WorldWideScience

Sample records for tmrnasmpb complex mimics

  1. Bovine Serum Albumin Metal Complexes for Mimic of SOD

    Indian Academy of Sciences (India)

    Key Lab. Eco-Environment-Related Polymer Materials of Ministry of Education, Key Lab. ... scaffold and the metal complex functioned as the catalytic active center. ... small molecule.22 It is found that the antioxidative ... and absence, respectively, of the measured compound. ... monitor the interaction of metal ions with BSA.

  2. Chemical and morphological gradient scaffolds to mimic hierarchically complex tissues: From theoretical modeling to their fabrication.

    Science.gov (United States)

    Marrella, Alessandra; Aiello, Maurizio; Quarto, Rodolfo; Scaglione, Silvia

    2016-10-01

    Porous multiphase scaffolds have been proposed in different tissue engineering applications because of their potential to artificially recreate the heterogeneous structure of hierarchically complex tissues. Recently, graded scaffolds have been also realized, offering a continuum at the interface among different phases for an enhanced structural stability of the scaffold. However, their internal architecture is often obtained empirically and the architectural parameters rarely predetermined. The aim of this work is to offer a theoretical model as tool for the design and fabrication of functional and structural complex graded scaffolds with predicted morphological and chemical features, to overcome the time-consuming trial and error experimental method. This developed mathematical model uses laws of motions, Stokes equations, and viscosity laws to describe the dependence between centrifugation speed and fiber/particles sedimentation velocity over time, which finally affects the fiber packing, and thus the total porosity of the 3D scaffolds. The efficacy of the theoretical model was tested by realizing engineered graded grafts for osteochondral tissue engineering applications. The procedure, based on combined centrifugation and freeze-drying technique, was applied on both polycaprolactone (PCL) and collagen-type-I (COL) to test the versatility of the entire process. A functional gradient was combined to the morphological one by adding hydroxyapatite (HA) powders, to mimic the bone mineral phase. Results show that 3D bioactive morphologically and chemically graded grafts can be properly designed and realized in agreement with the theoretical model. Biotechnol. Bioeng. 2016;113: 2286-2297. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  3. Comparative study of copper(II)-curcumin complexes as superoxide dismutase mimics and free radical scavengers.

    Science.gov (United States)

    Barik, Atanu; Mishra, Beena; Kunwar, Amit; Kadam, Ramakant M; Shen, Liang; Dutta, Sabari; Padhye, Subhash; Satpati, Ashis K; Zhang, Hong-Yu; Indira Priyadarsini, K

    2007-04-01

    Two stoichiometrically different copper(II) complexes of curcumin (stoichiometry, 1:1 and 1:2 for copper:curcumin), were examined for their superoxide dismutase (SOD) activity, free radical-scavenging ability and antioxidant potential. Both the complexes are soluble in lipids and DMSO. The formation constants of the complexes were determined by voltammetry. EPR spectra of the complexes in DMSO at 77K showed that the 1:2 Cu(II)-curcumin complex is square planar and the 1:1 Cu(II)-curcumin complex is distorted orthorhombic. Cu(II)-curcumin complex (1:1) with larger distortion from square planar structure shows higher SOD activity. These complexes inhibit gamma-radiation induced lipid peroxidation in liposomes and react with DPPH acting as free radical scavengers. One-electron oxidation of the two complexes by radiolytically generated azide radicals in Tx-100 micellar solutions produced phenoxyl radicals, indicating that the phenolic moiety of curcumin in the complexes participates in free radical reactions. Depending on the structure, these two complexes possess different SOD activities, free radical neutralizing abilities and antioxidant potentials. In addition, quantum chemical calculations with density functional theory have been performed to support the experimental observations.

  4. Designed ankyrin repeat proteins: a new approach to mimic complex antigens for diagnostic purposes?

    Directory of Open Access Journals (Sweden)

    Stefanie Hausammann

    Full Text Available Inhibitory antibodies directed against coagulation factor VIII (FVIII can be found in patients with acquired and congenital hemophilia A. Such FVIII-inhibiting antibodies are routinely detected by the functional Bethesda Assay. However, this assay has a low sensitivity and shows a high inter-laboratory variability. Another method to detect antibodies recognizing FVIII is ELISA, but this test does not allow the distinction between inhibitory and non-inhibitory antibodies. Therefore, we aimed at replacing the intricate antigen FVIII by Designed Ankyrin Repeat Proteins (DARPins mimicking the epitopes of FVIII inhibitors. As a model we used the well-described inhibitory human monoclonal anti-FVIII antibody, Bo2C11, for the selection on DARPin libraries. Two DARPins were selected binding to the antigen-binding site of Bo2C11, which mimic thus a functional epitope on FVIII. These DARPins inhibited the binding of the antibody to its antigen and restored FVIII activity as determined in the Bethesda assay. Furthermore, the specific DARPins were able to recognize the target antibody in human plasma and could therefore be used to test for the presence of Bo2C11-like antibodies in a large set of hemophilia A patients. These data suggest, that our approach might be used to isolate epitopes from different sets of anti-FVIII antibodies in order to develop an ELISA-based screening assay allowing the distinction of inhibitory and non-inhibitory anti-FVIII antibodies according to their antibody signatures.

  5. Ammonia formation by a thiolate-bridged diiron amide complex as a nitrogenase mimic

    Science.gov (United States)

    Li, Yang; Li, Ying; Wang, Baomin; Luo, Yi; Yang, Dawei; Tong, Peng; Zhao, Jinfeng; Luo, Lun; Zhou, Yuhan; Chen, Si; Cheng, Fang; Qu, Jingping

    2013-04-01

    Although nitrogenase enzymes routinely convert molecular nitrogen into ammonia under ambient temperature and pressure, this reaction is currently carried out industrially using the Haber-Bosch process, which requires extreme temperatures and pressures to activate dinitrogen. Biological fixation occurs through dinitrogen and reduced NxHy species at multi-iron centres of compounds bearing sulfur ligands, but it is difficult to elucidate the mechanistic details and to obtain stable model intermediate complexes for further investigation. Metal-based synthetic models have been applied to reveal partial details, although most models involve a mononuclear system. Here, we report a diiron complex bridged by a bidentate thiolate ligand that can accommodate HN=NH. Following reductions and protonations, HN=NH is converted to NH3 through pivotal intermediate complexes bridged by N2H3- and NH2- species. Notably, the final ammonia release was effected with water as the proton source. Density functional theory calculations were carried out, and a pathway of biological nitrogen fixation is proposed.

  6. 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.

  7. Carbon-Based Oxamate Cobalt(III) Complexes as Bioenzyme Mimics for Contaminant Elimination in High Backgrounds of Complicated Constituents.

    Science.gov (United States)

    Li, Nan; Zheng, Yun; Jiang, Xuemei; Zhang, Ran; Pei, Kemei; Chen, Wenxing

    2017-10-12

    Complex wastewater with massive components is now a serious environmental issue facing humanity. Selective removal of low-concentration contaminants in mixed constituents holds great promise for increasing water supplies. Bioenzymes like horseradish peroxidase exhibit oxidizing power and selectivity. Here, we manufactured its mimic through immobilizing non-heme oxamate anionic cobalt(III) complex ([Co III (opba)] - , opba = o-phenylenebis(oxamate)) onto pyridine (Py) modified multiwalled carbon nanotubes ([Co III (opba)] - -Py-MWCNTs, MWCNTs = multiwalled carbon nanotubes), where MWCNTs captured substrates and Py functioned as the fifth ligand. We chose typical azo dye (C.I. Acid Red 1) and antibiotic (ciprofloxacin) as model substrates. Without •OH, this catalyst could detoxify target micropollutants efficiently at pH from 8 to 11. It also remained efficient in repetitive tests, and the final products were non-poisonous OH-containing acids. Combined with radical scavenger tests and electron paramagnetic resonance result, we speculated that high-valent cobalt-oxo active species and oxygen atom transfer reaction dominated in the reaction pathway. According to density functional theory calculations, the electron spin density distribution order showed that electron-withdrawing ligand was beneficial for inward pulling the excess electron and lowering the corresponding energy levels, achieving an electrophilic-attack enhancement of the catalyst. With target removal property and recyclability, this catalyst is prospective in water detoxication.

  8. 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.

  9. Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex

    Science.gov (United States)

    Feng, Mei; Bell, David R.; Zhou, Ruhong

    2017-12-01

    The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

  10. A functional mimic of natural peroxidases : synthesis and catalytic activity of a non-heme iron peptide hydroperoxide complex

    NARCIS (Netherlands)

    Choma, CT; Schudde, EP; Kellogg, RM; Robillard, GT; Feringa, BL

    1998-01-01

    Site-selective attachment of unprotected peptides to a non-heme iron complex is achieved by displacing two halides on the catalyst by peptide caesium thiolates, This coupling approach should be compatible with any peptide sequence provided there is only a single reduced cysteine. The oxidation

  11. Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed alpha-Helical Protein Structures

    Science.gov (United States)

    Tavenor, Nathan Albert

    Protein-based supramolecular polymers (SMPs) are a class of biomaterials which draw inspiration from and expand upon the many examples of complex protein quaternary structures observed in nature: collagen, microtubules, viral capsids, etc. Designing synthetic supramolecular protein scaffolds both increases our understanding of natural superstructures and allows for the creation of novel materials. Similar to small-molecule SMPs, protein-based SMPs form due to self-assembly driven by intermolecular interactions between monomers, and monomer structure determines the properties of the overall material. Using protein-based monomers takes advantage of the self-assembly and highly specific molecular recognition properties encodable in polypeptide sequences to rationally design SMP architectures. The central hypothesis underlying our work is that alpha-helical coiled coils, a well-studied protein quaternary folding motif, are well-suited to SMP design through the addition of synthetic linkers at solvent-exposed sites. Through small changes in the structures of the cross-links and/or peptide sequence, we have been able to control both the nanoscale organization and the macroscopic properties of the SMPs. Changes to the linker and hydrophobic core of the peptide can be used to control polymer rigidity, stability, and dimensionality. The gaps in knowledge that this thesis sought to fill on this project were 1) the relationship between the molecular structure of the cross-linked polypeptides and the macroscopic properties of the SMPs and 2) a means of creating materials exhibiting multi-dimensional net or framework topologies. Separate from the above efforts on supramolecular architectures was work on improving backbone modification strategies for an alpha-helix in the context of a complex protein tertiary fold. Earlier work in our lab had successfully incorporated unnatural building blocks into every major secondary structure (beta-sheet, alpha-helix, loops and beta

  12. Evaluation of the antiproliferative, proapoptotic, and antiangiogenic effects of a double-stranded RNA mimic complexed with polycations in an experimental mouse model of leiomyoma.

    Science.gov (United States)

    García-Pascual, Carmen Maria; Ferrero, Hortensia; Juarez, Irene; Martínez, Jessica; Villanueva, Ana; Pozuelo-Rubio, Mercedes; Soengas, Marisol; Tormo, Damiá; Simón, Carlos; Gómez, Raúl; Pellicer, Antonio

    2016-02-01

    To assess the antiproliferative, proapoptotic, and antiangiogenic effects of the double-stranded RNA mimic polyinosine-polycytidylic acid (pIC) complexed with polyethylenimine [pIC(PEI)] in xenografted human leiomyomas. Heterologous leiomyoma mouse model. University-affiliated infertility center. Ovariectomized and hormone-replaced nude mice (n = 16) who received human leiomyoma fragment transplantation. Leiomyoma fragments placed in the peritoneum of 5-week-old nude female mice and treated with the vehicle (n = 8) or 0.6 mg/kg [pIC(PEI)] (n = 8) for 4 weeks. The size of the leiomyoma implants, and cellular proliferation (Ki67), vascularization (PECAM), and apoptosis (OH-ends) assessed by quantitative immunohistochemical/immunofluorescent analysis of the recovered implants. No significant differences were observed in the size of the leiomyoma implants between groups. Vascularization and proliferation were significantly decreased, and apoptosis was increased in the [pIC(PEI)]-treated group versus control. We hypothesize that the antiangiogenic and apoptotic effects exerted by [pIC(PEI)] might lead to a decrease in lesion size in this animal model if the compound is administered for longer periods of time. This study provides promising data on [pIC(PEI)] as a potential novel therapeutic agent against human leiomyoma. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. The crystal structure of an intermediate dimer of aspergilloglutamic peptidase that mimics the enzyme-activation product complex produced upon autoproteolysis.

    Science.gov (United States)

    Sasaki, Hiroshi; Kubota, Keiko; Lee, Woo C; Ohtsuka, Jun; Kojima, Masaki; Iwata, So; Nakagawa, Atsushi; Takahashi, Kenji; Tanokura, Masaru

    2012-07-01

    Aspergilloglutamic peptidase from Aspergillus niger var. macrosporus (AGP) is one of the so-called pepstatin-insensitive acid endopeptidases, which are distinct from the well-studied aspartic peptidases. Among the known homologues of the glutamic peptidases, AGP is a unique two-chain enzyme with a light chain and a heavy chain bound non-covalently with each other, and thus is an interesting target for protein structure-function relationship studies. In this article, we report the crystal structure of a dimeric form of the enzyme at a resolution of 1.6 Å. This form has a unique structure in which the C-terminal region of the light chain of one of the molecules binds to the active site cleft of the other molecule like a part of a substrate. This form mimics the enzyme-activation product complex produced upon autoproteolysis, and provides a structural clue that could help to clarify the activation mechanism. This type of dimeric structure of a peptidase is here reported for the first time.

  14. Engineering chimeric human and mouse major histocompatibility complex (MHC) class I tetramers for the production of T-cell receptor (TCR) mimic antibodies

    Science.gov (United States)

    Bentley, Carol; Yates, Jenna; Salimi, Maryam; Greig, Jenny; Wiblin, Sarah; Hassanali, Tasneem; Banham, Alison H.

    2017-01-01

    Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide. Here we describe the production of functional chimeric human-murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial expression and refolding efficiency. These chimeric tetramers were successfully used to generate TCRm antibodies against two epitopes derived from wild type tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in vaccination studies. Immunisation with chimeric tetramers yielded no antibodies recognising the human α3 domain and β2m and generated TCRm antibodies capable of specifically recognising the target peptide/MHC-I complex in fully human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric tetramers represent novel immunogens for TCRm antibody production and may also improve the yield of tetramers for groups using these reagents to monitor CD8 T-cell immune responses in HLA-A2 transgenic mouse models of immunotherapy. PMID:28448627

  15. 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.

  16. Structure of a SUMO-binding-motif mimic bound to Smt3p–Ubc9p: conservation of a noncovalent Ubiquitin-like protein–E2 complex as a platform for selective interactions within a SUMO pathway

    Science.gov (United States)

    Duda, David M.; van Waardenburg, Robert C. A. M.; Borg, Laura A.; McGarity, Sierra; Nourse, Amanda; Waddell, M. Brett; Bjornsti, Mary-Ann; Schulman, Brenda A.

    2007-01-01

    Summary The SUMO ubiquitin-like proteins play regulatory roles in cell division, transcription, DNA repair, and protein subcellular localization. Paralleling other ubiquitin-like proteins, SUMO proteins are proteolytically processed to maturity, conjugated to targets by E1-E2-E3 cascades, and subsequently recognized by specific downstream effectors containing a SUMO-binding motif (SBM). SUMO and its E2 from the budding yeast S. cerevisiae, Smt3p and Ubc9p, are encoded by essential genes. Here we describe the 1.9 Å resolution crystal structure of a noncovalent Smt3p–Ubc9p complex. Unexpectedly, a heterologous portion of the crystallized complex derived from the expression construct mimics an SBM, and binds Smt3p in a manner resembling SBM binding to human SUMO family members. In the complex, Smt3p binds a surface distal from Ubc9's catalytic cysteine. The structure implies that a single molecule of Smt3p cannot bind concurrently to both the noncovalent binding site and the catalytic cysteine of a single Ubc9p molecule. However, formation of higher-order complexes can occur, where a single Smt3p covalently linked to one Ubc9p's catalytic cysteine also binds noncovalently to another molecule of Ubc9p. Comparison with other structures from the SUMO pathway suggests that formation of the noncovalent Smt3p–Ubc9p complex occurs mutually exclusively with many other Smt3p and Ubc9p interactions in the conjugation cascade. By contrast, high-resolution insights into how Smt3p–Ubc9p can also interact with downstream recognition machineries come from contacts with the SBM mimic. Interestingly, the overall architecture of the Smt3p–Ubc9p complex is strikingly similar to recent structures from the ubiquitin pathway. The results imply that noncovalent ubiquitin-like protein–E2 complexes are conserved platforms, which function as parts of larger assemblies involved many protein post-translational regulatory pathways. PMID:17475278

  17. Dimers of beta 2-glycoprotein I mimic the in vitro effects of beta 2-glycoprotein I-anti-beta 2-glycoprotein I antibody complexes

    NARCIS (Netherlands)

    Lutters, B. C.; Meijers, J. C.; Derksen, R. H.; Arnout, J.; de Groot, P. G.

    2001-01-01

    Anti-beta(2)-glycoprotein I antibodies are thought to cause lupus anticoagulant activity by forming bivalent complexes with beta(2)-glycoprotein I (beta(2)GPI). To test this hypothesis, chimeric fusion proteins were constructed of the dimerization domain (apple 4) of factor XI and beta(2)GPI. Both a

  18. Aqueous Molecular Dynamics Simulations of the M. tuberculosis Enoyl-ACP Reductase-NADH System and Its Complex with a Substrate Mimic or Diphenyl Ethers Inhibitors

    Directory of Open Access Journals (Sweden)

    Camilo Henrique da Silva Lima

    2015-10-01

    Full Text Available Molecular dynamics (MD simulations of 12 aqueous systems of the NADH-dependent enoyl-ACP reductase from Mycobacterium tuberculosis (InhA were carried out for up to 20–40 ns using the GROMACS 4.5 package. Simulations of the holoenzyme, holoenzyme-substrate, and 10 holoenzyme-inhibitor complexes were conducted in order to gain more insight about the secondary structure motifs of the InhA substrate-binding pocket. We monitored the lifetime of the main intermolecular interactions: hydrogen bonds and hydrophobic contacts. Our MD simulations demonstrate the importance of evaluating the conformational changes that occur close to the active site of the enzyme-cofactor complex before and after binding of the ligand and the influence of the water molecules. Moreover, the protein-inhibitor total steric (ELJ and electrostatic (EC interaction energies, related to Gly96 and Tyr158, are able to explain 80% of the biological response variance according to the best linear equation, pKi = 7.772 − 0.1885 × Gly96 + 0.0517 × Tyr158 (R2 = 0.80; n = 10, where interactions with Gly96, mainly electrostatic, increase the biological response, while those with Tyr158 decrease. These results will help to understand the structure-activity relationships and to design new and more potent anti-TB drugs.

  19. 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.

  20. 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.

  1. TERM-MIMIC

    International Nuclear Information System (INIS)

    Annunziato, A.; Picchia, F.R.; Tampone, O.

    1990-01-01

    The current technological development of H/W and the diffusion of complex S/W have allowed a great increase of computerized systems for image processing that represents an important working tool in engineering of design, simulation, communication, etc. Due to the diffusion of informatic systems and their accessibility to an enlarged field of users, man-machine interface has assumed a fundamental importance. The use of graphic systems improves such a relationship in this field, by means of the immediate perception of information by the observer and it accentuates his interpretation capability. This is one of the reasons for the existence of specialized research areas to realize working tools and to develop design methodologies of man- machine interaction. Peculiarly, such an interaction becomes more relevant when the use of computer is devoted to the management and control of plant processes. Actually a bad or incomplete interpretation of the state of a controlled system, by the operator, could have repercussions both of economical (production) and safety aspects, either for the ambient or for man. Safety and efficiency increase obtained by computerized systems of plant supervision and control is now consolidated. Thus it is necessary that the interface operator-system (computer plus plant) be realized by means of techniques that make easier and faster the information exchange and the decision of intervention. This paper is aimed at presenting the application of overexposed concepts to the management of an experimental thermohydraulic plant for testing and qualification of industrial components, typically safety valves. The plant is operating at Experimental Engineering Division, Thermal Reactor Department of ENEA

  2. 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

  3. 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.

  4. Tri- and tetra-substituted cyclen based lanthanide(III) ion complexes as ribonuclease mimics: a study into the effect of log Ka, hydration and hydrophobicity on phosphodiester hydrolysis of the RNA-model 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP).

    Science.gov (United States)

    Fanning, Ann-Marie; Plush, Sally E; Gunnlaugsson, Thorfinnur

    2015-05-28

    A series of tetra-substituted 'pseudo' dipeptide ligands of cyclen (1,4,7,10,-tetraazacyclododecane) and a tri-substituted 3'-pyridine ligand of cyclen, and the corresponding lanthanide(III) complexes were synthesised and characterised as metallo-ribonuclease mimics. All complexes were shown to promote hydrolysis of the phosphodiester bond of 2-hydroxypropyl-4-nitrophenyl phosphate (HPNP, τ1/2 = 5.87 × 10(3) h), a well known RNA mimic. The La(III) and Eu(III) tri-substituted 3'-pyridine lanthanide(III) complexes being the most efficient in promoting such hydrolysis at pH 7.4 and at 37 °C; with τ1/2 = 1.67 h for La(III) and 1.74 h for Eu(III). The series was developed to provide the opportunity to investigate the consequences of altering the lanthanide(III) ion, coordination ability and hydrophobicity of a metallo-cavity on the rate of hydrolysis using the model phosphodiester, HPNP, at 37 °C. To further provide information on the role that the log Ka of the metal bound water plays in phosphodiester hydrolysis the protonation constants and the metal ion stability constants of both a tri and tetra-substituted 3'pyridine complex were determined. Our results highlighted several key features for the design of lanthanide(III) ribonucelase mimics; the presence of two metal bound water molecules are vital for pH dependent rate constants for Eu(III) complexes, optimal pH activity approximating physiological pH (∼7.4) may be achieved if the log Ka values for both MLOH and ML(OH)2 species occur in this region, small changes to hydrophobicity within the metallo cavity influence the rate of hydrolysis greatly and an amide adjacent to the metal ion capable of forming hydrogen bonds with the substrate is required for achieving fast hydrolysis.

  5. 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.

  6. 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

  7. 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

  8. Mechanism of H2O2 dismutation catalyzed by a new catalase mimic (a non-heme dibenzotetraaza[14]annulene-Fe(III) complex): a density functional theory investigation.

    Science.gov (United States)

    Wang, Xin; Li, Shuhua; Jiang, Yuansheng

    2004-10-04

    The mechanism of H(2)O(2) dismutation catalyzed by the dibenzotetraaza[14]annulene-Fe(III) complex ([Fe(C(24)H(22)N(4)O(4))](+)) which was recently reported (Paschke, J.; Kirsch, M.; Korth, H. G.; de Groot, H.; Sustmann, R. J. Am. Chem. Soc. 2001, 123, 11099) has been investigated by density functional theory using the B3LYP hybrid functional. The quartet potential energy profile of the catalytic reaction has been explored. In the whole catalytic cycle, the rate-determining step is found to be the O-O bond homolytic cleavage, without the assistance of solvent molecules in the second coordination shell. The calculated free energy barrier for this step is 10.8 kcal/mol, which is in reasonable agreement with the experimental facts. The calculations also show that the hydroxyl and hydroperoxyl radicals may be generated in the reaction processes, but they can be efficiently quenched in strongly exothermic steps. This study provides a satisfactory explanation to the observed efficiency of the H(2)O(2) dismutation catalyzed by this complex.

  9. 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...

  10. 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…

  11. 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....

  12. 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.

  13. 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

  14. 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.

  15. Base metal complexes as homogeneous catalysts and enzyme mimics.

    Science.gov (United States)

    Hu, Xile

    2011-01-01

    This article is a short overview of some recent research activity in the Laboratory of Inorganic Synthesis and Catalysis (LSCI) at EPFL-ISIC. It summarizes the work on Ni-catalyzed cross-coupling reactions of non-activated alkyl halides. It then describes and discusses the work on the bio-mimetic chemistry of [Fe]-hydrogenase.

  16. 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....

  17. 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.

  18. 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.

  19. 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].

  20. 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)

  1. 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.

  2. Malware Mimics for Network Security Assessment

    Science.gov (United States)

    2011-03-01

    systems; file systems and file formats; interpreted environments such as scripts ( PHP , Jscript, Batch and Shell scripts) and macros; and more. They...as MySQL should be used, though it will come at the cost of added complexity. In order to keep implementation as simple as possible (with an eye

  3. 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

  4. 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

  5. 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...

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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.

  14. 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

  15. 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.

  16. 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....

  17. 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.

  18. 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.

  19. Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.

    Science.gov (United States)

    Daige, Christopher L; Wiggins, Jason F; Priddy, Leslie; Nelligan-Davis, Terri; Zhao, Jane; Brown, David

    2014-10-01

    miR34a is a tumor-suppressor miRNA that functions within the p53 pathway to regulate cell-cycle progression and apoptosis. With apparent roles in metastasis and cancer stem cell development, miR34a provides an interesting opportunity for therapeutic development. A mimic of miR34a was complexed with an amphoteric liposomal formulation and tested in two different orthotopic models of liver cancer. Systemic dosing of the formulated miR34a mimic increased the levels of miR34a in tumors by approximately 1,000-fold and caused statistically significant decreases in the mRNA levels of several miR34a targets. The administration of the formulated miR34a mimic caused significant tumor growth inhibition in both models of liver cancer, and tumor regression was observed in more than one third of the animals. The antitumor activity was observed in the absence of any immunostimulatory effects or dose-limiting toxicities. Accumulation of the formulated miR34a mimic was also noted in the spleen, lung, and kidney, suggesting the potential for therapeutic use in other cancers. ©2014 American Association for Cancer Research.

  20. Annonaceous acetogenin mimic AA005 induces cancer cell death via apoptosis inducing factor through a caspase-3-independent mechanism

    OpenAIRE

    Han, Bing; Wang, Tong-Dan; Shen, Shao-Ming; Yu, Yun; Mao, Chan; Yao, Zhu-Jun; Wang, Li-Shun

    2015-01-01

    Background Annonaceous acetogenins are a family of natural products with antitumor activities. Annonaceous acetogenin mimic AA005 reportedly inhibits mammalian mitochondrial NADH-ubiquinone reductase (Complex I) and induces gastric cancer cell death. However, the mechanisms underlying its cell-death-inducing activity are unclear. Methods We used SW620 colorectal adenocarcinoma cells to study AA005 cytotoxic activity. Cell deaths were determined by Trypan blue assay and flow cytometry, and rel...

  1. 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.

  2. 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…

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Insights from the structure of a smallpox virus topoisomerase-DNA transition state mimic

    Science.gov (United States)

    Perry, Kay; Hwang, Young; Bushman, Frederic D.; Van Duyne, Gregory D.

    2010-01-01

    Summary Poxviruses encode their own type IB topoisomerases (TopIBs) which release superhelical tension generated by replication and transcription of their genomes. To investigate the reaction catalyzed viral TopIBs, we have determined the structure of a variola virus topoisomerase-DNA complex trapped as a vanadate transition state mimic. The structure reveals how the viral TopIB enzymes are likely to position the DNA duplex for ligation following relaxation of supercoils and identifies the sources of friction observed in single molecule experiments that argue against free rotation. The structure also identifies a conformational change in the leaving group sugar that must occur prior to cleavage and reveals a mechanism for promoting ligation following relaxation of supercoils that involves a novel Asp-minor groove interaction. Overall, the new structural data support a common catalytic mechanism for the TopIB superfamily but indicate distinct methods for controlling duplex rotation in the small vs. large enzyme subfamilies. PMID:20152159

  11. Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site.

    Science.gov (United States)

    Wang, Xiangxi; Zhu, Ling; Dang, Minghao; Hu, Zhongyu; Gao, Qiang; Yuan, Shuai; Sun, Yao; Zhang, Bo; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Wang, Junzhi; Fry, Elizabeth E; Stuart, David I; Rao, Zihe

    2017-01-24

    Hepatitis A virus (HAV) infects ∼1.4 million people annually and, although there is a vaccine, there are no licensed therapeutic drugs. HAV is unusually stable (making disinfection problematic) and little is known of how it enters cells and releases its RNA. Here we report a potent HAV-specific monoclonal antibody, R10, which neutralizes HAV infection by blocking attachment to the host cell. High-resolution cryo-EM structures of HAV full and empty particles and of the complex of HAV with R10 Fab reveal the atomic details of antibody binding and point to a receptor recognition site at the pentamer interface. These results, together with our observation that the R10 Fab destabilizes the capsid, suggest the use of a receptor mimic mechanism to neutralize virus infection, providing new opportunities for therapeutic intervention.

  12. 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.

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. Dynamic Changes in Host Gene Expression following In Vitro Viral Mimic Stimulation in Crocodile Cells

    Directory of Open Access Journals (Sweden)

    Subir Sarker

    2017-11-01

    Full Text Available The initial control of viral infection in a host is dominated by a very well orchestrated early innate immune system; however, very little is known about the ability of a host to control viral infection outside of mammals. The reptiles offer an evolutionary bridge between the fish and mammals, with the crocodile having evolved from the archosauria clade that included the dinosaurs, and being the largest living reptile species. Using an RNA-seq approach, we have defined the dynamic changes of a passaged primary crocodile cell line to stimulation with both RNA and DNA viral mimics. Cells displayed a marked upregulation of many genes known to be involved in the mammalian response to viral infection, including viperin, Mx1, IRF7, IRF1, and RIG-I with approximately 10% of the genes being uncharacterized transcripts. Both pathway and genome analysis suggested that the crocodile may utilize the main known mammalian TLR and cytosolic antiviral RNA signaling pathways, with the pathways being responsible for sensing DNA viruses less clear. Viral mimic stimulation upregulated the type I interferon, IFN-Omega, with many known antiviral interferon-stimulated genes also being upregulated. This work demonstrates for the first time that reptiles show functional regulation of many known and unknown antiviral pathways and effector genes. An enhanced knowledge of these ancient antiviral pathways will not only add to our understanding of the host antiviral innate response in non-mammalian species, but is critical to fully comprehend the complexity of the mammalian innate immune response to viral infection.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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)

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer

    Science.gov (United States)

    Carethers, John M; Stoffel, Elena M

    2015-01-01

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management. PMID:26309352

  10. Lynch syndrome and Lynch syndrome mimics: The growing complex landscape of hereditary colon cancer.

    Science.gov (United States)

    Carethers, John M; Stoffel, Elena M

    2015-08-21

    Hereditary non-polyposis colorectal cancer (HNPCC) was previously synonymous with Lynch syndrome; however, identification of the role of germline mutations in the DNA mismatch repair (MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer (CRC). Broadly, HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability (MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome (germline MMR mutation), Lynch-like syndrome (biallelic somatic MMR mutations), constitutional MMR deficiency syndrome (biallelic germline MMR mutations), and sporadic MSI CRC (somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions, others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.

  11. 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.

  12. A non-covalent peptide-based carrier for in vivo delivery of DNA mimics.

    Science.gov (United States)

    Morris, May C; Gros, Edwige; Aldrian-Herrada, Gudrun; Choob, Michael; Archdeacon, John; Heitz, Frederic; Divita, Gilles

    2007-01-01

    The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide-based delivery technologies hold a true promise for therapeutic applications of DNA mimics.

  13. 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

  14. 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…

  15. 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…

  16. 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 .

  17. 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)

  18. 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…

  19. 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

  20. 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.)

  1. 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

  2. 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

  3. 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

  4. 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.

  5. Bilateral Tubo Ovarian Abscess Mimics Ovarian Cancer on MRI and {sup 18F} FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Rakheja, Rajan; Hickeson, Marc [Royal Victoria Hospital, McGill Univ. Health Centre, Montreal (Canada); Makis, William [Brandon Regional Health Centre, Brandon (Canada)

    2011-09-15

    A 20 year old woman, who presented with a several week history of abdominal pain, was referred for magnetic resonance imaging (MRI) and {sup 18F} fluorodeoxy glucose (FDG) positron emission tomography (PET)/computed tomography (CT) after an ultrasound showed complex cystic masses arising from both ovaries. The MRI and {sup 18F} FDG PET/CT imaging characteristics of the ovarian masses were strongly suspicious for malignancy, and the masses were surgically removed. Histopathological evaluation revealed a bilateral tuboovarian abscess, with no evidence of malignancy. This case highlights a potentially serious pitfall in the evaluation of suspicious pelvic masses by {sup 18F} FDG PET/CT, Whereby a complex bilateral tuboovarian abscess may mimic the PET/CT imaging characteristics of an ovarian or pelvic malignancy.

  6. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland.

    Science.gov (United States)

    Johnson, Michael D; Kenney, Nicholas; Stoica, Adriana; Hilakivi-Clarke, Leena; Singh, Baljit; Chepko, Gloria; Clarke, Robert; Sholler, Peter F; Lirio, Apolonio A; Foss, Colby; Reiter, Ronald; Trock, Bruce; Paik, Soonmyoung; Martin, Mary Beth

    2003-08-01

    It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor. The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.

  7. 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)....

  8. Algorithm that mimics human perceptual grouping of dot patterns

    NARCIS (Netherlands)

    Papari, G.; Petkov, N.; Gregorio, MD; DiMaio,; Frucci, M; Musio, C

    2005-01-01

    We propose an algorithm that groups points similarly to how human observers do. It is simple, totally unsupervised and able to find clusters of complex and not necessarily convex shape. Groups are identified as the connected components of a Reduced Delaunay Graph (RDG) that we define in this paper.

  9. Design, synthesis, and characterization of a 39 amino acid peptide mimic of the main immunogenic region of the Torpedo acetylcholine receptor.

    Science.gov (United States)

    Trinh, Vu B; Foster, Alex J; Fairclough, Robert H

    2014-05-01

    We have designed a 39 amino acid peptide mimic of the conformation-dependent main immunogenic region (MIR) of the Torpedo acetylcholine receptor (TAChR) that joins three discontinuous segments of the Torpedo α-subunit, α(1-12), α(65-79), and α(110 - 115) with two GS linkers: This 39MIR-mimic was expressed in E. coli as a fusion protein with an intein-chitin-binding domain (IChBD) to permit affinity collection on chitin beads. Six MIR-directed monoclonal antibodies (mAbs) bind to this complex and five agonist/antagonist site directed mAbs do not. The complex of MIR-directed mAb-132A with 39MIR has a Kd of (2.11±0.11)×10(-10)M, which is smaller than (7.13±1.20)×10(-10)M for the complex of mAb-132A with α(1-161) and about the same as 3.4×10(-10)M for that of mAb-132A with TAChR. Additionally, the 39MIR-IChBD adsorbs all MIR-directed antibodies (Abs) from an experimental autoimmune myasthenia gravis (EAMG) rat serum. Hence, the 39MIR-mimic has the potential to inactivate or remove pathogenic Torpedo MIR-directed Abs from EAMG sera and to direct a magic bullet to the memory B-cells that produce those pathogenic Abs. The hope is to use this as a guide to produce a mimic of the human MIR on the way to an antigen specific therapeutic agent to treat MG. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. 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.

  11. Microfluidics to Mimic Blood Flow in Health and Disease

    Science.gov (United States)

    Sebastian, Bernhard; Dittrich, Petra S.

    2018-01-01

    Throughout history, capillary systems have aided the establishment of the fundamental laws of blood flow and its non-Newtonian properties. The advent of microfluidics technology in the 1990s propelled the development of highly integrated lab-on-a-chip platforms that allow highly accurate replication of vascular systems' dimensions, mechanical properties, and biological complexity. Applications include the detection of pathological changes to red blood cells, white blood cells, and platelets at unparalleled sensitivity and the efficacy assessment of drug treatment. Recent efforts have aimed at the development of microfluidics-based tests usable in a clinial environment or the replication of more complex diseases such as thrombosis. These microfluidic disease models enable the study of onset and progression of disease as well as the identification of key players and risk factors, which have led to a spectrum of clinically relevant findings.

  12. 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...

  13. [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.

  14. 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.

  15. 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.

  16. 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).

  17. 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.

  18. Disabling Cas9 by an anti-CRISPR DNA mimic.

    Science.gov (United States)

    Shin, Jiyung; Jiang, Fuguo; Liu, Jun-Jie; Bray, Nicolas L; Rauch, Benjamin J; Baik, Seung Hyun; Nogales, Eva; Bondy-Denomy, Joseph; Corn, Jacob E; Doudna, Jennifer A

    2017-07-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 gene editing technology is derived from a microbial adaptive immune system, where bacteriophages are often the intended target. Natural inhibitors of CRISPR-Cas9 enable phages to evade immunity and show promise in controlling Cas9-mediated gene editing in human cells. However, the mechanism of CRISPR-Cas9 inhibition is not known, and the potential applications for Cas9 inhibitor proteins in mammalian cells have not been fully established. We show that the anti-CRISPR protein AcrIIA4 binds only to assembled Cas9-single-guide RNA (sgRNA) complexes and not to Cas9 protein alone. A 3.9 Å resolution cryo-electron microscopy structure of the Cas9-sgRNA-AcrIIA4 complex revealed that the surface of AcrIIA4 is highly acidic and binds with a 1:1 stoichiometry to a region of Cas9 that normally engages the DNA protospacer adjacent motif. Consistent with this binding mode, order-of-addition experiments showed that AcrIIA4 interferes with DNA recognition but has no effect on preformed Cas9-sgRNA-DNA complexes. Timed delivery of AcrIIA4 into human cells as either protein or expression plasmid allows on-target Cas9-mediated gene editing while reducing off-target edits. These results provide a mechanistic understanding of AcrIIA4 function and demonstrate that inhibitors can modulate the extent and outcomes of Cas9-mediated gene editing.

  19. Secret handshakes: cell-cell interactions and cellular mimics.

    Science.gov (United States)

    Cohen, Daniel J; Nelson, W James

    2018-02-01

    Cell-cell junctions, acting as 'secret handshakes', mediate cell-cell interactions and make multicellularity possible. Work over the previous century illuminated key players comprising these junctions including the cadherin superfamily, nectins, CAMs, connexins, notch/delta, lectins, and eph/Ephrins. Recent work has focused on elucidating how interactions between these complex and often contradictory cues can ultimately give rise to large-scale organization in tissues. This effort, in turn, has enabled bioengineering advances such as cell-mimetic interfaces that allow us to better probe junction biology and to develop new biomaterials. This review details exciting, recent developments in these areas as well as providing both historical context and a discussion of some topical challenges and opportunities for the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation

    Science.gov (United States)

    Natalio, Filipe; André, Rute; Hartog, Aloysius F.; Stoll, Brigitte; Jochum, Klaus Peter; Wever, Ron; Tremel, Wolfgang

    2012-08-01

    Marine biofouling--the colonization of small marine microorganisms on surfaces that are directly exposed to seawater, such as ships' hulls--is an expensive problem that is currently without an environmentally compatible solution. Biofouling leads to increased hydrodynamic drag, which, in turn, causes increased fuel consumption and greenhouse gas emissions. Tributyltin-free antifouling coatings and paints based on metal complexes or biocides have been shown to efficiently prevent marine biofouling. However, these materials can damage the environment through metal leaching (for example, of copper and zinc) and bacteria resistance. Here, we show that vanadium pentoxide nanowires act like naturally occurring vanadium haloperoxidases to prevent marine biofouling. In the presence of bromide ions and hydrogen peroxide, the nanowires catalyse the oxidation of bromide ions to hypobromous acid (HOBr). Singlet molecular oxygen (1O2) is formed and this exerts strong antibacterial activity, which prevents marine biofouling without being toxic to marine biota. Vanadium pentoxide nanowires have the potential to be an alternative approach to conventional anti-biofouling agents.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Mn porphyrin-based SOD mimic, MnTnHex-2-PyP(5+), and non-SOD mimic, MnTBAP(3-), suppressed rat spinal cord ischemia/reperfusion injury via NF-κB pathways.

    Science.gov (United States)

    Celic, T; Španjol, J; Bobinac, M; Tovmasyan, A; Vukelic, I; Reboucas, J S; Batinic-Haberle, I; Bobinac, D

    2014-12-01

    Herein we have demonstrated that both superoxide dismutase (SOD) mimic, cationic Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP(3-)), protect against oxidative stress caused by spinal cord ischemia/reperfusion via suppression of nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N-alkylpyridylporphyrins were able to prevent the DNA binding of NF-κB in an aqueous system, whereas MnTBAP(3-) was not. Here, for the first time, in a complex in vivo system-animal model of spinal cord injury-a similar impact of MnTBAP(3-), at a dose identical to that of MnTnHex-2-PyP(5+), was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The downregulation of NF-κB, a major pro-inflammatory signaling protein regulating astrocyte activation, was detected and found to correlate well with the suppression of astrogliosis (as glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP(3-) with reactive nitrogen species (RNS) (.NO/HNO/ONOO(-)) suggests that RNS/MnTBAP(3-)-driven modification of NF-κB protein cysteines may be involved in its therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP(5+) which presumably occurs via reactive

  6. 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.

  7. 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.

  8. 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...

  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

    2016-01-01

    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

  10. 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.

  11. 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.

  12. 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...

  13. 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

  14. Potent Inhibitors of the Hepatitis C Virus NS3 Protease: Design and Synthesis of Macrocyclic Substrate-Based [beta]-Strand Mimics

    Energy Technology Data Exchange (ETDEWEB)

    Goudreau, Nathalie; Brochu, Christian; Cameron, Dale R.; Duceppe, Jean-Simon; Faucher, Anne-Marie; Ferland, Jean-Marie; Grand-Maître, Chantal; Poirier, Martin; Simoneau, Bruno; Tsantrizos, Youla S. (Boehringer)

    2008-06-30

    The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring {beta}-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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.

  6. 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…

  7. 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.

  8. 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

  9. 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

  10. 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...

  11. 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

  12. 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

  13. 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....

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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...

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site.

    Science.gov (United States)

    Dungan, Victoria J; Ortin, Yannick; Mueller-Bunz, Helge; Rutledge, Peter J

    2010-04-07

    Non-heme iron(II) oxidases (NHIOs) catalyse a diverse array of oxidative chemistry in Nature. As part of ongoing efforts to realize biomimetic, iron-mediated C-H activation, we report the synthesis of a new 'three-amine-one-carboxylate' ligand designed to complex with iron(II) and mimic the NHIO active site. The tetradentate ligand has been prepared as a single enantiomer in nine synthetic steps from N-Cbz-L-alanine, pyridine-2,6-dimethanol and diphenylamine, using Seebach oxazolidinone chemistry to control the stereochemistry. X-Ray crystal structures are reported for two important intermediates, along with variable temperature NMR experiments to probe the hindered interconversion of conformational isomers of several key intermediates, 2,6-disubstituted pyridine derivatives. The target ligand and an N-Cbz-protected precursor were each then complexed with iron(II) and tested for their ability to promote alkene dihydroxylation, using hydrogen peroxide as the oxidant.

  1. bond activation and catalysis by Ru -pac complexes

    Indian Academy of Sciences (India)

    and their reactivity towards oxidation of a few organic compounds. Keywords. Kinetics; catalysis; -O–O- bond activation; Ru-pac complex; oxidation. 1. Introduction. Ru-pac complexes exhibit catalytic properties,1 in homogeneous conditions in the presence of oxygen atom donors, that mimic the biological enzymatic oxi-.

  2. Inhibition of Poly(A)-binding protein with a synthetic RNA mimic reduces pain sensitization in mice.

    Science.gov (United States)

    Barragán-Iglesias, Paulino; Lou, Tzu-Fang; Bhat, Vandita D; Megat, Salim; Burton, Michael D; Price, Theodore J; Campbell, Zachary T

    2018-01-02

    Nociceptors rely on cap-dependent translation to rapidly induce protein synthesis in response to pro-inflammatory signals. Comparatively little is known regarding the role of the regulatory factors bound to the 3' end of mRNA in nociceptor sensitization. Poly(A)-binding protein (PABP) stimulates translation initiation by bridging the Poly(A) tail to the eukaryotic initiation factor 4F complex associated with the mRNA cap. Here, we use unbiased assessment of PABP binding specificity to generate a chemically modified RNA-based competitive inhibitor of PABP. The resulting RNA mimic, which we designated as the Poly(A) SPOT-ON, is more stable than unmodified RNA and binds PABP with high affinity and selectivity in vitro. We show that injection of the Poly(A) SPOT-ON at the site of an injury can attenuate behavioral response to pain. Collectively, these results suggest that PABP is integral for nociceptive plasticity. The general strategy described here provides a broad new source of mechanism-based inhibitors for RNA-binding proteins and is applicable for in vivo studies.

  3. Design and verification of a simple 3D dynamic model of speed skating which mimics observed forces and motions.

    Science.gov (United States)

    van der Kruk, E; Veeger, H E J; van der Helm, F C T; Schwab, A L

    2017-11-07

    Advice about the optimal coordination pattern for an individual speed skater, could be addressed by simulation and optimization of a biomechanical speed skating model. But before getting to this optimization approach one needs a model that can reasonably match observed behaviour. Therefore, the objective of this study is to present a verified three dimensional inverse skater model with minimal complexity, which models the speed skating motion on the straights. The model simulates the upper body transverse translation of the skater together with the forces exerted by the skates on the ice. The input of the model is the changing distance between the upper body and the skate, referred to as the leg extension (Euclidean distance in 3D space). Verification shows that the model mimics the observed forces and motions well. The model is most accurate for the position and velocity estimation (respectively 1.2% and 2.9% maximum residuals) and least accurate for the force estimations (underestimation of 4.5-10%). The model can be used to further investigate variables in the skating motion. For this, the input of the model, the leg extension, can be optimized to obtain a maximal forward velocity of the upper body. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  4. Astrocyte-neuron co-culture on microchips based on the model of SOD mutation to mimic ALS.

    Science.gov (United States)

    Kunze, Anja; Lengacher, Sylvain; Dirren, Elisabeth; Aebischer, Patrick; Magistretti, Pierre J; Renaud, Philippe

    2013-07-24

    Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. ALS is believed to be a non-cell autonomous condition, as other cell types, including astrocytes, have been implicated in disease pathogenesis. Hence, to facilitate the development of therapeutics against ALS, it is crucial to better understand the interactions between astrocytes and neural cells. Furthermore, cell culture assays are needed that mimic the complexity of cell to cell communication at the same time as they provide control over the different microenvironmental parameters. Here, we aim to validate a previously developed microfluidic system for an astrocyte-neuron cell culture platform, in which astrocytes have been genetically modified to overexpress either a human wild-type (WT) or a mutated form of the super oxide dismutase enzyme 1 (SOD1). Cortical neural cells were co-cultured with infected astrocytes and studied for up to two weeks. Using our microfluidic device that prevents direct cell to cell contact, we could evaluate neural cell response in the vicinity of astrocytes. We showed that neuronal cell density was reduced by about 45% when neurons were co-cultured with SOD-mutant astrocytes. Moreover, we demonstrated that SOD-WT overexpressing astrocytes reduced oxidative stress on cortical neurons that were in close metabolic contact. In contrast, cortical neurons in metabolic contact with SOD-mutant astrocytes lost their synapsin protein expression after severe glutamate treatment, an indication of the toxicity potentiating effect of the SOD-mutant enzyme.

  5. 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.

  6. Primary biliary cirrhosis is characterized by IgG3 antibodies cross-reactive with the major mitochondrial autoepitope and its Lactobacillus mimic.

    Science.gov (United States)

    Bogdanos, Dimitrios-Petrou; Baum, Harold; Okamoto, Manabu; Montalto, Paolo; Sharma, Umesh C; Rigopoulou, Eirini I; Vlachogiannakos, John; Ma, Yun; Burroughs, Andrew K; Vergani, Diego

    2005-08-01

    The serological hallmark of primary biliary cirrhosis (PBC) is the presence of pyruvate dehydrogenase complex E2 subunit (PDC-E2) antimitochondrial antibodies (AMAs). Anti-PDC-E2 antibodies cross-react specifically with mycobacterial hsp65, and we have demonstrated that the motif SxGDL[ILV]AE shared by PDC-E2(212-226) and hsp's is a cross-reactive target. Having found that this same motif is present only in beta-galactosidase of Lactobacillus delbrueckii (BGAL LACDE), we hypothesized that this homology would also lead to cross-reactivity. The mimics were tested via ELISA for reactivity and competitive cross-reactivity using sera from 100 AMA-positive and 23 AMA-negative PBC patients and 190 controls. An Escherichia coli (ECOLI) PDC-E2 mimic that has been pathogenetically linked to PBC but lacks this motif has been also tested. Anti-BGAL(266-280) LACDE antibodies were restricted to AMA-positive patients (54 of 95, 57%) and belonged to immunoglobulin (Ig) G3. Of the 190 controls, 22 (12%; P ECOLI PDC-E2 reactivity was virtually absent. BGAL(266-280)/PDC-E2(212-226) reactivity of the IgG3 isotype was found in 52 (52%) AMA-positive PBC patients but in only 1 of the controls (P ECOLI PDC-E2 mimics. In conclusion, IgG3 antibodies to BGAL LACDE cross-react with the major mitochondrial autoepitope and are characteristic of PBC.

  7. Annonaceous acetogenin mimic AA005 induces cancer cell death via apoptosis inducing factor through a caspase-3-independent mechanism.

    Science.gov (United States)

    Han, Bing; Wang, Tong-Dan; Shen, Shao-Ming; Yu, Yun; Mao, Chan; Yao, Zhu-Jun; Wang, Li-Shun

    2015-03-18

    Annonaceous acetogenins are a family of natural products with antitumor activities. Annonaceous acetogenin mimic AA005 reportedly inhibits mammalian mitochondrial NADH-ubiquinone reductase (Complex I) and induces gastric cancer cell death. However, the mechanisms underlying its cell-death-inducing activity are unclear. We used SW620 colorectal adenocarcinoma cells to study AA005 cytotoxic activity. Cell deaths were determined by Trypan blue assay and flow cytometry, and related proteins were characterized by western blot. Immunofluorescence and subcellular fractionation were used to evaluate AIF nuclear translocation. Reactive oxygen species were assessed by using redox-sensitive dye DCFDA. AA005 induces a unique type of cell death in colorectal adenocarcinoma cells, characterized by lack of caspase-3 activation or apoptotic body formation, sensitivity to poly (ADP-ribose) polymerase inhibitor Olaparib (AZD2281) but not pan-caspase inhibitor Z-VAD.fmk, and dependence on apoptosis-inducing factor (AIF). AA005 treatment also reduced expression of mitochondrial Complex I components, and leads to accumulation of intracellular reactive oxygen species (ROS) at the early stage. Blocking ROS formation significantly suppresses AA005-induced cell death in SW620 cells. Moreover, blocking activation of RIP-1 by necroptosis inhibitor necrotatin-1 inhibits AIF translocation and partially suppresses AA005-induced cell death in SW620 cells demonstrating that RIP-1 protein may be essential for cell death. AA005 may trigger the cell death via mediated by AIF through caspase-3 independent pathway. Our work provided new mechanisms for AA005-induced cancer cell death and novel clues for cancer treatment via AIF dependent cell death.

  8. 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...

  9. 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)

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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 ...

  16. 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...

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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)

  7. 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

  8. Mathematical Properties of Complex Networks

    Directory of Open Access Journals (Sweden)

    Angel Garrido

    2011-01-01

    Full Text Available Many researchers are attempting to create systems which
    mimic human thought, or understand speech, or beat to the best human chess-player [14]. Understanding intelligence and Creating intelligent artifacts both are the twin goals of Artificial Intelligence (AI.In more recent times, the interest is focused on problems related with Complex Networks [3, 5,6, 19], in particular on questions such as clustering search and identification. We attempt, in this paper, a panoramic vision of such mathematical methods in AI.

  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. Neglected ruptured flexor carpi ulnaris tendon mimics a soft tissue tumor in the wrist.

    Science.gov (United States)

    Rau, Chi-Lun; Yen, Tze-Hsun; Wu, Lien-Chen; Huang, Yi-You; Jaw, Fu-Shan; Liou, Tsan-Hon

    2014-04-01

    A wrist mass is rarely caused by a ruptured tendon in the forearm. The common pathologies are ganglia, tendon tenosynovitis, and giant cell tumors of tendon sheaths. Less common causes are nerve sheath tumors, vascular lesions, or an accessory muscle belly. The authors investigated a case of neglected ruptured flexor carpi ulnaris tendon that mimics a mass in the wrist. To the authors' knowledge, this is the first case report in relevant literature. During investigation, the high-resolution musculoskeletal ultrasound suggested a soft tissue tumor or a ruptured flexor carpi ulnaris tendon. The magnetic resonance imaging scan indicated an accessory flexor carpi ulnaris muscle belly. The diagnosis of ruptured flexor carpi ulnaris tendon was confirmed by surgical exploration. This case indicates that ultrasound may be better suited than magnetic resonance imaging in evaluating a wrist mass for its accuracy, availability, and portability.

  13. Cooperative interplay of let-7 mimic and HuR with MYC RNA.

    Science.gov (United States)

    Gunzburg, Menachem J; Sivakumaran, Andrew; Pendini, Nicole R; Yoon, Je-Hyun; Gorospe, Myriam; Wilce, Matthew C J; 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 single-stranded (ss)DNA complementary to the let-7 binding site, enhanced the affinity of HuR for a 122-nt MYC RNA encompassing both binding sites. This finding supports the biophysical principle of cooperative binding by an RBP and miRNA purely through interactions at distal mRNA binding sites.

  14. Preparation of Artificial Skin that Mimics Human Skin Surface and Mechanical Properties.

    Science.gov (United States)

    Shimizu, Rana; Nonomura, Yoshimune

    2018-01-01

    We have developed an artificial skin that mimics the morphological and mechanical properties of human skin. The artificial skin comprises a polyurethane block possessing a microscopically rough surface. We evaluated the tactile sensations when skin-care cream was applied to the artificial skin. Many subjects perceived smooth, moist, and soft feels during the application process. Cluster analysis showed that these characteristic tactile feels are similar to those when skin-care cream is applied to real human skin. Contact angle analysis showed that an oil droplet spread smoothly on the artificial skin surface, which occurred because there were many grooves several hundred micrometers in width on the skin surface. In addition, when the skin-care cream was applied, the change in frictional force during the dynamic friction process increased. These wetting and frictional properties are important factors controlling the similarity of artificial skin to real human skin.

  15. Enhanced photocatalytic hydrogen production from an MCM-41-immobilized photosensitizer-[Fe-Fe] hydrogenase mimic dyad.

    Science.gov (United States)

    Wang, Wen; Yu, Tianjun; Zeng, Yi; Chen, Jinping; Yang, Guoqiang; Li, Yi

    2014-11-01

    A covalently linked photosensitizer-catalytic center dyad Ps-Hy, consisting of two bis(2-phenylpyridine)(2,2'-bipyridine)iridium(iii) chromophores (Ps) and a diiron hydrogenase mimic (Hy) was constructed by using click reaction. Ps-Hy was incorporated into K(+)-exchanged molecular sieve MCM-41 to form a composite (Ps-Hy@MCM-41), which has been successfully applied to the photochemical production of hydrogen. The catalytic activity of Ps-Hy@MCM-41 is ∼3-fold higher as compared with that of Ps-Hy in the absence of MCM-41. The incorporation of Ps-Hy into MCM-41 stabilizes the catalyst, and consequently, advances the photocatalysis. The present study provides a potential strategy for improving catalytic efficiency of artificial photosynthesis systems using mesoporous molecular sieves.

  16. Systemic lupus erythematosis with antiphospholipid antibody syndrome: A mimic of Buerger′s disease

    Directory of Open Access Journals (Sweden)

    Vasugi Zoya

    2006-01-01

    Full Text Available This case report is about a past smoker who presented with history of recurrent ulcers and digital gangrene with claudication pain of the left foot for the past fifteen years. Clinical examination and angiogram showed disease involving the peripheral vessels of lowervlimb. This patient had been labeled as Buerger′s disease 15 years ago based on clinical and demographic profile of the illness. We felt that the progression of the disease despite the patient having stopped smoking 15 years ago along with the presence of elevated inflammatory markers in the blood with proteinuria was not in keeping with the nature of the disease. Furthur evaluation revealed that the patient had systemic lupus erythematosus with antiphospholipid antibody syndrome. This case highlights the need for a careful search for diseases, which can mimic Buerger′s disease in young smokers who present with peripheral vascular disease and who have an atypical clinical presentation or progression.

  17. Polyproline as a Minimal Antifreeze Protein Mimic That Enhances the Cryopreservation of Cell Monolayers.

    Science.gov (United States)

    Graham, Ben; Bailey, Trisha L; Healey, Joseph R J; Marcellini, Moreno; Deville, Sylvain; Gibson, Matthew I

    2017-12-11

    Tissue engineering, gene therapy, drug screening, and emerging regenerative medicine therapies are fundamentally reliant on high-quality adherent cell culture, but current methods to cryopreserve cells in this format can give low cell yields and require large volumes of solvent "antifreezes". Herein, we report polyproline as a minimum (bio)synthetic mimic of antifreeze proteins that is accessible by solution, solid-phase, and recombinant methods. We demonstrate that polyproline has ice recrystallisation inhibition activity linked to its amphipathic helix and that it enhances the DMSO cryopreservation of adherent cell lines. Polyproline may be a versatile additive in the emerging field of macromolecular cryoprotectants. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Hepatitis C virus infection can mimic type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis.

    Science.gov (United States)

    Pawlotsky, J M; Deforges, L; Bretagne, S; André, C; Métreau, J M; Thiers, V; Zafrani, E S; Goossens, M; Duval, J; Mavier, J P

    1993-01-01

    Hepatitis C virus (HCV) has been shown to induce anti-liver-kidney microsomal-1 (LKM1) antibody positive chronic active hepatitis, simulating type 2 autoimmune chronic active hepatitis. The cases of five patients presenting with features of type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis and extrahepatic autoimmune manifestations, in whom immunosuppressive treatment had no effect on liver disease are presented. In these patients, HCV infection could be shown by the presence in serum of anti-HCV antibodies and HCV-RNA detected by polymerase chain reaction. These cases suggest the following: (a) chronic HCV infection can mimic type 1, as well as type 2, autoimmune chronic active hepatitis; (b) HCV infection might be systematically sought in patients presenting with features of type 1 autoimmune chronic active hepatitis, with special care in patients who are unresponsive to immunosuppressive treatment. Images Figure PMID:7686122

  19. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

    Science.gov (United States)

    Pearson, Brandon L.; Simon, Jeremy M.; McCoy, Eric S.; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J.

    2016-01-01

    Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson's disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer's disease and Huntington's disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders. PMID:27029645

  20. Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions.

    Science.gov (United States)

    Arista-Nasr, J; Trolle-Silva, A; Aguilar-Ayala, E; Martínez-Benítez, B

    2016-01-01

    In most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. We consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. Thirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. The seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. The transport of DDT from chylomicrons to adipocytes does not mimic triacylglycerol transport

    Science.gov (United States)

    Kohan, Alison B.; Vandersall, Abbey E.; Yang, Qing; Xu, Min; Jandacek, Ronald J.; Tso, Patrick

    2012-01-01

    Despite being banned in the U.S., organochlorine toxins such as DDT are frequently detected in human adipose tissue. The main route of exposure is through the consumption of contaminated foods and subsequent intestinal packaging of DDT into chylomicrons. These chylomicrons, which also contain dietary triacylglycerol (TG), are delivered directly to peripheral tissues without first being metabolized by the liver. The physiological process by which these compounds are delivered from chylomicrons to adipose is not well understood, but is clinically relevant since it bypasses first-pass metabolism. Based on its highly lipophilic nature, it has been assumed that DDT is transferred to peripheral tissues similar to TG; however, this has not been measured. Here, we use the lymph fistula rat to isolate chylomicrons containing both DDT and TG. These chylomicrons are the in vivo DDT delivery vehicle. Using 3T3-L1 adipocytes, we investigated the rate at which DDT transfers from chylomicrons to adipocytes, and mediators of this process. This novel approach closely approximates the in vivo DDT exposure route. We show that: 1) DDT repartitions from chylomicrons to adipocytes, 2) this transport does not require hydrolysis of TG within the chylomicron, and is stimulated by the inhibition of LPL, 3) albumin does not inhibit DDT uptake, 4) DDT dissolved in DMSO does not appropriately mimic in vivo DDT transport; and most importantly, 5) DDT uptake from chylomicrons does not mimic the uptake of TG from the same particles. Understanding these factors is important for designing interventions for human populations exposed to DDT. PMID:22885168

  2. A Taylor-Made Design of Phenoxyfuranone-Type Strigolactone Mimic

    Directory of Open Access Journals (Sweden)

    Kosuke Fukui

    2017-06-01

    Full Text Available Strigolactones are a class of plant hormones that inhibit axillary bud outgrowth and are released from plant roots to act as a rhizosphere communication signal. The Orobanchaceae parasitic plant Striga hermonthica perceives strigolactone as its germination signal, indicating host presence. After germination, the Striga plant parasitises the host plant and suppresses host growth by draining photosynthetic products, water and other essential nutrients. Because of this way of life, this parasite threatens crop production in sub-Saharan Africa with infestation in crop fields and crop devastation. Crop protection in such areas is among the most concerning problems to be dealt with as immediately as possible. With respect to crop protection from Striga, many strigolactone agonists have been developed and used in research to reveal Striga biology, and have contributed to development of crop protection methods. However, an effective method has yet to be found. In a previous study, we reported debranones as a group of strigolactone mimics that inhibit axillary buds outgrowth with moderate stimulation activity for Striga germination. Debranones would be accessible because they are simply synthesized from commercially available phenols and bromo butenolide. Taking this advantage of debranones for Striga research, we tried to find the debranones stimulating Striga seed germination. To modulate functional selectivity and to enhance germination inducing activity of debranones, we studied structure–activity relationships. We investigated effects of substituent position and functional group on debranone activity and selectivity as a strigolactone mimic. As a result, we improved stimulation activity of debranones for Striga seed germination by chemical modification, and demonstrated the pharmacophore of debranones for selective modulation of distinct strigolactone responses.

  3. Functional Stroke Mimics: Incidence and Characteristics at a Primary Stroke Center in the Middle East

    Science.gov (United States)

    Wilkins, Stacy Schantz; Bourke, Paula; Salam, Abdul; Akhtar, Naveed; D'Souza, Atlantic; Kamran, Saadat; Bhutta, Zain; Shuaib, Ashfaq

    2018-01-01

    ABSTRACT Objective Approximately 30% of individuals who initially present with stroke are found to be stroke mimics (SM), with functional/psychological SM (FSM) accounting for up to 6.4% of all stroke presentations. Middle Eastern countries may have higher rates of somatization of emotional distress. The aim of this study was to evaluate the incidence and characteristics of FSM at a large general hospital in the Middle East. Methods All patients presenting with an initial diagnosis of stroke from June 2015 to September 2016 were eligible for this study. Clinical and sociodemographic data were obtained from the hospital's stroke database. All SM and strokes were diagnosed by Joint Commission International–certified stroke program neurologists. SM was defined as any discharge diagnosis (other than acute stroke) for symptoms that prompted initial admission for suspected stroke. FSM were compared with medical stroke mimics (MSM) and strokes (ischemic, hemorrhagic, and transient ischemic attacks). Results A total of 1961 patients were identified; 161 FSM (8.2%), 390 MSM (19.9%), and 1410 strokes (71.9%) (985 ischemic strokes, 196 transient ischemic attacks, 229 intracerebral hemorrhages). Admission with FSM was related to patients' nationality, with the highest frequency in Arabic (15.6%) and African (16.8%) patients. FSM patients were younger, more often female, and had fewer cardiovascular risk factors except for smoking compared with the strokes. FSM patients presented with more left-sided weakness and had more magnetic resonance imagings than the stroke and MSM groups. A total of 9.9% of FSM patients received thrombolysis versus only 0.5% of the MSM and 16.4% of ischemic strokes. Conclusions FSM frequencies varied by nationality, with Arab and African nationals being twice as prevalent. Stress, vulnerable status as expats, sociopolitical instability, and exposure to trauma are proposed as potential factors contributing to FSM. PMID:29394187

  4. Lipid bilayer-coated mesoporous silica nanoparticles carrying bovine hemoglobin towards an erythrocyte mimic.

    Science.gov (United States)

    Tu, Jing; Bussmann, Jeroen; Du, Guangsheng; Gao, Yue; Bouwstra, Joke A; Kros, Alexander

    2018-05-30

    Hemoglobin (Hb)-loaded mesoporous silica nanoparticles (MSNs) coated with a lipid bilayer (LB-MSNs) were investigated as an erythrocyte mimic. MSNs with a large average pore size (10 nm) act as a rigid core and provide a protective environment for Hb encapsulated inside the pores. The colloidal stability of Hb-loaded MSNs was enhanced upon the application of a lipid bilayer, through fusion of PEGylated liposomes onto the exterior surface of Hb-loaded MSNs. The morphology and mesostructure of the MSNs were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and surface area analysis. The Hb loading capacity (mg/g) in MSNs was studied by thermogravimetric analysis (TGA). UV-Vis absorption spectroscopy revealed that Hb inside MSNs had an identical, but slightly broadened peak in the Soret region compared to free Hb. Furthermore the encapsulated Hb exhibits similar peroxidase-like activity in catalyzing the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) with hydrogen peroxide. The introduction of a supported lipid bilayer (LB) demonstrated the potential to prevent premature Hb release (the burst release decreased from 25.50 ± 0.33% to 6.73 ± 0.83%) and increased the colloidal stability of the Hb-loaded MSNs (hydrodynamic diameter remained ∼250 nm for at least one week). The in vivo systemic circulation and biodistribution of LB-MSNs were studied in optically transparent zebrafish embryos, revealing that LB-MSNs have the potential to act as an erythrocyte mimic in transfusion therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. A Multiple Indicators Multiple Causes (MIMIC) model of internal barriers to drug treatment in China.

    Science.gov (United States)

    Qi, Chang; Kelly, Brian C; Liao, Yanhui; He, Haoyu; Luo, Tao; Deng, Huiqiong; Liu, Tieqiao; Hao, Wei; Wang, Jichuan

    2015-03-01

    Although evidence exists for distinct barriers to drug abuse treatment (BDATs), investigations of their inter-relationships and the effect of individual characteristics on the barrier factors have been sparse, especially in China. A Multiple Indicators Multiple Causes (MIMIC) model is applied for this target. A sample of 262 drug users were recruited from three drug rehabilitation centers in Hunan Province, China. We applied a MIMIC approach to investigate the effect of gender, age, marital status, education, primary substance use, duration of primary drug use, and drug treatment experience on the internal barrier factors: absence of problem (AP), negative social support (NSS), fear of treatment (FT), and privacy concerns (PC). Drug users of various characteristics were found to report different internal barrier factors. Younger participants were more likely to report NSS (-0.19, p=0.038) and PC (-0.31, p<0.001). Compared to other drug users, ice users were more likely to report AP (0.44, p<0.001) and NSS (0.25, p=0.010). Drug treatment experiences related to AP (0.20, p=0.012). In addition, differential item functioning (DIF) occurred in three items when participant from groups with different duration of drug use, ice use, or marital status. Individual characteristics had significant effects on internal barriers to drug treatment. On this basis, BDAT perceived by different individuals could be assessed before tactics were utilized to successfully remove perceived barriers to drug treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. TGF-β mimic proteins form an extended gene family in the murine parasite Heligmosomoides polygyrus.

    Science.gov (United States)

    Smyth, Danielle J; Harcus, Yvonne; White, Madeleine P J; Gregory, William F; Nahler, Janina; Stephens, Ian; Toke-Bjolgerud, Edward; Hewitson, James P; Ivens, Alasdair; McSorley, Henry J; Maizels, Rick M

    2018-04-01

    We recently reported the discovery of a new parasite-derived protein that functionally mimics the immunosuppressive cytokine transforming growth factor (TGF)-β. The Heligmosomoides polygyrus TGF-β Mimic (Hp-TGM) shares no homology to any TGF-β family member, however it binds the mammalian TGF-β receptor and induces expression of Foxp3, the canonical transcription factor of both mouse and human regulatory T cells. Hp-TGM consists of five atypical Complement Control Protein (CCP, Pfam 00084) domains, each lacking certain conserved residues and 12-15 amino acids longer than the 60-70 amino acids consensus domain, but with a recognizable 3-cysteine, tryptophan, cysteine motif. We now report on the identification of a family of nine related Hp-TGM homologues represented in the secreted proteome and transcriptome of H. polygyrus. Recombinant proteins from five of the nine new TGM members were tested for TGF-β activity, but only two were functionally active in an MFB-F11 reporter assay, and by the induction of T cell Foxp3 expression. Sequence comparisons reveal that proteins with functional activity are similar or identical to Hp-TGM across the first three CCP domains, but more variable in domains 4 and 5. Inactive proteins diverged in all domains, or lacked some domains entirely. Testing truncated versions of Hp-TGM confirmed that domains 1-3 are essential for full activity in vitro, while domains 4 and 5 are not required. Further studies will elucidate whether these latter domains fulfill other functions in promoting host immune regulation during infection and if the more divergent family members play other roles in immunomodulation. Copyright © 2018. Published by Elsevier Ltd.

  7. Percutaneous CT-Guided Core Needle Biopsy Versus Fine Needle Aspiration in Diagnosing Pneumonia and Mimics of Pneumonia

    International Nuclear Information System (INIS)

    Thanos, Loukas; Galani, Panagiota; Mylona, Sophia; Pomoni, Maria; Mpatakis, Nikolaos

    2004-01-01

    The purpose of this study was to determine the diagnostic value of percutaneous core needle biopsy (CNB) relative to fine needle aspiration (FNA) in patients with pneumonia and pneumonia mimics. In this prospective study we present our experience with 48 thoracic FNAs and CNBs carried out on 48 patients with pneumonia and pneumonia mimics. Samples were obtained from all patients using both CNB (with an automated 18-G core biopsy needle and a gun) and FNA (with a 22-G needle). A specific diagnosis was made in 10/48 cases (20.83%) by FNA and in 42/48 (87.5%) by CNB. The main complications encountered were pneumothorax (n = 4) and hemoptysis (n = 2), yielding a total complication rate of 12.5%. We concluded that CNB using an automated biopsy gun results in a higher diagnostic accuracy for pneumonia and pneumonia mimic biopsies than FNA. Complications should be considered and proper patient observation should follow the procedure

  8. A complex-like calculus for spherical vectorfields

    NARCIS (Netherlands)

    Graaf, de J.

    2011-01-01

    First, R^{1+d}, d in N, is turned into an algebra by mimicing the usual complex multiplication. Indeed the special case d = 1 reproduces C. For d > 1 the considered algebra is commutative, but non-associative and even non-alternative. Next, the Dijkhuis class of mappings (’vectorfields’) R^{1+d} ¿

  9. 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

  10. Orbital interactions and charge redistribution in weak hydrogen bonds: The Watson-Crick AT mimic adenine-2,4-difluorotoluene

    NARCIS (Netherlands)

    Fonseca Guerra, C.; Bickelhaupt, F.M.

    2003-01-01

    An overview is given of results that reestablish hydrogen bonding as an essential factor in DNA replication involving natural bases as well as less polar mimics and they also confirm the importance of steric factors, in line with Kool's experimental work. In addition they show that knowledge of the

  11. High-fidelity in vivo replication of DNA base shape mimics without Watson–Crick hydrogen bonds

    Science.gov (United States)

    Delaney, James C.; Henderson, Paul T.; Helquist, Sandra A.; Morales, Juan C.; Essigmann, John M.; Kool, Eric T.

    2003-01-01

    We report studies testing the importance of Watson–Crick hydrogen bonding, base-pair geometry, and steric effects during DNA replication in living bacterial cells. Nonpolar DNA base shape mimics of thymine and adenine (abbreviated F and Q, respectively) were introduced into Escherichia coli by insertion into a phage genome followed by transfection of the vector into bacteria. Genetic assays showed that these two base mimics were bypassed with moderate to high efficiency in the cells and with very high efficiency under damage-response (SOS induction) conditions. Under both sets of conditions, the T-shape mimic (F) encoded genetic information in the bacteria as if it were thymine, directing incorporation of adenine opposite it with high fidelity. Similarly, the A mimic (Q) directed incorporation of thymine opposite itself with high fidelity. The data establish that Watson–Crick hydrogen bonding is not necessary for high-fidelity replication of a base pair in vivo. The results suggest that recognition of DNA base shape alone serves as the most powerful determinant of fidelity during transfer of genetic information in a living organism. PMID:12676985

  12. Enzyme active site mimics based on TriAzaCyclophane (TAC)-scaffolded peptides and amino acid residues

    NARCIS (Netherlands)

    Albada, H.B.

    2009-01-01

    This thesis describes the scope and limitations of the application of TriAzaCyclophane (TAC)-scaffolded peptides or amino acid residues as enzyme active site mimics, as ligands in asymmetric catalysis and as hydrolysis catalysts attached to vancomycin. For the mimicry of functional group enzymes, of

  13. Retention of robot-assisted surgical skills in urological surgeons acquired using Mimic dV-Trainer.

    Science.gov (United States)

    Teishima, Jun; Hattori, Minoru; Inoue, Shogo; Ikeda, Kenichiro; Hieda, Keisuke; Ohara, Shinya; Egi, Hiroyuki; Ohdan, Hideki; Matsubara, Akio

    2014-07-01

    We assess the retention of robot-assisted surgical skills among urologic surgeons. The robot-assisted surgery skills of 20 urologic surgeons were assessed using a Mimic dV-Trainer program (Mimic Technologies, Inc., Seattle, WA) consisting of 6 tasks. These 20 surgeons had no previous experience either using the Mimic dV-Trainer or acting as the main surgeon in robot-assisted surgery. The surgeons completed the program 4 times in a row; after 1 year, they completed it again for a fifth time. Performance scores were recorded using the Mimic dV-Trainer's built-in algorithm. For all 6 tasks, there were significant improvements to the scores in the fourth trials compared with those in the first trials. The scores in the fifth trials did not significantly decline compared with those in the fourth trials. There was no significant difference between the fifth trial scores of surgeons with laparoscopic surgery skills/experience and those without. Our results indicate that fundamental robot-assisted surgical skills can be retained in the long-term after they are acquired.

  14. MiR-26b Mimic Inhibits Glioma Proliferation In Vitro and In Vivo Suppressing COX-2 Expression.

    Science.gov (United States)

    Chen, Zheng-Gang; Zheng, Chuan-Yi; Cai, Wang-Qing; Li, Da-Wei; Ye, Fu-Yue; Zhou, Jian; Wu, Ran; Yang, Kun

    2017-08-11

    Glioma is the most common malignant tumor of the nervous system. Studies have shown the microRNA (miR)-26b/cyclooxygenase (COX)-2 axis in the development and progression in many tumor cells. Our study aims to investigate the effect and mechanism of miR-26b/COX-2 axis in glioma. Decreased expression of miR-26b with increased level of COX-2 was found in glioma tissues compared with matched normal tissues. A strong negative correlation was observed between the level of miR-26b and COX-2 in 30 glioma tissues. The miR-26b was then overexpressed by transfecting miR-26b mimic into U-373 cells. The invasive cell number and wounld closing rate were reduced in U-373 cells transfected with miR-26b mimic. Besides, COX2 siRNA enhanced the effect of miR-26b mimic in suppressing the expression of p-ERK1 and p-JNK. Finally, the in vivo experiment revealed that miR-26b mimic transfection strongly reduced the tumor growth, tumor volume and the expression of matrix metalloproteinase (MMP)-2, MMP-9). Taken together, our research indicated a miR-26b/COX-2/ERK/JNK axis in regulating the motility of glioma in vitro and in vivo, providing a new sight for treatment of glioma.

  15. Insights into molecular recognition of LewisX mimics by DC-SIGN using NMR and molecular modelling

    International Nuclear Information System (INIS)

    Guzzi, C.; Angulo, J.; Rojo, J.; Nieto, P.M.; Doro, F.; Bernardi, A.; Thepaut, M.; Fieschi, F.; Thepaut, M.; Fieschi, F.

    2011-01-01

    In this work, we have studied in detail the binding of two α-fucosyl-amide-based mimics of Lewis X to DC-SIGN ECD (ECD = extracellular domain) using STD NMR and docking. We have concluded that the binding mode occurs mainly through the fucose moiety, in the same way as Lewis X . Similarly to other mimics containing mannose or fucose previously studied, we have shown that both compounds bind to DC-SIGN ECD in a multimodal fashion. In this case, the main contact is the interaction of two hydroxyl groups one equatorial and the other one axial (O3 and O4) of the fucose with the Ca 2+ as Lewis X and similarly to mannose-containing mimics (in this case the interacting groups are both in the equatorial position). Finally, we have measured the K D of one mimic that was 0.4 mM. Competitive STD NMR experiments indicate that the aromatic moiety provides additional binding contacts that increase the affinity. (authors)

  16. Mixture Item Response Theory-MIMIC Model: Simultaneous Estimation of Differential Item Functioning for Manifest Groups and Latent Classes

    Science.gov (United States)

    Bilir, Mustafa Kuzey

    2009-01-01

    This study uses a new psychometric model (mixture item response theory-MIMIC model) that simultaneously estimates differential item functioning (DIF) across manifest groups and latent classes. Current DIF detection methods investigate DIF from only one side, either across manifest groups (e.g., gender, ethnicity, etc.), or across latent classes…

  17. The pattern recognition molecule deleted in malignant brain tumors 1 (DMBT1) and synthetic mimics inhibit liposomal nucleic acid delivery

    DEFF Research Database (Denmark)

    Lund Hansen, Pernille; Blaich, Stephanie; End, Caroline

    2011-01-01

    Liposomal nucleic acid delivery is a preferred option for therapeutic settings. The cellular pattern recognition molecule DMBT1, secreted at high levels in various diseases, and synthetic mimics efficiently inhibit liposomal nucleic acid delivery to human cells. These findings may have relevance...

  18. Selective Disruption of Metabotropic Glutamate Receptor 5-Homer Interactions Mimics Phenotypes of Fragile X Syndrome in Mice.

    Science.gov (United States)

    Guo, Weirui; Molinaro, Gemma; Collins, Katie A; Hays, Seth A; Paylor, Richard; Worley, Paul F; Szumlinski, Karen K; Huber, Kimberly M

    2016-02-17

    Altered function of the Gq-coupled, Group 1 metabotropic glutamate receptors, specifically mGlu5, is implicated in multiple mouse models of autism and intellectual disability. mGlu5 dysfunction has been most well characterized in the fragile X syndrome mouse model, the Fmr1 knock-out (KO) mouse, where pharmacological and genetic reduction of mGlu5 reverses many phenotypes. mGlu5 is less associated with its scaffolding protein Homer in Fmr1 KO mice, and restoration of mGlu5-Homer interactions by genetic deletion of a short, dominant negative of Homer, H1a, rescues many phenotypes of Fmr1 KO mice. These results suggested that disruption of mGlu5-Homer leads to phenotypes of FXS. To test this idea, we examined mice with a knockin mutation of mGlu5 (F1128R; mGlu5(R/R)) that abrogates binding to Homer. Although FMRP levels were normal, mGlu5(R/R) mice mimicked multiple phenotypes of Fmr1 KO mice, including reduced mGlu5 association with the postsynaptic density, enhanced constitutive mGlu5 signaling to protein synthesis, deficits in agonist-induced translational control, protein synthesis-independent LTD, neocortical hyperexcitability, audiogenic seizures, and altered behaviors, including anxiety and sensorimotor gating. These results reveal new roles for the Homer scaffolds in regulation of mGlu5 function and implicate a specific molecular mechanism in a complex brain disease. Abnormal function of the metabotropic, or Gq-coupled, glutamate receptor 5 (mGlu5) has been implicated in neurodevelopmental disorders, including a genetic cause of intellectual disability and autism called fragile X syndrome. In brains of a mouse model of fragile X, mGlu5 is less associated with its binding partner Homer, a scaffolding protein that regulates mGlu5 localization to synapses and its ability to activate biochemical signaling pathways. Here we show that a mouse expressing a mutant mGlu5 that cannot bind to Homer is sufficient to mimic many of the biochemical, neurophysiological, and

  19. Can f(T) gravity theories mimic ΛCDM cosmic history

    Energy Technology Data Exchange (ETDEWEB)

    Setare, M.R.; Mohammadipour, N., E-mail: rezakord@ipm.ir, E-mail: N.Mohammadipour@uok.ac.ir [Department of Science, University of Kurdistan, Sanandaj (Iran, Islamic Republic of)

    2013-01-01

    Recently the teleparallel Lagrangian density described by the torsion scalar T has been extended to a function of T. The f(T) modified teleparallel gravity has been proposed as the natural gravitational alternative for dark energy to explain the late time acceleration of the universe. In order to reconstruct the function f(T) by demanding a background ΛCDM cosmology we assume that, (i) the background cosmic history provided by the flat ΛCDM (the radiation ere with ω{sub eff} = (1/3), matter and de Sitter eras with ω{sub eff} = 0 and ω{sub eff} = −1, respectively) (ii) the radiation dominate in the radiation era with Ω{sub 0r} = 1 and the matter dominate during the matter phases when Ω{sub 0m} = 1. We find the cosmological dynamical system which can obey the ΛCDM cosmic history. In each era, we find a critical lines that, the radiation dominated and the matter dominated are one points of them in the radiation and matter phases, respectively. Also, we drive the cosmologically viability condition for these models. We investigate the stability condition with respect to the homogeneous scalar perturbations in each era and we obtain the stability conditions for the fixed points in each eras. Finally, we reconstruct the function f(T) which mimics cosmic expansion history.

  20. Three-dimensional culture of buffalo granulosa cells in hanging drop mimics the preovulatory follicle stage.

    Science.gov (United States)

    Yadav, Monica; Agrawal, Himanshu; Pandey, Mamta; Singh, Dheer; Onteru, Suneel K

    2018-03-01

    Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three-dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 hr in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly-([2-hydroxyethyl methacrylate]) (polyHEMA) methods in the DMEM media containing 1 ng/ml FSH and 10 ng/ml IGF-1 for 144 hr. The expression profile of nine GC-specific transcripts; CYP19, TNFAIP6, AMH, PTI, NR4A1, FSHR, RUNX, LHR, and COX2/PTGS2; revealed that 3D-spheroids developed in hanging drop method maintained the GC phenotype of preovulatory follicles. Therefore, hanging drop method is a best method for culturing GCs to mimic the intrafollicular environment. © 2017 Wiley Periodicals, Inc.

  1. Secretory carcinoma of the breast and its histopathological mimics: value of markers for differential diagnosis.

    Science.gov (United States)

    Osako, Tomo; Takeuchi, Kengo; Horii, Rie; Iwase, Takuji; Akiyama, Futoshi

    2013-10-01

    Secretory carcinoma (SC) is a rare histological type of breast cancer, and ETV6-NTRK3 gene fusion is highly specific to it. The differential diagnoses of SC include acinic cell carcinoma (ACCA) and cystic hypersecretory carcinoma (CHC), as well as invasive ductal carcinoma (IDC). For patients with these rare but distinctive histological subtypes, SC and its histopathological mimics should be differentiated from each other. However, differential markers have not yet been assessed systematically, and we aimed to identify and evaluate novel and existing markers. We reviewed 19 cases diagnosed initially as SC using integrated diagnostic techniques, including morphology, immunohistochemistry and molecular pathology, and validated promising markers in 445 breast cancers. We reclassified 19 formerly diagnosed 'SCs' into nine SCs, three ACCAs, three CHCs, three IDCs and one microglandular adenosis. We confirmed that ETV6-NTRK3 gene rearrangement and amylase positivity are good diagnostic markers for SC and ACCA, respectively. Vacuolar staining for adipophilin, positivity for α-lactalbumin and negativity for ETV6 rearrangement are diagnostic markers for CHC. In this study, we propose a panel of four markers (ETV6 rearrangement, amylase, α-lactalbumin and adipophilin) for distinguishing SC, ACCA, CHC and IDC. This simple but robust panel will serve pathologists well as a practical guide for reaching an appropriate diagnosis. © 2013 John Wiley & Sons Ltd.

  2. 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.

  3. 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.

  4. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting

    Directory of Open Access Journals (Sweden)

    Marie Boutant

    2016-03-01

    Full Text Available Caloric restriction (CR has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD+-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF. Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different.

  5. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.

    Science.gov (United States)

    Boutant, Marie; Kulkarni, Sameer S; Joffraud, Magali; Raymond, Frédéric; Métairon, Sylviane; Descombes, Patrick; Cantó, Carles

    2016-03-08

    Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Gsk-3β Inhibitors Mimic the Cardioprotection Mediated by Ischemic Pre- and Postconditioning in Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Luisa F. González Arbeláez

    2013-01-01

    Full Text Available The aim of this study was to examine the effects of GSK-3β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR. Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI and 1-hour reperfusion (R; PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl or indirubin-3′-monoxime,5-iodo-(IMI as GSK-3β inhibitors. All interventions reduced the infarct size observed in IC group. The expressions of P-GSK-3β and P-Akt decreased in IC and were restored after PRE, POS, and GSK-3β inhibitors treatments. An increase of cytosolic MnSOD activity and lipid peroxidation and a decrease of GSH content observed in IC hearts were attenuated in PRE, POS, and LiCl or IMI treatments. An increase of P-GSK-3β/VDAC physical association and a partial recovery of mitochondrial permeability were also detected after interventions. These data show that, in SHR hearts, GSK-3β inhibitors mimic the cardioprotection afforded by PRE and POS and suggest that a decrease in mitochondrial permeability mediated by P-GSK-3β/VDAC interaction is a crucial event.

  7. A case report of gastric lymphocytic phlebitis, a rare mimic for malignancy.

    Science.gov (United States)

    Chan, Daniel L; Ravindran, Praveen; Chua, Dorothy; Smith, Jason D; Wong, King S; Ghusn, Michael A

    2017-01-01

    Lymphocytic phlebitis is a benign condition characterised by inflammation of the veins and rarely affects the gastrointestinal tract. Reported cases present as acute abdomen and involve the colon or small intestine. We report the fourth case of gastric lymphocytic phlebitis in the literature. A 74-year-old female presented with eight weeks of abdominal pain. Findings at endoscopy were suggestive of a malignant ulcer on the greater curvature of antrum, while biopsies showed chronic gastritis without malignancy. Appearance at diagnostic laparoscopy was consistent with a malignant gastric ulcer with serosal changes. Due to persistent pain and the macroscopic appearance, she proceeded to have an open subtotal gastrectomy and D2 lymph node clearance. Despite macroscopic appearance, the microscopic examination demonstrated no malignancy, and was consistent with lymphocytic phlebitis with overlying ulceration. This case was a mimic for gastric malignancy, with the benign diagnosis only being made after surgical resection. Gastric lymphocytic phlebitis is a rare differential diagnosis for gastric ulcers when biopsies are negative, although preoperative diagnosis is difficult given the lesions do not involve the mucosa. If clinical history and endoscopic findings are suspicious for malignancy, despite normal biopsies, an aggressive surgical resection remains reasonable given the rarity gastric lymphocytic phlebitis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. A case report of gastric lymphocytic phlebitis, a rare mimic for malignancy

    Directory of Open Access Journals (Sweden)

    Daniel L. Chan

    Full Text Available Introduction: Lymphocytic phlebitis is a benign condition characterised by inflammation of the veins and rarely affects the gastrointestinal tract. Reported cases present as acute abdomen and involve the colon or small intestine. We report the fourth case of gastric lymphocytic phlebitis in the literature. Presentation of case: A 74-year-old female presented with eight weeks of abdominal pain. Findings at endoscopy were suggestive of a malignant ulcer on the greater curvature of antrum, while biopsies showed chronic gastritis without malignancy. Appearance at diagnostic laparoscopy was consistent with a malignant gastric ulcer with serosal changes. Due to persistent pain and the macroscopic appearance, she proceeded to have an open subtotal gastrectomy and D2 lymph node clearance. Despite macroscopic appearance, the microscopic examination demonstrated no malignancy, and was consistent with lymphocytic phlebitis with overlying ulceration. Discussion: This case was a mimic for gastric malignancy, with the benign diagnosis only being made after surgical resection. Gastric lymphocytic phlebitis is a rare differential diagnosis for gastric ulcers when biopsies are negative, although preoperative diagnosis is difficult given the lesions do not involve the mucosa. Conclusion: If clinical history and endoscopic findings are suspicious for malignancy, despite normal biopsies, an aggressive surgical resection remains reasonable given the rarity gastric lymphocytic phlebitis. Keywords: Lymphocytic phlebitis, Gastrectomy, Gastric vasculitis, Gastric ulcer, Case report

  9. Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

    Directory of Open Access Journals (Sweden)

    Robert Root-Bernstein

    2017-10-01

    Full Text Available Human immunodeficiency virus (HIV hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR. This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS. Quantitative enzyme-linked immunoadsorption assays (ELISA demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections.

  10. A model system to mimic environmentally active surface film roughness and hydrophobicity.

    Science.gov (United States)

    Grant, Jacob S; Shaw, Scott K

    2017-10-01

    This work presents the development and initial assessment of a laboratory platform to allow quantitative studies on model urban films. The platform consists of stearic acid and eicosane mixtures that are solution deposited from hexanes onto smooth, solid substrates. We show that this model has distinctive capabilities to better mimic a naturally occurring film's morphology and hydrophobicity, two important parameters that have not previously been incorporated into model film systems. The physical and chemical properties of the model films are assessed using a variety of analytical instruments. The film thickness and roughness are probed via atomic force microscopy while the film composition, wettability, and water uptake are analyzed by Fourier transform infrared spectroscopy, contact angle goniometry, and quartz crystal microbalance, respectively. Simulated environmental maturation is achieved by exposing the film to regulated amounts of UV/ozone. Ultimately, oxidation of the film is monitored by the analytical techniques mentioned above and proceeds as expected to produce a utile model film system. Including variable roughness and tunable surface coverage results in several key advantages over prior model systems, and will more accurately represent native urban film behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Unofficial Economy Estimation by the MIMIC Model: the Case of Kenya, Namibia, Ghana and Nigeria

    Directory of Open Access Journals (Sweden)

    Dennis Nchor

    2015-01-01

    Full Text Available This study investigates the size and trend of the underground economies in selected African countries. Underground economies are present in all countries, but they are endemic in developing economies. Their presence is not necessarily bad for the economies, in which they prevail. It could however cause huge losses to government revenue and could also constitute serious violation of Labor regulations. The study uses the Multiple Indicators and Multiple Causes model (MIMIC, a variant of Simultaneous Equations Model (SEM. It involves two sets of variables: the observed variables and the indicator variables. The former include size of government, indirect tax rates, total tax rates, business regulation, interest rate on deposits, unemployment rate, quality of public services, and GDP per capita. The indicator variables were Labor participation rate in the official economy, the amount of cash held outside the banking system and growth in GDP per capita. This study found the average level of underground economies in Kenya, Namibia, Ghana and Nigeria as 33.7%, 29.1%, 36% and 47%, respectively. The estimated results show that the causes of shadow economic activities vary among the countries. The data was obtained from the World Bank country indicators and the International Financial Statistics.

  12. Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity

    Science.gov (United States)

    Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei; Eisenberg, David; Nowick, James S.

    2012-11-01

    The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β2-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles.

  13. Peptidoglycan glycosyltransferase substrate mimics as templates for the design of new antibacterial drugs

    Directory of Open Access Journals (Sweden)

    Adeline eDerouaux

    2013-03-01

    Full Text Available Peptidoglycan (PG is an essential net-like macromolecule that surrounds bacteria, gives them their shape, and protects them against their own high osmotic pressure. PG synthesis inhibition leads to bacterial cell lysis, making it an important target for many antibiotics. The final two reactions in PG synthesis are performed by penicillin-binding proteins (PBPs. Their glycosyltransferase (GT activity uses the lipid II precursor to synthesize glycan chains and their transpeptidase (TP activity catalyzes the cross-linking of two glycan chains via the peptide side chains. Inhibition of either of these two reactions leads to bacterial cell death. β-Lactam antibiotics target the transpeptidation reaction while antibiotic therapy based on inhibition of the GTs remains to be developed. Ongoing research is trying to fill this gap by studying the interactions of GTs with inhibitors and substrate mimics and utilizing the latter as templates for the design of new antibiotics. In this mini review we present an updated overview on the GTs and describe the structure-activity relationship of recently developed synthetic ligands.

  14. Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol

    International Nuclear Information System (INIS)

    Mitchell, J.B.; DeGraff, W.; Kaufman, D.; Krishna, M.C.; Samuni, A.; Finkelstein, E.; Ahn, M.S.; Hahn, S.M.; Gamson, J.; Russo, A.

    1991-01-01

    Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress

  15. Medical Textiles as Vascular Implants and Their Success to Mimic Natural Arteries

    Directory of Open Access Journals (Sweden)

    Charanpreet Singh

    2015-06-01

    Full Text Available Vascular implants belong to a specialised class of medical textiles. The basic purpose of a vascular implant (graft and stent is to act as an artificial conduit or substitute for a diseased artery. However, the long-term healing function depends on its ability to mimic the mechanical and biological behaviour of the artery. This requires a thorough understanding of the structure and function of an artery, which can then be translated into a synthetic structure based on the capabilities of the manufacturing method utilised. Common textile manufacturing techniques, such as weaving, knitting, braiding, and electrospinning, are frequently used to design vascular implants for research and commercial purposes for the past decades. However, the ability to match attributes of a vascular substitute to those of a native artery still remains a challenge. The synthetic implants have been found to cause disturbance in biological, biomechanical, and hemodynamic parameters at the implant site, which has been widely attributed to their structural design. In this work, we reviewed the design aspect of textile vascular implants and compared them to the structure of a natural artery as a basis for assessing the level of success as an implant. The outcome of this work is expected to encourage future design strategies for developing improved long lasting vascular implants.

  16. 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.

  17. Catalytic nanocrystalline coordination polymers as an efficient peroxidase mimic for labeling and optical immunoassays

    International Nuclear Information System (INIS)

    Čunderlová, Veronika; Hlaváček, Antonín; Horňáková, Veronika; Peterek, Miroslav; Němeček, Daniel; Skládal, Petr; Hampl, Aleš; Eyer, Luděk

    2016-01-01

    We report that nanocrystalline Prussian blue of the type Fe 4 [Fe(CN) 6 ] 3 is a powerful peroxidase mimic for use in labeling of biomolecules. The cubic nanocrystals typically have a diameter of 15 nm and are capable of catalyzing the oxidation of colorless 3,3′,5,5′-tetramethylbenzidine in the presence of H 2 O 2 to form an intensively colored product with an absorption maximum at 662 nm. The determined pseudo turnover number is ∼20,000 s −1 which is the highest value reported for nanoparticles of a size comparable to common proteins. We also present a method for the biotinylation of the surface of these nanocrystals, and show their use in competitive bioaffinity based assays of biotin and human serum albumin. The limits of detection are 0.35 and 0.27 μg mL −1 , respectively. The results prove the applicability of coordination polymers for signal amplification and also their compatibility with the format of enzyme linked immunosorbent assays. (author)

  18. Worm grunting, fiddling, and charming--humans unknowingly mimic a predator to harvest bait.

    Directory of Open Access Journals (Sweden)

    Kenneth C Catania

    Full Text Available BACKGROUND: For generations many families in and around Florida's Apalachicola National Forest have supported themselves by collecting the large endemic earthworms (Diplocardia mississippiensis. This is accomplished by vibrating a wooden stake driven into the soil, a practice called "worm grunting". In response to the vibrations, worms emerge to the surface where thousands can be gathered in a few hours. Why do these earthworms suddenly exit their burrows in response to vibrations, exposing themselves to predation? PRINCIPAL FINDINGS: Here it is shown that a population of eastern American moles (Scalopus aquaticus inhabits the area where worms are collected and that earthworms have a pronounced escape response from moles consisting of rapidly exiting their burrows to flee across the soil surface. Recordings of vibrations generated by bait collectors and moles suggest that "worm grunters" unknowingly mimic digging moles. An alternative possibility, that worms interpret vibrations as rain and surface to avoid drowning is not supported. CONCLUSIONS: Previous investigations have revealed that both wood turtles and herring gulls vibrate the ground to elicit earthworm escapes, indicating that a range of predators may exploit the predator-prey relationship between earthworms and moles. In addition to revealing a novel escape response that may be widespread among soil fauna, the results show that humans have played the role of "rare predators" in exploiting the consequences of a sensory arms race.

  19. 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.

  20. Designing Reliable Cohorts of Cardiac Patients across MIMIC and eICU

    Science.gov (United States)

    Chronaki, Catherine; Shahin, Abdullah; Mark, Roger

    2016-01-01

    The design of the patient cohort is an essential and fundamental part of any clinical patient study. Knowledge of the Electronic Health Records, underlying Database Management System, and the relevant clinical workflows are central to an effective cohort design. However, with technical, semantic, and organizational interoperability limitations, the database queries associated with a patient cohort may need to be reconfigured in every participating site. i2b2 and SHRINE advance the notion of patient cohorts as first class objects to be shared, aggregated, and recruited for research purposes across clinical sites. This paper reports on initial efforts to assess the integration of Medical Information Mart for Intensive Care (MIMIC) and Philips eICU, two large-scale anonymized intensive care unit (ICU) databases, using standard terminologies, i.e. LOINC, ICD9-CM and SNOMED-CT. Focus of this work is lab and microbiology observations and key demographics for patients with a primary cardiovascular ICD9-CM diagnosis. Results and discussion reflecting on reference core terminology standards, offer insights on efforts to combine detailed intensive care data from multiple ICUs worldwide. PMID:27774488

  1. BioMimic fabrication of electrospun nanofibers with high-throughput

    International Nuclear Information System (INIS)

    He Jihuan; Liu Yong; Xu Lan; Yu Jianyong; Sun Gang

    2008-01-01

    Spider-spun fiber is of extraordinary strength and toughness comparable to those of electrospun fiber, the later needs a very high voltage (from several thousands voltage to several ten thousands voltages) applied to water-soluble protein 'soup' that was produced by a spider, furthermore, its mechanical strength dramatically decreases comparable to spider silk. A possible mechanism in spider-spinning process is given, the distinct character in spider-spinning is that its spinneret consists of millions of nano scale tubes, and a bubble can be produced at the apex of each nano-tube. The surface tension of each bubble is extremely small such that it can be spun into nanofibers with an awfully small force, either by the spider's body weight or tension created by the rear legs. We mimic the spider-spinning in electrospinning using an aerated solution, which leads to various small bubbles on surface with very small surface tension, as a result the bubble can be easily electrospun into nanofibers with low applied voltage. This fabrication process possesses features of high productivity, versatility, in addition, the minimum diameter of nanofibers produced by this process can reach as small as 50 nm

  2. Fine-Needle Aspiration Cytology of Parathyroid Carcinoma Mimic Hürthle Cell Thyroid Neoplasm

    Directory of Open Access Journals (Sweden)

    Chutintorn Sriphrapradang

    2014-01-01

    Full Text Available Background. Fine-needle aspiration (FNA can cause misdiagnosis of cytomorphological findings between parathyroid and thyroid lesions. Case Presentation. A 31-year-old man presented with a palpable neck mass on the right thyroid lobe. FNA cytology was reported as intrathyroidal lymphoid hyperplasia. After 5 years, repeated FNA was done on the enlarged nodule with result of Hürthle cell lesion. Prior to right lobectomy, laboratories revealed elevated serum calcium and parathyroid hormone (PTH. Careful history taking revealed chronic knee pain and ossifying fibroma at the maxilla. Ultrasonography showed a 2.8 cm mass inferior to right thyroid lobe. Pathology from en bloc resection was parathyroid carcinoma and immunohistochemical study revealed positivity for PTH. Genetic analysis found somatic mutation of CDC73 gene in exon1 (c.70delG which caused premature stop codon in amino acid 26 (p.Glu24Lysfs2*. The final diagnosis was hyperparathyroidism-jaw tumor syndrome. Conclusions. FNA cytology of parathyroid can mimic thyroid lesion. It is important to consider and correlate the entire information from clinical history, laboratory, imaging, and FNA.

  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. Intratemporal facial nerve neuromas and their mimics: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Han, Moon Hee; Chang, Kee Hyun; Lee, Kyung Hwan; Cha, Sang Hoon; Kim, Chong Sun [Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Sang Joon [Chungang Gil General Hospital, Seoul (Korea, Republic of)

    1992-05-15

    CT and MR findings of nine cases with intra temporal facial nerve neuromas were described and compared with CT findings of 3 cases with facial nerve palsy and facial nerve canal erosion which may mimic facial nerve neuroma. The tympanic segment of the facial nerve was involved in 8 cases, mastoid segment in 7 cases and labyrinthine segment in 5 cases. The lesions were easily diagnosed with high resolution CT with bone algorithms by showing the expansion of bony structures along the course of the facial nerves. In 4 cases with large vertical segment tumors, extensive destruction of mastoid air cells and external auditory canals posed difficulty in making a diagnosis. Two out of 5 cases with labyrinthine segment involvement were presented as middle cranial fossa masses. MRI with enhancement was performed in 4 cases and was useful in characterizing the lesion as a tumor with its superior sensitivity to enhancement. Three cases of facial neuroma-mimicking lesion including post-inflammatory peri neural thickening, peri neural extension from parotid adenoid cystic carcinoma, and congenita; cholesteatoma showed irregular erosion or mild expansion of the facial nerve canal which may be helpful for differential diagnosis from neuromas.

  5. Complexity explained

    CERN Document Server

    Erdi, Peter

    2008-01-01

    This book explains why complex systems research is important in understanding the structure, function and dynamics of complex natural and social phenomena. Readers will learn the basic concepts and methods of complex system research.

  6. Complex chemistry

    International Nuclear Information System (INIS)

    Kim, Bong Gon; Kim, Jae Sang; Kim, Jin Eun; Lee, Boo Yeon

    2006-06-01

    This book introduces complex chemistry with ten chapters, which include development of complex chemistry on history coordination theory and Warner's coordination theory and new development of complex chemistry, nomenclature on complex with conception and define, chemical formula on coordination compound, symbol of stereochemistry, stereo structure and isomerism, electron structure and bond theory on complex, structure of complex like NMR and XAFS, balance and reaction on solution, an organo-metallic chemistry, biology inorganic chemistry, material chemistry of complex, design of complex and calculation chemistry.

  7. Orbital interactions and charge redistribution in weak hydrogen bonds: Watson-Crick GC mimic involving C-H proton donor and F proton acceptor groups

    NARCIS (Netherlands)

    Fonseca Guerra, C.; Baerends, E.J.; Bickelhaupt, F.M.

    2006-01-01

    The discovery by Kool and coworkers that 2,4-difluorotoluene (F) mimics thymine (T) in DNA replication has led to controversy regarding the question of whether this mimic has the capability of forming hydrogen bonds with adenine (A). Recently, we have provided evidence for an important role of both

  8. An athymic mouse model to mimic cobalt-60 cutaneous radiation injury

    Energy Technology Data Exchange (ETDEWEB)

    Mosca, Rodrigo Crespo; Ferreira, Danilo Cardenuto; Napolitano, Celia Marina; Santin, Stefany Plumeri; Dornelles, Leonardo Dalla Porta; Alvarenga, Eluara Ortigoso; Mathor, Monica Beatriz, E-mail: rcmosca@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Propose: Cutaneous wound from irradiation is the most common complication in radiotherapy treatment, and can be lead to mortality. We describe an athymic mouse model to mimic cutaneous radiation injury by Cobalt-60. Methods: A protocol was including dosimetry with silicon diodes,10x10x5 cm arrangement made by four lead bricks and PVC pipe designed to immobilize the athymic mouse in order to irradiate one clamped back skin point that was subdivided in four parts. To get the measurements of dose rates on the arrangement in Panoramic Irradiator, it was used a silicon diode encased in an opaque protection for ambient light and connected to an electric cable, forming a dosing probe. The currents generated in diode sensitive volume as a function of time of exposure to gamma radiation coming from the radiator, with dose rate of 0,015 Gy/min in positions 1, 0,021 Gy/min in position 2, 0,55 Gy/min in position 3 and 1,45 Gy/min in position four. After the dosimetry, each athymic mouse was anesthetized using Xylazine and Ketamine dilution and entered into a PVC pipe and a small portion of skin (1 cm{sup 3}) was clamped. This tube was then fixed to arrangement and the athymic mouse was irradiate for 60 min, than it was being returned to its cage. Results: The wound was visualized in all animals and photographed after 5 days of irradiation, with the emergence of ulceration after 9 days. No systemic or lethal sequelae occurred or visualized in any animals. Late clinical signs included a wound healing after 22 days. Conclusion: While still being a baseline study, we created a new functional preclinical animal model that can be used for new therapies and may improve radiotherapy management. (author)

  9. An athymic mouse model to mimic cobalt-60 cutaneous radiation injury

    International Nuclear Information System (INIS)

    Mosca, Rodrigo Crespo; Ferreira, Danilo Cardenuto; Napolitano, Celia Marina; Santin, Stefany Plumeri; Dornelles, Leonardo Dalla Porta; Alvarenga, Eluara Ortigoso; Mathor, Monica Beatriz

    2013-01-01

    Propose: Cutaneous wound from irradiation is the most common complication in radiotherapy treatment, and can be lead to mortality. We describe an athymic mouse model to mimic cutaneous radiation injury by Cobalt-60. Methods: A protocol was including dosimetry with silicon diodes,10x10x5 cm arrangement made by four lead bricks and PVC pipe designed to immobilize the athymic mouse in order to irradiate one clamped back skin point that was subdivided in four parts. To get the measurements of dose rates on the arrangement in Panoramic Irradiator, it was used a silicon diode encased in an opaque protection for ambient light and connected to an electric cable, forming a dosing probe. The currents generated in diode sensitive volume as a function of time of exposure to gamma radiation coming from the radiator, with dose rate of 0,015 Gy/min in positions 1, 0,021 Gy/min in position 2, 0,55 Gy/min in position 3 and 1,45 Gy/min in position four. After the dosimetry, each athymic mouse was anesthetized using Xylazine and Ketamine dilution and entered into a PVC pipe and a small portion of skin (1 cm 3 ) was clamped. This tube was then fixed to arrangement and the athymic mouse was irradiate for 60 min, than it was being returned to its cage. Results: The wound was visualized in all animals and photographed after 5 days of irradiation, with the emergence of ulceration after 9 days. No systemic or lethal sequelae occurred or visualized in any animals. Late clinical signs included a wound healing after 22 days. Conclusion: While still being a baseline study, we created a new functional preclinical animal model that can be used for new therapies and may improve radiotherapy management. (author)

  10. Sulfinylated Azadecalins act as functional mimics of a pollen germination stimulant in Arabidopsis pistils

    Science.gov (United States)

    Qin, Yuan; Wysocki, Ronald J; Somogyi, Arpad; Feinstein, Yelena; Franco, Jessica Y; Tsukamoto, Tatsuya; Dunatunga, Damayanthi; Levy, Clara; Smith, Steven; Simpson, Robert; Gang, David; Johnson, Mark A; Palanivelu, Ravishankar

    2011-01-01

    SUMMARY Polarized cell elongation is triggered by small molecule cues during development of diverse organisms. During plant reproduction, pollen interactions with the stigma result in the polar outgrowth of a pollen tube, which delivers sperm cells to the female gametophyte to effect double fertilization. In many plants, pistils stimulate pollen germination. However, in Arabidopsis, the effect of pistils on pollen germination and the pistil factors that stimulate pollen germination remain poorly characterized. Here, we demonstrate that stigma, style, and ovules in Arabidopsis pistils stimulate pollen germination. We isolated an Arabidopsis pistil extract fraction that stimulates Arabidopsis pollen germination, and employed ultrahigh resolution ESI FT-ICR and MS/MS techniques to accurately determine the mass (202.126 daltons) of a compound that is specifically present in this pistil extract fraction. Using the molecular formula (C10H19NOS) and tandem mass spectral fragmentation patterns of the m/z (mass to charge ratio) 202.126 ion, we postulated chemical structures, devised protocols, synthesized N-Methanesulfinyl 1- and 2-azadecalins that are close structural mimics of the m/z 202.126 ion, and showed that they are sufficient to stimulate Arabidopsis pollen germination in vitro (30 µM stimulated ~50% germination) and elicit accession-specific response. Although N-Methanesulfinyl 2-azadecalin stimulated pollen germination in three species of Lineage I of Brassicaceae, it did not induce a germination response in Sisymbrium irio (Lineage II of Brassicaceae) and tobacco, indicating that activity of the compound is not random. Our results show that Arabidopsis pistils promote germination by producing azadecalin-like molecules to ensure rapid fertilization by the appropriate pollen. PMID:21801250

  11. Shape-specific nanostructured protein mimics from de novo designed chimeric peptides.

    Science.gov (United States)

    Jiang, Linhai; Yang, Su; Lund, Reidar; Dong, He

    2018-01-30

    Natural proteins self-assemble into highly-ordered nanoscaled architectures to perform specific functions. The intricate functions of proteins have provided great impetus for researchers to develop strategies for designing and engineering synthetic nanostructures as protein mimics. Compared to the success in engineering fibrous protein mimetics, the design of discrete globular protein-like nanostructures has been challenging mainly due to the lack of precise control over geometric packing and intermolecular interactions among synthetic building blocks. In this contribution, we report an effective strategy to construct shape-specific nanostructures based on the self-assembly of chimeric peptides consisting of a coiled coil dimer and a collagen triple helix folding motif. Under salt-free conditions, we showed spontaneous self-assembly of the chimeric peptides into monodisperse, trigonal bipyramidal-like nanoparticles with precise control over the stoichiometry of two folding motifs and the geometrical arrangements relative to one another. Three coiled coil dimers are interdigitated on the equatorial plane while the two collagen triple helices are located in the axial position, perpendicular to the coiled coil plane. A detailed molecular model was proposed and further validated by small angle X-ray scattering experiments and molecular dynamics (MD) simulation. The results from this study indicated that the molecular folding of each motif within the chimeric peptides and their geometric packing played important roles in the formation of discrete protein-like nanoparticles. The peptide design and self-assembly mechanism may open up new routes for the construction of highly organized, discrete self-assembling protein-like nanostructures with greater levels of control over assembly accuracy.

  12. Cadmium mimics estrogen-driven cell proliferation and prolactin secretion from anterior pituitary cells.

    Directory of Open Access Journals (Sweden)

    Sonia A Ronchetti

    Full Text Available Cadmium (Cd is a heavy metal of considerable occupational and environmental concern affecting wildlife and human health. Recent studies indicate that Cd, like other heavy metals, can mimic effects of 17β-estradiol (E2 involving E2 receptor (ER activation. Lactotrophs, the most abundant cell type in anterior pituitary gland, are the main target of E2, which stimulates cell proliferation and increases prolactin secretion through ERα. The aim of this work was to examine whether Cd at nanomolar concentrations can induce cell proliferation and prolactin release in anterior pituitary cells in culture and whether these effects are mediated through ERs. Here we show that 10 nM Cd was able to stimulate lactotroph proliferation in anterior pituitary cell cultures from female Wistar rats and also in GH3 lactosomatotroph cell line. Proliferation of somatotrophs and gonadotrophs were not affected by Cd exposure. Cd promoted cell cycle progression by increasing cyclins D1, D3 and c-fos expression. Cd enhanced prolactin synthesis and secretion. Cd E2-like effects were blocked by the pure ERs antagonist ICI 182,780 supporting that Cd acts through ERs. Further, both Cd and E2 augmented full-length ERαexpression and its 46 kDa-splicing variant. In addition, when co-incubated Cd was shown to interact with E2 by inducing ERα mRNA expression which indicates an additive effect between them. This study shows for the first time that Cd at nanomolar concentration displays xenoestrogenic activities by inducing cell growth and stimulating prolactin secretion from anterior pituitary cells in an ERs-dependent manner. Cd acting as a potent xenoestrogen can play a key role in the aetiology of different pathologies of the anterior pituitary and in estrogen-responsive tissues which represent considerable risk to human health.

  13. Functionalized hybrid nanofibers to mimic native ECM for tissue engineering applications

    Energy Technology Data Exchange (ETDEWEB)

    Karuppuswamy, Priyadharsini [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore); Department Physics and Nanotechnology, SRM University, Kattankulathur, Chennai (India); Department of Engineering and System Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Venugopal, Jayarama Reddy, E-mail: nnijrv@nus.edu.sg [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore); Navaneethan, Balchandar [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore); Department Physics and Nanotechnology, SRM University, Kattankulathur, Chennai (India); Laiva, Ashang Luwang; Sridhar, Sreepathy; Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore (Singapore)

    2014-12-15

    Highlights: • Functionalized hybrid polymer mats fabricated for tissue engineering. • Hybrid polymer mats showed high surface area, high porosity and good wettability. • Incorporation of natural polymers modified the properties of nanofiber mats more biologically favorable for biomedical applications. - Abstract: Nanotechnology being one of the most promising technologies today shows an extremely huge potential in the field of tissue engineering to mimic the porous topography of natural extracellular matrix (ECM). Natural polymers are incorporated into the synthetic polymers to fabricate functionalized hybrid nanofibrous scaffolds, which improve cell and tissue compatibility. The present study identified the biopolymers – aloe vera, silk fibroin and curcumin incorporated into polycaprolactone (PCL) as suitable substrates for tissue engineering. Different combinations of PCL with natural polymers – PCL/aloe vera, PCL/silk fibroin, PCL/aloe vera/silk fibroin, PCL/aloe vera/silk fibroin/curcumin were electrospun into nanofibrous scaffolds. The fabricated two dimensional nanofibrous scaffolds showed high surface area, appropriate mechanical properties, hydrophilicity and porosity, required for the regeneration of diseased tissues. The nanofibrous scaffolds were characterized by Scanning electron microscope (SEM), porometry, Instron tensile tester, VCA optima contact angle measurement and FTIR to analyze the fiber diameter and morphology, porosity and pore size distribution, mechanical strength, wettability, chemical bonds and functional groups, respectively. The average fiber diameter of obtained fibers ranged from 250 nm to 350 nm and the tensile strength of PCL scaffolds at 4.49 MPa increased upto 8.3 MPa for PCL/silk fibroin scaffolds. Hydrophobicity of PCL decreased with the incorporation of natural polymers, especially for PCL/aloe vera scaffolds. The properties of as-spun nanofiber scaffolds showed their potential as promising scaffold materials in

  14. Earwigs ( Labidura riparia) mimic rotting-flesh odor to deceive vertebrate predators

    Science.gov (United States)

    Byers, John A.

    2015-08-01

    Many insects repel predators with caustic chemicals, while insects mimicking odors of wastes/dead insects to fool predators have not been documented. We found that the shore earwig, Labidura riparia (Dermaptera: Labiduridae) when bitten by anole lizards, Anolis carolinenesus, spits a rotting-flesh odor that deceives these insectivores into rejecting prey. Once a lizard attacked and rejected an earwig, the lizard did not attack another earwig during several weeks despite consuming other prey, indicating associative learning after one trial. The fetid odor was found in the head-prothorax containing salivary glands of both male and female earwigs and was comprised of ˜100 ng dimethyl disulfide and ˜600 ng dimethyl trisulfide. Nymphs had odorous sulfides after prolonged attacks by harvester ants, Pogonomyrmex rugosus, who were only deterred by the earwig's forceps. Sulfides released by the earwig are similar to odors of carrion/feces, which may be innately repulsive to some vertebrate predators. The mean initial discharge percentage (IDP) of sulfides from a cohort of earwigs was 62 %; however, IDPs of individuals were highly variable (3-99 %; mean 57 %). The discharge refill time (DRT) to refill 50 % of the earwig's allomone reservoir was estimated at 13 h. A positive relationship in sulfide amounts with body weight was found only in females in 2009, suggesting metabolic cost tradeoffs were revealed when sulfide content was half that in 2010. This is the first report of insects releasing sulfur-containing compounds that may mimic carrion-fecal odors as a deceptive defense against vertebrate predators.

  15. Functionalized hybrid nanofibers to mimic native ECM for tissue engineering applications

    International Nuclear Information System (INIS)

    Karuppuswamy, Priyadharsini; Venugopal, Jayarama Reddy; Navaneethan, Balchandar; Laiva, Ashang Luwang; Sridhar, Sreepathy; Ramakrishna, Seeram

    2014-01-01

    Highlights: • Functionalized hybrid polymer mats fabricated for tissue engineering. • Hybrid polymer mats showed high surface area, high porosity and good wettability. • Incorporation of natural polymers modified the properties of nanofiber mats more biologically favorable for biomedical applications. - Abstract: Nanotechnology being one of the most promising technologies today shows an extremely huge potential in the field of tissue engineering to mimic the porous topography of natural extracellular matrix (ECM). Natural polymers are incorporated into the synthetic polymers to fabricate functionalized hybrid nanofibrous scaffolds, which improve cell and tissue compatibility. The present study identified the biopolymers – aloe vera, silk fibroin and curcumin incorporated into polycaprolactone (PCL) as suitable substrates for tissue engineering. Different combinations of PCL with natural polymers – PCL/aloe vera, PCL/silk fibroin, PCL/aloe vera/silk fibroin, PCL/aloe vera/silk fibroin/curcumin were electrospun into nanofibrous scaffolds. The fabricated two dimensional nanofibrous scaffolds showed high surface area, appropriate mechanical properties, hydrophilicity and porosity, required for the regeneration of diseased tissues. The nanofibrous scaffolds were characterized by Scanning electron microscope (SEM), porometry, Instron tensile tester, VCA optima contact angle measurement and FTIR to analyze the fiber diameter and morphology, porosity and pore size distribution, mechanical strength, wettability, chemical bonds and functional groups, respectively. The average fiber diameter of obtained fibers ranged from 250 nm to 350 nm and the tensile strength of PCL scaffolds at 4.49 MPa increased upto 8.3 MPa for PCL/silk fibroin scaffolds. Hydrophobicity of PCL decreased with the incorporation of natural polymers, especially for PCL/aloe vera scaffolds. The properties of as-spun nanofiber scaffolds showed their potential as promising scaffold materials in

  16. AICAR stimulation metabolome widely mimics electrical contraction in isolated rat epitrochlearis muscle.

    Science.gov (United States)

    Miyamoto, Licht; Egawa, Tatsuro; Oshima, Rieko; Kurogi, Eriko; Tomida, Yosuke; Tsuchiya, Koichiro; Hayashi, Tatsuya

    2013-12-15

    Physical exercise has potent therapeutic and preventive effects against metabolic disorders. A number of studies have suggested that 5'-AMP-activated protein kinase (AMPK) plays a pivotal role in regulating carbohydrate and lipid metabolism in contracting skeletal muscles, while several genetically manipulated animal models revealed the significance of AMPK-independent pathways. To elucidate significance of AMPK and AMPK-independent signals in contracting skeletal muscles, we conducted a metabolomic analysis that compared the metabolic effects of 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside (AICAR) stimulation with the electrical contraction ex vivo in isolated rat epitrochlearis muscles, in which both α1- and α2-isoforms of AMPK and glucose uptake were equally activated. The metabolomic analysis using capillary electrophoresis time-of-flight mass spectrometry detected 184 peaks and successfully annotated 132 small molecules. AICAR stimulation exhibited high similarity to the electrical contraction in overall metabolites. Principal component analysis (PCA) demonstrated that the major principal component characterized common effects whereas the minor principal component distinguished the difference. PCA and a factor analysis suggested a substantial change in redox status as a result of AMPK activation. We also found a decrease in reduced glutathione levels in both AICAR-stimulated and contracting muscles. The muscle contraction-evoked influences related to the metabolism of amino acids, in particular, aspartate, alanine, or lysine, are supposed to be independent of AMPK activation. Our results substantiate the significance of AMPK activation in contracting skeletal muscles and provide novel evidence that AICAR stimulation closely mimics the metabolomic changes in the contracting skeletal muscles.

  17. A molecular docking study of phytochemical estrogen mimics from dietary herbal supplements.

    Science.gov (United States)

    Powers, Chelsea N; Setzer, William N

    2015-01-01

    The purpose of this study is to use a molecular docking approach to identify potential estrogen mimics or anti-estrogens in phytochemicals found in popular dietary herbal supplements. In this study, 568 phytochemicals found in 17 of the most popular herbal supplements sold in the United States were built and docked with two isoforms of the estrogen receptor, ERα and ERβ (a total of 27 different protein crystal structures). The docking results revealed six strongly docking compounds in Echinacea, three from milk thistle (Silybum marianum), three from Gingko biloba, one from Sambucus nigra, none from maca (Lepidium meyenii), five from chaste tree (Vitex agnus-castus), two from fenugreek (Trigonella foenum-graecum), and two from Rhodiola rosea. Notably, of the most popular herbal supplements for women, there were numerous compounds that docked strongly with the estrogen receptor: Licorice (Glycyrrhiza glabra) had a total of 26 compounds strongly docking to the estrogen receptor, 15 with wild yam (Dioscorea villosa), 11 from black cohosh (Actaea racemosa), eight from muira puama (Ptychopetalum olacoides or P. uncinatum), eight from red clover (Trifolium pratense), three from damiana (Turnera aphrodisiaca or T. diffusa), and three from dong quai (Angelica sinensis). Of possible concern were the compounds from men's herbal supplements that exhibited strong docking to the estrogen receptor: Gingko biloba had three compounds, gotu kola (Centella asiatica) had two, muira puama (Ptychopetalum olacoides or P. uncinatum) had eight, and Tribulus terrestris had six compounds. This molecular docking study has revealed that almost all popular herbal supplements contain phytochemical components that may bind to the human estrogen receptor and exhibit selective estrogen receptor modulation. As such, these herbal supplements may cause unwanted side effects related to estrogenic activity.

  18. A mimic of sexually-motivated homicide: insect stings and heat exhaustion in a forest.

    Science.gov (United States)

    Liu, Nancy X; Pollanen, Michael S

    2017-06-01

    We report the case a woman who was found dead in a forest. The body was nude and the position of the body suggested a sexually motivated homicide. We concluded that death was not related to homicide, but was related to the conjunction of environmental factors, including insect stings, and acute psychosis. A medicolegal death investigation with postmortem examination was undertaken to determine cause of death. At the scene, the body was supine with legs spread apart and the knees flexed, exposing the external genitalia. There were multiple apparent bruises on the body and neck. At autopsy, based on macroscopic and microscopic examination, the apparent bruises were found to be hemorrhagic insect bites. No significant injuries were present and no semen was found. Death appeared to be related to heat exhaustion and innumerable insect stings. Investigation of the medical history revealed longstanding schizoaffective disorder with episodic psychotic decompensations. In the past, during an acute psychotic episode the decedent removed her clothing and ran wildly in a forest, until she was rescued in a state of exhaustion and marked agitation, and taken to hospital for treatment. We concluded that the same circumstances had been repeated but with a fatal outcome. This case is an example of a mimic of sexually-motivated homicide and is a reminder to forensic pathologists to avoid tunnel vision. We need to be skeptical of the allure of common sense based on first impressions of the scene and the body. Forensic pathologists must be unafraid to scientifically explore improbable, but true, alternate explanations.

  19. ceRNAs in plants: computational approaches and associated challenges for target mimic research.

    Science.gov (United States)

    Paschoal, Alexandre Rossi; Lozada-Chávez, Irma; Domingues, Douglas Silva; Stadler, Peter F

    2017-05-30

    The competing endogenous RNA hypothesis has gained increasing attention as a potential global regulatory mechanism of microRNAs (miRNAs), and as a powerful tool to predict the function of many noncoding RNAs, including miRNAs themselves. Most studies have been focused on animals, although target mimic (TMs) discovery as well as important computational and experimental advances has been developed in plants over the past decade. Thus, our contribution summarizes recent progresses in computational approaches for research of miRNA:TM interactions. We divided this article in three main contributions. First, a general overview of research on TMs in plants is presented with practical descriptions of the available literature, tools, data, databases and computational reports. Second, we describe a common protocol for the computational and experimental analyses of TM. Third, we provide a bioinformatics approach for the prediction of TM motifs potentially cross-targeting both members within the same or from different miRNA families, based on the identification of consensus miRNA-binding sites from known TMs across sequenced genomes, transcriptomes and known miRNAs. This computational approach is promising because, in contrast to animals, miRNA families in plants are large with identical or similar members, several of which are also highly conserved. From the three consensus TM motifs found with our approach: MIM166, MIM171 and MIM159/319, the last one has found strong support on the recent experimental work by Reichel and Millar [Specificity of plant microRNA TMs: cross-targeting of mir159 and mir319. J Plant Physiol 2015;180:45-8]. Finally, we stress the discussion on the major computational and associated experimental challenges that have to be faced in future ceRNA studies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans

    Directory of Open Access Journals (Sweden)

    Denny Christine A

    2006-05-01

    Full Text Available Abstract Background Caloric restriction (CR has long been recognized as a dietary therapy that improves health and increases longevity. Little is known about the persistent effects of CR on plasma biomarkers (glucose, ketone bodies, and lipids following re-feeding in mice. It is also unclear how these biomarker changes in calorically restricted mice relate to those observed previously in calorically restricted humans. Results Three groups of individually housed adult female C57BL/6J (B6 mice (n = 4/group were fed a standard rodent chow diet either: (1 unrestricted (UR; (2 restricted for three weeks to reduce body weight by approximately 15–20% (R; or (3 restricted for three weeks and then re-fed unrestricted (ad libitum for an additional three weeks (R-RF. Body weight and food intake were measured throughout the study, while plasma lipids and levels of glucose and ketone bodies (β-hydroxybutyrate were measured at the termination of the study. Plasma glucose, phosphatidylcholine, cholesterol, and triglycerides were significantly lower in the R mice than in the UR mice. In contrast, plasma fatty acids and β-hydroxybutyrate were significantly higher in the R mice than in the UR mice. CR had no effect on plasma phosphatidylinositol levels. While body weight and plasma lipids of the R-RF mice returned to unrestricted levels upon re-feeding, food intake and glucose levels remained significantly lower than those prior to the initiation of CR. Conclusion CR establishes a new homeostatic state in B6 mice that persists for at least three weeks following ad libitum re-feeding. Moreover, the plasma biomarker changes observed in B6 mice during CR mimic those reported in humans on very low calorie diets or during therapeutic fasting.

  1. Somatostatin receptor 1 and 5 double knockout mice mimic neurochemical changes of Huntington's disease transgenic mice.

    Directory of Open Access Journals (Sweden)

    Padmesh S Rajput

    Full Text Available Selective degeneration of medium spiny neurons and preservation of medium sized aspiny interneurons in striatum has been implicated in excitotoxicity and pathophysiology of Huntington's disease (HD. However, the molecular mechanism for the selective sparing of medium sized aspiny neurons and vulnerability of projection neurons is still elusive. The pathological characteristic of HD is an extensive reduction of the striatal mass, affecting caudate putamen. Somatostatin (SST positive neurons are selectively spared in HD and Quinolinic acid/N-methyl-D-aspartic acid induced excitotoxicity, mimic the model of HD. SST plays neuroprotective role in excitotoxicity and the biological effects of SST are mediated by five somatostatin receptor subtypes (SSTR1-5.To delineate subtype selective biological responses we have here investigated changes in SSTR1 and 5 double knockout mice brain and compared with HD transgenic mouse model (R6/2. Our study revealed significant loss of dopamine and cAMP regulated phosphoprotein of 32 kDa (DARPP-32 and comparable changes in SST, N-methyl-D-aspartic acid receptors subtypes, calbindin and brain nitric oxide synthase expression as well as in key signaling proteins including calpain, phospho-extracellular-signal-regulated kinases1/2, synapsin-IIa, protein kinase C-α and calcineurin in SSTR1/5(-/- and R6/2 mice. Conversely, the expression of somatostatin receptor subtypes, enkephalin and phosphatidylinositol 3-kinases were strain specific. SSTR1/5 appears to be important in regulating NMDARs, DARPP-32 and signaling molecules in similar fashion as seen in HD transgenic mice.This is the first comprehensive description of disease related changes upon ablation of G- protein coupled receptor gene. Our results indicate that SST and SSTRs might play an important role in regulation of neurodegeneration and targeting this pathway can provide a novel insight in understanding the pathophysiology of Huntington's disease.

  2. Migrainous aura as stroke-mimic: The role of perfusion-computed tomography.

    Science.gov (United States)

    Ridolfi, Mariana; Granato, Antonio; Polverino, Paola; Furlanis, Giovanni; Ukmar, Maja; Zorzenon, Irene; Manganotti, Paolo

    2018-03-01

    The acute-onset of migrainuos aura (MA) can be erroneously diagnosed in Emergency Department (ED) as acute stroke (AS) and it can be classified as "stroke mimic" (SM). Perfusion computer tomography (PCT) may be useful to improve detection of infarcts. The aim of the study was to investigate the role in ED of PCT in improving diagnosis of migrainous aura. Data were compared with the well-defined perfusion patterns in patients with acute ischemic stroke. A standardized Stroke Protocol was planned. The protocol consisted in centralizing in ED all the patients with acute-onset of neurological symptoms compatible with cerebrovascular disease and in performing a general and neurological examination, hematological tests, brain non-contrast computed tomography (NCCT), CT angiography (CTA) of the supra-aortic and intracranial arteries and cerebral PCT. Patients with diagnosis of definite or probable acute stroke were hospitalized in Stroke Unit (SU). A six-months retrospective analysis of all the patients included in the Stroke Protocol and discharged from ED or from SU with a diagnosis of migraine with aura was performed. 172 patients were included in the Stroke Protocol and 6 patients were enrolled. NCCT, CTA and PCT were performed after 60-90 min from symptoms onset and revealed normal perfusion. Intravenous thrombolysis was performed only in one patient. Patients with acute-onset of neurological symptoms, who have rapid progressive improvement of symptoms, normal neuroimaging, in particular PCT, and preceding episodes of migraine with aura, may be considered as suffering from MA. In these cases, even if thrombolysis is safe, clinicians may defer a prompt aggressive treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Cirrus cloud mimic surfaces in the laboratory: organic acids, bases and NOx heterogeneous reactions

    Science.gov (United States)

    Sodeau, J.; Oriordan, B.

    2003-04-01

    CIRRUS CLOUD MIMIC SURFACES IN THE LABORATORY:ORGANIC ACIDS, BASES AND NOX HETEROGENEOUS REACTIONS. B. ORiordan, J. Sodeau Department of Chemistry and Environment Research Institute, University College Cork, Ireland j.sodeau@ucc.ie /Fax: +353-21-4902680 There are a variety of biogenic and anthropogenic sources for the simple carboxylic acids to be found in the troposphere giving rise to levels as high as 45 ppb in certain urban areas. In this regard it is of note that ants of genus Formica produce some 10Tg of formic acid each year; some ten times that produced by industry. The expected sinks are those generally associated with tropospheric chemistry: the major routes studied, to date, being wet and dry deposition. No studies have been carried out hitherto on the role of water-ice surfaces in the atmospheric chemistry of carboxylic acids and the purpose of this paper is to indicate their potential function in the heterogeneous release of atmospheric species such as HONO. The deposition of formic acid on a water-ice surface was studied using FT-RAIR spectroscopy over a range of temperatures between 100 and 165K. In all cases ionization to the formate (and oxonium) ions was observed. The results were confirmed by TPD (Temperature Programmed Desorption) measurements, which indicated that two distinct surface species adsorb to the ice. Potential reactions between the formic acid/formate ion surface and nitrogen dioxide were subsequently investigated by FT-RAIRS. Co-deposition experiments showed that N2O3 and the NO+ ion (associated with water) were formed as products. A mechanism is proposed to explain these results, which involves direct reaction between the organic acid and nitrogen dioxide. Similar experiments involving acetic acid also indicate ionization on a water-ice surface. The results are put into the context of atmospheric chemistry potentially occuring on cirrus cloud surfaces.

  4. Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.

    Science.gov (United States)

    Maini, Sabia; Fahlman, Brian M; Krol, Ed S

    2015-01-01

    Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  5. Optimized animal model to mimic the reality of stress-induced depression in the clinic.

    Science.gov (United States)

    Zhang, Yi; Wang, Yuting; Lei, Hui; Wang, Lei; Xue, Liang; Wang, Xin; Zhu, Xiongzhao

    2017-05-06

    Animal models are useful tools for verifying the relationship between stress and depression; however, an operational criterion for excluding the resilient animals from the analysis has not been established yet, which hinders the model's ability to more accurately mimic the scenario in humans. To induce depression-like symptoms, rats received maternal deprivation (MD) during PND1-14, and/or chronic unpredictable stress (CUS) exposure. The latent profile analysis (LPA) was used to determine latent subgroups in treatment naive adult rats. The percentile method was used to distinguish sensitive and non-sensitive behaviors in rats. The sucrose preference rate of treatment naive adult rats was fit using a Beta distribution, while immobility time was fit using a Gamma distribution. Indexes of behavioral tests revealed the 4-class model as the best fit for treatment naive adult rats. The incidence of stress-resilience in MD rats was significantly higher than that in CUS rats and MD + CUS rats. There was a significantly higher incidence of stress-resilience in CUS rats compared with MD + CUS rats. Recovery rate of anhedonia-like and sub anhedonia-like behaviors in CUS rats was significantly higher than that in MD and MD + CUS rats. There was a significantly higher recovery rate of anhedonia-like behaviors in MD rats compared to MD + CUS rats. The percentile method is suitable for setting up an operational cutoff to classify depression-like, sub depression-like, and resilient behaviors in rats exposed to MD and CUS.

  6. The glutathione mimic ebselen inhibits oxidative stress but not endoplasmic reticulum stress in endothelial cells.

    Science.gov (United States)

    Ahwach, Salma Makhoul; Thomas, Melanie; Onstead-Haas, Luisa; Mooradian, Arshag D; Haas, Michael J

    2015-08-01

    Reactive oxygen species are associated with cardiovascular disease, diabetes, and atherosclerosis, yet the use of antioxidants in clinical trials has been ineffective at improving outcomes. In endothelial cells, high-dextrose-induced oxidative stress and endoplasmic reticulum stress promote endothelial dysfunction leading to the recruitment and activation of peripheral blood lymphocytes and the breakdown of barrier function. Ebselen, a glutathione peroxidase 1 (GPX1) mimic, has been shown to improve β-cell function in diabetes and prevent atherosclerosis. To determine if ebselen inhibits both oxidative stress and endoplasmic reticulum (ER) stress in endothelial cells, we examined its effects in human umbilical vein endothelial cells (HUVEC) and human coronary artery endothelial cells (HCAEC) with and without high-dextrose. Oxidative stress and ER stress were measured by 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence and ER stress alkaline phosphatase assays, respectively. GPX1 over-expression and knockdown were performed by transfecting cells with a GPX1 expression construct or a GPX1-specific siRNA, respectively. Ebselen inhibited dextrose-induced oxidative stress but not ER stress in both HUVEC and HCAEC. Ebselen also had no effect on tunicamycin-induced ER stress in HCAEC. Furthermore, augmentation of GPX1 activity directly by sodium selenite supplementation or transfection of a GPX1 expression plasmid decreased dextrose-induced oxidative stress but not ER stress, while GPX1 knockout enhanced oxidative stress but had no effect on ER stress. These results suggest that ebselen targets only oxidative stress but not ER stress. Copyright © 2015. Published by Elsevier Inc.

  7. Minimal methylation classifier (MIMIC): A novel method for derivation and rapid diagnostic detection of disease-associated DNA methylation signatures.

    Science.gov (United States)

    Schwalbe, E C; Hicks, D; Rafiee, G; Bashton, M; Gohlke, H; Enshaei, A; Potluri, S; Matthiesen, J; Mather, M; Taleongpong, P; Chaston, R; Silmon, A; Curtis, A; Lindsey, J C; Crosier, S; Smith, A J; Goschzik, T; Doz, F; Rutkowski, S; Lannering, B; Pietsch, T; Bailey, S; Williamson, D; Clifford, S C

    2017-10-18

    Rapid and reliable detection of disease-associated DNA methylation patterns has major potential to advance molecular diagnostics and underpin research investigations. We describe the development and validation of minimal methylation classifier (MIMIC), combining CpG signature design from genome-wide datasets, multiplex-PCR and detection by single-base extension and MALDI-TOF mass spectrometry, in a novel method to assess multi-locus DNA methylation profiles within routine clinically-applicable assays. We illustrate the application of MIMIC to successfully identify the methylation-dependent diagnostic molecular subgroups of medulloblastoma (the most common malignant childhood brain tumour), using scant/low-quality samples remaining from the most recently completed pan-European medulloblastoma clinical trial, refractory to analysis by conventional genome-wide DNA methylation analysis. Using this approach, we identify critical DNA methylation patterns from previously inaccessible cohorts, and reveal novel survival differences between the medulloblastoma disease subgroups with significant potential for clinical exploitation.

  8. Single helically folded aromatic oligoamides that mimic the charge surface of double-stranded B-DNA

    Science.gov (United States)

    Ziach, Krzysztof; Chollet, Céline; Parissi, Vincent; Prabhakaran, Panchami; Marchivie, Mathieu; Corvaglia, Valentina; Bose, Partha Pratim; Laxmi-Reddy, Katta; Godde, Frédéric; Schmitter, Jean-Marie; Chaignepain, Stéphane; Pourquier, Philippe; Huc, Ivan

    2018-05-01

    Numerous essential biomolecular processes require the recognition of DNA surface features by proteins. Molecules mimicking these features could potentially act as decoys and interfere with pharmacologically or therapeutically relevant protein-DNA interactions. Although naturally occurring DNA-mimicking proteins have been described, synthetic tunable molecules that mimic the charge surface of double-stranded DNA are not known. Here, we report the design, synthesis and structural characterization of aromatic oligoamides that fold into single helical conformations and display a double helical array of negatively charged residues in positions that match the phosphate moieties in B-DNA. These molecules were able to inhibit several enzymes possessing non-sequence-selective DNA-binding properties, including topoisomerase 1 and HIV-1 integrase, presumably through specific foldamer-protein interactions, whereas sequence-selective enzymes were not inhibited. Such modular and synthetically accessible DNA mimics provide a versatile platform to design novel inhibitors of protein-DNA interactions.

  9. Phenol degradation catalyzed by a peroxidase mimic constructed through the grafting of heme onto metal-organic frameworks.

    Science.gov (United States)

    Jiang, Wei; Yang, Jiebing; Wang, Xinghuo; Han, Haobo; Yang, Yan; Tang, Jun; Li, Quanshun

    2018-01-01

    The aim of this work was to construct a peroxidase mimic for achieving the phenol degradation through Fenton reaction. The enzyme mimic was synthesized through the conjugation of heme with the amino group of 2-amino-1,4-benzene dicarboxylate in UiO-66-NH 2 (ZrMOF), namely Heme-ZrMOF. Compared to free heme, the composite Heme-ZrMOF exhibited an obviously enhanced ability for phenol degradation with up to 97.3% of phenol removal after 2h. Meanwhile, it could achieve the easy separation of catalyst from the system and the elimination of iron residues in the process of phenol degradation. Finally, the catalyst Heme-ZrMOF was observed to possess good recyclability in the phenol degradation with still 76.2% of phenol removal after 4 cycles. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Biocompatible Polymer Nanoformulation To Improve the Release and Safety of a Drug Mimic Molecule Detectable via ICP-MS.

    Science.gov (United States)

    Ferrari, Raffaele; Talamini, Laura; Violatto, Martina Bruna; Giangregorio, Paola; Sponchioni, Mattia; Morbidelli, Massimo; Salmona, Mario; Bigini, Paolo; Moscatelli, Davide

    2017-01-03

    Fluorescent poly(ε-caprolactone)-based nanoparticles (NPs) have been synthesized and successfully loaded with a titanium organometallic compound as a mimic of a water-insoluble drug. The nature of this nanovector enabled us to combine the quantification of the metal in tissues after systemic administration in healthy immunocompetent mice by inductively coupled plasma mass spectroscopy (ICP-MS) followed by the visualization of NPs in organ sections by confocal microscopy. This innovative method of nanodrug screening has enabled us to elucidate the crucial parameters of their kinetics. The organometallic compound is a good mimic of most anticancer drugs, and this approach is an interesting starting point to design the relevance of a broad range of nanoformulations in terms of safety and targeted delivery of the cargoes.

  11. Simultaneous Vascular Targeting and Tumor Targeting of Cerebral Breast Cancer Metastases Using a T-Cell Receptor Mimic Antibody

    Science.gov (United States)

    2014-05-01

    in May 2013, the difference between nude mice (which lack T- cells , but still have a partially functional adaptive and innate immune system) and NSG...Mangada J, Greiner DL, Handgretinger R. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human...Targeting of Cerebral Breast Cancer Metastases Using a T- Cell Receptor Mimic Antibody PRINCIPAL INVESTIGATOR: Ulrich Bickel

  12. 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.

  13. A latex agglutination test for the field determination of abnormal vitellogenin production in male fishes contaminated by estrogen mimics

    International Nuclear Information System (INIS)

    Magalhaes, Ilizabete; Pihan, Jean-Claude; Falla, Jairo

    2004-01-01

    Estrogen mimics are pollutants present in the aquatic environment. These compounds induce abnormalities in the reproductive system of male fishes, which lead to a total or partial male feminization, or to their demasculinization. Ultimately, these alterations could lead to a disappearance of the total contaminated fish population. Moreover, these toxic substances possess the capacity to mimic endogenous estrogens and to induce the abnormal production of vitellogenin (VTG) in male and immature fishes. The purpose of this research was to develop an easy, specific, cheap and fast method for diagnosing the contamination of male fishes by estrogen mimics, using VTG as biomarker. The selected method is based on a reverse latex agglutination test (rLAT), developed with monoclonal antibodies specific of this biomarker. The development of this VTG-rLAT has involved, firstly, the purification of carp VTG to produce monoclonal antibodies, specifics of this protein. One of these antibodies was selected to recover latex particles (diameter: 1 μm). Finally, the immunoreactivity of the VTG-rLAT was verified with different fish plasma samples from males treated with 17β-estradiol and non-treated males or females in vitellogenesis

  14. Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death

    Directory of Open Access Journals (Sweden)

    Sijia Liu

    2017-06-01

    Full Text Available Switchgrass (Panicum virgatum has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O-methyltransferase (COMT, a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT-deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

  15. Skin lesions over the pocket area that may mimic cardiac implantable electronic device infection: A case series.

    Science.gov (United States)

    Korantzopoulos, Panagiotis; Plakoutsi, Sofia; Florou, Elizabeth; Bechlioulis, Aris

    2018-05-21

    The early and correct diagnosis of cardiac implantable electronic device (CIED) infections is critical given that early aggressive treatment with complete removal of the system along with antimicrobial therapy dramatically improves outcomes. Pocket infection manifested by local signs of inflammation is the most common form of CIED infections. Conditions mimicking pocket infection have been described in the literature. These include various types of malignancy and rarely allergic reactions/contact dermatitis to pacemaker compounds. We aimed to describe skin lesions and disorders over the pocket area that mimic CIED infection. We present a series of 5 cases with skin lesions that mimic pocket infection. We document these cases with corresponding photographs. Most of them have not been described in this setting. We report the following cases of conditions that proved not to be CIED infection: One case of superficial cellulitis, one case of herpes zoster over the pocket area, one case of spontaneous bruising over the pocket a long time after implantation in a patient taking oral anticoagulation, and 2 cases of contact dermatitis due to prolonged postoperative application of povidone iodine. All cases had favorable outcome after conservative treatment and no CIED infection was developed during follow-up. Clinicians should be aware of rare conditions that mimic CIED infection. Incorrect diagnosis of these disorders may falsely lead to CIED extraction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Simultaneous Downregulation of MTHFR and COMT in Switchgrass Affects Plant Performance and Induces Lesion-Mimic Cell Death.

    Science.gov (United States)

    Liu, Sijia; Fu, Chunxiang; Gou, Jiqing; Sun, Liang; Huhman, David; Zhang, Yunwei; Wang, Zeng-Yu

    2017-01-01

    Switchgrass ( Panicum virgatum ) has been developed into a model lignocellulosic bioenergy crop. Downregulation of caffeic acid O -methyltransferase (COMT), a key enzyme in lignin biosynthesis, has been shown to alter lignification and increase biofuel yield in switchgrass. Methylenetetrahydrofolate reductase (MTHFR) mediates C1 metabolism and provides methyl units consumed by COMT. It was predicted that co-silencing of MTHFR and COMT would impact lignification even more than either of the single genes. However, our results showed that strong downregulation of MTHFR in a COMT -deficient background led to altered plant growth and development, but no significant change in lignin content or composition was found when compared with COMT plants. Another unexpected finding was that the double MTHFR/COMT downregulated plants showed a novel lesion-mimic leaf phenotype. Molecular analyses revealed that the lesion-mimic phenotype was caused by the synergistic effect of MTHFR and COMT genes, with MTHFR playing a predominant role. Microarray analysis showed significant induction of genes related to oxidative and defense responses. The results demonstrated the lack of additive effects of MTHFR and COMT on lignification. Furthermore, this research revealed an unexpected role of the two genes in the modulation of lesion-mimic cell death as well as their synergistic effects on agronomic performance.

  17. Characteristics and genetic mapping of a lesion mimic mutant pl(t) in japonica rice variety zhejing 22

    International Nuclear Information System (INIS)

    Chen Pingping; Zhang Xiaoming; Ye Shenghai; Zhao Ningchun; Lu Yanting; Liu Heqin; Jin Qingsheng; Yang Ling

    2010-01-01

    A lesion mimic mutant,obtained by radiation mutagenesis on the seeds of a japonica rice variety Zhejing 22, exhibited a lesion mimic phenotype during the whole growth stage under different environments. Genetic analysis indicated that the mutant trait was controlled by a single recessive gene named spl (t). Relying on simple sequence repeat (SSR) and recessive class analysis method to map the spl (t) gene with a F 2 population was constructed by crossing the mutant spl (t) with Zhenshan 97B.spl (t) was mapped in the interval of 0.8cM between RM7195 and RM27929 near centromere region on the short arm of chromosome 12.Blue trypan dye analyses indicated that the lesion mimic trait of the mutant was caused by the programmer cell death. Further study showed that the programmer cell death was caused by H 2 O 2 oxidative burst. By inoculation of bacterial leaf blight and blast strains, the resistances of the mutant were similar to the wild variety Zhejing 22. (authors)

  18. A peroxidase mimic with atom transfer radical polymerization activity constructed through the grafting of heme onto metal-organic frameworks.

    Science.gov (United States)

    Jiang, Wei; Pan, Yue; Yang, Jiebing; Liu, Yong; Yang, Yan; Tang, Jun; Li, Quanshun

    2018-07-01

    Atom transfer radical polymerization (ATRP) has been considered to be an efficient strategy for constructing functional macromolecules owing to its simple operation and versatile monomers, and thus it is of great significance to develop ideal catalysts with higher activity and perfect reusability. We constructed a peroxidase mimic through the grafting of heme onto metal-organic frameworks UiO-66-NH 2 (ZrMOF), namely Heme-ZrMOF. After the systematic characterization of structure, the composite Heme-ZrMOF was demonstrated to possess high peroxidase activity using 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) and 3,3',5,5'-tetramethylbenzidine as substrates. The enzyme mimic was then used as catalysts in the ATRP reactions of different monomers, in which favorable monomer conversion (44.6-98.0%) and product molecular weight (8600-25,600 g/mol) could be obtained. Compared to free heme, Heme-ZrMOF could efficiently achieve the easy separation of heme from the catalytic system and facilitate the ATRP reaction in an aqueous environment to avoid the utilization of organic solvents. In conclusion, the enzyme mimic Heme-ZrMOF could be potentially used as an effective catalyst for preparing well-defined polymers with biomedical applications. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Antioxidant activity of selenenamide-based mimic as a function of the aromatic thiols nucleophilicity, a DFT-SAPE model.

    Science.gov (United States)

    Kheirabadi, Ramesh; Izadyar, Mohammad

    2018-05-18

    The mechanism of action of the selenenamide 1 as a mimic of the glutathione peroxidase (GPx) was investigated by the density functional theory. The solvent-assisted proton exchange procedure was applied to model the catalytic behavior and antioxidant activity of this mimic. To have an insight into the charge transfer effect, different aromatic thiols, including electron donating substituents on the phenyl ring were considered. The catalytic behavior of the selenenamide was modeled in a four-step mechanism, described by the oxidation of the mimic, the reduction of the obtained product, selenoxide, the reduction of the selenenylsulfide and dehydration of selenenic acid. On the basis of the activation parameters, the final step of the proposed mechanism is the rate determining states of the catalytic cycle. Turnover frequency (TOF) analysis showed that the electron donating groups at the para-position of the phenyl ring of the PhSH do not affect the catalytic activity of the selenenamide in contrast to p-methyl thiophenol which indicates the highest nucleophilicity. The evaluation of the electronic contribution of the various donating groups on the phenyl ring of the aromatic thiols shows that the antioxidant activity of the selenenamide sufficiently increases in the presence of the electron-donating substitutions. Finally, the charge transfer process at the rate-determining state was investigated based on the natural bond orbital analysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food.

    Science.gov (United States)

    Goldstone, Anthony P; Prechtl, Christina G; Scholtz, Samantha; Miras, Alexander D; Chhina, Navpreet; Durighel, Giuliana; Deliran, Seyedeh S; Beckmann, Christian; Ghatei, Mohammad A; Ashby, Damien R; Waldman, Adam D; Gaylinn, Bruce D; Thorner, Michael O; Frost, Gary S; Bloom, Stephen R; Bell, Jimmy D

    2014-06-01

    Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food. In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data. Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task. Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food

  1. Various clinical conditions can mimic Crimean-Congo hemorrhagic fever in pediatric patients in endemic regions

    Directory of Open Access Journals (Sweden)

    Soner S. Kara

    2016-09-01

    Full Text Available Summary: Crimean-Congo hemorrhagic fever (CCHF is a tick-borne disease with high mortality. Many disorders can mimic CCHF. It is important to recognize the condition and to perform differential diagnosis in endemic countries. Twenty-one children aged 18 years or less with a preliminary diagnosis of CCHF were retrospectively evaluated. Real-time PCR and a confirmatory indirect immunofluorescence assay for negative results were performed. The diagnoses determined that 9 patients had (42.9% CCHF; 7 patients had (33.3% viral upper respiratory tract infections (URTI; 2 patients had (9.5% brucellosis; 1 patients had (4.7% periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA syndrome episode; 1 patient had (4.7% cerebral palsy, diabetes insipidus, acute gastroenteritis, and hypernatremic dehydration; and 1 patient had (4.7% cellulitis after a tick bite. The mean age of patients with CCHF was greater than that of the other patients (116.1 ± 53.6 vs. 94.1 ± 52.1 months, p = 0.02. Seventeen (81% of the children included had a history of tick bites, 2 (9.5% had a history of contact with a patient with CCHF, and 2 (9.5% had no exposure, but were living in an endemic region. Three patients had an underlying disorder: cerebral palsy and diabetes insipidus, epilepsy, or PFAPA. All of the children experienced fever. Other frequent symptoms were malaise, diarrhea, vomiting, and abdominal pain, but none of these differed statistically between the patient groups. CCHF patients had a longer mean duration of symptoms (10.56 ± 1.42 vs. 6.75 ± 3.62 days, p = 0.008 and a longer mean length of hospitalization (8.00 ± 2.08 vs. 3.58 ± 1.56 days, p < 0.001 than the other patients. At laboratory examination, patients with CCHF had statistically significant lower leukocyte and platelet counts, more prolonged coagulation parameters, and greater AST, ALT, LDH, and CK levels than the other patients. No mortality or complications occurred

  2. Face, content and concurrent validity of the Mimic® dV-Trainer for robot-assisted endoscopic surgery: a prospective study.

    Science.gov (United States)

    Egi, H; Hattori, M; Tokunaga, M; Suzuki, T; Kawaguchi, K; Sawada, H; Ohdan, H

    2013-01-01

    The aim of this study was to determine whether any correlation exists between the performance of the Mimic® dV-Trainer (Mimic Technologies, Seattle, Wash., USA) and the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, Calif., USA). Twelve participants were recruited, ranging from residents to consultants. We used four training tasks, consisting of 'Pick and Place', 'Peg Board', 'Thread the Rings' and 'Suture Sponge', from the software program of the Mimic dV-Trainer. The performance of the participants was recorded and measured. Additionally, we prepared the same tasks for the da Vinci Surgical System. All participants completed the tasks using the da Vinci Surgical System and were assessed according to time, the Objective Structured Assessment of Technical Skill checklist and the global rating score for endoscopic suturing assessed by two independent blinded observers. After performing these tasks, the participants completed a questionnaire that evaluated the Mimic dV-Trainer's face and content validity. The final results for each participant for the Mimic dV-Trainer and the da Vinci Surgical System were compared. All participants ranked the Mimic dV-Trainer as a realistic training platform that is useful for residency training. There was a significant relationship between the Mimic dV-Trainer and the da Vinci Surgical System in all four tasks. We verified the reliability of the assessment of the checklist and the global rating scores for endoscopic suturing assessed by the two blinded observers using Cronbach's alpha test (r = 0.803, 0.891). We evaluated the concurrent validity of the Mimic dV-Trainer and the da Vinci Surgical System. Our results suggest the possibility that training using the Mimic dV-Trainer may therefore be able to improve the operator's performance during live robot-assisted surgery. © 2013 S. Karger AG, Basel.

  3. GTP plus water mimics ATP in the active site of protein kianse CK2

    DEFF Research Database (Denmark)

    Niefind, K; Pütter, M; Guerra, B

    1999-01-01

    The structures of the catalytic subunit of protein kinase CK2 from Zea mays complexed with Mg2+ and with analogs of ATP or GTP were determined to 2.2 A resolution. Unlike most other protein kinases, CK2 from various sources shows 'dual-cosubstrate specificity', that is, the ability to efficiently...... use either ATP or GTP as a cosubstrate. The structures of these complexes demonstrate that water molecules are critical to switch the active site of CK2 from an ATP- to a GTP-compatible state. An understanding of the structural basis of dual-cosubstrate specificity may help in the design of drugs...

  4. (II) complexes

    African Journals Online (AJOL)

    activities of Schiff base tin (II) complexes. Neelofar1 ... Conclusion: All synthesized Schiff bases and their Tin (II) complexes showed high antimicrobial and ...... Singh HL. Synthesis and characterization of tin (II) complexes of fluorinated Schiff bases derived from amino acids. Spectrochim Acta Part A: Molec Biomolec.

  5. Testicular hemorrhage, necrosis, and vasculopathy: likely manifestations of intermittent torsion that clinically mimic a neoplasm.

    Science.gov (United States)

    Kao, Chia-Sui; Zhang, Chen; Ulbright, Thomas M

    2014-01-01

    parenchyma in all 30 cases. Clinical follow-up in 20 patients (4 to 131 mo, mean 38 mo) showed no evidence of recurrence in the contralateral testis or later development of systemic vasculitis. The histologic findings were compared with those in 11 orchiectomies resected for clinical acute torsion. All clinical acute torsion cases showed both parenchymal and fibrinoid vascular necrosis, and 10 had hemorrhage/hematoma; they lacked vasculitis, interstitial inflammation, and chronic vascular changes. Testicular vasculopathy, characterized by acute and chronic vascular injury, commonly occurs in testes with parenchymal hemorrhage and necrosis that clinically mimic a tumor. It shares the acute features of recent torsion but also has findings indicative of chronic injury. Testicular vasculopathy is most likely a result of chronic intermittent torsion that leads to localized hemorrhage/necrosis and should be distinguished from cases of systemic vasculitis given the significantly different clinical implications.

  6. Communication complexity and information complexity

    Science.gov (United States)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  7. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

    Science.gov (United States)

    Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-Ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D; Asano, Katsura

    2016-10-14

    ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. 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.

  9. A non-covalent peptide-based carrier for in vivo delivery of DNA mimics

    OpenAIRE

    Morris, May C.; Gros, Edwige; Aldrian-Herrada, Gudrun; Choob, Michael; Archdeacon, John; Heitz, Frederic; Divita, Gilles

    2007-01-01

    The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficien...

  10. Autophagy and apoptosis are differentially induced in neurons and astrocytes treated with an in vitro mimic of the ischemic penumbra.

    Directory of Open Access Journals (Sweden)

    Matthew E Pamenter

    Full Text Available The development of clinical stroke therapies remains elusive. The neuroprotective efficacies of thousands of molecules and compounds have not yet been determined; however, screening large volumes of potential targets in vivo is severely rate limiting. High throughput screens (HTS may be used to discover promising candidates, but this approach has been hindered by the lack of a simple in vitro model of the ischemic penumbra, a clinically relevant region of stroke-afflicted brain. Recently, our laboratory developed such a mimic (ischemic solution: IS suitable for HTS, but the etiology of stress pathways activated by this model are poorly understood. The aim of the present study was to determine if the cell death phenotype induced by IS accurately mimics the in vivo penumbra and thus whether our model system is suitable for use in HTS. We treated cultured neuron and astrocyte cell lines with IS for up to 48 hrs and examined cellular energy state ([ATP], cell and organelle morphology, and gene and molecular profiles related to stress pathways. We found that IS-treated cells exhibited a phenotype of mixed apoptosis/autophagy characteristic of the in vivo penumbra, including: (1 short-term elevation of [ATP] followed by progressive ATP depletion and Poly ADP Ribose Polymerase cleavage, (2 increased vacuole number in the cytoplasm, (3 mitochondrial rupture, decreased mitochondrial and cristae density, release of cytochrome C and apoptosis inducing factor, (4 chromatin condensation, nuclear lamin A and DNA cleavage, fragmentation of the nuclear envelope, and (5 altered expression of mRNA and proteins consistent with autophagy and apoptosis. We conclude that our in vitro model of the ischemic penumbra induces autophagy and apoptosis in cultured neuron and astrocyte cell lines and that this mimic solution is suitable for use in HTS to elucidate neuroprotective candidates against ischemic penumbral cell death.

  11. Live Cell Imaging Reveals Differential Modifications to Cytoplasmic Dynein Properties by Phospho- and Dephospho-mimic Mutations of the Intermediate Chain 2C S84

    Science.gov (United States)

    Blasier, Kiev R.; Humsi, Michael K.; Ha, Junghoon; Ross, Mitchell W.; Smiley, W. Russell; Inamdar, Nirja A.; Mitchell, David J.; Lo, Kevin W.-H.; Pfister, K. Kevin

    2014-01-01

    Cytoplasmic dynein is a multi-subunit motor protein responsible for intracellular cargo transport toward microtubule minus ends. There are multiple isoforms of the dynein intermediate chain (DYNC1I, IC) which is encoded by two genes. One way to regulate cytoplasmic dynein is by IC phosphorylation. The IC-2C isoform is expressed in all cells and the functional significance of phosphorylation on IC-2C serine 84 was investigated using live cell imaging of fluorescent protein-tagged wild type IC-2C (WT) and phospho- and dephospho-mimic mutant isoforms in axonal transport model systems. Both mutations modulated dynein functional properties. The dephospho-mimic mutant IC-2C S84A had greater co-localization with mitochondria than IC-2C wild-type (WT) or the phospho-mimic mutant IC-2C S84D. The dephospho-mimic mutant IC-2C S84A was also more likely to be motile than the phospho-mimic mutant IC-2C S84D or IC-2C WT. In contrast, the phospho-mimic mutant IC-2C S84D mutant was more likely to move in the retrograde direction than was the IC-2C S84A mutant. The phospho-mimic IC-2C S84D was also as likely as IC-2C WT to co-localize with mitochondria. Both the S84D phospho- and S84A, dephospho-mimic mutants were found to be capable of microtubule minus end directed (retrograde) movement in axons. They were also observed to be passively transported in the anterograde direction. These data suggest that the IC-2C S84 has a role in modulating dynein properties. PMID:24798412

  12. New synthesis of a stereoisomeric mixture of methyl 12-trishomofarnesoate, a juvenile hormone mimic useful in sericulture by increasing silk production.

    Science.gov (United States)

    Mori, Kenji

    2017-01-01

    A mixture of (E,Z)-isomers of methyl 12-trishomofarnesoate (methyl 3,7,11-trimethyl-2,6,10-pentadecatrienoate), a juvenile hormone mimic, was synthesized in nine steps (32.6% overall yield) by starting from only four commercially available materials: 2-hexanone, vinylmagnesium bromide, methyl acetoacetate and trimethyl phosphonoacetate. The mimic is useful in increasing the yield of silk by elongating the larval period of the silkworm, Bombyx mori (L.).

  13. Walk-related mimic word activates the extrastriate visual cortex in the human brain: an fMRI study.

    Science.gov (United States)

    Osaka, Naoyuki

    2009-03-02

    I present an fMRI study demonstrating that a mimic word highly suggestive of human walking, heard by the ear with eyes closed, significantly activates the visual cortex located in extrastriate occipital region (BA19, 18) and superior temporal sulcus (STS) while hearing non-sense words that do not imply walk under the same task does not activate these areas in humans. I concluded that BA19 and 18 would be a critical region for generating visual images of walking and related intentional stance, respectively, evoked by an onomatopoeia word that implied walking.

  14. Development of 3D out-of-plane SU-8 microlenses using modified micromolding in capillaries (MIMIC) technology

    Science.gov (United States)

    Llobera, A.; Wilke, R.; Johnson, D. W.; Büttgenbach, S.

    2006-04-01

    This paper describes a modification of the standard MIMIC technology, solving its main drawbacks, to define arrays of spherical or ellipsoidal microlenses. Perfectly symmetrical meniscuses have been obtained by using a XP SU-8 NO-2 layer beneath the PDMS mold. Moreover, the photostructurable properties of this polymer allow obtaining self-alignment structures for adequate fiber optics positioning. Microchannels ended with these meniscuses have been filled with standard SU-8 to obtain 3D microlenses. Agreement between theory and experimental results allows confirming the validity of the proposed technology.

  15. MIMIC-compatible GaAs and InP field effect controlled transferred electron (FECTED) oscillators

    Science.gov (United States)

    Scheiber, Helmut; Luebke, Kurt; Diskus, Christian G.; Thim, Hartwig W.; Gruetzmacher, D.

    1989-12-01

    A MIMIC-(millimeter and microwave integrated circuit) compatible transferred electron oscillator is investigated which utilizes the frequency-independent negative resistance of the stationary charge dipole domain that forms in the channel of a MESFET. The device structure, analysis, and simulation are described. Devices fabricated from GaAs and InP exhibit very high power levels of 56 mW at 29 GHz and 55 mW at 34 GHz, respectively. Continuous wave power levels are somewhat lower (30 mW).

  16. Complexity Plots

    KAUST Repository

    Thiyagalingam, Jeyarajan

    2013-06-01

    In this paper, we present a novel visualization technique for assisting the observation and analysis of algorithmic complexity. In comparison with conventional line graphs, this new technique is not sensitive to the units of measurement, allowing multivariate data series of different physical qualities (e.g., time, space and energy) to be juxtaposed together conveniently and consistently. It supports multivariate visualization as well as uncertainty visualization. It enables users to focus on algorithm categorization by complexity classes, while reducing visual impact caused by constants and algorithmic components that are insignificant to complexity analysis. It provides an effective means for observing the algorithmic complexity of programs with a mixture of algorithms and black-box software through visualization. Through two case studies, we demonstrate the effectiveness of complexity plots in complexity analysis in research, education and application. © 2013 The Author(s) Computer Graphics Forum © 2013 The Eurographics Association and Blackwell Publishing Ltd.

  17. Complexity Theory

    Science.gov (United States)

    Lee, William H K.

    2016-01-01

    A complex system consists of many interacting parts, generates new collective behavior through self organization, and adaptively evolves through time. Many theories have been developed to study complex systems, including chaos, fractals, cellular automata, self organization, stochastic processes, turbulence, and genetic algorithms.

  18. 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.

  19. Testing Group Mean Differences of Latent Variables in Multilevel Data Using Multiple-Group Multilevel CFA and Multilevel MIMIC Modeling.

    Science.gov (United States)

    Kim, Eun Sook; Cao, Chunhua

    2015-01-01

    Considering that group comparisons are common in social science, we examined two latent group mean testing methods when groups of interest were either at the between or within level of multilevel data: multiple-group multilevel confirmatory factor analysis (MG ML CFA) and multilevel multiple-indicators multiple-causes modeling (ML MIMIC). The performance of these methods were investigated through three Monte Carlo studies. In Studies 1 and 2, either factor variances or residual variances were manipulated to be heterogeneous between groups. In Study 3, which focused on within-level multiple-group analysis, six different model specifications were considered depending on how to model the intra-class group correlation (i.e., correlation between random effect factors for groups within cluster). The results of simulations generally supported the adequacy of MG ML CFA and ML MIMIC for multiple-group analysis with multilevel data. The two methods did not show any notable difference in the latent group mean testing across three studies. Finally, a demonstration with real data and guidelines in selecting an appropriate approach to multilevel multiple-group analysis are provided.

  20. Diversification patterns of pebble-mimic dragons are consistent with historical disruption of important habitat corridors in arid Australia.

    Science.gov (United States)

    Shoo, L P; Rose, R; Doughty, P; Austin, J J; Melville, J

    2008-08-01

    The pebble-mimic dragon lineage of Tympanocryptis is widely distributed in the stony, or 'gibber', deserts of Australia but is noticeably absent from intersecting areas of sand deserts. Past fluctuations in the extent and configuration of sandy desert habitat barriers are likely to have been an import factor promoting genetic differentiation in this group. We sequenced a approximately 1400bp region of mitochondrial DNA and a approximately 1400bp nuclear gene (RAG-1) to investigate phylogeographic structuring of species of pebble-mimic dragons. Our topology indicates an early split in this lineage between eastern and western parts of the arid zone that probably dates to the mid-Miocene. This split corresponds directly with large expanses of contemporary sandy habitat in the form of Great Sandy and Great Victoria Deserts. Our data indicate that this biogeographic barrier established very early on in the development of the arid zone and has persisted to present. Additional genetic structuring in the absence of recognized barriers suggests that an expanded view of potential habitat barriers in the arid zone is required.

  1. Nacre-mimic Reinforced Ag@reduced Graphene Oxide-Sodium Alginate Composite Film for Wound Healing.

    Science.gov (United States)

    Yan, Xu; Li, Fei; Hu, Kang-Di; Xue, Jingzhe; Pan, Xiao-Feng; He, Tao; Dong, Liang; Wang, Xiang-Ying; Wu, Ya-Dong; Song, Yong-Hong; Xu, Wei-Ping; Lu, Yang

    2017-10-23

    With the emerging of drug-resistant bacterial and fungal pathogens, there raise the interest of utilizing versatile antimicrobial biomaterials to treat the acute wound. Herein, we report the spraying mediated assembly of a bio-inspired Ag@reduced graphene-sodium alginate (AGSA) composite film for effective wound healing. The obtained film displayed lamellar microstructures similar to the typical "brick-and-mortar" structure in nacre. In this nacre-mimic structure, there are abundant interfacial interactions between nanosheets and polymeric matrix, leading to remarkable reinforcement. As a result, the tensile strength, toughness and Young's modulus have been improved 2.8, 2.3 and 2.7 times compared with pure sodium alginate film, respectively. In the wound healing study, the AGSA film showed effective antimicrobial activities towards Pseudomonas aeruginosa, Escherichia coli and Candida albicans, demonstrating the ability of protecting wound from pathogenic microbial infections. Furthermore, in vivo experiments on rats suggested the effect of AGSA film in promoting the recovery of wound sites. According to MTT assays, heamolysis evaluation and in vivo toxicity assessment, the composite film could be applied as a bio-compatible material in vitro and in vivo. Results from this work indicated such AGSA film has promising performance for wound healing and suggested great potential for nacre-mimic biomaterials in tissue engineering applications.

  2. [Establishment of a 3D finite element model of human skull using MSCT images and mimics software].

    Science.gov (United States)

    Huang, Ping; Li, Zheng-dong; Shao, Yu; Zou, Dong-hua; Liu, Ning-guo; Li, Li; Chen, Yuan-yuan; Wan, Lei; Chen, Yi-jiu

    2011-02-01

    To establish a human 3D finite element skull model, and to explore its value in biomechanics analysis. The cadaveric head was scanned and then 3D skull model was created using Mimics software based on 2D CT axial images. The 3D skull model was optimized by preprocessor along with creation of the surface and volume meshes. The stress changes, after the head was struck by an object or the head hit the ground directly, were analyzed using ANSYS software. The original 3D skull model showed a large number of triangles with a poor quality and high similarity with the real head, while the optimized model showed high quality surface and volume meshes with a small number of triangles comparatively. The model could show the local and global stress changes effectively. The human 3D skull model can be established using MSCT and Mimics software and provides a good finite element model for biomechanics analysis. This model may also provide a base for the study of head stress changes following different forces.

  3. The Small Glutathione Peroxidase Mimic 5P May Represent a New Strategy for the Treatment of Liver Cancer.

    Science.gov (United States)

    Yin, Juxin; Wang, Bingmei; Zhu, Xuejun; Qu, Xiaonan; Huang, Yi; Lv, Shaowu; Mu, Ying; Luo, Guimin

    2017-09-08

    Glutathione peroxidase (GPx) is an antioxidant protein containing selenium. Owing to the limitations of native GPx, considerable efforts have been made to develop GPx mimics. Here, a short 5-mer peptides (5P) was synthesized and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Enzyme coupled assays were used to evaluate GPx activity. The cell viability and apoptosis of H22 cells were tested, and mice bearing H22 cell-derived tumors were used to determine the effects of 5P on tumor inhibition. In comparison with other enzyme models, 5P provided a suitable substrate with proper catalytic site positions, resulting in enhanced catalytic activity. In our mouse model, 5P showed excellent inhibition of tumor growth and improved immunity. In summary, our findings demonstrated the design and synthesis of the small 5P molecule, which inhibited tumor growth and improved immunity. Notably, 5P could inhibit tumor growth without affecting normal growth. Based on these advantages, the novel mimic may have several clinical applications.

  4. Deuterohemin-Peptide Enzyme Mimic-Embedded Metal-Organic Frameworks through Biomimetic Mineralization with Efficient ATRP Catalytic Activity.

    Science.gov (United States)

    Jiang, Wei; Wang, Xinghuo; Chen, Jiawen; Liu, Ying; Han, Haobo; Ding, Yi; Li, Quanshun; Tang, Jun

    2017-08-16

    An enzyme mimic harboring iron porphyrin (DhHP-6) embedded in zeolite imidazolate framework-8 (ZIF-8) was constructed through a biomimetic mineralization approach to obtain composite DhHP-6@ZIF-8. The composite was then used as a catalyst in the atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMA 500 ) in which poly(PEGMA 500 ) could be synthesized with monomer conversion of 76.1% and M n of 45 900 g/mol, stronger than that obtained when using free DhHP-6 as a catalyst. More importantly, it could efficiently overcome the drawbacks of free DhHP-6 and achieve the easy separation of DhHP-6 from the catalytic system and the elimination of iron residues in the synthesized polymer. In addition, it exhibited an enhanced recyclability with monomer conversion of 75.7% after five cycles and favorable stability during the ATRP reaction with mimic-ZIF-8 composite developed through biomimetic mineralization can be potentially used as an effective catalyst for preparing well-defined polymers with biomedical applications.

  5. Impedimetric aptasensor for nuclear factor kappa B with peroxidase-like mimic coupled DNA nanoladders as enhancer.

    Science.gov (United States)

    Peng, Kanfu; Zhao, Hongwen; Xie, Pan; Hu, Shuang; Yuan, Yali; Yuan, Ruo; Wu, Xiongfei

    2016-07-15

    In this work, we developed a sensitive and universal aptasensor for nuclear factor kappa B (NF-κB) detection based on peroxidase-like mimic coupled DNA nanoladders for signal amplification. The dsDNA formed by capture DNA S1 and NF-κB binding aptamer (NBA) was firstly assembled on electrode surface. The presence of target NF-κB then led to the leave of NBA from electrode surface and thus provided the binding sites for immobilizing initiator to trigger in situ formation of DNA nanoladders on electrode surface. Since the peroxidase-like mimic manganese (III) meso-tetrakis (4-Nmethylpyridyl)-porphyrin (MnTMPyP) interacts with DNA nanoladders via groove binding, the insoluble benzo-4-chlorohexadienone (4-CD) precipitation derived from the oxidation of 4-chloro-1-naphthol (4-CN) could be formed on electrode surface in the presence of H2O2, resulting in a significantly amplified EIS signal output for quantitative target analysis. As a result, the developed aptasensor showed a low detection limit of 7pM and a wide linear range of 0.01-20nM. Featured with high sensitivity and label-free capability, the proposed sensing scheme can thus offer new opportunities for achieving sensitive, selective and stable detection of different types of target proteins. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Highly sensitive detection of influenza virus by boron-doped diamond electrode terminated with sialic acid-mimic peptide.

    Science.gov (United States)

    Matsubara, Teruhiko; Ujie, Michiko; Yamamoto, Takashi; Akahori, Miku; Einaga, Yasuaki; Sato, Toshinori

    2016-08-09

    The progression of influenza varies according to age and the presence of an underlying disease; appropriate treatment is therefore required to prevent severe disease. Anti-influenza therapy, such as with neuraminidase inhibitors, is effective, but diagnosis at an early phase of infection before viral propagation is critical. Here, we show that several dozen plaque-forming units (pfu) of influenza virus (IFV) can be detected using a boron-doped diamond (BDD) electrode terminated with a sialic acid-mimic peptide. The peptide was used instead of the sialyloligosaccharide receptor, which is the common receptor of influenza A and B viruses required during the early phase of infection, to capture IFV particles. The peptide, which was previously identified by phage-display technology, was immobilized by click chemistry on the BDD electrode, which has excellent electrochemical characteristics such as low background current and weak adsorption of biomolecules. Electrochemical impedance spectroscopy revealed that H1N1 and H3N2 IFVs were detectable in the range of 20-500 pfu by using the peptide-terminated BDD electrode. Our results demonstrate that the BDD device integrated with the receptor-mimic peptide has high sensitivity for detection of a low number of virus particles in the early phase of infection.

  7. Managing Complexity

    DEFF Research Database (Denmark)

    Maylath, Bruce; Vandepitte, Sonia; Minacori, Patricia

    2013-01-01

    and into French. The complexity of the undertaking proved to be a central element in the students' learning, as the collaboration closely resembles the complexity of international documentation workplaces of language service providers. © Association of Teachers of Technical Writing.......This article discusses the largest and most complex international learning-by-doing project to date- a project involving translation from Danish and Dutch into English and editing into American English alongside a project involving writing, usability testing, and translation from English into Dutch...

  8. Complex variables

    CERN Document Server

    Fisher, Stephen D

    1999-01-01

    The most important topics in the theory and application of complex variables receive a thorough, coherent treatment in this introductory text. Intended for undergraduates or graduate students in science, mathematics, and engineering, this volume features hundreds of solved examples, exercises, and applications designed to foster a complete understanding of complex variables as well as an appreciation of their mathematical beauty and elegance. Prerequisites are minimal; a three-semester course in calculus will suffice to prepare students for discussions of these topics: the complex plane, basic

  9. Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

    Science.gov (United States)

    Deatly, Anne M.; Lin, Yen-Huei; McCarthy, Maureen; Chen, Wei; Miller, Lynn Z.; Quiroz, Jorge; Nowak, Becky M.; Lerch, Robert A.; Udem, Stephen A.; Goodwin, Thomas J.

    2012-01-01

    Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse

  10. Softball Complex

    Science.gov (United States)

    Ellis, Jim

    1977-01-01

    The Parks and Recreation Department of Montgomery, Alabama, has developed a five-field softball complex as part of a growing community park with facilities for camping, golf, aquatics, tennis, and picnicking. (MJB)

  11. Lecithin Complex

    African Journals Online (AJOL)

    1Department of Food Science and Engineering, Xinyang College of Agriculture and ... Results: The UV and IR spectra of the complex showed an additive effect of polydatin-lecithin, in which .... Monochromatic Cu Ka radiation (wavelength =.

  12. 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)

  13. Single prostacyclin receptor of gel-filtered platelets provides a correlation with antiaggregatory potency of PGI2 mimics

    International Nuclear Information System (INIS)

    Eggerman, T.L.; Hartzell, C.J.; Selfe, S.; Andersen, N.H.

    1987-01-01

    Gel-filtered human platelets (GFP) display only a single binding site for [ 3 H]-PGI2: KD = 61nM, 234 fmol/10(8) platelets (1410 sites/platelet). Platelet-rich plasma (PRP) displays the same receptor density but the KD value increases to 123 nM due to protein binding of PGI2 which lowers its effective concentration. The [ 3 H]-PGI2/GFP binding assay has been used to evaluate the molecular basis of aggregation inhibition for prostacyclin analogs and mimics, three PGE type structures, and PGD2. Antiaggregatory IC50s and radioligand binding IC50s correlate for PGE2, E1, and six PGI2 analogs. PGD2, and to a lesser extent 6-oxo-PGE1, display greater antiaggregatory potency than expected based on PGI2-binding site affinity data

  14. Fractional Brownian motion run with a multi-scaling clock mimics diffusion of spherical colloids in microstructural fluids.

    Science.gov (United States)

    Park, Moongyu; Cushman, John Howard; O'Malley, Dan

    2014-09-30

    The collective molecular reorientations within a nematic liquid crystal fluid bathing a spherical colloid cause the colloid to diffuse anomalously on a short time scale (i.e., as a non-Brownian particle). The deformations and fluctuations of long-range orientational order in the liquid crystal profoundly influence the transient diffusive regimes. Here we show that an anisotropic fractional Brownian process run with a nonlinear multiscaling clock effectively mimics this collective and transient phenomenon. This novel process has memory, Gaussian increments, and a multiscale mean square displacement that can be chosen independently from the fractal dimension of a particle trajectory. The process is capable of modeling multiscale sub-, super-, or classical diffusion. The finite-size Lyapunov exponents for this multiscaling process are defined for future analysis of related mixing processes.

  15. Os cuboideum secundarium: A rare accessory ossicle with the potential to mimic a mass on magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kauffmann, Gregory; Stacy, G.S.

    2014-01-01

    Accessory ossicles are common incidental findings on radiographs of the ankle and foot. While typically asymptomatic and of no clinical significance, they are sometimes associated with local pain or even mistaken for pathological conditions such as fractures. Given the potential for misinterpretation, it is important to understand their typical locations and appearances. This case highlights an exceptionally rare accessory ossicle called the os cuboideum secundarium, located adjacent to the cuboid and calcaneus. Interestingly, this case demonstrates the potential for this rare ossicle to mimic a mass on magnetic resonance imaging (MRI). Furthermore, despite the significant improvements in the understanding of musculoskeletal pathology afforded by advancements in cross-sectional imaging techniques, this case is a reminder of certain pitfalls that remain. Lastly, it highlights the importance of radiographs as an initial diagnostic study in evaluating foot pain. (orig.)

  16. Music and 25% glucose for preterm babies during the pre-procedure for arterial puncture: facial mimics emphasis

    Directory of Open Access Journals (Sweden)

    Maria Vera Lúcia Moreira Leitão Cardoso

    2016-06-01

    Full Text Available We aimed to describe and quantify facial mimic movements of preterm babies during music and 25% glucose interventions at the pre-procedure for arterial puncture. A randomized controlled trial involving 48 videos of preterm attended in a public neonatal unit, in Fortaleza – Ceará. We collected data from footage analyses during the pre-procedure. Babies heard a lullaby song for 10 minutes in the experimental group; we administered 25% glucose in the control group at the end of the eighth minute, matching a total of 10 minutes of observation. We assessed the frequency of facial expressions: cry, sneeze, yawn, frown the forehead, focused sight, vague sight, sleeping and head movement. Statistically significant variable for the control group: vague sight (p=0.001 at the two last minutes of observation. We concluded that there was no association between most of facial movements and the studied interventions, except for a vague sight in the control group.

  17. 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.

  18. Glibenclamide Mimics Metabolic Effects of Metformin in H9c2 Cells.

    Science.gov (United States)

    Salani, Barbara; Ravera, Silvia; Fabbi, Patrizia; Garibaldi, Silvano; Passalacqua, Mario; Brunelli, Claudio; Maggi, Davide; Cordera, Renzo; Ameri, Pietro

    2017-01-01

    Sulfonylureas, such as glibenclamide, are antidiabetic drugs that stimulate beta-cell insulin secretion by binding to the sulfonylureas receptors (SURs) of adenosine triphosphate-sensitive potassium channels (KATP). Glibenclamide may be also cardiotoxic, this effect being ascribed to interference with the protective function of cardiac KATP channels for which glibenclamide has high affinity. Prompted by recent evidence that glibenclamide impairs energy metabolism of renal cells, we investigated whether this drug also affects the metabolism of cardiac cells. The cardiomyoblast cell line H9c2 was treated for 24 h with glibenclamide or metformin, a known inhibitor of the mitochondrial respiratory chain. Cell viability was evaluated by sulforodhamine B assay. ATP and AMP were measured according to the enzyme coupling method and oxygen consumption by using an amperometric electrode, while Fo-F1 ATP synthase activity assay was evaluated by chemiluminescent method. Protein expression was measured by western blot. Glibenclamide deregulated energy balance of H9c2 cardiomyoblasts in a way similar to that of metformin. It inhibited mitochondrial complexes I, II and III with ensuing impairment of oxygen consumption and ATP synthase activity, ATP depletion and increased AMPK phosphorylation. Furthermore, glibenclamide disrupted mitochondrial subcellular organization. The perturbation of mitochondrial energy balance was associated with enhanced anaerobic glycolysis, with increased activity of phosphofructo kinase, pyruvate kinase and lactic dehydrogenase. Interestingly, some additive effects of glibenclamide and metformin were observed. Glibenclamide deeply alters cell metabolism in cardiac cells by impairing mitochondrial organization and function. This may further explain the risk of cardiovascular events associated with the use of this drug, alone or in combination with metformin. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. Dengue virus-like particles mimic the antigenic properties of the infectious dengue virus envelope.

    Science.gov (United States)

    Metz, Stefan W; Thomas, Ashlie; White, Laura; Stoops, Mark; Corten, Markus; Hannemann, Holger; de Silva, Aravinda M

    2018-04-02

    The 4 dengue serotypes (DENV) are mosquito-borne pathogens that are associated with severe hemorrhagic disease. DENV particles have a lipid bilayer envelope that anchors two membrane glycoproteins prM and E. Two E-protein monomers form head-to-tail homodimers and three E-dimers align to form "rafts" that cover the viral surface. Some human antibodies that strongly neutralize DENV bind to quaternary structure epitopes displayed on E protein dimers or higher order structures forming the infectious virus. Expression of prM and E in cell culture leads to the formation of DENV virus-like particles (VLPs) which are smaller than wildtype virus particles and replication defective due to the absence of a viral genome. There is no data available that describes the antigenic landscape on the surface of flavivirus VLPs in comparison to the better studied infectious virion. A large panel of well characterized antibodies that recognize epitope of ranging complexity were used in biochemical analytics to obtain a comparative antigenic surface view of VLPs in respect to virus particles. DENV patient serum depletions were performed the show the potential of VLPs in serological diagnostics. VLPs were confirmed to be heterogeneous in size morphology and maturation state. Yet, we show that many highly conformational and quaternary structure-dependent antibody epitopes found on virus particles are efficiently displayed on DENV1-4 VLP surfaces as well. Additionally, DENV VLPs can efficiently be used as antigens to deplete DENV patient sera from serotype specific antibody populations. This study aids in further understanding epitopic landscape of DENV VLPs and presents a comparative antigenic surface view of VLPs in respect to virus particles. We propose the use VLPs as a safe and practical alternative to infectious virus as a vaccine and diagnostic antigen.

  20. 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.

  1. Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

    Directory of Open Access Journals (Sweden)

    Hua Tao

    2017-01-01

    Full Text Available Unveiling the key mechanism of temporal lobe epilepsy (TLE for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.. After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection, the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6 and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6 decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments.

  2. Conspecific mimics and low host plant availability reduce egg laying by Heliconius erato phyllis (Fabricius (Lepidoptera, Nymphalidae

    Directory of Open Access Journals (Sweden)

    Elna Mugrabi-Oliveira

    1996-01-01

    Full Text Available Oviposition response of Heliconius erato phyllis (Fabricius, 1775 (Lepidoptera, Nymphalidae to variation in host plant availability, Passiflora suberosa Linnaeus (Passifloraceae, and to presence of conspecific eggs and larvae was determined through choice experiments performed under insectary conditions. Freeze dried, painted eggs and larvae were used as mimics for testing presence of conspecific effects. Females laid more eggs on intact P. suberosa shoots without conspecifics than on those with H. erato phyllis egg and first instar mimics in both simultaneous and sequential choice trials. Oviposition response to variation in host plant availability was determined through no-choice trials, under host plant densities varying from 0.3 to 8.3 plants per female. Number of eggs laid per plant decreased exponentially with an increase in plant availability. On the contrary, daily oviposition rates (eggs /female/day increased with an increase in plant number, and levelled off when the number of plants available for oviposition was greater than potential fecundity of females. Thus, it is inferred from the results that females assess egg and larval load and prefer to lay eggs on shoots free from conspecifics. It is also inferred that they are able to recognize plant abundance and are unwilling to lay more than one egg per shoot even when host availability is scarce, as judged by reduction in daily oviposition rates under low host plant number. The consequences of laying isolated eggs on P. suberosa shoots are discussed from the viewpoint of intraspecific competition in the larval stage of H. erato phyllis.

  3. 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.

  4. In Vitro Analysis of Pseudomonas aeruginosa Virulence Using Conditions That Mimic the Environment at Specific Infection Sites.

    Science.gov (United States)

    Colmer-Hamood, J A; Dzvova, N; Kruczek, C; Hamood, A N

    2016-01-01

    Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes chronic lung infection in patients with cystic fibrosis (CF) and acute systemic infections in severely burned patients and immunocompromised patients including cancer patients undergoing chemotherapy and HIV infected individuals. In response to the environmental conditions at specific infection sites, P. aeruginosa expresses certain sets of cell-associated and extracellular virulence factors that produce tissue damage. Analyzing the mechanisms that govern the production of these virulence factors in vitro requires media that closely mimic the environmental conditions within the infection sites. In this chapter, we review studies based on media that closely resemble three in vivo conditions, the thick mucus accumulated within the lung alveoli of CF patients, the serum-rich wound bed and the bloodstream. Media resembling the CF alveolar mucus include standard laboratory media supplemented with sputum obtained from CF patients as well as prepared synthetic mucus media formulated to contain the individual components of CF sputum. Media supplemented with serum or individual serum components have served as surrogates for the soluble host components of wound infections, while whole blood has been used to investigate the adaptation of pathogens to the bloodstream. Studies using these media have provided valuable information regarding P. aeruginosa gene expression in different host environments as varying sets of genes were differentially regulated during growth in each medium. The unique effects observed indicate the essential role of these in vitro media that closely mimic the in vivo conditions in providing accurate information regarding the pathogenesis of P. aeruginosa infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Chemical modification of a phenoxyfuranone-type strigolactone mimic for selective effects on rice tillering or Striga hermonthica seed germination.

    Science.gov (United States)

    Takahashi, Ikuo; Fukui, Kosuke; Asami, Tadao

    2016-11-01

    We previously reported that a series of phenoxyfuranone compounds, designated 'debranones', mimic strigolactone (SL) activity. 4-Bromodebranone (4BD) is a functionally selective SL mimic that reduces the number of shoot branches on rice more potently than GR24, a typical synthetic SL analogue, but does not induce seed germination in the root-parasitic plant Striga hermonthica. To enhance the selective activity of debranones in stimulating the seed germination of root-parasitic plants, we prepared several analogues of 4BD in which the chlorine atom was substituted with an H atom at the o-, m- or p-position on the phenyl ring (designated 2-, 3-, or 4-chlorodebranone, respectively) or had a bicyclic group instead of the phenyl ring. We evaluated the biological activities of the compounds with rice tillering assays and S. hermonthica seed germination assays. Both assays showed that the substituent position affected debranone efficiency, and among the monochlorodebranones, 2-chlorodebranone was more effective than the other two isomers in both assays. When the activities of the bicyclic debranones were compared in the same two assays, one was more active than GR24 in the rice tillering assay. This debranone also stimulated the germination of S. hermonthica seeds. Thus, some debranone derivatives induced the germination of S. hermonthica seeds, although their activities were still ∼1/20 that of GR24. These results strongly suggest that further and rigorous structure-activity relationship studies of the debranones will identify derivatives that more potently stimulate the suicidal germination of S. hermonthica seeds. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  6. Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

    Science.gov (United States)

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

    2016-11-01

    Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

  7. A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.

    Science.gov (United States)

    Meng, Fanfei; Asghar, Sajid; Gao, Shiya; Su, Zhigui; Song, Jue; Huo, Meirong; Meng, Weidong; Ping, Qineng; Xiao, Yanyu

    2015-10-01

    In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.

    Science.gov (United States)

    Lawrence, Alexandra; Xu, Xin; Bible, Melissa D; Calve, Sarah; Neu, Corey P; Panitch, Alyssa

    2015-12-01

    The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Prolonged Elevated Heart Rate and 90-Day Survival in Acutely Ill Patients: Data From the MIMIC-III Database.

    Science.gov (United States)

    Sandfort, Veit; Johnson, Alistair E W; Kunz, Lauren M; Vargas, Jose D; Rosing, Douglas R

    2018-01-01

    We sought to evaluate the association of prolonged elevated heart rate (peHR) with survival in acutely ill patients. We used a large observational intensive care unit (ICU) database (Multiparameter Intelligent Monitoring in Intensive Care III [MIMIC-III]), where frequent heart rate measurements were available. The peHR was defined as a heart rate >100 beats/min in 11 of 12 consecutive hours. The outcome was survival status at 90 days. We collected heart rates, disease severity (simplified acute physiology scores [SAPS II]), comorbidities (Charlson scores), and International Classification of Diseases (ICD) diagnosis information in 31 513 patients from the MIMIC-III ICU database. Propensity score (PS) methods followed by inverse probability weighting based on the PS was used to balance the 2 groups (the presence/absence of peHR). Multivariable weighted logistic regression was used to assess for association of peHR with the outcome survival at 90 days adjusting for additional covariates. The mean age was 64 years, and the most frequent main disease category was circulatory disease (41%). The mean SAPS II score was 35, and the mean Charlson comorbidity score was 2.3. Overall survival of the cohort at 90 days was 82%. Adjusted logistic regression showed a significantly increased risk of death within 90 days in patients with an episode of peHR ( P < .001; odds ratio for death 1.79; confidence interval, 1.69-1.88). This finding was independent of median heart rate. We found a significant association of peHR with decreased survival in a large and heterogenous cohort of ICU patients.

  10. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  11. Subgroup complexes

    CERN Document Server

    Smith, Stephen D

    2011-01-01

    This book is intended as an overview of a research area that combines geometries for groups (such as Tits buildings and generalizations), topological aspects of simplicial complexes from p-subgroups of a group (in the spirit of Brown, Quillen, and Webb), and combinatorics of partially ordered sets. The material is intended to serve as an advanced graduate-level text and partly as a general reference on the research area. The treatment offers optional tracks for the reader interested in buildings, geometries for sporadic simple groups, and G-equivariant equivalences and homology for subgroup complexes.

  12. Complex manifolds

    CERN Document Server

    Morrow, James

    2006-01-01

    This book, a revision and organization of lectures given by Kodaira at Stanford University in 1965-66, is an excellent, well-written introduction to the study of abstract complex (analytic) manifolds-a subject that began in the late 1940's and early 1950's. It is largely self-contained, except for some standard results about elliptic partial differential equations, for which complete references are given. -D. C. Spencer, MathSciNet The book under review is the faithful reprint of the original edition of one of the most influential textbooks in modern complex analysis and geometry. The classic

  13. Complex Networks

    CERN Document Server

    Evsukoff, Alexandre; González, Marta

    2013-01-01

    In the last decade we have seen the emergence of a new inter-disciplinary field focusing on the understanding of networks which are dynamic, large, open, and have a structure sometimes called random-biased. The field of Complex Networks is helping us better understand many complex phenomena such as the spread of  deseases, protein interactions, social relationships, to name but a few. Studies in Complex Networks are gaining attention due to some major scientific breakthroughs proposed by network scientists helping us understand and model interactions contained in large datasets. In fact, if we could point to one event leading to the widespread use of complex network analysis is the availability of online databases. Theories of Random Graphs from Erdös and Rényi from the late 1950s led us to believe that most networks had random characteristics. The work on large online datasets told us otherwise. Starting with the work of Barabási and Albert as well as Watts and Strogatz in the late 1990s, we now know th...

  14. 1-O-alkyl-2-(omega-oxo)acyl-sn-glycerols from shark oil and human milk fat are potential precursors of PAF mimics and GHR

    DEFF Research Database (Denmark)

    Hartvigsen, Karsten; Ravandi, A.; Harkewicz, R.

    2006-01-01

    This study examines the feasibility that peroxidation and lipolysis of 1-O-alkyl-2,3-diacyl-sn-glycerols (DAGE) found in shark liver oil and human milk fat constitutes a potential source of dietary precursors of platelet activating factor (PAF) mimics and of gamma-hydroxybutyrate (GHB). Purified...... yielded 1-O-octadecyl-2-(9-oxo)nonanoyl-sn-glycerol, as the major core aldehyde. Because diradylglycerols with short fatty chains are absorbed in the intestine and react with cytidine diphosphate-choline in the enterocytes, it is concluded that formation of such PAF mimics as 1-O-alkyl-2-(omega...

  15. Managing Complexity

    Energy Technology Data Exchange (ETDEWEB)

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  16. Integrating plant-microbe interactions to understand soil C stabilization with the MIcrobial-MIneral Carbon Stabilization model (MIMICS)

    Science.gov (United States)

    Grandy, Stuart; Wieder, Will; Kallenbach, Cynthia; Tiemann, Lisa

    2014-05-01

    If soil organic matter is predominantly microbial biomass, plant inputs that build biomass should also increase SOM. This seems obvious, but the implications fundamentally change how we think about the relationships between plants, microbes and SOM. Plant residues that build microbial biomass are typically characterized by low C/N ratios and high lignin contents. However, plants with high lignin contents and high C/N ratios are believed to increase SOM, an entrenched idea that still strongly motivates agricultural soil management practices. Here we use a combination of meta-analysis with a new microbial-explicit soil biogeochemistry model to explore the relationships between plant litter chemistry, microbial communities, and SOM stabilization in different soil types. We use the MIcrobial-MIneral Carbon Stabilization (MIMICS) model, newly built upon the Community Land Model (CLM) platform, to enhance our understanding of biology in earth system processes. The turnover of litter and SOM in MIMICS are governed by the activity of r- and k-selected microbial groups and temperature sensitive Michaelis-Menten kinetics. Plant and microbial residues are stabilized short-term by chemical recalcitrance or long-term by physical protection. Fast-turnover litter inputs increase SOM by >10% depending on temperature in clay soils, and it's only in sandy soils devoid of physical protection mechanisms that recalcitrant inputs build SOM. These results challenge centuries of lay knowledge as well as conventional ideas of SOM formation, but are they realistic? To test this, we conducted a meta-analysis of the relationships between the chemistry of plant liter inputs and SOM concentrations. We find globally that the highest SOM concentrations are associated with plant inputs containing low C/N ratios. These results are confirmed by individual tracer studies pointing to greater stabilization of low C/N ratio inputs, particularly in clay soils. Our model and meta-analysis results suggest

  17. Absence of the kinase S6k1 mimics the effect of chronic endurance exercise on glucose tolerance and muscle oxidative stress

    Directory of Open Access Journals (Sweden)

    C. Binsch

    2017-11-01

    Conclusions: In high-fat fed mice, loss of S6K1 mimics endurance exercise training by reducing mitochondrial ROS production and upregulating oxidative utilization of ketone bodies. Pharmacological targeting of S6K1 may improve the outcome of exercise-based interventions in obesity and diabetes.

  18. Multi-Population Invariance with Dichotomous Measures: Combining Multi-Group and MIMIC Methodologies in Evaluating the General Aptitude Test in the Arabic Language

    Science.gov (United States)

    Sideridis, Georgios D.; Tsaousis, Ioannis; Al-harbi, Khaleel A.

    2015-01-01

    The purpose of the present study was to extend the model of measurement invariance by simultaneously estimating invariance across multiple populations in the dichotomous instrument case using multi-group confirmatory factor analytic and multiple indicator multiple causes (MIMIC) methodologies. Using the Arabic version of the General Aptitude Test…

  19. Synthesis and Functional Characterization of Novel Sialyl LewisX Mimic-Decorated Liposomes for E-selectin-Mediated Targeting to Inflamed Endothelial Cells.

    Science.gov (United States)

    Chantarasrivong, Chanikarn; Ueki, Akiharu; Ohyama, Ryutaro; Unga, Johan; Nakamura, Shinya; Nakanishi, Isao; Higuchi, Yuriko; Kawakami, Shigeru; Ando, Hiromune; Imamura, Akihiro; Ishida, Hideharu; Yamashita, Fumiyoshi; Kiso, Makoto; Hashida, Mitsuru

    2017-05-01

    Sialyl LewisX (sLeX) is a natural ligand of E-selectin that is overexpressed by inflamed and tumor endothelium. Although sLeX is a potential ligand for drug targeting, synthesis of the tetrasaccharide is complicated with many reaction steps. In this study, structurally simplified novel sLeX analogues were designed and linked with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG) for E-selectin-mediated liposomal delivery. The sLeX structural simplification strategies include (1) replacement of the Gal-GlcNAc disaccharide unit with lactose to reduce many initial steps and (2) substitution of neuraminic acid with a negatively charged group, i.e., 3'-sulfo, 3'-carboxymethyl (3'-CM), or 3'-(1-carboxy)ethyl (3'-CE). While all the liposomes developed were similar in particle size and charge, the 3'-CE sLeX mimic liposome demonstrated the highest uptake in inflammatory cytokine-treated human umbilical vein endothelial cells (HUVECs), being even more potent than native sLeX-decorated liposomes. Inhibition studies using antiselectin antibodies revealed that their uptake was mediated primarily by overexpressed E-selectin on inflamed HUVECs. Molecular dynamics simulations were performed to gain mechanistic insight into the E-selectin binding differences among native and mimic sLeX. The terminally branched methyl group of the 3'-CE sLeX mimic oriented and faced the bulk hydrophilic solution during E-selectin binding. Since this state is entropically unfavorable, the 3'-CE sLeX mimic molecule might be pushed toward the binding pocket of E-selectin by a hydrophobic effect, leading to a higher probability of hydrogen-bond formation than native sLeX and the 3'-CM sLeX mimic. This corresponded with the fact that the 3'-CE sLeX mimic liposome exhibited much greater uptake than the 3'-CM sLeX mimic liposome.

  20. Mounting evidence validates Ursolic Acid directly activates SIRT1: A powerful STAC which mimic endogenous activator of SIRT1.

    Science.gov (United States)

    Bakhtiari, Nuredin; Mirzaie, Sako; Hemmati, Roohullah; Moslemee-Jalalvand, Elham; Noori, Ali Reza; Kazemi, Jahanfard

    2018-05-16

    Ursolic Acid (UA), a pentacyclic triterpenoid compound, plays a vital role in aging process. However, the role of UA in the regulation of aging and longevity is still controversial as we have previously demonstrated that UA increases SIRT1 protein level in aged-mice. Here, we reveal that UA directly activates SIRT1 in silico, in vitro and in vivo. We have identified that UA binds to outer surface of SIRT1 and leads to tight binding of substrates to enzyme in comparison with Resveratrol (RSV) and control. Furthermore, our results indicate that UA drives the structure of SIRT1 toward a closed state (an active form of enzyme). Interestingly, our experimental findings are in agreement with the molecular dynamic results. Based on our data, UA increases the affinity of enzyme for both substrates with decreasing Km value, while enhances the Vmax of enzyme. Additionally, we have determined that UA heightened SIRT1 catalytic efficiency by 2 folds compared with RSV. Thereby, to identify the endogenous activator of SIRT1, UA was administrated to aged-mice and then the tissues were isolated. According to our results, it can be concluded that UA increases SIRT1 activity and mimics Lamin A and AROS behavior in the living cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Numerical investigation on soot particles emission in compression ignition diesel engine by using particulate mimic soot model

    Directory of Open Access Journals (Sweden)

    Ibrahim Fadzli

    2017-01-01

    Full Text Available Research via computational method, specifically by detailed-kinetic soot model offers much more advantages than the simple model as more detailed formation/oxidation process is taken into consideration, thus providing better soot mass concentration, soot size, soot number density as well as information regarding other related species. In the present computational study, investigation of in-cylinder soot concentration as well as other emissions in a single cylinder diesel engine has been conducted, using a commercial multidimensional CFD software, CONVERGE CFD. The simulation was carried out for a close-cycle combustion environment from inlet valve closing (IVC to exhaust valve opening (EVO. In this case, detailed-kinetic Particulate Mimic (PM soot model was implemented as to take benefit of the method of moment, instead of commonly implemented simple soot model. Analyses of the results are successfully plotted to demonstrate that the soot size and soot mass concentration are strongly dependent on the detailed soot formation and oxidation process rates. The calculated of soot mass concentration and average soot size at EVO provide the end value of 29.2 mg/m3 and 2.04 × 10−8 m, respectively. Besides, post-processing using EnSight shows the qualitative results of soot concentration along simulation period in the combustion chamber.

  2. Juveniles of the piscivorous dourado Salminus brasiliensis mimic the piraputanga Brycon hilarii as an alternative predation tactic

    Directory of Open Access Journals (Sweden)

    Eduardo Bessa

    Full Text Available In the district of Bom Jardim, in Nobres, Mato Grosso State, Brazil, there are clear water streams originating on karstic terrain. The dourado, Salminus brasiliensis, is an apex stalking predator in these streams. In clear waters, where visually oriented prey may perceive predator in advance, surprise is needed for successful attacks. These streams are cohabited by other Characiformes, like the frugivorous piraputanga Brycon hilarii, which lives in schools and exhibits body colour and shape similar to the dourados. Here we describe an alternative predatory tactic for juvenile dourado occurring in headwater streams of the Paraguay River basin, in which they act as an aggressive mimic of the piraputanga. Based on 43 h of observations in Bom Jardim, and on additional 11 h in the Bodoquena Plateau Rivers of Mato Grosso do Sul State, we quantified the number of rushes by dourados when they were among piraputangas or foraging alone, and observed the proportion of piraputangas per dourado in multispecific schools. Dourados of up to 30 cm total length (TL stayed among the piraputangas of similar size hiding within the school and going to the periphery of the school before rushing against prey. The dourados exhibited colours similar to the piraputangas. They not only stayed longer among piraputangas (78% of the observation time, but also rushed against prey more often than when foraging alone (53 rushes/h against 14 rushes/h, respectively.

  3. Therapeutic potential of brain-derived neurotrophic factor (BDNF and a small molecular mimics of BDNF for traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mary Wurzelmann

    2017-01-01

    Full Text Available Traumatic brain injury (TBI is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF, a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

  4. Therapeutic potential of brain-derived neurotrophic factor (BDNF) and a small molecular mimics of BDNF for traumatic brain injury.

    Science.gov (United States)

    Wurzelmann, Mary; Romeika, Jennifer; Sun, Dong

    2017-01-01

    Traumatic brain injury (TBI) is a major health problem worldwide. Following primary mechanical insults, a cascade of secondary injuries often leads to further neural tissue loss. Thus far there is no cure to rescue the damaged neural tissue. Current therapeutic strategies primarily target the secondary injuries focusing on neuroprotection and neuroregeneration. The neurotrophin brain-derived neurotrophic factor (BDNF) has significant effect in both aspects, promoting neuronal survival, synaptic plasticity and neurogenesis. Recently, the flavonoid 7,8-dihydroxyflavone (7,8-DHF), a small TrkB agonist that mimics BDNF function, has shown similar effects as BDNF in promoting neuronal survival and regeneration following TBI. Compared to BDNF, 7,8-DHF has a longer half-life and much smaller molecular size, capable of penetrating the blood-brain barrier, which makes it possible for non-invasive clinical application. In this review, we summarize functions of the BDNF/TrkB signaling pathway and studies examining the potential of BDNF and 7,8-DHF as a therapy for TBI.

  5. A Recombinant Secondary Antibody Mimic as a Target-specific Signal Amplifier and an Antibody Immobilizer in Immunoassays.

    Science.gov (United States)

    Min, Junseon; Song, Eun Kyung; Kim, Hansol; Kim, Kyoung Taek; Park, Tae Joo; Kang, Sebyung

    2016-04-11

    We construct a novel recombinant secondary antibody mimic, GST-ABD, which can bind to the Fc regions of target-bound primary antibodies and acquire multiple HRPs simultaneously. We produce it in tenth of mg quantities with a bacterial overexpression system and simple purification procedures, significantly reducing the manufacturing cost and time without the use of animals. GST-ABD is effectively conjugated with 3 HRPs per molecule on an average and selectively bind to the Fc region of primary antibodies derived from three different species (mouse, rabbit, and rat). HRP-conjugated GST-ABD (HRP-GST-ABD) is successfully used as an alternative to secondary antibodies to amplify target-specific signals in both ELISA and immunohistochemistry regardless of the target molecules and origin of primary antibodies used. GST-ABD also successfully serves as an anchoring adaptor on the surface of GSH-coated plates for immobilizing antigen-capturing antibodies in an orientation-controlled manner for sandwich-type indirect ELISA through simple molecular recognition without any complicated chemical modification.

  6. The taurine transporter substrate guanidinoethyl sulfonate mimics the action of taurine on long-term synaptic potentiation.

    Science.gov (United States)

    Suárez, Luz M; Muñoz, María-Dolores; González, José C; Bustamante, Julián; Del Río, Rafael Martín; Solís, José M

    2016-11-01

    Taurine is especially abundant in rodent brain where it appears to be involved in osmoregulation and synaptic plasticity mechanisms. The demonstration of a physiological role for taurine has been hampered by the difficulty in modifying taurine levels in most tissues, including the brain. We used an experimental strategy to reduce taurine levels, involving treatment with guanidinoethyl sulfonate (GES), a structural analogue of taurine that, among other properties, acts as a competitive inhibitor of taurine transport. GES delivered in the drinking water of rats for 1 month effectively reduced taurine levels in brain structures (hippocampus, cerebellum and cortex) and outside the brain (heart, muscle, kidney, liver and plasma) by between 50 and 80 %, depending on the tissue. This partial taurine depletion did not affect either basal synaptic transmission or the late phase of long-term potentiation (late-LTP) in hippocampal slices. In vivo microdialysis studies in the hippocampus revealed that GES treatment reduced extracellular taurine levels and the magnitude of taurine released in response to the application of either N-methyl-D-aspartate (NMDA) or a hypoosmotic solution, without affecting release mechanisms. Finally, we demonstrated in hippocampal slices that a brief GES application can mimic taurine action on the conversion of a decremental LTP into a perdurable late-LTP, concluding that GES might replace taurine function in some mechanisms such as those implicated in synaptic plasticity.

  7. Thermal responsive ion selectivity of uranyl peroxide nanocages: an inorganic mimic of K{sup +} ion channels

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yunyi; Sun, Xinyu; Liu, Tianbo [Department of Polymer Science, University of Akron, Akron, OH (United States); Szymanowski, Jennifer E.S.; Burns, Peter C. [Department of Civil Engineering and Geological Sciences, University of Notre Dame, Notre Dame, IN (United States)

    2016-06-06

    An actinyl peroxide cage cluster, Li{sub 48+m}K{sub 12}(OH){sub m}[UO{sub 2}(O{sub 2})(OH)]{sub 60} (H{sub 2}O){sub n} (m∼20 and n∼310; U{sub 60}), discriminates precisely between Na{sup +} and K{sup +} ions when heated to certain temperatures, a most essential feature for K{sup +} selective filters. The U{sub 60} clusters demonstrate several other features in common with K{sup +} ion channels, including passive transport of K{sup +} ions, a high flux rate, and the dehydration of U{sub 60} and K{sup +} ions. These qualities make U{sub 60} (a pure inorganic cluster) a promising ion channel mimic in an aqueous environment. Laser light scattering (LLS) and isothermal titration calorimetry (ITC) studies revealed that the tailorable ion selectivity of U{sub 60} clusters is a result of the thermal responsiveness of the U{sub 60} hydration shells. (copyright 2016 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Thermal responsive ion selectivity of uranyl peroxide nanocages. An inorganic mimic of K{sup +} ion channels

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Yunyi; Sun, Xinyu; Liu, Tianbo [Akron Univ., OH (United States). Dept. of Polymer Science; Szymanowski, Jennifer E.S.; Burns, Peter C. [Notre Dame Univ., IN (United States). Dept. of Civil Engineering and Geological Sciences

    2016-06-06

    An actinyl peroxide cage cluster, Li{sub 48+m}K{sub 12}(OH){sub m}[UO{sub 2}(O{sub 2})(OH)]{sub 60} (H{sub 2}O){sub n} (m∼20 and n∼310; U{sub 60}), discriminates precisely between Na{sup +} and K{sup +} ions when heated to certain temperatures, a most essential feature for K{sup +} selective filters. The U{sub 60} clusters demonstrate several other features in common with K{sup +} ion channels, including passive transport of K{sup +} ions, a high flux rate, and the dehydration of U{sub 60} and K{sup +} ions. These qualities make U{sub 60} (a pure inorganic cluster) a promising ion channel mimic in an aqueous environment. Laser light scattering (LLS) and isothermal titration calorimetry (ITC) studies revealed that the tailorable ion selectivity of U{sub 60} clusters is a result of the thermal responsiveness of the U{sub 60} hydration shells.

  9. Silencing of Stress-Regulated miRNAs in Plants by Short Tandem Target Mimic (STTM) Approach.

    Science.gov (United States)

    Teotia, Sachin; Tang, Guiliang

    2017-01-01

    In plants, microRNAs (miRNAs) regulate more than hundred target genes comprising largely transcription factors that control growth and development as well as stress responses. However, the exact functions of miRNA families could not be deciphered because each miRNA family has multiple loci in the genome, thus are functionally redundant. Therefore, an ideal approach to study the function of a miRNA family is to silence the expression of all members simultaneously, which is a daunting task. However, this can be partly overcome by Target Mimic (TM) approach that can knockdown an entire miRNA family. STTM is a modification of TM approach and complements it. STTMs have been successfully used in monocots and dicots to block miRNA functions. miR159 has been shown to be differentially regulated by various abiotic stresses including ABA in various plant species. Here, we describe in detail the protocol for designing STTM construct to block miR159 functions in Arabidopsis, with the potential to apply this technique on a number of other stress-regulated miRNAs in plants.

  10. Anti-inflammatory and Antibacterial Effects of Covalently Attached Biomembrane-Mimic Polymer Grafts on Gore-Tex Implants.

    Science.gov (United States)

    Jin, Young Ju; Kang, Sunah; Park, Pona; Choi, Dongkil; Kim, Dae Woo; Jung, Dongwook; Koh, Jaemoon; Jeon, Joohee; Lee, Myoungjin; Ham, Jiyeon; Seo, Ji-Hun; Jin, Hong-Ryul; Lee, Yan

    2017-06-07

    Expanded polytetrafluoroethylene (ePTFE), also known as Gore-Tex, is widely used as an implantable biomaterial in biomedical applications because of its favorable mechanical properties and biochemical inertness. However, infection and inflammation are two major complications with ePTFE implantations, because pathogenic bacteria can inhabit the microsized pores, without clearance by host immune cells, and the limited biocompatibility can induce foreign body reactions. To minimize these complications, we covalently grafted a biomembrane-mimic polymer, poly(2-methacryloyloxylethyl phosphorylcholine) (PMPC), by partial defluorination followed by UV-induced polymerization with cross-linkers on the ePTFE surface. PMPC grafting greatly reduced serum protein adsorption as well as fibroblast adhesion on the ePTFE surface. Moreover, the PMPC-grafted ePTFE surface exhibited a dramatic inhibition of the adhesion and growth of Staphylococcus aureus, a typical pathogenic bacterium in ePTFE implants, in the porous network. On the basis of an analysis of immune cells and inflammation-related factors, i.e., transforming growth factor-β (TGF-β) and myeloperoxidase (MPO), we confirmed that inflammation was efficiently alleviated in tissues around PMPC-grafted ePTFE plates implanted in the backs of rats. Covalent PMPC may be an effective strategy for promoting anti-inflammatory and antibacterial functions in ePTFE implants and to reduce side effects in biomedical applications of ePTFE.

  11. Modular design of synthetic protein mimics. Characterization of the helical conformation of a 13-residue peptide in crystals

    International Nuclear Information System (INIS)

    Karle, I.L.; Flippen-Anderson, J.L.; Uma, K.; Balaram, P.

    1989-01-01

    The incorporation of α-aminoisobutyryl (Aib) residues into peptide sequences facilitates helical folding. Aib-containing sequences have been chosen for the design of rigid helical segments in a modular approach to the construction of a synthetic protein mimic. The helical conformation of the synthetic peptide Boc-Aib-(Val-Ala-Leu-Aib) 3 -OMe in crystals is established by X-ray diffraction. The 13-residue apolar peptide adopts a helical form in the crystal with seven α-type hydrogen bonds in the middle and 3 10 -type hydrogen bonds at either end. The helices stack in columns, zigzag rather than linear, by means of direct NH hor-ellipsis OC head to tail hydrogen bonds. Leucyl side chains are extended on one side of the helix and valyl side chains on the other side. Water molecules form hydrogen bonds with several backbone carbonyl oxygens that also participate in α-helix hydrogen bonds. There is no apparent distortion of the helix caused by hydration

  12. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

    Science.gov (United States)

    Nagarkar-Jaiswal, Sonal; Lee, Pei-Tseng; Campbell, Megan E; Chen, Kuchuan; Anguiano-Zarate, Stephanie; Cantu Gutierrez, Manuel; Busby, Theodore; Lin, Wen-Wen; He, Yuchun; Schulze, Karen L; Booth, Benjamin W; Evans-Holm, Martha; Venken, Koen JT; Levis, Robert W; Spradling, Allan C; Hoskins, Roger A; Bellen, Hugo J

    2015-01-01

    Here, we document a collection of ∼7434 MiMIC (Minos Mediated Integration Cassette) insertions of which 2854 are inserted in coding introns. They allowed us to create a library of 400 GFP-tagged genes. We show that 72% of internally tagged proteins are functional, and that more than 90% can be imaged in unfixed tissues. Moreover, the tagged mRNAs can be knocked down by RNAi against GFP (iGFPi), and the tagged proteins can be efficiently knocked down by deGradFP technology. The phenotypes associated with RNA and protein knockdown typically correspond to severe loss of function or null mutant phenotypes. Finally, we demonstrate reversible, spatial, and temporal knockdown of tagged proteins in larvae and adult flies. This new strategy and collection of strains allows unprecedented in vivo manipulations in flies for many genes. These strategies will likely extend to vertebrates. DOI: http://dx.doi.org/10.7554/eLife.05338.001 PMID:25824290

  13. Complex variables

    CERN Document Server

    Flanigan, Francis J

    2010-01-01

    A caution to mathematics professors: Complex Variables does not follow conventional outlines of course material. One reviewer noting its originality wrote: ""A standard text is often preferred [to a superior text like this] because the professor knows the order of topics and the problems, and doesn't really have to pay attention to the text. He can go to class without preparation."" Not so here-Dr. Flanigan treats this most important field of contemporary mathematics in a most unusual way. While all the material for an advanced undergraduate or first-year graduate course is covered, discussion

  14. miR156a Mimic Represses the Epithelial-Mesenchymal Transition of Human Nasopharyngeal Cancer Cells by Targeting Junctional Adhesion Molecule A.

    Directory of Open Access Journals (Sweden)

    Yunhong Tian

    Full Text Available MicroRNAs (miRNAs have been documented as having an important role in the development of cancer. Broccoli is very popular in large groups of the population and has anticancer properties. Junctional adhesion molecule A (JAMA is preferentially concentrated at tight junctions and influences cell morphology and migration. Epithelial-mesenchymal transition (EMT is a developmental program associated with cancer progression and metastasis. In this study we aimed to investigate the role of miRNAs from broccoli in human nasopharyngeal cancer (NPC. We demonstrated that a total of 84 conserved miRNAs and 184 putative novel miRNAs were found in broccoli by sequencing technology. Among these, miR156a was expressed the most. In addition, synthetic miR156a mimic inhibited the EMT of NPC cells in vitro. Furthermore, it was confirmed that JAMA was the target of miR156a mimic as validated by 3' UTR luciferase reporter assays and western blotting. Knockdown of JAMA was consistent with the effects of miR156a mimic on the EMT of NPC, and the up-regulation of JAMA could partially restore EMT repressed by miR156a mimic. In conclusion, these results indicate that the miR156a mimic inhibits the EMT of NPC cells by targeting the 3' UTR of JAMA. These miRNA profiles of broccoli provide a fundamental basis for further research. Moreover, the discovery of miR156a may have clinical implications for the treatment of patients with NPC.

  15. miR156a Mimic Represses the Epithelial-Mesenchymal Transition of Human Nasopharyngeal Cancer Cells by Targeting Junctional Adhesion Molecule A.

    Science.gov (United States)

    Tian, Yunhong; Cai, Longmei; Tian, Yunming; Tu, Yinuo; Qiu, Huizhi; Xie, Guofeng; Huang, Donglan; Zheng, Ronghui; Zhang, Weijun

    2016-01-01

    MicroRNAs (miRNAs) have been documented as having an important role in the development of cancer. Broccoli is very popular in large groups of the population and has anticancer properties. Junctional adhesion molecule A (JAMA) is preferentially concentrated at tight junctions and influences cell morphology and migration. Epithelial-mesenchymal transition (EMT) is a developmental program associated with cancer progression and metastasis. In this study we aimed to investigate the role of miRNAs from broccoli in human nasopharyngeal cancer (NPC). We demonstrated that a total of 84 conserved miRNAs and 184 putative novel miRNAs were found in broccoli by sequencing technology. Among these, miR156a was expressed the most. In addition, synthetic miR156a mimic inhibited the EMT of NPC cells in vitro. Furthermore, it was confirmed that JAMA was the target of miR156a mimic as validated by 3' UTR luciferase reporter assays and western blotting. Knockdown of JAMA was consistent with the effects of miR156a mimic on the EMT of NPC, and the up-regulation of JAMA could partially restore EMT repressed by miR156a mimic. In conclusion, these results indicate that the miR156a mimic inhibits the EMT of NPC cells by targeting the 3' UTR of JAMA. These miRNA profiles of broccoli provide a fundamental basis for further research. Moreover, the discovery of miR156a may have clinical implications for the treatment of patients with NPC.

  16. Conditions that Mimic Parkinson's

    Science.gov (United States)

    ... with PSP also often have problems with swallowing (dysphagia), difficulty in producing speech (dysarthria), sleep problems and thinking problems. Page reviewed by Dr. Ryan Barmore, Movement Disorders Fellow at the University of Florida, a Parkinson’s Foundation Center of Excellence. 0 ‹ How a Diagnosis ...

  17. Complex dynamics

    CERN Document Server

    Carleson, Lennart

    1993-01-01

    Complex dynamics is today very much a focus of interest. Though several fine expository articles were available, by P. Blanchard and by M. Yu. Lyubich in particular, until recently there was no single source where students could find the material with proofs. For anyone in our position, gathering and organizing the material required a great deal of work going through preprints and papers and in some cases even finding a proof. We hope that the results of our efforts will be of help to others who plan to learn about complex dynamics and perhaps even lecture. Meanwhile books in the field a. re beginning to appear. The Stony Brook course notes of J. Milnor were particularly welcome and useful. Still we hope that our special emphasis on the analytic side will satisfy a need. This book is a revised and expanded version of notes based on lectures of the first author at UCLA over several \\Vinter Quarters, particularly 1986 and 1990. We owe Chris Bishop a great deal of gratitude for supervising the production of cour...

  18. Cosmic Complexity

    Science.gov (United States)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  19. Multidimensional approach to complex system resilience analysis

    International Nuclear Information System (INIS)

    Gama Dessavre, Dante; Ramirez-Marquez, Jose E.; Barker, Kash

    2016-01-01

    Recent works have attempted to formally define a general metric for quantifying resilience for complex systems as a relationship of performance of the systems against time. The technical content in the proposed work introduces a new model that allows, for the first time, to compare the system resilience among systems (or different modifications to a system), by introducing a new dimension to system resilience models, called stress, to mimic the definition of resilience in material science. The applicability and usefulness of the model is shown with a new heat map visualization proposed in this work, and it is applied to a simulated network resilience case to exemplify its potential benefits. - Highlights: • We analyzed two of the main current metrics of resilience. • We create a new model that relates events with the effects they have. • We develop a novel heat map visualization to compare system resilience. • We showed the model and visualization usefulness in a simulated case.

  20. New Gastrin Releasing Peptide Receptor-Directed [99mTc]Demobesin 1 Mimics: Synthesis and Comparative Evaluation.

    Science.gov (United States)

    Nock, Berthold A; Charalambidis, David; Sallegger, Werner; Waser, Beatrice; Mansi, Rosalba; Nicolas, Guillaume P; Ketani, Eleni; Nikolopoulou, Anastasia; Fani, Melpomeni; Reubi, Jean-Claude; Maina, Theodosia

    2018-04-12

    We have previously reported on the gastrin releasing peptide receptor (GRPR) antagonist [ 99m Tc]1, ([ 99m Tc]demobesin 1, 99m Tc-[N 4 '-diglycolate-dPhe 6 ,Leu-NHEt 13 ]BBN(6-13)). [ 99m Tc]1 has shown superior biological profile compared to analogous agonist-based 99m Tc-radioligands. We herein present a small library of [ 99m Tc]1 mimics generated after structural modifications in (a) the linker ([ 99m Tc]2, [ 99m Tc]3, [ 99m Tc]4), (b) the peptide chain ([ 99m Tc]5, [ 99m Tc]6), and (c) the C-terminus ([ 99m Tc]7 or [ 99m Tc]8). The effects of above modifications on the biological properties of analogs were studied in PC-3 cells and tumor-bearing SCID mice. All analogs showed subnanomolar affinity for the human GRPR, while most receptor-affine 4 and 8 behaved as potent GRPR antagonists in a functional internalization assay. In mice bearing PC-3 tumors, [ 99m Tc]1-[ 99m Tc]6 exhibited GRPR-specific tumor uptake, rapidly clearing from normal tissues. [ 99m Tc]4 displayed the highest tumor uptake (28.8 ± 4.1%ID/g at 1 h pi), which remained high even after 24 h pi (16.3 ± 1.8%ID/g), well surpassing that of [ 99m Tc]1 (5.4 ± 0.7%ID/g at 24 h pi).

  1. Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on fat, movement, and hormonal secretions.

    Directory of Open Access Journals (Sweden)

    Katherine A Cunningham

    2014-06-01

    Full Text Available AMP-activated protein kinase (AMPK is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, aak-1 and aak-2, encode for the catalytic subunit of AMPK in C. elegans. Here we show that in C. elegans loss of aak-2 mimics the effects of elevated serotonin signaling on fat reduction, slowed movement, and promoting exit from dauer arrest. Reconstitution of aak-2 in only the nervous system restored wild type fat levels and movement rate to aak-2 mutants and reconstitution in only the ASI neurons was sufficient to significantly restore dauer maintenance to the mutant animals. As in elevated serotonin signaling, inactivation of AAK-2 in the ASI neurons caused enhanced secretion of dense core vesicles from these neurons. The ASI neurons are the site of production of the DAF-7 TGF-β ligand and the DAF-28 insulin, both of which are secreted by dense core vesicles and play critical roles in whether animals stay in dauer or undergo reproductive development. These findings show that elevated levels of serotonin promote enhanced secretions of systemic regulators of pro-growth and differentiation pathways through inactivation of AAK-2. As such, AMPK is not only a recipient of hormonal signals but can also be an upstream regulator. Our data suggest that some of the physiological phenotypes previously attributed to peripheral AAK-2 activity on metabolic targets may instead be due to the role of this kinase in neural serotonin signaling.

  2. 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.

  3. Critical Role of Peripheral Vasoconstriction in Fatal Brain Hyperthermia Induced by MDMA (Ecstasy) under Conditions That Mimic Human Drug Use

    Science.gov (United States)

    Kim, Albert H.; Wakabayashi, Ken T.; Baumann, Michael H.; Shaham, Yavin

    2014-01-01

    MDMA (Ecstasy) is an illicit drug used by young adults at hot, crowed “rave” parties, yet the data on potential health hazards of its abuse remain controversial. Here, we examined the effect of MDMA on temperature homeostasis in male rats under standard laboratory conditions and under conditions that simulate drug use in humans. We chronically implanted thermocouple microsensors in the nucleus accumbens (a brain reward area), temporal muscle, and facial skin to measure temperature continuously from freely moving rats. While focusing on brain hyperthermia, temperature monitoring from the two peripheral locations allowed us to evaluate the physiological mechanisms (i.e., intracerebral heat production and heat loss via skin surfaces) that underlie MDMA-induced brain temperature responses. Our data confirm previous reports on high individual variability and relatively weak brain hyperthermic effects of MDMA under standard control conditions (quiet rest, 22−23°C), but demonstrate dramatic enhancements of drug-induced brain hyperthermia during social interaction (exposure to male conspecific) and in warm environments (29°C). Importantly, we identified peripheral vasoconstriction as a critical mechanism underlying the activity- and state-dependent potentiation of MDMA-induced brain hyperthermia. Through this mechanism, which prevents proper heat dissipation to the external environment, MDMA at a moderate nontoxic dose (9 mg/kg or ∼1/5 of LD50 in rats) can cause fatal hyperthermia under environmental conditions commonly encountered by humans. Our results demonstrate that doses of MDMA that are nontoxic under cool, quiet conditions can become highly dangerous under conditions that mimic recreational use of MDMA at rave parties or other hot, crowded venues. PMID:24899699

  4. A Short Peptide That Mimics the Binding Domain of TGF-β1 Presents Potent Anti-Inflammatory Activity.

    Directory of Open Access Journals (Sweden)

    Emília R Vaz

    Full Text Available The transforming growth factor beta 1 (TGF-β1 is a pleiotropic cytokine with multiple roles in development, wound healing, and immune regulation. TGF-β1-mediated immune dysfunction may lead to pathological conditions, such as inflammation. Chronic inflammatory process is characterized by a continuous release of pro-inflammatory cytokines, and the inhibition or the blockage of these cytokines signaling pathways are considered a target treatment. In this context, despite the high numbers of TGF-β-targeted pathways, the inducible regulatory T cells (iTreg to control inflammation seems to be a promising approach. Our aim was to develop novel peptides through phage display (PhD technology that could mimic TGF-β1 function with higher potency. Specific mimetic peptides were obtained through a PhD subtraction strategy from whole cell binding using TGF-β1 recombinant as a competitor during elution step. We have selected a peptide that seems to play an important role on cellular differentiation and modulation of TNF-α and IL-10 cytokines. The synthetic pm26TGF-β1 peptide tested in PBMC significantly down-modulated TNF-α and up-regulated IL-10 responses, leading to regulatory T cells (Treg phenotype differentiation. Furthermore, the synthetic peptide was able to decrease leukocytes rolling in BALB/C mice and neutrophils migration during inflammatory process in C57BL/6 mice. These data suggest that this peptide may be useful for the treatment of inflammatory diseases, especially because it displays potent anti-inflammatory properties and do not exhibit neutrophils' chemoattraction.

  5. Different Mechanisms of Soil Microbial Response to Global Change Result in Different Outcomes in the MIMICS-CN Model

    Science.gov (United States)

    Kyker-Snowman, E.; Wieder, W. R.; Grandy, S.

    2017-12-01

    Microbial-explicit models of soil carbon (C) and nitrogen (N) cycling have improved upon simulations of C and N stocks and flows at site-to-global scales relative to traditional first-order linear models. However, the response of microbial-explicit soil models to global change factors depends upon which parameters and processes in a model are altered by those factors. We used the MIcrobial-MIneral Carbon Stabilization Model with coupled N cycling (MIMICS-CN) to compare modeled responses to changes in temperature and plant inputs at two previously-modeled sites (Harvard Forest and Kellogg Biological Station). We spun the model up to equilibrium, applied each perturbation, and evaluated 15 years of post-perturbation C and N pools and fluxes. To model the effect of increasing temperatures, we independently examined the impact of decreasing microbial C use efficiency (CUE), increasing the rate of microbial turnover, and increasing Michaelis-Menten kinetic rates of litter decomposition, plus several combinations of the three. For plant inputs, we ran simulations with stepwise increases in metabolic litter, structural litter, whole litter (structural and metabolic), or labile soil C. The cumulative change in soil C or N varied in both sign and magnitude across simulations. For example, increasing kinetic rates of litter decomposition resulted in net releases of both C and N from soil pools, while decreasing CUE produced short-term increases in respiration but long-term accumulation of C in litter pools and shifts in soil C:N as microbial demand for C increased and biomass declined. Given that soil N cycling constrains the response of plant productivity to global change and that soils generate a large amount of uncertainty in current earth system models, microbial-explicit models are a critical opportunity to advance the modeled representation of soils. However, microbial-explicit models must be improved by experiments to isolate the physiological and stoichiometric

  6. Impact of preheating on the behavior of Listeria monocytogenes in a broth that mimics Camembert cheese composition.

    Science.gov (United States)

    Helloin, E; Bouttefroy, A; Gay, M; Phan Thanh, L

    2003-02-01

    The effect of preheating on the survival of L. monocytogenes in Richard's broth, which mimics the composition of Camembert cheese composition, was examined. Experiments were carried out to reproduce contamination of cheese with environmental heat-stressed cells of L. monocytogenes surviving hot-cleaning procedures. Cells in mid-log phase were heated for 30 min at 56 degrees C before being inoculated into Richard's broth. The pHs and temperatures of Richard's broth were chosen to recreate the conditions of curd dripping (pH 5, 25 degrees C), of the beginning of cheese ripening (pH 5, 12 degrees C), and of the beginning (pH 5, 4 degrees C) and the end (pH 7, 4 degrees C) of cheese storage. Immediately after heat treatment, the viability loss was especially high for strain 306715, which exhibited only 0.6% +/- 0.2% survival, compared with 22% +/- 8.7% for strain EGD. The percentages of the surviving heated cells that were injured were 93% +/- 8% for strain 306715 and 98% +/- 3% for strain EGD. The destruction of the surviving L. monocytogenes cells was accelerated when they encountered the pH and temperature conditions of Camembert cheese during manufacturing, ripening, and cold storage (pH 5 at 25, 12, and 4 degrees C, respectively). The multiplication of the surviving heated cells was retarded under favorable growth conditions similar to those of storage by the distributor and the consumer (pH 7 at 4 and 12 degrees C, respectively).

  7. Sea spray aerosol chemical composition: elemental and molecular mimics for laboratory studies of heterogeneous and multiphase reactions.

    Science.gov (United States)

    Bertram, Timothy H; Cochran, Richard E; Grassian, Vicki H; Stone, Elizabeth A

    2018-04-03

    Sea spray aerosol particles (SSA), formed through wave breaking at the ocean surface, contribute to natural aerosol particle concentrations in remote regions of Earth's atmosphere, and alter the direct and indirect effects of aerosol particles on Earth's radiation budget. In addition, sea spray aerosol serves as suspended surface area that can catalyze trace gas reactions. It has been shown repeatedly that sea spray aerosol is heavily enriched in organic material compared to the surface ocean. The selective enrichment of organic material complicates the selection of representative molecular mimics of SSA for laboratory or computational studies. In this review, we first provide a short introduction to SSA formation processes and discuss chemical transformations of SSA that occur in polluted coastal regions and remote pristine air. We then focus on existing literature of the chemical composition of nascent SSA generated in controlled laboratory experiments and field investigations. We combine the evidence on the chemical properties of nascent SSA with literature measurements of SSA water uptake to assess SSA molecular composition and liquid water content. Efforts to speciate SSA organic material into molecular classes and specific molecules have led to the identification of saccharides, alkanes, free fatty acids, anionic surfactants, dicarboxylic acids, amino acids, proteinaceous matter, and other large macromolecules. However to date, less than 25% of the organic mass of nascent SSA has been quantified at a molecular level. As discussed here, quantitative measurements of size resolved elemental ratios, combined with determinations of water uptake properties, provides unique insight on the concentration of ions within SSA as a function of particle size, pointing to a controlling role for relative humidity and the hygroscopicity of SSA organic material at small particle diameters.

  8. Biomechanics of the Proximal Radius Following Drilling of the Bicipital Tuberosity to Mimic Cortical Button Distal Biceps Repair Technique.

    Science.gov (United States)

    Oak, Nikhil R; Lien, John R; Brunfeldt, Alexander; Lawton, Jeffrey N

    2018-05-01

    A fracture through the proximal radius is a theoretical concern after cortical button distal biceps fixation in an active patient. The permanent, nonossified cortical defect and medullary tunnel is at risk during a fall eliciting rotational and compressive forces. We hypothesized that during simulated torsion and compression, in comparison with unaltered specimens, the cortical button distal biceps repair model would have decreased torsional and compressive strength and would fracture in the vicinity of the bicipital tuberosity bone tunnel. Sixteen fourth-generation composite radius Sawbones models were used in this controlled laboratory study. A bone tunnel was created through the bicipital tuberosity to mimic the exact bone tunnel, 8 mm near cortex and 3.2 mm far cortex, made for the BicepsButton distal biceps tendon repair. The radius was then prepared and mounted on either a torsional or compression testing device and compared with undrilled control specimens. Compression tests resulted in average failure loads of 9015.2 N in controls versus 8253.25 N in drilled specimens ( P = .074). Torsional testing resulted in an average failure torque of 27.3 Nm in controls and 19.3 Nm in drilled specimens ( P = .024). Average fracture angle was 35.1° in controls versus 21.1° in drilled. Gross fracture patterns were similar in compression testing; however, in torsional testing all fractures occurred through the bone tunnel in the drilled group. There are weaknesses in the vicinity of the bone tunnel in the proximal radius during biomechanical stress testing which may not be clinically relevant in nature. In cortical button fixation, distal biceps repairs creates a permanent, nonossified cortical defect with tendon interposed in the bone tunnel, which can alter the biomechanical properties of the proximal radius during compressive and torsional loading.

  9. The Runt domain of AML1 (RUNX1) binds a sequence-conserved RNA motif that mimics a DNA element.

    Science.gov (United States)

    Fukunaga, Junichi; Nomura, Yusuke; Tanaka, Yoichiro; Amano, Ryo; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Sakamoto, Taiichi; Kozu, Tomoko

    2013-07-01

    AML1 (RUNX1) is a key transcription factor for hematopoiesis that binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. Aberrations in the AML1 gene are frequently found in human leukemia. To better understand AML1 and its potential utility for diagnosis and therapy, we obtained RNA aptamers that bind specifically to the AML1 Runt domain. Enzymatic probing and NMR analyses revealed that Apt1-S, which is a truncated variant of one of the aptamers, has a CACG tetraloop and two stem regions separated by an internal loop. All the isolated aptamers were found to contain the conserved sequence motif 5'-NNCCAC-3' and 5'-GCGMGN'N'-3' (M:A or C; N and N' form Watson-Crick base pairs). The motif contains one AC mismatch and one base bulged out. Mutational analysis of Apt1-S showed that three guanines of the motif are important for Runt binding as are the three guanines of RDE, which are directly recognized by three arginine residues of the Runt domain. Mutational analyses of the Runt domain revealed that the amino acid residues used for Apt1-S binding were similar to those used for RDE binding. Furthermore, the aptamer competed with RDE for binding to the Runt domain in vitro. These results demonstrated that the Runt domain of the AML1 protein binds to the motif of the aptamer that mimics DNA. Our findings should provide new insights into RNA function and utility in both basic and applied sciences.

  10. Mir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cells.

    Directory of Open Access Journals (Sweden)

    Yuen Ngan Fan

    Full Text Available Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma and adult (glioblastoma brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1. Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

  11. Identification and Map-Based Cloning of the Light-Induced Lesion Mimic Mutant 1 (LIL1) Gene in Rice.

    Science.gov (United States)

    Zhou, Qian; Zhang, Zhifei; Liu, Tiantian; Gao, Bida; Xiong, Xingyao

    2017-01-01

    The hypersensitive response (HR) is a mechanism by which plants prevent the spread of pathogen. Despite extensive study, the molecular mechanisms underlying HR remain poorly understood. Lesion mimic mutants (LMMs), such as LIL1 that was identified in an ethylmethane sulfonate mutagenized population of Indica rice ( Oryza sativa L. ssp. Indica ) 93-11, can be used to study the HR. Under natural field conditions, the leaves of LIL1 mutant plants exhibited light-induced, small, rust-red lesions that first appeared at the leaf tips and subsequently expanded throughout the entire leaf blade to the leaf sheath. Histochemical staining indicated that LIL1 lesions displayed an abnormal accumulation of reactive oxygen species (ROS) and resulted from programmed cell death (PCD). The LIL1 mutants also displayed increased expression of defense-related genes and enhanced resistance to rice blast fungus ( Magnaporthe grisea ). Genetic analysis showed that mutation of LIL1 created a semi-dominant allele. Using 1,758 individuals in the F 2 population, LIL1 was mapped in a 222.3 kb region on the long arm of chromosome 7. That contains 12 predicted open reading frames (ORFs). Sequence analysis of these 12 candidate genes revealed a G to A base substitution in the fourth exon of LOC_Os07g30510, a putative cysteine-rich receptor-like kinase (CRK), which led to an amino acid change (Val 429 to Ile) in the LIL1 protein. Comparison of the transcript accumulation of the 12 candidate genes between LIL1 and 93-11 revealed that LOC_Os07g30510 was up-regulated significantly in LIL1 . Overexpression of the LOC_Os07g30510 gene from LIL1 induced a LIL1 -like lesion phenotype in Nipponbare. Thus, LIL1 is a novel LMM in rice that will facilitate the further study of the molecular mechanisms of HR and the rice blast resistance.

  12. Polyacrylic acid-coated cerium oxide nanoparticles: An oxidase mimic applied for colorimetric assay to organophosphorus pesticides.

    Science.gov (United States)

    Zhang, Shi-Xiang; Xue, Shi-Fan; Deng, Jingjing; Zhang, Min; Shi, Guoyue; Zhou, Tianshu

    2016-11-15

    It is important and urgent to develop reliable and highly sensitive methods that can provide on-site and rapid detection of extensively used organophosphorus pesticides (OPs) for their neurotoxicity. In this study, we developed a novel colorimetric assay for the detection of OPs based on polyacrylic acid-coated cerium oxide nanoparticles (PAA-CeO2) as an oxidase mimic and OPs as inhibitors to suppress the activity of acetylcholinesterase (AChE). Firstly, highly dispersed PAA-CeO2 was prepared in aqueous solution, which could catalyze the oxidation of TMB to produce a color reaction from colorless to blue. And the enzyme of AChE was used to catalyze the substrate of acetylthiocholine (ATCh) to produce thiocholine (TCh). As a thiol-containing compound with reducibility, TCh can decrease the oxidation of TMB catalyzed by PAA-CeO2. Upon incubated with OPs, the enzymatic activity of AChE was inhibited to produce less TCh, resulting in more TMB catalytically oxidized by PAA-CeO2 to show an increasing blue color. The two representative OPs, dichlorvos and methyl-paraoxon, were tested using our proposed assay. The novel assay showed notable color change in a concentration-dependent manner, and as low as 8.62 ppb dichlorvos and 26.73 ppb methyl-paraoxon can be readily detected. Therefore, taking advantage of such oxidase-like activity of PAA-CeO2, our proposed colorimetric assay can potentially be a screening tool for the precise and rapid evaluation of the neurotoxicity of a wealth of OPs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes.

    Science.gov (United States)

    Baxter, Melissa; Withey, Sarah; Harrison, Sean; Segeritz, Charis-Patricia; Zhang, Fang; Atkinson-Dell, Rebecca; Rowe, Cliff; Gerrard, Dave T; Sison-Young, Rowena; Jenkins, Roz; Henry, Joanne; Berry, Andrew A; Mohamet, Lisa; Best, Marie; Fenwick, Stephen W; Malik, Hassan; Kitteringham, Neil R; Goldring, Chris E; Piper Hanley, Karen; Vallier, Ludovic; Hanley, Neil A

    2015-03-01

    Hepatocyte-like cells (HLCs), differentiated from pluripotent stem cells by the use of soluble factors, can model human liver function and toxicity. However, at present HLC maturity and whether any deficit represents a true fetal state or aberrant differentiation is unclear and compounded by comparison to potentially deteriorated adult hepatocytes. Therefore, we generated HLCs from multiple lineages, using two different protocols, for direct comparison with fresh fetal and adult hepatocytes. Protocols were developed for robust differentiation. Multiple transcript, protein and functional analyses compared HLCs to fresh human fetal and adult hepatocytes. HLCs were comparable to those of other laboratories by multiple parameters. Transcriptional changes during differentiation mimicked human embryogenesis and showed more similarity to pericentral than periportal hepatocytes. Unbiased proteomics demonstrated greater proximity to liver than 30 other human organs or tissues. However, by comparison to fresh material, HLC maturity was proven by transcript, protein and function to be fetal-like and short of the adult phenotype. The expression of 81% phase 1 enzymes in HLCs was significantly upregulated and half were statistically not different from fetal hepatocytes. HLCs secreted albumin and metabolized testosterone (CYP3A) and dextrorphan (CYP2D6) like fetal hepatocytes. In seven bespoke tests, devised by principal components analysis to distinguish fetal from adult hepatocytes, HLCs from two different source laboratories consistently demonstrated fetal characteristics. HLCs from different sources are broadly comparable with unbiased proteomic evidence for faithful differentiation down the liver lineage. This current phenotype mimics human fetal rather than adult hepatocytes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  14. Mesothelioma patient derived tumor xenografts with defined BAP1 mutations that mimic the molecular characteristics of human malignant mesothelioma

    International Nuclear Information System (INIS)

    Kalra, Neetu; Zhang, Jingli; Thomas, Anish; Xi, Liqiang; Cheung, Mitchell; Talarchek, Jacqueline; Burkett, Sandra; Tsokos, Maria G; Chen, Yuanbin; Raffeld, Mark; Miettinen, Markku; Pastan, Ira; Testa, Joseph R; Hassan, Raffit

    2015-01-01

    The development and evaluation of new therapeutic approaches for malignant mesothelioma has been sparse due, in part, to lack of suitable tumor models. We established primary mesothelioma cultures from pleural and ascitic fluids of five patients with advanced mesothelioma. Electron microscopy and immunohistochemistry (IHC) confirmed their mesothelial origin. Patient derived xenografts were generated by injecting the cells in nude or SCID mice, and malignant potential of the cells was analyzed by soft agar colony assay. Molecular profiles of the primary patient tumors, early passage cell cultures, and patient derived xenografts were assessed using mutational analysis, fluorescence in situ hybridization (FISH) analysis and IHC. Primary cultures from all five tumors exhibited morphologic and IHC features consistent to those of mesothelioma cells. Mutations of BAP1 and CDKN2A were each detected in four tumors. BAP1 mutation was associated with the lack of expression of BAP1 protein. Three cell cultures, all of which were derived from BAP1 mutant primary tumors, exhibited anchorage independent growth and also formed tumors in mice, suggesting that BAP1 loss may enhance tumor growth in vivo. Both early passage cell cultures and mouse xenograft tumors harbored BAP1 mutations and CDKN2A deletions identical to those found in the corresponding primary patient tumors. The mesothelioma patient derived tumor xenografts with mutational alterations that mimic those observed in patient tumors which we established can be used for preclinical development of novel drug regimens and for studying the functional aspects of BAP1 biology in mesothelioma. The online version of this article (doi:10.1186/s12885-015-1362-2) contains supplementary material, which is available to authorized users

  15. Supramolecular Allosteric Cofacial Porphyrin Complexes

    International Nuclear Information System (INIS)

    Oliveri, Christopher G.; Gianneschi, Nathan C.; Nguyen, Son Binh T.; Mirkin, Chad A.; Stern, Charlotte L.; Wawrzak, Zdzislaw; Pink, Maren

    2008-01-01

    Nature routinely uses cooperative interactions to regulate cellular activity. For years, chemists have designed synthetic systems that aim toward harnessing the reactivity common to natural biological systems. By learning how to control these interactions in situ, one begins to allow for the preparation of man-made biomimetic systems that can efficiently mimic the interactions found in Nature. To this end, we have designed a synthetic protocol for the preparation of flexible metal-directed supramolecular cofacial porphyrin complexes which are readily obtained in greater than 90% yield through the use of new hemilabile porphyrin ligands with bifunctional ether-phosphine or thioether-phosphine substituents at the 5 and 15 positions on the porphyrin ring. The resulting architectures contain two hemilabile ligand-metal domains (Rh I or Cu I sites) and two cofacially aligned porphyrins (Zn II sites), offering orthogonal functionalities and allowing these multimetallic complexes to exist in two states, 'condensed' or 'open'. Combining the ether-phosphine ligand with the appropriate Rh I or Cu I transition-metal precursors results in 'open' macrocyclic products. In contrast, reacting the thioether-phosphine ligand with RhI or CuI precursors yields condensed structures that can be converted into their 'open' macrocyclic forms via introduction of additional ancillary ligands. The change in cavity size that occurs allows these structures to function as allosteric catalysts for the acyl transfer reaction between X-pyridylcarbinol (where X = 2, 3, or 4) and 1-acetylimidazole. For 3- and 4-pyridylcarbinol, the 'open' macrocycle accelerates the acyl transfer reaction more than the condensed analogue and significantly more than the porphyrin monomer. In contrast, an allosteric effect was not observed for 2-pyridylcarbinol, which is expected to be a weaker binder and is unfavorably constrained inside the macrocyclic cavity.

  16. Complex coacervate-based materials for biomedicine.

    Science.gov (United States)

    Blocher, Whitney C; Perry, Sarah L

    2017-07-01

    There has been increasing interest in complex coacervates for deriving and transporting biomaterials. Complex coacervates are a dense, polyelectrolyte-rich liquid that results from the electrostatic complexation of oppositely charged macroions. Coacervates have long been used as a strategy for encapsulation, particularly in food and personal care products. More recent efforts have focused on the utility of this class of materials for the encapsulation of small molecules, proteins, RNA, DNA, and other biomaterials for applications ranging from sensing to biomedicine. Furthermore, coacervate-related materials have found utility in other areas of biomedicine, including cartilage mimics, tissue culture scaffolds, and adhesives for wet, biological environments. Here, we discuss the self-assembly of complex coacervate-based materials, current challenges in the intelligent design of these materials, and their utility applications in the broad field of biomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1442. doi: 10.1002/wnan.1442 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  17. Cocomplexation of urea and UO22+ in a Schiff base macrocycle: a mimic of an enzyme binding site

    International Nuclear Information System (INIS)

    van Staveren, C.J.; Fenton, D.E.; Reinhoudt, D.N.; van Eerden, J.; Harkema, S.

    1987-01-01

    As part of the authors work on the complexation of neutral molecules by macrocyclic ligands, they are particularly interested in the complexation of urea. They have shown that urea can form complexes with (aza-)18-crown but the association constants of these complexes in water are very small (18-crown-6-urea, log K/sub s/ = 0.1). Protonation of urea effects stronger binding especially when the crown ether is sufficiently large to form an encapsulated complex (e.g., the complex benzo-27-crown-9-urea-HClO 4 ). Protonation of the weakly basic urea (pK/sub a/ = 0.1, water, 25 0 C) requires strongly acidic conditions and to avoid this they have introduced a covalently linked carboxylic group in the cavity of the macrocycle. A strong hydrogen bond of urea with 2-carboxyl-1,3-xylyl-30-crown-9 results in an encapsulated complex. The concept of using an electrophilic center to bind urea in the cavity of a crown ether proved to be a more general concept. A metal cation can serve as the electrophile as was shown by the isolation and single-crystal X-ray analysis of the 2,6-pyrido-27-crown-9-urea-LiClO 4 (1:2:1) complex in which one of the urea molecules is encapsulated. In an effort to bind an electrophilic metal ion in the crown ethers irreversibly they have concentrated their work on macrocycles of type 1, since the strong binding of quadridentate (salen type) Schiff bases with soft metal ions is well-known

  18. A Solid Binding Matrix/Mimic Receptor-Based Sensor System for Trace Level Determination of Iron Using Potential Measurements

    OpenAIRE

    Kamel, Ayman H.; Moreira, Felismina T. C.; Silva, Tamara I.; Sales, M. Goreti F.

    2011-01-01

    Iron(II)-(1,10-phenanthroline) complex imprinted membrane was prepared by ionic imprinting technology. In the first step, Fe(II) established a coordination linkage with 1,10-phenanthroline and functional monomer 2-vinylpyridine (2-VP). Next, the complex was copolymerized with ethylene glycol dimethacrylate (EGDMA) as a crosslinker in the presence of benzoyl peroxide (BPO) as an initiator. Potentiometric chemical sensors were designed by dispersing the iron(II)-imprinted polymer particles in 2...

  19. Straightforward Synthesis of Purine 4 '-Alkoxy-2 '-deoxynucleosides: First Report of Mixed Purine-Pyrimidine 4 '-Alkoxyoligodeoxynucleotides as New RNA Mimics

    Czech Academy of Sciences Publication Activity Database

    Petrová, Magdalena; Páv, Ondřej; Buděšínský, Miloš; Zborníková, Eva; Novák, Pavel; Rosenbergová, Šárka; Pačes, Ondřej; Liboska, Radek; Dvořáková, Ivana; Šimák, Ondřej; Rosenberg, Ivan

    2015-01-01

    Roč. 17, č. 14 (2015), s. 3426-3429 ISSN 1523-7060 R&D Projects: GA ČR GA13-26526S; GA ČR GA13-24880S; GA TA ČR TA03010598 Institutional support: RVO:61388963 Keywords : 4'-alkoxyoligodeoxynucleotides * RNA mimics * antisense Subject RIV: CC - Organic Chemistry Impact factor: 6.732, year: 2015

  20. Four-year follow-up of transient ischemic attacks, strokes, and mimics: a retrospective transient ischemic attack clinic cohort study.

    Science.gov (United States)

    Dutta, Dipankar; Bowen, Emily; Foy, Chris

    2015-05-01

    There is limited information on outcomes from rapid access transient ischemic attack (TIA) clinics. We present 4-year outcomes of TIAs, strokes, and mimics from a UK TIA clinic database. All patients referred between April 2010 and May 2012 were retrospectively identified and outcomes determined. End points were stroke, myocardial infarction, any vascular event (TIA, stroke, or myocardial infarction), and all-cause death. Data were analyzed by survival analysis. Of 1067 patients, 31.6% were TIAs, 18% strokes, and 50.4% mimics. Median assessment time was 4.5 days from onset and follow-up was for 34.9 months. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke, and 2.0% of mimics at the end of follow-up. Stroke risk at 90 days was 1.3% for patients diagnosed as TIA or stroke. Compared with mimics, hazard ratios for subsequent stroke were 3.88 (1.90-7.91) for TIA and 5.84 (2.81-12.11) for stroke. Hazard ratio for any subsequent vascular event was 2.91 (1.97-4.30) for TIA and 2.83 (1.81-4.41) for stroke. Hazard ratio for death was 1.68 (1.10-2.56) for TIA and 2.19 (1.38-3.46) for stroke. Our results show a lower 90-day stroke incidence after TIA or minor stroke than in earlier studies, suggesting that rapid access daily TIA clinics may be having a significant effect on reducing strokes. © 2015 American Heart Association, Inc.

  1. Effect of Media Modified To Mimic Cystic Fibrosis Sputum on the Susceptibility of Aspergillus fumigatus, and the Frequency of Resistance at One Center.

    Science.gov (United States)

    Stevens, David A; Moss, Richard B; Hernandez, Cathy; Clemons, Karl V; Martinez, Marife

    2016-04-01

    Studies of cystic fibrosis (CF) patient exacerbations attributed toPseudomonas aeruginosainfection have indicated a lack of correlation of outcome within vitrosusceptibility results. One explanation is that the media used for testing do not mimic the airway milieu, resulting in incorrect conclusions. Therefore, media have been devised to mimic CF sputum.Aspergillus fumigatusis the leading fungal pathogen in CF, and susceptibility testing is also used to decide therapeutic choices. We assessed whether media designed to mimic CF sputa would give different fungal susceptibility results than those of classical methods, assaying voriconazole, the most utilized anti-Aspergillusdrug in this setting, and 30 CFAspergillusisolates. The frequency of marked resistance (defined as an MIC of >4 μg/ml) in our CF unit by classical methods is 7%. Studies performed with classical methods and with digested sputum medium, synthetic sputum medium, and artificial sputum medium revealed prominent differences inAspergillussusceptibility results, as well as growth rate, with each medium. Clinical correlative studies are required to determine which results are most useful in predicting outcome. Comparison of MICs with non-CF isolates also indicated the CF isolates were generally more resistant. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Measurement of flow velocity fields in small vessel-mimic phantoms and vessels of small animals using micro ultrasonic particle image velocimetry (micro-EPIV)

    International Nuclear Information System (INIS)

    Qian Ming; Niu Lili; Jiang Bo; Jin Qiaofeng; Jiang Chunxiang; Zheng Hairong; Wang Yanping

    2010-01-01

    Determining a multidimensional velocity field within microscale opaque fluid flows is needed in areas such as microfluidic devices, biofluid mechanics and hemodynamics research in animal studies. The ultrasonic particle image velocimetry (EchoPIV) technique is appropriate for measuring opaque flows by taking advantage of PIV and B-mode ultrasound contrast imaging. However, the use of clinical ultrasound systems for imaging flows in small structures or animals has limitations associated with spatial resolution. This paper reports on the development of a high-resolution EchoPIV technique (termed as micro-EPIV) and its application in measuring flows in small vessel-mimic phantoms and vessels of small animals. Phantom experiments demonstrate the validity of the technique, providing velocity estimates within 4.1% of the analytically derived values with regard to the flows in a small straight vessel-mimic phantom, and velocity estimates within 5.9% of the computationally simulated values with regard to the flows in a small stenotic vessel-mimic phantom. Animal studies concerning arterial and venous flows of living rats and rabbits show that the micro-EPIV-measured peak velocities within several cardiac cycles are about 25% below the values measured by the ultrasonic spectral Doppler technique. The micro-EPIV technique is able to effectively measure the flow fields within microscale opaque fluid flows.

  3. Screening and identification of RhD antigen mimic epitopes from a phage display random peptide library for the serodiagnosis of haemolytic disease of the foetus and newborn.

    Science.gov (United States)

    Wang, Jiao; Song, Jingjing; Zhou, Shuimei; Fu, Yourong; Bailey, Jeffrey A; Shen, Changxin

    2018-01-16

    Identification of RhD antigen epitopes is a key component in understanding the pathogenesis of haemolytic disease of the foetus and newborn. Research has indicated that phage display libraries are useful tools for identifying novel mimic epitopes (mimotopes) which may help to determine antigen specificity. We selected the mimotopes of blood group RhD antigen by affinity panning a phage display library using monoclonal anti-D. After three rounds of biopanning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA) and then sent for sequencing and peptides synthesis. Next, competitive ELISA and erythrocyte haemagglutination inhibition tests were carried out to confirm the inhibitory activity of the synthetic peptide. To evaluate the diagnostic performance of the synthetic peptide, a diagnostic ELISA was examined. Fourteen of 35 phage clones that were chosen randomly from the titering plate were considered to be positive. Following DNA sequencing and translation, 11 phage clones were found to represent the same peptide - RMKMLMMLMRRK (P4) - whereas each of the other three clones represented a unique peptide. Through the competitive ELISA and erythrocyte haemagglutination inhibition tests, the peptide (P4) was verified to have the ability to mimic the RhD antigen. The diagnostic ELISA for P4 proved to be sensitive (82.61%) and specific (88.57%). This study reveals that the P4 peptide can mimic RhD antigen and paves the way for the development of promising targeted diagnostic and therapeutic platforms for haemolytic disease of the foetus and newborn.

  4. Measurement of flow velocity fields in small vessel-mimic phantoms and vessels of small animals using micro ultrasonic particle image velocimetry (micro-EPIV).

    Science.gov (United States)

    Qian, Ming; Niu, Lili; Wang, Yanping; Jiang, Bo; Jin, Qiaofeng; Jiang, Chunxiang; Zheng, Hairong

    2010-10-21

    Determining a multidimensional velocity field within microscale opaque fluid flows is needed in areas such as microfluidic devices, biofluid mechanics and hemodynamics research in animal studies. The ultrasonic particle image velocimetry (EchoPIV) technique is appropriate for measuring opaque flows by taking advantage of PIV and B-mode ultrasound contrast imaging. However, the use of clinical ultrasound systems for imaging flows in small structures or animals has limitations associated with spatial resolution. This paper reports on the development of a high-resolution EchoPIV technique (termed as micro-EPIV) and its application in measuring flows in small vessel-mimic phantoms and vessels of small animals. Phantom experiments demonstrate the validity of the technique, providing velocity estimates within 4.1% of the analytically derived values with regard to the flows in a small straight vessel-mimic phantom, and velocity estimates within 5.9% of the computationally simulated values with regard to the flows in a small stenotic vessel-mimic phantom. Animal studies concerning arterial and venous flows of living rats and rabbits show that the micro-EPIV-measured peak velocities within several cardiac cycles are about 25% below the values measured by the ultrasonic spectral Doppler technique. The micro-EPIV technique is able to effectively measure the flow fields within microscale opaque fluid flows.

  5. 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

    the most consistent and strongest staining biomarkers in diseased mice. This mouse appears to mimic human corneal disease. It is an appropriate model for testing of therapeutics to treat EB ocular disease. Copyright © 2018. Published by Elsevier Ltd.

  6. Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on insulin responsiveness and weight loss.

    Science.gov (United States)

    Martel, Cécile; Pinçon, Anthony; Bélanger, Alexandre Maxime; Luo, Xiaoyan; Gillis, Marc-Antoine; de Montgolfier, Olivia; Thorin-Trescases, Nathalie; Thorin, Éric

    2018-01-01

    Angiopoietin-like 2 (ANGPTL2) is an inflammatory adipokine linking obesity to insulin resistance. Intermittent fasting, on the other hand, is a lifestyle intervention able to prevent obesity and diabetes but difficult to implement and maintain. Our objectives were to characterize a link between ANGPTL2 and intermittent fasting and to investigate whether the knockdown of ANGPTL2 reproduces the benefits of intermittent fasting on weight gain and insulin responsiveness in knockdown and wild-type littermates mice. Intermittent fasting, access to food ad libitum once every other day, was initiated at the age of three months and maintained for four months. Intermittent fasting decreased by 63% (p < 0.05) gene expression of angptl2 in adipose tissue of wild-type mice. As expected, intermittent fasting improved insulin sensitivity (p < 0.05) and limited weight gain (p < 0.05) in wild-type mice. Knockdown mice fed ad libitum, however, were comparable to wild-type mice following the intermittent fasting regimen: insulin sensitivity and weight gain were identical, while intermittent fasting had no additional impact on these parameters in knockdown mice. Energy intake was similar between both wild-type fed intermittent fasting and ANGPTL2 knockdown mice fed ad libitum, suggesting that intermittent fasting and knockdown of ANGPTL2 equally lower feeding efficiency. These results suggest that the reduction of ANGPTL2 could be a useful and promising strategy to prevent obesity and insulin resistance, although further investigation of the mechanisms linking ANGPTL2 and intermittent fasting is warranted. Impact statement Intermittent fasting is an efficient diet pattern to prevent weight gain and improve insulin sensitivity. It is, however, a difficult regimen to follow and compliance is expected to be very low. In this work, we demonstrate that knockdown of ANGPTL2 in mice fed ad libitum mimics the beneficial effects of intermittent fasting on weight gain and insulin

  7. A novel experimental rat model of peripheral nerve scarring that reliably mimics post-surgical complications and recurring adhesions

    Directory of Open Access Journals (Sweden)

    Angela Lemke

    2017-08-01

    Full Text Available Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. These features can reoccur following external neurolysis, currently the most common surgical treatment for peripheral nerve scarring, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients. However, a clinically relevant model combining both histological and functional alterations has not been published to date. We therefore developed a reliable rat model that exhibits the essential pathological processes of peripheral nerve scarring. In our study, we present a novel method for the induction of nerve scarring by applying glutaraldehyde-containing glue that is known to cause nerve injury in humans. After a 3-week contact period with the sciatic nerve in female Sprague Dawley rats, we could demonstrate severe intra- and perineural scarring that resulted in grade 3 adhesions and major impairments in the electrophysiological peak amplitude compared with sham control (P=0.0478. Immunohistochemical analysis of the nerve structure revealed vigorous nerve inflammation and recruitment of T cells and macrophages. Also, distinct nerve degeneration was determined by immunostaining. These pathological alterations were further reflected in significant functional deficiencies, as determined by the analysis of relevant gait parameters as well as the quantification of the sciatic functional index starting at week 1 post-operation (P<0.01. Moreover, with this model we could, for the first time, demonstrate not only the primary formation, but also the recurrence, of severe adhesions 1 week after glue removal, imitating a major clinical challenge. As a comparison, we tested a

  8. Kinect Technology Game Play to Mimic Quake Catcher Network (QCN) Sensor Deployment During a Rapid Aftershock Mobilization Program (RAMP)

    Science.gov (United States)

    Kilb, D. L.; Yang, A.; Rohrlick, D.; Cochran, E. S.; Lawrence, J.; Chung, A. I.; Neighbors, C.; Choo, Y.

    2011-12-01

    The Kinect technology allows for hands-free game play, greatly increasing the accessibility of gaming for those uncomfortable using controllers. How it works is the Kinect camera transmits invisible near-infrared light and measures its "time of flight" to reflect off an object, allowing it to distinguish objects within 1 centimeter in depth and 3 mm in height and width. The middleware can also respond to body gestures and voice commands. Here, we use the Kinect Windows SDK software to create a game that mimics how scientists deploy seismic instruments following a large earthquake. The educational goal of the game is to allow the players to explore 3D space as they learn about the Quake Catcher Network's (QCN) Rapid Aftershock Mobilization Program (RAMP). Many of the scenarios within the game are taken from factual RAMP experiences. To date, only the PC platform (or a Mac running PC emulator software) is available for use, but we hope to move to other platforms (e.g., Xbox 360, iPad, iPhone) as they become available. The game is written in programming language C# using Microsoft XNA and Visual Studio 2010, graphic shading is added using High Level Shader Language (HLSL), and rendering is produced using XNA's graphics libraries. Key elements of the game include selecting sensor locations, adequately installing the sensor, and monitoring the incoming data. During game play aftershocks can occur unexpectedly, as can other problems that require attention (e.g., power outages, equipment failure, and theft). The player accrues points for quickly deploying the first sensor (recording as many initial aftershocks as possible), correctly installing the sensors (orientation with respect to north, properly securing, and testing), distributing the sensors adequately in the region, and troubleshooting problems. One can also net points for efficient use of game play time. Setting up for game play in your local environment requires: (1) the Kinect hardware ( $145); (2) a computer

  9. Optimal Hydrophobicity in Ring-Opening Metathesis Polymerization-Based Protein Mimics Required for siRNA Internalization.

    Science.gov (United States)

    deRonde, Brittany M; Posey, Nicholas D; Otter, Ronja; Caffrey, Leah M; Minter, Lisa M; Tew, Gregory N

    2016-06-13

    Exploring the role of polymer structure for the internalization of biologically relevant cargo, specifically siRNA, is of critical importance to the development of improved delivery reagents. Herein, we report guanidinium-rich protein transduction domain mimics (PTDMs) based on a ring-opening metathesis polymerization scaffold containing tunable hydrophobic moieties that promote siRNA internalization. Structure-activity relationships using Jurkat T cells and HeLa cells were explored to determine how the length of the hydrophobic block and the hydrophobic side chain compositions of these PTDMs impacted siRNA internalization. To explore the hydrophobic block length, two different series of diblock copolymers were synthesized: one series with symmetric block lengths and one with asymmetric block lengths. At similar cationic block lengths, asymmetric and symmetric PTDMs promoted siRNA internalization in the same percentages of the cell population regardless of the hydrophobic block length; however, with 20 repeat units of cationic charge, the asymmetric block length had greater siRNA internalization, highlighting the nontrivial relationships between hydrophobicity and overall cationic charge. To further probe how the hydrophobic side chains impacted siRNA internalization, an additional series of asymmetric PTDMs was synthesized that featured a fixed hydrophobic block length of five repeat units that contained either dimethyl (dMe), methyl phenyl (MePh), or diphenyl (dPh) side chains and varied cationic block lengths. This series was further expanded to incorporate hydrophobic blocks consisting of diethyl (dEt), diisobutyl (diBu), and dicyclohexyl (dCy) based repeat units to better define the hydrophobic window for which our PTDMs had optimal activity. High-performance liquid chromatography retention times quantified the relative hydrophobicities of the noncationic building blocks. PTDMs containing the MePh, diBu, and dPh hydrophobic blocks were shown to have superior

  10. A moderate increase in ambient temperature modulates the Atlantic cod (Gadus morhua spleen transcriptome response to intraperitoneal viral mimic injection

    Directory of Open Access Journals (Sweden)

    Hori Tiago S

    2012-08-01

    Full Text Available Abstract Background Atlantic cod (Gadus morhua reared in sea-cages can experience large variations in temperature, and these have been shown to affect their immune function. We used the new 20K Atlantic cod microarray to investigate how a water temperature change which, simulates that seen in Newfoundland during the spring-summer (i.e. from 10°C to 16°C, 1°C increase every 5 days impacted the cod spleen transcriptome response to the intraperitoneal injection of a viral mimic (polyriboinosinic polyribocytidylic acid, pIC. Results The temperature regime alone did not cause any significant increases in plasma cortisol levels and only minor changes in spleen gene transcription. However, it had a considerable impact on the fish spleen transcriptome response to pIC [290 and 339 significantly differentially expressed genes between 16°C and 10°C at 6 and 24 hours post-injection (HPI, respectively]. Seventeen microarray-identified transcripts were selected for QPCR validation based on immune-relevant functional annotations. Fifteen of these transcripts (i.e. 88%, including DHX58, STAT1, IRF7, ISG15, RSAD2 and IκBα, were shown by QPCR to be significantly induced by pIC. Conclusions The temperature increase appeared to accelerate the spleen immune transcriptome response to pIC. We found 41 and 999 genes differentially expressed between fish injected with PBS vs. pIC at 10°C and sampled at 6HPI and 24HPI, respectively. In contrast, there were 656 and 246 genes differentially expressed between fish injected with PBS vs. pIC at 16°C and sampled at 6HPI and 24HPI, respectively. Our results indicate that the modulation of mRNA expression of genes belonging to the NF-κB and type I interferon signal transduction pathways may play a role in controlling temperature-induced changes in the spleen’s transcript expression response to pIC. Moreover, interferon effector genes such as ISG15 and RSAD2 were differentially expressed between fish injected with

  11. A novel triple repeat mutant tau transgenic model that mimics aspects of pick's disease and fronto-temporal tauopathies.

    Directory of Open Access Journals (Sweden)

    Edward Rockenstein

    Full Text Available Tauopathies are a group of disorders leading to cognitive and behavioral impairment in the aging population. While four-repeat (4R Tau is more abundant in corticobasal degeneration, progressive supranuclear palsy, and Alzheimer's disease, three-repeat (3R Tau is the most abundant splice, in Pick's disease. A number of transgenic models expressing wild-type and mutant forms of the 4R Tau have been developed. However, few models of three-repeat Tau are available. A transgenic mouse model expressing three-repeat Tau was developed bearing the mutations associated with familial forms of Pick's disease (L266V and G272V mutations. Two lines expressing high (Line 13 and low (Line 2 levels of the three-repeat mutant Tau were analyzed. By Western blot, using antibodies specific to three-repeat Tau, Line 13 expressed 5-times more Tau than Line 2. The Tau expressed by these mice was most abundant in the frontal-temporal cortex and limbic system and was phosphorylated at residues detected by the PHF-1, AT8, CP9 and CP13 antibodies. The higher-expressing mice displayed hyperactivity, memory deficits in the water maze and alterations in the round beam. The behavioral deficits started at 6-8 months of age and were associated with a progressive increase in the accumulation of 3R Tau. By immunocytochemistry, mice from Line 13 displayed extensive accumulation of 3R Tau in neuronal cells bodies in the pyramidal neurons of the neocortex, CA1-3 regions, and dentate gyrus of the hippocampus. Aggregates in the granular cells had a globus appearance and mimic Pick's-like inclusions. There were abundant dystrophic neurites, astrogliosis and synapto-dendritic damage in the neocortex and hippocampus of the higher expresser line. The hippocampal lesions were moderately argyrophilic and Thioflavin-S negative. By electron microscopy, discrete straight filament aggregates were detected in some neurons in the hippocampus. This model holds promise for better understanding the

  12. Juveniles of the piscivorous dourado Salminus brasiliensis mimic the piraputanga Brycon hilarii as an alternative predation tactic

    Directory of Open Access Journals (Sweden)

    Eduardo Bessa

    2011-06-01

    Full Text Available In the district of Bom Jardim, in Nobres, Mato Grosso State, Brazil, there are clear water streams originating on karstic terrain. The dourado, Salminus brasiliensis, is an apex stalking predator in these streams. In clear waters, where visually oriented prey may perceive predator in advance, surprise is needed for successful attacks. These streams are cohabited by other Characiformes, like the frugivorous piraputanga Brycon hilarii, which lives in schools and exhibits body colour and shape similar to the dourados. Here we describe an alternative predatory tactic for juvenile dourado occurring in headwater streams of the Paraguay River basin, in which they act as an aggressive mimic of the piraputanga. Based on 43 h of observations in Bom Jardim, and on additional 11 h in the Bodoquena Plateau Rivers of Mato Grosso do Sul State, we quantified the number of rushes by dourados when they were among piraputangas or foraging alone, and observed the proportion of piraputangas per dourado in multispecific schools. Dourados of up to 30 cm total length (TL stayed among the piraputangas of similar size hiding within the school and going to the periphery of the school before rushing against prey. The dourados exhibited colours similar to the piraputangas. They not only stayed longer among piraputangas (78% of the observation time, but also rushed against prey more often than when foraging alone (53 rushes/h against 14 rushes/h, respectively.No distrito de Bom Jardim, Nobres, Mato Grosso, Brasil, existem rios de águas claras que se originam sobre terreno cárstico. O dourado, Salminus brasiliensis, é um predador perseguidor de topo de cadeia nestes rios. Em águas, onde presas visualmente orientadas são capazes de perceber antecipadamente o predador, o fator surpresa é necessário para ataques bem sucedidos. Estes córregos são coabitados por outros Characiformes, como a frugívora piraputanga, Brycon hilarii, a qual vive em cardumes e exibe colora

  13. A Solid Binding Matrix/Mimic Receptor-Based Sensor System for Trace Level Determination of Iron Using Potential Measurements

    Directory of Open Access Journals (Sweden)

    Ayman H. Kamel

    2011-01-01

    Full Text Available Iron(II-(1,10-phenanthroline complex imprinted membrane was prepared by ionic imprinting technology. In the first step, Fe(II established a coordination linkage with 1,10-phenanthroline and functional monomer 2-vinylpyridine (2-VP. Next, the complex was copolymerized with ethylene glycol dimethacrylate (EGDMA as a crosslinker in the presence of benzoyl peroxide (BPO as an initiator. Potentiometric chemical sensors were designed by dispersing the iron(II-imprinted polymer particles in 2-nitrophenyloctyl ether (o-NPOE plasticizer and then embedded in poly vinyl chloride (PVC matrix. The sensors showed a Nernstian response for [Fe(phen3]2+ with limit of detection 3.15 ng mL−1 and a Nernstian slope of 35.7 mV per decade.

  14. Antimalarial, antimicrobial, cytotoxic, DNA interaction and SOD like activities of tetrahedral copper(II) complexes

    Science.gov (United States)

    Mehta, Jugal V.; Gajera, Sanjay B.; Patel, Mohan N.

    2015-02-01

    The mononuclear copper(II) complexes with P, O-donor ligand and different fluoroquinolones have been synthesized and characterized by elemental analysis, electronic spectra, TGA, EPR, FT-IR and LC-MS spectroscopy. An antimicrobial efficiency of the complexes has been tested against five different microorganisms in terms of minimum inhibitory concentration (MIC) and displays very good antimicrobial activity. The binding strength and binding mode of the complexes with Herring Sperm DNA (HS DNA) have been investigated by absorption titration and viscosity measurement studies. The studies suggest the classical intercalative mode of DNA binding. Gel electrophoresis assay determines the ability of the complexes to cleave the supercoiled form of pUC19 DNA. Synthesized complexes have been tested for their SOD mimic activity using nonenzymatic NBT/NADH/PMS system and found to have good antioxidant activity. All the complexes show good cytotoxic and in vitro antimalarial activities.

  15. Modern moulage: evaluating the use of 3-dimensional prosthetic mimics in a dermatology teaching program for second-year medical students.

    Science.gov (United States)

    Garg, Amit; Haley, Heather-Lyn; Hatem, David

    2010-02-01

    To evaluate the effectiveness of a teaching method that uses 3-dimensional (3D) silicone-based prosthetic mimics of common serious lesions and eruptions and to compare learning outcomes with those achieved through the conventional method of lectures with 2-dimensional (2D) images. Prospective and comparative. University of Massachusetts Medical School. Ninety second-year medical students. A 1-hour teaching intervention using a lecture with 2D images (2D group) or using 3D prosthetic mimics of lesions and eruptions (3D group). Mean scores in the domains of morphology, lesion and rash recognition, lesion and rash management, and overall performance assessed at baseline, immediately after, and 3 months after each group's respective teaching intervention. Immediately after the teaching intervention, the 3D group had significantly higher mean percentage scores than did the 2D group for overall performance (71 vs 65, P = .03), lesion recognition (65 vs 56, P = .02), and rash management (80 vs 67, P = .01). Three months later, the 3D group still had significantly higher mean percentage scores than did the 2D group for lesion recognition (47 vs 40, P = .03). The 3D group better recognized lesions at 3 months compared with at baseline, whereas the 2D group was no better at recognizing lesions at 3 months compared with at baseline. Despite limited curricular time, the novel teaching method using 3D prosthetic mimics of lesions and eruptions improves immediate and long-term learning outcomes, in particular, lesion recognition. It is also a preferred teaching format among second-year medical students.

  16. Graphene-palladium nanowires based electrochemical sensor using ZnFe2O4-graphene quantum dots as an effective peroxidase mimic.

    Science.gov (United States)

    Liu, Weiyan; Yang, Hongmei; Ma, Chao; Ding, Ya-nan; Ge, Shenguang; Yu, Jinghua; Yan, Mei

    2014-12-10

    We proposed an electrochemical DNA sensor by using peroxidase-like magnetic ZnFe2O4-graphene quantum dots (ZnFe2O4/GQDs) nanohybrid as a mimic enzymatic label. Aminated graphene and Pd nanowires were successively modified on glassy carbon electrode, which improved the electronic transfer rate as well as increased the amount of immobilized capture ssDNA (S1). The nanohybrid ZnFe2O4/GQDs was prepared by assembling the GQDs on the surface of ZnFe2O4 through a photo-Fenton reaction, which was not only used as a mimic enzyme but also as a carrier to label complementary ssDNA (S3). By synergistically integrating highly catalytically activity of nano-sized GQDs and ZnFe2O4, the nanohybrid possessed highly-efficient peroxidase-like catalytic activity which could produce a large current toward the reduction of H2O2 for signal amplification. Thionine was used as an excellent electron mediator. Compared with traditional enzyme labels, the mimic enzyme ZnFe2O4/GQDs exhibited many advantages such as environment friendly and better stability. Under the optimal conditions, the approach provided a wide linear range from 10(-16) to 5×10(-9) M and low detection limit of 6.2×10(-17) M. The remarkable high catalytic capability could allow the nanohybrid to replace conventional peroxidase-based assay systems. The new, robust and convenient assay systems can be widely utilized for the identification of other target molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Strategies for the solid-phase diversification of poly-L-proline-type II peptide mimic scaffolds and peptide scaffolds through guanidinylation.

    Science.gov (United States)

    Flemer, Stevenson; Wurthmann, Alexander; Mamai, Ahmed; Madalengoitia, José S

    2008-10-03

    A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.

  18. Graphene–palladium nanowires based electrochemical sensor using ZnFe{sub 2}O{sub 4}–graphene quantum dots as an effective peroxidase mimic

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Weiyan; Yang, Hongmei; Ma, Chao; Ding, Ya-nan [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China); Ge, Shenguang [Shandong Provincial Key Laboratory of Preparation and Measurement of Building Materials, University of Jinan, Jinan 250022 (China); Yu, Jinghua [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China); Yan, Mei, E-mail: chm_yanm@126.com [Key Laboratory of Chemical Sensing and Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan 250022 (China)

    2014-12-10

    Highlights: • The nanohybrid ZnFe{sub 2}O{sub 4}/GQDs was developed by assembling the GQDs on the ZnFe{sub 2}O{sub 4} through a photo-Fenton reaction. • The ZnFe{sub 2}O{sub 4}/GQDs exhibited higher peroxidase-like activity and better stability than each individual and HRP. • An electrochemical sensor was fabricated using ZnFe{sub 2}O{sub 4}/GQDs nanohybrid as a mimic enzymatic to detect DNA. • Graphene and Pd nanowires were modified on the glassy carbon electrode, which improved the electronic transfer rate. - Abstract: We proposed an electrochemical DNA sensor by using peroxidase-like magnetic ZnFe{sub 2}O{sub 4}–graphene quantum dots (ZnFe{sub 2}O{sub 4}/GQDs) nanohybrid as a mimic enzymatic label. Aminated graphene and Pd nanowires were successively modified on glassy carbon electrode, which improved the electronic transfer rate as well as increased the amount of immobilized capture ssDNA (S1). The nanohybrid ZnFe{sub 2}O{sub 4}/GQDs was prepared by assembling the GQDs on the surface of ZnFe{sub 2}O{sub 4} through a photo-Fenton reaction, which was not only used as a mimic enzyme but also as a carrier to label complementary ssDNA (S3). By synergistically integrating highly catalytically activity of nano-sized GQDs and ZnFe{sub 2}O{sub 4}, the nanohybrid possessed highly-efficient peroxidase-like catalytic activity which could produce a large current toward the reduction of H{sub 2}O{sub 2} for signal amplification. Thionine was used as an excellent electron mediator. Compared with traditional enzyme labels, the mimic enzyme ZnFe{sub 2}O{sub 4}/GQDs exhibited many advantages such as environment friendly and better stability. Under the optimal conditions, the approach provided a wide linear range from 10{sup −16} to 5 × 10{sup −9} M and low detection limit of 6.2 × 10{sup −17} M. The remarkable high catalytic capability could allow the nanohybrid to replace conventional peroxidase-based assay systems. The new, robust and convenient assay systems

  19. Graphene–palladium nanowires based electrochemical sensor using ZnFe2O4–graphene quantum dots as an effective peroxidase mimic

    International Nuclear Information System (INIS)

    Liu, Weiyan; Yang, Hongmei; Ma, Chao; Ding, Ya-nan; Ge, Shenguang; Yu, Jinghua; Yan, Mei

    2014-01-01

    Highlights: • The nanohybrid ZnFe 2 O 4 /GQDs was developed by assembling the GQDs on the ZnFe 2 O 4 through a photo-Fenton reaction. • The ZnFe 2 O 4 /GQDs exhibited higher peroxidase-like activity and better stability than each individual and HRP. • An electrochemical sensor was fabricated using ZnFe 2 O 4 /GQDs nanohybrid as a mimic enzymatic to detect DNA. • Graphene and Pd nanowires were modified on the glassy carbon electrode, which improved the electronic transfer rate. - Abstract: We proposed an electrochemical DNA sensor by using peroxidase-like magnetic ZnFe 2 O 4 –graphene quantum dots (ZnFe 2 O 4 /GQDs) nanohybrid as a mimic enzymatic label. Aminated graphene and Pd nanowires were successively modified on glassy carbon electrode, which improved the electronic transfer rate as well as increased the amount of immobilized capture ssDNA (S1). The nanohybrid ZnFe 2 O 4 /GQDs was prepared by assembling the GQDs on the surface of ZnFe 2 O 4 through a photo-Fenton reaction, which was not only used as a mimic enzyme but also as a carrier to label complementary ssDNA (S3). By synergistically integrating highly catalytically activity of nano-sized GQDs and ZnFe 2 O 4 , the nanohybrid possessed highly-efficient peroxidase-like catalytic activity which could produce a large current toward the reduction of H 2 O 2 for signal amplification. Thionine was used as an excellent electron mediator. Compared with traditional enzyme labels, the mimic enzyme ZnFe 2 O 4 /GQDs exhibited many advantages such as environment friendly and better stability. Under the optimal conditions, the approach provided a wide linear range from 10 −16 to 5 × 10 −9 M and low detection limit of 6.2 × 10 −17 M. The remarkable high catalytic capability could allow the nanohybrid to replace conventional peroxidase-based assay systems. The new, robust and convenient assay systems can be widely utilized for the identification of other target molecules

  20. Mimic Phosphorylation of a βC1 Protein Encoded by TYLCCNB Impairs Its Functions as a Viral Suppressor of RNA Silencing and a Symptom Determinant.

    Science.gov (United States)

    Zhong, Xueting; Wang, Zhan Qi; Xiao, Ruyuan; Cao, Linge; Wang, Yaqin; Xie, Yan; Zhou, Xueping

    2017-08-15

    Phosphorylation of the βC1 protein encoded by the betasatellite of tomato yellow leaf curl China virus (TYLCCNB-βC1) by SNF1-related protein kinase 1 (SnRK1) plays a critical role in defense of host plants against geminivirus infection in Nicotiana benthamiana However, how phosphorylation of TYLCCNB-βC1 impacts its pathogenic functions during viral infection remains elusive. In this study, we identified two additional tyrosine residues in TYLCCNB-βC1 that are phosphorylated by SnRK1. The effects of TYLCCNB-βC1 phosphorylation on its functions as a viral suppressor of RNA silencing (VSR) and a symptom determinant were investigated via phosphorylation mimic mutants in N. benthamiana plants. Mutations that mimic phosphorylation of TYLCCNB-βC1 at tyrosine 5 and tyrosine 110 attenuated disease symptoms during viral infection. The phosphorylation mimics weakened the ability of TYLCCNB-βC1 to reverse transcriptional gene silencing and to suppress posttranscriptional gene silencing and abolished its interaction with N. benthamiana ASYMMETRIC LEAVES 1 in N. benthamiana leaves. The mimic phosphorylation of TYLCCNB-βC1 had no impact on its protein stability, subcellular localization, or self-association. Our data establish an inhibitory effect of phosphorylation of TYLCCNB-βC1 on its pathogenic functions as a VSR and a symptom determinant and provide a mechanistic explanation of how SnRK1 functions as a host defense factor. IMPORTANCE Tomato yellow leaf curl China virus (TYLCCNV), which causes a severe yellow leaf curl disease in China, is a monopartite geminivirus associated with the betasatellite (TYLCCNB). TYLCCNB encodes a single pathogenicity protein, βC1 (TYLCCNB-βC1), which functions as both a viral suppressor of RNA silencing (VSR) and a symptom determinant. Here, we show that mimicking phosphorylation of TYLCCNB-βC1 weakens its ability to reverse transcriptional gene silencing, to suppress posttranscriptional gene silencing, and to interact with N

  1. The analysis of novel microRNA mimic sequences in cancer cells reveals lack of specificity in stem-loop RT-qPCR-based microRNA detection.

    Science.gov (United States)

    Winata, Patrick; Williams, Marissa; McGowan, Eileen; Nassif, Najah; van Zandwijk, Nico; Reid, Glen

    2017-11-17

    MicroRNAs are frequently downregulated in cancer, and restoring expression has tumour suppressive activity in tumour cells. Our recent phase I clinical trial investigated microRNA-based therapy in patients with malignant pleural mesothelioma. Treatment with TargomiRs, microRNA mimics with novel sequence packaged in EGFR antibody-targeted bacterial minicells, revealed clear signs of clinical activity. In order to detect delivery of microRNA mimics to tumour cells in future clinical trials, we tested hydrolysis probe-based assays specific for the sequence of the novel mimics in transfected mesothelioma cell lines using RT-qPCR. The custom assays efficiently and specifically amplified the consensus mimics. However, we found that these assays gave a signal when total RNA from untransfected and control mimic-transfected cells were used as templates. Further investigation revealed that the reverse transcription step using stem-loop primers appeared to introduce substantial non-specific amplification with either total RNA or synthetic RNA templates. This suggests that reverse transcription using stem-loop primers suffers from an intrinsic lack of specificity for the detection of highly similar microRNAs in the same family, especially when analysing total RNA. These results suggest that RT-qPCR is unlikely to be an effective means to detect delivery of microRNA mimic-based drugs to tumour cells in patients.

  2. Electrocardiogram artifact caused by rigors mimicking narrow complex tachycardia: a case report.

    Science.gov (United States)

    Matthias, Anne Thushara; Indrakumar, Jegarajah

    2014-02-04

    The electrocardiogram (ECG) is useful in the diagnosis of cardiac and non-cardiac conditions. Rigors due to shivering can cause electrocardiogram artifacts mimicking various cardiac rhythm abnormalities. We describe an 80-year-old Sri Lankan man with an abnormal electrocardiogram mimicking narrow complex tachycardia during the immediate post-operative period. Electrocardiogram changes caused by muscle tremor during rigors could mimic a narrow complex tachycardia. Identification of muscle tremor as a cause of electrocardiogram artifact can avoid unnecessary pharmacological and non-pharmacological intervention to prevent arrhythmias.

  3. A novel enzyme-mimic nanosensor based on quantum dot-Au nanoparticle@silica mesoporous microsphere for the detection of glucose

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yang; Ma, Qiang; Liu, Ziping [Department of Analytical Chemistry, College of Chemistry, Jilin University, Qianjin Street 2699, Changchun 130012 (China); Wang, Xinyan [Changchun Institute of Applied Chemistry Chinese Academy of Sciences, Changchun 130022 (China); Su, Xingguang, E-mail: suxg@jlu.edu.cn [Department of Analytical Chemistry, College of Chemistry, Jilin University, Qianjin Street 2699, Changchun 130012 (China)

    2014-08-20

    Highlights: • Design QD-Au NP@silica mesoporous microspheres as a novel enzyme-mimic nanosensor. • Composition of two kinds of nanoparticle can be controlled through silica layers coating. • Our nanosensor for glucose detection has high sensitivity and selectivity. - Abstract: QD-Au NP@silica mesoporous microspheres have been fabricated as a novel enzyme-mimic nanosensor. CdTe quantum dots (QDs) were loaded into the core, and Au nanoparticles (NPs) were encapsulated in the outer mesoporous shell. QDs and Au NPs were separated in the different space of the nanosensor, which prevent the potential energy or electron transfer process between QDs and Au NPs. As biomimetic catalyst, Au NPs in the mesoporous silica shell can catalytically oxidize glucose as glucose oxidase (GOx)-mimicking. The resultant hydrogen peroxide can quench the photoluminescence (PL) signal of QDs in the microsphere core. Therefore the nanosensor based on the decrease of the PL intensity of QDs was established for the glucose detection. The linear range for glucose was in the range of 5–200 μM with a detection limit (3σ) of 1.32 μM.

  4. 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

  5. Instrumental intelligent test of food sensory quality as mimic of human panel test combining multiple cross-perception sensors and data fusion.

    Science.gov (United States)

    Ouyang, Qin; Zhao, Jiewen; Chen, Quansheng

    2014-09-02

    Instrumental test of food quality using perception sensors instead of human panel test is attracting massive attention recently. A novel cross-perception multi-sensors data fusion imitating multiple mammal perception was proposed for the instrumental test in this work. First, three mimic sensors of electronic eye, electronic nose and electronic tongue were used in sequence for data acquisition of rice wine samples. Then all data from the three different sensors were preprocessed and merged. Next, three cross-perception variables i.e., color, aroma and taste, were constructed using principal components analysis (PCA) and multiple linear regression (MLR) which were used as the input of models. MLR, back-propagation artificial neural network (BPANN) and support vector machine (SVM) were comparatively used for modeling, and the instrumental test was achieved for the comprehensive quality of samples. Results showed the proposed cross-perception multi-sensors data fusion presented obvious superiority to the traditional data fusion methodologies, also achieved a high correlation coefficient (>90%) with the human panel test results. This work demonstrated that the instrumental test based on the cross-perception multi-sensors data fusion can actually mimic the human test behavior, therefore is of great significance to ensure the quality of products and decrease the loss of the manufacturers. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells

    Science.gov (United States)

    Pickard, Mark R.; Williams, Gwyn T.

    2016-01-01

    Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone-sensitive and –insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies. PMID:26862727

  7. Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch

    Energy Technology Data Exchange (ETDEWEB)

    Howe, John A.; Xiao, Li; Fischmann, Thierry O.; Wang, Hao; Tang, Haifeng; Villafania, Artjohn; Zhang, Rumin; Barbieri, Christopher M.; Roemer, Terry (Merck)

    2016-08-02

    Bacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil is structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs.

  8. Selective extraction and determination of chlorogenic acids as combined quality markers in herbal medicines using molecularly imprinted polymers based on a mimic template.

    Science.gov (United States)

    Ji, Wenhua; Zhang, Mingming; Yan, Huijiao; Zhao, Hengqiang; Mu, Yan; Guo, Lanping; Wang, Xiao

    2017-12-01

    We describe a solid-phase extraction adsorbent based on molecularly imprinted polymers (MIPs), prepared with use of a mimic template. The MIPs were used for the selective extraction and determination of three chlorogenic acids as combined quality markers for Lonicera japonica and Lianhua qingwen granules. The morphologies and surface groups of the MIPs were assessed by scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, and Fourier transform infrared spectroscopy. The adsorption isotherms, kinetics, and selectivity of the MIPs were systematically compared with those of non-molecularly imprinted polymers. The MIPs showed high selectivity toward three structurally similar chlorogenic acids (chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid). A procedure using molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography was established for the determination of three chlorogenic acids from Lonicera japonica and Lianhua qingwen granules. The recoveries of the chlorogenic acids ranged from 93.1% to 101.4%. The limits of detection and limits of quantification for the three chlorogenic acids were 0.003 mg g -1 and 0.01 mg g -1 , respectively. The newly developed method is thus a promising technique for the enrichment and determination of chlorogenic acids from herbal medicines. Graphical Abstract Mimic molecularly imprinted polymers for the selective extraction of chlorogenic acids.

  9. The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein

    Science.gov (United States)

    Ko, Tzu-Ping; Liao, Yi-Ting; Hsu, Kai-Cheng

    2017-01-01

    DNA mimicry is a direct and effective strategy by which the mimic competes with DNA for the DNA binding sites on other proteins. Until now, only about a dozen proteins have been shown to function via this strategy, including the DNA mimic protein DMP19 from Neisseria meningitides. We have shown previously that DMP19 dimer prevents the operator DNA from binding to the transcription factor NHTF. Here, we provide new evidence that DMP19 monomer can also interact with the Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration and isothermal titration calorimetry assays, we found that DMP19 uses its monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated mass spectrometry was used to investigate the binding mode of DMP19 monomer and HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that the DNA binding affinity of HU is affected by DMP19. These results showed that DMP19 is bifunctional in the gene regulation of Neisseria through its variable oligomeric forms. PMID:29220372

  10. Dual-functional Pt-on-Pd supported on reduced graphene oxide hybrids: peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic.

    Science.gov (United States)

    Zhang, Xiahong; Wu, Genghuang; Cai, Zhixiong; Chen, Xi

    2015-03-01

    In this study, a facile hydrothermal method was developed to synthesize Pt-on-Pd supported on reduced graphene oxide (Pt-on-Pd/RGO) hybrids. Because of the synergistic effect between Pt-on-Pd and RGO, the obtained Pt-on-Pd/RGO had superior peroxidase-mimic activities in H2O2 reduction and TMB oxidation. The reaction medium was optimized and a sensing approach for H2O2 was developed with a linear range from 0.98 to 130.7 μM of H2O2. In addition, the characteristic of electrocatalytic oxidation of methanol was investigated. The peak current density value, j(f), for the Pt-on-Pd/RGO hybrid (328 mA mg(Pt)(-1)) was about 1.85 fold higher than that of commercial Pt black (177 mA mg(Pt)(-1)) and, also, more durable electrocatalytic activity could be obtained. For the first time, the dual-functional Pt-on-Pd/RGO with peroxidase-mimic activity and an enhanced electrocatalytic oxidation characteristic was reported. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Complex analysis and geometry

    CERN Document Server

    Silva, Alessandro

    1993-01-01

    The papers in this wide-ranging collection report on the results of investigations from a number of linked disciplines, including complex algebraic geometry, complex analytic geometry of manifolds and spaces, and complex differential geometry.

  12. Complex Systems: An Introduction

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 14; Issue 9. Complex Systems: An Introduction - Anthropic Principle, Terrestrial Complexity, Complex Materials. V K Wadhawan. General Article Volume 14 Issue 9 September 2009 pp 894-906 ...

  13. Reaction-diffusion controlled growth of complex structures

    Science.gov (United States)

    Noorduin, Willem; Mahadevan, L.; Aizenberg, Joanna

    2013-03-01

    Understanding how the emergence of complex forms and shapes in biominerals came about is both of fundamental and practical interest. Although biomineralization processes and organization strategies to give higher order architectures have been studied extensively, synthetic approaches to mimic these self-assembled structures are highly complex and have been difficult to emulate, let alone replicate. The emergence of solution patterns has been found in reaction-diffusion systems such as Turing patterns and the BZ reaction. Intrigued by this spontaneous formation of complexity we explored if similar processes can lead to patterns in the solid state. We here identify a reaction-diffusion system in which the shape of the solidified products is a direct readout of the environmental conditions. Based on insights in the underlying mechanism, we developed a toolbox of engineering strategies to deterministically sculpt patterns and shapes, and combine different morphologies to create a landscape of hierarchical multi scale-complex tectonic architectures with unprecedented levels of complexity. These findings may hold profound implications for understanding, mimicking and ultimately expanding upon nature's morphogenesis strategies, allowing the synthesis of advanced highly complex microscale materials and devices. WLN acknowledges the Netherlands Organization for Scientific Research for financial support

  14. Low-generation dendrimers with a calixarene core and based on a chiral C2-symmetric pyrrolidine as iminosugar mimics

    Directory of Open Access Journals (Sweden)

    Marco Marradi

    2012-06-01

    Full Text Available The preparation of low-generation dendrimers based on a simple calix[4]arene scaffold by insertion of the iminosugar-analogue C2-symmetric 3,4-dihydroxypyrrolidine is described. This methodology allows a rapid incorporation of a considerable number of iminosugar-like moieties in a reduced volume and in a well-defined geometry. The inclusion of alkali-metal ions (sodium and potassium in the polar cavity defined by the acetamide moieties at the lower rim of the calixarene was demonstrated, which allows also the rigidification of the dendrimer structure and the iminosugar presentation in the clusters. The combination of the supramolecular properties of calixarenes with the advantage of a dendrimeric presentation of repetitive units opens up the possibility of generating well-defined multivalent and multifaceted systems with more complex and/or biologically relevant iminosugars.

  15. Enzyme mimics of spinel-type CoxNi1−xFe2O4 magnetic nanomaterial for eletroctrocatalytic oxidation of hydrogen peroxide

    International Nuclear Information System (INIS)

    Luo, Liqiang; Zhang, Yuting; Li, Fang; Si, Xiaojing; Ding, Yaping; Deng, Dongmei; Wang, Tianlin

    2013-01-01

    Graphical abstract: -- Highlights: •Spinel-type Co x Ni 1−x Fe 2 O 4 (x = 0, 0.2, 0.4, 0.5, 0.6, 0.8, 1.0) were synthesized. •Co x Ni 1−x Fe 2 O 4 were first employed as novel enzyme mimic sensing materials of H 2 O 2 . •Co 0.5 Ni 0.5 Fe 2 O 4 /CPE showed excellent electrocatalytic activity to H 2 O 2 . •Co 0.5 Ni 0.5 Fe 2 O 4 /CPE was successfully applied to determine H 2 O 2 in toothpastes. -- Abstract: A series of spinel-type Co x Ni 1−x Fe 2 O 4 (x = 0, 0.2, 0.4, 0.5, 0.6, 0.8, 1.0) magnetic nanomaterials were solvothermally synthesized as enzyme mimics for the eletroctrocatalytic oxidation of H 2 O 2 . X-ray diffraction and scanning electron microscope were employed to characterize the composition, structure and morphology of the material. The electrochemical properties of spinel-type Co x Ni 1−x Fe 2 O 4 with different (Co/Ni) molar ratio toward H 2 O 2 oxidation were investigated, and the results demonstrated that Co 0.5 Ni 0.5 Fe 2 O 4 modified carbon paste electrode (Co 0.5 Ni 0.5 Fe 2 O 4 /CPE) possessed the best electrocatalytic activity for H 2 O 2 oxidation. Under optimum conditions, the calibration curve for H 2 O 2 determination on Co 0.5 Ni 0.5 Fe 2 O 4 /CPE was linear in a wide range of 1.0 × 10 −8 –1.0 × 10 −3 M with low detection limit of 3.0 × 10 −9 M (S/N = 3). The proposed Co 0.5 Ni 0.5 Fe 2 O 4 /CPE was also applied to the determination of H 2 O 2 in commercial toothpastes with satisfactory results, indicating that Co x Ni 1−x Fe 2 O 4 is a promising hydrogen peroxidase mimics for the detection of H 2 O 2

  16. Deoxynivalenol-mimic nanobody isolated from a naïve phage display nanobody library and its application in immunoassay.

    Science.gov (United States)

    Qiu, Yu-Lou; He, Qing-Hua; Xu, Yang; Bhunia, Arun K; Tu, Zhui; Chen, Bo; Liu, Yuan-Yuan

    2015-08-05

    In this study, using mycotoxin deoxynivalenol (DON) as a model hapten, we developed a nanobody-based environmental friendly immunoassay for sensitive detection of DON. Two nanobodies (N-28 and N-31) which bind to anti-DON monoclonal antibody (MAb) were isolated from a naive phage display library. These nanobodies are clonable, thermally stable and mycotoxin-free products and can be served as coating antigen mimetics in heterologous immunoassay. The half inhibition concentration (IC50) of the immunoassay developed with N-28 and N-31 was 8.77 ± 0.41 ng mL(-1) and 19.97 ± 0.84 ng mL(-1), respectively, which were 18- and 8-fold more sensitive than the conventional coating antigen (DON-BSA) based immunoassay. In order to better understand the molecular mechanism of antigen mimicry by nanobody, the 3D structure of "nanobody (N-28) - anti-DON MAb" complex was presented and verified by molecular modeling and alanine-scanning mutagenesis. The results showed that hydrogen bond and hydrophobic interaction formed between Thr 102 - Ser 106 of N-28 and CDR H3 residues of anti-DON antibody may contribute to their binding. This novel concept of enhancing sensitivity of immunoassay for DON based on nanobody may provide potential applications in a general method for immunoassay of various food chemical contaminants. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Structural analyses of Legionella LepB reveal a new GAP fold that catalytically mimics eukaryotic RasGAP.

    Science.gov (United States)

    Yu, Qin; Hu, Liyan; Yao, Qing; Zhu, Yongqun; Dong, Na; Wang, Da-Cheng; Shao, Feng

    2013-06-01

    Rab GTPases are emerging targets of diverse bacterial pathogens. Here, we perform biochemical and structural analyses of LepB, a Rab GTPase-activating protein (GAP) effector from Legionella pneumophila. We map LepB GAP domain to residues 313-618 and show that the GAP domain is Rab1 specific with a catalytic activity higher than the canonical eukaryotic TBC GAP and the newly identified VirA/EspG family of bacterial RabGAP effectors. Exhaustive mutation analyses identify Arg444 as the arginine finger, but no catalytically essential glutamine residues. Crystal structures of LepB313-618 alone and the GAP domain of Legionella drancourtii LepB in complex with Rab1-GDP-AlF3 support the catalytic role of Arg444, and also further reveal a 3D architecture and a GTPase-binding mode distinct from all known GAPs. Glu449, structurally equivalent to TBC RabGAP glutamine finger in apo-LepB, undergoes a drastic movement upon Rab1 binding, which induces Rab1 Gln70 side-chain flipping towards GDP-AlF3 through a strong ionic interaction. This conformationally rearranged Gln70 acts as the catalytic cis-glutamine, therefore uncovering an unexpected RasGAP-like catalytic mechanism for LepB. Our studies highlight an extraordinary structural and catalytic diversity of RabGAPs, particularly those from bacterial pathogens.

  18. PX-RICS-deficient mice mimic autism spectrum disorder in Jacobsen syndrome through impaired GABAA receptor trafficking.

    Science.gov (United States)

    Nakamura, Tsutomu; Arima-Yoshida, Fumiko; Sakaue, Fumika; Nasu-Nishimura, Yukiko; Takeda, Yasuko; Matsuura, Ken; Akshoomoff, Natacha; Mattson, Sarah N; Grossfeld, Paul D; Manabe, Toshiya; Akiyama, Tetsu

    2016-03-16

    Jacobsen syndrome (JBS) is a rare congenital disorder caused by a terminal deletion of the long arm of chromosome 11. A subset of patients exhibit social behavioural problems that meet the diagnostic criteria for autism spectrum disorder (ASD); however, the underlying molecular pathogenesis remains poorly understood. PX-RICS is located in the chromosomal region commonly deleted in JBS patients with autistic-like behaviour. Here we report that PX-RICS-deficient mice exhibit ASD-like social behaviours and ASD-related comorbidities. PX-RICS-deficient neurons show reduced surface γ-aminobutyric acid type A receptor (GABAAR) levels and impaired GABAAR-mediated synaptic transmission. PX-RICS, GABARAP and 14-3-3ζ/θ form an adaptor complex that interconnects GABAAR and dynein/dynactin, thereby facilitating GABAAR surface expression. ASD-like behavioural abnormalities in PX-RICS-deficient mice are ameliorated by enhancing inhibitory synaptic transmission with a GABAAR agonist. Our findings demonstrate a critical role of PX-RICS in cognition and suggest a causal link between PX-RICS deletion and ASD-like behaviour in JBS patients.

  19. Osteosclerotic metaphyseal dysplasia: a skeletal dysplasia that may mimic lead poisoning in a child with hypotonia and seizures

    International Nuclear Information System (INIS)

    Mennel, Emilie A.; John, Susan D.

    2003-01-01

    We report the case of a 23-month-old male with hypotonia, developmental delay, and complex seizures. Radiographs revealed profound sclerosis of the metaphyses and epiphyses of the long and short bones in the extremities, with a unique pattern of distribution. Sclerosis also involved the anterior ribs, iliac crests, talus, and calcaneus. The skull and vertebral bodies appeared unaffected. Blood lead levels were normal. We believe that this constellation of clinical and radiographic abnormalities closely resembles osteosclerotic metaphyseal dysplasia (OMD) due to an autosomal recessive defect. Characteristic skeletal findings were instrumental in determining the diagnosis. OMD is a very rare sclerosing bone disorder, first described in 1993. The syndrome is characterized clinically by developmental delay of a progressive nature, hypotonia, elevated alkaline phosphatase, and late-onset spastic paraplegia. We encountered a young child with these neurologic symptoms who displayed sclerotic metaphyseal changes on hand radiographs obtained to determine the bone age. Lead poisoning, a known cause of metaphyseal sclerosis, was initially suspected. Careful analysis of the metaphyseal bone changes helped to distinguish this bone dysplasia from lead poisoning and other causes of metaphyseal sclerosis. (orig.)

  20. Occupational stress and psychopathology in health professionals: an explorative study with the multiple indicators multiple causes (MIMIC) model approach.

    Science.gov (United States)

    Iliceto, Paolo; Pompili, Maurizio; Spencer-Thomas, Sally; Ferracuti, Stefano; Erbuto, Denise; Lester, David; Candilera, Gabriella; Girardi, Paolo

    2013-03-01

    Occupational stress is a multivariate process involving sources of pressure, psycho-physiological distress, locus of control, work dissatisfaction, depression, anxiety, mental health disorders, hopelessness, and suicide ideation. Healthcare professionals are known for higher rates of occupational-related distress (burnout and compassion fatigue) and higher rates of suicide. The purpose of this study was to explain the relationships between occupational stress and some psychopathological dimensions in a sample of health professionals. We investigated 156 nurses and physicians, 62 males and 94 females, who were administered self-report questionnaires to assess occupational stress [occupational stress inventory (OSI)], temperament (temperament evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire), and hopelessness (Beck hopelessness scale). The best Multiple Indicators Multiple Causes model with five OSI predictors yielded the following results: χ2(9) = 14.47 (p = 0.11); χ2/df = 1.60; comparative fit index = 0.99; root mean square error of approximation = 0.05. This model provided a good fit to the empirical data, showing a strong direct influence of casual variables such as work dissatisfaction, absence of type A behavior, and especially external locus of control, psychological and physiological distress on latent variable psychopathology. Occupational stress is in a complex relationship with temperament and hopelessness and also common among healthcare professionals.

  1. Gaze-related mimic word activates the frontal eye field and related network in the human brain: an fMRI study.

    Science.gov (United States)

    Osaka, Naoyuki; Osaka, Mariko

    2009-09-18

    This is an fMRI study demonstrating new evidence that a mimic word highly suggestive of an eye gaze, heard by the ear, significantly activates the frontal eye field (FEF), inferior frontal gyrus (IFG), dorsolateral premotor area (PMdr) and superior parietal lobule (SPL) connected with the frontal-parietal network. However, hearing a non-sense words that did not imply gaze under the same task does not activate this area in humans. We concluded that the FEF would be a critical area for generating/processing an active gaze, evoked by an onomatopoeia word that implied gaze closely associated with social skill. We suggest that the implied active gaze may depend on prefrontal-parietal interactions that modify cognitive gaze led by spatial visual attention associated with the SPL.

  2. A pseudoatom in a cage: trimetallofullerene Y(3)@C(80) mimics y(3)n@c(80) with nitrogen substituted by a pseudoatom.

    Science.gov (United States)

    Popov, Alexey A; Zhang, Lin; Dunsch, Lothar

    2010-02-23

    Y(3)C(80) obtained in the synthesis of nitride clusterfullerenes Y(3)N@C(2n) (2n = 80-88) by the reactive atmosphere method is found to be a genuine trimetallofullerene, Y(3)@C(80), with low ionization potential and divalent state of yttrium atoms. DFT studies of the electronic structure of Y(3)@C(80) show that this molecule mimics Y(3)N@C(80) with the pseudoatom (PA) instead of the nitrogen atom. Topology analysis of the electron density and electron localization function show that yttrium atoms form Y-PA bonds rather than direct Y-Y bonds. Molecular dynamics simulations show that the Y(3)PA cluster is as rigid as Y(3)N and rotates inside the fullerene cage as a single entity.

  3. A Rare Multifocal Pattern of Type 2 Autoimmune Pancreatitis with Negative IgG4: A Potential Diagnostic Pitfall That May Mimic Multifocal Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Partha Hota

    2018-02-01

    Full Text Available Autoimmune pancreatitis (AIP is an increasingly recognized form of acute pancreatitis characterized by obstructive jaundice with a rapid and dramatic treatment response to steroid therapy. Recently, AIP has been divided into two distinct phenotypes: lymphoplasmocytic sclerosing pancreatitis AIP (type 1 and idiopathic duct-centric pancreatitis AIP (type 2; each of which have their own distinct demographics, diagnostic criteria, and histopathological features. We report, to the best of our knowledge, the first case of a multifocal pattern of type 2 AIP characterized with both CT and MR imaging. This rare imaging pattern of AIP may mimic the appearance of more worrisome malignant etiologies such as multifocal pancreatic adenocarcinoma or lymphoma, with overlapping imaging characteristics potentially complicating or delaying diagnosis. Therefore, recognition of this atypical pattern of AIP and avoidance of this potential diagnostic pitfall is crucial.

  4. Downy mildew resistance induced by Trichoderma harzianum T39 in susceptible grapevines partially mimics transcriptional changes of resistant genotypes

    Science.gov (United States)

    2012-01-01

    Background Downy mildew, caused by Plasmopara viticola, is one of the most severe diseases of grapevine and is commonly controlled by fungicide treatments. The beneficial microorganism Trichoderma harzianum T39 (T39) can induce resistance to downy mildew, although the molecular events associated with this process have not yet been elucidated in grapevine. A next generation RNA sequencing (RNA-Seq) approach was used to study global transcriptional changes associated with resistance induced by T39 in Vitis vinifera Pinot Noir leaves. The long-term aim was to develop strategies to optimize the use of this agent for downy mildew control. Results More than 14.8 million paired-end reads were obtained for each biological replicate of T39-treated and control leaf samples collected before and 24 h after P. viticola inoculation. RNA-Seq analysis resulted in the identification of 7,024 differentially expressed genes, highlighting the complex transcriptional reprogramming of grapevine leaves during resistance induction and in response to pathogen inoculation. Our data show that T39 has a dual effect: it directly modulates genes related to the microbial recognition machinery, and it enhances the expression of defence-related processes after pathogen inoculation. Whereas several genes were commonly affected by P. viticola in control and T39-treated plants, opposing modulation of genes related to responses to stress and protein metabolism was found. T39-induced resistance partially inhibited some disease-related processes and specifically activated defence responses after P. viticola inoculation, causing a significant reduction of downy mildew symptoms. Conclusions The global transcriptional analysis revealed that defence processes known to be implicated in the reaction of resistant genotypes to downy mildew were partially activated by T39-induced resistance in susceptible grapevines. Genes identified in this work are an important source of markers for selecting novel

  5. The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration.

    Science.gov (United States)

    Veskoukis, Aristidis S; Goutianos, Georgios; Paschalis, Vassilis; Margaritelis, Nikos V; Tzioura, Aikaterini; Dipla, Konstantina; Zafeiridis, Andreas; Vrabas, Ioannis S; Kyparos, Antonios; Nikolaidis, Michalis G

    2016-04-01

    The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

  6. In vivo activity of miR-34a mimics delivered by stable nucleic acid lipid particles (SNALPs against multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Maria Teresa Di Martino

    Full Text Available Multiple myeloma (MM is a disease with an adverse outcome and new therapeutic strategies are urgently awaited. A rising body of evidence supports the notion that microRNAs (miRNAs, master regulators of eukaryotic gene expression, may exert anti-MM activity. Here, we evaluated the activity of synthetic miR-34a in MM cells. We found that transfection of miR-34a mimics in MM cells induces a significant change of gene expression with relevant effects on multiple signal transduction pathways. We detected early inactivation of pro-survival and proliferative kinases Erk-2 and Akt followed at later time points by caspase-6 and -3 activation and apoptosis induction. To improve the in vivo delivery, we encapsulated miR-34a mimics in stable nucleic acid lipid particles (SNALPs. We found that SNALPs miR-34a were highly efficient in vitro in inhibiting growth of MM cells. Then, we investigated the activity of the SNALPs miR-34a against MM xenografts in SCID mice. We observed significant tumor growth inhibition (p<0.05 which translated in mice survival benefits (p=0.0047. Analysis of miR-34a and NOTCH1 expression in tumor retrieved from animal demonstrated efficient delivery and gene modulation induced by SNALPs miR-34a in the absence of systemic toxicity. We here therefore provide evidence that SNALPs miR-34a may represent a promising tool for miRNA-therapeutics in MM.

  7. Instrumental intelligent test of food sensory quality as mimic of human panel test combining multiple cross-perception sensors and data fusion

    International Nuclear Information System (INIS)

    Ouyang, Qin; Zhao, Jiewen; Chen, Quansheng

    2014-01-01

    Highlights: • To develop a novel instrumental intelligent test methodology for food sensory analysis. • A novel data fusion was used in instrumental intelligent test methodology. • Linear and nonlinear tools were comparatively used for modeling. • The instrumental test methodology can be imitative of human test behavior. - Abstract: Instrumental test of food quality using perception sensors instead of human panel test is attracting massive attention recently. A novel cross-perception multi-sensors data fusion imitating multiple mammal perception was proposed for the instrumental test in this work. First, three mimic sensors of electronic eye, electronic nose and electronic tongue were used in sequence for data acquisition of rice wine samples. Then all data from the three different sensors were preprocessed and merged. Next, three cross-perception variables i.e., color, aroma and taste, were constructed using principal components analysis (PCA) and multiple linear regression (MLR) which were used as the input of models. MLR, back-propagation artificial neural network (BPANN) and support vector machine (SVM) were comparatively used for modeling, and the instrumental test was achieved for the comprehensive quality of samples. Results showed the proposed cross-perception multi-sensors data fusion presented obvious superiority to the traditional data fusion methodologies, also achieved a high correlation coefficient (>90%) with the human panel test results. This work demonstrated that the instrumental test based on the cross-perception multi-sensors data fusion can actually mimic the human test behavior, therefore is of great significance to ensure the quality of products and decrease the loss of the manufacturers

  8. Facile synthesis of enzyme-embedded magnetic metal-organic frameworks as a reusable mimic multi-enzyme system: mimetic peroxidase properties and colorimetric sensor.

    Science.gov (United States)

    Hou, Chen; Wang, Yang; Ding, Qinghua; Jiang, Long; Li, Ming; Zhu, Weiwei; Pan, Duo; Zhu, Hao; Liu, Mingzhu

    2015-11-28

    This work reports a facile and easily-achieved approach for enzyme immobilization by embedding glucose oxidase (GOx) in magnetic zeolitic imidazolate framework 8 (mZIF-8) via a de novo approach. As a demonstration of the power of such materials, the resulting GOx embedded mZIF-8 (mZIF-8@GOx) was utilized as a colorimetric sensor for rapid detection of glucose. This method was constructed on the basis of metal-organic frameworks (MOFs), which possessed very fascinating peroxidase-like properties, and the cascade reaction for the visual detection of glucose was combined into one step through the mZIF-8@GOx based mimic multi-enzyme system. After characterization by electron microscopy, X-ray diffraction, nitrogen sorption, fourier transform infrared spectroscopy and vibrating sample magnetometry, the as-prepared mZIF-8@GOx was confirmed with the robust core-shell structure, the monodisperse nanoparticle had an average diameter of about 200 nm and displayed superparamagnetism with a saturation magnetization value of 40.5 emu g(-1), it also exhibited a large surface area of 396.10 m(2) g(-1). As a peroxidase mimic, mZIF-8 was verified to be highly stable and of low cost, and showed a strong affinity towards H2O2. Meanwhile, the mZIF-8 embedded GOx also exhibited improved activity, stability and greatly enhanced selectivity in glucose detection. Moreover, the mZIF-8@GOx had excellent recyclability with high activity (88.7% residual activity after 12 times reuse).

  9. Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer.

    Science.gov (United States)

    Feng, Hao; Ou, Bao-Chi; Zhao, Jing-Kun; Yin, Shuai; Lu, Ai-Guo; Oechsle, Eva; Thasler, Wolfgang E

    2017-09-01

    Pancreatic cancer 3D in vitro models including multicellular tumor spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor spheroid, and organotypic models provided powerful platforms to mimic in vivo tumor. Recent work supports that circulating tumor cell (CTC) clusters are more efficient in metastasis seeding than single CTCs. The purpose of this study is to establish 3D culture models which can mimic single CTC, monoclonal CTC clusters, and the expansion of macrometastases. Seven pancreatic ductal adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid formation assay, immunoblotting, and literature review were performed to investigate molecular biomarkers and the morphological characteristics of pancreatic tumor spheroids. Single cells experienced different growth patterns to form SCTS, like signet ring-like cells, blastula-like structures, and solid core spheroids. However, golf ball-like hollow spheroids could also be detected, especially when DanG and Capan-1 cells were cultivated with fibroblast-conditioned medium (p cell lines could also establish tumor spheroid with hanging drop plates by adding methylated cellulose. Tumor spheroids derived from pancreatic cancer cell line DanG possessed asymmetrically distributed proliferation center, immune-checkpoint properties. ß-catenin, Ki-67, and F-actin were active surrounding the crater-like structure distributing on the inner layer of viable rim cover of the spheroids, which was relevant to well-differentiated tumor cells. It is possible to establish 3D CTC cluster models from homogenous PDA cell lines using hanging drop and ultra-low attachment plates. PDA cell line displays its own intrinsic properties or heterogeneity. The mechanism of formation of the crater-like structure as well as golf ball-like structure needs further exploration.

  10. Characterization and mapping of a novel light-dependent lesion mimic mutant Imm6 in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    XIAO Gui-qing[1,2; ZHANG Hal-wen[3; LU Xiang-yang[1,2; HUANG Rong-feng[3

    2015-01-01

    A novel rice lesion mimic mutant (LMM) was isolated from an ethane methyl sulfonate (EMS)-induced 02428 mutant bank. The mutant, tentatively designated as Imm6, develops necrotic lesions in the whole growth period along with changes in several important agronomic traits. We found that the initiation of the lesions was induced by light and cell death occurred in Imm6 accompanied with accumulation of reactive oxygen species (ROS). The lower chlorophyll content, soluble protein content and superoxide dismutase (SOD) activity, the higher malondialdehyde (MDA) content were detected in Imm6 than in the wild type (WT). Moreover, the observation by transmission electronic microscope (TEM) demonstrated that some organelles were damaged and the stroma lamella of chloroplast was irregular and loose in mesophyll cell of Imm6. In addition, Imm6 was more resistant than WT to rice blast fungus Magnaporthe grisea infection, which was consistent with increased expression of four genes involved in the defense-related reaction. Genetic analysis showed that mutant trait of Imm6 is inherited as a monogenic recessive nuclear gene located on the long arm of chromosome 6. Using simple sequence repeat (SSR) markers, the target gene was finally delimited to an interval of 80.8 kb between markers MM2359 and MM2370, containing 7 annotated genes. Taken together, our results provide the information to identify a new gene involved in rice lesion mimic, which will be helpful in clarifying the mechanism of cell death and disease resistance in rice.

  11. Foraging behavior of three bee species in a natural mimicry system: female flowers which mimic male flowers in Ecballium elaterium (Cucurbitaceae).

    Science.gov (United States)

    Dukas, Reuyen

    1987-12-01

    The behavior of Apis mellifera and two species of solitary bees which forage in the flowers of monoecious Ecballium elaterium (L.) A. Rich (Cucurbitaceae) were compared. The female flowers of E. elaterium resemble male flowers visually but are nectarless, and their number is relatively smaller. Apis mellifera was found to discriminate between the two genders and to pay relatively fewer visits to female flowers (mean of 30% relative to male flowers) from the beginning of their activity in the morning. The time spent by honeybees in female flowers is very short compared to that spent in male flowers. It is surmised that the bees remember the differences between the flowers where they foraged on the previous days. In contrast, the two species of solitary bees Lasioglossum politum (Morawitz) (Halictidae) and Ceratina mandibularis Fiese (Anthophoridae) visit the female flowers with nearly equal frequencies at the beginning of each foraging day and stay longer in these flowers. Over the day there is a decline in the relative frequency of visits to female flowers and also in the mean time spent in them. The study shows that bees can collect rewards at high efficiency from the flowers of Ecballium elaterium because of their partial discrimination ability and the scarcity of the mimic flowers. It is suggested that the memory pattern of some solitary bees may be different from that of Apis mellifera. It seems that the limited memory and discrimination ability of bees can lead to a high frequency of visits to the mimic flowers during a long flowering season.

  12. Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence.

    Science.gov (United States)

    Di Martino, Maria T; Leone, Emanuela; Amodio, Nicola; Foresta, Umberto; Lionetti, Marta; Pitari, Maria R; Cantafio, Maria E Gallo; Gullà, Annamaria; Conforti, Francesco; Morelli, Eugenio; Tomaino, Vera; Rossi, Marco; Negrini, Massimo; Ferrarini, Manlio; Caraglia, Michele; Shammas, Masood A; Munshi, Nikhil C; Anderson, Kenneth C; Neri, Antonino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2012-11-15

    Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a. Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo. Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity. Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a-based treatment strategies in MM patients. ©2012 AACR.

  13. Instrumental intelligent test of food sensory quality as mimic of human panel test combining multiple cross-perception sensors and data fusion

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Qin; Zhao, Jiewen; Chen, Quansheng, E-mail: qschen@ujs.edu.cn

    2014-09-02

    Highlights: • To develop a novel instrumental intelligent test methodology for food sensory analysis. • A novel data fusion was used in instrumental intelligent test methodology. • Linear and nonlinear tools were comparatively used for modeling. • The instrumental test methodology can be imitative of human test behavior. - Abstract: Instrumental test of food quality using perception sensors instead of human panel test is attracting massive attention recently. A novel cross-perception multi-sensors data fusion imitating multiple mammal perception was proposed for the instrumental test in this work. First, three mimic sensors of electronic eye, electronic nose and electronic tongue were used in sequence for data acquisition of rice wine samples. Then all data from the three different sensors were preprocessed and merged. Next, three cross-perception variables i.e., color, aroma and taste, were constructed using principal components analysis (PCA) and multiple linear regression (MLR) which were used as the input of models. MLR, back-propagation artificial neural network (BPANN) and support vector machine (SVM) were comparatively used for modeling, and the instrumental test was achieved for the comprehensive quality of samples. Results showed the proposed cross-perception multi-sensors data fusion presented obvious superiority to the traditional data fusion methodologies, also achieved a high correlation coefficient (>90%) with the human panel test results. This work demonstrated that the instrumental test based on the cross-perception multi-sensors data fusion can actually mimic the human test behavior, therefore is of great significance to ensure the quality of products and decrease the loss of the manufacturers.

  14. Complex differential geometry

    CERN Document Server

    Zheng, Fangyang

    2002-01-01

    The theory of complex manifolds overlaps with several branches of mathematics, including differential geometry, algebraic geometry, several complex variables, global analysis, topology, algebraic number theory, and mathematical physics. Complex manifolds provide a rich class of geometric objects, for example the (common) zero locus of any generic set of complex polynomials is always a complex manifold. Yet complex manifolds behave differently than generic smooth manifolds; they are more coherent and fragile. The rich yet restrictive character of complex manifolds makes them a special and interesting object of study. This book is a self-contained graduate textbook that discusses the differential geometric aspects of complex manifolds. The first part contains standard materials from general topology, differentiable manifolds, and basic Riemannian geometry. The second part discusses complex manifolds and analytic varieties, sheaves and holomorphic vector bundles, and gives a brief account of the surface classifi...

  15. Complex and symplectic geometry

    CERN Document Server

    Medori, Costantino; Tomassini, Adriano

    2017-01-01

    This book arises from the INdAM Meeting "Complex and Symplectic Geometry", which was held in Cortona in June 2016. Several leading specialists, including young researchers, in the field of complex and symplectic geometry, present the state of the art of their research on topics such as the cohomology of complex manifolds; analytic techniques in Kähler and non-Kähler geometry; almost-complex and symplectic structures; special structures on complex manifolds; and deformations of complex objects. The work is intended for researchers in these areas.

  16. NMR Study on the Inclusion Complexes of β-Cyclodextrin with Isoflavones

    Directory of Open Access Journals (Sweden)

    Rui Zhao

    2016-03-01

    Full Text Available The structure of the inclusion complexes of β-cyclodextrin (β-CD with daidzein and daidzin in D2O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD cavity with different orientations. For the β-CD/daidzin system, a 1:1 complex was formed with the flavonoid part of daidzin entering the CD cavity from the wide rim. The inclusion complexes determined by NMR were constructed using molecular docking. Furthermore, the mixture of puerarin, daidzein and daidzin, which are the major isoflavonoid components present in Radix puerariae, was analyzed by diffusion-ordered spectroscopy (DOSY alone and upon addition of β-CD in order to mimic chromatographic conditions and compare their binding affinities.

  17. Presence of voltage-gated potassium channel complex antibody in a case of genetic prion disease.

    Science.gov (United States)

    Jammoul, Adham; Lederman, Richard J; Tavee, Jinny; Li, Yuebing

    2014-06-05

    Voltage-gated potassium channel (VGKC) complex antibody-mediated encephalitis is a recently recognised entity which has been reported to mimic the clinical presentation of Creutzfeldt-Jakob disease (CJD). Testing for the presence of this neuronal surface autoantibody in patients presenting with subacute encephalopathy is therefore crucial as it may both revoke the bleak diagnosis of prion disease and allow institution of potentially life-saving immunotherapy. Tempering this optimistic view is the rare instance when a positive VGKC complex antibody titre occurs in a definite case of prion disease. We present a pathologically and genetically confirmed case of CJD with elevated serum VGKC complex antibody titres. This case highlights the importance of interpreting the result of a positive VGKC complex antibody with caution and in the context of the overall clinical manifestation. 2014 BMJ Publishing Group Ltd.

  18. Redox-dependent substrate-cofactor interactions in the Michaelis-complex of a flavin-dependent oxidoreductase

    Science.gov (United States)

    Werther, Tobias; Wahlefeld, Stefan; Salewski, Johannes; Kuhlmann, Uwe; Zebger, Ingo; Hildebrandt, Peter; Dobbek, Holger

    2017-07-01

    How an enzyme activates its substrate for turnover is fundamental for catalysis but incompletely understood on a structural level. With redox enzymes one typically analyses structures of enzyme-substrate complexes in the unreactive oxidation state of the cofactor, assuming that the interaction between enzyme and substrate is independent of the cofactors oxidation state. Here, we investigate the Michaelis complex of the flavoenzyme xenobiotic reductase A with the reactive reduced cofactor bound to its substrates by X-ray crystallography and resonance Raman spectroscopy and compare it to the non-reactive oxidized Michaelis complex mimics. We find that substrates bind in different orientations to the oxidized and reduced flavin, in both cases flattening its structure. But only authentic Michaelis complexes display an unexpected rich vibrational band pattern uncovering a strong donor-acceptor complex between reduced flavin and substrate. This interaction likely activates the catalytic ground state of the reduced flavin, accelerating the reaction within a compressed cofactor-substrate complex.

  19. Oligocyclopentadienyl transition metal complexes

    Energy Technology Data Exchange (ETDEWEB)

    de Azevedo, Cristina G.; Vollhardt, K. Peter C.

    2002-01-18

    Synthesis, characterization, and reactivity studies of oligocyclopentadienyl transition metal complexes, namely those of fulvalene, tercyclopentadienyl, quatercyclopentadienyl, and pentacyclopentadienyl(cyclopentadienyl) are the subject of this account. Thermal-, photo-, and redox chemistries of homo- and heteropolynuclear complexes are described.

  20. Photocytotoxic lanthanide complexes

    Indian Academy of Sciences (India)

    Among many applications of lanthanides, gadolinium complexes are used as magnetic resonance imaging (MRI) contrast agents in clinical radiology and luminescent lanthanides for bioanalysis, imaging and sensing. The chemistry of photoactive lanthanide complexes showing biological applications is of recent origin.

  1. ComplexRec 2017

    DEFF Research Database (Denmark)

    a single step in the user's more complex background need. These background needs can often place a variety of constraints on which recommendations are interesting to the user and when they are appropriate. However, relatively little research has been done on these complex recommendation scenarios....... The ComplexRec 2017 workshop addressed this by providing an interactive venue for discussing approaches to recommendation in complex scenarios that have no simple one-size-fits-all-solution....

  2. Enhanced Cellulose Degradation Using Cellulase-Nanosphere Complexes

    Science.gov (United States)

    Blanchette, Craig; Lacayo, Catherine I.; Fischer, Nicholas O.; Hwang, Mona; Thelen, Michael P.

    2012-01-01

    Enzyme catalyzed conversion of plant biomass to sugars is an inherently inefficient process, and one of the major factors limiting economical biofuel production. This is due to the physical barrier presented by polymers in plant cell walls, including semi-crystalline cellulose, to soluble enzyme accessibility. In contrast to the enzymes currently used in industry, bacterial cellulosomes organize cellulases and other proteins in a scaffold structure, and are highly efficient in degrading cellulose. To mimic this clustered assembly of enzymes, we conjugated cellulase obtained from Trichoderma viride to polystyrene nanospheres (cellulase:NS) and tested the hydrolytic activity of this complex on cellulose substrates from purified and natural sources. Cellulase:NS and free cellulase were equally active on soluble carboxymethyl cellulose (CMC); however, the complexed enzyme displayed a higher affinity in its action on microcrystalline cellulose. Similarly, we found that the cellulase:NS complex was more efficient in degrading natural cellulose structures in the thickened walls of cultured wood cells. These results suggest that nanoparticle-bound enzymes can improve catalytic efficiency on physically intractable substrates. We discuss the potential for further enhancement of cellulose degradation by physically clustering combinations of different glycosyl hydrolase enzymes, and applications for using cellulase:NS complexes in biofuel production. PMID:22870287

  3. Enhanced cellulose degradation using cellulase-nanosphere complexes.

    Science.gov (United States)

    Blanchette, Craig; Lacayo, Catherine I; Fischer, Nicholas O; Hwang, Mona; Thelen, Michael P

    2012-01-01

    Enzyme catalyzed conversion of plant biomass to sugars is an inherently inefficient process, and one of the major factors limiting economical biofuel production. This is due to the physical barrier presented by polymers in plant cell walls, including semi-crystalline cellulose, to soluble enzyme accessibility. In contrast to the enzymes currently used in industry, bacterial cellulosomes organize cellulases and other proteins in a scaffold structure, and are highly efficient in degrading cellulose. To mimic this clustered assembly of enzymes, we conjugated cellulase obtained from Trichoderma viride to polystyrene nanospheres (cellulase:NS) and tested the hydrolytic activity of this complex on cellulose substrates from purified and natural sources. Cellulase:NS and free cellulase were equally active on soluble carboxymethyl cellulose (CMC); however, the complexed enzyme displayed a higher affinity in its action on microcrystalline cellulose. Similarly, we found that the cellulase:NS complex was more efficient in degrading natural cellulose structures in the thickened walls of cultured wood cells. These results suggest that nanoparticle-bound enzymes can improve catalytic efficiency on physically intractable substrates. We discuss the potential for further enhancement of cellulose degradation by physically clustering combinations of different glycosyl hydrolase enzymes, and applications for using cellulase:NS complexes in biofuel production.

  4. Enhanced cellulose degradation using cellulase-nanosphere complexes.

    Directory of Open Access Journals (Sweden)

    Craig Blanchette

    Full Text Available Enzyme catalyzed conversion of plant biomass to sugars is an inherently inefficient process, and one of the major factors limiting economical biofuel production. This is due to the physical barrier presented by polymers in plant cell walls, including semi-crystalline cellulose, to soluble enzyme accessibility. In contrast to the enzymes currently used in industry, bacterial cellulosomes organize cellulases and other proteins in a scaffold structure, and are highly efficient in degrading cellulose. To mimic this clustered assembly of enzymes, we conjugated cellulase obtained from Trichoderma viride to polystyrene nanospheres (cellulase:NS and tested the hydrolytic activity of this complex on cellulose substrates from purified and natural sources. Cellulase:NS and free cellulase were equally active on soluble carboxymethyl cellulose (CMC; however, the complexed enzyme displayed a higher affinity in its action on microcrystalline cellulose. Similarly, we found that the cellulase:NS complex was more efficient in degrading natural cellulose structures in the thickened walls of cultured wood cells. These results suggest that nanoparticle-bound enzymes can improve catalytic efficiency on physically intractable substrates. We discuss the potential for further enhancement of cellulose degradation by physically clustering combinations of different glycosyl hydrolase enzymes, and applications for using cellulase:NS complexes in biofuel production.

  5. Complex Correspondence Principle

    International Nuclear Information System (INIS)

    Bender, Carl M.; Meisinger, Peter N.; Hook, Daniel W.; Wang Qinghai

    2010-01-01

    Quantum mechanics and classical mechanics are distinctly different theories, but the correspondence principle states that quantum particles behave classically in the limit of high quantum number. In recent years much research has been done on extending both quantum and classical mechanics into the complex domain. These complex extensions continue to exhibit a correspondence, and this correspondence becomes more pronounced in the complex domain. The association between complex quantum mechanics and complex classical mechanics is subtle and demonstrating this relationship requires the use of asymptotics beyond all orders.

  6. Uranium thiolate complexes

    International Nuclear Information System (INIS)

    Leverd, Pascal C.

    1994-01-01

    This research thesis proposes a new approach to the chemistry of uranium thiolate complexes as these compounds are very promising for various uses (in bio-inorganic chemistry, in some industrial processes like oil desulphurization). It more particularly addresses the U-S bond or more generally bonds between polarizable materials and hard metals. The author thus reports the study of uranium organometallic thiolates (tricyclo-penta-dienic and mono-cyclo-octa-tetraenylic complexes), and of uranium homoleptic thiolates (tetra-thiolate complexes, hexa-thiolate complexes, reactivity of homoleptic thiolate complexes) [fr

  7. Synthesis and properties of the para-trimethylammonium analogues of green fluorescence protein (GFP) chromophore: The mimic of protonated GFP chromophore.

    Science.gov (United States)

    Fanjiang, Ming-Wei; Li, Ming-Ju; Sung, Robert; Sung, Kuangsen

    2018-04-01

    At low pH, protons from the external, bulk solution can protonate the phenoxide group of the p-HBDI chromophore in wild-type green fluorescent protein (wtGFP) and its mutants, and likely continue to tentatively protonate the phenol hydroxyl group of the same chromophores. Because the protonated GFP chromophore is a transient, we prepare the stable p-trimethylammonium analogues (2a and 2b) of the GFP chromophore to mimic it and explore their properties. What we found is that the p-trimethylammonium analogues of the GFP chromophore have the highly electrophilic amidine carbon, blue-shifted electronic absorption, smaller molar absorptivity, smaller fluorescent quantum yield, and faster E-Z thermoisomerization rate. The amidine carbon of the p-trimethylammonium analogue (2b) of the GFP chromophore is the only site that is attacked by very weak nucleophile of water, resulting in ring-opening of the imidazolinone moiety. The half-life of its decay rate in D 2 O is around 33 days. Actually, acid-catalyzed hydrolysis of p-HBDI also results in ring-opening of the imidazolinone moiety. The ratio of the acid-catalyzed hydrolysis rate constants [k obs (p-HBDI)/k obs (1b)] between p-HBDI and 1b (p-dimethylammonium analogue of the GFP chromophore) is dramatically increased from 0.30 at pH = 2 to 0.63 at pH = 0. This is the evidence that more and more phenol hydroxyl groups of p-HBDI are tentatively protonated in a low-pH aqueous solution and that accelerates hydrolysis of p-HBDI in the way similar to the quaternary ammonium derivatives 2a and 2b in water. With this view point, 2a and 2b still can partially mimic the cationic p-HBDI with the protonated phenol hydroxyl group. Implication of the experiment is that the amidine carbon of the chromophore in wtGFP and its mutants at very low pH should be highly electrophilic. Whether ring-opening of the imidazolinone moiety of the GFP chromophore would occur or not depends on if water molecules can reach the amidine carbon of

  8. Low Complexity Transmission Scheme with Full Diversity for Two-Path Relay Networks

    KAUST Repository

    Fareed, Muhammad Mehboob

    2014-01-06

    In this work, we present a new low complexity scheme for two-path relay network to harvest maximum achievable diversity. We analyze the performance of the newly proposed two-path relay network by calculating the symbol error rate (SER) for arbitrary location of relays. It is shown that with this newly proposed scheme, two-path relay networks can mimic a 2x2 multiple-input mulitple-output (MIMO) system and achieve full diversity order of four. Simulations results are provided to verify and illustrate the analytical results.

  9. Low Complexity Transmission Scheme with Full Diversity for Two-Path Relay Networks

    KAUST Repository

    Fareed, Muhammad Mehboob; Yang, Hong-Chuan; Alouini, Mohamed-Slim

    2014-01-01

    In this work, we present a new low complexity scheme for two-path relay network to harvest maximum achievable diversity. We analyze the performance of the newly proposed two-path relay network by calculating the symbol error rate (SER) for arbitrary location of relays. It is shown that with this newly proposed scheme, two-path relay networks can mimic a 2x2 multiple-input mulitple-output (MIMO) system and achieve full diversity order of four. Simulations results are provided to verify and illustrate the analytical results.

  10. 2-Methoxypyridine as a Thymidine Mimic in Watson-Crick Base Pairs of DNA and PNA: Synthesis, Thermal Stability, and NMR Structural Studies.

    Science.gov (United States)

    Novosjolova, Irina; Kennedy, Scott D; Rozners, Eriks

    2017-11-02

    The development of nucleic acid base-pair analogues that use new modes of molecular recognition is important both for fundamental research and practical applications. The goal of this study was to evaluate 2-methoxypyridine as a cationic thymidine mimic in the A-T base pair. The hypothesis was that including protonation in the Watson-Crick base pairing scheme would enhance the thermal stability of the DNA double helix without compromising the sequence selectivity. DNA and peptide nucleic acid (PNA) sequences containing the new 2-methoxypyridine nucleobase (P) were synthesized and studied by using UV thermal melting and NMR spectroscopy. Introduction of P nucleobase caused a loss of thermal stability of ≈10 °C in DNA-DNA duplexes and ≈20 °C in PNA-DNA duplexes over a range of mildly acidic to neutral pH. Despite the decrease in thermal stability, the NMR structural studies showed that P-A formed the expected protonated base pair at pH 4.3. Our study demonstrates the feasibility of cationic unnatural base pairs; however, future optimization of such analogues will be required. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. MiT Family Translocation-Associated Renal Cell Carcinoma: A Contemporary Update With Emphasis on Morphologic, Immunophenotypic, and Molecular Mimics.

    Science.gov (United States)

    Magers, Martin J; Udager, Aaron M; Mehra, Rohit

    2015-10-01

    Translocation-associated renal cell carcinoma (t-RCC) is a relatively uncommon subtype of renal cell carcinoma characterized by recurrent gene rearrangements involving the TFE3 or TFEB loci. TFE3 and TFEB are members of the microphthalmia transcription factor (MiT) family, which regulates differentiation in melanocytes and osteoclasts, and MiT family gene fusions activate unique molecular programs that can be detected immunohistochemically. Although the overall clinical behavior of t-RCC is variable, emerging molecular data suggest the possibility of targeted approaches to advanced disease. Thus, distinguishing t-RCC from its morphologic, immunophenotypic, and molecular mimics may have important clinical implications. The differential diagnosis for t-RCC includes a variety of common renal neoplasms, particularly those demonstrating clear cell and papillary features; in addition, because of immunophenotypic overlap and/or shared molecular abnormalities (ie, TFE3 gene rearrangement), a distinctive set of nonepithelial renal tumors may also warrant consideration. Directed ancillary testing is an essential aspect to the workup of t-RCC cases and may include a panel of immunohistochemical stains, such as PAX8, pancytokeratins, epithelial membrane antigen, carbonic anhydrase IX, HMB-45, and Melan-A. Dual-color, break-apart fluorescent in situ hybridization for TFE3 or TFEB gene rearrangement may be helpful in diagnostically challenging cases or when molecular confirmation is needed.

  12. Uricase-free on-demand colorimetric biosensing of uric acid enabled by integrated CoP nanosheet arrays as a monolithic peroxidase mimic.

    Science.gov (United States)

    He, Yanfang; Qi, Fei; Niu, Xiangheng; Zhang, Wenchi; Zhang, Xifeng; Pan, Jianming

    2018-08-27

    In clinical diagnosis, monitoring of uric acid (UA) is generally realized by combining uricase with natural peroxidase. The use of bio-enzymes, however, shadows some highlights of these methods due to their vulnerable activities against environments. Herein, we report a novel biosensor for the natural enzyme-free colorimetric detection of UA by using CoP nanosheet arrays grown on Ni foam (NF) as a monolithic peroxidase mimic. The integrated nanozyme can be put into and taken out from reaction systems conveniently with only tweezers, making it possible for on-demand analysis. As demonstrated, the obtained CoP/NF exhibits outstanding peroxidase-like activity to trigger the oxidation reaction of colorless 3,3'5,5'-tetramethylbenzidine (TMB) to a blue product (TMBox) mediated by H 2 O 2 . It is found that the blue TMBox can be reduced to colorless TMB again by UA selectively, thus the presence of UA in solutions will suppress the color reaction of TMB. Based on this principle, an uricase-free biosensor is developed for the photometric determination of UA, providing a wide detection range of 1-200 μM and a limit of detection down to 1.0 μM. In addition, the fabricated biosensor can be applied for measuring UA in clinical samples with merits of simple operation and good reliability, exhibiting its great promise in clinical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. A Nampt inhibitor FK866 mimics vitamin B3 deficiency by causing senescence of human fibroblastic Hs68 cells via attenuation of NAD(+)-SIRT1 signaling.

    Science.gov (United States)

    Song, Tuzz-Ying; Yeh, Shu-Lan; Hu, Miao-Lin; Chen, Mei-Yau; Yang, Nae-Cherng

    2015-12-01

    Vitamin B3 (niacin) deficiency can cause pellagra with symptoms of dermatitis, diarrhea and dementia. However, it is unclear whether the vitamin B3 deficiency causes human aging. FK866 (a Nampt inhibitor) can reduce intracellular NAD(+) level and induce senescence of human Hs68 cells. However, the mechanisms underlying FK866-induced senescence of Hs68 cells are unclear. In this study, we used FK866 to mimic the effects of vitamin B3 deficiency to reduce the NAD(+) level and investigated the mechanisms of FK866-induced senescence of Hs68 cells. We hypothesized that FK866 induced the senescence of Hs68 cells via an attenuation of NAD(+)-silent information regulator T1 (SIRT1) signaling. We found that FK866 induced cell senescence and diminished cellular NAD(+) levels and SIRT1 activity (detected by acetylation of p53), and these effects were dramatically antagonized by co-treatment with nicotinic acid, nicotinamide, or NAD(+). In contrast, the protein expression of SIRT1, AMP-activated protein kinase, mammalian target of rapamycin, and nicotinamide phosphoribosyltransferase (Nampt) was not affected by FK866. In addition, the role of GSH in the FK866-induced cells senescence may be limited, as N-acetylcysteine did not antagonize FK866-induced cell senescence. These results suggest that FK866 induces cell senescence via attenuation of NAD(+)-SIRT1 signaling. The effects of vitamin B3 deficiency on human aging warrant further investigation.

  14. Amide linkages mimic phosphates in RNA interactions with proteins and are well tolerated in the guide strand of short interfering RNAs.

    Science.gov (United States)

    Mutisya, Daniel; Hardcastle, Travis; Cheruiyot, Samwel K; Pallan, Pradeep S; Kennedy, Scott D; Egli, Martin; Kelley, Melissa L; Smith, Anja van Brabant; Rozners, Eriks

    2017-08-21

    While the use of RNA interference (RNAi) in molecular biology and functional genomics is a well-established technology, in vivo applications of synthetic short interfering RNAs (siRNAs) require chemical modifications. We recently found that amides as non-ionic replacements for phosphodiesters may be useful modifications for optimization of siRNAs. Herein, we report a comprehensive study of systematic replacement of a single phosphate with an amide linkage throughout the guide strand of siRNAs. The results show that amides are surprisingly well tolerated in the seed and central regions of the guide strand and increase the silencing activity when placed between nucleosides 10 and 12, at the catalytic site of Argonaute. A potential explanation is provided by the first crystal structure of an amide-modified RNA-DNA with Bacillus halodurans RNase H1. The structure reveals how small changes in both RNA and protein conformation allow the amide to establish hydrogen bonding interactions with the protein. Molecular dynamics simulations suggest that these alternative binding modes may compensate for interactions lost due to the absence of a phosphodiester moiety. Our results suggest that an amide can mimic important hydrogen bonding interactions with proteins required for RNAi activity and may be a promising modification for optimization of biological properties of siRNAs. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Multiple Myeloma Presenting as Massive Amyloid Deposition in a Parathyroid Gland Associated with Amyloid Goiter: A Medullary Thyroid Carcinoma Mimic on Intra-operative Frozen Section.

    Science.gov (United States)

    Hill, Kirk; Diaz, Jason; Hagemann, Ian S; Chernock, Rebecca D

    2018-06-01

    Clinical examples of amyloid deposition in parathyroid glands are exceedingly rare and usually present as an incidental finding in a patient with amyloid goiter. Here, we present the first histologically documented case of parathyroid amyloid deposition that presented as a mass. The patient did not have hyperparathyroidism. The parathyroid gland was submitted for intra-operative frozen section and concern for medullary thyroid carcinoma was raised. An important histologic clue arguing against medullary thyroid carcinoma was the evenly dispersed nature of the amyloid. Histologic perinuclear clearing and parathyroid hormone immunohistochemistry confirmed parathyroid origin on permanent sections. The patient was also found to have associated amyloid goiter. Mass spectrometry of the amyloid showed it to be composed of kappa light chains. On further work-up, the patient was diagnosed with multiple myeloma. Awareness of parathyroid amyloid deposition is important as it is a histologic mimic of medullary thyroid carcinoma, especially on frozen section. Amyloid typing with evaluation for multiple myeloma in any patient with kappa or lambda light chain restriction is also important.

  16. Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The “Study of Origin”

    Directory of Open Access Journals (Sweden)

    Leo Pruimboom

    2016-01-01

    Full Text Available Chronic low-grade inflammation and insulin resistance are intimately related entities that are common to most, if not all, chronic diseases of affluence. We hypothesized that a short-term intervention based on “ancient stress factors” may improve anthropometrics and clinical chemical indices. We executed a pilot study of whether a 10-day mimic of a hunter-gatherer lifestyle favorably affects anthropometrics and clinical chemical indices. Fifty-five apparently healthy subjects, in 5 groups, engaged in a 10-day trip through the Pyrenees. They walked 14 km/day on average, carrying an 8-kilo backpack. Raw food was provided and self-prepared and water was obtained from waterholes. They slept outside in sleeping bags and were exposed to temperatures ranging from 12 to 42°C. Anthropometric data and fasting blood samples were collected at baseline and the study end. We found important significant changes in most outcomes favoring better metabolic functioning and improved anthropometrics. Coping with “ancient mild stress factors,” including physical exercise, thirst, hunger, and climate, may influence immune status and improve anthropometrics and metabolic indices in healthy subjects and possibly patients suffering from metabolic and immunological disorders.

  17. Impact of a high magnetic field on the orientation of gravitactic unicellular organisms--a critical consideration about the application of magnetic fields to mimic functional weightlessness.

    Science.gov (United States)

    Hemmersbach, Ruth; Simon, Anja; Waßer, Kai; Hauslage, Jens; Christianen, Peter C M; Albers, Peter W; Lebert, Michael; Richter, Peter; Alt, Wolfgang; Anken, Ralf

    2014-03-01

    The gravity-dependent behavior of Paramecium biaurelia and Euglena gracilis have previously been studied on ground and in real microgravity. To validate whether high magnetic field exposure indeed provides a ground-based facility to mimic functional weightlessness, as has been suggested earlier, both cell types were observed during exposure in a strong homogeneous magnetic field (up to 30 T) and a strong magnetic field gradient. While swimming, Paramecium cells were aligned along the magnetic field lines; orientation of Euglena was perpendicular, demonstrating that the magnetic field determines the orientation and thus prevents the organisms from the random swimming known to occur in real microgravity. Exposing Astasia longa, a flagellate that is closely related to Euglena but lacks chloroplasts and the photoreceptor, as well as the chloroplast-free mutant E. gracilis 1F, to a high magnetic field revealed no reorientation to the perpendicular direction as in the case of wild-type E. gracilis, indicating the existence of an anisotropic structure (chloroplasts) that determines the direction of passive orientation. Immobilized Euglena and Paramecium cells could not be levitated even in the highest available magnetic field gradient as sedimentation persisted with little impact of the field on the sedimentation velocities. We conclude that magnetic fields are not suited as a microgravity simulation for gravitactic unicellular organisms due to the strong effect of the magnetic field itself, which masks the effects known from experiments in real microgravity.

  18. Amide linkages mimic phosphates in RNA interactions with proteins and are well tolerated in the guide strand of short interfering RNAs

    Energy Technology Data Exchange (ETDEWEB)

    Mutisya, Daniel; Hardcastle, Travis; Cheruiyot, Samwel K.; Pallan, Pradeep S.; Kennedy, Scott D.; Egli, Martin; Kelley, Melissa L.; Smith, Anja van Brabant; Rozners, Eriks

    2017-06-27

    While the use of RNA interference (RNAi) in molecular biology and functional genomics is a well-established technology, in vivo applications of synthetic short interfering RNAs (siRNAs) require chemical modifications. We recently found that amides as non-ionic replacements for phosphodiesters may be useful modifications for optimization of siRNAs. Herein, we report a comprehensive study of systematic replacement of a single phosphate with an amide linkage throughout the guide strand of siRNAs. The results show that amides are surprisingly well tolerated in the seed and central regions of the guide strand and increase the silencing activity when placed between nucleosides 10 and 12, at the catalytic site of Argonaute. A potential explanation is provided by the first crystal structure of an amide-modified RNA–DNA with Bacillus halodurans RNase H1. The structure reveals how small changes in both RNA and protein conformation allow the amide to establish hydrogen bonding interactions with the protein. Molecular dynamics simulations suggest that these alternative binding modes may compensate for interactions lost due to the absence of a phosphodiester moiety. Our results suggest that an amide can mimic important hydrogen bonding interactions with proteins required for RNAi activity and may be a promising modification for optimization of biological properties of siRNAs.

  19. Optimal dose and timing of insulin Aspart to mimic first phase insulin response in patients with recently onset type 2 diabetes

    DEFF Research Database (Denmark)

    Gredal, C.; Rosenfalck, A.; Dejgaard, A.

    2008-01-01

    OBJECTIVE: To assess the optimal dose and timing of subcutaneous injection of insulin Aspart (IAsp) in relation to meal to mimic first phase insulin response in patients with recently diagnosed type 2 diabetes. DESIGN AND METHODS: Twenty patients were randomised in a double blind, double dummy...... design to four standard meal tests with pre-meal injection of insulin Aspart 0.08 IU/kg BW 30 min before the meal, insulin Aspart 0.04 IU/kg BW 30 or 15 min before the meal and placebo. RESULTS: All three insulin regimes significantly reduced postprandial glucose increment (area under the curve AUC(-30...... injection of IAsp 0.08 IU/kg BW. No difference in postprandial glucose profile was demonstrated whether IAsp 0.04 IU/kg BW was administrated 15 or 30 min before mealtime. CONCLUSIONS: IAsp 0.04IU/kg BW injected subcutaneously 15 or 30 min before meal reduced the postprandial blood glucose increment without...

  20. The T4 Phage DNA Mimic Protein Arn Inhibits the DNA Binding Activity of the Bacterial Histone-like Protein H-NS*

    Science.gov (United States)

    Ho, Chun-Han; Wang, Hao-Ching; Ko, Tzu-Ping; Chang, Yuan-Chih; Wang, Andrew H.-J.

    2014-01-01

    The T4 phage protein Arn (Anti restriction nuclease) was identified as an inhibitor of the restriction enzyme McrBC. However, until now its molecular mechanism remained unclear. In the present study we used structural approaches to investigate biological properties of Arn. A structural analysis of Arn revealed that its shape and negative charge distribution are similar to dsDNA, suggesting that this protein could act as a DNA mimic. In a subsequent proteomic analysis, we found that the bacterial histone-like protein H-NS interacts with Arn, implying a new function. An electrophoretic mobility shift assay showed that Arn prevents H-NS from binding to the Escherichia coli hns and T4 p8.1 promoters. In vitro gene expression and electron microscopy analyses also indicated that Arn counteracts the gene-silencing effect of H-NS on a reporter gene. Because McrBC and H-NS both participate in the host defense system, our findings suggest that T4 Arn might knock down these mechanisms using its DNA mimicking properties. PMID:25118281

  1. Fabrication of PDMS through-holes using the MIMIC method and the surface treatment by atmospheric-pressure CH4/He RF plasma

    Science.gov (United States)

    Choi, Jongchan; Lee, Kyeong-Hwan; Yang, Sung

    2011-09-01

    This note presents a simple fabrication process for patterning micro through-holes in a PDMS layer by a combination of the micromolding in capillaries (MIMIC) method and the surface treatment by atmospheric-pressure CH4/He RF plasma. The fabrication process is confirmed by forming micro through-holes with various shapes including circle, C-shape, open microfluidic channel and hemisphere. All micro through-holes of various shapes in a wide range of diameters and heights are well fabricated by the proposed method. Also, a 3D micromixer containing a PDMS micro through-hole layer formed by the proposed method is built and its performance is tested as another practical demonstration of the proposed fabrication method. Therefore, we believe that the proposed fabrication process will build a PDMS micro through-hole layer in a simple and easy way and will contribute to developing highly efficient multi-layered microfluidic systems, which may require PDMS micro through-hole layers.

  2. Simplicial complexes of graphs

    CERN Document Server

    Jonsson, Jakob

    2008-01-01

    A graph complex is a finite family of graphs closed under deletion of edges. Graph complexes show up naturally in many different areas of mathematics, including commutative algebra, geometry, and knot theory. Identifying each graph with its edge set, one may view a graph complex as a simplicial complex and hence interpret it as a geometric object. This volume examines topological properties of graph complexes, focusing on homotopy type and homology. Many of the proofs are based on Robin Forman's discrete version of Morse theory. As a byproduct, this volume also provides a loosely defined toolbox for attacking problems in topological combinatorics via discrete Morse theory. In terms of simplicity and power, arguably the most efficient tool is Forman's divide and conquer approach via decision trees; it is successfully applied to a large number of graph and digraph complexes.

  3. On Complex Random Variables

    Directory of Open Access Journals (Sweden)

    Anwer Khurshid

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE In this paper, it is shown that a complex multivariate random variable  is a complex multivariate normal random variable of dimensionality if and only if all nondegenerate complex linear combinations of  have a complex univariate normal distribution. The characteristic function of  has been derived, and simpler forms of some theorems have been given using this characterization theorem without assuming that the variance-covariance matrix of the vector  is Hermitian positive definite. Marginal distributions of  have been given. In addition, a complex multivariate t-distribution has been defined and the density derived. A characterization of the complex multivariate t-distribution is given. A few possible uses of this distribution have been suggested.

  4. Cobalt(III) complex

    Indian Academy of Sciences (India)

    Administrator

    e, 40 µM complex, 10 hrs after dissolution, f, 40 µM complex, after irradiation dose 15 Gy. and H-atoms result in reduction of Co(III) to Co. (II). 6. It is interesting to see in complex containing multiple ligands what is the fate of electron adduct species formed by electron addition. Reduction to. Co(II) and intramolecular transfer ...

  5. Complex Systems and Dependability

    CERN Document Server

    Zamojski, Wojciech; Sugier, Jaroslaw

    2012-01-01

    Typical contemporary complex system is a multifaceted amalgamation of technical, information, organization, software and human (users, administrators and management) resources. Complexity of such a system comes not only from its involved technical and organizational structure but mainly from complexity of information processes that must be implemented in the operational environment (data processing, monitoring, management, etc.). In such case traditional methods of reliability analysis focused mainly on technical level are usually insufficient in performance evaluation and more innovative meth

  6. Lanthanide complexes with pivaloylacetone

    International Nuclear Information System (INIS)

    Eliseeva, S.V.; Chugarov, N.V.; Kuz'mina, N.P.; Martynenko, L.I.; Nichiporuk, R.V.; Ivanov, S.A.

    2003-01-01

    Complexes Ln(pa) 3 ·2H 2 O (Ln=La, Gd, Lu, Hpa - pivaloylacetone) are synthesized and investigated by the methods of element, IR spectroscopic and thermal analyses. Behaviour of the complexes during heating in vacuum is compared with such one for acetylacetonates and dipivaloylmethanates. Structure of the complexes in solution is studied by 1 H NMR and MALDI-MS [ru

  7. Phospholyl-uranium complexes

    International Nuclear Information System (INIS)

    Gradoz, Philippe

    1993-01-01

    After having reported a bibliographical study on penta-methylcyclopentadienyl uranium complexes, and a description of the synthesis and radioactivity of uranium (III) and (IV) boron hydrides compounds, this research thesis reports the study of mono and bis-tetramethyl-phospholyl uranium complexes comprising chloride, boron hydride, alkyl and alkoxide ligands. The third part reports the comparison of structures, stabilities and reactions of homologue complexes in penta-methylcyclopentadienyl and tetramethyl-phospholyl series. The last part addresses the synthesis of tris-phospholyl uranium (III) and (IV) complexes. [fr

  8. Nuclear weapons complex

    International Nuclear Information System (INIS)

    Rezendes, V.S.

    1991-03-01

    In this book, GAO characterizes DOE's January 1991 Nuclear Weapons Complex Reconfiguration Study as a starting point for reaching agreement on solutions to many of the complex's safety and environmental problems. Key decisions still need to be made about the size of the complex, where to relocate plutonium operations, what technologies to use for new tritium production, and what to do with excess plutonium. The total cost for reconfiguring and modernizing the complex is still uncertain, and some management issues remain unresolved. Congress faces a difficult task in making test decisions given the conflicting demands for scarce resources in a time of growing budget deficits and war in the Persian Gulf

  9. Conducting metal dithiolate complexes

    DEFF Research Database (Denmark)

    Underhill, A. E.; Ahmad, M. M.; Turner, D. J.

    1985-01-01

    Further work on the chemical composition of the one-dimensional metallic metal dithiolene complex Li-Pt(mnt) is reported. The electrical conduction and thermopower properties of the nickel and palladium complexes are reported and compared with those of the platinum compound......Further work on the chemical composition of the one-dimensional metallic metal dithiolene complex Li-Pt(mnt) is reported. The electrical conduction and thermopower properties of the nickel and palladium complexes are reported and compared with those of the platinum compound...

  10. Intrarenal neuroblastoma mimics Wilms' tumor

    International Nuclear Information System (INIS)

    Muniz, Maria T. Cartaxo; Soares, Andrezza B.; Freitas, Elizabete M.; Araujo, Marcela; Pureza, Leda M.M.; Morais, Adriana; Antunes, Consuelo; Salles, Terezinha de J. Marques; Borges, Josenilda C.; Morais, Vera L.L. de; Romualdo Filho, Jose; Magalhaes, Mario H.

    2005-01-01

    This work reports the case history of a child with intrarenal neuroblastoma, initially diagnosed as Wilms' tumor. The patient, a one year and three months old girl, presented a hard abdominal mass on the left flank that extended to the meso gastric region, plus fever and paleness. The ultrasound of the entire abdomen revealed an intrarenal mass. Biopsy with fine needle in many points of the tumor revealed Wilms' tumor. The scarcely of the material, however, made immunohistoquemistry impossible at that moment. Because of the child's severe condition the SIOP protocol was started. As no clinical response was observed, an exploratory laparotomy was indicated with partial resection of the tumor and bone marrow aspiration (MO). The histopathologic study revealed a malignant neoplasia of small cells, poorly differentiated. IHQ was negative for WT-1 and positive for NB-84, synaptofisin, cromogranine. N-myc amplification was observed by molecular biology. The bone marrow aspiration identified metastatic small round cells infiltration. Intrarenal neuroblastoma is a rare entity that clinically and radiographically resembles Wilms' tumor. The objective of this case report is to show the importance of immunohistochemical and molecular analysis in the diagnosis of intrarenal neuroblastoma. (author)

  11. Artifacts that mimic ballistic magnetoresistance

    International Nuclear Information System (INIS)

    Egelhoff, W.F. . E-mail : egelhoff@nist.gov; Gan, L.; Ettedgui, H.; Kadmon, Y.; Powell, C.J.; Chen, P.J.; Shapiro, A.J.; McMichael, R.D.; Mallett, J.J.; Moffat, T.P.; Stiles, M.D.; Svedberg, E.B.

    2005-01-01

    We have investigated the circumstances underlying recent reports of very large values of ballistic magnetoresistance (BMR) in nanocontacts between magnetic wires. We find that the geometries used are subject to artifacts due to motion of the wires that distort the nanocontact thereby changing its electrical resistance. Since these nanocontacts are often of atomic scale, reliable experiments would require stability on the atomic scale. No method for achieving such stability in macroscopic wires is apparent. We conclude that macroscopic magnetic wires cannot be used to establish the validity of the BMR effect

  12. From Sugars to Sugar Mimics

    DEFF Research Database (Denmark)

    The mechanism of enzymatic cleavage of glycosides has been continuously under debate and design of new glycosidase inhibitors has been based on structural similarity of putative intermediates or transition states. Recently the aminocyclopentanols have drawn considerable attention as potent glycos...

  13. Cyclodextrin Aldehydes are Oxidase Mimics

    DEFF Research Database (Denmark)

    Fenger, Thomas Hauch; Bjerre, Jeannette; Bols, Mikael

    2009-01-01

    Cyclodextrins containing 6-aldehyde groups were found to catalyse oxidation of aminophenols in the presence of hydrogen peroxide. The catalysis followed Michaelis-Menten kinetics and is related to the catalysis previously observed with cyclodextrin ketones. A range of different cyclodextrin aldeh...

  14. Mangrove leaf transportation : Do mimic

    NARCIS (Netherlands)

    Gillis, L.G; Zimmer, M.; Bouma, T.J.

    2016-01-01

    Mangrove forests are typically located in the catchment areas of the terrestrial zoneand can be adjacent to oceanic ecosystems (e.g. seagrass beds and coral reefs). These forests arethought to provide ecosystem services by retaining particulate organic matter such as detritalleaves that can

  15. Electron transfer reactions of ruthenium(II) complexes with polyphenolic acids in micelles

    Energy Technology Data Exchange (ETDEWEB)

    Rajeswari, Angusamy [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India); Department of Chemistry, Fatima College, Madurai 625 018 (India); Ramdass, Arumugam [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India); Research Department of Chemistry, Aditanar College of Arts and Science, Tiruchendur 628 216 (India); Muthu Mareeswaran, Paulpandian [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India); Department of Industrial Chemistry, Alagappa University, Karaikudi 630 003 (India); Rajagopal, Seenivasan, E-mail: rajagopalseenivasan@yahoo.com [School of Chemistry, Madurai Kamaraj University, Madurai 625 021 (India)

    2016-02-15

    The electron transfer in a microhetrogeneous system is a perfect mimic of biological electron transfer. The electron transfer between biologically important phenolic acids and ruthenium (II) complexes is systematically studied in the presence of anionic and cationic micelles. The photophysical properties of these ruthenium (II) complexes with anionic and cationic micelles and their binding abilities with these two type of micelles are also studies using absorption, emission and excited state lifetime spectral techniques. Pseudophase Ion Exchange (PIE) Model is applied to derive mechanism of electron transfer in two types of micelles. - Highlights: • Effect of microhetrogeneous system is studied using ruthenium (II) complexes and gallic acid is studied. • Pseudophase Ion exchange model is applied to derive the mechanism. • Binding constants are in the range of 10{sup 2}–10{sup 4} M{sup −1}.

  16. Reduced-Complexity Deterministic Annealing for Vector Quantizer Design

    Directory of Open Access Journals (Sweden)

    Ortega Antonio

    2005-01-01

    Full Text Available This paper presents a reduced-complexity deterministic annealing (DA approach for vector quantizer (VQ design by using soft information processing with simplified assignment measures. Low-complexity distributions are designed to mimic the Gibbs distribution, where the latter is the optimal distribution used in the standard DA method. These low-complexity distributions are simple enough to facilitate fast computation, but at the same time they can closely approximate the Gibbs distribution to result in near-optimal performance. We have also derived the theoretical performance loss at a given system entropy due to using the simple soft measures instead of the optimal Gibbs measure. We use thederived result to obtain optimal annealing schedules for the simple soft measures that approximate the annealing schedule for the optimal Gibbs distribution. The proposed reduced-complexity DA algorithms have significantly improved the quality of the final codebooks compared to the generalized Lloyd algorithm and standard stochastic relaxation techniques, both with and without the pairwise nearest neighbor (PNN codebook initialization. The proposed algorithms are able to evade the local minima and the results show that they are not sensitive to the choice of the initial codebook. Compared to the standard DA approach, the reduced-complexity DA algorithms can operate over 100 times faster with negligible performance difference. For example, for the design of a 16-dimensional vector quantizer having a rate of 0.4375 bit/sample for Gaussian source, the standard DA algorithm achieved 3.60 dB performance in 16 483 CPU seconds, whereas the reduced-complexity DA algorithm achieved the same performance in 136 CPU seconds. Other than VQ design, the DA techniques are applicable to problems such as classification, clustering, and resource allocation.

  17. Lewis Acid Assisted Nitrate Reduction with Biomimetic Molybdenum Oxotransferase Complex.

    Science.gov (United States)

    Elrod, Lee Taylor; Kim, Eunsuk

    2018-03-05

    The reduction of nitrate (NO 3 - ) to nitrite (NO 2 - ) is of significant biological and environmental importance. While Mo IV (O) and Mo VI (O) 2 complexes that mimic the active site structure of nitrate reducing enzymes are prevalent, few of these model complexes can reduce nitrate to nitrite through oxygen atom transfer (OAT) chemistry. We present a novel strategy to induce nitrate reduction chemistry of a previously known catalyst Mo IV (O)(SN) 2 (2), where SN = bis(4- tert-butylphenyl)-2-pyridylmethanethiolate, that is otherwise incapable of achieving OAT with nitrate. Addition of nitrate with the Lewis acid Sc(OTf) 3 (OTf = trifluoromethanesulfonate) to 2 results in an immediate and clean conversion of 2 to Mo VI (O) 2 (SN) 2 (1). The Lewis acid additive further reacts with the OAT product, nitrite, to form N 2 O and O 2 . This work highlights the ability of Sc 3+ additives to expand the reactivity scope of an existing Mo IV (O) complex together with which Sc 3+ can convert nitrate to stable gaseous molecules.

  18. Single-stranded nucleic acids promote SAMHD1 complex formation.

    Science.gov (United States)

    Tüngler, Victoria; Staroske, Wolfgang; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; Schmidt, Franziska; Krug, Claudia; Lorenz, Mike; Chara, Osvaldo; Schwille, Petra; Lee-Kirsch, Min Ae

    2013-06-01

    SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.

  19. Peripheral neuropathy in complex inherited diseases: an approach to diagnosis.

    Science.gov (United States)

    Rossor, Alexander M; Carr, Aisling S; Devine, Helen; Chandrashekar, Hoskote; Pelayo-Negro, Ana Lara; Pareyson, Davide; Shy, Michael E; Scherer, Steven S; Reilly, Mary M

    2017-10-01

    Peripheral neuropathy is a common finding in patients with complex inherited neurological diseases and may be subclinical or a major component of the phenotype. This review aims to provide a clinical approach to the diagnosis of this complex group of patients by addressing key questions including the predominant neurological syndrome associated with the neuropathy, for example, spasticity, the type of neuropathy and the other neurological and non-neurological features of the syndrome. Priority is given to the diagnosis of treatable conditions. Using this approach, we associated neuropathy with one of three major syndromic categories: (1) ataxia, (2) spasticity and (3) global neurodevelopmental impairment. Syndromes that do not fall easily into one of these three categories can be grouped according to the predominant system involved in addition to the neuropathy, for example, cardiomyopathy and neuropathy. We also include a separate category of complex inherited relapsing neuropathy syndromes, some of which may mimic Guillain-Barré syndrome, as many will have a metabolic aetiology and be potentially treatable. © 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.

  20. Visual Complexity: A Review

    Science.gov (United States)

    Donderi, Don C.

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from…