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Sample records for helix-based fibrils driven

  1. Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

    Science.gov (United States)

    Honda, Ryo; Kuwata, Kazuo

    2018-02-01

    Amyloid fibrils are filamentous protein aggregates associated with the pathogenesis of a wide variety of human diseases. The formation of such aggregates typically follows nucleation-dependent kinetics, wherein the assembly and structural conversion of amyloidogenic proteins into oligomeric aggregates (nuclei) is the rate-limiting step of the overall reaction. In this study, we sought to gain structural insights into the oligomeric nuclei of the human prion protein (PrP) by preparing a series of deletion mutants lacking 14-44 of the C-terminal 107 residues of PrP and examined the kinetics and thermodynamics of these mutants in amyloid formation. An analysis of the experimental data using the concepts of the Φ-value analysis indicated that the helix 2 region (residues 168-196) acquires an amyloid-like β-sheet during nucleation, whereas the other regions preserves a relatively disordered structure in the nuclei. This finding suggests that the helix 2 region serves as the nucleation site for the assembly of amyloid fibrils.-Honda, R., Kuwata, K. Evidence for a central role of PrP helix 2 in the nucleation of amyloid fibrils.

  2. Multiple helix ecosystems for sustainable competitiveness

    CERN Document Server

    Ferreira, João; Farinha, Luís; Fernandes, Nuno

    2016-01-01

    This book discusses the main issues, challenges, opportunities, and trends involving the interactions between academia, industry, government and society. Specifically, it aims to explore how these interactions enhance the ways in which companies deliver products and services in order to achieve sustainable competitiveness in the marketplace. Sustainable competitiveness has been widely discussed by academics and practitioners, considering the importance of protecting the environment while sustaining the economic goals of organizations. The Quintuple Helix innovation model is a framework for facilitating knowledge, innovation and sustainable competitive advantage. It embeds the Triple and the Quadruple Helix models by adding a fifth helix, the “natural environment.” The Triple Helix model focuses on the university-industry-government triad, while the Quadruple adds civil society (the media- and culture-driven public) as a fourth helix. The Quintuple Helix model facilitates research, public policy, and pract...

  3. Aggregation and fibrillation of bovine serum albumin

    DEFF Research Database (Denmark)

    Holm, NK; Jespersen, SK; Thomassen, LV

    2007-01-01

    The all-alpha helix multi-domain protein bovine serum albumin (BSA) aggregates at elevated temperatures. Here we show that these thermal aggregates have amyloid properties. They bind the fibril-specific dyes Thioflavin T and Congo Red, show elongated although somewhat worm-like morphology...

  4. SDS-Induced Fibrillation of α-Synuclein

    DEFF Research Database (Denmark)

    Giehm, L.; Oliveira, Cristiano Luis Pinto De; Pedersen, J.S.

    2010-01-01

    . In this fibrillogenic complex, 4 αSN molecules initially associate with 40-50 SDS molecules to form a shared micelle that gradually grows in size. The complex initially exhibits a mixture of random coil and α-helix, but incubation results in a structural conversion into β-sheet structure and concomitant formation......-stabilized micelles. Thus, fibrillation in this case occurs by a process of continuous accretion rather than by the rate-limiting accumulation of a distinct nucleus. The morphology of the SDS-induced fibrils does not exhibit the classical rod-like structures formed by αSN when aggregated by agitation in the absence...

  5. Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.

    Science.gov (United States)

    Perumal, Shiamalee; Antipova, Olga; Orgel, Joseph P R O

    2008-02-26

    We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.

  6. Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids

    Energy Technology Data Exchange (ETDEWEB)

    García-González, Victor [Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, DF (Mexico); Mas-Oliva, Jaime, E-mail: jmas@ifc.unam.mx [Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México, DF (Mexico); División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510 México, DF (Mexico)

    2013-04-26

    Highlights: •The secondary structure of a C-terminal peptide derived from CETP was studied. •Lipids modulate secondary structure changes of a C-terminal peptide derived from CETP. •Lysophosphatidic acid maintains a functional α-helix and prevents fibril formation. •Transfer of lipids by CETP is related to the presence of an α-helix at its C-end. -- Abstract: Cholesteryl-ester transfer protein (CETP) is a plasmatic protein involved in neutral lipid transfer between lipoproteins. Focusing on the last 12 C-terminus residues we have previously shown that mutation D{sub 470}N promotes a conformational change towards a β-secondary structure. In turn, this modification leads to the formation of oligomers and fibrillar structures, which cause cytotoxic effects similar to the ones provoked by amyloid peptides. In this study, we evaluated the role of specific lipid arrangements on the structure of peptide helix-Z (D{sub 470}N) through the use of thioflavin T fluorescence, peptide bond absorbance, circular dichroism and electron microscopy. The results indicate that the use of micelles formed with lysophosphatidylcholine and lysophosphatidic acid (LPA) under neutral pH induce a conformational transition of peptide helix-Z containing a β-sheet conformation to a native α-helix structure, therefore avoiding the formation of amyloid fibrils. In contrast, incubation with phosphatidic acid does not change the profile for the β-sheet conformation. When the electrostatic charge at the surface of micelles or vesicles is regulated through the use of lipids such as phospholipid and LPA, minimal changes and the presence of β-structures were recorded. Mixtures with a positive net charge diminished the percentage of β-structure and the amount of amyloid fibrils. Our results suggest that the degree of solvation determined by the presence of a free hydroxyl group on lipids such as LPA is a key condition that can modulate the secondary structure and the consequent formation of

  7. Amyloid fibril formation of peptides derived from the C-terminus of CETP modulated by lipids

    International Nuclear Information System (INIS)

    García-González, Victor; Mas-Oliva, Jaime

    2013-01-01

    Highlights: •The secondary structure of a C-terminal peptide derived from CETP was studied. •Lipids modulate secondary structure changes of a C-terminal peptide derived from CETP. •Lysophosphatidic acid maintains a functional α-helix and prevents fibril formation. •Transfer of lipids by CETP is related to the presence of an α-helix at its C-end. -- Abstract: Cholesteryl-ester transfer protein (CETP) is a plasmatic protein involved in neutral lipid transfer between lipoproteins. Focusing on the last 12 C-terminus residues we have previously shown that mutation D 470 N promotes a conformational change towards a β-secondary structure. In turn, this modification leads to the formation of oligomers and fibrillar structures, which cause cytotoxic effects similar to the ones provoked by amyloid peptides. In this study, we evaluated the role of specific lipid arrangements on the structure of peptide helix-Z (D 470 N) through the use of thioflavin T fluorescence, peptide bond absorbance, circular dichroism and electron microscopy. The results indicate that the use of micelles formed with lysophosphatidylcholine and lysophosphatidic acid (LPA) under neutral pH induce a conformational transition of peptide helix-Z containing a β-sheet conformation to a native α-helix structure, therefore avoiding the formation of amyloid fibrils. In contrast, incubation with phosphatidic acid does not change the profile for the β-sheet conformation. When the electrostatic charge at the surface of micelles or vesicles is regulated through the use of lipids such as phospholipid and LPA, minimal changes and the presence of β-structures were recorded. Mixtures with a positive net charge diminished the percentage of β-structure and the amount of amyloid fibrils. Our results suggest that the degree of solvation determined by the presence of a free hydroxyl group on lipids such as LPA is a key condition that can modulate the secondary structure and the consequent formation of amyloid

  8. Exercise-based cardiac rehabilitation for adults with atrial fibrillation

    DEFF Research Database (Denmark)

    Risom, Signe Stelling; Zwisler, Ann-Dorthe; Johansen, Pernille Palm

    2017-01-01

    BACKGROUND: Exercise-based cardiac rehabilitation may benefit adults with atrial fibrillation or those who had been treated for atrial fibrillation. Atrial fibrillation is caused by multiple micro re-entry circuits within the atrial tissue, which result in chaotic rapid activity in the atria....... OBJECTIVES: To assess the benefits and harms of exercise-based rehabilitation programmes, alone or with another intervention, compared with no-exercise training controls in adults who currently have AF, or have been treated for AF. SEARCH METHODS: We searched the following electronic databases; CENTRAL...... the benefits and harms of exercise-based cardiac rehabilitation for adults with atrial fibrillation on patient-relevant outcomes....

  9. Structure–mechanics relationships of collagen fibrils in the osteogenesis imperfecta mouse model

    Science.gov (United States)

    Andriotis, O. G.; Chang, S. W.; Vanleene, M.; Howarth, P. H.; Davies, D. E.; Shefelbine, S. J.; Buehler, M. J.; Thurner, P. J.

    2015-01-01

    The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry. PMID:26468064

  10. Sequence dependent aggregation of peptides and fibril formation

    Science.gov (United States)

    Hung, Nguyen Ba; Le, Duy-Manh; Hoang, Trinh X.

    2017-09-01

    Deciphering the links between amino acid sequence and amyloid fibril formation is key for understanding protein misfolding diseases. Here we use Monte Carlo simulations to study the aggregation of short peptides in a coarse-grained model with hydrophobic-polar (HP) amino acid sequences and correlated side chain orientations for hydrophobic contacts. A significant heterogeneity is observed in the aggregate structures and in the thermodynamics of aggregation for systems of different HP sequences and different numbers of peptides. Fibril-like ordered aggregates are found for several sequences that contain the common HPH pattern, while other sequences may form helix bundles or disordered aggregates. A wide variation of the aggregation transition temperatures among sequences, even among those of the same hydrophobic fraction, indicates that not all sequences undergo aggregation at a presumable physiological temperature. The transition is found to be the most cooperative for sequences forming fibril-like structures. For a fibril-prone sequence, it is shown that fibril formation follows the nucleation and growth mechanism. Interestingly, a binary mixture of peptides of an aggregation-prone and a non-aggregation-prone sequence shows the association and conversion of the latter to the fibrillar structure. Our study highlights the role of a sequence in selecting fibril-like aggregates and also the impact of a structural template on fibril formation by peptides of unrelated sequences.

  11. Single-photon absorption of isolated collagen mimetic peptides and triple-helix models in the VUV-X energy range

    NARCIS (Netherlands)

    Schwob, Lucas; Lalande, Mathieu; Rangama, Jimmy; Egorov, Dmitrii; Hoekstra, Ronnie; Pandey, Rahul; Eden, Samuel; Schlathölter, Thomas; Vizcaino, Violaine; Poully, Jean-Christophe

    2017-01-01

    Cartilage and tendons owe their special mechanical properties to the fibrous collagen structure. These strong fibrils are aggregates of a sub-unit consisting of three collagen proteins wound around each other in a triple helix. Even though collagen is the most abundant protein in the human body, the

  12. The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution.

    Science.gov (United States)

    Fidler, Aaron L; Boudko, Sergei P; Rokas, Antonis; Hudson, Billy G

    2018-04-09

    The cellular microenvironment, characterized by an extracellular matrix (ECM), played an essential role in the transition from unicellularity to multicellularity in animals (metazoans), and in the subsequent evolution of diverse animal tissues and organs. A major ECM component are members of the collagen superfamily -comprising 28 types in vertebrates - that exist in diverse supramolecular assemblies ranging from networks to fibrils. Each assembly is characterized by a hallmark feature, a protein structure called a triple helix. A current gap in knowledge is understanding the mechanisms of how the triple helix encodes and utilizes information in building scaffolds on the outside of cells. Type IV collagen, recently revealed as the evolutionarily most ancient member of the collagen superfamily, serves as an archetype for a fresh view of fundamental structural features of a triple helix that underlie the diversity of biological activities of collagens. In this Opinion, we argue that the triple helix is a protein structure of fundamental importance in building the extracellular matrix, which enabled animal multicellularity and tissue evolution. © 2018. Published by The Company of Biologists Ltd.

  13. Stabilization and anomalous hydration of collagen fibril under heating.

    Directory of Open Access Journals (Sweden)

    Sasun G Gevorkian

    Full Text Available BACKGROUND: Type I collagen is the most common protein among higher vertebrates. It forms the basis of fibrous connective tissues (tendon, chord, skin, bones and ensures mechanical stability and strength of these tissues. It is known, however, that separate triple-helical collagen macromolecules are unstable at physiological temperatures. We want to understand the mechanism of collagen stability at the intermolecular level. To this end, we study the collagen fibril, an intermediate level in the collagen hierarchy between triple-helical macromolecule and tendon. METHODOLOGY/PRINCIPAL FINDING: When heating a native fibril sample, its Young's modulus decreases in temperature range 20-58°C due to partial denaturation of triple-helices, but it is approximately constant at 58-75°C, because of stabilization by inter-molecular interactions. The stabilization temperature range 58-75°C has two further important features: here the fibril absorbs water under heating and the internal friction displays a peak. We relate these experimental findings to restructuring of collagen triple-helices in fibril. A theoretical description of the experimental results is provided via a generalization of the standard Zimm-Bragg model for the helix-coil transition. It takes into account intermolecular interactions of collagen triple-helices in fibril and describes water adsorption via the Langmuir mechanism. CONCLUSION/SIGNIFICANCE: We uncovered an inter-molecular mechanism that stabilizes the fibril made of unstable collagen macromolecules. This mechanism can be relevant for explaining stability of collagen.

  14. Computational study of the fibril organization of polyglutamine repeats reveals a common motif identified in beta-helices.

    Science.gov (United States)

    Zanuy, David; Gunasekaran, Kannan; Lesk, Arthur M; Nussinov, Ruth

    2006-04-21

    The formation of fibril aggregates by long polyglutamine sequences is assumed to play a major role in neurodegenerative diseases such as Huntington. Here, we model peptides rich in glutamine, through a series of molecular dynamics simulations. Starting from a rigid nanotube-like conformation, we have obtained a new conformational template that shares structural features of a tubular helix and of a beta-helix conformational organization. Our new model can be described as a super-helical arrangement of flat beta-sheet segments linked by planar turns or bends. Interestingly, our comprehensive analysis of the Protein Data Bank reveals that this is a common motif in beta-helices (termed beta-bend), although it has not been identified so far. The motif is based on the alternation of beta-sheet and helical conformation as the protein sequence is followed from the N to the C termini (beta-alpha(R)-beta-polyPro-beta). We further identify this motif in the ssNMR structure of the protofibril of the amyloidogenic peptide Abeta(1-40). The recurrence of the beta-bend suggests a general mode of connecting long parallel beta-sheet segments that would allow the growth of partially ordered fibril structures. The design allows the peptide backbone to change direction with a minimal loss of main chain hydrogen bonds. The identification of a coherent organization beyond that of the beta-sheet segments in different folds rich in parallel beta-sheets suggests a higher degree of ordered structure in protein fibrils, in agreement with their low solubility and dense molecular packing.

  15. Teaching helix and problems connected with helix using GeoGebra

    Science.gov (United States)

    Bímová, Daniela

    2017-12-01

    The contribution presents the dynamic applets created in GeoGebra that show the origin and main properties of a helix and it also presents some constructive problems connected with the helix. There are created the step by step algorithms of some constructions in the chosen applets. Three-dimensional applets include illustrative helix samples and spatial animations that help students better see problems concerning the helix spatially. There is mentioned the website in the contribution on which there is situated GeoGebra book dedicated to the topic "Helix" and containing the mentioned applets. The created applets and materials of the GeoGebra book "Helix" help in teaching and studying the course Constructive Geometry determined for the students of the Faculty of Mechanical Engineering of the Technical University of Liberec.

  16. Nearly reversible conformational change of amyloid fibrils as revealed by pH-jump experiments.

    Science.gov (United States)

    Yamaguchi, Kei-ichi; Kamatari, Yuji O; Fukuoka, Mayuko; Miyaji, Reiji; Kuwata, Kazuo

    2013-10-01

    pH-jump induced conformational transitions between substates of preformed amyloid fibrils made by a fragmented peptide of helix 2 (H2 peptide) of MoPrP were detected, and their kinetics were analyzed using a novel pH-jump apparatus specially designed for observing amyloids. Previously, we reported that H2 peptide formed ordered fibrils with a minimum at 207 nm on CD spectra at pH 2.9 (named pH 2.9 fibrils), but formed aggregate-like fibrils with a minimum at 220 nm at pH 7.5 (named pH 7.5 fibrils). When pH-jump from 2.9 to 7.5 was performed, the CD spectrum changed instantly, but the finally observed ellipticities were clearly distinct from those of pH 7.5 fibrils. Thus, the finally observed state is termed 'pH 7.5-like fibrils'. However, pH 7.5-like fibrils reverted to the conformation very similar to that of the pH 2.9 fibrils when the pH of the solution was restored to 2.9. Then, we examined the kinetics of the nearly reversible conformational changes between pH 2.9 fibrils and pH 7.5-like fibrils using ANS fluorescence stopped-flow, and we observed relatively fast phases (0.7-18 s(-1)). In contrast, the conversion between pH 7.5-like fibrils and pH 7.5 fibrils never occurred (<0.2 day(-1)). Thus, H2 fibrils can be switched readily between distinct conformations separated by a low energy barrier, while a large energy barrier clearly separated the different conformations. These conformational varieties of amyloid fibrils may explain the physical basis of the diversity in prion.

  17. From Family Based to Industrial Based Production: Local Economic Development Initiatives and the HELIX Model

    Directory of Open Access Journals (Sweden)

    Bartjan W Pennink

    2013-01-01

    Full Text Available To build a strong local economy, good practice tells us that each community should undertake a collaborative, strategically planned process to understand and then act upon its own strengths, weaknesses, opportunities and threats. From this perspective we start with the local communities but how is this related to the perspective from the Helix model in which three actors are explicitly introduced: the Government, the Industry and the Universities? The purpose of local economic development (LED is to build up the economic capacity of a local area to improve its economic future and the quality of life for all. To support  the Local Economic Development in remote areas,   a program  has been developed based on the LED frame work of the world bank. This approach and  the experiences over  the past years with this program are  described in the first part.  In the second part of the paper, We analyse work done with that program with the help of the social capital concept and the triple helix model.  In all cases it is important to pay attention to who is taken the initiative after the first move (and it is not always the governance as actor and for the triple helix we suggest  that the concepts of (national Government, Industry and University need a translation to Local Governance Agency, Cooperation or other ways of cooperation of local communities and Local Universities. Although a push from outside might help  a local region in development the endogenous factors are  also needed. Keywords: Triple Helix model, Local Economic Development, Local Actors, Double Triangle within the Helix Model

  18. Phason thermal transport of three-helix state in insulating chiral magnets

    Science.gov (United States)

    Tatara, Gen

    2018-06-01

    Thermal dynamics of the three-helix state in a chiral magnet is studied based on a phason representation. Although phason representation is convenient for intuitive description, it is not straightforwardly compatible with microscopic linear response calculation of transport phenomena, because it is a (semi)macroscopic picture obtained by a coarse graining. By separating the slow phason mode and fast magnon mode, we show that phason thermal dynamics is driven by thermal magnon flow via the spin-transfer effect. The magnon and phason velocities are calculated by use of thermal vector potential formalism.

  19. High-Pressure-Driven Reversible Dissociation of α-Synuclein Fibrils Reveals Structural Hierarchy.

    Science.gov (United States)

    Piccirilli, Federica; Plotegher, Nicoletta; Ortore, Maria Grazia; Tessari, Isabella; Brucale, Marco; Spinozzi, Francesco; Beltramini, Mariano; Mariani, Paolo; Militello, Valeria; Lupi, Stefano; Perucchi, Andrea; Bubacco, Luigi

    2017-10-17

    The analysis of the α-synuclein (aS) aggregation process, which is involved in Parkinson's disease etiopathogenesis, and of the structural feature of the resulting amyloid fibrils may shed light on the relationship between the structure of aS aggregates and their toxicity. This may be considered a paradigm of the ground work needed to tackle the molecular basis of all the protein-aggregation-related diseases. With this aim, we used chemical and physical dissociation methods to explore the structural organization of wild-type aS fibrils. High pressure (in the kbar range) and alkaline pH were used to disassemble fibrils to collect information on the hierarchic pathway by which distinct β-sheets sequentially unfold using the unique possibility offered by high-pressure Fourier transform infrared spectroscopy. The results point toward the formation of kinetic traps in the energy landscape of aS fibril disassembly and the presence of transient partially folded species during the process. Since we found that the dissociation of wild-type aS fibrils by high pressure is reversible upon pressure release, the disassembled molecules likely retain structural information that favors fibril reformation. To deconstruct the role of the different regions of aS sequence in this process, we measured the high-pressure dissociation of amyloids formed by covalent chimeric dimers of aS (syn-syn) and by the aS deletion mutant that lacks the C-terminus, i.e., aS (1-99). The results allowed us to single out the role of dimerization and that of the C-terminus in the complete maturation of fibrillar aS. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. TOWARDS UNDERSTANDING OF HELIX B BASED CONFORMATIONAL DISEASES IN SERPIN

    Directory of Open Access Journals (Sweden)

    Mohamad Aman Jairajpuri

    2012-12-01

    Full Text Available Serine protease inhibitors (serpins are a unique family of protease inhibitors that are prone to polymer formation due to their metastable nature and a complex inhibition mechanism that involves large scale conformational change. Helix B is in the shutter region near the strand 2A and strand 3A of �-sheet A, where reactive centre loop inserts during the serpin inhibition mechanism. Helix B region in serpins is a mutation hotspot for naturally occurring variants that result in pathological conditions due to polymerization. Helix B residues are completely buried in the native state and loop inserted latent state but not in the inhibitory loop inserted cleaved conformation. Native to cleaved transition during inhibition forms a large cavity in the shutter region, which invariably is the largest cavity in most serpins in native state. In a recent paper we had for the first time hypothesized that exposure of helix B at the N-terminal end is important for smooth insertion of the reactive center loop during serpin inhibition mechanism. It is therefore possible that natural variant that induces conformational deformation of helix B probably alter the cavity size which increases the rate of loop-sheet interaction between the monomers resulting in increased polymerization.

  1. Insulin amyloid fibrillation studied by terahertz spectroscopy and other biophysical methods

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Rui [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); He, Mingxia [College of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin 300072 (China); Su, Rongxin, E-mail: surx@tju.edu.cn [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072 (China); Yu, Yanjun [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Qi, Wei; He, Zhimin [State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tianjin Key Laboratory of Membrane Science and Desalination Technology, Tianjin University, Tianjin 300072 (China)

    2010-01-01

    Assembly and fibrillation of amyloid proteins are believed to play a key role in the etiology of various human diseases, including Alzheimer's, Parkinson's, Huntington's and type II diabetes. Insights into conformational changes and formation processes during amyloid fibrillation are essential for the clinical diagnosis and drug discovery. To study the changes in secondary, tertiary, quaternary structures, and the alteration in the collective vibrational mode density of states during the amyloid fibrillation, bovine insulin in 20% acetic acid was incubated at 60 {sup o}C, and its multi-level structures were followed by various biophysical techniques, including circular dichroism (CD), thioflavin T fluorescence (ThT), dynamic light scattering (DLS), electron microscopy, and terahertz (THz) absorption spectroscopy. The experimental data demonstrated a transformation of {alpha}-helix into {beta}-sheet starting at 26 h. This was followed by the aggregation of insulin, as shown by ThT binding, with a transition midpoint at 41 h, and by the bulk formation of mature aggregates after about 71 h. THz is a quick and non-invasive technique, which has the advantage of allowing the study of the conformational state of biomolecules and tissues. We first applied THz spectroscopy to study the amyloid fibrillation. At the terahertz frequency range of 0.2-2.0 THz, there was an apparent increase in both the absorbance and refractive index in THz spectra. Thus, THz is expected to provide a new way of looking into amyloid fibrillation.

  2. How does domain replacement affect fibril formation of the rabbit/human prion proteins.

    Directory of Open Access Journals (Sweden)

    Xu Yan

    Full Text Available It is known that in vivo human prion protein (PrP have the tendency to form fibril deposits and are associated with infectious fatal prion diseases, while the rabbit PrP does not readily form fibrils and is unlikely to cause prion diseases. Although we have previously demonstrated that amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and macromolecular crowding has different effects on fibril formation of the rabbit/human PrPs, we do not know which domains of PrPs cause such differences. In this study, we have constructed two PrP chimeras, rabbit chimera and human chimera, and investigated how domain replacement affects fibril formation of the rabbit/human PrPs.As revealed by thioflavin T binding assays and Sarkosyl-soluble SDS-PAGE, the presence of a strong crowding agent dramatically promotes fibril formation of both chimeras. As evidenced by circular dichroism, Fourier transform infrared spectroscopy, and proteinase K digestion assays, amyloid fibrils formed by human chimera have secondary structures and proteinase K-resistant features similar to those formed by the human PrP. However, amyloid fibrils formed by rabbit chimera have proteinase K-resistant features and secondary structures in crowded physiological environments different from those formed by the rabbit PrP, and secondary structures in dilute solutions similar to the rabbit PrP. The results from transmission electron microscopy show that macromolecular crowding caused human chimera but not rabbit chimera to form short fibrils and non-fibrillar particles.We demonstrate for the first time that the domains beyond PrP-H2H3 (β-strand 1, α-helix 1, and β-strand 2 have a remarkable effect on fibrillization of the rabbit PrP but almost no effect on the human PrP. Our findings can help to explain why amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and why macromolecular crowding has different

  3. AFM-based force spectroscopy measurements of mature amyloid fibrils of the peptide glucagon

    DEFF Research Database (Denmark)

    Dong, M. D.; Hovgaard, M. B.; Mamdouh, W.

    2008-01-01

    We report on the mechanical characterization of individual mature amyloid fibrils by atomic force microscopy (AFM) and AFM-based single-molecule force spectroscopy (SMFS). These self-assembling materials, formed from the 29-residue amphiphatic peptide hormone glucagon, were found to display...... a reversible elastic behaviour. Based on AFM morphology and SMFS studies, we suggest that the observed elasticity is due to a force-induced conformational transition which is reversible due to the beta-helical conformation of protofibrils, allowing a high degree of extension. The elastic properties...... of such mature fibrils contribute to their high stability, suggesting that the internal hydrophobic interactions of amyloid fibrils are likely to be of fundamental importance in the assembly of amyloid fibrils and therefore for the understanding of the progression of their associated pathogenic disorders...

  4. Studies of the structure of insulin fibrils by Fourier transform infrared (FTIR) spectroscopy and electron microscopy.

    Science.gov (United States)

    Nielsen, L; Frokjaer, S; Carpenter, J F; Brange, J

    2001-01-01

    Fibril formation (aggregation) of insulin was investigated in acid media by visual inspection, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. Insulin fibrillated faster in hydrochloric acid than in acetic acid at elevated temperatures, whereas the fibrillation tendencies were reversed at ambient temperatures. Electron micrographs showed that bovine insulin fibrils consisted of long fibers with a diameter of 5 to 10 nm and lengths of several microns. The fibrils appeared either as helical filaments (in hydrochloric acid) or arranged laterally in bundles (in acetic acid, NaCl). Freeze-thawing cycles broke the fibrils into shorter segments. FTIR spectroscopy showed that the native secondary structure of insulin was identical in hydrochloric acid and acetic acid, whereas the secondary structure of fibrils formed in hydrochloric acid was different from that formed in acetic acid. Fibrils of bovine insulin prepared by heating or agitating an acid solution of insulin showed an increased content of beta-sheet (mostly intermolecular) and a decrease in the intensity of the alpha-helix band. In hydrochloric acid, the frequencies of the beta-sheet bands depended on whether the fibrillation was induced by heating or agitation. This difference was not seen in acetic acid. Freeze-thawing cycles of the fibrils in hydrochloric acid caused an increase in the intensity of the band at 1635 cm(-1) concomitant with reduction of the band at 1622 cm(-1). The results showed that the structure of insulin fibrils is highly dependent on the composition of the acid media and on the treatment. Copyright 2001 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 90: 29-37, 2001

  5. Triple Helix going abroad?

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull; Hu, Yimei

    2014-01-01

    The aim of the article is to explore to what extent the Tripple helix is being internationalized. Each of the helixes have their own internationalization rationale but the article show by small example that the helix itself is being internationalized and integrated with the host country tripple h...

  6. A carboxylated Zn-phthalocyanine inhibits fibril formation of Alzheimer's amyloid β peptide.

    Science.gov (United States)

    Tabassum, Shatera; Sheikh, Abdullah M; Yano, Shozo; Ikeue, Takafumi; Handa, Makoto; Nagai, Atsushi

    2015-02-01

    Amyloid β (Aβ), a 39-42 amino acid peptide derived from amyloid precursor protein, is deposited as fibrils in Alzheimer's disease brains, and is considered to play a major role in the pathogenesis of the disease. We have investigated the effects of a water-soluble Zn-phthalocyanine, ZnPc(COONa)₈, a macrocyclic compound with near-infrared optical properties, on Aβ fibril formation in vitro. A thioflavin T fluorescence assay showed that ZnPc(COONa)₈ significantly inhibited Aβ fibril formation, increasing the lag time and dose-dependently decreasing the plateau level of fibril formation. Moreover, it destabilized pre-formed Aβ fibrils, resulting in an increase in low-molecular-weight species. After fibril formation in the presence of ZnPc(COONa)₈, immunoprecipitation of Aβ₁₋₄₂ using Aβ-specific antibody followed by near-infrared scanning demonstrated binding of ZnPc(COONa)₈ to Aβ₁₋₄₂. A study using the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid showed that ZnPc(COONa)8 decreased the hydrophobicity during Aβ₁₋₄₂ fibril formation. CD spectroscopy showed an increase in the α helix structure and a decrease in the β sheet structure of Aβ₁₋₄₀ in fibril-forming buffer containing ZnPc(COONa)₈. SDS/PAGE and a dot-blot immunoassay showed that ZnPc(COONa)₈ delayed the disappearance of low-molecular-weight species and the appearance of higher-molecular-weight oligomeric species of Aβ₁₋₄₂. A cell viability assay showed that ZnPc(COONa)₈ was not toxic to a neuronal cell line (A1), but instead protected A1 cells against Aβ₁₋₄₂-induced toxicity. Overall, our results indicate that ZnPc(COONa)₈ binds to Aβ and decreases the hydrophobicity, and this change is unfavorable for Aβ oligomerization and fibril formation. © 2014 FEBS.

  7. Atrial fibrillation: To map or not to map?

    NARCIS (Netherlands)

    A. Yaksh (Ameeta); C. Kik (Charles); S.P. Knops (Simon); J.W. Roos-Hesselink (Jolien); A.J.J.C. Bogers (Ad); F. Zijlstra (Felix); M.A. Allessie (Maurits); N.M.S. de Groot (Natasja)

    2014-01-01

    textabstractIsolation of the pulmonary veins may be an effective treatment modality for eliminating atrial fibrillation (AF) episodes but unfortunately not for all patients. When ablative therapy fails, it is assumed that AF has progressed from a trigger-driven to a substrate-mediated arrhythmia.

  8. α-helix to β-hairpin transition of human amylin monomer

    Science.gov (United States)

    Singh, Sadanand; Chiu, Chi-cheng; Reddy, Allam S.; de Pablo, Juan J.

    2013-04-01

    The human islet amylin polypeptide is produced along with insulin by pancreatic islets. Under some circumstances, amylin can aggregate to form amyloid fibrils, whose presence in pancreatic cells is a common pathological feature of Type II diabetes. A growing body of evidence indicates that small, early stage aggregates of amylin are cytotoxic. A better understanding of the early stages of the amylin aggregation process and, in particular, of the nucleation events leading to fibril growth could help identify therapeutic strategies. Recent studies have shown that, in dilute solution, human amylin can adopt an α-helical conformation, a β-hairpin conformation, or an unstructured coil conformation. While such states have comparable free energies, the β-hairpin state exhibits a large propensity towards aggregation. In this work, we present a detailed computational analysis of the folding pathways that arise between the various conformational states of human amylin in water. A free energy surface for amylin in explicit water is first constructed by resorting to advanced sampling techniques. Extensive transition path sampling simulations are then employed to identify the preferred folding mechanisms between distinct minima on that surface. Our results reveal that the α-helical conformer of amylin undergoes a transformation into the β-hairpin monomer through one of two mechanisms. In the first, misfolding begins through formation of specific contacts near the turn region, and proceeds via a zipping mechanism. In the second, misfolding occurs through an unstructured coil intermediate. The transition states for these processes are identified. Taken together, the findings presented in this work suggest that the inter-conversion of amylin between an α-helix and a β-hairpin is an activated process and could constitute the nucleation event for fibril growth.

  9. Generating structured light with phase helix and intensity helix using reflection-enhanced plasmonic metasurface at 2 μm

    Science.gov (United States)

    Zhao, Yifan; Du, Jing; Zhang, Jinrun; Shen, Li; Wang, Jian

    2018-04-01

    Mid-infrared (2-20 μm) light has been attracting great attention in many areas of science and technology. Beyond the extended wavelength range from visible and near-infrared to mid-infrared, shaping spatial structures may add opportunities to grooming applications of mid-infrared photonics. Here, we design and fabricate a reflection-enhanced plasmonic metasurface and demonstrate efficient generation of structured light with the phase helix and intensity helix at 2 μm. This work includes two distinct aspects. First, structured light (phase helix, intensity helix) generation at 2 μm, which is far beyond the ability of conventional spatial light modulators, is enabled by the metasurface with sub-wavelength engineered structures. Second, the self-referenced intensity helix against environmental noise is generated without using a spatially separated light. The demonstrations may open up advanced perspectives to structured light applications at 2 μm, such as phase helix for communications and non-communications (imaging, sensing) and intensity helix for enhanced microscopy and advanced metrology.

  10. A Classification of Basic Helix-Loop-Helix Transcription Factors of Soybean

    Directory of Open Access Journals (Sweden)

    Karen A. Hudson

    2015-01-01

    Full Text Available The complete genome sequence of soybean allows an unprecedented opportunity for the discovery of the genes controlling important traits. In particular, the potential functions of regulatory genes are a priority for analysis. The basic helix-loop-helix (bHLH family of transcription factors is known to be involved in controlling a wide range of systems critical for crop adaptation and quality, including photosynthesis, light signalling, pigment biosynthesis, and seed pod development. Using a hidden Markov model search algorithm, 319 genes with basic helix-loop-helix transcription factor domains were identified within the soybean genome sequence. These were classified with respect to their predicted DNA binding potential, intron/exon structure, and the phylogeny of the bHLH domain. Evidence is presented that the vast majority (281 of these 319 soybean bHLH genes are expressed at the mRNA level. Of these soybean bHLH genes, 67% were found to exist in two or more homeologous copies. This dataset provides a framework for future studies on bHLH gene function in soybean. The challenge for future research remains to define functions for the bHLH factors encoded in the soybean genome, which may allow greater flexibility for genetic selection of growth and environmental adaptation in this widely grown crop.

  11. Alginate-Collagen Fibril Composite Hydrogel

    Directory of Open Access Journals (Sweden)

    Mahmoud Baniasadi

    2015-02-01

    Full Text Available We report on the synthesis and the mechanical characterization of an alginate-collagen fibril composite hydrogel. Native type I collagen fibrils were used to synthesize the fibrous composite hydrogel. We characterized the mechanical properties of the fabricated fibrous hydrogel using tensile testing; rheometry and atomic force microscope (AFM-based nanoindentation experiments. The results show that addition of type I collagen fibrils improves the rheological and indentation properties of the hydrogel.

  12. The Triple Helix Model and the Knowledge-Based Economy

    NARCIS (Netherlands)

    Leydesdorff, L.; Meyer, M.

    2010-01-01

    The Triple Helix model of university-industry-government relations can be generalized from a neo-institutional model of networks of relations to a neo-evolutionary model of how three selection environments operate upon one another. Two selection mechanisms operating upon each other can mutually

  13. Origin and Diversification of Basic-Helix-Loop-Helix Proteins in Plants

    OpenAIRE

    Pires, Nuno; Dolan, Liam

    2009-01-01

    Basic helix-loop-helix (bHLH) proteins are a class of transcription factors found throughout eukaryotic organisms. Classification of the complete sets of bHLH proteins in the sequenced genomes of Arabidopsis thaliana and Oryza sativa (rice) has defined the diversity of these proteins among flowering plants. However, the evolutionary relationships of different plant bHLH groups and the diversity of bHLH proteins in more ancestral groups of plants are currently unknown. In this study, we use wh...

  14. Triple-helix molecular switch-based aptasensors and DNA sensors.

    Science.gov (United States)

    Bagheri, Elnaz; Abnous, Khalil; Alibolandi, Mona; Ramezani, Mohammad; Taghdisi, Seyed Mohammad

    2018-07-15

    Utilization of traditional analytical techniques is limited because they are generally time-consuming and require high consumption of reagents, complicated sample preparation and expensive equipment. Therefore, it is of great interest to achieve sensitive, rapid and simple detection methods. It is believed that nucleic acids assays, especially aptamers, are very important in modern life sciences for target detection and biological analysis. Aptamers and DNA-based sensors have been widely used for the design of various sensors owing to their unique features. In recent years, triple-helix molecular switch (THMS)-based aptasensors and DNA sensors have been broadly utilized for the detection and analysis of different targets. The THMS relies on the formation of DNA triplex via Watson-Crick and Hoogsteen base pairings under optimal conditions. This review focuses on recent progresses in the development and applications of electrochemical, colorimetric, fluorescence and SERS aptasensors and DNA sensors, which are based on THMS. Also, the advantages and drawbacks of these methods are discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Recognition and Binding of a Helix-Loop-Helix Peptide to Carbonic Anhydrase Occurs via Partly Folded Intermediate Structures

    Science.gov (United States)

    Lignell, Martin; Becker, Hans-Christian

    2010-01-01

    Abstract We have studied the association of a helix-loop-helix peptide scaffold carrying a benzenesulfonamide ligand to carbonic anhydrase using steady-state and time-resolved fluorescence spectroscopy. The helix-loop-helix peptide, developed for biosensing applications, is labeled with the fluorescent probe dansyl, which serves as a polarity-sensitive reporter of the binding event. Using maximum entropy analysis of the fluorescence lifetime of dansyl at 1:1 stoichiometry reveals three characteristic fluorescence lifetime groups, interpreted as differently interacting peptide/protein structures. We characterize these peptide/protein complexes as mostly bound but unfolded, bound and partly folded, and strongly bound and folded. Furthermore, analysis of the fluorescence anisotropy decay resulted in three different dansyl rotational correlation times, namely 0.18, 1.2, and 23 ns. Using the amplitudes of these times, we can correlate the lifetime groups with the corresponding fluorescence anisotropy component. The 23-ns rotational correlation time, which appears with the same amplitude as a 17-ns fluorescence lifetime, shows that the dansyl fluorophore follows the rotational diffusion of carbonic anhydrase when it is a part of the folded peptide/protein complex. A partly folded and partly hydrated interfacial structure is manifested in an 8-ns dansyl fluorescence lifetime and a 1.2-ns rotational correlation time. This structure, we believe, is similar to a molten-globule-like interfacial structure, which allows segmental movement and has a higher degree of solvent exposure of dansyl. Indirect excitation of dansyl on the helix-loop-helix peptide through Förster energy transfer from one or several tryptophans in the carbonic anhydrase shows that the helix-loop-helix scaffold binds to a tryptophan-rich domain of the carbonic anhydrase. We conclude that binding of the peptide to carbonic anhydrase involves a transition from a disordered to an ordered structure of the

  16. Rising rates of hospital admissions for atrial fibrillation

    DEFF Research Database (Denmark)

    Friberg, Jens; Buch, Nina Pernille Gardshodn; Scharling, Henrik

    2003-01-01

    Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study).......Atrial fibrillation is a common arrhythmia associated with excess morbidity and mortality. We studied temporal changes in hospital admission rates for atrial fibrillation using data from a prospective population-based cohort study spanning 2 decades (the Copenhagen City Heart Study)....

  17. Chirality-specific lift forces of helix under shear flows: Helix perpendicular to shear plane.

    Science.gov (United States)

    Zhang, Qi-Yi

    2017-02-01

    Chiral objects in shear flow experience a chirality-specific lift force. Shear flows past helices in a low Reynolds number regime were studied using slender-body theory. The chirality-specific lift forces in the vorticity direction experienced by helices are dominated by a set of helix geometry parameters: helix radius, pitch length, number of turns, and helix phase angle. Its analytical formula is given. The chirality-specific forces are the physical reasons for the chiral separation of helices in shear flow. Our results are well supported by the latest experimental observations. © 2016 Wiley Periodicals, Inc.

  18. Synthesis and characterization of fluorinated magnetic core-shell nanoparticles for inhibition of insulin amyloid fibril formation

    International Nuclear Information System (INIS)

    Skaat, Hadas; Margel, Shlomo; Belfort, Georges

    2009-01-01

    Maghemite (γ-Fe 2 O 3 ) magnetic nanoparticles of 15.0 ± 2.1 nm are formed by nucleation followed by controlled growth of maghemite thin films on gelatin-iron oxide nuclei. Uniform magnetic γ-Fe 2 O 3 /poly (2,2,3,3,4,4,4-heptafluorobutyl acrylate) (γ-Fe 2 O 3 /PHFBA) core-shell nanoparticles are prepared by emulsion polymerization of the fluorinated monomer 2,2,3,3,4,4,4-heptafluorobutyl acrylate (HFBA) in the presence of the maghemite nanoparticles. The kinetics of the insulin fibrillation process in the absence and in the presence of the γ-Fe 2 O 3 /PHFBA core-shell nanoparticles are elucidated. A significant direct slow transition from α-helix to β-sheets during insulin fibril formation is observed in the presence of the γ-Fe 2 O 3 /PHFBA nanoparticles. This is in contradiction to our previous manuscript, which illustrated that the γ-Fe 2 O 3 core nanoparticles do not affect the kinetics of the formation of the insulin fibrils, and to other previous publications that describe acceleration of the fibrillation process by using various types of nanoparticles. These core-shell nanoparticles may therefore be also useful for the inhibition of conformational changes of other amyloidogenic proteins that lead to neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, mad cow and prion diseases.

  19. Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain.

    Science.gov (United States)

    Law, S F; Zhang, Y Z; Fashena, S J; Toby, G; Estojak, J; Golemis, E A

    1999-10-10

    HEF1, p130(Cas), and Efs define a family of multidomain docking proteins which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion. HEF1 function has been specifically implicated in signaling pathways important for cell adhesion and differentiation in lymphoid and epithelial cells. While the SH3 domains and SH2-binding site domains (substrate domains) of HEF1 family proteins are well characterized and binding partners known, to date the highly conserved carboxy-terminal domains of the three proteins have lacked functional definition. In this study, we have determined that the carboxy-terminal domain of HEF1 contains a divergent helix-loop-helix (HLH) motif. This motif mediates HEF1 homodimerization and HEF1 heterodimerization with a recognition specificity similar to that of the transcriptional regulatory HLH proteins Id2, E12, and E47. We had previously demonstrated that the HEF1 carboxy-terminus expressed as a separate domain in yeast reprograms cell division patterns, inducing constitutive pseudohyphal growth. Here we show that pseudohyphal induction by HEF1 requires an intact HLH, further supporting the idea that this motif has an effector activity for HEF1, and implying that HEF1 pseudohyphal activity derives in part from interactions with yeast helix-loop-helix proteins. These combined results provide initial insight into the mode of function of the HEF1 carboxy-terminal domain and suggest that the HEF1 protein may interact with cellular proteins which control differentiation. Copyright 1999 Academic Press.

  20. Helix-Hopes on Finite Hyperfields

    Directory of Open Access Journals (Sweden)

    Thomas Vougiouklis

    2016-12-01

    Full Text Available Hyperstructure theory can overcome restrictions which ordinary algebraic structures have. A hyperproduct on non-square ordinary matrices can be defined by using the so called helix-hyperoperations. We study the helix-hyperstructures on the representations using ordinary fields. The related theory can be faced by defining the hyperproduct on the set of non square matrices. The main tools of the Hyperstructure Theory are the fundamental relations which connect the largest class of hyperstructures, the Hv-structures, with the corresponding classical ones. We focus on finite dimensional helix-hyperstructures and on small Hv-fields, as well.

  1. Mode conversions by a discontinuous junction of two helix loaded waveguides

    International Nuclear Information System (INIS)

    Choe, J.Y.; Ahn, S.; Ganquly, A.K.; Uhm, H.S.

    1983-01-01

    For various reasons, it is desirable to vary the primary propagating mode from one section of the waveguide to another. We choose the base structure to be the sheath helix loaded waveguide. Specifically, we join two physically different helix loaded waveguides axisymmetrically, thereby providing the required discontinuities at the junction (Z = 0). The helix loaded waveguide is more advantageous to the simple waveguide in that the helix mode that exists uniquely in the helix waveguide in addition to the usual fast wave hybrid modes, is without cutoff and thus behaves like a transmission line. In order to obtain the mode conversion rates, we expand the waves in the both sides of the junction with its own eigenmodes including the evanescent modes, and by matching fields at the junction (Z = 0) obtain the matrix equation for the coefficients for the eigenmodes in both sides. By choosing the propagating incident wave (Z = 0) the resulting outgoing waves in the other end (Z > 0) will be computed from the matrix equation. A computer program is devised to solve the suitably truncated matrix equation, and the numerical examples for the mode conversion rates with the parameter variations will be presented. The relevant physical parameters to yield discontinuities at the junction are the radii of the outer conductor and the helix wire and the pitch angle of the helix. Special emphases are on the conversion rates from the helix mode (Z 0) for the application to the tapered gyrotron amplifier

  2. Atrial Fibrillation: Diagnosis

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Diagnosis Past Issues / Winter 2015 Table of Contents ... of your body's cells and organs. Read More "Atrial Fibrillation" Articles Atrial Fibrillation / Who Is at Risk for ...

  3. Kinetics and mechanical stability of the fibril state control fibril formation time of polypeptide chains: A computational study

    Science.gov (United States)

    Kouza, Maksim; Co, Nguyen Truong; Li, Mai Suan; Kmiecik, Sebastian; Kolinski, Andrzej; Kloczkowski, Andrzej; Buhimschi, Irina Alexandra

    2018-06-01

    Fibril formation resulting from protein misfolding and aggregation is a hallmark of several neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite much progress in the understanding of the protein aggregation process, the factors governing fibril formation rates and fibril stability have not been fully understood. Using lattice models, we have shown that the fibril formation time is controlled by the kinetic stability of the fibril state but not by its energy. Having performed all-atom explicit solvent molecular dynamics simulations with the GROMOS43a1 force field for full-length amyloid beta peptides Aβ40 and Aβ42 and truncated peptides, we demonstrated that kinetic stability can be accessed via mechanical stability in such a way that the higher the mechanical stability or the kinetic stability, the faster the fibril formation. This result opens up a new way for predicting fibril formation rates based on mechanical stability that may be easily estimated by steered molecular dynamics.

  4. Destruction of α-synuclein based amyloid fibrils by a low temperature plasma jet

    Science.gov (United States)

    Karakas, Erdinc; Munyanyi, Agatha; Greene, Lesley; Laroussi, Mounir

    2010-10-01

    Amyloid fibrils are ordered beta-sheet aggregates that are associated with a number of neurodegenerative diseases such as Alzheimer and Parkinson. At present, there is no cure for these progressive and debilitating diseases. Here we report initial studies that indicate that low temperature atmospheric pressure plasma can break amyloid fibrils into smaller units in vitro. The plasma was generated by the "plasma pencil," a device capable of emitting a long, low temperature plasma plume/jet. This avenue of research may facilitate the development of a plasma-based medical treatment.

  5. Destruction of α-synuclein based amyloid fibrils by a low temperature plasma jet

    International Nuclear Information System (INIS)

    Karakas, Erdinc; Laroussi, Mounir; Munyanyi, Agatha; Greene, Lesley

    2010-01-01

    Amyloid fibrils are ordered beta-sheet aggregates that are associated with a number of neurodegenerative diseases such as Alzheimer and Parkinson. At present, there is no cure for these progressive and debilitating diseases. Here we report initial studies that indicate that low temperature atmospheric pressure plasma can break amyloid fibrils into smaller units in vitro. The plasma was generated by the 'plasma pencil', a device capable of emitting a long, low temperature plasma plume/jet. This avenue of research may facilitate the development of a plasma-based medical treatment.

  6. Crosslinked Aspartic Acids as Helix-Nucleating Templates.

    Science.gov (United States)

    Zhao, Hui; Liu, Qi-Song; Geng, Hao; Tian, Yuan; Cheng, Min; Jiang, Yan-Hong; Xie, Ming-Sheng; Niu, Xiao-Gang; Jiang, Fan; Zhang, Ya-Ou; Lao, Yuan-Zhi; Wu, Yun-Dong; Xu, Nai-Han; Li, Zi-Gang

    2016-09-19

    Described is a facile helix-nucleating template based on a tethered aspartic acid at the N-terminus [terminal aspartic acid (TD)]. The nucleating effect of the template is subtly influenced by the substituent at the end of the side-chain-end tether as indicated by circular dichroism, nuclear magnetic resonance, and molecular dynamics simulations. Unlike most nucleating strategies, the N-terminal amine is preserved, thus enabling further modification. Peptidomimetic estrogen receptor modulators (PERMs) constructed using this strategy show improved therapeutic properties. The current strategy can be regarded as a good complement to existing helix-stabilizing methods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [Atrial fibrillation].

    Science.gov (United States)

    Spinar, J; Vítovec, J

    2003-09-01

    Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

  8. Agent-based modeling traction force mediated compaction of cell-populated collagen gels using physically realistic fibril mechanics.

    Science.gov (United States)

    Reinhardt, James W; Gooch, Keith J

    2014-02-01

    Agent-based modeling was used to model collagen fibrils, composed of a string of nodes serially connected by links that act as Hookean springs. Bending mechanics are implemented as torsional springs that act upon each set of three serially connected nodes as a linear function of angular deflection about the central node. These fibrils were evaluated under conditions that simulated axial extension, simple three-point bending and an end-loaded cantilever. The deformation of fibrils under axial loading varied <0.001% from the analytical solution for linearly elastic fibrils. For fibrils between 100 μm and 200 μm in length experiencing small deflections, differences between simulated deflections and their analytical solutions were <1% for fibrils experiencing three-point bending and <7% for fibrils experiencing cantilever bending. When these new rules for fibril mechanics were introduced into a model that allowed for cross-linking of fibrils to form a network and the application of cell traction force, the fibrous network underwent macroscopic compaction and aligned between cells. Further, fibril density increased between cells to a greater extent than that observed macroscopically and appeared similar to matrical tracks that have been observed experimentally in cell-populated collagen gels. This behavior is consistent with observations in previous versions of the model that did not allow for the physically realistic simulation of fibril mechanics. The significance of the torsional spring constant value was then explored to determine its impact on remodeling of the simulated fibrous network. Although a stronger torsional spring constant reduced the degree of quantitative remodeling that occurred, the inclusion of torsional springs in the model was not necessary for the model to reproduce key qualitative aspects of remodeling, indicating that the presence of Hookean springs is essential for this behavior. These results suggest that traction force mediated matrix

  9. Gibberellin-regulated gene in the basal region of rice leaf sheath encodes basic helix-loop-helix transcription factor.

    Science.gov (United States)

    Komatsu, Setsuko; Takasaki, Hironori

    2009-07-01

    Genes regulated by gibberellin (GA) during leaf sheath elongation in rice seedlings were identified using the transcriptome approach. mRNA from the basal regions of leaf sheaths treated with GA3 was analyzed by high-coverage gene expression profiling. 33,004 peaks were detected, and 30 transcripts showed significant changes in the presence of GA3. Among these, basic helix-loop-helix transcription factor (AK073385) was significantly upregulated. Quantitative PCR analysis confirmed that expression of AK073385 was controlled by GA3 in a time- and dose-dependent manner. Basic helix-loop-helix transcription factor (AK073385) is therefore involved in the regulation of gene expression by GA3.

  10. Synthesis and characterization of fluorinated magnetic core-shell nanoparticles for inhibition of insulin amyloid fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Skaat, Hadas; Margel, Shlomo [Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900 (Israel); Belfort, Georges [Howard P Isermann Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180 (United States)], E-mail: ch348@mail.biu.ac.il, E-mail: belfog@rpi.edu, E-mail: Shlomo.margel@mail.biu.ac.il

    2009-06-03

    Maghemite ({gamma}-Fe{sub 2}O{sub 3}) magnetic nanoparticles of 15.0 {+-} 2.1 nm are formed by nucleation followed by controlled growth of maghemite thin films on gelatin-iron oxide nuclei. Uniform magnetic {gamma}-Fe{sub 2}O{sub 3}/poly (2,2,3,3,4,4,4-heptafluorobutyl acrylate) ({gamma}-Fe{sub 2}O{sub 3}/PHFBA) core-shell nanoparticles are prepared by emulsion polymerization of the fluorinated monomer 2,2,3,3,4,4,4-heptafluorobutyl acrylate (HFBA) in the presence of the maghemite nanoparticles. The kinetics of the insulin fibrillation process in the absence and in the presence of the {gamma}-Fe{sub 2}O{sub 3}/PHFBA core-shell nanoparticles are elucidated. A significant direct slow transition from {alpha}-helix to {beta}-sheets during insulin fibril formation is observed in the presence of the {gamma}-Fe{sub 2}O{sub 3}/PHFBA nanoparticles. This is in contradiction to our previous manuscript, which illustrated that the {gamma}-Fe{sub 2}O{sub 3} core nanoparticles do not affect the kinetics of the formation of the insulin fibrils, and to other previous publications that describe acceleration of the fibrillation process by using various types of nanoparticles. These core-shell nanoparticles may therefore be also useful for the inhibition of conformational changes of other amyloidogenic proteins that lead to neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, mad cow and prion diseases.

  11. Confinement-induced liquid crystalline transitions in amyloid fibril cholesteric tactoids

    Science.gov (United States)

    Nyström, Gustav; Arcari, Mario; Mezzenga, Raffaele

    2018-04-01

    Chirality is ubiquitous in nature and plays crucial roles in biology, medicine, physics and materials science. Understanding and controlling chirality is therefore an important research challenge with broad implications. Unlike other chiral colloids, such as nanocellulose or filamentous viruses, amyloid fibrils form nematic phases but appear to miss their twisted form, the cholesteric or chiral nematic phases, despite a well-defined chirality at the single fibril level. Here we report the discovery of cholesteric phases in amyloids, using β-lactoglobulin fibrils shortened by shear stresses. The physical behaviour of these new cholesteric materials exhibits unprecedented structural complexity, with confinement-driven ordering transitions between at least three types of nematic and cholesteric tactoids. We use energy functional theory to rationalize these results and observe a chirality inversion from the left-handed amyloids to right-handed cholesteric droplets. These findings deepen our understanding of cholesteric phases, advancing their use in soft nanotechnology, nanomaterial templating and self-assembly.

  12. Democracy and environment as references for quadruple and quintuple helix innovation systems

    Science.gov (United States)

    Carayannis, Elias G.; Campbell, David F. J.; Orr, Barron J.

    2015-04-01

    The perspective of democracy and the ecological context define key references for knowledge production and innovation in innovation systems. Particularly under conditions of environmental change where enhancing the potential for adaptation is critical, this requires a closer look at ecological responsibility and sensitivity in the different innovation models and governance regimes. The "Quintuple Helix" innovation model is an approach that stresses the necessary socio-ecological transition of society and economy by adding an environment helix to an innovation system already made up of three (university-industry-government) or four (civil society relations) helices in a way that supports adaptation by incorporating global warming as both a challenge to and a driver of innovation. There is the proposition that knowledge production and innovation co-evolve with democracy (Carayannis and Campbell, 2014). In the Triple Helix model (Etzkowitz and Leydesdorff, 2000) the existence of a democracy does not appear to be necessary for knowledge production and innovation. However, the Quadruple Helix (Carayannis and Campbell, 2009, 2010 and 2014) is defined and represented by additional key attributes and components: "media-based and culture-based public", "civil society" and "arts, artistic research and arts-based innovation" (Bast, Carayannis and Campbell, 2015). Implications of this are that the fourth helix in the Quadruple Helix innovation systems brings in and represents the perspective of "dimension of democracy" or the "context of democracy" for knowledge in general and knowledge production and innovation in more particular. Within theories of democracy there is a competition between narrow and broader concepts of democracy (Campbell, 2013). This is particularly true when democracy is to be understood to transcend more substantially the narrow understanding of being primarily based on or being primarily rooted in government institutions (within a Triple Helix

  13. Double-helix stellarator

    International Nuclear Information System (INIS)

    Moroz, P.E.

    1997-09-01

    A new stellarator configuration, the Double-Helix Stellarator (DHS), is introduced. This novel configuration features a double-helix center post as the only helical element of the stellarator coil system. The DHS configuration has many unique characteristics. One of them is the extreme low plasma aspect ratio, A ∼ 1--1.2. Other advantages include a high enclosed volume, appreciable rotational transform, and a possibility of extreme-high-β MHD equilibria. Moreover, the DHS features improved transport characteristics caused by the absence of the magnetic field ripple on the outboard of the torus. Compactness, simplicity and modularity of the coil system add to the DHS advantages for fusion applications

  14. "helix Nebula - the Science Cloud", a European Science Driven Cross-Domain Initiative Implemented in via AN Active Ppp Set-Up

    Science.gov (United States)

    Lengert, W.; Mondon, E.; Bégin, M. E.; Ferrer, M.; Vallois, F.; DelaMar, J.

    2015-12-01

    Helix Nebula, a European science cross-domain initiative building on an active PPP, is aiming to implement the concept of an open science commons[1] while using a cloud hybrid model[2] as the proposed implementation solution. This approach allows leveraging and merging of complementary data intensive Earth Science disciplines (e.g. instrumentation[3] and modeling), without introducing significant changes in the contributors' operational set-up. Considering the seamless integration with life-science (e.g. EMBL), scientific exploitation of meteorological, climate, and Earth Observation data and models open an enormous potential for new big data science. The work of Helix Nebula has shown that is it feasible to interoperate publicly funded infrastructures, such as EGI [5] and GEANT [6], with commercial cloud services. Such hybrid systems are in the interest of the existing users of publicly funded infrastructures and funding agencies because they will provide "freedom and choice" over the type of computing resources to be consumed and the manner in which they can be obtained. But to offer such freedom and choice across a spectrum of suppliers, various issues such as intellectual property, legal responsibility, service quality agreements and related issues need to be addressed. Finding solutions to these issues is one of the goals of the Helix Nebula initiative. [1] http://www.egi.eu/news-and-media/publications/OpenScienceCommons_v3.pdf [2] http://www.helix-nebula.eu/events/towards-the-european-open-science-cloud [3] e.g. https://sentinel.esa.int/web/sentinel/sentinel-data-access [5] http://www.egi.eu/ [6] http://www.geant.net/

  15. Fibril formation from pea protein and subsequent gel formation.

    Science.gov (United States)

    Munialo, Claire Darizu; Martin, Anneke H; van der Linden, Erik; de Jongh, Harmen H J

    2014-03-19

    The objective of this study was to characterize fibrillar aggregates made using pea proteins, to assemble formed fibrils into protein-based gels, and to study the rheological behavior of these gels. Micrometer-long fibrillar aggregates were observed after pea protein solutions had been heated for 20 h at pH 2.0. Following heating of pea proteins, it was observed that all of the proteins were hydrolyzed into peptides and that 50% of these peptides were assembled into fibrils. Changes on a structural level in pea proteins were studied using circular dichroism, transmission electron microscopy, and particle size analysis. During the fibril assembly process, an increase in aggregate size was observed, which coincided with an increase in thioflavin T binding, indicating the presence of β-sheet aggregates. Fibrils made using pea proteins were more branched and curly. Gel formation of preformed fibrils was induced by slow acidification from pH 7.0 to a final pH of around pH 5.0. The ability of pea protein-based fibrillar gels to fracture during an amplitude sweep was comparable to those of soy protein and whey protein-based fibrillar gels, although gels prepared from fibrils made using pea protein and soy protein were weaker than those of whey protein. The findings show that fibrils can be prepared from pea protein, which can be incorporated into protein-based fibrillar gels.

  16. Identification of Transthyretin Fibril Formation Inhibitors Using Structure-Based Virtual Screening.

    Science.gov (United States)

    Ortore, Gabriella; Martinelli, Adriano

    2017-08-22

    Transthyretin (TTR) is the primary carrier for thyroxine (T 4 ) in cerebrospinal fluid and a secondary carrier in blood. TTR is a stable homotetramer, but certain factors, genetic or environmental, could promote its degradation to form amyloid fibrils. A docking study using crystal structures of wild-type TTR was planned; our aim was to design new ligands that are able to inhibit TTR fibril formation. The computational protocol was thought to overcome the multiple binding modes of the ligands induced by the peculiarity of the TTR binding site and by the pseudosymmetry of the site pockets, which generally weaken such structure-based studies. Two docking steps, one that is very fast and a subsequent step that is more accurate, were used to screen the Aldrich Market Select database. Five compounds were selected, and their activity toward inhibiting TTR fibril formation was assessed. Three compounds were observed to be actives, two of which have the same potency as the positive control, and the other was found to be a promising lead compound. These results validate a computational protocol that is able to archive information on the key interactions between database compounds and TTR, which is valuable for supporting further studies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Atrial Fibrillation: Treatment

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Treatment Past Issues / Winter 2015 Table of Contents Treatment for atrial fibrillation depends on how often you have symptoms, how ...

  18. Polymorphism of amyloid fibrils formed by a peptide from the yeast prion protein Sup35: AFM and Tip-Enhanced Raman Scattering studies

    Energy Technology Data Exchange (ETDEWEB)

    Krasnoslobodtsev, Alexey V., E-mail: akrasnos@unomaha.edu [Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198 (United States); Department of Physics, University of Nebraska Omaha, Omaha, NE 68182 (United States); Deckert-Gaudig, Tanja [IPHT-Leibniz Institute of Photonic Technology, Albert-Einstein-Str. 9, D-07745 Jena (Germany); Zhang, Yuliang [Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198 (United States); Deckert, Volker [IPHT-Leibniz Institute of Photonic Technology, Albert-Einstein-Str. 9, D-07745 Jena (Germany); Institute for Physical Chemistry and Abbe Center of Photonics, University of Jena, Helmholtzweg 4, D-07743 Jena (Germany); Lyubchenko, Yuri L., E-mail: ylyubchenko@unmc.edu [Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198 (United States)

    2016-06-15

    Aggregation of prion proteins is the cause of various prion related diseases. The infectious form of prions, amyloid aggregates, exist as multiple strains. The strains are thought to represent structurally different prion protein molecules packed into amyloid aggregates, but the knowledge on the structure of different types of aggregates is limited. Here we report on the use of AFM (Atomic Force Microscopy) and TERS (Tip-Enhanced Raman Scattering) to study morphological heterogeneity and access underlying conformational features of individual amyloid aggregates. Using AFM we identified the morphology of amyloid fibrils formed by the peptide (CGNNQQNY) from the yeast prion protein Sup35 that is critically involved in the aggregation of the full protein. TERS results demonstrate that morphologically different amyloid fibrils are composed of a distinct set of conformations. Fibrils formed at pH 5.6 are composed of a mixture of peptide conformations (β-sheets, random coil and α-helix) while fibrils formed in pH~2 solution primarily have β-sheets. Additionally, peak positions in the amide III region of the TERS spectra suggested that peptides have parallel arrangement of β-sheets for pH~2 fibrils and antiparallel arrangement for fibrils formed at pH 5.6. We also developed a methodology for detailed analysis of the peptide secondary structure by correlating intensity changes of Raman bands in different regions of TERS spectra. Such correlation established that structural composition of peptides is highly localized with large contribution of unordered secondary structures on a fibrillar surface. - Highlights: • Amyloid polymorphs were characterized by AFM and TERS. • A mixture of peptide secondary structures in fibrils were identified using TERS. • TERS recognizes packing arrangement (parallel versus antiparallel) of peptides. • TERS is a powerful tool for high resolution structural analysis of fibrils.

  19. Private Venture Capital’s Investment on University Spin-Offs: A Case Study of Tsinghua University Based on Triple Helix Model

    DEFF Research Database (Denmark)

    Gao, Yuchen; Hu, Yimei; Wang, Jingyi

    2015-01-01

    and transition economies where governments are transforming their roles. Thus the main purpose of this study is to investigate how private venture capitals’ investment willingness on university spin-offs are influenced by universities and governments under the Chinese context based on the triple helix model....... Through an in-depth case study on the interactions of triple helix actors of Tsinghua University’s spin-offs, it is found that government and university developing an environment of marketization exert positive influences on the investment willingness of private venture capitals. Whilst financial direct...

  20. Stroke prevention in hospitalized patients with atrial fibrillation: a population-based study.

    Science.gov (United States)

    Nagpal, Seema; Anderson, David; Putnam, Wayne; Flowerdew, Gordon; Gardner, Martin; Cox, Jafna

    2003-01-01

    Oral anticoagulants reduce the incidence of stroke by 68%, yet suboptimal use has been documented in surveys of patients with atrial fibrillation. The present study examined current patterns of anticoagulant use for patients hospitalized with atrial fibrillation across an entire health care system. Improving Cardiovascular Outcomes in Nova Scotia (ICONS) is a prospective cohort study involving all patients hospitalized in Nova Scotia with atrial fibrillation, among other conditions. Consecutive inpatients with atrial fibrillation from October 15, 1997 to October 14, 1998 were studied. Detailed demographic and clinical data were collected and the proportion of patients using antithrombotic therapy was tabulated by risk category. Multivariate logistic regression was used to assess the relationship of various demographic and clinical factors with the use of antithrombotic agents. There were 2202 patients hospitalized with atrial fibrillation; 644 admitted specifically for this condition. Only 21% of patients admitted with atrial fibrillation were on warfarin sodium at admission and this increased by time of discharge. Diabetes was negatively correlated with warfarin sodium use. Histories of prosthetic valve replacement, stroke/transient ischemic attack, and heart failure were positively associated with anticoagulant use on admission. Patients with prosthetic valve replacement, heart failure, or hyperlipidemia were most likely to receive anticoagulants at discharge. Antithrombotic agents remain underused by patients with atrial fibrillation. While higher risk patients are generally targeted, this is not invariably the case; thus, diabetics remain under treated. Further work is needed to explain such anomalous practice and promote optimal antithrombotic therapy use.

  1. Atrial Fibrillation: Complications

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: Complications Past Issues / Winter 2015 Table of Contents ... has two major complications—stroke and heart failure. Atrial Fibrillation and Stroke Click to enlarge image This illustration ...

  2. Nature of the Charged-Group Effect on the Stability of the C-Peptide Helix

    Science.gov (United States)

    Shoemaker, Kevin R.; Kim, Peter S.; Brems, David N.; Marqusee, Susan; York, Eunice J.; Chaiken, Irwin M.; Stewart, John M.; Baldwin, Robert L.

    1985-04-01

    The residues responsible for the pH-dependent stability of the helix formed by the isolated C-peptide (residues 1-13 of ribonuclease A) have been identified by chemical synthesis of analogues and measurement of their helix-forming properties. Each of the residues ionizing between pH 2 and pH 8 has been replaced separately by an uncharged residue. Protonation of Glu-2- is responsible for the sharp decrease in helix stability between pH 5 and pH 2, and deprotonation of His-12+ causes a similar decrease between pH 5 and pH 8. Glu-9- is not needed for helix stability. The results cannot be explained by the Zimm-Bragg model and host-guest data for α -helix formation, which predict that the stability of the C-peptide helix should increase when Glu-2- is protonated or when His-12+ is deprotonated. Moreover, histidine+ is a strong helix-breaker in host-guest studies. In proteins, acidic and basic residues tend to occur at opposite ends of α -helices: acidic residues occur preferentially near the NH2-terminal end and basic residues near the COOH-terminal end. A possible explanation, based on a helix dipole model, has been given [Blagdon, D. E. & Goodman, M. (1975) Biopolymers 14, 241-245]. Our results are consistent with the helix dipole model and they support the suggestion that the distribution of charged residues in protein helices reflects the helix-stabilizing propensity of those residues. Because Glu-9 is not needed for helix stability, a possible Glu-9-\\cdots His-12+ salt bridge does not contribute significantly to helix stability. The role of a possible Glu-2-\\cdots Arg-10+ salt bridge has not yet been evaluated. A charged-group effect on α -helix stability in water has also been observed in a different peptide system [Ihara, S., Ooi, T. & Takahashi, S. (1982) Biopolymers 21, 131-145]: block copolymers containing (Ala)20 and (Glu)20 show partial helix formation at low temperatures, pH 7.5, where the glutamic acid residues are ionized. (Glu)20(Ala)20Phe forms a

  3. Ab initio theory of helix <-> coil phase transition

    DEFF Research Database (Denmark)

    Yakubovich, Alexander V.; Solov'yov, Ilia; Solov'yov, Andrey V.

    2008-01-01

    In this paper, we suggest a theoretical method based on the statistical mechanics for treating the alpha-helix <-> random coil transition in alanine polypeptides. We consider this process as a first-order phase transition and develop a theory which is free of model parameters and is based solely ...

  4. The swimming of a perfect deforming helix

    Science.gov (United States)

    Koens, Lyndon; Zhang, Hang; Mourran, Ahmed; Lauga, Eric

    2017-11-01

    Many bacteria rotate helical flagellar filaments in order to swim. When at rest or rotated counter-clockwise these flagella are left handed helices but they undergo polymorphic transformations to right-handed helices when the motor is reversed. These helical deformations themselves can generate motion, with for example Rhodobacter sphaeroides using the polymorphic transformation of the flagellum to generate rotation, or Spiroplasma propagating a change of helix handedness across its body's length to generate forward motion. Recent experiments reported on an artificial helical microswimmer generating motion without a propagating change in handedness. Made of a temperature sensitive gel, these swimmers moved by changing the dimensions of the helix in a non-reciprocal way. Inspired by these results and helix's ubiquitous presence in the bacterial world, we investigate how a deforming helix moves within a viscous fluid. Maintaining a single handedness along its entire length, we discuss how a perfect deforming helix can create a non-reciprocal swimming stroke, identify its principle directions of motion, and calculate the swimming kinematics asymptotically.

  5. Does perceived stress increase the risk of atrial fibrillation? A population-based cohort study in Denmark

    DEFF Research Database (Denmark)

    Graff, Simon; Prior, Anders; Fenger-Grøn, Morten

    2017-01-01

    Background Psychological stress is associated with increased risk of acute cardiovascular diseases, as myocardial infarction. We recently found a higher risk of atrial fibrillation following an acute stressful life event, but it remains unknown whether this also applies to common and less acute....... Conclusions This large population-based cohort study did not reveal a higher risk of atrial fibrillation among persons with a high degree of perceived stress after adjustment for participants' baseline characteristics....

  6. Polymorphism complexity and handedness inversion in serum albumin amyloid fibrils.

    Science.gov (United States)

    Usov, Ivan; Adamcik, Jozef; Mezzenga, Raffaele

    2013-12-23

    Protein-based amyloid fibrils can show a great variety of polymorphic structures within the same protein precursor, although the origins of these structural homologues remain poorly understood. In this work we investigate the fibrillation of bovine serum albumin--a model globular protein--and we follow the polymorphic evolution by a statistical analysis of high-resolution atomic force microscopy images, complemented, at larger length scales, by concepts based on polymer physics formalism. We identify six distinct classes of coexisting amyloid fibrils, including flexible left-handed twisted ribbons, rigid right-handed helical ribbons and nanotubes. We show that the rigid fibrils originate from flexible fibrils through two diverse polymorphic transitions, first, via a single-fibril transformation when the flexible left-handed twisted ribbons turn into the helical left-handed ribbons, to finally evolve into nanotube-like structures, and second, via a double-fibril transformation when two flexible left-handed twisted ribbons wind together resulting in a right-handed twisted ribbon, followed by a rigid right-handed helical ribbon polymorphic conformation. Hence, the change in handedness occurs with an increase in the level of the fibril's structural organization.

  7. Exposure-Based Therapy for Symptom Preoccupation in Atrial Fibrillation

    DEFF Research Database (Denmark)

    Särnholm, Josefin; Skúladóttir, Helga; Rück, Christian

    2017-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia. Patients often experience a range of symptoms resulting in a markedly reduced quality of life, and commonly show symptom preoccupation in terms of avoidance and control behaviors. Cognitive behavior therapy (CBT) has been shown...... with symptomatic paroxysmal (intermittent) atrial fibrillation who were assessed pre- and posttreatment and at 6-month follow-up. The CBT lasted 10 weeks and included exposure to physical sensations similar to AF symptoms, exposure to avoided situations or activities, and behavioral activation. We observed large...

  8. SAS-Based Studies of Protein Fibrillation

    DEFF Research Database (Denmark)

    Marasini, Carlotta; Vestergaard, Bente

    2017-01-01

    Protein fibrillation is associated with a number of fatal amyloid diseases (e.g. Alzheimer's and Parkinson's diseases). From a structural point of view, the aggregation process starts from an ensemble of native states that convert into transiently formed oligomers, higher order assemblies and pro...... and highlight existing reports, exemplifying the wealth of information that can be derived from the method....

  9. Designing cooperatively folded abiotic uni- and multimolecular helix bundles

    Science.gov (United States)

    de, Soumen; Chi, Bo; Granier, Thierry; Qi, Ting; Maurizot, Victor; Huc, Ivan

    2018-01-01

    Abiotic foldamers, that is foldamers that have backbones chemically remote from peptidic and nucleotidic skeletons, may give access to shapes and functions different to those of peptides and nucleotides. However, design methodologies towards abiotic tertiary and quaternary structures are yet to be developed. Here we report rationally designed interactional patterns to guide the folding and assembly of abiotic helix bundles. Computational design facilitated the introduction of hydrogen-bonding functionalities at defined locations on the aromatic amide backbones that promote cooperative folding into helix-turn-helix motifs in organic solvents. The hydrogen-bond-directed aggregation of helices not linked by a turn unit produced several thermodynamically and kinetically stable homochiral dimeric and trimeric bundles with structures that are distinct from the designed helix-turn-helix. Relative helix orientation within the bundles may be changed from parallel to tilted on subtle solvent variations. Altogether, these results prefigure the richness and uniqueness of abiotic tertiary structure behaviour.

  10. Contemporary approach to stroke prevention in atrial fibrillation: Risks, benefits, and new options.

    Science.gov (United States)

    Stock, Jonathan; Malm, Brian J

    2018-04-04

    Atrial fibrillation is a common diagnosis affecting nearly 3 million adults in the United States. Morbidity and mortality in these patients is driven largely by the associated increased risk of thromboembolic complications, especially stroke. Atrial fibrillation is a stronger risk factor than hypertension, coronary disease, or heart failure and is associated with an approximately five-fold increased risk. Mitigating stroke risk can be challenging and requires accurate assessment of stroke risk factors and careful selection of appropriate therapy. Anticoagulation, including the more recently introduced direct oral anticoagulants, is the standard of care for most patients. In addition, emerging non-pharmacologic mechanical interventions are playing an expanding role in reducing stroke risk in select patients. In this review we highlight the current approach to stroke risk stratification in atrial fibrillation and discuss in detail the mechanism, risks, and benefits of current and evolving therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Design and synthesis of DNA four-helix bundles

    Energy Technology Data Exchange (ETDEWEB)

    Rangnekar, Abhijit; Gothelf, Kurt V [Department of Chemistry, Centre for DNA Nanotechnology (CDNA) and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, DK-8000 Aarhus C (Denmark); LaBean, Thomas H, E-mail: kvg@chem.au.dk, E-mail: thl@cs.duke.edu [Department of Chemistry, Duke University, Durham, NC 27708 (United States)

    2011-06-10

    The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.

  12. Design and synthesis of DNA four-helix bundles

    International Nuclear Information System (INIS)

    Rangnekar, Abhijit; Gothelf, Kurt V; LaBean, Thomas H

    2011-01-01

    The field of DNA nanotechnology has evolved significantly in the past decade. Researchers have succeeded in synthesizing tile-based structures and using them to form periodic lattices in one, two and three dimensions. Origami-based structures have also been used to create nanoscale structures in two and three dimensions. Design and construction of DNA bundles with fixed circumference has added a new dimension to the field. Here we report the design and synthesis of a DNA four-helix bundle. It was found to be extremely rigid and stable. When several such bundles were assembled using appropriate sticky-ends, they formed micrometre-long filaments. However, when creation of two-dimensional sheet-like arrays of the four-helix bundles was attempted, nanoscale rings were observed instead. The exact reason behind the nanoring formation is yet to be ascertained, but it provides an exciting prospect for making programmable circular nanostructures using DNA.

  13. Ruby-Helix: an implementation of helical image processing based on object-oriented scripting language.

    Science.gov (United States)

    Metlagel, Zoltan; Kikkawa, Yayoi S; Kikkawa, Masahide

    2007-01-01

    Helical image analysis in combination with electron microscopy has been used to study three-dimensional structures of various biological filaments or tubes, such as microtubules, actin filaments, and bacterial flagella. A number of packages have been developed to carry out helical image analysis. Some biological specimens, however, have a symmetry break (seam) in their three-dimensional structure, even though their subunits are mostly arranged in a helical manner. We refer to these objects as "asymmetric helices". All the existing packages are designed for helically symmetric specimens, and do not allow analysis of asymmetric helical objects, such as microtubules with seams. Here, we describe Ruby-Helix, a new set of programs for the analysis of "helical" objects with or without a seam. Ruby-Helix is built on top of the Ruby programming language and is the first implementation of asymmetric helical reconstruction for practical image analysis. It also allows easier and semi-automated analysis, performing iterative unbending and accurate determination of the repeat length. As a result, Ruby-Helix enables us to analyze motor-microtubule complexes with higher throughput to higher resolution.

  14. Cost of illness of atrial fibrillation: a nationwide study of societal impact.

    Science.gov (United States)

    Johnsen, Søren Paaske; Dalby, Lene Worsaae; Täckström, Tomas; Olsen, Jens; Fraschke, Anina

    2017-11-10

    The prevalence of atrial fibrillation is increasing rapidly; however, to date, population-based data are lacking on the attributable cost of illness of atrial fibrillation from a societal perspective, including both direct and indirect costs. The study was an incidence-based cost-of-illness study based on national registries covering the entire population of Denmark. We identified all patients with a first-time hospital diagnosis of atrial fibrillation between 2001 and 2012. For every atrial fibrillation patient, we identified three age- and sex-matched controls from the general population. Both the total and the attributable costs of atrial fibrillation were estimated based on individual level information on hospital care (in- and out-patient contacts), primary sector care, use of prescription drugs and productivity loss. Average 3-year societal costs per patient attributable to atrial fibrillation were estimated to be €20,403-26,544 during the study period. The costs were highest during the first year after diagnosis of atrial fibrillation. Admission costs constituted the largest cost component, whereas primary sector costs and medicine costs only constituted minor components. The attributable costs were more than two-fold higher among patients experiencing a stroke. The total 3-year cost attributable to atrial fibrillation in Denmark was estimated to be €219-295 million. The societal costs attributable to atrial fibrillation are significant. Reducing the need for hospitalizations, in particular from stroke, is a key factor in controlling the costs.

  15. Structure of bacteriophage [phi]29 head fibers has a supercoiled triple repeating helix-turn-helix motif

    Energy Technology Data Exchange (ETDEWEB)

    Xiang, Ye; Rossmann, Michael G. (Purdue)

    2011-12-22

    The tailed bacteriophage {phi}29 capsid is decorated with 55 fibers attached to quasi-3-fold symmetry positions. Each fiber is a homotrimer of gene product 8.5 (gp8.5) and consists of two major structural parts, a pseudohexagonal base and a protruding fibrous portion that is about 110 {angstrom} in length. The crystal structure of the C-terminal fibrous portion (residues 112-280) has been determined to a resolution of 1.6 {angstrom}. The structure is about 150 {angstrom} long and shows three distinct structural domains designated as head, neck, and stem. The stem region is a unique three-stranded helix-turn-helix supercoil that has not previously been described. When fitted into a cryoelectron microscope reconstruction of the virus, the head structure corresponded to a disconnected density at the distal end of the fiber and the neck structure was located in weak density connecting it to the fiber. Thin section studies of Bacillus subtilis cells infected with fibered or fiberless {phi}29 suggest that the fibers might enhance the attachment of the virions onto the host cell wall.

  16. Helix probe areas for the utilization of geothermal power. A practical example; Helix-Sondenfelder zur Nutzung von Erdwaerme. Ein Praxisbeispiel

    Energy Technology Data Exchange (ETDEWEB)

    Kuebert, Markus; Walker-Hertkorn, Simone [tewag Technologie - Erdwaermeanlagen - Umweltschutz GmbH, Starzach (Germany); Tietz, Jan [REHAU AG und Co., Erlangen-Eltersdorf (Germany); Riepold, Markus; Gloeckl, Andreas [MR Tiefbau GmbH, Brunnen (Germany)

    2013-02-01

    Thanks to their spiral shape so-called helix probes with a tube length of 40 meter have a height of only three meter: A lot of heat exchange area in a small space. Thus, helix probes are an ideal solution for the utilization of geothermal energy at places at which one cannot drill deeply due to geothermal reasons. Under this aspect, the contribution under consideration reports on the planning of a helix probe area being sustainably adapted to the user requirements for the new construction of a production facility.

  17. 77 FR 11121 - Scientific Information Request on Treatment of Atrial Fibrillation

    Science.gov (United States)

    2012-02-24

    ... Information Request on Treatment of Atrial Fibrillation AGENCY: Agency for Healthcare Research and Quality... Review of the Treatment of Atrial Fibrillation, which is currently being conducted by the Evidence-based... the treatment of atrial fibrillation. The EHC Program is dedicated to identifying as many studies as...

  18. A biomechanical model for fibril recruitment: Evaluation in tendons and arteries.

    Science.gov (United States)

    Bevan, Tim; Merabet, Nadege; Hornsby, Jack; Watton, Paul N; Thompson, Mark S

    2018-06-06

    Simulations of soft tissue mechanobiological behaviour are increasingly important for clinical prediction of aneurysm, tendinopathy and other disorders. Mechanical behaviour at low stretches is governed by fibril straightening, transitioning into load-bearing at recruitment stretch, resulting in a tissue stiffening effect. Previous investigations have suggested theoretical relationships between stress-stretch measurements and recruitment probability density function (PDF) but not derived these rigorously nor evaluated these experimentally. Other work has proposed image-based methods for measurement of recruitment but made use of arbitrary fibril critical straightness parameters. The aim of this work was to provide a sound theoretical basis for estimating recruitment PDF from stress-stretch measurements and to evaluate this relationship using image-based methods, clearly motivating the choice of fibril critical straightness parameter in rat tail tendon and porcine artery. Rigorous derivation showed that the recruitment PDF may be estimated from the second stretch derivative of the first Piola-Kirchoff tissue stress. Image-based fibril recruitment identified the fibril straightness parameter that maximised Pearson correlation coefficients (PCC) with estimated PDFs. Using these critical straightness parameters the new method for estimating recruitment PDF showed a PCC with image-based measures of 0.915 and 0.933 for tendons and arteries respectively. This method may be used for accurate estimation of fibril recruitment PDF in mechanobiological simulation where fibril-level mechanical parameters are important for predicting cell behaviour. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Atrial fibrillation and hyperthyroidism: A literature review.

    Science.gov (United States)

    Reddy, Vivek; Taha, Wael; Kundumadam, Shanker; Khan, Mazhar

    Atrial fibrillation is the most common arrhythmia worldwide with increasing frequency noted with age. Hyperthyroidism is a well-known cause of atrial fibrillation with a 16%-60% prevalence of atrial fibrillation in patients with known hyperthyroidism Ross et al. (2016). While hyperthyroidism as a causative factor of atrial fibrillation is well established, this literature review aims to answer several questions on this topic including: 1. The relationship of atrial fibrillation to hyperthyroidism 2. Atrial fibrillation as a predictor of hyperthyroidism 3. The pathophysiology of thyrotoxic atrial fibrillation 4. Subclinical hyperthyroidism and the relationship with atrial fibrillation 5. Cardioversion and Catheter ablation of hyperthyroid patients with atrial fibrillation 6. Thrombotic risk of hyperthyroid patients with atrial fibrillation 7. Management of Thyrotoxic Atrial fibrillation 8. Pharmacological rhythm control in patients with hyperthyroidism and atrial fibrillation 9. Treatment of Hyperthyroidism to prevent atrial fibrillation 10. Clinical Implications of Hyperthyroidism and Atrial Fibrillation. Copyright © 2017 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  20. Solid-State-NMR-Structure-Based Inhibitor Design to Achieve Selective Inhibition of the Parallel-in-Register β-Sheet versus Antiparallel Iowa Mutant β-Amyloid Fibrils.

    Science.gov (United States)

    Cheng, Qinghui; Qiang, Wei

    2017-06-08

    Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has been widely applied to characterize the high-resolution structures of β-amyloid (Aβ) fibrils. While these structures provide crucial molecular insights on the deposition of amyloid plaques in Alzheimer's diseases (AD), ssNMR structures have been rarely used so far as the basis for designing inhibitors. It remains a challenge because the ssNMR-basedfibril structures were usually obtained with sparsely isotope-labeled peptides with limited experimental constraints, where the structural models, especially the side-chain coordinates, showed restricted precision. However, these structural models often possess a higher accuracy within the hydrophobic core regions with more well-defined experimental data, which provide potential targets for the molecular design. This work presents an ssNMR-based molecular design to achieve selective inhibition of a particular type of Aβ fibrillar structure, which was formed with the Iowa mutant of Aβ with parallel-in-register β-sheet hydrophobic core. The results show that short peptides that mimic the C-terminal β-strands of the fibril may have a preference in binding to the parallel Aβ fibrils rather than the antiparallel fibrils, mainly due to the differences in the high-resolution structures in the fibril elongation interfaces. The Iowa mutant Aβ fibrils are utilized in this work mainly as a model to demonstrate the feasibility of the strategy because it is relatively straightforward to distinguish the parallel and antiparallel fibril structures using ssNMR. Our results suggest that it is potentially feasible to design structure-selective inhibitors and/or diagnostic agents to Aβ fibrils using ssNMR-based structural models.

  1. Design, synthesis, and evaluation of an alpha-helix mimetic library targeting protein-protein interactions.

    Science.gov (United States)

    Shaginian, Alex; Whitby, Landon R; Hong, Sukwon; Hwang, Inkyu; Farooqi, Bilal; Searcey, Mark; Chen, Jiandong; Vogt, Peter K; Boger, Dale L

    2009-04-22

    The design and solution-phase synthesis of an alpha-helix mimetic library as an integral component of a small-molecule library targeting protein-protein interactions are described. The iterative design, synthesis, and evaluation of the candidate alpha-helix mimetic was initiated from a precedented triaryl template and refined by screening the designs for inhibition of MDM2/p53 binding. Upon identifying a chemically and biologically satisfactory design and consistent with the screening capabilities of academic collaborators, the corresponding complete library was assembled as 400 mixtures of 20 compounds (20 x 20 x 20-mix), where the added subunits are designed to mimic all possible permutations of the naturally occurring i, i + 4, i + 7 amino acid side chains of an alpha-helix. The library (8000 compounds) was prepared using a solution-phase synthetic protocol enlisting acid/base liquid-liquid extractions for purification on a scale that insures its long-term availability for screening campaigns. Screening of the library for inhibition of MDM2/p53 binding not only identified the lead alpha-helix mimetic upon which the library was based, but also suggests that a digestion of the initial screening results that accompany the use of such a comprehensive library can provide insights into the nature of the interaction (e.g., an alpha-helix mediated protein-protein interaction) and define the key residues and their characteristics responsible for recognition.

  2. Stop-and-go kinetics in amyloid fibrillation

    DEFF Research Database (Denmark)

    Ferkinghoff-Borg, Jesper; Fonslet, Jesper; Andersen, Christian Beyschau

    2010-01-01

    Many human diseases are associated with protein aggregation and fibrillation. We present experiments on in vitro glucagon fibrillation using total internal reflection fluorescence microscopy, providing real-time measurements of single-fibril growth. We find that amyloid fibrils grow in an intermi......Many human diseases are associated with protein aggregation and fibrillation. We present experiments on in vitro glucagon fibrillation using total internal reflection fluorescence microscopy, providing real-time measurements of single-fibril growth. We find that amyloid fibrils grow...

  3. Interactions between the mixotrophic dinoflagellate Takayama helix and common heterotrophic protists.

    Science.gov (United States)

    Ok, Jin Hee; Jeong, Hae Jin; Lim, An Suk; Lee, Kyung Ha

    2017-09-01

    The phototrophic dinoflagellate Takayama helix that is known to be harmful to abalone larvae has recently been revealed to be mixotrophic. Although mixotrophy elevates the growth rate of T. helix by 79%-185%, its absolute growth rate is still as low as 0.3d -1 . Thus, if the mortality rate of T. helix due to predation is high, this dinoflagellate may not easily prevail. To investigate potential effective protistan grazers on T. helix, feeding by diverse heterotrophic dinoflagellates such as engulfment-feeding Oxyrrhis marina, Gyrodinium dominans, Gyrodinium moestrupii, Polykrikos kofoidii, and Noctiluca scintillans, peduncle-feeding Aduncodinium glandula, Gyrodiniellum shiwhaense, Luciella masanensis, and Pfiesteria piscicida, pallium-feeding Oblea rotunda and Protoperidinium pellucidum, and the naked ciliates Pelagostrobilidium sp. (ca. 40μm in cell length) and Strombidinopsis sp. (ca. 150μm in cell length) on T. helix was explored. Among the tested heterotrophic protists, O. marina, G. dominans, G. moestrupii, A. glandula, L. masanensis, P. kofoidii, P. piscicida, and Strombidinopsis sp. were able to feed on T. helix. The growth rates of all these predators except Strombidinopsis sp. with T. helix prey were lower than those without the prey. The growth rate of Strombidinopsis sp. on T. helix was almost zero although the growth rate of Strombidinopsis sp. with T. helix prey was higher than those without the prey. Moreover, T. helix fed on O. marina and P. pellucidum and lysed the cells of P. kofoidii and G. shiwhaense. With increasing the concentrations of T. helix, the growth rates of O. marina and P. kofoidii decreased, but those of G. dominans and L. masanensis largely did not change. Therefore, reciprocal predation, lysis, no feeding, and the low ingestion rates of the common protists preying on T. helix may result in a low mortality rate due to predation, thereby compensating for this species' low growth rate. Copyright © 2017 Elsevier B.V. All rights

  4. Comparative Study on the Adaptation and Growth Dynamics of the Helix pomatia and Helix aspersa Muller Terrestrial Snails Under Different Feeding Regimes

    Directory of Open Access Journals (Sweden)

    Adrian Toader-Williams

    2010-05-01

    Full Text Available We used Helix pomatia and Helix aspersa species and measure their growth as the snails were approaching the hibernation season. Helix pomatia 2yo shown a decrease in weight while being raised in enclosed parcels of 4sqm the younger Helix pomatia 1yo as well as Helix aspersa Muller demonstrated the ability to adapt relatively fast to the same conditions. We established 5 experimental lots in a Helix pomatia farm, GPS coordinates N46.606040 E23.599950. Control lot contained Taraxacum officinales, Sonchus oleraceus, Equisetum arvense and Atriplex hortensis, wild flora found within the farm. The other lots contained the same plants as the control lot plus different combinations of imported plants from other areals. The H. pomatia 2yo weight decreased in the control lot by a mean of -3.86% while H. aspersa 1yo marked an increase of +16.89% in the same lot during the same period. The lot containing lupinus polyphyllus delivered snails with weight gain of +24.66% for H. pomatia 2yo and an increase of only +1.98% for H. aspersa 1yo. As a contrast, H. pomatia 2yo gained only +7.72% while H. aspersa 1yo gained +28.89%, in the lot containing Lavanda officinalis, Foeniculum vulgare and Hyssopus officinalis among the other plants.

  5. Atrial fibrillation and delayed gastric emptying.

    Directory of Open Access Journals (Sweden)

    Isadora C Botwinick

    Full Text Available BACKGROUND: Atrial fibrillation and delayed gastric emptying (DGE are common after pancreaticoduodenectomy. Our aim was to investigate a potential relationship between atrial fibrillation and DGE, which we defined as failure to tolerate a regular diet by the 7(th postoperative day. METHODS: We performed a retrospective chart review of 249 patients who underwent pancreaticoduodenectomy at our institution between 2000 and 2009. Data was analyzed with Fisher exact test for categorical variables and Mann-Whitney U or unpaired T-test for continuous variables. RESULTS: Approximately 5% of the 249 patients included in the analysis experienced at least one episode of postoperative atrial fibrillation. Median age of patients with atrial fibrillation was 74 years, compared with 66 years in patients without atrial fibrillation (p = 0.0005. Patients with atrial fibrillation were more likely to have a history of atrial fibrillation (p = 0.03. 92% of the patients with atrial fibrillation suffered from DGE, compared to 46% of patients without atrial fibrillation (p = 0.0007. This association held true when controlling for age. CONCLUSION: Patients with postoperative atrial fibrillation are more likely to experience delayed gastric emptying. Interventions to manage delayed gastric function might be prudent in patients at high risk for postoperative atrial fibrillation.

  6. Surgery for atrial fibrillation.

    Science.gov (United States)

    Viganò, M; Graffigna, A; Ressia, L; Minzioni, G; Pagani, F; Aiello, M; Gazzoli, F

    1996-01-01

    The mechanisms of atrial fibrillation arc multiple reentry circuits spinning around the atrial surface, and these baffle any attempt to direct surgical interruption. The purpose of this article is to report the surgical experience in the treatment of isolated and concomitant atrial fibrillation at the Cardiac Surgical Institute of the University of Pavia. In cases of atrial fibrillation secondary to mitral/valve disease, surgical isolation of the left atrium at the time of mitral valve surgery can prevent atrial fibrillation from involving the right atrium, which can exert its diastolic pump function on the right ventricle. Left atrial isolation was performed on 205 patients at the time of mitral valve surgery. Atrial partitioning ("maze operation") creates straight and blind atrial alleys so that non-recentry circuits can take place. Five patients underwent this procedure. In eight-cases of atrial fibrillation secondary to atrial septal defect, the adult patients with atrial septal defect and chronic or paroxysmal atrial fibrillation underwent surgical isolation of the right atrium associated which surgical correction of the defect, in order to let sinus rhythm govern the left atrium and the ventricles. "Lone" atrial fibrillation occurs in hearts with no detectable organic disease. Bi-atrial isolation with creation of an atrial septal internodal "corridor" was performed on 14 patients. In cases of atrial fibrillation secondary to mitral valve disease, left atrial isolation was performed on 205 patients at the time of mitral valve surgery with an overall sinus rhythm recovery of 44%. In the same period, sinus rhythm was recovered and persisted in only 19% of 252 patients who underwent mitral valve replacement along (P < 0.001). Sinus rhythm was less likely to recover in patients with right atriomegaly requiring tricuspid valve annuloplasty: 59% vs 84% (P < 0.001). Restoration of the right atrial function raised the cardiac index from 2.25 +/- 0.55 1/min per m2

  7. Atrial fibrillation - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000237.htm Atrial fibrillation - discharge To use the sharing features on this ... have been in the hospital because you have atrial fibrillation . This condition occurs when your heart beats faster ...

  8. Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study

    NARCIS (Netherlands)

    L. Herrera (Lizbeth); I. Leal (Ingrid); F. Lapi (Francesco); M.J. Schuemie (Martijn); V. Arcoraci (Vincenzo); F. Cipriani (Francesco); E. Sessa (E.); A. Vaccheri (Alberto); C. Piccinni (C.); T. Staniscia (Tommaso); A. Vestri (Annarita); M. Di Bari (M.); G. Corrao (Giovanni); A. Zambon (A.); D Gregori (Dario); F. Carle (F.); M.C.J.M. Sturkenboom (Miriam); G. Mazzaglia (Giampiero); G. Trifirò (Gianluca)

    2015-01-01

    textabstractSummary: Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with

  9. Government and Governance of Regional Triple Helix Interactions

    Science.gov (United States)

    Danson, Mike; Todeva, Emanuela

    2016-01-01

    This conceptual paper contributes to the discussion of the role of regional government and regional Triple Helix constellations driving economic development and growth within regional boundaries. The impact of regionalism and subsidiarity on regional Triple Helix constellations, and the questions of governmentality, governance and institutional…

  10. A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia

    Science.gov (United States)

    The basic helix-loop-helix (bHLH) transcription factors (TFs) play important roles in regulating multiple biological processes in plants. However, there are few reports about the function of bHLHs in flower senescence. In this study, a bHLH TF, PhFBH4, was found to be dramatically upregulated during...

  11. Double helix vortex breakdown in a turbulent swirling annular jet flow

    Science.gov (United States)

    Vanierschot, M.; Percin, M.; van Oudheusden, B. W.

    2018-03-01

    In this paper, we report on the structure and dynamics of double helix vortex breakdown in a turbulent annular swirling jet. Double helix breakdown has been reported previously for the laminar flow regime, but this structure has rarely been observed in turbulent flow. The flow field is investigated experimentally by means of time-resolved tomographic particle image velocimetry. Notwithstanding the axisymmetric nature of the time-averaged flow, analysis of the instantaneous three-dimensional (3D) vortical structures shows the existence of a vortex core along the central axis which breaks up into a double helix downstream. The winding sense of this double helix is opposite to the swirl direction (m =-2 ) and it is wrapped around a central vortex breakdown bubble. This structure is quite different from double helix breakdown found in laminar flows where the helix is formed in the wake of the bubble and not upstream. The double helix precesses around the central axis of the jet with a precessing frequency corresponding to a Strouhal number of 0.27.

  12. An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions.

    Science.gov (United States)

    Grison, Claire M; Miles, Jennifer A; Robin, Sylvie; Wilson, Andrew J; Aitken, David J

    2016-09-05

    A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key β-amino acid component in the design of α/β/γ-peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  13. IFITM3 requires an amphipathic helix for antiviral activity.

    Science.gov (United States)

    Chesarino, Nicholas M; Compton, Alex A; McMichael, Temet M; Kenney, Adam D; Zhang, Lizhi; Soewarna, Victoria; Davis, Matthew; Schwartz, Olivier; Yount, Jacob S

    2017-10-01

    Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3-dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections. The homologous amphipathic helix within IFITM1 is also required for the inhibition of infection, indicating that IFITM proteins possess a conserved mechanism of antiviral action. We further demonstrate that the amphipathic helix of IFITM3 is required to block influenza virus hemagglutinin-mediated membrane fusion. Overall, our results provide evidence that IFITM proteins utilize an amphipathic helix for inhibiting virus fusion. © 2017 The Authors.

  14. Effect of Hedera helix on lung histopathology in chronic asthma.

    Science.gov (United States)

    Hocaoglu, Arzu Babayigit; Karaman, Ozkan; Erge, Duygu Olmez; Erbil, Guven; Yilmaz, Osman; Kivcak, Bijen; Bagriyanik, H Alper; Uzuner, Nevin

    2012-12-01

    Hedera helix is widely used to treat bronchial asthma for many years. However, effects of this herb on lung histopathology is still far from clear. We aimed to determine the effect of oral administration of Hedera helix on lung histopathology in a murine model of chronic asthma.BALB/c mice were divided into four groups; I (Placebo), II (Hedera helix), III (Dexamethasone) and IV (Control). All mice except controls were sensitized and challenged with ovalbumin. Then, mice in group I received saline, group II 100 mg/kg Hedera helix and group III 1 mg/kg dexamethasone via orogastic gavage once daily for one week. Airway histopathology was evaluated by using light and electron microscopy in all groups.Goblet cell numbers and thicknesses of basement membrane were found significantly lower in group II, but there was no statistically significant difference in terms of number of mast cells, thicknesses of epithelium and subepithelial smooth muscle layers between group I and II. When Hedera helix and dexamethasone groups were compared with each other, thickness of epithelium, subepithelial muscle layers, number of mast cells and goblet cells of group III were significantly ameliorated when compared with the group II. Although Hedera helix administration reduced only goblet cell counts and the thicknesses of basement membrane in the asthmatic airways, dexamethasone ameliorated all histopathologic parameters except thickness of basement membrane better than Hedera helix.

  15. Acute hospital, community, and indirect costs of stroke associated with atrial fibrillation: population-based study.

    LENUS (Irish Health Repository)

    Hannon, Niamh

    2014-10-30

    No economic data from population-based studies exist on acute or late hospital, community, and indirect costs of stroke associated with atrial fibrillation (AF-stroke). Such data are essential for policy development, service planning, and cost-effectiveness analysis of new therapeutic agents.

  16. Nanomechanical properties of single amyloid fibrils

    International Nuclear Information System (INIS)

    Sweers, K K M; Bennink, M L; Subramaniam, V

    2012-01-01

    Amyloid fibrils are traditionally associated with neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease or Creutzfeldt-Jakob disease. However, the ability to form amyloid fibrils appears to be a more generic property of proteins. While disease-related, or pathological, amyloid fibrils are relevant for understanding the pathology and course of the disease, functional amyloids are involved, for example, in the exceptionally strong adhesive properties of natural adhesives. Amyloid fibrils are thus becoming increasingly interesting as versatile nanobiomaterials for applications in biotechnology. In the last decade a number of studies have reported on the intriguing mechanical characteristics of amyloid fibrils. In most of these studies atomic force microscopy (AFM) and atomic force spectroscopy play a central role. AFM techniques make it possible to probe, at nanometer length scales, and with exquisite control over the applied forces, biological samples in different environmental conditions. In this review we describe the different AFM techniques used for probing mechanical properties of single amyloid fibrils on the nanoscale. An overview is given of the existing mechanical studies on amyloid. We discuss the difficulties encountered with respect to the small fibril sizes and polymorphic behavior of amyloid fibrils. In particular, the different conformational packing of monomers within the fibrils leads to a heterogeneity in mechanical properties. We conclude with a brief outlook on how our knowledge of these mechanical properties of the amyloid fibrils can be exploited in the construction of nanomaterials from amyloid fibrils. (topical review)

  17. Curcumin Protects β-Lactoglobulin Fibril Formation and Fibril-Induced Neurotoxicity in PC12 Cells.

    Directory of Open Access Journals (Sweden)

    Mansooreh Mazaheri

    Full Text Available In this study the β-lactoglobulin fibrillation, in the presence or absence of lead ions, aflatoxin M1 and curcumin, was evaluated using ThT fluorescence, Circular dichroism spectroscopy and atomic force microscopy. To investigate the toxicity of the different form of β-Lg fibrils, in the presence or absence of above toxins and curcumin, we monitored changes in the level of reactive oxygen species and morphology of the differentiated neuron-like PC12 cells. The cell viability, cell body area, average neurite length, neurite width, number of primary neurites, percent of bipolar cells and node/primary neurite ratios were used to assess the growth and complexity of PC12 cells exposed to different form of β-Lg fibrils. Incubation of β-Lg with curcumin resulted in a significant decrease in ROS levels even in the presence of lead ions and aflatoxin M1. The β-Lg fibrils formed in the presence of lead ions and aflatoxin M1 attenuated the growth and complexity of PC12 cells compared with other form of β-Lg fibrils. However, the adverse effects of these toxins and protein fibrils were negated in the presence of curcumin. Furthermore, the antioxidant and inhibitory effects of curcumin protected PC12 cells against fibril neurotoxicity and enhanced their survival. Thus, curcumin may provide a protective effect toward β-Lg, and perhaps other protein, fibrils mediated neurotoxicity.

  18. The basic helix-loop-helix region of the transcriptional repressor hairy and enhancer of split 1 is preorganized to bind DNA

    NARCIS (Netherlands)

    Popovic, Matija; Wienk, Hans; Coglievina, Maristella; Boelens, Rolf; Pongor, Sándor; Pintar, Alessandro

    2014-01-01

    Hairy and enhancer of split 1, one of the main downstream effectors in Notch signaling, is a transcriptional repressor of the basic helix-loop-helix (bHLH) family. Using nuclear magnetic resonance methods, we have determined the structure and dynamics of a recombinant protein, H1H, which includes an

  19. Toward understanding insulin fibrillation.

    Science.gov (United States)

    Brange, J; Andersen, L; Laursen, E D; Meyn, G; Rasmussen, E

    1997-05-01

    Formation of insulin fibrils is a physical process by which partially unfolded insulin molecules interact with each other to form linear aggregates. Shielding of hydrophobic domains is the main driving force for this process, but formation of intermolecular beta-sheet may further stabilize the fibrillar structure. Conformational displacement of the B-chain C-terminal with exposure of nonpolar, aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in the fibrillation process. Recent crystal analyses and molecular modeling studies have suggested that when insulin fibrillates this exposed domain interacts with a hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17, and B18, normally buried when three insulin dimers form a hexamer. In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin. In contrast, the IgE response increased with increasing content of insulin in fibrillar form. Strategies and practical approaches to prevent insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric structure and blockage of hydrophobic interfaces by addition of surfactants are the most effective means of counteracting insulin fibrillation.

  20. Efficient Fatigue Analysis of Helix Elements in Umbilicals and Flexible Risers: Theory and Applications

    Directory of Open Access Journals (Sweden)

    Geir Skeie

    2012-01-01

    Full Text Available Fatigue analysis of structural components such as helix tensile armors and steel tubes is a critical design issue for dynamic umbilicals and flexible pipes. The basis for assessment of fatigue damage of such elements is the long-term stress cycle distribution at critical locations on the helix elements caused by long-term environmental loading on the system. The long-term stress cycle distribution will hence require global dynamic time domain analysis followed by a detailed cross-sectional analysis in a large number of irregular sea states. An overall computational consistent and efficient fatigue analysis scheme is outlined with due regard of the cross-sectional analysis technique required for fatigue stress calculation with particular attention to the helix elements. The global cross-section is exposed to pure bending, tensile, torsion, and pressure loading. The state of the different cross-section elements is based on the global response. Special emphasis is placed on assessment of friction stresses caused by the stick-slip behavior of helix elements in bending that are of special importance for fatigue life assessments. The described cross-sectional analysis techniques are based on an extensive literature survey and are hence considered to represent industry consensus. The performance of the described calculation scheme is illustrated by case studies.

  1. A magnetic torsional wave near the Galactic Centre traced by a 'double helix' nebula.

    Science.gov (United States)

    Morris, Mark; Uchida, Keven; Do, Tuan

    2006-03-16

    The magnetic field in the central few hundred parsecs of the Milky Way has a dipolar geometry and is substantially stronger than elsewhere in the Galaxy, with estimates ranging up to a milligauss (refs 1-6). Characterization of the magnetic field at the Galactic Centre is important because it can affect the orbits of molecular clouds by exerting a drag on them, inhibit star formation, and could guide a wind of hot gas or cosmic rays away from the central region. Here we report observations of an infrared nebula having the morphology of an intertwined double helix about 100 parsecs from the Galaxy's dynamical centre, with its axis oriented perpendicular to the Galactic plane. The observed segment is about 25 parsecs in length, and contains about 1.25 full turns of each of the two continuous, helically wound strands. We interpret this feature as a torsional Alfvén wave propagating vertically away from the Galactic disk, driven by rotation of the magnetized circumnuclear gas disk. The direct connection between the circumnuclear disk and the double helix is ambiguous, but the images show a possible meandering channel that warrants further investigation.

  2. Genome-wide identification and analysis of basic helix-loop-helix domains in dog, Canis lupus familiaris.

    Science.gov (United States)

    Wang, Xu-Hua; Wang, Yong; Liu, A-Ke; Liu, Xiao-Ting; Zhou, Yang; Yao, Qin; Chen, Ke-Ping

    2015-04-01

    The basic helix-loop-helix (bHLH) domain is a highly conserved amino acid motif that defines a group of DNA-binding transcription factors. bHLH proteins play essential regulatory roles in a variety of biological processes in animal, plant, and fungus. The domestic dog, Canis lupus familiaris, is a good model organism for genetic, physiological, and behavioral studies. In this study, we identified 115 putative bHLH genes in the dog genome. Based on a phylogenetic analysis, 51, 26, 14, 4, 12, and 4 dog bHLH genes were assigned to six separate groups (A-F); four bHLH genes were categorized as ''orphans''. Within-group evolutionary relationships inferred from the phylogenetic analysis were consistent with positional conservation, other conserved domains flanking the bHLH motif, and highly conserved intron/exon patterns in other vertebrates. Our analytical results confirmed the GenBank annotations of 89 dog bHLH proteins and provided information that could be used to update the annotations of the remaining 26 dog bHLH proteins. These data will provide good references for further studies on the structures and regulatory functions of bHLH proteins in the growth and development of dogs, which may help in understanding the mechanisms that underlie the physical and behavioral differences between dogs and wolves.

  3. A new assay format for NF-kappaB based on a DNA triple helix and a fluorescence resonance energy transfer.

    Science.gov (United States)

    Altevogt, Dominik; Hrenn, Andrea; Kern, Claudia; Clima, Lilia; Bannwarth, Willi; Merfort, Irmgard

    2009-10-07

    Herein we report a feasibility study for a new concept to detect DNA binding protein NF-kappaB based on a DNA triple helix formation in combination with a fluorescence resonance energy transfer (FRET). The new principle avoids expensive antibodies and radioactivity and might have implications for assays of other DNA binding proteins.

  4. Mechanical unfolding reveals stable 3-helix intermediates in talin and α-catenin.

    Directory of Open Access Journals (Sweden)

    Vasyl V Mykuliak

    2018-04-01

    Full Text Available Mechanical stability is a key feature in the regulation of structural scaffolding proteins and their functions. Despite the abundance of α-helical structures among the human proteome and their undisputed importance in health and disease, the fundamental principles of their behavior under mechanical load are poorly understood. Talin and α-catenin are two key molecules in focal adhesions and adherens junctions, respectively. In this study, we used a combination of atomistic steered molecular dynamics (SMD simulations, polyprotein engineering, and single-molecule atomic force microscopy (smAFM to investigate unfolding of these proteins. SMD simulations revealed that talin rod α-helix bundles as well as α-catenin α-helix domains unfold through stable 3-helix intermediates. While the 5-helix bundles were found to be mechanically stable, a second stable conformation corresponding to the 3-helix state was revealed. Mechanically weaker 4-helix bundles easily unfolded into a stable 3-helix conformation. The results of smAFM experiments were in agreement with the findings of the computational simulations. The disulfide clamp mutants, designed to protect the stable state, support the 3-helix intermediate model in both experimental and computational setups. As a result, multiple discrete unfolding intermediate states in the talin and α-catenin unfolding pathway were discovered. Better understanding of the mechanical unfolding mechanism of α-helix proteins is a key step towards comprehensive models describing the mechanoregulation of proteins.

  5. Uniform spatial distribution of collagen fibril radii within tendon implies local activation of pC-collagen at individual fibrils

    Science.gov (United States)

    Rutenberg, Andrew D.; Brown, Aidan I.; Kreplak, Laurent

    2016-08-01

    Collagen fibril cross-sectional radii show no systematic variation between the interior and the periphery of fibril bundles, indicating an effectively constant rate of collagen incorporation into fibrils throughout the bundle. Such spatially homogeneous incorporation constrains the extracellular diffusion of collagen precursors from sources at the bundle boundary to sinks at the growing fibrils. With a coarse-grained diffusion equation we determine stringent bounds, using parameters extracted from published experimental measurements of tendon development. From the lack of new fibril formation after birth, we further require that the concentration of diffusing precursors stays below the critical concentration for fibril nucleation. We find that the combination of the diffusive bound, which requires larger concentrations to ensure homogeneous fibril radii, and lack of nucleation, which requires lower concentrations, is only marginally consistent with fully processed collagen using conservative bounds. More realistic bounds may leave no consistent concentrations. Therefore, we propose that unprocessed pC-collagen diffuses from the bundle periphery followed by local C-proteinase activity and subsequent collagen incorporation at each fibril. We suggest that C-proteinase is localized within bundles, at fibril surfaces, during radial fibrillar growth. The much greater critical concentration of pC-collagen, as compared to fully processed collagen, then provides broad consistency between homogeneous fibril radii and the lack of fibril nucleation during fibril growth.

  6. Digoxin for atrial fibrillation and atrial flutter

    DEFF Research Database (Denmark)

    Sethi, Naqash J; Nielsen, Emil E; Safi, Sanam

    2018-01-01

    BACKGROUND: During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless...... of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo......, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm...

  7. Sucrose modulates insulin amyloid-like fibril formation: effect on the aggregation mechanism and fibril morphology

    DEFF Research Database (Denmark)

    Marasini, Carlotta; Foderà, Vito; Vestergaard, Bente

    2017-01-01

    the protein self-assembly pathways. Using a combination of fluorescence spectroscopy, synchrotron radiation circular dichroism and transmission electron microscopy, we study the kinetics of formation and structural properties of human insulin fibrils in the presence of sucrose. The presence of sucrose results...... in a delay of the onset of fibrillation. Moreover, it leads to a dramatic change in both the morphology and overall amount of fibrils. Our results emphasize that the detailed composition of protein surroundings likely influences not only the fibrillation kinetics but also the balance between different...

  8. Atrial fibrillation or flutter

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000184.htm Atrial fibrillation or flutter To use the sharing features on this page, please enable JavaScript. Atrial fibrillation or flutter is a common type of abnormal ...

  9. Extreme bendability of DNA double helix due to bending asymmetry

    NARCIS (Netherlands)

    Salari, H.; Eslami-Mossallam, B.; Nederi, S.; Ejtehadi, M.R.

    2015-01-01

    Experimental data of the DNA cyclization (J-factor) at short length scales exceed the theoretical expectation based on the wormlike chain (WLC) model by several orders of magnitude. Here, we propose that asymmetric bending rigidity of the double helix in the groove direction can be responsible for

  10. DNA-like double helix formed by peptide nucleic acid

    DEFF Research Database (Denmark)

    Wittung, P; Nielsen, Peter E.; Buchardt, O

    1994-01-01

    Although the importance of the nucleobases in the DNA double helix is well understood, the evolutionary significance of the deoxyribose phosphate backbone and the contribution of this chemical entity to the overall helical structure and stability of the double helix is not so clear. Peptide nucleic...

  11. Genetics Home Reference: familial atrial fibrillation

    Science.gov (United States)

    ... Twitter Home Health Conditions Familial atrial fibrillation Familial atrial fibrillation Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Familial atrial fibrillation is an inherited abnormality of the heart's normal ...

  12. Hydroxyproline Ring Pucker Causes Frustration of Helix Parameters in the Collagen Triple Helix

    Science.gov (United States)

    Ying Chow, W.; Bihan, Dominique; Forman, Chris J.; Slatter, David A.; Reid, David G.; Wales, David J.; Farndale, Richard W.; Duer, Melinda J.

    2015-07-01

    Collagens, the most abundant proteins in mammals, are defined by their triple-helical structures and distinctive Gly-Xaa-Yaa repeating sequence, where Xaa is often proline and Yaa, hydroxyproline (Hyp/O). It is known that hydroxyproline in the Yaa position stabilises the triple helix, and that lack of proline hydroxylation in vivo leads to dysfunctional collagen extracellular matrix assembly, due to a range of factors such as a change in hydration properties. In addition, we note that in model peptides, when Yaa is unmodified proline, the Xaa proline has a strong propensity to adopt an endo ring conformation, whilst when Yaa is hydroxyproline, the Xaa proline adopts a range of endo and exo conformations. Here we use a combination of solid-state NMR spectroscopy and potential energy landscape modelling of synthetic triple-helical collagen peptides to understand this effect. We show that hydroxylation of the Yaa proline causes the Xaa proline ring conformation to become metastable, which in turn confers flexibility on the triple helix.

  13. An NMR-based quenched hydrogen exchange investigation of model amyloid fibrils formed by cold shock protein A.

    Science.gov (United States)

    Alexandrescu, A T

    2001-01-01

    Acid-denatured cold shock protein A (CspA) self-assembles into polymers with properties typical of amyloid fibrils. In the present work, a quenched hydrogen exchange experiment was used to probe the interactions of CspA fibrils with solvent. Exchange was initiated by incubating suspensions of fibrils in D2O, and quenched by flash freezing. Following lyophilization, exchange-quenched samples were dissolved in 90% DMSO/10% D2O, giving DMSO-denatured monomers. Intrinsic exchange rates for denatured CspA in 90% DMSO/10% D2O (pH* 4.5) were sufficiently slow (approximately 1 x 10(-3) min-1) to enable quantification of NMR signal intensity decays due to H/D exchange in the fibrils. Hydrogen exchange rate constants for CspA fibrils were found to vary less than 3-fold from a mean value of 5 x 10(-5) min-1. The uniformity of rate constants suggests that exchange is in the EX1 limit, and that the mechanism of exchange involves a cooperative dissociation of CspA monomers from fibrils, concomitant with unfolding. Previous studies indicated that the highest protection factors in native CspA are approximately 10(3), and that protection factors for the acid-denatured monomer precursors of CspA fibrils are close to unity. Because exchange in is in the EX1 regime, it is only possible to place a lower limit of at least 10(5) on protection factors in CspA fibrils. The observation that all amide protons are protected from exchange indicates that the entire CspA polypeptide chain is structured in the fibrils.

  14. Tunable single photonic defect-mode in cholesteric liquid crystals with laser-induced local modifications of helix

    International Nuclear Information System (INIS)

    Yoshida, Hiroyuki; Lee, Chee Heng; Fujii, Akihiko; Ozaki, Masanori

    2006-01-01

    The authors demonstrate a tunable single photonic defect-mode in a single cholesteric liquid crystal material based on a structural defect introduced by local modification of the helix. An unpolymerized region of cholesteric liquid crystal acting as the defect was left between two polymerized regions via a two-photon excitation laser-lithography process. Upon polymerization, the cholesteric liquid crystal helix elongated and became thermally stable, and a single photonic defect mode was exhibited due to the contrast in the helix pitch at the defect. The defect mode showed tunability upon heating, and a 36 nm redshift was seen over a temperature range of 30 deg. C

  15. Atrial Fibrillation - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Atrial Fibrillation URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Atrial Fibrillation - Multiple Languages To use the sharing features on ...

  16. "Special Issue": Regional Dimensions of the Triple Helix Model

    Science.gov (United States)

    Todeva, Emanuela; Danson, Mike

    2016-01-01

    This paper introduces the rationale for the special issue and its contributions, which bridge the literature on regional development and the Triple Helix model. The concept of the Triple Helix at the sub-national, and specifically regional, level is established and examined, with special regard to regional economic development founded on…

  17. A smallest 6 kda metalloprotease, mini-matrilysin, in living world: a revolutionary conserved zinc-dependent proteolytic domain- helix-loop-helix catalytic zinc binding domain (ZBD

    Directory of Open Access Journals (Sweden)

    Yu Wei-Hsuan

    2012-05-01

    Full Text Available Abstract Background The Aim of this study is to study the minimum zinc dependent metalloprotease catalytic folding motif, helix B Met loop-helix C, with proteolytic catalytic activities in metzincin super family. The metzincin super family share a catalytic domain consisting of a twisted five-stranded β sheet and three long α helices (A, B and C. The catalytic zinc is at the bottom of the cleft and is ligated by three His residues in the consensus sequence motif, HEXXHXXGXXH, which is located in helix B and part of the adjacent Met turn region. An interesting question is - what is the minimum portion of the enzyme that still possesses catalytic and inhibitor recognition?” Methods We have expressed a 60-residue truncated form of matrilysin which retains only the helix B-Met turn-helix C region and deletes helix A and the five-stranded β sheet which form the upper portion of the active cleft. This is only 1/4 of the full catalytic domain. The E. coli derived 6 kDa MMP-7 ZBD fragments were purified and refolded. The proteolytic activities were analyzed by Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay and CM-transferrin zymography analysis. SC44463, BB94 and Phosphoramidon were computationally docked into the 3day structure of the human MMP7 ZBD and TAD and thermolysin using the docking program GOLD. Results This minimal 6 kDa matrilysin has been refolded and shown to have proteolytic activity in the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 peptide assay. Triton X-100 and heparin are important factors in the refolding environment for this mini-enzyme matrilysin. This minienzyme has the proteolytic activity towards peptide substrate, but the hexamer and octamer of the mini MMP-7 complex demonstrates the CM-transferrin proteolytic activities in zymographic analysis. Peptide digestion is inhibited by SC44463, specific MMP7 inhibitors, but not phosphorimadon. Interestingly, the mini MMP-7 can be processed by autolysis and producing ~ 6

  18. Loop-to-helix transition in the structure of multidrug regulator AcrR at the entrance of the drug-binding cavity

    Energy Technology Data Exchange (ETDEWEB)

    Manjasetty, Babu A.; Halavaty, Andrei S.; Luan, Chi-Hao; Osipiuk, Jerzy; Mulligan, Rory; Kwon, Keehwan; Anderson, Wayne F.; Joachimiak, Andrzej

    2016-04-01

    Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56 Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices a4 and a7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helix a4 is stabilized by the hydrogen bond between Glu67 (helix a4) and Gln130 (helix a7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix a4. This local conformational switch of helix a4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution smallmolecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol.

  19. Transmission electron microscopy of amyloid fibrils.

    Science.gov (United States)

    Gras, Sally L; Waddington, Lynne J; Goldie, Kenneth N

    2011-01-01

    Transmission Electron Microscopy of negatively stained and cryo-prepared specimens allows amyloid fibrils to be visualised at high resolution in a dried or a hydrated state, and is an essential method for characterising the morphology of fibrils and pre-fibrillar species. We outline the key steps involved in the preparation and observation of samples using negative staining and cryo-electron preservation. We also discuss methods to measure fibril characteristics, such as fibril width, from electron micrographs.

  20. Integrating new approaches to atrial fibrillation management

    DEFF Research Database (Denmark)

    Kotecha, Dipak; Breithardt, Günter; Camm, A John

    2018-01-01

    There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse...... of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new...

  1. Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators

    DEFF Research Database (Denmark)

    van Walraven, Carl; Hart, Robert G; Connolly, Stuart

    2009-01-01

    contains patient level-data from randomized trials of stroke prevention in atrial fibrillation. We used Cox regression models with age as a continuous variable that controlled for sex, year of randomization, and history of cerebrovascular disease, diabetes, hypertension, and congestive heart failure......BACKGROUND AND PURPOSE: Stroke risk increases with age in patients who have nonvalvular atrial fibrillation. It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age. The objective of this study was to determine the effect of age...... on the relative efficacy of oral anticoagulants (OAC) and antiplatelet (AP) therapy (including acetylsalicylic acid and triflusal) on ischemic stroke, serious bleeding, and vascular events in patients with atrial fibrillation. METHODS: This is an analysis of the Atrial Fibrillation Investigators database, which...

  2. Classification and evolutionary analysis of the basic helix-loop-helix gene family in the green anole lizard, Anolis carolinensis.

    Science.gov (United States)

    Liu, Ake; Wang, Yong; Zhang, Debao; Wang, Xuhua; Song, Huifang; Dang, Chunwang; Yao, Qin; Chen, Keping

    2013-08-01

    Helix-loop-helix (bHLH) proteins play essential regulatory roles in a variety of biological processes. These highly conserved proteins form a large transcription factor superfamily, and are commonly identified in large numbers within animal, plant, and fungal genomes. The bHLH domain has been well studied in many animal species, but has not yet been characterized in non-avian reptiles. In this study, we identified 102 putative bHLH genes in the genome of the green anole lizard, Anolis carolinensis. Based on phylogenetic analysis, these genes were classified into 43 families, with 43, 24, 16, 3, 10, and 3 members assigned into groups A, B, C, D, E, and F, respectively, and 3 members categorized as "orphans". Within-group evolutionary relationships inferred from the phylogenetic analysis were consistent with highly conserved patterns observed for introns and additional domains. Results from phylogenetic analysis of the H/E(spl) family suggest that genome and tandem gene duplications have contributed to this family's expansion. Our classification and evolutionary analysis has provided insights into the evolutionary diversification of animal bHLH genes, and should aid future studies on bHLH protein regulation of key growth and developmental processes.

  3. Picosecond dissociation of amyloid fibrils with infrared laser: A nonequilibrium simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Hoang Viet, Man; Roland, Christopher, E-mail: cmroland@ncsu.edu; Sagui, Celeste, E-mail: sagui@ncsu.edu [Department of Physics, North Carolina State University, Raleigh, North Carolina 27695-8202 (United States); Derreumaux, Philippe; Nguyen, Phuong H., E-mail: phuong.nguyen@ibpc.fr [Laboratoire de Biochimie Théorique, UPR 9080, CNRS Université Denis Diderot, Sorbonne Paris Cité IBPC, 13 rue Pierre et Marie Curie, 75005 Paris (France); Li, Mai Suan [Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw (Poland); Institute for Computational Science and Technology, SBI Building, Quang Trung Software City, Tan Chanh Hiep Ward, District 12, Ho Chi Minh City (Viet Nam)

    2015-10-21

    Recently, mid-infrared free-electron laser technology has been developed to dissociate amyloid fibrils. Here, we present a theoretical framework for this type of experiment based on laser-induced nonequilibrium all-atom molecular dynamics simulations. We show that the fibril is destroyed due to the strong resonance between its amide I vibrational modes and the laser field. The effects of laser irradiation are determined by a balance between fibril formation and dissociation. While the overall rearrangements of the fibril finish over short time scales, the interaction between the peptides and the solvent continues over much longer times indicating that the waters play an important role in the dissociation process. Our results thus provide new insights into amyloid fibril dissociation by laser techniques and open up new venues to investigate the complex phenomena associated with amyloidogenesis.

  4. The C-Terminal RpoN Domain of sigma54 Forms an unpredictedHelix-Turn-Helix Motif Similar to domains of sigma70

    Energy Technology Data Exchange (ETDEWEB)

    Doucleff, Michaeleen; Malak, Lawrence T.; Pelton, Jeffrey G.; Wemmer, David E.

    2005-11-01

    The ''{delta}'' subunit of prokaryotic RNA-polymerase allows gene-specific transcription initiation. Two {sigma} families have been identified, {sigma}{sup 70} and {sigma}{sup 54}, which use distinct mechanisms to initiate transcription and share no detectable sequence homology. Although the {sigma}{sup 70}-type factors have been well characterized structurally by x-ray crystallography, no high-resolution structural information is available for the {sigma}{sup 54}-type factors. Here we present the NMR derived structure of the C-terminal domain of {sigma}{sup 54} from Aquifex aeolicus. This domain (Thr323 to Gly389), which contains the highly conserved RpoN box sequence, consists of a poorly structured N-terminal tail followed by a three-helix bundle, which is surprisingly similar to domains of the {sigma}{sup 70}-type proteins. Residues of the RpoN box, which have previously been shown to be critical for DNA binding, form the second helix of an unpredicted helix-turn-helix motif. This structure's homology with other DNA binding proteins, combined with previous biochemical data, suggest how the C-terminal domain of {sigma}{sup 54} binds to DNA.

  5. Identification of basic/helix-loop-helix transcription factors reveals candidate genes involved in anthocyanin biosynthesis from the strawberry white-flesh mutant

    OpenAIRE

    Zhao, Fengli; Li, Gang; Hu, Panpan; Zhao, Xia; Li, Liangjie; Wei, Wei; Feng, Jiayue; Zhou, Houcheng

    2018-01-01

    As the second largest transcription factor family in plant, the basic helix-loop-helix (bHLH) transcription factor family, characterized by the conserved bHLH domain, plays a central regulatory role in many biological process. However, the bHLH transcription factor family of strawberry has not been systematically identified, especially for the anthocyanin biosynthesis. Here, we identified a total of 113 bHLH transcription factors and described their chromosomal distribution and bioinformatics...

  6. Chondroitin Sulfate Perlecan Enhances Collagen Fibril Formation

    DEFF Research Database (Denmark)

    Kvist, A. J.; Johnson, A. E.; Mörgelin, M.

    2006-01-01

    in collagen type II fibril assembly by perlecan-null chondrocytes. Cartilage perlecan is a heparin sulfate or a mixed heparan sulfate/chondroitin sulfate proteoglycan. The latter form binds collagen and accelerates fibril formation in vitro, with more defined fibril morphology and increased fibril diameters...... produced in the presence of perlecan. Interestingly, the enhancement of collagen fibril formation is independent on the core protein and is mimicked by chondroitin sulfate E but neither by chondroitin sulfate D nor dextran sulfate. Furthermore, perlecan chondroitin sulfate contains the 4,6-disulfated...... disaccharides typical for chondroitin sulfate E. Indeed, purified glycosaminoglycans from perlecan-enriched fractions of cartilage extracts contain elevated levels of 4,6-disulfated chondroitin sulfate disaccharides and enhance collagen fibril formation. The effect on collagen assembly is proportional...

  7. Atrial fibrillation and survival in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Justin Timothy A

    2004-11-01

    Full Text Available Abstract Background Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer. Patients and methods A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively. Results A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test. However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival. Conclusion The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.

  8. Interaction of magnetic nanoparticles with lysozyme amyloid fibrils

    Energy Technology Data Exchange (ETDEWEB)

    Gdovinová, Veronika [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia); Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Tomašovičová, Natália, E-mail: nhudak@saske.sk [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia); Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Batko, Ivan; Batková, Marianna; Balejčíková, Lucia [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia); Garamus, Vasyl M. [Helmholtz-Zentrum Geesthacht: Zentrum fr Material, und Kstenforschung GmbH, Max-Plank-Strae 1, Geesthacht 216502 (Germany); Petrenko, Viktor I. [Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Physics Department, Taras Shevchenko Kyiv National University, Volodymyrska Street 64, 01601 Kyiv (Ukraine); Avdeev, Mikhail V. [Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, 141980 Dubna, Moscow Region (Russian Federation); Kopčanský, Peter [Institute of Experimental Physics SAS, Watsonova 47, 040 01 Košice (Slovakia)

    2017-06-01

    This work is devoted to the structural study of complex solutions of magnetic nanoparticles with lysozyme amyloid fibrils due to possible ordering of such system by applying the external magnetic field. The interaction of magnetic nanoparticles with amyloid fibrils has been followed by atomic force microscopy and small-angle X-ray scattering. It has been observed that magnetic nanoparticles (MNPs) adsorb to lysozyme amyloid fibrils. It was found that MNPs alter amyloids structures, namely the diameter of lysozyme amyloid fibrils is increased whereas the length of fibrils is decreased. In the same time MNPs do not change the helical pitch significantly. - Highlights: • Solution of MNPs with lysozyme amyloid fibrils was characterized by AFM and SAXS. • MNPs adsorb to lysozyme amyloid fibrils. • Diameter and size of lysozyme amyloid fibrils change due to doping with MNPs.

  9. Atrial Fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Sherer, Jason A; Ko, Darae

    2017-01-01

    The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending...... on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established...

  10. The contrasting effect of macromolecular crowding on amyloid fibril formation.

    Directory of Open Access Journals (Sweden)

    Qian Ma

    Full Text Available Amyloid fibrils associated with neurodegenerative diseases can be considered biologically relevant failures of cellular quality control mechanisms. It is known that in vivo human Tau protein, human prion protein, and human copper, zinc superoxide dismutase (SOD1 have the tendency to form fibril deposits in a variety of tissues and they are associated with different neurodegenerative diseases, while rabbit prion protein and hen egg white lysozyme do not readily form fibrils and are unlikely to cause neurodegenerative diseases. In this study, we have investigated the contrasting effect of macromolecular crowding on fibril formation of different proteins.As revealed by assays based on thioflavin T binding and turbidity, human Tau fragments, when phosphorylated by glycogen synthase kinase-3β, do not form filaments in the absence of a crowding agent but do form fibrils in the presence of a crowding agent, and the presence of a strong crowding agent dramatically promotes amyloid fibril formation of human prion protein and its two pathogenic mutants E196K and D178N. Such an enhancing effect of macromolecular crowding on fibril formation is also observed for a pathological human SOD1 mutant A4V. On the other hand, rabbit prion protein and hen lysozyme do not form amyloid fibrils when a crowding agent at 300 g/l is used but do form fibrils in the absence of a crowding agent. Furthermore, aggregation of these two proteins is remarkably inhibited by Ficoll 70 and dextran 70 at 200 g/l.We suggest that proteins associated with neurodegenerative diseases are more likely to form amyloid fibrils under crowded conditions than in dilute solutions. By contrast, some of the proteins that are not neurodegenerative disease-associated are unlikely to misfold in crowded physiological environments. A possible explanation for the contrasting effect of macromolecular crowding on these two sets of proteins (amyloidogenic proteins and non-amyloidogenic proteins has been

  11. Loop-to-helix transition in the structure of multidrug regulator AcrR at the entrance of the drug-binding cavity.

    Science.gov (United States)

    Manjasetty, Babu A; Halavaty, Andrei S; Luan, Chi-Hao; Osipiuk, Jerzy; Mulligan, Rory; Kwon, Keehwan; Anderson, Wayne F; Joachimiak, Andrzej

    2016-04-01

    Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices α4 and α7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helix α4 is stabilized by the hydrogen bond between Glu67 (helix α4) and Gln130 (helix α7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix α4. This local conformational switch of helix α4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution small-molecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol. Copyright © 2016. Published by Elsevier Inc.

  12. MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.

    Directory of Open Access Journals (Sweden)

    Manuel Hora

    Full Text Available Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS, using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms.

  13. Nucleic acid helix structure determination from NMR proton chemical shifts

    Energy Technology Data Exchange (ETDEWEB)

    Werf, Ramon M. van der; Tessari, Marco; Wijmenga, Sybren S., E-mail: S.Wijmenga@science.ru.nl [Radboud University Nijmegen, Department of Biophysical Chemistry, Institute of Molecules and Materials (Netherlands)

    2013-06-15

    We present a method for de novo derivation of the three-dimensional helix structure of nucleic acids using non-exchangeable proton chemical shifts as sole source of experimental restraints. The method is called chemical shift de novo structure derivation protocol employing singular value decomposition (CHEOPS) and uses iterative singular value decomposition to optimize the structure in helix parameter space. The correct performance of CHEOPS and its range of application are established via an extensive set of structure derivations using either simulated or experimental chemical shifts as input. The simulated input data are used to assess in a defined manner the effect of errors or limitations in the input data on the derived structures. We find that the RNA helix parameters can be determined with high accuracy. We finally demonstrate via three deposited RNA structures that experimental proton chemical shifts suffice to derive RNA helix structures with high precision and accuracy. CHEOPS provides, subject to further development, new directions for high-resolution NMR structure determination of nucleic acids.

  14. Cable-type flexible lithium ion battery based on hollow multi-helix electrodes

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Yo Han; Woo, Sang-Wook; Jung, Hye-Ran; Yu, Hyung Kyun; Kim, Kitae; Oh, Byung Hun; Ahn, Soonho; Kim, Je Young [Battery R and D, LG Chem, Ltd., 104-1 Moonji-dong, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Sang-Young [School of Chemical Engineering, Kangwon National University, Chuncheon, Kangwondo (Korea, Republic of); Song, Seung-Wan [Graduate School of Green Energy Technology, Department of Fine Chemical Engineering and Applied Chemistry, Chungnam National University, Daejeon (Korea, Republic of); Cho, Jaephil [School of Energy Engineering and Converging Research Center for Innovative Battery Technologies, Ulsan National Institute of Science and Technology (UNIST), Ulsan (Korea, Republic of); Shin, Heon-Cheol [School of Materials Science and Engineering, Pusan National University, Busan (Korea, Republic of)

    2012-10-02

    The mechanical flexibility of a cable-type battery reaches levels far beyond what is possible with conventional designs. The hollow-spiral (helical) multi-helix anode architecture is critical to the robustness under mechanical stress and facilitates electrolyte wetting of the battery components. This design enables the battery to reliably power an LED screen or an MP3 player even under severe mechanical twisting and bending. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  15. Nanomechanical mapping of hydrated rat tail tendon collagen I fibrils.

    Science.gov (United States)

    Baldwin, Samuel J; Quigley, Andrew S; Clegg, Charlotte; Kreplak, Laurent

    2014-10-21

    Collagen fibrils play an important role in the human body, providing tensile strength to connective tissues. These fibrils are characterized by a banding pattern with a D-period of 67 nm. The proposed origin of the D-period is the internal staggering of tropocollagen molecules within the fibril, leading to gap and overlap regions and a corresponding periodic density fluctuation. Using an atomic force microscope high-resolution modulus maps of collagen fibril segments, up to 80 μm in length, were acquired at indentation speeds around 10(5) nm/s. The maps revealed a periodic modulation corresponding to the D-period as well as previously undocumented micrometer scale fluctuations. Further analysis revealed a 4/5, gap/overlap, ratio in the measured modulus providing further support for the quarter-staggered model of collagen fibril axial structure. The modulus values obtained at indentation speeds around 10(5) nm/s are significantly larger than those previously reported. Probing the effect of indentation speed over four decades reveals two distinct logarithmic regimes of the measured modulus and point to the existence of a characteristic molecular relaxation time around 0.1 ms. Furthermore, collagen fibrils exposed to temperatures between 50 and 62°C and cooled back to room temperature show a sharp decrease in modulus and a sharp increase in fibril diameter. This is also associated with a disappearance of the D-period and the appearance of twisted subfibrils with a pitch in the micrometer range. Based on all these data and a similar behavior observed for cross-linked polymer networks below the glass transition temperature, we propose that collagen I fibrils may be in a glassy state while hydrated.

  16. Atrial fibrillation and the 4P medicine.

    Science.gov (United States)

    Censi, Federica; Cianfrocca, Cinzia; Purificato, Ivana

    2013-01-01

    Although the paradigm of the 4P medicine - Predictive, Personalized, Preemptive, and Participatory - has been suggested several years ago, its application to atrial fibrillation is still far away. Given the increasing prevalence and incidence of this pathology it is the time to promote preventive strategies, by identifying the risk factors associated to life style and by incentivizing innovative diagnostic technologies. The promotion of the correct life style and of the use of diagnostic devices based on innovative and reliable technologies, represent a first step towards the full realization of the revolution of 4P medicine in atrial fibrillation.

  17. Atrial fibrillation and the 4P medicine

    Directory of Open Access Journals (Sweden)

    Federica Censi

    2013-09-01

    Full Text Available Although the paradigm of the 4P medicine - Predictive, Personalized, Preemptive, and Participatory - has been suggested several years ago, its application to atrial fibrillation is still far away. Given the increasing prevalence and incidence of this pathology it is the time to promote preventive strategies, by identifying the risk factors associated to life style and by incentivizing innovative diagnostic technologies. The promotion of the correct life style and of the use of diagnostic devices based on innovative and reliable technologies, represent a first step towards the full realization of the revolution of 4P medicine in atrial fibrillation.

  18. Facilitating Quintuple helix innovation with urban living labs

    OpenAIRE

    Baccarne, Bastiaan; Schuurman, Dimitri; De Marez, Lieven

    2015-01-01

    This paper discusses the Urban Living Lab approach as a way to put the Quintuple Helix model for innovation into practice. In this analysis we focus on the concepts innovation democracy, ‘mode 3’ knowledge production, the innovation ecosystem as a system of societal subsystems and socioecological transition. The empirical analysis is performed by means of a multidimensional case study design, applied on a project-based ad hoc collaborative innovation development process in an ecological doma...

  19. Genome-wide identification of basic helix-loop-helix and NF-1 motifs underlying GR binding sites in male rat hippocampus

    DEFF Research Database (Denmark)

    Pooley, John R.; Flynn, Ben P.; Grøntved, Lars

    2017-01-01

    linked to structural and organizational roles, an absence of major tethering partners for GRs, and little or no evidence for binding at negative glucocorticoid response elements. A basic helix-loop-helix motif closely resembling a NeuroD1 or Olig2 binding site was found underlying a subset of GR binding......Glucocorticoids regulate hippocampal function in part by modulating gene expression through the glucocorticoid receptor (GR). GR binding is highly cell type specific, directed to accessible chromatin regions established during tissue differentiation. Distinct classes of GR binding sites...

  20. Risk of atrial fibrillation in diabetes mellitus

    DEFF Research Database (Denmark)

    Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B

    2016-01-01

    AIM: Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients...... with diabetes compared to the background population in Denmark. METHODS AND RESULTS: Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes...... and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background...

  1. Helix-helix inversion of an optically-inactive π-conjugated foldamer triggered by concentration changes of a single enantiomeric guest leading to a change in the helical stability.

    Science.gov (United States)

    Liu, Lijia; Ousaka, Naoki; Horie, Miki; Mamiya, Fumihiko; Yashima, Eiji

    2016-09-27

    A preferred-handed helicity induced in an optically-inactive poly(phenyleneethynylene)-based foldamer bearing carboxylic acid pendants upon complexation with a single enantiomeric diamine was subsequently inverted into the opposite helix upon further addition of the diamine, accompanied by a remarkable change in the stability of the helices.

  2. Broadband and high-efficiency vortex beam generator based on a hybrid helix array.

    Science.gov (United States)

    Fang, Chaoqun; Wu, Chao; Gong, Zhijie; Zhao, Song; Sun, Anqi; Wei, Zeyong; Li, Hongqiang

    2018-04-01

    The vortex beam which carries the orbital angular momentum has versatile applications, such as high-resolution imaging, optical communications, and particle manipulation. Generating vortex beams with the Pancharatnam-Berry (PB) phase has drawn considerable attention for its unique spin-to-orbital conversion features. Despite the PB phase being frequency independent, an optical element with broadband high-efficiency circular polarization conversion feature is still needed for the broadband high-efficiency vortex beam generation. In this work, a broadband and high-efficiency vortex beam generator based on the PB phase is built with a hybrid helix array. Such devices can generate vortex beams with arbitrary topological charge. Moreover, vortex beams with opposite topological charge can be generated with an opposite handedness incident beam that propagates backward. The measured efficiency of our device is above 65% for a wide frequency range, with the relative bandwidth of 46.5%.

  3. Regional Dimensions of the Triple Helix Model: Setting the Context

    Science.gov (United States)

    Todeva, Emanuela; Danson, Mike

    2016-01-01

    This paper introduces the rationale for the special issue and its contributions, which bridge the literature on regional development and the Triple Helix model. The concept of the Triple Helix at the sub-national, and specifically regional, level is established and examined, with special regard to regional economic development founded on…

  4. FMRFamide receptors of Helix aspersa

    International Nuclear Information System (INIS)

    Payza, K.

    1988-01-01

    A receptor binding assay and an isolated heart bioassay were used to identify and characterize the FMRFamide receptors in Helix. In the heart bioassay, FMRFamide increased myocardial contraction force. A potent FMRFamide analog, desaminoTyr-Phe-norLeu-arg-Phe-amide (daYFnLRFamide), was used as a radioiodinated receptor ligand. The high affinity binding of 125 I-daYFnLRFamide at 0 degree C to Helix brain membranes was reversible, saturable, pH-dependent and specific, with a K D of 13-14 nM. A lower affinity (245 nM) site was also observed. Radioligand binding sites were also identified in the heart, male reproductive organs and digestive organs. The structure-activity relations (SAR) of cardiostimulation correlated with the specificity of 125 I-daYFnLRFamide binding to brain and heart receptors. The SAR were similar to those of other molluscan FMRFamide bioassays, except that they showed a marked preference for some analogs with blocked amino-terminals

  5. Relevance of Electrical Remodeling in Human Atrial Fibrillation Results of the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial Mechanisms of Atrial Fibrillation Study

    NARCIS (Netherlands)

    Healey, Jeff S.; Israel, Carsten W.; Connolly, Stuart J.; Hohnloser, Stefan H.; Nair, Girish M.; Divakaramenon, Syamkumar; Capucci, Alessandro; Van Gelder, Isabelle C.; Lau, Chu-Pak; Gold, Michael R.; Carlson, Mark; Themeles, Ellison; Morillo, Carlos A.

    Background-In animal models of atrial fibrillation (AF), changes in atrial electrophysiological properties are associated with the development of AF. Their relevance to human AF is unclear. Methods and Results-The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the

  6. Elevated temperature triggers human respiratory syncytial virus F protein six-helix bundle formation

    International Nuclear Information System (INIS)

    Yunus, Abdul S.; Jackson, Trent P.; Crisafi, Katherine; Burimski, Irina; Kilgore, Nicole R.; Zoumplis, Dorian; Allaway, Graham P.; Wild, Carl T.; Salzwedel, Karl

    2010-01-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by the fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of 'membrane-anchored' RSV F protein to elevated temperature (45-55 deg. C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the mechanism of

  7. Pharmacological Treatment for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Kaoru Sugi, MD PhD

    2005-01-01

    Full Text Available Pharmacological treatment for atrial fibrillation has a variety of purposes, such as pharmacological defibrillation, maintenance of sinus rhythm, heart rate control to prevent congestive heart failure and prevention of both cerebral infarction and atrial remodeling. Sodium channel blockers are superior to potassium channel blockers for atrial defibrillation, while both sodium and potassium channel blockers are effective in the maintenance of sinus rhythm. In general, digitalis or Ca antagonists are used to control heart rate during atrial fibrillation to prevent congestive heart failure, while amiodarone or bepridil also reduce heart rates during atrial fibrillation. Anticoagulant therapy with warfarin is recommended to prevent cerebral infarction and angiotensin converting enzyme antagonists or angiotensin II receptor blockers are also used to prevent atrial remodeling. One should select appropriate drugs for treatment of atrial fibrillation according to the patient's condition.

  8. Fracture mechanics of collagen fibrils

    DEFF Research Database (Denmark)

    Svensson, Rene B; Mulder, Hindrik; Kovanen, Vuokko

    2013-01-01

    Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within...... fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an important factor that has been shown to influence mechanical behavior of the tendons. To improve our understanding of how molecular bonds translate into tendon mechanics, we used an atomic force microscopy...... technique to measure the mechanical behavior of individual collagen fibrils loaded to failure. Fibrils from human patellar tendons, rat-tail tendons (RTTs), NaBH₄ reduced RTTs, and tail tendons of Zucker diabetic fat rats were tested. We found a characteristic three-phase stress-strain behavior in the human...

  9. Atrial fibrillation in the elderly

    Science.gov (United States)

    Franken, Roberto A.; Rosa, Ronaldo F.; Santos, Silvio CM

    2012-01-01

    This review discusses atrial fibrillation according to the guidelines of Brazilian Society of Cardiac Arrhythmias and the Brazilian Cardiogeriatrics Guidelines. We stress the thromboembolic burden of atrial fibrillation and discuss how to prevent it as well as the best way to conduct cases of atrial fibrillatios in the elderly, reverting the arrhythmia to sinus rhythm, or the option of heart rate control. The new methods to treat atrial fibrillation, such as radiofrequency ablation, new oral direct thrombin inhibitors and Xa factor inhibitors, as well as new antiarrhythmic drugs, are depicted. PMID:22916053

  10. On the helix equation

    Directory of Open Access Journals (Sweden)

    Taouil Hajer

    2012-08-01

    Full Text Available This paper is devoted to the helices processes, i.e. the solutions H : ℝ × Ω → ℝd, (t, ω ↦ H(t, ω of the helix equation egin{eqnarray} H(0,o=0; quad H(s+t,o= H(s,Phi(t,o +H(t,oonumber end{eqnarray} H ( 0 ,ω = 0 ;   H ( s + t,ω = H ( s, Φ ( t,ω + H ( t,ω where Φ : ℝ × Ω → Ω, (t, ω ↦ Φ(t, ω is a dynamical system on a measurable space (Ω, ℱ. More precisely, we investigate dominated solutions and non differentiable solutions of the helix equation. For the last case, the Wiener helix plays a fundamental role. Moreover, some relations with the cocycle equation defined by Φ, are investigated. Ce papier est consacré aux hélices, c’est-à-dire les solutions H : ℝ × Ω → ℝd, (t, ω ↦ H(t, ω de l’équation fonctionnelle egin{eqnarray} H(0,o=0; quad H(s+t,o= H(s,Phi(t,o +H(t,o onumber end{eqnarray} H ( 0 ,ω = 0 ;   H ( s + t,ω = H ( s, Φ ( t,ω + H ( t,ω où Φ : ℝ × Ω → Ω, (t, ω ↦ Φ(t, ω est un système dynamique défini sur un espace mesurable (Ω, ℱ. Plus présisément, nous déterminons d’abord les hélices dominées puis nous caractérisons les hélices non différentiables. Dans ce dernier cas, l’hélice de Wiener joue un rôle important. Nous précisons aussi quelques relations des hélices avec les cocycles définis par Φ.

  11. Genome-wide identification and analysis of the chicken basic helix-loop-helix factors.

    Science.gov (United States)

    Liu, Wu-Yi; Zhao, Chun-Jiang

    2010-01-01

    Members of the basic helix-loop-helix (bHLH) family of transcription factors play important roles in a wide range of developmental processes. In this study, we conducted a genome-wide survey using the chicken (Gallus gallus) genomic database, and identified 104 bHLH sequences belonging to 42 gene families in an effort to characterize the chicken bHLH transcription factor family. Phylogenetic analyses revealed that chicken has 50, 21, 15, 4, 8, and 3 bHLH members in groups A, B, C, D, E, and F, respectively, while three members belonging to none of these groups were classified as ''orphans". A comparison between chicken and human bHLH repertoires suggested that both organisms have a number of lineage-specific bHLH members in the proteomes. Chromosome distribution patterns and phylogenetic analyses strongly suggest that the bHLH members should have arisen through gene duplication at an early date. Gene Ontology (GO) enrichment statistics showed 51 top GO annotations of biological processes counted in the frequency. The present study deepens our understanding of the chicken bHLH transcription factor family and provides much useful information for further studies using chicken as a model system.

  12. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers

    Directory of Open Access Journals (Sweden)

    Rasool Suhail

    2007-09-01

    Full Text Available Abstract Background Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD, amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular Aβ and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results We immunized rabbits with a morphologically homogeneous population of Aβ42 fibrils. The resulting immune serum (OC specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 × G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type

  13. On the role of fibril mechanics in the work of separation of fibrillating interfaces

    NARCIS (Netherlands)

    Vossen, B.G.; Sluis, van der O.; Schreurs, P.J.G.; Geers, M.G.D.; Neggers, J.; Hoefnagels, J.P.M.

    2015-01-01

    High values for the work of separation have been reported in peel tests on fibrillating interfacial systems. The exact origin of these high values is not properly understood, since it remains unclear which dissipative mechanisms related to fibrillation cause a significant increase in the work of

  14. A genome-wide survey on basic helix-loop-helix transcription factors in giant panda.

    Directory of Open Access Journals (Sweden)

    Chunwang Dang

    Full Text Available The giant panda (Ailuropoda melanoleuca is a critically endangered mammalian species. Studies on functions of regulatory proteins involved in developmental processes would facilitate understanding of specific behavior in giant panda. The basic helix-loop-helix (bHLH proteins play essential roles in a wide range of developmental processes in higher organisms. bHLH family members have been identified in over 20 organisms, including fruit fly, zebrafish, mouse and human. Our present study identified 107 bHLH family members being encoded in giant panda genome. Phylogenetic analyses revealed that they belong to 44 bHLH families with 46, 25, 15, 4, 11 and 3 members in group A, B, C, D, E and F, respectively, while the remaining 3 members were assigned into "orphan". Compared to mouse, the giant panda does not encode seven bHLH proteins namely Beta3a, Mesp2, Sclerax, S-Myc, Hes5 (or Hes6, EBF4 and Orphan 1. These results provide useful background information for future studies on structure and function of bHLH proteins in the regulation of giant panda development.

  15. Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics

    DEFF Research Database (Denmark)

    Qvist, Ina; Hendriks, Jeroen M L; Møller, Dorthe S

    2016-01-01

    OBJECTIVE: A previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse...

  16. Organizing product innovation: hierarchy, market or triple-helix networks?

    Science.gov (United States)

    Fitjar, Rune Dahl; Gjelsvik, Martin; Rodríguez-Pose, Andrés

    This paper assesses the extent to which the organization of the innovation effort in firms, as well as the geographical scale at which this effort is pursued, affects the capacity to benefit from product innovations. Three alternative modes of organization are studied: hierarchy, market and triple-helix-type networks. Furthermore, we consider triple-helix networks at three geographical scales: local, national and international. These relationships are tested on a random sample of 763 firms located in five urban regions of Norway which reported having introduced new products or services during the preceding 3 years. The analysis shows that firms exploiting internal hierarchy or triple-helix networks with a wide range of partners managed to derive a significantly higher share of their income from new products, compared to those that mainly relied on outsourcing within the market. In addition, the analysis shows that the geographical scale of cooperation in networks, as well as the type of partner used, matters for the capacity of firms to benefit from product innovation. In particular, firms that collaborate in international triple-helix-type networks involving suppliers, customers and R&D institutions extract a higher share of their income from product innovations, regardless of whether they organize the processes internally or through the network.

  17. Spectral of electrocardiographic RR intervals to indicate atrial fibrillation

    Science.gov (United States)

    Nuryani, Nuryani; Satrio Nugroho, Anto

    2017-11-01

    Atrial fibrillation is a serious heart diseases, which is associated on the risk of death, and thus an early detection of atrial fibrillation is necessary. We have investigated spectral pattern of electrocardiogram in relation to atrial fibrillation. The utilized feature of electrocardiogram is RR interval. RR interval is the time interval between a two-consecutive R peaks. A series of RR intervals in a time segment is converted to a signal with a frequency domain. The frequency components are investigated to find the components which significantly associate to atrial fibrillation. A segment is defined as atrial fibrillation or normal segments by considering a defined number of atrial fibrillation RR in the segment. Using clinical data of 23 patients with atrial fibrillation, we find that the frequency components could be used to indicate atrial fibrillation.

  18. Atrial natriuretic peptide in patients with heart failure and chronic atrial fibrillation : Role of duration of at atrial fibrillation

    NARCIS (Netherlands)

    Van Den Berg, MP; Crijns, HJGM; Van Veldhuisen, DJ; Van Gelder, IC; De Kam, PJ; Lie, KI

    The purpose of this study was to analyze the determinants of atrial natriuretic peptide level in patients with congestive heart failure and atrial fibrillation. In particular, the duration of atrial fibrillation was analyzed because atrial fibrillation per se might have a specific effect on atrial

  19. Influence of dendrimer's structure on its activity against amyloid fibril formation

    International Nuclear Information System (INIS)

    Klajnert, B.; Cortijo-Arellano, M.; Cladera, J.; Bryszewska, M.

    2006-01-01

    Inhibition of fibril assembly is a potential therapeutic strategy in neurodegenerative disorders such as prion and Alzheimer's diseases. Highly branched, globular polymers-dendrimers-are novel promising inhibitors of fibril formation. In this study, the effect of polyamidoamine (PAMAM) dendrimers (generations 3rd, 4th, and 5th) on amyloid aggregation of the prion peptide PrP 185-208 and the Alzheimer's peptide Aβ 1-28 was examined. Amyloid fibrils were produced in vitro and their formation was monitored using the dye thioflavin T (ThT). Fluorescence studies were complemented with electron microscopy. The results show that the higher the dendrimer generation, the larger the degree of inhibition of the amyloid aggregation process and the more effective are dendrimers in disrupting the already existing fibrils. A hypothesis on dendrimer-peptide interaction mechanism is presented based on the dendrimers' molecular structure

  20. Helical undulator based on partial redistribution of uniform magnetic field

    Science.gov (United States)

    Balal, N.; Bandurkin, I. V.; Bratman, V. L.; Fedotov, A. E.

    2017-12-01

    A new type of helical undulator based on redistribution of magnetic field of a solenoid by ferromagnetic helix has been proposed and studied both in theory and experiment. Such undulators are very simple and efficient for promising sources of coherent spontaneous THz undulator radiation from dense electron bunches formed in laser-driven photo-injectors.

  1. Atrial fibrillation and vascular disease-a bad combination

    DEFF Research Database (Denmark)

    Bjerring Olesen, Jonas; Gislason, Gunnar Hilmar; Torp-Pedersen, Christian

    2012-01-01

    This article provides an overview of (i) the risk of stroke associated with vascular disease (acute coronary syndromes and peripheral artery disease) in patients with atrial fibrillation, (ii) the frequent coexistence of vascular disease in patients with atrial fibrillation and, (iii...... fibrillation. Indeed, patients with atrial fibrillation often had coexisting vascular disease (around 18%), and the combination of the two diseases substantially increases the risk of future cardiovascular events. The increased risk associated with peripheral artery disease in atrial fibrillation is even more...... pronounced. Patients with atrial fibrillation and stable vascular disease should be treated with oral anticoagulation only, although when these patients present with acute coronary syndrome and/or undergo coronary stenting, concomitant treatment with antiplatelet drugs is indicated. To guide antithrombotic...

  2. Human telomeric DNA: G-quadruplex, i-motif and Watson–Crick double helix

    Science.gov (United States)

    Phan, Anh Tuân; Mergny, Jean-Louis

    2002-01-01

    Human telomeric DNA composed of (TTAGGG/CCCTAA)n repeats may form a classical Watson–Crick double helix. Each individual strand is also prone to quadruplex formation: the G-rich strand may adopt a G-quadruplex conformation involving G-quartets whereas the C-rich strand may fold into an i-motif based on intercalated C·C+ base pairs. Using an equimolar mixture of the telomeric oligonucleotides d[AGGG(TTAGGG)3] and d[(CCCTAA)3CCCT], we defined which structures existed and which would be the predominant species under a variety of experimental conditions. Under near-physiological conditions of pH, temperature and salt concentration, telomeric DNA was predominantly in a double-helix form. However, at lower pH values or higher temperatures, the G-quadruplex and/or the i-motif efficiently competed with the duplex. We also present kinetic and thermodynamic data for duplex association and for G-quadruplex/i-motif unfolding. PMID:12409451

  3. Genetic basis of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Oscar Campuzano

    2016-12-01

    Full Text Available Atrial fibrillation is the most common sustained arrhythmia and remains as one of main challenges in current clinical practice. The disease may be induced secondary to other diseases such as hypertension, valvular heart disease, and heart failure, conferring an increased risk of stroke and sudden death. Epidemiological studies have provided evidence that genetic factors play an important role and up to 30% of clinically diagnosed patients may have a family history of atrial fibrillation. To date, several rare variants have been identified in a wide range of genes associated with ionic channels, calcium handling protein, fibrosis, conduction and inflammation. Important advances in clinical, genetic and molecular basis have been performed over the last decade, improving diagnosis and treatment. However, the genetics of atrial fibrillation is complex and pathophysiological data remains still unraveling. A better understanding of the genetic basis will induce accurate risk stratification and personalized clinical treatment. In this review, we have focused on current genetics basis of atrial fibrillation.

  4. Thyrotoxic atrial fibrillation.

    Science.gov (United States)

    Parmar, Malvinder S

    2005-01-04

    Atrial fibrillation is the most common cardiac complication of hyperthyroidism and occurs in 15% of patients with hyperthyroidism. It is associated with a higher risk of thromboembolism that often involves the central nervous system. Oral anticoagulation is important in the majority of these patients to prevent thromboembolic complications. These patients require adjustment in the dose of various rate-controlling agents because of increased clearance associated with hyperthyroidism and a decrease in warfarin dosage because of increased clearance of vitamin K-dependent clotting factors. The management of thyrotoxic atrial fibrillation is summarized in this clinical review.

  5. Defining the structural requirements for a helix in 23 S ribosomal RNA that confers erythromycin resistance

    DEFF Research Database (Denmark)

    Douthwaite, S; Powers, T; Lee, J Y

    1989-01-01

    The helix spanning nucleotides 1198 to 1247 (helix 1200-1250) in Escherichia coli 23 S ribosomal RNA (rRNA) is functionally important in protein synthesis, and deletions in this region confer erythromycin resistance. In order to define the structural requirements for resistance, we have dissected...... deletion mutants show a sensitive phenotype. Deletions that extend into the base-pairing between GCC1208 and GGU1240 result in non-functional 23 S RNAs, which consequently do not confer resistance. A number of phylogenetically conserved nucleotides have been shown to be non-essential for 23 S RNA function....... However, removal of either these or non-conserved nucleotides from helix 1200-1250 measurably reduces the efficiency of 23 S RNA in forming functional ribosomes. We have used chemical probing and a modified primer extension method to investigate erythromycin binding to wild-type and resistant ribosomes...

  6. Viologen-Phosphorus Dendrimers Inhibit α-Synuclein Fibrillation.

    Science.gov (United States)

    Milowska, Katarzyna; Grochowina, Justyna; Katir, Nadia; El Kadib, Abdelkrim; Majoral, Jean-Pierre; Bryszewska, Maria; Gabryelak, Teresa

    2013-03-04

    Inhibition of α-synuclein (ASN) fibril formation is a potential therapeutic strategy in Parkinson's disease and other synucleinopathies. The aim of this study was to examine the role of viologen-phosphorus dendrimers in the α-synuclein fibrillation process and to assess the structural changes in α-synuclein under the influence of dendrimers. ASN interactions with phosphonate and pegylated surface-reactive viologen-phosphorus dendrimers were examined by measuring the zeta potential, which allowed determining the number of dendrimer molecules that bind to the ASN molecule. The fibrillation kinetics and the structural changes were examined using ThT fluorescence and CD spectroscopy. Depending on the concentration of the used dendrimer and the nature of the reactive groups located on the surface, ASN fibrillation kinetics can be significantly reduced, and even, in the specific case of phosphonate dendrimers, the fibrillation can be totally inhibited at low concentrations. The presented results indicate that viologen-phosphorus dendrimers are able to inhibit ASN fibril formation and may be used as fibrillar regulating agents in neurodegenerative disorders.

  7. Helical undulator based on partial redistribution of uniform magnetic field

    Directory of Open Access Journals (Sweden)

    N. Balal

    2017-12-01

    Full Text Available A new type of helical undulator based on redistribution of magnetic field of a solenoid by ferromagnetic helix has been proposed and studied both in theory and experiment. Such undulators are very simple and efficient for promising sources of coherent spontaneous THz undulator radiation from dense electron bunches formed in laser-driven photo-injectors.

  8. Double helix vortex breakdown in a turbulent swirling annular jet flow

    NARCIS (Netherlands)

    Vanierschot, M.; Perçin, M.; van Oudheusden, B.W.

    2018-01-01

    In this paper, we report on the structure and dynamics of double helix vortex breakdown in a turbulent annular swirling jet. Double helix breakdown has been reported previously for the laminar flow regime, but this structure has rarely been observed in turbulent flow. The flow field is

  9. Unraveling the Role of the C-terminal Helix Turn Helix of the Coat-binding Domain of Bacteriophage P22 Scaffolding Protein*

    Science.gov (United States)

    Padilla-Meier, G. Pauline; Gilcrease, Eddie B.; Weigele, Peter R.; Cortines, Juliana R.; Siegel, Molly; Leavitt, Justin C.; Teschke, Carolyn M.; Casjens, Sherwood R.

    2012-01-01

    Many viruses encode scaffolding and coat proteins that co-assemble to form procapsids, which are transient precursor structures leading to progeny virions. In bacteriophage P22, the association of scaffolding and coat proteins is mediated mainly by ionic interactions. The coat protein-binding domain of scaffolding protein is a helix turn helix structure near the C terminus with a high number of charged surface residues. Residues Arg-293 and Lys-296 are particularly important for coat protein binding. The two helices contact each other through hydrophobic side chains. In this study, substitution of the residues of the interface between the helices, and the residues in the β-turn, by aspartic acid was used examine the importance of the conformation of the domain in coat binding. These replacements strongly affected the ability of the scaffolding protein to interact with coat protein. The severity of the defect in the association of scaffolding protein to coat protein was dependent on location, with substitutions at residues in the turn and helix 2 causing the most significant effects. Substituting aspartic acid for hydrophobic interface residues dramatically perturbs the stability of the structure, but similar substitutions in the turn had much less effect on the integrity of this domain, as determined by circular dichroism. We propose that the binding of scaffolding protein to coat protein is dependent on angle of the β-turn and the orientation of the charged surface on helix 2. Surprisingly, formation of the highly complex procapsid structure depends on a relatively simple interaction. PMID:22879595

  10. Genome-Wide Identification and Analysis of the Chicken Basic Helix-Loop-Helix Factors

    Directory of Open Access Journals (Sweden)

    Wu-yi Liu

    2010-01-01

    Full Text Available Members of the basic helix-loop-helix (bHLH family of transcription factors play important roles in a wide range of developmental processes. In this study, we conducted a genome-wide survey using the chicken (Gallus gallus genomic database, and identified 104 bHLH sequences belonging to 42 gene families in an effort to characterize the chicken bHLH transcription factor family. Phylogenetic analyses revealed that chicken has 50, 21, 15, 4, 8, and 3 bHLH members in groups A, B, C, D, E, and F, respectively, while three members belonging to none of these groups were classified as ‘‘orphans’’. A comparison between chicken and human bHLH repertoires suggested that both organisms have a number of lineage-specific bHLH members in the proteomes. Chromosome distribution patterns and phylogenetic analyses strongly suggest that the bHLH members should have arisen through gene duplication at an early date. Gene Ontology (GO enrichment statistics showed 51 top GO annotations of biological processes counted in the frequency. The present study deepens our understanding of the chicken bHLH transcription factor family and provides much useful information for further studies using chicken as a model system.

  11. The role of protonation in protein fibrillation

    DEFF Research Database (Denmark)

    Jeppesen, Martin D; Westh, Peter; Otzen, Daniel E

    2010-01-01

    Many proteins fibrillate at low pH despite a high population of charged side chains. Therefore exchange of protons between the fibrillating peptide and its surroundings may play an important role in fibrillation. Here, we use isothermal titration calorimetry to measure exchange of protons between...... buffer and the peptide hormone glucagon during fibrillation. Glucagon absorbs or releases protons to an extent which allows it to attain a net charge of zero in the fibrillar state, both at acidic and basic pH. Similar results are obtained for lysozyme. This suggests that side chain pKa values change...

  12. RR-Interval variance of electrocardiogram for atrial fibrillation detection

    Science.gov (United States)

    Nuryani, N.; Solikhah, M.; Nugoho, A. S.; Afdala, A.; Anzihory, E.

    2016-11-01

    Atrial fibrillation is a serious heart problem originated from the upper chamber of the heart. The common indication of atrial fibrillation is irregularity of R peak-to-R-peak time interval, which is shortly called RR interval. The irregularity could be represented using variance or spread of RR interval. This article presents a system to detect atrial fibrillation using variances. Using clinical data of patients with atrial fibrillation attack, it is shown that the variance of electrocardiographic RR interval are higher during atrial fibrillation, compared to the normal one. Utilizing a simple detection technique and variances of RR intervals, we find a good performance of atrial fibrillation detection.

  13. The economics of atrial fibrillation: a time for review and prioritization.

    Science.gov (United States)

    Cadilhac, Dominique A

    2012-08-01

    Stroke associated with atrial fibrillation may occur in up to one third of people who experience an ischemic event, and results in greater stroke severity and poorer health outcomes. The ageing population in developed and developing countries will lead to an increase in the prevalence of atrial fibrillation in society. Detecting people who have atrial fibrillation and ensuring optimal prevention management is essential for reducing the burden of stroke worldwide. There is evidence that use of anticoagulants is inadequate in primary and secondary prevention of stroke. New anticoagulants that have fewer side effects and population screening tools are available. However, there is little information available about the cost-effectiveness of these new options for atrial fibrillation detection and stroke prevention management over current practice. Since resources for spending in health are limited, it is essential that formal economic analyses are undertaken to ensure there are informed and evidence-based decisions on where to best invest stroke prevention resources. It is essential that renewed efforts in the area of atrial fibrillation and options for stroke prevention are undertaken within the public health research community. © 2012 The Author. International Journal of Stroke © 2012 World Stroke Organization.

  14. Atrial fibrillation in fracture patients treated with oral bisphosphonates

    DEFF Research Database (Denmark)

    Abrahamsen, B; Eiken, P; Brixen, K

    2009-01-01

    OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995-2005). SUBJ......OBJECTIVES: To determine if patients receiving oral bisphosphonates are at excess risk of atrial fibrillation (AF), stroke and myocardial infarction. DESIGN: Register-based restricted cohort study. SETTING: National Hospital Discharge Register and National Prescriptions Database (1995...... to adherence. There was no increased risk of ischaemic stroke and an increased risk of myocardial infarction was not significant after adjustment for comorbidity. CONCLUSIONS: The increased occurrence of AF in fracture patients who are users of oral bisphosphonates should be attributed to targeting...

  15. The Discovery of the Double Helix

    CERN Multimedia

    CERN. Geneva

    2011-01-01

    Professor James D. Watson has kindly agreed to make a presentation on the 1953 finding of the Double Helix at the Cavendish Laboratory by Francis Crick and himself. Being one of the greatest scientific discoveries in human history, little else needs to be added.

  16. Evidence of structurally continuous collagen fibrils in tendon

    DEFF Research Database (Denmark)

    Svensson, Rene B; Herchenhan, Andreas; Starborg, Tobias

    2017-01-01

    favor continuity. This study initially set out to trace the full length of individual fibrils in adult human tendons, using serial block face-scanning electron microscopy. But even with this advanced technique the required length could not be covered. Instead a statistical approach was used on a large...... volume of fibrils in shorter image stacks. Only a single end was observed after tracking 67.5 mm of combined fibril lengths, in support of fibril continuity. To shed more light on this observation, the full length of a short tendon (mouse stapedius, 125 μm) was investigated and continuity of individual...... fibrils was confirmed. In light of these results, possible mechanisms that could reconcile the opposing findings on fibril continuity are discussed. STATEMENT OF SIGNIFICANCE: Connective tissues hold all parts of the body together and are mostly constructed from thin threads of the protein collagen...

  17. Chirality and chiroptical properties of amyloid fibrils.

    Science.gov (United States)

    Dzwolak, Wojciech

    2014-09-01

    Chirality of amyloid fibrils-linear beta-sheet-rich aggregates of misfolded protein chains-often manifests in morphological traits such as helical twist visible in atomic force microscopy and in chiroptical properties accessible to vibrational circular dichroism (VCD). According to recent studies the relationship between molecular chirality of polypeptide building blocks and superstructural chirality of amyloid fibrils may be more intricate and less deterministic than previously assumed. Several puzzling experimental findings have put into question earlier intuitive ideas on: 1) the bottom-up chirality transfer upon amyloidogenic self-assembly, and 2) the structural origins of chiroptical properties of protein aggregates. For example, removal of a single amino acid residue from an amyloidogenic all-L peptide was shown to reverse handedness of fibrils. On the other hand, certain types of amyloid aggregates revealed surprisingly strong VCD spectra with the sign and shape dependent on the conditions of fibrillation. Hence, microscopic and chiroptical studies have highlighted chirality as one more aspect of polymorphism of amyloid fibrils. This brief review is intended to outline the current state of research on amyloid-like fibrils from the perspective of their structural and superstructural chirality and chiroptical properties. © 2014 Wiley Periodicals, Inc.

  18. Modeling generic aspects of ideal fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Michel, D., E-mail: denis.michel@live.fr [Universite de Rennes1-IRSET, Campus de Beaulieu Bat. 13, 35042 Rennes (France)

    2016-01-21

    Many different proteins self-aggregate into insoluble fibrils growing apically by reversible addition of elementary building blocks. But beyond this common principle, the modalities of fibril formation are very disparate, with various intermediate forms which can be reshuffled by minor modifications of physico-chemical conditions or amino-acid sequences. To bypass this complexity, the multifaceted phenomenon of fibril formation is reduced here to its most elementary principles defined for a linear prototype of fibril. Selected generic features, including nucleation, elongation, and conformational recruitment, are modeled using minimalist hypotheses and tools, by separating equilibrium from kinetic aspects and in vitro from in vivo conditions. These reductionist approaches allow to bring out known and new rudiments, including the kinetic and equilibrium effects of nucleation, the dual influence of elongation on nucleation, the kinetic limitations on nucleation and fibril numbers, and the accumulation of complexes in vivo by rescue from degradation. Overlooked aspects of these processes are also pointed: the exponential distribution of fibril lengths can be recovered using various models because it is attributable to randomness only. It is also suggested that the same term “critical concentration” is used for different things, involved in either nucleation or elongation.

  19. Proinsulin C-peptide interferes with insulin fibril formation

    International Nuclear Information System (INIS)

    Landreh, Michael; Stukenborg, Jan-Bernd; Willander, Hanna; Söder, Olle; Johansson, Jan; Jörnvall, Hans

    2012-01-01

    Highlights: ► Insulin and C-peptide can interact under insulin fibril forming conditions. ► C-peptide is incorporated into insulin aggregates and alters aggregation lag time. ► C-peptide changes insulin fibril morphology and affects backbone accessibility. ► C-peptide may be a regulator of fibril formation by β-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic β-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  20. Proinsulin C-peptide interferes with insulin fibril formation

    Energy Technology Data Exchange (ETDEWEB)

    Landreh, Michael [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden); Stukenborg, Jan-Bernd [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Willander, Hanna [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Soeder, Olle [Department of Women' s and Children' s Health, Astrid Lindgren Children' s Hospital, Pediatric Endocrinology Unit, Karolinska Institutet and University Hospital, S-17176 Stockholm (Sweden); Johansson, Jan [KI-Alzheimer' s Disease Research Center, NVS Department, Karolinska Institutet, S-141 86 Stockholm (Sweden); Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, S-751 23 Uppsala (Sweden); Joernvall, Hans, E-mail: Hans.Jornvall@ki.se [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm (Sweden)

    2012-02-17

    Highlights: Black-Right-Pointing-Pointer Insulin and C-peptide can interact under insulin fibril forming conditions. Black-Right-Pointing-Pointer C-peptide is incorporated into insulin aggregates and alters aggregation lag time. Black-Right-Pointing-Pointer C-peptide changes insulin fibril morphology and affects backbone accessibility. Black-Right-Pointing-Pointer C-peptide may be a regulator of fibril formation by {beta}-cell granule proteins. -- Abstract: Insulin aggregation can prevent rapid insulin uptake and cause localized amyloidosis in the treatment of type-1 diabetes. In this study, we investigated the effect of C-peptide, the 31-residue peptide cleaved from proinsulin, on insulin fibrillation at optimal conditions for fibrillation. This is at low pH and high concentration, when the fibrils formed are regular and extended. We report that C-peptide then modulates the insulin aggregation lag time and profoundly changes the fibril appearance, to rounded clumps of short fibrils, which, however, still are Thioflavine T-positive. Electrospray ionization mass spectrometry also indicates that C-peptide interacts with aggregating insulin and is incorporated into the aggregates. Hydrogen/deuterium exchange mass spectrometry further reveals reduced backbone accessibility in insulin aggregates formed in the presence of C-peptide. Combined, these effects are similar to those of C-peptide on islet amyloid polypeptide fibrillation and suggest that C-peptide has a general ability to interact with amyloidogenic proteins from pancreatic {beta}-cell granules. Considering the concentrations, these peptide interactions should be relevant also during physiological secretion, and even so at special sites post-secretory or under insulin treatment conditions in vivo.

  1. Modulating Transmembrane α-Helix Interactions through pH-Sensitive Boundary Residues.

    Science.gov (United States)

    Ng, Derek P; Deber, Charles M

    2016-08-09

    Changes in pH can alter the structure and activity of proteins and may be used by the cell to control molecular function. This coupling can also be used in non-native applications through the design of pH-sensitive biomolecules. For example, the pH (low) insertion peptide (pHLIP) can spontaneously insert into a lipid bilayer when the pH decreases. We have previously shown that the α-helicity and helix-helix interactions of the TM2 α-helix of the proteolipid protein (PLP) are sensitive to the local hydrophobicity at its C-terminus. Given that there is an ionizable residue (Glu-88) at the C-terminus of this transmembrane (TM) segment, we hypothesized that changing the ionization state of this residue through pH may alter the local hydrophobicity of the peptide enough to affect both its secondary structure and helix-helix interactions. To examine this phenomenon, we synthesized peptide analogues of the PLP TM2 α-helix (wild-type sequence (66)AFQYVIYGTASFFFLYGALLLAEGF(90)). Using circular dichroism and Förster resonance energy transfer in the membrane-mimetic detergent sodium dodecyl sulfate, we found that a decrease in pH increases both peptide α-helicity and the extent of self-association. This pH-dependent effect is due specifically to the presence of Glu-88 at the C-terminus. Additional experiments in which Phe-90 was mutated to residues of varying hydrophobicities indicated that the strength of this effect is dependent on the local hydrophobicity near Glu-88. Our results have implications for the design of TM peptide switches and improve our understanding of how membrane protein structure and activity can be regulated through local molecular environmental changes.

  2. Protein Polymerization into Fibrils from the Viewpoint of Nucleation Theory.

    Science.gov (United States)

    Kashchiev, Dimo

    2015-11-17

    The assembly of various proteins into fibrillar aggregates is an important phenomenon with wide implications ranging from human disease to nanoscience. Using general kinetic results of nucleation theory, we analyze the polymerization of protein into linear or helical fibrils in the framework of the Oosawa-Kasai (OK) model. We show that while within the original OK model of linear polymerization the process does not involve nucleation, within a modified OK model it is nucleation-mediated. Expressions are derived for the size of the fibril nucleus, the work for fibril formation, the nucleation barrier, the equilibrium and stationary fibril size distributions, and the stationary fibril nucleation rate. Under otherwise equal conditions, this rate decreases considerably when the short (subnucleus) fibrils lose monomers much more frequently than the long (supernucleus) fibrils, a feature that should be born in mind when designing a strategy for stymying or stimulating fibril nucleation. The obtained dependence of the nucleation rate on the concentration of monomeric protein is convenient for experimental verification and for use in rate equations accounting for nucleation-mediated fibril formation. The analysis and the results obtained for linear fibrils are fully applicable to helical fibrils whose formation is describable by a simplified OK model. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Artificial atrial fibrillation in the dog. An artifact?

    NARCIS (Netherlands)

    Strackee, J.; Hoelen, A.J.; Zimmerman, A.N.E.; Meijler, F.L.

    R-R interval sequences during artificial atrial fibrillation in dogs were studied in the same way as in patients in a previous study and compared with results obtained in dogs with spontaneous atrial fibrillation. Artificial atrial fibrillation was effected by right atrial stimulation in three

  4. Exploring the membrane fusion mechanism through force-induced disassembly of HIV-1 six-helix bundle

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Kai [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang, Yong [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Lou, Jizhong, E-mail: jlou@ibp.ac.cn [Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China); Beijing Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101 (China)

    2016-05-13

    Enveloped virus, such as HIV-1, employs membrane fusion mechanism to invade into host cell. HIV-1 gp41 ectodomain uses six-helix bundle configuration to accomplish this process. Using molecular dynamic simulations, we confirmed the stability of this six-helix bundle by showing high occupancy of hydrogen bonds and hydrophobic interactions. Key residues and interactions important for the bundle integration were characterized by force-induced unfolding simulations of six-helix bundle, exhibiting the collapse order of these groups of interactions. Moreover, our results in some way concerted with a previous theory that the formation of coiled-coil choose a route which involved cooperative interactions between the N-terminal and C-terminal helix. -- Highlights: •Unfolding of HIV-1 gp41 six-helix bundle is studied by molecular dynamics simulations. •Specific interactions responsible for the stability of HIV-1 envelope post-fusion conformation were identified. •The gp41 six-helix bundle transition inducing membrane fusion might be a cooperative process of the three subunits.

  5. Metastable Amyloid Phases and their Conversion to Mature Fibrils

    Science.gov (United States)

    Muschol, Martin; Miti, Tatiana; Mulaj, Mentor; Schmit, Jeremy

    Self-assembly of proteins into amyloid fibrils plays a key role in both functional biological responses and pathogenic disorders which include Alzheimer's disease and type II diabetes. Amyloid fibril assembly frequently generates compact oligomeric and curvilinear polymeric intermediates which are implicated to be toxic to cells. Yet, the relation between these early-stage oligomeric aggregates and late-stage rigid fibrils, which are the hallmark structure of amyloid plaques, has remained unclear. Our measurements indicate that lysozyme amyloid oligomers and their curvilinear fibrils only form after crossing a salt and protein concentration dependent threshold. These oligomeric aggregates are structurally distinct from rigid fibrils and are metastable against nucleation and growth of rigid fibrils. Our experimental transition boundaries match well with colloidal model predictions accounting for salt-modulated charge repulsion. We also report our preliminary findings on the mechanism by which these metastable oligomeric phases are converted into stable amyloid fibrils.

  6. Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's Aβ peptide

    International Nuclear Information System (INIS)

    Garvey, Megan; Tepper, Katharina; Haupt, Caroline; Knuepfer, Uwe; Klement, Karolin; Meinhardt, Jessica; Horn, Uwe; Balbach, Jochen; Faendrich, Marcus

    2011-01-01

    Highlights: → Sodium phosphate buffer accelerated Aβ(1-40) nucleation relative to HEPES. → Aβ(1-40) fibrils formed in the two buffers show only minor structural differences. → NMR revealed that Aβ(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of Aβ peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of Aβ and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of Aβ peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of Aβ fibrillation. The three histidine residues at positions 6, 13 and 14 of Aβ(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

  7. HYPERTHYROIDISM AND ATRIAL FIBRILLATION

    Directory of Open Access Journals (Sweden)

    I. M. Marusenko

    2017-01-01

    Full Text Available Review on a problem of the development of atrial fibrillation in patients with thyrotoxicosis is presented. Thyrotoxicosis is one of the most frequent endocrine diseases, conceding only to a diabetes mellitus. The most frequent reasons of hyperthyroidism are Graves’ disease and functional thyroid autonomy. The authors give an analysis of data on the cardiac effects of thyrotoxicosis, features of heart remodeling under the influence of thyroid hyperfunction, prevalence of atrial fibrillation in thyrotoxicosis, depending on age, as well as the possibility of restoring sinus rhythm in the combination of these diseases. Particular attention is paid to the effect on the heart of subclinical thyrotoxicosis, which is defined as a dysfunction of the thyroid gland, characterized by low serum concentration of thyrotropin, normal values of free thyroxine and free triiodothyronine. Subclinical hyperthyroidism is also capable of causing heart remodeling and diastolic dysfunction.Prevalence of thyrotoxicosis in elderly people is higher in areas of iodine deficiency; it is relevant for our country due to the large territory of iodine deficiency. In elderly patients, the cardiac effects of thyrotoxicosis prevail in the clinical picture, that makes it difficult to diagnose endocrine disorders, and correction of thyrotoxicosis is critically important for the successful control of the heart rhythm. The article also discusses the problem of thyrotoxic cardiomyopathy, caused by the toxic effect of excess thyroid hormones: features of this heart disorder, factors affecting its formation, clinical significance and contribution to the development of rhythm disturbances. The greatest significance is the development of atrial fibrillation as a result of thyrotox-icosis in older patients who already have various cardiovascular diseases.Atrial fibrillation is the most frequent heart rhythm disorder in thyrotoxicosis. The main cause of arrhythmia in hyperthyroidism is the

  8. FPGA helix tracking algorithm for PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Yutie; Galuska, Martin; Gessler, Thomas; Kuehn, Wolfgang; Lange, Jens Soeren; Muenchow, David; Spruck, Bjoern [II. Physikalisches Institut, Giessen University (Germany); Ye, Hua [Institute of High Energy Physics, Beijing (China); Collaboration: PANDA-Collaboration

    2015-07-01

    The PANDA detector is a general-purpose detector for physics with high luminosity cooled antiproton beams, planed to operate at the FAIR facility in Darmstadt, Germany. The central detector includes a silicon Micro Vertex Detector (MVD) and a Straw Tube Tracker (STT). Without any hardware trigger, large amounts of raw data are streaming into the data acquisition system. The data reduction task is performed in the online system by reconstruction algorithms programmed on FPGAs (Field Programmable Gate Arrays) as first level and on a farm of GPUs or PCs as a second level. One important part in the system is the online track reconstruction. In this presentation, an online tracking algorithm for helix tracking reconstruction in the solenoidal field is shown. The tracking algorithm is composed by two parts, a road finding module followed by an iterative helix parameter calculation module. A performance study using C++ and the status of the VHDL implementation are presented.

  9. Intersegment interactions and helix-coil transition within the generalized model of polypeptide chains approach

    Science.gov (United States)

    Badasyan, A. V.; Hayrapetyan, G. N.; Tonoyan, Sh. A.; Mamasakhlisov, Y. Sh.; Benight, A. S.; Morozov, V. F.

    2009-09-01

    The generalized model of polypeptide chains is extended to describe the helix-coil transition in a system comprised of two chains interacting side-by-side. The Hamiltonian of the model takes into account four possible types of interactions between repeated units of the two chains, i.e., helix-helix, helix-coil, coil-helix, and coil-coil. Analysis reveals when the energy Ihh+Icc of (h-h, c-c) interactions overwhelms the energy Ihc+Ich of mixed (h-c, c-h) interactions, the correlation length rises substantially, resulting in narrowing of the transition interval. In the opposite case, when Ihh+Icchelix formation and disfavored intersegment interactions from the same theoretical perspective.

  10. Atrial Fibrillation and Hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Jayaprasad N

    2005-10-01

    Full Text Available Atrial fibrillation occurs in 10 – 15% of patients with hyperthyroidism. Low serum thyrotropin concentration is an independent risk factor for atrial fibrillation. Thyroid hormone contributes to arrythmogenic activity by altering the electrophysiological characteristics of atrial myocytes by shortening the action potential duration, enhancing automaticity and triggered activity in the pulmonary vein cardio myocytes. Hyperthyroidism results in excess mortality from increased incidence of circulatory diseases and dysrhythmias. Incidence of cerebral embolism is more in hyperthyroid patients with atrial fibrillation, especially in the elderly and anti-coagulation is indicated in them. Treatment of hyperthyroidism results in conversion to sinus rhythm in up to two-third of patients. Beta-blockers reduce left ventricular hypertrophy and atrial and ventricular arrhythmias in patients with hyperthyroidism. Treatment of sub clinical hyperthyroidism is controversial. Optimizing dose of thyroxine treatment in those with replacement therapy and beta-blockers is useful in exogenous subclinical hyperthyroidism.

  11. Core sequence of PAPf39 amyloid fibrils and mechanism of pH-dependent fibril formation: the role of monomer conformation.

    Science.gov (United States)

    French, Kinsley C; Makhatadze, George I

    2012-12-21

    PAPf39, a 39-residue peptide fragment from human prostatic acidic phosphatase, has been shown to form amyloid fibrils in semen (SEVI), which increase HIV infectivity by up to 5 orders of magnitude. The sequence of the PAPf39 fibrillar core was identified using hydrogen-deuterium exchange (HDX) mass spectrometry and protease protection assays. The central and C-terminal regions are highly protected from HDX and proteolytic cleavage and, thus, are part of the fibrillar core. Conversely, the N-terminal region is unprotected from HDX and proteolytic cleavage, suggesting that it is exposed and not part of the fibrillar core. This finding was tested using two N-terminal truncated variants, PAPf39Δ1-8 and PAPf39Δ1-13. Both variants formed amyloid fibrils at neutral pH. However, these variants showed a markedly different pH dependence of fibril formation versus that of PAPf39. PAPf39 fibrils can form at pH 7.7, but not at pH 5.5 or 2.5, while both N-terminally truncated variants can form fibrils at these pH values. Thus, the N-terminal region is not necessary for fibril formation but modulates the pH dependence of PAPf39 fibril formation. PAPf39Δ1-8 and PAPf39Δ1-13 are capable of seeding PAPf39 fibril formation at neutral pH, suggesting that these variants are structurally compatible with PAPf39, yet no mixed fibril formation occurs between the truncated variants and PAPf39 at low pH. This suggests that pH affects the PAPf39 monomer conformational ensemble, which is supported by far-UV circular dichroism spectroscopy. A conceptual model describing the pH dependence of PAPf39 aggregation is proposed and provides potential biological implications.

  12. Regulation of TCF ETS-domain transcription factors by helix-loop-helix motifs.

    Science.gov (United States)

    Stinson, Julie; Inoue, Toshiaki; Yates, Paula; Clancy, Anne; Norton, John D; Sharrocks, Andrew D

    2003-08-15

    DNA binding by the ternary complex factor (TCF) subfamily of ETS-domain transcription factors is tightly regulated by intramolecular and intermolecular interactions. The helix-loop-helix (HLH)-containing Id proteins are trans-acting negative regulators of DNA binding by the TCFs. In the TCF, SAP-2/Net/ERP, intramolecular inhibition of DNA binding is promoted by the cis-acting NID region that also contains an HLH-like motif. The NID also acts as a transcriptional repression domain. Here, we have studied the role of HLH motifs in regulating DNA binding and transcription by the TCF protein SAP-1 and how Cdk-mediated phosphorylation affects the inhibitory activity of the Id proteins towards the TCFs. We demonstrate that the NID region of SAP-1 is an autoinhibitory motif that acts to inhibit DNA binding and also functions as a transcription repression domain. This region can be functionally replaced by fusion of Id proteins to SAP-1, whereby the Id moiety then acts to repress DNA binding in cis. Phosphorylation of the Ids by cyclin-Cdk complexes results in reduction in protein-protein interactions between the Ids and TCFs and relief of their DNA-binding inhibitory activity. In revealing distinct mechanisms through which HLH motifs modulate the activity of TCFs, our results therefore provide further insight into the role of HLH motifs in regulating TCF function and how the inhibitory properties of the trans-acting Id HLH proteins are themselves regulated by phosphorylation.

  13. Selective intercalation of six ligands molecules in a self-assembled triple helix

    NARCIS (Netherlands)

    Mateos timoneda, Miguel; Kerckhoffs, J.M.C.A.; Reinhoudt, David; Crego Calama, Mercedes

    2007-01-01

    The addition of a ligand molecule to an artificial self-assembled triple helix leads to the selective intercalation of two hydrogen-bonded trimers in specific binding pockets. Furthermore, the triple helix suffers large conformational rearrangements in order to accommodate the ligand molecules in a

  14. Thermal helix-coil transition in UV irradiated collagen from rat tail tendon.

    Science.gov (United States)

    Sionkowska, A; Kamińska, A

    1999-05-01

    The thermal helix-coil transition in UV irradiated collagen solution, collagen film and pieces of rat tail tendon (RTT) were compared. Their thermal stability's were determined by differential scanning calorimeter (DSC) and by viscometric measurements. The denaturation temperatures of collagen solution, film and pieces of RTT were different. The helix-coil transition occur near 40 degrees C in collagen solution, near 112 degrees C in collagen film, and near 101 degrees C in pieces of RTT. After UV irradiation the thermal helix-coil transition of collagen samples were changed. These changes depend on the degree of hydratation.

  15. Ultrafast Hydrogen-Bonding Dynamics in Amyloid Fibrils.

    Science.gov (United States)

    Pazos, Ileana M; Ma, Jianqiang; Mukherjee, Debopreeti; Gai, Feng

    2018-06-08

    While there are many studies on the subject of hydrogen bonding dynamics in biological systems, few, if any, have investigated this fundamental process in amyloid fibrils. Herein, we seek to add insight into this topic by assessing the dynamics of a hydrogen bond buried in the dry interface of amyloid fibrils. To prepare a suitable model peptide system for this purpose, we introduce two mutations into the amyloid-forming Aβ(16-22) peptide. The first one is a lysine analog at position 19, which is used to help form structurally homogeneous fibrils, and the second one is an aspartic acid derivative (DM) at position 17, which is intended (1) to be used as a site-specific infrared probe and (2) to serve as a hydrogen-bond acceptor to lysine so that an inter-β-sheet hydrogen bond can be formed in the fibrils. Using both infrared spectroscopy and atomic force microscopy, we show that (1) this mutant peptide indeed forms well defined fibrils, (2) when bulk solvent is removed, there is no detectable water present in the fibrils, (3) infrared results obtained with the DM probe are consistent with a protofibril structure that is composed of two antiparallel β-sheets stacked in a parallel fashion, leading to formation of the expected hydrogen bond. Using two-dimensional infrared spectroscopy, we further show that the dynamics of this hydrogen bond occur on a timescale of ~2.3 ps, which is attributed to the rapid rotation of the -NH3+ group of lysine around its Cε-Nζ bond. Taken together, these results suggest that (1) DM is a useful infrared marker in facilitating structure determination of amyloid fibrils and (2) even in the tightly packed core of amyloid fibrils certain amino acid sidechains can undergo ultrafast motions, hence contributing to the thermodynamic stability of the system.

  16. A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

    Science.gov (United States)

    Zhang, Liang; Navaratna, Tejas; Thurber, Greg M.

    2016-01-01

    Stabilized peptides address several limitations to peptide-based imaging agents and therapeutics such as poor stability and low affinity due to conformational flexibility. There is also active research in developing these compounds for intracellular drug targeting, and significant efforts have been invested to determine the effects of helix stabilization on intracellular delivery. However, much less is known about the impact on other pharmacokinetic parameters such as plasma clearance and bioavailability. We investigated the effect of different fluorescent helix-stabilizing linkers with varying lipophilicity on subcutaneous (SC) bioavailability using the glucagon-like peptide-1 (GLP-1) receptor ligand exendin as a model system. The stabilized peptides showed significantly higher protease resistance and increased bioavailability independent of linker hydrophilicity, and all subcutaneously delivered conjugates were able to successfully target the islets of Langerhans with high specificity. The lipophilic peptide variants had slower absorption and plasma clearance than their respective hydrophilic conjugates, and the absolute bioavailability was also lower likely due to the longer residence times in the skin. The ease and efficiency of double-click helix stabilization chemistries is a useful tool for increasing the bioavailability of peptide therapeutics, many of which suffer from rapid in vivo protease degradation. Helix stabilization using linkers of varying lipophilicity can further control SC absorption and clearance rates to customize plasma pharmacokinetics. PMID:27327034

  17. Embolic Risk in Atrial Fibrillation that Arises from Hyperthyroidism

    Science.gov (United States)

    Traube, Elie; Coplan, Neil L.

    2011-01-01

    Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: national organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism. PMID:21720457

  18. Triple helix interactions for eco-innovation

    DEFF Research Database (Denmark)

    Hermann, Roberto Rivas; Riisgaard, Henrik; Remmen, Arne

    the role of science parks in promoting eco-innovation. This study uses qualitative data gathered in two units of analysis: Panama Canal Authority and City of Knowledge Science Park. The study examines how Triple Helix interactions have built the regional system of eco-innovation at the Panama Canal...

  19. Solitons in an isolated helix chain

    DEFF Research Database (Denmark)

    Christiansen, Peter Leth; Zolotaryuk, Alexander; Savin, A.V.

    1997-01-01

    as a generalization of the well-known one-dimensional Fermi-Pasta-Ulam model to include transverse degrees of freedom of the chain molecules. In the particular case of the alpha-helix molecular chain, the intermolecular interactions involved into the model are the point-point bonds connecting the first-, second...

  20. An unusual helix-turn-helix protease inhibitory motif in a novel trypsin inhibitor from seeds of Veronica (Veronica hederifolia L.).

    Science.gov (United States)

    Conners, Rebecca; Konarev, Alexander V; Forsyth, Jane; Lovegrove, Alison; Marsh, Justin; Joseph-Horne, Timothy; Shewry, Peter; Brady, R Leo

    2007-09-21

    The storage tissues of many plants contain protease inhibitors that are believed to play an important role in defending the plant from invasion by pests and pathogens. These proteinaceous inhibitor molecules belong to a number of structurally distinct families. We describe here the isolation, purification, initial inhibitory properties, and three-dimensional structure of a novel trypsin inhibitor from seeds of Veronica hederifolia (VhTI). The VhTI peptide inhibits trypsin with a submicromolar apparent K(i) and is expected to be specific for trypsin-like serine proteases. VhTI differs dramatically in structure from all previously described families of trypsin inhibitors, consisting of a helix-turn-helix motif, with the two alpha helices tightly associated by two disulfide bonds. Unusually, the crystallized complex is in the form of a stabilized acyl-enzyme intermediate with the scissile bond of the VhTI inhibitor cleaved and the resulting N-terminal portion of the inhibitor remaining attached to the trypsin catalytic serine 195 by an ester bond. A synthetic, truncated version of the VhTI peptide has also been produced and co-crystallized with trypsin but, surprisingly, is seen to be uncleaved and consequently forms a noncovalent complex with trypsin. The VhTI peptide shows that effective enzyme inhibitors can be constructed from simple helical motifs and provides a new scaffold on which to base the design of novel serine protease inhibitors.

  1. Atrial fibrillation

    African Journals Online (AJOL)

    ABEOLUGBENGAS

    Mean blood pressures were 126.03± ... optimal. Keywords: Atrial fibrillation, thrombosis, CHADS2 Score, stroke risk, hypertensive heart disease, ... general population and the average age group ... Appendix 1) to stratify the stroke risk and we.

  2. Collagen Fibrils: Nature's Highly Tunable Nonlinear Springs.

    Science.gov (United States)

    Andriotis, Orestis G; Desissaire, Sylvia; Thurner, Philipp J

    2018-03-21

    Tissue hydration is well known to influence tissue mechanics and can be tuned via osmotic pressure. Collagen fibrils are nature's nanoscale building blocks to achieve biomechanical function in a broad range of biological tissues and across many species. Intrafibrillar covalent cross-links have long been thought to play a pivotal role in collagen fibril elasticity, but predominantly at large, far from physiological, strains. Performing nanotensile experiments of collagen fibrils at varying hydration levels by adjusting osmotic pressure in situ during atomic force microscopy experiments, we show the power the intrafibrillar noncovalent interactions have for defining collagen fibril tensile elasticity at low fibril strains. Nanomechanical tensile tests reveal that osmotic pressure increases collagen fibril stiffness up to 24-fold in transverse (nanoindentation) and up to 6-fold in the longitudinal direction (tension), compared to physiological saline in a reversible fashion. We attribute the stiffening to the density and strength of weak intermolecular forces tuned by hydration and hence collagen packing density. This reversible mechanism may be employed by cells to alter their mechanical microenvironment in a reversible manner. The mechanism could also be translated to tissue engineering approaches for customizing scaffold mechanics in spatially resolved fashion, and it may help explain local mechanical changes during development of diseases and inflammation.

  3. Kinetically controlled thermal response of beta2-microglobulin amyloid fibrils.

    Science.gov (United States)

    Sasahara, Kenji; Naiki, Hironobu; Goto, Yuji

    2005-09-23

    Calorimetric measurements were carried out using a differential scanning calorimeter in the temperature range from 10 to 120 degrees C for characterizing the thermal response of beta2-microglobulin amyloid fibrils. The thermograms of amyloid fibril solution showed a remarkably large decrease in heat capacity that was essentially released upon the thermal unfolding of the fibrils, in which the magnitude of negative heat capacity change was not explicable in terms of the current accessible surface area model of protein structural thermodynamics. The heat capacity-temperature curve of amyloid fibrils prior to the fibril unfolding exhibited an unusual dependence on the fibril concentration and the heating rate. Particularly, the heat needed to induce the thermal response was found to be linearly dependent on the heating rate, indicating that its thermal response is under a kinetic control and precluding the interpretation in terms of equilibrium thermodynamics. Furthermore, amyloid fibrils of amyloid beta peptides also exhibited a heating rate-dependent exothermic process before the fibril unfolding, indicating that the kinetically controlled thermal response may be a common phenomenon to amyloid fibrils. We suggest that the heating rate-dependent negative change in heat capacity is coupled to the association of amyloid fibrils with characteristic hydration pattern.

  4. Normal and reversed supramolecular chirality of insulin fibrils probed by vibrational circular dichroism at the protofilament level of fibril structure.

    Science.gov (United States)

    Kurouski, Dmitry; Dukor, Rina K; Lu, Xuefang; Nafie, Laurence A; Lednev, Igor K

    2012-08-08

    Fibrils are β-sheet-rich aggregates that are generally composed of several protofibrils and may adopt variable morphologies, such as twisted ribbons or flat-like sheets. This polymorphism is observed for many different amyloid associated proteins and polypeptides. In a previous study we proposed the existence of another level of amyloid polymorphism, namely, that associated with fibril supramolecular chirality. Two chiral polymorphs of insulin, which can be controllably grown by means of small pH variations, exhibit opposite signs of vibrational circular dichroism (VCD) spectra. Herein, using atomic force microscopy (AFM) and scanning electron microscopy (SEM), we demonstrate that indeed VCD supramolecular chirality is correlated not only by the apparent fibril handedness but also by the sense of supramolecular chirality from a deeper level of chiral organization at the protofilament level of fibril structure. Our microscopic examination indicates that normal VCD fibrils have a left-handed twist, whereas reversed VCD fibrils are flat-like aggregates with no obvious helical twist as imaged by atomic force microscopy or scanning electron microscopy. A scheme is proposed consistent with observed data that features a dynamic equilibrium controlled by pH at the protofilament level between left- and right-twist fibril structures with distinctly different aggregation pathways for left- and right-twisted protofilaments. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  5. Structural and functional aspects of winged-helix domains at the core of transcription initiation complexes.

    Science.gov (United States)

    Teichmann, Martin; Dumay-Odelot, Hélène; Fribourg, Sébastien

    2012-01-01

    The winged helix (WH) domain is found in core components of transcription systems in eukaryotes and prokaryotes. It represents a sub-class of the helix-turn-helix motif. The WH domain participates in establishing protein-DNA and protein-protein-interactions. Here, we discuss possible explanations for the enrichment of this motif in transcription systems.

  6. Structural studies of polypeptides: Mechanism of immunoglobin catalysis and helix propagation in hybrid sequence, disulfide containing peptides

    Energy Technology Data Exchange (ETDEWEB)

    Storrs, Richard Wood [Univ. of California, Berkeley, CA (United States)

    1992-08-01

    Catalytic immunoglobin fragments were studied Nuclear Magnetic Resonance spectroscopy to identify amino acid residues responsible for the catalytic activity. Small, hybrid sequence peptides were analyzed for helix propagation following covalent initiation and for activity related to the protein from which the helical sequence was derived. Hydrolysis of p-nitrophenyl carbonates and esters by specific immunoglobins is thought to involve charge complementarity. The pK of the transition state analog P-nitrophenyl phosphate bound to the immunoglobin fragment was determined by 31P-NMR to verify the juxtaposition of a positively charged amino acid to the binding/catalytic site. Optical studies of immunoglobin mediated photoreversal of cis, syn cyclobutane thymine dimers implicated tryptophan as the photosensitizing chromophore. Research shows the chemical environment of a single tryptophan residue is altered upon binding of the thymine dimer. This tryptophan residue was localized to within 20 Å of the binding site through the use of a nitroxide paramagnetic species covalently attached to the thymine dimer. A hybrid sequence peptide was synthesized based on the bee venom peptide apamin in which the helical residues of apamin were replaced with those from the recognition helix of the bacteriophage 434 repressor protein. Oxidation of the disufide bonds occured uniformly in the proper 1-11, 3-15 orientation, stabilizing the 434 sequence in an α-helix. The glycine residue stopped helix propagation. Helix propagation in 2,2,2-trifluoroethanol mixtures was investigated in a second hybrid sequence peptide using the apamin-derived disulfide scaffold and the S-peptide sequence. The helix-stop signal previously observed was not observed in the NMR NOESY spectrum. Helical connectivities were seen throughout the S-peptide sequence. The apamin/S-peptide hybrid binded to the S-protein (residues 21-166 of ribonuclease A) and reconstituted enzymatic activity.

  7. Structural studies of polypeptides: Mechanism of immunoglobin catalysis and helix propagation in hybrid sequence, disulfide containing peptides

    Energy Technology Data Exchange (ETDEWEB)

    Storrs, R.W.

    1992-08-01

    Catalytic immunoglobin fragments were studied Nuclear Magnetic Resonance spectroscopy to identify amino acid residues responsible for the catalytic activity. Small, hybrid sequence peptides were analyzed for helix propagation following covalent initiation and for activity related to the protein from which the helical sequence was derived. Hydrolysis of p-nitrophenyl carbonates and esters by specific immunoglobins is thought to involve charge complementarity. The pK of the transition state analog P-nitrophenyl phosphate bound to the immunoglobin fragment was determined by [sup 31]P-NMR to verify the juxtaposition of a positively charged amino acid to the binding/catalytic site. Optical studies of immunoglobin mediated photoreversal of cis, syn cyclobutane thymine dimers implicated tryptophan as the photosensitizing chromophore. Research shows the chemical environment of a single tryptophan residue is altered upon binding of the thymine dimer. This tryptophan residue was localized to within 20 [Angstrom] of the binding site through the use of a nitroxide paramagnetic species covalently attached to the thymine dimer. A hybrid sequence peptide was synthesized based on the bee venom peptide apamin in which the helical residues of apamin were replaced with those from the recognition helix of the bacteriophage 434 repressor protein. Oxidation of the disufide bonds occured uniformly in the proper 1-11, 3-15 orientation, stabilizing the 434 sequence in an [alpha]-helix. The glycine residue stopped helix propagation. Helix propagation in 2,2,2-trifluoroethanol mixtures was investigated in a second hybrid sequence peptide using the apamin-derived disulfide scaffold and the S-peptide sequence. The helix-stop signal previously observed was not observed in the NMR NOESY spectrum. Helical connectivities were seen throughout the S-peptide sequence. The apamin/S-peptide hybrid binded to the S-protein (residues 21-166 of ribonuclease A) and reconstituted enzymatic activity.

  8. Unfolding four-helix bundles

    Science.gov (United States)

    Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

    2011-03-01

    A geometrical model has been developed to describe the early stages of unfolding of cytochromes c‧ and c-b562 . Calculations are based on a step-wise extension of the polypeptide chain subject to the constraint that the spatial relationship among the residues of each triplet is fixed by the native-state crystallographic data. The response of each protein to these structural perturbations allows the evolution of each of the four helices in these two proteins to be differentiated. It is found that the two external helices in c‧ unfold before its two internal helices, whereas exactly the opposite behaviour is demonstrated by c-b562 . Each of these cytochromes has an extended, internal, non-helical ('turning') region that initially lags behind the most labile helix but then, at a certain stage (identified for each cytochrome), unravels before any of the four helices present in the native structure. It is believed that these predictions will be useful in guiding future experimental studies on the unfolding of these two cytochromes.

  9. [Relations between FANS, PPI and atrial fibrillation].

    Science.gov (United States)

    Ricci, Fabrizio; De Caterina, Raffaele

    2013-05-01

    Recent evidence supports the existence of an association between the use of non-steroidal anti-inflammatory drugs and the risk of atrial fibrillation. Anti-inflammatory drugs are widely used for the treatment of systemic inflammatory disorders, and chronic inflammation is a well-known risk factor for the development of myocardial fibrosis. The latter accounts for atrial inhomogeneities of conduction, thus triggering and perpetuating atrial fibrillation. Atrial inflammatory remodeling may therefore be responsible for the higher incidence of atrial fibrillation among patients assuming steroidal and non-steroidal anti-inflammatory drugs because of an underlying inflammatory disorders. Alternative theories contemplate gastroesophageal reflux, which is extremely common during the use of non-steroidal anti-inflammatory drugs and may trigger atrial fibrillation, as mediating the above-mentioned association.

  10. Optimized molecular dynamics force fields applied to the helix-coil transition of polypeptides.

    Science.gov (United States)

    Best, Robert B; Hummer, Gerhard

    2009-07-02

    Obtaining the correct balance of secondary structure propensities is a central priority in protein force-field development. Given that current force fields differ significantly in their alpha-helical propensities, a correction to match experimental results would be highly desirable. We have determined simple backbone energy corrections for two force fields to reproduce the fraction of helix measured in short peptides at 300 K. As validation, we show that the optimized force fields produce results in excellent agreement with nuclear magnetic resonance experiments for folded proteins and short peptides not used in the optimization. However, despite the agreement at ambient conditions, the dependence of the helix content on temperature is too weak, a problem shared with other force fields. A fit of the Lifson-Roig helix-coil theory shows that both the enthalpy and entropy of helix formation are too small: the helix extension parameter w agrees well with experiment, but its entropic and enthalpic components are both only about half the respective experimental estimates. Our structural and thermodynamic analyses point toward the physical origins of these shortcomings in current force fields, and suggest ways to address them in future force-field development.

  11. Peptide-oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

    DEFF Research Database (Denmark)

    Lou, Chenguang; Martos-Maldonado, Manuel C.; Madsen, Charlotte Stahl

    2016-01-01

    Peptide-based structures can be designed to yield artificial proteins with specific folding patterns and functions. Template-based assembly of peptide units is one design option, but the use of two orthogonal self-assembly principles, oligonucleotide triple helix and a coiled coil protein domain ...

  12. Preparation of Amyloid Fibrils Seeded from Brain and Meninges.

    Science.gov (United States)

    Scherpelz, Kathryn P; Lu, Jun-Xia; Tycko, Robert; Meredith, Stephen C

    2016-01-01

    Seeding of amyloid fibrils into fresh solutions of the same peptide or protein in disaggregated form leads to the formation of replicate fibrils, with close structural similarity or identity to the original fibrillar seeds. Here we describe procedures for isolating fibrils composed mainly of β-amyloid (Aβ) from human brain and from leptomeninges, a source of cerebral blood vessels, for investigating Alzheimer's disease and cerebral amyloid angiopathy. We also describe methods for seeding isotopically labeled, disaggregated Aβ peptide solutions for study using solid-state NMR and other techniques. These methods should be applicable to other types of amyloid fibrils, to Aβ fibrils from mice or other species, tissues other than brain, and to some non-fibrillar aggregates. These procedures allow for the examination of authentic amyloid fibrils and other protein aggregates from biological tissues without the need for labeling the tissue.

  13. Inactivation of colicin Y by intramembrane helix–helix interaction with its immunity protein

    Czech Academy of Sciences Publication Activity Database

    Šmajs, D.; Doležalová, M.; Macek, Pavel; Žídek, L.

    2008-01-01

    Roč. 275, č. 21 (2008), s. 5325-5331 ISSN 1742-464X Institutional research plan: CEZ:AV0Z50200510 Keywords : colicin immunity * colicin y * helix-helix interaction Subject RIV: CE - Biochemistry Impact factor: 3.139, year: 2008

  14. The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Langkilde, Annette E., E-mail: annette.langkilde@sund.ku.dk [University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Morris, Kyle L.; Serpell, Louise C. [University of Sussex, Falmer, Brighton (United Kingdom); Svergun, Dmitri I. [European Molecular Biology Laboratory, Hamburg Outstation, 22607 Hamburg (Germany); Vestergaard, Bente [University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

    2015-04-01

    The aggregation process and the fibril state of an amyloidogenic peptide suggest monomer addition to be the prevailing mechanism of elongation and a model of the peptide packing in the fibrils has been obtained. Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and α-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a β-sheet arrangement reminiscent of the β-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods.

  15. PH4 of petunia is an R2R3-MYB protein that activates vacuolar acidification through interactions with Basic-Helix-Loop-Helix transcription factors of the anthocyanin pathway.

    NARCIS (Netherlands)

    Quattrocchio, F.M.; Verweij, C.W.; Spelt, C.E.; Mol, J.N.M.; Koes, R.E.

    2007-01-01

    The Petunia hybrids genes ANTHOCYANIN1 (AN1) and AN2 encode transcription factors with a basic-helix-loop-helix (BHLH) and a MYB domain, respectively, that are required for anthocyanin synthesis and acidification of the vacuole in petal cells. Mutation of PH4 results in a bluer flower color,

  16. How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin*

    Science.gov (United States)

    Malmos, Kirsten Gade; Bjerring, Morten; Jessen, Christian Moestrup; Nielsen, Erik Holm Toustrup; Poulsen, Ebbe T.; Christiansen, Gunna; Vosegaard, Thomas; Skrydstrup, Troels; Enghild, Jan J.; Pedersen, Jan Skov; Otzen, Daniel E.

    2016-01-01

    Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAG interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3–7. Small angle x-ray scattering indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT·heparin complexes form β-sheet-rich heparin-covered fibrils. Solid-state NMR reveals that heparin does not alter the sCT fibrillary core around Lys11 but makes changes to Val8 on the exterior side of the β-strand, possibly through contacts to Lys18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting with both monomeric and aggregated sCT. PMID:27281819

  17. Cryoballoon Ablation for Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Jason G. Andrade, MD

    2012-03-01

    Full Text Available Focal point-by-point radiofrequency catheter ablation has shown considerable success in the treatment of paroxysmal atrial fibrillation. However, it is not without limitations. Recent clinical and preclinical studies have demonstrated that cryothermal ablation using a balloon catheter (Artic Front©, Medtronic CryoCath LP provides an effective alternative strategy to treating atrial fibrillation. The objective of this article is to review efficacy and safety data surrounding cryoballoon ablation for paroxysmal and persistent atrial fibrillation. In addition, a practical step-by-step approach to cryoballoon ablation is presented, while highlighting relevant literature regarding: 1 the rationale for adjunctive imaging, 2 selection of an appropriate cryoballoon size, 3 predictors of efficacy, 4 advanced trouble-shooting techniques, and 5 strategies to reduce procedural complications, such as phrenic nerve palsy.

  18. Fibril assembly in whey protein mixtures

    NARCIS (Netherlands)

    Bolder, S.G.

    2007-01-01

    The objective of this thesis was to study fibril assembly in mixtures of whey proteins. The effect of the composition of the protein mixture on the structures and the resulting phase behaviour was investigated. The current work has shown that beta-lactoglobulin is responsible for the fibril assembly

  19. Human Islet Amyloid Polypeptide Fibril Binding to Catalase: A Transmission Electron Microscopy and Microplate Study

    Directory of Open Access Journals (Sweden)

    Nathaniel G. N. Milton

    2010-01-01

    Full Text Available The diabetes-associated human islet amyloid polypeptide (IAPP is a 37-amino-acid peptide that forms fibrils in vitro and in vivo. Human IAPP fibrils are toxic in a similar manner to Alzheimer's amyloid-β (Aβ and prion protein (PrP fibrils. Previous studies have shown that catalase binds to Aβ fibrils and appears to recognize a region containing the Gly-Ala-Ile-Ile sequence that is similar to the Gly-Ala-Ile-Leu sequence found in human IAPP residues 24-27. This study presents a transmission electron microscopy (TEM—based analysis of fibril formation and the binding of human erythrocyte catalase to IAPP fibrils. The results show that human IAPP 1-37, 8-37, and 20-29 peptides form fibrils with diverse and polymorphic structures. All three forms of IAPP bound catalase, and complexes of IAPP 1-37 or 8-37 with catalase were identified by immunoassay. The binding of biotinylated IAPP to catalase was high affinity with a KD of 0.77nM, and could be inhibited by either human or rat IAPP 1-37 and 8-37 forms. Fibrils formed by the PrP 118-135 peptide with a Gly-Ala-Val-Val sequence also bound catalase. These results suggest that catalase recognizes a Gly-Ala-Ile-Leu—like sequence in amyloid fibril-forming peptides. For IAPP 1-37 and 8-37, the catalase binding was primarily directed towards fibrillar rather than ribbon-like structures, suggesting differences in the accessibility of the human IAPP 24-27 Gly-Ala-Ile-Leu region. This suggests that catalase may be able to discriminate between different structural forms of IAPP fibrils. The ability of catalase to bind IAPP, Aβ, and PrP fibrils demonstrates the presence of similar accessible structural motifs that may be targets for antiamyloid therapeutic development.

  20. Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Helen P McWilliams-Koeppen

    Full Text Available Light chain (AL amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(PH-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.

  1. Lysine as helix C-capping residue in a synthetic peptide.

    Science.gov (United States)

    Esposito, G; Dhanapal, B; Dumy, P; Varma, V; Mutter, M; Bodenhausen, G

    1997-01-01

    The structure of the synthetic peptide CH3CO(Leu-Ser-Leu-Leu-Leu-Ser-Leu)3Lys-NH2 in trifluoroethanol/water 60/40 (volume ratio) was characterized by two-dimensional nmr spectroscopy. The peptide, closely related to the amphiphilic helix models designed by W. F. De-Grado and co-workers to mimic protein ion channels [(1988) Science, Vol. 240, p. 1177-1181], folds into a regular helix spanning residues 1-20. Evidence for a helix C-terminal capping conformation, involving the terminal lysine residue, was observed from Overhauser effects and checked for consistency by restrained molecular dynamics simulations. The side-chain amino group of Lys22 forms a hydrogen bond with the carbonyl of Leu18, and the distorted helical geometry of the terminal dipeptide allows the inclusion of a water bridge between the backbone NH of the Lys22 residue and the carbonyls of Leu19 and Ser20.

  2. Thermodynamic Effects of Replacements of Pro Residues in Helix Interiors of Maltose-Binding Protein

    OpenAIRE

    Prajapati, RS; Lingaraju, GM; Bacchawat, Kiran; Surolia, Avadhesha; Varadarajan, Raghavan

    2003-01-01

    Introduction of Pro residues into helix interiors results in protein destabilization. It is currently unclear if the converse substitution (i.e., replacement of Pro residues that naturally occur in helix interiors would be stabilizing). Maltose-binding protein is a large 370-amino acid protein that contains 21 Pro residues. Of these, three nonconserved residues (P48, P133, and P159) occur at helix interiors. Each of the residues was replaced with Ala and Ser. Stabilities were characterized by...

  3. Atrial Fibrillation in Eight New World Camelids.

    Science.gov (United States)

    Bozorgmanesh, R; Magdesian, K G; Estell, K E; Stern, J A; Swain, E A; Griffiths, L G

    2016-01-01

    There is limited information on the incidence of clinical signs, concurrent illness and treatment options for atrial fibrillation (AF) in New World Camelids (NWC). Describe clinical signs and outcome of AF in NWC. Eight New World Camelids admitted with AF. A retrospective observational study of camelids diagnosed with AF based on characteristic findings on electrocardiogram (ECG). All animals had an irregularly irregular heart rhythm detected on physical examination and 4 cases had obtunded mentation on admission. Three camelids were diagnosed with AF secondary to oleander intoxication, 3 animals had underlying cardiovascular disease, 1 was diagnosed with lone AF and 1 had AF diagnosed on examination for a urethral obstruction. Five of eight animals survived to discharge and nonsurvivors consisted of animals which died or were euthanized as a result of cardiovascular disease (2/8) or extra-cardiac disease unrelated to the AF (1/8). Atrial fibrillation occurs in NWC in association with cardiovascular disease, extra-cardiac disease or as lone AF. Amiodarone and transthoracic cardioversion were attempted in one llama with lone AF, but were unsuccessful. Atrial fibrillation was recorded in 0.1% of admissions. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  4. Maze Procedures for Atrial Fibrillation, From History to Practice.

    Science.gov (United States)

    Kik, Charles; Bogers, Ad J J C

    2011-10-01

    Atrial fibrillation may result in significant symptoms, (systemic) thrombo-embolism, as well as tachycardia-induced cardiomyopathy with cardiac failure, and consequently be associated with significant morbidity and mortality. Nowadays symptomatic atrial fibrillation can be treated with catheter-based ablation, surgical ablation or hybrid approaches. In this setting a fairly large number of surgical approaches and procedures are described and being practised. It should be clear that the Cox-maze procedure resulted from building up evidence and experience in different steps, while some of the present surgical approaches and techniques are being based only on technical feasibility with limited experience, rather than on a process of consequent methodology. Some of the issues still under debate are whether or not the maze procedure can be limited to the left atrium or even to isolation of the pulmonary veins or that bi-atrial procedures are indicated, whether or not cardiopulmonary bypass is to be applied and which route of exposure facilitates an optimal result. In addition, maze procedures are not procedures guide by electrophysiological mapping. At least in theory not in all patients all lesions of the maze procedures are necessary. A history and aspects of current practise in surgical treatment of atrial fibrillation is presented.

  5. One Peptide Reveals the Two Faces of α-Helix Unfolding-Folding Dynamics.

    Science.gov (United States)

    Jesus, Catarina S H; Cruz, Pedro F; Arnaut, Luis G; Brito, Rui M M; Serpa, Carlos

    2018-04-12

    The understanding of fast folding dynamics of single α-helices comes mostly from studies on rationally designed peptides displaying sequences with high helical propensity. The folding/unfolding dynamics and energetics of α-helix conformations in naturally occurring peptides remains largely unexplored. Here we report the study of a protein fragment analogue of the C-peptide from bovine pancreatic ribonuclease-A, RN80, a 13-amino acid residue peptide that adopts a highly populated helical conformation in aqueous solution. 1 H NMR and CD structural studies of RN80 showed that α-helix formation displays a pH-dependent bell-shaped curve, with a maximum near pH 5, and a large decrease in helical content in alkaline pH. The main forces stabilizing this short α-helix were identified as a salt bridge formed between Glu-2 and Arg-10 and the cation-π interaction involving Tyr-8 and His-12. Thus, deprotonation of Glu-2 or protonation of His-12 are essential for the RN80 α-helix stability. In the present study, RN80 folding and unfolding were triggered by laser-induced pH jumps and detected by time-resolved photoacoustic calorimetry (PAC). The photoacid proton release, amino acid residue protonation, and unfolding/folding events occur at different time scales and were clearly distinguished using time-resolved PAC. The partial unfolding of the RN80 α-helix, due to protonation of Glu-2 and consequent breaking of the stabilizing salt bridge between Glu-2 and Arg-10, is characterized by a concentration-independent volume expansion in the sub-microsecond time range (0.8 mL mol -1 , 369 ns). This small volume expansion reports the cost of peptide backbone rehydration upon disruption of a solvent-exposed salt bridge, as well as backbone intrinsic expansion. On the other hand, RN80 α-helix folding triggered by His-12 protonation and subsequent formation of a cation-π interaction leads to a microsecond volume contraction (-6.0 mL mol -1 , ∼1.7 μs). The essential role of two

  6. Lost life years attributable to stroke among patients with nonvalvular atrial fibrillation: a nationwide population-based follow-up study

    DEFF Research Database (Denmark)

    Frost, Lars; Andersen, Ljubica; Johnsen, Søren Paaske

    2007-01-01

    Registry of Patients from calendar year 1980 to 2002, and no previous or concomitant diagnosis of stroke or heart valve disease. All patients were followed in the Danish National Registry of Patients for occurrence of an incident diagnosis of stroke of any type (ischemic and/or hemorrhagic......AIM: We assessed the number of lost life years attributable to stroke among patients with a hospital diagnosis of nonvalvular atrial fibrillation. METHODS: We identified all patients, aged 40-89 years, with an incident hospital diagnosis of atrial fibrillation or flutter in the Danish National...... lost life years by sex, age, and time to incident stroke after diagnosis of atrial fibrillation, adjusted for conditions of comorbidity and calendar year of diagnosis of atrial fibrillation. RESULTS: The mean loss of life years attributable to incident stroke within 20 years after a first diagnosis...

  7. Conformational Diffusion and Helix Formation Kinetics

    International Nuclear Information System (INIS)

    Hummer, Gerhard; Garcia, Angel E.; Garde, Shekhar

    2000-01-01

    The time, temperature, and sequence dependences of helix formation kinetics of fully atomistic peptide models in explicit solvent are described quantitatively by a diffusive search within the coil state with barrierless transitions into the helical state. Conformational diffusion leads to nonexponential kinetics and jump-width dependences in temperature jump experiments. (c) 2000 The American Physical Society

  8. Conformational Diffusion and Helix Formation Kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Hummer, Gerhard [Laboratory of Chemical Physics, Building 5, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520 (United States); Garcia, Angel E. [Theoretical Biology and Biophysics Group T-10, MS K710, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Garde, Shekhar [Department of Chemical Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, New York 12180 (United States)

    2000-09-18

    The time, temperature, and sequence dependences of helix formation kinetics of fully atomistic peptide models in explicit solvent are described quantitatively by a diffusive search within the coil state with barrierless transitions into the helical state. Conformational diffusion leads to nonexponential kinetics and jump-width dependences in temperature jump experiments. (c) 2000 The American Physical Society.

  9. Posibilities of cardiac pacemaker use in paroxsysmal atrial fibrilation

    Directory of Open Access Journals (Sweden)

    Borut Kamenik

    2005-12-01

    Full Text Available Background: Prevention of atrial fibrillation is a big therapeutic challenge because of all known negative consequences of this the most frequent cardiac arrhythmia. Numerous of clinical studies showed bad control or ineffectiveness of antiarhythmic drugs. Nonfarmakological therapies like surgical treatment, radiofrequency ablation and atrial pacing are being tested. Effectiveness of atrial pacing in prevention of paroxysmal artial fibrillation has been documented in numerous prospective studies and is effective for a long time interval, but only for patients with bradicardic underlying cardiac rhythm. In Normocardic rhythm or normal AV conduction the effective Atrial fibrillation prevention was not proven. The mechanism of action is based on premature atrial complex suppression, reduction of dispersion of refractoriness after short-long cycles and reduction of interatrial conduction delay. The atrial stimulation site or multi-site atrial pacing could be effective in AF prevention when interatrial conduction delay is present; otherwise the difference is not significant.Conclusions: In bradicardic patient who has frequent paroxysms of atrial fibrillation, regardless if bradycardia is due to ineffective antiarrhythmic drug treathement, implantation of DDDR pacemaker with atrial prevention algorhythm is indicated. If the P-wave duration is >120 milliseconds multi-site atrial pacing or septal atrial pacing should be considered. Pacemaker diagnostic tools could be used for adequate start of anticoagulant therapy and control of effectiveness of anthyarhythmic drug therapy.

  10. Disruption of the LOV-Jalpha helix interaction activates phototropin kinase activity.

    Science.gov (United States)

    Harper, Shannon M; Christie, John M; Gardner, Kevin H

    2004-12-28

    Light plays a crucial role in activating phototropins, a class of plant photoreceptors that are sensitive to blue and UV-A wavelengths. Previous studies indicated that phototropin uses a bound flavin mononucleotide (FMN) within its light-oxygen-voltage (LOV) domain to generate a protein-flavin covalent bond under illumination. In the C-terminal LOV2 domain of Avena sativa phototropin 1, formation of this bond triggers a conformational change that results in unfolding of a helix external to this domain called Jalpha [Harper, S. M., et al. (2003) Science 301, 1541-1545]. Though the structural effects of illumination were characterized, it was unknown how these changes are coupled to kinase activation. To examine this, we made a series of point mutations along the Jalpha helix to disrupt its interaction with the LOV domain in a manner analogous to light activation. Using NMR spectroscopy and limited proteolysis, we demonstrate that several of these mutations displace the Jalpha helix from the LOV domain independently of illumination. When placed into the full-length phototropin protein, these point mutations display constitutive kinase activation, without illumination of the sample. These results indicate that unfolding of the Jalpha helix is the critical event in regulation of kinase signaling for the phototropin proteins.

  11. The inhalation toxicology of p-aramid fibrils.

    Science.gov (United States)

    Donaldson, Ken

    2009-01-01

    The pandemic of lung disease caused by asbestos has cast suspicion on any industrial fibrous material that can become airborne in respirable form in workplaces, such that the respirable fibres might be inhaled. Fibre toxicology arose as a sub-specialty of particle toxicology to address the specialised nature of fibre effects and has evolved substantially in the last 25 years. It has yielded valuable information on the dosimetry, structure-activity relationships, and mechanism involved in toxicological effects of a range of fibrous materials, including asbestos, other naturally occurring fibrous materials, and synthetic vitreous fibres. A robust structure/activity paradigm has emerged from this research that highlights fibre length, thinness, and biopersistence as major factors in determining the pathogenicity of a fibre. p-Aramid is a manufactured fibre composed of synthetic polyamide (poly paraphenylene terephthalamide) manufactured on a commercial scale since 1970 by polymerisation and spinning steps. It is used as an advanced composite and in fabrics, body armour, friction materials, etc. Respirable fibrils of p-aramid can be released from the fibres during working and can become airborne. A considerable body of research has been carried out into the hazard posed by inhaled p-aramid fibrils, and this review considers this body of literature and summarises the state-of-the-science in the toxicology of p-aramid fibrils in the light of the existing overarching fibre toxicology paradigm. The peer-reviewed studies demonstrate that p-aramid fibrils can be long and thin but that the fibrils are not biopersistent. Residence in the milieu of the lungs leads to fibre shortening, allowing efficient and complete phagocytosis and effective clearance. Subsequently the p-aramid hazard is low, and this is confirmed in animal studies. The mechanism of shortening of p-aramid fibrils is not well-understood, but may involve the action of macrophages on the fibrils following

  12. Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

    Science.gov (United States)

    Herrera, L; Leal, I; Lapi, F; Schuemie, M; Arcoraci, V; Cipriani, F; Sessa, E; Vaccheri, A; Piccinni, C; Staniscia, T; Vestri, A; Di Bari, M; Corrao, G; Zambon, A; Gregori, D; Carle, F; Sturkenboom, M; Mazzaglia, G; Trifiro, G

    2015-05-01

    Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (reference point. A subgroup analysis by individual BP was then carried out. In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

  13. 13-Helix folding of a β/γ-peptide manifold designed from a "minimal-constraint" blueprint.

    Science.gov (United States)

    Grison, Claire M; Robin, Sylvie; Aitken, David J

    2016-06-14

    A bottom-up design rationale was adopted to devise β/γ-peptide foldamer manifolds which would adopt preferred 13-helix conformations, relying on minimal steric imposition brought by the constituent amino acid residues. In this way, a well-defined 13-helix conformer was revealed for short oligomers of trans-2-aminocyclobutanecarboxylic acid and γ(4)-amino acids in alternation, which gave good topological superposition upon an α-helix motif.

  14. Elasticity in Physically Cross-Linked Amyloid Fibril Networks

    Science.gov (United States)

    Cao, Yiping; Bolisetty, Sreenath; Adamcik, Jozef; Mezzenga, Raffaele

    2018-04-01

    We provide a constitutive model of semiflexible and rigid amyloid fibril networks by combining the affine thermal model of network elasticity with the Derjaguin-Landau-Vervey-Overbeek (DLVO) theory of electrostatically charged colloids. When compared to rheological experiments on β -lactoglobulin and lysozyme amyloid networks, this approach provides the correct scaling of elasticity versus both concentration (G ˜c2.2 and G ˜c2.5 for semiflexible and rigid fibrils, respectively) and ionic strength (G ˜I4.4 and G ˜I3.8 for β -lactoglobulin and lysozyme, independent from fibril flexibility). The pivotal role played by the screening salt is to reduce the electrostatic barrier among amyloid fibrils, converting labile physical entanglements into long-lived cross-links. This gives a power-law behavior of G with I having exponents significantly larger than in other semiflexible polymer networks (e.g., actin) and carrying DLVO traits specific to the individual amyloid fibrils.

  15. Reovirus FAST Proteins Drive Pore Formation and Syncytiogenesis Using a Novel Helix-Loop-Helix Fusion-Inducing Lipid Packing Sensor.

    Directory of Open Access Journals (Sweden)

    Jolene Read

    2015-06-01

    Full Text Available Pore formation is the most energy-demanding step during virus-induced membrane fusion, where high curvature of the fusion pore rim increases the spacing between lipid headgroups, exposing the hydrophobic interior of the membrane to water. How protein fusogens breach this thermodynamic barrier to pore formation is unclear. We identified a novel fusion-inducing lipid packing sensor (FLiPS in the cytosolic endodomain of the baboon reovirus p15 fusion-associated small transmembrane (FAST protein that is essential for pore formation during cell-cell fusion and syncytiogenesis. NMR spectroscopy and mutational studies indicate the dependence of this FLiPS on a hydrophobic helix-loop-helix structure. Biochemical and biophysical assays reveal the p15 FLiPS preferentially partitions into membranes with high positive curvature, and this partitioning is impeded by bis-ANS, a small molecule that inserts into hydrophobic defects in membranes. Most notably, the p15 FLiPS can be functionally replaced by heterologous amphipathic lipid packing sensors (ALPS but not by other membrane-interactive amphipathic helices. Furthermore, a previously unrecognized amphipathic helix in the cytosolic domain of the reptilian reovirus p14 FAST protein can functionally replace the p15 FLiPS, and is itself replaceable by a heterologous ALPS motif. Anchored near the cytoplasmic leaflet by the FAST protein transmembrane domain, the FLiPS is perfectly positioned to insert into hydrophobic defects that begin to appear in the highly curved rim of nascent fusion pores, thereby lowering the energy barrier to stable pore formation.

  16. Electromechanical vortex filaments during cardiac fibrillation

    Science.gov (United States)

    Christoph, J.; Chebbok, M.; Richter, C.; Schröder-Schetelig, J.; Bittihn, P.; Stein, S.; Uzelac, I.; Fenton, F. H.; Hasenfuß, G.; Gilmour, R. F., Jr.; Luther, S.

    2018-03-01

    The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.

  17. Does in-hospital ventricular fibrillation affect prognosis after myocardial infarction?

    DEFF Research Database (Denmark)

    Jensen, G V; Torp-Pedersen, C; Hildebrandt, P

    1997-01-01

    with ventricular fibrillation in time intervals, indicated that the importance of ventricular fibrillation for risk of death was exhausted during the initial 60 days after infarction. CONCLUSION: Ventricular fibrillation is associated with an independent increased risk of death within 0-60 days after infarction......AIM: The aim of this study was to estimate the prognostic information to be gained from ventricular fibrillation in patients with myocardial infarction. METHODS AND RESULTS: We studied 4259 consecutive patients with myocardial infarction admitted to one centre in 1977-1988. Five hundred and twenty......-eight (12.4%) of the patients had ventricular fibrillation in hospital. The following risk factors were included in multivariate models to estimate their importance for 30-day and long-term (median 7 year) prognosis: age, gender, ventricular fibrillation, congestive heart failure, pulmonary oedema...

  18. Atrial fibrillation

    DEFF Research Database (Denmark)

    Olesen, Morten S; Nielsen, Morten W; Haunsø, Stig

    2014-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting 1-2% of the general population. A number of studies have demonstrated that AF, and in particular lone AF, has a substantial genetic component. Monogenic mutations in lone and familial AF, although rare, have been recognized...

  19. Contact Stress Analysis for Gears of Different Helix Angle Using Finite Element Method

    Directory of Open Access Journals (Sweden)

    Patil Santosh

    2014-07-01

    Full Text Available The gear contact stress problem has been a great point of interest for many years, but still an extensive research is required to understand the various parameters affecting this stress. Among such parameters, helix angle is one which has played a crucial role in variation of contact stress. Numerous studies have been carried out on spur gear for contact stress variation. Hence, the present work is an attempt to study the contact stresses among the helical gear pairs, under static conditions, by using a 3D finite element method. The helical gear pairs on which the analysis is carried are 0, 5, 15, 25 degree helical gear sets. The Lagrange multiplier algorithm has been used between the contacting pairs to determine the stresses. The helical gear contact stress is evaluated using FE model and results have also been found at different coefficient of friction, varying from 0.0 to 0.3. The FE results have been further compared with the analytical calculations. The analytical calculations are based upon Hertz and AGMA equations, which are modified to include helix angle. The commercial finite element software was used in the study and it was shown that this approach can be applied to gear design efficiently. The contact stress results have shown a decreasing trend, with increase in helix angle.

  20. The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

    International Nuclear Information System (INIS)

    Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G.

    2012-01-01

    Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: ► All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. ► Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. ► Lys and Arg mutations most dramatically destabilize collagen fibril properties. ► Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

  1. Geometry of the toroidal N-helix: optimal-packing and zero-twist

    DEFF Research Database (Denmark)

    Olsen, Kasper; Bohr, Jakob

    2012-01-01

    Two important geometrical properties of N-helix structures are influenced by bending. One is maximizing the volume fraction, which is called optimal-packing, and the other is having a vanishing strain-twist coupling, which is called zero-twist. Zero-twist helices rotate neither in one nor...... helix. General N-helices are discussed, as well as zero-twist helices for N > 1. The derived geometrical restrictions are gradually modified by changing the aspect ratio of the torus....

  2. Essential Oils May Lead α-Synuclein towards Toxic Fibrils Formation

    Directory of Open Access Journals (Sweden)

    Dina Morshedi

    2016-01-01

    Full Text Available α-Synuclein (α-Syn fibrillation links with Parkinson’s disease (PD and several related syndromes. It is believed that exposure to the factors which promote fibrillation may induce and progress such neurodegenerative diseases (NDs. Herein, the effects of some wildly used essential oils including Myrtus communis (M. communis on α-Syn fibrillation were examined. M. communis particularly increased α-Syn fibrillation in a concentration dependent manner. Given that applications of M. communis are very extensive in Asian societies, especially Zoroastrians, this study was extended towards its role on α-Syn fibrillation/cytotoxicity. By using a unilamellar vesicle, it was shown that the aggregated species with tendency to perturb membrane were increased in the presence of M. communis. In this regard, the cytotoxicity of α-Syn on SH-SH5Y cells was also increased significantly. Inappropriately, the effects of fibrillation inhibitors, baicalein and cuminaldehyde, were modulated in the presence of M. communis. However, major components of M. communis did not induce fibrillation and also the effect of M. communis was limited on other fibrinogenic proteins. Assuming that essential oils have the ability to pass through the blood brain barrier (BBB along with the popular attention on aromatherapy for the incurable ND, these findings suggest an implementation of fibrillation tests for essential oils.

  3. Prediction of paroxysmal atrial fibrillation using recurrence plot-based features of the RR-interval signal

    International Nuclear Information System (INIS)

    Mohebbi, Maryam; Ghassemian, Hassan

    2011-01-01

    Atrial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of stroke. Predicting the onset of paroxysmal AF (PAF), based on noninvasive techniques, is clinically important and can be invaluable in order to avoid useless therapeutic intervention and to minimize risks for the patients. In this paper, we propose an effective PAF predictor which is based on the analysis of the RR-interval signal. This method consists of three steps: preprocessing, feature extraction and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the RR-interval signal is extracted. In the next step, the recurrence plot (RP) of the RR-interval signal is obtained and five statistically significant features are extracted to characterize the basic patterns of the RP. These features consist of the recurrence rate, length of longest diagonal segments (L max  ), average length of the diagonal lines (L mean ), entropy, and trapping time. Recurrence quantification analysis can reveal subtle aspects of dynamics not easily appreciated by other methods and exhibits characteristic patterns which are caused by the typical dynamical behavior. In the final step, a support vector machine (SVM)-based classifier is used for PAF prediction. The performance of the proposed method in prediction of PAF episodes was evaluated using the Atrial Fibrillation Prediction Database (AFPDB) which consists of both 30 min ECG recordings that end just prior to the onset of PAF and segments at least 45 min distant from any PAF events. The obtained sensitivity, specificity, positive predictivity and negative predictivity were 97%, 100%, 100%, and 96%, respectively. The proposed methodology presents better results than other existing approaches

  4. Dronedarone in high-risk permanent atrial fibrillation

    DEFF Research Database (Denmark)

    Connolly, Stuart J; Camm, A John; Halperin, Jonathan L

    2011-01-01

    Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events...... in high-risk permanent atrial fibrillation....

  5. Newer Anticoagulants for Non-Valvular Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Joseph M. Harburger

    2012-05-01

    Full Text Available Non-valvular atrial fibrillation is a recognized risk factor for stroke and systemic embolism. It has been clearly established that warfarin reduces the risk of stroke and systemic embolism in persons with atrial fibrillation and additional risk factors for stroke. The use of warfarin, however, requires frequent monitoring, and there is great variability in patient response to warfarin. Warfarin interacts with several medications and foods. In addition, warfarin use portends a significant risk of bleeding. For these reasons, warfarin is frequently not prescribed to persons for whom the drug would provide a clear benefit. Over the past decade, attempts have been made to develop drugs that are at least as safe and effective as warfarin for the treatment of atrial fibrillation that do not require monitoring nor have as many interactions. Initial studies of compounds in this regard ultimately failed due to safety concerns, but over the past two years two novel agents have been approved by the United States Food and Drug Association for anticoagulation in non-valvular atrial fibrillation, another drug is under review, and additional compounds are being studied. This article will review the use of warfarin and these new agents in the treatment of non-valvular atrial fibrillation.

  6. Probing the mechanism of insulin fibril formation with insulin mutants.

    Science.gov (United States)

    Nielsen, L; Frokjaer, S; Brange, J; Uversky, V N; Fink, A L

    2001-07-27

    The molecular basis of insulin fibril formation was investigated by studying the structural properties and kinetics of fibril formation of 20 different human insulin mutants at both low pH (conditions favoring monomer/dimer) and at pH 7.4 (conditions favoring tetramer/hexamer). Small-angle X-ray scattering showed insulin to be monomeric in 20% acetic acid, 0.1 M NaCl, pH 2. The secondary structure of the mutants was assessed using far-UV circular dichroism, and the tertiary structure was determined using near-UV circular dichroism, quenching of intrinsic fluorescence by acrylamide and interactions with the hydrophobic probe 1-anilino-8-naphthalene-sulfonic acid (ANS). The kinetics of fibril formation were monitored with the fluorescent dye, Thioflavin T. The results indicate that the monomer is the state from which fibrils arise, thus under some conditions dissociation of hexamers may be rate limiting or partially rate limiting. The insulin mutants were found to retain substantial nativelike secondary and tertiary structure under all conditions studied. The results suggest that fibril formation of the insulin mutants is controlled by specific molecular interactions that are sensitive to variations in the primary structure. The observed effects of several mutations on the rate of fibril formation are inconsistent with a previously suggested model for fibrillation [Brange, J., Whittingham, J., Edwards, D., Youshang, Z., Wollmer, A., Brandenburg, D., Dodson, G., and Finch, J. (1997) Curr. Sci. 72, 470-476]. Two surfaces on the insulin monomer are identified as potential interacting sites in insulin fibrils, one consisting of the residues B10, B16, and B17 and the other consisting of at least the residues A8 and B25. The marked increase in the lag time for fibril formation with mutations to more polar residues, as well as mutations to charged residues, demonstrates the importance of both hydrophobic and electrostatic interactions in the initial stages of fibrillation

  7. Treatment Guidelines of Atrial Fibrillation (AFib or AF)

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Treatment Guidelines of Atrial Fibrillation (AFib or AF) Updated:Jun 28,2017 What are the treatment guidelines for atrial fibrillation? Medical guidelines are written by ...

  8. Progesterone modulation of transmembrane helix-helix interactions between the α-subunit of Na/K-ATPase and phospholipid N-methyltransferase in the oocyte plasma membrane

    Directory of Open Access Journals (Sweden)

    Askari Amir

    2010-05-01

    Full Text Available Abstract Background Progesterone binding to the surface of the amphibian oocyte initiates the meiotic divisions. Our previous studies with Rana pipiens oocytes indicate that progesterone binds to a plasma membrane site within the external loop between the M1 and M2 helices of the α-subunit of Na/K-ATPase, triggering a cascade of lipid second messengers and the release of the block at meiotic prophase. We have characterized this site, using a low affinity ouabain binding isoform of the α1-subunit. Results Preparations of isolated plasma membranes from Rana oocytes demonstrate that physiological levels of progesterone (or the non-metabolizable progestin R5020 successively activate phosphatidylethanolamine-N-methyltransferase (PE-NMT and sphingomyelin synthase within seconds. Inhibition of PE-NMT blocks the progesterone induction of meiosis in intact oocytes, whereas its initial product, phosphatidylmonomethylethanolamine (PME, can itself initiate meiosis in the presence of the inhibitor. Published X-ray crystallographic data on Na/K-ATPase, computer-generated 3D projections, heptad repeat analysis and hydrophobic cluster analysis of the transmembrane helices predict that hydrophobic residues L, V, V, I, F and Y of helix M2 of the α1-subunit interact with F, L, G, L, L and F, respectively, of helix M3 of PE-NMT. Conclusion We propose that progesterone binding to the first external loop of the α1-subunit facilitates specific helix-helix interactions between integral membrane proteins to up-regulate PE-NMT, and, that successive interactions between two or more integral plasma membrane proteins induce the signaling cascades which result in completion of the meiotic divisions.

  9. Iowa Mutant Apolipoprotein A-I (ApoA-IIowa) Fibrils Target Lysosomes.

    Science.gov (United States)

    Kameyama, Hirokazu; Nakajima, Hiroyuki; Nishitsuji, Kazuchika; Mikawa, Shiho; Uchimura, Kenji; Kobayashi, Norihiro; Okuhira, Keiichiro; Saito, Hiroyuki; Sakashita, Naomi

    2016-07-28

    The single amino acid mutation G26R in human apolipoprotein A-I (apoA-IIowa) is the first mutation that was associated with familial AApoA1 amyloidosis. The N-terminal fragments (amino acid residues 1-83) of apoA-I containing this mutation deposit as amyloid fibrils in patients' tissues and organs, but the mechanisms of cellular degradation and cytotoxicity have not yet been clarified. In this study, we demonstrated degradation of apoA-IIowa fibrils via the autophagy-lysosomal pathway in human embryonic kidney 293 cells. ApoA-IIowa fibrils induced an increase in lysosomal pH and the cytosolic release of the toxic lysosomal protease cathepsin B. The mitochondrial dysfunction caused by apoA-IIowa fibrils depended on cathepsin B and was ameliorated by increasing the degradation of apoA-IIowa fibrils. Thus, although apoA-IIowa fibril transport to lysosomes and fibril degradation in lysosomes may have occurred, the presence of an excess number of apoA-IIowa fibrils, more than the lysosomes could degrade, may be detrimental to cells. Our results thus provide evidence that the target of apoA-IIowa fibrils is lysosomes, and we thereby gained a novel insight into the mechanism of AApoA1 amyloidosis.

  10. Amide proton solvent protection in amylin fibrils probed by quenched hydrogen exchange NMR.

    Directory of Open Access Journals (Sweden)

    Andrei T Alexandrescu

    Full Text Available Amylin is an endocrine hormone that accumulates in amyloid plaques in patients with advanced type 2 diabetes. The amyloid plaques have been implicated in the destruction of pancreatic β-cells, which synthesize amylin and insulin. To better characterize the secondary structure of amylin in amyloid fibrils we assigned the NMR spectrum of the unfolded state in 95% DMSO and used a quenched hydrogen-deuterium exchange technique to look at amide proton solvent protection in the fibrils. In this technique, partially exchanged fibrils are dissolved in 95% DMSO and information about amide proton occupancy in the fibrils is determined from DMSO-denatured monomers. Hydrogen exchange lifetimes at pH 7.6 and 37°C vary between ∼5 h for the unstructured N-terminus to 600 h for amide protons in the two β-strands that form inter-molecular hydrogen bonds between amylin monomers along the length of the fibril. Based on the protection data we conclude that residues A8-H18 and I26-Y37 comprise the two β-strands in amylin fibrils. There is variation in protection within the β-strands, particularly for strand β1 where only residues F15-H18 are strongly protected. Differences in protection appear to be due to restrictions on backbone dynamics imposed by the packing of two-layers of C2-symmetry-related β-hairpins in the protofilament structure, with strand β1 positioned on the surface and β2 in the interior.

  11. The effect of point mutations on structure and mechanical properties of collagen-like fibril: A molecular dynamics study

    Energy Technology Data Exchange (ETDEWEB)

    Marlowe, Ashley E.; Singh, Abhishek; Yingling, Yaroslava G., E-mail: yara_yingling@ncsu.edu

    2012-12-01

    Understanding sequence dependent mechanical and structural properties of collagen fibrils is important for the development of artificial biomaterials for medical and nanotechnological applications. Moreover, point mutations are behind many collagen associated diseases, including Osteogenesis Imperfecta (OI). We conducted a combination of classical and steered atomistic molecular dynamics simulations to examine the effect of point mutations on structure and mechanical properties of short collagen fibrils which include mutations of glycine to alanine, aspartic acid, cysteine, and serine or mutations of hydroxyproline to arginine, asparagine, glutamine, and lysine. We found that all mutations disrupt structure and reduce strength of the collagen fibrils, which may affect the hierarchical packing of the fibrils. The glycine mutations were more detrimental to mechanical strength of the fibrils (WT > Ala > Ser > Cys > Asp) than that of hydroxyproline (WT > Arg > Gln > Asn > Lys). The clinical outcome for glycine mutations agrees well with the trend in reduction of fibril's tensile strength predicted by our simulations. Overall, our results suggest that the reduction in mechanical properties of collagen fibrils may be used to predict the clinical outcome of mutations. Highlights: Black-Right-Pointing-Pointer All mutations disrupt structure and bonding pattern and reduce strength of the collagen fibrils. Black-Right-Pointing-Pointer Gly based mutations are worst to mechanical integrity of fibrils than that of Hyp. Black-Right-Pointing-Pointer Lys and Arg mutations most dramatically destabilize collagen fibril properties. Black-Right-Pointing-Pointer Clinical outcome of mutations may be related to the reduced mechanical properties of fibrils.

  12. Meta-analysis identifies six new susceptibility loci for atrial fibrillation

    NARCIS (Netherlands)

    Ellinor, Patrick T; Lunetta, Kathryn L; Albert, Christine M; Glazer, Nicole L; Ritchie, Marylyn D; Smith, Albert V; Arking, Dan E; Müller-Nurasyid, Martina; Krijthe, Bouwe P; Lubitz, Steven A; Bis, Joshua C; Chung, Mina K; Dörr, Marcus; Ozaki, Kouichi; Roberts, Jason D; Smith, J Gustav; Pfeufer, Arne; Sinner, Moritz F; Lohman, Kurt; Ding, Jingzhong; Smith, Nicholas L; Smith, Jonathan D; Rienstra, Michiel; Rice, Kenneth M; Van Wagoner, David R; Magnani, Jared W; Wakili, Reza; Clauss, Sebastian; Rotter, Jerome I; Steinbeck, Gerhard; Launer, Lenore J; Davies, Robert W; Borkovich, Matthew; Harris, Tamara B; Lin, Honghuang; Völker, Uwe; Völzke, Henry; Milan, David J; Hofman, Albert; Boerwinkle, Eric; Chen, Lin Y; Soliman, Elsayed Z; Voight, Benjamin F; Li, Guo; Chakravarti, Aravinda; Kubo, Michiaki; Tedrow, Usha B; Rose, Lynda M; Ridker, Paul M; Conen, David; Tsunoda, Tatsuhiko; Furukawa, Tetsushi; Sotoodehnia, Nona; Xu, Siyan; Kamatani, Naoyuki; Levy, Daniel; Nakamura, Yusuke; Parvez, Babar; Mahida, Saagar; Furie, Karen L; Rosand, Jonathan; Muhammad, Raafia; Psaty, Bruce M; Meitinger, Thomas; Perz, Siegfried; Wichmann, H-Erich; Witteman, Jacqueline C M; Kao, W H Linda; Kathiresan, Sekar; Roden, Dan M; Uitterlinden, Andre G; Rivadeneira, Fernando; McKnight, Barbara; Sjögren, Marketa; Newman, Anne B; Liu, Yongmei; Gollob, Michael H; Melander, Olle; Tanaka, Toshihiro; Stricker, Bruno H Ch; Felix, Stephan B; Alonso, Alvaro; Darbar, Dawood; Barnard, John; Chasman, Daniel I; Heckbert, Susan R; Benjamin, Emelia J; Gudnason, Vilmundur; Kääb, Stefan

    Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation

  13. Analysis of brain natriuretic peptide in 30 patients with atrial fibrillation

    International Nuclear Information System (INIS)

    Jin Qiang; Lu Jianghui; Li Weipeng; Yuan Yuan; Sun Weili

    2009-01-01

    To investigate the relationship between atrial fibrillation and brain natriuretic peptide (BNP), plasma levels of BNP in 30 patients with atrial fibrillation and 30 health controls were assayed and compared. The results showed that plasma levels of BNP in patients with atrial fibrillation were significantly higher than those of health controls (P<0.05). When the patients with atrial fibrillation were restored sinus rhythm, the concentration of BNP decreased significantly (P<0.05). BNP was a sensitive marker of cardiac dysfunction, and BNP was positively correlated with atrial fibrillation. (authors)

  14. Viscoelastic behavior of discrete human collagen fibrils

    DEFF Research Database (Denmark)

    Svensson, Rene; Hassenkam, Tue; P, Hansen

    2010-01-01

    Whole tendon and fibril bundles display viscoelastic behavior, but to the best of our knowledge this property has not been directly measured in single human tendon fibrils. In the present work an atomic force microscopy (AFM) approach was used for tensile testing of two human patellar tendon fibr...

  15. DNA binding specificity of the basic-helix-loop-helix protein MASH-1.

    Science.gov (United States)

    Meierhan, D; el-Ariss, C; Neuenschwander, M; Sieber, M; Stackhouse, J F; Allemann, R K

    1995-09-05

    Despite the high degree of sequence similarity in their basic-helix-loop-helix (BHLH) domains, MASH-1 and MyoD are involved in different biological processes. In order to define possible differences between the DNA binding specificities of these two proteins, we investigated the DNA binding properties of MASH-1 by circular dichroism spectroscopy and by electrophoretic mobility shift assays (EMSA). Upon binding to DNA, the BHLH domain of MASH-1 underwent a conformational change from a mainly unfolded to a largely alpha-helical form, and surprisingly, this change was independent of the specific DNA sequence. The same conformational transition could be induced by the addition of 20% 2,2,2-trifluoroethanol. The apparent dissociation constants (KD) of the complexes of full-length MASH-1 with various oligonucleotides were determined from half-saturation points in EMSAs. MASH-1 bound as a dimer to DNA sequences containing an E-box with high affinity KD = 1.4-4.1 x 10(-14) M2). However, the specificity of DNA binding was low. The dissociation constant for the complex between MASH-1 and the highest affinity E-box sequence (KD = 1.4 x 10(-14) M2) was only a factor of 10 smaller than for completely unrelated DNA sequences (KD = approximately 1 x 10(-13) M2). The DNA binding specificity of MASH-1 was not significantly increased by the formation of an heterodimer with the ubiquitous E12 protein. MASH-1 and MyoD displayed similar binding site preferences, suggesting that their different target gene specificities cannot be explained solely by differential DNA binding. An explanation for these findings is provided on the basis of the known crystal structure of the BHLH domain of MyoD.

  16. Personalized management of atrial fibrillation

    DEFF Research Database (Denmark)

    Kirchhof, Paulus; Breithardt, Günter; Aliot, Etienne

    2013-01-01

    The management of atrial fibrillation (AF) has seen marked changes in past years, with the introduction of new oral anticoagulants, new antiarrhythmic drugs, and the emergence of catheter ablation as a common intervention for rhythm control. Furthermore, new technologies enhance our ability......, and hospitalizations. During the fourth Atrial Fibrillation competence NETwork/European Heart Rhythm Association (AFNET/EHRA) consensus conference, we identified the following opportunities to personalize management of AF in a better manner with a view to improve outcomes by integrating atrial morphology and damage...

  17. Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation.

    Science.gov (United States)

    Michaels, Thomas C T; Šarić, Anđela; Habchi, Johnny; Chia, Sean; Meisl, Georg; Vendruscolo, Michele; Dobson, Christopher M; Knowles, Tuomas P J

    2018-04-20

    Understanding how normally soluble peptides and proteins aggregate to form amyloid fibrils is central to many areas of modern biomolecular science, ranging from the development of functional biomaterials to the design of rational therapeutic strategies against increasingly prevalent medical conditions such as Alzheimer's and Parkinson's diseases. As such, there is a great need to develop models to mechanistically describe how amyloid fibrils are formed from precursor peptides and proteins. Here we review and discuss how ideas and concepts from chemical reaction kinetics can help to achieve this objective. In particular, we show how a combination of theory, experiments, and computer simulations, based on chemical kinetics, provides a general formalism for uncovering, at the molecular level, the mechanistic steps that underlie the phenomenon of amyloid fibril formation.

  18. Chemical Kinetics for Bridging Molecular Mechanisms and Macroscopic Measurements of Amyloid Fibril Formation

    Science.gov (United States)

    Michaels, Thomas C. T.; Šarić, Anđela; Habchi, Johnny; Chia, Sean; Meisl, Georg; Vendruscolo, Michele; Dobson, Christopher M.; Knowles, Tuomas P. J.

    2018-04-01

    Understanding how normally soluble peptides and proteins aggregate to form amyloid fibrils is central to many areas of modern biomolecular science, ranging from the development of functional biomaterials to the design of rational therapeutic strategies against increasingly prevalent medical conditions such as Alzheimer's and Parkinson's diseases. As such, there is a great need to develop models to mechanistically describe how amyloid fibrils are formed from precursor peptides and proteins. Here we review and discuss how ideas and concepts from chemical reaction kinetics can help to achieve this objective. In particular, we show how a combination of theory, experiments, and computer simulations, based on chemical kinetics, provides a general formalism for uncovering, at the molecular level, the mechanistic steps that underlie the phenomenon of amyloid fibril formation.

  19. The Basic/Helix-Loop-Helix Protein Family in Gossypium: Reference Genes and Their Evolution during Tetraploidization.

    Directory of Open Access Journals (Sweden)

    Qian Yan

    Full Text Available Basic/helix-loop-helix (bHLH proteins comprise one of the largest transcription factor families and play important roles in diverse cellular and molecular processes. Comprehensive analyses of the composition and evolution of the bHLH family in cotton are essential to elucidate their functions and the molecular basis of cotton development. By searching bHLH homologous genes in sequenced diploid cotton genomes (Gossypium raimondii and G. arboreum, a set of cotton bHLH reference genes containing 289 paralogs were identified and named as GobHLH001-289. Based on their phylogenetic relationships, these cotton bHLH proteins were clustered into 27 subfamilies. Compared to those in Arabidopsis and cacao, cotton bHLH proteins generally increased in number, but unevenly in different subfamilies. To further uncover evolutionary changes of bHLH genes during tetraploidization of cotton, all genes of S5a and S5b subfamilies in upland cotton and its diploid progenitors were cloned and compared, and their transcript profiles were determined in upland cotton. A total of 10 genes of S5a and S5b subfamilies (doubled from A- and D-genome progenitors maintained in tetraploid cottons. The major sequence changes in upland cotton included a 15-bp in-frame deletion in GhbHLH130D and a long terminal repeat retrotransposon inserted in GhbHLH062A, which eliminated GhbHLH062A expression in various tissues. The S5a and S5b bHLH genes of A and D genomes (except GobHLH062 showed similar transcription patterns in various tissues including roots, stems, leaves, petals, ovules, and fibers, while the A- and D-genome genes of GobHLH110 and GobHLH130 displayed clearly different transcript profiles during fiber development. In total, this study represented a genome-wide analysis of cotton bHLH family, and revealed significant changes in sequence and expression of these genes in tetraploid cottons, which paved the way for further functional analyses of bHLH genes in the cotton genus.

  20. Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes

    International Nuclear Information System (INIS)

    Morgan, Rhodri M. L.; Pal, Mohinder; Roe, S. Mark; Pearl, Laurence H.; Prodromou, Chrisostomos

    2015-01-01

    A helix swap involving the fifth helix between two adjacently bound Tah1 molecules restores the normal binding environment of the conserved MEEVD peptide of Hsp90. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes with Hsp90 and Tah1. Specific co-chaperone adaptors facilitate the recruitment of client proteins to the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus linking an eclectic set of client proteins to the R2TP complex for their assembly and regulation by Hsp90. Rather than the normal complement of seven α-helices seen in other tetratricopeptide repeat (TPR) domains, Tah1 unusually consists of the first five only. Consequently, the methionine of the MEEVD peptide remains exposed to solvent when bound by Tah1. In solution Tah1 appears to be predominantly monomeric, and recent structures have failed to explain how Tah1 appears to prevent the formation of mixed TPR domain-containing complexes such as Cpr6–(Hsp90) 2 –Tah1. To understand this further, the crystal structure of Tah1 in complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap involving the fifth α-helix between two adjacently bound Tah1 molecules. Dimerization of Tah1 restores the normal binding environment of the bound Hsp90 methionine residue by reconstituting a TPR binding site similar to that in seven-helix-containing TPR domain proteins. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes

  1. Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, Rhodri M. L.; Pal, Mohinder; Roe, S. Mark; Pearl, Laurence H., E-mail: laurence.pearl@sussex.ac.uk; Prodromou, Chrisostomos, E-mail: laurence.pearl@sussex.ac.uk [University of Sussex, Falmer, Brighton BN1 9RQ (United Kingdom)

    2015-05-01

    A helix swap involving the fifth helix between two adjacently bound Tah1 molecules restores the normal binding environment of the conserved MEEVD peptide of Hsp90. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes with Hsp90 and Tah1. Specific co-chaperone adaptors facilitate the recruitment of client proteins to the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus linking an eclectic set of client proteins to the R2TP complex for their assembly and regulation by Hsp90. Rather than the normal complement of seven α-helices seen in other tetratricopeptide repeat (TPR) domains, Tah1 unusually consists of the first five only. Consequently, the methionine of the MEEVD peptide remains exposed to solvent when bound by Tah1. In solution Tah1 appears to be predominantly monomeric, and recent structures have failed to explain how Tah1 appears to prevent the formation of mixed TPR domain-containing complexes such as Cpr6–(Hsp90){sub 2}–Tah1. To understand this further, the crystal structure of Tah1 in complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap involving the fifth α-helix between two adjacently bound Tah1 molecules. Dimerization of Tah1 restores the normal binding environment of the bound Hsp90 methionine residue by reconstituting a TPR binding site similar to that in seven-helix-containing TPR domain proteins. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes.

  2. Fluorophores, environments, and quantification techniques in the analysis of transmembrane helix interaction using FRET.

    Science.gov (United States)

    Khadria, Ambalika S; Senes, Alessandro

    2015-07-01

    Förster resonance energy transfer (FRET) has been widely used as a spectroscopic tool in vitro to study the interactions between transmembrane (TM) helices in detergent and lipid environments. This technique has been instrumental to many studies that have greatly contributed to quantitative understanding of the physical principles that govern helix-helix interactions in the membrane. These studies have also improved our understanding of the biological role of oligomerization in membrane proteins. In this review, we focus on the combinations of fluorophores used, the membrane mimetic environments, and measurement techniques that have been applied to study model systems as well as biological oligomeric complexes in vitro. We highlight the different formalisms used to calculate FRET efficiency and the challenges associated with accurate quantification. The goal is to provide the reader with a comparative summary of the relevant literature for planning and designing FRET experiments aimed at measuring TM helix-helix associations. © 2015 Wiley Periodicals, Inc.

  3. Poisson's ratio of collagen fibrils measured by small angle X-ray scattering of strained bovine pericardium

    Energy Technology Data Exchange (ETDEWEB)

    Wells, Hannah C.; Sizeland, Katie H.; Kayed, Hanan R.; Haverkamp, Richard G., E-mail: r.haverkamp@massey.ac.nz [School of Engineering and Advanced Technology, Massey University, Private Bag 11222, Palmerston North 4442 (New Zealand); Kirby, Nigel; Hawley, Adrian; Mudie, Stephen T. [Australian Synchrotron, 800 Blackburn Road, Clayton, Victoria 3168 (Australia)

    2015-01-28

    Type I collagen is the main structural component of skin, tendons, and skin products, such as leather. Understanding the mechanical performance of collagen fibrils is important for understanding the mechanical performance of the tissues that they make up, while the mechanical properties of bulk tissue are well characterized, less is known about the mechanical behavior of individual collagen fibrils. In this study, bovine pericardium is subjected to strain while small angle X-ray scattering (SAXS) patterns are recorded using synchrotron radiation. The change in d-spacing, which is a measure of fibril extension, and the change in fibril diameter are determined from SAXS. The tissue is strained 0.25 (25%) with a corresponding strain in the collagen fibrils of 0.045 observed. The ratio of collagen fibril width contraction to length extension, or the Poisson's ratio, is 2.1 ± 0.7 for a tissue strain from 0 to 0.25. This Poisson's ratio indicates that the volume of individual collagen fibrils decreases with increasing strain, which is quite unlike most engineering materials. This high Poisson's ratio of individual fibrils may contribute to high Poisson's ratio observed for tissues, contributing to some of the remarkable properties of collagen-based materials.

  4. Lifetime risk of atrial fibrillation according to optimal, borderline, or elevated levels of risk factors: cohort study based on longitudinal data from the Framingham Heart Study

    Science.gov (United States)

    Staerk, Laila; Wang, Biqi; Preis, Sarah R; Larson, Martin G; Lubitz, Steven A; Ellinor, Patrick T; McManus, David D; Ko, Darae; Weng, Lu-Chen; Lunetta, Kathryn L; Frost, Lars; Benjamin, Emelia J

    2018-01-01

    Abstract Objective To examine the association between risk factor burdens—categorized as optimal, borderline, or elevated—and the lifetime risk of atrial fibrillation. Design Community based cohort study. Setting Longitudinal data from the Framingham Heart Study. Participants Individuals free of atrial fibrillation at index ages 55, 65, and 75 years were assessed. Smoking, alcohol consumption, body mass index, blood pressure, diabetes, and history of heart failure or myocardial infarction were assessed as being optimal (that is, all risk factors were optimal), borderline (presence of borderline risk factors and absence of any elevated risk factor), or elevated (presence of at least one elevated risk factor) at index age. Main outcome measure Lifetime risk of atrial fibrillation at index age up to 95 years, accounting for the competing risk of death. Results At index age 55 years, the study sample comprised 5338 participants (2531 (47.4%) men). In this group, 247 (4.6%) had an optimal risk profile, 1415 (26.5%) had a borderline risk profile, and 3676 (68.9%) an elevated risk profile. The prevalence of elevated risk factors increased gradually when the index ages rose. For index age of 55 years, the lifetime risk of atrial fibrillation was 37.0% (95% confidence interval 34.3% to 39.6%). The lifetime risk of atrial fibrillation was 23.4% (12.8% to 34.5%) with an optimal risk profile, 33.4% (27.9% to 38.9%) with a borderline risk profile, and 38.4% (35.5% to 41.4%) with an elevated risk profile. Overall, participants with at least one elevated risk factor were associated with at least 37.8% lifetime risk of atrial fibrillation. The gradient in lifetime risk across risk factor burden was similar at index ages 65 and 75 years. Conclusions Regardless of index ages at 55, 65, or 75 years, an optimal risk factor profile was associated with a lifetime risk of atrial fibrillation of about one in five; this risk rose to more than one in three in individuals with at least

  5. Interactions between an alpha-helix and a beta-sheet. Energetics of alpha/beta packing in proteins.

    Science.gov (United States)

    Chou, K C; Némethy, G; Rumsey, S; Tuttle, R W; Scheraga, H A

    1985-12-05

    Conformational energy computations have been carried out to determine the favorable ways of packing a right-handed alpha-helix on a right-twisted antiparallel or parallel beta-sheet. Co-ordinate transformations have been developed to relate the position and orientation of the alpha-helix to the beta-sheet. The packing was investigated for a CH3CO-(L-Ala)16-NHCH3 alpha-helix interacting with five-stranded beta-sheets composed of CH3CO-(L-Val)6-NHCH3 chains. All internal and external variables for both the alpha-helix and the beta-sheet were allowed to change during energy minimization. Four distinct classes of low-energy packing arrangements were found for the alpha-helix interacting with both the parallel and the anti-parallel beta-sheet. The classes differ in the orientation of the axis of the alpha-helix relative to the direction of the strands of the right-twisted beta-sheet. In the class with the most favorable arrangement, the alpha-helix is oriented along the strands of the beta-sheet, as a result of attractive non-bonded side-chain-side-chain interactions along the entire length of the alpha-helix. A class with nearly perpendicular orientation of the helix axis to the strands is also of low energy, because it allows similarly extensive attractive interactions. In the other two classes, the helix is oriented diagonally relative to the strands of the beta-sheet. In one of them, it interacts with the convex surface near the middle of the saddle-shaped twisted beta-sheet. In the other, it is oriented along the concave diagonal of the beta-sheet and, therefore, it interacts only with the corner regions of the sheet, so that this packing is energetically less favorable. The packing arrangements involving an antiparallel and a parallel beta-sheet are generally similar, although the antiparallel beta-sheet has been found to be more flexible. The major features of 163 observed alpha/beta packing arrangements in 37 proteins are accounted for in terms of the computed

  6. Bending of Euler-Bernoulli nanobeams based on the strain-driven and stress-driven nonlocal integral models: a numerical approach

    Science.gov (United States)

    Oskouie, M. Faraji; Ansari, R.; Rouhi, H.

    2018-04-01

    Eringen's nonlocal elasticity theory is extensively employed for the analysis of nanostructures because it is able to capture nanoscale effects. Previous studies have revealed that using the differential form of the strain-driven version of this theory leads to paradoxical results in some cases, such as bending analysis of cantilevers, and recourse must be made to the integral version. In this article, a novel numerical approach is developed for the bending analysis of Euler-Bernoulli nanobeams in the context of strain- and stress-driven integral nonlocal models. This numerical approach is proposed for the direct solution to bypass the difficulties related to converting the integral governing equation into a differential equation. First, the governing equation is derived based on both strain-driven and stress-driven nonlocal models by means of the minimum total potential energy. Also, in each case, the governing equation is obtained in both strong and weak forms. To solve numerically the derived equations, matrix differential and integral operators are constructed based upon the finite difference technique and trapezoidal integration rule. It is shown that the proposed numerical approach can be efficiently applied to the strain-driven nonlocal model with the aim of resolving the mentioned paradoxes. Also, it is able to solve the problem based on the strain-driven model without inconsistencies of the application of this model that are reported in the literature.

  7. Helix-length compensation studies reveal the adaptability of the VS ribozyme architecture

    OpenAIRE

    Lacroix-Labonté, Julie; Girard, Nicolas; Lemieux, Sébastien; Legault, Pascale

    2011-01-01

    Compensatory mutations in RNA are generally regarded as those that maintain base pairing, and their identification forms the basis of phylogenetic predictions of RNA secondary structure. However, other types of compensatory mutations can provide higher-order structural and evolutionary information. Here, we present a helix-length compensation study for investigating structure–function relationships in RNA. The approach is demonstrated for stem-loop I and stem-loop V of the Neurospora VS riboz...

  8. Gate-controlled switching between persistent and inverse persistent spin helix states

    International Nuclear Information System (INIS)

    Yoshizumi, K.; Sasaki, A.; Kohda, M.; Nitta, J.

    2016-01-01

    We demonstrate gate-controlled switching between persistent spin helix (PSH) state and inverse PSH state, which are detected by quantum interference effect on magneto-conductance. These special symmetric spin states showing weak localization effect give rise to a long spin coherence when the strength of Rashba spin-orbit interaction (SOI) is close to that of Dresselhaus SOI. Furthermore, in the middle of two persistent spin helix states, where the Rashba SOI can be negligible, the bulk Dresselhaus SOI parameter in a modulation doped InGaAs/InAlAs quantum well is determined.

  9. Gate-controlled switching between persistent and inverse persistent spin helix states

    Energy Technology Data Exchange (ETDEWEB)

    Yoshizumi, K.; Sasaki, A.; Kohda, M.; Nitta, J. [Department of Materials Science, Tohoku University, Sendai 980-8579 (Japan)

    2016-03-28

    We demonstrate gate-controlled switching between persistent spin helix (PSH) state and inverse PSH state, which are detected by quantum interference effect on magneto-conductance. These special symmetric spin states showing weak localization effect give rise to a long spin coherence when the strength of Rashba spin-orbit interaction (SOI) is close to that of Dresselhaus SOI. Furthermore, in the middle of two persistent spin helix states, where the Rashba SOI can be negligible, the bulk Dresselhaus SOI parameter in a modulation doped InGaAs/InAlAs quantum well is determined.

  10. The Quadruple Helix Model Enhancing Innovative Performance Of Indonesian Creative Industry

    Directory of Open Access Journals (Sweden)

    Sri Wahyu Lelly Hana Setyanti

    2017-11-01

    Full Text Available The creative industry in Indonesia has contributed positively to the national economic growth. Creative industry grows from the creativity and innovation performance of the business actors. The challenge of creative industry is how to completely understand the creative and innovative processes in business management. Therefore it requires an approach that combines the synergy between academicians entrepreneurs government and society in a quadruple helix model. The objective of this research is to develop a creativity model through a quadruple helix model in improving innovation performance of the creative industry.

  11. Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Saikat; Shi, Heliang; Habte, Habtom H.; Qin, Yali; Cho, Michael W., E-mail: mcho@iastate.edu

    2016-03-15

    The C-terminal alpha-helix of gp41 membrane-proximal external region (MPER; {sup 671}NWFDITNWLWYIK{sup 683}) encompassing 4E10/10E8 epitopes is an attractive target for HIV-1 vaccine development. We previously reported that gp41-HR1-54Q, a trimeric protein comprised of the MPER in the context of a stable six-helix bundle (6HB), induced strong immune responses against the helix, but antibodies were directed primarily against the non-neutralizing face of the helix. To better target 4E10/10E8 epitopes, we generated four putative fusion intermediates by introducing double point mutations or deletions in the heptad repeat region 1 (HR1) that destabilize 6HB in varying degrees. One variant, HR1-∆10-54K, elicited antibodies in rabbits that targeted W672, I675 and L679, which are critical for 4E10/10E8 recognition. Overall, the results demonstrated that altering structural parameters of 6HB can influence immunogenic properties of the MPER and antibody targeting. Further exploration of this strategy could allow development of immunogens that could lead to induction of 4E10/10E8-like antibodies. - Highlights: • Four gp41 MPER-based immunogens that resemble fusion intermediates were generated. • C-terminal region of MPER that contains 4E10/10E8 epitopes was highly immunogenic. • Altering 6HB structure can influence immunogenic properties of the MPER. • Induced antibodies targeted multiple residues critical for 4E10/10E8 binding. • Development of immunogens based on fusion intermediates is a promising strategy.

  12. Evaluation of a Pilot Surveillance System: Health and Environment Linked for Information Exchange in Atlanta (HELIX-Atlanta)

    Science.gov (United States)

    Meyer, P.; Shire, J.; Qualters, Judy; Daley, Randolph; Fiero, Leslie Todorov; Autry, Andy; Avchen, Rachel; Stock, Allison; Correa, Adolofo; Siffel, Csaba; hide

    2007-01-01

    CDC and its partners established the Health and Environment Linked for Information Exchange, Atlanta (HELIX-Atlanta) demonstration project, to develop linking and analysis methods that could be used by the National Environmental Public Health Tracking (EPHT) Network. Initiated in October 2003, the Metropolitan Atlanta-based collaborative conducted four projects: asthma and particulate air pollution, birth defects and ozone and particulate air pollution, childhood leukemia and traffic emissions, and children's blood lead testing and neighborhood risk factors for lead poisoning. This report provides an overview of the HELIX-Atlanta projects' goals, methods and outcomes. We discuss priority attributes and common issues and challenges and offer recommendations for implementation of the nascent national environmental public health tracking network.

  13. Fibril Formation from Pea Protein and Sesequent Gel Formation

    NARCIS (Netherlands)

    Munialo, C.D.; Martin, A.H.; Linden, van der E.; Jongh, de H.H.J.

    2014-01-01

    The objective of this study was to characterize fibrillar aggregates made using pea proteins, to assemble formed fibrils into protein-based gels, and to study the rheological behavior of these gels. Micrometer-long fibrillar aggregates were observed after pea protein solutions had been heated for 20

  14. Fibril Formation from Pea Protein and Subsequent Gel Formation

    NARCIS (Netherlands)

    Munialo, XC.D.; Martin, A.H.; Linden, E. van der; Jongh, H.H.J de

    2014-01-01

    The objective of this study was to characterize fibrillar aggregates made using pea proteins, to assemble formed fibrils into protein-based gels, and to study the rheological behavior of these gels. Micrometer-long fibrillar aggregates were observed after pea protein solutions had been heated for 20

  15. Mechanical properties of amyloid-like fibrils defined by secondary structures

    Science.gov (United States)

    Bortolini, C.; Jones, N. C.; Hoffmann, S. V.; Wang, C.; Besenbacher, F.; Dong, M.

    2015-04-01

    Amyloid and amyloid-like fibrils represent a generic class of highly ordered nanostructures that are implicated in some of the most fatal neurodegenerative diseases. On the other hand, amyloids, by possessing outstanding mechanical robustness, have also been successfully employed as functional biomaterials. For these reasons, physical and chemical factors driving fibril self-assembly and morphology are extensively studied - among these parameters, the secondary structures and the pH have been revealed to be crucial, since a variation in pH changes the fibril morphology and net chirality during protein aggregation. It is important to quantify the mechanical properties of these fibrils in order to help the design of effective strategies for treating diseases related to the presence of amyloid fibrils. In this work, we show that by changing pH the mechanical properties of amyloid-like fibrils vary as well. In particular, we reveal that these mechanical properties are strongly related to the content of secondary structures. We analysed and estimated the Young's modulus (E) by comparing the persistence length (Lp) - measured from the observation of TEM images by using statistical mechanics arguments - with the mechanical information provided by peak force quantitative nanomechanical property mapping (PF-QNM). The secondary structure content and the chirality are investigated by means of synchrotron radiation circular dichroism (SR-CD). Results arising from this study could be fruitfully used as a protocol to investigate other medical or engineering relevant peptide fibrils.Amyloid and amyloid-like fibrils represent a generic class of highly ordered nanostructures that are implicated in some of the most fatal neurodegenerative diseases. On the other hand, amyloids, by possessing outstanding mechanical robustness, have also been successfully employed as functional biomaterials. For these reasons, physical and chemical factors driving fibril self-assembly and morphology

  16. In vitro fibrillization of Alzheimer’s amyloid-β peptide (1-42)

    Energy Technology Data Exchange (ETDEWEB)

    Tiiman, Ann [Department of Gene Technology, Tallinn University of Technology, Tallinn 12618 (Estonia); Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, 106 91 (Sweden); Krishtal, Jekaterina; Palumaa, Peep; Tõugu, Vello, E-mail: vello.tougu@ttu.ee [Department of Gene Technology, Tallinn University of Technology, Tallinn 12618 (Estonia)

    2015-09-15

    The amyloid deposition in the form of extracellular fibrillar aggregates of amyloid-β (Aβ) peptide is a critical pathological event in Alzheimer’s disease. Here, we report a systematic investigation of the effects of environmental factors on the kinetics of Aβ fibrillization in vitro. The effects of Aβ42 peptide concentration, temperature, pH, added solvents and the ratio of Aβ40 and Aβ42 on the peptide fibrillization under agitated conditions was studied. The analysis show that the rate of fibril growth by monomer addition is not limited by diffusion but by rearrangement in the monomer structure, which is enhanced by low concentrations of fluorinated alcohols and characterized by the activation energy of 12 kcal/mol. Fibrillization rate decreases at pH values below 7.0 where simultaneous protonation of His 13 and 14 inhibits fibril formation. The lag period for Aβ42 was only twofold shorter and the fibril growth rate twofold faster than those of Aβ40. Lag period was shortened and the fibrillization rate was increased only at 90% content of Aβ42.

  17. Aspects epidemiologiques et etiologiques de la fibrillation ...

    African Journals Online (AJOL)

    Conclusion : La fibrillation auriculaire est fréquente chez l'adulte noir togolais. Ses étiologies sont dominées par l'hypertension artérielle et les cardiomyopathies dilatées. complications and stoke. Aim: Our aim was to study epidemiologic and etiologic aspects of atrial fibrillation in black togolese in hospital circle. Material ...

  18. FPGA helix tracking algorithm for PANDA

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Yutie; Galuska, Martin; Gessler, Thomas; Kuehn, Wolfgang; Lange, Jens Soeren; Muenchow, David [II. Physikalisches Institut, University of Giessen (Germany); Ye, Hua [Institute of High Energy Physics, CAS (China); Collaboration: PANDA-Collaboration

    2016-07-01

    The PANDA detector is a general-purpose detector for physics with high luminosity cooled antiproton beams, planed to operate at the FAIR facility in Darmstadt, Germany. The central detector includes a silicon Micro Vertex Detector (MVD) and a Straw Tube Tracker (STT). Without any hardware trigger, large amounts of raw data are streaming into the data acquisition system. The data reduction task is performed in the online system by reconstruction algorithms programmed on FPGAs (Field Programmable Gate Arrays) as first level and on a farm of GPUs or PCs as a second level. One important part in the system is the online track reconstruction. In this presentation, an online tracking algorithm for helix tracking reconstruction in the solenoidal field is shown. The VHDL-based algorithm is tested with different types of events, at different event rate. Furthermore, a study of T0 extraction from the tracking algorithm is performed. A concept of simultaneous tracking and T0 determination is presented.

  19. Fluctuations in the DNA double helix

    Science.gov (United States)

    Peyrard, M.; López, S. C.; Angelov, D.

    2007-08-01

    DNA is not the static entity suggested by the famous double helix structure. It shows large fluctuational openings, in which the bases, which contain the genetic code, are temporarily open. Therefore it is an interesting system to study the effect of nonlinearity on the physical properties of a system. A simple model for DNA, at a mesoscopic scale, can be investigated by computer simulation, in the same spirit as the original work of Fermi, Pasta and Ulam. These calculations raise fundamental questions in statistical physics because they show a temporary breaking of equipartition of energy, regions with large amplitude fluctuations being able to coexist with regions where the fluctuations are very small, even when the model is studied in the canonical ensemble. This phenomenon can be related to nonlinear excitations in the model. The ability of the model to describe the actual properties of DNA is discussed by comparing theoretical and experimental results for the probability that base pairs open an a given temperature in specific DNA sequences. These studies give us indications on the proper description of the effect of the sequence in the mesoscopic model.

  20. pH-jump induced α-helix folding of poly-L-glutamic acid

    International Nuclear Information System (INIS)

    Donten, Mateusz L.; Hamm, Peter

    2013-01-01

    Highlights: ► pH-jump as truly biomimetic tool to initiate non-equilibrium dynamics of biomolecules. ► Design criteria to widen the applicability of pH-jumps are developed. ► Folding of poly-L-Glu in dependence of starting pH, pH jump size and helix length. ► Length dependence provides strong evidence for a nucleation–propagation scenario. - Abstract: pH jumps are a truly biomimetic technique to initiate non-equilibrium dynamics of biomolecules. In this work, the pH jump induced α-helix folding of poly-L-glutamic acid is investigated upon proton release from o-nitrobenzaldehyde. The aim of this work is twofold: On the one hand, design criteria of pH jump experiments are discussed, on the other hand, the folding mechanism of poly-L-glutamic acid is clarified by probing the IR response of the amide I band. Its folding kinetics is studied in dependence of the starting pD, the size of the pD jump and the length of the helix. While no dependence on the first two parameters could be detected, the folding time varies from 0.6 μs to 1.8 μs for helix lengths of 20 residue to 440 residue, respectively. It converges to a long-length limit at about 50 residue, a result which is attributed to a nucleation–propagation mechanism

  1. Risk of atrial fibrillation and stroke in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Lindhardsen, Jesper; Ahlehoff, Ole; Gislason, Gunnar Hilmar

    2012-01-01

    To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke.......To determine if patients with rheumatoid arthritis have increased risk of atrial fibrillation and stroke....

  2. Structural and functional characteristics of myocard in patients with different forms of atrial fibrillation

    Directory of Open Access Journals (Sweden)

    L. I. Vasilyeva

    2015-02-01

    Full Text Available Aim. To study structural and functional characteristics of myocard in patients with different forms of atrial fibrillation. Atrial fibrillation is the most prevalent arrhythmia in clinical practice. Atrial fibrillation is a progressive disease: the duration of paroxysms increases over time and paroxysmal atrial fibrillation transforms to persistent, the last one becomes refractory to pharmacological and electrical cardioversion in time and transforms to permanent. So assessment of myocardial remodeling in patients with persistent and permanent atrial fibrillation is very actual. Methods and results. According to the aim of the study 133 patients with persistent atrial fibrillation and 100 patients with permanent atrial fibrillation were included into the study. Echocardiographic parameters of left and right atria function were studied. Conclusion. It was found that patients with persistent and permanent atrial fibrillation are characterized with both left and right atrias remodeling. Remodeling of the atrias is less pronounced in patients with permanent atrial fibrillation in comparison with persistent atrial fibrillation patients and arrhythmia recurrence.

  3. The atrial fibrillation ablation pilot study

    DEFF Research Database (Denmark)

    Arbelo, Elena; Brugada, Josep; Hindricks, Gerhard

    2014-01-01

    AIMS: The Atrial Fibrillation Ablation Pilot Study is a prospective registry designed to describe the clinical epidemiology of patients undergoing an atrial fibrillation (AFib) ablation, and the diagnostic/therapeutic processes applied across Europe. The aims of the 1-year follow-up were to analyse...... was achieved in 40.7% of patients (43.7% in paroxysmal AF; 30.2% in persistent AF; 36.7% in long-lasting persistent AF). A second ablation was required in 18% of the cases and 43.4% were under antiarrhythmic treatment. Thirty-three patients (2.5%) suffered an adverse event, 272 (21%) experienced a left atrial...... tachycardia, and 4 patients died (1 haemorrhagic stroke, 1 ventricular fibrillation in a patient with ischaemic heart disease, 1 cancer, and 1 of unknown cause). CONCLUSION: The AFib Ablation Pilot Study provided crucial information on the epidemiology, management, and outcomes of catheter ablation of AFib...

  4. Replica Exchange Simulations of the Thermodynamics of Aβ Fibril Growth

    Science.gov (United States)

    Takeda, Takako; Klimov, Dmitri K.

    2009-01-01

    Abstract Replica exchange molecular dynamics and an all-atom implicit solvent model are used to probe the thermodynamics of deposition of Alzheimer's Aβ monomers on preformed amyloid fibrils. Consistent with the experiments, two deposition stages have been identified. The docking stage occurs over a wide temperature range, starting with the formation of the first peptide-fibril interactions at 500 K. Docking is completed when a peptide fully adsorbs on the fibril edge at the temperature of 380 K. The docking transition appears to be continuous, and occurs without free energy barriers or intermediates. During docking, incoming Aβ monomer adopts a disordered structure on the fibril edge. The locking stage occurs at the temperature of ≈360 K and is characterized by the rugged free energy landscape. Locking takes place when incoming Aβ peptide forms a parallel β-sheet structure on the fibril edge. Because the β-sheets formed by locked Aβ peptides are typically off-registry, the structure of the locked phase differs from the structure of the fibril interior. The study also reports that binding affinities of two distinct fibril edges with respect to incoming Aβ peptides are different. The peptides bound to the concave edge have significantly lower free energy compared to those bound on the convex edge. Comparison with the available experimental data is discussed. PMID:19167295

  5. Heart failure and atrial fibrillation: current concepts and controversies.

    Science.gov (United States)

    Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

    1997-01-01

    Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

  6. Mechanism of death at high temperatures in Helix and Patella

    Energy Technology Data Exchange (ETDEWEB)

    Grainger, J N.R.

    1975-10-01

    In Patella vulgata and Helix aspersa which had been killed by exposure to high temperatures, the rates of oxygen consumption of gill, foot muscle and hepatopancreas are remarkably steady when measured at lower temperatures, although the absolute levels are in some cases different from normal animals. These tissues are thus substantially metabolically intact in heat dead individuals. In Helix there is a fall in blood sodium and a rise in blood potassium during heat death. In Patella there is a marked rise in blood Na/sup +/ and a consequent disturbance of the Na/sup +//K/sup +/ ratio. These ionic disturbances are thought to be a prime cause of heat death. The significance of the results is discussed.

  7. Patient-Reported Outcomes for Quality of Life Assessment in Atrial Fibrillation: A Systematic Review of Measurement Properties.

    Science.gov (United States)

    Kotecha, Dipak; Ahmed, Amar; Calvert, Melanie; Lencioni, Mauro; Terwee, Caroline B; Lane, Deirdre A

    2016-01-01

    Atrial fibrillation is a large and growing burden across all types of healthcare. Both incidence and prevalence are expected to double in the next 20 years, with huge impact on hospital admissions, costs and patient quality of life. Patient wellbeing determines the management strategy for atrial fibrillation, including the use of rhythm control therapy and the clinical success of heart rate control. Hence, evaluation of quality of life is an emerging and important part of the assessment of patients with atrial fibrillation. Although a number of questionnaires to assess quality of life in atrial fibrillation are available, a comprehensive overview of their measurement properties is lacking. We performed a systematic review of the measurement properties of atrial fibrillation-specific health-related quality of life questionnaires. Methodological quality was assessed using the Consensus based Standards for selection of health Measurement Instruments (COSMIN) checklist, with measurement properties rated for quality against optimal criteria and levels of evidence. We screened 2,216 articles, of which eight articles describing five questionnaires were eligible for inclusion: Atrial Fibrillation 6 (AF6), Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT), Atrial Fibrillation Quality of Life Questionnaire (AFQLQ), Atrial Fibrillation Quality of Life (AFQoL), and Quality of Life in Atrial Fibrillation (QLAF). Good reliability (internal consistency and test-retest reliability) was demonstrated for AF6, AFEQT, AFQLQ and AFQoL. Content, construct and criterion validity were positively rated only in AFEQT. Responsiveness was positively rated only in AFEQT, but with limited evidence. Overall, AFEQT showed strong positive evidence for 2 of 9 measurement properties, compared to one for AFQoL and none for the remaining questionnaires. Given the low ratings for many measurement properties, no single questionnaire can be recommended, although AFEQT performed strongest. Further

  8. Structural evaluation of an amyloid fibril model using small-angle x-ray scattering

    Science.gov (United States)

    Dahal, Eshan; Choi, Mina; Alam, Nadia; Bhirde, Ashwinkumar A.; Beaucage, Serge L.; Badano, Aldo

    2017-08-01

    Amyloid fibrils are highly structured protein aggregates associated with a wide range of diseases including Alzheimer’s and Parkinson’s. We report a structural investigation of an amyloid fibril model prepared from a commonly used plasma protein (bovine serum albumin (BSA)) using small-angle x-ray scattering (SAXS) technique. As a reference, the size estimates from SAXS are compared to dynamic light scattering (DLS) data and the presence of amyloid-like fibrils is confirmed using Congo red absorbance assay. Our SAXS results consistently show the structural transformation of BSA from spheroid to rod-like elongated structures during the fibril formation process. We observe the elongation of fibrils over two months with fibril length growing from 35.9  ±  3.0 nm to 51.5  ±  2.1 nm. Structurally metastable fibrils with distinct SAXS profiles have been identified. As proof of concept, we demonstrate the use of such distinct SAXS profiles to detect fibrils in the mixture solutions of two species by estimating their volume fractions. This easily detectable and well-characterized amyloid fibril model from BSA can be readily used as a control or standard reference to further investigate SAXS applications in the detection of structurally diverse amyloid fibrils associated with protein aggregation diseases.

  9. Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

    Directory of Open Access Journals (Sweden)

    Sinjan Choudhary

    Full Text Available We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

  10. Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

    Science.gov (United States)

    Choudhary, Sinjan; Save, Shreyada N; Kishore, Nand; Hosur, Ramakrishna V

    2016-01-01

    We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage. However, when presented as a mixture, we also see contribution of hydrophobic interactions. Thus, a co-operative adjustment of polar and hydrophobic interactions between the chaperones and the protein surface seems to drive the synergistic effects in the fibrillation process. In insulin, this synergy is quantitatively similar in all the stages of the fibrillation process. These observations would have significant implications for understanding protein folding concepts, in general, and for designing combination therapies against protein fibrillation, in particular.

  11. From Fibril Formation to Fibril Properties and Rheology of Food Materials

    NARCIS (Netherlands)

    Linden, van der E.; Venema, P.

    2013-01-01

    For control and design of food properties it is important to understand how molecules and their interactions give rise to formation of microstructures and resulting rheological properties. This will be illustrated by discussing the formation and properties of fibrils in aqueous and non-aqueous

  12. Visualisation of collagen fibrils in joint cartilage using STIM

    International Nuclear Information System (INIS)

    Reinert, T.; Reibetanz, U.; Vogt, J.; Butz, T.; Werner, A.; Gruender, W.

    2001-01-01

    The scanning transmission ion microscopy (STIM) method was used to investigate the collagen network structure of the articular cartilage from a pig's knee in comparison with high resolution nuclear magnetic resonance imaging (microscopic NMR-tomography) and polarised light microscopy (PLM). Single collagen fibrils down to 200 nm in diameter were visualised. It was proved that the cartilage collagen network consists partly of zones of oriented fibrils as suggested by NMR measurements. Radially oriented fibrils were found in the zone near the calcified zone (hypertrophic zone) of both tibia and femur, and in the tibial radial zone. Tangentially oriented fibrils were found in the femoral and tibial superficial zone and in a second zone of the femoral cartilage. Polarisation light microscopy reveals broader zones of orientation than it was found with STIM

  13. Insulin fibrillation: The influence and coordination of Zn2+

    DEFF Research Database (Denmark)

    Frankær, Christian Grundahl; Sønderby, Pernille; Bang, Maria Blanner

    2017-01-01

    fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy. The results were validated with fibre diffraction, Transmission...... Electron Microscopy and Thioflavin T fluorescence measurements. It is well-known that Zn2+ ions coordinate and stabilize the hexameric forms of insulin. However, this study is the first to show that zinc indeed binds to the insulin fibrils. Furthermore, zinc influences the kinetics and the morphology...... of the fibrils. It also shows that zinc coordinates to histidine residues in an environment, which is similar to the coordination seen in the insulin R6 hexamers, where three histidine residues and a chloride ion is coordinating the zinc....

  14. De novo design, synthesis and characterisation of MP3, a new catalytic four-helix bundle hemeprotein.

    Science.gov (United States)

    Faiella, Marina; Maglio, Ornella; Nastri, Flavia; Lombardi, Angela; Lista, Liliana; Hagen, Wilfred R; Pavone, Vincenzo

    2012-12-07

    A new artificial metalloenzyme, MP3 (MiniPeroxidase 3), designed by combining the excellent structural properties of four-helix bundle protein scaffolds with the activity of natural peroxidases, was synthesised and characterised. This new hemeprotein model was developed by covalently linking the deuteroporphyrin to two peptide chains of different compositions to obtain an asymmetric helix-loop-helix/heme/helix-loop-helix sandwich arrangement, characterised by 1) a His residue on one chain that acts as an axial ligand to the iron ion; 2) a vacant distal site that is able to accommodate exogenous ligands or substrates; and 3) an Arg residue in the distal site that should assist in hydrogen peroxide activation to give an HRP-like catalytic process. MP3 was synthesised and characterised as its iron complex. CD measurements revealed the high helix-forming propensity of the peptide, confirming the appropriateness of the model procedure; UV/Vis, MCD and EPR experiments gave insights into the coordination geometry and the spin state of the metal. Kinetic experiments showed that Fe(III)-MP3 possesses peroxidase-like activity comparable to R38A-hHRP, highlighting the possibility of mimicking the functional features of natural enzymes. The synergistic application of de novo design methods, synthetic procedures, and spectroscopic characterisation, described herein, demonstrates a method by which to implement and optimise catalytic activity for an enzyme mimetic. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.

    Directory of Open Access Journals (Sweden)

    The Quyen Nguyen

    Full Text Available Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC. Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain. Such a difference in orientation gives rise, at the N-terminal part of the groove, to the formation of one hydrophobic pocket, as well as to electrostatic variations at the groove surface. We present a comprehensive structural analysis of available KLC1/2-TPR domain structures that highlights that ligand binding into the groove can be specific of one or the other N-terminal capping helix orientations. Further, structural analysis reveals that the N-terminal capping helix is always involved in crystal packing contacts, especially in a TPR1:TPR1' contact which highlights its propensity to be a protein-protein interaction site. Together, these results underline that the structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding.

  16. Polymorphism, metastable species and interconversion: the many states of glucagon fibrils

    DEFF Research Database (Denmark)

    Ghodke, Shirin D; Jensen, Grethe Vestergaard; Svane, Anna Sigrid P.

    2014-01-01

    physicochemical conditions such as high temperature, pressure, mechanical and chemical stress. Factors such as peptide concentration, accessible surface area, surface hydration of the glucagon molecular state, contact surface, temperature and ionic strength all contribute to fibrillar structure and stability...... fibril upon incubation at elevated temperatures (but not vice versa), indicating that fibrils are fundamentally malleable if they have not attained the most stable fibrillar state. While the effect of pressure on glucagon is complex (accelerating fibrillation at intermediate pressures and decelerating...... it at higher pressures), the thermal expansion coefficients obtained from these studies agree well with our previous calorimetric studies to reveal reduced or increased hydration of fibrils (leading to reduced or increased stability) depending on fibrillation conditions. Finally, we report...

  17. NONPOTENTIALITY OF CHROMOSPHERIC FIBRILS IN NOAA ACTIVE REGIONS 11092 AND 9661

    International Nuclear Information System (INIS)

    Jing Ju; Yuan Yuan; Xu Yan; Wang Haimin; Reardon, Kevin; Wiegelmann, Thomas

    2011-01-01

    In this paper, we present a method to automatically segment chromospheric fibrils from Hα observations and further identify their orientation. We assume that chromospheric fibrils are aligned with the magnetic field. By comparing the orientation of the fibrils with the azimuth of the embedding chromospheric magnetic field extrapolated from a potential field model, the shear angle, a measure of nonpotentiality, along the fibrils is readily deduced. Following this approach, we make a quantitative assessment of the nonpotentiality of fibrils in two NOAA active regions (ARs): (1) the relatively simple AR 11092, observed with very high resolution by Interferometric Bidimensional Spectrometer, and (2) a β-γ-δ AR 9661, observed with median resolution by Big Bear Solar Observatory before and after an X1.6 flare.

  18. Direct visualization of HIV-enhancing endogenous amyloid fibrils in human semen

    Science.gov (United States)

    Usmani, Shariq M.; Zirafi, Onofrio; Müller, Janis; Sandi-Monroy, Nathallie; Yadav, Jay K.; Meier, Christoph; Weil, Tanja; Roan, Nadia R.; Greene, Warner C.; Walther, Paul; Nilsson, K. Peter R.; Hammarström, Per; Wetzel, Ronald; Pilcher, Christopher D.; Gagsteiger, Friedrich; Fändrich, Marcus; Kirchhoff, Frank; Münch, Jan

    2014-01-01

    Naturally occurring fragments of the abundant semen proteins prostatic acid phosphatase (PAP) and semenogelins form amyloid fibrils in vitro. These fibrils boost HIV infection and may play a key role in the spread of the AIDS pandemic. However, the presence of amyloid fibrils in semen remained to be demonstrated. Here, we use state of the art confocal and electron microscopy techniques for direct imaging of amyloid fibrils in human ejaculates. We detect amyloid aggregates in all semen samples and find that they partially consist of PAP fragments, interact with HIV particles and increase viral infectivity. Our results establish semen as a body fluid that naturally contains amyloid fibrils that are exploited by HIV to promote its sexual transmission. PMID:24691351

  19. Controlling chirality with helix inversion in cholesteric liquid crystals

    NARCIS (Netherlands)

    Katsonis, Nathalie Hélène; Lacaze, E.; Ferrarini, A.

    2012-01-01

    The helical organization of cholesteric liquid crystals is omnipresent in living matter. Achieving control over the structure of the cholesteric helix consequently holds great potential for developing stimuli-responsive materials matching the level of sophistication of biological systems. In

  20. What Is Atrial Fibrillation?

    Science.gov (United States)

    ANSWERS by heart Cardiovascular Conditions What Is Atrial Fibrillation? Your heart has a natural pacemaker, called the “sinus node,” that makes electrical signals. These signals cause the heart to contract and pump ...

  1. Antihypertensive treatment and risk of atrial fibrillation

    DEFF Research Database (Denmark)

    Marott, Sarah C W; Nielsen, Sune F; Benn, Marianne

    2014-01-01

    AIMS: To examine the associations between antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), β-blockers, diuretics, or calcium-antagonists, and risk of atrial fibrillation. We examined these associations using the entire Danish...... population from 1995 through 2010. METHODS AND RESULTS: Excluding medication used in atrial fibrillation, we matched individuals on ACEi monotherapy 1:1 with individuals on β-blocker (n = 48 658), diuretic (n = 69 630), calcium-antagonist (n = 57 646), and ARB monotherapy (n = 20 158). Likewise, individuals...... on ARB monotherapy were matched 1:1 with individuals on β-blocker (n = 20 566), diuretic (n = 20 832), calcium-antagonist (n = 20 232), and ACEi monotherapy (n = 20 158). All were free of atrial fibrillation and of predisposing diseases like heart failure, ischaemic heart disease, diabetes mellitus...

  2. Artificial Intelligence Methods Applied to Parameter Detection of Atrial Fibrillation

    Science.gov (United States)

    Arotaritei, D.; Rotariu, C.

    2015-09-01

    In this paper we present a novel method to develop an atrial fibrillation (AF) based on statistical descriptors and hybrid neuro-fuzzy and crisp system. The inference of system produce rules of type if-then-else that care extracted to construct a binary decision system: normal of atrial fibrillation. We use TPR (Turning Point Ratio), SE (Shannon Entropy) and RMSSD (Root Mean Square of Successive Differences) along with a new descriptor, Teager- Kaiser energy, in order to improve the accuracy of detection. The descriptors are calculated over a sliding window that produce very large number of vectors (massive dataset) used by classifier. The length of window is a crisp descriptor meanwhile the rest of descriptors are interval-valued type. The parameters of hybrid system are adapted using Genetic Algorithm (GA) algorithm with fitness single objective target: highest values for sensibility and sensitivity. The rules are extracted and they are part of the decision system. The proposed method was tested using the Physionet MIT-BIH Atrial Fibrillation Database and the experimental results revealed a good accuracy of AF detection in terms of sensitivity and specificity (above 90%).

  3. Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Robin Lemmens

    2011-01-01

    Full Text Available Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease.

  4. Equilibrium shift in solution: molecular shape recognition and precipitation of a synthetic double helix using helicene-grafted silica nanoparticles.

    Science.gov (United States)

    Miyagawa, Masamichi; Ichinose, Wataru; Yamaguchi, Masahiko

    2014-01-27

    Chiral silica nanoparticles (70 nm) grafted with (P)-helicene recognized the molecular shape of double helix and random coil (P)-ethynylhelicene oligomers in solution. A mixture of the (P)-nanoparticles and double helix precipitated much faster than a mixture of the (P)-nanoparticles and random coil, and the precipitate contained only the double helix. The mixture of the (P)-nanoparticles and (P)-ethynylhelicene pentamer reversibly dispersed in trifluoromethylbenzene upon heating at 70 °C and precipitated upon cooling at 25 °C. When a 10:90 equilibrium mixture of the double helix and random coil in solution was treated with the (P)-nanoparticles, the double helix was precipitated in 53% yield and was accompanied by equilibrium shift. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Analysis of amyloid fibrils in the cheetah (Acinonyx jubatus).

    Science.gov (United States)

    Bergström, Joakim; Ueda, Mitsuharu; Une, Yumi; Sun, Xuguo; Misumi, Shogo; Shoji, Shozo; Ando, Yukio

    2006-06-01

    Recently, a high prevalence of amyloid A (AA) amyloidosis has been documented among captive cheetahs worldwide. Biochemical analysis of amyloid fibrils extracted from the liver of a Japanese captive cheetah unequivocally showed that protein AA was the main fibril constituent. Further characterization of the AA fibril components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis revealed three main protein AA bands with approximate molecular weights of 8, 10 and 12 kDa. Mass spectrometry analysis of the 12-kDa component observed in SDS-PAGE and Western blotting confirmed the molecular weight of a 12,381-Da peak. Our finding of a 12-kDa protein AA component provides evidence that the cheetah SAA sequence is longer than the previously reported 90 amino acid residues (approximately 10 kDa), and hence SAA is part of the amyloid fibril.

  6. La fibrillation auriculaire chez le noir Africain: Aspects ...

    African Journals Online (AJOL)

    In this retrospective work realized during two years (1st january 2002 to 31 december 2003), relative to 300 cases hospitalized at the Cardiology Institute of Abidjan, the authors have studied the epidemiologic, etiologic and prognosis factors of black african atrial fibrillation in hospital cercle. The atrial fibrillation was the most ...

  7. Analysis of XFEL serial diffraction data from individual crystalline fibrils

    Directory of Open Access Journals (Sweden)

    David H. Wojtas

    2017-11-01

    Full Text Available Serial diffraction data collected at the Linac Coherent Light Source from crystalline amyloid fibrils delivered in a liquid jet show that the fibrils are well oriented in the jet. At low fibril concentrations, diffraction patterns are recorded from single fibrils; these patterns are weak and contain only a few reflections. Methods are developed for determining the orientation of patterns in reciprocal space and merging them in three dimensions. This allows the individual structure amplitudes to be calculated, thus overcoming the limitations of orientation and cylindrical averaging in conventional fibre diffraction analysis. The advantages of this technique should allow structural studies of fibrous systems in biology that are inaccessible using existing techniques.

  8. Phylogeny, Functional Annotation, and Protein Interaction Network Analyses of the Xenopus tropicalis Basic Helix-Loop-Helix Transcription Factors

    Directory of Open Access Journals (Sweden)

    Wuyi Liu

    2013-01-01

    Full Text Available The previous survey identified 70 basic helix-loop-helix (bHLH proteins, but it was proved to be incomplete, and the functional information and regulatory networks of frog bHLH transcription factors were not fully known. Therefore, we conducted an updated genome-wide survey in the Xenopus tropicalis genome project databases and identified 105 bHLH sequences. Among the retrieved 105 sequences, phylogenetic analyses revealed that 103 bHLH proteins belonged to 43 families or subfamilies with 46, 26, 11, 3, 15, and 4 members in the corresponding supergroups. Next, gene ontology (GO enrichment analyses showed 65 significant GO annotations of biological processes and molecular functions and KEGG pathways counted in frequency. To explore the functional pathways, regulatory gene networks, and/or related gene groups coding for Xenopus tropicalis bHLH proteins, the identified bHLH genes were put into the databases KOBAS and STRING to get the signaling information of pathways and protein interaction networks according to available public databases and known protein interactions. From the genome annotation and pathway analysis using KOBAS, we identified 16 pathways in the Xenopus tropicalis genome. From the STRING interaction analysis, 68 hub proteins were identified, and many hub proteins created a tight network or a functional module within the protein families.

  9. Automatic detection of atrial fibrillation in cardiac vibration signals.

    Science.gov (United States)

    Brueser, C; Diesel, J; Zink, M D H; Winter, S; Schauerte, P; Leonhardt, S

    2013-01-01

    We present a study on the feasibility of the automatic detection of atrial fibrillation (AF) from cardiac vibration signals (ballistocardiograms/BCGs) recorded by unobtrusive bedmounted sensors. The proposed system is intended as a screening and monitoring tool in home-healthcare applications and not as a replacement for ECG-based methods used in clinical environments. Based on BCG data recorded in a study with 10 AF patients, we evaluate and rank seven popular machine learning algorithms (naive Bayes, linear and quadratic discriminant analysis, support vector machines, random forests as well as bagged and boosted trees) for their performance in separating 30 s long BCG epochs into one of three classes: sinus rhythm, atrial fibrillation, and artifact. For each algorithm, feature subsets of a set of statistical time-frequency-domain and time-domain features were selected based on the mutual information between features and class labels as well as first- and second-order interactions among features. The classifiers were evaluated on a set of 856 epochs by means of 10-fold cross-validation. The best algorithm (random forests) achieved a Matthews correlation coefficient, mean sensitivity, and mean specificity of 0.921, 0.938, and 0.982, respectively.

  10. Observation of helix associations for insertion of a retinal molecule and distortions of helix structures in bacteriorhodopsin

    Science.gov (United States)

    Urano, Ryo; Okamoto, Yuko

    2015-12-01

    We applied a newly proposed prediction method for membrane protein structures to bacteriorhodopsin that has distorted transmembrane helices in the native structure. This method uses an implicit membrane model, which restricts sampling space during folding in a membrane region, and includes helix bending. Replica-exchange simulations were performed with seven transmembrane helices only without a retinal molecule. Obtained structures were classified into clusters of similar structures, which correspond to local-minimum free energy states. The two lowest free energy states corresponded to a native-like structure with the correct empty space for retinal and a structure with this empty space filled with a helix. Previous experiments of bacteriorhodopsin suggested that association of transmembrane helices enables them to make a room for insertion of a retinal. Our results are consistent with these results. Moreover, distortions of helices in the native-like structures were successfully reproduced. In the distortions, whereas the locations of kinks for all helices were similar to those of Protein Data Bank's data, the amount of bends was more similar for helices away from the retinal than for those close to the retinal in the native structure. This suggests a hypothesis that the amino-acid sequence specifies the location of kinks in transmembrane helices and that the amount of distortions depends on the interactions with the surrounding molecules such as neighboring helices, lipids, and retinal.

  11. Kinetics for exchange of imino protons in the d(C-G-C-G-A-A-T-T-C-G-C-G) double helix and in two similar helices that contain a G . T base pair, d(C-G-T-G-A-A-T-T-C-G-C-G), and an extra adenine, d(C-G-C-A-G-A-A-T-T-C-G-C-G).

    Science.gov (United States)

    Pardi, A; Morden, K M; Patel, D J; Tinoco, I

    1982-12-07

    The relaxation lifetimes of imino protons from individual base pairs were measured in (I) a perfect helix, d(C-G-C-G-A-A-T-T-C-G-C-G), (II) this helix with a G . C base pair replaced with a G . T base pair, d(C-G-T-G-A-A-T-T-C-G-C-G), and (III) the perfect helix with an extra adenine base in a mismatch, d(C-G-C-A-G-A-A-T-T-C-G-C-G). The lifetimes were measured by saturation recovery proton nuclear magnetic resonance experiments performed on the imino protons of these duplexes. The measured lifetimes of the imino protons were shown to correspond to chemical exchange lifetimes at higher temperatures and spin-lattice relaxation times at lower temperatures. Comparison of the lifetimes in these duplexes showed that the destabilizing effect of the G . T base pair in II affected the opening rate of only the nearest-neighbor base pairs. For helix III, the extra adenine affected the opening rates of all the base pairs in the helix and thus was a larger perturbation for opening of the base pairs than the G . T base pair. The temperature dependence of the exchange rates of the imino proton in the perfect helix gives values of 14-15 kcal/mol for activation energies of A . T imino protons. These relaxation rates were shown to correspond to exchange involving individual base pair opening in this helix, which means that one base-paired imino proton can exchange independent of the others. For the other two helices that contain perturbations, much larger activation energies for exchange of the imino protons were found, indicating that a cooperative transition involving exchange of at least several base pairs was the exchange mechanism of the imino protons. The effects of a perturbation in a helix on the exchange rates and the mechanisms for exchange of imino protons from oligonucleotide helices are discussed.

  12. Atrial Fibrillation: When the heart is not in rhythm | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Atrial Fibrillation Atrial Fibrillation: When the heart is not in rhythm Past ... show, Deal With It . Photo: TBS/Deal Understanding Atrial Fibrillation Atrial fibrillation (AFib) is the most common type ...

  13. Fibrillization kinetics of insulin solution in an interfacial shearing flow

    Science.gov (United States)

    Balaraj, Vignesh; McBride, Samantha; Hirsa, Amir; Lopez, Juan

    2015-11-01

    Although the association of fibril plaques with neurodegenerative diseases like Alzheimer's and Parkinson's is well established, in-depth understanding of the roles played by various physical factors in seeding and growth of fibrils is far from well known. Of the numerous factors affecting this complex phenomenon, the effect of fluid flow and shear at interfaces is paramount as it is ubiquitous and the most varying factor in vivo. Many amyloidogenic proteins have been found to denature upon contact at hydrophobic interfaces due to the self-assembling nature of protein in its monomeric state. Here, fibrillization kinetics of insulin solution is studied in an interfacial shearing flow. The transient surface rheological response of the insulin solution to the flow and its effect on the bulk fibrillization process has been quantified. Minute differences in hydrophobic characteristics between two variants of insulin- Human recombinant and Bovine insulin are found to result in very different responses. Results presented will be in the form of fibrillization assays, images of fibril plaques formed, and changes in surface rheological properties of the insulin solution. The interfacial velocity field, measured from images (via Brewster Angle Microscopy), is compared with computations. Supported by NNX13AQ22G, National Aeronautics and Space Administration.

  14. Organized Atrial Tachycardias after Atrial Fibrillation Ablation

    Science.gov (United States)

    Castrejón-Castrejón, Sergio; Ortega, Marta; Pérez-Silva, Armando; Doiny, David; Estrada, Alejandro; Filgueiras, David; López-Sendón, José L.; Merino, José L.

    2011-01-01

    The efficacy of catheter-based ablation techniques to treat atrial fibrillation is limited not only by recurrences of this arrhythmia but also, and not less importantly, by new-onset organized atrial tachycardias. The incidence of such tachycardias depends on the type and duration of the baseline atrial fibrillation and specially on the ablation technique which was used during the index procedure. It has been repeatedly reported that the more extensive the left atrial surface ablated, the higher the incidence of organized atrial tachycardias. The exact origin of the pathologic substrate of these trachycardias is not fully understood and may result from the interaction between preexistent regions with abnormal electrical properties and the new ones resultant from radiofrequency delivery. From a clinical point of view these atrial tachycardias tend to remit after a variable time but in some cases are responsible for significant symptoms. A precise knowledge of the most frequent types of these arrhythmias, of their mechanisms and components is necessary for a thorough electrophysiologic characterization if a new ablation procedure is required. PMID:21941669

  15. Time-Driven Activity-Based Costing in Emergency Medicine.

    Science.gov (United States)

    Yun, Brian J; Prabhakar, Anand M; Warsh, Jonathan; Kaplan, Robert; Brennan, John; Dempsey, Kyle E; Raja, Ali S

    2016-06-01

    Value in emergency medicine is determined by both patient-important outcomes and the costs associated with achieving them. However, measuring true costs is challenging. Without an understanding of costs, emergency department (ED) leaders will be unable to determine which interventions might improve value for their patients. Although ongoing research may determine which outcomes are meaningful, an accurate costing system is also needed. This article reviews current costing mechanisms in the ED and their pitfalls. It then describes how time-driven activity-based costing may be superior to these current costing systems. Time-driven activity-based costing, in addition to being a more accurate costing system, can be used for process improvements in the ED. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  16. The safety of flecainide treatment of atrial fibrillation

    DEFF Research Database (Denmark)

    Almroth, H; Andersson, Torben Bech; Fengsrud, E

    2011-01-01

    To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events.......To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events....

  17. Surgical Ablation of Atrial Fibrillation Using Energy Sources.

    Science.gov (United States)

    Brick, Alexandre Visconti; Braile, Domingo Marcolino

    2015-01-01

    Surgical ablation, concomitant with other operations, is an option for treatment in patients with chronic atrial fibrillation. The aim of this study is to present a literature review on surgical ablation of atrial fibrillation in patients undergoing cardiac surgery, considering energy sources and return to sinus rhythm. A comprehensive survey was performed in the literature on surgical ablation of atrial fibrillation considering energy sources, sample size, study type, outcome (early and late), and return to sinus rhythm. Analyzing studies with immediate results (n=5), the percentage of return to sinus rhythm ranged from 73% to 96%, while those with long-term results (n=20) (from 12 months on) ranged from 62% to 97.7%. In both of them, there was subsequent clinical improvement of patients who underwent ablation, regardless of the energy source used. Surgical ablation of atrial fibrillation is essential for the treatment of this arrhythmia. With current technology, it may be minimally invasive, making it mandatory to perform a procedure in an attempt to revert to sinus rhythm in patients requiring heart surgery.

  18. Data for ion and seed dependent fibril assembly of a spidroin core domain

    Directory of Open Access Journals (Sweden)

    Martin Humenik

    2015-09-01

    Full Text Available This data article includes size exclusion chromatography data of soluble eADF4(C16, an engineered spider silk variant based on the core domain sequence of the natural dragline silk protein ADF4 of Araneus diadematus, in combination with light scattering; the protein is monomeric before assembly. The assembled mature fibrils were visualized by transmission electron microscopy (TEM and atomic force microscopy (AFM. Sonicated fibrils were used as seeds to by-pass the nucleation lag phase in eADF4(C16 assembly. We also provide data on the sedimentation kinetics of spider silk in the presence of different NaCl concentrations revealing very slow protein aggregation in comparison to the fast assembly triggered by phosphate ions published previously [1]. Experiments in the Data article represent supporting material for our work published recently [1], which described the assembly mechanism of recombinant eADF4(C16 fibrils.

  19. Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment

    Science.gov (United States)

    Conde, João; Oliva, Nuria; Atilano, Mariana; Song, Hyun Seok; Artzi, Natalie

    2016-03-01

    The therapeutic potential of miRNA (miR) in cancer is limited by the lack of efficient delivery vehicles. Here, we show that a self-assembled dual-colour RNA-triple-helix structure comprising two miRNAs--a miR mimic (tumour suppressor miRNA) and an antagomiR (oncomiR inhibitor)--provides outstanding capability to synergistically abrogate tumours. Conjugation of RNA triple helices to dendrimers allows the formation of stable triplex nanoparticles, which form an RNA-triple-helix adhesive scaffold upon interaction with dextran aldehyde, the latter able to chemically interact and adhere to natural tissue amines in the tumour. We also show that the self-assembled RNA-triple-helix conjugates remain functional in vitro and in vivo, and that they lead to nearly 90% levels of tumour shrinkage two weeks post-gel implantation in a triple-negative breast cancer mouse model. Our findings suggest that the RNA-triple-helix hydrogels can be used as an efficient anticancer platform to locally modulate the expression of endogenous miRs in cancer.

  20. Changes in plasma atrial natriuretic factor in patients with idiopathic atrial fibrillation

    International Nuclear Information System (INIS)

    Du Tongxin; Xia Xiaojie; Qu Wei; Wang Shukui; Sun Junjiang

    2002-01-01

    To observe the changes in plasma atrial natriuretic factor (AFN) in patients with idiopathic atrial fibrillation and investigate its mechanism, plasma ANF, platelet count and hematocrit were detected in 21 cases with transient idiopathic atrial fibrillation (group A, A1 representing attack, while A2 termination), 28 with persistent idiopathic atrial fibrillation (group B), 27 suffered from rheumatic heart disease with mitral stenosis and persistent atrial fibrillation (group C), 32 with transient supraventricular tachycardia (group D) and 20 normal controls (group E). It was found that the level of ANF was significantly higher in patients with attacking transient idiopathic atrial fibrillation than that in group A2, D and E (P 0.05), while there was significant difference in hematocrit in group A1 compared with group A2, D, E (P < 0.01). It suggested that ANF and hematocrit play an important role in the attack of idiopathic atrial fibrillation

  1. Alcohol consumption and risk of atrial fibrillation

    DEFF Research Database (Denmark)

    Tolstrup, Janne Schurmann; Wium-Andersen, Marie Kim; Ørsted, David Dynnes

    2016-01-01

    BACKGROUND: The aim of this study was to test the hypothesis that alcohol consumption, both observational (self-reported) and estimated by genetic instruments, is associated with a risk of atrial fibrillation and to determine whether people with high cardiovascular risk are more sensitive towards...... alcohol than people with low risk. METHODS: We used data for a total of 88,782 men and women from the Copenhagen City Heart Study 1991-1994 and 2001-2003 and the Copenhagen General Population Study 2003-2010. Information on incident cases of atrial fibrillation was obtained from a validated nationwide...... register. As a measure of alcohol exposure, both self-reported consumption and genetic variations in alcohol metabolizing genes (ADH1B/ADH1C) were used as instrumental variables. The endpoint was admission to hospital for atrial fibrillation as recorded in a validated hospital register. RESULTS: A total...

  2. Strong contributions from vertical triads to helix-partner preferences in parallel coiled coils.

    Science.gov (United States)

    Steinkruger, Jay D; Bartlett, Gail J; Woolfson, Derek N; Gellman, Samuel H

    2012-09-26

    Pairing preferences in heterodimeric coiled coils are determined by complementarities among side chains that pack against one another at the helix-helix interface. However, relationships between dimer stability and interfacial residue identity are not fully understood. In the context of the "knobs-into-holes" (KIH) packing pattern, one can identify two classes of interactions between side chains from different helices: "lateral", in which a line connecting the adjacent side chains is perpendicular to the helix axes, and "vertical", in which the connecting line is parallel to the helix axes. We have previously analyzed vertical interactions in antiparallel coiled coils and found that one type of triad constellation (a'-a-a') exerts a strong effect on pairing preferences, while the other type of triad (d'-d-d') has relatively little impact on pairing tendencies. Here, we ask whether vertical interactions (d'-a-d') influence pairing in parallel coiled-coil dimers. Our results indicate that vertical interactions can exert a substantial impact on pairing specificity, and that the influence of the d'-a-d' triad depends on the lateral a' contact within the local KIH motif. Structure-informed bioinformatic analyses of protein sequences reveal trends consistent with the thermodynamic data derived from our experimental model system in suggesting that heterotriads involving Leu and Ile are preferred over homotriads involving Leu and Ile.

  3. Women Sex Importance in Stroke Patients with Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Cemile Handan Mısırlı

    2014-08-01

    Full Text Available OBJECTIVE: It was shown the differences in age, risk factors and treatment between women and men in stroke patients with atrial fibrillation METHODS: The stroke patients with atrial fibrillation who were hospitalized in our department at the last 2 years were seperated into 2 groups of aged above 75 and below 75, investigated with CHADS2 and CHA2DS2VASc scores and looked at the sex differences of women and men. RESULTS: Stroke ratio according to sex was statistically meaningful especially in women above the age of 75. Risc factors also were founded in elderly women and CHA2DS2VASc scores were higher in women than men so more anticoagulan treatment were begun. No differences were shown between sexes at lone atrial fibrillation and no treatment were begun. CONCLUSION: Women with atrial fibrillation had more risk factors, higher stroke rate and higher anticoagulation treatment.

  4. What can triple helix frameworks offer to the analysis of eco-innovation dynamics? Theoretical and methodological considerations

    DEFF Research Database (Denmark)

    Yang, Yan; Holgaard, Jette Egelund; Remmen, Arne

    2012-01-01

    stakeholder groups are interacting in this connection. Taking the triple helix as the theoretical departure point, this paper discusses the opportunities offered by these triple helix frameworks for analyzing eco-innovation dynamics from both theoretical and practical perspectives. It adds to the debate about......Bringing environmental concerns into focus of innovation processes will in several cases also expand the numbers of actors involved. Eco-innovation and triple helix are often frameworks applied to analyse how environmental concerns are integrated in the innovation processes and how different...

  5. Mouse senile amyloid fibrils deposited in skeletal muscle exhibit amyloidosis-enhancing activity.

    Directory of Open Access Journals (Sweden)

    Jinze Qian

    2010-05-01

    Full Text Available Amyloidosis describes a group of protein folding diseases in which amyloid proteins are abnormally deposited in organs and/or tissues as fine fibrils. Mouse senile amyloidosis is a disorder in which apolipoprotein A-II (apoA-II deposits as amyloid fibrils (AApoAII and can be transmitted from one animal to another both by the feces and milk excreted by mice with amyloidosis. Thus, mouse AApoAII amyloidosis has been demonstrated to be a "transmissible disease". In this study, to further characterize the transmissibility of amyloidosis, AApoAII amyloid fibrils were injected into transgenic Apoa2(cTg(+/- and normal R1.P1-Apoa2(c mice to induce AApoAII systemic amyloidosis. Two months later, AApoAII amyloid deposits were found in the skeletal muscles of amyloid-affected mice, primarily in the blood vessels and in the interstitial tissues surrounding muscle fibers. When amyloid fibrils extracted from the skeletal muscles were subjected to Western blot analysis, apoA-II was detected. Amyloid fibril fractions isolated from the muscles not only demonstrated the structure of amyloid fibrils but could also induce amyloidosis in young mice depending on its fibril conformation. These findings present a possible pathogenesis of amyloidosis: transmission of amyloid fibril conformation through muscle, and shed new light on the etiology involved in amyloid disorders.

  6. Atrial Fibrillation and Gastro-Oesophageal Reflux Disease - Controversies and Challenges.

    Science.gov (United States)

    Floria, Mariana; Barboi, Oana; Rezus, Ciprian; Ambarus, Valentin; Cijevschi-Prelipcean, Cristina; Balan, Gheorghe; Drug, Vasile Liviu

    2015-01-01

    Atrial fibrillation and gastro-oesophageal reflux are common manifestations in daily practice. The atria and the oesophagus are closely located and have similar nerve innervations. Over the last years, it has been observed that atrial fibrillation development and reflux disease could be related. Atrial fibrillation occurrence could be due to vagal nerve overstimulation. This, in association with vagal nerve-mediated parasympathetic stimulation, has also been observed in patients with gastro-oesophageal reflux. These mechanisms, in addition to inflammation, seem to be implicated in the pathophysiology of both diseases. Despite these associations supported by clinical and experimental studies, this relationship is still considered controversial. This review summarizes critical data regarding the association of gastro-oesophageal reflux and atrial fibrillation as well as their clinical implications.

  7. Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study.

    Science.gov (United States)

    Pallisgaard, Jannik L; Schjerning, Anne-Marie; Lindhardt, Tommi B; Procida, Kristina; Hansen, Morten L; Torp-Pedersen, Christian; Gislason, Gunnar H

    2016-04-01

    Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients with diabetes compared to the background population in Denmark. Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02-0.02), 0.99 (0.98-1.01), 8.89 (8.81-8.98) and 20.0 (19.9-20.2) in the background population and 0.13 (0.09-0.20), 2.10 (2.00-2.20), 8.41 (8.10-8.74) and 20.1 (19.4-20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52-3.60), 1.52 (1.47-1.56), 1.20 (1.18-1.23) and 0.99 (0.97-1.01) in the four age groups, respectively. Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients. Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high

  8. The Penta Helix Model of Innovation in Oman: An HEI Perspective

    Directory of Open Access Journals (Sweden)

    Alrence S Halibas

    2017-05-01

    government in Oman. HEI engagement is perceivably still weak. HEIs have yet to come out as a strong leading force in promoting systems of innovation. There is clear awareness of the need to adopt leading-edge practices in innovation strategy and management, curriculum and assessment, staff support and reward systems, funding and ICT infrastructure, research commercialization and IP management, and community engagement. Recommendations for Practitioners: There is need to conduct more in-depth analyses about the synergy and partnerships between key players of the Penta Helix model. A large-scale survey will help completely reveal the status and impact of innovation practices in the region and among HEIs. Recommendation for Researchers: There is need to conduct more in-depth analyses about the synergy and partnerships between key players of the Penta Helix model. A large-scale survey will help completely reveal the status and impact of innovation practices in the region and among HEIs. Impact on Society: The paper hopes to influence policy. It fully intends to convince policymakers increase the adoption of strategic interventions. The paper is not a theoretical description of the problem. It suggests several concrete courses of action. Future Research: The paper has seen the need to measure the effectiveness of the current innovation practices among key players in the innovation network and how these practices advance Oman’s knowledge economy. We propose a Likert-based bottom-up engagement metric.

  9. Living Labs as boundary-spanners between Triple Helix actors

    NARCIS (Netherlands)

    van Geenhuizen, M.S.

    2016-01-01

    Living labs are an increasingly popular methodology to enhance innovation. Living labs aim to span boundaries between different organizations, among others Triple helix actors, by acting as a network organization typically in a real-life environment to foster co-creation by user-groups. This paper

  10. New risk factors for atrial fibrillation : causes of 'not-so-lone atrial fibrillation'

    NARCIS (Netherlands)

    Schoonderwoerd, Bas A.; Smit, Marcelle D.; Pen, Lucas; Van Gelder, Isabelle C.

    Atrial fibrillation (AF) is a prevalent arrhythmia in patients with cardiovascular disease. The classical risk factors for developing AF include hypertension, valvular disease, (ischaemic) cardiomyopathy, diabetes mellitus, and thyroid disease. In some patients with AF, no underlying

  11. Observation of the efficacy of radiofrequency catheter ablation on patients with different forms of atrial fibrillation.

    Science.gov (United States)

    Zhao, R-C; Han, W; Han, J; Yu, J; Guo, J; Fu, J-L; Li, Z; Zhao, R-Z

    2016-10-01

    To study the efficacy and safety of radiofrequency catheter ablation (RFCA) in patients with different forms of atrial fibrillation. By retrospective analysis, we summarize 720 cases, where patients diagnosed with atrial fibrillation in our hospital were treated with RFCA from February 2010 to October 2014. Among the cases, 425 were diagnosed with paroxysmal atrial fibrillation and 295 with non-paroxysmal atrial fibrillation (including persistent atrial fibrillation and permanent atrial fibrillation). All patients were followed up until June 2015 to compare and analyze the differences in operation success rates, complications and recurrence rates. 395 cases (92.9%) of paroxysmal atrial fibrillation and 253 cases (85.8%) with non-paroxysmal atrial fibrillation were subject to surgery and followed up. The age of onset, disease course, underlying diseases, left atrial diameter and combined anti-arrhythmics of patients with paroxysmal atrial fibrillation were lower than those of patients with non-paroxysmal atrial fibrillation, and the differences were statistically significant (p success rate of the first ablation was higher than that of non-paroxysmal atrial fibrillation. Procedure time, procedure method, complications and recurrence rate of patients with paroxysmal atrial fibrillation were lower than those of non-paroxysmal atrial fibrillation group, and the differences were statistically significant (p failure caused by atrial fibrillation in the two groups, the difference was not statistically significant (Apoplexy: p = 0.186; Heart failure: p = 0.170). The individual ablation success rate was higher for paroxysmal atrial fibrillation, and long-term follow-up showed that the occurrence of apoplexy and heart failure was not different from the non-paroxysmal atrial fibrillation group.

  12. Role of amphipathic helix of a herpesviral protein in membrane deformation and T cell receptor downregulation.

    Directory of Open Access Journals (Sweden)

    Chan-Ki Min

    2008-11-01

    Full Text Available Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip of T lymphotropic Herpesvirus saimiri (HVS is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation.

  13. Assembly of α-synuclein fibrils in nanoscale studied by peptide truncation and AFM

    International Nuclear Information System (INIS)

    Zhang Feng; Lin Xiaojing; Ji Lina; Du Haining; Tang Lin; He Jianhua; Hu Jun; Hu Hongyu

    2008-01-01

    α-Synuclein (α-Syn) fibrils are the major component of Lewy bodies that are closely associated with the pathogenesis of Parkinson's disease, but the mechanism for the fibril assembly remains poorly understood. Here we report using a combination of peptide truncation and atomic force microscopy (AFM) to elucidate the self-assembly and morphology of the α-Syn fibrils. The results show that protease K significantly slims the fibrils from the mean height of ∼6.6 to ∼4.7 nm, whereas chaotropic denaturant urea completely breaks down the fibrils into small particles. The in situ enzymatic digestion also results in thinning of the fibrils, giving rise to some nicks on the fibrils. Moreover, N- or C-terminally truncated α-Syn fragments assemble into thinner filaments with the heights depending on the peptide lengths. A nine-residue peptide corresponding to the homologous GAV-motif sequence can form very thin (∼2.2 nm) but long (>1 μm) filaments. Thus, the central sequence of α-Syn forms a fibrillar core by cross-β-structure that is flanked by two flexible termini, and the orientation of the fibril growth is perpendicular to the β-sheet structures

  14. A rare polyglycine type II-like helix motif in naturally occurring proteins.

    Science.gov (United States)

    Warkentin, Eberhard; Weidenweber, Sina; Schühle, Karola; Demmer, Ulrike; Heider, Johann; Ermler, Ulrich

    2017-11-01

    Common structural elements in proteins such as α-helices or β-sheets are characterized by uniformly repeating, energetically favorable main chain conformations which additionally exhibit a completely saturated hydrogen-bonding network of the main chain NH and CO groups. Although polyproline or polyglycine type II helices (PP II or PG II ) are frequently found in proteins, they are not considered as equivalent secondary structure elements because they do not form a similar self-contained hydrogen-bonding network of the main chain atoms. In this context our finding of an unusual motif of glycine-rich PG II -like helices in the structure of the acetophenone carboxylase core complex is of relevance. These PG II -like helices form hexagonal bundles which appear to fulfill the criterion of a (largely) saturated hydrogen-bonding network of the main-chain groups and therefore may be regarded in this sense as a new secondary structure element. It consists of a central PG II -like helix surrounded by six nearly parallel PG II -like helices in a hexagonal array, plus an additional PG II -like helix extending the array outwards. Very related structural elements have previously been found in synthetic polyglycine fibers. In both cases, all main chain NH and CO groups of the central PG II -helix are saturated by either intra- or intermolecular hydrogen-bonds, resulting in a self-contained hydrogen-bonding network. Similar, but incomplete PG II -helix patterns were also previously identified in a GTP-binding protein and an antifreeze protein. © 2017 Wiley Periodicals, Inc.

  15. Determination of collagen fibril structure and orientation in connective tissues by X-ray diffraction

    Science.gov (United States)

    Wilkinson, S. J.; Hukins, D. W. L.

    1999-08-01

    Elastic scattering of X-rays can provide the following information on the fibrous protein collagen: its molecular structure, the axial arrangement of rod-like collagen molecules in a fibril, the lateral arrangement of molecules within a fibril, and the orientation of fibrils within a biological tissue. The first part of the paper reviews the principles involved in deducing this information. The second part describes a new computer program for measuring the equatorial intensity distribution, that provides information on the lateral arrangement of molecules within a fibril, and the angular distribution of the equatorial peaks that provides information on the orientation of fibrils. Orientation of fibrils within a tissue is quantified by the orientation distribution function, g( φ), which represents the probability of finding a fibril oriented between φ and φ+ δφ. The application of the program is illustrated by measurement of g( φ) for the collagen fibrils in demineralised cortical bone from cow tibia.

  16. Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    Min-Hui Jiang

    2013-11-01

    Full Text Available OBJECTIVE: The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343 is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension. METHODS: A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75 were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies. RESULTS: The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037. The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007. Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (p<0.01 and p<0.05, respectively. CONCLUSIONS: The results obtained in this study indicate that the angiotensin-converting enzyme 2350 G/A polymorphism is associated with atrial fibrillation and that the A allele shows an increased risk for atrial fibrillation in Han Chinese patients with essential hypertension.

  17. Decision-making interventions to stop the global atrial fibrillation-related stroke tsunami.

    Science.gov (United States)

    Cerasuolo, Joshua O; Montero-Odasso, Manuel; Ibañez, Agustin; Doocy, Shannon; Lip, Gregory Yh; Sposato, Luciano A

    2017-04-01

    Atrial fibrillation affects 33.5 million people worldwide and its prevalence is expected to double by 2050 because of the aging population. Atrial fibrillation confers a 5-fold higher risk of ischemic stroke compared to sinus rhythm. We present our view of the role of shared medical decision-making to combat global underutilization of oral anticoagulation for stroke prevention in atrial fibrillation patients. Oral anticoagulation underuse is widespread as it is present within atrial fibrillation patients of all risk strata and in countries across all income levels. Reasons for oral anticoagulation underuse include but are probably not limited to poor risk stratification, over-interpretation of contraindications, and discordance between physician prescription preferences and actual administration. By comparing a catastrophic event to the consequences of atrial fibrillation related strokes, it may help physicians and patients understand the negative outcomes associated with oral anticoagulation under-utilization and the magnitude to which oral anticoagulations neutralize atrial fibrillation burden.

  18. Role of sequence and structural polymorphism on the mechanical properties of amyloid fibrils.

    Directory of Open Access Journals (Sweden)

    Gwonchan Yoon

    Full Text Available Amyloid fibrils playing a critical role in disease expression, have recently been found to exhibit the excellent mechanical properties such as elastic modulus in the order of 10 GPa, which is comparable to that of other mechanical proteins such as microtubule, actin filament, and spider silk. These remarkable mechanical properties of amyloid fibrils are correlated with their functional role in disease expression. This suggests the importance in understanding how these excellent mechanical properties are originated through self-assembly process that may depend on the amino acid sequence. However, the sequence-structure-property relationship of amyloid fibrils has not been fully understood yet. In this work, we characterize the mechanical properties of human islet amyloid polypeptide (hIAPP fibrils with respect to their molecular structures as well as their amino acid sequence by using all-atom explicit water molecular dynamics (MD simulation. The simulation result suggests that the remarkable bending rigidity of amyloid fibrils can be achieved through a specific self-aggregation pattern such as antiparallel stacking of β strands (peptide chain. Moreover, we have shown that a single point mutation of hIAPP chain constituting a hIAPP fibril significantly affects the thermodynamic stability of hIAPP fibril formed by parallel stacking of peptide chain, and that a single point mutation results in a significant change in the bending rigidity of hIAPP fibrils formed by antiparallel stacking of β strands. This clearly elucidates the role of amino acid sequence on not only the equilibrium conformations of amyloid fibrils but also their mechanical properties. Our study sheds light on sequence-structure-property relationships of amyloid fibrils, which suggests that the mechanical properties of amyloid fibrils are encoded in their sequence-dependent molecular architecture.

  19. Atrial fibrillation driven by micro-anatomic intramural re-entry revealed by simultaneous sub-epicardial and sub-endocardial optical mapping in explanted human hearts.

    Science.gov (United States)

    Hansen, Brian J; Zhao, Jichao; Csepe, Thomas A; Moore, Brandon T; Li, Ning; Jayne, Laura A; Kalyanasundaram, Anuradha; Lim, Praise; Bratasz, Anna; Powell, Kimerly A; Simonetti, Orlando P; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L; Weiss, Raul; Hummel, John D; Fedorov, Vadim V

    2015-09-14

    The complex architecture of the human atria may create physical substrates for sustained re-entry to drive atrial fibrillation (AF). The existence of sustained, anatomically defined AF drivers in humans has been challenged partly due to the lack of simultaneous endocardial-epicardial (Endo-Epi) mapping coupled with high-resolution 3D structural imaging. Coronary-perfused human right atria from explanted diseased hearts (n = 8, 43-72 years old) were optically mapped simultaneously by three high-resolution CMOS cameras (two aligned Endo-Epi views (330 µm2 resolution) and one panoramic view). 3D gadolinium-enhanced magnetic resonance imaging (GE-MRI, 80 µm3 resolution) revealed the atrial wall structure varied in thickness (1.0 ± 0.7-6.8 ± 2.4 mm), transmural fiber angle differences, and interstitial fibrosis causing transmural activation delay from 23 ± 11 to 43 ± 22 ms at increased pacing rates. Sustained AF (>90 min) was induced by burst pacing during pinacidil (30-100 µM) perfusion. Dual-sided sub-Endo-sub-Epi optical mapping revealed that AF was driven by spatially and temporally stable intramural re-entry with 107 ± 50 ms cycle length and transmural activation delay of 67 ± 31 ms. Intramural re-entrant drivers were captured primarily by sub-Endo mapping, while sub-Epi mapping visualized re-entry or 'breakthrough' patterns. Re-entrant drivers were anchored on 3D micro-anatomic tracks (15.4 ± 2.2 × 6.0 ± 2.3 mm2, 2.9 ± 0.9 mm depth) formed by atrial musculature characterized by increased transmural fiber angle differences and interstitial fibrosis. Targeted radiofrequency ablation of the tracks verified these re-entries as drivers of AF. Integrated 3D structural-functional mapping of diseased human right atria ex vivo revealed that the complex atrial microstructure caused significant differences between Endo vs. Epi activation during pacing and sustained AF driven by intramural re-entry anchored to fibrosis-insulated atrial bundles. Published on

  20. Role of the future creative universities in the triple helix of science and technology corridors

    Directory of Open Access Journals (Sweden)

    Iraj nabipour

    2015-01-01

    Full Text Available The science and technology corridor is a complex cluster containing universities, science parks, research centers, high-tech companies, venture capital, institutional and physical infrastructures, and human capital in a defined geography with its unique management and legal structure in association with the business space and knowledge-based products. In fact, the science and technology corridor reflects the concept of development based on the knowledge region (the especial region for science and technology. The knowledge region is clearly a triple helix phenomenon par excellence: universities, governments and businesses combine their efforts to construct a common advantage which they would not be able to offer on their own. The future creative universities in connection with the knowledge city-regions not only will deal with innovation and entrepreneurial training but also produce a competitive, vibrant environment with high indices for quality of life and full of green technologies. In this article, we will present functional interactions of the creative universities in the triple helix, particularly the missions for the Iranian universities of medical sciences. As a theoretical model, the complex interactions of Bushehr University of Medical Sciences and Health Services with Bushehr Science and Technology Corridor will be discussed.

  1. Screening for Atrial Fibrillation

    DEFF Research Database (Denmark)

    Freedman, Ben; Camm, John; Calkins, Hugh

    2017-01-01

    Approximately 10% of ischemic strokes are associated with atrial fibrillation (AF) first diagnosed at the time of stroke. Detecting asymptomatic AF would provide an opportunity to prevent these strokes by instituting appropriate anticoagulation. The AF-SCREEN international collaboration was formed...

  2. Michler’s Hydrol Blue: A Sensitive Probe for Amyloid Fibril Detection

    KAUST Repository

    Kitts, Catherine C.

    2011-05-03

    Michler\\'s hydrol blue (MHB) is investigated with respect to photophysical properties in varied solvent environment and when bound to insulin and lysozyme fibrils. The MHB chromophore is shown to act like a molecular rotor and bind well to amyloid fibrils, where it exhibits a characteristic red-shift in its excitation spectrum and an increase in the emission quantum yield upon binding. MHB is more sensitive to environmental changes than Thioflavin T (ThT) and furthermore, in contrast to the latter amyloid probe, can differentiate between insulin and lysozyme fibrils by a more red-shifted excitation spectrum for insulin fibrils. To support the experimental observations, time-dependent density functional theory (TDDFT) calculations were performed on MHB at several levels of theory. The predicted changes of spectral properties as a function of the environment are in good agreement with the experimental results. Linear dichroism (LD) is used to determine the orientation of the MHB within the fibrils. It was shown through LD and molecular modeling that MHB aligns itself preferentially parallel with the amyloid fiber at an angle of 14°-22° to the fibril axis and along the grooves of the β-sheet. © 2011 American Chemical Society.

  3. Artificially modified collagen fibril orientation affects leather tear strength.

    Science.gov (United States)

    Kelly, Susyn J; Wells, Hannah C; Sizeland, Katie H; Kirby, Nigel; Edmonds, Richard L; Ryan, Tim; Hawley, Adrian; Mudie, Stephen; Haverkamp, Richard G

    2018-07-01

    Ovine leather has around half the tear strength of bovine leather and is therefore not suitable for high-value applications such as shoes. Tear strength has been correlated with the natural collagen fibril alignment (orientation index, OI). It is hypothesized that it could be possible to artificially increase the OI of the collagen fibrils and that an artificial increase in OI could increase tear strength. Ovine skins, after pickling and bating, were strained biaxially during chrome tanning. The strain ranged from 2 to 15% of the initial sample length, either uniformly in both directions by 10% or with 3% in one direction and 15% in the other. Once tanned, the leather tear strengths were measured and the collagen fibril orientation was measured using synchrotron-based small-angle X-ray scattering. The OI increased as a result of strain during tanning from 0.48 to 0.79 (P = 0.001) measured edge-on and the thickness-normalized tear strength increased from 27 to 43 N mm -1 (P leather was strained 10% in two orthogonal directions. This is evidence to support a causal relationship between high OI (measured edge-on), highly influenced by thickness, and tear strength. It also provides a method to produce stronger leather. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  4. Conjugated Quantum Dots Inhibit the Amyloid β (1–42 Fibrillation Process

    Directory of Open Access Journals (Sweden)

    Garima Thakur

    2011-01-01

    Full Text Available Nanoparticles have enormous potential in diagnostic and therapeutic studies. We have demonstrated that the amyloid beta mixed with and conjugated to dihydrolipoic acid- (DHLA capped CdSe/ZnS quantum dots (QDs of size approximately 2.5 nm can be used to reduce the fibrillation process. Transmission electron microscopy (TEM and atomic force microscopy (AFM were used as tools for analysis of fibrillation. There is a significant change in morphology of fibrils when amyloid β (1–42 (Aβ (1–42 is mixed or conjugated to the QDs. The length and the width of the fibrils vary under modified conditions. Thioflavin T (ThT fluorescence supports the decrease in fibril formation in presence of DHLA-capped QDs.

  5. Salbutamol Abuse is Associated with Ventricular Fibrillation

    Directory of Open Access Journals (Sweden)

    Emin UYSAL

    2015-06-01

    Full Text Available SUMMARY: Salbutamol-induced cardiac complications are well-established. Herein, we describe a case of a 24-year female who was admitted to the emergency department because of a suicide attempt with salbutamol (76 mg. Salbutamol abuse induced the development of supraventricular tachycardia and ventricular fibrillation. Regular sinus rhythm was restored with defibrillation. The hypokalemic patient who stayed in the intensive care unit was discharged after 48 hours of hospitalization. Key words: Salbutamol, suicide, ventricular fibrillation

  6. Evidence for novel beta-sheet structures in Iowa mutant beta-amyloid fibrils.

    Science.gov (United States)

    Tycko, Robert; Sciarretta, Kimberly L; Orgel, Joseph P R O; Meredith, Stephen C

    2009-07-07

    Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-Abeta40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-Abeta40 forms fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-Abeta40 and the wild-type peptide WT-Abeta40, respectively) and without a lag phase. Electron microscopy shows that D23N-Abeta40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 A and a broad reflection at 9.4 A, which is notably smaller than the value for WT-Abeta40 fibrils (10.4 A). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-Abeta40 fibrils containing the in-register, parallel beta-sheet structure commonly found in WT-Abeta40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-Abeta40 fibrils and the unusual vasculotropic clinical picture in these patients.

  7. Identification of a basic helix-loop-helix-type transcription regulator gene in Aspergillus oryzae by systematically deleting large chromosomal segments.

    Science.gov (United States)

    Jin, Feng Jie; Takahashi, Tadashi; Machida, Masayuki; Koyama, Yasuji

    2009-09-01

    We previously developed two methods (loop-out and replacement-type recombination) for generating large-scale chromosomal deletions that can be applied to more effective chromosomal engineering in Aspergillus oryzae. In this study, the replacement-type method is used to systematically delete large chromosomal DNA segments to identify essential and nonessential regions in chromosome 7 (2.93 Mb), which is the smallest A. oryzae chromosome and contains a large number of nonsyntenic blocks. We constructed 12 mutants harboring deletions that spanned 16- to 150-kb segments of chromosome 7 and scored phenotypic changes in the resulting mutants. Among the deletion mutants, strains designated Delta5 and Delta7 displayed clear phenotypic changes involving growth and conidiation. In particular, the Delta5 mutant exhibited vigorous growth and conidiation, potentially beneficial characteristics for certain industrial applications. Further deletion analysis allowed identification of the AO090011000215 gene as the gene responsible for the Delta5 mutant phenotype. The AO090011000215 gene was predicted to encode a helix-loop-helix binding protein belonging to the bHLH family of transcription factors. These results illustrate the potential of the approach for identifying novel functional genes.

  8. Fabrication experiments for large helix heat exchangers

    International Nuclear Information System (INIS)

    Burgsmueller, P.

    1978-01-01

    The helical tube has gained increasing attention as a heat transfer element for various kinds of heat exchangers over the last decade. Regardless of reactor type and heat transport medium, nuclear steam generators of the helix type are now in operation, installlation, fabrication or in the project phase. As a rule, projects are based on the extrapolation of existing technologies. In the particlular case of steam generators for HTGR power stations, however, existing experience is with steam generators of up to about 2 m diameter whereas several projects involve units more than twice as large. For this reason it was felt that a fabrication experiment was necessary in order to verify the feasibility of modern steam generator designs. A test rig was erected in the SULZER steam generator shops at Mantes, France, and skilled personnel and conventional production tools were employed in conducting experiments relating to the coiling, handling and threading of large helices. (Auth.)

  9. [Atrial fibrillation as consequence and cause of structural changes of atria].

    Science.gov (United States)

    Aparina, O P; Chikhireva, L N; Stukalova, O V; Mironova, N A; Kashtanova, S Iu; Ternovoĭ, S K; Golitsyn, S P

    2014-01-01

    Changes of atrial structure and function are the contributors of atrial fibrillation clinical course, complications and treatment effectiveness. Effects of inflammation and mechanical stretch on atrial structural remodeling leading to atrial fibrillation are reviewed in the article. Contemporary invasive and non-invasive methods of evaluation (including late gadolinium enhancement magnetic resonance imaging) of patients with atrial structural remodeling in atrial fibrillation are also described.

  10. Fibril growth kinetics link buffer conditions and topology of 3D collagen I networks.

    Science.gov (United States)

    Kalbitzer, Liv; Pompe, Tilo

    2018-02-01

    Three-dimensional fibrillar networks reconstituted from collagen I are widely used as biomimetic scaffolds for in vitro and in vivo cell studies. Various physicochemical parameters of buffer conditions for in vitro fibril formation are well known, including pH-value, ion concentrations and temperature. However, there is a lack of a detailed understanding of reconstituting well-defined 3D network topologies, which is required to mimic specific properties of the native extracellular matrix. We screened a wide range of relevant physicochemical buffer conditions and characterized the topology of the reconstituted 3D networks in terms of mean pore size and fibril diameter. A congruent analysis of fibril formation kinetics by turbidimetry revealed the adjustment of the lateral growth phase of fibrils by buffer conditions to be key in the determination of pore size and fibril diameter of the networks. Although the kinetics of nucleation and linear growth phase were affected by buffer conditions as well, network topology was independent of those two growth phases. Overall, the results of our study provide necessary insights into how to engineer 3D collagen matrices with an independent control over topology parameters, in order to mimic in vivo tissues in in vitro experiments and tissue engineering applications. The study reports a comprehensive analysis of physicochemical conditions of buffer solutions to reconstitute defined 3D collagen I matrices. By a combined analysis of network topology, i.e., pore size and fibril diameter, and the kinetics of fibril formation we can reveal the dependence of 3D network topology on buffer conditions, such as pH-value, phosphate concentration and sodium chloride content. With those results we are now able to provide engineering strategies to independently tune the topology parameters of widely used 3D collagen scaffolds based on the buffer conditions. By that, we enable the straightforward mimicking of extracellular matrices of in vivo

  11. Nonlinear time-dependent simulation of helix traveling wave tubes

    International Nuclear Information System (INIS)

    Peng Wei-Feng; Yang Zhong-Hai; Hu Yu-Lu; Li Jian-Qing; Lu Qi-Ru; Li Bin

    2011-01-01

    A one-dimensional nonlinear time-dependent theory for helix traveling wave tubes is studied. A generalized electromagnetic field is applied to the expression of the radio frequency field. To simulate the variations of the high frequency structure, such as the pitch taper and the effect of harmonics, the spatial average over a wavelength is substituted by a time average over a wave period in the equation of the radio frequency field. Under this assumption, the space charge field of the electron beam can be treated by a space charge wave model along with the space charge coefficient. The effects of the radio frequency and the space charge fields on the electrons are presented by the equations of the electron energy and the electron phase. The time-dependent simulation is compared with the frequency-domain simulation for a helix TWT, which validates the availability of this theory. (interdisciplinary physics and related areas of science and technology)

  12. Analysis of eco-innovation with triple helix approach: case-study of biofloc catfish farming in Yogyakarta

    Science.gov (United States)

    Purwadi, D.; Nurlaily, I.

    2018-03-01

    Concerning environmental into focus of innovation process will expand the number of actor involved. Eco-innovation and triple helix are often frameworks applied to analyse how environmental concern are integrated in innovation process and how different stakeholder groups are having inter relation. Case study from biofloc catfish farming in Yogyakarta is presented to demonstrate a possible approach for researching the success of triple helix frameworks. This case is considered on basic of the result of a survey among farmers, academician and government. The paper concludes the creating of full triple helix encounters problem in practice. It also includes suggestion for further research on fisheries development.

  13. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study.

    Science.gov (United States)

    Selmer, Christian; Olesen, Jonas Bjerring; Hansen, Morten Lock; Lindhardsen, Jesper; Olsen, Anne-Marie Schjerning; Madsen, Jesper Clausager; Faber, Jens; Hansen, Peter Riis; Pedersen, Ole Dyg; Torp-Pedersen, Christian; Gislason, Gunnar Hilmar

    2012-11-27

    To examine the risk of atrial fibrillation in relation to the whole spectrum of thyroid function in a large cohort of patients. Population based cohort study of general practice patients identified by linkage of nationwide registries at the individual level. Primary care patients in the city of Copenhagen. Registry data for 586,460 adults who had their thyroid function evaluated for the first time by their general practitioner during 2000-10 and who were without previously recorded thyroid disease or atrial fibrillation. Poisson regression models used to estimate risk of atrial fibrillation by thyroid function. Of the 586,460 individuals in the study population (mean (SD) age 50.2 (16.9) years, 39% men), 562,461 (96.0%) were euthyroid, 1670 (0.3%) had overt hypothyroidism, 12,087 (2.0%) had subclinical hypothyroidism, 3966 (0.7%) had overt hyperthyroidism, and 6276 (1.0%) had subclinical hyperthyroidism. Compared with the euthyroid individuals, the risk of atrial fibrillation increased with decreasing levels of thyroid stimulating hormone (TSH) from high normal euthyroidism (incidence rate ratio 1.12 (95% CI 1.03 to 1.21)) to subclinical hyperthyroidism with reduced TSH (1.16 (0.99 to 1.36)) and subclinical hyperthyroidism with supressed TSH (1.41 (1.25 to 1.59)). Both overt and subclinical hypothyroidism were associated with a lower risk of atrial fibrillation. The risk of atrial fibrillation was closely associated with thyroid activity, with a low risk in overt hypothyroidism, high risk in hyperthyroidism, and a TSH level dependent association with risk of atrial fibrillation across the spectrum of subclinical thyroid disease.

  14. Kevlar: Transitioning Helix for Research to Practice

    Science.gov (United States)

    2016-03-01

    x86 binaries, although it can be targeted to any platform that is targeted by IDA Pro. Currently, IDA Pro targets more than 40 processors and...effects its own transformations. Helix/Kevlar then automatically generates SPRI rules for any program variants by essentially performing a “ smart diff...execute permission on the pages of memory it uses, leaving only execute (but not write) permission on the code cache. Strata also watches for attempts

  15. Visible-Light-Driven BiOI-Based Janus Micromotor in Pure Water.

    Science.gov (United States)

    Dong, Renfeng; Hu, Yan; Wu, Yefei; Gao, Wei; Ren, Biye; Wang, Qinglong; Cai, Yuepeng

    2017-02-08

    Light-driven synthetic micro-/nanomotors have attracted considerable attention due to their potential applications and unique performances such as remote motion control and adjustable velocity. Utilizing harmless and renewable visible light to supply energy for micro-/nanomotors in water represents a great challenge. In view of the outstanding photocatalytic performance of bismuth oxyiodide (BiOI), visible-light-driven BiOI-based Janus micromotors have been developed, which can be activated by a broad spectrum of light, including blue and green light. Such BiOI-based Janus micromotors can be propelled by photocatalytic reactions in pure water under environmentally friendly visible light without the addition of any other chemical fuels. The remote control of photocatalytic propulsion by modulating the power of visible light is characterized by velocity and mean-square displacement analysis of optical video recordings. In addition, the self-electrophoresis mechanism has been confirmed for such visible-light-driven BiOI-based Janus micromotors by demonstrating the effects of various coated layers (e.g., Al 2 O 3 , Pt, and Au) on the velocity of motors. The successful demonstration of visible-light-driven Janus micromotors holds a great promise for future biomedical and environmental applications.

  16. Atrial fibrillation and risk of stroke

    DEFF Research Database (Denmark)

    Christiansen, Christine Benn; Gerds, Thomas A.; Olesen, Jonas Bjerring

    2016-01-01

    AIM: Although the relation between stroke risk factors and stroke in patients with atrial fibrillation (AF) has been extensively examined, only few studies have explored the association of AF and the risk of ischaemic stroke/systemic thromboembolism/transient ischaemic attack (stroke.......5-10.6), and 15.4% (14.5-16.4), respectively. CONCLUSIONS: Stroke/TE/TIA risk was particularly increased when prior stroke/TE/TIA was present. Atrial fibrillation is associated with an increase in risk of stroke/TE/TIA in the absence of other risk factors but only a moderate increase in risk when other risk...

  17. Initiation of anticoagulation in atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, A.; Staerk, L.; Fosbøl, E. L.

    2017-01-01

    Background: The use of non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prophylaxis in atrial fibrillation (AF) is increasing rapidly. We compared characteristics of AF patients initiated on NOACs versus vitamin K antagonists (VKAs). Methods: Using Danish nationwide registry data, we...... compared with a VKA [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.28–1.43]. By contrast, patients with a history of myocardial infarction were less likely to be initiated on a NOAC compared with a VKA (OR 0.72, 95% CI 0.67–0.77). Conclusions: Atrial fibrillation patients who were initiated...

  18. Fibril morphology and tendon mechanical properties in patellar tendinopathy: effects of heavy slow resistance training

    DEFF Research Database (Denmark)

    Kongsgaard, Mads; Qvortrup, Klaus; Larsen, Jytte Overgaard

    2010-01-01

    BACKGROUND: Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying functional mechanisms remain elusive. PURPOSE: To investigate fibril morphology and mechanical properties...... assessed symptoms/function and maximal tendon pain during activity. Tendon biopsy samples were analyzed for fibril density, volume fraction, and mean fibril area. Tendon mechanical properties were assessed using force and ultrasonography samplings. RESULTS: Patients improved in symptoms/function (P = .02...... area decreased (-26% +/- 21%, P = .04) in tendinopathic tendons after HSR. CONCLUSION: Fibril morphology is abnormal in tendinopathy, but tendon mechanical properties are not. Clinical improvements after HSR were associated with changes in fibril morphology toward normal fibril density and mean fibril...

  19. Is Supramolecular Filament Chirality the Underlying Cause of Major Morphology Differences in Amyloid Fibrils?

    Science.gov (United States)

    2015-01-01

    The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for “normal” left-hand-helical filaments and below pH 2 for “reversed” right-hand-helical filaments. From AFM or SEM images, left-helical filaments form multifilament braids of left-twisted fibrils while the right-helical filaments form parallel filament rows of fibrils with a flat tape-like morphology, the two major classes of fibril morphology that from deep UV resonance Raman scattering exhibit the same cross-β-core secondary structure. Here we investigate whether fibril supramolecular chirality is the underlying cause of the major morphology differences in all amyloid fibrils by showing that the morphology (twisted versus flat) of fibrils of lysozyme, apo-α-lactalbumin, HET-s (218–289) prion, and a short polypeptide fragment of transthyretin, TTR (105–115), directly correlates to their supramolecular chirality as revealed by VCD. The result is strong evidence that the chiral supramolecular organization of filaments is the principal underlying cause of the morphological heterogeneity of amyloid fibrils. Because fibril morphology is linked to cell toxicity, the chirality of amyloid aggregates should be explored in the widely used in vitro models of amyloid-associated diseases. PMID:24484302

  20. Is supramolecular filament chirality the underlying cause of major morphology differences in amyloid fibrils?

    Science.gov (United States)

    Kurouski, Dmitry; Lu, Xuefang; Popova, Ludmila; Wan, William; Shanmugasundaram, Maruda; Stubbs, Gerald; Dukor, Rina K; Lednev, Igor K; Nafie, Laurence A

    2014-02-12

    The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for "normal" left-hand-helical filaments and below pH 2 for "reversed" right-hand-helical filaments. From AFM or SEM images, left-helical filaments form multifilament braids of left-twisted fibrils while the right-helical filaments form parallel filament rows of fibrils with a flat tape-like morphology, the two major classes of fibril morphology that from deep UV resonance Raman scattering exhibit the same cross-β-core secondary structure. Here we investigate whether fibril supramolecular chirality is the underlying cause of the major morphology differences in all amyloid fibrils by showing that the morphology (twisted versus flat) of fibrils of lysozyme, apo-α-lactalbumin, HET-s (218-289) prion, and a short polypeptide fragment of transthyretin, TTR (105-115), directly correlates to their supramolecular chirality as revealed by VCD. The result is strong evidence that the chiral supramolecular organization of filaments is the principal underlying cause of the morphological heterogeneity of amyloid fibrils. Because fibril morphology is linked to cell toxicity, the chirality of amyloid aggregates should be explored in the widely used in vitro models of amyloid-associated diseases.

  1. Intracellular Calcium Dynamics and Autonomic Stimulation in Atrial Fibrillation: Mechanisms and Implications

    Directory of Open Access Journals (Sweden)

    Chung-Chuan Chou, MD

    2008-01-01

    Full Text Available While atrial fibrillation is characterized by the co-existence of multiple activation waves within the atria, rapid activations in the pulmonary veins play an important role for the initiation and maintenance of atrial fibrillation. In addition to reentry, non-reentrant mechanisms resulting from abnormal intracellular calcium handling and intracellular calcium overload can also be responsible for these rapid activations in the pulmonary veins. Meanwhile, alterations of autonomic tone, involving both the sympathetic and parasympathetic nervous system, have been implicated in initiating paroxysmal atrial fibrillation. But the effectiveness of autonomic modulation as an adjunctive therapeutic strategy to catheter ablation of atrial fibrillation has been inconsistent. The interactions between the autonomic nervous system and atrial fibrillation are more complex than currently understood and further mechanistic and clinical studies are warranted.

  2. Stretched versus compressed exponential kinetics in α-helix folding

    International Nuclear Information System (INIS)

    Hamm, Peter; Helbing, Jan; Bredenbeck, Jens

    2006-01-01

    In a recent paper (J. Bredenbeck, J. Helbing, J.R. Kumita, G.A. Woolley, P. Hamm, α-helix formation in a photoswitchable peptide tracked from picoseconds to microseconds by time resolved IR spectroscopy, Proc. Natl. Acad. Sci USA 102 (2005) 2379), we have investigated the folding of a photo-switchable α-helix with a kinetics that could be fit by a stretched exponential function exp(-(t/τ) β ). The stretching factor β became smaller as the temperature was lowered, a result which has been interpreted in terms of activated diffusion on a rugged energy surface. In the present paper, we discuss under which conditions diffusion problems occur with stretched exponential kinetics (β 1). We show that diffusion problems do have a strong tendency to yield stretched exponential kinetics, yet, that there are conditions (strong perturbation from equilibrium, performing the experiment in the folding direction) under which compressed exponential kinetics would be expected instead. We discuss the kinetics on free energy surfaces predicted by simple initiation-propagation models (zipper models) of α-helix folding, as well as by folding funnel models. We show that our recent experiment has been performed under condition for which models with strong downhill driving force, such as the zipper model, would predict compressed, rather than stretched exponential kinetics, in disagreement with the experimental observation. We therefore propose that the free energy surface along a reaction coordinate that governs the folding kinetics must be relatively flat and has a shape similar to a 1D golf course. We discuss how this conclusion can be unified with the thermodynamically well established zipper model by introducing an additional kinetic reaction coordinate

  3. Increased amount of atrial fibrosis in patients with atrial fibrillation secondary to mitral valve disease

    NARCIS (Netherlands)

    Geuzebroek, Guillaume S. C.; van Amersfoorth, Shirley C. M.; Hoogendijk, Mark G.; Kelder, Johannes C.; van Hemel, Norbert M.; de Bakker, Jacques M. T.; Coronel, Ruben

    2012-01-01

    Objective: Atrial fibrosis is related to atrial fibrillation but may differ in patients with mitral valve disease or lone atrial fibrillation. Therefore, we studied atrial fibrosis in patients with atrial fibrillation + mitral valve disease or with lone atrial fibrillation and compared it with

  4. Rotational symmetry and the transformation of innovation systems in a Triple Helix of university-industry-government relations

    NARCIS (Netherlands)

    Ivanova, I.A.; Leydesdorff, L.

    2014-01-01

    Using a mathematical model, we show that a Triple Helix (TH) system contains self-interaction, and therefore self-organization of innovations can be expected in waves, whereas a Double Helix (DH) remains determined by its linear constituents. (The mathematical model is fully elaborated in the

  5. How curcumin affords effective protection against amyloid fibrillation in insulin?

    DEFF Research Database (Denmark)

    Rabiee, Atefeh; Ebrahim Habibi, Azadeh; Ghasemi, Atiyeh Ghasemi

    2013-01-01

    Since the formation of amyloid structures from proteins was recognized in numerous diseases, many efforts have been devoted to the task of finding effective anti-amyloidogenic compounds. In a number of these investigations, the existence of “generic” compounds is implicitly acknowledged. Curcumin...... been shown effectively influenced by micro molar concentrations of curcumin. Under amyloidogenic conditions (pH 2.5 and 37°C), the compound was observed to inhibit fibril formation of insulin in a dose-dependent manner. Moreover, addition of curcumin to the protein incubated in such conditions...... at different time points resulted in reduced amounts of final fibrils. Disaggregation of pre-formed fibrils was also observed upon addition of curcumin, as well as reduction in final fibril amounts after seeding. Overall, this compound appears to be able to interact with native, intermediate and fibrillar...

  6. Does Myocardial Infarction Beget Atrial Fibrillation and Atrial Fibrillation Beget Myocardial Infarction?

    NARCIS (Netherlands)

    Vermond, Rob A.; Van Gelder, Isabelle C.; Crijns, Harry J.; Rienstra, Michiel

    2015-01-01

    Atrial fibrillation (AF) affects millions of people worldwide.(1) It is already known several decades that AF is not a benign condition, and it's associated with a 5-fold increased risk of stroke, 3-fold increased risk of heart failure, and doubling of risk of dementia and death.(2-4) Myocardial

  7. The generalized model of polypeptide chain describing the helix-coil transition in biopolymers

    International Nuclear Information System (INIS)

    Mamasakhlisov, E.S.; Badasyan, A.V.; Tsarukyan, A.V.; Grigoryan, A.V.; Morozov, V.F.

    2005-07-01

    In this paper we summarize some results of our theoretical investigations of helix-coil transition both in single-strand (polypeptides) and two-strand (polynucleotides) macromolecules. The Hamiltonian of the Generalized Model of Polypeptide Chain (GMPC) is introduced to describe the system in which the conformations are correlated over some dimensional range Δ (it equals 3 for polypeptide, because one H-bond fixes three pairs of rotation, for double strand DNA it equals to one chain rigidity because of impossibility of loop formation on the scale less than Δ). The Hamiltonian does not contain any parameter designed especially for helix-coil transition and uses pure molecular microscopic parameters (the energy of hydrogen bond formation, reduced partition function of repeated unit, the number of repeated units fixed by one hydrogen bond, the energies of interaction between the repeated units and the solvent molecules). To calculate averages we evaluate the partition function using the transfer-matrix approach. The GMPC allowed to describe the influence of a number of factors, affecting the transition, basing on a unified microscopic approach. Thus we obtained, that solvents change transition temperature and interval in different ways, depending on type of solvent and on energy of solvent- macromolecule interaction; stacking on the background of H-bonding increases stability and decreases cooperativity of melting. For heterogeneous DNA we could analytically derive well known formulae for transition temperature and interval. In the framework of GMPC we calculate and show the difference of two order parameters of helix-coil transition - the helicity degree, and the average fraction of repeated units in helical conformation. Given article has the aim to review the results obtained during twenty years in the context of GMPC. (author)

  8. Mutations in conserved helix 69 of 23S rRNA of Thermus thermophilus that affect capreomycin resistance but not posttranscriptional modifications

    DEFF Research Database (Denmark)

    Monshupanee, Tanakarn; Gregory, Steven T; Douthwaite, Stephen

    2008-01-01

    of previously reported capreomycin resistance base substitutions. Capreomycin resistance in other bacteria has been shown to result from inactivation of the TlyA methyltransferase which 2'-O methylates C1920 of 23S rRNA. Inactivation of the tlyA gene in T. thermophilus does not affect its sensitivity...... for resistance to the tuberactinomycin antibiotic capreomycin. Two base substitutions, A1913U and mU1915G, and a single base deletion, DeltamU1915, were identified in helix 69 of 23S rRNA, a structural element that forms part of an interribosomal subunit bridge with the decoding center of 16S rRNA, the site...... to capreomycin. Finally, none of the mutations in helix 69 interferes with methylation at C1920 or with pseudouridylation at positions 1911 and 1917. We conclude that the resistance phenotype is a consequence of structural changes introduced by the mutations....

  9. Amyloid Fibrils as Building Blocks for Natural and Artificial Functional Materials.

    Science.gov (United States)

    Knowles, Tuomas P J; Mezzenga, Raffaele

    2016-08-01

    Proteinaceous materials based on the amyloid core structure have recently been discovered at the origin of biological functionality in a remarkably diverse set of roles, and attention is increasingly turning towards such structures as the basis of artificial self-assembling materials. These roles contrast markedly with the original picture of amyloid fibrils as inherently pathological structures. Here we outline the salient features of this class of functional materials, both in the context of the functional roles that have been revealed for amyloid fibrils in nature, as well as in relation to their potential as artificial materials. We discuss how amyloid materials exemplify the emergence of function from protein self-assembly at multiple length scales. We focus on the connections between mesoscale structure and material function, and demonstrate how the natural examples of functional amyloids illuminate the potential applications for future artificial protein based materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Management of atrial fibrillation in the setting of heart failure

    NARCIS (Netherlands)

    Crijns, HJGM; VandenBerg, MP; VanGelder, IC; VanVeldhuisen, DJ

    Heart failure is often complicated by atrial fibrillation. Once atrial fibrillation has started it further enhances heart failure due to uncontrolled rate with shortened filling time and provocation of tachycardiomyopathy. Absent atrial kick and irregularity of the ventricular rhythm also

  11. Embolic risk in atrial fibrillation that arises from hyperthyroidism: review of the medical literature.

    Science.gov (United States)

    Traube, Elie; Coplan, Neil L

    2011-01-01

    Atrial fibrillation, the most common cardiac complication of hyperthyroidism, occurs in an estimated 10% to 25% of overtly hyperthyroid patients. The prevalence of atrial fibrillation increases with age in the general population and in thyrotoxic patients. Other risk factors for atrial fibrillation in thyrotoxic patients include male sex, ischemic or valvular heart disease, and congestive heart failure. The incidence of arterial embolism or stroke in thyrotoxic atrial fibrillation is less clear. There are many reports of arterial thromboembolism associated with hyperthyroidism, including cases of young adults without coexisting risk factors other than thyrotoxic atrial fibrillation. The use of anticoagulative agents to prevent thromboembolic sequelae of thyrotoxic atrial fibrillation is controversial: National organizations provide conflicting recommendations in their practice guidelines. Herein, we review the medical literature and examine the evidence behind the recommendations in order to determine the best approach to thromboembolic prophylaxis in patients who have atrial fibrillation that is associated with hyperthyroidism.

  12. Hydrated and Dehydrated Tertiary Interactions–Opening and Closing–of a Four-Helix Bundle Peptide

    Science.gov (United States)

    Lignell, Martin; Tegler, Lotta T.; Becker, Hans-Christian

    2009-01-01

    Abstract The structural heterogeneity and thermal denaturation of a dansyl-labeled four-helix bundle homodimeric peptide was studied with steady-state and time-resolved fluorescence spectroscopy and with circular dichroism (CD). At room temperature the fluorescence decay of the polarity-sensitive dansyl, located in the hydrophobic core region, can be described by a broad distribution of fluorescence lifetimes, reflecting the heterogeneous microenvironment. However, the lifetime distribution is nearly bimodal, which we ascribe to the presence of two major conformational subgroups. Since the fluorescence lifetime reflects the water content of the four-helix bundle conformations, we can use the lifetime analysis to monitor the change in hydration state of the hydrophobic core of the four-helix bundle. Increasing the temperature from 9°C to 23°C leads to an increased population of molten-globule-like conformations with a less ordered helical backbone structure. The fluorescence emission maximum remains constant in this temperature interval, and the hydrophobic core is not strongly affected. Above 30°C the structural dynamics involve transient openings of the four-helix bundle structure, as evidenced by the emergence of a water-quenched component and less negative CD. Above 60°C the homodimer starts to dissociate, as shown by the increasing loss of CD and narrow, short-lived fluorescence lifetime distributions. PMID:19619472

  13. Increased helix and protein stability through the introduction of a new tertiary hydrogen bond.

    Science.gov (United States)

    Peterson, R W; Nicholson, E M; Thapar, R; Klevit, R E; Scholtz, J M

    1999-03-12

    In an effort to quantify the importance of hydrogen bonding and alpha-helix formation to protein stability, a capping box motif was introduced into the small phosphocarrier protein HPr. Previous studies had confirmed that Ser46, at the N-cap position of the short helix-B in HPr, serves as an N-cap in solution. Thus, only a single-site mutation was required to produce a canonical S-X-X-E capping box: Lys49 at the N3 position was substituted with a glutamic acid residue. Thermal and chemical denaturation studies on the resulting K49E HPr show that the designed variant is approximately 2 kcal mol-1 more stable than the wild-type protein. However, NMR studies indicate that the side-chain of Glu49 does not participate in the expected capping H-bond interaction, but instead forms a new tertiary H-bond that links helix-B to the four-stranded beta-sheet of HPr. Here, we demonstrate that a strategy in which new non-native H-bonds are introduced can generate proteins with increased stability. We discuss why the original capping box design failed, and compare the energetic consequences of the new tertiary side-chain to main-chain H-bond with a local (helix-capping) side-chain to main-chain H-bond on the protein's global stability. Copyright 1999 Academic Press.

  14. Does an interdisciplinary outpatient atrial fibrillation (AF) clinic affect the number of acute AF admissions?

    DEFF Research Database (Denmark)

    Frydensberg, Vivi Skibdal; Brandes, Axel

    2018-01-01

    AIMS AND OBJECTIVES: To investigate the impact of a multidisciplinary outpatient clinic for patients with atrial fibrillation (AF-clinic) on the number of acute hospitalizations for atrial fibrillation compared with usual outpatient care for this condition before the establishment of the AF-clinic....... BACKGROUND: Guidelines recommend a structured outpatient clinic follow-up in multidisciplinary teams for patients with atrial fibrillation due to fewer hospitalizations and death. However the evidence base is weak. DESIGN: The study is a retrospective cohort study including a total of 129 patients from...... the cardiac outpatient clinic at a large Danish University Hospital. The study population consisted of two groups: a usual care group before a dedicated AF-clinic was established (n=73) and the AF-clinic group (n=56). The primary endpoint was acute hospitalization for AF. METHODS: Cox regression was used...

  15. Modulation of atrial fibrillation

    NARCIS (Netherlands)

    Geuzebroek, G.S.C.

    2013-01-01

    In this thesis we investigate the results of various surgical procedures for atrial fibrillation which have been performed in the last 2 decades in the Sint Antonius Hospital, Nieuwegein, The Netherlands. In the 1990s the classical Maze III procedure was the main surgical technique for

  16. Longitudinal and concurrent dimensional changes of cellulose aggregate fibrils during sorption stages

    International Nuclear Information System (INIS)

    Lee, Jung Myoung; Pawlak, Joel J.; Heitmann, John A.

    2010-01-01

    Atomic force microscopy (AFM) studies of the dimensional changes of cellulose microfibril materials, called cellulose aggregate fibrils (approx. 100 μm x 3 μm x 300 nm), exposed to two distinct relative humidities of 80% and 23% for 24 h and then suddenly subjected to 50% RH and 23 deg. C show that the fibrils are responsive to the surrounding environments in a nonspecific fashion. AFM images (10 μm x 10 μm) of the individual straight cellulose aggregate fibrils were taken as a function of elapsed time during both desorption and adsorption of moisture. The longitudinal distance between discrete natural defects observed on the cellulose aggregate fibrils as well as the width, cross-sectional area, and height of the cellulose aggregate fibril were measured from the AFM images. The length of the cellulose aggregate fibrils was found to have reduced after exposure to either high or low relative humidity, and then placement in ambient conditions. Over time in ambient conditions, the cellulose aggregate fibrils progressively relaxed to their original length during both desorption and adsorption of moisture. However, the relaxation rate during adsorption was faster than that during desorption. The possible explanations for this phenomenon are discussed including the sample preparation method, volume conservation, entropy elasticity, and free volume theory. The changes in the width, height, and cross-sectional area are also discussed.

  17. The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

    DEFF Research Database (Denmark)

    Langkilde, Annette Eva; Morris, Kyle L; Serpell, Louise C

    2015-01-01

    Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the G......Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril...

  18. Cryoballoon Catheter Ablation in Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Cevher Ozcan

    2011-01-01

    Full Text Available Pulmonary vein isolation with catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation refractory or intolerant to antiarrhythmic medications. The cryoballoon catheter was recently approved for this procedure. In this paper, the basics of cryothermal energy ablation are reviewed including its ability of creating homogenous lesion formation, minimal destruction to surrounding vasculature, preserved tissue integrity, and lower risk of thrombus formation. Also summarized here are the publications describing the clinical experience with the cryoballoon catheter ablation in both paroxysmal and persistent atrial fibrillation, its safety and efficacy, and discussions on the technical aspect of the cryoballoon ablation procedure.

  19. Ebstein's anomaly as a cause of paroxysmal atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Damjanović Miodrag R.

    2008-01-01

    Full Text Available Background. Ebstein's anomaly is characterized by a displacement of the tricuspid valve toward apex, because of anomalous attachment of the tricuspid leaflets. There are type B of Wolff-Parkinson-White (WPW syndrome and paroxysmal arrhythmias in more than a half of all patients. Case report. We presented a female, 32-year old, with frequent paroxysms of atrial fibrillation. After conversion of rhythm an ECG showed WPW syndrome. Echocardiographic examination discovered normal size of the left cardiac chambers with paradoxical ventricular septal motion. The right ventricle was very small because of its atrialization. The origin of the tricuspid valve was 20 mm closer to apex of the right ventricle than the origin of the mitral valve. Electrophysiological examination showed a posterolateral right accesorial pathway. Atrial fibrillation was induced very easily in electrophysiological laboratory and a successful ablation of accessorial pathway was made. There were no WPW syndrome and paroxysms of atrial fibrillation after that. Conclusion. Ebstein's anomaly is one of the reasons of paroxysmal atrial fibrillation, especially in young persons with WPW syndrome.

  20. Surface characterization of insulin protofilaments and fibril polymorphs using tip-enhanced Raman spectroscopy (TERS).

    Science.gov (United States)

    Kurouski, Dmitry; Deckert-Gaudig, Tanja; Deckert, Volker; Lednev, Igor K

    2014-01-07

    Amyloid fibrils are β-sheet-rich protein aggregates that are strongly associated with a variety of neurodegenerative maladies, such as Alzheimer's and Parkinson's diseases. Even if the secondary structure of such fibrils is well characterized, a thorough understanding of their surface organization still remains elusive. Tip-enhanced Raman spectroscopy (TERS) is one of a few techniques that allow the direct characterization of the amino acid composition and the protein secondary structure of the amyloid fibril surface. Herein, we investigated the surfaces of two insulin fibril polymorphs with flat (flat) and left-twisted (twisted) morphology. It was found that the two differ substantially in both amino acid composition and protein secondary structure. For example, the amounts of Tyr, Pro, and His differ, as does the number of carboxyl groups on the respective surfaces, whereas the amounts of Phe and of positively charged amino and imino groups remain similar. In addition, the surface of protofilaments, the precursors of the mature flat and twisted fibrils, was investigated using TERS. The results show substantial differences with respect to the mature fibrils. A correlation of amino acid frequencies and protein secondary structures on the surface of protofilaments and on flat and twisted fibrils allowed us to propose a hypothetical mechanism for the propagation to specific fibril polymorphs. This knowledge can shed a light on the toxicity of amyloids and define the key factors responsible for fibril polymorphism. Finally, this work demonstrates the potential of TERS for the surface characterization of amyloid fibril polymorphs. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  1. Helix Nebula Science Cloud pilot phase open session

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    This Helix Nebula Science Cloud (HNSciCloud) public session is open to everyone and will be webcast. The session will provide the audience with an overview of the HNSciCloud pre-commercial procurement project and the innovative cloud platforms that have been developed. A number of practical use-cases from the physics community will be presented as well as the next steps to be undertaken.

  2. An amphipathic alpha-helix controls multiple roles of brome mosaic virus protein 1a in RNA replication complex assembly and function.

    Directory of Open Access Journals (Sweden)

    Ling Liu

    2009-03-01

    Full Text Available Brome mosaic virus (BMV protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER membranes as a peripheral membrane protein, induces ER membrane invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2a(Pol and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic alpha-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a-ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a-membrane association and abolishes ER membrane invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2a(Pol accumulation. The second class of helix A mutations not only maintains efficient 1a-membrane association but also amplifies the number of 1a-induced membrane invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2a(Pol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.

  3. Warfarin Use in Patients With Atrial Fibrillation Undergoing Hemodialysis: A Nationwide Population-Based Study.

    Science.gov (United States)

    Yoon, Chang-Yun; Noh, Juhwan; Jhee, Jong Hyun; Chang, Tae Ik; Kang, Ea Wha; Kee, Youn Kyung; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jung, Su-Young; Oh, Hyung Jung; Park, Jung Tak; Han, Seung Hyeok; Kang, Shin-Wook; Kim, Changsoo; Yoo, Tae-Hyun

    2017-09-01

    The aim of this study is to elucidate the effects of warfarin use in patients with atrial fibrillation undergoing dialysis using a population-based Korean registry. Data were extracted from the Health Insurance Review and Assessment Service, which is a nationwide, mandatory social insurance database of all Korean citizens enrolled in the National Health Information Service between 2009 and 2013. Thromboembolic and hemorrhagic outcomes were analyzed according to warfarin use. Overall and propensity score-matched cohorts were analyzed by Cox proportional hazards models. Among 9974 hemodialysis patients with atrial fibrillation, the mean age was 66.6±12.2 years, 5806 (58.2%) were men, and 2921 (29.3%) used warfarin. After propensity score matching to adjust for all described baseline differences, 5548 subjects remained, and differences in baseline variables were distributed equally between warfarin users and nonusers. During a mean follow-up duration of 15.9±11.1 months, ischemic and hemorrhagic stroke occurred in 678 (6.8%) and 227 (2.3%) patients, respectively. In a multiple Cox model, warfarin use was significantly associated with an increased risk of hemorrhagic stroke (hazard ratio, 1.44; 95% confidence interval, 1.09-1.91; P =0.010) in the overall cohort. Furthermore, a significant relationship between warfarin use and hemorrhagic stroke was found in propensity-matched subjects (hazard ratio, 1.56; 95% confidence interval, 1.10-2.22; P =0.013). However, the ratios for ischemic stroke were not significantly different in either the propensity-matched (hazard ratio, 0.95; 95% confidence interval, 0.78-1.15; P =0.569) or overall cohort (hazard ratio, 1.06; 95% confidence interval, 0.90-1.26; P =0.470). Our findings suggest that warfarin should be used carefully in hemodialysis patients, given the higher risk of hemorrhagic events and the lack of ability to prevent thromboembolic complications. © 2017 American Heart Association, Inc.

  4. Atrial fibrillation and bleeding complication - risk factors and risk marker

    NARCIS (Netherlands)

    Breithardt, G.; Ravens, U.; Kirchhof, P.; van Gelder, I. C.

    2012-01-01

    The development of atrial fibrillation (AF) is closely linked to risk factors like hypertension and heart failure, diabetes mellitus, myocardial infarction and valvular heart disease. These factors partly overlap with those which determine the progression of atrial fibrillation and the incidence of

  5. Long working hours as a risk factor for atrial fibrillation

    DEFF Research Database (Denmark)

    Kivimäki, Mika; Nyberg, Solja T.; Batty, G. David

    2017-01-01

    long hours (≤55 per week) and those working standard 35-40 h/week. Methods and results In this prospective multi-cohort study from the Individual-Participant-Data Meta-Analysis in Working Populations (IPD-Work) Consortium, the study population was 85 494 working men and women (mean age 43.4 years...... of atrial fibrillation (10-year cumulative incidence 12.4 per 1000). After adjustment for age, sex and socioeconomic status, individuals working long hours had a 1.4-fold increased risk of atrial fibrillation compared with those working standard hours (hazard ratio = 1.42, 95% CI= 1.13-1.80, P= 0......Aims Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working...

  6. Population-based study of ABCD2 score, carotid stenosis, and atrial fibrillation for early stroke prediction after transient ischemic attack: the North Dublin TIA study.

    LENUS (Irish Health Repository)

    Sheehan, Orla C

    2010-05-01

    Transient ischemic attack (TIA) etiologic data and the ABCD(2) score may improve early stroke risk prediction, but studies are required in population-based cohorts. We investigated the external validity of the ABCD(2) score, carotid stenosis, and atrial fibrillation for prediction of early recurrent stroke after TIA.

  7. [Panic disorder and atrial fibrillation].

    Science.gov (United States)

    Olazabal Eizaguirre, N; Chavez, R; González-Torres, M A; Gaviria, M

    2013-10-01

    This paper studies the relationship between atrial fibrillation and panic disorder. There are often doubts on the differential diagnosis in emergency services and general medical settings. Panic disorder prevalence rates have been found to be high in patients suffering from atrial fibrillation. Various studies have observed that patients diagnosed with anxiety disorders frequently have higher cardiovascular disease rates compared to the general population. Usually, patients suffering from panic disorder exhibit somatic complaints suggesting coronary disease, such as chest pain or palpitations. The aim is to make the correct diagnosis and treatment for these different illnesses, and to decrease the costs due to misdiagnosis. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  8. Systematic examination of polymorphism in amyloid fibrils by molecular-dynamics simulation.

    Science.gov (United States)

    Berryman, Joshua T; Radford, Sheena E; Harris, Sarah A

    2011-05-04

    Amyloid fibrils often exhibit polymorphism. Polymorphs are formed when proteins or peptides with identical sequences self-assemble into fibrils containing substantially different arrangements of the β-strands. We used atomistic molecular-dynamics simulation to examine the thermodynamic stability of a amyloid fibrils in different polymorphic forms by performing a systematic investigation of sequence and symmetry space for a series of peptides with a range of physicochemical properties. We show that the stability of fibrils depends on both sequence and the symmetry because these factors determine the availability of favorable interactions between the peptide strands within a sheet and in intersheet packing. By performing a detailed analysis of these interactions as a function of symmetry, we obtained a series of simple design rules that can be used to determine which polymorphs of a given sequence are most likely to form thermodynamically stable fibrils. These rules can potentially be employed to design peptide sequences that aggregate into a preferred polymorphic form for nanotechnological purposes. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. The Impact of Age on the Epidemiology of Atrial Fibrillation Hospitalizations

    Science.gov (United States)

    Naderi, Sahar; Wang, Yun; Miller, Amy L.; Rodriguez, Fátima; Chung, Mina K.; Radford, Martha J.; Foody, JoAnne M.

    2015-01-01

    Background Given 4 million individuals in the United States suffer from atrial fibrillation, understanding the epidemiology of this disease is crucial. We sought to identify and characterize the impact of age on national atrial fibrillation hospitalization patterns. Methods The study sample was drawn from the 2009–2010 Nationwide Inpatient Sample (NIS). Patients hospitalized with a principal ICD9 discharge diagnosis of atrial fibrillation were included. Patients were categorized as “older” (65 and older) or “younger” (under 65 years) for the purposes of analysis. The outcomes measured included hospitalization rate, length of stay, in-hospital mortality, and discharge status. Results We identified 192,846 atrial fibrillation hospitalizations. There was significant geographic variation in hospitalizations for both younger and older age groups. States with high hospitalizations differed from those states known to have high stroke mortality. Younger patients (33% of the sample) were more likely to be obese (21% versus 8%, patrial fibrillation hospitalizations in contemporary practice. Younger patients are healthier, with a different distribution of risk factors, than older patients who have higher associated morbidity and mortality. PMID:24332722

  10. RelB and RelE of Escherichia coli Form a Tight Complex That Represses Transcription via The Ribbon-Helix-Helix Motif in RelB

    DEFF Research Database (Denmark)

    Overgaard, Martin; Borch, Jonas; Gerdes, Kenn

    2009-01-01

    RelB, the Ribbon-Helix-Helix (RHH) repressor encoded by the relBE toxin-antitoxin locus of Escherichia coli, forms a tight complex with RelE and thereby counteracts the mRNA cleavage activity of RelE. In addition, RelB dimers repress the strong relBE promoter and this repression by RelB is enhanced...... by RelE - that is - RelE functions as a transcriptional co-repressor. RelB is a Lon protease substrate and Lon is required both for activation of relBE transcription and for activation of the mRNA cleavage activity of RelE. Here we characterize the molecular interactions important for transcriptional...... motif recognizes four 6 bp repeats within the bipartite binding site. The spacing between each half-site was found to be essential for cooperative interactions between adjacently bound RelB dimers stabilized by the co-repressor RelE. Kinetic and stoichiometric measurements of the interaction between Rel...

  11. Patients with atrial fibrillation and permanent pacemaker

    DEFF Research Database (Denmark)

    Dalgaard, Frederik; Ruwald, Martin H; Lindhardt, Tommi Bo

    2018-01-01

    BACKGROUND: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). METHODS: Through Danish......,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p

  12. Viscoelastic behavior of discrete human collagen fibrils

    DEFF Research Database (Denmark)

    Svensson, René; Hassenkam, Tue; Hansen, Philip

    2010-01-01

    Whole tendon and fibril bundles display viscoelastic behavior, but to the best of our knowledge this property has not been directly measured in single human tendon fibrils. In the present work an atomic force microscopy (AFM) approach was used for tensile testing of two human patellar tendon...... saline, cyclic testing was performed in the pre-yield region at different strain rates, and the elastic response was determined by a stepwise stress relaxation test. The elastic stress-strain response corresponded to a second-order polynomial fit, while the viscous response showed a linear dependence...

  13. Effect of environmental factors on the kinetics of insulin fibril formation: elucidation of the molecular mechanism.

    Science.gov (United States)

    Nielsen, L; Khurana, R; Coats, A; Frokjaer, S; Brange, J; Vyas, S; Uversky, V N; Fink, A L

    2001-05-22

    In the search for the molecular mechanism of insulin fibrillation, the kinetics of insulin fibril formation were studied under different conditions using the fluorescent dye thioflavin T (ThT). The effect of insulin concentration, agitation, pH, ionic strength, anions, seeding, and addition of 1-anilinonaphthalene-8-sulfonic acid (ANS), urea, TMAO, sucrose, and ThT on the kinetics of fibrillation was investigated. The kinetics of the fibrillation process could be described by the lag time for formation of stable nuclei (nucleation) and the apparent rate constant for the growth of fibrils (elongation). The addition of seeds eliminated the lag phase. An increase in insulin concentration resulted in shorter lag times and faster growth of fibrils. Shorter lag times and faster growth of fibrils were seen at acidic pH versus neutral pH, whereas an increase in ionic strength resulted in shorter lag times and slower growth of fibrils. There was no clear correlation between the rate of fibril elongation and ionic strength. Agitation during fibril formation attenuated the effects of insulin concentration and ionic strength on both lag times and fibril growth. The addition of ANS increased the lag time and decreased the apparent growth rate for insulin fibril formation. The ANS-induced inhibition appears to reflect the formation of amorphous aggregates. The denaturant, urea, decreased the lag time, whereas the stabilizers, trimethylamine N-oxide dihydrate (TMAO) and sucrose, increased the lag times. The results indicated that both nucleation and fibril growth were controlled by hydrophobic and electrostatic interactions. A kinetic model, involving the association of monomeric partially folded intermediates, whose concentration is stimulated by the air-water interface, leading to formation of the critical nucleus and thence fibrils, is proposed.

  14. Effects of anoxia on the extra- and intracellular acid-base status in the land snail helix lucorum (L.): lack of evidence for a relationship between pyruvate kinase down-regulation and acid-base status

    Science.gov (United States)

    Michaelidis; Pallidou; Vakouftsi

    1999-06-01

    The aims of the present study were to describe a possible correlation between the regulation of the key glycolytic enzyme pyruvate kinase and the acid-base status in the haemolymph and in several other tissues of land snails during anoxia. To illustrate whether such a relationship exists, we determined (i) the acid-base variables in the haemolymph and tissues of the land snail Helix lucorum, (ii) the kinetic properties of pyruvate kinase from several tissues and (iii) the levels of the anaerobic end-products d-lactate and succinate in the haemolymph and tissues of aerobic and anoxic Helix lucorum. The results showed that the pH of haemolymph (pHe) decreased significantly over the first 20 h of anoxia and then recovered slowly towards control values. A similar pattern was observed for intracellular pH (pHi), which decreased significantly over the first 16 h of anoxia and slowly returned towards control levels. The reduction and recovery of pHi and pHe seem to reflect the rate of anaerobic metabolism. The main anaerobic end-products, d-lactate and succinate, accumulated rapidly during the initial stages of anoxia and more slowly as anoxia progressed. The decrease in the rate of accumulation of anaerobic end-products during prolonged anoxia was due to the conversion of tissue pyruvate kinase to a less active form. The results demonstrate a correlation between pyruvate kinase down-regulation and the recovery of acid-base status in the haemolymph and the tissues of land snails during anoxia.

  15. Michler’s Hydrol Blue: A Sensitive Probe for Amyloid Fibril Detection

    KAUST Repository

    Kitts, Catherine C.; Beke-Somfai, Tamás; Nordén, Bengt

    2011-01-01

    amyloid probe, can differentiate between insulin and lysozyme fibrils by a more red-shifted excitation spectrum for insulin fibrils. To support the experimental observations, time-dependent density functional theory (TDDFT) calculations were performed

  16. Helix Nebula - the Science Cloud: a public-private partnership to build a multidisciplinary cloud platform for data intensive science

    Science.gov (United States)

    Jones, Bob; Casu, Francesco

    2013-04-01

    The feasibility of using commercial cloud services for scientific research is of great interest to research organisations such as CERN, ESA and EMBL, to the suppliers of cloud-based services and to the national and European funding agencies. Through the Helix Nebula - the Science Cloud [1] initiative and with the support of the European Commission, these stakeholders are driving a two year pilot-phase during which procurement processes and governance issues for a framework of public/private partnership will be appraised. Three initial flagship use cases from high energy physics, molecular biology and earth-observation are being used to validate the approach, enable a cost-benefit analysis to be undertaken and prepare the next stage of the Science Cloud Strategic Plan [2] to be developed and approved. The power of Helix Nebula lies in a shared set of services for initially 3 very different sciences each supporting a global community and thus building a common e-Science platform. Of particular relevance is the ESA sponsored flagship application SuperSites Exploitation Platform (SSEP [3]) that offers the global geo-hazard community a common platform for the correlation and processing of observation data for supersites monitoring. The US-NSF Earth Cube [4] and Ocean Observatory Initiative [5] (OOI) are taking a similar approach for data intensive science. The work of Helix Nebula and its recent architecture model [6] has shown that is it technically feasible to allow publicly funded infrastructures, such as EGI [7] and GEANT [8], to interoperate with commercial cloud services. Such hybrid systems are in the interest of the existing users of publicly funded infrastructures and funding agencies because they will provide "freedom of choice" over the type of computing resources to be consumed and the manner in which they can be obtained. But to offer such freedom-of choice across a spectrum of suppliers, various issues such as intellectual property, legal responsibility

  17. Comparison and Analysis of 3,4 dihydrocylmandelic acid (DHMA) and noremetanephrine (NMN) on Amyloid-Beta 40 Monomer for treatment of Alzheimer's Disease using Molecular Dynamics Simulation

    Science.gov (United States)

    Choi, Woosung; Jee, Sang Eun; Jang, Seung Soon

    Alzheimer's disease (AD) is type of degenerative dementia caused memory loss and behavior problem. Main reason of AD is Amyloid-Beta 40(A β) mostly composed of α -helix form misfolds to insoluble fibrils and soluble oilgomer. This insoluble fibrils aggregate with beta sheet structure and form the plaque which is caused nurotoxicity in brain. Both 3,4 dihydrocylmandelic acid (DHMA) and noremetanephrine (NMN) are the metabolite of norepinephrine in brain . Also these are inhibit the changing formation of fibrils and maintain the α -helix structure. In this computational modeling study, both NMN and DHMA molecules were modified and analyzed for specific effect on the A β-monomer using molecular dynamics simulation. Using molecular dynamic simulation, NMN and DHMA act as modulator on three A β-monomer batches and could observe the conformational changing of these A β-monomer under the physiologocal condition. This computational experiment is designed to compare and analyze both of chemicals for determining which chamecal would be more effective on the conformation of A β 40 monomer.

  18. Ventricular fibrillation development following atrial fibrillation after the ingestion of sildenaphil in a patient with Wolff-Parkinson-White syndrome.

    Science.gov (United States)

    Inci, Sinan; Izgu, Ibrahim; Aktas, Halil; Dogan, Pinar; Dogan, Ali

    2015-08-01

    Complications in the accessory pathway in Wolff-Parkinson-White (WPW) syndrome could cause different clinical conditions by inducing different arrhythmias. Atrial fibrillation (AF) is one of these arrhythmias and is important as it causes life-threatening arrhythmias. It is known that some drugs, underlying cardiac diseases, and the number of accessory pathways, cause a predisposition to this condition. In the current report, we presented a patient with WPW who was admitted to the emergency department with AF, wide QRS and a rapid ventricular response that progressed to ventricular fibrillation.

  19. NMR studies of abasic sites in DNA duplexes: deoxyadenosine stacks into the helix opposite the cyclic analog of 2-deoxyribose

    International Nuclear Information System (INIS)

    Kalnik, M.W.; Chang, C.N.; Grollman, A.P.; Patel, D.J.

    1988-01-01

    Proton and phosphorus NMR studies are reported for the complementary d(C-A-T-G-A-G-T-A-C) x d(G-T-A-C-F-C-A-T-G) nonanucleotide duplex (designated AP/sub F/ 9-mer duplex) which contains a stable abasic site analog, F, in the center of the helix. This oligodeoxynucleotide contains a modified tetrahydrofuran moiety, isosteric with 2-deoxyribofuranose, which serves as a structural analog of a natural apurinic/apyrimidinic site. Exchangeable and nonexchangeable base and sugar protons, including those located at the abasic site, have been assigned in the complementary AP/sub F/ 9-mer duplex by recording and analyzing two-dimensional phase-sensitive NOESY data sets in H 2 O and D 2 O solution at low temperature (0 0 C). These studies indicate that A5 inserts into the helix opposite the abasic site F14 and stacks with flanking G4 x C15 and G6 x C13 Watson-Crick base pairs. Base-sugar proton NOE connectivities were measured through G4-A5-G6 on the unmodified strand and between the base protons of C15 and the sugar protons of the 5'-flanking residue F14 on the modified strand. These studies establish that all glycosidic torsion angles are anti and that the helix is right-handed at and adjacent to the abasic site in the AP/sub F/ 9-mer duplex. Two of the 16 phosphodiester groups exhibit phosphorus resonances outside the normal spectral dispersion indicative of altered torsion angles at two of the phosphate groups in the backbone of the AP/sub F/ 9-mer duplex

  20. Aggregation properties of a short peptide that mediates amyloid fibril ...

    Indian Academy of Sciences (India)

    Short peptides have been identified from amyloidogenic proteins that form amyloid fibrils in isolation. The ... proteins. These peptide fibrils have the conformational features of β-structure that .... water and immediately deposited on freshly cleaved surface of mica .... with the peptide via electrostatic interactions. NaCl would.

  1. Management of Newly Diagnosed Atrial Fibrillation in an Outpatient Clinic Setting

    DEFF Research Database (Denmark)

    Thrysoee, Lars; Strömberg, Anna; Brandes, Axel

    2018-01-01

    fibrillation is not a fatal disease in itself was very important for patients. At the same time, visiting the clinic was overwhelming, information was difficult to understand, and patients found it difficult to be involved in decision-making. CONCLUSIONS: This study indicates that patients were uncertain......AIMS: To gain in-depth knowledge of patients' experiences of the consultation processes at a multidisciplinary atrial fibrillation outpatient clinic in a university hospital in Denmark. BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia associated with morbidity and mortality...... if not diagnosed and treated as recommended. Patients with newly diagnosed atrial fibrillation preferably should be managed in an outpatient setting which includes medical examination, patient education and decision making on medical therapy. DESIGN: This is a qualitative study of 14 patients newly diagnosed...

  2. Effect of TFE on the Helical Content of AK17 and HAL-1 Peptides: Theoretical Insights into the Mechanism of Helix Stabilization.

    Science.gov (United States)

    Vymětal, Jiří; Bednárová, Lucie; Vondrášek, Jiří

    2016-02-18

    Fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) are among the most frequently used cosolvents in experiment studies of peptides. They have significant effects on secondary structure and a particularly strong promotion of α-helix is induced by TFE. In this study we validated recently proposed force field parameters for TFE in molecular dynamics simulations with two model peptides-alanine-rich AK-17 and antimicrobial peptide halictine-1 (HAL-1). In the case of HAL-1, we characterized the effect of TFE on this peptide experimentally by ECD spectroscopy. Our TFE model in question reproduced the helix-promoting effect of TFE and provided insight into the mechanisms of TFE action on peptides. Our simulations confirmed the preferential interaction of TFE molecules with α-helices, although the TFE molecules accumulate in the vicinity of the peptides in various conformations. Moreover, we observed a significant effect of TFE on the thermodynamics of the helix-coil transition and a change in local conformational preferences in the unfolded (coil) state induced by TFE. In addition, our simulation-based analysis suggests that different mechanisms participate in helix stabilization in both model peptides in water and TFE solution. Our results thus support the picture of complex TFE action on peptides that is further diversified by the identity and intrinsic properties of the peptide.

  3. Optimizing cellulose fibrillation for the production of cellulose nanofibrils by a disk grinder

    Science.gov (United States)

    Chuanshuang Hu; Yu Zhao; Kecheng Li; J.Y. Zhu; Roland Gleisner

    2015-01-01

    The fibrillation of a bleached kraft eucalyptus pulp was investigated by means of a laboratory-scale disk grinder for the production of cellulose nanofibrils (CNF), while the parameters disk rotating speed, solid loading, and fibrillation duration were varied. The cumulative energy consumption was monitored during fibrillation. The degree of polymerization (DP) and...

  4. Advanced glycation end products induce differential structural modifications and fibrillation of albumin

    Science.gov (United States)

    Awasthi, Saurabh; Sankaranarayanan, Kamatchi; Saraswathi, N. T.

    2016-06-01

    Glycation induced amyloid fibrillation is fundamental to the development of many neurodegenerative and cardiovascular complications. Excessive non-enzymatic glycation in conditions such as hyperglycaemia results in the increased accumulation of advanced glycation end products (AGEs). AGEs are highly reactive pro-oxidants, which can lead to the activation of inflammatory pathways and development of oxidative stress. Recently, the effect of non-enzymatic glycation on protein structure has been the major research area, but the role of specific AGEs in such structural alteration and induction of fibrillation remains undefined. In this study, we determined the specific AGEs mediated structural modifications in albumin mainly considering carboxymethyllysine (CML), carboxyethyllysine (CEL), and argpyrimidine (Arg-P) which are the major AGEs formed in the body. We studied the secondary structural changes based on circular dichroism (CD) and spectroscopic analysis. The AGEs induced fibrillation was determined by Congo red binding and examination of scanning and transmission electron micrographs. The amyloidogenic regions in the sequence of BSA were determined using FoldAmyloid. It was observed that CEL modification of BSA leads to the development of fibrillar structures, which was evident from both secondary structure changes and TEM analysis.

  5. Use of Vitamins K antagonists in non-valvular atrial fibrillation ...

    African Journals Online (AJOL)

    Introduction: atrial fibrillation is the commonest cardiac rythm disorder. Thromboembolic accidents are common complications that should be prevented by anticoagulant treatment. The aim of our study is to assess the use of vitamins K antagonists in the prevention of thromboembolic risk in atrial fibrillation. Methods: it was a ...

  6. Clinical characteristics, management, and control of permanent vs. nonpermanent atrial fibrillation: insights from the RealiseAF survey.

    LENUS (Irish Health Repository)

    Murin, Jan

    2014-01-01

    Atrial fibrillation can be categorized into nonpermanent and permanent atrial fibrillation. There is less information on permanent than on nonpermanent atrial fibrillation patients. This analysis aimed to describe the characteristics and current management, including the proportion of patients with successful atrial fibrillation control, of these atrial fibrillation subsets in a large, geographically diverse contemporary sample.

  7. Failure of antiarrhythmic drugs to prevent experimental reperfusion ventricular fibrillation.

    Science.gov (United States)

    Naito, M; Michelson, E L; Kmetzo, J J; Kaplinsky, E; Dreifus, L S

    1981-01-01

    Ninety-nine adult mongrel dogs underwent acute ligation of the proximal left anterior descending coronary artery. Thirty minutes later, the occlusion was released to evaluate the effectiveness of five antiarrhythmic protocols in eliminating reperfusion ventricular fibrillation. The five protocols included: protocol 1 --i.v. lidocaine, preligation and prerelease (n = 19); protocol 2 -- i.v. lidocaine, prereperfusion only (n = 22); protocol 3 -- chronic, oral, daily amiodarone for 2 weeks preligation (n = 19); protocol 4 -- i.v. procainamide, preligation and prereperfusion (n = 21); and protocol 5 -- i.v. verapamil, prereperfusion (n = 18). Each regimen was evaluated with respect to the incidence of reperfusion ventricular fibrillation in dogs that survived to reperfusion, and the results were compared to 77 control dogs that underwent identical coronary artery occlusion and release procedures without drug therapy. The incidence of reperfusion ventricular fibrillation was as follows: protocol 1 -- seven of 15 dogs (47%); protocol 2 -- six of 18 (33%); protocol 3 -- 11 of 16 dogs (69%); protocol 4 -- eight of 17 dogs (47%); and protocol 5 -- 10 of 17 dogs (59%), compared with 36 of 60 (60%) in control dogs. Using chi-square analysis, protocol 2 was beneficial (p antecedent coronary artery ligation periods, and predictive risk indexes for the occurrence of reperfusion ventricular fibrillation were developed. the Mantel-Haenszel method of statistical analysis revealed that none of these protocols resulted in a statistically significant reduction in the incidence of reperfusion ventricular fibrillation. Thus, use of these predictive indexes plus appropriate statistical methods has revealed, unexpectedly, limitations in the efficacy of a spectrum of antiarrhythmic agents in preventing reperfusion ventricular fibrillation.

  8. An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1.

    Science.gov (United States)

    Herlo, Rasmus; Lund, Viktor K; Lycas, Matthew D; Jansen, Anna M; Khelashvili, George; Andersen, Rita C; Bhatia, Vikram; Pedersen, Thomas S; Albornoz, Pedro B C; Johner, Niklaus; Ammendrup-Johnsen, Ina; Christensen, Nikolaj R; Erlendsson, Simon; Stoklund, Mikkel; Larsen, Jannik B; Weinstein, Harel; Kjærulff, Ole; Stamou, Dimitrios; Gether, Ulrik; Madsen, Kenneth L

    2018-05-15

    BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. One-dimensional nonlinear theory for rectangular helix traveling-wave tube

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Chengfang, E-mail: fchffchf@126.com; Zhao, Bo; Yang, Yudong; Ju, Yongfeng [Faculty of Electronic Information Engineering, Huaiyin Institute of Technology, Huai' an 223003 (China); Wei, Yanyu [School of Physical Electronics, University of Electronic and Technology of China, Chengdu 610054 (China)

    2016-08-15

    A 1-D nonlinear theory of a rectangular helix traveling-wave tube (TWT) interacting with a ribbon beam is presented in this paper. The RF field is modeled by a transmission line equivalent circuit, the ribbon beam is divided into a sequence of thin rectangular electron discs with the same cross section as the beam, and the charges are assumed to be uniformly distributed over these discs. Then a method of computing the space-charge field by solving Green's Function in the Cartesian Coordinate-system is fully described. Nonlinear partial differential equations for field amplitudes and Lorentz force equations for particles are solved numerically using the fourth-order Runge-Kutta technique. The tube's gain, output power, and efficiency of the above TWT are computed. The results show that increasing the cross section of the ribbon beam will improve a rectangular helix TWT's efficiency and reduce the saturated length.

  10. Modeling of arylamide helix mimetics in the p53 peptide binding site of hDM2 suggests parallel and anti-parallel conformations are both stable.

    Directory of Open Access Journals (Sweden)

    Jonathan C Fuller

    Full Text Available The design of novel α-helix mimetic inhibitors of protein-protein interactions is of interest to pharmaceuticals and chemical genetics researchers as these inhibitors provide a chemical scaffold presenting side chains in the same geometry as an α-helix. This conformational arrangement allows the design of high affinity inhibitors mimicking known peptide sequences binding specific protein substrates. We show that GAFF and AutoDock potentials do not properly capture the conformational preferences of α-helix mimetics based on arylamide oligomers and identify alternate parameters matching solution NMR data and suitable for molecular dynamics simulation of arylamide compounds. Results from both docking and molecular dynamics simulations are consistent with the arylamides binding in the p53 peptide binding pocket. Simulations of arylamides in the p53 binding pocket of hDM2 are consistent with binding, exhibiting similar structural dynamics in the pocket as simulations of known hDM2 binders Nutlin-2 and a benzodiazepinedione compound. Arylamide conformations converge towards the same region of the binding pocket on the 20 ns time scale, and most, though not all dihedrals in the binding pocket are well sampled on this timescale. We show that there are two putative classes of binding modes for arylamide compounds supported equally by the modeling evidence. In the first, the arylamide compound lies parallel to the observed p53 helix. In the second class, not previously identified or proposed, the arylamide compound lies anti-parallel to the p53 helix.

  11. Spectroscopic study of Alzheimer's amyloid fibrils using terahertz time domain spectroscopy

    International Nuclear Information System (INIS)

    Jung, Euna; Kim, Jeonghoi; Han, Younho; Moon, Kiwon; Lim, Meehyun; Han, Haewook; Park, Joonhyuck; Kim, Sungjee

    2008-01-01

    Alzheimer's disease, one of the most common neurodegenerative diseases, is characterized by extensive amyloid deposition. Amyloid deposits contain the abundant fibrils formed by amyloid β protein (Aβ). Because amyloid fibrils are associated with amyloid diseases, including Alzheimer's disease, type 2 diabetes, prion disease, Parkinson's disease, senile systemic amyloidosis and Huntington's disease, there has been considerable interest within the biomedical and biochemical research communities. In transmission electron microscopic (TEM)images, amyloid firils are 0.1∼10μm long and approximately 10nm wide. Amyloid fibrils commonly exhibit self assembled filaments, often described as twisted or parallel assemblies of finer protofilaments. They are formed by the spontaneous aggregation of a wide variety of peptides and proteins. Structural studies of amyloid fibrils have revealed that the common structural motif of virtually all amyloid fibrils consists of cross β sheets in which the peptide strands are arranged perpendicular to the long axis of the fiber. But little was known until recently about the molecular level structures of amyloid fibils. Therefore, spectroscopic investigation of both amyloid fibrils and Aβ at the molecular level can provide the significant evidence for the molecular understanding of amyloidogenesis and for the development of innovative therapeutic and diagnostic approaches. We used terahertz time domain spectroscopy (THz TDS)to investigate both Aβ and amyloid fibril. THz TDS, developed over the last two decades, is a powerful tool to extract the properties of biomaterials and provides unique spectral signatures of biomolecules within 0.1∼10THz, which exists between microwave and infrared frequency range. Current interest in THz radiation arises from its capability of probing the delocalized collective vibrational modes in proteins. Studying the collective modes of proteins in THz frequency range can play an important role in

  12. Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations

    International Nuclear Information System (INIS)

    Yoon, Gwonchan; Lee, Myeongsang; Kim, Kyungwoo; In Kim, Jae; Joon Chang, Hyun; Baek, Inchul; Na, Sungsoo; Eom, Kilho

    2015-01-01

    Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties. (paper)

  13. Susceptibility tensor imaging and tractography of collagen fibrils in the articular cartilage.

    Science.gov (United States)

    Wei, Hongjiang; Gibbs, Eric; Zhao, Peida; Wang, Nian; Cofer, Gary P; Zhang, Yuyao; Johnson, G Allan; Liu, Chunlei

    2017-11-01

    To investigate the B 0 orientation-dependent magnetic susceptibility of collagen fibrils within the articular cartilage and to determine whether susceptibility tensor imaging (STI) can detect the 3D collagen network within cartilage. Multiecho gradient echo datasets (100-μm isotropic resolution) were acquired from fixed porcine articular cartilage specimens at 9.4 T. The susceptibility tensor was calculated using phase images acquired at 12 or 15 different orientations relative to B 0 . The susceptibility anisotropy of the collagen fibril was quantified and diffusion tensor imaging (DTI) was compared against STI. 3D tractography was performed to visualize and track the collagen fibrils with DTI and STI. STI experiments showed the distinct and significant anisotropic magnetic susceptibility of collagen fibrils within the articular cartilage. STI can be used to measure and quantify susceptibility anisotropy maps. Furthermore, STI provides orientation information of the underlying collagen network via 3D tractography. The findings of this study demonstrate that STI can characterize the orientation variation of collagen fibrils where diffusion anisotropy fails. We believe that STI could serve as a sensitive and noninvasive marker to study the collagen fibrils microstructure. Magn Reson Med 78:1683-1690, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  14. Atrial fibrillation associated with chocolate intake abuse and chronic salbutamol inhalation abuse.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo; La Rosa, Felice Carmelo; Rocca, Roberto La

    2010-11-19

    The use of substances as the substrate for atrial fibrillation is not frequently recognized. Chocolate is derived from the roasted seeds of the plant theobroma cacao and its components are the methylxanthine alkaloids theobromine and caffeine. Caffeine is a methylxanthine whose primary biological effect is the competitive antagonism of the adenosine receptor. Normal consumption of caffeine was not associated with risk of atrial fibrillation or flutter. Sympathomimetic effects, due to circulating catecholamines cause the cardiac manifestations of caffeine overdose toxicity, produce tachyarrhythmias such as supraventricular tachycardia, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation.The commonly used doses of inhaled or nebulized salbutamol induced no acute myocardial ischaemia, arrhythmias or changes in heart rate variability in patients with coronary artery disease and clinically stable asthma or chronic obstructive pulmonary disease. Two-week salbutamol treatment shifts the cardiovascular autonomic regulation to a new level characterized by greater sympathetic responsiveness and slight beta2-receptor tolerance. We present a case of atrial fibrillation associated with chocolate intake abuse in a 19-year-old Italian woman with chronic salbutamol inhalation abuse. This case focuses attention on chocolate intake abuse associated with chronic salbutamol abuse as the substrate for atrial fibrillation. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

  15. Electrochemical DNA probe for Hg(2+) detection based on a triple-helix DNA and Multistage Signal Amplification Strategy.

    Science.gov (United States)

    Wang, Huan; Zhang, Yihe; Ma, Hongmin; Ren, Xiang; Wang, Yaoguang; Zhang, Yong; Wei, Qin

    2016-12-15

    In this work, an ultrasensitive electrochemical sensor was developed for detection of Hg(2+). Gold nanoparticles decorated bovine serum albumin reduction of graphene oxide (AuNP-BSA-rGO) were used as subsurface material for the immobilization of triple-helix DNA. The triple-helix DNA containing a thiol labelled single-stranded DNA (sDNA) and a thymine-rich DNA (T-rich DNA), which could be unwinded in the present of Hg(2+) to form more stable thymine-Hg(2+)-thymine (T-Hg(2+)-T) complex. T-Hg(2+)-T complex was then removed and the sDNA was left on the electrode. At this time, gold nanoparticle carrying thiol labelled cytosine-rich complementary DNA (cDNA-AuNP) could bind with the free sDNA. Meanwhile, the other free cDNA on AuNP could bind with each other in the present of Ag(+) to form the stable cytosine-Ag(+)-cytosine (C-Ag(+)-C) complex and circle amplification. Plenty of C-Ag(+)-C could form silver nanoclusters by electrochemical reduction and the striping signal of Ag could be measured for purpose of the final electrochemical detection of Hg(2+). This sensor could detect Hg(2+) over a wide concentration range from 0.1 to 130nM with a detection limit of 0.03nM. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Characterization of fibrillation process of α-synuclein at the initial stage

    International Nuclear Information System (INIS)

    Tashiro, Mitsuru; Kojima, Masaki; Kihara, Hiroshi; Kasai, Kouki; Kamiyoshihara, Tomoaki; Ueda, Kenji; Shimotakahara, Sakurako

    2008-01-01

    α-Synuclein is the major component of the filamentous Lewy bodies and Lewy-related neurites, neuropathological hallmarks of Parkinson's disease. Although numerous studies on α-synuclein fibrillation have been reported, the molecular mechanisms of aggregation and fibrillation at the initial stage are still unclear. In the present study, structural properties and propensities to form fibrils of α-synuclein at the initial stage were investigated using 2D 1 H- 15 N NMR spectroscopy, electron microscope, and small angle X-ray scattering (SAXS). Observation of the 2D 1 H- 15 N HSQC spectra indicated significant attenuation of many cross peak intensities in the regions of KTKEGV-type repeats and the non-Aβ component of Alzheimer's disease amyloid (NAC), suggesting that these regions contributed fibril formation. Oligomerization comprising heptamer was successfully monitored at the initial stage using the time-dependent SAXS measurements

  17. Fibrillation of Aspen by Alkaline Cold Pre-treatment and Vibration Milling

    Directory of Open Access Journals (Sweden)

    Kärt KÄRNER

    2016-09-01

    Full Text Available In this article an attempt to fibrillate aspen bleached chemi-thermo mechanical pulp (BCTMP fibre in an environmentally friendly way is reported. The effects of various NaOH, KOH, urea and ethanol aqueous solutions at lowered temperature were tested for pre-treatment. The pre-treatment was followed by vibration milling aiming to peel off outer cell wall layers and to fibrillate S2 layer of the aspen wood fibre. The effects of the treatments were evaluated by scanning electron microscopy (SEM. The results show that it is possible to fibrillate BCTMP aspen fibres by using alkaline aqueous solutions at low temperatures followed by a mechanical treatment. A strong dependence on fibrillation of cellulose on temperature, time and alkali concentration was established.DOI: http://dx.doi.org/10.5755/j01.ms.22.3.7412

  18. Influence of Aluminium and EGCG on Fibrillation and Aggregation of Human Islet Amyloid Polypeptide

    Directory of Open Access Journals (Sweden)

    Zhi-Xue Xu

    2016-01-01

    Full Text Available The abnormal fibrillation of human islet amyloid polypeptide (hIAPP has been implicated in the development of type II diabetes. Aluminum is known to trigger the structural transformation of many amyloid proteins and induce the formation of toxic aggregate species. The (−-epigallocatechin gallate (EGCG is considered capable of binding both metal ions and amyloid proteins with inhibitory effect on the fibrillation of amyloid proteins. However, the effect of Al(III/EGCG complex on hIAPP fibrillation is unclear. In the present work, we sought to view insight into the structures and properties of Al(III and EGCG complex by using spectroscopic experiments and quantum chemical calculations and also investigated the influence of Al(III and EGCG on hIAPP fibrillation and aggregation as well as their combined interference on this process. Our studies demonstrated that Al(III could promote fibrillation and aggregation of hIAPP, while EGCG could inhibit the fibrillation of hIAPP and lead to the formation of hIAPP amorphous aggregates instead of the ordered fibrils. Furthermore, we proved that the Al(III/EGCG complex in molar ratio of 1 : 1 as Al(EGCG(H2O2 could inhibit the hIAPP fibrillation more effectively than EGCG alone. The results provide the invaluable reference for the new drug development to treat type II diabetes.

  19. Albumin fibrillization induces apoptosis via integrin/FAK/Akt pathway

    Directory of Open Access Journals (Sweden)

    Liang Chi-Ming

    2009-01-01

    Full Text Available Abstract Background Numerous proteins can be converted to amyloid-like fibrils to increase cytotoxicity and induce apoptosis, but the methods generally require a high concentration of protein, vigorous shaking, or fibril seed. As well, the detailed mechanism of the cytotoxic effects is not well characterized. In this study, we have developed a novel process to convert native proteins into the fibrillar form. We used globular bovine serum albumin (BSA as a model protein to verify the properties of the fibrillar protein, investigated its cellular effects and studied the signaling cascade induced by the fibrillar protein. Results We induced BSA, a non-cytotoxic globular protein, to become fibril by a novel process involving Superdex-200 column chromatography in the presence of anionic or zwittergenic detergent(s. The column pore size was more important than column matrix composite in fibril formation. The fibrillar BSA induced apoptosis in BHK-21 cell as well as breast cancer cell line T47D. Pre-treating cells with anti-integrin antibodies blocked the apoptotic effect. Fibrillar BSA, but not globular BSA, bound to integrin, dephosphorylated focal adhesion kinase (FAK, Akt and glycogen synthase kinase-3β (GSK-3β. Conclusion We report on a novel process for converting globular proteins into fibrillar form to cause apoptosis by modulating the integrin/FAK/Akt/GSK-3β/caspase-3 signaling pathway. Our findings may be useful for understanding the pathogenesis of amyloid-like fibrils and applicable for the development of better therapeutic agents that target the underlying mechanism(s of the etiologic agents.

  20. Clear cell hidradenocarcinoma of the ear helix: report of primary ear helix adnexal carcinoma with regional lymph node metastasis.

    Science.gov (United States)

    Bae, Tae Hui; Kang, Shin Hyuk; Kim, Han Koo; Kim, Woo Seob; Kim, Mi Kyung

    2014-07-01

    Clear cell hidradenocarcinoma is a rare tumor of eccrine sweat gland origin that has a predilection for the head and neck. It has an indolent growth pattern and a higher incidence of regional and distant metastases. Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. We report a case of an 89-year-old female patient with clear cell hidradenocarcinoma manifesting in the right ear helix that metastasized to the right parotid gland who was treated by wide local excision and radiation therapy.

  1. Risk Factors for Atrial Fibrillation

    NARCIS (Netherlands)

    B.P. Krijthe (Bouwe)

    2013-01-01

    textabstractAtrial fibrillation is a common cardiac arrhythmia that is characterized by rapid disorganized atrial electrical activity resulting in absence of atrial contractions. It is diagnosed on the basis of typical findings on an electrocardiogram (ECG). The characteristic ECG findings are

  2. Impact of body mass index on mortality and hospitalisation of patients with atrial fibrillation.

    Science.gov (United States)

    Ball, Jocasta; Løchen, Maja-Lisa; Carrington, Melinda J; Wiley, Joshua F; Stewart, Simon

    2018-04-01

    Atrial fibrillation represents a substantial clinical and public health issue. The definitive impact of body mass index on prognosis of patients with chronic (persistent or permanent) atrial fibrillation remains undetermined. The purpose of this study was to investigate the association of body mass index with health outcomes (mortality and re-hospitalisation) of patients with chronic atrial fibrillation. Using data from the Standard versus Atrial Fibrillation spEcific managemenT strategY (SAFETY) trial (a randomised controlled trial of home-based, atrial fibrillation-specific disease management), we performed post-hoc analyses of mortality and re-hospitalisation outcomes during minimum 24-month follow-up according to baseline body mass index profile. Of 297 participants (mean age 71±11 years, 47% female, mean body mass index 29.6±6.7 kg/m 2 ), 35.0% of participants were overweight (body mass index 25.0-29.9 kg/m 2 ) and 43.1% were obese (body mass index≥30 kg/m 2 ). During follow-up, n=42 died including 16/65 (24.6%) classified as normal body mass index, 16/104 (15.4%) classified as overweight and 10/128 (7.8%) classified as obese. Increasing body mass index was not associated with increased mortality but was associated with re-hospitalisation due to cardiovascular disease with greater length-of-stay (odds ratio 1.05; 95% confidence interval 1.00-1.09, p=0.032). Obese individuals experienced increased unplanned admissions compared to overweight individuals (incidence rate ratio 0.71; 95% confidence interval 0.53-0.96, p=0.028), and increased cardiovascular-related (incidence rate ratio 0.58; 95% confidence interval 0.39-0.86, p=0.007) and all-cause admissions (incidence rate ratio 0.63; 95% confidence interval 0.45-0.89, p=0.008) compared to those classified as normal body mass index. Overweight and obesity were not associated with survival in patients with chronic atrial fibrillation but were associated with more frequent hospital care and prolonged stay.

  3. Stroke risk associated with balloon based catheter ablation for atrial fibrillation: Rationale and design of the MACPAF Study

    Directory of Open Access Journals (Sweden)

    Schultheiss Heinz-Peter

    2010-07-01

    Full Text Available Abstract Background Catheter ablation of the pulmonary veins has become accepted as a standard therapeutic approach for symptomatic paroxysmal atrial fibrillation (AF. However, there is some evidence for an ablation associated (silent stroke risk, lowering the hope to limit the stroke risk by restoration of rhythm over rate control in AF. The purpose of the prospective randomized single-center study "Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation" (MACPAF is to compare the efficacy and safety of two balloon based pulmonary vein ablation systems in patients with symptomatic paroxysmal AF. Methods/Design Patients are randomized 1:1 for the Arctic Front® or the HD Mesh Ablator® catheter for left atrial catheter ablation (LACA. The predefined endpoints will be assessed by brain magnetic resonance imaging (MRI, neuro(psychological tests and a subcutaneously implanted reveal recorder for AF detection. According to statistics 108 patients will be enrolled. Discussion Findings from the MACPAF trial will help to balance the benefits and risks of LACA for symptomatic paroxysmal AF. Using serial brain MRIs might help to identify patients at risk for LACA-associated cerebral thromboembolism. Potential limitations of the study are the single-center design, the existence of a variety of LACA-catheters, the missing placebo-group and the impossibility to assess the primary endpoint in a blinded fashion. Trial registration clinicaltrials.gov NCT01061931

  4. Clinical Differences between Subtypes of Atrial Fibrillation and Flutter: Cross-Sectional Registry of 407 Patients

    Directory of Open Access Journals (Sweden)

    Eduardo Dytz Almeida

    2015-01-01

    Full Text Available Introduction: Atrial fibrillation and atrial flutter account for one third of hospitalizations due to arrhythmias, determining great social and economic impacts. In Brazil, data on hospital care of these patients is scarce. Objective: To investigate the arrhythmia subtype of atrial fibrillation and flutter patients in the emergency setting and compare the clinical profile, thromboembolic risk and anticoagulants use. Methods: Cross-sectional retrospective study, with data collection from medical records of every patient treated for atrial fibrillation and flutter in the emergency department of Instituto de Cardiologia do Rio Grande do Sul during the first trimester of 2012. Results: We included 407 patients (356 had atrial fibrillation and 51 had flutter. Patients with paroxysmal atrial fibrillation were in average 5 years younger than those with persistent atrial fibrillation. Compared to paroxysmal atrial fibrillation patients, those with persistent atrial fibrillation and flutter had larger atrial diameter (48.6 ± 7.2 vs. 47.2 ± 6.2 vs. 42.3 ± 6.4; p < 0.01 and lower left ventricular ejection fraction (66.8 ± 11 vs. 53.9 ± 17 vs. 57.4 ± 16; p < 0.01. The prevalence of stroke and heart failure was higher in persistent atrial fibrillation and flutter patients. Those with paroxysmal atrial fibrillation and flutter had higher prevalence of CHADS2 score of zero when compared to those with persistent atrial fibrillation (27.8% vs. 18% vs. 4.9%; p < 0.01. The prevalence of anticoagulation in patients with CHA2DS2-Vasc ≤ 2 was 40%. Conclusions: The population in our registry was similar in its comorbidities and demographic profile to those of North American and European registries. Despite the high thromboembolic risk, the use of anticoagulants was low, revealing difficulties for incorporating guideline recommendations. Public health strategies should be adopted in order to improve these rates.

  5. The Effect of a Helix-Coil Transition on the Extension Elasticity

    Science.gov (United States)

    Buhot, Arnaud; Halperin, Avi

    2000-03-01

    The secondary structure of a polymer affects its deformation behavior in accordance with the Le Chatelier principle. An important example of such secondary structure is the alpha helix encountered in polypeptides. Similar structure was recently proposed for PEO in aqueous media. Our discussion concerns the coupling of the cooperative helix-coil transition and the extension elasticity. In particular, we analyze the extension of a long single chain by use of optical tweezers or AFM. We consider chains that exist in the coil-state when unperturbed. The transition nevertheless occurs because the extension favors the low entropy helical state. As a result, the corresponding force law exhibits a plateau. The analysis of this situation involves two ingredients: (I) the stretching free energy penalty for a rod-coil mutiblock copolymer (II) the entropy associated with the possible placements of the rod and coil blocks.

  6. Chiral transformation: From single nanowire to double helix

    KAUST Repository

    Wang, Yong

    2011-12-21

    We report a new type of water-soluble ultrathin Au-Ag alloy nanowire (NW), which exhibits unprecedented behavior in a colloidal solution. Upon growth of a thin metal (Pd, Pt, or Au) layer, the NW winds around itself to give a metallic double helix. We propose that the winding originates from the chirality within the as-synthesized Au-Ag NWs, which were induced to untwist upon metal deposition. © 2011 American Chemical Society.

  7. Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs

    NARCIS (Netherlands)

    Shiroshita-Takeshita, A; Brundel, BJJM; Lavoie, J; Nattel, S

    2006-01-01

    Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by

  8. The human early-life exposome (HELIX): project rationale and design.

    Science.gov (United States)

    Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

    2014-06-01

    Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

  9. Right- and left-handed three-helix proteins. I. Experimental and simulation analysis of differences in folding and structure.

    Science.gov (United States)

    Glyakina, Anna V; Pereyaslavets, Leonid B; Galzitskaya, Oxana V

    2013-09-01

    Despite the large number of publications on three-helix protein folding, there is no study devoted to the influence of handedness on the rate of three-helix protein folding. From the experimental studies, we make a conclusion that the left-handed three-helix proteins fold faster than the right-handed ones. What may explain this difference? An important question arising in this paper is whether the modeling of protein folding can catch the difference between the protein folding rates of proteins with similar structures but with different folding mechanisms. To answer this question, the folding of eight three-helix proteins (four right-handed and four left-handed), which are similar in size, was modeled using the Monte Carlo and dynamic programming methods. The studies allowed us to determine the orders of folding of the secondary-structure elements in these domains and amino acid residues which are important for the folding. The obtained data are in good correlation with each other and with the experimental data. Structural analysis of these proteins demonstrated that the left-handed domains have a lesser number of contacts per residue and a smaller radius of cross section than the right-handed domains. This may be one of the explanations of the observed fact. The same tendency is observed for the large dataset consisting of 332 three-helix proteins (238 right- and 94 left-handed). From our analysis, we found that the left-handed three-helix proteins have some less-dense packing that should result in faster folding for some proteins as compared to the case of right-handed proteins. Copyright © 2013 Wiley Periodicals, Inc.

  10. On Mixed Data and Event Driven Design for Adaptive-Critic-Based Nonlinear $H_{\\infty}$ Control.

    Science.gov (United States)

    Wang, Ding; Mu, Chaoxu; Liu, Derong; Ma, Hongwen

    2018-04-01

    In this paper, based on the adaptive critic learning technique, the control for a class of unknown nonlinear dynamic systems is investigated by adopting a mixed data and event driven design approach. The nonlinear control problem is formulated as a two-player zero-sum differential game and the adaptive critic method is employed to cope with the data-based optimization. The novelty lies in that the data driven learning identifier is combined with the event driven design formulation, in order to develop the adaptive critic controller, thereby accomplishing the nonlinear control. The event driven optimal control law and the time driven worst case disturbance law are approximated by constructing and tuning a critic neural network. Applying the event driven feedback control, the closed-loop system is built with stability analysis. Simulation studies are conducted to verify the theoretical results and illustrate the control performance. It is significant to observe that the present research provides a new avenue of integrating data-based control and event-triggering mechanism into establishing advanced adaptive critic systems.

  11. Genome-wide analysis of basic/helix-loop-helix gene family in peanut and assessment of its roles in pod development.

    Directory of Open Access Journals (Sweden)

    Chao Gao

    Full Text Available The basic/helix-loop-helix (bHLH proteins constitute a superfamily of transcription factors that are known to play a range of regulatory roles in eukaryotes. Over the past few decades, many bHLH family genes have been well-characterized in model plants, such as Arabidopsis, rice and tomato. However, the bHLH protein family in peanuts has not yet been systematically identified and characterized. Here, 132 and 129 bHLH proteins were identified from two wild ancestral diploid subgenomes of cultivated tetraploid peanuts, Arachis duranensis (AA and Arachis ipaensis (BB, respectively. Phylogenetic analysis indicated that these bHLHs could be classified into 19 subfamilies. Distribution mapping results showed that peanut bHLH genes were randomly and unevenly distributed within the 10 AA chromosomes and 10 BB chromosomes. In addition, 120 bHLH gene pairs between the AA-subgenome and BB-subgenome were found to be orthologous and 101 of these pairs were highly syntenic in AA and BB chromosomes. Furthermore, we confirmed that 184 bHLH genes expressed in different tissues, 22 of which exhibited tissue-specific expression. Meanwhile, we identified 61 bHLH genes that may be potentially involved in peanut-specific subterranean. Our comprehensive genomic analysis provides a foundation for future functional dissection and understanding of the regulatory mechanisms of bHLH transcription factors in peanuts.

  12. Quantification of anaesthetic effects on atrial fibrillation rate by partial least-squares

    International Nuclear Information System (INIS)

    Cervigón, R; Moreno, J; Pérez-Villacastín, J; Reilly, R B; Castells, F

    2012-01-01

    The mechanism underlying atrial fibrillation (AF) remains poorly understood. Multiple wandering propagation wavelets drifting through both atria under hierarchical models are not understood. Some pharmacological drugs, known as antiarrhythmics, modify the cardiac ionic currents supporting the fibrillation process within the atria and may modify the AF propagation dynamics terminating the fibrillation process. Other medications, theoretically non-antiarrhythmic, may slightly affect the fibrillation process in non-defined mechanisms. We evaluated whether the most commonly used anaesthetic agent, propofol, affects AF patterns. Partial least-squares (PLS) analysis was performed to reduce significant noise into the main latent variables to find the differences between groups. The final results showed an excellent discrimination between groups with slow atrial activity during the propofol infusion. (paper)

  13. Salt- and pH-Triggered Helix-Coil Transition of Ionic Polypeptides under Physiology Conditions.

    Science.gov (United States)

    Yuan, Jingsong; Zhang, Yi; Sun, Yue; Cai, Zhicheng; Yang, Lijiang; Lu, Hua

    2018-06-11

    Controlling the helix-coil transition of polypeptides under physiological conditions is an attractive way toward smart functional materials. Here, we report the synthesis of a series of tertiary amine-functionalized ethylene glycol (EG x )-linked polypeptide electrolytes with their secondary structures tunable under physiological conditions. The resultant polymers, denoted as P(EG x DMA-Glu) ( x = 1, 2, and 3), show excellent aqueous solubility (>20 mg/mL) regardless of their charge states. Unlike poly-l-lysine that can form a helix only at pH above 10, P(EG x DMA-Glu) undergo a pH-dependent helix-coil switch with their transition points within the physiological range (pH ∼5.3-6.5). Meanwhile, P(EG x DMA-Glu) exhibit an unusual salt-induced helical conformation presumably owing to the unique properties of EG x linkers. Together, the current work highlights the importance of fine-tuning the linker chemistry in achieving conformation-switchable polypeptides and represents a facile approach toward stimuli-responsive biopolymers for advanced biological applications.

  14. Structure of the Membrane Anchor of Pestivirus Glycoprotein Erns, a Long Tilted Amphipathic Helix

    Science.gov (United States)

    Aberle, Daniel; Muhle-Goll, Claudia; Bürck, Jochen; Wolf, Moritz; Reißer, Sabine; Luy, Burkhard; Wenzel, Wolfgang; Ulrich, Anne S.; Meyers, Gregor

    2014-01-01

    Erns is an essential virion glycoprotein with RNase activity that suppresses host cellular innate immune responses upon being partially secreted from the infected cells. Its unusual C-terminus plays multiple roles, as the amphiphilic helix acts as a membrane anchor, as a signal peptidase cleavage site, and as a retention/secretion signal. We analyzed the structure and membrane binding properties of this sequence to gain a better understanding of the underlying mechanisms. CD spectroscopy in different setups, as well as Monte Carlo and molecular dynamics simulations confirmed the helical folding and showed that the helix is accommodated in the amphiphilic region of the lipid bilayer with a slight tilt rather than lying parallel to the surface. This model was confirmed by NMR analyses that also identified a central stretch of 15 residues within the helix that is fully shielded from the aqueous layer, which is C-terminally followed by a putative hairpin structure. These findings explain the strong membrane binding of the protein and provide clues to establishing the Erns membrane contact, processing and secretion. PMID:24586172

  15. What patients want and need to know about atrial fibrillation

    Directory of Open Access Journals (Sweden)

    McCabe PJ

    2011-11-01

    Full Text Available Pamela J McCabe Saint Mary's Hospital, Mayo Clinic, Rochester, MN, USA Abstract: Clinicians in a variety of settings are called upon to care for patients diagnosed with atrial fibrillation (AF, a common chronic condition that affects up to 3 million people in the USA. Evidence-based guidelines provide clinicians with direction for treatment of AF, but recommended content for educating patients and counseling about self-management of AF is not included in published guidelines. When patients believe they have a good understanding of AF they report fewer symptoms, perceive greater control over AF, and attribute less emotional distress to AF. Thus, providing patients with information about AF and how to manage it is important for promoting positive outcomes. The purpose of this article is to offer evidence-based recommendations for content to include in self-management education and counseling for patients with AF. Approaches for educating and counseling patients related to AF pathophysiology, the nature of AF (its cause, consequences, and trajectory, treatments, action plans, and symptom management, and managing the psychosocial challenges of living with AF, are discussed. Keywords: atrial fibrillation, patient education, self-management education, counseling

  16. SclR, a basic helix-loop-helix transcription factor, regulates hyphal morphology and promotes sclerotial formation in Aspergillus oryzae.

    Science.gov (United States)

    Jin, Feng Jie; Takahashi, Tadashi; Matsushima, Ken-ichiro; Hara, Seiichi; Shinohara, Yasutomo; Maruyama, Jun-ichi; Kitamoto, Katsuhiko; Koyama, Yasuji

    2011-07-01

    Most known basic-region helix-loop-helix (bHLH) proteins belong to a superfamily of transcription factors often involved in the control of growth and differentiation. Therefore, inappropriate expression of genes encoding bHLH proteins is frequently associated with developmental dysfunction. In our previously reported study, a novel bHLH protein-encoding gene (AO090011000215) of Aspergillus oryzae was identified. The gene-disrupted strain was found to produce dense conidia, but sparse sclerotia, relative to the parent strain. Here, to further analyze its function, we generated an overexpressing strain using the A. oryzae amyB gene promoter. Genetic overexpression led to a large number of initial hyphal aggregations and then the formation of mature sclerotia; it was therefore designated sclR (sclerotium regulator). At the same time, the sclR-overexpressing strain also displayed both delayed and decreased conidiation. Scanning electron microscopy indicated that the aerial hyphae of the sclR-overexpressing strain were extremely branched and intertwined with each other. In the generation of the SclR-enhanced green fluorescent protein (EGFP) expression strain, the SclR-EGFP protein fusion was conditionally detected in the nuclei. In addition, the loss of sclR function led to rapid protein degradation and cell lysis in dextrin-polypeptone-yeast extract liquid medium. Taken together, these observations indicate that SclR plays an important role in hyphal morphology, asexual conidiospore formation, and the promotion of sclerotial production, even retaining normal cell function, at least in submerged liquid culture.

  17. Stroke prevention in atrial fibrillation

    DEFF Research Database (Denmark)

    Fanaroff, Alexander C; Steffel, Jan; Alexander, John H

    2018-01-01

    of anticoagulation for atrial fibrillation (AF). Observational studies employing RWD are useful for describing how oral anticoagulants are used in clinical practice, but generally cannot be used to make claims regarding comparative treatment effects. Questions regarding treatment effect generally are best answered...

  18. Clinical application of low energy intracardiac cardioversion of atrial fibrillation

    International Nuclear Information System (INIS)

    Wu Liqun; Gu Gang; Su Kan; Su Renying; Shen Yongchu; Shen Weifeng

    2002-01-01

    Objective: To evaluate the efficacy and safety of low energy intracardiac cardioversion in persistent atria fibrillation. Methods: Low energy intracardiac cardioversion was performed by delivering R wave-synchronized biphasic shocks in 7 patients (4 men, 3 women) with persistent atrial fibrillation. Prior to the procedure, all patients underwent transesophageal echocardiographic examinations to rule out the presence of intracardiac thrombus and received subcutaneous injection of low molecular weight heparin for 3-5 days. Two custom-made 6 Fr catheters (Rhythm Technologies of Getz, USA) were used for de-fibrillation shock delivery. One catheter was positioned in the lower right atrium so that the majority of the catheter electrodes had firm contact with the right atrial free wall. The second catheter was placed randomly either in coronary sinus through right internal jugular vein or in the left pulmonary artery through femoral vein. In addition, a standard diagnostic 6-F quadrupolar catheter was placed at the right ventricular apex for ventricular synchronization and postshock ventricular pacing. Shocks were delivered by Implant Support Device (Model 4510, Teleceronics). After conversion, all patients were treated with intravenous amiodarone in the first 24 hours followed by oral administration. Results: In all 7 patients cardioversion of atrial fibrillation to sinus rhythm was successfully obtained. A mean of 2 ± 1 shocks per patient has been delivered with a total amount of 13 shocks. The average delivered energy was 7.8 ± 2.2 Joules. No complication occurred. At a mean follow-up of 18 ± 9 months, 4 of the 7 patients treated successfully showed sinus rhythm there after. Atrial fibrillation recurred in 3 patients at the second, fifth day and eighth month after cardioversion. Conclusions: Low energy intracardiac cardioversion is effective and safe, and can be easily performed in patients without general anesthesia. It offers a new option for restoring sinus

  19. Effect of Stirring and Seeding on Whey Protein Fibril Formation

    NARCIS (Netherlands)

    Bolder, S.G.; Sagis, L.M.C.; Venema, P.; Linden, van der E.

    2007-01-01

    The effect of stirring and seeding on the formation of fibrils in whey protein isolate (WPI) solutions was studied. More fibrils of a similar length are formed when WPI is stirred during heating at pH 2 and 80 C compared to samples that were heated at rest. Addition of seeds did not show an

  20. Amyloid Fibril Polymorphism: Almost Identical on the Atomic Level, Mesoscopically Very Different.

    Science.gov (United States)

    Seuring, Carolin; Verasdonck, Joeri; Ringler, Philippe; Cadalbert, Riccardo; Stahlberg, Henning; Böckmann, Anja; Meier, Beat H; Riek, Roland

    2017-03-02

    Amyloid polymorphism of twisted and straight β-endorphin fibrils was studied by negative-stain transmission electron microscopy, scanning transmission electron microscopy, and solid-state nuclear magnetic resonance spectroscopy. Whereas fibrils assembled in the presence of salt formed flat, striated ribbons, in the absence of salt they formed mainly twisted filaments. To get insights into their structural differences at the atomic level, 3D solid-state NMR spectra of both fibril types were acquired, allowing the detection of the differences in chemical shifts of 13 C and 15 N atoms in both preparations. The spectral fingerprints and therefore the chemical shifts are very similar for both fibril types. This indicates that the monomer structure and the molecular interfaces are almost the same but that these small differences do propagate to produce flat and twisted morphologies at the mesoscopic scale. This finding is in agreement with both experimental and theoretical considerations on the assembly of polymers (including amyloids) under different salt conditions, which attribute the mesoscopic difference of flat versus twisted fibrils to electrostatic intermolecular repulsions.

  1. Health and Environment Linked for Information Exchange in Atlanta (HELIX-Atlanta): A Pilot Tracking System

    Science.gov (United States)

    Rickman, Doug; Shire, J.; Qualters, J.; Mitchell, K.; Pollard, S.; Rao, R.; Kajumba, N.; Quattrochi, D.; Estes, M., Jr.; Meyer, P.; hide

    2009-01-01

    Objectives. To provide an overview of four environmental public health surveillance projects developed by CDC and its partners for the Health and Environment Linked for Information Exchange, Atlanta (HELIX-Atlanta) and to illustrate common issues and challenges encountered in developing an environmental public health tracking system. Methods. HELIX-Atlanta, initiated in October 2003 to develop data linkage and analysis methods that can be used by the National Environmental Public Health Tracking Network (Tracking Network), conducted four projects. We highlight the projects' work, assess attainment of the HELIX-Atlanta goals and discuss three surveillance attributes. Results. Among the major challenges was the complexity of analytic issues which required multidiscipline teams with technical expertise. This expertise and the data resided across multiple organizations. Conclusions:Establishing formal procedures for sharing data, defining data analysis standards and automating analyses, and committing staff with appropriate expertise is needed to support wide implementation of environmental public health tracking.

  2. Biophysical aspects and novel treatments of atrial fibrillation.

    Science.gov (United States)

    Gigli, Lorenzo; Rosa, Gian M; Tagliasacchi, Maria I; Bonaventura, Aldo; Liberale, Luca; Montecucco, Fabrizio; Carbone, Federico; Bertero, Giovanni; Brunelli, Claudio

    2017-04-01

    Atrial fibrillation (AF) is a cardiac arrhythmia caused by various mechanisms, such as multiple re-entering wavelets, high frequency activity, and rotor sources. This narrative review was based on papers found on PubMed and MEDLINE up to May 2016. The search terms were "atrial fibrillation" in combination with "catheter ablation, pathophysiology, antiarrhythmic drugs". Antiarrhythmic drugs are the cornerstone of therapy in AF, but their efficacy and safety might have to be improved. In case of failure of pharmacologic therapies, other treatments can be considered. A better understanding of the important role of the pulmonary veins has led to new approaches, such as ablation procedures, which were initially only surgical, while percutaneous options were later added. However, these strategies may present various technical complications also when performed by skilled operators. A promising field of investigation is the genetics of AF, as highlighted by studies on the role of micro-RNA. Relevant improvement on the knowledge of the electrophysiological basis of genesis and maintenance of AF has been done in order to treat a very common arrhythmia, but further studies, as those in the genetics field, can open new challenging therapeutic horizons.

  3. Real life anticoagulation treatment of patients with atrial fibrillation in Germany

    DEFF Research Database (Denmark)

    Wilke, Thomas; Groth, Antje; Pfannkuche, Matthias

    2015-01-01

    Oral anticoagulation (OAC) with either new oral anticoagulants (NOACs) or Vitamin-K antagonists (VKAs) is recommended by guidelines for patients with atrial fibrillation (AF) and a moderate to high risk of stroke. Based on a claims-based data set the aim of this study was to quantify the stroke-r...... that both patient/disease characteristics and treatment environment/general prescribing behaviour of physicians may explain the OAC under-use in AF patients....

  4. Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

    Science.gov (United States)

    Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

    2018-01-01

    An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

  5. Use of 1–4 interaction scaling factors to control the conformational equilibrium between α-helix and β-strand

    International Nuclear Information System (INIS)

    Pang, Yuan-Ping

    2015-01-01

    Highlights: • 1–4 interaction scaling factors are used to adjust conformational energy. • This article reports the effects of these factors on protein conformations. • Reducing these factors changes a helix to a strand in molecular dynamics simulation. • Increasing these factors causes the reverse conformational change. • These factors control the conformational equilibrium between helix and strand. - Abstract: 1–4 interaction scaling factors are used in AMBER forcefields to reduce the exaggeration of short-range repulsion caused by the 6–12 Lennard-Jones potential and a nonpolarizable charge model and to obtain better agreements of small-molecule conformational energies with experimental data. However, the effects of these scaling factors on protein secondary structure conformations have not been investigated until now. This article reports the finding that the 1–4 interactions among the protein backbone atoms separated by three consecutive covalent bonds are more repulsive in the α-helix conformation than in two β-strand conformations. Therefore, the 1–4 interaction scaling factors of protein backbone torsions ϕ and ψ control the conformational equilibrium between α-helix and β-strand. Molecular dynamics simulations confirm that reducing the ϕ and ψ scaling factors readily converts the α-helix conformation of AcO-(AAQAA) 3 -NH 2 to a β-strand conformation, and the reverse occurs when these scaling factors are increased. These results suggest that the ϕ and ψ scaling factors can be used to generate the α-helix or β-strand conformation in situ and to control the propensities of a forcefield for adopting secondary structure elements

  6. Semi-automatic software based detection of atrial fibrillation in acute ischaemic stroke and transient ischaemic attack

    DEFF Research Database (Denmark)

    Nickelsen, M N; Snoer, A; Ali, A M

    2017-01-01

    (12.6%) patients were diagnosed with PAF (atrial fibrillation > 30 s). Pathfinder SL software including a systematic control of events registered 16 (94.1%) patients with PAF. Manually 15 (88.2%) patients were detected with PAF. Pathfinder SL had a negative predictive value of 99% and sensitivity...

  7. The changing face of glucagon fibrillation: Structural polymorphism and conformational imprinting

    DEFF Research Database (Denmark)

    Pedersen, J.S.; Dikov, D.; Flink, J.L.

    2006-01-01

    concentration) appear less thermostable than those formed under more challenging conditions (high temperatures, low glucagon or low salt concentrations). Properties of preformed fibrils used for seeding are inherited in a prion-like manner. Thus, we conclude that the structure of fibrils formed by glucagon...

  8. Apixaban in patients at risk of stroke undergoing atrial fibrillation ablation

    DEFF Research Database (Denmark)

    Kirchhof, Paulus; Haeusler, Karl Georg; Blank, Benjamin

    2018-01-01

    Aims: It is recommended to perform atrial fibrillation ablation with continuous anticoagulation. Continuous apixaban has not been tested. Methods and results: We compared continuous apixaban (5 mg b.i.d.) to vitamin K antagonists (VKA, international normalized ratio 2-3) in atrial fibrillation pa...

  9. Cardiovascular exercise and burden of arrhythmia in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Skielboe, Ane Katrine; Bandholm, Thomas Quaade; Hakmann, Stine

    2017-01-01

    BACKGROUND: Physical activity at moderate-high intensity is recommended to prevent lifestyle diseases. Patients with atrial fibrillation are at risk of a sedentary lifestyle due to fear of exercise-induced episodes of atrial fibrillation. The burden of arrhythmia can be reduced by physical exercise...

  10. Insulin fibrillation: The influence and coordination of Zn2+

    DEFF Research Database (Denmark)

    Frankær, Christian Grundahl; Sønderby, Pernille; Bang, Maria Blanner

    2017-01-01

    fibrils has been debated for some years. We have therefore investigated the influence and binding geometry of zinc in fibrillated insulin using extended X-ray absorption fine-structure and X-ray absorption near-edge structure spectroscopy. The results were validated with fibre diffraction, Transmission...

  11. Rhythm-based heartbeat duration normalization for atrial fibrillation detection.

    Science.gov (United States)

    Islam, Md Saiful; Ammour, Nassim; Alajlan, Naif; Aboalsamh, Hatim

    2016-05-01

    Screening of atrial fibrillation (AF) for high-risk patients including all patients aged 65 years and older is important for prevention of risk of stroke. Different technologies such as modified blood pressure monitor, single lead ECG-based finger-probe, and smart phone using plethysmogram signal have been emerging for this purpose. All these technologies use irregularity of heartbeat duration as a feature for AF detection. We have investigated a normalization method of heartbeat duration for improved AF detection. AF is an arrhythmia in which heartbeat duration generally becomes irregularly irregular. From a window of heartbeat duration, we estimate the possible rhythm of the majority of heartbeats and normalize duration of all heartbeats in the window based on the rhythm so that we can measure the irregularity of heartbeats for both AF and non-AF rhythms in the same scale. Irregularity is measured by the entropy of distribution of the normalized duration. Then we classify a window of heartbeats as AF or non-AF by thresholding the measured irregularity. The effect of this normalization is evaluated by comparing AF detection performances using duration with the normalization, without normalization, and with other existing normalizations. Sensitivity and specificity of AF detection using normalized heartbeat duration were tested on two landmark databases available online and compared with results of other methods (with/without normalization) by receiver operating characteristic (ROC) curves. ROC analysis showed that the normalization was able to improve the performance of AF detection and it was consistent for a wide range of sensitivity and specificity for use of different thresholds. Detection accuracy was also computed for equal rates of sensitivity and specificity for different methods. Using normalized heartbeat duration, we obtained 96.38% accuracy which is more than 4% improvement compared to AF detection without normalization. The proposed normalization

  12. Atrial fibrillation pearls and perils of management.

    Science.gov (United States)

    Kudenchuk, P J

    1996-01-01

    Atrial fibrillation, a common arrhythmia, is responsible for considerable cardiovascular morbidity. Its management demands more than antiarrhythmic therapy alone, but must address the causes and consequences of the arrhythmia. Although remediable causes are infrequently found, a thorough search for associated heart disease or its risk factors results in better-informed patient management. Controlling the ventricular response and protecting from thromboembolic complications are important initial goals of therapy and may include the administration of aspirin in younger, low-risk patients. Older patients and those with risk factors for systemic embolism are not adequately protected from stroke complications by aspirin therapy alone. It remains controversial whether all high-risk patients should receive warfarin and at what intensity. Whether and how sinus rhythm should be restored and maintained poses the greatest therapeutic controversy for atrial fibrillation. The mortal risk of antiarrhythmic therapy is substantially greater in patients with evidence of heart failure. In such persons, the risks and benefits of maintaining normal sinus rhythm with antiarrhythmic medications should be weighted carefully. A definitive cure for atrial fibrillation remains elusive, but promising surgical and catheter ablation therapies are being developed. PMID:8686300

  13. Lysosomal enzyme cathepsin B enhances the aggregate forming activity of exogenous α-synuclein fibrils.

    Science.gov (United States)

    Tsujimura, Atsushi; Taguchi, Katsutoshi; Watanabe, Yoshihisa; Tatebe, Harutsugu; Tokuda, Takahiko; Mizuno, Toshiki; Tanaka, Masaki

    2015-01-01

    The formation of intracellular aggregates containing α-synuclein (α-Syn) is one of the key steps in the progression of Parkinson's disease and dementia with Lewy bodies. Recently, it was reported that pathological α-Syn fibrils can undergo cell-to-cell transmission and form Lewy body-like aggregates. However, little is known about how they form α-Syn aggregates from fibril seeds. Here, we developed an assay to study the process of aggregate formation using fluorescent protein-tagged α-Syn-expressing cells and examined the aggregate forming activity of exogenous α-Syn fibrils. α-Syn fibril-induced formation of intracellular aggregates was suppressed by a cathepsin B specific inhibitor, but not by a cathepsin D inhibitor. α-Syn fibrils pretreated with cathepsin B in vitro enhanced seeding activity in cells. Knockdown of cathepsin B also reduced fibril-induced aggregate formation. Moreover, using LAMP-1 immunocytochemistry and live-cell imaging, we observed that these aggregates initially occurred in the lysosome. They then rapidly grew larger and moved outside the boundary of the lysosome within one day. These results suggest that the lysosomal protease cathepsin B is involved in triggering intracellular aggregate formation by α-Syn fibrils. Copyright © 2015. Published by Elsevier Inc.

  14. Dronedarone: a novel antiarrhythmic agent for the treatment of atrial fibrillation.

    Science.gov (United States)

    Duray, Gabor Z; Ehrlich, Joachim R; Hohnloser, Stefan H

    2010-01-01

    To describe the electrophysiological profile and the clinical portfolio of dronedarone, a new multichannel-blocking antiarrhythmic drug developed for the treatment of atrial fibrillation. Dronedarone is a derivative of amiodarone that is free of iodine and less lipophilic. The drug has - as its predecessor - multichannel-blocking efficacy and in addition vasodilating effects. It reduces the incidence of ventricular fibrillation in several experimental models. Dronedarone has undergone thorough clinical evaluation in various patient populations. In two large trials, the drug was shown to postpone the recurrence of atrial fibrillation after cardioversion relative to placebo. In a trial in unstable heart failure patients, there was excess mortality in the dronedarone arm. This trial was stopped prematurely and prompted the conduct of a large outcome study. The ATHENA trial demonstrated a significant reduction in cardiovascular hospitalizations and death in atrial fibrillation patients randomly assigned to receive dronedarone or placebo. This large trial in more than 4600 patients revealed no signs of excess mortality or morbidity in patients receiving dronedarone. On the basis of the results of five international, multicenter, randomized clinical trials involving nearly 6300 patients, dronedarone was approved by the FDA for treatment of nonpermanent atrial fibrillation to reduce the risk of cardiovascular hospitalization.

  15. Signal analysis of ventricular fibrillation

    NARCIS (Netherlands)

    Herbschleb, J.N.; Heethaar, R.M.; Tweel, L.H. van der; Zimmerman, A.N.E.; Meijler, F.L.

    Signal analysis of electro(cardio)grams during ventricular fibrillation (VF) in dogs and human patients indicates more organization and regularity than the official WHO definition suggests. The majority of the signal is characterized by a power spectrum with narrow, equidistant peaks. In a further

  16. Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

    Science.gov (United States)

    Sirish, Padmini; Li, Ning; Timofeyev, Valeriy; Zhang, Xiao-Dong; Wang, Lianguo; Yang, Jun; Lee, Kin Sing Stephen; Bettaieb, Ahmed; Ma, Sin Mei; Lee, Jeong Han; Su, Demetria; Lau, Victor C; Myers, Richard E; Lieu, Deborah K; López, Javier E; Young, J Nilas; Yamoah, Ebenezer N; Haj, Fawaz; Ripplinger, Crystal M; Hammock, Bruce D; Chiamvimonvat, Nipavan

    2016-05-01

    Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-β. This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation. © 2016 American Heart Association, Inc.

  17. Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers.

    Science.gov (United States)

    Ravens, Ursula; Odening, Katja E

    2017-08-01

    Despite the epidemiological scale of atrial fibrillation, current treatment strategies are of limited efficacy and safety. Ideally, novel drugs should specifically correct the pathophysiological mechanisms responsible for atrial fibrillation with no other cardiac or extracardiac actions. Atrial-selective drugs are directed toward cellular targets with sufficiently different characteristics in atria and ventricles to modify only atrial function. Several potassium (K + ) channels with either predominant expression in atria or distinct electrophysiological properties in atria and ventricles can serve as atrial-selective drug targets. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting I Kur , the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting I K,ACh , the Ca 2+ -activated K + channels of small conductance (SK) conducting I SK , and the two pore domain K + (K2P) channels TWIK-1, TASK-1 and TASK-3 that are responsible for voltage-independent background currents I TWIK-1 , I TASK-1 , and I TASK-3 . Here, we briefly review the characteristics of these K + channels and their roles in atrial fibrillation. The antiarrhythmic potential of drugs targeting the described channels is discussed as well as their putative value in treatment of atrial fibrillation. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The type II collagen fragments Helix-II and CTX-II reveal different enzymatic pathways of human cartilage collagen degradation

    DEFF Research Database (Denmark)

    Charni-Ben Tabassi, N; Desmarais, S; Jensen, Anne-Christine Bay

    2008-01-01

    human recombinant cathepsins (Cats) and matrix-metalloproteases (MMPs). Next, we analyzed the spontaneous release of Helix-II and CTX-II from cartilage sections of patients with knee OA who were immediately deep frozen after joint replacement to preserve endogenous enzyme activity until assay. Cartilage....... Cat D was unable to digest intact cartilage. MMPs-1, -3, -7, -9, and -13 efficiently released CTX-II, but only small amount of Helix-II. Neither CTX-II nor Helix-II alone was able to reflect accurately the collagenolytic activity of Cats and MMPs as reflected by the release of hydroxyproline. In OA...

  19. Risk of atrial fibrillation as a function of the electrocardiographic PR interval

    DEFF Research Database (Denmark)

    Nielsen, Jonas Bille; Pietersen, Adrian; Graff, Claus

    2013-01-01

    Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF).......Prolongation of the PR interval has been associated with an increased risk of incident atrial fibrillation (AF)....

  20. Helix Nebula and CERN: A Symbiotic approach to exploiting commercial clouds

    CERN Document Server

    Barreiro Megino, Fernando Harald; Kucharczyk, Katarzyna; Medrano Llamas, Ramón; van der Ster, Daniel

    2014-01-01

    The recent paradigm shift toward cloud computing in IT, and general interest in "Big Data" in particular, have demonstrated that the computing requirements of HEP are no longer globally unique. Indeed, the CERN IT department and LHC experiments have already made significant R&D investments in delivering and exploiting cloud computing resources. While a number of technical evaluations of interesting commercial offerings from global IT enterprises have been performed by various physics labs, further technical, security, sociological, and legal issues need to be address before their large-scale adoption by the research community can be envisaged. Helix Nebula - the Science Cloud is an initiative that explores these questions by joining the forces of three European research institutes (CERN, ESA and EMBL) with leading European commercial IT enterprises. The goals of Helix Nebula are to establish a cloud platform federating multiple commercial cloud providers, along with new business models, which can sustain ...

  1. Helix Nebula and CERN: A Symbiotic approach to exploiting commercial clouds

    CERN Multimedia

    Barreiro Megino, Fernando Harald; Kucharczyk, Katarzyna; Medrano Llamas, Ramón; van der Ster, Daniel

    2013-01-01

    The recent paradigm shift toward cloud computing in IT, and general interest in "Big Data" in particular, have demonstrated that the computing requirements of HEP are no longer globally unique. Indeed, the CERN IT department and LHC experiments have already made significant R&D; investments in delivering and exploiting cloud computing resources. While a number of technical evaluations of interesting commercial offerings from global IT enterprises have been performed by various physics labs, further technical, security, sociological, and legal issues need to be address before their large-scale adoption by the research community can be envisaged. Helix Nebula - the Science Cloud is an initiative that explores these questions by joining the forces of three European research institutes (CERN, ESA and EMBL) with leading European commercial IT enterprises. The goals of Helix Nebula are to establish a cloud platform federating multiple commercial cloud providers, along with new business models, which can sustain...

  2. Elevated endogenous expression of the dominant negative basic helix-loop-helix protein ID1 correlates with significant centrosome abnormalities in human tumor cells

    Directory of Open Access Journals (Sweden)

    Gutmann Anja

    2010-01-01

    Full Text Available Abstract Background ID proteins are dominant negative inhibitors of basic helix-loop-helix transcription factors that have multiple functions during development and cellular differentiation. Ectopic (over-expression of ID1 extends the lifespan of primary human epithelial cells. High expression levels of ID1 have been detected in multiple human malignancies, and in some have been correlated with unfavorable clinical prognosis. ID1 protein is localized at the centrosomes and forced (over-expression of ID1 results in errors during centrosome duplication. Results Here we analyzed the steady state expression levels of the four ID-proteins in 18 tumor cell lines and assessed the number of centrosome abnormalities. While expression of ID1, ID2, and ID3 was detected, we failed to detect protein expression of ID4. Expression of ID1 correlated with increased supernumerary centrosomes in most cell lines analyzed. Conclusions This is the first report that shows that not only ectopic expression in tissue culture but endogenous levels of ID1 modulate centrosome numbers. Thus, our findings support the hypothesis that ID1 interferes with centrosome homeostasis, most likely contributing to genomic instability and associated tumor aggressiveness.

  3. Dewetting transition assisted clearance of (NFGAILS) amyloid fibrils from cell membranes by graphene

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jiajia; Yang, Zaixing; Gu, Zonglin [Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123 (China); Li, Haotian [Bio-X Lab, Department of Physics, Zhejiang University, Hangzhou 310027 (China); Garate, Jose Antonio [IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Zhou, Ruhong, E-mail: ruhongz@us.ibm.com [Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Jiangsu Provincial Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123 (China); IBM Thomas J. Watson Research Center, Yorktown Heights, New York 10598 (United States); Department of Chemistry, Columbia University, New York, New York 10027 (United States)

    2014-12-14

    Clearance of partially ordered oligomers and monomers deposited on cell membrane surfaces is believed to be an effective route to alleviate many potential protein conformational diseases (PCDs). With large-scale all-atom molecular dynamics simulations, here we show that graphene nanosheets can easily and quickly win a competitive adsorption of human islet amyloid polypeptides (hIAPP{sub 22-28}) NFGAILS and associated fibrils against cell membrane, due to graphene's unique two-dimensional, highly hydrophobic surface with its all-sp{sup 2} hybrid structure. A nanoscale dewetting transition was observed at the interfacial region between the fibril (originally deposited on the membrane) and the graphene nanosheet, which significantly assisted the adsorption of fibrils onto graphene from the membrane. The π–π stacking interaction between Phe23 and graphene played a crucial role, providing the driving force for the adsorption at the graphene surface. This study renders new insight towards the importance of water during the interactions between amyloid peptides, the phospholipidic membrane, and graphene, which might shed some light on future developments of graphene-based nanomedicine for preventing/curing PCDs like type II diabetes mellitus.

  4. Dewetting transition assisted clearance of (NFGAILS) amyloid fibrils from cell membranes by graphene

    International Nuclear Information System (INIS)

    Liu, Jiajia; Yang, Zaixing; Gu, Zonglin; Li, Haotian; Garate, Jose Antonio; Zhou, Ruhong

    2014-01-01

    Clearance of partially ordered oligomers and monomers deposited on cell membrane surfaces is believed to be an effective route to alleviate many potential protein conformational diseases (PCDs). With large-scale all-atom molecular dynamics simulations, here we show that graphene nanosheets can easily and quickly win a competitive adsorption of human islet amyloid polypeptides (hIAPP 22-28 ) NFGAILS and associated fibrils against cell membrane, due to graphene's unique two-dimensional, highly hydrophobic surface with its all-sp 2 hybrid structure. A nanoscale dewetting transition was observed at the interfacial region between the fibril (originally deposited on the membrane) and the graphene nanosheet, which significantly assisted the adsorption of fibrils onto graphene from the membrane. The π–π stacking interaction between Phe23 and graphene played a crucial role, providing the driving force for the adsorption at the graphene surface. This study renders new insight towards the importance of water during the interactions between amyloid peptides, the phospholipidic membrane, and graphene, which might shed some light on future developments of graphene-based nanomedicine for preventing/curing PCDs like type II diabetes mellitus

  5. Interactive Information Service Technology of Tea Industry Based on Demand-Driven

    OpenAIRE

    Shi , Xiaohui; Chen , Tian’en

    2013-01-01

    International audience; Information service technology is a bridge between user and information resource, also is the critical factor to weight the quality of information service. Focusing on the information service features of tea industry, the demand-driven and interaction of information service were emphasized in this paper. User and market as the major criterion for testing the quality of information service, the interactive information service mode based on the demand-driven was proposed...

  6. SAFETY OF AMIODARONE USAGE IN PATIENTS WITH WOLFF-PARKINSON-WHITE SYNDROME AND ATRIAL FIBRILLATION

    Directory of Open Access Journals (Sweden)

    D. A. Kuzhel

    2010-01-01

    Full Text Available Amiodarone is one of the basic antiarrhytmic drugs for atrial fibrillation treatment. However application of amiodarone in patients with atrial fibrillation and Wolff-Parkinson-White syndrome can induce ventricular fibrillation. Amiodarone usage in these patients should be accompanied by readiness for performance of resuscitation. This is confirmed by clinical case presentation.

  7. 78 FR 11207 - Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation...

    Science.gov (United States)

    2013-02-15

    ...] Clinical Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation; Guidance for... devices intended for the treatment of atrial fibrillation. DATES: Submit either electronic or written... Study Designs for Surgical Ablation Devices for Treatment of Atrial Fibrillation'' to the Division of...

  8. Sex-related differences in risk factors, type of treatment received and outcomes in patients with atrial fibrillation and acute stroke: Results from the RAF-study (Early Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibrillation)

    OpenAIRE

    Antonenko, Kateryna; Paciaroni, Maurizio; Agnelli, Giancarlo; Falocci, Nicola; Becattini, Cecilia; Marcheselli, Simona; Rueckert, Christina; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Csiba, Laszló; Szabó, Lilla; Sohn, Sung-Il; Tassinari, Tiziana; Abdul-Rahim, Azmil H

    2016-01-01

    Introduction: Atrial fibrillation is an independent risk factor of thromboembolism. Women with atrial fibrillation are at a higher overall risk for stroke compared to men with atrial fibrillation. The aim of this study was to evaluate for sex differences in patients with acute stroke and atrial fibrillation, regarding risk factors, treatments received and outcomes.\\ud Methods Data were analyzed from the “Recurrence and Cerebral Bleeding in Patients with Acute Ischemic Stroke and Atrial Fibril...

  9. Helix Nebula and CERN: A Symbiotic approach to exploiting commercial clouds

    Science.gov (United States)

    Barreiro Megino, Fernando H.; Jones, Robert; Kucharczyk, Katarzyna; Medrano Llamas, Ramón; van der Ster, Daniel

    2014-06-01

    The recent paradigm shift toward cloud computing in IT, and general interest in "Big Data" in particular, have demonstrated that the computing requirements of HEP are no longer globally unique. Indeed, the CERN IT department and LHC experiments have already made significant R&D investments in delivering and exploiting cloud computing resources. While a number of technical evaluations of interesting commercial offerings from global IT enterprises have been performed by various physics labs, further technical, security, sociological, and legal issues need to be address before their large-scale adoption by the research community can be envisaged. Helix Nebula - the Science Cloud is an initiative that explores these questions by joining the forces of three European research institutes (CERN, ESA and EMBL) with leading European commercial IT enterprises. The goals of Helix Nebula are to establish a cloud platform federating multiple commercial cloud providers, along with new business models, which can sustain the cloud marketplace for years to come. This contribution will summarize the participation of CERN in Helix Nebula. We will explain CERN's flagship use-case and the model used to integrate several cloud providers with an LHC experiment's workload management system. During the first proof of concept, this project contributed over 40.000 CPU-days of Monte Carlo production throughput to the ATLAS experiment with marginal manpower required. CERN's experience, together with that of ESA and EMBL, is providing a great insight into the cloud computing industry and highlighted several challenges that are being tackled in order to ease the export of the scientific workloads to the cloud environments.

  10. Fibril deformation under load of the rabbit Achilles tendon and medial collateral ligament femoral entheses.

    Science.gov (United States)

    Sevick, Johnathan L; Abusara, Ziad; Andrews, Stephen H; Xu, Minjia; Khurshid, Saad; Chatha, Jansher; Hart, David A; Shrive, Nigel G

    2018-04-10

    Microscopic visualization under load of the region connecting ligaments/tendons to bone, the enthesis, has been performed previously; however, specific investigation of individual fibril deformation may add insight to such studies. Detailed visualization of fibril deformation would inform on the mechanical strategies employed by this tissue in connecting two mechanically disparate materials. Clinically, an improved understanding of enthesis mechanics may help guide future restorative efforts for torn or injured ligaments/tendons, where the enthesis is often a point of weakness. In this study, a custom ligament/tendon enthesis loading device was designed and built, a unique method of sample preparation was devised, and second harmonic and two-photon fluorescence microscopy were used to capture the fibril-level load response of the rabbit Achilles tendon and medial collateral ligament femoral entheses. A focus was given to investigation of the mechanical problem of fibril embedment. Resultant images indicate a rapid (occurring over approximately 60 μm) change in fibril orientation at the interface of ligament/tendon and calcified fibrocartilage early in the loading regime, before becoming relatively constant. Such a change in fibril angle helps confirm the materially graded region demonstrated by others, while, in this case, providing additional insight into fibril bending. We speculate that the scale of the mechanical problem (i.e., fibril diameters being on the order of 250 nm) allows fibrils to bend over the small (relative to the imaging field of view, but large relative to fibril diameter) distances observed; thus, potentially lessening required embedment lengths. Nevertheless, this behavior merits further investigation to be confirmed. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Imaging β-amyloid fibrils in Alzheimer's disease: a critical analysis through simulation of amyloid fibril polymerization

    International Nuclear Information System (INIS)

    Shoghi-Jadid, Kooresh; Barrio, Jorge R.; Kepe, Vladimir; Wu, H.-M.; Small, Gary W.; Phelps, Michael E.; Huang, S.-C.

    2005-01-01

    The polymerization of β-amyloid (Aβ) peptides into fibrillary plaques is implicated, in part, in the pathogenesis of Alzheimer's disease. Aβ molecular imaging probes (Aβ-MIPs) have been introduced in an effort to quantify amyloid burden or load, in subjects afflicted with AD by invoking the classic PET receptor model for the quantitation of neuronal receptor density. In this communication, we explore conceptual differences between imaging the density of amyloid fibril polymers and neuronal receptors. We formulate a mathematical model for the polymerization of Aβ with parameters that are mapped to biological modulators of fibrillogenesis and introduce a universal measure for amyloid load to accommodate various interactions of Aβ-MIPs with fibrils. Subsequently, we hypothesize four Aβ-MIPs and utilize the fibrillogenesis model to simulate PET tissue time activity curves (TACs). Given the unique nature of polymer growth and resulting PET TAC, the four probes report differing amyloid burdens for a given brain pathology, thus complicating the interpretation of PET images. In addition, we introduce the notion of an MIP's resolution, apparent maximal binding site concentration, optimal kinetic topology and its resolving power in characterizing the pathological progression of AD and the effectiveness of drug therapy. The concepts introduced in this work call for a new paradigm that goes beyond the classic parameters B max and K D to include binding characteristics to polymeric peptide aggregates such as amyloid fibrils, neurofibrillary tangles and prions

  12. Binding and Inhibitory Effect of the Dyes Amaranth and Tartrazine on Amyloid Fibrillation in Lysozyme.

    Science.gov (United States)

    Basu, Anirban; Suresh Kumar, Gopinatha

    2017-02-16

    Interaction of two food colorant dyes, amaranth and tartrazine, with lysozyme was studied employing multiple biophysical techniques. The dyes exhibited hypochromic changes in the presence of lysozyme. The intrinsic fluorescence of lysozyme was quenched by both dyes; amaranth was a more efficient quencher than tartrazine. The equilibrium constant of amaranth was higher than that of tartarzine. From FRET analysis, the binding distances for amaranth and tartrazine were calculated to be 4.51 and 3.93 nm, respectively. The binding was found to be dominated by non-polyelectrolytic forces. Both dyes induced alterations in the microenvironment surrounding the tryptophan and tyrosine residues of the protein, with the alterations being comparatively higher for the tryptophans than the tyrosines. The interaction caused significant loss in the helicity of lysozyme, the change being higher with amaranth. The binding of both dyes was exothermic. The binding of amaranth was enthalpy driven, while that of tartrazine was predominantly entropy driven. Amaranth delayed lysozyme fibrillation at 25 μM, while tartrazine had no effect even at 100 μM. Nevertheless, both dyes had a significant inhibitory effect on fibrillogenesis. The present study explores the potential antiamyloidogenic property of these azo dyes used as food colorants.

  13. Protein disulfide isomerase interacts with tau protein and inhibits its fibrillization.

    Directory of Open Access Journals (Sweden)

    Li-Rong Xu

    Full Text Available BACKGROUND: Tau protein is implicated in the pathogenesis of neurodegenerative disorders such as tauopathies including Alzheimer disease, and Tau fibrillization is thought to be related to neuronal toxicity. Physiological inhibitors of Tau fibrillization hold promise for developing new strategies for treatment of Alzheimer disease. Because protein disulfide isomerase (PDI is both an enzyme and a chaperone, and implicated in neuroprotection against Alzheimer disease, we want to know whether PDI can prevent Tau fibrillization. In this study, we have investigated the interaction between PDI and Tau protein and the effect of PDI on Tau fibrillization. METHODOLOGY/PRINCIPAL FINDINGS: As evidenced by co-immunoprecipitation and confocal laser scanning microscopy, human PDI interacts and co-locates with some endogenous human Tau on the endoplasmic reticulum of undifferentiated SH-SY5Y neuroblastoma cells. The results from isothermal titration calorimetry show that one full-length human PDI binds to one full-length human Tau (or human Tau fragment Tau244-372 monomer with moderate, micromolar affinity at physiological pH and near physiological ionic strength. As revealed by thioflavin T binding assays, Sarkosyl-insoluble SDS-PAGE, and transmission electron microscopy, full-length human PDI remarkably inhibits both steps of nucleation and elongation of Tau244-372 fibrillization in a concentration-dependent manner. Furthermore, we find that two molecules of the a-domain of human PDI interact with one Tau244-372 molecule with sub-micromolar affinity, and inhibit both steps of nucleation and elongation of Tau244-372 fibrillization more strongly than full-length human PDI. CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time that human PDI binds to Tau protein mainly through its thioredoxin-like catalytic domain a, forming a 1∶1 complex and preventing Tau misfolding. Our findings suggest that PDI could act as a physiological inhibitor of Tau

  14. Slender Ca ii H Fibrils Mapping Magnetic Fields in the Low Solar Chromosphere

    Energy Technology Data Exchange (ETDEWEB)

    Jafarzadeh, S.; Rutten, R. J.; Szydlarski, M. [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, NO-0315 Oslo (Norway); Solanki, S. K.; Wiegelmann, T.; Riethmüller, T. L.; Noort, M. van; Barthol, P.; Gandorfer, A.; Gizon, L.; Hirzberger, J. [Max Planck Institute for Solar System Research, Justus-von-Liebig-Weg 3, D-37077 Göttingen (Germany); Rodríguez, J. Blanco [Grupo de Astronomía y Ciencias del Espacio, Universidad de Valencia, E-46980 Paterna, Valencia (Spain); Iniesta, J. C. del Toro; Suárez, D. Orozco [Instituto de Astrofísica de Andalucía (CSIC), Apartado de Correos 3004, E-18080 Granada (Spain); Knölker, M. [High Altitude Observatory, National Center for Atmospheric Research, P.O. Box 3000, Boulder, CO 80307-3000 (United States); Pillet, V. Martínez [National Solar Observatory, 3665 Discovery Drive, Boulder, CO 80303 (United States); Schmidt, W., E-mail: shahin.jafarzadeh@astro.uio.no [Kiepenheuer-Institut für Sonnenphysik, Schöneckstr. 6, D-79104 Freiburg (Germany)

    2017-04-01

    A dense forest of slender bright fibrils near a small solar active region is seen in high-quality narrowband Ca ii H images from the SuFI instrument onboard the Sunrise balloon-borne solar observatory. The orientation of these slender Ca ii H fibrils (SCF) overlaps with the magnetic field configuration in the low solar chromosphere derived by magnetostatic extrapolation of the photospheric field observed with Sunrise/IMaX and SDO/HMI. In addition, many observed SCFs are qualitatively aligned with small-scale loops computed from a novel inversion approach based on best-fit numerical MHD simulation. Such loops are organized in canopy-like arches over quiet areas that differ in height depending on the field strength near their roots.

  15. The Impact of the ‘Austrian’ Mutation of the Amyloid Precursor Protein Transmembrane Helix is Communicated to the Hinge Region

    DEFF Research Database (Denmark)

    Stelzer, Walter; Scharnagl, Christina; Leurs, Ulrike

    2016-01-01

    The transmembrane helix of the amyloid precursor protein is subject to proteolytic cleavages by γ-secretase at different sites resulting in Aβ peptides of different length and toxicity. A number of point mutations within this transmembrane helix alter the cleavage pattern thus enhancing production...... destabilizes amide hydrogen bonds in the hinge which connects dimerization and cleavage regions. Weaker intrahelical hydrogen bonds at the hinge may enhance helix bending and thereby affect recognition of the transmembrane substrate by the enzyme and/or presentation of its cleavage sites to the catalytic cleft....

  16. Smartphone electrographic monitoring for atrial fibrillation in acute ischemic stroke and transient ischemic attack.

    Science.gov (United States)

    Tu, Hans T; Chen, Ziyuan; Swift, Corey; Churilov, Leonid; Guo, Ruibing; Liu, Xinfeng; Jannes, Jim; Mok, Vincent; Freedman, Ben; Davis, Stephen M; Yan, Bernard

    2017-10-01

    Rationale Paroxysmal atrial fibrillation is a common and preventable cause of devastating strokes. However, currently available monitoring methods, including Holter monitoring, cardiac telemetry and event loop recorders, have drawbacks that restrict their application in the general stroke population. AliveCor™ heart monitor, a novel device that embeds miniaturized electrocardiography (ECG) in a smartphone case coupled with an application to record and diagnose the ECG, has recently been shown to provide an accurate and sensitive single lead ECG diagnosis of atrial fibrillation. This device could be used by nurses to record a 30-s ECG instead of manual pulse taking and automatically provide a diagnosis of atrial fibrillation. Aims To compare the proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring with current standard practice. Sample size 296 Patients. Design Consecutive ischemic stroke and transient ischemic attack patients presenting to participating stroke units without known atrial fibrillation will undergo intermittent AliveCor™ ECG monitoring administered by nursing staff at the same frequency as the vital observations of pulse and blood pressure until discharge, in addition to the standard testing paradigm of each participating stroke unit to detect paroxysmal atrial fibrillation. Study outcome Proportion of patients with paroxysmal atrial fibrillation detected by AliveCor™ ECG monitoring compared to 12-lead ECG, 24-h Holter monitoring and cardiac telemetry. Discussion Use of AliveCor™ heart monitor as part of routine stroke unit nursing observation has the potential to be an inexpensive non-invasive method to increase paroxysmal atrial fibrillation detection, leading to improvement in stroke secondary prevention.

  17. Rendezvous of the "Third Kind": Triple Helix Origins and Future Possibilities

    Science.gov (United States)

    Etzkowitz, Henry

    2015-01-01

    The Triple Helix, representing university-industry-government interactions, was rooted in a 1993 International Workshop on University-Industry Relations at UNAM's Centro Para la Innovacion Technologica in Mexico City. Impelled by Mexican reality, where university-industry interactions and the institutions themselves operated within a governmental…

  18. Unpredictable responses of garden snail (Helix aspersa) populations to climate change

    NARCIS (Netherlands)

    Bezemer, T.M.; Knight, K.J.

    2001-01-01

    We studied the impact of climate change on the population dynamics of the garden snail (Helix aspersa) in the Ecotron controlled environment facility. The experimental series ran for three plant generations, allowing the snails to reproduce. We investigated the isolated and combined effects of

  19. A copula-based sampling method for data-driven prognostics

    International Nuclear Information System (INIS)

    Xi, Zhimin; Jing, Rong; Wang, Pingfeng; Hu, Chao

    2014-01-01

    This paper develops a Copula-based sampling method for data-driven prognostics. The method essentially consists of an offline training process and an online prediction process: (i) the offline training process builds a statistical relationship between the failure time and the time realizations at specified degradation levels on the basis of off-line training data sets; and (ii) the online prediction process identifies probable failure times for online testing units based on the statistical model constructed in the offline process and the online testing data. Our contributions in this paper are three-fold, namely the definition of a generic health index system to quantify the health degradation of an engineering system, the construction of a Copula-based statistical model to learn the statistical relationship between the failure time and the time realizations at specified degradation levels, and the development of a simulation-based approach for the prediction of remaining useful life (RUL). Two engineering case studies, namely the electric cooling fan health prognostics and the 2008 IEEE PHM challenge problem, are employed to demonstrate the effectiveness of the proposed methodology. - Highlights: • We develop a novel mechanism for data-driven prognostics. • A generic health index system quantifies health degradation of engineering systems. • Off-line training model is constructed based on the Bayesian Copula model. • Remaining useful life is predicted from a simulation-based approach

  20. Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute, subchronic, and chronic inhalation studies in rats.

    Science.gov (United States)

    Kelly, D P; Merriman, E A; Kennedy, G L; Lee, K P

    1993-10-01

    The deposition and clearance of lung-deposited Kevlar para-aramid fibrils (subfibers) have been investigated as part of a subchronic and chronic inhalation toxicity testing program. Fibrils recovered from lung tissue in para-aramid-exposed Sprague-Dawley rats were microscopically counted and measured after exposures to airborne fibrils which were about 12 microns median length (ML) and < 0.3 micron median diameter. In each of three studies lung-recovered fibrils were progressively shorter with increasing residence time in the lungs. Twenty-eight days after a single 6-hr exposure at 400 respirable fibrils per cubic centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns. Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3 or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4 microns. In the 2-year study, the lung-fiber accumulation rate/exposure concentration was similar for the three highest concentrations and was about 3 x greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25 f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be reduced to < 5 microns in the lung was markedly less at lower exposure concentration and shorter exposure time. The primary shortening mechanism is proposed to be long fibril cutting by enzymatic attack at fibril defects. However, length-selective fibril deposition and clearance may contribute to shortening in the first few days after exposure. The enzymatic cutting hypothesis is supported by measured increases in numbers of short fibers following cessation of exposures, continued shortening of the fibril length distribution up to 2 years following exposure, and in vitro fibril shortening after 3 months in a proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are less durable in the lungs of rats than expected from

  1. Use of 1–4 interaction scaling factors to control the conformational equilibrium between α-helix and β-strand

    Energy Technology Data Exchange (ETDEWEB)

    Pang, Yuan-Ping, E-mail: pang@mayo.edu

    2015-02-06

    Highlights: • 1–4 interaction scaling factors are used to adjust conformational energy. • This article reports the effects of these factors on protein conformations. • Reducing these factors changes a helix to a strand in molecular dynamics simulation. • Increasing these factors causes the reverse conformational change. • These factors control the conformational equilibrium between helix and strand. - Abstract: 1–4 interaction scaling factors are used in AMBER forcefields to reduce the exaggeration of short-range repulsion caused by the 6–12 Lennard-Jones potential and a nonpolarizable charge model and to obtain better agreements of small-molecule conformational energies with experimental data. However, the effects of these scaling factors on protein secondary structure conformations have not been investigated until now. This article reports the finding that the 1–4 interactions among the protein backbone atoms separated by three consecutive covalent bonds are more repulsive in the α-helix conformation than in two β-strand conformations. Therefore, the 1–4 interaction scaling factors of protein backbone torsions ϕ and ψ control the conformational equilibrium between α-helix and β-strand. Molecular dynamics simulations confirm that reducing the ϕ and ψ scaling factors readily converts the α-helix conformation of AcO-(AAQAA){sub 3}-NH{sub 2} to a β-strand conformation, and the reverse occurs when these scaling factors are increased. These results suggest that the ϕ and ψ scaling factors can be used to generate the α-helix or β-strand conformation in situ and to control the propensities of a forcefield for adopting secondary structure elements.

  2. Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Okin, Peter M; Hille, Darcy A; Wachtell, Kristian

    2015-01-01

    , diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse...... patients with atrial fibrillation has not been examined. METHODS AND RESULTS: All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during...... fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may...

  3. Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, Anna; Fosbøl, Emil Loldrup; Kim, Sunghee

    2016-01-01

    BACKGROUND: We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS: Using the ORBIT-AF, we compared symptoms and disease...

  4. Cost-effectiveness of a specialized atrial fibrillation clinic vs. usual care in patients with atrial fibrillation

    NARCIS (Netherlands)

    Hendriks, Jeroen; Tomini, Florian; van Asselt, Thea; Crijns, Harry; Vrijhoef, Hubertus

    AIMS: A recent randomized controlled trial demonstrated significant reductions in cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation (AF) compared with usual care. The aim of the present study is to assess

  5. Cost-effectiveness of a specialized atrial fibrillation clinic vs. usual care in patients with atrial fibrillation

    NARCIS (Netherlands)

    Hendriks, J.M.L.; Tomini, F.; van Asselt, A.D.I.; Crijns, H.J.G.M.; Vrijhoef, H.J.M.

    2013-01-01

    Aims A recent randomized controlled trial demonstrated significant reductions in cardiovascular hospitalizations and deaths with a nurse-led integrated chronic care approach in patients with atrial fibrillation (AF) compared with usual care. The aim of the present study is to assess

  6. Managing atrial fibrillation in the elderly: critical appraisal of dronedarone

    Directory of Open Access Journals (Sweden)

    Trigo P

    2011-12-01

    Full Text Available Paula Trigo, Gregory W FischerDepartment of Anesthesiology, Mount Sinai School of Medicine, New York, NY, USAAbstract: Atrial fibrillation is the most commonly seen arrhythmia in the geriatric population and is associated with increased cardiovascular morbidity and mortality. Treatment of the elderly with atrial fibrillation remains challenging for physicians, because this unique subpopulation is characterized by multiple comorbidities requiring chronic use of numerous medications, which can potentially lead to severe drug interactions. Furthermore, age-related changes in the cardiovascular system as well as other physiological changes result in altered drug pharmacokinetics. Dronedarone is a new drug recently approved for the treatment of arrhythmias, such as atrial fibrillation and/or atrial flutter. Dronedarone is a benzofuran amiodarone analog which lacks the iodine moiety and contains a methane sulfonyl group that decreases its lipophilicity. These differences in chemical structure are responsible for making dronedarone less toxic than amiodarone which, in turn, results in fewer side effects. Adverse events for dronedarone include gastrointestinal side effects and rash. No dosage adjustments are required for patients with renal impairment. However, the use of dronedarone is contraindicated in the presence of severe hepatic dysfunction.Keywords: atrial fibrillation, elderly, antiarrhythmic agents, amiodarone, dronedarone

  7. Genome-wide identification, classification, and functional analysis of the basic helix-loop-helix transcription factors in the cattle, Bos Taurus.

    Science.gov (United States)

    Li, Fengmei; Liu, Wuyi

    2017-06-01

    The basic helix-loop-helix (bHLH) transcription factors (TFs) form a huge superfamily and play crucial roles in many essential developmental, genetic, and physiological-biochemical processes of eukaryotes. In total, 109 putative bHLH TFs were identified and categorized successfully in the genomic databases of cattle, Bos Taurus, after removing redundant sequences and merging genetic isoforms. Through phylogenetic analyses, 105 proteins among these bHLH TFs were classified into 44 families with 46, 25, 14, 3, 13, and 4 members in the high-order groups A, B, C, D, E, and F, respectively. The remaining 4 bHLH proteins were sorted out as 'orphans.' Next, these 109 putative bHLH proteins identified were further characterized as significantly enriched in 524 significant Gene Ontology (GO) annotations (corrected P value ≤ 0.05) and 21 significantly enriched pathways (corrected P value ≤ 0.05) that had been mapped by the web server KOBAS 2.0. Furthermore, 95 bHLH proteins were further screened and analyzed together with two uncharacterized proteins in the STRING online database to reconstruct the protein-protein interaction network of cattle bHLH TFs. Ultimately, 89 bHLH proteins were fully mapped in a network with 67 biological process, 13 molecular functions, 5 KEGG pathways, 12 PFAM protein domains, and 25 INTERPRO classified protein domains and features. These results provide much useful information and a good reference for further functional investigations and updated researches on cattle bHLH TFs.

  8. The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.

    Directory of Open Access Journals (Sweden)

    Chai Ann Ng

    Full Text Available The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS domain (residues 26-135 as well as an amphipathic α-helix (residues 13-23 and an initial unstructured segment (residues 2-9. Deletion of residues 2-25, only the unstructured segment (residues 2-9 or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.

  9. Restrictions on TWT Helix Voltage Ripple for Acceptable Notch Filter Performance

    Energy Technology Data Exchange (ETDEWEB)

    Hyslop, B.

    1984-12-01

    An ac ripple on the helix voltage of the 1-2 GHz TWT's creates FM sidebands that cause amplitude and phase modulation of the microwave TWT output signal. A limit of 16 volts peak-to-peak is required for acceptable superconducting notch filter performance.

  10. Computational analysis of protein-protein interfaces involving an alpha helix: insights for terphenyl-like molecules binding.

    Science.gov (United States)

    Isvoran, Adriana; Craciun, Dana; Martiny, Virginie; Sperandio, Olivier; Miteva, Maria A

    2013-06-14

    Protein-Protein Interactions (PPIs) are key for many cellular processes. The characterization of PPI interfaces and the prediction of putative ligand binding sites and hot spot residues are essential to design efficient small-molecule modulators of PPI. Terphenyl and its derivatives are small organic molecules known to mimic one face of protein-binding alpha-helical peptides. In this work we focus on several PPIs mediated by alpha-helical peptides. We performed computational sequence- and structure-based analyses in order to evaluate several key physicochemical and surface properties of proteins known to interact with alpha-helical peptides and/or terphenyl and its derivatives. Sequence-based analysis revealed low sequence identity between some of the analyzed proteins binding alpha-helical peptides. Structure-based analysis was performed to calculate the volume, the fractal dimension roughness and the hydrophobicity of the binding regions. Besides the overall hydrophobic character of the binding pockets, some specificities were detected. We showed that the hydrophobicity is not uniformly distributed in different alpha-helix binding pockets that can help to identify key hydrophobic hot spots. The presence of hydrophobic cavities at the protein surface with a more complex shape than the entire protein surface seems to be an important property related to the ability of proteins to bind alpha-helical peptides and low molecular weight mimetics. Characterization of similarities and specificities of PPI binding sites can be helpful for further development of small molecules targeting alpha-helix binding proteins.

  11. Cardiac monitoring for detection of atrial fibrillation after TIA: A systematic review and meta-analysis.

    Science.gov (United States)

    Korompoki, Eleni; Del Giudice, Angela; Hillmann, Steffi; Malzahn, Uwe; Gladstone, David J; Heuschmann, Peter; Veltkamp, Roland

    2017-01-01

    Background and purpose The detection rate of atrial fibrillation has not been studied specifically in transient ischemic attack (TIA) patients although extrapolation from ischemic stroke may be inadequate. We conducted a systematic review and meta-analysis to determine the rate of newly diagnosed atrial fibrillation using different methods of ECG monitoring in TIA. Methods A comprehensive literature search was performed following a pre-specified protocol the PRISMA statement. Prospective observational studies and randomized controlled trials were considered that included TIA patients who underwent cardiac monitoring for >12 h. Primary outcome was frequency of detection of atrial fibrillation ≥30 s. Analyses of subgroups and of duration and type of monitoring were performed. Results Seventeen studies enrolling 1163 patients were included. The pooled atrial fibrillation detection rate for all methods was 4% (95% CI: 2-7%). Yield of monitoring was higher in selected (higher age, more extensive testing for arrhythmias before enrolment, or presumed cardioembolic/cryptogenic cause) than in unselected cohorts (7% vs 3%). Pooled mean atrial fibrillation detection rates rose with duration of monitoring: 4% (24 h), 5% (24 h to 7 days) and 6% (>7 days), respectively. Yield of non-invasive was significantly lower than that of invasive monitoring (4% vs. 11%). Significant heterogeneity was observed among studies (I 2 =60.61%). Conclusion This first meta-analysis of atrial fibrillation detection in TIA patients finds a lower atrial fibrillation detection rate in TIA than reported for IS and TIA cohorts in previous meta-analyses. Prospective studies are needed to determine actual prevalence of atrial fibrillation and optimal diagnostic procedure for atrial fibrillation detection in TIA.

  12. The Effect of Milk Constituents and Crowding Agents on Amyloid Fibril Formation by κ-Casein.

    Science.gov (United States)

    Liu, Jihua; Dehle, Francis C; Liu, Yanqin; Bahraminejad, Elmira; Ecroyd, Heath; Thorn, David C; Carver, John A

    2016-02-17

    When not incorporated into the casein micelle, κ-casein, a major milk protein, rapidly forms amyloid fibrils at physiological pH and temperature. In this study, the effects of milk components (calcium, lactose, lipids, and heparan sulfate) and crowding agents on reduced and carboxymethylated (RCM) κ-casein fibril formation was investigated using far-UV circular dichroism spectroscopy, thioflavin T binding assays, and transmission electron microscopy. Longer-chain phosphatidylcholine lipids, which form the lining of milk ducts and milk fat globules, enhanced RCM κ-casein fibril formation irrespective of whether the lipids were in a monomeric or micellar state, whereas shorter-chain phospholipids and triglycerides had little effect. Heparan sulfate, a component of the milk fat globule membrane and catalyst of amyloid deposition in extracellular tissue, had little effect on the kinetics of RCM κ-casein fibril formation. Major nutritional components such as calcium and lactose also had no significant effect. Macromolecular crowding enhances protein-protein interactions, but in contrast to other fibril-forming species, the extent of RCM κ-casein fibril formation was reduced by the presence of a variety of crowding agents. These data are consistent with a mechanism of κ-casein fibril formation in which the rate-determining step is dissociation from the oligomer to give the highly amyloidogenic monomer. We conclude that the interaction of κ-casein with membrane-associated phospholipids along its secretory pathway may contribute to the development of amyloid deposits in mammary tissue. However, the formation of spherical oligomers such as casein micelles is favored over amyloid fibrils in the crowded environment of milk, within which the occurrence of amyloid fibrils is low.

  13. Product design pattern based on big data-driven scenario

    Directory of Open Access Journals (Sweden)

    Conggang Yu

    2016-07-01

    Full Text Available This article discusses about new product design patterns in the big data era, gives designer a new rational thinking way, and is a new way to understand the design of the product. Based on the key criteria of the product design process, category, element, and product are used to input the data, which comprises concrete data and abstract data as an enlargement of the criteria of product design process for the establishment of a big data-driven product design pattern’s model. Moreover, an experiment and a product design case are conducted to verify the feasibility of the new pattern. Ultimately, we will conclude that the data-driven product design has two patterns: one is the concrete data supporting the product design, namely “product–data–product” pattern, and the second is based on the value of the abstract data for product design, namely “data–product–data” pattern. Through the data, users are involving themselves in the design development process. Data and product form a huge network, and data plays a role of connection or node. So the essence of the design is to find a new connection based on element, and to find a new node based on category.

  14. Dynamic behavior of small heat shock protein inhibition on amyloid fibrillization of a small peptide (SSTSAA) from RNase A

    International Nuclear Information System (INIS)

    Xi, Dong; Dong, Xiao; Deng, Wei; Lai, Luhua

    2011-01-01

    Highlights: ► Mechanism of small heat shock protein inhibition on fibril formation was studied. ► Peptide SSTSAA with modified ends was used for amyloid fibril formation. ► FRET signal was followed during the fibril formation. ► Mj HSP16.5 inhibits fibril formation when introduced in the lag phase. ► Mj HSP16.5 slows down fibril formation when introduced after the lag phase. -- Abstract: Small heat shock proteins, a class of molecular chaperones, are reported to inhibit amyloid fibril formation in vitro, while the mechanism of inhibition remains unknown. In the present study, we investigated the mechanism by which Mj HSP16.5 inhibits amyloid fibril formation of a small peptide (SSTSAA) from RNase A. A model peptide (dansyl-SSTSAA-W) was designed by introducing a pair of fluorescence resonance energy transfer (FRET) probes into the peptide, allowing for the monitoring of fibril formation by this experimental model. Mj HSP16.5 completely inhibited fibril formation of the model peptide at a molar ratio of 1:120. The dynamic process of fibril formation, revealed by FRET, circular dichroism, and electron microscopy, showed a lag phase of about 2 h followed by a fast growth period. The effect of Mj HSP16.5 on amyloid fibril formation was investigated by adding it into the incubation solution during different growth phases. Adding Mj HSP16.5 to the incubating peptide before or during the lag phase completely inhibited fibril formation. However, introducing Mj HSP16.5 after the lag phase only slowed down the fibril formation process by adhering to the already formed fibrils. These findings provide insight into the inhibitory roles of small heat shock proteins on amyloid fibril formation at the molecular level.

  15. Dynamic behavior of small heat shock protein inhibition on amyloid fibrillization of a small peptide (SSTSAA) from RNase A

    Energy Technology Data Exchange (ETDEWEB)

    Xi, Dong [BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Center for Theoretical Biology, Peking University, Beijing 100871 (China); Dong, Xiao; Deng, Wei [BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Lai, Luhua, E-mail: lhlai@pku.edu.cn [BNLMS, State Key Laboratory of Structural Chemistry for Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871 (China); Center for Theoretical Biology, Peking University, Beijing 100871 (China)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Mechanism of small heat shock protein inhibition on fibril formation was studied. Black-Right-Pointing-Pointer Peptide SSTSAA with modified ends was used for amyloid fibril formation. Black-Right-Pointing-Pointer FRET signal was followed during the fibril formation. Black-Right-Pointing-Pointer Mj HSP16.5 inhibits fibril formation when introduced in the lag phase. Black-Right-Pointing-Pointer Mj HSP16.5 slows down fibril formation when introduced after the lag phase. -- Abstract: Small heat shock proteins, a class of molecular chaperones, are reported to inhibit amyloid fibril formation in vitro, while the mechanism of inhibition remains unknown. In the present study, we investigated the mechanism by which Mj HSP16.5 inhibits amyloid fibril formation of a small peptide (SSTSAA) from RNase A. A model peptide (dansyl-SSTSAA-W) was designed by introducing a pair of fluorescence resonance energy transfer (FRET) probes into the peptide, allowing for the monitoring of fibril formation by this experimental model. Mj HSP16.5 completely inhibited fibril formation of the model peptide at a molar ratio of 1:120. The dynamic process of fibril formation, revealed by FRET, circular dichroism, and electron microscopy, showed a lag phase of about 2 h followed by a fast growth period. The effect of Mj HSP16.5 on amyloid fibril formation was investigated by adding it into the incubation solution during different growth phases. Adding Mj HSP16.5 to the incubating peptide before or during the lag phase completely inhibited fibril formation. However, introducing Mj HSP16.5 after the lag phase only slowed down the fibril formation process by adhering to the already formed fibrils. These findings provide insight into the inhibitory roles of small heat shock proteins on amyloid fibril formation at the molecular level.

  16. Effect of atrial preference pacing on reducing long-term burden of atrial fibrillation:a clinical study

    International Nuclear Information System (INIS)

    Xu Jianfeng; Chen Yueguang; Su Yangang; Zhang Dadong

    2010-01-01

    Objective: To evaluate the clinical effect of atrial preference pacing (APP) on the prevention of paroxysmal atrial fibrillation. Methods: Based on the type of implanted pacemaker, 46 patients with sick sinus syndrome and paroxysmal atrial fibrillation were divided into two groups. Dual-chamber pacemaker equipped with APP function was implanted in patients of group APP (n=21), while conventional dual-chamber pacemaker was implanted in patients of control group (n=25). The patients were followed up for six months, the maximum P wave duration (Pmax), the P wave dispersion (Pd), the structure of heart chambers, the data of automatic mode switch (AMS) and the total burden of atrial fibrillation were estimated,and the results were statistically analyzed and compared between two groups. Results: The basic clinical characteristics of two groups were comparable. After six months pacing, the difference in Pmax between two groups was of no significance (115.0 ± 10.1 ms vs 122.0 ± 11.0 ms, P > 0.05), while the increase of Pd in control group was more obvious than that in group APP (32.7 ± 4.2 ms vs 20.1 ± 5.3 ms, P 0.05), and also no remarkable difference in the left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) could be found (P > 0.05). Moreover, no significant difference existed between two groups (P > 0.05). After six months pacing,in group APP the frequencies of AMS decreased more sharply (145 ± 37 times vs 327 ± 13 times, P < 0.05), the duration of AMS shortened more apparently (73 ± 15 hours vs 139 ± 28 hours, P < 0.05) and the total burden of atrial fibrillation was alleviated more obviously (13 ± 5% vs 28 ± 6%, P < 0.05) when compared to those in control group. Conclusion: Atrial preference pacing can coordinate the anisotropy of double atrial depolarization, reduce the frequencies of long-term paroxysmal atrial fibrillation, shorten the duration of atrial fibrillation

  17. Gastroesophageal reflux disease and atrial fibrillation: a nationwide population-based study.

    Directory of Open Access Journals (Sweden)

    Chin-Chou Huang

    Full Text Available OBJECTIVES: Precise mechanisms of atrial fibrillation (AF are uncertain, but their association with esophageal disorders has been recently proposed. The association between gastroesophageal reflux disease (GERD, the most common gastroesophageal disorder, and AF remains undetermined. We therefore aimed to investigate the association between GERD and later development of AF. METHODS AND RESULTS: Patients with GERD were identified from the 1,000,000-person cohort dataset sampled from the Taiwan National Health Insurance database. The study cohort comprised 29,688 newly diagnosed adult GERD patients; 29,597 randomly selected age-, gender-, comobidity-matched subjects comprised the comparison cohort. Cox proportional hazard regressions were performed as a means of comparing the AF-free survival rate for the two cohorts. During a maximum three years of follow-up, a total of 351 patients experienced AF, including 184 (0.62% patients in the GERD cohort and 167 (0.56% in the control group. The log-rank test showed that patients with GERD had significantly higher incidence of AF than those without GERD (p = 0.024. After Cox proportional hazard regression model analysis, GERD was independently associated with the increased risk of AF (hazard ratio, 1.31; 95% confidence interval, 1.06-1.61, p = 0.013. CONCLUSION: GERD was independently associated with an increased risk of future AF in a nationwide population-based cohort.

  18. Glass-like dynamics of the strain-induced coil/helix transition on a permanent polymer network.

    Science.gov (United States)

    Ronsin, O; Caroli, C; Baumberger, T

    2016-02-14

    We study the stress response to a step strain of covalently bonded gelatin gels in the temperature range where triple helix reversible crosslink formation is prohibited. We observe slow stress relaxation towards a T-dependent finite asymptotic level. We show that this is assignable to the strain-induced coil → helix transition, previously evidenced by Courty et al. [Proc. Natl. Acad. Sci. U. S. A. 102, 13457 (2005)], of a fraction of the polymer strands. Relaxation proceeds, in a first stage, according to a stretched exponential dynamics, then crosses over to a terminal simple exponential decay. The respective characteristic times τK and τf exhibit an Arrhenius-like T-dependence with an associated energy E incompatibly larger than the activation barrier height for the isomerisation process which sets the clock for an elementary coil → helix transformation event. We tentatively assign this glass-like slowing down of the dynamics to the long-range couplings due to the mechanical noise generated by the local elementary events in this random elastic medium.

  19. Structure of the membrane anchor of pestivirus glycoprotein E(rns, a long tilted amphipathic helix.

    Directory of Open Access Journals (Sweden)

    Daniel Aberle

    2014-02-01

    Full Text Available E(rns is an essential virion glycoprotein with RNase activity that suppresses host cellular innate immune responses upon being partially secreted from the infected cells. Its unusual C-terminus plays multiple roles, as the amphiphilic helix acts as a membrane anchor, as a signal peptidase cleavage site, and as a retention/secretion signal. We analyzed the structure and membrane binding properties of this sequence to gain a better understanding of the underlying mechanisms. CD spectroscopy in different setups, as well as Monte Carlo and molecular dynamics simulations confirmed the helical folding and showed that the helix is accommodated in the amphiphilic region of the lipid bilayer with a slight tilt rather than lying parallel to the surface. This model was confirmed by NMR analyses that also identified a central stretch of 15 residues within the helix that is fully shielded from the aqueous layer, which is C-terminally followed by a putative hairpin structure. These findings explain the strong membrane binding of the protein and provide clues to establishing the E(rns membrane contact, processing and secretion.

  20. Structure of the membrane anchor of pestivirus glycoprotein E(rns), a long tilted amphipathic helix.

    Science.gov (United States)

    Aberle, Daniel; Muhle-Goll, Claudia; Bürck, Jochen; Wolf, Moritz; Reißer, Sabine; Luy, Burkhard; Wenzel, Wolfgang; Ulrich, Anne S; Meyers, Gregor

    2014-02-01

    E(rns) is an essential virion glycoprotein with RNase activity that suppresses host cellular innate immune responses upon being partially secreted from the infected cells. Its unusual C-terminus plays multiple roles, as the amphiphilic helix acts as a membrane anchor, as a signal peptidase cleavage site, and as a retention/secretion signal. We analyzed the structure and membrane binding properties of this sequence to gain a better understanding of the underlying mechanisms. CD spectroscopy in different setups, as well as Monte Carlo and molecular dynamics simulations confirmed the helical folding and showed that the helix is accommodated in the amphiphilic region of the lipid bilayer with a slight tilt rather than lying parallel to the surface. This model was confirmed by NMR analyses that also identified a central stretch of 15 residues within the helix that is fully shielded from the aqueous layer, which is C-terminally followed by a putative hairpin structure. These findings explain the strong membrane binding of the protein and provide clues to establishing the E(rns) membrane contact, processing and secretion.