling the Tyr sites on the protein surface, we can manipulate the assembly orientation to respectively generate 1D nanotubes and 2D nanosheets. The excellent stability endowed the self-assembled protein architectures with promising applications. We further integrated quantum dots (QDs) possessing optical and electronic properties with the 2D nanosheets to fabricate chloroplast mimics. By attaching different sized QDs as donor and acceptor chromophores to the negatively charged surface of SP1-based protein nanosheets via electrostatic interactions, we successfully developed an artificial light-harvesting system. The assembled protein nanosheets structurally resembled the natural thylakoids, and the QDs can achieve pronounced FRET phenomenon just like the chlorophylls. Therefore, the coassembled system was meaningful to explore the photosynthetic process in vitro, as it was designed to mimic the natural chloroplast.

  3. Temperature and cholera toxin B are factors that influence formation of membrane nanotubes in RT4 and T24 urothelial cancer cell lines

    Directory of Open Access Journals (Sweden)

    Doron Kabaso

    2011-03-01

    Full Text Available Doron Kabaso1*, Maruša Lokar1*, Veronika Kralj-Iglic2, Peter Veranic3, Aleš Iglic11Laboratory of Biophysics, Faculty of Electrical Engineering, 2Laboratory of Clinical Biophysics, Faculty of Medicine, 3Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; *These two authors equally share the first authorshipAbstract: The growth of membrane nanotubes is crucial for intercellular communication in both normal development and pathological conditions. Therefore, identifying factors that influence their stability and formation are important for both basic research and in development of potential treatments of pathological states. Here we investigate the effect of cholera toxin B (CTB and temperature on two pathological model systems: urothelial cell line RT4, as a model system of a benign tumor, and urothelial cell line T24, as a model system of a metastatic tumor. In particular, the number of intercellular membrane nanotubes (ICNs; ie, membrane nanotubes that bridge neighboring cells was counted. In comparison with RT4 cells, we reveal a significantly higher number in the density of ICNs in T24 cells not derived from RT4 without treatments (P = 0.005, after 20 minutes at room temperature (P = 0.0007, and following CTB treatment (P = 0.000025. The binding of CTB to GM1–lipid complexes in membrane exvaginations or tips of membrane nanotubes may reduce the positive spontaneous (intrinsic curvature of GM1–lipid complexes, which may lead to lipid mediated attractive interactions between CTB–GM1–lipid complexes, their aggregation and consequent formation of enlarged spherical tips of nanotubes. The binding of CTB to GM1 molecules in the outer membrane leaflet of membrane exvaginations and tips of membrane nanotubes may also increase the area difference between the two leaflets and in this way facilitate the growth of membrane nanotubes.Keywords: cancer cells, membrane nanotubes, cholera toxin

  4. Robotic membranes

    DEFF Research Database (Denmark)

    Ramsgaard Thomsen, Mette

    2008-01-01

    The relationship between digital and analogue is often constructed as one of opposition. The perception that the world is permeated with underlying patterns of data, describing events and matter alike, suggests that information can be understood apart from the substance to which it is associated......, and that its encoded logic can be constructed and reconfigured as an isolated entity. This disembodiment of information from materiality implies that an event like a thunderstorm, or a material like a body, can be described equally by data, in other words it can be read or written. The following prototypes......, Vivisection and Strange Metabolisms, were developed at the Centre for Information Technology and Architecture (CITA) at the Royal Danish Academy of Fine Arts in Copenhagen as a means of engaging intangible digital data with tactile physical material. As robotic membranes, they are a dual examination...

  5. Estimating the size of non-observed economy in Croatia using the MIMIC approach

    Directory of Open Access Journals (Sweden)

    Vjekoslav Klarić

    2011-03-01

    Full Text Available This paper gives a quick overview of the approaches that have been used in the research of shadow economy, starting with the definitions of the terms “shadow economy” and “non-observed economy”, with the accent on the ISTAT/Eurostat framework. Several methods for estimating the size of the shadow economy and the non-observed economy are then presented. The emphasis is placed on the MIMIC approach, one of the methods used to estimate the size of the nonobserved economy. After a glance at the theory behind it, the MIMIC model is then applied to the Croatian economy. Considering the described characteristics of different methods, a previous estimate of the size of the non-observed economy in Croatia is chosen to provide benchmark values for the MIMIC model. Using those, the estimates of the size of non-observed economy in Croatia during the period 1998-2009 are obtained.

  6. Reproducing a Prospective Clinical Study as a Computational Retrospective Study in MIMIC-II.

    Science.gov (United States)

    Kury, Fabrício S P; Huser, Vojtech; Cimino, James J

    2015-01-01

    In this paper we sought to reproduce, as a computational retrospective study in an EHR database (MIMIC-II), a recent large prospective clinical study: the 2013 publication, by the Japanese Association for Acute Medicine (JAAM), about disseminated intravascular coagulation, in the journal Critical Care (PMID: 23787004). We designed in SQL and Java a set of electronic phenotypes that reproduced the study's data sampling, and used R to perform the same statistical inference procedures. All produced source code is available online at https://github.com/fabkury/paamia2015. Our program identified 2,257 eligible patients in MIMIC-II, and the results remarkably agreed with the prospective study. A minority of the needed data elements was not found in MIMIC-II, and statistically significant inferences were possible in the majority of the cases.

  7. MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice*

    Science.gov (United States)

    Irani, Sara; Pan, Xiaoyue; Peck, Bailey C. E.; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M. Mahmood

    2016-01-01

    High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe−/− mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. PMID:27365390

  8. Antimicrobial Effects of Novel Triple Antibiotic Paste-Mimic Scaffolds on Actinomyces naeslundii Biofilm.

    Science.gov (United States)

    Albuquerque, Maria T P; Ryan, Stuart J; Münchow, Eliseu A; Kamocka, Maria M; Gregory, Richard L; Valera, Marcia C; Bottino, Marco C

    2015-08-01

    Actinomyces naeslundii has been recovered from traumatized permanent teeth diagnosed with necrotic pulps. In this work, a triple antibiotic paste (TAP)-mimic scaffold is proposed as a drug-delivery strategy to eliminate A. naeslundii dentin biofilm. Metronidazole, ciprofloxacin, and minocycline were added to a polydioxanone (PDS) polymer solution and spun into fibrous scaffolds. Fiber morphology, mechanical properties, and drug release were investigated by using scanning electron microscopy, microtensile testing, and high-performance liquid chromatography, respectively. Human dentin specimens (4 × 4 × 1 mm(3), n = 4/group) were inoculated with A. naeslundii (ATCC 43146) for 7 days for biofilm formation. The infected dentin specimens were exposed to TAP-mimic scaffolds, TAP solution (positive control), and pure PDS (drug-free scaffold). Dentin infected (7-day biofilm) specimens were used for comparison (negative control). Confocal laser scanning microscopy was done to determine bacterial viability. Scaffolds displayed a submicron mean fiber diameter (PDS = 689 ± 312 nm and TAP-mimic = 718 ± 125 nm). Overall, TAP-mimic scaffolds showed significantly (P ≤ .040) lower mechanical properties than PDS. Within the first 24 hours, a burst release for all drugs was seen. A sustained maintenance of metronidazole and ciprofloxacin was observed over 4 weeks, but not for minocycline. Confocal laser scanning microscopy demonstrated complete elimination of all viable bacteria exposed to the TAP solution. Meanwhile, TAP-mimic scaffolds led to a significant (P mimic scaffolds hold significant potential in the eradication/elimination of bacterial biofilm, a critical step in regenerative endodontics. Copyright © 2015 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  9. MicroRNA-30c Mimic Mitigates Hypercholesterolemia and Atherosclerosis in Mice.

    Science.gov (United States)

    Irani, Sara; Pan, Xiaoyue; Peck, Bailey C E; Iqbal, Jahangir; Sethupathy, Praveen; Hussain, M Mahmood

    2016-08-26

    High plasma cholesterol levels are a major risk factor for atherosclerosis. Plasma cholesterol can be reduced by inhibiting lipoprotein production; however, this is associated with steatosis. Previously we showed that lentivirally mediated hepatic expression of microRNA-30c (miR-30c) reduced hyperlipidemia and atherosclerosis in mice without causing hepatosteatosis. Because viral therapy would be formidable, we examined whether a miR-30c mimic can be used to mitigate hyperlipidemia and atherosclerosis without inducing steatosis. Delivery of a miR-30c mimic to the liver diminished diet-induced hypercholesterolemia in C57BL/6J mice. Reductions in plasma cholesterol levels were significantly correlated with increases in hepatic miR-30c levels. Long term dose escalation studies showed that miR-30c mimic caused sustained reductions in plasma cholesterol with no obvious side effects. Furthermore, miR-30c mimic significantly reduced hypercholesterolemia and atherosclerosis in Apoe(-/-) mice. Mechanistic studies showed that miR-30c mimic had no effect on LDL clearance but reduced lipoprotein production by down-regulating microsomal triglyceride transfer protein expression. MiR-30c had no effect on fatty acid oxidation but reduced lipid synthesis. Additionally, whole transcriptome analysis revealed that miR-30c mimic significantly down-regulated hepatic lipid synthesis pathways. Therefore, miR-30c lowers plasma cholesterol and mitigates atherosclerosis by reducing microsomal triglyceride transfer protein expression and lipoprotein production and avoids steatosis by diminishing lipid syntheses. It mitigates atherosclerosis most likely by reducing lipoprotein production and plasma cholesterol. These findings establish that increasing hepatic miR-30c levels is a viable treatment option for reducing hypercholesterolemia and atherosclerosis. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Secretion of Bacterial Lipoproteins: Through the Cytoplasmic Membrane, the Periplasm and Beyond

    Science.gov (United States)

    Zückert, Wolfram R.

    2014-01-01

    Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., grampositive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporterlike LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the “+2 rule”. Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

  11. Role of phosphatidylinositol 4,5-bisphosphate in regulating EHD2 plasma membrane localization.

    Directory of Open Access Journals (Sweden)

    Laura C Simone

    Full Text Available The four mammalian C-terminal Eps15 homology domain-containing proteins (EHD1-EHD4 play pivotal roles in endocytic membrane trafficking. While EHD1, EHD3 and EHD4 associate with intracellular tubular/vesicular membranes, EHD2 localizes to the inner leaflet of the plasma membrane. Currently, little is known about the regulation of EHD2. Thus, we sought to define the factors responsible for EHD2's association with the plasma membrane. The subcellular localization of endogenous EHD2 was examined in HeLa cells using confocal microscopy. Although EHD partner proteins typically mediate EHD membrane recruitment, EHD2 was targeted to the plasma membrane independent of two well-characterized binding proteins, syndapin2 and EHBP1. Additionally, the EH domain of EHD2, which facilitates canonical EHD protein interactions, was not required to direct overexpressed EHD2 to the cell surface. On the other hand, several lines of evidence indicate that the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2 plays a crucial role in regulating EHD2 subcellular localization. Pharmacologic perturbation of PIP2 metabolism altered PIP2 plasma membrane distribution (as assessed by confocal microscopy, and caused EHD2 to redistribute away from the plasma membrane. Furthermore, overexpressed EHD2 localized to PIP2-enriched vacuoles generated by active Arf6. Finally, we show that although cytochalasin D caused actin microfilaments to collapse, EHD2 was nevertheless maintained at the plasma membrane. Intriguingly, cytochalasin D induced relocalization of both PIP2 and EHD2 to actin aggregates, supporting a role of PIP2 in controlling EHD2 subcellular localization. Altogether, these studies emphasize the significance of membrane lipid composition for EHD2 subcellular distribution and offer new insights into the regulation of this important endocytic protein.

  12. Modulation and interactions of charged biomimetic membranes with bivalent ions

    Science.gov (United States)

    Kazadi Badiambile, Adolphe

    The biological membrane of an eukaryotic cell is a two-dimensional structure of mostly phospholipids with embedded proteins. This two-dimensional structure plays many key roles in the life of a cell. Transmembrane proteins, for example, play the role of a gate for different ions (such as Ca2+). Also found are peripheral proteins that are used as enzymes for different purposes in the inner leaflet of the plasma membrane. Phospholipids, in particular play three key roles. Firstly, some members of this group are used to store energy. Secondly, the hydrophobic and hydrophilic properties inherent to phospholipids enable them to be used as building blocks of the cell membrane by forming an asymmetric bilayer. This provides a shielding protection against the outer environment while at the same time keeping the organelles and cytosol from leaking out of the cell. Finally lipids are involved in regulating the aggregation of proteins in the membrane. In addition, some subspecies such as phosphatidylinositol (PtdIns) are second messenger molecules in their own right, thus playing an important role in cellular signaling events. In my work presented in this thesis, I am focusing on the role of some phospholipids as signaling molecules and in particular the physicochemical underpinnings that could be used in their spatiotemporal organization in the cellular plasma membrane. I am specifically concerned with the important family of phosphatidylinositol lipids. PtdIns are very well known for their role as signaling molecules in numerous cell events. They are located in the inner leaflet of the plasma membrane as well as part of the membrane of other organelles. Studies of these signaling molecules in their in vivo environment present many challenges: Firstly, the complexity of interactions due to the numerous entities present in eukaryotic cell membranes makes it difficult to establish clear cause and effect relationships. Secondly, due to their size, our inability to probe these

  13. Design and synthesis of an antigenic mimic of the Ebola glycoprotein

    OpenAIRE

    Rutledge, Ryan D.; Huffman, Brian J.; Cliffel, David E.; Wright, David W.

    2008-01-01

    An antigenic mimic of the Ebola glycoprotein was synthesized and tested for its ability to be recognized by an anti-Ebola glycoprotein antibody. Epitope-mapping procedures yielded a suitable epitope that, when presented on the surface of a nanoparticle, forms a structure that is recognized by an antibody specific for the native protein. This mimic-antibody interaction has been quantitated through ELISA and QCM-based methods and yielded an affinity (Kd = 12 × 10−6 M) within two orders of magni...

  14. Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Duelund, Lars; Pakkanen, Kirsi Inkeri

    2010-01-01

    triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in diameter, which forms spontaneously, and remains stable on at least the microsecond time scale. The results give credence to the hotly debated existence of mobile neutral lipid...... aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model...

  15. Modification of Salmonella Lipopolysaccharides Prevents the Outer Membrane Penetration of Novobiocin

    Energy Technology Data Exchange (ETDEWEB)

    Nobre, Thatyane M.; Martynowycz, Michael W.; Andreev, Konstantin; Kuzmenko, Ivan; Nikaido, Hiroshi; Gidalevitz, David

    2015-12-01

    Small hydrophilic antibiotics traverse the outer membrane of Gram-negative bacteria through porin channels. Large lipophilic agents traverse the outer membrane through its bilayer, containing a majority of lipopolysaccharides in its outer leaflet. Genes controlled by the two-component regulatory system PhoPQ modify lipopolysaccharides. We isolate lipopolysaccharides from isogenic mutants of Salmonella sp., one lacking the modification, the other fully modified. These lipopolysaccharides were reconstituted asmonolayers at the air-water interface, and their properties, aswell as their interaction with a large lipophilic drug, novobiocin, was studied. X-ray reflectivity showed that the drug penetrated the monolayer of the unmodified lipopolysaccharides reaching the hydrophobic region,butwas prevented fromthis penetration intothemodified lipopolysaccharides.Results correlatewith behavior of bacterial cells, which become resistant to antibiotics after PhoPQ-regulated modifications. Grazing incidence x-ray diffraction showed that novobiocin produced a striking increase in crystalline coherence length, and the size of the near-crystalline domains.

  16. Free energies of stable and metastable pores in lipid membranes under tension.

    Science.gov (United States)

    den Otter, Wouter K

    2009-11-28

    The free energy profile of pore formation in a lipid membrane, covering the entire range from a density fluctuation in an intact bilayer to a large tension-stabilized pore, has been calculated by molecular dynamics simulations with a coarse-grained lipid model. Several fixed elongations are used to obtain the Helmholtz free energy as a function of pore size for thermodynamically stable, metastable, and unstable pores, and the system-size dependence of these elongations is discussed. A link to the Gibbs free energy at constant tension, commonly known as the Litster model, is established by a Legendre transformation. The change of genus upon pore formation is exploited to estimate the saddle-splay modulus or Gaussian curvature modulus of the membrane leaflets. Details are provided of the simulation approach, which combines the potential of mean constraint force method with a reaction coordinate based on the local lipid density.

  17. To die or not to die? Lessons from lesion mimic mutants

    KAUST Repository

    Bruggeman, Quentin; Raynaud, Cé cile; Benhamed, Moussa; Delarue, Marianne

    2015-01-01

    ) the involvements of chloroplasts and light energy, (ii) the roles of sphingolipids and fatty acids, (iii) a signal perception at the plasma membrane that requires efficient membrane trafficking, (iv) secondary messengers such as ion fluxes and ROS and (v

  18. Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

    Science.gov (United States)

    Ju, Jingfang

    2018-01-01

    Background Resistance to 5-Fluorouracil (5-FU) based chemotherapy is the major reason for failure of treating patients with advanced colorectal cancer. Materials and methods In this study, we developed a novel miR-129 mimic with potent efficacy in eliminating resistant colon cancer stem cells both in vitro and in vivo. We integrated 5-FU into miR-129 by replacing Uracil (U) to generate 5-FU-miR-129 mimics (Mimic-1). Results Mimic-1 is a strong therapeutic candidate with a number of unique features. Mimic-1 can be delivered to cancer cells without any transfection reagents (e.g. lipids, viral vector, nanoparticles). Mimic-1 is more potent at inhibiting cell proliferation and inducing cell cycle arrest at G1 phase than native miR-129 and the other mimics tested, while retaining target specificity. Mimic-1 prevents colon cancer metastasis in vivo without toxicity. Conclusion This represents a significant advancement in the development of a nontoxic and highly potent miRNA based cancer therapeutics and establishes a foundation for further developing Mimic-1 as a novel anti-cancer therapeutic for treating colorectal cancer. PMID:29507661

  19. Extracellular membrane vesicles in blood products-biology and clinical relevance

    Directory of Open Access Journals (Sweden)

    Emilija Krstova Krajnc

    2016-01-01

    Full Text Available Extracellular membrane vesicles are fragments shed from plasma membranes off all cell types that are undergoing apoptosis or are being subjected to various types of stimulation or stress.  Even in the process of programmed cell death (apoptosis, cell fall apart of varying size vesicles. They expose phosphatidylserine (PS on the outer leaflet of their membrane, and bear surface membrane antigens reflecting their cellular origin. Extracellular membrane vesicles have been isolated from many types of biological fluids, including serum, cerebrospinal fluid, urine, saliva, tears and conditioned culture medium. Flow cytometry is one of the many different methodological approaches that have been used to analyze EMVs. The method attempts to characterize the EMVs cellular origin, size, population, number, and structure. EMVs are present and accumulate in blood products (erythrocytes, platelets as well as in fresh frozen plasma during storage. The aim of this review is to highlight the importance of extracellular vesicles as a cell-to-cell communication system and the role in the pathogenesis of different diseases. Special emphasis will be given to the implication of extracellular membrane vesicles in blood products and their clinical relevance. Although our understanding of the role of  EMVs in disease is far from comprehensive, they display promise as biomarkers for different diseases in the future and also as a marker of quality and safety in the quality control of blood products.

  20. Synergistic Effect of MiR-146a Mimic and Cetuximab on Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Suning Huang

    2014-01-01

    Full Text Available Previously, we found that the expression of microRNA-146a (miR-146a was downregulated in hepatocellular carcinoma (HCC formalin-fixed paraffin-embedded (FFPE tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

  1. Unmasking Hyperthyroidism in the Elderly: How to distinguish hyperthyroidism from conditions that mimic the symptoms

    OpenAIRE

    Gordon, Michael; Isenberg, Yoel; Bain, Jerald

    1992-01-01

    Hyperthyroidism in the elderly can mimic symptoms suggestive of aging or concomitant illnesses. The disease can cause serious problems and disabilities in older individuals. A strong sense of suspicion, the appropriate use of screening tests, and, when indicated, more definitive investigations usually results in the accurate diagnosis of a condition for which there is effective treatment.

  2. Vesicles to concentrate iron in low-Iron media: An attempt to mimic marine siderophores

    Czech Academy of Sciences Publication Activity Database

    Bednárová, Lucie; Brandel, J.; d'Hardemare, A. d. M.; Bednár, J.; Serratrice, G.; Pierre, J. L.

    2008-01-01

    Roč. 14, č. 12 (2008), s. 3680-3686 ISSN 0947-6539 Institutional research plan: CEZ:AV0Z40550506 Keywords : iron * marine siderophore mimics * micelles * self-assembly * vesicles Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.454, year: 2008

  3. Families, schools, and student achievement inequality: a multilevel MIMIC model approach

    Czech Academy of Sciences Publication Activity Database

    Tsai, S. L.; Smith, Michael; Hauser, R. M.

    2017-01-01

    Roč. 90, č. 1 (2017), s. 64-88 ISSN 0038-0407 R&D Projects: GA ČR GCP404/12/J006; GA ČR GB14-36154G Institutional support: RVO:67985998 Keywords : MIMIC model * educational inequality * academic performance Subject RIV: AO - Sociology, Demography OBOR OECD: Sociology Impact factor: 2.697, year: 2016

  4. Fluorescent discrimination between traces of chemical warfare agents and their mimics.

    Science.gov (United States)

    Díaz de Greñu, Borja; Moreno, Daniel; Torroba, Tomás; Berg, Alexander; Gunnars, Johan; Nilsson, Tobias; Nyman, Rasmus; Persson, Milton; Pettersson, Johannes; Eklind, Ida; Wästerby, Pär

    2014-03-19

    An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.

  5. Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

    DEFF Research Database (Denmark)

    Rehfeld, A; Dissing, S; Skakkebæk, N E

    2016-01-01

    Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic...

  6. The immune impact of mimic endoscopic retrograde appendicitis therapy and appendectomy on rabbits of acute appendicitis.

    Science.gov (United States)

    Liu, Suqin; Pei, Fenghua; Wang, Xinhong; Li, Deliang; Zhao, Lixia; Song, Yanyan; Chen, Zhendong; Liu, Bingrong

    2017-09-12

    This study was conducted to evaluate the immune impact of mimic endoscopic retrograde appendicitis therapy and appendectomy on rabbits of acute suppurative appendicitis and to determine whether TLR4/MYD88/NF-κB signaling pathway was activated in this process. 48 rabbits were assigned into 4 groups: group I, the mimic endoscopic retrograde appendicitis therapy group; group II, the appendectomy group; group III, the model group; and group IV, the blank group. White blood cells decreased, while levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, interleukin-4, and interleukin-10 increased on the 2 nd day in group I and II. IgA in feces decreased at 2 weeks, while fecal microbiota changed at 2 and 4 weeks after appendectomy. CD8 + cells in appendix of group I increased within 8 weeks. Upregulated expression of TLR4, MYD88, and nuclear NF-κB were detected on the 2 nd day in group I and II. Mimic endoscopic retrograde appendicitis therapy and appendectomy are effective ways for acute suppurative appendicitis. Mimic endoscopic retrograde appendicitis therapy was more preferable due to its advantage in maintaining intestinal immune function. TLR4/MYD88/NF-κB signaling pathway was activated in acute phase of appendicitis.

  7. Self-Assembly of Multi-nanozymes to Mimic an Intracellular Antioxidant Defense System.

    Science.gov (United States)

    Huang, Yanyan; Liu, Zhen; Liu, Chaoqun; Ju, Enguo; Zhang, Yan; Ren, Jinsong; Qu, Xiaogang

    2016-06-01

    In this work, for the first time, we constructed a novel multi-nanozymes cooperative platform to mimic intracellular antioxidant enzyme-based defense system. V2 O5 nanowire served as a glutathione peroxidase (GPx) mimic while MnO2 nanoparticle was used to mimic superoxide dismutase (SOD) and catalase (CAT). Dopamine was used as a linker to achieve the assembling of the nanomaterials. The obtained V2 O5 @pDA@MnO2 nanocomposite could serve as one multi-nanozyme model to mimic intracellular antioxidant enzyme-based defense procedure in which, for example SOD, CAT, and GPx co-participate. In addition, through assembling with dopamine, the hybrid nanocomposites provided synergistic antioxidative effect. Importantly, both in vitro and in vivo experiments demonstrated that our biocompatible system exhibited excellent intracellular reactive oxygen species (ROS) removal ability to protect cell components against oxidative stress, showing its potential application in inflammation therapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Recent advances in compartmentalized synthetic architectures as drug carriers, cell mimics and artificial organelles

    DEFF Research Database (Denmark)

    York-Durán, María José; Gallardo, Maria Godoy; Labay, Cédric Pierre

    2017-01-01

    significant research attention and these assemblies are proposed as candidate materials for a range of biomedical applications. In this Review article, the recent successes of multicompartment architectures as carriers for the delivery of therapeutic cargo or the creation of micro- and nanoreactors that mimic...

  9. A novel nitrogen-dependent gene associates with the lesion mimic trait in wheat

    Science.gov (United States)

    Lesion mimic (LM) refers to hypersensitive reaction-like (HRL) symptoms that appears on leaf tissue in the absence of plant pathogens. In a wheat line P7001, LM showed up on the leaves under the 0 g nitrogen (N) treatment, but disappeared when sufficient N was supplied, suggesting that LM is N-respo...

  10. Antibacterial TAP-mimic electrospun polymer scaffold: effects on P. gingivalis-infected dentin biofilm.

    Science.gov (United States)

    Albuquerque, Maria Tereza P; Evans, Joshua D; Gregory, Richard L; Valera, Marcia C; Bottino, Marco C

    2016-03-01

    This study sought to investigate, in vitro, the effects of a recently developed triple antibiotic paste (TAP)-mimic polymer nanofibrous scaffold against Porphyromonas gingivalis-infected dentin biofilm. Dentin specimens (4 × 4 × 1 mm(3)) were prepared from human canines. The specimens were sterilized, inoculated with P. gingivalis (ATCC 33277), and incubated for 1 week to allow for biofilm formation. Infected dentin specimens were exposed for 3 days to the following treatments: antibiotic-free polydioxanone scaffold (PDS, control), PDS + 25 wt% TAP [25 mg of each antibiotic (metronidazole, ciprofloxacin, and minocycline) per mL of the PDS polymer solution], or a saturated TAP-based solution (50 mg of each antibiotic per mL of saline solution). In order to serve as the negative control, infected dentin specimens were left untreated (bacteria only). To determine the antimicrobial efficacy of the TAP-mimic scaffold, a colony-forming unit (CFU) per milliliter (n = 10/group) measurement was performed. Furthermore, additional specimens (n = 2/group) were prepared to qualitatively study biofilm inhibition via scanning electron microscopy (SEM). Statistics were performed, and significance was set at the 5% level. Both the TAP-mimic scaffold and the positive control (TAP solution) led to complete bacterial elimination, differing statistically (p mimic scaffold against an established P. gingivalis-infected dentin biofilm. Collectively, the data suggest that the proposed nanofibrous scaffold might be used as an alternative to the advocated clinical gold standard (i.e., TAP) for intracanal disinfection prior to regenerative endodontics.

  11. Evaluation of MIMIC-Model Methods for DIF Testing with Comparison to Two-Group Analysis

    Science.gov (United States)

    Woods, Carol M.

    2009-01-01

    Differential item functioning (DIF) occurs when an item on a test or questionnaire has different measurement properties for 1 group of people versus another, irrespective of mean differences on the construct. This study focuses on the use of multiple-indicator multiple-cause (MIMIC) structural equation models for DIF testing, parameterized as item…

  12. Synergistic effect of MiR-146a mimic and cetuximab on hepatocellular carcinoma cells.

    Science.gov (United States)

    Huang, Suning; He, Rongquan; Rong, Minhua; Dang, Yiwu; Chen, Gang

    2014-01-01

    Previously, we found that the expression of microRNA-146a (miR-146a) was downregulated in hepatocellular carcinoma (HCC) formalin-fixed paraffin-embedded (FFPE) tissues compared to the adjacent noncancerous hepatic tissues. In the current study, we have explored the in vitro effect of miR-146a on the malignant phenotypes of HCC cells. MiR-146a mimic could suppress cell growth and increase cellular apoptosis in HCC cell lines HepG2, HepB3, and SNU449, as assessed by spectrophotometry, fluorimetry, and fluorescence microscopy, respectively. Furthermore, western blot showed that miR-146a mimic downregulated EGFR, ERK1/2, and stat5 signalings. These effects were less potent compared to that of a siRNA targeting EGFR, a known target gene of miR-146a. Moreover, miR-146a mimic could enhance the cell growth inhibition and apoptosis induction impact of various EGFR targeting agents. The most potent combination was miR-146a mimic with cetuximab, presenting a synergistic effect. In conclusion, miR-146a plays a vital role in the cell growth and apoptosis of HCC cells and inducing miR-146a level might be a critical targeted molecular therapy strategy for HCC.

  13. MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes

    Science.gov (United States)

    Venken, Koen J. T.; Schulze, Karen L.; Haelterman, Nele A.; Pan, Hongling; He, Yuchun; Evans-Holm, Martha; Carlson, Joseph W.; Levis, Robert W.; Spradling, Allan C.; Hoskins, Roger A.; Bellen, Hugo J.

    2011-01-01

    We demonstrate the versatility of a collection of insertions of the transposon Minos mediated integration cassette (MiMIC), in Drosophila melanogaster. MiMIC contains a gene-trap cassette and the yellow+ marker flanked by two inverted bacteriophage ΦC31 attP sites. MiMIC integrates almost at random in the genome to create sites for DNA manipulation. The attP sites allow the replacement of the intervening sequence of the transposon with any other sequence through recombinase mediated cassette exchange (RMCE). We can revert insertions that function as gene traps and cause mutant phenotypes to wild type by RMCE and modify insertions to control GAL4 or QF overexpression systems or perform lineage analysis using the Flp system. Insertions within coding introns can be exchanged with protein-tag cassettes to create fusion proteins to follow protein expression and perform biochemical experiments. The applications of MiMIC vastly extend the Drosophila melanogaster toolkit. PMID:21985007

  14. Validation of Triphasic Mixture Theory for a Mimic of Intervertebral Disk Tissue

    NARCIS (Netherlands)

    Oomens, C.W.J.; Heus, de H.J.; Huyghe, J.M.R.J.; Nelissen, J.G.L.; Janssen, J.D.

    1995-01-01

    This paper describes experimental studies an synthetic madel materials that mimic the mechanical behavior af intervertebral disk tissue. The results are used ta validate the triphasic mixture theory to describe soft charged hydrated materiais. Permeability and swelling pressure experiments were used

  15. Bourgeois Males of the Peacock Blenny, Salaria pavo, Discriminate Female Mimics from Females?

    DEFF Research Database (Denmark)

    Gonçalves, David; Matos, Ricardo Jorge Santa Clara; Fagundes, Teresa

    2005-01-01

    In a Portuguese population of Salaria pavo, two types of reproductively active males occur: large bourgeois males that defend nests and have fully developed secondary sex characters (SSC) and small sneaker males that mimic the females' morphology and behaviour to approach nests and parasitize...

  16. Recent advances on polymeric membranes for membrane reactors

    KAUST Repository

    Buonomenna, M. G.; Choi, Seung Hak

    2012-01-01

    . The successful use of membranes in membrane reactors is primary the result of two developments concerning: (i) membrane materials and (ii) membrane structures. The selection of a suited material and preparation technique depends on the application the membrane

  17. Extensive preclinical investigation of polymersomal formulation of doxorubicin versus Doxil-mimic formulation.

    Science.gov (United States)

    Alibolandi, Mona; Abnous, Khalil; Mohammadi, Marzieh; Hadizadeh, Farzin; Sadeghi, Fatemeh; Taghavi, Sahar; Jaafari, Mahmoud Reza; Ramezani, Mohammad

    2017-10-28

    Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate

  18. Membrane association and localization dynamics of the Ebola virus matrix protein VP40.

    Science.gov (United States)

    Gc, Jeevan B; Gerstman, Bernard S; Chapagain, Prem P

    2017-10-01

    The Ebola virus matrix protein VP40 is a major structural protein that provides the scaffolding for new Ebola virus particles. For this, VP40 is first trafficked to the lower leaflet of the plasma membrane (PM) in its dimeric form. Once associated with the PM, the VP40 dimers undergo structural rearrangements and oligomerize into hexamers and filaments that make up the virus matrix. Therefore, association of the VP40 dimers and their stabilization at the PM is a crucial step in the Ebola life-cycle. To understand the molecular details of the VP40 dimer-PM interactions, we investigated the dimer association with the inner leaflet of the PM using detailed all-atom molecular dynamics (MD) simulations. The formation of the dimer-PM complex is facilitated by the interactions of the VP40 lysine residues and the anionic lipids POPS, POPI, and PIP 2 in the PM. In contrast, the dimer fails to associate with a membrane without POPS, POPI, or PIP 2 lipids. We explored the mechanisms of the association and identified important residues and lipids involved in localization and stabilization of VP40 dimers at the PM. MD simulations elucidate the role of a C-terminal α-helix alignment parallel to the lipid bilayer surface as well as the creation of membrane defects that allow partial insertion of the hydrophobic residue V276 into the membrane to further stabilize the VP40 dimer-PM complex. Understanding the mechanisms of the VP40 dimer-PM association that facilitate oligomerization can be important for potentially targeting the VP40 for small molecules that can interfere with the virus life-cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Membrane selectivity and disordering mechanism of antimicrobial peptide protegrin-1

    Science.gov (United States)

    Ishitsuka, Yuji

    Protegrin-1 (PG-1) is a beta-sheet antimicrobial peptide (AMP), a class of peptides innate to various organisms and functions as a defense agent against harmful microorganisms by means of membrane disordering. Characteristic chemical and structural properties of AMPs allow selective interaction against invaders' cell membranes. Despite their enormous biomedical potential, progress towards developing them into therapeutic agents has been hampered by a lack of insight into their mechanism of action. AMP insertion assays using Langmuir monolayers reveal that both electrostatic properties of the lipid head group as well as the packing density of the lipid tail group play important roles in determining the membrane selectivity of AMPs. These results help elucidate how the AMP selectively targets the cell membrane of microorganisms over the cell membrane of the host. In addition, these results also explain the higher hemolytic ability of PG-1 against human red blood cells (RBCs) compared to the hemolytic ability of PG-1 against sheep and pig RBCs. Synchrotron X-ray reflectivity shows that PG-1 penetrates into the lipid layer. Grazing incidence X-ray diffraction and fluorescence microscopy indicate that the insertion of PG-1 disorders tail group packing. Membrane selectivity and insertion location information of AMPs with different primary sequence and secondary structure have been obtained by using a truncated version of PG-1: PC-17, and an alpha-helical AMP, LL-37, respectively. The similarity of the membrane disordering process across these various peptides motivated us to test the membrane disordering effect of molecules designed to mimic these peptides. Peptide-mimics based on meta-phenylene ethynylenes demonstrate similar membrane disordering effects, showing that the potency of AMPs is derived from their overall chemical and structural properties, rather than exact peptide sequence. Atomic force microscopy (AFM) was used to directly image first, the PG-1

  20. Spheres of influence: Porphyromonas gingivalis outer membrane vesicles.

    Science.gov (United States)

    Gui, M J; Dashper, S G; Slakeski, N; Chen, Y-Y; Reynolds, E C

    2016-10-01

    Outer membrane vesicles (OMVs) are asymmetrical single bilayer membranous nanostructures produced by Gram-negative bacteria important for bacterial interaction with the environment. Porphyromonas gingivalis, a keystone pathogen associated with chronic periodontitis, produces OMVs that act as a virulence factor secretion system contributing to its pathogenicity. Despite their biological importance, the mechanisms of OMV biogenesis have not been fully elucidated. The ~14 times more curvature of the OMV membrane than cell outer membrane (OM) indicates that OMV biogenesis requires energy expenditure for significant curvature of the OMV membrane. In P. gingivalis, we propose that this may be achieved by upregulating the production of certain inner or outer leaflet lipids, which causes localized outward curvature of the OM. This results in selection of anionic lipopolysaccharide (A-LPS) and associated C-terminal domain (CTD) -family proteins on the outer surface due to their ability to accommodate the curvature. Deacylation of A-LPS may further enable increased curvature leading to OMV formation. Porphyromonas gingivalis OMVs that are selectively enriched in CTD-family proteins, largely the gingipains, can support bacterial coaggregation, promote biofilm development and act as an intercessor for the transport of non-motile bacteria by motile bacteria. The P. gingivalis OMVs are also believed to contribute to host interaction and colonization, evasion of immune defense mechanisms, and destruction of periodontal tissues. They may be crucial for both micro- and macronutrient capture, especially heme and probably other assimilable compounds for its own benefit and that of the wider biofilm community. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Use of ceragenins to create novel biofouling resistant water-treatment membranes.

    Energy Technology Data Exchange (ETDEWEB)

    Hibbs, Michael R.; Altman, Susan Jeanne; Feng, Yanshu (Brigham Young University, Provo, UT); Savage, Paul B. (Brigham Young University, Provo, UT); Pollard, Jacob (Brigham Young University, Provo, UT); Sanchez, Andres L. (LMATA, Albuquerque, NM); Fellows, Benjamin D.; Jones, Howland D. T.; McGrath, Lucas K. (LMATA, Albuquerque, NM)

    2008-12-01

    Scoping studies have demonstrated that ceragenins, when linked to water-treatment membranes have the potential to create biofouling resistant water-treatment membranes. Ceragenins are synthetically produced molecules that mimic antimicrobial peptides. Evidence includes measurements of CSA-13 prohibiting the growth of and killing planktonic Pseudomonas fluorescens. In addition, imaging of biofilms that were in contact of a ceragenin showed more dead cells relative to live cells than in a biofilm that had not been treated with a ceragenin. This work has demonstrated that ceragenins can be attached to polyamide reverse osmosis (RO) membranes, though work needs to improve the uniformity of the attachment. Finally, methods have been developed to use hyperspectral imaging with multivariate curve resolution to view ceragenins attached to the RO membrane. Future work will be conducted to better attach the ceragenin to the RO membranes and more completely test the biocidal effectiveness of the ceragenins on the membranes.

  2. Use of a parallel artificial membrane system to evaluate passive absorption and elimination in small fish.

    Science.gov (United States)

    Kwon, Jung-Hwan; Katz, Lynn E; Liljestrand, Howard M

    2006-12-01

    A parallel artificial lipid membrane system was developed to mimic passive mass transfer of hydrophobic organic chemicals in fish. In this physical model system, a membrane filter-supported lipid bilayer separates two aqueous phases that represent the external and internal aqueous environments of fish. To predict bioconcentration kinetics in small fish with this system, literature absorption and elimination rates were analyzed with an allometric diffusion model to quantify the mass transfer resistances in the aqueous and lipid phases of fish. The effect of the aqueous phase mass transfer resistance was controlled by adjusting stirring intensity to mimic bioconcentration rates in small fish. Twenty-three simple aromatic hydrocarbons were chosen as model compounds for purposes of evaluation. For most of the selected chemicals, literature absorption/elimination rates fall into the range predicted from measured membrane permeabilities and elimination rates of the selected chemicals determined by the diffusion model system.

  3. Magnetically controlled permeability membranes

    KAUST Repository

    Kosel, Jurgen

    2013-10-31

    A bioactive material delivery system can include a thermoresponsive polymer membrane and nanowires distributed within the thermoresponsive polymer membrane. Magnetic activation of a thermoresponsive polymer membrane can take place via altering the magnetization or dimensions of nanowires dispersed or ordered within the membrane matrix.

  4. Magnetically controlled permeability membranes

    KAUST Repository

    Kosel, Jü rgen; Khashab, Niveen M.; Zaher, Amir

    2013-01-01

    A bioactive material delivery system can include a thermoresponsive polymer membrane and nanowires distributed within the thermoresponsive polymer membrane. Magnetic activation of a thermoresponsive polymer membrane can take place via altering the magnetization or dimensions of nanowires dispersed or ordered within the membrane matrix.

  5. Methods for attaching polymerizable ceragenins to water treatment membranes using amine and amide linkages

    Science.gov (United States)

    Hibbs, Michael; Altman, Susan J.; Jones, Howland D.T.; Savage, Paul B.

    2013-10-15

    This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

  6. Methods for attaching polymerizable ceragenins to water treatment membranes using silane linkages

    Science.gov (United States)

    Hibbs, Michael; Altman, Susan J.; Jones, Howland D. T.; Savage, Paul B.

    2013-09-10

    This invention relates to methods for chemically grafting and attaching ceragenin molecules to polymer substrates; methods for synthesizing ceragenin-containing copolymers; methods for making ceragenin-modified water treatment membranes and spacers; and methods of treating contaminated water using ceragenin-modified treatment membranes and spacers. Ceragenins are synthetically produced antimicrobial peptide mimics that display broad-spectrum bactericidal activity. Alkene-functionalized ceragenins (e.g., acrylamide-functionalized ceragenins) can be attached to polyamide reverse osmosis membranes using amine-linking, amide-linking, UV-grafting, or silane-coating methods. In addition, silane-functionalized ceragenins can be directly attached to polymer surfaces that have free hydroxyls.

  7. Triazacyclophane (TAC)-scaffolded histidine and aspartic acid residues as mimics of non-heme metalloenzyme active sites

    NARCIS (Netherlands)

    Albada, H.B.; Soulimani, F.; Jacobs, H.J.F.; Versluis, C.; Weckhuysen, B.M.; Liskamp, R.M.J.

    2012-01-01

    We describe the synthesis and coordination behaviour to copper(II) of two close structural triazacyclophane-based mimics of two often encountered aspartic acid and histidine containing metalloenzyme active sites. Coordination of these mimics to copper(I) and their reaction with molecular oxygen

  8. Membrane interactions of ionic liquids and imidazolium salts.

    Science.gov (United States)

    Wang, Da; Galla, Hans-Joachim; Drücker, Patrick

    2018-06-01

    Room-temperature ionic liquids (RTILs) have attracted considerable attention in recent years due to their versatile properties such as negligible volatility, inflammability, high extractive selectivity and thermal stability. In general, RTILs are organic salts with a melting point below ~100 °C determined by the asymmetry of at least one of their ions. Due to their amphiphilic character, strong interactions with biological materials can be expected. However, rising attention has appeared towards their similarity and interaction with biomolecules. By employing structural modifications, the biochemical properties of RTILs can be designed to mimic lipid structures and to tune their hydrophobicity towards a lipophilic behavior. This is evident for the interaction with lipid-membranes where some of these compounds present membrane-disturbing effects or cellular toxicity. Moreover, they can form micelles or lipid-like bilayer structures by themselves. Both aspects, cellular effects and membrane-forming capacities, of a novel class of lipophilic imidazolium salts will be discussed.

  9. Tethered and Polymer Supported Bilayer Lipid Membranes: Structure and Function

    Directory of Open Access Journals (Sweden)

    Jakob Andersson

    2016-05-01

    Full Text Available Solid supported bilayer lipid membranes are model systems to mimic natural cell membranes in order to understand structural and functional properties of such systems. The use of a model system allows for the use of a wide variety of analytical tools including atomic force microscopy, impedance spectroscopy, neutron reflectometry, and surface plasmon resonance spectroscopy. Among the large number of different types of model membranes polymer-supported and tethered lipid bilayers have been shown to be versatile and useful systems. Both systems consist of a lipid bilayer, which is de-coupled from an underlying support by a spacer cushion. Both systems will be reviewed, with an emphasis on the effect that the spacer moiety has on the bilayer properties.

  10. Characterizing the structure of lipodisq nanoparticles for membrane protein spectroscopic studies.

    Science.gov (United States)

    Zhang, Rongfu; Sahu, Indra D; Liu, Lishan; Osatuke, Anna; Comer, Raven G; Dabney-Smith, Carole; Lorigan, Gary A

    2015-01-01

    Membrane protein spectroscopic studies are challenging due to the difficulty introduced in preparing homogenous and functional hydrophobic proteins incorporated into a lipid bilayer system. Traditional membrane mimics such as micelles or liposomes have proved to be powerful in solubilizing membrane proteins for biophysical studies, however, several drawbacks have limited their applications. Recently, a nanosized complex termed lipodisq nanoparticles was utilized as an alternative membrane mimic to overcome these caveats by providing a homogeneous lipid bilayer environment. Despite all the benefits that lipodisq nanoparticles could provide to enhance the biophysical studies of membrane proteins, structural characterization in different lipid compositions that closely mimic the native membrane environment is still lacking. In this study, the formation of lipodisq nanoparticles using different weight ratios of POPC/POPG lipids to SMA polymers was characterized via solid-state nuclear magnetic resonance (SSNMR) spectroscopy and dynamic light scattering (DLS). A critical weight ratio of (1/1.25) for the complete solubilization of POPC/POPG vesicles has been observed and POPC/POPG vesicles turned clear instantaneously upon the addition of the SMA polymer. The size of lipodisq nanoparticles formed from POPC/POPG lipids at this weight ratio of (1/1.25) was found to be about 30 nm in radius. We also showed that upon the complete solubilization of POPC/POPG vesicles by SMA polymers, the average size of the lipodisq nanoparticles is weight ratio dependent, when more SMA polymers were introduced, smaller lipodisq nanoparticles were obtained. The results of this study will be helpful for a variety of biophysical experiments when specific size of lipid disc is required. Further, this study will provide a proper path for researchers working on membrane proteins to obtain pertinent structure and dynamic information in a physiologically relevant membrane mimetic environment

  11. The Kemp elimination in membrane mimetic reaction media. Probing catalytic properties of cationic vesicles formed from a double-tailed amphiphile and linear long-tailed alcohols or alkyl pyranosides

    NARCIS (Netherlands)

    Klijn, JE; Engberts, JBFN

    2004-01-01

    Vesicles formed from synthetic, double-tailed amphiphiles are often used as mimics for biological membranes. However, biological membranes are a complex mixture of various compounds. In the present paper we describe a first attempt to study the importance of additives on vesicular catalysis. The

  12. The anti-calcification potential of a silsesquioxane nanocomposite polymer under in vitro conditions: potential material for synthetic leaflet heart valve.

    Science.gov (United States)

    Ghanbari, Hossein; Kidane, Asmeret G; Burriesci, Gaetano; Ramesh, Bala; Darbyshire, Arnold; Seifalian, Alexander M

    2010-11-01

    Calcification currently represents a major cause of failure of biological tissue heart valves. It is a complex phenomenon influenced by a number of biochemical and mechanical factors. Recent advances in material science offer new polymers with improved properties, potentially suitable for synthetic leaflets heart valves manufacturing. In this study, the calcification-resistance efficacy and mechanical and surface properties of a new nanocomposite polymeric material (polyhedral oligomeric silsesquioxane-poly(carbonate-urea)urethane; POSS-PCU) which has been developed by our group are assessed by means of in vitro testing. In particular, thin sheets of nanocomposite, glutaraldehyde-fixed bovine pericardium (BP) and polyurethane (PU) were exposed to a calcium solution into a specially designed in vitro accelerated physiological pulsatile pressure system for a period of 31days and a total of 4×10(7) cycles. The samples were investigated for signs of calcification after exposure to calcium solution by means of X-ray, microscopic and chemical inspections. Mechanical and surface properties were also studied using stress-strain behaviour and surface morphology and hydrophobicity. Comparison shows that, in the experimental conditions, the level of calcification for the nanocomposite is considerably lower than for the fixed BP (p=0.008) and PU samples (p=0.015). Also, mechanical properties were unchanged in POSS-PCU, while there was a significant deterioration in PU samples (pnanocomposite remained more hydrophobic than the PU sample (pnanocomposite in synthetic leaflets heart valves may lead to potential advantages in terms of long-term performances and durability. Copyright © 2010. Published by Elsevier Ltd.

  13. Informed consent and placebo effects: a content analysis of information leaflets to identify what clinical trial participants are told about placebos.

    Directory of Open Access Journals (Sweden)

    Felicity L Bishop

    Full Text Available Placebo groups are used in randomised clinical trials (RCTs to control for placebo effects, which can be large. Participants in trials can misunderstand written information particularly regarding technical aspects of trial design such as randomisation; the adequacy of written information about placebos has not been explored. We aimed to identify what participants in major RCTs in the UK are told about placebos and their effects.We conducted a content analysis of 45 Participant Information Leaflets (PILs using quantitative and qualitative methodologies. PILs were obtained from trials on a major registry of current UK clinical trials (the UKCRN database. Eligible leaflets were received from 44 non-commercial trials but only 1 commercial trial. The main limitation is the low response rate (13.5%, but characteristics of included trials were broadly representative of all non-commercial trials on the database. 84% of PILs were for trials with 50:50 randomisation ratios yet in almost every comparison the target treatments were prioritized over the placebos. Placebos were referred to significantly less frequently than target treatments (7 vs. 27 mentions, p<001 and were significantly less likely than target treatments to be described as triggering either beneficial effects (1 vs. 45, p<001 or adverse effects (4 vs. 39, p<001. 8 PILs (18% explicitly stated that the placebo treatment was either undesirable or ineffective.PILs from recent high quality clinical trials emphasise the benefits and adverse effects of the target treatment, while largely ignoring the possible effects of the placebo. Thus they provide incomplete and at times inaccurate information about placebos. Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled

  14. Are anticoagulant independent mechanical valves within reach-fast prototype fabrication and in vitro testing of innovative bi-leaflet valve models.

    Science.gov (United States)

    Scotten, Lawrence N; Siegel, Rolland

    2015-08-01

    Exploration for causes of prosthetic valve thrombogenicity has frequently focused on forward or post-closure flow detail. In prior laboratory studies, we uncovered high amplitude flow velocities of short duration close to valve closure implying potential for substantial shear stress with subsequent initiation of blood coagulation pathways. This may be relevant to widely accepted clinical disparity between mechanical and tissue valves vis-à-vis thrombogenicity. With a series of prototype bi-leaflet mechanical valves, we attempt reduction of closure related velocities with the objective of identifying a prototype valve with thrombogenic potential similar to our tissue valve control. This iterative design approach may find application in preclinical assessment of valves for anticoagulation independence. Tested valves included: prototype mechanical bi-leaflet BVs (n=56), controls (n=2) and patented early prototype mechanicals (n=2) from other investigators. Pulsatile and quasi-steady flow systems were used for testing. Projected dynamic valve area (PDVA) was measured using previously described novel technology. Flow velocity over the open and closing periods was determined by volumetric flow rate/PDVA. For the closed valve interval, use was made of data obtained from quasi-steady back pressure/flow tests. Performance was ranked by a proposed thrombogenicity potential index (TPI) relative to tissue and mechanical control valves. Optimization of the prototype valve designs lead to a 3-D printed model (BV3D). For the mitral/aortic site, BV3D has lower TPI (1.10/1.47) relative to the control mechanical valve (3.44/3.93) and similar to the control tissue valve (ideal TPI ≤1.0). Using unique technology, rapid prototyping and thrombogenicity ranking, optimization of experimental valves for reduced thrombogenic potential was expedited and simplified. Innovative mechanical valve configurations were identified that merit consideration for further development which may bring

  15. Engineering plant membranes using droplet interface bilayers.

    Science.gov (United States)

    Barlow, N E; Smpokou, E; Friddin, M S; Macey, R; Gould, I R; Turnbull, C; Flemming, A J; Brooks, N J; Ces, O; Barter, L M C

    2017-03-01

    Droplet interface bilayers (DIBs) have become widely recognised as a robust platform for constructing model membranes and are emerging as a key technology for the bottom-up assembly of synthetic cell-like and tissue-like structures. DIBs are formed when lipid-monolayer coated water droplets are brought together inside a well of oil, which is excluded from the interface as the DIB forms. The unique features of the system, compared to traditional approaches (e.g., supported lipid bilayers, black lipid membranes, and liposomes), is the ability to engineer multi-layered bilayer networks by connecting multiple droplets together in 3D, and the capability to impart bilayer asymmetry freely within these droplet architectures by supplying droplets with different lipids. Yet despite these achievements, one potential limitation of the technology is that DIBs formed from biologically relevant components have not been well studied. This could limit the reach of the platform to biological systems where bilayer composition and asymmetry are understood to play a key role. Herein, we address this issue by reporting the assembly of asymmetric DIBs designed to replicate the plasma membrane compositions of three different plant species; Arabidopsis thaliana , tobacco, and oats, by engineering vesicles with different amounts of plant phospholipids, sterols and cerebrosides for the first time. We show that vesicles made from our plant lipid formulations are stable and can be used to assemble asymmetric plant DIBs. We verify this using a bilayer permeation assay, from which we extract values for absolute effective bilayer permeation and bilayer stability. Our results confirm that stable DIBs can be assembled from our plant membrane mimics and could lead to new approaches for assembling model systems to study membrane translocation and to screen new agrochemicals in plants.

  16. Physical model for membrane protrusions during spreading

    International Nuclear Information System (INIS)

    Chamaraux, F; Ali, O; Fourcade, B; Keller, S; Bruckert, F

    2008-01-01

    During cell spreading onto a substrate, the kinetics of the contact area is an observable quantity. This paper is concerned with a physical approach to modeling this process in the case of ameboid motility where the membrane detaches itself from the underlying cytoskeleton at the leading edge. The physical model we propose is based on previous reports which highlight that membrane tension regulates cell spreading. Using a phenomenological feedback loop to mimic stress-dependent biochemistry, we show that the actin polymerization rate can be coupled to the stress which builds up at the margin of the contact area between the cell and the substrate. In the limit of small variation of membrane tension, we show that the actin polymerization rate can be written in a closed form. Our analysis defines characteristic lengths which depend on elastic properties of the membrane–cytoskeleton complex, such as the membrane–cytoskeleton interaction, and on molecular parameters, the rate of actin polymerization. We discuss our model in the case of axi-symmetric and non-axi-symmetric spreading and we compute the characteristic time scales as a function of fundamental elastic constants such as the strength of membrane–cytoskeleton adherence

  17. Uptake and release protocol for assessing membrane binding and permeation by way of isothermal titration calorimetry.

    Science.gov (United States)

    Tsamaloukas, Alekos D; Keller, Sandro; Heerklotz, Heiko

    2007-01-01

    The activity of many biomolecules and drugs crucially depends on whether they bind to biological membranes and whether they translocate to the opposite lipid leaflet and trans aqueous compartment. A general strategy to measure membrane binding and permeation is the uptake and release assay, which compares two apparent equilibrium situations established either by the addition or by the extraction of the solute of interest. Only solutes that permeate the membrane sufficiently fast do not show any dependence on the history of sample preparation. This strategy can be pursued for virtually all membrane-binding solutes, using any method suitable for detecting binding. Here, we present in detail one example that is particularly well developed, namely the nonspecific membrane partitioning and flip-flop of small, nonionic solutes as characterized by isothermal titration calorimetry. A complete set of experiments, including all sample preparation procedures, can typically be accomplished within 2 days. Analogous protocols for studying charged solutes, virtually water-insoluble, hydrophobic compounds or specific ligands are also considered.

  18. Biomaterial delivery of morphogens to mimic the natural healing cascade in bone.

    Science.gov (United States)

    Mehta, Manav; Schmidt-Bleek, Katharina; Duda, Georg N; Mooney, David J

    2012-09-01

    Complications in treatment of large bone defects using bone grafting still remain. Our understanding of the endogenous bone regeneration cascade has inspired the exploration of a wide variety of growth factors (GFs) in an effort to mimic the natural signaling that controls bone healing. Biomaterial-based delivery of single exogenous GFs has shown therapeutic efficacy, and this likely relates to its ability to recruit and promote replication of cells involved in tissue development and the healing process. However, as the natural bone healing cascade involves the action of multiple factors, each acting in a specific spatiotemporal pattern, strategies aiming to mimic the critical aspects of this process will likely benefit from the usage of multiple therapeutic agents. This article reviews the current status of approaches to deliver single GFs, as well as ongoing efforts to develop sophisticated delivery platforms to deliver multiple lineage-directing morphogens (multiple GFs) during bone healing. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Sensitive fluorescence on-off probes for the fast detection of a chemical warfare agent mimic.

    Science.gov (United States)

    Khan, Muhammad Shar Jhahan; Wang, Ya-Wen; Senge, Mathias O; Peng, Yu

    2018-01-15

    Two highly sensitive probes bearing a nucleophilic imine moiety have been utilized for the selective detection of chemical warfare agent (CWA) mimics. Diethyl chlorophosphate (DCP) was used as mimic CWAs. Both iminocoumarin-benzothiazole-based probes not only demonstrated a remarkable fluorescence ON-OFF response and good recognition, but also exhibited fast response times (10s) along with color changes upon addition of DCP. Limits of detection for the two sensors 1 and 2 were calculated as 0.065μM and 0.21μM, respectively, which are much lower than most other reported probes. These two probes not only show high sensitivity and selectivity in solution, but can also be applied for the recognition of DCP in the gas state, with significant color changes easily observed by the naked eye. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Knockdown of Rice microRNA166 by Short Tandem Target Mimic (STTM).

    Science.gov (United States)

    Teotia, Sachin; Zhang, Dabing; Tang, Guiliang

    2017-01-01

    Small RNAs, including microRNAs (miRNAs), are abundant in plants and play key roles in controlling plant development and physiology. miRNAs regulate the expression of the target genes involved in key plant processes. Due to functional redundancy among miRNA family members in plants, an ideal approach to silence the expression of all members simultaneously, for their functional characterization, is desirable. Target mimic (TM) was the first approach to achieve this goal. Short tandem target mimic (STTM) is a potent approach complementing TM for silencing miRNAs in plants. STTMs have been successfully used in dicots to block miRNA functions. Here, we describe in detail the protocol for designing STTM construct to block miRNA functions in rice. Such approach can be applied to silence miRNAs in other monocots as well.

  1. Collagen VII deficient mice show morphologic and histologic corneal changes that phenotypically mimic human dystrophic epidermolysis bullosa of the eye.

    Science.gov (United States)

    Chen, Vicki M; Shelke, Rajani; Nyström, Alexander; Laver, Nora; Sampson, James F; Zhiyi, Cao; Bhat, Najma; Panjwani, Noorjahan

    2018-06-16

    Absence of collagen VII causes blistering of the skin, eyes and many other tissues. This disease is termed dystrophic epidermolysis bullosa (DEB). Corneal fibrosis occurs in up to 41% and vision loss in up to 64% of patients. Standard treatments are supportive and there is no cure. The immune-histologic and morphologic changes in the corneas of the mouse model for this disease have not been described in the literature. Our purpose is to characterize the eyes of these mice to determine if this is an appropriate model for study of human therapeutics. Western blot analysis (WB) and immunohistochemistry (IHC) were performed to assess the relative collagen VII protein levels and its location within the cornea. Additional IHC for inflammatory and fibrotic biomarkers alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), proteinase 3, tenascin C and collagen III were performed. Clinical photographs documenting opacification of the corneas of animals of differing ages were assessed and scored independently by 2 examiners. Histology was then used to investigate morphologic changes. IHC and WB confirmed that these mice are deficient in collagen VII production at the level of the basement membrane when compared with wild-types. IHC showed anomalous deposition of collagen III throughout the stroma. Of the 5 biomarkers tested, TGF-β showed the strongest and most consistently staining. Photographs documented corneal opacities only in mice older than 10 weeks, opacities were not seen in younger animals. Histology showed multiple abnormalities, including epithelial hyperplasia, ulceration, fibrosis, edema, dysplasia, neovascularization and bullae formation. The collagen VII hypomorphic mouse shows reduced collagen VII production at the level of the corneal basement membrane. Corneal changes are similar to pathology seen in humans with this disease. The presence of anomalous stromal collagen III and TGF-β appear to be

  2. Recognition of GPCRs by peptide ligands and membrane compartments theory: structural studies of endogenous peptide hormones in membrane environment.

    Science.gov (United States)

    Sankararamakrishnan, Ramasubbu

    2006-04-01

    One of the largest family of cell surface proteins, G-protein coupled receptors (GPCRs) regulate virtually all known physiological processes in mammals. With seven transmembrane segments, they respond to diverse range of extracellular stimuli and represent a major class of drug targets. Peptidergic GPCRs use endogenous peptides as ligands. To understand the mechanism of GPCR activation and rational drug design, knowledge of three-dimensional structure of receptor-ligand complex is important. The endogenous peptide hormones are often short, flexible and completely disordered in aqueous solution. According to "Membrane Compartments Theory", the flexible peptide binds to the membrane in the first step before it recognizes its receptor and the membrane-induced conformation is postulated to bind to the receptor in the second step. Structures of several peptide hormones have been determined in membrane-mimetic medium. In these studies, micelles, reverse micelles and bicelles have been used to mimic the cell membrane environment. Recently, conformations of two peptide hormones have also been studied in receptor-bound form. Membrane environment induces stable secondary structures in flexible peptide ligands and membrane-induced peptide structures have been correlated with their bioactivity. Results of site-directed mutagenesis, spectroscopy and other experimental studies along with the conformations determined in membrane medium have been used to interpret the role of individual residues in the peptide ligand. Structural differences of membrane-bound peptides that belong to the same family but differ in selectivity are likely to explain the mechanism of receptor selectivity and specificity of the ligands. Knowledge of peptide 3D structures in membrane environment has potential applications in rational drug design.

  3. Structural Mimics of the [Fe]-Hydrogenase: A Complete Set for Group VIII Metals.

    Science.gov (United States)

    Barik, Chandan Kr; Ganguly, Rakesh; Li, Yongxin; Leong, Weng Kee

    2018-06-18

    A set of structural mimics of the [Fe]-hydrogenase active site comprising all the group VIII metals, viz., [M(2-NHC(O)C 5 H 4 N)(CO) 2 (2-S-C 5 H 4 N)], has been synthesized. They exist as a mixture of isomers in solution, and the relative stability of the isomers depends on the nature of the metal and the substituent at the 6-position of the pyridine ligand.

  4. Artificial cell mimics as simplified models for the study of cell biology.

    Science.gov (United States)

    Salehi-Reyhani, Ali; Ces, Oscar; Elani, Yuval

    2017-07-01

    Living cells are hugely complex chemical systems composed of a milieu of distinct chemical species (including DNA, proteins, lipids, and metabolites) interconnected with one another through a vast web of interactions: this complexity renders the study of cell biology in a quantitative and systematic manner a difficult task. There has been an increasing drive towards the utilization of artificial cells as cell mimics to alleviate this, a development that has been aided by recent advances in artificial cell construction. Cell mimics are simplified cell-like structures, composed from the bottom-up with precisely defined and tunable compositions. They allow specific facets of cell biology to be studied in isolation, in a simplified environment where control of variables can be achieved without interference from a living and responsive cell. This mini-review outlines the core principles of this approach and surveys recent key investigations that use cell mimics to address a wide range of biological questions. It will also place the field in the context of emerging trends, discuss the associated limitations, and outline future directions of the field. Impact statement Recent years have seen an increasing drive to construct cell mimics and use them as simplified experimental models to replicate and understand biological phenomena in a well-defined and controlled system. By summarizing the advances in this burgeoning field, and using case studies as a basis for discussion on the limitations and future directions of this approach, it is hoped that this minireview will spur others in the experimental biology community to use artificial cells as simplified models with which to probe biological systems.

  5. A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

    Directory of Open Access Journals (Sweden)

    Marcus Baumann

    2017-11-01

    Full Text Available An assembled suite of flow-based transformations have been used to rapidly scale-up the production of a novel auxin mimic-based herbicide which was required for preliminary field trials. The overall synthetic approach and optimisation studies are described along with a full description of the final reactor configurations employed for the synthesis as well as the downstream processing of the reaction streams.

  6. Acute aortic dissection mimics acute inferoposterior wall myocardial infarction in a Marfan syndrome patient

    OpenAIRE

    Phowthongkum, Prasit

    2010-01-01

    A 30-year old man with acute chest pain was diagnosed with acute inferoposterior wall myocardial infarction following electrocardiography. After a failed coronary angiography, an echocardiogram revealed an aortic intimal flap after which acute aortic dissection was diagnosed. The patient received a successful Bentall operation without immediate complication. Retrospective examination then confirmed the diagnosis of Marfan syndrome. This case demonstrates acute aortic dissection may mimic acut...

  7. Acute aortic dissection mimics acute inferoposterior wall myocardial infarction in a Marfan syndrome patient.

    Science.gov (United States)

    Phowthongkum, Prasit

    2010-01-01

    A 30-year old man with acute chest pain was diagnosed with acute inferoposterior wall myocardial infarction following electrocardiography. After a failed coronary angiography, an echocardiogram revealed an aortic intimal flap after which acute aortic dissection was diagnosed. The patient received a successful Bentall operation without immediate complication. Retrospective examination then confirmed the diagnosis of Marfan syndrome. This case demonstrates acute aortic dissection may mimic acute myocardial infarction.

  8. Noise analysis and mimic experiments for loose part accident in the primary coolant loop of PWR

    International Nuclear Information System (INIS)

    Yang Xiuzhou; Cheng Tingxiang; Zhang Bin

    1994-01-01

    The basic principle of loose part monitoring is to detect and measure the structure transfer sound generated by impacting of metal loose part with accelerators and to identify and diagnose by the micro-processor. This paper introduces the theoretical base of loose part monitoring, the location and mass estimation of loose part, and three mimic experiment applying noise analysis techniques. It provides some useful preparations for the development of loose part monitoring system

  9. A sensitive colorimetric aptasensor based on trivalent peroxidase-mimic DNAzyme and magnetic nanoparticles.

    Science.gov (United States)

    Liu, Shuwen; Xu, Naihan; Tan, Chunyan; Fang, Wei; Tan, Ying; Jiang, Yuyang

    2018-08-14

    In this study, a novel colorimetric aptasensor was prepared by coupling trivalent peroxidase-mimic DNAzyme and magnetic nanoparticles for highly sensitive and selective detection of target proteins. A three G-quadruplex (G4) DNA-hemin complex was employed as the trivalent peroxidase-mimic DNAzyme, in which hemin assisted the G4-DNA to fold into a catalytic conformation and act as an enzyme. The design of the aptasensor includes magnetic nanoparticles (MNPs), complementary DNA (cDNA) modified with biotin, and a label-free single strand DNA (ssDNA) including the aptamer and trivalent peroxidase-mimic DNAzyme. The trivalent DNAzyme, which has the highest catalytic activity among multivalent DNAzymes, catalyzed the H 2 O 2 -mediated oxidation of ABTS. The colorless ABTS was oxidized to produce a blue-green product that can be clearly distinguished by the naked eye. The aptamer and trivalent peroxidase-mimic DNAzyme promote the specificity and sensitivity of this detection method, which can be generalized for other targets by simply replacing the corresponding aptamers. To demonstrate the feasible use of the aptasensor for target detection, a well-known tumor biomarker MUC1 was evaluated as the model target. The limits of detection were determined to be 5.08 and 5.60 nM in a linear range of 50-1000 nM in a buffer solution and 10% serum system, respectively. This colorimetric and label-free aptasensor with excellent sensitivity and strong anti-interference ability has potential application in disease diagnoses, prognosis tracking, and therapeutic evaluation. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Characterization and fine mapping of a light-dependent leaf lesion mimic mutant 1 in rice.

    Science.gov (United States)

    Wang, Jing; Ye, Bangquan; Yin, Junjie; Yuan, Can; Zhou, Xiaogang; Li, Weitao; He, Min; Wang, Jichun; Chen, Weilan; Qin, Peng; Ma, Bintian; Wang, Yuping; Li, Shigui; Chen, Xuewei

    2015-12-01

    Plants that spontaneously produce lesion mimics or spots, without any signs of obvious adversity, such as pesticide and mechanical damage, or pathogen infection, are so-called lesion mimic mutants (lmms). In rice, many lmms exhibit enhanced resistance to pathogens, which provides a unique opportunity to uncover the molecular mechanism underlying lmms. We isolated a rice light-dependent leaf lesion mimic mutant 1 (llm1). Lesion spots appeared in the leaves of the llm1 mutant at the tillering stage. Furthermore, the mutant llm1 had similar agronomic traits to wild type rice. Trypan blue and diamiobenzidine staining analyses revealed that the lesion spot formation on the llm1 mutant was due to programmed cell death and reactive oxygen species. The chloroplasts were severely damaged in the llm1 mutant, suggesting that chloroplast damage was associated with the formation of lesion spots in llm1. More importantly, llm1 exhibited enhanced resistance to bacterial blight pathogens within increased expression of pathogenesis related genes (PRs). Using a map-based cloning approach, we delimited the LLM1 locus to a 121-kb interval between two simple sequence repeat markers, RM17470 and RM17473, on chromosome 4. We sequenced the candidate genes on the interval and found that a base mutation had substituted adenine phosphate for thymine in the last exon of LOC_Os04g52130, which led to an amino acid change (Asp(388) to Val) in the llm1 mutant. Our investigation showed that the putative coproporphyrinogen III oxidase (CPOX) encoded by LOC_Os04g52130 was produced by LLM1 and that amino acid Asp(388) was essential for CPOX function. Our study provides the basis for further investigations into the mechanism underlying lesion mimic initiation associated with LLM1. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  11. Independent monitor unit calculation for intensity modulated radiotherapy using the MIMiC multileaf collimator

    International Nuclear Information System (INIS)

    Chen Zhe; Xing Lei; Nath, Ravinder

    2002-01-01

    A self-consistent monitor unit (MU) and isocenter point-dose calculation method has been developed that provides an independent verification of the MU for intensity modulated radiotherapy (IMRT) using the MIMiC (Nomos Corporation) multileaf collimator. The method takes into account two unique features of IMRT using the MIMiC: namely the gantry-dynamic arc delivery of intensity modulated photon beams and the slice-by-slice dose delivery for large tumor volumes. The method converts the nonuniform beam intensity planned at discrete gantry angles of 5 deg. or 10 deg. into conventional nonmodulated beam intensity apertures of elemental arc segments of 1 deg. This approach more closely simulates the actual gantry-dynamic arc delivery by MIMiC. Because each elemental arc segment is of uniform intensity, the MU calculation for an IMRT arc is made equivalent to a conventional arc with gantry-angle dependent beam apertures. The dose to the isocenter from each 1 deg. elemental arc segment is calculated by using the Clarkson scatter summation technique based on measured tissue-maximum-ratio and output factors, independent of the dose calculation model used in the IMRT planning system. For treatments requiring multiple treatment slices, the MU for the arc at each treatment slice takes into account the MU, leakage and scatter doses from other slices. This is achieved by solving a set of coupled linear equations for the MUs of all involved treatment slices. All input dosimetry data for the independent MU/isocenter point-dose calculation are measured directly. Comparison of the MU and isocenter point dose calculated by the independent program to those calculated by the Corvus planning system and to direct measurements has shown good agreement with relative difference less than ±3%. The program can be used as an independent initial MU verification for IMRT plans using the MIMiC multileaf collimators

  12. Glutathione peroxidase mimic ebselen improves glucose-stimulated insulin secretion in murine islets.

    Science.gov (United States)

    Wang, Xinhui; Yun, Jun-Won; Lei, Xin Gen

    2014-01-10

    Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. Ebselen improved GSIS in islets of all four tested genotypes. The rescue in the GPX1 knockout resulted from a coordinated transcriptional regulation of four key GSIS regulators and was mediated by the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)-mediated signaling pathways. In contrast, CuDIPs improved GSIS only in the SOD1 knockout and suppressed gene expression of the PGC-1α pathway. Islets from the GPX1 and(or) SOD1 knockout mice provided metabolically controlled intracellular hydrogen peroxide (H2O2) and superoxide conditions for the present study to avoid confounding effects. Bioinformatics analyses of gene promoters and expression profiles guided the search for upstream signaling pathways to link the ebselen-initiated H2O2 scavenging to downstream key events of GSIS. The RNA interference was applied to prove PGC-1α as the main mediator for that link. Our study revealed a novel metabolic use and clinical potential of ebselen in rescuing GSIS in the GPX1-deficient islets and mice, along with distinct differences between the GPX and SOD mimics in this regard. These findings highlight the necessities and opportunities of discretional applications of various antioxidant enzyme mimics in treating insulin secretion disorders. REBOUND TRACK: This work was rejected during standard peer review and rescued by Rebound Peer Review (Antioxid Redox Signal 16: 293-296, 2012) with the following serving as open reviewers: Regina Brigelius-Flohe, Vadim Gladyshev, Dexing Hou, and Holger Steinbrenner.

  13. Outer membrane lipoprotein biogenesis: Lol is not the end.

    Science.gov (United States)

    Konovalova, Anna; Silhavy, Thomas J

    2015-10-05

    Bacterial lipoproteins are lipid-anchored proteins that contain acyl groups covalently attached to the N-terminal cysteine residue of the mature protein. Lipoproteins are synthesized in precursor form with an N-terminal signal sequence (SS) that targets translocation across the cytoplasmic or inner membrane (IM). Lipid modification and SS processing take place at the periplasmic face of the IM. Outer membrane (OM) lipoproteins take the localization of lipoproteins (Lol) export pathway, which ends with the insertion of the N-terminal lipid moiety into the inner leaflet of the OM. For many lipoproteins, the biogenesis pathway ends here. We provide examples of lipoproteins that adopt complex topologies in the OM that include transmembrane and surface-exposed domains. Biogenesis of such lipoproteins requires additional steps beyond the Lol pathway. In at least one case, lipoprotein sequences reach the cell surface by being threaded through the lumen of a beta-barrel protein in an assembly reaction that requires the heteropentomeric Bam complex. The inability to predict surface exposure reinforces the importance of experimental verification of lipoprotein topology and we will discuss some of the methods used to study OM protein topology. © 2015 The Author(s).

  14. Gibberellic and kaurenoic hybrid strigolactone mimics for seed germination of parasitic weeds.

    Science.gov (United States)

    Pereira, Rondinelle G; Cala, Antonio; Fernández-Aparicio, Mónica; Molinillo, José Mg; Boaventura, Maria Ad; Macías, Francisco A

    2017-12-01

    Parasitic weeds are widespread and cause significant losses in important crops. Their germination requires the detection of crop-derived molecules such as strigolactones. Strigolactone mimics are germination-inducing molecules with the potential to apply a suicidal germination strategy for seed bank control of parasitic weeds. The D-ring, which is instrumental in the germination process of seeds of parasitic weeds, was attached to gibberellin (GA 3 ) and kaurenoic acid as the scaffold. It was shown that indeed strigolactone mimics prepared from GA 3 and kaurenoic acid are active as stimulants when a D-ring is present; some of the mimics are as active as GR24. The starting molecules were plant hormones that had previous growth-regulating activity in other organisms and the products showed enhanced activity towards parasitic weeds. The information generated may contribute to a better understanding of the germination biochemistry of the weed species used. Further research is required in this area but it is clear that the results are promising. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  15. MIMIC: An Innovative Methodology for Determining Mobile Laser Scanning System Point Density

    Directory of Open Access Journals (Sweden)

    Conor Cahalane

    2014-08-01

    Full Text Available Understanding how various Mobile Mapping System (MMS laser hardware configurations and operating parameters exercise different influence on point density is important for assessing system performance, which in turn facilitates system design and MMS benchmarking. Point density also influences data processing, as objects that can be recognised using automated algorithms generally require a minimum point density. Although obtaining the necessary point density impacts on hardware costs, survey time and data storage requirements, a method for accurately and rapidly assessing MMS performance is lacking for generic MMSs. We have developed a method for quantifying point clouds collected by an MMS with respect to known objects at specified distances using 3D surface normals, 2D geometric formulae and line drawing algorithms. These algorithms were combined in a system called the Mobile Mapping Point Density Calculator (MIMIC and were validated using point clouds captured by both a single scanner and a dual scanner MMS. Results from MIMIC were promising: when considering the number of scan profiles striking the target, the average error equated to less than 1 point per scan profile. These tests highlight that MIMIC is capable of accurately calculating point density for both single and dual scanner MMSs.

  16. A collection of target mimics for comprehensive analysis of microRNA function in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Marco Todesco

    2010-07-01

    Full Text Available Many targets of plant microRNAs (miRNAs are thought to play important roles in plant physiology and development. However, because plant miRNAs are typically encoded by medium-size gene families, it has often been difficult to assess their precise function. We report the generation of a large-scale collection of knockdowns for Arabidopsis thaliana miRNA families; this has been achieved using artificial miRNA target mimics, a recently developed technique fashioned on an endogenous mechanism of miRNA regulation. Morphological defects in the aerial part were observed for approximately 20% of analyzed families, all of which are deeply conserved in land plants. In addition, we find that non-cleavable mimic sites can confer translational regulation in cis. Phenotypes of plants expressing target mimics directed against miRNAs involved in development were in several cases consistent with previous reports on plants expressing miRNA-resistant forms of individual target genes, indicating that a limited number of targets mediates most effects of these miRNAs. That less conserved miRNAs rarely had obvious effects on plant morphology suggests that most of them do not affect fundamental aspects of development. In addition to insight into modes of miRNA action, this study provides an important resource for the study of miRNA function in plants.

  17. Instructions to mimic improve facial emotion recognition in people with sub-clinical autism traits.

    Science.gov (United States)

    Lewis, Michael B; Dunn, Emily

    2017-11-01

    People tend to mimic the facial expression of others. It has been suggested that this helps provide social glue between affiliated people but it could also aid recognition of emotions through embodied cognition. The degree of facial mimicry, however, varies between individuals and is limited in people with autism spectrum conditions (ASC). The present study sought to investigate the effect of promoting facial mimicry during a facial-emotion-recognition test. In two experiments, participants without an ASC diagnosis had their autism quotient (AQ) measured. Following a baseline test, they did an emotion-recognition test again but half of the participants were asked to mimic the target face they saw prior to making their responses. Mimicry improved emotion recognition, and further analysis revealed that the largest improvement was for participants who had higher scores on the autism traits. In fact, recognition performance was best overall for people who had high AQ scores but also received the instruction to mimic. Implications for people with ASC are explored.

  18. Early diagnosis of amyotrophic lateral sclerosis mimic syndromes: pros and cons of current clinical diagnostic criteria.

    Science.gov (United States)

    Cortés-Vicente, Elena; Pradas, Jesús; Marín-Lahoz, Juan; De Luna, Noemi; Clarimón, Jordi; Turon-Sans, Janina; Gelpí, Ellen; Díaz-Manera, Jordi; Illa, Isabel; Rojas-Garcia, Ricard

    2017-08-01

    To describe the frequency and clinical characteristics of patients referred to a tertiary neuromuscular clinic as having amyotrophic lateral sclerosis (ALS) but who were re-diagnosed as having an ALS mimic syndrome, and to identify the reasons that led to the revision of the diagnosis. We reviewed the final diagnosis of all patients prospectively registered in the Sant Pau-MND register from 1 January 2004 to 31 December 2015. A detailed clinical evaluation and a clinically-guided electrophysiological study were performed at first evaluation. Twenty of 314 (6.4%) patients included were re-diagnosed as having a condition other than ALS, in 18 cases already at first evaluation. An alternative specific diagnosis was identified in 17 of those 20, consisting of a wide range of conditions. The main finding leading to an alternative diagnosis was the result of the electrophysiological study. Fifty per cent did not fulfil the El Escorial revised criteria (EECr) for ALS. The most common clinical phenotype at onset in patients with ALS mimic syndromes was progressive muscular atrophy (PMA). Misdiagnosing ALS is still a common problem. Early identification of ALS mimic syndromes is possible based on atypical clinical features and a clinically-guided electrophysiological study. Patients should be attended in specialised centres. The application of EECr helps to identify ALS misdiagnoses.

  19. MicroRNA-122 mimic transfection contributes to apoptosis in HepG2 cells.

    Science.gov (United States)

    Huang, Hongyan; Zhu, Yueyong; Li, Shaoyang

    2015-11-01

    There is currently a requirement for effective treatment strategies for human hepatocellular carcinoma (HCC), a leading cause of cancer‑associated mortality. MicroRNA-122 (miR-122), a repressor of the endogenous apoptosis regulator Bcl‑w, is frequently downregulated in HCC. Thus, it is hypothesized that the activation of miR‑122 may induce selective hepatocellular apoptosis via caspase activation in a model of HCC. In the present study, an miR‑122 mimic transfection was performed in HepG2 cells, and used to investigate the role and therapeutic potential of miR‑122 in the regulation of HCC‑derived cell lines. The apoptotic rates of HepG2 cells were significantly increased following miR‑122 mimic transfection. Reverse transcription‑polymerase chain reaction analysis revealed that Bcl‑w mRNA was significantly reduced, while the mRNA levels of caspase‑9 and caspase‑3 were markedly increased. The immunocytochemistry results supported the mRNA trends. Collectively, the present results suggest that endogenous miR‑122 contributes to HepG2 apoptosis and that transfection of mimic miR‑122 normalizes apoptotic levels in a model of HCC.

  20. Fast and efficient Drosophila melanogaster gene knock-ins using MiMIC transposons.

    Science.gov (United States)

    Vilain, Sven; Vanhauwaert, Roeland; Maes, Ine; Schoovaerts, Nils; Zhou, Lujia; Soukup, Sandra; da Cunha, Raquel; Lauwers, Elsa; Fiers, Mark; Verstreken, Patrik

    2014-10-08

    Modern molecular genetics studies necessitate the manipulation of genes in their endogenous locus, but most of the current methodologies require an inefficient donor-dependent homologous recombination step to locally modify the genome. Here we describe a methodology to efficiently generate Drosophila knock-in alleles by capitalizing on the availability of numerous genomic MiMIC transposon insertions carrying recombinogenic attP sites. Our methodology entails the efficient PhiC31-mediated integration of a recombination cassette flanked by unique I-SceI and/or I-CreI restriction enzyme sites into an attP-site. These restriction enzyme sites allow for double-strand break-mediated removal of unwanted flanking transposon sequences, while leaving the desired genomic modifications or recombination cassettes. As a proof-of-principle, we mutated LRRK, tau, and sky by using different MiMIC elements. We replaced 6 kb of genomic DNA encompassing the tau locus and 35 kb encompassing the sky locus with a recombination cassette that permits easy integration of DNA at these loci and we also generated a functional LRRK(HA) knock in allele. Given that ~92% of the Drosophila genes are located within the vicinity (MiMIC element, our methodology enables the efficient manipulation of nearly every locus in the fruit fly genome without the need for inefficient donor-dependent homologous recombination events. Copyright © 2014 Vilain et al.

  1. Mimic Carbonic Anhydrase Using Metal-Organic Frameworks for CO2 Capture and Conversion.

    Science.gov (United States)

    Jin, Chaonan; Zhang, Sainan; Zhang, Zhenjie; Chen, Yao

    2018-02-19

    Carbonic anhydrase (CA) is a zinc-containing metalloprotein, in which the Zn active center plays the key role to transform CO 2 into carbonate. Inspired by nature, herein we used metal-organic frameworks (MOFs) to mimic CA for CO 2 conversion, on the basis of the structural similarity between the Zn coordination in MOFs and CA active center. The biomimetic activity of MOFs was investigated by detecting the hydrolysis of para-nitrophenyl acetate, which is a model reaction used to evaluate CA activity. The biomimetic materials (e.g., CFA-1) showed good catalytic activity, and excellent reusability, and solvent and thermal stability, which is very important for practical applications. In addition, ZIF-100 and CFA-1 were used to mimic CA to convert CO 2 gas, and exhibited good efficiency on CO 2 conversion compared with those of other porous materials (e.g., MCM-41, active carbon). This biomimetic study revealed a novel CO 2 treatment method. Instead of simply using MOFs to absorb CO 2 , ZIF-100 and CFA-1 were used to mimic CA for in situ CO 2 conversion, which provides a new prospect in the biological and industrial applications of MOFs.

  2. Sensitive electrochemical assaying of DNA methyltransferase activity based on mimic-hybridization chain reaction amplified strategy.

    Science.gov (United States)

    Zhang, Linqun; Liu, Yuanjian; Li, Ying; Zhao, Yuewu; Wei, Wei; Liu, Songqin

    2016-08-24

    A mimic-hybridization chain reaction (mimic-HCR) amplified strategy was proposed for sensitive electrochemically detection of DNA methylation and methyltransferase (MTase) activity In the presence of methylated DNA, DNA-gold nanoparticles (DNA-AuNPs) were captured on the electrode by sandwich-type assembly. It then triggered mimic-HCR of two hairpin probes to produce many long double-helix chains for numerous hexaammineruthenium (III) chloride ([Ru(NH3)6](3+), RuHex) inserting. As a result, the signal for electrochemically detection of DNA MTase activity could be amplified. If DNA was non-methylated, however, the sandwich-type assembly would not form because the short double-stranded DNAs (dsDNA) on the Au electrode could be cleaved and digested by restriction endonuclease HpaII (HapII) and exonuclease III (Exo III), resulting in the signal decrement. Based on this, an electrochemical approach for detection of M.SssI MTase activity with high sensitivity was developed. The linear range for M.SssI MTase activity was from 0.05 U mL(-1) to 10 U mL(-1), with a detection limit down to 0.03 U mL(-1). Moreover, this detecting strategy held great promise as an easy-to-use and highly sensitive method for other MTase activity and inhibition detection by exchanging the corresponding DNA sequence. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Differential effects of lesion mimic mutants in barley on disease development by facultative pathogens

    Science.gov (United States)

    McGrann, Graham R. D.; Steed, , Andrew; Burt, Christopher; Nicholson, Paul; Brown, James K. M.

    2015-01-01

    Lesion mimic mutants display spontaneous necrotic spots and chlorotic leaves as a result of mis-regulated cell death programmes. Typically these mutants have increased resistance to biotrophic pathogens but their response to facultative fungi that cause necrotrophic diseases is less well studied. The effect of altered cell death regulation on the development of disease caused by Ramularia collo-cygni, Fusarium culmorum and Oculimacula yallundae was explored using a collection of barley necrotic (nec) lesion mimic mutants. nec8 mutants displayed lower levels of all three diseases compared to nec9 mutants, which had increased R. collo-cygni but decreased F. culmorum disease symptoms. nec1 mutants reduced disease development caused by both R. collo-cygni and F. culmorum. The severity of the nec1-induced lesion mimic phenotype and F. culmorum symptom development was reduced by mutation of the negative cell death regulator MLO. The significant reduction in R. collo-cygni symptoms caused by nec1 was completely abolished in the presence of the mlo-5 allele and both symptoms and fungal biomass were greater than in the wild-type. These results indicate that physiological pathways involved in regulation of cell death interact with one another in their effects on different fungal pathogens. PMID:25873675

  4. Settlement pattern of Posidonia oceanica epibionts along a gradient of ocean acidification: an approach with mimics

    Directory of Open Access Journals (Sweden)

    L. DONNARUMMA

    2014-02-01

    Full Text Available Effects of ocean acidification (OA on the colonization/settlement pattern of the epibiont community of the leaves and rhizomesof the Mediterranean seagrass,Posidoniaoceanica, have been studied at volcanic CO2vents off Ischia (Italy, using “mimics”as artificial substrates. The experiments were conducted in shallowPosidoniastands (2-3 m depth, in three stations on the northand three on the south sides of the study area, distributed along a pH gradient. At each station, 4 rhizome mimics and 6 artificialleaves were collected every three months (Sept 2009-Sept 2010. The epibionts on both leaf and rhizome mimics showed clearchanges along the pH gradient; coralline algae and calcareous invertebrates (bryozoans, serpulid polychaetes and barnacles weredominant at control stations but progressively disappeared at the most acidified stations. In these extremely low pH sites theassemblage was dominated by filamentous algae and non calcareous taxa such as hydroids and tunicates. Settlement pattern onthe artificial leaves and rhizome mimics over time showed a consistent distribution pattern along the pH gradient and highlightedthe peak of recruitment of the various organisms in different periods according to their life history.Posidoniamimics at theacidified station showed a poor and very simplified assemblage where calcifying epibionts seemed less competitive for space. Thisprofound difference in epiphyte communities in low pH conditions suggests cascading effects on the food web of the meadow and,consequently, on the functioning of the system

  5. Electrostatically induced recruitment of membrane peptides into clusters requires ligand binding at both interfaces.

    Directory of Open Access Journals (Sweden)

    Yuri N Antonenko

    Full Text Available Protein recruitment to specific membrane locations may be governed or facilitated by electrostatic attraction, which originates from a multivalent ligand. Here we explored the energetics of a model system in which this simple electrostatic recruitment mechanism failed. That is, basic poly-L-lysine binding to one leaflet of a planar lipid bilayer did not recruit the triply-charged peptide (O-Pyromellitylgramicidin. Clustering was only observed in cases where PLL was bound to both channel ends. Clustering was indicated (i by the decreased diffusional PLL mobility D(PLL and (ii by an increased lifetime τ(PLL of the clustered channels. In contrast, if PLL was bound to only one leaflet, neither D(PLL nor τ(P changed. Simple calculations suggest that electrostatic repulsion of the unbound ends prevented neighboring OPg dimers from approaching each other. We believe that a similar mechanism may also operate in cell signaling and that it may e.g. contribute to the controversial results obtained for the ligand driven dimerization of G protein-coupled receptors.

  6. Fish skin as a model membrane: structure and characteristics.

    Science.gov (United States)

    Konrádsdóttir, Fífa; Loftsson, Thorsteinn; Sigfússon, Sigurdur Dadi

    2009-01-01

    Synthetic and cell-based membranes are frequently used during drug formulation development for the assessment of drug availability. However, most of the currently used membranes do not mimic mucosal membranes well, especially the aqueous mucous layer of the membranes. In this study we evaluated catfish (Anarichas lupus L) skin as a model membrane. Permeation of hydrocortisone, lidocaine hydrochloride, benzocaine, diethylstilbestrol, naproxen, picric acid and sodium nitrate through skin from a freshly caught catfish was determined in Franz diffusion cells. Both lipophilic and hydrophilic molecules permeate through catfish skin via hydrated channels or aqueous pores. No correlation was observed between the octanol/water partition coefficient of the permeating molecules and their permeability coefficient through the skin. Permeation through catfish skin was found to be diffusion controlled. The results suggest that permeation through the fish skin proceeds via a diffusion-controlled process, a process that is similar to drug permeation through the aqueous mucous layer of a mucosal membrane. In addition, the fish skin, with its collagen matrix structure, appears to possess similar properties to the eye sclera.

  7. miR-370 mimic inhibits replication of Japanese encephalitis virus in glioblastoma cells.

    Science.gov (United States)

    Li, Wenjuan; Cheng, Peng; Nie, Shangdan; Cui, Wen

    2016-01-01

    Japanese encephalitis (JE) is one of the most severe viral infections of the central nervous system. No effective treatment for JE currently exists, because its pathogenesis remains largely unknown. The present study was designed to screen the potential microRNAs (miRNAs) involved in JE. Glioblastoma cells were collected, after being infected with the Japanese encephalitis virus (JEV). Total miRNAs were extracted and analyzed using an miRNA chip. One of the most severely affected miRNAs was selected, and the role of miR-370 in JEV infection was investigated. Cell viability and apoptosis of the host cells were evaluated. JEV replication was detected via analysis of gene E expression. Real-time polymerase chain reaction was used to determine the levels of endogenous miR-370 and expression of innate immunity-related genes. Following JEV infection, 114 miRNAs were affected, as evidenced by the miRNA chip. Among them, 30 miRNAs were upregulated and 84 were downregulated. The changes observed in five miRNAs were confirmed by real-time polymerase chain reaction. One of the significantly downregulated miRNAs was miR-370. Therefore, miR-370 mimic was transfected into the cells, following which the levels of endogenous miR-370 were significantly elevated. Concurrently, JEV replication was significantly reduced 24 hours after transfection of miR-370 mimic. Functionally, miR-370 mimic mitigated both JEV-induced apoptosis and the inhibition of host cell proliferation. Following JEV infection, interferon-β and nuclear factor-kappa B were upregulated, whereas miR-370 mimic prevented the upregulation of the genes induced by JEV infection. The present study demonstrated that miR-370 expression in host cells is downregulated following JEV infection, which further mediates innate immunity-related gene expression. Taken together, miR-370 mimic might be useful to prevent viral replication and infection-induced host cell injury.

  8. The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study

    Directory of Open Access Journals (Sweden)

    Jamshid Jamali

    2017-01-01

    Full Text Available Evaluating measurement equivalence (also known as differential item functioning (DIF is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

  9. Characterization and mapping of complementary lesion-mimic genes lm1 and lm2 in common wheat.

    Science.gov (United States)

    Yao, Qin; Zhou, Ronghua; Fu, Tihua; Wu, Weiren; Zhu, Zhendong; Li, Aili; Jia, Jizeng

    2009-10-01

    A lesion-mimic phenotype appeared in a segregating population of common wheat cross Yanzhan 1/Zaosui 30. The parents had non-lesion normal phenotypes. Shading treatment and histochemical analyses showed that the lesions were caused by light-dependent cell death and were not associated with pathogens. Studies over two cropping seasons showed that some lines with more highly expressed lesion-mimic phenotypes exhibited significantly lower grain yields than those with the normal phenotype, but there were no significant effects in the lines with weakly expressed lesion-mimic phenotypes. Among yield traits, one-thousand grain weight was the most affected by lesion-mimic phenotypes. Genetic analysis indicated that this was a novel type of lesion mimic, which was caused by interaction of recessive genes derived from each parent. The lm1 (lesion mimic 1) locus from Zaosui 30 was flanked by microsatellite markers Xwmc674 and Xbarc133/Xbarc147 on chromosome 3BS, at genetic distances of 1.2 and 3.8 cM, respectively, whereas lm2 from Yanzhan 1 was mapped between microsatellite markers Xgwm513 and Xksum154 on chromosome 4BL, at genetic distances of 1.5 and 3 cM, respectively. The linked microsatellite makers identified in this study might be useful for evaluating whether potential parents with normal phenotype are carriers of lesion-mimic alleles.

  10. The Effect of Small Sample Size on Measurement Equivalence of Psychometric Questionnaires in MIMIC Model: A Simulation Study.

    Science.gov (United States)

    Jamali, Jamshid; Ayatollahi, Seyyed Mohammad Taghi; Jafari, Peyman

    2017-01-01

    Evaluating measurement equivalence (also known as differential item functioning (DIF)) is an important part of the process of validating psychometric questionnaires. This study aimed at evaluating the multiple indicators multiple causes (MIMIC) model for DIF detection when latent construct distribution is nonnormal and the focal group sample size is small. In this simulation-based study, Type I error rates and power of MIMIC model for detecting uniform-DIF were investigated under different combinations of reference to focal group sample size ratio, magnitude of the uniform-DIF effect, scale length, the number of response categories, and latent trait distribution. Moderate and high skewness in the latent trait distribution led to a decrease of 0.33% and 0.47% power of MIMIC model for detecting uniform-DIF, respectively. The findings indicated that, by increasing the scale length, the number of response categories and magnitude DIF improved the power of MIMIC model, by 3.47%, 4.83%, and 20.35%, respectively; it also decreased Type I error of MIMIC approach by 2.81%, 5.66%, and 0.04%, respectively. This study revealed that power of MIMIC model was at an acceptable level when latent trait distributions were skewed. However, empirical Type I error rate was slightly greater than nominal significance level. Consequently, the MIMIC was recommended for detection of uniform-DIF when latent construct distribution is nonnormal and the focal group sample size is small.

  11. Hybrid adsorptive membrane reactor

    Science.gov (United States)

    Tsotsis, Theodore T [Huntington Beach, CA; Sahimi, Muhammad [Altadena, CA; Fayyaz-Najafi, Babak [Richmond, CA; Harale, Aadesh [Los Angeles, CA; Park, Byoung-Gi [Yeosu, KR; Liu, Paul K. T. [Lafayette Hill, PA

    2011-03-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  12. Premature rupture of membranes

    Science.gov (United States)

    ... gov/ency/patientinstructions/000512.htm Premature rupture of membranes To use the sharing features on this page, ... water that surrounds your baby in the womb. Membranes or layers of tissue hold in this fluid. ...

  13. Oxygen transport membrane

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a novel composite oxygen transport membrane as well as its preparation and uses thereof.......The present invention relates to a novel composite oxygen transport membrane as well as its preparation and uses thereof....

  14. Membrane with integrated spacer

    NARCIS (Netherlands)

    Balster, J.H.; Stamatialis, Dimitrios; Wessling, Matthias

    2010-01-01

    Many membrane processes are severely influenced by concentration polarisation. Turbulence promoting spacers placed in between the membranes can reduce the diffusional resistance of concentration polarisation by inducing additional mixing. Electrodialysis (ED) used for desalination suffers from

  15. Gel layer formation on membranes in Membrane Bioreactors

    NARCIS (Netherlands)

    Van den Brink, P.F.H.

    2014-01-01

    The widespread application of membrane bioreactors (MBRs) for municipal wastewater treatment is hampered by membrane fouling. Fouling increases energy demand, reduces process performance and creates the need for more frequent (chemical) membrane cleaning or replacement. Membrane fouling in MBRs is

  16. Smart membranes for monitoring membrane based desalination processes

    KAUST Repository

    Laleg-Kirati, Taous-Meriem; Karam, Ayman M.

    2017-01-01

    Various examples are related to smart membranes for monitoring membrane based process such as, e.g., membrane distillation processes. In one example, a membrane, includes a porous surface and a plurality of sensors (e.g., temperature, flow and

  17. Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide

    Science.gov (United States)

    Wang, Yukun; Chen, Charles H.; Hu, Dan; Ulmschneider, Martin B.; Ulmschneider, Jakob P.

    2016-11-01

    Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures--formed by a single sequence--may be a key feature in preventing bacterial resistance and could explain why sequence-function relationships in AMPs remain elusive.

  18. In vivo preclinical evaluation of the accuracy of toroidal-shaped HIFU treatments using a tumor-mimic model

    International Nuclear Information System (INIS)

    N'Djin, W A; Melodelima, D; Parmentier, H; Chapelon, J Y; Rivoire, M

    2010-01-01

    The pig is an ideal animal model for preclinical evaluation of HIFU treatments, especially in the liver. However, there is no liver tumor model available for pigs. In this work, we propose to study an in vivo tumor-mimic model as a tool for evaluating if a sonographycally guided HIFU treatment, delivered by a toroidal-shaped device dedicated for the treatment of liver metastases, is correctly located in the liver. One centimeter tumor-mimics were created in liver tissues. These tumor-mimics were detectable on ultrasound imaging and on gross pathology. Two studies were carried out. First, an in vivo study of tolerance at mid-term (30 days, 10 pigs) revealed that tumor-mimics are suitable for studying HIFU treatments at a preclinical stage, since local and biological tolerances were excellent. The dimensions of the tumor-mimics were reproducible (diameter at day 0: 9.7 ± 2.0 mm) and were the same as a function of time (p = 0.64). A second in vivo study was carried out in ten pigs. Tumor mimics were used as targets in liver tissues in order to determine if the HIFU treatment is correctly located in the liver. A procedure of extensive HIFU ablation using multiple HIFU lesions juxtaposed manually was then tested on eight tumor-mimics. In 88% of the cases (seven out of eight), tumor-mimics were treated with negative margins (≥1 mm) in all directions. On average, negative margins measured 10.0 ± 6.7 mm. These tumor-mimics constitute an excellent reference for studying in vivo the accuracy of HIFU therapy in the liver.

  19. Cholesterol Promotes Protein Binding by Affecting Membrane Electrostatics and Solvation Properties.

    Science.gov (United States)

    Doktorova, Milka; Heberle, Frederick A; Kingston, Richard L; Khelashvili, George; Cuendet, Michel A; Wen, Yi; Katsaras, John; Feigenson, Gerald W; Vogt, Volker M; Dick, Robert A

    2017-11-07

    Binding of the retroviral structural protein Gag to the cellular plasma membrane is mediated by the protein's matrix (MA) domain. Prominent among MA-PM interactions is electrostatic attraction between the positively charged MA domain and the negatively charged plasma membrane inner leaflet. Previously, we reported that membrane association of HIV-1 Gag, as well as purified Rous sarcoma virus (RSV) MA and Gag, depends strongly on the presence of acidic lipids and is enhanced by cholesterol (Chol). The mechanism underlying this enhancement was unclear. Here, using a broad set of in vitro and in silico techniques we addressed molecular mechanisms of association between RSV MA and model membranes, and investigated how Chol enhances this association. In neutron scattering experiments with liposomes in the presence or absence of Chol, MA preferentially interacted with preexisting POPS-rich clusters formed by nonideal lipid mixing, binding peripherally to the lipid headgroups with minimal perturbation to the bilayer structure. Molecular dynamics simulations showed a stronger MA-bilayer interaction in the presence of Chol, and a large Chol-driven increase in lipid packing and membrane surface charge density. Although in vitro MA-liposome association is influenced by disparate variables, including ionic strength and concentrations of Chol and charged lipids, continuum electrostatic theory revealed an underlying dependence on membrane surface potential. Together, these results conclusively show that Chol affects RSV MA-membrane association by making the electrostatic potential at the membrane surface more negative, while decreasing the penalty for lipid headgroup desolvation. The presented approach can be applied to other viral and nonviral proteins. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. Model cell membranes

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Nylander, Tommy; Cardenas Gomez, Marite

    2014-01-01

    The high complexity of biological membranes has motivated the development and application of a wide range of model membrane systems to study biochemical and biophysical aspects of membranes in situ under well defined conditions. The aim is to provide fundamental understanding of processes control...

  1. Idiopathic epiretinal membrane

    NARCIS (Netherlands)

    Bu, Shao-Chong; Kuijer, Roelof; Li, Xiao-Rong; Hooymans, Johanna M M; Los, Leonoor I

    2014-01-01

    Background: Idiopathic epiretinal membrane (iERM) is a fibrocellular membrane that proliferates on the inner surface of the retina at the macular area. Membrane contraction is an important sight-threatening event and is due to fibrotic remodeling. Methods: Analysis of the current literature

  2. Meniscus Membranes For Separation

    Science.gov (United States)

    Dye, Robert C.; Jorgensen, Betty; Pesiri, David R.

    2005-09-20

    Gas separation membranes, especially meniscus-shaped membranes for gas separations are disclosed together with the use of such meniscus-shaped membranes for applications such as thermal gas valves, pre-concentration of a gas stream, and selective pre-screening of a gas stream. In addition, a rapid screening system for simultaneously screening polymer materials for effectiveness in gas separation is provided.

  3. Meniscus membranes for separations

    Science.gov (United States)

    Dye, Robert C [Irvine, CA; Jorgensen, Betty [Jemez Springs, NM; Pesiri, David R [Aliso Viejo, CA

    2004-01-27

    Gas separation membranes, especially meniscus-shaped membranes for gas separations are disclosed together with the use of such meniscus-shaped membranes for applications such as thermal gas valves, pre-concentration of a gas stream, and selective pre-screening of a gas stream. In addition, a rapid screening system for simultaneously screening polymer materials for effectiveness in gas separation is provided.

  4. Impact of the β-Lactam Resistance Modifier (−-Epicatechin Gallate on the Non-Random Distribution of Phospholipids across the Cytoplasmic Membrane of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Helena Rosado

    2015-07-01

    Full Text Available The polyphenol (−-epicatechin gallate (ECg inserts into the cytoplasmic membrane (CM of methicillin-resistant Staphylococcus aureus (MRSA and reversibly abrogates resistance to β-lactam antibiotics. ECg elicits an increase in MRSA cell size and induces thickened cell walls. As ECg partially delocalizes penicillin-binding protein PBP2 from the septal division site, reduces PBP2 and PBP2a complexation and induces CM remodelling, we examined the impact of ECg membrane intercalation on phospholipid distribution across the CM and determined if ECg affects the equatorial, orthogonal mode of division. The major phospholipids of the staphylococcal CM, lysylphosphatidylglycerol (LPG, phosphatidylglycerol (PG, and cardiolipin (CL, were distributed in highly asymmetric fashion; 95%–97% of LPG was associated with the inner leaflet whereas PG (~90% and CL (~80% were found predominantly in the outer leaflet. ECg elicited small, significant changes in LPG distribution. Atomic force microscopy established that ECg-exposed cells divided in similar fashion to control bacteria, with a thickened band of encircling peptidoglycan representing the most recent plane of cell division, less distinct ribs indicative of previous sites of orthogonal division and concentric rings and “knobbles” representing stages of peptidoglycan remodelling during the cell cycle. Preservation of staphylococcal membrane lipid asymmetry and mode of division in sequential orthogonal planes appear key features of ECg-induced stress.

  5. Separation membrane development

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.W. [Savannah River Technology Center, Aiken, SC (United States)

    1998-08-01

    A ceramic membrane has been developed to separate hydrogen from other gases. The method used is a sol-gel process. A thin layer of dense ceramic material is coated on a coarse ceramic filter substrate. The pore size distribution in the thin layer is controlled by a densification of the coating materials by heat treatment. The membrane has been tested by permeation measurement of the hydrogen and other gases. Selectivity of the membrane has been achieved to separate hydrogen from carbon monoxide. The permeation rate of hydrogen through the ceramic membrane was about 20 times larger than Pd-Ag membrane.

  6. Microporous silica membranes

    DEFF Research Database (Denmark)

    Boffa, Vittorio; Yue, Yuanzheng

    2012-01-01

    Hydrothermal stability is a crucial factor for the application of microporous silica-based membranes in industrial processes. Indeed, it is well established that steam exposure may cause densification and defect formation in microporous silica membranes, which are detrimental to both membrane...... permeability and selectivity. Numerous previous studies show that microporous transition metal doped-silica membranes are hydrothermally more stable than pure silica membranes, but less permeable. Here we present a quantitative study on the impact of type and concentration of transition metal ions...... on the microporous structure, stability and permeability of amorphous silica-based membranes, providing information on how to design chemical compositions and synthetic paths for the fabrication of silica-based membranes with a well accessible and highly stabile microporous structure....

  7. Clustering on Membranes

    DEFF Research Database (Denmark)

    Johannes, Ludger; Pezeshkian, Weria; Ipsen, John H

    2018-01-01

    Clustering of extracellular ligands and proteins on the plasma membrane is required to perform specific cellular functions, such as signaling and endocytosis. Attractive forces that originate in perturbations of the membrane's physical properties contribute to this clustering, in addition to direct...... protein-protein interactions. However, these membrane-mediated forces have not all been equally considered, despite their importance. In this review, we describe how line tension, lipid depletion, and membrane curvature contribute to membrane-mediated clustering. Additional attractive forces that arise...... from protein-induced perturbation of a membrane's fluctuations are also described. This review aims to provide a survey of the current understanding of membrane-mediated clustering and how this supports precise biological functions....

  8. Molecular mechanisms of protein-cholesterol interactions in plasma membranes: Functional distinction between topological (tilted) and consensus (CARC/CRAC) domains.

    Science.gov (United States)

    Fantini, Jacques; Di Scala, Coralie; Baier, Carlos J; Barrantes, Francisco J

    2016-09-01

    The molecular mechanisms that control the multiple possible modes of protein association with membrane cholesterol are remarkably convergent. These mechanisms, which include hydrogen bonding, CH-π stacking and dispersion forces, are used by a wide variety of extracellular proteins (e.g. microbial or amyloid) and membrane receptors. Virus fusion peptides penetrate the membrane of host cells with a tilted orientation that is compatible with a transient interaction with cholesterol; this tilted orientation is also characteristic of the process of insertion of amyloid proteins that subsequently form oligomeric pores in the plasma membrane of brain cells. Membrane receptors that are associated with cholesterol generally display linear consensus binding motifs (CARC and CRAC) characterized by a triad of basic (Lys/Arg), aromatic (Tyr/phe) and aliphatic (Leu/Val) amino acid residues. In some cases, the presence of both CARC and CRAC within the same membrane-spanning domain allows the simultaneous binding of two cholesterol molecules, one in each membrane leaflet. In this review the molecular basis and the functional significance of the different modes of protein-cholesterol interactions in plasma membranes are discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Identification of Chemical Agents (Mimics) Residues after Destructive Adsorption Using TPD and UV-vis-IR and Raman

    National Research Council Canada - National Science Library

    Klabunde, Kenneth J

    2001-01-01

    Instrumentation was purchased that helps characterize the chemical structures and chemical reactions that occur when nanocrystalline metal oxides carry out destructive adsorption of chemical agents mimics. The residues (adducts...

  10. Application of dynamic membranes in anaerobic membranes in anaerobic membrane bioreactor systems

    NARCIS (Netherlands)

    Erşahin, M.E.

    2015-01-01

    Anaerobic membrane bioreactors (AnMBRs) physically ensure biomass retention by the application of a membrane filtration process. With growing application experiences from aerobic membrane bioreactors (MBRs), the combination of membrane and anaerobic processes has received much attention and become

  11. Effectiveness of a large mimic panel in an existing nuclear power plant central control board

    International Nuclear Information System (INIS)

    Kubota, Ryuji; Satoh, Hiroyuki; Sasajima, Katsuhiro; Kawano, Ryutaro; Shibuya Shinya

    1999-01-01

    We conducted the analysis of the nuclear power plant (NPP) operators' behaviors under emergency conditions by using training simulators as a joint research project by Japanese BWR groups for twelve years. In the phase-IV of this project we executed two kinds of experiments to evaluate the effectiveness of the interfaces. One was for evaluations of the interfaces such as CRTs with touch screen, a large mimic panel, and a hierarchical annunciator system introduced in the newly developed ABWR type central control board. The other was that we analyzed the operators' behaviors in emergency conditions by using the first generation BWR type central control board which was added new interfaces such as a large display screen and demarcation on the board to help operators to understand the plant. The demarcation is one of the visual interface improvements and its technique is that a line enclosing several components causes them to be perceived as a group.The result showed that both the large display panel Introduced in ABWR central control board and the large display screen in the existing BWR type central control board improved the performance of the NPP operators in the experiments. It was expected that introduction of the large mimic panel into the existing BWR type central control boards would improve operators' performance. However, in the case of actual installation of the large display board into the existing central control boards, there are spatial and hardware constraints. Therefore the size of lamps, lines connecting from symbols of the pumps or valves to the others' will have to be modified under these constraints. It is important to evaluate the displayed information on the large display board before actual installation. We made experiments to solve these problems by using TEPCO's research simulator which is added a large mimic panel. (author)

  12. Próteses de comunicação e alinhamento comportamental sobre impressos hospitalares Communication prostheses and behavioral alignment in hospital leaflets

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Vasconcellos-Silva

    2003-08-01

    Full Text Available Realizou-se revisão da literatura sobre publicações que descrevem experiências com material impresso distribuído ao público leigo em instituições hospitalares. Excluindo impressos para profissionais ou portadores de incapacidades, dentre 146 trabalhos, foram obtidos 75 artigos que ilustram o padrão atual de racionalidade da produção, uso e avaliação deste tipo de recurso. Esses artigos investem no poder da "informação impressa ideal" para alinhar comportamentos à agenda biomédica hospitalar. A racionalidade instrumental que os permeia percebe o "pacote informativo perfeito" como aquele que explicita eficientemente seus conteúdos técnicos, para fins de convencimento unilateral, atualizado segundo escalas de legibilidade, adornado por projeto gráfico e enfatizando prioridades definidas pelos profissionais. Tais "próteses de comunicação" seriam passíveis de validação eletrônica, por intermédio de softwares competentes em adequar "doses" e conteúdos. Discute-se a informação como fármaco, o cognitivismo, a ausência de pesquisas de recepção e a necessidade da ação comunicativa, para desconstrução de tais sistemas de pensamento fechados no ambiente hospitalar.Review was made of publications that describe experience with printed material distributed to the lay public in hospital institutions. From the 146 leaflets examined, those aimed at professionals or disabled people, thus leaving 75 papers that illustrate the present pattern for the rationality behind the production, use and evaluation of this type of resource. In a general manner, such leaflets invest in the power of "ideal printed information" to align behavior with the hospital's biomedical agenda. The underlying rationality that permeates them perceives the "perfect information package" as one that efficiently describes its technical content for the purpose of unidirectional persuasion, is up-to-date in relation to readability scales and embellished by

  13. Synthetic miR-145 Mimic Enhances the Cytotoxic Effect of the Antiangiogenic Drug Sunitinib in Glioblastoma.

    Science.gov (United States)

    Liu, Hongwei; Liu, Zhixiong; Jiang, Bing; Huo, Lei; Liu, Jinfang; Lu, Jingchen

    2015-06-01

    Although aggressive therapeutic regimen has been applied in the treatment of Glioblastoma (GBM), the prognosis of patients with GBM remains poor. Preclinical studies have demonstrated the efficacy of Suntinib in GBM both in vitro and in vivo. In this study, we showed that the cytotoxicity was enhanced by transfection with miR-145 mimic. In addition, we suggested that the enhanced cytotoxicity of Sunitinib by miR-145 mimic was mediated by inhibition of both P-gp and Bcrp.

  14. Creation of a Tumor-Mimic Model Using a Muscle Paste for Radiofrequency Ablation of the Lung

    International Nuclear Information System (INIS)

    Kawai, T.; Kaminou, T.; Sugiura, K.; Hashimoto, M.; Ohuchi, Y.; Adachi, A.; Fujioka, S.; Ito, H.; Nakamura, K.; Ogawa, T.

    2009-01-01

    The purpose of this study was to develop an easily created tumor-mimic model and evaluate its efficacy for radiofrequency ablation (RFA) of the lung. The bilateral lungs of eight living adult swine were used. A tumor-mimic model was made by percutaneous injection of 1.0 ml muscle paste through the bone biopsy needle into the lung. An RFA probe was then inserted into the tumor mimics immediately after tumor creation. Ablation time, tissue impedance, and temperature were recorded. The tumor mimics and their coagulated regions were evaluated microscopically and macroscopically. The muscle paste was easily injected into the lung parenchyma through the bone biopsy needle and well visualized under fluoroscopy. In 10 of 12 sites the tumor mimics were oval shaped, localized, and homogeneous on gross specimens. Ten tumor mimics were successfully ablated, and four locations were ablated in the normal lung parenchyma as controls. In the tumor and normal lung parenchyma, ablation times were 8.9 ± 3.5 and 4.4 ± 1.6 min, respectively; tissue impedances at the start of ablation were 100.6 ± 16.6 and 145.8 ± 26.8 Ω, respectively; and temperatures at the end of ablation were 66.0 ± 7.9 and 57.5 ± 7.6 o C, respectively. The mean size of tumor mimics was 13.9 x 8.2 mm, and their coagulated area was 18.8 x 13.1 mm. In the lung parenchyma, the coagulated area was 15.3 x 12.0 mm. In conclusion, our tumor-mimic model using muscle paste can be easily and safely created and can be ablated using the ablation algorithm in the clinical setting.

  15. Low-energy ion beam bombardment effect on the plant-cell-envelope mimetic membrane for DNA transfer

    Energy Technology Data Exchange (ETDEWEB)

    Prakrajang, K., E-mail: k.prakrajang@gmail.com [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Sangwijit, K.; Anuntalabhochai, S. [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Wanichapichart, P. [Membrane Science and Technology Research Center, Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla 90112 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.th [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

    2012-09-01

    This study is a systematic analysis of the mechanisms involved in ion-beam induced DNA transfer, an important application of ion beam biotechnology. Cellulose membranes were used to mimic the plant cell envelope. Ion beams of argon (Ar) or nitrogen (N) at an energy of 25 keV bombarded the cellulose membranes at fluences ranging from 10{sup 15} to 10{sup 16} ions/cm{sup 2}. The damage to the ion-beam-bombarded membranes was characterized using infrared spectroscopy, a micro tensile test and scanning electron microscopy (SEM). Chain scission was the dominant radiation damage type in the membrane. DNA diffusion across the membrane was significantly increased after ion beam bombardment. The increase in DNA transfer is therefore attributed to chain scission, which increases the permeability by increasing the number of pores in the membrane.

  16. Low-energy ion beam bombardment effect on the plant-cell-envelope mimetic membrane for DNA transfer

    International Nuclear Information System (INIS)

    Prakrajang, K.; Sangwijit, K.; Anuntalabhochai, S.; Wanichapichart, P.; Yu, L.D.

    2012-01-01

    This study is a systematic analysis of the mechanisms involved in ion-beam induced DNA transfer, an important application of ion beam biotechnology. Cellulose membranes were used to mimic the plant cell envelope. Ion beams of argon (Ar) or nitrogen (N) at an energy of 25 keV bombarded the cellulose membranes at fluences ranging from 10 15 to 10 16 ions/cm 2 . The damage to the ion-beam-bombarded membranes was characterized using infrared spectroscopy, a micro tensile test and scanning electron microscopy (SEM). Chain scission was the dominant radiation damage type in the membrane. DNA diffusion across the membrane was significantly increased after ion beam bombardment. The increase in DNA transfer is therefore attributed to chain scission, which increases the permeability by increasing the number of pores in the membrane.

  17. Chondromyxoid fibroma of the rib mimics a chondrosarcoma on 18F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William (Dept. of Nuclear Medicine, Brandon Regional Health Centre, Brandon (Canada)), email: makisw79@yahoo.com; Ciarallo, Anthony; Lisbona, Robert (Dept. of Nuclear Medicine, Royal Victoria Hospital, McGill Univ. Health Centre, Montreal (Canada))

    2011-06-15

    Chondromyxoid fibroma (CMF) is a rare benign bone tumor of chondroid origin that occurs mostly in the metaphyses of long bones. CMF can occasionally mimic a chondrosarcoma on CT, and the literature on the 18F-FDG PET/CT imaging characteristics of CMF tumors is limited. In the presented case, a large histologically proven CMF chest wall mass was initially misinterpreted as a chondrosarcoma. This case highlights a potential pitfall in the PET/CT evaluation of these rare benign bone tumors

  18. Synthesis of 3-alkyl enol mimics inhibitors of type II dehydroquinase: factors influencing their inhibition potency.

    Science.gov (United States)

    Blanco, Beatriz; Sedes, Antía; Peón, Antonio; Lamb, Heather; Hawkins, Alastair R; Castedo, Luis; González-Bello, Concepción

    2012-05-14

    Several 3-alkylaryl mimics of the enol intermediate in the reaction catalyzed by type II dehydroquinase were synthesized to investigate the effect on the inhibition potency of replacing the oxygen atom in the side chain by a carbon atom. The length and the rigidity of the spacer was also studied. The inhibitory properties of the reported compounds against type II dehydroquinase from Mycobacterium tuberculosis and Helicobacter pylori are also reported. The binding modes of these analogs in the active site of both enzymes were studied by molecular docking using GOLD 5.0 and dynamic simulations studies.

  19. Mucous retention cyst of temporal bone: a mimic of cholesteatoma on DW-MRI.

    Science.gov (United States)

    Karandikar, Amit; Goh, Julian; Loke, Siu Cheng; Yeo, Seng Beng; Tan, Tiong Yong

    2013-01-01

    Non-EPI DW imaging is increasingly being used as a sensitive sequence in detecting cholesteatomas especially if CT findings are not confirmatory. Cholesteatoma appears as a hyperintense focus on DWI. We present two cases of mucous retention cysts in the mastoid temporal bone/middle ear cavity, which present as hyperintense on non-EPI DWI and potentially may mimic cholesteatomas. Differentiating between the two conditions is important, as surgery can be avoided in mucous retention cysts. We have also discussed ways to differentiate between these two conditions on MRI. To our knowledge, this entity is not reported previously. © 2013 Elsevier Inc. All rights reserved.

  20. Estimating the size of non-observed economy in Croatia using the MIMIC approach

    OpenAIRE

    Vjekoslav Klaric

    2011-01-01

    This paper gives a quick overview of the approaches that have been used in the research of shadow economy, starting with the defi nitions of the terms “shadow economy” and “non-observed economy”, with the accent on the ISTAT/Eurostat framework. Several methods for estimating the size of the shadow economy and the non-observed economy are then presented. The emphasis is placed on the MIMIC approach, one of the methods used to estimate the size of the nonobserved economy. After a glance at the ...

  1. Cooperative interplay of let-7 mimic and HuR with MYC RNA

    OpenAIRE

    Gunzburg, Menachem J; Sivakumaran, Andrew; Pendini, Nicole R; Yoon, Je-Hyun; Gorospe, Myriam; Wilce, Matthew Cj; Wilce, Jacqueline A

    2015-01-01

    Both RNA-binding proteins (RBP) and miRNA play important roles in the regulation of mRNA expression, often acting together to regulate a target mRNA. In some cases the RBP and miRNA have been reported to act competitively, but in other instances they function cooperatively. Here, we investigated HuR function as an enhancer of let-7-mediated translational repression of c-Myc despite the separation of their binding sites. Using an in vitro system, we determined that a let-7 mimic, consisting of...

  2. Effector Mimics and Integrated Decoys, the Never-Ending Arms Race between Rice and Xanthomonas oryzae.

    Science.gov (United States)

    Zuluaga, Paola; Szurek, Boris; Koebnik, Ralf; Kroj, Thomas; Morel, Jean-Benoit

    2017-01-01

    Plants are constantly challenged by a wide range of pathogens and have therefore evolved an array of mechanisms to defend against them. In response to these defense systems, pathogens have evolved strategies to avoid recognition and suppress plant defenses (Brown and Tellier, 2011). Three recent reports dealing with the resistance of rice to Xanthomonas oryzae have added a new twist to our understanding of this fascinating co-evolutionary arms race (Ji et al., 2016; Read et al., 2016; Triplett et al., 2016). They show that pathogens also develop sophisticated effector mimics to trick recognition.

  3. Exaggerated Arthropod Bite: A Case Report and Review of the Mimics

    Directory of Open Access Journals (Sweden)

    Sagah Ahmed

    2018-01-01

    Full Text Available Exaggerated arthropod bite reactions causing hemorrhagic or necrotic bullous lesions can mimic other serious conditions such as cutaneous anthrax, brown recluse spider bite, and tularemia. A 55- year-old, healthy woman presented to the emergency department with a 3.5-centimeter painless, collapsed hemorrhagic bulla at the left costal margin. She was afebrile and had no systemic symptoms. Laboratory evaluation was unremarkable. She was prescribed silver sulfadiazine cream and mupirocin ointment. The area denuded two days later and the lesion completely healed. This case illustrates the broad differential to be considered when evaluating patients with hemorrhagic bullous lesions.

  4. Arterial tortuosity syndrome: An extremely rare disease presenting as a mimic of pulmonary sling

    Directory of Open Access Journals (Sweden)

    Amy Farkas, MD

    2018-02-01

    Full Text Available Pulmonary sling is the anatomic variant defined by the aberrant origin of the left pulmonary artery from the right pulmonary artery. This patient presented with a mimic of pulmonary sling as a result of an extremely rare condition, arterial tortuosity syndrome (ATS. The patient was first diagnosed with pulmonary sling on prenatal echocardiogram performed by cardiology. Computed tomography angiography of the chest obtained at birth to evaluate respiratory depression demonstrated ATS. The early detection of ATS has been demonstrated to improve patient outcome. This case provides an overview of the typical imaging features of ATS to aid radiologists in making this uncommon diagnosis.

  5. TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

    Science.gov (United States)

    Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

    2010-06-15

    We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

  6. Asthma mimic: Case report and literature review of vocal cord nodule associated with wheezing.

    Science.gov (United States)

    Kashif, Muhammad; Singh, Tushi; Aslam, Ahsan; Khaja, Misbahuddin

    2017-01-01

    Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. Various clinical conditions can mimic asthma, such as foreign body aspiration, subglottic stenosis, congestive heart failure, diffuse panbronchiolitis, aortic arch anomalies, reactive airway dysfunction syndrome, chronic obstructive pulmonary disease, retrosternal goiter, vocal cord tumors, other airway tumors, and vocal cord dysfunction. Upper airway obstruction can be a life-threatening emergency. Here, we present the case of a 58-year-old female with recurrent hospital visits for wheezing and exacerbations of asthma, who was later found to have a vocal cord nodule confirmed to be squamous cell carcinoma, which was mimicking like asthma.

  7. Probing lipid membrane electrostatics

    Science.gov (United States)

    Yang, Yi

    The electrostatic properties of lipid bilayer membranes play a significant role in many biological processes. Atomic force microscopy (AFM) is highly sensitive to membrane surface potential in electrolyte solutions. With fully characterized probe tips, AFM can perform quantitative electrostatic analysis of lipid membranes. Electrostatic interactions between Silicon nitride probes and supported zwitterionic dioleoylphosphatidylcholine (DOPC) bilayer with a variable fraction of anionic dioleoylphosphatidylserine (DOPS) were measured by AFM. Classical Gouy-Chapman theory was used to model the membrane electrostatics. The nonlinear Poisson-Boltzmann equation was numerically solved with finite element method to provide the potential distribution around the AFM tips. Theoretical tip-sample electrostatic interactions were calculated with the surface integral of both Maxwell and osmotic stress tensors on tip surface. The measured forces were interpreted with theoretical forces and the resulting surface charge densities of the membrane surfaces were in quantitative agreement with the Gouy-Chapman-Stern model of membrane charge regulation. It was demonstrated that the AFM can quantitatively detect membrane surface potential at a separation of several screening lengths, and that the AFM probe only perturbs the membrane surface potential by external field created by the internai membrane dipole moment. The analysis yields a dipole moment of 1.5 Debye per lipid with a dipole potential of +275 mV for supported DOPC membranes. This new ability to quantitatively measure the membrane dipole density in a noninvasive manner will be useful in identifying the biological effects of the dipole potential. Finally, heterogeneous model membranes were studied with fluid electric force microscopy (FEFM). Electrostatic mapping was demonstrated with 50 nm resolution. The capabilities of quantitative electrostatic measurement and lateral charge density mapping make AFM a unique and powerful

  8. Emulsification using microporous membranes

    Directory of Open Access Journals (Sweden)

    Goran T. Vladisavljević

    2011-10-01

    Full Text Available Membrane emulsification is a process of injecting a pure dispersed phase or pre-emulsion through a microporous membrane into the continuous phase. As a result of the immiscibility of the two phases, droplets of the dispersed phase are formed at the outlets of membrane pores. The droplets formed in the process are removed from the membrane surface by applying cross-flow or stirring of the continuous phase or using a dynamic (rotating or vibrating membrane. The most commonly used membrane for emulsification is the Shirasu Porous Glass (SPG membrane, fabricated through spinodal decomposition in a melt consisting of Japanese volcanic ash (Shirasu, boric acid and calcium carbonate. Microsieve membranes are increasingly popular as an alternative to highly tortuous glass and ceramic membranes. Microsieves are usually fabricated from nickel by photolithography and electroplating or they can be manufactured from silicon nitride via Reactive Ion Etching (RIE. An advantage of microsieves compared to the SPG membrane is in much higher transmembrane fluxes and higher tolerance to fouling by the emulsion ingredients due to the existence of short, straight through pores. Unlike conventional emulsification devices such as high-pressure valve homogenisers and rotor-stator devices, membrane emulsification devices permit a precise control over the mean pore size over a wide range and during the process insignificant amount of energy is dissipated as heat. The drop size is primarily determined by the pore size, but it depends also on other parameters, such as membrane wettability, emulsion formulation, shear stress on the membrane surface, transmembrane pressure, etc.

  9. Lipopolysaccharide biogenesis and transport at the outer membrane of Gram-negative bacteria.

    Science.gov (United States)

    Sperandeo, Paola; Martorana, Alessandra M; Polissi, Alessandra

    2017-11-01

    The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer containing a unique glycolipid, lipopolysaccharide (LPS) in its outer leaflet. LPS molecules confer to the OM peculiar permeability barrier properties enabling Gram-negative bacteria to exclude many toxic compounds, including clinically useful antibiotics, and to survive harsh environments. Transport of LPS poses several problems to the cells due to the amphipatic nature of this molecule. In this review we summarize the current knowledge on the LPS transport machinery, discuss the challenges associated with this process and present the solutions that bacterial cells have evolved to address the problem of LPS transport and assembly at the cell surface. Finally, we discuss how knowledge on LPS biogenesis can be translated for the development of novel antimicrobial therapies. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016. Published by Elsevier B.V.

  10. Dual-energy CT for the evaluation of urinary calculi: Image interpretation, pitfalls and stone mimics

    International Nuclear Information System (INIS)

    Jepperson, M.A.; Cernigliaro, J.G.; Sella, D.; Ibrahim, E.; Thiel, D.D.; Leng, S.; Haley, W.E.

    2013-01-01

    Urolithiasis is a common disease with a reported prevalence between 4% and 20% in developed countries. Determination of urinary calculi composition is a key factor in preoperative evaluation, treatment, and stone recurrence prevention. Prior to the introduction of dual-energy computed tomography (DECT), available methods for determining urinary stone composition were only available after stone extraction, and thereby unable to aid in optimized stone management prior to intervention. DECT utilizes the attenuation difference produced by two different x-ray energy spectra to quantify urinary calculi composition as uric acid or non-uric acid (with likely further classification in the future) while still providing the information attained with a conventional CT. Knowledge of DECT imaging pitfalls and stone mimics is important, as the added benefit of dual-energy analysis is the determination of stone composition, which in turn affects all aspects of stone management. This review briefly describes DECT principles, scanner types and acquisition protocols for the evaluation of urinary calculi as they relate to imaging pitfalls (inconsistent characterization of small stones, small dual-energy field of view, and mischaracterization from surrounding material) and stone mimics (drainage devices) that may adversely impact clinical decisions. We utilize our clinical experience from scanning over 1200 patients with this new imaging technique to present clinically relevant examples of imaging pitfalls and possible mechanisms for resolution

  11. Intact Rapid Facial Mimicry as well as Generally Reduced Mimic Responses in Stable Schizophrenia Patients

    Science.gov (United States)

    Chechko, Natalya; Pagel, Alena; Otte, Ellen; Koch, Iring; Habel, Ute

    2016-01-01

    Spontaneous emotional expressions (rapid facial mimicry) perform both emotional and social functions. In the current study, we sought to test whether there were deficits in automatic mimic responses to emotional facial expressions in patients (15 of them) with stable schizophrenia compared to 15 controls. In a perception-action interference paradigm (the Simon task; first experiment), and in the context of a dual-task paradigm (second experiment), the task-relevant stimulus feature was the gender of a face, which, however, displayed a smiling or frowning expression (task-irrelevant stimulus feature). We measured the electromyographical activity in the corrugator supercilii and zygomaticus major muscle regions in response to either compatible or incompatible stimuli (i.e., when the required response did or did not correspond to the depicted facial expression). The compatibility effect based on interactions between the implicit processing of a task-irrelevant emotional facial expression and the conscious production of an emotional facial expression did not differ between the groups. In stable patients (in spite of a reduced mimic reaction), we observed an intact capacity to respond spontaneously to facial emotional stimuli. PMID:27303335

  12. A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone.

    Science.gov (United States)

    Pruitt, Rory N; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R; Ronald, Pamela C

    2017-07-01

    The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides. Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides. Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence. These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. © 2017 UT-Battelle LLC. New Phytologist © 2017 New Phytologist Trust.

  13. Intravital Confocal and Two-photon Imaging of Dual-color Cells and Extracellular Matrix Mimics

    Science.gov (United States)

    Bal, Ufuk; Andresen, Volker; Baggett, Brenda; Utzinger, Urs

    2013-01-01

    To optimize imaging of cells in three dimensional culture we studied confocal backscattering, Second Harmonic Generation (SHG) and autofluorescence as source of contrast in extracellular matrix (ECM) mimics and evaluated the attenuation as well as bleaching of endogenous cellular fluorescence signals. All common ECM mimics exhibit contrast observable with confocal reflectance microscopy. SHG imaging on collagen I based hydrogels provides high contrast and good optical penetration depth. Agarose is a useful embedding medium because it allows for large optical penetration and exhibits minimal autofluorescence while still providing good reflectance to detect voids in the embedding medium. We labeled breast cancer cells’ outline with DsRed2 and nucleus with eGFP. DsRed2 can be excited with confocal imaging at 568nm, and with two photon excitation (TPE) in the red and longer NIR. eGFP was excited at 488nm for confocal and in the NIR for TPE. While there is small difference in the bleaching rate for eGFP between confocal and TPE we observed significant difference for DsRed2 where bleaching is strongest during TPE in the red wavelengths and smallest during confocal imaging. After a few hundred microns depth in a collagen I hydrogel, TPE fluorescence becomes twice as strong compared to confocal imaging. PMID:23380006

  14. Co-creation of information leaflets to meet the support needs of people living with complex regional pain syndrome (CRPS) through innovative use of wiki technology.

    Science.gov (United States)

    Rodham, Karen; Gavin, Jeff; Coulson, Neil; Watts, Leon

    2016-01-01

    People living with complex regional pain syndrome (CRPS) experience frustration with the lack of knowledge and understanding of CRPS as a pain condition. We report on our attempt to address this issue. People living with CRPS taking part in a larger study were invited to co-construct a CRPS wiki page that addressed the areas in which they had experienced the most difficulty. A blank wiki page was set up for participants to populate with issues they felt needed to be raised and addressed. Participants failed to engage with the wiki technology. We modified our procedure and completed an inductive analysis of a sister-forum which participants were using as part of the larger study. Six issues of importance were identified. We used the discussion forum threads to populate the themes. Due to a continued lack of engagement with the wiki technology, the team decided to create a suite of leaflets which were piloted with delegates at a CRPS patient conference. Future work should be mindful of the extent to which patients are able and willing to share their experiences through such technology. Striking the balance between patient-endorsed and researcher-driven co-creation of such material is imperative.

  15. Ion-conducting membranes

    Science.gov (United States)

    Masel, Richard I.; Sajjad, Syed Dawar; Gao, Yan; Liu, Zengcai; Chen, Qingmei

    2017-12-26

    An anion-conducting polymeric membrane comprises a terpolymer of styrene, vinylbenzyl-R.sub.s and vinylbenzyl-R.sub.x. R.sub.s is a positively charged cyclic amine group. R.sub.x is at least one constituent selected from the group consisting Cl, OH and a reaction product between an OH or Cl and a species other than a simple amine or a cyclic amine. The total weight of the vinylbenzyl-R.sub.x groups is greater than 0.3% of the total weight of the membrane. In a preferred embodiment, the membrane is a Helper Membrane that increases the faradaic efficiency of an electrochemical cell into which the membrane is incorporated, and also allows product formation at lower voltages than in cells without the Helper Membrane.

  16. Gas separation with membranes

    International Nuclear Information System (INIS)

    Schulz, G.; Michele, H.; Werner, U.

    1982-01-01

    Gas separation with membranes has already been tested in numerous fields of application, e.g. uranium enrichment of H 2 separation. In many of these processes the mass transfer units, so-called permeators, have to be connected in tandem in order to achieve high concentrations. A most economical operating method provides for each case an optimization of the cascades with regard to the membrane materials, construction and design of module. By utilization of the concentration gradient along the membrane a new process development has been accomplished - the continuously operating membrane rectification unit. Investment and operating costs can be reduced considerably for a number of separating processes by combining a membrane rectification unit with a conventional recycling cascade. However, the new procedure requires that the specifications for the module construction, flow design, and membrane properties be reconsidered. (orig.) [de

  17. Membrane fluidization by alcohols inhibits DesK-DesR signalling in Bacillus subtilis.

    Science.gov (United States)

    Vaňousová, Kateřina; Beranová, Jana; Fišer, Radovan; Jemioła-Rzemińska, Malgorzata; Matyska Lišková, Petra; Cybulski, Larisa; Strzałka, Kazimierz; Konopásek, Ivo

    2018-03-01

    After cold shock, the Bacillus subtilis desaturase Des introduces double bonds into the fatty acids of existing membrane phospholipids. The synthesis of Des is regulated exclusively by the two-component system DesK/DesR; DesK serves as a sensor of the state of the membrane and triggers Des synthesis after a decrease in membrane fluidity. The aim of our work is to investigate the biophysical changes in the membrane that are able to affect the DesK signalling state. Using linear alcohols (ethanol, propanol, butanol, hexanol, octanol) and benzyl alcohol, we were able to suppress Des synthesis after a temperature downshift. The changes in the biophysical properties of the membrane caused by alcohol addition were followed using membrane fluorescent probes and differential scanning calorimetry. We found that the membrane fluidization induced by alcohols was reflected in an increased hydration at the lipid-water interface. This is associated with a decrease in DesK activity. The addition of alcohol mimics a temperature increase, which can be measured isothermically by fluorescence anisotropy. The effect of alcohols on the membrane periphery is in line with the concept of the mechanism by which two hydrophilic motifs located at opposite ends of the transmembrane region of DesK, which work as a molecular caliper, sense temperature-dependent variations in membrane properties. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor

    2015-01-22

    The present application offers a solution to the current problems associated with recovery and recycling of precious metals from scrap material, discard articles, and other items comprising one or more precious metals. The solution is premised on a microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  19. Development of a stealth carrier system for structural studies of membrane proteins in solution

    DEFF Research Database (Denmark)

    Maric, Selma

    Structural studies of membrane proteins remain a great experimental challenge. Functional reconstitution into artificial carriers that mimic the native bilayer environment allows for the handling of membrane proteins in solution and enables the use of small-angle scattering techniques for fast...... and reliable structural analysis. The difficulty with this approach is that the carrier discs contribute to the measured scattering intensity in a highly non-trivial fashion, making subsequent data analysis challenging. This thesis presents the development of a specifically deuterated, stealth nanodisc system...

  20. Guanidino groups greatly enhance the action of antimicrobial peptidomimetics against bacterial cytoplasmic membranes

    DEFF Research Database (Denmark)

    Andreev, Konstantin; Bianchi, Christopher; Laursen, Jonas Striegler

    2014-01-01

    Antimicrobial peptides or their synthetic mimics are a promising class of potential new antibiotics. Herein we assess the effect of the type of cationic side chain (i.e., guanidino vs. amino groups) on the membrane perturbing mechanism of antimicrobial α-peptide-β-peptoid chimeras. Langmuir...... of the measurements using an array of techniques, including high-resolution synchrotron surface X-ray scattering, epifluorescence microscopy, and in vitro antimicrobial activity to study the molecular mechanisms of peptidomimetic interaction with bacterial membranes. We found guanidino group-containing chimeras...

  1. Pengaruh Penyuluhan dengan Metode Ceramah dan Leaflet terhadap Pengetahuan dan Sikap Ibu tentang Pola Pemberian Makanan Pendamping ASI (MP ASI) pada Anak 6-24 Bulan di Desa Pantai Gemi Kecamatan Stabat Kabupaten Langkat Tahun 2011

    OpenAIRE

    Suraya, Rani

    2011-01-01

    Complementary feeding practices are often inappropriate, for example early feeding practices, no variation, and inadequate of frequency of feeding. Therefore, the children experience undernutrition. Inappropriate complementary feeding practices are caused by low of knowledge and attitude of mothers. This study aims to determine the influence of health education with oral communication and leaflet on mother’s knowledge and attitude regarding complementary feeding practices to the children o...

  2. Gas separation membranes

    Science.gov (United States)

    Schell, William J.

    1979-01-01

    A dry, fabric supported, polymeric gas separation membrane, such as cellulose acetate, is prepared by casting a solution of the polymer onto a shrinkable fabric preferably formed of synthetic polymers such as polyester or polyamide filaments before washing, stretching or calendering (so called griege goods). The supported membrane is then subjected to gelling, annealing, and drying by solvent exchange. During the processing steps, both the fabric support and the membrane shrink a preselected, controlled amount which prevents curling, wrinkling or cracking of the membrane in flat form or when spirally wound into a gas separation element.

  3. Anion exchange membrane

    Science.gov (United States)

    Verkade, John G; Wadhwa, Kuldeep; Kong, Xueqian; Schmidt-Rohr, Klaus

    2013-05-07

    An anion exchange membrane and fuel cell incorporating the anion exchange membrane are detailed in which proazaphosphatrane and azaphosphatrane cations are covalently bonded to a sulfonated fluoropolymer support along with anionic counterions. A positive charge is dispersed in the aforementioned cations which are buried in the support to reduce the cation-anion interactions and increase the mobility of hydroxide ions, for example, across the membrane. The anion exchange membrane has the ability to operate at high temperatures and in highly alkaline environments with high conductivity and low resistance.

  4. Photoresponsive nanostructured membranes

    KAUST Repository

    Madhavan, Poornima

    2016-07-26

    The perspective of adding stimuli-response to isoporous membranes stimulates the development of separation devices with pores, which would open or close under control of environment chemical composition, temperature or exposure to light. Changes in pH and temperature have been previously investigated. In this work, we demonstrate for the first time the preparation of photoresponsive isoporous membranes, applying self-assembly non-solvent induced phase separation to a new light responsive block copolymer. First, we optimized the membrane formation by using poly(styrene-b-anthracene methyl methacrylate-b-methylmethacrylate) (PS-b-PAnMMA-b-PMMA) copolymer, identifying the most suitable solvent, copolymer block length, and other parameters. The obtained final triblock copolymer membrane morphologies were characterized using atomic force and electron microscopy. The microscopic analysis reveals that the PS-b-PAnMMA-b-PMMA copolymer can form both lamellar and ordered hexagonal nanoporous structures on the membrane top layer in appropriate solvent compositions. The nanostructured membrane emits fluorescence due to the presence of the anthracene mid-block. On irradiation of light the PS-b-PAnMMA-b-PMMA copolymer membranes has an additional stimuli response. The anthracene group undergoes conformational changes by forming [4 + 4] cycloadducts and this alters the membrane\\'s water flux and solute retention. © 2016 The Royal Society of Chemistry.

  5. Self-assembled tethered bimolecular lipid membranes.

    Science.gov (United States)

    Sinner, Eva-Kathrin; Ritz, Sandra; Naumann, Renate; Schiller, Stefan; Knoll, Wolfgang

    2009-01-01

    This chapter describes some of the strategies developed in our group for designing, constructing and structurally and functionally characterizing tethered bimolecular lipid membranes (tBLM). We introduce this platform as a novel model membrane system that complements the existing ones, for example, Langmuir monolayers, vesicular liposomal dispersions and bimolecular ("black") lipid membranes. Moreover, it offers the additional advantage of allowing for studies of the influence of membrane structure and order on the function of integral proteins, for example, on how the composition and organization of lipids in a mixed membrane influence the ion translocation activity of integral channel proteins. The first strategy that we introduce concerns the preparation of tethered monolayers by the self-assembly of telechelics. Their molecular architecture with a headgroup, a spacer unit (the "tether") and the amphiphile that mimics the lipid molecule allows them to bind specifically to the solid support thus forming the proximal layer of the final architecture. After fusion of vesicles that could contain reconstituted proteins from a liposomal dispersion in contact to this monolayer the tethered bimolecular lipid membrane is obtained. This can then be characterized by a broad range of surface analytical techniques, including surface plasmon spectroscopies, the quartz crystal microbalance, fluorescence and IR spectroscopies, and electrochemical techniques, to mention a few. It is shown that this concept allows for the construction of tethered lipid bilayers with outstanding electrical properties including resistivities in excess of 10 MOmega cm2. A modified strategy uses the assembly of peptides as spacers that couple covalently via their engineered sulfhydryl or lipoic acid groups at the N-terminus to the employed gold substrate, while their C-terminus is being activated afterward for the coupling of, for example, dimyristoylphosphatidylethanol amine (DMPE) lipid molecules

  6. Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

    International Nuclear Information System (INIS)

    Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

    2004-01-01

    Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

  7. A disease-causing mutation illuminates the protein membrane topology of the kidney-expressed prohibitin homology (PHB) domain protein podocin.

    Science.gov (United States)

    Schurek, Eva-Maria; Völker, Linus A; Tax, Judit; Lamkemeyer, Tobias; Rinschen, Markus M; Ungrue, Denise; Kratz, John E; Sirianant, Lalida; Kunzelmann, Karl; Chalfie, Martin; Schermer, Bernhard; Benzing, Thomas; Höhne, Martin

    2014-04-18

    Mutations in the NPHS2 gene are a major cause of steroid-resistant nephrotic syndrome, a severe human kidney disorder. The NPHS2 gene product podocin is a key component of the slit diaphragm cell junction at the kidney filtration barrier and part of a multiprotein-lipid supercomplex. A similar complex with the podocin ortholog MEC-2 is required for touch sensation in Caenorhabditis elegans. Although podocin and MEC-2 are membrane-associated proteins with a predicted hairpin-like structure and amino and carboxyl termini facing the cytoplasm, this membrane topology has not been convincingly confirmed. One particular mutation that causes kidney disease in humans (podocin(P118L)) has also been identified in C. elegans in genetic screens for touch insensitivity (MEC-2(P134S)). Here we show that both mutant proteins, in contrast to the wild-type variants, are N-glycosylated because of the fact that the mutant C termini project extracellularly. Podocin(P118L) and MEC-2(P134S) did not fractionate in detergent-resistant membrane domains. Moreover, mutant podocin failed to activate the ion channel TRPC6, which is part of the multiprotein-lipid supercomplex, indicative of the fact that cholesterol recruitment to the ion channels, an intrinsic function of both proteins, requires C termini facing the cytoplasmic leaflet of the plasma membrane. Taken together, this study demonstrates that the carboxyl terminus of podocin/MEC-2 has to be placed at the inner leaflet of the plasma membrane to mediate cholesterol binding and contribute to ion channel activity, a prerequisite for mechanosensation and the integrity of the kidney filtration barrier.

  8. Lipid nanotechnologies for structural studies of membrane-associated proteins.

    Science.gov (United States)

    Stoilova-McPhie, Svetla; Grushin, Kirill; Dalm, Daniela; Miller, Jaimy

    2014-11-01

    We present a methodology of lipid nanotubes (LNT) and nanodisks technologies optimized in our laboratory for structural studies of membrane-associated proteins at close to physiological conditions. The application of these lipid nanotechnologies for structure determination by cryo-electron microscopy (cryo-EM) is fundamental for understanding and modulating their function. The LNTs in our studies are single bilayer galactosylceramide based nanotubes of ∼20 nm inner diameter and a few microns in length, that self-assemble in aqueous solutions. The lipid nanodisks (NDs) are self-assembled discoid lipid bilayers of ∼10 nm diameter, which are stabilized in aqueous solutions by a belt of amphipathic helical scaffold proteins. By combining LNT and ND technologies, we can examine structurally how the membrane curvature and lipid composition modulates the function of the membrane-associated proteins. As proof of principle, we have engineered these lipid nanotechnologies to mimic the activated platelet's phosphtaidylserine rich membrane and have successfully assembled functional membrane-bound coagulation factor VIII in vitro for structure determination by cryo-EM. The macromolecular organization of the proteins bound to ND and LNT are further defined by fitting the known atomic structures within the calculated three-dimensional maps. The combination of LNT and ND technologies offers a means to control the design and assembly of a wide range of functional membrane-associated proteins and complexes for structural studies by cryo-EM. The presented results confirm the suitability of the developed methodology for studying the functional structure of membrane-associated proteins, such as the coagulation factors, at a close to physiological environment. © 2014 Wiley Periodicals, Inc.

  9. IFN-γ Induces Mimic Extracellular Trap Cell Death in Lung Epithelial Cells Through Autophagy-Regulated DNA Damage.

    Science.gov (United States)

    Lin, Chiou-Feng; Chien, Shun-Yi; Chen, Chia-Ling; Hsieh, Chia-Yuan; Tseng, Po-Chun; Wang, Yu-Chih

    2016-02-01

    Treatment of interferon-γ (IFN-γ) causes cell growth inhibition and cytotoxicity in lung epithelial malignancies. Regarding the induction of autophagy related to IFN-γ signaling, this study investigated the link between autophagy and IFN-γ cytotoxicity. In A549 human lung cancer cells, IFN-γ treatment induced concurrent apoptotic and nonapoptotic events. Unexpectedly, the nonapoptotic cells present mimic extracellular trap cell death (ETosis), which was regulated by caspase-3 and by autophagy induction through immunity-related GTPase family M protein 1 and activating transcription factor 6. Furthermore, IFN-γ signaling controlled mimic ETosis through a mechanism involving an autophagy- and Fas-associated protein with death domain-controlled caspase-8/-3 activation. Following caspase-mediated lamin degradation, IFN-γ caused DNA damage-associated ataxia telangiectasia and Rad3-related protein (ATR)/ataxia telangiectasia mutated (ATM)-regulated mimic ETosis. Upon ATR/ATM signaling, peptidyl arginine deiminase 4 (PAD4)-mediated histone 3 citrullination promoted mimic ETosis. Such IFN-γ-induced effects were defective in PC14PE6/AS2 human lung cancer cells, which were unsusceptible to IFN-γ-induced autophagy. Due to autophagy-based caspase cascade activation, IFN-γ triggers unconventional caspase-mediated DNA damage, followed by ATR/ATM-regulated PAD4-mediated histone citrullination during mimic ETosis in lung epithelial malignancy.

  10. Targeted delivery of microRNA 146b mimic to hepatocytes by lactosylated PDMAEMA nanoparticles for the treatment of NAFLD.

    Science.gov (United States)

    He, Shuying; Guo, Weihong; Deng, Feihong; Chen, Kequan; Jiang, Yonghong; Dong, Minyu; Peng, Liang; Chen, Xueqing

    2018-03-21

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and precision therapeutic will be a benefit for the NAFLD regression. In this study, we observed low microRNA 146 b (miR-146 b) expression in NAFLD mice model induced by methionine-choline-deficient diet (MCD) compared with control group. Furthermore, miR-146b -/- mice induced MCD exhibited severe liver steatosis and hepatitis. A bio-distribution study showed that novel Lactosylated PDMAEMA nanoparticles effectively targeted hepatocytes Lac-PDMAEMA. We coupled miR-146b mimic with Lac-PDMAEMA and then were administrated to NAFLD mice model, which could obviously alleviate the hepatic steatosis. Lac-PDMAEMA effectively delivered miR-146b mimic to hepatocytes with a ∼8-fold upregulation of miR-146b mimic targeting MyD88 and IRAK1, and in turn suppressed the expression of PPARγ. Meanwhile, TNF-α and IL-6 mRNA levels were decreased after administration of Lac-PDMAEMA/miR-146b mimic. So, we made a conclusion that targeted delivering miR-146b mimic to the hepatocytes by, coupling Lac-PDMAEMA nanoparticles could effectively alleviate the hepatic steatosis in NAFLD mice, which maybe bring a new and effective way to intervene and therapy the NAFLD.

  11. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

    Science.gov (United States)

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.

  12. Plasma membrane ATPases

    DEFF Research Database (Denmark)

    Palmgren, Michael Broberg; Bækgaard, Lone; Lopez Marques, Rosa Laura

    2011-01-01

    The plasma membrane separates the cellular contents from the surrounding environment. Nutrients must enter through the plasma membrane in order to reach the cell interior, and toxic metabolites and several ions leave the cell by traveling across the same barrier. Biological pumps in the plasma me...

  13. Polymide gas separation membranes

    Science.gov (United States)

    Ding, Yong; Bikson, Benjamin; Nelson, Joyce Katz

    2004-09-14

    Soluble polyamic acid salt (PAAS) precursors comprised of tertiary and quaternary amines, ammonium cations, sulfonium cations, or phosphonium cations, are prepared and fabricated into membranes that are subsequently imidized and converted into rigid-rod polyimide articles, such as membranes with desirable gas separation properties. A method of enhancing solubility of PAAS polymers in alcohols is also disclosed.

  14. Enantioseparation with liquid membranes

    NARCIS (Netherlands)

    Gössi, Angelo; Riedl, Wolfgang; Schuur, Boelo

    Chiral resolution of racemic products is a challenging and important task in the pharmaceutical, agrochemical, flavor, polymer and fragrances industries. One of the options for these challenging separations is to use liquid membranes. Although liquid membranes have been known for almost four decades

  15. Silicon nitride nanosieve membrane

    NARCIS (Netherlands)

    Tong, D.H.; Jansen, Henricus V.; Gadgil, V.J.; Bostan, C.G.; Berenschot, Johan W.; van Rijn, C.J.M.; Elwenspoek, Michael Curt

    2004-01-01

    An array of very uniform cylindrical nanopores with a pore diameter as small as 25 nm has been fabricated in an ultrathin micromachined silicon nitride membrane using focused ion beam (FIB) etching. The pore size of this nanosieve membrane was further reduced to below 10 nm by coating it with

  16. Membrane capacitive deionization

    NARCIS (Netherlands)

    Biesheuvel, P.M.; Wal, van der A.

    2010-01-01

    Membrane capacitive deionization (MCDI) is an ion-removal process based on applying an electrical potential difference across an aqueous solution which flows in between oppositely placed porous electrodes, in front of which ion-exchange membranes are positioned. Due to the applied potential, ions

  17. Photoresponsive nanostructured membranes

    KAUST Repository

    Madhavan, Poornima; Sutisna, Burhannudin; Sougrat, Rachid; Nunes, Suzana Pereira

    2016-01-01

    The perspective of adding stimuli-response to isoporous membranes stimulates the development of separation devices with pores, which would open or close under control of environment chemical composition, temperature or exposure to light. Changes in pH and temperature have been previously investigated. In this work, we demonstrate for the first time the preparation of photoresponsive isoporous membranes, applying self-assembly non-solvent induced phase separation to a new light responsive block copolymer. First, we optimized the membrane formation by using poly(styrene-b-anthracene methyl methacrylate-b-methylmethacrylate) (PS-b-PAnMMA-b-PMMA) copolymer, identifying the most suitable solvent, copolymer block length, and other parameters. The obtained final triblock copolymer membrane morphologies were characterized using atomic force and electron microscopy. The microscopic analysis reveals that the PS-b-PAnMMA-b-PMMA copolymer can form both lamellar and ordered hexagonal nanoporous structures on the membrane top layer in appropriate solvent compositions. The nanostructured membrane emits fluorescence due to the presence of the anthracene mid-block. On irradiation of light the PS-b-PAnMMA-b-PMMA copolymer membranes has an additional stimuli response. The anthracene group undergoes conformational changes by forming [4 + 4] cycloadducts and this alters the membrane's water flux and solute retention. © 2016 The Royal Society of Chemistry.

  18. Education on tick bite and Lyme borreliosis prevention, aimed at schoolchildren in the Netherlands: comparing the effects of an online educational video game versus a leaflet or no intervention.

    Science.gov (United States)

    Beaujean, D J M A; Gassner, F; Wong, A; Steenbergen, J E; Crutzen, R; Ruwaard, D

    2016-11-16

    Lyme disease or Lyme borreliosis (LB) is the most common tick-borne disease both in the United States and Europe. Children, in particular, are at high risk of contracting LB. Since child-specific educational tools on ticks, tick bites and LB are lacking, we developed an online educational video game. In this study, we compared the effectiveness of an online educational video game versus a newly developed leaflet aimed to improve prevention of tick bites and LB among Dutch schoolchildren. A total of 887 children, aged 9-13 years and attending the two final years of primary schooling, were recruited from 25 primary schools in June and July 2012. They were assigned through cluster randomization to one of three intervention groups: 'game' (22.4%), 'leaflet' (35.6%) or 'control' (41.9%). Prior to and directly following intervention, the children were asked to complete a short questionnaire. The main outcome measures were knowledge, perception (perceived susceptibility and importance) and preventive behavior in relation to tick bites and LB. Generalized linear mixed models were used to analyze the data. In the game group, the leaflet group and the control group, knowledge about ticks and tick bites improved significantly. The game was also an effective tool for improving preventive behavior; the frequency of checking for ticks increased significantly. However, there were no significant differences in knowledge improvement between the interventions. The game outperformed the leaflet in terms of improving preventive behavior, whereas the frequency of tick checks increased significantly. But this frequency didn't increase more than in the control group. The positive knowledge effects observed in the control group suggests the presence of a mere measurement effect related to completion of the questionnaire. The game did not outperform the leaflet or control group on all outcome measures. Therefore, the game may be of value as a complementary role, in addition to other media

  19. Design, construction, and characterization of high-performance membrane fusion devices with target-selectivity.

    Science.gov (United States)

    Kashiwada, Ayumi; Yamane, Iori; Tsuboi, Mana; Ando, Shun; Matsuda, Kiyomi

    2012-01-31

    Membrane fusion proteins such as the hemagglutinin glycoprotein have target recognition and fusion accelerative domains, where some synergistically working elements are essential for target-selective and highly effective native membrane fusion systems. In this work, novel membrane fusion devices bearing such domains were designed and constructed. We selected a phenylboronic acid derivative as a recognition domain for a sugar-like target and a transmembrane-peptide (Leu-Ala sequence) domain interacting with the target membrane, forming a stable hydrophobic α-helix and accelerating the fusion process. Artificial membrane fusion behavior between the synthetic devices in which pilot and target liposomes were incorporated was characterized by lipid-mixing and inner-leaflet lipid-mixing assays. Consequently, the devices bearing both the recognition and transmembrane domains brought about a remarkable increase in the initial rate for the membrane fusion compared with the devices containing the recognition domain alone. In addition, a weakly acidic pH-responsive device was also constructed by replacing three Leu residues in the transmembrane-peptide domain by Glu residues. The presence of Glu residues made the acidic pH-dependent hydrophobic α-helix formation possible as expected. The target-selective liposome-liposome fusion was accelerated in a weakly acidic pH range when the Glu-substituted device was incorporated in pilot liposomes. The use of this pH-responsive device seems to be a potential strategy for novel applications in a liposome-based delivery system. © 2011 American Chemical Society

  20. Aspartate tightens the anchoring of staphylococcal lipoproteins to the cytoplasmic membrane.

    Science.gov (United States)

    Kumari, Nimerta; Götz, Friedrich; Nguyen, Minh-Thu

    2017-12-01

    In gram-negative bacteria, the ABC transporter LolCDE complex translocates outer membrane-specific lipoproteins (Lpp) from the inner membrane to the outer membrane. Lpp possessing aspartate (Asp) at position +2 are not translocated because it functions as a LolCDE avoidance signal. In gram-positive bacteria, lacking an outer membrane and the Lol system, Lpp are only anchored at the outer leaflet of the cytoplasmic membrane. However, the release of Lpp particularly in pathogenic or commensal species is crucial for immune modulation. Here, we provide evidence that in Staphylococcus aureus Asp at position +2 plays a role in withholding Lpp to the cytoplasmic membrane. Screening of published exoproteomic data of S. aureus revealed that Lpp mainly with Gly or Ser at position +2 were found in exoproteome, but there was no Lpp with Asp+2. The occurrence of Lpp with Asp+2 is infrequent in gram-positive bacteria. In S. aureus USA300 only seven of the 67 Lpp possess Asp+2; among them five Lpp represented Lpl lipoproteins involved in host cell invasion. Our study demonstrated that replacing the Asp+2 present in Lpl8 with a Ser enhances its release into the supernatant. However, there is no different release of Asp+2 and Ser+2 in mprF mutant that lacks the positive charge of lysyl-phosphatidylglycerol (Lys-PG). Moreover, substitution of Ser+2 by Asp in SitC (MntC) did not lead to a decreased release indicating that in staphylococci positions +3 and +4 might also be important for a tighter anchoring of Lpp. Here, we show that Asp in position +2 and adjacent amino acids contribute in tightening the anchoring of Lpp by interaction of the negative charged Asp with the positive charged Lys-PG. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.