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Sample records for intrinsic protein mip

  1. Major intrinsic proteins (MIPs) in plants: a complex gene family with major impacts on plant phenotype.

    Science.gov (United States)

    Forrest, Kerrie L; Bhave, Mrinal

    2007-10-01

    The ubiquitous cell membrane proteins called aquaporins are now firmly established as channel proteins that control the specific transport of water molecules across cell membranes in all living organisms. The aquaporins are thus likely to be of fundamental significance to all facets of plant growth and development affected by plant-water relations. A majority of plant aquaporins have been found to share essential structural features with the human aquaporin and exhibit water-transporting ability in various functional assays, and some have been shown experimentally to be of critical importance to plant survival. Furthermore, substantial evidence is now available from a number of plant species that shows differential gene expression of aquaporins in response to abiotic stresses such as salinity, drought, or cold and clearly establishes the aquaporins as major players in the response of plants to conditions that affect water availability. This review summarizes the function and regulation of these genes to develop a greater understanding of the response of plants to water insufficiency, and particularly, to identify tolerant genotypes of major crop species including wheat and rice and plants that are important in agroforestry.

  2. Chlamydia trachomatis Mip-like protein

    DEFF Research Database (Denmark)

    Lundemose, AG; Rousch, DA; Birkelund, Svend

    1992-01-01

    A 27 kDa Chlamydia trachomatis Mip-like protein with homology of a 175-amino-acid C-terminal fragment to the surface-exposed Legionella pneumophila mip-gene product has previously been described. In this paper the entire chlamydia Mip-like sequence of C. trachomatis serovar L2 (lymphogranuloma...... venereum (LGV) biovar) is presented. The sequence shows high similarity to the legionella Mip protein and its C-terminal region, like that of the legionella Mip, has high amino acid similarity to eukaryotic and prokaryotic FK506-binding proteins. The chlamydial mip-like gene was detected by polymerase...... chain reaction (PCR) in other C. trachomatis serovars and by sequencing of the mip-like genes of serovars B and E (trachoma biovar) was shown to be highly conserved within the two major biovars of C. trachomatis. Monoclonal and polyclonal antibodies raised against the recombinant Mip-like protein failed...

  3. Chlamydia trachomatis Mip-like protein

    DEFF Research Database (Denmark)

    Lundemose, AG; Rousch, DA; Birkelund, Svend

    1992-01-01

    venereum (LGV) biovar) is presented. The sequence shows high similarity to the legionella Mip protein and its C-terminal region, like that of the legionella Mip, has high amino acid similarity to eukaryotic and prokaryotic FK506-binding proteins. The chlamydial mip-like gene was detected by polymerase...... to demonstrate surface-exposed epitopes on infectious elementary bodies or reproductive reticulate body forms either by immunofluorescence or immuno-gold electron microscopy. However, a complement-dependent inhibition of up to 91% of infectivity for cell cultures was observed with antibodies to the N...

  4. Major Intrinsic Proteins in Biomimetic Membranes

    DEFF Research Database (Denmark)

    Helix Nielsen, Claus

    2010-01-01

    will generally have finite permeabilities to both electrolytes and non-electrolytes. The feasibility of a biomimetic MIP device thus depends on the relative transport contribution from both protein and biomimetic support matrix. Also the biomimetic matrix must be encapsulated in order to protect it and make....../separation technology, a unique class of membrane transport proteins is especially interesting the major intrinsic proteins (MIPs). Generally, MIPs conduct water molecules and selected solutes in and out of the cell while preventing the passage of other solutes, a property critical for the conservation of the cells...... it sufficiently stable in a final application. Here, I specifically discuss the feasibility of developing osmotic biomimetic MIP membranes, but the technical issues are of general concern in the design of biomimetic membranes capable of supporting selective transmembrane fluxes....

  5. Nucleotide sequence analysis of the Legionella micdadei mip gene, encoding a 30-kilodalton analog of the Legionella pneumophila Mip protein

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Cianciotto, N P; Hindersson, P

    1991-01-01

    After the demonstration of analogs of the Legionella pneumophila macrophage infectivity potentiator (Mip) protein in other Legionella species, the Legionella micdadei mip gene was cloned and expressed in Escherichia coli. DNA sequence analysis of the L. micdadei mip gene contained in the plasmid p...

  6. MIPs and Aptamers for Recognition of Proteins in Biomimetic Sensing

    Directory of Open Access Journals (Sweden)

    Marcus Menger

    2016-07-01

    Full Text Available Biomimetic binders and catalysts have been generated in order to substitute the biological pendants in separation techniques and bioanalysis. The two major approaches use either “evolution in the test tube” of nucleotides for the preparation of aptamers or total chemical synthesis for molecularly imprinted polymers (MIPs. The reproducible production of aptamers is a clear advantage, whilst the preparation of MIPs typically leads to a population of polymers with different binding sites. The realization of binding sites in the total bulk of the MIPs results in a higher binding capacity, however, on the expense of the accessibility and exchange rate. Furthermore, the readout of the bound analyte is easier for aptamers since the integration of signal generating labels is well established. On the other hand, the overall negative charge of the nucleotides makes aptamers prone to non-specific adsorption of positively charged constituents of the sample and the “biological” degradation of non-modified aptamers and ionic strength-dependent changes of conformation may be challenging in some application.

  7. Protein intrinsic disorder in plants.

    Science.gov (United States)

    Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

    2013-09-12

    To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  8. Protein intrinsic disorder in plants

    Directory of Open Access Journals (Sweden)

    Florencio ePazos

    2013-09-01

    Full Text Available To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously with different partners. Similarly, they also serve as signal integrators in signalling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms can not escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

  9. Overexpression of MIP2, a novel WD-repeat protein, promotes proliferation of H9c2 cells

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Xing, E-mail: weixing22@163.com [Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078 (China); Institute of Cardiovascular Disease, Department of Pathophysiology, School of Medicine, University of South China, 28 Changsheng Xi Road, Hengyang, Hunan 421001 (China); Song, Lan; Jiang, Lei; Wang, Guiliang; Luo, Xinjing; Zhang, Bin [Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078 (China); Xiao, Xianzhong, E-mail: xianzhongxiao@hotmail.com [Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078 (China)

    2010-03-19

    WD40 repeat proteins have a wide range of diverse biological functions including signal transduction, cell cycle regulation, RNA splicing, and transcription. Myocardial ischemic preconditioning up-regulated protein 2 (MIP2) is a novel member of the WD40 repeat proteins superfamily that contains five WD40 repeats. Little is known about its biological role, and the purpose of this study was to determine the role of MIP2 in regulating cellular proliferation. Transfection and constitutive expression of MIP2 in the rat cardiomyoblast cell line H9c2 results in enhanced growth of those cells as measured by cell number and is proportional to the amount of MIP2 expressed. Overexpression of MIP2 results in a shorter cell cycle, as measured by flow cytometry. Collectively, these data suggest that MIP2 may participate in the progression of cell proliferation in H9c2 cells.

  10. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...

  11. The Macrophage Inflammatory Proteins MIP1α (CCL3 and MIP2α (CXCL2 in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

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    Ulrike Dapunt

    2014-01-01

    Full Text Available Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3 and MIP2α (CXCL2 was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis.

  12. Differential scanning microcalorimetry of intrinsically disordered proteins.

    Science.gov (United States)

    Permyakov, Sergei E

    2012-01-01

    Ultrasensitive differential scanning calorimetry (DSC) is an indispensable thermophysical technique enabling to get direct information on enthalpies accompanying heating/cooling of dilute biopolymer solutions. The thermal dependence of protein heat capacity extracted from DSC data is a valuable source of information on intrinsic disorder level of a protein. Application details and limitations of DSC technique in exploration of protein intrinsic disorder are described.

  13. Major Intrinsic Proteins in Biomimetic Membranes

    DEFF Research Database (Denmark)

    Helix Nielsen, Claus

    2010-01-01

    this challenge by developing membranes in the form of lipid bilayers in which specialized transport proteins are incorporated. This raises the question: is it possible to mimic biological membranes and create a membrane based sensor and/or separation device? In the development of a biomimetic sensor...... or as sensor devices based on e.g., the selective permeation of metalloids. In principle a MIP based membrane sensor/separation device requires the supporting biomimetic matrix to be virtually impermeable to anything but water or the solute in question. In practice, however, a biomimetic support matrix...... will generally have finite permeabilities to both electrolytes and non-electrolytes. The feasibility of a biomimetic MIP device thus depends on the relative transport contribution from both protein and biomimetic support matrix. Also the biomimetic matrix must be encapsulated in order to protect it and make...

  14. Major intrinsic proteins and arsenic transport in plants: new players and their potential role.

    Science.gov (United States)

    Bienert, Gerd P; Jahn, Thomas P

    2010-01-01

    Arsenic (As) is a toxic and highly abundant metalloid that endangers human health through drinking water and the food chain. The most common forms of As in the environment re arsenate [As(V)] and arsenite [As(III)]. As(V) is a nonfunctional phosphate analog that enters the food chain via plant phosphate transporters. Recently, evidence was provided that uptake of As(III)--the second most abundant As species in soils--is mediated by plant nodulin26-like intrinsic proteins (NIPs), a subfamily of plant major intrinsic proteins (MIPs). Specific NIPs are also essential for the uptake of the metalloids boron and silicon and aquaglyceroporins from microbes and mammals were shown to be the major routes of As uptake. Therefore As(III) transport through MIPs is a conserved and ancient feature. In this chapter we summarize the current view on As transport in plants and address the potential physiological significance of As(III) transport through NIPs.

  15. Functions of intrinsic disorder in transmembrane proteins

    DEFF Research Database (Denmark)

    Kjaergaard, Magnus; Kragelund, Birthe B.

    2017-01-01

    mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding......Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane...... proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine...

  16. Frustration-induced protein intrinsic disorder.

    Science.gov (United States)

    Matsushita, Katsuyoshi; Kikuchi, Macoto

    2013-03-14

    Spontaneous folding into a specific native structure is the most important property of protein to perform their biological functions within organisms. Spontaneous folding is understood on the basis of an energy landscape picture based on the minimum frustration principle. Therefore, frustration seemingly only leads to protein functional disorder. However, frustration has recently been suggested to have a function in allosteric regulation. Functional frustration has the possibility to be a key to our deeper understanding of protein function. To explore another functional frustration, we theoretically examined structural frustration, which is designed to induce intrinsic disorder of a protein and its function through the coupled folding and binding. We extended the Wako-Saitô-Muñoz-Eaton model to take into account a frustration effect. With the model, we analyzed the binding part of neuron-restrictive silencer factor and showed that designed structural frustration in it induces intrinsic disorder. Furthermore, we showed that the folding and the binding are cooperative in interacting with a target protein. The cooperativity enables an intrinsically disordered protein to exhibit a sharp switch-like folding response to binding chemical potential change. Through this switch-like response, the structural frustration may contribute to the regulation function of interprotein interaction of the intrinsically disordered protein.

  17. New subfamilies of major intrinsic proteins in fungi suggest novel transport properties in fungal channels: implications for the host-fungal interactions.

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    Verma, Ravi Kumar; Prabh, Neel Duti; Sankararamakrishnan, Ramasubbu

    2014-08-12

    Aquaporins (AQPs) and aquaglyceroporins (AQGPs) belong to the superfamily of Major Intrinsic Proteins (MIPs) and are involved in the transport of water and neutral solutes across the membranes. MIP channels play significant role in plant-fungi symbiotic relationship and are believed to be important in host-pathogen interactions in human fungal diseases. In plants, at least five major MIP subfamilies have been identified. Fungal MIP subfamilies include orthodox aquaporins and five subgroups within aquaglyceroporins. XIP subfamily is common to both plants and fungi. In this study, we have investigated the extent of diversity in fungal MIPs and explored further evolutionary relationships with the plant MIP counterparts. We have extensively analyzed the available fungal genomes and examined nearly 400 fungal MIPs. Phylogenetic analysis and homology modeling exhibit the existence of a new MIP cluster distinct from any of the known fungal MIP subfamilies. All members of this cluster are found in microsporidia which are unicellular fungal parasites. Members of this family are small in size, charged and have hydrophobic residues in the aromatic/arginine selectivity filter and these features are shared by small and basic intrinsic proteins (SIPs), one of the plant MIP subfamilies. We have also found two new subfamilies (δ and γ2) within the AQGP group. Fungal AQGPs are the most diverse and possess the largest number of subgroups. We have also identified distinguishing features in loops E and D in the newly identified subfamilies indicating their possible role in channel transport and gating. Fungal SIP-like MIP family is distinct from any of the known fungal MIP families including orthodox aquaporins and aquaglyceroporins. After XIPs, this is the second MIP subfamily from fungi that may have possible evolutionary link with a plant MIP subfamily. AQGPs in fungi are more diverse and possess the largest number of subgroups. The aromatic/arginine selectivity filter of SIP

  18. Liposomes or traditional adjuvants: induction of bactericidal activity by the macrophage infectivity potentiator protein (Mip) of Neisseria meningitidis.

    Science.gov (United States)

    Costoya, Liliana; Marzoa, Juan; Ferreirós, Carlos; Criado, Maria Teresa

    2017-08-01

    Currently, one of the main approaches to achieve a vaccine for serogroup B Neisseria meningitidis is based on outer membrane proteins with low antigenic variability among strains. Since these proteins tend to be minor components of the outer membrane, recombinant production is required to obtain them in sufficient amounts for evaluation and development of vaccines. In this study, we analysed the ability of recombinant macrophage infectivity potentiator (rMip) protein to induce protective bactericidal activity in mice. The rMip protein was cloned from N. meningitidis strain H44/76 and was used to immunise mice, and the sera obtained were tested against the homologous and several heterologous N. meningitidis strains. The sera were obtained using the rMip alone, with adjuvant Al(OH) 3 , or after inclusion into liposomes. Bactericidal activity was variable depending on the strain, although high titres were seen against strains H44/76 and NmP27. Liposomes enhanced fourfold the reactivity against the homologous strain. The results presented suggest that the rMip protein should be considered a promising candidate for the improvement of future protein-based vaccines. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  19. Putative new groups of invertebrate water channels based on the snail Helix pomatia L. (Helicidae) MIP protein identification and phylogenetic analysis.

    Science.gov (United States)

    Kosicka, Ewa; Grobys, Daria; Kmita, Hanna; Lesicki, Andrzej; Pieńkowska, Joanna R

    2016-12-01

    Water channel proteins, classified as a family of Membrane Intrinsic Proteins (MIPs) superfamily, enable rapid movement of water and small uncharged molecules through biological membranes. Although water channel proteins are required in several important processes characteristic for the animals, such as osmoregulation, mucus secretion, or defense against desiccation, molluscs, until now, have been very poorly explored in this aspect. Therefore, we decided to study MIPs in Helix pomatia L. applied as a model in studies on terrestrial snail physiology. Our studies consisted in: the snail organ transcriptome sequencing and consecutive bioinformatic analysis of the predicted protein, estimation of the encoding transcript expression (qPCR), investigation of the predicted protein function in the yeast Saccharomyces cerevisiae cells, and the phylogenetic analysis. We identified six water channel proteins, named HpAQP1 to HpAQP6. All of them were proven to transport water, two of them (HpAQP3 and HpAQP4) were also shown to be able to transport glycerol, and other two (HpAQP5 and HpAQP6) to transport H 2 O 2 . Phylogenetic analysis indicated that the proteins either fell into aquaporins (HpAQP1, HpAQP2 and HpAQP5) or formed new groups of invertebrate water channel proteins, not described until now, that we suggest to term malacoglyceroporins (HpAQP3 and HpAQP4) and malacoaquaporins (HpAQP6). Thus, the classification of animal water channels based on the vertebrate proteins and including aquaporin, aquaglyceroporin, S-aquaporin and AQP8-type grades does not reflect diversity of these proteins in invertebrates. The obtained results provide important data concerning diversity of water channel protein repertoire in aquatic and terrestrial invertebrates and should also contribute to the improvement of animal water channel classification system. Copyright © 2016 Elsevier GmbH. All rights reserved.

  20. Computer Simulations of Intrinsically Disordered Proteins

    Science.gov (United States)

    Chong, Song-Ho; Chatterjee, Prathit; Ham, Sihyun

    2017-05-01

    The investigation of intrinsically disordered proteins (IDPs) is a new frontier in structural and molecular biology that requires a new paradigm to connect structural disorder to function. Molecular dynamics simulations and statistical thermodynamics potentially offer ideal tools for atomic-level characterizations and thermodynamic descriptions of this fascinating class of proteins that will complement experimental studies. However, IDPs display sensitivity to inaccuracies in the underlying molecular mechanics force fields. Thus, achieving an accurate structural characterization of IDPs via simulations is a challenge. It is also daunting to perform a configuration-space integration over heterogeneous structural ensembles sampled by IDPs to extract, in particular, protein configurational entropy. In this review, we summarize recent efforts devoted to the development of force fields and the critical evaluations of their performance when applied to IDPs. We also survey recent advances in computational methods for protein configurational entropy that aim to provide a thermodynamic link between structural disorder and protein activity.

  1. A tonoplast intrinsic protein in Gardenia jasminoides

    Science.gov (United States)

    Gao, Lan; Li, Hao-Ming

    2017-08-01

    Physiological and molecular studies proved that plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) subfamily of aquaporins play key functions in plant water homeostasis. Five specialized subgroups (TIP1-5) of TIPs have been found in higher plants, in which the TIP1 and TIP2 isoforms are the largest arbitrary groups. TIPs have high water-transport activity than PIPs, some TIPs can transport other small molecule such as urea, ammonia, hydrogen peroxide, and carbon dioxide. In this work, the structure of the putative tonoplast aquaporin from Gardenia jasminoides (GjTIP) was analyzed. Its transcript level has increased during fruit maturation. A phylogenetic analysis indicates that the protein belongs to TIP1 subfamily. A three-dimensional model structure of GjTIP was built based on crystal structure of an ammonia-permeable AtTIP2-1 from Arabidopsis thaliana. The model structure displayed as a homo-tetramer, each monomer has six trans-membrane and two half-membrane-spanning α helices. The data suggests that the GjTIP has tendency to be a mixed function aquaporin, might involve in water, urea and hydrogen peroxide transport, and the gating machanism founded in some AQPs involving pH and phosphorylation response have not been proved in GjTIP.

  2. Intrinsically disordered proteins drive membrane curvature.

    Science.gov (United States)

    Busch, David J; Houser, Justin R; Hayden, Carl C; Sherman, Michael B; Lafer, Eileen M; Stachowiak, Jeanne C

    2015-07-24

    Assembly of highly curved membrane structures is essential to cellular physiology. The prevailing view has been that proteins with curvature-promoting structural motifs, such as wedge-like amphipathic helices and crescent-shaped BAR domains, are required for bending membranes. Here we report that intrinsically disordered domains of the endocytic adaptor proteins, Epsin1 and AP180 are highly potent drivers of membrane curvature. This result is unexpected since intrinsically disordered domains lack a well-defined three-dimensional structure. However, in vitro measurements of membrane curvature and protein diffusivity demonstrate that the large hydrodynamic radii of these domains generate steric pressure that drives membrane bending. When disordered adaptor domains are expressed as transmembrane cargo in mammalian cells, they are excluded from clathrin-coated pits. We propose that a balance of steric pressure on the two surfaces of the membrane drives this exclusion. These results provide quantitative evidence for the influence of steric pressure on the content and assembly of curved cellular membrane structures.

  3. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P

    1995-01-01

    in bronchoalveolar lavage (BAL) fluids by Western blot analysis. Anti-MIP-1 alpha administered at commencement of IgG immune complex- or LPS-induced injury resulted in significant reductions in BAL neutrophils as well as in injury as measured by pulmonary vascular permeability. Under such conditions, in both models...

  4. Increased replication of T-cell-tropic HIV strains and CXC-chemokine receptor-4 induction in T cells treated with macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines.

    Science.gov (United States)

    Dolei, A; Biolchini, A; Serra, C; Curreli, S; Gomes, E; Dianzani, F

    1998-01-22

    To study, in T-lymphoid cells, the effects of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines on the replication of T-cell-tropic HIV-1 strains, since it has been reported that beta-chemokines interfere with the replication of macrophage-tropic HIV-1 strains, but not T-cell-tropic strains. Freshly phytohaemagglutinin (PHA)-activated peripheral blood lymphocytes (PBL) and cultured PHA-activated T cells from healthy volunteers, as well as the C8166 T-cell line, were treated overnight with beta-chemokines before infection with T-cell-tropic HIV-1 isolates, or human T-lymphotropic virus type IIIB. HIV replication was followed by detecting the production of infectious particles, p24 antigen, and viral sequences. CXC-chemokine receptor (CXCR)-4 expression was followed by detection and quantification of specific transcripts. Pretreatment of T cells with MIP-1alpha, MIP-1beta and RANTES affected T-cell-tropic strains, increased the replication of HIV-1beta and HIV-1RPdT strains dose-dependently, as well as virus absorption and provirus DNA accumulation. These findings were associated with increased accumulation of CXCR-4 transcripts, and mediated by the protein tyrosine kinase signalling. Moreover, beta-chemokines stimulated PBL proliferation. Beta-chemokines increase the adsorption and replication of at least some T-cell-tropic HIV-1 strains, and this is related to stimulated expression of the CXCR-4 coreceptor.

  5. Type I J-domain NbMIP1 proteins are required for both Tobacco mosaic virus infection and plant innate immunity.

    Directory of Open Access Journals (Sweden)

    Yumei Du

    Full Text Available Tm-2² is a coiled coil-nucleotide binding-leucine rich repeat resistance protein that confers durable extreme resistance against Tomato mosaic virus (ToMV and Tobacco mosaic virus (TMV by recognizing the viral movement protein (MP. Here we report that the Nicotiana benthamiana J-domain MIP1 proteins (NbMIP1s associate with tobamovirus MP, Tm-2² and SGT1. Silencing of NbMIP1s reduced TMV movement and compromised Tm-2²-mediated resistance against TMV and ToMV. Furthermore, silencing of NbMIP1s reduced the steady-state protein levels of ToMV MP and Tm-2². Moreover, NbMIP1s are required for plant resistance induced by other R genes and the nonhost pathogen Pseudomonas syringae pv. tomato (Pst DC3000. In addition, we found that SGT1 associates with Tm-2² and is required for Tm-2²-mediated resistance against TMV. These results suggest that NbMIP1s function as co-chaperones during virus infection and plant immunity.

  6. Helical propensity in an intrinsically disordered protein accelerates ligand binding

    DEFF Research Database (Denmark)

    Iesmantavicius, Vytautas; Dogan, Jakob; Jemth, Per

    2014-01-01

    domain of the activator for thyroid hormone and retinoid receptors (ACTR) is intrinsically disordered and folds upon binding to the nuclear coactivator binding domain (NCBD) of the CREB binding protein. A number of mutants was designed that selectively perturbs the amount of secondary structure......Many intrinsically disordered proteins fold upon binding to other macromolecules. The secondary structure present in the well-ordered complex is often formed transiently in the unbound state. The consequence of such transient structure for the binding process is, however, not clear. The activation...... the notion of preformed secondary structure as an important determinant for molecular recognition in intrinsically disordered proteins....

  7. Outer membrane proteomics of kanamycin-resistant Escherichia coli identified MipA as a novel antibiotic resistance-related protein.

    Science.gov (United States)

    Li, Hui; Zhang, Dan-feng; Lin, Xiang-min; Peng, Xuan-xian

    2015-06-01

    Antibiotic-resistant bacteria are a great threat to human health and food safety and there is an urgent need to understand the mechanisms of resistance for combating these bacteria. In the current study, comparative proteomic methodologies were applied to identify Escherichia coli K-12 outer membrane (OM) proteins related to kanamycin resistance. Mass spectrometry and western blotting results revealed that OM proteins TolC, Tsx and OstA were up-regulated, whereas MipA, OmpA, FadL and OmpW were down-regulated in kanamycin-resistant E. coli K-12 strain. Genetic deletion of tolC (ΔtolC-Km) led to a 2-fold decrease in the minimum inhibitory concentration (MIC) of kanamycin and deletion of mipA (ΔmipA-Km) resulted in a 4-fold increase in the MIC of kanamycin. Changes in the MICs for genetically modified strains could be completely recovered by gene complementation. Compared with the wild-type strain, the survival capability of ΔompA-Km was significantly increased and that of Δtsx-Km was significantly decreased. We further evaluated the role and expression of MipA in response to four other antibiotics including nalidixic acid, streptomycin, chloramphenicol and aureomycin, which suggested that MipA was a novel OM protein related to antibiotic resistance. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Lipid Directed Intrinsic Membrane Protein Segregation

    DEFF Research Database (Denmark)

    Hansen, Jesper S.; Thompson, James R.; Helix Nielsen, Claus

    2013-01-01

    We demonstrate a new approach for direct reconstitution of membrane proteins during giant vesicle formation. We show that it is straightforward to create a tissue-like giant vesicle film swelled with membrane protein using aquaporin SoPIP2;1 as an illustration. These vesicles can also be easily h...

  9. DSS1/Sem1, a multifunctional and intrinsically disordered protein

    DEFF Research Database (Denmark)

    Kragelund, Birthe Brandt; Schenstrøm, Signe Marie; Rebula, Caio A.

    2016-01-01

    DSS1/Sem1 is a versatile intrinsically disordered protein. Besides being a bona fide subunit of the 26S proteasome, DSS1 associates with other protein complexes, including BRCA2-RPA, involved in homologous recombination; the Csn12-Thp3 complex, involved in RNA splicing; the integrator, involved...

  10. Identification of mip-like genes in the genus Legionella

    DEFF Research Database (Denmark)

    Cianciotto, N P; Bangsborg, Jette Marie; Eisenstein, B I

    1990-01-01

    with specific Mip antisera. Moreover, the cloned mip analog from Legionella micdadei encoded the cross-reactive protein. Thus, mip is conserved and specific to L. pneumophila, but mip-like genes are present throughout the genus, perhaps potentiating the intracellular infectivity of all Legionella species....

  11. Identification of mip-like genes in the genus Legionella

    DEFF Research Database (Denmark)

    Cianciotto, N P; Bangsborg, Jette Marie; Eisenstein, B I

    1990-01-01

    in the genus Legionella, a large panel of Legionella strains was examined by Southern hybridization and immunoblot analyses for the presence and expression of mip-related sequences. Strains representing all 14 serogroups of L. pneumophila contained a mip gene and expressed a 24-kilodalton Mip protein. Although...... with specific Mip antisera. Moreover, the cloned mip analog from Legionella micdadei encoded the cross-reactive protein. Thus, mip is conserved and specific to L. pneumophila, but mip-like genes are present throughout the genus, perhaps potentiating the intracellular infectivity of all Legionella species....

  12. Chlamydia trachomatis contains a protein similar to the Legionella pneumophila mip gene product

    DEFF Research Database (Denmark)

    Lundemose, AG; Birkelund, Svend; Fey, SJ

    1991-01-01

    A 27kDa Chlamydia trachomatis L2 protein was characterized by the use of monoclonal antibodies and by two-dimensional gel electrophoresis. The protein was shown to be located in the membrane of reticulate bodies as well as elementary bodies. Its synthesis could be detected from 10 hours post...

  13. Biochemical Study of Anti-Inflammatory Proteins vCCI and vMIP-II

    Science.gov (United States)

    2014-07-17

    not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. University of California - Merced 5200 North...Lake Road Merced , CA 95343 -5705 ABSTRACT Number of Papers published in peer-reviewed journals: Biochemical study of anti-inflammatory proteins vCCI and...inflammatory protein" Merced , CA. October 2012. 4. Invited Seminar: "Biochemical Design and Investigation of HIV entry inhibitors". California

  14. Function and regulation of plant major intrinsic proteins

    DEFF Research Database (Denmark)

    Popovic, Milan

    detoxification. Plant Noduline 26-like Intrinsic Proteins (NIPs) can channel As(III) and consequently influence the detoxification process. The role of the Tonoplast Intrinsic Proteins (TIPs) in As(III) detoxification remains to be clarified, yet TIPs could have an impact on As(III) accumulation in plant cell...... to development of plants with levated arsenic tolerance. Plants with the ability to hyperaccumulate arsenic could find its use in soil remediation while crop plants with efficient arsenic detoxification mechanisms could be used for food production in areas polluted with arsenic....

  15. Characterization of a Legionella micdadei mip mutant

    DEFF Research Database (Denmark)

    O'Connell, W A; Bangsborg, Jette Marie; Cianciotto, N P

    1995-01-01

    The pathogenesis of Legionella micdadei is dependent upon its ability to infect alveolar phagocytes. To better understand the basis of intracellular infection by this organism, we examined the importance of its Mip surface protein. In Legionella pneumophila, Mip promotes infection of both human m...... into the phagocyte. Similarly, the mutant was less able to parasitize Hartmannella amoebae. Taken together, these data argue that Mip specifically potentiates intracellular growth by L. micdadei....

  16. The dynamic multisite interactions between two intrinsically disordered proteins

    KAUST Repository

    Wu, Shaowen

    2017-05-11

    Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well characterized folding upon binding to dynamic fuzzy complex. To date, most studies concern the binding of an IDP to a structured protein, while the Interaction between two IDPs is poorly understood. In this study, we combined NMR, smFRET, and molecular dynamics (MD) simulation to characterize the interaction between two IDPs, the C-terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed that CTD and NuMA form a fuzzy complex with remaining structural disorder. Multiple binding sites on both proteins were identified by MD and mutagenesis studies. Our study provides an atomic scenario in which two IDPs bearing multiple binding sites interact with each other in dynamic equilibrium. The combined approach employed here could be widely applicable for investigating IDPs and their dynamic interactions.

  17. Folding propensity of intrinsically disordered proteins by osmotic stress

    International Nuclear Information System (INIS)

    Mansouri, Amanda L.; Grese, Laura N.; Rowe, Erica L.

    2016-01-01

    Proteins imparted with intrinsic disorder conduct a range of essential cellular functions. To better understand the folding and hydration properties of intrinsically disordered proteins (IDPs), we used osmotic stress to induce conformational changes in nuclear co-activator binding domain (NCBD) and activator for thyroid hormone and retinoid receptor (ACTR). Osmotic stress was applied by the addition of small and polymeric osmolytes, where we discovered that water contributions to NCBD folding always exceeded those for ACTR. Both NCBD and ACTR were found to gain a-helical structure with increasing osmotic stress, consistent with their folding upon NCBD/ACTR complex formation. Using small-angle neutron scattering (SANS), we further characterized NCBD structural changes with the osmolyte ethylene glycol. Here a large reduction in overall size initially occurred before substantial secondary structural change. In conclusion, by focusing on folding propensity, and linked hydration changes, we uncover new insights that may be important for how IDP folding contributes to binding.

  18. High GC content causes orphan proteins to be intrinsically disordered.

    Directory of Open Access Journals (Sweden)

    Walter Basile

    2017-03-01

    Full Text Available De novo creation of protein coding genes involves the formation of short ORFs from noncoding regions; some of these ORFs might then become fixed in the population. These orphan proteins need to, at the bare minimum, not cause serious harm to the organism, meaning that they should for instance not aggregate. Therefore, although the creation of short ORFs could be truly random, the fixation should be subjected to some selective pressure. The selective forces acting on orphan proteins have been elusive, and contradictory results have been reported. In Drosophila young proteins are more disordered than ancient ones, while the opposite trend is present in yeast. To the best of our knowledge no valid explanation for this difference has been proposed. To solve this riddle we studied structural properties and age of proteins in 187 eukaryotic organisms. We find that, with the exception of length, there are only small differences in the properties between proteins of different ages. However, when we take the GC content into account we noted that it could explain the opposite trends observed for orphans in yeast (low GC and Drosophila (high GC. GC content is correlated with codons coding for disorder promoting amino acids. This leads us to propose that intrinsic disorder is not a strong determining factor for fixation of orphan proteins. Instead these proteins largely resemble random proteins given a particular GC level. During evolution the properties of a protein change faster than the GC level causing the relationship between disorder and GC to gradually weaken.

  19. Phosphorylation of Intrinsically Disordered Regions in Remorin Proteins

    Directory of Open Access Journals (Sweden)

    Macarena eMarín

    2012-05-01

    Full Text Available Plant-specific remorin proteins reside in subdomains of plasma membranes, originally termed membrane rafts. They probably facilitate cellular signal transduction by direct interaction with signalling proteins such as receptor-like kinases (RLKs and may dynamically modulate their lateral segregation within plasma membranes. Recent evidence suggests such functions of remorins during plant-microbe interactions and innate immune responses, where differential phosphorylation of some of these proteins has been described to be dependent on the perception of the microbe-associated molecular pattern (MAMP flg22 and the presence of the NBS-LRR resistance protein RPM1. A number of specifically phosphorylated residues in their highly variable and intrinsically disordered N-terminal regions have been identified. Sequence diversity of these evolutionary distinct domains suggests that remorins may serve a wide range of biological functions. Here, we describe patterns and features of intrinsic disorder in remorin protein and discuss possible functional implications of phosphorylation within these rapidly evolving domains.

  20. Length-dependent prediction of protein intrinsic disorder

    Directory of Open Access Journals (Sweden)

    Dunker A Keith

    2006-04-01

    Full Text Available Abstract Background Due to the functional importance of intrinsically disordered proteins or protein regions, prediction of intrinsic protein disorder from amino acid sequence has become an area of active research as witnessed in the 6th experiment on Critical Assessment of Techniques for Protein Structure Prediction (CASP6. Since the initial work by Romero et al. (Identifying disordered regions in proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997, our group has developed several predictors optimized for long disordered regions (>30 residues with prediction accuracy exceeding 85%. However, these predictors are less successful on short disordered regions (≤30 residues. A probable cause is a length-dependent amino acid compositions and sequence properties of disordered regions. Results We proposed two new predictor models, VSL2-M1 and VSL2-M2, to address this length-dependency problem in prediction of intrinsic protein disorder. These two predictors are similar to the original VSL1 predictor used in the CASP6 experiment. In both models, two specialized predictors were first built and optimized for short (≤30 residues and long disordered regions (>30 residues, respectively. A meta predictor was then trained to integrate the specialized predictors into the final predictor model. As the 10-fold cross-validation results showed, the VSL2 predictors achieved well-balanced prediction accuracies of 81% on both short and long disordered regions. Comparisons over the VSL2 training dataset via 10-fold cross-validation and a blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were significantly more accurate than several existing predictors of intrinsic protein disorder. Conclusion The VSL2 predictors are applicable to disordered regions of any length and can accurately identify the short disordered regions that are often misclassified by our previous disorder predictors. The success of the VSL2 predictors

  1. Binding mechanisms of intrinsically disordered proteins: theory, simulation, and experiment

    Directory of Open Access Journals (Sweden)

    Luca Mollica

    2016-09-01

    Full Text Available In recent years, protein science has been revolutionized by the discovery of intrinsically disordered proteins (IDPs. In contrast to the classical paradigm that a given protein sequence corresponds to a defined structure and an associated function, we now know that proteins can be functional in the absence of a stable three-dimensional structure. In many cases, disordered proteins or protein regions become structured, at least locally, upon interacting with their physiological partners. Many, sometimes conflicting, hypotheses have been put forward regarding the interaction mechanisms of IDPs and the potential advantages of disorder for protein-protein interactions. Whether disorder may increase, as proposed e.g. in the fly-casting hypothesis, or decrease binding rates, increase or decrease binding specificity, or what role pre-formed structure might play in interactions involving IDPs (conformational selection vs. induced fit, are subjects of intense debate. Experimentally, these questions remain difficult to address. Here, we review experimental studies of binding mechanisms of IDPs using NMR spectroscopy and transient kinetic techniques, as well as the underlying theoretical concepts and numerical methods that can be applied to describe these interactions at the atomic level. The available literature suggests that the kinetic and thermodynamic parameters characterizing interactions involving IDPs can vary widely and that there may be no single common mechanism that can explain the different binding modes observed experimentally. Rather, disordered proteins appear to make combined use of features such as pre-formed structure and flexibility, depending on the individual system and the functional context.

  2. Intrinsically Disordered Proteins in a Physics-Based World

    Directory of Open Access Journals (Sweden)

    Jianhan Chen

    2010-12-01

    Full Text Available Intrinsically disordered proteins (IDPs are a newly recognized class of functional proteins that rely on a lack of stable structure for function. They are highly prevalent in biology, play fundamental roles, and are extensively involved in human diseases. For signaling and regulation, IDPs often fold into stable structures upon binding to specific targets. The mechanisms of these coupled binding and folding processes are of significant importance because they underlie the organization of regulatory networks that dictate various aspects of cellular decision-making. This review first discusses the challenge in detailed experimental characterization of these heterogeneous and dynamics proteins and the unique and exciting opportunity for physics-based modeling to make crucial contributions, and then summarizes key lessons from recent de novo simulations of the structure and interactions of several regulatory IDPs.

  3. Random coil chemical shift for intrinsically disordered proteins

    DEFF Research Database (Denmark)

    Kjærgaard, Magnus; Brander, Søren; Poulsen, Flemming Martin

    2011-01-01

    Secondary chemical shift analysis is the main NMR method for detection of transiently formed secondary structure in intrinsically disordered proteins. The quality of the secondary chemical shifts is dependent on an appropriate choice of random coil chemical shifts. We report random coil chemical....... Temperature has a non-negligible effect on the (13)C random coil chemical shifts, so temperature coefficients are reported for the random coil chemical shifts to allow extrapolation to other temperatures. The pH dependence of the histidine random coil chemical shifts is investigated in a titration series...

  4. Backbone and side-chain ¹H, ¹³C and ¹⁵N assignments of the PPIase domain of macrophage infectivity potentiator (Mip) protein from Coxiella burnetii.

    Science.gov (United States)

    Tse, Man-Kit; Cheung, Stanley K K; Ke, Yi-hong; Lau, Candy C Y; Sze, Kong-Hung; Yuen, Kwok-Yung

    2014-04-01

    Coxiella burnetii is an obligate intracellular gram-negative bacterium uniquely evolved to thrive in the inhospitable phagolysosome of macrophage. C. burnetii causes Q fever in humans and animals, which is emerging as a global public health concern. It is highly infectious and designated as a category B biowarfare agent because of its ubiquitous nature, abundant natural reservoirs, high resistance to environmental conditions, ease of transmission and low infectious dose. The lack of knowledge and awareness of C. burnetii leads to under-reporting and under-diagnosing of Q fever cases. Therefore, further understanding of the interactions between the infected host and the bacteria is necessary. C. burnetii macrophage infectivity potentiator (cb-Mip) is a secreted protein of 230 amino acids involving in intracellular survival of the pathogen. cb-Mip belongs to the family of FK506 binding protein, which possesses peptidyl-prolyl cis/trans isomerase (PPIase) activity. Besides acting as a PPIase, Mip protein homolog has been identified as virulence factor of many intracellular pathogenic microorganisms. In the present study, we report the near complete resonance assignments of the PPIase domain-containing region of Mip protein of C. burnetii. Secondary structure prediction based on chemical shift index analysis indicates that the protein adopts a predominately beta-strand structure, which is consistent with the crystal structure of homologous Mip protein in Legionella pneumophila.

  5. Identification of Inhibitors of Biological Interactions Involving Intrinsically Disordered Proteins

    Directory of Open Access Journals (Sweden)

    Daniela Marasco

    2015-04-01

    Full Text Available Protein–protein interactions involving disordered partners have unique features and represent prominent targets in drug discovery processes. Intrinsically Disordered Proteins (IDPs are involved in cellular regulation, signaling and control: they bind to multiple partners and these high-specificity/low-affinity interactions play crucial roles in many human diseases. Disordered regions, terminal tails and flexible linkers are particularly abundant in DNA-binding proteins and play crucial roles in the affinity and specificity of DNA recognizing processes. Protein complexes involving IDPs are short-lived and typically involve short amino acid stretches bearing few “hot spots”, thus the identification of molecules able to modulate them can produce important lead compounds: in this scenario peptides and/or peptidomimetics, deriving from structure-based, combinatorial or protein dissection approaches, can play a key role as hit compounds. Here, we propose a panoramic review of the structural features of IDPs and how they regulate molecular recognition mechanisms focusing attention on recently reported drug-design strategies in the field of IDPs.

  6. Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

    Science.gov (United States)

    Uversky, Vladimir N

    2016-03-25

    Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Enhanced Boron Tolerance in Plants Mediated by Bidirectional Transport Through Plasma Membrane Intrinsic Proteins.

    Science.gov (United States)

    Mosa, Kareem A; Kumar, Kundan; Chhikara, Sudesh; Musante, Craig; White, Jason C; Dhankher, Om Parkash

    2016-02-23

    High boron (B) concentration is toxic to plants that limit plant productivity. Recent studies have shown the involvement of the members of major intrinsic protein (MIP) family in controlling B transport. Here, we have provided experimental evidences showing the bidirectional transport activity of rice OsPIP1;3 and OsPIP2;6. Boron transport ability of OsPIP1;3 and OsPIP2;6 were displayed in yeast HD9 mutant strain (∆fps1∆acr3∆ycf1) as a result of increased B sensitivity, influx and accumulation by OsPIP1;3, and rapid efflux activity by OsPIP2;6. RT-PCR analysis showed strong upregulation of OsPIP1;3 and OsPIP2;6 transcripts in roots by B toxicity. Transgenic Arabidopsis lines overexpressing OsPIP1;3 and OsPIP2;6 exhibited enhanced tolerance to B toxicity. Furthermore, B concentration was significantly increased after 2 and 3 hours of tracer boron ((10)B) treatment. Interestingly, a rapid efflux of (10)B from the roots of the transgenic plants was observed within 1 h of (10)B treatment. Boron tolerance in OsPIP1;3 and OsPIP2;6 lines was inhibited by aquaporin inhibitors, silver nitrate and sodium azide. Our data proved that OsPIP1;3 and OsPIP2;6 are indeed involved in both influx and efflux of boron transport. Manipulation of these PIPs could be highly useful in improving B tolerance in crops grown in high B containing soils.

  8. Comprehensive large-scale assessment of intrinsic protein disorder.

    Science.gov (United States)

    Walsh, Ian; Giollo, Manuel; Di Domenico, Tomás; Ferrari, Carlo; Zimmermann, Olav; Tosatto, Silvio C E

    2015-01-15

    Intrinsically disordered regions are key for the function of numerous proteins. Due to the difficulties in experimental disorder characterization, many computational predictors have been developed with various disorder flavors. Their performance is generally measured on small sets mainly from experimentally solved structures, e.g. Protein Data Bank (PDB) chains. MobiDB has only recently started to collect disorder annotations from multiple experimental structures. MobiDB annotates disorder for UniProt sequences, allowing us to conduct the first large-scale assessment of fast disorder predictors on 25 833 different sequences with X-ray crystallographic structures. In addition to a comprehensive ranking of predictors, this analysis produced the following interesting observations. (i) The predictors cluster according to their disorder definition, with a consensus giving more confidence. (ii) Previous assessments appear over-reliant on data annotated at the PDB chain level and performance is lower on entire UniProt sequences. (iii) Long disordered regions are harder to predict. (iv) Depending on the structural and functional types of the proteins, differences in prediction performance of up to 10% are observed. The datasets are available from Web site at URL: http://mobidb.bio.unipd.it/lsd. Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions.

    Science.gov (United States)

    Gruet, Antoine; Dosnon, Marion; Blocquel, David; Brunel, Joanna; Gerlier, Denis; Das, Rahul K; Bonetti, Daniela; Gianni, Stefano; Fuxreiter, Monika; Longhi, Sonia; Bignon, Christophe

    2016-02-01

    Despite the partial disorder-to-order transition that intrinsically disordered proteins often undergo upon binding to their partners, a considerable amount of residual disorder may be retained in the bound form, resulting in a fuzzy complex. Fuzzy regions flanking molecular recognition elements may enable partner fishing through non-specific, transient contacts, thereby facilitating binding, but may also disfavor binding through various mechanisms. So far, few computational or experimental studies have addressed the effect of fuzzy appendages on partner recognition by intrinsically disordered proteins. In order to shed light onto this issue, we used the interaction between the intrinsically disordered C-terminal domain of the measles virus (MeV) nucleoprotein (NTAIL ) and the X domain (XD) of the viral phosphoprotein as model system. After binding to XD, the N-terminal region of NTAIL remains conspicuously disordered, with α-helical folding taking place only within a short molecular recognition element. To study the effect of the N-terminal fuzzy region on NTAIL /XD binding, we generated N-terminal truncation variants of NTAIL , and assessed their binding abilities towards XD. The results revealed that binding increases with shortening of the N-terminal fuzzy region, with this also being observed with hsp70 (another MeV NTAIL binding partner), and for the homologous NTAIL /XD pairs from the Nipah and Hendra viruses. Finally, similar results were obtained when the MeV NTAIL fuzzy region was replaced with a highly dissimilar artificial disordered sequence, supporting a sequence-independent inhibitory effect of the fuzzy region. © 2015 Federation of European Biochemical Societies.

  10. Intrinsically Disordered Proteins and the Origins of Multicellular Organisms

    Science.gov (United States)

    Dunker, A. Keith

    In simple multicellular organisms all of the cells are in direct contact with the surrounding milieu, whereas in complex multicellular organisms some cells are completely surrounded by other cells. Current phylogenetic trees indicate that complex multicellular organisms evolved independently from unicellular ancestors about 10 times, and only among the eukaryotes, including once for animals, twice each for green, red, and brown algae, and thrice for fungi. Given these multiple independent evolutionary lineages, we asked two questions: 1. Which molecular functions underpinned the evolution of multicellular organisms?; and, 2. Which of these molecular functions depend on intrinsically disordered proteins (IDPs)? Compared to unicellularity, multicellularity requires the advent of molecules for cellular adhesion, for cell-cell communication and for developmental programs. In addition, the developmental programs need to be regulated over space and time. Finally, each multicellular organism has cell-specific biochemistry and physiology. Thus, the evolution of complex multicellular organisms from unicellular ancestors required five new classes of functions. To answer the second question we used Key-words in Swiss Protein ranked for associations with predictions of protein structure or disorder. With a Z-score of 18.8 compared to random-function proteins, à differentiation was the biological process most strongly associated with IDPs. As expected from this result, large numbers of individual proteins associated with differentiation exhibit substantial regions of predicted disorder. For the animals for which there is the most readily available data all five of the underpinning molecular functions for multicellularity were found to depend critically on IDP-based mechanisms and other evidence supports these ideas. While the data are more sparse, IDPs seem to similarly underlie the five new classes of functions for plants and fungi as well, suggesting that IDPs were indeed

  11. An Extended Guinier Analysis for Intrinsically Disordered Proteins.

    Science.gov (United States)

    Zheng, Wenwei; Best, Robert B

    2018-03-21

    Guinier analysis allows model-free determination of the radius of gyration (R g ) of a biomolecule from X-ray or neutron scattering data, in the limit of very small scattering angles. Its range of validity is well understood for globular proteins, but is known to be more restricted for unfolded or intrinsically disordered proteins (IDPs). We have used ensembles of disordered structures from molecular dynamics simulations to investigate which structural properties cause deviations from the Guinier approximation at small scattering angles. We find that the deviation from the Guinier approximation is correlated with the polymer scaling exponent ν describing the unfolded ensemble. We therefore introduce an empirical, ν-dependent, higher-order correction term, to augment the standard Guinier analysis. We test the new fitting scheme using all-atom simulation data for several IDPs and experimental data for both an IDP and a destabilized mutant of a folded protein. In all cases tested, we achieve an accuracy of the inferred R g within ∼3% of the true R g . The method is straightforward to implement and extends the range of validity to a maximum qR g of ∼2 versus ∼1.1 for Guinier analysis. Compared with the Guinier or Debye approaches, our method allows data from wider angles with lower noise to be used to analyze scattering data accurately. In addition to R g , our fitting scheme also yields estimates of the scaling exponent ν in excellent agreement with the reference ν determined from the underlying molecular ensemble. Published by Elsevier Ltd.

  12. Domain distribution and intrinsic disorder in hubs in the human protein-protein interaction network.

    Science.gov (United States)

    Patil, Ashwini; Kinoshita, Kengo; Nakamura, Haruki

    2010-08-01

    Intrinsic disorder and distributed surface charge have been previously identified as some of the characteristics that differentiate hubs (proteins with a large number of interactions) from non-hubs in protein-protein interaction networks. In this study, we investigated the differences in the quantity, diversity, and functional nature of Pfam domains, and their relationship with intrinsic disorder, in hubs and non-hubs. We found that proteins with a more diverse domain composition were over-represented in hubs when compared with non-hubs, with the number of interactions in hubs increasing with domain diversity. Conversely, the fraction of intrinsic disorder in hubs decreased with increasing number of ordered domains. The difference in the levels of disorder was more prominent in hubs and non-hubs with fewer domains. Functional analysis showed that hubs were enriched in kinase and adaptor domains acting primarily in signal transduction and transcription regulation, whereas non-hubs had more DNA-binding domains and were involved in catalytic activity. Consistent with the differences in the functional nature of their domains, hubs with two or more domains were more likely to connect distinct functional modules in the interaction network when compared with single domain hubs. We conclude that the availability of greater number and diversity of ordered domains, in addition to the tendency to have promiscuous domains, differentiates hubs from non-hubs and provides an additional means of achieving interaction promiscuity. Further, hubs with fewer domains use greater levels of intrinsic disorder to facilitate interaction promiscuity with the prevalence of disorder decreasing with increasing number of ordered domains.

  13. Domain distribution and intrinsic disorder in hubs in the human protein–protein interaction network

    OpenAIRE

    Patil, Ashwini; Kinoshita, Kengo; Nakamura, Haruki

    2010-01-01

    Intrinsic disorder and distributed surface charge have been previously identified as some of the characteristics that differentiate hubs (proteins with a large number of interactions) from non-hubs in protein–protein interaction networks. In this study, we investigated the differences in the quantity, diversity, and functional nature of Pfam domains, and their relationship with intrinsic disorder, in hubs and non-hubs. We found that proteins with a more diverse domain composition were over-re...

  14. Structural predictions of neurobiologically relevant G-protein coupled receptors and intrinsically disordered proteins.

    Science.gov (United States)

    Rossetti, Giulia; Dibenedetto, Domenica; Calandrini, Vania; Giorgetti, Alejandro; Carloni, Paolo

    2015-09-15

    G protein coupled receptors (GPCRs) and intrinsic disordered proteins (IDPs) are key players for neuronal function and dysfunction. Unfortunately, their structural characterization is lacking in most cases. From one hand, no experimental structure has been determined for the two largest GPCRs subfamilies, both key proteins in neuronal pathways. These are the odorant (450 members out of 900 human GPCRs) and the bitter taste receptors (25 members) subfamilies. On the other hand, also IDPs structural characterization is highly non-trivial. They exist as dynamic, highly flexible structural ensembles that undergo conformational conversions on a wide range of timescales, spanning from picoseconds to milliseconds. Computational methods may be of great help to characterize these neuronal proteins. Here we review recent progress from our lab and other groups to develop and apply in silico methods for structural predictions of these highly relevant, fascinating and challenging systems. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Identification of a novel splice-site mutation in MIP in a Chinese congenital cataract family.

    Science.gov (United States)

    Jiang, Jin; Jin, Chongfei; Wang, Wei; Tang, Xiajing; Shentu, Xingchao; Wu, Renyi; Wang, Yao; Xia, Kun; Yao, Ke

    2009-01-01

    To map the locus and identify the gene causing autosomal dominant congenital cataract (ADCC) with "snail-like" phenotype in a large Chinese family. Clinical and ophthalmologic examinations were conducted on family members and documented by slit lamp photography. Linkage analysis was performed with an initial 41 microsatellite markers, then 3 additional markers flanking the major intrinsic protein (MIP) gene. Mutations were screened by DNA sequencing and verified by restriction fragment length polymorphism (RFLP) analysis. Significant two-point LOD scores were obtained at 5 markers flanking MIP with the highest 3.08 (theta=0.00) at marker D12S1632. Mutation screening of MIP identified a heterozygous G>A transition at the acceptor splice site of intron 3 (IVS3 -1 G>A), abolishing a BstSF I restriction site in one allele of all the affected individuals. We identified a novel splice-site mutation (IVS3 -1 G>A in MIP) in a Chinese ADCC family. To our knowledge, this is the first report on an acceptor splice-site mutation in human genes associated with ADCC.

  16. The lifestyle switch protein Bd0108 of Bdellovibrio bacteriovorus is an intrinsically disordered protein.

    Directory of Open Access Journals (Sweden)

    Gerd Prehna

    Full Text Available Bdellovibrio bacteriovorus is a δ-proteobacterium that preys upon Salmonella spp., E. coli, and other Gram-negative bacteria. Bdellovibrio can grow axenically (host-independent, HI, rare and mutation-driven or subsist via a predatory lifecycle (host-dependent, HD, the usual case. Upon contact with prey, B. bacteriovorus enters the host periplasm from where it slowly drains the host cytosol of nutrients for its own replication. At the core of this mechanism is a retractile pilus, whose architecture is regulated by the protein Bd0108 and its interaction with the neighboring gene product Bd0109. Deletion of bd0108 results in negligible pilus formation, whereas an internal deletion (the one that instigates host-independence causes mis-regulation of pilus length. These mutations, along with a suite of naturally occurring bd0108 mutant strains, act to control the entry to HI growth. To further study the molecular mechanism of predatory regulation, we focused on the apparent lifecycle switch protein Bd0108. Here we characterize the solution structure and dynamics of Bd0108 using nuclear magnetic resonance (NMR spectroscopy complemented with additional biophysical methods. We then explore the interaction between Bd0108 and Bd0109 in detail utilizing isothermal titration calorimetry (ITC and NMR spectroscopy. Together our results demonstrate that Bd0108 is an intrinsically disordered protein (IDP and that the interaction with Bd0109 is of low affinity. Furthermore, we observe that Bd0108 retains an IDP nature while binding Bd0109. From our data we conclude that Bdellovibrio bacteriovorus utilizes an intrinsically disordered protein to regulate its pilus and control predation signaling.

  17. A novel Glycine soja tonoplast intrinsic protein gene responds to abiotic stress and depresses salt and dehydration tolerance in transgenic Arabidopsis thaliana.

    Science.gov (United States)

    Wang, Xi; Li, Yong; Ji, Wei; Bai, Xi; Cai, Hua; Zhu, Dan; Sun, Xiao-Li; Chen, Lian-Jiang; Zhu, Yan-Ming

    2011-07-15

    Tonoplast intrinsic protein (TIP) is a subfamily of the aquaporin (AQP), also known as major intrinsic protein (MIP) family, and regulates water movement across vacuolar membranes. Some reports have implied that TIP genes are associated with plant tolerance to some abiotic stresses that cause water loss, such as drought and high salinity. In our previous work, we found that an expressed sequence tag (EST) representing a TIP gene in our Glycine soja EST library was inducible by abiotic stresses. This TIP was subsequently isolated from G. soja with cDNA library screening, EST assembly and PCR, and named as GsTIP2;1. The expression patterns of GsTIP2;1 in G. soja under low temperature, salt and dehydration stress were different in leaves and roots. Though GsTIP2;1 is a stress-induced gene, overexpression of GsTIP2;1 in Arabidopsis thaliana depressed tolerance to salt and dehydration stress, but did not affect seedling growth under cold or favorable conditions. Higher dehydration speed was detected in Arabidopsis plants overexpressing GsTIP2;1, implying GsTIP2;1 might mediate stress sensitivity by enhancing water loss in the plant. Such a result is not identical to previous reports, providing some new information about the relationship between TIP and plant abiotic stress tolerance. Copyright © 2011 Elsevier GmbH. All rights reserved.

  18. Assembly of the intrinsic factor domains and oligomerization of the protein in the presence of cobalamin

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars

    2004-01-01

    Human intrinsic factor (IF) was purified from the recombinant plant Arabidopsis thaliana by affinity chromatography. Cobalamin (Cbl) saturated protein was separated by gel filtration into peaks I and II, which contained according to SDS electrophoresis the 50 kDa full-length protein IF(50...

  19. Intrinsic disorder modulates protein self-assembly and aggregation.

    Science.gov (United States)

    De Simone, Alfonso; Kitchen, Craig; Kwan, Ann H; Sunde, Margaret; Dobson, Christopher M; Frenkel, Daan

    2012-05-01

    Protein molecules have evolved to adopt distinctive and well-defined functional and soluble states under physiological conditions. In some circumstances, however, proteins can self-assemble into fibrillar aggregates designated as amyloid fibrils. In vivo these processes are normally associated with severe pathological conditions but can sometimes have functional relevance. One such example is the hydrophobins, whose aggregation at air-water interfaces serves to create robust protein coats that help fungal spores to resist wetting and thus facilitate their dispersal in the air. We have performed multiscale simulations to address the molecular determinants governing the formation of functional amyloids by the class I fungal hydrophobin EAS. Extensive samplings of full-atom replica-exchange molecular dynamics and coarse-grained simulations have allowed us to identify factors that distinguish aggregation-prone from highly soluble states of EAS. As a result of unfavourable entropic terms, highly dynamical regions are shown to exert a crucial influence on the propensity of the protein to aggregate under different conditions. More generally, our findings suggest a key role that specific flexible structural elements can play to ensure the existence of soluble and functional states of proteins under physiological conditions.

  20. System-wide analysis reveals intrinsically disordered proteins are prone to ubiquitylation after misfolding stress.

    Science.gov (United States)

    Ng, Alex H M; Fang, Nancy N; Comyn, Sophie A; Gsponer, Jörg; Mayor, Thibault

    2013-09-01

    Damaged and misfolded proteins that are no longer functional in the cell need to be eliminated. Failure to do so might lead to their accumulation and aggregation, a hallmark of many neurodegenerative diseases. Protein quality control pathways play a major role in the degradation of these proteins, which is mediated mainly by the ubiquitin proteasome system. Despite significant focus on identifying ubiquitin ligases involved in these pathways, along with their substrates, a systems-level understanding of these pathways has been lacking. For instance, as misfolded proteins are rapidly ubiquitylated, unconjugated ubiquitin is rapidly depleted from the cell upon misfolding stress; yet it is unknown whether certain targets compete more efficiently to be ubiquitylated. Using a system-wide approach, we applied statistical and computational methods to identify characteristics enriched among proteins that are further ubiquitylated after heat shock. We discovered that distinct populations of structured and, surprisingly, intrinsically disordered proteins are prone to ubiquitylation. Proteomic analysis revealed that abundant and highly structured proteins constitute the bulk of proteins in the low-solubility fraction after heat shock, but only a portion is ubiquitylated. In contrast, ubiquitylated, intrinsically disordered proteins are enriched in the low-solubility fraction after heat shock. These proteins have a very low abundance in the cell, are rarely encoded by essential genes, and are enriched in binding motifs. In additional experiments, we confirmed that several of the identified intrinsically disordered proteins were ubiquitylated after heat shock and demonstrated for two of them that their disordered regions are important for ubiquitylation after heat shock. We propose that intrinsically disordered regions may be recognized by the protein quality control machinery and thereby facilitate the ubiquitylation of proteins after heat shock.

  1. Virtual reality analysis of intrinsic protein geometry with applications to cis peptide planes

    OpenAIRE

    Hou, Yanzhen; Dai, Jin; Ilieva, Nevena; Niemi, Antti J.; Peng, Xubiao; He, Jianfeng

    2017-01-01

    A protein is traditionally visualised as a piecewise linear discrete curve, and its geometry is conventionally characterised by the extrinsically determined Ramachandran angles. However, a protein backbone has also two independent intrinsic geometric structures, due to the peptide planes and the side chains. Here we adapt and develop modern 3D virtual reality techniques to scrutinize the atomic geometry along a protein backbone, in the vicinity of a peptide plane. For this we compare backbone...

  2. Functional roles of intrinsic disorder in CRISPR-associated protein Cas9.

    Science.gov (United States)

    Du, Zhihua; Uversky, Vladimir N

    2017-08-22

    Protein intrinsic disorder is an important characteristic commonly detected in multifunctional or RNA- and DNA-binding proteins. Due to their high conformational flexibility and solvent accessibility, intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) execute diverse functions including interaction with multiple partners, and are frequently subjected to various post-translational modifications. Recent studies on the components comprising the CRISPR (clustered regularly interspaced short palindromic repeats) system have elucidated the crystal structure of Cas9 proteins and the mechanism by which the Cas9-sgRNA complex recognizes and cleaves its target DNA. Yet the extent and functional implications of intrinsic disorder in the Cas9 protein have never been fully assessed. Here, we present a comprehensive computational analysis based on both sequence and structural data in an attempt to investigate the roles of IDPRs in the functioning of Cas9 proteins of different origin. We conclude that among the functional roles of IDPRs in Cas9 proteins are recognition of the target DNA and mediation of nucleic acid and protein binding.

  3. Towards the Structural Characterization of Intrinsically Disordered Proteins by SAXS and MD Simulation

    Science.gov (United States)

    Oroguchi, Tomotaka; Ikeguchi, Mitsunori; Sato, Mamoru

    2011-01-01

    Dynamical structures of intrinsically disordered proteins (IDPs) and multi-domain proteins that include large ID regions between the domains are unable to be determined by such conventional methods as X-ray crystallography and electron microscopy. Small-angle X-ray scattering (SAXS) is suitable to determine low-resolution structures of proteins and protein complexes in solution, but the structural data on protein dynamics are averaged over the structural ensemble in protein solution. To overcome this problem, we have developed a novel method, named MD-SAXS, of the combined use of SAXS and molecular dynamics (MD) simulation to analyze protein dynamics in solution of multi-subunit protein complexes and multi-domain proteins toward the structural characterization of IDPs. Here we show validity of the method through the structural characterization of restriction Endonuclease EcoO109I.

  4. High dimensional and high resolution pulse sequences for backbone resonance assignment of intrinsically disordered proteins

    Czech Academy of Sciences Publication Activity Database

    Zawadzka-Kazimierczuk, A.; Kozminski, W.; Šanderová, Hana; Krásný, Libor

    2012-01-01

    Roč. 52, č. 4 (2012), s. 329-337 ISSN 0925-2738 R&D Projects: GA ČR GA204/09/0583 Institutional research plan: CEZ:AV0Z50200510 Keywords : Intrinsically disordered proteins * Non-uniform sampling * Backbone assignment Subject RIV: EE - Microbiology, Virology Impact factor: 2.845, year: 2012

  5. DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex

    NARCIS (Netherlands)

    Ketterer, Philip; Ananth, Adithya N; Laman Trip, Diederik S; Mishra, Ankur; Bertosin, Eva; Ganji, Mahipal; van der Torre, Jaco; Onck, Patrick; Dietz, Hendrik; Dekker, Cees

    2018-01-01

    The nuclear pore complex (NPC) is the gatekeeper for nuclear transport in eukaryotic cells. A key component of the NPC is the central shaft lined with intrinsically disordered proteins (IDPs) known as FG-Nups, which control the selective molecular traffic. Here, we present an approach to realize

  6. Brain expressed and X-linked (Bex proteins are intrinsically disordered proteins (IDPs and form new signaling hubs.

    Directory of Open Access Journals (Sweden)

    Eva M Fernandez

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in complex organisms. Due to their promiscuous nature and their ability to adopt several conformations IDPs constitute important points of network regulation. The family of Brain Expressed and X-linked (Bex proteins consists of 5 members in humans (Bex1-5. Recent reports have implicated Bex proteins in transcriptional regulation and signaling pathways involved in neurodegeneration, cancer, cell cycle and tumor growth. However, structural and biophysical data for this protein family is almost non-existent. We used bioinformatics analyses to show that Bex proteins contain long regions of intrinsic disorder which are conserved across all members. Moreover, we confirmed the intrinsic disorder by circular dichroism spectroscopy of Bex1 after expression and purification in E. coli. These observations strongly suggest that Bex proteins constitute a new group of IDPs. Based on these findings, together with the demonstrated promiscuity of Bex proteins and their involvement in different signaling pathways, we propose that Bex family members play important roles in the formation of protein network hubs.

  7. Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype

    Directory of Open Access Journals (Sweden)

    Yoo Chong

    2011-10-01

    Full Text Available Abstract Background Matrix-assisted laser desorption/ionization (MALDI mass spectrometry (MS has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype. Methods Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Results Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets. Conclusions Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.

  8. Binding induced conformational changes of proteins correlate with their intrinsic fluctuations: a case study of antibodies

    Directory of Open Access Journals (Sweden)

    Keskin Ozlem

    2007-05-01

    Full Text Available Abstract Background How antibodies recognize and bind to antigens can not be totally explained by rigid shape and electrostatic complimentarity models. Alternatively, pre-existing equilibrium hypothesis states that the native state of an antibody is not defined by a single rigid conformation but instead with an ensemble of similar conformations that co-exist at equilibrium. Antigens bind to one of the preferred conformations making this conformation more abundant shifting the equilibrium. Results Here, two antibodies, a germline antibody of 36–65 Fab and a monoclonal antibody, SPE7 are studied in detail to elucidate the mechanism of antibody-antigen recognition and to understand how a single antibody recognizes different antigens. An elastic network model, Anisotropic Network Model (ANM is used in the calculations. Pre-existing equilibrium is not restricted to apply to antibodies. Intrinsic fluctuations of eight proteins, from different classes of proteins, such as enzymes, binding and transport proteins are investigated to test the suitability of the method. The intrinsic fluctuations are compared with the experimentally observed ligand induced conformational changes of these proteins. The results show that the intrinsic fluctuations obtained by theoretical methods correlate with structural changes observed when a ligand is bound to the protein. The decomposition of the total fluctuations serves to identify the different individual modes of motion, ranging from the most cooperative ones involving the overall structure, to the most localized ones. Conclusion Results suggest that the pre-equilibrium concept holds for antibodies and the promiscuity of antibodies can also be explained this hypothesis: a limited number of conformational states driven by intrinsic motions of an antibody might be adequate to bind to different antigens.

  9. Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers.

    Science.gov (United States)

    Quiroz, Felipe García; Chilkoti, Ashutosh

    2015-11-01

    Proteins and synthetic polymers that undergo aqueous phase transitions mediate self-assembly in nature and in man-made material systems. Yet little is known about how the phase behaviour of a protein is encoded in its amino acid sequence. Here, by synthesizing intrinsically disordered, repeat proteins to test motifs that we hypothesized would encode phase behaviour, we show that the proteins can be designed to exhibit tunable lower or upper critical solution temperature (LCST and UCST, respectively) transitions in physiological solutions. We also show that mutation of key residues at the repeat level abolishes phase behaviour or encodes an orthogonal transition. Furthermore, we provide heuristics to identify, at the proteome level, proteins that might exhibit phase behaviour and to design novel protein polymers consisting of biologically active peptide repeats that exhibit LCST or UCST transitions. These findings set the foundation for the prediction and encoding of phase behaviour at the sequence level.

  10. p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept

    Science.gov (United States)

    Uversky, Vladimir N.

    2016-01-01

    Although it is one of the most studied proteins, p53 continues to be an enigma. This protein has numerous biological functions, possesses intrinsically disordered regions crucial for its functionality, can form both homo-tetramers and isoform-based hetero-tetramers, and is able to interact with many binding partners. It contains numerous posttranslational modifications, has several isoforms generated by alternative splicing, alternative promoter usage or alternative initiation of translation, and is commonly mutated in different cancers. Therefore, p53 serves as an important illustration of the protein structure–function continuum concept, where the generation of multiple proteoforms by various mechanisms defines the ability of this protein to have a multitude of structurally and functionally different states. Considering p53 in the light of a proteoform-based structure–function continuum represents a non-canonical and conceptually new contemplation of structure, regulation, and functionality of this important protein. PMID:27834926

  11. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

    Science.gov (United States)

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease. PMID:27453073

  12. Proteins with Intrinsically Disordered Domains Are Preferentially Recruited to Polyglutamine Aggregates.

    Directory of Open Access Journals (Sweden)

    Maggie P Wear

    Full Text Available Intracellular protein aggregation is the hallmark of several neurodegenerative diseases. Aggregates formed by polyglutamine (polyQ-expanded proteins, such as Huntingtin, adopt amyloid-like structures that are resistant to denaturation. We used a novel purification strategy to isolate aggregates formed by human Huntingtin N-terminal fragments with expanded polyQ tracts from both yeast and mammalian (PC-12 cells. Using mass spectrometry we identified the protein species that are trapped within these polyQ aggregates. We found that proteins with very long intrinsically-disordered (ID domains (≥ 100 amino acids and RNA-binding proteins were disproportionately recruited into aggregates. The removal of the ID domains from selected proteins was sufficient to eliminate their recruitment into polyQ aggregates. We also observed that several neurodegenerative disease-linked proteins were reproducibly trapped within the polyQ aggregates purified from mammalian cells. Many of these proteins have large ID domains and are found in neuronal inclusions in their respective diseases. Our study indicates that neurodegenerative disease-associated proteins are particularly vulnerable to recruitment into polyQ aggregates via their ID domains. Also, the high frequency of ID domains in RNA-binding proteins may explain why RNA-binding proteins are frequently found in pathological inclusions in various neurodegenerative diseases.

  13. Molecular Dynamics Simulations of a Powder Model of the Intrinsically Disordered Protein Tau.

    Science.gov (United States)

    Fichou, Yann; Heyden, Matthias; Zaccai, Giuseppe; Weik, Martin; Tobias, Douglas J

    2015-10-01

    The tau protein, whose aggregates are involved in Alzheimer's disease, is an intrinsically disordered protein (IDP) that regulates microtubule activity in neurons. An IDP lacks a single, well-defined structure and, rather, constantly exchanges among multiple conformations. In order to study IDP dynamics, the combination of experimental techniques, such as neutron scattering, and computational techniques, such as molecular dynamics (MD) simulations, is a powerful approach. Amorphous hydrated powder samples have been very useful for studying protein internal dynamics experimentally, e.g., using neutron scattering. Thus, there is demand for realistic in silico models of hydrated protein powders. Here we present an MD simulation analysis of a powder hydrated at 0.4 g water/g protein of the IDP tau in the temperature range 20-300 K. By comparing with neutron scattering data, we identify the protein-water interface as the predominant feature determining IDP dynamics. The so-called protein dynamical transition is shown to be attenuated, but not suppressed, in the parts of the protein that are not exposed to the solvent. In addition, we find similarities in the mean-squared displacements of the core of a globular protein and "dry" clusters formed by the IDP in hydrated powders. Thus, the ps to ns dynamics of proteins in hydrated powders originate mainly from those residues in contact with solvent. We propose that by measuring the dynamics of protein assemblies, such as aggregates, one might assess qualitatively their state of hydration.

  14. Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII

    NARCIS (Netherlands)

    Koppelman, S.J.

    1995-01-01

    Protein S is a vitamin K-dependent nonenzymatic anticoagulant protein that acts as a cofactor to activated protein C. Recently it was shown that protein S inhibits the prothrombinase reaction independent of activated protein C. In this study, we show that protein S can also inhibit the intrinsic

  15. The Impact of O-Glycan Chemistry on the Stability of Intrinsically Disordered Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Beckham, Gregg T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Prates, Erica T [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Crowley, Michael F [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Guan, Xiaoyang [University of Colorado; Li, Yaohao [University of Colorado; Wang, Xinfeng [University of Colorado; Chaffey, Patrick K. [University of Colorado; Skaf, Munir S. [University of Campinas; Tan, Zhongping [University of Colorado

    2018-03-02

    Protein glycosylation is a diverse post-translational modification that serves myriad biological functions. O-linked glycans in particular vary widely in extent and chemistry in eukaryotes, with secreted proteins from fungi and yeast commonly exhibiting O-mannosylation in intrinsically disordered regions of proteins, likely for proteolysis protection, among other functions. However, it is not well understood why mannose is often the preferred glycan, and more generally, if the neighboring protein sequence and glycan have coevolved to protect against proteolysis in glycosylated intrinsically disordered proteins (IDPs). Here, we synthesized variants of a model IDP, specifically a natively O-mannosylated linker from a fungal enzyme, with a-O-linked mannose, glucose, and galactose moieties, along with a non-glycosylated linker. Upon exposure to thermolysin, O-mannosylation, by far, provides the highest extent of proteolysis protection. To explain this observation, extensive molecular dynamics simulations were conducted, revealing that the axial configuration of the C2-hydroxyl group (2-OH) of a-mannose adjacent to the glycan-peptide bond strongly influences the conformational features of the linker. Specifically, a-mannose restricts the torsions of the IDP main chain more than other glycans whose equatorial 2-OH groups exhibit interactions that favor perpendicular glycan-protein backbone orientation. We suggest that IDP stiffening due to O-mannosylation impairs protease action, with contributions from protein-glycan interactions, protein flexibility, and protein stability. Our results further imply that resistance to proteolysis is an important driving force for evolutionary selection of a-mannose in eukaryotic IDPs, and more broadly, that glycan motifs for proteolysis protection likely coevolve with the protein sequence to which they attach.

  16. Amphipathic helical peptides hamper protein-protein interactions of the intrinsically disordered chromatin nuclear protein 1 (NUPR1).

    Science.gov (United States)

    Santofimia-Castaño, Patricia; Rizzuti, Bruno; Abián, Olga; Velázquez-Campoy, Adrián; Iovanna, Juan L; Neira, José L

    2018-03-09

    NUPR1 is a multifunctional intrinsically disordered protein (IDP) involved, among other functions, in chromatin remodelling, and development of pancreatic ductal adenocarcinoma (PDAC). It interacts with several biomolecules through hydrophobic patches around residues Ala33 and Thr68. The drug trifluoperazine (TFP), which hampers PDAC development in xenografted mice, also binds to those regions. Because of the large size of the hot-spot interface of NUPR1, small molecules could not be adequate to modulate its functions. We explored how amphipathic helical-designed peptides were capable of interacting with wild-type NUPR1 and the Thr68Gln mutant, inhibiting the interaction with NUPR1 protein partners. We used in vitro biophysical techniques (fluorescence, circular dichroism (CD), nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC)), in silico studies (docking and molecular dynamics (MD)), and in cellulo protein ligation assays (PLAs) to study the interaction. Peptide dissociation constants towards wild-type NUPR1 were ~ 3 μM, whereas no interaction was observed with the Thr68Gln mutant. Peptides interacted with wild-type NUPR1 residues around Ala33 and residues at the C terminus, as shown by NMR. The computational results clarified the main determinants of the interactions, providing a mechanism for the ligand-capture that explains why peptide binding was not observed for Thr68Gln mutant. Finally, the in cellulo assays indicated that two out of four peptides inhibited the interaction of NUPR1 with the C-terminal region of the Polycomb RING protein 1 (C-RING1B). Designed peptides can be used as lead compounds to inhibit NUPR1 interactions. Peptides may be exploited as drugs to target IDPs. Copyright © 2018. Published by Elsevier B.V.

  17. Domain distribution and intrinsic disorder in hubs in the human protein–protein interaction network

    Science.gov (United States)

    Patil, Ashwini; Kinoshita, Kengo; Nakamura, Haruki

    2010-01-01

    Intrinsic disorder and distributed surface charge have been previously identified as some of the characteristics that differentiate hubs (proteins with a large number of interactions) from non-hubs in protein–protein interaction networks. In this study, we investigated the differences in the quantity, diversity, and functional nature of Pfam domains, and their relationship with intrinsic disorder, in hubs and non-hubs. We found that proteins with a more diverse domain composition were over-represented in hubs when compared with non-hubs, with the number of interactions in hubs increasing with domain diversity. Conversely, the fraction of intrinsic disorder in hubs decreased with increasing number of ordered domains. The difference in the levels of disorder was more prominent in hubs and non-hubs with fewer domains. Functional analysis showed that hubs were enriched in kinase and adaptor domains acting primarily in signal transduction and transcription regulation, whereas non-hubs had more DNA-binding domains and were involved in catalytic activity. Consistent with the differences in the functional nature of their domains, hubs with two or more domains were more likely to connect distinct functional modules in the interaction network when compared with single domain hubs. We conclude that the availability of greater number and diversity of ordered domains, in addition to the tendency to have promiscuous domains, differentiates hubs from non-hubs and provides an additional means of achieving interaction promiscuity. Further, hubs with fewer domains use greater levels of intrinsic disorder to facilitate interaction promiscuity with the prevalence of disorder decreasing with increasing number of ordered domains. PMID:20509167

  18. Prediction of Spontaneous Protein Deamidation from Sequence-Derived Secondary Structure and Intrinsic Disorder.

    Directory of Open Access Journals (Sweden)

    J Ramiro Lorenzo

    Full Text Available Asparagine residues in proteins undergo spontaneous deamidation, a post-translational modification that may act as a molecular clock for the regulation of protein function and turnover. Asparagine deamidation is modulated by protein local sequence, secondary structure and hydrogen bonding. We present NGOME, an algorithm able to predict non-enzymatic deamidation of internal asparagine residues in proteins in the absence of structural data, using sequence-based predictions of secondary structure and intrinsic disorder. Compared to previous algorithms, NGOME does not require three-dimensional structures yet yields better predictions than available sequence-only methods. Four case studies of specific proteins show how NGOME may help the user identify deamidation-prone asparagine residues, often related to protein gain of function, protein degradation or protein misfolding in pathological processes. A fifth case study applies NGOME at a proteomic scale and unveils a correlation between asparagine deamidation and protein degradation in yeast. NGOME is freely available as a webserver at the National EMBnet node Argentina, URL: http://www.embnet.qb.fcen.uba.ar/ in the subpage "Protein and nucleic acid structure and sequence analysis".

  19. Relation between Protein Intrinsic Normal Mode Weights and Pre-Existing Conformer Populations.

    Science.gov (United States)

    Ozgur, Beytullah; Ozdemir, E Sila; Gursoy, Attila; Keskin, Ozlem

    2017-04-20

    Intrinsic fluctuations of a protein enable it to sample a large repertoire of conformers including the open and closed forms. These distinct forms of the protein called conformational substates pre-exist together in equilibrium as an ensemble independent from its ligands. The role of ligand might be simply to alter the equilibrium toward the most appropriate form for binding. Normal mode analysis is proved to be useful in identifying the directions of conformational changes between substates. In this study, we demonstrate that the ratios of normalized weights of a few normal modes driving the protein between its substates can give insights about the ratios of kinetic conversion rates of the substates, although a direct relation between the eigenvalues and kinetic conversion rates or populations of each substate could not be observed. The correlation between the normalized mode weight ratios and the kinetic rate ratios is around 83% on a set of 11 non-enzyme proteins and around 59% on a set of 17 enzymes. The results are suggestive that mode motions carry intrinsic relations with thermodynamics and kinetics of the proteins.

  20. The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers

    Science.gov (United States)

    Hu, Yufeng; Chen, Zhenhang; Fu, Yanjun; He, Qingzhong; Jiang, Lun; Zheng, Jiangge; Gao, Yina; Mei, Pinchao; Chen, Zhongzhou; Ren, Xueqin

    2015-03-01

    Flexibility is an intrinsic property of proteins and essential for their biological functions. However, because of structural flexibility, obtaining high-quality crystals of proteins with heterogeneous conformations remain challenging. Here, we show a novel approach to immobilize traditional precipitants onto molecularly imprinted polymers (MIPs) to facilitate protein crystallization, especially for flexible proteins. By applying this method, high-quality crystals of the flexible N-terminus of human fragile X mental retardation protein are obtained, whose absence causes the most common inherited mental retardation. A novel KH domain and an intermolecular disulfide bond are discovered, and several types of dimers are found in solution, thus providing insights into the function of this protein. Furthermore, the precipitant-immobilized MIPs (piMIPs) successfully facilitate flexible protein crystal formation for five model proteins with increased diffraction resolution. This highlights the potential of piMIPs for the crystallization of flexible proteins.

  1. First Experimental Assessment of Protein Intrinsic Disorder Involvement in an RNA Virus Natural Adaptive Process.

    Science.gov (United States)

    Charon, Justine; Barra, Amandine; Walter, Jocelyne; Millot, Pauline; Hébrard, Eugénie; Moury, Benoît; Michon, Thierry

    2018-01-01

    Intrinsic disorder (ID) in proteins is defined as a lack of stable structure in physiological conditions. Intrinsically disordered regions (IDRs) are highly abundant in some RNA virus proteomes. Low topological constraints exerted on IDRs are expected to buffer the effect of numerous deleterious mutations and could be related to the remarkable adaptive potential of RNA viruses to overcome resistance of their host. To experimentally test this hypothesis in a natural pathosystem, a set of four variants of Potato virus Y (PVY; Potyvirus genus) containing various ID degrees in the Viral genome-linked (VPg) protein, a key determinant of potyvirus adaptation, was designed. To estimate the ID contribution to the VPg-based PVY adaptation, the adaptive ability of the four PVY variants was monitored in the pepper host (Capsicum annuum) carrying a recessive resistance gene. Intriguingly, the two mutants with the highest ID content displayed a significantly higher ability to restore infection in the resistant host, whereas the less intrinsically disordered mutant was unable to restore infection. The role of ID on virus adaptation may be due either to a larger exploration of evolutionary pathways or the minimization of fitness penalty caused by resistance-breaking mutations. This pioneering study strongly suggests the positive impact of ID in an RNA virus adaptive capacity. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Intrinsically Disordered Segments Affect Protein Half-Life in the Cell and during Evolution

    Directory of Open Access Journals (Sweden)

    Robin van der Lee

    2014-09-01

    Full Text Available Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast, mouse, and human proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives than proteins without these features. The lengths of the disordered segments that affect protein half-life are compatible with the structure of the proteasome. Divergence in terminal and internal disordered segments in yeast proteins originating from gene duplication leads to significantly altered half-life. Many paralogs that are affected by such changes participate in signaling, where altered protein half-life will directly impact cellular processes and function. Thus, natural variation in the length and position of disordered segments may affect protein half-life and could serve as an underappreciated source of genetic variation with important phenotypic consequences.

  3. Characterization of pore structure in cement-based materials using pressurization-depressurization cycling mercury intrusion porosimetry (PDC-MIP)

    International Nuclear Information System (INIS)

    Zhou Jian; Ye Guang; Breugel, Klaas van

    2010-01-01

    Numerous mercury intrusion porosimetry (MIP) studies have been carried out to investigate the pore structure in cement-based materials. However, the standard MIP often results in an underestimation of large pores and an overestimation of small pores because of its intrinsic limitation. In this paper, an innovative MIP method is developed in order to provide a more accurate estimation of pore size distribution. The new MIP measurements are conducted following a unique mercury intrusion procedure, in which the applied pressure is increased from the minimum to the maximum by repeating pressurization-depressurization cycles instead of a continuous pressurization followed by a continuous depressurization. Accordingly, this method is called pressurization-depressurization cycling MIP (PDC-MIP). By following the PDC-MIP testing sequence, the volumes of the throat pores and the corresponding ink-bottle pores can be determined at every pore size. These values are used to calculate pore size distribution by using the newly developed analysis method. This paper presents an application of PDC-MIP on the investigation of the pore size distribution in cement-based materials. The experimental results of PDC-MIP are compared with those measured by standard MIP. The PDC-MIP is further validated with the other experimental methods and numerical tool, including nitrogen sorption, backscanning electron (BSE) image analysis, Wood's metal intrusion porosimetry (WMIP) and the numerical simulation by the cement hydration model HYMOSTRUC3D.

  4. Investigation of proliferation and migration of tongue squamous cell carcinoma promoted by three chemokines, MIP-3α, MIP-1β, and IP-10

    Directory of Open Access Journals (Sweden)

    Chu H

    2017-08-01

    Full Text Available Hongxing Chu,1,* Bo Jia,1,* Xiaoling Qiu,2 Jie Pan,1 Xiang Sun,1 Zhiping Wang,1 Jianjiang Zhao1 1Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China; 2Department of Endodontology, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Abstract: The aim of this work was to investigate the role of chemokines in proliferation and migration of tongue squamous cell carcinoma (TSCC. Out of the 80 cytokines surveyed by a human cytokine antibody array, three chemokines, macrophage inflammatory protein-3α (MIP-3α, macrophage inflammatory protein-1β (MIP-1β, and interferon gamma-induced protein 10 (IP-10, showed elevated expression in TSCC cells (CAL-27 and UM-1, compared to the oral mucosal epithelial cells. Immunohistochemistry confirmed the high level of expression of MIP-3α in the TSCC tissues, especially in the high clinical stages. Furthermore, Western blot and immunofluorescence staining indicated that C-C chemokine receptor type 5, C-C chemokine receptor type 6, and C-X-C motif chemokine receptor 3, which are the receptors for MIP-3α, MIP-1β, and IP-10, respectively, were expressed in the TSCC cells. Viability assay showed MIP-3α, MIP-1β, and IP-10 led to the proliferation of the CAL-27 cells. Interestingly, MIP-1β and IP-10 also induced apoptosis in the TSCC cells. Transwell invasion assay showed MIP-3α and IP-10 could increase the invasive capability of TSCC cells; consistently, the enzymatic activities of matrix metalloproteinase-2 and matrix metalloproteinase-9 increased in the MIP-3α- and IP-10-treated cells. In summary, our results indicate the expression of MIP-3α, MIP-1β, and IP-10 increased in the TSCC cells. The elevated expression of MIP-3α and IP-10 promoted proliferation and migration of TSCC. These chemokines, along with their receptors, could be potential biomarkers and

  5. Primary structure and solution conditions determine conformational ensemble properties of intrinsically disordered proteins

    Science.gov (United States)

    Mao, Hsuan-Han Alberto

    Intrinsically disordered proteins (IDPs) are a class of proteins that do not exhibit well-defined three-dimensional structures. The absence of structure is intrinsic to their amino acid sequences, which are characterized by low hydrophobicity and high net charge per residue compared to folded proteins. Contradicting the classic structure-function paradigm, IDPs are capable of interacting with high specificity and affinity, often acquiring order in complex with protein and nucleic acid binding partners. This phenomenon is evident during cellular activities involving IDPs, which include transcriptional and translational regulation, cell cycle control, signal transduction, molecular assembly, and molecular recognition. Although approximately 30% of eukaryotic proteomes are intrinsically disordered, the nature of IDP conformational ensembles remains unclear. In this dissertation, we describe relationships connecting characteristics of IDP conformational ensembles to their primary structures and solution conditions. Using molecular simulations and fluorescence experiments on a set of base-rich IDPs, we find that net charge per residue segregates conformational ensembles along a globule-to-coil transition. Speculatively generalizing this result, we propose a phase diagram that predicts an IDP's average size and shape based on sequence composition and use it to generate hypotheses for a broad set of intrinsically disordered regions (IDRs). Simulations reveal that acid-rich IDRs, unlike their oppositely charged base-rich counterparts, exhibit disordered globular ensembles despite intra-chain repulsive electrostatic interactions. This apparent asymmetry is sensitive to simulation parameters for representing alkali and halide salt ions, suggesting that solution conditions modulate IDP conformational ensembles. We refine the ion parameters using a calibration procedure that relies exclusively on crystal lattice properties. Simulations with these parameters recover swollen

  6. Unified understanding of folding and binding mechanisms of globular and intrinsically disordered proteins.

    Science.gov (United States)

    Arai, Munehito

    2018-01-06

    Extensive experimental and theoretical studies have advanced our understanding of the mechanisms of folding and binding of globular proteins, and coupled folding and binding of intrinsically disordered proteins (IDPs). The forces responsible for conformational changes and binding are common in both proteins; however, these mechanisms have been separately discussed. Here, we attempt to integrate the mechanisms of coupled folding and binding of IDPs, folding of small and multi-subdomain proteins, folding of multimeric proteins, and ligand binding of globular proteins in terms of conformational selection and induced-fit mechanisms as well as the nucleation-condensation mechanism that is intermediate between them. Accumulating evidence has shown that both the rate of conformational change and apparent rate of binding between interacting elements can determine reaction mechanisms. Coupled folding and binding of IDPs occurs mainly by induced-fit because of the slow folding in the free form, while ligand binding of globular proteins occurs mainly by conformational selection because of rapid conformational change. Protein folding can be regarded as the binding of intramolecular segments accompanied by secondary structure formation. Multi-subdomain proteins fold mainly by the induced-fit (hydrophobic collapse) mechanism, as the connection of interacting segments enhances the binding (compaction) rate. Fewer hydrophobic residues in small proteins reduce the intramolecular binding rate, resulting in the nucleation-condensation mechanism. Thus, the folding and binding of globular proteins and IDPs obey the same general principle, suggesting that the coarse-grained, statistical mechanical model of protein folding is promising for a unified theoretical description of all mechanisms.

  7. Novel methods based on 13C detection to study intrinsically disordered proteins

    Science.gov (United States)

    Felli, Isabella C.; Pierattelli, Roberta

    2014-04-01

    Intrinsically disordered proteins (IDPs) are characterized by highly flexible solvent exposed backbones and can sample many different conformations. These properties confer them functional advantages, complementary to those of folded proteins, which need to be characterized to expand our view of how protein structural and dynamic features affect function beyond the static picture of a single well defined 3D structure that has influenced so much our way of thinking. NMR spectroscopy provides a unique tool for the atomic resolution characterization of highly flexible macromolecules in general and of IDPs in particular. The peculiar properties of IDPs however have profound effects on spectroscopic parameters. It is thus worth thinking about these aspects to make the best use of the great potential of NMR spectroscopy to contribute to this fascinating field of research. In particular, after many years of dealing with exclusively heteronuclear NMR experiments based on 13C direct detection, we would like here to address their relevance when studying IDPs.

  8. Sensing of heavy metal ions by intrinsic TMV coat protein fluorescence

    Science.gov (United States)

    Bayram, Serene S.; Green, Philippe; Blum, Amy Szuchmacher

    2018-04-01

    We propose the use of a cysteine mutant of TMV coat protein as a signal transducer for the selective sensing and quantification of the heavy metal ions, Cd2+, Pb2+, Zn2+ and Ni2+ based on intrinsic tryptophan quenching. TMV coat protein is inexpensive, can be mass-produced since it is expressed and extracted from E-coli. It also displays several different functional groups, enabling a wide repertoire of bioconjugation chemistries; thus it can be easily integrated into functional devices. In addition, TMV-ion interactions have been widely reported and utilized for metallization to generate organic-inorganic hybrid composite novel materials. Building on these previous observations, we herein determine, for the first time, the TMV-ion binding constants assuming the static fluorescence quenching model. We also show that by comparing TMV-ion interactions between native and denatured coat protein, we can distinguish between chemically similar heavy metal ions such as cadmium and zinc ions.

  9. Random coil chemical shift for intrinsically disordered proteins: effects of temperature and pH

    International Nuclear Information System (INIS)

    Kjaergaard, Magnus; Brander, Søren; Poulsen, Flemming M.

    2011-01-01

    Secondary chemical shift analysis is the main NMR method for detection of transiently formed secondary structure in intrinsically disordered proteins. The quality of the secondary chemical shifts is dependent on an appropriate choice of random coil chemical shifts. We report random coil chemical shifts and sequence correction factors determined for a GGXGG peptide series following the approach of Schwarzinger et al. (J Am Chem Soc 123(13):2970–2978, 2001). The chemical shifts are determined at neutral pH in order to match the conditions of most studies of intrinsically disordered proteins. Temperature has a non-negligible effect on the 13 C random coil chemical shifts, so temperature coefficients are reported for the random coil chemical shifts to allow extrapolation to other temperatures. The pH dependence of the histidine random coil chemical shifts is investigated in a titration series, which allows the accurate random coil chemical shifts to be obtained at any pH. By correcting the random coil chemical shifts for the effects of temperature and pH, systematic biases of the secondary chemical shifts are minimized, which will improve the reliability of detection of transient secondary structure in disordered proteins.

  10. Decoding the intrinsic mechanism that prohibits ALIX interaction with ESCRT and viral proteins.

    Science.gov (United States)

    Zhou, Xi; Si, Jiali; Corvera, Joe; Gallick, Gary E; Kuang, Jian

    2010-12-15

    The adaptor protein ALIX [ALG-2 (apoptosis-linked-gene-2 product)-interacting protein X] links retroviruses to ESCRT (endosomal sorting complex required for transport) machinery during retroviral budding. This function of ALIX requires its interaction with the ESCRT-III component CHMP4 (charged multivesicular body protein 4) at the N-terminal Bro1 domain and retroviral Gag proteins at the middle V domain. Since cytoplasmic or recombinant ALIX is unable to interact with CHMP4 or retroviral Gag proteins under non-denaturing conditions, we constructed ALIX truncations and mutations to define the intrinsic mechanism through which ALIX interactions with these partner proteins are prohibited. Our results demonstrate that an intramolecular interaction between Patch 2 in the Bro1 domain and the TSG101 (tumour susceptibility gene 101 protein)-docking site in the proline-rich domain locks ALIX into a closed conformation that renders ALIX unable to interact with CHMP4 and retroviral Gag proteins. Relieving the intramolecular interaction of ALIX, by ectopically expressing a binding partner for one of the intramolecular interaction sites or by deleting one of these sites, promotes ALIX interaction with these partner proteins and facilitates ALIX association with the membrane. Ectopic expression of a GFP (green fluorescent protein)-ALIX mutant with a constitutively open conformation, but not the wild-type protein, increases EIAV (equine infectious anaemia virus) budding from HEK (human embryonic kidney)-293 cells. These findings predict that relieving the autoinhibitory intramolecular interaction of ALIX is a critical step for ALIX to participate in retroviral budding.

  11. Triple resonance 15N NMR relaxation experiments for studies of intrinsically disordered proteins

    Czech Academy of Sciences Publication Activity Database

    Srb, Pavel; Nováček, J.; Kadeřávek, P.; Rabatinová, Alžběta; Krásný, Libor; Žídková, Jitka; Bobálová, Janette; Sklenář, V.; Žídek, L.

    2017-01-01

    Roč. 69, č. 3 (2017), s. 133-146 ISSN 0925-2738 R&D Projects: GA ČR GA13-16842S; GA MŠk(CZ) LO1304 Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:68081715 Keywords : nuclear magnetic resonance * relaxation * non-uniform sampling * intrinsically disordered proteins Subject RIV: CB - Analytical Chemistry, Separation; EE - Microbiology, Virology (MBU-M); CB - Analytical Chemistry, Separation (UIACH-O) OBOR OECD: Analytical chemistry; Microbiology (MBU-M); Analytical chemistry (UIACH-O) Impact factor: 2.410, year: 2016

  12. Protein intrinsic disorder in Arabidopsis NAC transcription factors

    DEFF Research Database (Denmark)

    O'Shea, Charlotte; Jensen, Mikael Kryger; Stender, Emil G.P.

    2015-01-01

    because of its simple MoRF pattern and its ability to interact with RCD1 (radical-induced cell death 1). Experiments in yeast and thermodynamic characterization suggest that its single MoRF region is sufficient for both transcriptional activation and interaction with RCD1. The remainder of the large......Protein ID (intrinsic disorder) plays a significant, yet relatively unexplored role in transcription factors (TFs). In the present paper, analysis of the transcription regulatory domains (TRDs) of six phylogenetically representative, plant-specific NAC [no apical meristem, ATAF (Arabidopsis...

  13. Insights into the Immunological Properties of Intrinsically Disordered Malaria Proteins Using Proteome Scale Predictions.

    Directory of Open Access Journals (Sweden)

    Andrew J Guy

    Full Text Available Malaria remains a significant global health burden. The development of an effective malaria vaccine remains as a major challenge with the potential to significantly reduce morbidity and mortality. While Plasmodium spp. have been shown to contain a large number of intrinsically disordered proteins (IDPs or disordered protein regions, the relationship of protein structure to subcellular localisation and adaptive immune responses remains unclear. In this study, we employed several computational prediction algorithms to identify IDPs at the proteome level of six Plasmodium spp. and to investigate the potential impact of protein disorder on adaptive immunity against P. falciparum parasites. IDPs were shown to be particularly enriched within nuclear proteins, apical proteins, exported proteins and proteins localised to the parasitophorous vacuole. Furthermore, several leading vaccine candidates, and proteins with known roles in host-cell invasion, have extensive regions of disorder. Presentation of peptides by MHC molecules plays an important role in adaptive immune responses, and we show that IDP regions are predicted to contain relatively few MHC class I and II binding peptides owing to inherent differences in amino acid composition compared to structured domains. In contrast, linear B-cell epitopes were predicted to be enriched in IDPs. Tandem repeat regions and non-synonymous single nucleotide polymorphisms were found to be strongly associated with regions of disorder. In summary, immune responses against IDPs appear to have characteristics distinct from those against structured protein domains, with increased antibody recognition of linear epitopes but some constraints for MHC presentation and issues of polymorphisms. These findings have major implications for vaccine design, and understanding immunity to malaria.

  14. Large-scale analysis of intrinsic disorder flavors and associated functions in the protein sequence universe.

    Science.gov (United States)

    Necci, Marco; Piovesan, Damiano; Tosatto, Silvio C E

    2016-12-01

    Intrinsic disorder (ID) in proteins has been extensively described for the last decade; a large-scale classification of ID in proteins is mostly missing. Here, we provide an extensive analysis of ID in the protein universe on the UniProt database derived from sequence-based predictions in MobiDB. Almost half the sequences contain an ID region of at least five residues. About 9% of proteins have a long ID region of over 20 residues which are more abundant in Eukaryotic organisms and most frequently cover less than 20% of the sequence. A small subset of about 67,000 (out of over 80 million) proteins is fully disordered and mostly found in Viruses. Most proteins have only one ID, with short ID evenly distributed along the sequence and long ID overrepresented in the center. The charged residue composition of Das and Pappu was used to classify ID proteins by structural propensities and corresponding functional enrichment. Swollen Coils seem to be used mainly as structural components and in biosynthesis in both Prokaryotes and Eukaryotes. In Bacteria, they are confined in the nucleoid and in Viruses provide DNA binding function. Coils & Hairpins seem to be specialized in ribosome binding and methylation activities. Globules & Tadpoles bind antigens in Eukaryotes but are involved in killing other organisms and cytolysis in Bacteria. The Undefined class is used by Bacteria to bind toxic substances and mediate transport and movement between and within organisms in Viruses. Fully disordered proteins behave similarly, but are enriched for glycine residues and extracellular structures. © 2016 The Protein Society.

  15. Fast hydrogen exchange affects 15N relaxation measurements in intrinsically disordered proteins

    International Nuclear Information System (INIS)

    Kim, Seho; Wu, Kuen-Phon; Baum, Jean

    2013-01-01

    Unprotected amide protons can undergo fast hydrogen exchange (HX) with protons from the solvent. Generally, NMR experiments using the out-and-back coherence transfer with amide proton detection are affected by fast HX and result in reduced signal intensity. When one of these experiments, 1 H– 15 N HSQC, is used to measure the 15 N transverse relaxation rate (R 2 ), the measured R 2 rate is convoluted with the HX rate (k HX ) and has higher apparent R 2 values. Since the 15 N R 2 measurement is important for analyzing protein backbone dynamics, the HX effect on the R 2 measurement is investigated and described here by multi-exponential signal decay. We demonstrate these effects by performing 15 N R 2 CPMG experiments on α-synuclein, an intrinsically disordered protein, in which the amide protons are exposed to solvent. We show that the HX effect on R 2 CPMG can be extracted by the derived equation. In conclusion, the HX effect may be pulse sequence specific and results from various sources including the J coupling evolution, the change of steady state water proton magnetization, and the D 2 O content in the sample. To avoid the HX effect on the analysis of relaxation data of unprotected amides, it is suggested that NMR experimental conditions insensitive to the HX should be considered or that intrinsic R 2 CPMG values be obtained by methods described herein.

  16. Conformational disorder in folded and intrinsically disordered proteins from nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Salmon, Loic

    2010-01-01

    Biological macromolecules are, by essence, dynamical systems. While the importance of this flexibility is nowadays well established, the accurate characterization of the conformational disorder of these systems remains an important challenge. Nuclear magnetic resonance spectroscopy is a unique tool to probe these motions at atomic level, through the analysis of spin relaxation or residual dipolar couplings. The latter allows all motions occurring at timescales faster than the millisecond to be investigated, including physiologically important timescales. The information presents in those couplings is interpreted here using mainly analytical approaches in order to quantify the amounts of dynamics present in folded protein, to determine the direction of those motions and to obtain structural information within this conformational disorder. These analytical approaches are complemented by numerical methods, that allowed the observation of phenomena from a different point of view or the investigation of other systems such as intrinsically disordered proteins. All of these studies demonstrate an important complementarity between structural order and conformational disorder. (author)

  17. An Overview of Predictors for Intrinsically Disordered Proteins over 2010–2014

    Directory of Open Access Journals (Sweden)

    Jianzong Li

    2015-09-01

    Full Text Available The sequence-structure-function paradigm of proteins has been changed by the occurrence of intrinsically disordered proteins (IDPs. Benefiting from the structural disorder, IDPs are of particular importance in biological processes like regulation and signaling. IDPs are associated with human diseases, including cancer, cardiovascular disease, neurodegenerative diseases, amyloidoses, and several other maladies. IDPs attract a high level of interest and a substantial effort has been made to develop experimental and computational methods. So far, more than 70 prediction tools have been developed since 1997, within which 17 predictors were created in the last five years. Here, we presented an overview of IDPs predictors developed during 2010–2014. We analyzed the algorithms used for IDPs prediction by these tools and we also discussed the basic concept of various prediction methods for IDPs. The comparison of prediction performance among these tools is discussed as well.

  18. Discovery of Cryoprotective Activity in Human Genome-Derived Intrinsically Disordered Proteins

    Directory of Open Access Journals (Sweden)

    Naoki Matsuo

    2018-01-01

    Full Text Available Intrinsically disordered proteins (IDPs are an emerging phenomenon. They may have a high degree of flexibility in their polypeptide chains, which lack a stable 3D structure. Although several biological functions of IDPs have been proposed, their general function is not known. The only finding related to their function is the genetically conserved YSK2 motif present in plant dehydrins. These proteins were shown to be IDPs with the YSK2 motif serving as a core region for the dehydrins’ cryoprotective activity. Here we examined the cryoprotective activity of randomly selected IDPs toward the model enzyme lactate dehydrogenase (LDH. All five IDPs that were examined were in the range of 35–45 amino acid residues in length and were equally potent at a concentration of 50 μg/mL, whereas folded proteins, the PSD-95/Dlg/ZO-1 (PDZ domain, and lysozymes had no potency. We further examined their cryoprotective activity toward glutathione S-transferase as an example of the other enzyme, and toward enhanced green fluorescent protein as a non-enzyme protein example. We further examined the lyophilization protective activity of the peptides toward LDH, which revealed that some IDPs showed a higher activity than that of bovine serum albumin (BSA. Based on these observations, we propose that cryoprotection is a general feature of IDPs. Our findings may become a clue to various industrial applications of IDPs in the future.

  19. On the importance of polar interactions for complexes containing intrinsically disordered proteins.

    Directory of Open Access Journals (Sweden)

    Eric T C Wong

    Full Text Available There is a growing recognition for the importance of proteins with large intrinsically disordered (ID segments in cell signaling and regulation. ID segments in these proteins often harbor regions that mediate molecular recognition. Coupled folding and binding of the recognition regions has been proposed to confer high specificity to interactions involving ID segments. However, researchers recently questioned the origin of the interaction specificity of ID proteins because of the overrepresentation of hydrophobic residues in their interaction interfaces. Here, we focused on the role of polar and charged residues in interactions mediated by ID segments. Making use of the extended nature of most ID segments when in complex with globular proteins, we first identified large numbers of complexes between globular proteins and ID segments by using radius-of-gyration-based selection criteria. Consistent with previous studies, we found the interfaces of these complexes to be enriched in hydrophobic residues, and that these residues contribute significantly to the stability of the interaction interface. However, our analyses also show that polar interactions play a larger role in these complexes than in structured protein complexes. Computational alanine scanning and salt-bridge analysis indicate that interfaces in ID complexes are highly complementary with respect to electrostatics, more so than interfaces of globular proteins. Follow-up calculations of the electrostatic contributions to the free energy of binding uncovered significantly stronger Coulombic interactions in complexes harbouring ID segments than in structured protein complexes. However, they are counter-balanced by even higher polar-desolvation penalties. We propose that polar interactions are a key contributing factor to the observed high specificity of ID segment-mediated interactions.

  20. Highly selective BSA imprinted polyacrylamide hydrogels facilitated by a metal-coding MIP approach.

    Science.gov (United States)

    El-Sharif, H F; Yapati, H; Kalluru, S; Reddy, S M

    2015-12-01

    We report the fabrication of metal-coded molecularly imprinted polymers (MIPs) using hydrogel-based protein imprinting techniques. A Co(II) complex was prepared using (E)-2-((2 hydrazide-(4-vinylbenzyl)hydrazono)methyl)phenol; along with iron(III) chloroprotoporphyrin (Hemin), vinylferrocene (VFc), zinc(II) protoporphyrin (ZnPP) and protoporphyrin (PP), these complexes were introduced into the MIPs as co-monomers for metal-coding of non-metalloprotein imprints. Results indicate a 66% enhancement for bovine serum albumin (BSA) protein binding capacities (Q, mg/g) via metal-ion/ligand exchange properties within the metal-coded MIPs. Specifically, Co(II)-complex-based MIPs exhibited 92 ± 1% specific binding with Q values of 5.7 ± 0.45 mg BSA/g polymer and imprinting factors (IF) of 14.8 ± 1.9 (MIP/non-imprinted (NIP) control). The selectivity of our Co(II)-coded BSA MIPs were also tested using bovine haemoglobin (BHb), lysozyme (Lyz), and trypsin (Tryp). By evaluating imprinting factors (K), each of the latter proteins was found to have lower affinities in comparison to cognate BSA template. The hydrogels were further characterised by thermal analysis and differential scanning calorimetry (DSC) to assess optimum polymer composition. The development of hydrogel-based molecularly imprinted polymer (HydroMIPs) technology for the memory imprinting of proteins and for protein biosensor development presents many possibilities, including uses in bio-sample clean-up or selective extraction, replacement of biological antibodies in immunoassays and biosensors for medicine and the environment. Biosensors for proteins and viruses are currently expensive to develop because they require the use of expensive antibodies. Because of their biomimicry capabilities (and their potential to act as synthetic antibodies), HydroMIPs potentially offer a route to the development of new low-cost biosensors. Herein, a metal ion-mediated imprinting approach was employed to metal-code our

  1. p15PAF is an intrinsically disordered protein with nonrandom structural preferences at sites of interaction with other proteins.

    Science.gov (United States)

    De Biasio, Alfredo; Ibáñez de Opakua, Alain; Cordeiro, Tiago N; Villate, Maider; Merino, Nekane; Sibille, Nathalie; Lelli, Moreno; Diercks, Tammo; Bernadó, Pau; Blanco, Francisco J

    2014-02-18

    We present to our knowledge the first structural characterization of the proliferating-cell-nuclear-antigen-associated factor p15(PAF), showing that it is monomeric and intrinsically disordered in solution but has nonrandom conformational preferences at sites of protein-protein interactions. p15(PAF) is a 12 kDa nuclear protein that acts as a regulator of DNA repair during DNA replication. The p15(PAF) gene is overexpressed in several types of human cancer. The nearly complete NMR backbone assignment of p15(PAF) allowed us to measure 86 N-H(N) residual dipolar couplings. Our residual dipolar coupling analysis reveals nonrandom conformational preferences in distinct regions, including the proliferating-cell-nuclear-antigen-interacting protein motif (PIP-box) and the KEN-box (recognized by the ubiquitin ligase that targets p15(PAF) for degradation). In accordance with these findings, analysis of the (15)N R2 relaxation rates shows a relatively reduced mobility for the residues in these regions. The agreement between the experimental small angle x-ray scattering curve of p15(PAF) and that computed from a statistical coil ensemble corrected for the presence of local secondary structural elements further validates our structural model for p15(PAF). The coincidence of these transiently structured regions with protein-protein interaction and posttranslational modification sites suggests a possible role for these structures as molecular recognition elements for p15(PAF). Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. Effects of molecular crowding on the dynamics of intrinsically disordered proteins.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Inside cells, the concentration of macromolecules can reach up to 400 g/L. In such crowded environments, proteins are expected to behave differently than in vitro. It has been shown that the stability and the folding rate of a globular protein can be altered by the excluded volume effect produced by a high density of macromolecules. However, macromolecular crowding effects on intrinsically disordered proteins (IDPs are less explored. These proteins can be extremely dynamic and potentially sample a wide ensemble of conformations under non-denaturing conditions. The dynamic properties of IDPs are intimately related to the timescale of conformational exchange within the ensemble, which govern target recognition and how these proteins function. In this work, we investigated the macromolecular crowding effects on the dynamics of several IDPs by measuring the NMR spin relaxation parameters of three disordered proteins (ProTα, TC1, and α-synuclein with different extents of residual structures. To aid the interpretation of experimental results, we also performed an MD simulation of ProTα. Based on the MD analysis, a simple model to correlate the observed changes in relaxation rates to the alteration in protein motions under crowding conditions was proposed. Our results show that 1 IDPs remain at least partially disordered despite the presence of high concentration of other macromolecules, 2 the crowded environment has differential effects on the conformational propensity of distinct regions of an IDP, which may lead to selective stabilization of certain target-binding motifs, and 3 the segmental motions of IDPs on the nanosecond timescale are retained under crowded conditions. These findings strongly suggest that IDPs function as dynamic structural ensembles in cellular environments.

  3. Genome-scale prediction of proteins with long intrinsically disordered regions.

    Science.gov (United States)

    Peng, Zhenling; Mizianty, Marcin J; Kurgan, Lukasz

    2014-01-01

    Proteins with long disordered regions (LDRs), defined as having 30 or more consecutive disordered residues, are abundant in eukaryotes, and these regions are recognized as a distinct class of biologically functional domains. LDRs facilitate various cellular functions and are important for target selection in structural genomics. Motivated by the lack of methods that directly predict proteins with LDRs, we designed Super-fast predictor of proteins with Long Intrinsically DisordERed regions (SLIDER). SLIDER utilizes logistic regression that takes an empirically chosen set of numerical features, which consider selected physicochemical properties of amino acids, sequence complexity, and amino acid composition, as its inputs. Empirical tests show that SLIDER offers competitive predictive performance combined with low computational cost. It outperforms, by at least a modest margin, a comprehensive set of modern disorder predictors (that can indirectly predict LDRs) and is 16 times faster compared to the best currently available disorder predictor. Utilizing our time-efficient predictor, we characterized abundance and functional roles of proteins with LDRs over 110 eukaryotic proteomes. Similar to related studies, we found that eukaryotes have many (on average 30.3%) proteins with LDRs with majority of proteomes having between 25 and 40%, where higher abundance is characteristic to proteomes that have larger proteins. Our first-of-its-kind large-scale functional analysis shows that these proteins are enriched in a number of cellular functions and processes including certain binding events, regulation of catalytic activities, cellular component organization, biogenesis, biological regulation, and some metabolic and developmental processes. A webserver that implements SLIDER is available at http://biomine.ece.ualberta.ca/SLIDER/. Copyright © 2013 Wiley Periodicals, Inc.

  4. Intrinsic Tryptophan Fluorescence in the Detection and Analysis of Proteins: A Focus on Förster Resonance Energy Transfer Techniques

    Directory of Open Access Journals (Sweden)

    Amar B. T. Ghisaidoobe

    2014-12-01

    Full Text Available F resonance energy transfer (FRET occurs when the distance between a donor fluorophore and an acceptor is within 10 nm, and its application often necessitates fluorescent labeling of biological targets. However, covalent modification of biomolecules can inadvertently give rise to conformational and/or functional changes. This review describes the application of intrinsic protein fluorescence, predominantly derived from tryptophan (\\(\\uplambda_{\\textsc{ex}}\\sim\\ nm, \\(\\uplambda_{\\textsc{em}}\\sim\\ 350 nm, in protein-related research and mainly focuses on label-free FRET techniques. In terms of wavelength and intensity, tryptophan fluorescence is strongly influenced by its (or the proteinlocal environment, which, in addition to fluorescence quenching, has been applied to study protein conformational changes. Intrinsic F resonance energy transfer (iFRET, a recently developed technique, utilizes the intrinsic fluorescence of tryptophan in conjunction with target-specific fluorescent probes as FRET donors and acceptors, respectively, for real time detection of native proteins.

  5. Programming molecular self-assembly of intrinsically disordered proteins containing sequences of low complexity

    Science.gov (United States)

    Simon, Joseph R.; Carroll, Nick J.; Rubinstein, Michael; Chilkoti, Ashutosh; López, Gabriel P.

    2017-06-01

    Dynamic protein-rich intracellular structures that contain phase-separated intrinsically disordered proteins (IDPs) composed of sequences of low complexity (SLC) have been shown to serve a variety of important cellular functions, which include signalling, compartmentalization and stabilization. However, our understanding of these structures and our ability to synthesize models of them have been limited. We present design rules for IDPs possessing SLCs that phase separate into diverse assemblies within droplet microenvironments. Using theoretical analyses, we interpret the phase behaviour of archetypal IDP sequences and demonstrate the rational design of a vast library of multicomponent protein-rich structures that ranges from uniform nano-, meso- and microscale puncta (distinct protein droplets) to multilayered orthogonally phase-separated granular structures. The ability to predict and program IDP-rich assemblies in this fashion offers new insights into (1) genetic-to-molecular-to-macroscale relationships that encode hierarchical IDP assemblies, (2) design rules of such assemblies in cell biology and (3) molecular-level engineering of self-assembled recombinant IDP-rich materials.

  6. Metalloido-porins: Essentiality of Nodulin 26-like intrinsic proteins in metalloid transport.

    Science.gov (United States)

    Pommerrenig, Benjamin; Diehn, Till Arvid; Bienert, Gerd Patrick

    2015-09-01

    Metalloids are a group of physiologically important elements ranging from the essential to the highly toxic. Arsenic, antimony, germanium, and tellurium are highly toxic to plants themselves and to consumers of metalloid-contaminated plants. Boron, silicon, and selenium fulfill essential or beneficial functions in plants. However, when present at high concentrations, boron and selenium cause toxicity symptoms that are detrimental to plant fitness and yield. Consequently, all plants require efficient membrane transport systems to control the uptake and extrusion of metalloids into or out of the plant and their distribution within the plant body. Several Nodulin 26-like intrinsic proteins (NIPs) that belong to the aquaporin plant water channel protein family facilitate the diffusion of uncharged metalloid species. Genetic, physiological, and molecular evidence is that NIPs from primitive to higher plants not only transport all environmentally important metalloids, but that these proteins have a major role in the uptake, translocation, and extrusion of metalloids in plants. As most of the metalloid-permeable NIP aquaporins are impermeable or are poorly permeable to water, these NIP channel proteins should be considered as physiologically essential metalloido-porins. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  7. A Method for Systematic Assessment of Intrinsically Disordered Protein Regions by NMR

    Directory of Open Access Journals (Sweden)

    Natsuko Goda

    2015-07-01

    Full Text Available Intrinsically disordered proteins (IDPs that lack stable conformations and are highly flexible have attracted the attention of biologists. Therefore, the development of a systematic method to identify polypeptide regions that are unstructured in solution is important. We have designed an “indirect/reflected” detection system for evaluating the physicochemical properties of IDPs using nuclear magnetic resonance (NMR. This approach employs a “chimeric membrane protein”-based method using the thermostable membrane protein PH0471. This protein contains two domains, a transmembrane helical region and a C-terminal OB (oligonucleotide/oligosaccharide binding-fold domain (named NfeDC domain, connected by a flexible linker. NMR signals of the OB-fold domain of detergent-solubilized PH0471 are observed because of the flexibility of the linker region. In this study, the linker region was substituted with target IDPs. Fifty-three candidates were selected using the prediction tool POODLE and 35 expression vectors were constructed. Subsequently, we obtained 15N-labeled chimeric PH0471 proteins with 25 IDPs as linkers. The NMR spectra allowed us to classify IDPs into three categories: flexible, moderately flexible, and inflexible. The inflexible IDPs contain membrane-associating or aggregation-prone sequences. This is the first attempt to use an indirect/reflected NMR method to evaluate IDPs and can verify the predictions derived from our computational tools.

  8. The Drosophila LIN54 homolog Mip120 controls two aspects of oogenesis

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    Mei-Hsin Cheng

    2017-07-01

    Full Text Available The conserved multi-protein MuvB core associates with the Myb oncoproteins and with the RB-E2F-DP tumor suppressor proteins in complexes that regulate cell proliferation, differentiation, and apoptosis. Drosophila Mip120, a homolog of LIN54, is a sequence-specific DNA-binding protein within the MuvB core. A mutant of Drosophila mip120 was previously shown to cause female and male sterility. We now show that Mip120 regulates two different aspects of oogenesis. First, in the absence of the Mip120 protein, egg chambers arrest during the transition from stage 7 to 8 with a failure of the normal program of chromosomal dynamics in the ovarian nurse cells. Specifically, the decondensation, disassembly and dispersion of the endoreplicated polytene chromosomes fail to occur without Mip120. The conserved carboxy-terminal DNA-binding and protein-protein interaction domains of Mip120 are necessary but not sufficient for this process. Second, we show that a lack of Mip120 causes a dramatic increase in the expression of benign gonial cell neoplasm (bgcn, a gene that is normally expressed in only a small number of cells within the ovary including the germline stem cells.

  9. Actin capping protein and its inhibitor CARMIL: how intrinsically disordered regions function

    International Nuclear Information System (INIS)

    Takeda, Shuichi; Maéda, Yuichiro; Koike, Ryotaro; Ota, Motonori; Nitanai, Yasushi; Minakata, Shiho

    2011-01-01

    The actin capping protein (CP) tightly binds to the barbed end of actin filaments to block further elongation. The β-tentacle in CP is an important region that ensures stable interaction with actin filaments. CARMIL inhibits the interaction of CP with actin filaments via the C-terminal portion containing the CP-binding motif, located in an intrinsically disordered region. We have proposed an allosteric inhibition model in which CARMIL suppresses CP by the population shift mechanism. Here, we solved a crystal structure of CP in complex with a CARMIL-derived peptide, CA32. The new structure clearly represents the α-helical form of the β-tentacle that was invisible in other CP/CARMIL peptide complex structures. In addition, we exhaustively performed a normal mode analysis with the elastic network model on all available crystal structures of the CP/CARMIL peptide complexes, including the new structure. We concluded that the CP-binding motif is necessary and sufficient for altering the fluctuation of CP, which is essential for attenuating the barbed-end-capping activity along the population shift mechanism. The roles and functions of the β-tentacle and the CP-binding motif are discussed in terms of their intrinsically disordered nature

  10. Actin capping protein and its inhibitor CARMIL: how intrinsically disordered regions function

    Science.gov (United States)

    Takeda, Shuichi; Koike, Ryotaro; Nitanai, Yasushi; Minakata, Shiho; Maéda, Yuichiro; Ota, Motonori

    2011-06-01

    The actin capping protein (CP) tightly binds to the barbed end of actin filaments to block further elongation. The β-tentacle in CP is an important region that ensures stable interaction with actin filaments. CARMIL inhibits the interaction of CP with actin filaments via the C-terminal portion containing the CP-binding motif, located in an intrinsically disordered region. We have proposed an allosteric inhibition model in which CARMIL suppresses CP by the population shift mechanism. Here, we solved a crystal structure of CP in complex with a CARMIL-derived peptide, CA32. The new structure clearly represents the α-helical form of the β-tentacle that was invisible in other CP/CARMIL peptide complex structures. In addition, we exhaustively performed a normal mode analysis with the elastic network model on all available crystal structures of the CP/CARMIL peptide complexes, including the new structure. We concluded that the CP-binding motif is necessary and sufficient for altering the fluctuation of CP, which is essential for attenuating the barbed-end-capping activity along the population shift mechanism. The roles and functions of the β-tentacle and the CP-binding motif are discussed in terms of their intrinsically disordered nature.

  11. Microsecond molecular dynamics simulations of intrinsically disordered proteins involved in the oxidative stress response.

    Directory of Open Access Journals (Sweden)

    Elio A Cino

    Full Text Available Intrinsically disordered proteins (IDPs are abundant in cells and have central roles in protein-protein interaction networks. Interactions between the IDP Prothymosin alpha (ProTα and the Neh2 domain of Nuclear factor erythroid 2-related factor 2 (Nrf2, with a common binding partner, Kelch-like ECH-associated protein 1(Keap1, are essential for regulating cellular response to oxidative stress. Misregulation of this pathway can lead to neurodegenerative diseases, premature aging and cancer. In order to understand the mechanisms these two disordered proteins employ to bind to Keap1, we performed extensive 0.5-1.0 microsecond atomistic molecular dynamics (MD simulations and isothermal titration calorimetry experiments to investigate the structure/dynamics of free-state ProTα and Neh2 and their thermodynamics of bindings. The results show that in their free states, both ProTα and Neh2 have propensities to form bound-state-like β-turn structures but to different extents. We also found that, for both proteins, residues outside the Keap1-binding motifs may play important roles in stabilizing the bound-state-like structures. Based on our findings, we propose that the binding of disordered ProTα and Neh2 to Keap1 occurs synergistically via preformed structural elements (PSEs and coupled folding and binding, with a heavy bias towards PSEs, particularly for Neh2. Our results provide insights into the molecular mechanisms Neh2 and ProTα bind to Keap1, information that is useful for developing therapeutics to enhance the oxidative stress response.

  12. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    Directory of Open Access Journals (Sweden)

    Wouter Boomsma

    2016-02-01

    Full Text Available The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work

  13. Sensing of heavy metal ions by intrinsic TMV coat protein fluorescence.

    Science.gov (United States)

    Bayram, Serene S; Green, Philippe; Blum, Amy Szuchmacher

    2018-04-15

    We propose the use of a cysteine mutant of TMV coat protein as a signal transducer for the selective sensing and quantification of the heavy metal ions, Cd 2+ , Pb 2+ , Zn 2+ and Ni 2+ based on intrinsic tryptophan quenching. TMV coat protein is inexpensive, can be mass-produced since it is expressed and extracted from E-coli. It also displays several different functional groups, enabling a wide repertoire of bioconjugation chemistries; thus it can be easily integrated into functional devices. In addition, TMV-ion interactions have been widely reported and utilized for metallization to generate organic-inorganic hybrid composite novel materials. Building on these previous observations, we herein determine, for the first time, the TMV-ion binding constants assuming the static fluorescence quenching model. We also show that by comparing TMV-ion interactions between native and denatured coat protein, we can distinguish between chemically similar heavy metal ions such as cadmium and zinc ions. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Anchoring Intrinsically Disordered Proteins to Multiple Targets: Lessons from N-Terminus of the p53 Protein

    Directory of Open Access Journals (Sweden)

    Yongqi Huang

    2011-02-01

    Full Text Available Anchor residues, which are deeply buried upon binding, play an important role in protein–protein interactions by providing recognition specificity and facilitating the binding kinetics. Up to now, studies on anchor residues have been focused mainly on ordered proteins. In this study, we investigated anchor residues in intrinsically disordered proteins (IDPs which are flexible in the free state. We identified the anchor residues of the N-terminus of the p53 protein (Glu17–Asn29, abbreviated as p53N which are involved in binding with two different targets (MDM2 and Taz2, and analyzed their side chain conformations in the unbound states. The anchor residues in the unbound p53N were found to frequently sample conformations similar to those observed in the bound complexes (i.e., Phe19, Trp23, and Leu26 in the p53N-MDM2 complex, and Leu22 in the p53N-Taz2 complex. We argue that the bound-like conformations of the anchor residues in the unbound state are important for controlling the specific interactions between IDPs and their targets. Further, we propose a mechanism to account for the binding promiscuity of IDPs in terms of anchor residues and molecular recognition features (MoRFs.

  15. Understanding the Role of Intrinsic Disorder of Viral Proteins in the Oncogenicity of Different Types of HPV.

    Science.gov (United States)

    Tamarozzi, Elvira Regina; Giuliatti, Silvana

    2018-01-09

    Intrinsic disorder is very important in the biological function of several proteins, and is directly linked to their foldability during interaction with their targets. There is a close relationship between the intrinsically disordered proteins and the process of carcinogenesis involving viral pathogens. Among these pathogens, we have highlighted the human papillomavirus (HPV) in this study. HPV is currently among the most common sexually transmitted infections, besides being the cause of several types of cancer. HPVs are divided into two groups, called high- and low-risk, based on their oncogenic potential. The high-risk HPV E6 protein has been the target of much research, in seeking treatments against HPV, due to its direct involvement in the process of cell cycle control. To understand the role of intrinsic disorder of the viral proteins in the oncogenic potential of different HPV types, the structural characteristics of intrinsically disordered regions of high and low-risk HPV E6 proteins were analyzed. In silico analyses of primary sequences, prediction of tertiary structures, and analyses of molecular dynamics allowed the observation of the behavior of such disordered regions in these proteins, thereby proving a direct relationship of structural variation with the degree of oncogenicity of HPVs. The results obtained may contribute to the development of new therapies, targeting the E6 oncoprotein, for the treatment of HPV-associated diseases.

  16. Sequence charge decoration dictates coil-globule transition in intrinsically disordered proteins

    Science.gov (United States)

    Firman, Taylor; Ghosh, Kingshuk

    2018-03-01

    We present an analytical theory to compute conformations of heteropolymers—applicable to describe disordered proteins—as a function of temperature and charge sequence. The theory describes coil-globule transition for a given protein sequence when temperature is varied and has been benchmarked against the all-atom Monte Carlo simulation (using CAMPARI) of intrinsically disordered proteins (IDPs). In addition, the model quantitatively shows how subtle alterations of charge placement in the primary sequence—while maintaining the same charge composition—can lead to significant changes in conformation, even as drastic as a coil (swelled above a purely random coil) to globule (collapsed below a random coil) and vice versa. The theory provides insights on how to control (enhance or suppress) these changes by tuning the temperature (or solution condition) and charge decoration. As an application, we predict the distribution of conformations (at room temperature) of all naturally occurring IDPs in the DisProt database and notice significant size variation even among IDPs with a similar composition of positive and negative charges. Based on this, we provide a new diagram-of-states delineating the sequence-conformation relation for proteins in the DisProt database. Next, we study the effect of post-translational modification, e.g., phosphorylation, on IDP conformations. Modifications as little as two-site phosphorylation can significantly alter the size of an IDP with everything else being constant (temperature, salt concentration, etc.). However, not all possible modification sites have the same effect on protein conformations; there are certain "hot spots" that can cause maximal change in conformation. The location of these "hot spots" in the parent sequence can readily be identified by using a sequence charge decoration metric originally introduced by Sawle and Ghosh. The ability of our model to predict conformations (both expanded and collapsed states) of IDPs at

  17. Intrinsic nucleic acid dynamics modulates HIV-1 nucleocapsid protein binding to its targets.

    Directory of Open Access Journals (Sweden)

    Ali Bazzi

    Full Text Available HIV-1 nucleocapsid protein (NC is involved in the rearrangement of nucleic acids occurring in key steps of reverse transcription. The protein, through its two zinc fingers, interacts preferentially with unpaired guanines in single-stranded sequences. In mini-cTAR stem-loop, which corresponds to the top half of the cDNA copy of the transactivation response element of the HIV-1 genome, NC was found to exhibit a clear preference for the TGG sequence at the bottom of mini-cTAR stem. To further understand how this site was selected among several potential binding sites containing unpaired guanines, we probed the intrinsic dynamics of mini-cTAR using (13C relaxation measurements. Results of spin relaxation time measurements have been analyzed using the model-free formalism and completed by dispersion relaxation measurements. Our data indicate that the preferentially recognized guanine in the lower part of the stem is exempt of conformational exchange and highly mobile. In contrast, the unrecognized unpaired guanines of mini-cTAR are involved in conformational exchange, probably related to transient base-pairs. These findings support the notion that NC preferentially recognizes unpaired guanines exhibiting a high degree of mobility. The ability of NC to discriminate between close sequences through their dynamic properties contributes to understanding how NC recognizes specific sites within the HIV genome.

  18. Intrinsic Nucleic Acid Dynamics Modulates HIV-1 Nucleocapsid Protein Binding to Its Targets

    Science.gov (United States)

    Bazzi, Ali; Zargarian, Loussiné; Chaminade, Françoise; De Rocquigny, Hugues; René, Brigitte; Mély, Yves; Fossé, Philippe; Mauffret, Olivier

    2012-01-01

    HIV-1 nucleocapsid protein (NC) is involved in the rearrangement of nucleic acids occurring in key steps of reverse transcription. The protein, through its two zinc fingers, interacts preferentially with unpaired guanines in single-stranded sequences. In mini-cTAR stem-loop, which corresponds to the top half of the cDNA copy of the transactivation response element of the HIV-1 genome, NC was found to exhibit a clear preference for the TGG sequence at the bottom of mini-cTAR stem. To further understand how this site was selected among several potential binding sites containing unpaired guanines, we probed the intrinsic dynamics of mini-cTAR using 13C relaxation measurements. Results of spin relaxation time measurements have been analyzed using the model-free formalism and completed by dispersion relaxation measurements. Our data indicate that the preferentially recognized guanine in the lower part of the stem is exempt of conformational exchange and highly mobile. In contrast, the unrecognized unpaired guanines of mini-cTAR are involved in conformational exchange, probably related to transient base-pairs. These findings support the notion that NC preferentially recognizes unpaired guanines exhibiting a high degree of mobility. The ability of NC to discriminate between close sequences through their dynamic properties contributes to understanding how NC recognizes specific sites within the HIV genome. PMID:22745685

  19. Coiled-Coil Domains of SUN Proteins as Intrinsic Dynamic Regulators.

    Science.gov (United States)

    Nie, Si; Ke, Huimin; Gao, Feng; Ren, Jinqi; Wang, Mingzhu; Huo, Lin; Gong, Weimin; Feng, Wei

    2016-01-05

    SUN proteins are the core components of LINC complexes that span across the nuclear envelope for nuclear positioning and migration. SUN proteins contain at least one predicted coiled-coil domain preceding the SUN domain. Here, we found that the two coiled-coil domains (CC1 and CC2) of SUN2 exhibit distinct oligomeric states. CC2 is a monomer in solution. The structure of the CC2-SUN monomer revealed that CC2 unexpectedly folds as a three-helix bundle that interacts with the SUN domain and locks it in an inactive conformation. In contrast, CC1 is a trimer. The structure of the CC1 trimer demonstrated that CC1 is an imperfect coiled coil for the trimerization and activation of the SUN domain. Modulations of CC1 and CC2 dictate different oligomeric states of CC1-CC2-SUN, which is essential for LINC complex formation. Thus, the two coiled-coil domains of SUN2 act as the intrinsic dynamic regulators for controlling the SUN domain activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Reducing operational costs through MIPS management

    NARCIS (Netherlands)

    Kwiatkowski, L.M.; Verhoef, C.

    2015-01-01

    We focus on an approach to reducing the costs of running applications. MIPS, which is a traditional acronym for millions of instructions per second, have evolved to become a measurement of processing power and CPU resource consumption. The need for controlling MIPS attributed costs is indispensable

  1. FoldIndex((c)) : a simple tool to predict whether a given protein sequence is intrinsically unfolded

    NARCIS (Netherlands)

    Prilusky, J; Felder, CE; Zeev-Ben-Mordehai, T; Rydberg, EH; Man, O; Beckmann, J.S.; Silman, I.; Sussman, J.L.

    2005-01-01

    An easy-to-use, versatile and freely available graphic web server, FoldIndex© is described: it predicts if a given protein sequence is intrinsically unfolded implementing the algorithm of Uversky and co-workers, which is based on the average residue hydrophobicity and net charge of the sequence.

  2. Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state

    International Nuclear Information System (INIS)

    Launay, Hélène; Barré, Patrick; Puppo, Carine; Manneville, Stéphanie; Gontero, Brigitte; Receveur-Bréchot, Véronique

    2016-01-01

    The redox switch protein CP12 is a key player of the regulation of the Benson–Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. - Highlights: • CP12 is predicted to form two helices in its N-terminal sequence. • Reduced CP12 is disordered as a random coil according to SAXS. • Limited or no transient structures are observed in reduced CP12 by NMR.

  3. Absence of residual structure in the intrinsically disordered regulatory protein CP12 in its reduced state

    Energy Technology Data Exchange (ETDEWEB)

    Launay, Hélène; Barré, Patrick [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France); Puppo, Carine [Aix-Marseille Université, Centre National de la Recherche Scientifique, UMR 7281, Laboratoire de Bioénergétique et Ingénierie des Protéines, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20 (France); Manneville, Stéphanie [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France); Gontero, Brigitte [Aix-Marseille Université, Centre National de la Recherche Scientifique, UMR 7281, Laboratoire de Bioénergétique et Ingénierie des Protéines, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20 (France); Receveur-Bréchot, Véronique, E-mail: veronique.brechot@inserm.fr [Laboratory of integrative Structural and Chemical Biology (iSCB), Centre de Recherche en Cancérologie de Marseille (CRCM), CNRS UMR 7258, INSERM U 1068, Institut Paoli-Calmettes, Aix-Marseille Universités, Marseille 13009 (France)

    2016-08-12

    The redox switch protein CP12 is a key player of the regulation of the Benson–Calvin cycle. Its oxidation state is controlled by the formation/dissociation of two intramolecular disulphide bridges during the day/night cycle. CP12 was known to be globally intrinsically disordered on a large scale in its reduced state, while being partly ordered in the oxidised state. By combining Nuclear Magnetic Resonance and Small Angle X-ray Scattering experiments, we showed that, contrary to secondary structure or disorder predictions, reduced CP12 is fully disordered, with no transient or local residual structure likely to be precursor of the structures identified in the oxidised active state and/or in the bound state with GAPDH or PRK. These results highlight the diversity of the mechanisms of regulation of conditionally disordered redox switches, and question the stability of oxidised CP12 scaffold. - Highlights: • CP12 is predicted to form two helices in its N-terminal sequence. • Reduced CP12 is disordered as a random coil according to SAXS. • Limited or no transient structures are observed in reduced CP12 by NMR.

  4. Hyperphosphorylation of intrinsically disordered tau protein induces an amyloidogenic shift in its conformational ensemble.

    Directory of Open Access Journals (Sweden)

    Shaolong Zhu

    Full Text Available Tau is an intrinsically disordered protein (IDP whose primary physiological role is to stabilize microtubules in neuronal axons at all stages of development. In Alzheimer's and other tauopathies, tau forms intracellular insoluble amyloid aggregates known as neurofibrillary tangles, a process that appears in many cases to be preceded by hyperphosphorylation of tau monomers. Understanding the shift in conformational bias induced by hyperphosphorylation is key to elucidating the structural factors that drive tau pathology, however, as an IDP, tau is not amenable to conventional structural characterization. In this work, we employ a straightforward technique based on Time-Resolved ElectroSpray Ionization Mass Spectrometry (TRESI-MS and Hydrogen/Deuterium Exchange (HDX to provide a detailed picture of residual structure in tau, and the shifts in conformational bias induced by hyperphosphorylation. By comparing the native and hyperphosphorylated ensembles, we are able to define specific conformational biases that can easily be rationalized as enhancing amyloidogenic propensity. Representative structures for the native and hyperphosphorylated tau ensembles were generated by refinement of a broad sample of conformations generated by low-computational complexity modeling, based on agreement with the TRESI-HDX profiles.

  5. Deletion of the p107/p130-binding domain of Mip130/LIN-9 bypasses the requirement for CDK4 activity for the dissociation of Mip130/LIN-9 from p107/p130-E2F4 complex.

    Science.gov (United States)

    Sandoval, Raudel; Pilkinton, Mark; Colamonici, Oscar R

    2009-10-15

    Mip130/LIN-9 is part of a large complex that includes homologs of the Drosophila dREAM (drosophila RB-like, E2F, and Myb) and C. elegans DRM complexes. This complex also includes proteins such as Mip40/LIN-37, Mip120/LIN-54, and LIN-52. In mammalian cells, Mip130/LIN-9 specifically associates with the p107/p130-E2F4 repressor complex in G0/G1 and with B-Myb in S-phase. However, little is known about how the transition occurs and whether Mip130/LIN-9 contributes to the repressor effect of p107/p130. In this report, we demonstrate that Mip130/LIN-9, Mip40/LIN-37, Mip120/LIN-54, and Sin3b form a core complex, the Mip Core Complex or LIN Complex (MCC/LINC), which is detectable in all phases of the cell cycle. This complex specifically recruits transcriptional repressors such as p107, p130, E2F4 and HDAC1 in G0/G1, and B-Myb in S-phase. Importantly, we provide strong evidence that the transition between repressors and activators of transcription is mediated by CDK4, through the phosphorylation of the pocket proteins, p107 and p130. The requirement for CDK4 activity is bypassed by the deletion of the first 84 amino acids (Mip130/LIN-9(Delta84)), since this mutant is unable to interact with p107/p130 in G0/G1, while maintaining its association with B-Myb. Importantly, the Mip130/LIN-9(Delta84) allele rescues the low expression of G1/S genes observed in CDK4(-/-) MEFs demonstrating that Mip130/LIN-9 contributes to the repression of these E2F-regulated genes in G0/G1.

  6. CAMEX-4 MIPS SODAR V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  7. CAMEX-4 MIPS FIELD MILL V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  8. CAMEX-4 MIPS CEILOMETER V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  9. Monitoring structural changes in intrinsically disordered proteins using QCM-D: application to the bacterial cell division protein ZipA.

    Science.gov (United States)

    Mateos-Gil, Pablo; Tsortos, Achilleas; Vélez, Marisela; Gizeli, Electra

    2016-05-05

    The sensitivity of QCM-D to molecular hydrodynamic properties is applied in this work to study conformational changes of the intrinsically disordered protein ZipA. Acoustic measurements can clearly follow ZipA's unstructured domain expansion and contraction with salt content and be correlated with changes in the hydrodynamic radius of 1.8 nm or less.

  10. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    Predictive studies suggest that the known sequences of the N-terminal segment of surfactant protein SP-C from animal species have an intrinsic tendency to form beta-turns, but there are important differences on the probable location of these motifs in different SP-C species. Our hypothesis...... is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP......-C, and studied their structural behaviour in solution and in phospholipid bilayers and monolayers. In these peptides, leucine at position 1 of both sequences has been replaced by tryptophan in order to allow their study by fluorescence spectroscopy. Far-u.v. circular dichroism spectra of the peptides in aqueous...

  11. MicroProteins

    DEFF Research Database (Denmark)

    Eguen, Teinai Ebimienere; Straub, Daniel; Graeff, Moritz

    2015-01-01

    MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining characterist......MicroProteins (miPs) are short, usually single-domain proteins that, in analogy to miRNAs, heterodimerize with their targets and exert a dominant-negative effect. Recent bioinformatic attempts to identify miPs have resulted in a list of potential miPs, many of which lack the defining...

  12. Mapping Residual Structure in Intrinsically Disordered Proteins at Residue Resolution Using Millisecond Hydrogen/Deuterium Exchange and Residue Averaging

    Science.gov (United States)

    Keppel, Theodore R.; Weis, David D.

    2015-04-01

    Measurement of residual structure in intrinsically disordered proteins can provide insights into the mechanisms by which such proteins undergo coupled binding and folding. The present work describes an approach to measure residual structure in disordered proteins using millisecond hydrogen/deuterium (H/D) exchange in a conventional bottom-up peptide-based workflow. We used the exchange mid-point, relative to a totally deuterated control, to quantify the rate of H/D exchange in each peptide. A weighted residue-by-residue average of these midpoints was used to map the extent of residual structure at near single-residue resolution. We validated this approach both by simulating a disordered protein and experimentally using the p300 binding domain of ACTR, a model disordered protein already well-characterized by other approaches. Secondary structure elements mapped in the present work are in good agreement with prior nuclear magnetic resonance measurements. The new approach was somewhat limited by a loss of spatial resolution and subject to artifacts because of heterogeneities in intrinsic exchange. Approaches to correct these limitations are discussed.

  13. Intrinsically disordered and pliable Starmaker-like protein from medaka (Oryzias latipes controls the formation of calcium carbonate crystals.

    Directory of Open Access Journals (Sweden)

    Mirosława Różycka

    Full Text Available Fish otoliths, biominerals composed of calcium carbonate with a small amount of organic matrix, are involved in the functioning of the inner ear. Starmaker (Stm from zebrafish (Danio rerio was the first protein found to be capable of controlling the formation of otoliths. Recently, a gene was identified encoding the Starmaker-like (Stm-l protein from medaka (Oryzias latipes, a putative homologue of Stm and human dentine sialophosphoprotein. Although there is no sequence similarity between Stm-l and Stm, Stm-l was suggested to be involved in the biomineralization of otoliths, as had been observed for Stm even before. The molecular properties and functioning of Stm-l as a putative regulatory protein in otolith formation have not been characterized yet. A comprehensive biochemical and biophysical analysis of recombinant Stm-l, along with in silico examinations, indicated that Stm-l exhibits properties of a coil-like intrinsically disordered protein. Stm-l possesses an elongated and pliable structure that is able to adopt a more ordered and rigid conformation under the influence of different factors. An in vitro assay of the biomineralization activity of Stm-l indicated that Stm-l affected the size, shape and number of calcium carbonate crystals. The functional significance of intrinsically disordered properties of Stm-l and the possible role of this protein in controlling the formation of calcium carbonate crystals is discussed.

  14. Synergistic inhibition of the intrinsic factor X activation by protein S and C4b-binding protein

    NARCIS (Netherlands)

    Koppelman, S. J.; van't Veer, C.; Sixma, J. J.; Bouma, B. N.

    1995-01-01

    The complement protein C4b-binding protein plays an important role in the regulation of the protein C anticoagulant pathway. C4b-binding protein can bind to protein S, thereby inhibiting the cofactor activity of protein S for activated protein C. In this report, we describe a new role for

  15. Combining a PagP fusion protein system with nickel ion-catalyzed cleavage to produce intrinsically disordered proteins in E. coli.

    Science.gov (United States)

    Zahran, Somaya; Pan, Jonathan S; Liu, Philip B; Hwang, Peter M

    2015-12-01

    Many proteins contain intrinsically disordered regions that are highly solvent-exposed and susceptible to post-translational modifications. Studying these protein segments is critical to understanding their physiologic regulation, but proteolytic degradation can make them difficult to express and purify. We have designed a new protein expression vector that fuses the target protein to the N-terminus of the integral membrane protein, PagP. The two proteins are connected by a short linker containing the sequence SRHW, previously shown to be optimal for nickel ion-catalyzed cleavage. The methodology is demonstrated for an intrinsically disordered segment of cardiac troponin I. cTnI[135-209]-SRHW-PagP-His6 fusion protein was overexpressed in Escherichia coli, accumulating in insoluble inclusion bodies. The protein was solubilized, purified using nickel affinity chromatography, and then cleaved with 0.5mM NiSO4 at pH 9.0 and 45 °C, all in 6M guanidine-HCl. Nickel ion-catalyzed peptide bond hydrolysis is an effective chemical cleavage technique under denaturing conditions that preclude the use of proteases. Moreover, nickel-catalyzed cleavage is more specific than the most commonly used agent, cyanogen bromide, which cleaves C-terminal to methionine residues. We were able to produce 15 mg of purified cTnI[135-209] from 1L of M9 minimal media using this protocol. The methodology is more generally applicable to the production of intrinsically disordered protein segments. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Effects of Macromolecular Crowding on an Intrinsically Disordered Protein Characterized by Small-Angle Neutron Scattering with Contrast Matching

    Science.gov (United States)

    Johansen, Daniel; Jeffries, Cy M.J.; Hammouda, Boualem; Trewhella, Jill; Goldenberg, David P.

    2011-01-01

    Small-angle neutron scattering was used to examine the effects of molecular crowding on an intrinsically disordered protein, the N protein of bacteriophage λ, in the presence of high concentrations of a small globular protein, bovine pancreatic trypsin inhibitor (BPTI). The N protein was labeled with deuterium, and the D2O concentration of the solvent was adjusted to eliminate the scattering contrast between the solvent and unlabeled BPTI, leaving only the scattering signal from the unfolded protein. The scattering profile observed in the absence of BPTI closely matched that predicted for an ensemble of random conformations. With BPTI added to a concentration of 65 mg/mL, there was a clear change in the scattering profile representing an increase in the mass fractal dimension of the unfolded protein, from 1.7 to 1.9, as expected if crowding favors more compact conformations. The crowding protein also inhibited aggregation of the unfolded protein. At 130 mg/mL BPTI, however, the fractal dimension was not significantly different from that measured at the lower concentration, contrary to the predictions of models that treat the unfolded conformations as convex particles. These results are reminiscent of the behavior of polymers in concentrated melts, suggesting that these synthetic mixtures may provide useful insights into the properties of unfolded proteins under crowding conditions. PMID:21320458

  17. Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

    International Nuclear Information System (INIS)

    Knott, Michael; Best, Robert B.

    2014-01-01

    Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an “induced fit” or “conformational selection” mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD

  18. Structural and hydrodynamic properties of an intrinsically disordered region of a germ cell-specific protein on phase separation.

    Science.gov (United States)

    Brady, Jacob P; Farber, Patrick J; Sekhar, Ashok; Lin, Yi-Hsuan; Huang, Rui; Bah, Alaji; Nott, Timothy J; Chan, Hue Sun; Baldwin, Andrew J; Forman-Kay, Julie D; Kay, Lewis E

    2017-09-26

    Membrane encapsulation is frequently used by the cell to sequester biomolecules and compartmentalize their function. Cells also concentrate molecules into phase-separated protein or protein/nucleic acid "membraneless organelles" that regulate a host of biochemical processes. Here, we use solution NMR spectroscopy to study phase-separated droplets formed from the intrinsically disordered N-terminal 236 residues of the germ-granule protein Ddx4. We show that the protein within the concentrated phase of phase-separated Ddx4, [Formula: see text], diffuses as a particle of 600-nm hydrodynamic radius dissolved in water. However, NMR spectra reveal sharp resonances with chemical shifts showing [Formula: see text] to be intrinsically disordered. Spin relaxation measurements indicate that the backbone amides of [Formula: see text] have significant mobility, explaining why high-resolution spectra are observed, but motion is reduced compared with an equivalently concentrated nonphase-separating control. Observation of a network of interchain interactions, as established by NOE spectroscopy, shows the importance of Phe and Arg interactions in driving the phase separation of Ddx4, while the salt dependence of both low- and high-concentration regions of phase diagrams establishes an important role for electrostatic interactions. The diffusion of a series of small probes and the compact but disordered 4E binding protein 2 (4E-BP2) protein in [Formula: see text] are explained by an excluded volume effect, similar to that found for globular protein solvents. No changes in structural propensities of 4E-BP2 dissolved in [Formula: see text] are observed, while changes to DNA and RNA molecules have been reported, highlighting the diverse roles that proteinaceous solvents play in dictating the properties of dissolved solutes.

  19. Insights into Unfolded Proteins from the Intrinsic ϕ/ψ Propensities of the AAXAA Host-Guest Series

    Science.gov (United States)

    Towse, Clare-Louise; Vymetal, Jiri; Vondrasek, Jiri; Daggett, Valerie

    2016-01-01

    Various host-guest peptide series are used by experimentalists as reference conformational states. One such use is as a baseline for random-coil NMR chemical shifts. Comparison to this random-coil baseline, through secondary chemical shifts, is used to infer protein secondary structure. The use of these random-coil data sets rests on the perception that the reference chemical shifts arise from states where there is little or no conformational bias. However, there is growing evidence that the conformational composition of natively and nonnatively unfolded proteins fail to approach anything that can be construed as random coil. Here, we use molecular dynamics simulations of an alanine-based host-guest peptide series (AAXAA) as a model of unfolded and denatured states to examine the intrinsic propensities of the amino acids. We produced ensembles that are in good agreement with the experimental NMR chemical shifts and confirm that the sampling of the 20 natural amino acids in this peptide series is be far from random. Preferences toward certain regions of conformational space were both present and dependent upon the environment when compared under conditions typically used to denature proteins, i.e., thermal and chemical denaturation. Moreover, the simulations allowed us to examine the conformational makeup of the underlying ensembles giving rise to the ensemble-averaged chemical shifts. We present these data as an intrinsic backbone propensity library that forms part of our Structural Library of Intrinsic Residue Propensities to inform model building, to aid in interpretation of experiment, and for structure prediction of natively and nonnatively unfolded states. PMID:26789758

  20. Combining short- and long-range fluorescence reporters with simulations to explore the intramolecular dynamics of an intrinsically disordered protein

    Science.gov (United States)

    Zosel, Franziska; Haenni, Dominik; Soranno, Andrea; Nettels, Daniel; Schuler, Benjamin

    2017-10-01

    Intrinsically disordered proteins (IDPs) are increasingly recognized as a class of molecules that can exert essential biological functions even in the absence of a well-defined three-dimensional structure. Understanding the conformational distributions and dynamics of these highly flexible proteins is thus essential for explaining the molecular mechanisms underlying their function. Single-molecule fluorescence spectroscopy in combination with Förster resonance energy transfer (FRET) is a powerful tool for probing intramolecular distances and the rapid long-range distance dynamics in IDPs. To complement the information from FRET, we combine it with photoinduced electron transfer (PET) quenching to monitor local loop-closure kinetics at the same time and in the same molecule. Here we employed this combination to investigate the intrinsically disordered N-terminal domain of HIV-1 integrase. The results show that both long-range dynamics and loop closure kinetics on the sub-microsecond time scale can be obtained reliably from a single set of measurements by the analysis with a comprehensive model of the underlying photon statistics including both FRET and PET. A more detailed molecular interpretation of the results is enabled by direct comparison with a recent extensive atomistic molecular dynamics simulation of integrase. The simulations are in good agreement with experiment and can explain the deviation from simple models of chain dynamics by the formation of persistent local secondary structure. The results illustrate the power of a close combination of single-molecule spectroscopy and simulations for advancing our understanding of the dynamics and detailed mechanisms in unfolded and intrinsically disordered proteins.

  1. Intrinsic structural differences in the N-terminal segment of pulmonary surfactant protein SP-C from different species

    DEFF Research Database (Denmark)

    Plasencia, I; Rivas, L; Casals, C

    2001-01-01

    is that intrinsic structural determinants of the sequence of the N-terminal region of SP-C could define conformation, acylation and perhaps surface properties of the mature protein. To test this hypothesis we have synthesized peptides corresponding to the 13-residue N-terminal sequence of porcine and canine SP...... the packing of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) monolayers, the effects being always higher in anionic than in zwitterionic lipids, and also substantially higher in films containing canine peptide in comparison to porcine peptide. Acylation of cysteines at the N...

  2. Bioinformatic analysis and molecular modelling of human ameloblastin suggest a two-domain intrinsically unstructured calcium-binding protein

    Czech Academy of Sciences Publication Activity Database

    Vymětal, Jiří; Slabý, I.; Spahr, A.; Vondrášek, Jiří; Lyngstadaas, S. P.

    2008-01-01

    Roč. 116, č. 2 (2008), s. 124-134 ISSN 0909-8836 R&D Projects: GA ČR GA203/05/0009; GA ČR GA203/06/1727; GA MŠk LC512 Grant - others:EU(XE) QLK3-CT-2001-00090 Institutional research plan: CEZ:AV0Z40550506 Keywords : ameloblastin * bioinformatic modelling * calcium * intrinsically unstructured protein Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.957, year: 2008

  3. Structural models of intrinsically disordered and calcium-bound folded states of a protein adapted for secretion

    OpenAIRE

    O’Brien, Darragh P.; Hernandez, Belen; Durand, Dominique; Hourdel, Véronique; Sotomayor-Pérez, Ana-Cristina; Vachette, Patrice; Ghomi, Mahmoud; Chamot-Rooke, Julia; Ladant, Daniel; Brier, Sébastien; Chenal, Alexandre

    2016-01-01

    International audience; Many Gram-negative bacteria use Type I secretion systems, T1SS, to secrete virulence factors that contain calcium-binding Repeat-in-ToXin (RTX) motifs. Here, we present structural models of an RTX protein, RD, in both its intrinsically disordered calcium-free Apo-state and its folded calcium-bound Holo-state. Apo-RD behaves as a disordered polymer chain comprising several statistical elements that exhibit local rigidity with residual secondary structure. Holo-RD is a f...

  4. Uncoupling of stem cell inhibition from monocyte chemoattraction in MIP-1alpha by mutagenesis of the proteoglycan binding site.

    Science.gov (United States)

    Graham, G J; Wilkinson, P C; Nibbs, R J; Lowe, S; Kolset, S O; Parker, A; Freshney, M G; Tsang, M L; Pragnell, I B

    1996-12-02

    We have studied the role of proteoglycans in the function of Macrophage Inflammatory Protein-1 alpha (MIP-1alpha), a member of the proteoglycan binding chemokine family. Sequence and peptide analysis has identified a basic region within MIP-1alpha which appears to be the major determinant of proteoglycan binding and we have now produced a mutant of MIP-1alpha lacking the basic charges on two of the amino acids within this proteoglycan binding site. This mutant (Hep Mut) appears to have lost the ability to bind to proteoglycans. Bioassay of Hep Mut indicates that it has retained stem cell inhibitory properties but has a compromised activity as a monocyte chemoattractant, thus suggesting uncoupling of these two properties of MIP-1alpha. Receptor studies have indicated that the inactivity of Hep Mut on human monocytes correlates with its inability to bind to CCR1, a cloned human MIP-1alpha receptor. In addition, studies using proteoglycan deficient cells transfected with CCR1 have indicated that the proteoglycan binding site in MIP-1alpha is a site that is also involved in the docking of MIP-1alpha to the monocyte receptor. The site for interaction with the stem cell receptor must therefore be distinct, suggesting that MIP-1alpha utilizes different receptors for these two different biological processes.

  5. Characterization of a Legionella micdadei mip mutant

    DEFF Research Database (Denmark)

    O'Connell, W A; Bangsborg, Jette Marie; Cianciotto, N P

    1995-01-01

    macrophages and freshwater protozoa. Southern hybridization and immunoblot analyses demonstrated that mip sequences were present and expressed within a panel of virulent L. micdadei strains. Using allelic exchange mutagenesis, we then constructed an L. micdadei strain that completely and specifically lacked...

  6. Minimal effects of macromolecular crowding on an intrinsically disordered protein: a small-angle neutron scattering study.

    Science.gov (United States)

    Goldenberg, David P; Argyle, Brian

    2014-02-18

    Small-angle neutron scattering was used to study the effects of macromolecular crowding by two globular proteins, i.e., bovine pancreatic trypsin inhibitor and equine metmyoglobin, on the conformational ensemble of an intrinsically disordered protein, the N protein of bacteriophage λ. The λ N protein was uniformly labeled with (2)H, and the concentrations of D2O in the samples were adjusted to match the neutron scattering contrast of the unlabeled crowding proteins, thereby masking their contribution to the scattering profiles. Scattering from the deuterated λ N was recorded for samples containing up to 0.12 g/mL bovine pancreatic trypsin inhibitor or 0.2 g/mL metmyoglobin. The radius of gyration of the uncrowded protein was estimated to be 30 Å and was found to be remarkably insensitive to the presence of crowders, varying by scattering profiles were also used to estimate the fractal dimension of λ N, which was found to be ∼1.8 in the absence or presence of crowders, indicative of a well-solvated and expanded random coil under all of the conditions examined. These results are contrary to the predictions of theoretical treatments and previous experimental studies demonstrating compaction of unfolded proteins by crowding with polymers such as dextran and Ficoll. A computational simulation suggests that some previous treatments may have overestimated the effective volumes of disordered proteins and the variation of these volumes within an ensemble. The apparent insensitivity of λ N to crowding may also be due in part to weak attractive interactions with the crowding proteins, which may compensate for the effects of steric exclusion. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Directory of Open Access Journals (Sweden)

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  8. DisoMCS: Accurately Predicting Protein Intrinsically Disordered Regions Using a Multi-Class Conservative Score Approach.

    Directory of Open Access Journals (Sweden)

    Zhiheng Wang

    Full Text Available The precise prediction of protein intrinsically disordered regions, which play a crucial role in biological procedures, is a necessary prerequisite to further the understanding of the principles and mechanisms of protein function. Here, we propose a novel predictor, DisoMCS, which is a more accurate predictor of protein intrinsically disordered regions. The DisoMCS bases on an original multi-class conservative score (MCS obtained by sequence-order/disorder alignment. Initially, near-disorder regions are defined on fragments located at both the terminus of an ordered region connecting a disordered region. Then the multi-class conservative score is generated by sequence alignment against a known structure database and represented as order, near-disorder and disorder conservative scores. The MCS of each amino acid has three elements: order, near-disorder and disorder profiles. Finally, the MCS is exploited as features to identify disordered regions in sequences. DisoMCS utilizes a non-redundant data set as the training set, MCS and predicted secondary structure as features, and a conditional random field as the classification algorithm. In predicted near-disorder regions a residue is determined as an order or a disorder according to the optimized decision threshold. DisoMCS was evaluated by cross-validation, large-scale prediction, independent tests and CASP (Critical Assessment of Techniques for Protein Structure Prediction tests. All results confirmed that DisoMCS was very competitive in terms of accuracy of prediction when compared with well-established publicly available disordered region predictors. It also indicated our approach was more accurate when a query has higher homologous with the knowledge database.The DisoMCS is available at http://cal.tongji.edu.cn/disorder/.

  9. The intrinsic flexibility of the aptamer targeting the ribosomal protein S8 is a key factor for the molecular recognition.

    Science.gov (United States)

    Autiero, Ida; Ruvo, Menotti; Improta, Roberto; Vitagliano, Luigi

    2018-04-01

    Aptamers are RNA/DNA biomolecules representing an emerging class of protein interactors and regulators. Despite the growing interest in these molecules, current understanding of chemical-physical basis of their target recognition is limited. Recently, the characterization of the aptamer targeting the protein-S8 has suggested that flexibility plays important functional roles. We investigated the structural versatility of the S8-aptamer by molecular dynamics simulations. Five different simulations have been conducted by varying starting structures and temperatures. The simulation of S8-aptamer complex provides a dynamic view of the contacts occurring at the complex interface. The simulation of the aptamer in ligand-free state indicates that its central region is intrinsically endowed with a remarkable flexibility. Nevertheless, none of the trajectory structures adopts the structure observed in the S8-aptamer complex. The aptamer ligand-bound is very rigid in the simulation carried out at 300 K. A structural transition of this state, providing insights into the aptamer-protein recognition process, is observed in a simulation carried out at 400 K. These data indicate that a key event in the binding is linked to the widening of the central region of the aptamer. Particularly relevant is switch of the A26 base from its ligand-free state to a location that allows the G13-C28 base-pairing. Intrinsic flexibility of the aptamer is essential for partner recognition. Present data indicate that S8 recognizes the aptamer through an induced-fit rather than a population-shift mechanism. The present study provides deeper understanding of the structural basis of the structural versatility of aptamers. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. CAMEX-4 MIPS 915 MHZ DOPPLER WIND PROFILER V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CAMEX-4 MIPS 915 MHZ Doppler Wind Profiler dataset was collected by the University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS),...

  11. A 5-bp insertion in Mip causes recessive congenital cataract in KFRS4/Kyo rats.

    Directory of Open Access Journals (Sweden)

    Kei Watanabe

    Full Text Available We discovered a new cataract mutation, kfrs4, in the Kyoto Fancy Rat Stock (KFRS background. Within 1 month of birth, all kfrs4/kfrs4 homozygotes developed cataracts, with severe opacity in the nuclei of the lens. In contrast, no opacity was observed in the kfrs4/+ heterozygotes. We continued to observe these rats until they reached 1 year of age and found that cataractogenesis did not occur in kfrs4/+ rats. To define the histological defects in the lenses of kfrs4 rats, sections of the eyes of these rats were prepared. Although the lenses of kfrs4/kfrs4 homozygotes showed severely disorganised fibres and vacuolation, the lenses of kfrs4/+ heterozygotes appeared normal and similar to those of wild-type rats. We used positional cloning to identify the kfrs4 mutation. The mutation was mapped to an approximately 9.7-Mb region on chromosome 7, which contains the Mip gene. This gene is responsible for a dominant form of cataract in humans and mice. Sequence analysis of the mutant-derived Mip gene identified a 5-bp insertion. This insertion is predicted to inactivate the MIP protein, as it produces a frameshift that results in the synthesis of 6 novel amino acid residues and a truncated protein that lacks 136 amino acids in the C-terminal region, and no MIP immunoreactivity was observed in the lens fibre cells of kfrs4/kfrs4 homozygous rats using an antibody that recognises the C- and N-terminus of MIP. In addition, the kfrs4/+ heterozygotes showed reduced expression of Mip mRNA and MIP protein and the kfrs4/kfrs4 homozygotes showed no expression in the lens. These results indicate that the kfrs4 mutation conveys a loss-of-function, which leads to functional inactivation though the degradation of Mip mRNA by an mRNA decay mechanism. Therefore, the kfrs4 rat represents the first characterised rat model with a recessive mutation in the Mip gene.

  12. Arsenite induces apoptosis in human mesenchymal stem cells by altering Bcl-2 family proteins and by activating intrinsic pathway

    International Nuclear Information System (INIS)

    Yadav, Santosh; Shi Yongli; Wang Feng; Wang He

    2010-01-01

    Purpose: Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs. Methods: MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAs III ) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed. Results: iAs III induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAs III in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway. Conclusion: iAs III can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.

  13. The intrinsically disordered structural platform of the plant defence hub protein RPM1-interacting protein 4 provides insights into its mode of action in the host-pathogen interface and evolution of the nitrate-induced domain protein family.

    Science.gov (United States)

    Sun, Xiaolin; Greenwood, David R; Templeton, Matthew D; Libich, David S; McGhie, Tony K; Xue, Bin; Yoon, Minsoo; Cui, Wei; Kirk, Christopher A; Jones, William T; Uversky, Vladimir N; Rikkerink, Erik H A

    2014-09-01

    Arabidopsis thaliana (At) RPM1-interacting protein 4 (RIN4), targeted by many defence-suppressing bacterial type III effectors and monitored by several resistance proteins, regulates plant immune responses to pathogen-associated molecular patterns and type III effectors. Little is known about the overall protein structure of AtRIN4, especially in its unbound form, and the relevance of structure to its diverse biological functions. AtRIN4 contains two nitrate-induced (NOI) domains and is a member of the NOI family. Using experimental and bioinformatic approaches, we demonstrate that the unbound AtRIN4 is intrinsically disordered under physiological conditions. The intrinsically disordered polypeptide chain of AtRIN4 is interspersed with molecular recognition features (MoRFs) and anchor-identified long-binding regions, potentially allowing it to undergo disorder-to-order transitions upon binding to partner(s). A poly-l-proline II structure, often responsible for protein recognition, is also identified in AtRIN4. By performing bioinformatics analyses on RIN4 homologues from different plant species and the NOI proteins from Arabidopsis, we infer the conservation of intrinsic disorder, MoRFs and long-binding regions of AtRIN4 in other plant species and the NOI family. Intrinsic disorder and MoRFs could provide RIN4 proteins with the binding promiscuity and plasticity required to act as hubs in a pivotal position within plant defence signalling cascades. © 2014 FEBS.

  14. The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence Padrão de infiltração de células do sistema imune na cromomicose: envolvimento de MIP-1 alfa da persistência fúngica

    Directory of Open Access Journals (Sweden)

    Vanuza Cristina Sá

    2007-02-01

    Full Text Available Chromoblastomycosis (CR is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68, Langerhans'cells (S100, lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56 and neutrophils (CD15. The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha, chemokine receptors (CXCR3 and CCR1 and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15+ and CD56+ were significantly lower than CD3+, CD4+, CD20+ and CD68+ cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.A cromomicose é micose subcutânea crônica sistêmica caracterizada por resposta inflamatória crônica granulomatosa. No entanto, existem poucos dados a respeito do padrão de subtipos de leucócitos na cromomicose e sobre as vias envolvidas no recrutamento destas células. O objetivo deste trabalho foi avaliar os tipos celulares, bem como a expressão de quimiocinas, receptores de quimiocinas e enzimas em lesões de cromomicose. O infiltrado inflamatório foi caracterizado por meio de técnica imuno-histoquímica utilizando os seguintes marcadores CD68 (macrófagos, S100 (células de Langerhans, CD3, CD4, CD8, CD45RO, CD20 e CD56 (linfócitos e CD15 (neutrófilos. A expressão de MIP-1alfa (Proteína Inflamat

  15. Intrinsic alterations in the partial molar volume on the protein denaturation: surficial Kirkwood-Buff approach.

    Science.gov (United States)

    Yu, Isseki; Takayanagi, Masayoshi; Nagaoka, Masataka

    2009-03-19

    The partial molar volume (PMV) of the protein chymotrypsin inhibitor 2 (CI2) was calculated by all-atom MD simulation. Denatured CI2 showed almost the same average PMV value as that of native CI2. This is consistent with the phenomenological question of the protein volume paradox. Furthermore, using the surficial Kirkwood-Buff approach, spatial distributions of PMV were analyzed as a function of the distance from the CI2 surface. The profiles of the new R-dependent PMV indicate that, in denatured CI2, the reduction in the solvent electrostatic interaction volume is canceled out mainly by an increment in thermal volume in the vicinity of its surface. In addition, the PMV of the denatured CI2 was found to increase in the region in which the number density of water atoms is minimum. These results provide a direct and detailed picture of the mechanism of the protein volume paradox suggested by Chalikian et al.

  16. Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

    Directory of Open Access Journals (Sweden)

    Jenkins Dafyd J

    2008-01-01

    Full Text Available Abstract Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusion Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic

  17. Liquid demixing of intrinsically disordered proteins is seeded by poly(ADP-ribose)

    DEFF Research Database (Denmark)

    Altmeyer, Matthias; Neelsen, Kai J; Teloni, Federico

    2015-01-01

    disordered proteins at DNA break sites. Demixing, which relies on electrostatic interactions between positively charged RGG repeats and negatively charged PAR, is amplified by aggregation-prone prion-like domains, and orchestrates the earliest cellular responses to DNA breakage. We propose that PAR...

  18. On the interaction between intrinsic proteins and phosphatidylglycerol in the membrane of Acholeplasma laidlawii

    NARCIS (Netherlands)

    Bevers, E.M.; Wang, H.H.; Kamp, J.A.F. op den; Deenen, L.L.M. van

    1979-01-01

    About 30% of the phosphatidylglycerol in oleic acid-enriched Acholeplasma laidlawii membranes are not hydrolyzed at temperatures below 10 °C by phospholipase A2 from porcine pancreas. Removal of 53% of the membrane proteins by proteolysis did not reduce the size of this inaccessible

  19. Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.

    Science.gov (United States)

    Conn, Kristen L; Wasson, Peter; McFarlane, Steven; Tong, Lily; Brown, James R; Grant, Kyle G; Domingues, Patricia; Boutell, Chris

    2016-05-01

    Small ubiquitin-like modifier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity. Posttranslational modifications with small ubiquitin-like modifier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated with the suppression of

  20. Modulation of firing and synaptic transmission of serotonergic neurons by intrinsic G protein-coupled receptors and ion channels

    Directory of Open Access Journals (Sweden)

    Takashi eMaejima

    2013-05-01

    Full Text Available Serotonergic neurons project to virtually all regions of the CNS and are consequently involved in many critical physiological functions such as mood, sexual behavior, feeding, sleep/wake cycle, memory, cognition, blood pressure regulation, breathing and reproductive success. Therefore serotonin release and serotonergic neuronal activity have to be precisely controlled and modulated by interacting brain circuits to adapt to specific emotional and environmental states. We will review the current knowledge about G protein-coupled receptors and ion channels involved in the regulation of serotonergic system, how their regulation is modulating the intrinsic activity of serotonergic neurons and its transmitter release and will discuss the latest methods for controlling the modulation of serotonin release and intracellular signaling in serotonergic neurons in vitro and in vivo.

  1. Members of rice plasma membrane intrinsic proteins subfamily are involved in arsenite permeability and tolerance in plants.

    Science.gov (United States)

    Mosa, Kareem A; Kumar, Kundan; Chhikara, Sudesh; Mcdermott, Joseph; Liu, Zijuan; Musante, Craig; White, Jason C; Dhankher, Om Parkash

    2012-12-01

    Rice accumulates high level of arsenic (As) in its edible parts and thus plays an important role in the transfer of As into the food chain. However, the mechanisms of As uptake and its detoxification in rice are not well understood. Recently, members of the Nodulin 26-like intrinsic protein (NIP) subfamily of plant aquaporins were shown to transport arsenite in rice and Arabidopsis. Here we report that members of the rice plasma membrane intrinsic protein (PIP) subfamily are also involved in As tolerance and transport. Based on the homology search with the mammalian AQP9 and yeast Fps1 arsenite transporters, we identified and cloned five rice PIP gene subfamily members. qRT-PCR analysis of PIPs in rice root and shoot tissues revealed a significant down regulation of transcripts encoding OsPIP1;2, OsPIP1;3, OsPIP2;4, OsPIP2;6, and OsPIP2;7 in response to arsenite treatment. Heterologous expression of OsPIP2;4, OsPIP2;6, and OsPIP2;7 in Xenopus laevis oocytes significantly increased the uptake of arsenite. Overexpression of OsPIP2;4, OsPIP2;6, and OsPIP2;7 in Arabidopsis yielded enhanced arsenite tolerance and higher biomass accumulation. Further, these transgenic plants showed no significant accumulation of As in shoot and root tissues in long term uptake assays. Whereas, short duration exposure to arsenite caused both active influx and efflux of As in the roots. The data suggests a bidirectional arsenite permeability of rice PIPs in plants. These rice PIPs genes will be highly useful for engineering important food and biofuel crops for enhanced crop productivity on contaminated soils without increasing the accumulation of toxic As in the biomass or edible tissues.

  2. A novel hepacivirus with an unusually long and intrinsically disordered NS5A protein in a wild Old World primate.

    Science.gov (United States)

    Lauck, Michael; Sibley, Samuel D; Lara, James; Purdy, Michael A; Khudyakov, Yury; Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Switzer, William M; Chapman, Colin A; Hughes, Austin L; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L

    2013-08-01

    GB virus B (GBV-B; family Flaviviridae, genus Hepacivirus) has been studied in New World primates as a model for human hepatitis C virus infection, but the distribution of GBV-B and its relatives in nature has remained obscure. Here, we report the discovery of a novel and highly divergent GBV-B-like virus in an Old World monkey, the black-and-white colobus (Colobus guereza), in Uganda. The new virus, guereza hepacivirus (GHV), clusters phylogenetically with GBV-B and recently described hepaciviruses infecting African bats and North American rodents, and it shows evidence of ancient recombination with these other hepaciviruses. Direct sequencing of reverse-transcribed RNA from blood plasma from three of nine colobus monkeys yielded near-complete GHV genomes, comprising two distinct viral variants. The viruses contain an exceptionally long nonstructural 5A (NS5A) gene, approximately half of which codes for a protein with no discernible homology to known proteins. Computational structure-based analyses indicate that the amino terminus of the GHV NS5A protein may serve a zinc-binding function, similar to the NS5A of other viruses within the family Flaviviridae. However, the 521-amino-acid carboxy terminus is intrinsically disordered, reflecting an unusual degree of structural plasticity and polyfunctionality. These findings shed new light on the natural history and evolution of the hepaciviruses and on the extent of structural variation within the Flaviviridae.

  3. Biosynthesis of vanillin by the fungus Pycnoporus sanguineus MIP 95001

    Directory of Open Access Journals (Sweden)

    Sabrina Moro Villela Pacheco

    2013-09-01

    Full Text Available Vanillin (a substance popularly known as vanilla flavor is one of the most widely used compounds, mainly by food and pharmaceutical industries. This substance can be obtained from the orchid Vanilla planifolia, but this is costly and time consuming. Thus, other methods for obtaining vanillin have been studied. Within this context, the aim of this work was to study the biosynthesis of vanillin by three strains of Pycnoporus sanguineus through the use of vanillic acid as a precursor. The strains were cultured in Petri dishes with a potato dextrose agar medium. Fragments of the media with the fungus were then inoculated in Erlenmeyer flasks with a liquid medium of potato broth and 0.3 g.L-1 of vanillic acid. The flasks remained in a shaker for eight days at 28°C and 120 rpm. Samples were withdrawn once a day (0.8 mL.day-1 for analysis of vanillin, glucose, total phenols, total proteins, and laccase. The results showed that only the MIP 95001 strain promoted the biosynthesis of vanillin. The highest concentration of vanillin was detected on the fourth day of cultivation (8.75 mg.dL-1. The results illustrate the ability to biosynthesize vanillin using Pycnoporus sanguineus (MIP 95001, which suggests a possible route for the biotechnological production of this flavor.

  4. Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD.

    Science.gov (United States)

    Mesrouze, Yannick; Bokhovchuk, Fedir; Meyerhofer, Marco; Fontana, Patrizia; Zimmermann, Catherine; Martin, Typhaine; Delaunay, Clara; Erdmann, Dirk; Schmelzle, Tobias; Chène, Patrick

    2017-04-21

    TEAD ( TEA /ATTS d omain) transcription factors are the most distal effectors of the Hippo pathway. YAP ( Y es- a ssociated p rotein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation. In this report, combining single site-directed mutagenesis and double mutant analyses, we conduct a detailed analysis on the role of several residues located at the YAP:TEAD interface. Our results provide quantitative understanding of the interactions taking place at the YAP:TEAD interface and give insights into the formation of the YAP:TEAD complex and more particularly on the interaction between TEAD and the Ω-loop found in YAP.

  5. Direct detection of carbon and nitrogen nuclei for high-resolution analysis of intrinsically disordered proteins using NMR spectroscopy.

    Science.gov (United States)

    Gibbs, E B; Kriwacki, R W

    2018-01-16

    Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for characterizing the structural and dynamic properties of intrinsically disordered proteins and protein regions (IDPs & IDRs). However, the application of NMR to IDPs has been limited by poor chemical shift dispersion in two-dimensional (2D) 1 H- 15 N heteronuclear correlation spectra. Among the various detection schemes available for heteronuclear correlation spectroscopy, 13 C direct-detection has become a mainstay for investigations of IDPs owing to the favorable chemical shift dispersion in 2D 13 C'- 15 N correlation spectra. Recent advances in cryoprobe technology have enhanced the sensitivity for direct detection of both 13 C and 15 N resonances at high magnetic field strengths, thus prompting the development of 15 N direct-detect experiments to complement established 13 C-detection experiments. However, the application of 15 N-detection has not been widely explored for IDPs. Here we compare 1 H, 13 C, and 15 N detection schemes for a variety of 2D heteronuclear correlation spectra and evaluate their performance on the basis of resolution, chemical shift dispersion, and sensitivity. We performed experiments with a variety of disordered systems ranging in size and complexity; from a small IDR (99 amino acids), to a large low complexity IDR (185 amino acids), and finally a ∼73 kDa folded homopentameric protein that also contains disordered regions (133 amino acids/monomer). We conclude that, while requiring high sample concentration and long acquisition times, 15 N-detection often offers enhanced resolution over other detection schemes in studies of disordered protein regions with low complexity sequences. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Small Angle Neutron Scattering Studies of R67 Dihydrofolate Reductase, a Tetrameric Protein with Intrinsically Disordered N-Termini.

    Science.gov (United States)

    Bhojane, Purva P; Duff, Michael R; Bafna, Khushboo; Agarwal, Pratul; Stanley, Christopher; Howell, Elizabeth E

    2017-11-07

    R67 dihydrofolate reductase (DHFR) is a homotetramer with a single active site pore and no sequence or structural homology with chromosomal DHFRs. The R67 enzyme provides resistance to trimethoprim, an active site-directed inhibitor of Escherichia coli DHFR. Sixteen to twenty N-terminal amino acids are intrinsically disordered in the R67 dimer crystal structure. Chymotrypsin cleavage of 16 N-terminal residues results in an active enzyme with a decreased stability. The space sampled by the disordered N-termini of R67 DHFR was investigated using small angle neutron scattering. From a combined analysis using molecular dynamics and the program SASSIE ( http://www.smallangles.net/sassie/SASSIE_HOME.html ), the apoenzyme displays a radius of gyration (R g ) of 21.46 ± 0.50 Å. Addition of glycine betaine, an osmolyte, does not result in folding of the termini as the R g increases slightly to 22.78 ± 0.87 Å. SASSIE fits of the latter SANS data indicate that the disordered N-termini sample larger regions of space and remain disordered, suggesting they might function as entropic bristles. Pressure perturbation calorimetry also indicated that the volume of R67 DHFR increases upon addition of 10% betaine and decreased at 20% betaine because of the dehydration of the protein. Studies of the hydration of full-length R67 DHFR in the presence of the osmolytes betaine and dimethyl sulfoxide find around 1250 water molecules hydrating the protein. Similar studies with truncated R67 DHFR yield around 400 water molecules hydrating the protein in the presence of betaine. The difference of ∼900 waters indicates the N-termini are well-hydrated.

  7. Proteus: a random forest classifier to predict disorder-to-order transitioning binding regions in intrinsically disordered proteins

    Science.gov (United States)

    Basu, Sankar; Söderquist, Fredrik; Wallner, Björn

    2017-05-01

    The focus of the computational structural biology community has taken a dramatic shift over the past one-and-a-half decades from the classical protein structure prediction problem to the possible understanding of intrinsically disordered proteins (IDP) or proteins containing regions of disorder (IDPR). The current interest lies in the unraveling of a disorder-to-order transitioning code embedded in the amino acid sequences of IDPs/IDPRs. Disordered proteins are characterized by an enormous amount of structural plasticity which makes them promiscuous in binding to different partners, multi-functional in cellular activity and atypical in folding energy landscapes resembling partially folded molten globules. Also, their involvement in several deadly human diseases (e.g. cancer, cardiovascular and neurodegenerative diseases) makes them attractive drug targets, and important for a biochemical understanding of the disease(s). The study of the structural ensemble of IDPs is rather difficult, in particular for transient interactions. When bound to a structured partner, an IDPR adapts an ordered conformation in the complex. The residues that undergo this disorder-to-order transition are called protean residues, generally found in short contiguous stretches and the first step in understanding the modus operandi of an IDP/IDPR would be to predict these residues. There are a few available methods which predict these protean segments from their amino acid sequences; however, their performance reported in the literature leaves clear room for improvement. With this background, the current study presents `Proteus', a random forest classifier that predicts the likelihood of a residue undergoing a disorder-to-order transition upon binding to a potential partner protein. The prediction is based on features that can be calculated using the amino acid sequence alone. Proteus compares favorably with existing methods predicting twice as many true positives as the second best method (55

  8. Characterization of Leishmania donovani aquaporins shows presence of subcellular aquaporins similar to tonoplast intrinsic proteins of plants.

    Directory of Open Access Journals (Sweden)

    Neha Biyani

    Full Text Available Leishmania donovani, a protozoan parasite, resides in the macrophages of the mammalian host. The aquaporin family of proteins form important components of the parasite-host interface. The parasite-host interface could be a potential target for chemotherapy. Analysis of L. major and L. infantum genomes showed the presence of five aquaporins (AQPs annotated as AQP9 (230aa, AQP putative (294aa, AQP-like protein (279aa, AQP1 (314aa and AQP-like protein (596aa. We report here the structural modeling, localization and functional characterization of the AQPs from L. donovani. LdAQP1, LdAQP9, LdAQP2860 and LdAQP2870 have the canonical NPA-NPA motifs, whereas LdAQP putative has a non-canonical NPM-NPA motif. In the carboxyl terminal to the second NPA box of all AQPs except AQP1, a valine/alanine residue was found instead of the arginine. In that respect these four AQPs are similar to tonoplast intrinsic proteins in plants, which are localized to intracellular organelles. Confocal microscopy of L. donovani expressing GFP-tagged AQPs showed an intracellular localization of LdAQP9 and LdAQP2870. Real-time PCR assays showed expression of all aquaporins except LdAQP2860, whose level was undetectable. Three-dimensional homology modeling of the AQPs showed that LdAQP1 structure bears greater topological similarity to the aquaglyceroporin than to aquaporin of E. coli. The pore of LdAQP1 was very different from the rest in shape and size. The cavity of LdAQP2860 was highly irregular and undefined in geometry. For functional characterization, four AQP proteins were heterologously expressed in yeast. In the fps1Δ yeast cells, which lacked the key aquaglyceroporin, LdAQP1 alone displayed an osmosensitive phenotype indicating glycerol transport activity. However, expression of LdAQP1 and LdAQP putative in a yeast gpd1Δ strain, deleted for glycerol production, conferred osmosensitive phenotype indicating water transport activity or aquaporin function. Our analysis

  9. Molecular Dynamics Simulations of Intrinsically Disordered Proteins: On the Accuracy of the TIP4P-D Water Model and the Representativeness of Protein Disorder Models.

    Science.gov (United States)

    Henriques, João; Skepö, Marie

    2016-07-12

    Here, we first present a follow-up to a previous work by our group on the problematic of molecular dynamics simulations of intrinsically disordered proteins (IDPs) [ Henriques et al. J. Chem. Theory Comput. 2015 , 11 , 3420 - 3431 ], using the recently developed TIP4P-D water model. When used in conjunction with the standard AMBER ff99SB-ILDN force field and applied to the simulation of Histatin 5, our IDP model, we obtain results which are in excellent agreement with the best performing IDP-suitable force field from the earlier study and with experiment. We then assess the representativeness of the IDP models used in these and similar studies, finding that most are too short in comparison to the average IDP and contain a bias toward hydrophilic amino acid residues. Moreover, several key order- and disorder-promoting residues are also found to be misrepresented. It seems appropriate for future studies to address these issues.

  10. Mycobacterium tuberculosis copper-regulated protein SocB is an intrinsically disordered protein that folds upon interaction with a synthetic phospholipid bilayer.

    Science.gov (United States)

    Nowicka, Urszula; Hoffman, Morgan; Randles, Leah; Shi, Xiaoshan; Khavrutskii, Lyuba; Stefanisko, Karen; Tarasova, Nadya I; Darwin, K Heran; Walters, Kylie J

    2016-02-01

    Multiple genes in Mycobacterium tuberculosis (Mtb) are regulated by copper including socAB (small orf induced by copper A and B), which is induced by copper and repressed by RicR (regulated in copper repressor). socA and socB encode hypothetical proteins of 61 and 54 amino acids, respectively. Here, we use biophysical and computational methods to evaluate the SocB structure. We find that SocB lacks evidence for secondary structure, with no thermal cooperative unfolding event, according to circular dichroism measurements. 2D NMR spectra similarly exhibit hallmarks of a disordered structural state, which is also supported by analyzing SocB diffusion. Altogether, these findings suggest that by itself SocB is intrinsically disordered. Interestingly, SocB interacts with a synthetic phospholipid bilayer and becomes helical, which suggests that it may be membrane-associated. © 2015 Wiley Periodicals, Inc.

  11. Hamiltonian Switch Metropolis Monte Carlo Simulations for Improved Conformational Sampling of Intrinsically Disordered Regions Tethered to Ordered Domains of Proteins.

    Science.gov (United States)

    Mittal, Anuradha; Lyle, Nicholas; Harmon, Tyler S; Pappu, Rohit V

    2014-08-12

    There is growing interest in the topic of intrinsically disordered proteins (IDPs). Atomistic Metropolis Monte Carlo (MMC) simulations based on novel implicit solvation models have yielded useful insights regarding sequence-ensemble relationships for IDPs modeled as autonomous units. However, a majority of naturally occurring IDPs are tethered to ordered domains. Tethering introduces additional energy scales and this creates the challenge of broken ergodicity for standard MMC sampling or molecular dynamics that cannot be readily alleviated by using generalized tempering methods. We have designed, deployed, and tested our adaptation of the Nested Markov Chain Monte Carlo sampling algorithm. We refer to our adaptation as Hamiltonian Switch Metropolis Monte Carlo (HS-MMC) sampling. In this method, transitions out of energetic traps are enabled by the introduction of an auxiliary Markov chain that draws conformations for the disordered region from a Boltzmann distribution that is governed by an alternative potential function that only includes short-range steric repulsions and conformational restraints on the ordered domain. We show using multiple, independent runs that the HS-MMC method yields conformational distributions that have similar and reproducible statistical properties, which is in direct contrast to standard MMC for equivalent amounts of sampling. The method is efficient and can be deployed for simulations of a range of biologically relevant disordered regions that are tethered to ordered domains.

  12. Concentrated Solutions of Single-Chain Nanoparticles: A Simple Model for Intrinsically Disordered Proteins under Crowding Conditions.

    Science.gov (United States)

    Moreno, Angel J; Lo Verso, Federica; Arbe, Arantxa; Pomposo, José A; Colmenero, Juan

    2016-03-03

    By means of large-scale computer simulations and small-angle neutron scattering (SANS), we investigate solutions of single-chain nanoparticles (SCNPs), covering the whole concentration range from infinite dilution to melt density. The analysis of the conformational properties of the SCNPs reveals that these synthetic nano-objects share basic ingredients with intrinsically disordered proteins (IDPs), as topological polydispersity, generally sparse conformations, and locally compact domains. We investigate the role of the architecture of the SCNPs in their collapse behavior under macromolecular crowding. Unlike in the case of linear macromolecules, which experience the usual transition from self-avoiding to Gaussian random-walk conformations, crowding leads to collapsed conformations of SCNPs resembling those of crumpled globules. This behavior is already found at volume fractions (about 30%) that are characteristic of crowding in cellular environments. The simulation results are confirmed by the SANS experiments. Our results for SCNPs--a model system free of specific interactions--propose a general scenario for the effect of steric crowding on IDPs: collapse from sparse conformations at high dilution to crumpled globular conformations in cell environments.

  13. A J-modulated protonless NMR experiment characterizes the conformational ensemble of the intrinsically disordered protein WIP

    Energy Technology Data Exchange (ETDEWEB)

    Rozentur-Shkop, Eva; Goobes, Gil; Chill, Jordan H., E-mail: Jordan.Chill@biu.ac.il [Bar Ilan University, Department of Chemistry (Israel)

    2016-12-15

    Intrinsically disordered proteins (IDPs) are multi-conformational polypeptides that lack a single stable three-dimensional structure. It has become increasingly clear that the versatile IDPs play key roles in a multitude of biological processes, and, given their flexible nature, NMR is a leading method to investigate IDP behavior on the molecular level. Here we present an IDP-tailored J-modulated experiment designed to monitor changes in the conformational ensemble characteristic of IDPs by accurately measuring backbone one- and two-bond J({sup 15}N,{sup 13}Cα) couplings. This concept was realized using a unidirectional (H)NCO {sup 13}C-detected experiment suitable for poor spectral dispersion and optimized for maximum coverage of amino acid types. To demonstrate the utility of this approach we applied it to the disordered actin-binding N-terminal domain of WASp interacting protein (WIP), a ubiquitous key modulator of cytoskeletal changes in a range of biological systems. One- and two-bond J({sup 15}N,{sup 13}Cα) couplings were acquired for WIP residues 2–65 at various temperatures, and in denaturing and crowding environments. Under native conditions fitted J-couplings identified in the WIP conformational ensemble a propensity for extended conformation at residues 16–23 and 45–60, and a helical tendency at residues 28–42. These findings are consistent with a previous study of the based upon chemical shift and RDC data and confirm that the WIP{sup 2–65} conformational ensemble is biased towards the structure assumed by this fragment in its actin-bound form. The effects of environmental changes upon this ensemble were readily apparent in the J-coupling data, which reflected a significant decrease in structural propensity at higher temperatures, in the presence of 8 M urea, and under the influence of a bacterial cell lysate. The latter suggests that crowding can cause protein unfolding through protein–protein interactions that stabilize the unfolded

  14. Conformationally selective multidimensional chemical shift ranges in proteins from a PACSY database purged using intrinsic quality criteria

    International Nuclear Information System (INIS)

    Fritzsching, Keith J.; Hong, Mei; Schmidt-Rohr, Klaus

    2016-01-01

    We have determined refined multidimensional chemical shift ranges for intra-residue correlations ( 13 C– 13 C, 15 N– 13 C, etc.) in proteins, which can be used to gain type-assignment and/or secondary-structure information from experimental NMR spectra. The chemical-shift ranges are the result of a statistical analysis of the PACSY database of >3000 proteins with 3D structures (1,200,207 13 C chemical shifts and >3 million chemical shifts in total); these data were originally derived from the Biological Magnetic Resonance Data Bank. Using relatively simple non-parametric statistics to find peak maxima in the distributions of helix, sheet, coil and turn chemical shifts, and without the use of limited “hand-picked” data sets, we show that ∼94 % of the 13 C NMR data and almost all 15 N data are quite accurately referenced and assigned, with smaller standard deviations (0.2 and 0.8 ppm, respectively) than recognized previously. On the other hand, approximately 6 % of the 13 C chemical shift data in the PACSY database are shown to be clearly misreferenced, mostly by ca. −2.4 ppm. The removal of the misreferenced data and other outliers by this purging by intrinsic quality criteria (PIQC) allows for reliable identification of secondary maxima in the two-dimensional chemical-shift distributions already pre-separated by secondary structure. We demonstrate that some of these correspond to specific regions in the Ramachandran plot, including left-handed helix dihedral angles, reflect unusual hydrogen bonding, or are due to the influence of a following proline residue. With appropriate smoothing, significantly more tightly defined chemical shift ranges are obtained for each amino acid type in the different secondary structures. These chemical shift ranges, which may be defined at any statistical threshold, can be used for amino-acid type assignment and secondary-structure analysis of chemical shifts from intra-residue cross peaks by inspection or by using a

  15. Conformationally selective multidimensional chemical shift ranges in proteins from a PACSY database purged using intrinsic quality criteria

    Energy Technology Data Exchange (ETDEWEB)

    Fritzsching, Keith J., E-mail: kfritzsc@brandeis.edu [Brandeis University, Department of Chemistry (United States); Hong, Mei [Massachusetts Institute of Technology, Department of Chemistry (United States); Schmidt-Rohr, Klaus, E-mail: srohr@brandeis.edu [Brandeis University, Department of Chemistry (United States)

    2016-02-15

    We have determined refined multidimensional chemical shift ranges for intra-residue correlations ({sup 13}C–{sup 13}C, {sup 15}N–{sup 13}C, etc.) in proteins, which can be used to gain type-assignment and/or secondary-structure information from experimental NMR spectra. The chemical-shift ranges are the result of a statistical analysis of the PACSY database of >3000 proteins with 3D structures (1,200,207 {sup 13}C chemical shifts and >3 million chemical shifts in total); these data were originally derived from the Biological Magnetic Resonance Data Bank. Using relatively simple non-parametric statistics to find peak maxima in the distributions of helix, sheet, coil and turn chemical shifts, and without the use of limited “hand-picked” data sets, we show that ∼94 % of the {sup 13}C NMR data and almost all {sup 15}N data are quite accurately referenced and assigned, with smaller standard deviations (0.2 and 0.8 ppm, respectively) than recognized previously. On the other hand, approximately 6 % of the {sup 13}C chemical shift data in the PACSY database are shown to be clearly misreferenced, mostly by ca. −2.4 ppm. The removal of the misreferenced data and other outliers by this purging by intrinsic quality criteria (PIQC) allows for reliable identification of secondary maxima in the two-dimensional chemical-shift distributions already pre-separated by secondary structure. We demonstrate that some of these correspond to specific regions in the Ramachandran plot, including left-handed helix dihedral angles, reflect unusual hydrogen bonding, or are due to the influence of a following proline residue. With appropriate smoothing, significantly more tightly defined chemical shift ranges are obtained for each amino acid type in the different secondary structures. These chemical shift ranges, which may be defined at any statistical threshold, can be used for amino-acid type assignment and secondary-structure analysis of chemical shifts from intra

  16. Intrinsic Motivation.

    Science.gov (United States)

    the activity. There has been very little research and theorizing which considers the topic of intrinsic motivation , yet there is a substantial amount...reported within the framework of intrinsic motivation , yet the paper reinterprets the work within that framework. It considers several approaches of

  17. A new family of intrinsically disordered proteins: structural characterization of the major phasin PhaF from Pseudomonas putida KT2440.

    Directory of Open Access Journals (Sweden)

    Beatriz Maestro

    Full Text Available Phasins are intracellular polyhydroxyalkanoat4e (PHA-associated proteins involved in the stabilization of these bacterial carbon storage granules. Despite its importance in PHA metabolism and regulation, only few reports have focused so far on the structure of these proteins. In this work we have investigated the structure and stability of the PhaF phasin from Pseudomonas putida KT2440, a protein that is involved in PHA granule stabilization and distribution to daughter cells upon cell division. A structural, three-dimensional model of the protein was built from homology modeling procedures and consensus secondary structure predictions. The model predicts that PhaF is an elongated protein, with a long, amphipathic N-terminal helix with PHA binding capacity, followed by a short leucine zipper involved in protein oligomerization and a superhelical C-terminal domain wrapped around the chromosomal DNA. Hydrodynamic, spectroscopical and thermodynamic experiments validated the model and confirmed both that free PhaF is a tetramer in solution and that most part of the protein is intrinsically disordered in the absence of its ligands. The results lay a molecular basis for the explanation of the biological role of PhaF and, along with an exhaustive analysis of phasin sequence databases, suggest that intrinsic disorder and oligomerization through coiled-coils may be a widespread mechanism among these proteins.

  18. Roles of Soybean Plasma Membrane Intrinsic Protein GmPIP2;9 in Drought Tolerance and Seed Development

    Directory of Open Access Journals (Sweden)

    Linghong Lu

    2018-04-01

    Full Text Available Aquaporins play an essential role in water uptake and transport in vascular plants. The soybean genome contains a total of 22 plasma membrane intrinsic protein (PIP genes. To identify candidate PIPs important for soybean yield and stress tolerance, we studied the transcript levels of all 22 soybean PIPs. We found that a GmPIP2 subfamily member, GmPIP2;9, was predominately expressed in roots and developing seeds. Here, we show that GmPIP2;9 localized to the plasma membrane and had high water channel activity when expressed in Xenopus oocytes. Using transgenic soybean plants expressing a native GmPIP2;9 promoter driving a GUS-reporter gene, it was found high GUS expression in the roots, in particular, in the endoderm, pericycle, and vascular tissues of the roots of transgenic plants. In addition, GmPIP2;9 was also highly expressed in developing pods. GmPIP2;9 expression significantly increased in short term of polyethylene glycol (PEG-mediated drought stress treatment. GmPIP2;9 overexpression increased tolerance to drought stress in both solution cultures and soil plots. Drought stress in combination with GmPIP2;9 overexpression increased net CO2 assimilation of photosynthesis, stomata conductance, and transpiration rate, suggesting that GmPIP2;9-overexpressing transgenic plants were less stressed than wild-type (WT plants. Furthermore, field experiments showed that GmPIP2;9-overexpressing plants had significantly more pod numbers and larger seed sizes than WT plants. In summary, the study demonstrated that GmPIP2;9 has water transport activity. Its relative high expression levels in roots and developing pods are in agreement with the phenotypes of GmPIP2;9-overexpressing plants in drought stress tolerance and seed development.

  19. On the Exciton Coupling between Two Chlorophyll Pigments in the Absence of a Protein Environment: Intrinsic Effects Revealed by Theory and Experiment (German ed)

    Science.gov (United States)

    2016-07-29

    other micro - environmental effects. In pioneering experiments, Shafizadeh et al.[13] utilized two-color pump-probe spectroscopy to mea- sure the lowest...Chlorophyll Pigments in the Absence of a Protein Environment : Intrinsic Effects Revealed by Theory and Experiment Bruce F. Milne,* Christina Kjær, Jørgen...alone can produce a large portion of the color shift observed in photosynthetic macro - molecular assemblies. The absorption wavelengths of

  20. Glucuronidation as a mechanism of intrinsic drug resistance in colon cancer cells: contribution of drug transport proteins

    NARCIS (Netherlands)

    Cummings, Jeffrey; Zelcer, Noam; Allen, John D.; Yao, Denggao; Boyd, Gary; Maliepaard, Mark; Friedberg, Thomas H.; Smyth, John F.; Jodrell, Duncan I.

    2004-01-01

    We have recently shown that drug conjugation catalysed by UDP-glucuronosyltransferases (UGTs) functions as an intrinsic mechanism of resistance to the topoisomerase I inhibitors 7-ethyl-10-hydroxycamptothecin and NU/ICRF 505 in human colon cancer cells and now report on the role of drug transport in

  1. Characterization and quantification of intact 26S proteasome proteins by real-time measurement of intrinsic fluorescence prior to top-down mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Jason D Russell

    Full Text Available Quantification of gas-phase intact protein ions by mass spectrometry (MS is impeded by highly-variable ionization, ion transmission, and ion detection efficiencies. Therefore, quantification of proteins using MS-associated techniques is almost exclusively done after proteolysis where peptides serve as proxies for estimating protein abundance. Advances in instrumentation, protein separations, and informatics have made large-scale sequencing of intact proteins using top-down proteomics accessible to the proteomics community; yet quantification of proteins using a top-down workflow has largely been unaddressed. Here we describe a label-free approach to determine the abundance of intact proteins separated by nanoflow liquid chromatography prior to MS analysis by using solution-phase measurements of ultraviolet light-induced intrinsic fluorescence (UV-IF. UV-IF is measured directly at the electrospray interface just prior to the capillary exit where proteins containing at least one tryptophan residue are readily detected. UV-IF quantification was demonstrated using commercially available protein standards and provided more accurate and precise protein quantification than MS ion current. We evaluated the parallel use of UV-IF and top-down tandem MS for quantification and identification of protein subunits and associated proteins from an affinity-purified 26S proteasome sample from Arabidopsis thaliana. We identified 26 unique proteins and quantified 13 tryptophan-containing species. Our analyses discovered previously unidentified N-terminal processing of the β6 (PBF1 and β7 (PBG1 subunit - such processing of PBG1 may generate a heretofore unknown additional protease active site upon cleavage. In addition, our approach permitted the unambiguous identification and quantification both isoforms of the proteasome-associated protein DSS1.

  2. MIP-1α enhances Jurkat cell transendothelial migration by up-regulating endothelial adhesion molecules VCAM-1 and ICAM-1.

    Science.gov (United States)

    Ma, Yi-Ran; Ma, Ying-Huan

    2014-11-01

    The aim of this study is to evaluate the expression of macrophage inflammatory protein-1α (MIP-1α) in Jurkat cells and its effect on transendothelial migration. In the present study, human acute lymphoblastic leukemia Jurkat cells (Jurkat cells) were used as a model of T cells in human T-cell acute lymphoblastic leukemia (T-ALL), which demonstrated significantly higher MIP-1α expression compared with that in normal T-cell controls. The ability of Jurkat cells to cross a human brain microvascular endothelial cell (HBMEC) monolayer was almost completely abrogated by MIP-1α siRNA. In addition, the overexpression of MIP-1α resulted in the up-regulated expression of endothelial adhesion molecules, which enhanced the migration of Jurkat cells through a monolayer of HBMEC. MIP-1α levels in Jurkat cells appeared to be an important factor for its transendothelial migration, which may provide the theoretical basis to understand the mechanisms of brain metastases of T-ALL at cellular and molecular levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Influence of the CCR-5/MIP-1 α axis in the pathogenesis of Rocio virus encephalitis in a mouse model.

    Science.gov (United States)

    Chávez, Juliana H; França, Rafael F O; Oliveira, Carlo J F; de Aquino, Maria T P; Farias, Kleber J S; Machado, Paula R L; de Oliveira, Thelma F M; Yokosawa, Jonny; Soares, Edson G; da Silva, João S; da Fonseca, Benedito A L; Figueiredo, Luiz T M

    2013-11-01

    Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in Brazil and its immunopathogenesis remains poorly understood. CC-chemokine receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory protein (MIP-1 α). Both molecules are associated with inflammatory cells migration during infections. In this study, we demonstrated the importance of the CCR5 and MIP-1 α, in the outcome of viral encephalitis of ROCV-infected mice. CCR5 and MIP-1 α knockout mice survived longer than wild-type (WT) ROCV-infected animals. In addition, knockout mice had reduced inflammation in the brain. Assessment of brain viral load showed mice virus detection five days post-infection in wild-type and CCR5-/- mice, while MIP-1 α-/- mice had lower viral loads seven days post-infection. Knockout mice required a higher lethal dose than wild-type mice as well. The CCR5/MIP-1 α axis may contribute to migration of infected cells to the brain and consequently affect the pathogenesis during ROCV infection.

  4. CAMEX-4 MIPS 915 MHZ DOPPLER WIND PROFILER V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  5. CAMEX-4 MIPS MICROWAVE PROFILING RADIOMETER V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  6. CAMEX-4 MIPS SURFACE STATION 1 V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  7. CAMEX-4 MIPS SURFACE STATION 2 V1

    Data.gov (United States)

    National Aeronautics and Space Administration — The University of Alabama in Huntsville (UAH) Mobile Integrated Profiling System (MIPS) is a mobile atmospheric profiling system. It includes a 915 MHz Doppler...

  8. The virus-encoded chemokine vMIP-II inhibits virus-induced Tc1-driven inflammation

    DEFF Research Database (Denmark)

    Lindow, Morten; Nansen, Anneline; Bartholdy, Christina

    2003-01-01

    The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of T cells with a type 1 cytokine profile. For the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit....... Consistent with these in vitro findings treatment with vMIP-II inhibited the adoptive transfer of a virus-specific delayed-type hypersensitivity response in vivo, but only when antigen-primed donor cells were transferred via the intravenous route and required to migrate actively, not when the cells were......-induced signals are pivotal in directing antiviral effector cells toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type 1 T-cell-mediated inflammation....

  9. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

  10. Submission to GenBank of the Plasma membrane intrinsic protein (PIP) Subfamily in Cotton – GenBank Accession No. GU998827-GU998830 and GenBank Accession TPA;inferential No. BK007045-BK007052

    Science.gov (United States)

    The plasma membrane intrinsic proteins (PIP) are one of the five aquaporin protein subfamilies. Aquaporin proteins are known to facilitate water transport through biological membranes. In order to identify NIP aquaporin gene candidates in cotton (Gossypium hirsutum L.), in silico and molecular clon...

  11. A phosphorylation-motif for tuneable helix stabilisation in intrinsically disordered proteins - Lessons from the sodium proton exchanger 1 (NHE1)

    DEFF Research Database (Denmark)

    Hendus-Altenburger, Ruth; Lambrughi, Matteo; Terkelsen, Thilde Bagger

    2017-01-01

    ). Using NMR spectroscopy, we found that two out of those six phosphorylation sites had a stabilizing effect on transient helices. One of these was further investigated by circular dichroism and NMR spectroscopy as well as by molecular dynamic simulations, which confirmed the stabilizing effect...... of relevance for understanding disease-promoting mutations that for example interfere with signalling for instance through constitutive active and often cancer-promoting signalling.......-spread role in phosphorylation-mediated regulation of intrinsically disordered proteins. The identification of such motifs is important for understanding the molecular mechanism of cellular signalling, and is crucial for the development of predictors for the structural effect of phosphorylation; a tool...

  12. The production of intrinsically labeled milk and meat protein is feasible and provides functional tools for human nutrition research

    NARCIS (Netherlands)

    Pennings, B.; Pellikaan, W.F.; Senden, J.M.G.; Vuuren, van A.M.; Sikkema, J.; Loon, van L.J.C.

    2011-01-01

    Administration of labeled, free amino acids does not allow direct assessment of in vivo dietary protein digestion and absorption kinetics. Consequently, dietary protein sources with labeled amino acids incorporated within their protein matrix are required. The aim of the present study was to produce

  13. Arabidopsis FHY3 and FAR1 Regulate Light-Induced myo-Inositol Biosynthesis and Oxidative Stress Responses by Transcriptional Activation of MIPS1.

    Science.gov (United States)

    Ma, Lin; Tian, Tian; Lin, Rongcheng; Deng, Xing-Wang; Wang, Haiyang; Li, Gang

    2016-04-04

    myo-Inositol-1-phosphate synthase (MIPS) catalyzes the limiting step of inositol biosynthesis and has crucial roles in plant growth and development. In response to stress, the transcription of MIPS1 is induced and the biosynthesis of inositol or inositol derivatives is promoted by unknown mechanisms. Here, we found that the light signaling protein FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its homolog FAR-RED IMPAIRED RESPONSE1 (FAR1) regulate light-induced inositol biosynthesis and oxidative stress responses by activating the transcription of MIPS1. Disruption of FHY3 and FAR1 caused light-induced cell death after dark-light transition, precocious leaf senescence, and increased sensitivity to oxidative stress. Reduction of salicylic acid (SA) accumulation by overexpression of SALICYLIC ACID 3-HYDROXYLASE largely suppressed the cell death phenotype of fhy3 far1 mutant plants, suggesting that FHY3- and FAR1-mediated cell death is dependent on SA. Furthermore, comparative analysis of chromatin immunoprecipitation sequencing and microarray results revealed that FHY3 and FAR1 directly target both MIPS1 and MIPS2. The fhy3 far1 mutant plants showed severely decreased MIPS1/2 transcript levels and reduced inositol levels. Conversely, constitutive expression of MIPS1 partially rescued the inositol contents, caused reduced transcript levels of SA-biosynthesis genes, and prevented oxidative stress in fhy3 far1. Taken together, our results indicate that the light signaling proteins FHY3 and FAR1 directly bind the promoter of MIPS1 to activate its expression and thereby promote inositol biosynthesis to prevent light-induced oxidative stress and SA-dependent cell death. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  14. Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

    Directory of Open Access Journals (Sweden)

    Yanbo Liu

    2015-07-01

    Full Text Available Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while down-regulation of phosphor-nephrin, and an increased binding of c-mip to NF-κB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-κB/RelA in IL-17 treated cells. Persistent activation of NF-κB up-regulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip.

  15. Preliminary economic feasibility study of MIP (Medical Isotopes Producer)

    International Nuclear Information System (INIS)

    Mon, G. H.; O, S. Y.

    2004-01-01

    Preliminary economic feasibility study of MIP (Medical Isotopes Producer), which is used liquid nuclear fuel to produce medical isotopes of Mo-99 and Sr-89, was performed. To do this, this study was estimated the IRR(Internal Rate of Return) and PBP(Pay-back Period) about optimistic and pessimistic cases for market penetration of Asia and U.S.A. isotope markets. And sensitivity analysis is also performed about capital cost and price of Mo-99 and Sr-89. According to the results, IRR was between 14.9% and 24.3%, and PBP was between 4.8 years and 7.8 years. These suggest that MIP has economic merits. MIP can produce other medical isotopes such as Sr-90, I-131, Xe-133, Cs-137. So, it is necessary to do cost-benefit analysis considering production of these other isotopes

  16. Obs4MIPS: Satellite Observations for Model Evaluation

    Science.gov (United States)

    Ferraro, R.; Waliser, D. E.; Gleckler, P. J.

    2017-12-01

    This poster will review the current status of the obs4MIPs project, whose purpose is to provide a limited collection of well-established and documented datasets for comparison with Earth system models (https://www.earthsystemcog.org/projects/obs4mips/). These datasets have been reformatted to correspond with the CMIP5 model output requirements, and include technical documentation specifically targeted for their use in model output evaluation. The project holdings now exceed 120 datasets with observations that directly correspond to CMIP5 model output variables, with new additions in response to the CMIP6 experiments. With the growth in climate model output data volume, it is increasing more difficult to bring the model output and the observations together to do evaluations. The positioning of the obs4MIPs datasets within the Earth System Grid Federation (ESGF) allows for the use of currently available and planned online tools within the ESGF to perform analysis using model output and observational datasets without necessarily downloading everything to a local workstation. This past year, obs4MIPs has updated its submission guidelines to closely align with changes in the CMIP6 experiments, and is implementing additional indicators and ancillary data to allow users to more easily determine the efficacy of an obs4MIPs dataset for specific evaluation purposes. This poster will present the new guidelines and indicators, and update the list of current obs4MIPs holdings and their connection to the ESGF evaluation and analysis tools currently available, and being developed for the CMIP6 experiments.

  17. The viral KSHV chemokine vMIP-II inhibits the migration of Naive and activated human NK cells by antagonizing two distinct chemokine receptors.

    Directory of Open Access Journals (Sweden)

    Rachel Yamin

    2013-08-01

    Full Text Available Natural killer (NK cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90% expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56(Dim CD16(Pos while the remaining 10% are CD16 negative and express CD56 in high levels (CD56(Bright CD16(Neg. NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi's sarcoma-associated herpesvirus (KSHV is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6 and chemokines (vMIP-I, vMIP-II, vMIP-III affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56(Dim CD16(Pos NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells.

  18. The viral KSHV chemokine vMIP-II inhibits the migration of Naive and activated human NK cells by antagonizing two distinct chemokine receptors.

    Science.gov (United States)

    Yamin, Rachel; Kaynan, Noa S; Glasner, Ariella; Vitenshtein, Alon; Tsukerman, Pinchas; Bauman, Yoav; Ophir, Yael; Elias, Shlomo; Bar-On, Yotam; Gur, Chamutal; Mandelboim, Ofer

    2013-08-01

    Natural killer (NK) cells are innate immune cells able to rapidly kill virus-infected and tumor cells. Two NK cell populations are found in the blood; the majority (90%) expresses the CD16 receptor and also express the CD56 protein in intermediate levels (CD56(Dim) CD16(Pos)) while the remaining 10% are CD16 negative and express CD56 in high levels (CD56(Bright) CD16(Neg)). NK cells also reside in some tissues and traffic to various infected organs through the usage of different chemokines and chemokine receptors. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human virus that has developed numerous sophisticated and versatile strategies to escape the attack of immune cells such as NK cells. Here, we investigate whether the KSHV derived cytokine (vIL-6) and chemokines (vMIP-I, vMIP-II, vMIP-III) affect NK cell activity. Using transwell migration assays, KSHV infected cells, as well as fusion and recombinant proteins, we show that out of the four cytokine/chemokines encoded by KSHV, vMIP-II is the only one that binds to the majority of NK cells, affecting their migration. We demonstrate that vMIP-II binds to two different receptors, CX3CR1 and CCR5, expressed by naïve CD56(Dim) CD16(Pos) NK cells and activated NK cells, respectively. Furthermore, we show that the binding of vMIP-II to CX3CR1 and CCR5 blocks the binding of the natural ligands of these receptors, Fractalkine (Fck) and RANTES, respectively. Finally, we show that vMIP-II inhibits the migration of naïve and activated NK cells towards Fck and RANTES. Thus, we present here a novel mechanism in which KSHV uses a unique protein that antagonizes the activity of two distinct chemokine receptors to inhibit the migration of naïve and activated NK cells.

  19. The gene expression profiling of hepatocellular carcinoma by a network analysis approach shows a dominance of intrinsically disordered proteins (IDPs) between hub nodes.

    Science.gov (United States)

    Singh, Sakshi; Colonna, Giovanni; Di Bernardo, Giovanni; Bergantino, Francesca; Cammarota, Marcella; Castello, Giuseppe; Costantini, Susan

    2015-11-01

    We have analyzed the transcriptomic data from patients with hepatocellular carcinoma (HCC) after viral HCV infection at the various stages of the disease by means of a networking analysis using the publicly available E-MTAB-950 dataset. The data was compared with those obtained in our group from HepG2 cells, a cancer cell line that lacks the viral infection. By sequential pruning of data, and also taking into account the data from cells of healthy patients as blanks, we were able to obtain a distribution of hub genes for the various stages that characterize the disease and finally, we isolated a metabolic sub-net specific to HCC alone. The general picture is that the basic organization to energetically and metabolically sustain the cells in both the normal and diseased conditions is the same, but a complex cluster of sub-networks controlled by hub genes drives the HCC progression with high metabolic flexibility and plasticity. In particular, we have extracted a sub-net of genes strictly correlated to other hub genes of the network from HepG2 cells, but specific for the HCC and mainly devoted to: (i) control at chromatin levels of cell division; (ii) control of ergastoplasmatic stress through protein degradation and misfolding; (iii) control of the immune response also through an increase of mature T-cells in the thymus. This sub-net is characterized by 26 hub genes coding for intrinsically disordered proteins with a high ability to interact with numerous molecular partners. Moreover, we have also noted that periphery molecules, that is, with one or very few interactions (e.g., cytokines or post-translational enzymes), which do not have a central role in the clusters that make up the global metabolic network, essentially have roles as information transporters. The results evidence a strong presence of intrinsically disordered proteins with key roles as hubs in the sub-networks that characterize the various stages of the disease, conferring a structural plasticity to

  20. The AgMIP Framework to Evaluate Agricultural Pathways

    Science.gov (United States)

    Ruane, Alex

    2015-01-01

    This talk will describe the community and research framework that AgMIP has built to enable evidence-based adaptation investment. We provide expertise on the ground and connect various disciplines in order to allow specific adaptations to be evaluated for their biophysical and socio-economic ramifications.

  1. Insights into Unfolded Proteins from the Intrinsic phi/psi Propensities of the AAXAA Host-Guest Series

    Czech Academy of Sciences Publication Activity Database

    Towse, C. L.; Vymětal, Jiří; Vondrášek, Jiří; Daggett, V.

    2016-01-01

    Roč. 110, č. 2 (2016), s. 348-361 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LH11020 Institutional support: RVO:61388963 Keywords : polyproline-II helix * beta-sheet protein * random-coil behavior Subject RIV: BO - Biophysics Impact factor: 3.656, year: 2016

  2. Contrasting effects of rh-MIP-1 alpha and TGF-beta 1 on chronic myeloid leukemia progenitors in vitro.

    Science.gov (United States)

    Holyoake, T L; Freshney, M G; Sproul, A M; Richmond, L J; Alcorn, M J; Steward, W P; Fitzsimons, E; Dunlop, D J; Franklin, I M; Pragnell, I B

    1993-10-01

    In chronic myeloid leukemia (CML) an abnormality at the stem cell level results in unregulated expansion of myeloid progenitors. The mechanism underlying this uncontrolled proliferation remains unclear. An in vitro clonogenic assay which detects the human counterpart of the murine colony forming unit (CFU) CFU-A/CFU-S day 12 was described in a report of our recent findings. CML bone marrow samples were found to proliferate in the CFU-A assay, producing colonies morphologically indistinguishable from normal controls. The bcr/abl transcripts were sought in the RNA from individual colonies using the polymerase chain reaction (PCR). For the five CML samples tested to date, the majority of CFU-A colonies at diagnosis or in early chronic phase were found to be bcr/abl positive. For normal controls both macrophage inflammatory protein-1 alpha (MIP-1 alpha) and transforming growth factor-beta 1 (TGF-beta 1) inhibited the proliferation of CFU-A colonies when directly added to the assay. In contrast, CML progenitors responded normally to TGF-beta 1, but showed no response to MIP-1 alpha. In suicide assays, for five normal bone marrow samples, CFU-A progenitors induced into S-phase returned to a quiescent state after treatment with MIP-1 alpha. CML progenitors demonstrated inherently high cycle status which showed no definite response to MIP-1 alpha. However, TGF-beta 1 resulted in quiescence of CML progenitor cycling. In conclusion, the primitive progenitors from CML samples were inhibited normally by TGF-beta 1 but showed no response to MIP-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. 24 CFR 203.268 - Pro rata payment of periodic MIP.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Pro rata payment of periodic MIP...-Periodic Payment § 203.268 Pro rata payment of periodic MIP. (a) If the insurance contract is terminated... rata MIP shall not be due or payable where the mortgagee notifies the Commissioner that foreclosure or...

  4. Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1β dependent upregulation of MYO3A gene in breast cancer cells

    Science.gov (United States)

    Baghel, Khemraj Singh; Tewari, Brij Nath; Shrivastava, Richa; Malik, Showkat Ahmad; Lone, Mehraj U-Din; Jain, Nem Kumar; Tripathi, Chakrapani; Kanchan, Ranjana Kumari; Dixit, Sameer; Singh, Kavita; Mitra, Kalyan; Negi, Mahendra Pal Singh; Srivastava, Mukesh; Misra, Sanjeev; Bhatt, Madan Lal Brahma; Bhadauria, Smrati

    2016-01-01

    ABSTRACT The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or “niche” interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1β in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1β. The MIP-1β-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1β and MYO3A. Both, MIP-1β and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1β/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1β potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient

  5. The Tudor domain protein Spindlin1 is involved in intrinsic antiviral defense against incoming hepatitis B Virus and herpes simplex virus type 1.

    Directory of Open Access Journals (Sweden)

    Aurélie Ducroux

    2014-09-01

    Full Text Available Hepatitis B virus infection (HBV is a major risk factor for the development of hepatocellular carcinoma. HBV replicates from a covalently closed circular DNA (cccDNA that remains as an episome within the nucleus of infected cells and serves as a template for the transcription of HBV RNAs. The regulatory protein HBx has been shown to be essential for cccDNA transcription in the context of infection. Here we identified Spindlin1, a cellular Tudor-domain protein, as an HBx interacting partner. We further demonstrated that Spindlin1 is recruited to the cccDNA and inhibits its transcription in the context of infection. Spindlin1 knockdown induced an increase in HBV transcription and in histone H4K4 trimethylation at the cccDNA, suggesting that Spindlin1 impacts on epigenetic regulation. Spindlin1-induced transcriptional inhibition was greater for the HBV virus deficient for the expression of HBx than for the HBV WT virus, suggesting that HBx counteracts Spindlin1 repression. Importantly, we showed that the repressive role of Spindlin1 is not limited to HBV transcription but also extends to other DNA virus that replicate within the nucleus such as Herpes Simplex Virus type 1 (HSV-1. Taken together our results identify Spindlin1 as a critical component of the intrinsic antiviral defense and shed new light on the function of HBx in HBV infection.

  6. In vitro assembly into virus-like particles is an intrinsic quality of Pichia pastoris derived HCV core protein

    International Nuclear Information System (INIS)

    Acosta-Rivero, Nelson; Rodriguez, Armando; Musacchio, Alexis; Falcon, Viviana; Suarez, Viana M.; Martinez, Gillian; Guerra, Ivis; Paz-Lago, Dalila; Morera, Yanelys; Rosa, Maria C. de la; Morales-Grillo, Juan; Duenas-Carrera, Santiago

    2004-01-01

    Different variants of hepatitis C virus core protein (HCcAg) have proved to self-assemble in vitro into virus-like particles (VLPs). However, difficulties in obtaining purified mature HCcAg have limited these studies. In this study, a high degree of monomeric HCcAg purification was accomplished using chromatographic procedures under denaturing conditions. Size exclusion chromatography and sucrose density gradient centrifugation of renatured HCcAg (in the absence of structured RNA) under reducing conditions suggested that it assembled into empty capsids. The electron microscopy analysis of renatured HCcAg showed the presence of spherical VLPs with irregular shapes and an average diameter of 35 nm. Data indicated that HCcAg monomers assembled in vitro into VLPs in the absence of structured RNA, suggesting that recombinant HCcAg used in this work contains all the information necessary for the assembly process. However, they also suggest that some cellular factors might be required for the proper in vitro assembly of capsids

  7. Phosphotyrosine biased enrichment of tryptic peptides from cancer cells by combining pY-MIP and TiO2 affinity resins

    DEFF Research Database (Denmark)

    Bllaci, Loreta; Torsetnes, Silje Bøen; Wierzbicka, Celina Katarzyna

    2017-01-01

    from HeLa cells. The combination of pY-MIP and TiO2 based phosphopeptide enrichment provided more than 90% selectivity for phosphopeptides. Mass spectrometry signal intensities were enhanced for most pY-phosphopeptides (approximately 70%) when using the pY-MIP-TiO2 combination as compared to TiO2 alone......Protein phosphorylation at distinct tyrosine residues (pY) is essential for fast, specific and accurate signal transduction in cells. Enrichment of pY-containing peptides derived from phosphoproteins is commonly facilitated by use of immobilized anti-pY antibodies prior to phosphoproteomics...

  8. Ectopic overexpression of a novel Glycine soja stress-induced plasma membrane intrinsic protein increases sensitivity to salt and dehydration in transgenic Arabidopsis thaliana plants.

    Science.gov (United States)

    Wang, Xi; Cai, Hua; Li, Yong; Zhu, Yanming; Ji, Wei; Bai, Xi; Zhu, Dan; Sun, Xiaoli

    2015-01-01

    Plasma membrane intrinsic proteins (PIPs) belong to the aquaporin family and facilitate water movement across plasma membranes. Existing data indicate that PIP genes are associated with the abilities of plants to tolerate certain stress conditions. A review of our Glycine soja expressed sequence tag (EST) dataset revealed that abiotic stress stimulated expression of a PIP, herein designated as GsPIP2;1 (GenBank_Accn: FJ825766). To understand the roles of this PIP in stress tolerance, we generated a coding sequence for GsPIP2;1 by in silico elongation and cloned the cDNA by 5'-RACE. Semiquantitative RT-PCR showed that GsPIP2;1 expression was stimulated in G. soja leaves by cold, salt, or dehydration stress, whereas the same stresses suppressed GsPIP2;1 expression in the roots. Transgenic Arabidopsis thaliana plants overexpressing GsPIP2;1 grew normally under unstressed and cold conditions, but exhibited depressed tolerance to salt and dehydration stresses. Moreover, greater changes in water potential were detected in the transgenic A. thaliana shoots, implying that GsPIP2;1 may negatively impact stress tolerance by regulating water potential. These results, deviating from those obtained in previous reports, provide new insights into the relationship between PIPs and abiotic stress tolerance in plants.

  9. The intrinsically disordered N-terminal arm of the brome mosaic virus coat protein specifically recognizes the RNA motif that directs the initiation of viral RNA replication.

    Science.gov (United States)

    Jacobs, Alexander; Hoover, Haley; Smith, Edward; Clemmer, David E; Kim, Chul-Hyun; Kao, C Cheng

    2018-01-09

    In the brome mosaic virus (BMV) virion, the coat protein (CP) selectively contacts the RNA motifs that regulate translation and RNA replication (Hoover et al., 2016. J. Virol. 90, 7748). We hypothesize that the unstructured N-terminal arm (NTA) of the BMV CP can specifically recognize RNA motifs. Using ion mobility spectrometry-mass spectrometry, we demonstrate that peptides containing the NTA of the CP were found to preferentially bind to an RNA hairpin motif that directs the initiation of BMV RNA synthesis. RNA binding causes the peptide to change from heterogeneous structures to a single family of structures. Fluorescence anisotropy, fluorescence quenching and size exclusion chromatography experiments all confirm that the NTA can specific recognize the RNA motif. The peptide introduced into plants along with BMV virion increased accumulation of the BMV CP and accelerated the rate of minus-strand RNA synthesis. The intrinsically disordered BMV NTA could thus specifically recognize BMV RNAs to affect viral infection. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Advanced oxidation protein products induce chondrocyte apoptosis via receptor for advanced glycation end products-mediated, redox-dependent intrinsic apoptosis pathway.

    Science.gov (United States)

    Wu, Qian; Zhong, Zhao-Ming; Zhu, Si-Yuan; Liao, Cong-Rui; Pan, Ying; Zeng, Ji-Huan; Zheng, Shuai; Ding, Ruo-Ting; Lin, Qing-Song; Ye, Qing; Ye, Wen-Bin; Li, Wei; Chen, Jian-Ting

    2016-01-01

    Pro-inflammatory cytokine-induced chondrocyte apoptosis is a primary cause of cartilage destruction in the progression of rheumatoid arthritis (RA). Advanced oxidation protein products (AOPPs), a novel pro-inflammatory mediator, have been confirmed to accumulate in patients with RA. However, the effect of AOPPs accumulation on chondrocyte apoptosis and the associated cellular mechanisms remains unclear. The present study demonstrated that the plasma formation of AOPPs was enhanced in RA rats compared with normal. Then, chondrocyte were treated with AOPPs-modified rat serum albumin (AOPPs-RSA) in vitro. Exposure of chondrocyte to AOPPs activated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and increased expression of NADPH oxidase subunits, which was mediated by receptor for advanced glycation end products (RAGE), but not scavenger receptor CD36. Moreover, AOPPs challenge triggered NADPH oxidase-dependent ROS generation which induced mitochondrial dysfunction and endoplasmic reticulum stress resulted in activation of caspase family that eventually lead to apoptosis. Lastly, blockade of RAGE, instead of CD36, largely attenuated these signals. Our study demonstrated first time that AOPPs induce chondrocyte apoptosis via RAGE-mediated and redox-dependent intrinsic apoptosis pathway in vitro. These data implicates that AOPPs may represent a novel pathogenic factor that contributes to RA progression. Targeting AOPPs-triggered cellular mechanisms might emerge as a promising therapeutic option for patients with RA.

  11. Mitochondrial protein acetylation as a cell-intrinsic, evolutionary driver of fat storage: chemical and metabolic logic of acetyl-lysine modifications.

    Science.gov (United States)

    Ghanta, Sirisha; Grossmann, Ruth E; Brenner, Charles

    2013-01-01

    Hormone systems evolved over 500 million years of animal natural history to motivate feeding behavior and convert excess calories to fat. These systems produced vertebrates, including humans, who are famine-resistant but sensitive to obesity in environments of persistent overnutrition. We looked for cell-intrinsic metabolic features, which might have been subject to an evolutionary drive favoring lipogenesis. Mitochondrial protein acetylation appears to be such a system. Because mitochondrial acetyl-coA is the central mediator of fuel oxidation and is saturable, this metabolite is postulated to be the fundamental indicator of energy excess, which imprints a memory of nutritional imbalances by covalent modification. Fungal and invertebrate mitochondria have highly acetylated mitochondrial proteomes without an apparent mitochondrially targeted protein lysine acetyltransferase. Thus, mitochondrial acetylation is hypothesized to have evolved as a nonenzymatic phenomenon. Because the pKa of a nonperturbed Lys is 10.4 and linkage of a carbonyl carbon to an ε amino group cannot be formed with a protonated Lys, we hypothesize that acetylation occurs on residues with depressed pKa values, accounting for the propensity of acetylation to hit active sites and suggesting that regulatory Lys residues may have been under selective pressure to avoid or attract acetylation throughout animal evolution. In addition, a shortage of mitochondrial oxaloacetate under ketotic conditions can explain why macronutrient insufficiency also produces mitochondrial hyperacetylation. Reduced mitochondrial activity during times of overnutrition and undernutrition would improve fitness by virtue of resource conservation. Micronutrient insufficiency is predicted to exacerbate mitochondrial hyperacetylation. Nicotinamide riboside and Sirt3 activity are predicted to relieve mitochondrial inhibition.

  12. Proline substitutions in a Mip-like peptidyl-prolyl cis-trans isomerase severely affect its structure, stability, shape and activity

    Directory of Open Access Journals (Sweden)

    Soumitra Polley

    2015-01-01

    Full Text Available FKBP22, an Escherichia coli-specific peptidyl-prolyl cis-trans isomerase, shows substantial homology with the Mip-like virulence factors. Mip-like proteins are homodimeric and possess a V-shaped conformation. Their N-terminal domains form dimers, whereas their C-terminal domains bind protein/peptide substrates and distinct inhibitors such as rapamycin and FK506. Interestingly, the two domains of the Mip-like proteins are separated by a lengthy, protease-susceptible α-helix. To delineate the structural requirement of this domain-connecting region in Mip-like proteins, we have investigated a recombinant FKBP22 (rFKBP22 and its three point mutants I65P, V72P and A82P using different probes. Each mutant harbors a Pro substitution mutation at a distinct location in the hinge region. We report that the three mutants are not only different from each other but also different from rFKBP22 in structure and activity. Unlike rFKBP22, the three mutants were unfolded by a non-two state mechanism in the presence of urea. In addition, the stabilities of the mutants, particularly I65P and V72P, differed considerably from that of rFKBP22. Conversely, the rapamycin binding affinity of no mutant was different from that of rFKBP22. Of the mutants, I65P showed the highest levels of structural/functional loss and dissociated partly in solution. Our computational study indicated a severe collapse of the V-shape in I65P due to the anomalous movement of its C-terminal domains. The α-helical nature of the domain-connecting region is, therefore, critical for the Mip-like proteins.

  13. Five and four dimensional experiments for robust backbone resonance assignment of large intrinsically disordered proteins: application to Tau3x protein

    International Nuclear Information System (INIS)

    Żerko, Szymon; Byrski, Piotr; Włodarczyk-Pruszyński, Paweł; Górka, Michał; Ledolter, Karin; Masliah, Eliezer; Konrat, Robert; Koźmiński, Wiktor

    2016-01-01

    New experiments dedicated for large IDPs backbone resonance assignment are presented. The most distinctive feature of all described techniques is the employment of MOCCA-XY16 mixing sequences to obtain effective magnetization transfers between carbonyl carbon backbone nuclei. The proposed 4 and 5 dimensional experiments provide a high dispersion of obtained signals making them suitable for use in the case of large IDPs (application to 354 a. a. residues of Tau protein 3x isoform is presented) as well as provide both forward and backward connectivities. What is more, connecting short chains interrupted with proline residues is also possible. All the experiments employ non-uniform sampling.

  14. Five and four dimensional experiments for robust backbone resonance assignment of large intrinsically disordered proteins: application to Tau3x protein

    Energy Technology Data Exchange (ETDEWEB)

    Żerko, Szymon; Byrski, Piotr; Włodarczyk-Pruszyński, Paweł; Górka, Michał [University of Warsaw, Faculty of Chemistry, Biological and Chemical Research Centre (Poland); Ledolter, Karin [University of Vienna, Department of Computational and Structural Biology, Max F. Perutz Laboratories (Austria); Masliah, Eliezer [University of California, San Diego, Departments of Neuroscience and Pathology (United States); Konrat, Robert [University of Vienna, Department of Computational and Structural Biology, Max F. Perutz Laboratories (Austria); Koźmiński, Wiktor, E-mail: kozmin@chem.uw.edu.pl [University of Warsaw, Faculty of Chemistry, Biological and Chemical Research Centre (Poland)

    2016-08-15

    New experiments dedicated for large IDPs backbone resonance assignment are presented. The most distinctive feature of all described techniques is the employment of MOCCA-XY16 mixing sequences to obtain effective magnetization transfers between carbonyl carbon backbone nuclei. The proposed 4 and 5 dimensional experiments provide a high dispersion of obtained signals making them suitable for use in the case of large IDPs (application to 354 a. a. residues of Tau protein 3x isoform is presented) as well as provide both forward and backward connectivities. What is more, connecting short chains interrupted with proline residues is also possible. All the experiments employ non-uniform sampling.

  15. Rice calcium-dependent protein kinase OsCPK17 targets plasma membrane intrinsic protein and sucrose phosphate synthase and is required for a proper cold stress response

    KAUST Repository

    Almadanim, M. Cecília

    2017-01-19

    Calcium-dependent protein kinases (CDPKs) are involved in plant tolerance mechanisms to abiotic stresses. Although CDPKs are recognized as key messengers in signal transduction, the specific role of most members of this family remains unknown. Here we test the hypothesis that OsCPK17 plays a role in rice cold stress response by analyzing OsCPK17 knockout, silencing, and overexpressing rice lines under low temperature. Altered OsCPK17 gene expression compromises cold tolerance performance, without affecting the expression of key cold stress-inducible genes. A comparative phosphoproteomic approach led to the identification of six potential in vivo OsCPK17 targets, which are associated with sugar and nitrogen metabolism, and with osmotic regulation. To test direct interaction, in vitro kinase assays were performed, showing that the sucrose phosphate synthase OsSPS4, and the aquaporin OsPIP2;1/OsPIP2;6 are phosphorylated by OsCPK17 in a calcium-dependent manner. Altogether, our data indicates that OsCPK17 is required for a proper cold stress response in rice, likely affecting the activity of membrane channels and sugar metabolism.

  16. MIPS Observations of the Fabulous Four Debris Disks

    Science.gov (United States)

    Su, K. Y. L.; Stansberry, J. A.; Rieke, G. H.; Trilling, D. E.; Stapelfeldt, K. R.; Werner, M. W.; Beichman, C.; Chen, C.; Marengo, M.; Megeath, T.; Backman, D.; van Cleve, J.

    2004-12-01

    The Multiband Imaging Photometer for Spitzer (MIPS) provides long-wavelength capability with imaging bands at 24, 70, and 160 um. We will present the MIPS images of the Fabulous Four Debris Disks: Beta Pictoris (A5 V), Epsilon Eridani (K2 V), Fomalhaut (A3 V) and Vega (A0 V). These systems discovered by IRAS possess large far-infrared excess emission above photosphere, indicating the existence of a circumstellar dusty disk. Given the main-sequence ages of these stars ( ˜12 Myr for Beta Pictoris, ˜730 Myr for Epsilon Eridani, ˜200 Myr for Fomalhaut, and ˜350 Myr for Vega), the dust in the systems could not be primordial as it would have been removed by radiation pressure and Poynting-Robertson drag on relatively short time scales ( ˜1E4 yr). The second-generation dust in such debris disks is thought to arise primarily from collisions between planetesimals (asteroids) and from cometary activity; however, details about the debris formation and evolution are not well understood. With the sensitivity and angular resolution of the Spitizer Space Telescope, the structures of these nearby debris disks were mapped in great detail to study the disks' spatial structures at mid- to far-infrared wavelengths. These high spatial resolution images provide unprecedented new constraints on the the dust properties in the systems and limits on the origin of dusty debris. Support for this work was provided by NASA through Contract Number 960785 issued by JPL/Caltech.

  17. Role of macrophage inflammatory protein-1alpha in T-cell-mediated immunity to viral infection

    DEFF Research Database (Denmark)

    Madsen, Andreas N; Nansen, Anneline; Christensen, Jan P

    2003-01-01

    The immune response to lymphocytic choriomeningitis virus in mice lacking macrophage inflammatory protein-1alpha (MIP-1alpha) was evaluated. Generation of virus-specific effector T cells is unimpaired in MIP-1alpha-deficient mice. Furthermore, MIP-1alpha is not required for T-cell-mediated virus...... control or virus-induced T-cell-dependent inflammation. Thus, MIP-1alpha is not mandatory for T-cell-mediated antiviral immunity....

  18. Legionella-protozoa-nematode interactions in aquatic biofilms and influence of Mip on Caenorhabditis elegans colonization.

    Science.gov (United States)

    Rasch, Janine; Krüger, Stefanie; Fontvieille, Dominique; Ünal, Can M; Michel, Rolf; Labrosse, Aurélie; Steinert, Michael

    2016-09-01

    Legionella pneumophila, the causative agent of Legionnaireś disease, is naturally found in aquatic habitats. The intracellular life cycle within protozoa pre-adapted the "accidental" human pathogen to also infect human professional phagocytes like alveolar macrophages. Previous studies employing the model organism Caenorhabditis elegans suggest that also nematodes might serve as a natural host for L. pneumophila. Here, we report for the first time from a natural co-habitation of L. pneumophila and environmental nematode species within biofilms of a warm water spring. In addition, we identified the protozoan species Oxytricha bifaria, Stylonychia mytilus, Ciliophrya sp. which have never been described as potential interaction partners of L. pneumophila before. Modeling and dissection of the Legionella-protozoa-nematode interaction revealed that C. elegans ruptures Legionella-infected amoebal cells and by this means incorporate the pathogen. Further infection studies revealed that the macrophage infectivity potentiator (Mip) protein of L. pneumophila, which is known to bind collagen IV during human lung infection, promotes the colonization of the intestinal tract of L4 larvae of C. elegans and negatively influences the life span of the worms. The Mip-negative L. pneumophila mutant exhibited a 32-fold reduced colonization rate of the nematodes after 48h when compared to the wild-type strain. Taken together, these studies suggest that nematodes may serve as natural hosts for L. pneumophila, promote their persistence and dissemination in the environment, and co-evolutionarily pre-adapt the pathogen for interactions with extracellular constituents of human lung tissue. Copyright © 2016 Elsevier GmbH. All rights reserved.

  19. Molecular Characterization of LRB7 Gene and a Water Channel Protein TIP2 in Chorispora bungeana

    Science.gov (United States)

    Liang, Zhaoxu; Di, Cuixia; Fang, Weikuan; Wu, Kaichao; Chen, Maoshan; He, Shanshan; Zeng, Yuan; Jing, Yan; Liang, Jun; Tan, Fang; Li, Song; Chen, Tuo; Liu, Guangxiu

    2016-01-01

    Background. Water channel proteins, also called aquaporins, are integral membrane proteins from major intrinsic protein (MIP) family and involved in several pathways including not only water transport but also cell signaling, reproduction, and photosynthesis. The full cDNA and protein sequences of aquaporin in Chorispora bungeana Fisch. & C.A. Mey (C. bungeana) are still unknown. Results. In this study, PCR and rapid amplification of cDNA ends approaches were used to clone the full cDNA of LRB7 (GenBank accession number: EU636988) of C. bungeana. Sequence analysis indicated that it was 1235 bp, which had two introns and encoded a protein of 250 amino acids. Structure analysis revealed that the protein had two conserved NPA motifs, one of which is MIP signature sequence (SGxHxNPAVT), six membrane helix regions, and additional membrane-embedded domains. Phylogenetic analysis suggested that the protein was from TIP2 subgroup. Surprisingly, semiquantitative RT-PCR experiment and western blot analysis showed that LRB7 and TIP2 were only detectable in roots, unlike Arabidopsis and Raphanus. Connecting with our previous studies, LRB7 was supported to associate with chilling-tolerance in C. bungeana. Conclusion. This is the first time to characterize the full sequences of LRB7 gene and water channel protein in C. bungeana. Our findings contribute to understanding the water transports in plants under low temperatures. PMID:27689074

  20. Molecular Characterization of LRB7 Gene and a Water Channel Protein TIP2 in Chorispora bungeana

    Directory of Open Access Journals (Sweden)

    Ming Li

    2016-01-01

    Full Text Available Background. Water channel proteins, also called aquaporins, are integral membrane proteins from major intrinsic protein (MIP family and involved in several pathways including not only water transport but also cell signaling, reproduction, and photosynthesis. The full cDNA and protein sequences of aquaporin in Chorispora bungeana Fisch. & C.A. Mey (C. bungeana are still unknown. Results. In this study, PCR and rapid amplification of cDNA ends approaches were used to clone the full cDNA of LRB7 (GenBank accession number: EU636988 of C. bungeana. Sequence analysis indicated that it was 1235 bp, which had two introns and encoded a protein of 250 amino acids. Structure analysis revealed that the protein had two conserved NPA motifs, one of which is MIP signature sequence (SGxHxNPAVT, six membrane helix regions, and additional membrane-embedded domains. Phylogenetic analysis suggested that the protein was from TIP2 subgroup. Surprisingly, semiquantitative RT-PCR experiment and western blot analysis showed that LRB7 and TIP2 were only detectable in roots, unlike Arabidopsis and Raphanus. Connecting with our previous studies, LRB7 was supported to associate with chilling-tolerance in C. bungeana. Conclusion. This is the first time to characterize the full sequences of LRB7 gene and water channel protein in C. bungeana. Our findings contribute to understanding the water transports in plants under low temperatures.

  1. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Overview and Progress

    Science.gov (United States)

    Rosenzweig, C.; Hatfield, J.; Jones, J. W.; Ruane, A. C.

    2012-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is an international effort to assess the state of global agricultural modeling and to understand climate impacts on the agricultural sector. AgMIP connects the climate science, crop modeling, and agricultural economic modeling communities to generate probabilistic projections of current and future climate impacts. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. This presentation will describe the general approach of AgMIP and highlight its findings and activities. AgMIP crop model intercomparisons have been established for wheat (27 models participating), maize (25 models), and rice (15+ models), and are being established for sugarcane, soybean, sorghum/millet, and peanut. In coordination with these pilots, methodologies to utilize weather generators and downscaled climate simulations for agricultural applications are under development. An AgMIP global agricultural economics model intercomparison with participation of 11 international groups is ongoing, and a number of global biophysical models are currently being evaluated for future climate impacts on agricultural lands both as part of the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) and for contribution to the IPCC Fifth Assessment Report (AR5). AgMIP is also organizing regional research efforts, and has already held workshops in South America, Sub-Saharan Africa, South Asia, Europe, and North America. Outcomes from these meetings have informed AgMIP activities, and 10 research teams from Sub-Saharan Africa and South Asia have been selected for project funding. Additional activities are planned for Australia and East Asia. As the AgMIP research community continues to work towards its goals, three key cross-cutting scientific challenges have emerged and are being

  2. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor

    DEFF Research Database (Denmark)

    Tran, E H; Kuziel, W A; Owens, T

    2000-01-01

    Macrophage inflammatory protein (MIP)-1alpha is a chemokine that is associated with Th1 cytokine responses. Expression and antibody blocking studies have implicated MIP-1alpha in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). We examined the role of MIP-1alpha...

  3. Household MIPS. Natural resource consumption of Finnish households and its reduction; KotiMIPS. Kotitalouksien luonnonvarojen kulutus ja sen pienentaeminen

    Energy Technology Data Exchange (ETDEWEB)

    Kotakorpi, E.; Laehteenoja, S.; Lettenmeier, M.

    2008-10-15

    In the study the natural resource consumption of 27 Finnish households was calculated using the MIPS method (Material Input per Service unit). The households monitored their consumption over a 6-week period in seven sub-sectors - housing, mobility, tourism, foodstuffs, household goods and appliances, leisure time activities, and packaging and household wastes. In the consumption monitoring only the households' direct consumption was taken into account and not consumption due to, e.g. public services. MIPS figures were calculated for five natural resource categories: abiotic natural resources, biotic natural resources, water, air and erosion. Service performance was expressed as kilograms per person per year. The calculation of natural resource consumption was based, to a large extent, on previously carried out sub-studies under the main FIN-MIPS study on households. The sub-studies focused on foodstuffs, leisure time activities, tourism, household goods and appliances, and construction. All the people participating in the study were interested in environmental matters to a greater extent than the average Finn. Nevertheless, the difference between the household consuming the most natural resources, and the one consuming the least, was approximately 10-fold. Especially in mobility and tourism there were appreciable differences between the households. The most material-intensive sub-sectors of consumption with reference to the households studied are housing, mobility and tourism. The TMR (total material requirement, i.e. abiotic and biotic natural resources and erosion combined) is approximately 10,000 kg/person per year. In the case of foodstuffs the average TMR per person per year is around 4,000 kg, in relation to household goods, for appliances about 2,000 kg, and for packaging and household waste management approximately 200 kg. The precise definition of each sub-sector in the study has an influence on the results. The ranking of the different sub-sectors of

  4. A New Effort for Atmospherical Forecast: Meteorological Image Processing Software (MIPS) for Astronomical Observations

    Science.gov (United States)

    Shameoni Niaei, M.; Kilic, Y.; Yildiran, B. E.; Yüzlükoglu, F.; Yesilyaprak, C.

    2016-12-01

    We have described a new software (MIPS) about the analysis and image processing of the meteorological satellite (Meteosat) data for an astronomical observatory. This software will be able to help to make some atmospherical forecast (cloud, humidity, rain) using meteosat data for robotic telescopes. MIPS uses a python library for Eumetsat data that aims to be completely open-source and licenced under GNU/General Public Licence (GPL). MIPS is a platform independent and uses h5py, numpy, and PIL with the general-purpose and high-level programming language Python and the QT framework.

  5. The Pliocene Model Intercomparison Project (PlioMIP) Phase 2: Scientific objectives and experimental design

    Science.gov (United States)

    Haywood, Alan M.; Dowsett, Harry J.; Dolan, Aisling M.; Rowley, David; Abe-Ouchi, Ayako; Otto-Bliesner, Bette; Chandler, Mark A.; Hunter, Stephen J.; Lunt, Daniel J.; Pound, Matthew; Salzmann, Ulrich

    2016-01-01

    The Pliocene Model Intercomparison Project (PlioMIP) is a co-ordinated international climate modelling initiative to study and understand climate and environments of the Late Pliocene, as well as their potential relevance in the context of future climate change. PlioMIP examines the consistency of model predictions in simulating Pliocene climate and their ability to reproduce climate signals preserved by geological climate archives. Here we provide a description of the aim and objectives of the next phase of the model intercomparison project (PlioMIP Phase 2), and we present the experimental design and boundary conditions that will be utilized for climate model experiments in Phase 2. 

  6. Plasma cytokines eotaxin, MIP-1α, MCP-4, and vascular endothelial growth factor in acute lower respiratory tract infection

    DEFF Research Database (Denmark)

    Relster, Mette Marie; Holm, Anette; Pedersen, Court

    2017-01-01

    ), monocyte chemoattractant protein 4 (MCP-4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI....... Patients were stratified according to etiology and severity of LRTI, based on baseline C-reactive protein and CURB-65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP-4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable...... the full potential of eotaxin, MCP-4, MIP-1α, and VEGF as biomarkers for LRTI because of their low predictive power and a high interindividual variation of cytokine levels....

  7. COHERENT MIP USING DUAL-TREE QUATERNION WAVELET TRANSFORM FOR GEOMETRIC IMAGE FEATURES

    OpenAIRE

    Nishant W. Labade*, Prof. Rajesh N. Patil

    2016-01-01

    In this paper, Coherent Multiscale Image Processing(C-MIP) technique is proposed alongwith an algorithm. Dual-Tree Quaternion Wavelet Transform (DT-QWT) is multiscale analysis tool for Geometric Image Features (GIF) of C-MIP. DT-QWT can be easily analysed using Dual Tree filter banks. For verification of properties of DT-QWT of an image, complete flow for searching and analysing geometrical structure is proposed. The proposed algorithm finds dissimilarity between two given images alongwith su...

  8. Molecularly imprinted polymer (MIP) membrane assisted direct spray ionization mass spectrometry for agrochemicals screening in foodstuffs.

    Science.gov (United States)

    Pereira, Igor; Rodrigues, Marcella Ferreira; Chaves, Andréa Rodrigues; Vaz, Boniek Gontijo

    2018-02-01

    Paper spray ionization (PSI) has some limitations such as low sensitivity and ionization suppression when complex samples are analyzed. The use of sample preparation devices directly coupled to MS can avoid these restrictions. Molecularly imprinted polymers (MIPs) are materials widely used as adsorbent in sample preparation methods such as solid-phase extraction and solid-phase microextraction, and they can provide specifics cavities with affinity to a target molecule. Here, we introduce a new MIP membrane spray ionization method combining MIP and PSI. MIP was synthesized directly on a cellulose membrane. Monuron and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) were used as template molecules in MIP synthesis for diuron and 2,4-D (2,4-dichlorophenoxyacetic acid) analyte sequesters, respectively. Apple, banana and grape methanolic extracts were used as matrices. The MIP membrane spray showed signal intensities of diuron and 2,4-D that were much higher compared to those obtained by non-imprinted polymers(NIP). Calibration curves exhibited R 2 > 0.99 for diuron and 2,4-D in all fruit extracts analyzed. LODs were found less than 0.60µgL -1 and LLOQs were found less than 2.00µgL -1 . The coefficients of variation and relative errors were less than 15% for almost all analyses. The apparent recovery test results ranged between 92,5% and 116.9%. Finally, the MIP membrane spray method was employed for the quantification of diuron and 2,4-D in real samples. Diuron contents were only found in three bananas (4.0, 6.5, and 9.9µgL -1 ). The proposed MIP membrane spray ionization method was straightforward, fast to carry out and provided satisfactory results for analyses of diuron and 2,4-D in apple, banana and grape samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. AgMIP: Next Generation Models and Assessments

    Science.gov (United States)

    Rosenzweig, C.

    2014-12-01

    Next steps in developing next-generation crop models fall into several categories: significant improvements in simulation of important crop processes and responses to stress; extension from simplified crop models to complex cropping systems models; and scaling up from site-based models to landscape, national, continental, and global scales. Crop processes that require major leaps in understanding and simulation in order to narrow uncertainties around how crops will respond to changing atmospheric conditions include genetics; carbon, temperature, water, and nitrogen; ozone; and nutrition. The field of crop modeling has been built on a single crop-by-crop approach. It is now time to create a new paradigm, moving from 'crop' to 'cropping system.' A first step is to set up the simulation technology so that modelers can rapidly incorporate multiple crops within fields, and multiple crops over time. Then the response of these more complex cropping systems can be tested under different sustainable intensification management strategies utilizing the updated simulation environments. Model improvements for diseases, pests, and weeds include developing process-based models for important diseases, frameworks for coupling air-borne diseases to crop models, gathering significantly more data on crop impacts, and enabling the evaluation of pest management strategies. Most smallholder farming in the world involves integrated crop-livestock systems that cannot be represented by crop modeling alone. Thus, next-generation cropping system models need to include key linkages to livestock. Livestock linkages to be incorporated include growth and productivity models for grasslands and rangelands as well as the usual annual crops. There are several approaches for scaling up, including use of gridded models and development of simpler quasi-empirical models for landscape-scale analysis. On the assessment side, AgMIP is leading a community process for coordinated contributions to IPCC AR6

  10. The MIVS [Modular Integrated Video System] Image Processing System (MIPS) for assisting in the optical surveillance data review process

    International Nuclear Information System (INIS)

    Horton, R.D.

    1990-01-01

    The MIVS (Modular Integrated Video System) Image Processing System (MIPS) is designed to review MIVS surveillance data automatically and identify IAEA defined objects of safeguards interest. To achieve this, MIPS uses both digital image processing and neural network techniques to detect objects of safeguards interest in an image and assist an inspector in the review of the MIVS video tapes. MIPS must be ''trained'' i.e., given example images showing the objects that it must recognize, for each different facility. Image processing techniques are used to first identify significantly changed areas of the image. A neural network is then used to determine if the image contains the important object(s). The MIPS algorithms have demonstrated the capability to detect when a spent fuel shipping cask is present in an image after MIPS is properly trained to detect the cask. The algorithms have also demonstrated the ability to reject uninteresting background activities such as people and crane movement. When MIPS detects an important object, the corresponding image is stored to another media and later replayed for the inspector to review. The MIPS algorithms are being implemented in commercially available hardware: an image processing subsystem and an 80386 Personal Computer. MIPS will have a high-level easy-to-use system interface to allow inspectors to train MIPS on MIVS data from different facilities and on various safeguards significant objects. This paper describes the MIPS algorithms, hardware implementation, and system configuration. 3 refs., 10 figs

  11. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Progress and Preliminary Results

    Science.gov (United States)

    Rosenzweig, C.

    2011-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a distributed climate-scenario simulation exercise for historical model intercomparison and future climate change conditions with participation of multiple crop and agricultural trade modeling groups around the world. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Recent progress and the current status of AgMIP will be presented, highlighting three areas of activity: preliminary results from crop pilot studies, outcomes from regional workshops, and emerging scientific challenges. AgMIP crop modeling efforts are being led by pilot studies, which have been established for wheat, maize, rice, and sugarcane. These crop-specific initiatives have proven instrumental in testing and contributing to AgMIP protocols, as well as creating preliminary results for aggregation and input to agricultural trade models. Regional workshops are being held to encourage collaborations and set research activities in motion for key agricultural areas. The first of these workshops was hosted by Embrapa and UNICAMP and held in Campinas, Brazil. Outcomes from this meeting have informed crop modeling research activities within South America, AgMIP protocols, and future regional workshops. Several scientific challenges have emerged and are currently being addressed by AgMIP researchers. Areas of particular interest include geospatial weather generation, ensemble methods for climate scenarios and crop models, spatial aggregation of field-scale yields to regional and global production, and characterization of future changes in climate variability.

  12. The development and implementation of MOSAIQ Integration Platform (MIP) based on the radiotherapy workflow

    Science.gov (United States)

    Yang, Xin; He, Zhen-yu; Jiang, Xiao-bo; Lin, Mao-sheng; Zhong, Ning-shan; Hu, Jiang; Qi, Zhen-yu; Bao, Yong; Li, Qiao-qiao; Li, Bao-yue; Hu, Lian-ying; Lin, Cheng-guang; Gao, Yuan-hong; Liu, Hui; Huang, Xiao-yan; Deng, Xiao-wu; Xia, Yun-fei; Liu, Meng-zhong; Sun, Ying

    2017-03-01

    To meet the special demands in China and the particular needs for the radiotherapy department, a MOSAIQ Integration Platform CHN (MIP) based on the workflow of radiation therapy (RT) has been developed, as a supplement system to the Elekta MOSAIQ. The MIP adopts C/S (client-server) structure mode, and its database is based on the Treatment Planning System (TPS) and MOSAIQ SQL Server 2008, running on the hospital local network. Five network servers, as a core hardware, supply data storage and network service based on the cloud services. The core software, using C# programming language, is developed based on Microsoft Visual Studio Platform. The MIP server could offer network service, including entry, query, statistics and print information for about 200 workstations at the same time. The MIP was implemented in the past one and a half years, and some practical patient-oriented functions were developed. And now the MIP is almost covering the whole workflow of radiation therapy. There are 15 function modules, such as: Notice, Appointment, Billing, Document Management (application/execution), System Management, and so on. By June of 2016, recorded data in the MIP are as following: 13546 patients, 13533 plan application, 15475 RT records, 14656 RT summaries, 567048 billing records and 506612 workload records, etc. The MIP based on the RT workflow has been successfully developed and clinically implemented with real-time performance, data security, stable operation. And it is demonstrated to be user-friendly and is proven to significantly improve the efficiency of the department. It is a key to facilitate the information sharing and department management. More functions can be added or modified for further enhancement its potentials in research and clinical practice.

  13. Merit-Based Incentive Payment System (MIPS): Harsh Choices For Interventional Pain Management Physicians.

    Science.gov (United States)

    Manchikanti, Laxmaiah; Helm Ii, Standiford; Benyamin, Ramsin M; Hirsch, Joshua A

    2016-01-01

    The Merit-based Incentive Payment System (MIPS) was created by the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to improve the health of all Americans by providing incentives and policies to improve patient health outcomes. MIPS combines 3 existing programs, Meaningful Use (MU), now called Advancing Care Information (ACI), contributing 25% of the composite score; Physician Quality Reporting System (PQRS), changed to Quality, contributing 50% of the composite score; and Value-based Payment (VBP) system to Resource Use or cost, contributing 10% of the composite score. Additionally, Clinical Practice Improvement Activities (CPIA), contributing 15% of the composite score, create multiple strategic goals to design incentives that drive movement toward delivery system reform principles with inclusion of Advanced Alternative Payment Models (APMs). Under the present proposal, the Centers for Medicare and Medicaid Services (CMS) has estimated approximately 30,000 to 90,000 providers from a total of over 761,000 providers will be exempt from MIPS. About 87% of solo practitioners and 70% of practitioners in groups of less than 10 will be subjected to negative payments or penalties ranging from 4% to 9%. In addition, MIPS also will affect a provider's reputation by making performance measures accessible to consumers and third-party physician rating Web sites.The MIPS composite performance scoring method, at least in theory, utilizes weights for each performance category, exceptional performance factors to earn bonuses, and incorporates the special circumstances of small practices.In conclusion, MIPS has the potential to affect practitioners negatively. Interventional Pain Medicine practitioners must understand the various MIPS measures and how they might participate in order to secure a brighter future. Medicare Access and CHIP Reauthorization Act of 2015, merit-based incentive payment system, quality performance measures, resource use, clinical practice

  14. Synthesis and Study of Guest-Rebinding of MIP Based on MAA Prepared using Theophylline Template

    Science.gov (United States)

    Nurhayati, T.; Yanti; Royani, I.; Widayani; Khairurrijal

    2016-08-01

    A molecularly imprinted polymer (MIP) based on methacrylic acid (MAA) monomer and theophylline template has been synthesized using a modified bulk polymerization method. Theophylline was employed as a template and it formed a complex with MAA through hydrogen bonding. Self-assembly of template-monomer was followed by cross-linking process using ethylene glycol dimethacrylate (EGDMA) cross-linker. The polymerization process was initiated by thermal decomposition of benzoyl peroxide (BPO) as the initiator at 60oC after cooling treatment at -5oC. After 7 hours, a rigid polymer was obtained and followed by grinding the polymer and removing the template. As a reference, a nonimprinted polymer (NIP) has also been synthesized using similar procedure by excluding the template. FTIR study was carried out to investigate the presence of theophylline in the as- prepared polymer, MIP, and NIP. The spectra indicated that theophylline was successfully incorporated in the as-prepared polymer. This result was also confirmed by EDS analysis showing that N atoms of the as-prepared polymer were derived from amino group of theophylline. Furthermore, the polymer particles of MIP were irregular in shape and size as shown by its SEM image. The capability of guest-rebinding of the MIP was analyzed through Batchwise guest-binding experiment. The results showed that for initial concentration of theophylline in methanol/chloroform (1/1, v/v) of 0.333 mM, the binding capacity of the MIP was 23.22 /mol/g. Compared to the MIP, the adsorption capacity of the NIP was only 3.73 /mol/g. This result shows that MIP has higher affinity than NIP.

  15. Effects of β-hydroxy-β-methylbutyrate free acid and cold water immersion on expression of CR3 and MIP-1β following resistance exercise.

    Science.gov (United States)

    Gonzalez, Adam M; Fragala, Maren S; Jajtner, Adam R; Townsend, Jeremy R; Wells, Adam J; Beyer, Kyle S; Boone, Carleigh H; Pruna, Gabriel J; Mangine, Gerald T; Bohner, Jonathan D; Fukuda, David H; Stout, Jeffrey R; Hoffman, Jay R

    2014-04-01

    The inflammatory response to muscle-damaging exercise requires monocyte mobilization and adhesion. Complement receptor type 3 (CR3) and macrophage inflammatory protein (MIP)-1β enables monocyte recruitment, adhesion, and subsequent infiltration into damaged muscle tissue. The purpose of this study was to examine the effects of cold water immersion (CWI) and/or β-hydroxy-β-methylbutyrate free acid (HMB-FA) on CR3 expression and MIP-1β concentration after four sets of up to 10 repetitions of squat, dead lift, and split squat exercises at 70-80% 1-repetition maximum. Thirty-nine resistance-trained men (22.2 ± 2.5 yr) were randomly divided into four groups: 1) placebo (PL), 2) HMB-FA, 3) HMB-FA-CWI, and 4) PL-CWI. The HMB-FA groups ingested 3 g/day, and CWI groups were submersed into 10-12°C water for 10 min after exercise. Blood was sampled at baseline (PRE), immediately post- (IP), 30 min post- (30P), 24 h post- (24P), and 48 h post (48P)-exercise. Circulating MIP-1β was assayed and CR3 expression on CD14+ monocytes was measured by flow cytometry. Without treatment, CR3 expression significantly elevated at 30P compared with other time points (P = 0.030-0.047). HMB-FA significantly elevated the percentage of monocytes expressing CR3 between IP and 24P (P = 0.046) and between IP and 48P (P = 0.046). No time effect was observed for MIP-1β concentration. The recovery modalities showed to attenuate the rise in CR3 following exercise. Additionally, supplementation with HMB-FA significantly elevated the percentage of monocytes expressing CR3 during recovery. Although the time course that inflammatory responses are most beneficial remains to be determined, recovery modalities may alter immune cell mobilization and adhesion mechanisms during tissue recovery.

  16. Intrinsic insulin secretion capacity might be preserved by discontinuing anti-programmed cell death protein 1 antibody treatment in 'anti-programmed cell death protein 1 antibody-induced' fulminant type 1 diabetes.

    Science.gov (United States)

    Sakai, Gota; Saito, Daigo; Nakajima, Ritsuko; Hatano, Masako; Noguchi, Yuichi; Kurihara, Susumu; Katayama, Shigehiro; Inoue, Ikuo; Noda, Mitsuhiko; Shimada, Akira

    2018-03-01

    Intrinsic insulin secretion capacity may be preserved by discontinuing anti-PD-1 antibody treatment in 'anti-PD-1 antibody-induced'fulminant type 1 diabetes. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  17. Intrinsically Disordered Enamel Matrix Protein Ameloblastin Forms Ribbon-like Supramolecular Structures via an N-terminal Segment Encoded by Exon 5

    Czech Academy of Sciences Publication Activity Database

    Wald, Tomáš; Osičková, Adriana; Šulc, Miroslav; Benada, Oldřich; Semerádtová, A.; Řežábková, Lenka; Veverka, Václav; Bednárová, Lucie; Malý, J.; Macek, Pavel; Šebo, Peter; Slabý, Ivan; Vondrášek, Jiří; Osička, Radim

    2013-01-01

    Roč. 288, č. 31 (2013), s. 22333-22345 ISSN 0021-9258 R&D Projects: GA ČR GAP302/10/0427 Institutional support: RVO:61388971 ; RVO:61388963 ; RVO:67985823 ; RVO:86652036 Keywords : Ameloblastin * Extracellular Matrix Proteins * Amelogenin Subject RIV: CE - Biochemistry; CE - Biochemistry (FGU-C) Impact factor: 4.600, year: 2013

  18. Intrinsic contractures of the hand.

    Science.gov (United States)

    Paksima, Nader; Besh, Basil R

    2012-02-01

    Contractures of the intrinsic muscles of the fingers disrupt the delicate and complex balance of intrinsic and extrinsic muscles, which allows the hand to be so versatile and functional. The loss of muscle function primarily affects the interphalangeal joints but also may affect etacarpophalangeal joints. The resulting clinical picture is often termed, intrinsic contracture or intrinsic-plus hand. Disruption of the balance between intrinsic and extrinsic muscles has many causes and may be secondary to changes within the intrinsic musculature or the tendon unit. This article reviews diagnosis, etiology, and treatment algorithms in the management of intrinsic contractures of the fingers. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Biomimetic polymers in analytical chemistry. Part 1: preparation and applications of MIP (Molecularly Imprinted Polymers) in extraction and separation techniques

    International Nuclear Information System (INIS)

    Tarley, Cesar Ricardo Teixeira; Sotomayor, Maria del Pilar Taboada; Kubota, Lauro Tatsuo

    2005-01-01

    MIPs are synthetic polymers that are used as biomimetic materials simulating the mechanism verified in natural entities such as antibodies and enzymes. Although MIPs have been successfully used as an outstanding tool for enhancing the selectivity or different analytical approaches, such as separation science and electrochemical and optical sensors, several parameters must be optimized during their synthesis. Therefore, the state-of-the-art of MIP production as well as the different polymerization methods are discussed. The potential selectivity of MIPs in the extraction and separation techniques focusing mainly on environmental, clinical and pharmaceutical samples as applications for analytical purposes is presented. (author)

  20. Predicting Intrinsic Motivation

    Science.gov (United States)

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the…

  1. BQP35 is a novel member of the intrinsically unstructured protein (IUP) family which is a potential antigen for the sero-diagnosis of Babesia sp. BQ1 (Lintan) infection.

    Science.gov (United States)

    Guan, Guiquan; Moreau, Emmanuelle; Liu, Junlong; Ma, Miling; Rogniaux, Hélène; Liu, Aihong; Niu, Qingli; Li, Youquan; Ren, Qiaoyun; Luo, Jianxun; Chauvin, Alain; Yin, Hong

    2012-07-06

    A new gene of Babesia sp. BQ1 (Lintan) (BQP35) was cloned by screening a merozoite cDNA expression library with infected sheep serum and using rapid amplification of cDNA ends (RACE). The nucleotide sequence of the cDNA was 1140bp with an open reading frame (ORF) of 936bp encoding a 35-kDa predicted polypeptide with 311 amino acid residues. Comparison of BQP35 cDNA and genomic DNA sequences showed that BQP35 does not possess an intron. Recombinant BQP35 (rBQP35), expressed in a prokaryotic expression system, showed abnormally slow migration on SDS-PAGE. Gel shifting, amino acid sequence and in silico disorder region prediction indicated that BQP35 protein has characteristics of intrinsically unstructured proteins (IUPs). This is the first description of such proteins in the Babesia genus. BQP35 induced antibodies production as early as one week after Babesia sp. BQ1 (Lintan) infection in sheep. No cross-reaction was observed with sera from sheep infected with other ovine piroplasms dominant in China, except with Babesia sp. Tianzhu. The interest of BQP35 as a diagnostic antigen is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Role of CC chemokines (macrophage inflammatory protein-1 beta, monocyte chemoattractant protein-1, RANTES) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Bless, N M; Huber-Lang, M; Guo, R F

    2000-01-01

    The role of the CC chemokines, macrophage inflammatory protein-1 beta (MIP-1 beta), monocyte chemotactic peptide-1 (MCP-1), and RANTES, in acute lung inflammatory injury induced by intrapulmonary deposition of IgG immune complexes injury in rats was determined. Rat MIP-1 beta, MCP-1, and RANTES w...

  3. Pliocene Model Intercomparison (PlioMIP) Phase 2: Scientific Objectives and Experimental Design

    Science.gov (United States)

    Haywood, A. M.; Dowsett, H. J.; Dolan, A. M.; Rowley, D.; Abe-Ouchi, A.; Otto-Bliesner, B.; Chandler, M. A.; Hunter, S. J.; Lunt, D. J.; Pound, M.; hide

    2015-01-01

    The Pliocene Model Intercomparison Project (PlioMIP) is a co-ordinated international climate modelling initiative to study and understand climate and environments of the Late Pliocene, and their potential relevance in the context of future climate change. PlioMIP operates under the umbrella of the Palaeoclimate Modelling Intercomparison Project (PMIP), which examines multiple intervals in Earth history, the consistency of model predictions in simulating these intervals and their ability to reproduce climate signals preserved in geological climate archives. This paper provides a thorough model intercomparison project description, and documents the experimental design in a detailed way. Specifically, this paper describes the experimental design and boundary conditions that will be utilized for the experiments in Phase 2 of PlioMIP.

  4. Molecular anatomy of CCR5 engagement by physiologic and viral chemokines and HIV-1 envelope glycoproteins: differences in primary structural requirements for RANTES, MIP-1 alpha, and vMIP-II Binding.

    Science.gov (United States)

    Navenot, J M; Wang, Z X; Trent, J O; Murray, J L; Hu, Q X; DeLeeuw, L; Moore, P S; Chang, Y; Peiper, S C

    2001-11-09

    Molecular analysis of CCR5, the cardinal coreceptor for HIV-1 infection, has implicated the N-terminal extracellular domain (N-ter) and regions vicinal to the second extracellular loop (ECL2) in this activity. It was shown that residues in the N-ter are necessary for binding of the physiologic ligands, RANTES (CCL5) and MIP-1 alpha (CCL3). vMIP-II, encoded by the Kaposi's sarcoma-associated herpesvirus, is a high affinity CCR5 antagonist, but lacks efficacy as a coreceptor inhibitor. Therefore, we compared the mechanism for engagement by vMIP-II of CCR5 to its interaction with physiologic ligands. RANTES, MIP-1 alpha, and vMIP-II bound CCR5 at high affinity, but demonstrated partial cross-competition. Characterization of 15 CCR5 alanine scanning mutants of charged extracellular amino acids revealed that alteration of acidic residues in the distal N-ter abrogated binding of RANTES, MIP-1 alpha, and vMIP-II. Whereas mutation of residues in ECL2 of CCR5 dramatically reduced the binding of RANTES and MIP-1 alpha and their ability to induce signaling, interaction with vMIP-II was not altered by any mutation in the exoloops of the receptor. Paradoxically, monoclonal antibodies to N-ter epitopes did not block chemokine binding, but those mapped to ECL2 were effective inhibitors. A CCR5 chimera with the distal N-ter residues of CXCR2 bound MIP-1 alpha and vMIP-II with an affinity similar to that of the wild-type receptor. Engagement of CCR5 by vMIP-II, but not RANTES or MIP-1 alpha blocked the binding of monoclonal antibodies to the receptor, providing additional evidence for a distinct mechanism for viral chemokine binding. Analysis of the coreceptor activity of randomly generated mouse-human CCR5 chimeras implicated residues in ECL2 between H173 and V197 in this function. RANTES, but not vMIP-II blocked CCR5 M-tropic coreceptor activity in the fusion assay. The insensitivity of vMIP-II binding to mutations in ECL2 provides a potential rationale to its inefficiency as an

  5. Actin filament-associated protein 1 (AFAP-1) is a key mediator in inflammatory signaling-induced rapid attenuation of intrinsic P-gp function in human brain capillary endothelial cells.

    Science.gov (United States)

    Hoshi, Yutaro; Uchida, Yasuo; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

    2017-04-01

    The purpose of this study was to identify regulatory molecule(s) involved in the inflammatory signaling-induced decrease in P-glycoprotein (P-gp) efflux function at the blood-brain barrier (BBB) that may occur in brain diseases. We confirmed that in vivo P-gp efflux activity at the BBB was decreased without any change in P-gp protein expression level in a mouse model of acute inflammation induced by 3 mg/kg lipopolysaccharide. In a human BBB model cell line (human brain capillary endothelial cells; hCMEC/D3), 1-h treatment with 10 ng/mL tumor necrosis factor-α (TNF-α; an inflammatory mediator) rapidly reduced P-gp efflux activity, but had no effect on P-gp protein expression level. To clarify the non-transcriptional mechanism that causes the decrease in intrinsic efflux activity of P-gp in acute inflammation, we applied comprehensive quantitative phosphoproteomics to compare hCMEC/D3 cells treated with TNF-α and vehicle (control). Actin filament-associated protein-1 (AFAP-1), MAPK1, and transcription factor AP-1 (AP-1) were significantly phosphorylated in TNF-α-treated cells, and were selected as candidate proteins. In validation experiments, knockdown of AFAP-1 expression blocked the reduction in P-gp efflux activity by TNF-α treatment, whereas inhibition of MAPK function or knockdown of AP-1 expression did not. Quantitative targeted absolute proteomics revealed that the reduction in P-gp activity by TNF-α did not require any change in P-gp protein expression levels in the plasma membrane. Our results demonstrate that AFAP-1 is a key mediator in the inflammatory signaling-induced, translocation-independent rapid attenuation of P-gp efflux activity in human brain capillary endothelial cells. © 2017 International Society for Neurochemistry.

  6. The Millon Index of Personality Styles Revised (MIPS-R) in Portugal: Gender Differences

    OpenAIRE

    Pires, Rute; Fagulha, Teresa; Silva, Danilo R.

    2007-01-01

    This study aims to determine whether males and females differ in the personality styles mesured with the Portuguese version of the Millon Index of Personality Styles Revised, MIPS-R (Millon, 2004). The MIPS-R is a 180-item, True/False inventory designed to measure personality styles of normally functioning adults between the ages of 18 and 65+. It is a theory-based inventory, grounded in biosocial and evolutionary theory, and comprises 12 pairs of scales organized into three main areas: Motiv...

  7. A chemometric analysis of ligand-induced changes in intrinsic fluorescence of folate binding protein indicates a link between altered conformational structure and physico-chemical characteristics

    DEFF Research Database (Denmark)

    Bruun, Susanne W; Holm, Jan; Hansen, Steen Ingemann

    2009-01-01

    Ligand binding alters the conformational structure and physico-chemical characteristics of bovine folate binding protein (FBP). For the purpose of achieving further information we analyzed ligand (folate and methotrexate)-induced changes in the fluorescence landscape of FBP. Fluorescence excitation...... of folate accords fairly well with the disappearance of strongly hydrophobic tryptophan residues from the solvent-exposed surface of FBP. The PARAFAC has thus proven useful to establish a hitherto unexplained link between parallel changes in conformational structure and physico-chemical characteristics...... of FBP induced by folate binding. Parameters for ligand binding derived from PARAFAC analysis of the fluorescence data were qualitatively and quantitatively similar to those obtained from binding of radiofolate to FBP. Herein, methotrexate exhibited a higher affinity for FBP than in competition...

  8. Intrinsic and Extrinsic Motivation

    OpenAIRE

    Roland Bénabou; Jean Tirole

    2003-01-01

    A central tenet of economics is that individuals respond to incentives. For psychologists and sociologists, in contrast, rewards and punishments are often counterproductive, because they undermine "intrinsic motivation". We reconcile these two views, showing how performance incentives offered by an informed principal (manager, teacher, parent) can adversely impact an agent's (worker, child) perception of the task, or of his own abilities. Incentives are then only weak reinforcers in the short...

  9. Attenuation of the ELAV1-like protein HuR sensitizes adenocarcinoma cells to the intrinsic apoptotic pathway by increasing the translation of caspase-2L.

    Science.gov (United States)

    Winkler, C; Doller, A; Imre, G; Badawi, A; Schmid, T; Schulz, S; Steinmeyer, N; Pfeilschifter, J; Rajalingam, K; Eberhardt, W

    2014-07-10

    Caspase-2 represents the most conserved member of the caspase family, which exhibits features of both initiator and effector caspases. Using ribonucleoprotein (RNP)-immunoprecipitation assay, we identified the proapoptotic caspase-2L encoding mRNA as a novel target of the ubiquitous RNA-binding protein HuR in DLD-1 colon carcinoma cells. Unexpectedly, crosslinking-RNP and RNA probe pull-down experiments revealed that HuR binds exclusively to the caspase-2-5' untranslated region (UTR) despite that the 3' UTR of the mRNA bears several adenylate- and uridylate-rich elements representing the prototypical HuR binding sites. By using RNAi-mediated loss-of-function approach, we observed that HuR regulates the mRNA and in turn the protein levels of caspase-2 in a negative manner. Silencing of HuR did not affect the stability of caspase-2 mRNA but resulted in an increased redistribution of caspase-2 transcripts from RNP particles to translational active polysomes implicating that HuR exerts a direct repressive effect on caspase-2 translation. Consistently, in vitro translation of a luciferase reporter gene under the control of an upstream caspase-2-5'UTR was strongly impaired after the addition of recombinant HuR, whereas translation of caspase-2 coding region without the 5'UTR is not affected by HuR confirming the functional role of the caspase-2-5'UTR. Functionally, an elevation in caspase-2 level by HuR knockdown correlated with an increased sensitivity of cells to apoptosis induced by staurosporine- and pore-forming toxins as implicated by their significant accumulation in the sub G1 phase and an increase in caspase-2, -3 and poly ADP-ribose polymerase cleavage, respectively. Importantly, HuR knockdown cells remained insensitive toward STS-induced apoptosis if cells were additionally transfected with caspase-2-specific siRNAs. Collectively, our findings support the hypothesis that HuR by acting as an endogenous inhibitor of caspase-2-driven apoptosis may essentially

  10. The IntFOLD server: an integrated web resource for protein fold recognition, 3D model quality assessment, intrinsic disorder prediction, domain prediction and ligand binding site prediction.

    Science.gov (United States)

    Roche, Daniel B; Buenavista, Maria T; Tetchner, Stuart J; McGuffin, Liam J

    2011-07-01

    The IntFOLD server is a novel independent server that integrates several cutting edge methods for the prediction of structure and function from sequence. Our guiding principles behind the server development were as follows: (i) to provide a simple unified resource that makes our prediction software accessible to all and (ii) to produce integrated output for predictions that can be easily interpreted. The output for predictions is presented as a simple table that summarizes all results graphically via plots and annotated 3D models. The raw machine readable data files for each set of predictions are also provided for developers, which comply with the Critical Assessment of Methods for Protein Structure Prediction (CASP) data standards. The server comprises an integrated suite of five novel methods: nFOLD4, for tertiary structure prediction; ModFOLD 3.0, for model quality assessment; DISOclust 2.0, for disorder prediction; DomFOLD 2.0 for domain prediction; and FunFOLD 1.0, for ligand binding site prediction. Predictions from the IntFOLD server were found to be competitive in several categories in the recent CASP9 experiment. The IntFOLD server is available at the following web site: http://www.reading.ac.uk/bioinf/IntFOLD/.

  11. Comparing projections of future changes in runoff from hydrological and biome models in ISI-MIP

    NARCIS (Netherlands)

    Davie, J. C. S.; Falloon, P. D.; Kahana, R.; Dankers, R.; Betts, R.; Portmann, F. T.; Wisser, D.; Clark, D. B.; Ito, A.; Masaki, Y.; Nishina, K.; Fekete, B.; Tessler, Z.; Wada, Y.; Liu, X.; Tang, Q.; Hagemann, S.; Stacke, T.; Pavlick, R.; Schaphoff, S.; Gosling, S. N.; Franssen, W.; Arnell, N.

    2013-01-01

    Future changes in runoff can have important implications for water resources and flooding. In this study, runoff projections from ISI-MIP (Inter-sectoral Impact Model Intercomparison Project) simulations forced with HadGEM2-ES bias-corrected climate data under the Representative Concentration

  12. Comparing projections of future changes in runoff from hydrological and biome models in ISI-MIP

    NARCIS (Netherlands)

    Davie, J.C.S.; Falloon, P.D.; Kahana, R.; Dankers, R.; Betts, R.; Portmann, F.T.; Wisser, D.; Clark, D.B.; Ito, A.; Masaki, Y.; Nishina, K.; Fekete, B.; Tessler, Z.; Wada, Y.; Liu, X.; Tang, Q.; Hagemann, S.; Stacke, T.; Pavlick, R.; Schaphoff, S.; Gosling, S.N.; Franssen, W.H.P.; Arnell, N.

    2013-01-01

    Future changes in runoff can have important implications for water resources and flooding. In this study, runoff projections from ISI-MIP (Inter-sectoral Impact Model Inter-comparison Project) simulations forced with HadGEM2-ES bias-corrected climate data under the Representative Concentration

  13. Magnetically separable polymer (Mag-MIP) for selective analysis of biotin in food samples.

    Science.gov (United States)

    Uzuriaga-Sánchez, Rosario Josefina; Khan, Sabir; Wong, Ademar; Picasso, Gino; Pividori, Maria Isabel; Sotomayor, Maria Del Pilar Taboada

    2016-01-01

    This work presents an efficient method for the preparation of magnetic nanoparticles modified with molecularly imprinted polymers (Mag-MIP) through core-shell method for the determination of biotin in milk food samples. The functional monomer acrylic acid was selected from molecular modeling, EGDMA was used as cross-linking monomer and AIBN as radical initiator. The Mag-MIP and Mag-NIP were characterized by FTIR, magnetic hysteresis, XRD, SEM and N2-sorption measurements. The capacity of Mag-MIP for biotin adsorption, its kinetics and selectivity were studied in detail. The adsorption data was well described by Freundlich isotherm model with adsorption equilibrium constant (KF) of 1.46 mL g(-1). The selectivity experiments revealed that prepared Mag-MIP had higher selectivity toward biotin compared to other molecules with different chemical structure. The material was successfully applied for the determination of biotin in diverse milk samples using HPLC for quantification of the analyte, obtaining the mean value of 87.4% recovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Protocols and pilot studies

    NARCIS (Netherlands)

    Rosenzweig, C.; Jones, W.; Hatfield, J.L.; Ruane, A.C.; Boote, K.J.; Thorburn, P.; Antle, J.M.; Nelson, G.C.; Porter, C.; Janssen, S.J.C.; Asseng, S.; Basso, B.; Ewert, F.; Wallach, D.; Baigorria, G.; Winter, J.M.

    2013-01-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a major international effort linking the climate, crop, and economic modeling communities with cutting-edge information technology to produce improved crop and economic models and the next generation of climate impact

  15. Intrinsic and extrinsic mortality reunited

    DEFF Research Database (Denmark)

    Koopman, Jacob J E; Wensink, Maarten J; Rozing, Maarten P

    2015-01-01

    Intrinsic and extrinsic mortality are often separated in order to understand and measure aging. Intrinsic mortality is assumed to be a result of aging and to increase over age, whereas extrinsic mortality is assumed to be a result of environmental hazards and be constant over age. However......, allegedly intrinsic and extrinsic mortality have an exponentially increasing age pattern in common. Theories of aging assert that a combination of intrinsic and extrinsic stressors underlies the increasing risk of death. Epidemiological and biological data support that the control of intrinsic as well...... as extrinsic stressors can alleviate the aging process. We argue that aging and death can be better explained by the interaction of intrinsic and extrinsic stressors than by classifying mortality itself as being either intrinsic or extrinsic. Recognition of the tight interaction between intrinsic and extrinsic...

  16. Cell intrinsic control of axon regeneration

    Science.gov (United States)

    Mar, Fernando M; Bonni, Azad; Sousa, Mónica M

    2014-01-01

    Although neurons execute a cell intrinsic program of axonal growth during development, following the establishment of connections, the developmental growth capacity declines. Besides environmental challenges, this switch largely accounts for the failure of adult central nervous system (CNS) axons to regenerate. Here, we discuss the cell intrinsic control of axon regeneration, including not only the regulation of transcriptional and epigenetic mechanisms, but also the modulation of local protein translation, retrograde and anterograde axonal transport, and microtubule dynamics. We further explore the causes underlying the failure of CNS neurons to mount a vigorous regenerative response, and the paradigms demonstrating the activation of cell intrinsic axon growth programs. Finally, we present potential mechanisms to support axon regeneration, as these may represent future therapeutic approaches to promote recovery following CNS injury and disease. PMID:24531721

  17. High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuker; Carlton, Victoria E.H.; Karlin-Neumann, George; Sapolsky, Ronald; Zhang, Li; Moorhead, Martin; Wang, Zhigang C.; Richardson, Andrea L.; Warren, Robert; Walther, Axel; Bondy, Melissa; Sahin, Aysegul; Krahe, Ralf; Tuna, Musaffe; Thompson, Patricia A.; Spellman, Paul T.; Gray, Joe W.; Mills, Gordon B.; Faham, Malek

    2009-02-24

    A major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small ({approx}40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE. MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

  18. The Pliocene Model Intercomparison Project (PlioMIP) Phase 2: Scientific Objectives and Experimental Design

    Science.gov (United States)

    Haywood, Alan M.; Dowsett, Harry J.; Dolan, Aisling M.; Rowley, David; Abe-Ouchi, Ayako; Otto-Bliesner, Bette; Chandler, Mark A.; Hunter, Stephen J.; Lunt, Daniel J.; Pound, Matthew; hide

    2016-01-01

    The Pliocene Model Intercomparison Project (PlioMIP) is a co-ordinated international climate modelling initiative to study and understand climate and environments of the Late Pliocene, as well as their potential relevance in the context of future climate change. PlioMIP examines the consistency of model predictions in simulating Pliocene climate and their ability to reproduce climate signals preserved by geological climate archives. Here we provide a description of the aim and objectives of the next phase of the model intercomparison project (PlioMIP Phase 2), and we present the experimental design and boundary conditions that will be utilized for climate model experiments in Phase 2. Following on from PlioMIP Phase 1, Phase 2 will continue to be a mechanism for sampling structural uncertainty within climate models. However, Phase 1 demonstrated the requirement to better understand boundary condition uncertainties as well as uncertainty in the methodologies used for data-model comparison. Therefore, our strategy for Phase 2 is to utilize state-of-the-art boundary conditions that have emerged over the last 5 years. These include a new palaeogeographic reconstruction, detailing ocean bathymetry and land-ice surface topography. The ice surface topography is built upon the lessons learned from offline ice sheet modelling studies. Land surface cover has been enhanced by recent additions of Pliocene soils and lakes. Atmospheric reconstructions of palaeo-CO2 are emerging on orbital timescales, and these are also incorporated into PlioMIP Phase 2. New records of surface and sea surface temperature change are being produced that will be more temporally consistent with the boundary conditions and forcings used within models. Finally we have designed a suite of prioritized experiments that tackle issues surrounding the basic understanding of the Pliocene and its relevance in the context of future climate change in a discrete way.

  19. The Multi-Isotope Process (MIP) Monitor Project: FY12 Progress and Accomplishments

    Energy Technology Data Exchange (ETDEWEB)

    Coble, Jamie B.; Orton, Christopher R.; Jordan, David V.; Schwantes, Jon M.; Bender, Sarah; Dayman, Kenneth J.; Unlu, Kenan; Landsberger, Sheldon

    2012-09-27

    The Multi-Isotope Process (MIP) Monitor, being developed at Pacific Northwest National Laboratory (PNNL), provides an efficient approach to monitoring the process conditions in reprocessing facilities in support of the goal of "...(minimization of) the risks of nuclear proliferation and terrorism." The MIP Monitor measures distributions of a suite of indicator (radioactive) isotopes present within product and waste streams of a nuclear reprocessing facility. These indicator isotopes are monitored on-line by gamma spectrometry and compared, in near-real-time, to spectral patterns representing "normal" process conditions using multivariate pattern recognition software. The monitor utilizes this multivariate analysis and gamma spectroscopy of reprocessing streams to detect small changes in the gamma spectrum, which may indicate changes in process conditions. Multivariate analysis methods common in chemometrics, such as principal component analysis (PCA) and partial least squares regression (PLS), act as pattern recognition techniques, which can detect small deviations from the expected, nominal condition. By targeting multiple gamma-emitting indicator isotopes, the MIP Monitor approach is compatible with the use of small, portable, relatively high-resolution gamma detectors that may be easily deployed throughout an existing facility. The automated multivariate analysis can provide a level of data obscurity, giving a built-in information barrier to protect sensitive or proprietary operational data. Proof-of-concept simulations and experiments have been performed in previous years to demonstrate the validity of this tool in a laboratory setting. Development of the MIP Monitor approach continues to evaluate the efficacy of the monitor for automated, real-time or near-real-time application. This report details follow-on research and development efforts sponsored by the U.S. Department of Energy Fuel Cycle Research and Development related to the MIP Monitor for fiscal year

  20. The Agriculture Model Intercomparison and Improvement Project (AgMIP) (Invited)

    Science.gov (United States)

    Rosenzweig, C.

    2010-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a distributed climate-scenario simulation exercise for historical model intercomparison and future climate change conditions with participation of multiple crop and world agricultural trade modeling groups around the world. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Historical period results will spur model improvement and interaction among major modeling groups, while future period results will lead directly to tests of adaptation and mitigation strategies across a range of scales. AgMIP will consist of a multi-scale impact assessment utilizing the latest methods for climate and agricultural scenario generation. Scenarios and modeling protocols will be distributed on the web, and multi-model results will be collated and analyzed to ensure the widest possible coverage of agricultural crops and regions. AgMIP will place regional changes in agricultural production in a global context that reflects new trading opportunities, imbalances, and shortages in world markets resulting from climate change and other driving forces for food supply. Such projections are essential inputs from the Vulnerability, Impacts, and Adaptation (VIA) research community to the Intergovernmental Panel on Climate Change Fifth Assessment (AR5), now underway, and the UN Framework Convention on Climate Change. They will set the context for local-scale vulnerability and adaptation studies, supply test scenarios for national-scale development of trade policy instruments, provide critical information on changing supply and demand for water resources, and elucidate interactive effects of climate change and land use change. AgMIP will not only provide crucially-needed new global estimates of how climate change will affect food supply and hunger in the

  1. High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP microarrays

    Directory of Open Access Journals (Sweden)

    Bondy Melissa

    2009-02-01

    Full Text Available Abstract Background A major challenge facing DNA copy number (CN studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE. DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (~40 bp target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue. Results Using an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%, with only a modest loss in performance in FFPE. Conclusion MIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.

  2. Myocardial Ablation of G Protein-Coupled Receptor Kinase 2 (GRK2 Decreases Ischemia/Reperfusion Injury through an Anti-Intrinsic Apoptotic Pathway.

    Directory of Open Access Journals (Sweden)

    Qian Fan

    Full Text Available Studies from our lab have shown that decreasing myocardial G protein-coupled receptor kinase 2 (GRK2 activity and expression can prevent heart failure progression after myocardial infarction. Since GRK2 appears to also act as a pro-death kinase in myocytes, we investigated the effect of cardiomyocyte-specific GRK2 ablation on the acute response to cardiac ischemia/reperfusion (I/R injury. To do this we utilized two independent lines of GRK2 knockout (KO mice where the GRK2 gene was deleted in only cardiomyocytes either constitutively at birth or in an inducible manner that occurred in adult mice prior to I/R. These GRK2 KO mice and appropriate control mice were subjected to a sham procedure or 30 min of myocardial ischemia via coronary artery ligation followed by 24 hrs reperfusion. Echocardiography and hemodynamic measurements showed significantly improved post-I/R cardiac function in both GRK2 KO lines, which correlated with smaller infarct sizes in GRK2 KO mice compared to controls. Moreover, there was significantly less TUNEL positive myocytes, less caspase-3, and -9 but not caspase-8 activities in GRK2 KO mice compared to control mice after I/R injury. Of note, we found that lowering cardiac GRK2 expression was associated with significantly lower cytosolic cytochrome C levels in both lines of GRK2 KO mice after I/R compared to corresponding control animals. Mechanistically, the anti-apoptotic effects of lowering GRK2 expression were accompanied by increased levels of Bcl-2, Bcl-xl, and increased activation of Akt after I/R injury. These findings were reproduced in vitro in cultured cardiomyocytes and GRK2 mRNA silencing. Therefore, lowering GRK2 expression in cardiomyocytes limits I/R-induced injury and improves post-ischemia recovery by decreasing myocyte apoptosis at least partially via Akt/Bcl-2 mediated mitochondrial protection and implicates mitochondrial-dependent actions, solidifying GRK2 as a pro-death kinase in the heart.

  3. Intrinsically Disordered Side of the Zika Virus Proteome

    Directory of Open Access Journals (Sweden)

    Rajanish Giri

    2016-11-01

    Full Text Available Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766. Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs and this finding is consistent with previous reports on the involvement of IDPs in shell formation and virulence of the Flaviviridae family. We found abundant IDPRs in Capsid, NS2B, NS3, NS4A, and NS5 proteins that are involved in mature particle formation and replication. In our view, the intrinsic disorder-focused analysis of ZIKV proteins could be important for the development of new disorder-based drugs.

  4. Three-Dimensional Conformal Radiotherapy in Prostate Cancer Patients: Rise in Interleukin 6 (IL-6) but not IL-2, IL-4, IL-5, Tumor Necrosis Factor-{alpha}, MIP-1-{alpha}, and LIF Levels

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira Lopes, Carlos [Universidade do Vale do Paraiba, Centro de Oncologia Radioterapica do Vale do Paraiba, Universidade do Vale do Paraiba Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba, Sao Jose dos Campos, Sao Paulo (Brazil); Callera, Fernando, E-mail: fcallera@gmail.com [Centro de Hematologia Onco-hematologia e Transplantes de Medula Ossea do Vale do Paraiba, Sao Paulo (Brazil)

    2012-03-15

    Purpose: To investigate the effect of radiotherapy (RT) on serum levels of interleukin-2 (IL-2), IL-4, IL-5, IL-6, tumor necrosis factor alpha (TNF-{alpha}), macrophage inflammatory protein-1-alpha (MIP-1-{alpha}) and leukemia inhibitory factor (LIF) in patients with prostate cancer. Methods and Materials: Forty eight patients with prostate cancer received three-dimensional conformal blocking radiation therapy with a linear accelerator. IL-2, IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were measured by the related immunoassay kit 1 day before the beginning of RT and during RT at days 15 and 30. Results: The mean IL-2 values were elevated before and during the RT in contrast with those of IL-4, IL-5, IL-6, TNF-{alpha}, MIP-1-{alpha}, and LIF, which were within the normal range under the same conditions. Regarding markers IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF, comparisons among the three groups (before treatment and 15 and 30 days during RT) did not show significant differences. Although values were within the normal range, there was a significant rise in IL-6 levels at day 15 of RT (p = 0.0049) and a decline at day 30 to levels that were similar to those observed before RT. Conclusions: IL-6 appeared to peak after 15 days of RT before returning to pre-RT levels. In contrast, IL-2, IL-4, IL-5, TNF-{alpha}, MIP-1-{alpha}, and LIF levels were not sensitive to irradiation. The increased levels of IL-6 following RT without the concurrent elevation of other cytokines involved in the acute phase reaction did not suggest a classical inflammatory response to radiation exposure. Further studies should be designed to elucidate the role of IL-6 levels in patients with prostate cancer treated with RT.

  5. Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

    OpenAIRE

    Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.; Christodoulides, Myron

    2014-01-01

    A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human protein...

  6. New Results from the Geoengineering Model Intercomparison Project (GeoMIP)

    Science.gov (United States)

    Robock, A.; Kravitz, B.

    2013-12-01

    The Geoengineering Model Intercomparison Project (GeoMIP) was designed to determine robust climate system model responses to Solar Radiation Management (SRM). While mitigation (reducing greenhouse gases emissions) is the most effective way of reducing future climate change, SRM (the deliberate modification of incoming solar radiation) has been proposed as a means of temporarily alleviating some of the effects of global warming. For society to make informed decisions as to whether SRM should ever be implemented, information is needed on the benefits, risks, and side effects, and GeoMIP seeks to aid in that endeavor. GeoMIP has organized four standardized climate model simulations involving reduction of insolation or increased amounts of stratospheric sulfate aerosols to counteract increasing greenhouse gases. Thirteen comprehensive atmosphere-ocean general circulation models have participated in the project so far. GeoMIP is a 'CMIP Coordinated Experiment' as part of the Climate Model Intercomparison Project 5 (CMIP5) and has been endorsed by SPARC (Stratosphere-troposphere Processes And their Role in Climate). GeoMIP has held three international workshops and has produced a number of recent journal articles. GeoMIP has found that if increasing greenhouse gases could be counteracted with insolation reduction, the global average temperature could be kept constant, but global average precipitation would reduce, particularly in summer monsoon regions around the world. Temperature changes would also not be uniform. The tropics would cool, but high latitudes would warm, with continuing, but reduced sea ice and ice sheet melting. Temperature extremes would still increase, but not as much as without SRM. If SRM were halted all at once, there would be rapid temperature and precipitation increases at 5-10 times the rates from gradual global warming. SRM combined with CO2 fertilization would have small impacts on rice production in China, but would increase maize production

  7. A cross-sectional study: serum CCL3/MIP-1α levels may reflect lumbar intervertebral disk degeneration in Han Chinese people

    Directory of Open Access Journals (Sweden)

    Zhang YL

    2018-03-01

    Full Text Available Yi-Li Zhang,1,2,* Bei Li,1,2,* Zeng-Huan Zhou1 1School of Public Health, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 2School of Health Services Management, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Background: The macrophage inflammatory protein-1α (MIP-1α, also named chemokine cytokine ligand 3 (CCL3, has been detected in nucleus pulposus and increased following cytokine stimulation. Objective: The current study was performed to explore the relationship between serum CCL3/MIP-1α levels with lumbar intervertebral disk degeneration (IDD. Patients and methods: A total of 132 disk degeneration patients confirmed by magnetic resonance imaging and 126 healthy controls were enrolled in the current study. Radiological evaluation of the IDD was conducted using a 3.0-T magnetic resonance imaging scanner for entire lumbar vertebra region. Degeneration of intervertebral disk was assessed by Schneiderman criteria. Serum CCL3/MIP-1α levels were investigated using a sandwich enzyme-linked immunosorbent assay. The Visual Analog Scale scores and Oswestry Disability Index index were recorded for clinical severity. Results: Elevated concentrations of CCL3 in serum were found in IDD patients compared with asymptomatic volunteers. The case group included 49 IDD patients with grade 1, 42 with grade 2, and 41 with grade 3. Grade 3 and 2 had significantly higher CCL3 concentrations in serum compared with those with grade 1. The serum CCL3 levels were positively related to the degree of disk degeneration. In addition, the serum CCL3 levels also demonstrated a significant correlation with the clinical severity determined by Visual Analog Scale scores and Oswestry Disability Index index. Conclusion: Serum CCL3 may serve as a biomarker of IDD. Keywords: chemokine cytokine ligand 3, intervertebral disk degeneration, cross

  8. How do Proteins Misfold and Aggregate?

    Indian Academy of Sciences (India)

    samrat

    Brain. Alzheimer's disease. Intrinsically disordered. Tau protein. Brain. Transmissible spongiform encephalopathy α-helical. Prion protein. Protein deposit. Disease. Type of structure. Amyloido- genic proteins. Skin & muscle. Injection-localized amyloidosis. Largely α - helical. Insulin. Brain. Parkinson's disease. Intrinsically.

  9. Role of microProteins in controlling diverse biological pathways

    DEFF Research Database (Denmark)

    Dolde, Ulla Margrit

    a synthetic microProtein approach, we demonstrate that microProteins are able to regulate multi-domain proteins belonging to different protein classes. Furthermore, these results revealed that microProteins may provide a useful tool for post-translational regulation due to their role in protein regulation....... orthologous microProteins, miP1a and miP1b were identified using a computational analysis. MiP1a and miP1b are small B-Box containing proteins that interact with and negatively regulate CONSTANS (CO), a major regulator of flowering in Arabidopsis thaliana. They are known to be the first micro...... T (FT) expression. In agreement with the late flowering of overexpression plants, loss-of-function mutants of both miP1a and miP1b, generated using CRISPR/Cas9 genome engineering, showed also a slightly early flowering phenotype. In a forward genetic screen using transgenic plants overexpressing mi...

  10. Appendix 2. Guide for Running AgMIP Climate Scenario Generation Tools with R in Windows, Version 2.3

    Science.gov (United States)

    Hudson, Nicholas; Ruane, Alexander Clark

    2013-01-01

    This Guide explains how to create climate series and climate change scenarios by using the AgMip Climate team's methodology as outlined in the AgMIP Guide for Regional Assessment: Handbook of Methods and Procedures. It details how to: install R and the required packages to run the AgMIP Climate Scenario Generation scripts, and create climate scenarios from CMIP5 GCMs using a 30-year baseline daily weather dataset. The Guide also outlines a workflow that can be modified for application to your own climate data.

  11. MicroProtein-mediated recruitment of CONSTANS into a TOPLESS trimeric complex represses flowering in Arabidopsis

    DEFF Research Database (Denmark)

    Graeff, Moritz; Straub, Daniel; Eguen, Tenai E.

    2016-01-01

    Arabidopsis thaliana microProteins, miP1a and miP1b, physically interact with CONSTANS (CO) a potent regulator of flowering time. The miP1a/b-type microProteins evolved in dicotyledonous plants and have an additional carboxy-terminal PF(V/L)FL motif. This motif enables miP1a/b microProteins to interact......MicroProteins are short, single domain proteins that act by sequestering larger, multi-domain proteins into non-functional complexes. MicroProteins have been identified in plants and animals, where they are mostly involved in the regulation of developmental processes. Here we show that two...... with TOPLESS/TOPLESS-RELATED (TPL/TPR) proteins. Interaction of CO with miP1a/b/TPL causes late flowering due to a failure in the induction of FLOWERING LOCUS T (FT) expression under inductive long day conditions. Both miP1a and miP1b are expressed in vascular tissue, where CO and FT are active. Genetically...

  12. Role for macrophage inflammatory protein-2 in lipopolysaccharide-induced lung injury in rats

    DEFF Research Database (Denmark)

    Schmal, H; Shanley, T P; Jones, M L

    1996-01-01

    Macrophage inflammatory protein-2 (MIP-2) is a C-X-C chemokine that possesses chemotactic activity for neutrophils. Rat MIP-2 was cloned and expressed as a 7.9-kDa peptide that exhibited dose-dependent neutrophil chemotactic activity at concentrations from 10 to 250 nM. Rabbit polyclonal Ab...

  13. A spatial mean-variance MIP model for energy market risk analysis

    International Nuclear Information System (INIS)

    Yu, Zuwei

    2003-01-01

    The paper presents a short-term market risk model based on the Markowitz mean-variance method for spatial electricity markets. The spatial nature is captured using the correlation of geographically separated markets and the consideration of wheeling administration. The model also includes transaction costs and other practical constraints, resulting in a mixed integer programming (MIP) model. The incorporation of those practical constraints makes the model more attractive than the traditional Markowitz portfolio model with continuity. A case study is used to illustrate the practical application of the model. The results show that the MIP portfolio efficient frontier is neither smooth nor concave. The paper also considers the possible extension of the model to other energy markets, including natural gas and oil markets

  14. A spatial mean-variance MIP model for energy market risk analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zuwei Yu [Purdue University, West Lafayette, IN (United States). Indiana State Utility Forecasting Group and School of Industrial Engineering

    2003-05-01

    The paper presents a short-term market risk model based on the Markowitz mean-variance method for spatial electricity markets. The spatial nature is captured using the correlation of geographically separated markets and the consideration of wheeling administration. The model also includes transaction costs and other practical constraints, resulting in a mixed integer programming (MIP) model. The incorporation of those practical constraints makes the model more attractive than the traditional Markowitz portfolio model with continuity. A case study is used to illustrate the practical application of the model. The results show that the MIP portfolio efficient frontier is neither smooth nor concave. The paper also considers the possible extension of the model to other energy markets, including natural gas and oil markets. (author)

  15. A spatial mean-variance MIP model for energy market risk analysis

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zuwei [Indiana State Utility Forecasting Group and School of Industrial Engineering, Purdue University, Room 334, 1293 A.A. Potter, West Lafayette, IN 47907 (United States)

    2003-05-01

    The paper presents a short-term market risk model based on the Markowitz mean-variance method for spatial electricity markets. The spatial nature is captured using the correlation of geographically separated markets and the consideration of wheeling administration. The model also includes transaction costs and other practical constraints, resulting in a mixed integer programming (MIP) model. The incorporation of those practical constraints makes the model more attractive than the traditional Markowitz portfolio model with continuity. A case study is used to illustrate the practical application of the model. The results show that the MIP portfolio efficient frontier is neither smooth nor concave. The paper also considers the possible extension of the model to other energy markets, including natural gas and oil markets.

  16. Pliocene Model Intercomparison Project (PlioMIP): Experimental Design and Boundary Conditions (Experiment 2)

    Science.gov (United States)

    Haywood, A. M.; Dowsett, H. J.; Robinson, M. M.; Stoll, D. K.; Dolan, A. M.; Lunt, D. J.; Otto-Bliesner, B.; Chandler, M. A.

    2011-01-01

    The Palaeoclimate Modelling Intercomparison Project has expanded to include a model intercomparison for the mid-Pliocene warm period (3.29 to 2.97 million yr ago). This project is referred to as PlioMIP (the Pliocene Model Intercomparison Project). Two experiments have been agreed upon and together compose the initial phase of PlioMIP. The first (Experiment 1) is being performed with atmosphere only climate models. The second (Experiment 2) utilizes fully coupled ocean-atmosphere climate models. Following on from the publication of the experimental design and boundary conditions for Experiment 1 in Geoscientific Model Development, this paper provides the necessary description of differences and/or additions to the experimental design for Experiment 2.

  17. A spatial mean-variance MIP model for energy market risk analysis

    International Nuclear Information System (INIS)

    Zuwei Yu

    2003-01-01

    The paper presents a short-term market risk model based on the Markowitz mean-variance method for spatial electricity markets. The spatial nature is captured using the correlation of geographically separated markets and the consideration of wheeling administration. The model also includes transaction costs and other practical constraints, resulting in a mixed integer programming (MIP) model. The incorporation of those practical constraints makes the model more attractive than the traditional Markowitz portfolio model with continuity. A case study is used to illustrate the practical application of the model. The results show that the MIP portfolio efficient frontier is neither smooth nor concave. The paper also considers the possible extension of the model to other energy markets, including natural gas and oil markets. (author)

  18. Performance of Molecular Inversion Probes (MIP) in Allele CopyNumber Determination

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yuker; Moorhead, Martin; Karlin-Neumann, George; Wang,Nicolas J.; Ireland, James; Lin, Steven; Chen, Chunnuan; Heiser, LauraM.; Chin, Koei; Esserman, Laura; Gray, Joe W.; Spellman, Paul T.; Faham,Malek

    2007-05-14

    We have developed a new protocol for using MolecularInversion Probes (MIP) to accurately and specifically measure allele copynumber (ACN). The new protocol provides for significant improvementsincluding the reduction of input DNA (from 2?g) by more than 25 fold (to75ng total genomic DNA), higher overall precision resulting in one orderof magnitude lower false positive rate, and greater dynamic range withaccurate absolute copy number up to 60 copies.

  19. Measurement of Photomultipier Plateau Curves and Single MIP response in the AD detector at ALICE

    CERN Document Server

    Sanchez Falero, Sebastian De Jesus

    2015-01-01

    The Alice Diffractive (AD) detector is a forward detector in the ALICE experiment at CERN. It is aimed to the triggering on diffractive events and extends the pseudorapidity coverage to about 4.9 < /n/ < 6.3. In this work, a PMT's efficiency plateau and single MIP response are measured using a replica of the detector's scintillator modules, electronic and data acquisition system and cosmic rays as particle source.

  20. The Proposed MACRA/MIPS Threshold for Patient-Facing Encounters: What It Means for Radiologists.

    Science.gov (United States)

    Rosenkrantz, Andrew B; Hirsch, Joshua A; Allen, Bibb; Wang, Wenyi; Hughes, Danny R; Nicola, Gregory N

    2017-03-01

    In implementing the Merit-Based Incentive Payment System (MIPS), CMS will provide special considerations to physicians with infrequent face-to-face patient encounters by reweighting MIPS performance categories to account for the unique circumstances facing these providers. The aim of this study was to determine the impact of varying criteria on the fraction of radiologists who are likely to receive special considerations for performance assessment under MIPS. Data from the 2014 Medicare Physician and Other Supplier file for 28,710 diagnostic radiologists were used to determine the fraction of radiologists meeting various proposed criteria for receiving special considerations. For each definition, the fraction of patient-facing encounters among all billed codes was determined for those radiologists not receiving special considerations. When using the criterion proposed by CMS that physicians will receive special considerations if billing ≤25 evaluation and management services or surgical codes, 72.0% of diagnostic radiologists would receive special considerations, though such encounters would represent only 2.1% of billed codes among remaining diagnostic radiologists without special considerations. If CMS were to apply an alternative criterion of billing ≤100 evaluation and management codes exclusively, 98.8% of diagnostic radiologists would receive special considerations. At this threshold, patient-facing encounters would represent approximately 10% of billed codes among remaining radiologists without special considerations. The current CMS proposed criterion for special considerations would result in a considerable fraction of radiologists being evaluated on the basis of measures that are not reflective of their practice and beyond their direct control. Alternative criteria could help ensure that radiologists are provided a fair opportunity for success in performance review under the MIPS. Copyright © 2016 American College of Radiology. Published by Elsevier

  1. Intrinsic Chevrolets at the SSC

    International Nuclear Information System (INIS)

    Brodsky, S.J.; Collins, J.C.; Ellis, S.D.; Gunion, J.F.; Mueller, A.H.

    1984-01-01

    The possibility of the production at high energy of heavy quarks, supersymmetric particles and other large mass colored systems via the intrinsic twist-six components in the proton wave function is discussed. While the existing data do not rule out the possible relevance of intrinsic charm production at present energies, the extrapolation of such intrinsic contributions to very high masses and energies suggests that they will not play an important role at the SSC

  2. The Multi-Isotope Process (MIP) Monitor Project: FY13 Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Meier, David E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Coble, Jamie B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Jordan, David V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mcdonald, Luther W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Forrester, Joel B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Schwantes, Jon M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Unlu, Kenan [Pennsylvania State Univ., University Park, PA (United States); Landsberger, Sheldon [Univ. of Texas, Austin, TX (United States); Bender, Sarah [Pennsylvania State Univ., University Park, PA (United States); Dayman, Kenneth J. [Univ. of Texas, Austin, TX (United States); Reilly, Dallas D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-09-01

    The Multi-Isotope Process (MIP) Monitor provides an efficient approach to monitoring the process conditions in reprocessing facilities in support of the goal of “… (minimization of) the risks of nuclear proliferation and terrorism.” The MIP Monitor measures the distribution of the radioactive isotopes in product and waste streams of a nuclear reprocessing facility. These isotopes are monitored online by gamma spectrometry and compared, in near-real-time, to spectral patterns representing “normal” process conditions using multivariate analysis and pattern recognition algorithms. The combination of multivariate analysis and gamma spectroscopy allows us to detect small changes in the gamma spectrum, which may indicate changes in process conditions. By targeting multiple gamma-emitting indicator isotopes, the MIP Monitor approach is compatible with the use of small, portable, relatively high-resolution gamma detectors that may be easily deployed throughout an existing facility. The automated multivariate analysis can provide a level of data obscurity, giving a built-in information barrier to protect sensitive or proprietary operational data. Proof-of-concept simulations and experiments have been performed in previous years to demonstrate the validity of this tool in a laboratory setting for systems representing aqueous reprocessing facilities. However, pyroprocessing is emerging as an alternative to aqueous reprocessing techniques.

  3. Ship Routing with Pickup and Delivery for a Maritime Oil Transportation System: MIP Model and Heuristics

    Directory of Open Access Journals (Sweden)

    Vinícius P. Rodrigues

    2016-09-01

    Full Text Available This paper examines a ship routing problem with pickup and delivery and time windows for maritime oil transportation, motivated by the production and logistics activities of an oil company operating in the Brazilian coast. The transportation costs from offshore platforms to coastal terminals are an important issue in the search for operational excellence in the oil industry, involving operations that demand agile and effective decision support systems. This paper presents an optimization approach to address this problem, based on a mixed integer programming (MIP model and a novel and exploratory application of two tailor-made MIP heuristics, based on relax-and-fix and time decomposition procedures. The model minimizes fuel costs of a heterogeneous fleet of oil tankers and costs related to freighting contracts. The model also considers company-specific constraints for offshore oil transportation. Computational experiments based on the mathematical models and the related MIP heuristics are presented for a set of real data provided by the company, which confirm the potential of optimization-based methods to find good solutions for problems of moderate sizes.

  4. An Efficient and Secure m-IPS Scheme of Mobile Devices for Human-Centric Computing

    Directory of Open Access Journals (Sweden)

    Young-Sik Jeong

    2014-01-01

    Full Text Available Recent rapid developments in wireless and mobile IT technologies have led to their application in many real-life areas, such as disasters, home networks, mobile social networks, medical services, industry, schools, and the military. Business/work environments have become wire/wireless, integrated with wireless networks. Although the increase in the use of mobile devices that can use wireless networks increases work efficiency and provides greater convenience, wireless access to networks represents a security threat. Currently, wireless intrusion prevention systems (IPSs are used to prevent wireless security threats. However, these are not an ideal security measure for businesses that utilize mobile devices because they do not take account of temporal-spatial and role information factors. Therefore, in this paper, an efficient and secure mobile-IPS (m-IPS is proposed for businesses utilizing mobile devices in mobile environments for human-centric computing. The m-IPS system incorporates temporal-spatial awareness in human-centric computing with various mobile devices and checks users’ temporal spatial information, profiles, and role information to provide precise access control. And it also can extend application of m-IPS to the Internet of things (IoT, which is one of the important advanced technologies for supporting human-centric computing environment completely, for real ubiquitous field with mobile devices.

  5. WCRP COordinated Regional Downscaling EXperiment (CORDEX: a diagnostic MIP for CMIP6

    Directory of Open Access Journals (Sweden)

    W. J. Gutowski Jr.

    2016-11-01

    Full Text Available The COordinated Regional Downscaling EXperiment (CORDEX is a diagnostic model intercomparison project (MIP in CMIP6. CORDEX builds on a foundation of previous downscaling intercomparison projects to provide a common framework for downscaling activities around the world. The CORDEX Regional Challenges provide a focus for downscaling research and a basis for making use of CMIP6 global climate model (GCM output to produce downscaled projected changes in regional climates and assess sources of uncertainties in the projections, all of which can potentially be distilled into climate change information for vulnerability, impacts and adaptation studies. CORDEX Flagship Pilot Studies advance regional downscaling by targeting one or more of the CORDEX Regional Challenges. A CORDEX-CORE framework is planned that will produce a baseline set of homogeneous high-resolution, downscaled projections for regions worldwide. In CMIP6, CORDEX coordinates with ScenarioMIP and is structured to allow cross comparisons with HighResMIP and interaction with the CMIP6 VIACS Advisory Board.

  6. AgMIP: New Results from Sub-Saharan Africa and South Asia Regional Integrated Assessments

    Science.gov (United States)

    Rosenzweig, C.

    2014-12-01

    AgMIP conducted the first set of comprehensive regional integrated assessments of climate change impacts on smallholder farmers in Sub-Saharan Africa and South Asia led by researchers from the regions themselves. The project developed new methods integrating climate, crop, livestock and economic models to conduct climate change impact assessments that characterize impacts on smallholder groups. AgMIP projections of climate change impacts on agriculture are more realistic than previous assessments because they take agricultural development into account. Using the best available data and models, the assessments directly evaluated yield, income, and poverty outcomes including the effects of adaptation packages and development pathways. Results show that even with agricultural development, climate change generally will exert negative pressure on yields of smallholder farmers in Sub-Saharan Africa and South Asia. Without adaptation, climate change leads to increased poverty in some locations in Sub-Saharan Africa and South Asia compared to a future in which climate change does not occur. Adaptation can significantly improve smallholder farmer responses to climate change. AgMIP expert teams identified improved varieties, sowing practices, fertilizer application, and irrigation applications as prioritized adaptation strategies. These targeted adaptation packages were able to overcome a portion of detrimental impacts but could not compensate completely in many locations. Even in cases where average impact is near zero, vulnerability (i.e., those at risk of loss) can be substantial even when mean impacts are positive.

  7. Resource Use in the Production and Consumption System—The MIPS Approach

    Directory of Open Access Journals (Sweden)

    Christa Liedtke

    2014-08-01

    Full Text Available The concept Material Input per Service Unit (MIPS was developed 20 years ago as a measure for the overall natural resource use of products and services. The material intensity analysis is used to calculate the material footprint of any economic activities in production and consumption. Environmental assessment has developed extensive databases for life cycle inventories, which can additionally be adopted for material intensity analysis. Based on practical experience in measuring material footprints on the micro level, this paper presents the current state of research and methodology development: it shows the international discussions on the importance of accounting methodologies to measure progress in resource efficiency. The MIPS approach is presented and its micro level application for assessing value chains, supporting business management, and operationalizing sustainability strategies is discussed. Linkages to output-oriented Life Cycle Assessment as well as to Material Flow Analysis (MFA at the macro level are pointed out. Finally we come to the conclusion that the MIPS approach provides relevant knowledge on resource and energy input at the micro level for fact-based decision-making in science, policy, business, and consumption.

  8. Intrinsically dynamic population models

    Directory of Open Access Journals (Sweden)

    Robert Schoen

    2005-03-01

    Full Text Available Intrinsically dynamic models (IDMs depict populations whose cumulative growth rate over a number of intervals equals the product of the long term growth rates (that is the dominant roots or dominant eigenvalues associated with each of those intervals. Here the focus is on the birth trajectory produced by a sequence of population projection (Leslie matrices. The elements of a Leslie matrix are represented as straightforward functions of the roots of the matrix, and new relationships are presented linking the roots of a matrix to its Net Reproduction Rate and stable mean age of childbearing. Incorporating mortality changes in the rates of reproduction yields an IDM when the subordinate roots are held constant over time. In IDMs, the birth trajectory generated by any specified sequence of Leslie matrices can be found analytically. In the Leslie model with 15 year age groups, the constant subordinate root assumption leads to reasonable changes in the age pattern of fertility, and equations (27 and (30 provide the population size and structure that result from changing levels of net reproduction. IDMs generalize the fixed rate stable population model. They can characterize any observed population, and can provide new insights into dynamic demographic behavior, including the momentum associated with gradual or irregular paths to zero growth.

  9. Insights into the Molecular Mechanisms of Alzheimer’s and Parkinson’s Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology

    Directory of Open Access Journals (Sweden)

    Orkid Coskuner-Weber

    2018-01-01

    Full Text Available Amyloid-β and α-synuclein are intrinsically disordered proteins (IDPs, which are at the center of Alzheimer’s and Parkinson’s disease pathologies, respectively. These IDPs are extremely flexible and do not adopt stable structures. Furthermore, both amyloid-β and α-synuclein can form toxic oligomers, amyloid fibrils and other type of aggregates in Alzheimer’s and Parkinson’s diseases. Experimentalists face challenges in investigating the structures and thermodynamic properties of these IDPs in their monomeric and oligomeric forms due to the rapid conformational changes, fast aggregation processes and strong solvent effects. Classical molecular dynamics simulations complement experiments and provide structural information at the atomic level with dynamics without facing the same experimental limitations. Artificial missense mutations are employed experimentally and computationally for providing insights into the structure-function relationships of amyloid-β and α-synuclein in relation to the pathologies of Alzheimer’s and Parkinson’s diseases. Furthermore, there are several natural genetic variations that play a role in the pathogenesis of familial cases of Alzheimer’s and Parkinson’s diseases, which are related to specific genetic defects inherited in dominant or recessive patterns. The present review summarizes the current understanding of monomeric and oligomeric forms of amyloid-β and α-synuclein, as well as the impacts of artificial and pathological missense mutations on the structural ensembles of these IDPs using molecular dynamics simulations. We also emphasize the recent investigations on residual secondary structure formation in dynamic conformational ensembles of amyloid-β and α-synuclein, such as β-structure linked to the oligomerization and fibrillation mechanisms related to the pathologies of Alzheimer’s and Parkinson’s diseases. This information represents an important foundation for the successful and

  10. AgMIP 1.5°C Assessment: Mitigation and Adaptation at Coordinated Global and Regional Scales

    Science.gov (United States)

    Rosenzweig, C.

    2016-12-01

    The AgMIP 1.5°C Coordinated Global and Regional Integrated Assessments of Climate Change and Food Security (AgMIP 1.5 CGRA) is linking site-based crop and livestock models with similar models run on global grids, and then links these biophysical components with economics models and nutrition metrics at regional and global scales. The AgMIP 1.5 CGRA assessment brings together experts in climate, crop, livestock, economics, nutrition, and food security to define the 1.5°C Protocols and guide the process throughout the assessment. Scenarios are designed to consistently combine elements of intertwined storylines of future society including socioeconomic development (Shared Socioeconomic Pathways), greenhouse gas concentrations (Representative Concentration Pathways), and specific pathways of agricultural sector development (Representative Agricultural Pathways). Shared Climate Policy Assumptions will be extended to provide additional agricultural detail on mitigation and adaptation strategies. The multi-model, multi-disciplinary, multi-scale integrated assessment framework is using scenarios of economic development, adaptation, mitigation, food policy, and food security. These coordinated assessments are grounded in the expertise of AgMIP partners around the world, leading to more consistent results and messages for stakeholders, policymakers, and the scientific community. The early inclusion of nutrition and food security experts has helped to ensure that assessment outputs include important metrics upon which investment and policy decisions may be based. The CGRA builds upon existing AgMIP research groups (e.g., the AgMIP Wheat Team and the AgMIP Global Gridded Crop Modeling Initiative; GGCMI) and regional programs (e.g., AgMIP Regional Teams in Sub-Saharan Africa and South Asia), with new protocols for cross-scale and cross-disciplinary linkages to ensure the propagation of expert judgment and consistent assumptions.

  11. Phase Noise Squeezing Based Parametric Bifurcation Tracking of MIP-Coated Microbeam MEMS Sensor for TNT Explosive Gas Sensing

    Science.gov (United States)

    2014-06-08

    Standard Form 298 (Rev 8/98) Prescribed by ANSI Std. Z39.18 805-893-8133 W911NF-09-D-0001 Conference Proceeding 55012-LS-ICB.688 a. REPORT 14...Based Parametric Bifurcation Tracking of Mip-Coated Microbeam MEMS Sensor for TNT Explosive Gas Sensing See Attached The views, opinions and/or...2050 1 ABSTRACT Phase Noise-Squeezing-Based Parametric Bifurcation Tracking of Mip-Coated Microbeam MEMS Sensor for TNT Explosive Gas Sensing

  12. Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

    Science.gov (United States)

    Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.

    2014-01-01

    A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (−LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. PMID:25452551

  13. Recombinant protein truncation strategy for inducing bactericidal antibodies to the macrophage infectivity potentiator protein of Neisseria meningitidis and circumventing potential cross-reactivity with human FK506-binding proteins.

    Science.gov (United States)

    Bielecka, Magdalena K; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E; Christodoulides, Myron

    2015-02-01

    A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human proteins, we immunized mice with recombinant truncated type I rMIP proteins that lacked the globular domain and the signal leader peptide (LP) signal sequence (amino acids 1 to 22) and contained the His purification tag at either the N or C terminus (C-term). The immunogenicity of truncated rMIP proteins was compared to that of full (i.e., full-length) rMIP proteins (containing the globular domain) with either an N- or C-terminal His tag and with or without the LP sequence. By comparing the functional murine antibody responses to these various constructs, we determined that C-term His truncated rMIP (-LP) delivered in liposomes induced high levels of antibodies that bound to the surface of wild-type but not Δmip mutant meningococci and showed bactericidal activity against homologous type I MIP (median titers of 128 to 256) and heterologous type II and III (median titers of 256 to 512) strains, thereby providing at least 82% serogroup B strain coverage. In contrast, in constructs lacking the LP, placement of the His tag at the N terminus appeared to abrogate bactericidal activity. The strategy used in this study would obviate any potential concerns regarding the use of MIP antigens for inclusion in bacterial vaccines. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. [MIP-1α promotes the migration ability of Jurkat cell through human brain microvascular endothelial cell monolayer].

    Science.gov (United States)

    Ma, Yi-Ran; Zhang, Shuang; Sun, Ying; Liu, Yi-Yang; Song, Qian; Hao, Yi-Wen

    2014-02-01

    This study was purposed to explore the mechanism of central nervous system (CNS) leukemia resulting from brain metastasis of human acute T-cell leukemia (T-ALL) cells and the role of MIP-1α in migration of Jurkat cells through human brain microvascular endothelial cells (HBMEC). The real-time PCR, siRNA test, transendothelial migration test, endothelial permeability assay and cell adhesion assay were used to detect MIP-1α expression, penetration and migration ability as well as adhesion capability respectively. The results showed that the MIP-1α expression in Jurkat cells was higher than that in normal T cells and CCRF-HSB2, CCRF-CEM , SUP-T1 cells. The MIP-1α secreted from Jurkat cells enhanced the ability of Jurkat cells to penetrate through HBMEC, the ability of Jurkat cells treated by MIP-1α siRNA to adhere to HBMEC and to migrate trans endothelial cells decreased. It is concluded that the MIP-1α secreted from Jurkat cells participates in process of penetrating the Jurkat cells through HBMEC monolayer.

  15. A MIP-based biomimetic sensor for the impedimetric detection of histamine in different pH environments

    Energy Technology Data Exchange (ETDEWEB)

    Bongaers, E.; Alenus, J.; Horemans, F.; Weustenraed, A.; Cleij, T.J. [Institute for Materials Research, Hasselt University, Diepenbeek (Belgium); Lutsen, L. [IMEC, Division IMOMEC, Diepenbeek (Belgium); Vanderzande, D.; Wagner, P. [Institute for Materials Research, Hasselt University, Diepenbeek (Belgium); IMEC, Division IMOMEC, Diepenbeek (Belgium); Troost, F.J.; Brummer, R.J. [Gastroenterology and Hepatology, Department of Internal Medicine, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, Maastricht (Netherlands)

    2010-04-15

    The development of novel biosensors is a rapidly growing field. Substituting the biological receptor layer from the biosensor with a synthetic receptor opens the door for the development of biomimetic sensors that are chemically and physically inert, as opposed to the sensors containing biological recognition elements. Using molecularly imprinted polymers (MIPs) the specificity and affinity of biological receptors can be mimicked. In addition, a MIP-based sensor can measure in harsh environments. Histamine occurs in harsh environments in food and bodily fluids and is chosen as the target molecule for impedimetric detection. When 10 nM histamine is present in pH neutral environments, the impedance increases 45% with respect to the impedance of the sensor without histamine. Specificity is tested with respect to histidine. The influence of the pH on the performance of the sensor is tested. In a pH range of pH 5-12 the MIPs are stable, although they exhibit a varying degree of protonation. The same holds true for the target molecule of which the protonation also varies with the pH of the solution. It is shown that the pH dependent degree of protonation of both the MIP and the histamine has a large impact on the binding of histamine to the nanocavity in the MIP. Hence, the detection of histamine by a MIP-based sensor is affected by the pH of the solution. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  16. Intrinsic disorder here, there, and everywhere, and nowhere to escape from it.

    Science.gov (United States)

    Uversky, Vladimir N

    2017-09-01

    The concept of protein intrinsic disorder persistently penetrates into all areas of modern protein science. It cannot be ignored anymore, and cannot be shrugged off, as it represents a vital feature (or, more correctly, a broad spectrum of important features), which, when added to and mixed with features arising from the well established protein structure-function paradigm, complete the picture of a functioning protein. The field of protein intrinsic disorder is very dynamic and fast developing. This Multi-Author Review represents a snapshot of this field by introducing some recent advances. Articles assembled in this Multi-Author Review introduce some of the new aspects of intrinsic disorder, outline some fascinating ideas related to the intrinsically disordered proteins, their structure, and functionality, and show challenges related to the analysis of proteins carrying intrinsic disorder.

  17. Detergent-induced aggregation of an amyloidogenic intrinsically ...

    Indian Academy of Sciences (India)

    Shruti Arya

    2017-11-02

    Nov 2, 2017 ... Intrinsically disordered proteins (IDPs) belong to an important class of proteins that do not fold up spontaneously. The conformational .... naphthalenesulfonic acid ammonium salt (ANS) and sodium hydrogen phosphate .... becomes fluorescent upon binding to hydrophobic pock- ets and undergoes a ...

  18. Detergent-induced aggregation of an amyloidogenic intrinsically ...

    Indian Academy of Sciences (India)

    Shruti Arya

    2017-11-02

    Nov 2, 2017 ... Abstract. Intrinsically disordered proteins (IDPs) belong to an important class of proteins that do not fold up spontaneously. The conformational flexibility of IDPs allows them to adopt a wide range of conformations depending upon their biochemical environment. Many IDPs undergo profound conformational ...

  19. Identification of novel components in microProtein signalling

    DEFF Research Database (Denmark)

    Rodrigues, Vandasue Lily

    findings suggest that these interacting components are part of a larger repressor complex preventing premature floral transition. Till date, all the miPs described in plants target transcription factors. The lack of diversity of protein target classes can be attributed to the lack of functional...... characterization of smaller proteins. Using a computational approach, we identified putative microProteins that could target a diverse variety of protein classes. Using a synthetic microProtein approach, we demonstrate that miPs can target a diverse variety of target proteins, which makes them of interest...

  20. A macrophage inflammatory protein homolog encoded by guinea pig cytomegalovirus signals via CC chemokine receptor 1

    International Nuclear Information System (INIS)

    Penfold, Mark; Miao Zhenhua; Wang Yu; Haggerty, Shannon; Schleiss, Mark R.

    2003-01-01

    Cytomegaloviruses encode homologs of cellular immune effector proteins, including chemokines (CKs) and CK receptor-like G protein-coupled receptors (GPCRs). Sequence of the guinea pig cytomegalovirus (GPCMV) genome identified an open reading frame (ORF) which predicted a 101 amino acid (aa) protein with homology to the macrophage inflammatory protein (MIP) subfamily of CC (β) CKs, designated GPCMV-MIP. To assess functionality of this CK, recombinant GPCMV-MIP was expressed in HEK293 cells and assayed for its ability to bind to and functionally interact with a variety of GPCRs. Specific signaling was observed with the hCCR1 receptor, which could be blocked with hMIP -1α in competition experiments. Migration assays revealed that GPCMV-MIP was able to induce chemotaxis in hCCR1-L1.2 cells. Antisera raised against a GST-MIP fusion protein immunoprecipitated species of ∼12 and 10 kDa from GPCMV-inoculated tissue culture lysates, and convalescent antiserum from GPCMV-infected animals was immunoreactive with GST-MIP by ELISA assay. These results represent the first substantive in vitro characterization of a functional CC CK encoded by a cytomegalovirus

  1. Ship Routing with Pickup and Delivery for a Maritime Oil Transportation System: MIP Modeland Heuristics

    DEFF Research Database (Denmark)

    Rodrigues, Vinicius Picanco; Morabito, Reinaldo; Yamashita, Denise

    2016-01-01

    This paper examines a ship routing problem with pickup and delivery and time windowsfor maritime oil transportation, motivated by the production and logistics activities of an oil companyoperating in the Brazilian coast. The transportation costs from offshore platforms to coastal terminalsare...... application of two tailor-made MIP heuristics, based on relax-and-fix and timedecomposition procedures. The model minimizes fuel costs of a heterogeneous fleet of oil tankersand costs related to freighting contracts. The model also considers company-specific constraints foroffshore oil transportation...

  2. The Agricultural Model Intercomparison and Improvement Project (AgMIP): Protocols and Pilot Studies

    Science.gov (United States)

    Rosenzweig, C.; Jones, J. W.; Hatfield, J. L.; Ruane, A. C.; Boote, K. J.; Thorburn, P.; Antle, J. M.; Nelson, G. C.; Porter, C.; Janssen, S.; hide

    2012-01-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is a major international effort linking the climate, crop, and economic modeling communities with cutting-edge information technology to produce improved crop and economic models and the next generation of climate impact projections for the agricultural sector. The goals of AgMIP are to improve substantially the characterization of world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. Analyses of the agricultural impacts of climate variability and change require a transdisciplinary effort to consistently link state-of-the-art climate scenarios to crop and economic models. Crop model outputs are aggregated as inputs to regional and global economic models to determine regional vulnerabilities, changes in comparative advantage, price effects, and potential adaptation strategies in the agricultural sector. Climate, Crop Modeling, Economics, and Information Technology Team Protocols are presented to guide coordinated climate, crop modeling, economics, and information technology research activities around the world, along with AgMIP Cross-Cutting Themes that address uncertainty, aggregation and scaling, and the development of Representative Agricultural Pathways (RAPs) to enable testing of climate change adaptations in the context of other regional and global trends. The organization of research activities by geographic region and specific crops is described, along with project milestones. Pilot results demonstrate AgMIP's role in assessing climate impacts with explicit representation of uncertainties in climate scenarios and simulations using crop and economic models. An intercomparison of wheat model simulations near Obregón, Mexico reveals inter-model differences in yield sensitivity to [CO2] with model uncertainty holding approximately steady as concentrations rise, while uncertainty related to choice of crop model increases with

  3. Study on some factors affecting the results in the use of MIP method in concrete research

    International Nuclear Information System (INIS)

    Kumar, Rakesh; Bhattacharjee, B.

    2003-01-01

    Effects of rate of pressure application and forms and type of sample on porosity and pore size distribution of concrete estimated through mercury intrusion porosimetry (MIP) are presented in this experimental work. Two different forms of concrete sample, namely, crushed chunks of concrete and small core drilled out from the concrete beam specimens, were used for this study. The results exhibit that the rate of pressure application in mercury porosimetry has little effect on porosity and pore size distribution of concrete. It is also demonstrated that small cores drilled out from large concrete specimens are preferable as samples for performing porosimetry test on concrete

  4. Intrinsically Passive Handling and Grasping

    NARCIS (Netherlands)

    Stramigioli, Stefano; Scherpen, Jacquelien M.A.; Khodabandehloo, Koorosh

    2000-01-01

    The paper presents a control philosophy called Intrinsically Passive Control, which has the feature to properly behave during interaction with any passive objects. The controlled robot will never become unstable due to the physical structure of the controller.

  5. Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1β

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Li; DeRider, Michele; McCornack, Milissa A.; Jao, Chris; Isern, Nancy G.; Ness, Traci; Moyer, Richard; Liwang, Patricia J.

    2006-09-19

    Chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both the immune response and inflammation-related diseases. The poxvirus-encoded viral CC chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting as a potent inhibitor of chemokine action. We have used heteronuclear multidimensional NMR to determine the first structure of an orthopoxvirus vCCI in complex with a human CC chemokine MIP-1β. vCCI binds to the chemokine with 1:1 stoichiometry, using residues from its β-sheet II to interact with the a surface of MIP-1β that includes the N-terminus, the following residues in the so-called N-loop20’s region, and the 40’s loop. This structure reveals a general strategy of vCCI for selective chemokine binding, as vCCI appears to interact most stronglyinteracts most directly with residues that are conserved among a subset of CC chemokines, but are not conservednot among the other chemokine subfamilies. This structure reveals a general strategy of vCCI for selective chemokine binding. Chemokines play critical roles in the immune system, causing chemotaxis of a variety of cells to sites of infection and inflammation, as well as mediating cell homing and immune system development 1(Baggiolini 2001). To date, about 50 chemokines have been identified, and these small proteins (7-14 kDa) are believed to function by binding with endothelial or matrix glycosaminoglycans to form a concentration gradient that is then sensed by high affinity, 7-transmembrane domain G-protein coupled chemokine receptors on the surface of immune cells surface. The chemokine system is critical for host defense in healthy individuals, butand can also lead to diseases including asthma, arthritis, and atherosclerosis in the case of malfunction, often due to inappropriate inflammation and subsequent tissue damage 2(Gerard and Rollins 2001). There are four subfamilies of chemokines, CC

  6. Detection of trace microcystin-LR on a 20 MHz QCM sensor coated with in situ self-assembled MIPs.

    Science.gov (United States)

    He, Hao; Zhou, Lianqun; Wang, Yi; Li, Chuanyu; Yao, Jia; Zhang, Wei; Zhang, Qingwen; Li, Mingyu; Li, Haiwen; Dong, Wen-fei

    2015-01-01

    A 20 MHz quartz crystal microbalance (QCM) sensor coated with in situ self-assembled molecularly imprinted polymers (MIPs) was presented for the detection of trace microcystin-LR (MC-LR) in drinking water. The sensor performance obtained using the in situ self-assembled MIPs was compared with traditionally synthesized MIPs on 20 MHz and normal 10 MHz QCM chip. The results show that the response increases by more than 60% when using the in situ self-assembly method compared using the traditionally method while the 20 MHz QCM chip provides four-fold higher response than the 10 MHz one. Therefore, the in situ self-assembled MIPs coated on a high frequency QCM chip was used in the sensor performance test to detect MC-LR in tap water. It showed a limit of detection (LOD) of 0.04 nM which is lower than the safety guideline level (1 nM MC-LR) of drinking water in China. The low sensor response to other analogs indicated the high specificity of the sensor to MC-LR. The sensor showed high stability and low signal variation less than 2.58% after regeneration. The lake water sample analysis shows the sensor is possible for practical use. The combination of the higher frequency QCM with the in situ self-assembled MIPs provides a good candidate for the detection of other small molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Fairy tails: Flexibility and function of intrinsically disordered extensions in the photosynthetic world

    Directory of Open Access Journals (Sweden)

    Gabriel eThieulin-Pardo

    2015-05-01

    Full Text Available Intrinsically Disordered Proteins (IDPs, or protein fragments also called Intrinsically Disordered Regions (IDRs, display high flexibility as the result of their amino acid composition. They can adopt multiple roles. In globular proteins, IDRs are usually found as loops and linkers between secondary structure elements. However, not all disordered fragments are loops: some proteins bear an intrinsically disordered extension at their C- or N-terminus, and this flexibility can affect the protein as a whole. In this review, we focus on the disordered N- and C-terminal extensions of globular proteins from photosynthetic organisms. Using the examples of the A2B2-GAPDH and the α Rubisco activase isoform, we show that intrinsically disordered extensions can help regulate their host protein in response to changes in light, thereby participating in photosynthesis regulation. As IDPs are famous for their large number of protein partners, we used the examples of the NAC, bZIP, TCP and GRAS transcription factor families to illustrate the fact that intrinsically disordered extremities can allow a protein to have an increased number of partners, which directly affects its regulation. Finally, for proteins from the cryptochrome light receptor family, we describe how a new role for the photolyase proteins may emerge by the addition of an intrinsically disordered extension, while still allowing the protein to absorb blue light. This review has highlighted the diverse repercussions of the disordered extension on the regulation and function of their host protein and outlined possible future research avenues.

  8. Diclofenac, a selective COX-2 inhibitor, inhibits DMH-induced colon tumorigenesis through suppression of MCP-1, MIP-1α and VEGF.

    Science.gov (United States)

    Kaur, Jasmeet; Sanyal, S N

    2011-09-01

    Angiogenesis is a physiological process involving growth of new blood vessels from pre-existing ones; however, it also plays a critical role in tumor progression. It favors the transition from hyperplasia to neoplasia, that is, from a state of cellular multiplication to uncontrolled proliferation. Therefore targeting angiogenesis will be profitable as a mechanism to inhibit tumor's lifeline. Further, it is important to understand the cross-communication between vascular endothelial growth factor (VEGF)-master switch in angiogenesis and other molecules in the neoplastic and pro-inflammatory milieu. We studied the role of two important chemokines [monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-lα] alongwith VEGF and matrix metalloproteinases (MMPs) in non-steroidal anti-inflammatory drugs (NSAIDs)-induced chemopreventive effect in experimental colon cancer in rat. 1,2-Dimethylhydrazine (DMH, 30 mg/kg body weight, subcutaneously (s.c.) once-a-week) for 18 wk was used as pro-carcinogen and diclofenac (8 mg/kg body weight, orally daily) as the preferential cyclooxygenase-2 (COX-2) inhibitor. Expression of COX-2 and VEGF was found to be significantly elevated in the DMH-treated group as compared to the control, which was lowered notably by Diclofenac co-administration with DMH. Gelatin zymography showed prominent MMP-9 activity in the DMH-treated rats, while the activity was nearly absent in all the other groups. Expression of MCP-1 was found to be markedly increased whereas MIP-1α expression was found to be decreased in colonic mucosa from DMH-treated rats, which was reversed in the DMH + Diclofenac group. Our results indicate potential role of chemokines alongwith VEGF in angiogenesis in DMH-induced cancer and its chemoprevention with diclofenac. Copyright ©2011 Wiley-Liss, Inc.

  9. MIP Models and Hybrid Algorithms for Simultaneous Job Splitting and Scheduling on Unrelated Parallel Machines

    Science.gov (United States)

    Ozmutlu, H. Cenk

    2014-01-01

    We developed mixed integer programming (MIP) models and hybrid genetic-local search algorithms for the scheduling problem of unrelated parallel machines with job sequence and machine-dependent setup times and with job splitting property. The first contribution of this paper is to introduce novel algorithms which make splitting and scheduling simultaneously with variable number of subjobs. We proposed simple chromosome structure which is constituted by random key numbers in hybrid genetic-local search algorithm (GAspLA). Random key numbers are used frequently in genetic algorithms, but it creates additional difficulty when hybrid factors in local search are implemented. We developed algorithms that satisfy the adaptation of results of local search into the genetic algorithms with minimum relocation operation of genes' random key numbers. This is the second contribution of the paper. The third contribution of this paper is three developed new MIP models which are making splitting and scheduling simultaneously. The fourth contribution of this paper is implementation of the GAspLAMIP. This implementation let us verify the optimality of GAspLA for the studied combinations. The proposed methods are tested on a set of problems taken from the literature and the results validate the effectiveness of the proposed algorithms. PMID:24977204

  10. MIP models and hybrid algorithms for simultaneous job splitting and scheduling on unrelated parallel machines.

    Science.gov (United States)

    Eroglu, Duygu Yilmaz; Ozmutlu, H Cenk

    2014-01-01

    We developed mixed integer programming (MIP) models and hybrid genetic-local search algorithms for the scheduling problem of unrelated parallel machines with job sequence and machine-dependent setup times and with job splitting property. The first contribution of this paper is to introduce novel algorithms which make splitting and scheduling simultaneously with variable number of subjobs. We proposed simple chromosome structure which is constituted by random key numbers in hybrid genetic-local search algorithm (GAspLA). Random key numbers are used frequently in genetic algorithms, but it creates additional difficulty when hybrid factors in local search are implemented. We developed algorithms that satisfy the adaptation of results of local search into the genetic algorithms with minimum relocation operation of genes' random key numbers. This is the second contribution of the paper. The third contribution of this paper is three developed new MIP models which are making splitting and scheduling simultaneously. The fourth contribution of this paper is implementation of the GAspLAMIP. This implementation let us verify the optimality of GAspLA for the studied combinations. The proposed methods are tested on a set of problems taken from the literature and the results validate the effectiveness of the proposed algorithms.

  11. Preparation of MIP-based QCM nanosensor for detection of caffeic acid.

    Science.gov (United States)

    Gültekin, Aytaç; Karanfil, Gamze; Kuş, Mahmut; Sönmezoğlu, Savaş; Say, Rıdvan

    2014-02-01

    In the present work, a new caffeic acid imprinted quartz crystal microbalance (QCM) nanosensor has been designed for selective assignation of caffeic acid in plant materials. Methacrylamidoantipyrine-iron(III) [MAAP-Fe(III)] as metal-chelating monomer has been used to prepare selective molecular imprinted polymer (MIP). MIP film for detection of caffeic acid has been developed on QCM electrode and selectivity experiments and analytical performance of caffeic acid imprinted QCM nanosensor has been studied. The caffeic acid imprinted QCM nanosensor has been characterized by AFM. After the characterization studies, imprinted and non-imprinted nanosensors was connected to QCM system for studies of connection of the target molecule, selectivity and the detection of amount of target molecule in real samples. The detection limit was found to be 7.8 nM. The value of Langmuir constant (b) (4.06 × 10(6)) that was acquired using Langmuir graph demonstrated that the affinity of binding sites was strong. Also, selectivity of prepared caffeic acid imprinted nanosensor was found as being high compared to chlorogenic acid. Finally, the caffeic acid levels in plant materials was determined by the prepared QCM nanosensor. © 2013 Published by Elsevier B.V.

  12. The AgMIP Coordinated Climate-Crop Modeling Project (C3MP): Methods and Protocols

    Science.gov (United States)

    Shukla, Sonali P.; Ruane, Alexander Clark

    2014-01-01

    Climate change is expected to alter a multitude of factors important to agricultural systems, including pests, diseases, weeds, extreme climate events, water resources, soil degradation, and socio-economic pressures. Changes to carbon dioxide concentration ([CO2]), temperature, and water (CTW) will be the primary drivers of change in crop growth and agricultural systems. Therefore, establishing the CTW-change sensitivity of crop yields is an urgent research need and warrants diverse methods of investigation. Crop models provide a biophysical, process-based tool to investigate crop responses across varying environmental conditions and farm management techniques, and have been applied in climate impact assessment by using a variety of methods (White et al., 2011, and references therein). However, there is a significant amount of divergence between various crop models' responses to CTW changes (Rotter et al., 2011). While the application of a site-based crop model is relatively simple, the coordination of such agricultural impact assessments on larger scales requires consistent and timely contributions from a large number of crop modelers, each time a new global climate model (GCM) scenario or downscaling technique is created. A coordinated, global effort to rapidly examine CTW sensitivity across multiple crops, crop models, and sites is needed to aid model development and enhance the assessment of climate impacts (Deser et al., 2012). To fulfill this need, the Coordinated Climate-Crop Modeling Project (C3MP) (Ruane et al., 2014) was initiated within the Agricultural Model Intercomparison and Improvement Project (AgMIP; Rosenzweig et al., 2013). The submitted results from C3MP Phase 1 (February 15, 2013-December 31, 2013) are currently being analyzed. This chapter serves to present and update the C3MP protocols, discuss the initial participation and general findings, comment on needed adjustments, and describe continued and future development. AgMIP aims to improve

  13. Model Evaluation and Uncertainty in Agricultural Impacts Assessments: Results and Strategies from the Agricultural Model Intercomparison and Improvement Project (AgMIP)

    Science.gov (United States)

    Rosenzweig, C.; Hatfield, J.; Jones, J. W.; Ruane, A. C.

    2012-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) is an international effort to assess the state of global agricultural modeling and to understand climate impacts on the agricultural sector. AgMIP connects the climate science, crop modeling, and agricultural economic modeling communities to generate probabilistic projections of current and future climate impacts. The goals of AgMIP are to improve substantially the characterization of risk of hunger and world food security due to climate change and to enhance adaptation capacity in both developing and developed countries. This presentation will describe the general approach of AgMIP, highlight AgMIP efforts to evaluate climate, crop, and economic models, and discuss AgMIP uncertainty assessments. Model evaluation efforts will be outlined using examples from various facets of AgMIP, including climate scenario generation, the wheat crop model intercomparison, and the global agricultural economics model intercomparison being led in collaboration with the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP). Strategies developed to quantify uncertainty in each component of AgMIP, as well as the propagation of uncertainty through the climate-crop-economic modeling framework, will be detailed and preliminary uncertainty assessments that highlight crucial areas requiring improved models and data collection will be introduced.

  14. AgMIP's Transdisciplinary Agricultural Systems Approach to Regional Integrated Assessment of Climate Impacts, Vulnerability, and Adaptation

    Science.gov (United States)

    Antle, John M.; Valdivia, Roberto O.; Boote, Kenneth J.; Janssen, Sander; Jones, James W.; Porter, Cheryl H.; Rosenzweig, Cynthia; Ruane, Alexander C.; Thorburn, Peter J.

    2015-01-01

    This chapter describes methods developed by the Agricultural Model Intercomparison and Improvement Project (AgMIP) to implement a transdisciplinary, systems-based approach for regional-scale (local to national) integrated assessment of agricultural systems under future climate, biophysical, and socio-economic conditions. These methods were used by the AgMIP regional research teams in Sub-Saharan Africa and South Asia to implement the analyses reported in their respective chapters of this book. Additional technical details are provided in Appendix 1.The principal goal that motivates AgMIP's regional integrated assessment (RIA) methodology is to provide scientifically rigorous information needed to support improved decision-making by various stakeholders, ranging from local to national and international non-governmental and governmental organizations.

  15. Extended-gate field-effect transistor (EG-FET) with molecularly imprinted polymer (MIP) film for selective inosine determination.

    Science.gov (United States)

    Iskierko, Zofia; Sosnowska, Marta; Sharma, Piyush Sindhu; Benincori, Tiziana; D'Souza, Francis; Kaminska, Izabela; Fronc, Krzysztof; Noworyta, Krzysztof

    2015-12-15

    A novel recognition unit of chemical sensor for selective determination of the inosine, renal disfunction biomarker, was devised and prepared. For that purpose, inosine-templated molecularly imprinted polymer (MIP) film was deposited on an extended-gate field-effect transistor (EG-FET) signal transducing unit. The MIP film was prepared by electrochemical polymerization of bis(bithiophene) derivatives bearing cytosine and boronic acid substituents, in the presence of the inosine template and a thiophene cross-linker. After MIP film deposition, the template was removed, and was confirmed by UV-visible spectroscopy. Subsequently, the film composition was characterized by spectroscopic techniques, and its morphology and thickness were determined by AFM. The finally MIP film-coated extended-gate field-effect transistor (EG-FET) was used for signal transduction. This combination is not widely studied in the literature, despite the fact that it allows for facile integration of electrodeposited MIP film with FET transducer. The linear dynamic concentration range of the chemosensor was 0.5-50 μM with inosine detectability of 0.62 μM. The obtained detectability compares well to the levels of the inosine in body fluids which are in the range 0-2.9 µM for patients with diagnosed diabetic nephropathy, gout or hyperuricemia, and can reach 25 µM in certain cases. The imprinting factor for inosine, determined from piezomicrogravimetric experiments with use of the MIP film-coated quartz crystal resonator, was found to be 5.5. Higher selectivity for inosine with respect to common interferents was also achieved with the present molecularly engineered sensing element. The obtained analytical parameters of the devised chemosensor allow for its use for practical sample measurements. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. FIB and MIP: understanding nanoscale porosity in molecularly imprinted polymers via 3D FIB/SEM tomography.

    Science.gov (United States)

    Neusser, G; Eppler, S; Bowen, J; Allender, C J; Walther, P; Mizaikoff, B; Kranz, C

    2017-10-05

    We present combined focused ion beam/scanning electron beam (FIB/SEM) tomography as innovative method for differentiating and visualizing the distribution and connectivity of pores within molecularly imprinted polymers (MIPs) and non-imprinted control polymers (NIPs). FIB/SEM tomography is used in cell biology for elucidating three-dimensional structures such as organelles, but has not yet been extensively applied for visualizing the heterogeneity of nanoscopic pore networks, interconnectivity, and tortuosity in polymers. To our best knowledge, the present study is the first application of this strategy for analyzing the nanoscale porosity of MIPs. MIPs imprinted for propranolol - and the corresponding NIPs - were investigated establishing FIB/SEM tomography as a viable future strategy complementing conventional isotherm studies. For visualizing and understanding the properties of pore networks in detail, polymer particles were stained with osmium tetroxide (OsO 4 ) vapor, and embedded in epoxy resin. Staining with OsO 4 provides excellent contrast during high-resolution SEM imaging. After optimizing the threshold to discriminate between the stained polymer matrix, and pores filled with epoxy resin, a 3D model of the sampled volume may be established for deriving not only the pore volume and pore surface area, but also to visualize the interconnectivity and tortuosity of the pores within the sampled polymer volume. Detailed studies using different types of cross-linkers and the effect of hydrolysis on the resulting polymer properties have been investigated. In comparison of MIP and NIP, it could be unambiguously shown that the interconnectivity of the visualized pores in MIPs is significantly higher vs. the non-imprinted polymer, and that the pore volume and pore area is 34% and approx. 35% higher within the MIP matrix. This confirms that the templating process not only induces selective binding sites, but indeed also affects the physical properties of such

  17. Intrinsic disorder in the BK channel and its interactome.

    Directory of Open Access Journals (Sweden)

    Zhenling Peng

    Full Text Available The large-conductance Ca2+-activated K+ (BK channel is broadly expressed in various mammalian cells and tissues such as neurons, skeletal and smooth muscles, exocrine cells, and sensory cells of the inner ear. Previous studies suggest that BK channels are promiscuous binders involved in a multitude of protein-protein interactions. To gain a better understanding of the potential mechanisms underlying BK interactions, we analyzed the abundance, distribution, and potential mechanisms of intrinsic disorder in 27 BK channel variants from mouse cochlea, 104 previously reported BK-associated proteins (BKAPS from cytoplasmic and membrane/cytoskeletal regions, plus BK β- and γ-subunits. Disorder was evaluated using the MFDp algorithm, which is a consensus-based predictor that provides a strong and competitive predictive quality and PONDR, which can determine long intrinsically disordered regions (IDRs. Disorder-based binding sites or molecular recognition features (MoRFs were found using MoRFpred and ANCHOR. BKAP functions were categorized based on Gene Ontology (GO terms. The analyses revealed that the BK variants contain a number of IDRs. Intrinsic disorder is also common in BKAPs, of which ∼ 5% are completely disordered. However, intrinsic disorder is very differently distributed within BK and its partners. Approximately 65% of the disordered segments in BK channels are long (IDRs (>50 residues, whereas >60% of the disordered segments in BKAPs are short IDRs that range in length from 4 to 30 residues. Both α and γ subunits showed various amounts of disorder as did hub proteins of the BK interactome. Our analyses suggest that intrinsic disorder is important for the function of BK and its BKAPs. Long IDRs in BK are engaged in protein-protein and protein-ligand interactions, contain multiple post-translational modification sites, and are subjected to alternative splicing. The disordered structure of BK and its BKAPs suggests one of the underlying

  18. Biossíntese de vanilina pelo fungo Pycnoporus sanguineus MIP 95001

    Directory of Open Access Journals (Sweden)

    Sabrina Moro Villela Pacheco

    2013-06-01

    A vanilina (substância popularmente conhecida como aroma de baunilha é um dos compostos mais utilizados, principalmente pelas indústrias alimentícias e farmacêuticas. Esta substância pode ser obtida da orquídea Vanilla planifolia, porém, este é um processo oneroso e demorado. Por esse motivo, outros métodos para a obtenção da vanilina vêm sendo estudados. Dentro deste contexto, o objetivo deste trabalho foi estudar a biossíntese de vanilina por três isolados de Pycnoporus sanguineus através do uso de ácido vanílico como precursor. Os isolados foram cultivados em placas de Petri com meio ágar batata dextrose. Fragmentos destes cultivos foram inoculados em Erlenmeyers com meio líquido de caldo de batata e 0,3 g.L-1 de ácido vanílico. Os frascos permaneceram em shaker por oito dias a 28oC e 120 rpm. Foram retiradas diárias (0,8 mL.dia-1 para análise de vanilina, glicose, fenois totais, enzima lacase e proteínas totais. Os resultados revelaram que apenas a cepa MIP 95001 promoveu a biossíntese da vanilina. A maior concentração de vanilina foi detectada no quarto dia de cultivo (8,75 mg.dL-1. De forma geral, os resultados apresentados ilustram a possibilidade de biossintetizar a vanilina pelo Pycnoporus sanguineus (MIP 95001, evidenciando uma possível rota biotecnológica para a produção deste aroma.

  19. Dust Processing in Supernova Remnants: Spitzer MIPS SED and IRS Observations

    Science.gov (United States)

    Hewitt, John W.; Petre, Robert; Katsuda Satoru; Andersen, M.; Rho, J.; Reach, W. T.; Bernard, J. P.

    2011-01-01

    We present Spitzer MIPS SED and IRS observations of 14 Galactic Supernova Remnants previously identified in the GLIMPSE survey. We find evidence for SNR/molecular cloud interaction through detection of [OI] emission, ionic lines, and emission from molecular hydrogen. Through black-body fitting of the MIPS SEDs we find the large grains to be warm, 29-66 K. The dust emission is modeled using the DUSTEM code and a three component dust model composed of populations of big grains, very small grains, and polycyclic aromatic hydrocarbons. We find the dust to be moderately heated, typically by 30-100 times the interstellar radiation field. The source of the radiation is likely hydrogen recombination, where the excitation of hydrogen occurred in the shock front. The ratio of very small grains to big grains is found for most of the molecular interacting SNRs to be higher than that found in the plane of the Milky Way, typically by a factor of 2--3. We suggest that dust shattering is responsible for the relative over-abundance of small grains, in agreement with prediction from dust destruction models. However, two of the SNRs are best fit with a very low abundance of carbon grains to silicate grains and with a very high radiation field. A likely reason for the low abundance of small carbon grains is sputtering. We find evidence for silicate emission at 20 $\\mu$m in their SEDs, indicating that they are young SNRs based on the strong radiation field necessary to reproduce the observed SEDs.

  20. Intravenous spiral CT angiography for assessment before orthotopic liver transplantation: Comparison between tomography, MIP, 3-dimensional surface imaging and intraarterial DSA; Intravenoese Spiral-CT-Angiographie zur Evaluation vor orthotoper Lebertransplantation: Vergleiche zwischen Schnittbilddarstellung, MIP, dreidimensionaler Oberflaechendarstellung und intraarterieller DSA

    Energy Technology Data Exchange (ETDEWEB)

    Hidajat, N. [Medizinische Fakultaet der Humboldt-Univ., Berlin (Germany). Strahlenklinik und Poliklinik; Vogl, T.J. [Medizinische Fakultaet der Humboldt-Univ., Berlin (Germany). Strahlenklinik und Poliklinik; Moeller, M. [Medizinische Fakultaet der Humboldt-Univ., Berlin (Germany). Strahlenklinik und Poliklinik; Bechstein, W.O. [Medizinische Fakultaet der Humboldt-Univ., Berlin (Germany). Klinik und Poliklinik fuer Allgemein- und Transplantationschirurgie; Felix, R. [Medizinische Fakultaet der Humboldt-Univ., Berlin (Germany). Strahlenklinik und Poliklinik

    1996-11-01

    Purpose: To analyse the efficacy of intravenous spiral CT angiography (SCTA) for the evaluation before orthotopic liver transplantation (oLT) compared with DSA. Methods: Spiral CT was performed on 31 potential recipients of a liver graft in order to examine hepatic vessels, coeliac axis, splenic artery and superior mesenteric artery. The arterial vessels were reconstructed in `Maximum Intensity Projection (MIP)` and `Shaded Surface Display (SSD)`-technique. The axial images, MIP and SSD were compared in 25 patients with DSA with regard to the visualisation of the vascular anatomy, detectability of stenosis and vascular diameters. Results: The type of arterial liver supply could be determined via SCTA in all patients. Stenosis of the coeliac axis was seen in ten patients on the DSA, MIP and SSD and in eight patients on the axial images. Occlusion of the hepatic artery was clearly visualised in two patients on the DSA, axial images and MIP and in one patient on the SSD. There was no false positive diagnosis with SCTA. SSD was seen as the best technique to visualise the vessels without overshadowing. There were no significant differences between the diamters measured from the axial images, MIP and SSD images in transversal direction and the DSA images (p>0.05). Conclusion: SCTA is a greatly promising method for the imaging of vessels supplying the liver before oLT, and may convey more diagnostic information than DSA. (orig.) [Deutsch] Ziel: Bewertung der Einsetzbarkeit in intravenoesen Spiral-CT-Angiographie (SCTA) zur Evaluation vor orthotoper Lebertransplantation (oLT) im Vergleich zur DSA. Methoden: Es wurde bei 31 Patienten vor moeglicher oLT eine SCTA der Lebergefaesse einschliesslich des Truncus coeliacus, der A. lienalis und A. mesenterica superior durchgefuehrt. Die arteriellen Gefaesse wurden mittels `Maximum-Intensitaets-Projektion (MIP)`- und `Oberflaechenschattierungs(SSD)`-Technik rekonstruiert. Die Schnittbilder, MIP und SSD, wurden bei 25 Patienten

  1. Characterization of Partial Intrinsic Symmetries

    NARCIS (Netherlands)

    Shehu, Aurela; Brunton, Alan; Wuhrer, Stefanie; Wand, Michael

    2014-01-01

    We present a mathematical framework and algorithm for characterizing and extracting partial intrinsic symmetries of surfaces, which is a fundamental building block for many modern geometry processing algorithms. Our goal is to compute all “significant” symmetry information of the shape, which we

  2. Reading: Intrinsic versus Extrinsic Motivation.

    Science.gov (United States)

    Ediger, Marlow

    Much debate centers on motivating student in reading achievement. Should students feel motivated from within (intrinsic motivation), or is it better to have extrinsic motivation whereby external stimuli are used to help learners achieve optimally in reading? This paper aims to analyze the two points of view about motivating students in reading…

  3. Intrinsic volumes of symmetric cones

    OpenAIRE

    Amelunxen, Dennis; Bürgisser, Peter

    2012-01-01

    We compute the intrinsic volumes of the cone of positive semidefinite matrices over the real numbers, over the complex numbers, and over the quaternions, in terms of integrals related to Mehta's integral. Several applications for the probabilistic analysis of semidefinite programming are given.

  4. Acoustic resonance spectroscopy intrinsic seals

    International Nuclear Information System (INIS)

    Olinger, C.T.; Burr, T.; Vnuk, D.R.

    1994-01-01

    We have begun to quantify the ability of acoustic resonance spectroscopy (ARS) to detect the removal and replacement of the lid of a simulated special nuclear materials drum. Conceptually, the acoustic spectrum of a container establishcs a baseline fingerprint, which we refer to as an intrinsic seal, for the container. Simply removing and replacing the lid changes some of the resonant frequencies because it is impossible to exactly duplicate all of the stress patterns between the lid and container. Preliminary qualitative results suggested that the ARS intrinsic seal could discriminate between cases where a lid has or has not been removed. The present work is directed at quantifying the utility of the ARS intrinsic seal technique, including the technique's sensitivity to ''nuisance'' effects, such as temperature swings, movement of the container, and placement of the transducers. These early quantitative tests support the potential of the ARS intrinsic seal application, but also reveal a possible sensitivity to nuisance effects that could limit environments or conditions under which the technique is effective

  5. Intrinsic Motivation in Physical Education

    Science.gov (United States)

    Davies, Benjamin; Nambiar, Nathan; Hemphill, Caroline; Devietti, Elizabeth; Massengale, Alexandra; McCredie, Patrick

    2015-01-01

    This article describes ways in which educators can use Harter's perceived competence motivation theory, the achievement goal theory, and self-determination theory to develop students' intrinsic motivation to maintain physical fitness, as demonstrated by the Sound Body Sound Mind curriculum and proven effective by the 2013 University of…

  6. Síntese e caracterização de MIP com fenilalanina visando sua aplicação na técnica de SPE

    Directory of Open Access Journals (Sweden)

    Layla Talita de Oliveira Alves

    2015-12-01

    Full Text Available Polímeros Molecularmente Impressos (MIPs são polímeros sintéticos que apresentam alta seletividade a uma molécula de interesse. O objetivo deste trabalho foi a síntese e caracterização de MIPs para aplicação na extração em fase sólida (SPE, visando a determinação de fenilalanina. Os MIPs foram sintetizados a partir do MAA, fenilalanina, EGDMA, AIBN, em clorofórmio. Também foi sintetizado o polímero não-impresso (NIP, para controle da seletividade dos MIPs. A dessorção da fenilalanina foi realizada em extrator Soxhlet. Os MIPs e NIP foram caracterizados pelas técnicas de análise: FTIR, UV-Vis, MEV, DSC e TG. O MIP apresentou maior capacidade adsortiva à fenilalanina do que o NIP, com uma taxa média de adsorção de 55% comparada a 11% para o NIP. Por MEV o MIP apresentou superfície mais porosa, importante característica para aplicação em SPE. Os estudos realizados mostraram que o MIP sintetizado apresentou grande potencial para aplicação em técnica de SPE.

  7. Human intrinsic factor expressed in the plant Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Laursen, Niels B; Nexø, Ebba

    2003-01-01

    Intrinsic factor (IF) is the gastric protein that promotes the intestinal uptake of vitamin B12. Gastric IF from animal sources is used in diagnostic tests and in vitamin pills. However, administration of animal IF to humans becomes disadvantageous because of possible pathogenic transmission...

  8. Diagnostic potential of virtual bronchoscopy: advantages in comparison with axial CT slices, MPR and mIP?

    International Nuclear Information System (INIS)

    Rapp-Bernhardt, U.; Doehring, W.; Bernhardt, T.M.; Welte, T.; Kropf, S.

    2000-01-01

    The aim of this study was to evaluate the diagnostic potential of virtual endoscopy (VE) and to compare it with axial CT slices, multiplanar reconstructions (MPR), minimal intensity projections (mIP), and bronchoscopy in patients diagnosed with bronchogenic carcinoma. Thirty patients underwent a spiral CT. Axial CT images were transferred to an Onyx workstation (Silicon Graphics, Sun Microsystems, Mountain View, Calif.) for performing virtual endoscopy. Accuracy for this procedure was tested by three radiologists on a monitor in comparison with axial CT slices, MPR, mIP, and bronchoscopy concerning the localization and degree of stenoses. Endoluminal tumors were identified by virtual bronchoscopy with no statistically significant difference of localization or grading of stenosis in comparison with bronchoscopy, axial CT slices, MPR and mIP. Axial CT slices, MPR, and mIP showed poorer results with over- or underestimation of stenoses compared with VE and bronchoscopy. Passing of stenoses was only possible with VE in 5 patients. Virtual endoscopy is a non-invasive method for identification of endoluminal tumors and is comparable to real bronchoscopy. (orig.)

  9. Molecular typing of Legionella pneumophila from air-conditioning cooling waters using mip gene, SBT, and FAFLP methods.

    Science.gov (United States)

    Gong, Xiangli; Li, Juntao; Zhang, Ying; Hou, Shuiping; Qu, Pinghua; Yang, Zhicong; Chen, Shouyi

    2017-08-01

    Legionella spp. are important waterborne pathogens. Molecular typing has become an important method for outbreaks investigations and source tracking of Legionnaires. In a survey program conducted by the Guangzhou Center for Disease Control and Prevention, multiple serotypes Legionella pneumophila (L. pneumophila) were isolated from waters in air-conditioning cooling towers in urban Guangzhou region, China between 2008 and 2011. Three genotyping methods, mip (macrophage infectivity potentiator) genotyping, SBT (sequence-based typing), and FAFLP (fluorescent amplified fragment length polymorphism analysis) were used to type these waterborne L. pneumophila isolates. The three methods were capable of typing all the 134 isolates and a reference strain of L. pneumophila (ATCC33153), with discriminatory indices of 0.7034, 0.9218, and 0.9376, for the mip, SBT, and FAFLP methods respectively. Among the 9 serotypes of the 134 isolates, 10, 50, and 34 molecular types were detected by the mip, SBT, and FAFLP methods respectively. The mip genotyping and SBT typing are more feasible for inter-laboratory results sharing and comparison of different types of L. pneumophila. The SBT and FAFLP typing methods were rapid with higher discriminatory abilities. Combinations of two or more of the typing methods enables more accurate typing of Legionella isolates for outbreak investigations and source tracking of Legionnaires. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Standardization of MIP technique in three-dimensional CT portography: usefulness in evaluation of portosystemic collaterals in cirrhotic patients

    International Nuclear Information System (INIS)

    Kim, Jong Gi; Kim, Yong; Kim, Chang Won; Lee, Jun Woo; Lee, Suk Hong

    2003-01-01

    To assess the usefulness of three-dimensional CT portography using a standardized maximum intensity projection (MIP) technique for the evaluation of portosystemic collaterals in cirrhotic patients. In 25 cirrhotic patients with portosystemic collaterals, three-phase CT using a multide-tector-row helical CT scanner was performed to evaluate liver disease. Late arterial-phase images were transferred to an Advantage Windows 3.1 workstation (Gener Electric). Axial images were reconstructed by means of three-dimensional CT portography, using both a standardized and a non-standardized MIP technique, and the respective reconstruction times were determined. Three-dimensional CT portography with the standardized technique involved eight planes, namely the spleno-portal confluence axis (coronal, lordotic coronal, lordotic coronal RAO 30 .deg. C, and lordotic coronal LAO 30 .deg. C), the left renal vein axis (lordotic coronal), and axial MIP images (lower esophagus level, gastric fundus level and splenic hilum). The eight MIP images obtained in each case were interpreted by two radiologists, who reached a consensus in their evaluation. The portosystemic collaterals evaluated were as follows: left gastric vein dilatation; esophageal, paraesophageal, gastric, and splenic varix; paraumbilical vein dilatation; gastro-renal, spleno-renal, and gastro-spleno-renal shunt; mesenteric, retroperitoneal, and omental collaterals. The average reconstruction time using the non-standardized MIP technique was 11 minutes 23 seconds, and with the standardized technique, the time was 6 minutes 5 seconds. Three-dimensional CT portography with the standardized technique demonstrated left gastric vein dilatation (n=25), esophageal varix (n=18), paraesophageal varix (n=13), gastric varix (n=4), splenic varix (n=4), paraumbilical vein dilatation (n=4), gastro-renal shunt (n=3), spleno-renal shunt (n=3), and gastro-spleno-renal shunt (n=1). Using three-dimensional CT protography and the non

  11. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. The AgMIP Coordinated Global and Regional Assessments (CGRA) of Climate Change Impacts on Agriculture and Food Security

    Science.gov (United States)

    Ruane, Alex; Rosenzweig, Cynthia; Elliott, Joshua; Antle, John

    2015-01-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) has been working since 2010 to construct a protocol-based framework enabling regional assessments (led by regional experts and modelers) that can provide consistent inputs to global economic and integrated assessment models. These global models can then relay important global-level information that drive regional decision-making and outcomes throughout an interconnected agricultural system. AgMIPs community of nearly 800 climate, crop, livestock, economics, and IT experts has improved the state-of-the-art through model intercomparisons, validation exercises, regional integrated assessments, and the launch of AgMIP programs on all six arable continents. AgMIP is now launching Coordinated Global and Regional Assessments (CGRA) of climate change impacts on agriculture and food security to link global and regional crop and economic models using a protocol-based framework. The CGRA protocols are being developed to utilize historical observations, climate projections, and RCPsSSPs from CMIP5 (and potentially CMIP6), and will examine stakeholder-driven agricultural development and adaptation scenarios to provide cutting-edge assessments of climate changes impact on agriculture and food security. These protocols will build on the foundation of established protocols from AgMIPs 30+ activities, and will emphasize the use of multiple models, scenarios, and scales to enable an accurate assessment of related uncertainties. The CGRA is also designed to provide the outputs necessary to feed into integrated assessment models (IAMs), nutrition and food security assessments, nitrogen and carbon cycle models, and additional impact-sector assessments (e.g., water resources, land-use, biomes, urban areas). This presentation will describe the current status of CGRA planning and initial prototype experiments to demonstrate key aspects of the protocols before wider implementation ahead of the IPCC Sixth Assessment

  13. The AgMIP Coordinated Global and Regional Assessments (CGRA) of Climate Change Impacts on Agriculture and Food Security

    Science.gov (United States)

    Ruane, A. C.; Rosenzweig, C.; Antle, J. M.; Elliott, J. W.

    2015-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) has been working since 2010 to construct a protocol-based framework enabling regional assessments (led by regional experts and modelers) that can provide consistent inputs to global economic and integrated assessment models. These global models can then relay important global-level information that drive regional decision-making and outcomes throughout an interconnected agricultural system. AgMIP's community of nearly 800 climate, crop, livestock, economics, and IT experts has improved the state-of-the-art through model intercomparisons, validation exercises, regional integrated assessments, and the launch of AgMIP programs on all six arable continents. AgMIP is now launching Coordinated Global and Regional Assessments (CGRA) of climate change impacts on agriculture and food security to link global and regional crop and economic models using a protocol-based framework. The CGRA protocols are being developed to utilize historical observations, climate projections, and RCPs/SSPs from CMIP5 (and potentially CMIP6), and will examine stakeholder-driven agricultural development and adaptation scenarios to provide cutting-edge assessments of climate change's impact on agriculture and food security. These protocols will build on the foundation of established protocols from AgMIP's 30+ activities, and will emphasize the use of multiple models, scenarios, and scales to enable an accurate assessment of related uncertainties. The CGRA is also designed to provide the outputs necessary to feed into integrated assessment models (IAMs), nutrition and food security assessments, nitrogen and carbon cycle models, and additional impact-sector assessments (e.g., water resources, land-use, biomes, urban areas). This presentation will describe the current status of CGRA planning and initial prototype experiments to demonstrate key aspects of the protocols before wider implementation ahead of the IPCC Sixth Assessment

  14. How much of our environment do we need?. MIPS - a measuring method for an ecological economy; Wieviel Umwelt braucht der Mensch?. MIPS - Das Mass fuer oekologisches Wirtschaften

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt-Bleek, F.; Klueting, R.

    1994-12-31

    This book illustrates how much of our environment we use up with the products and services associated with everyday life, how large the ecological impact of our consume society actually is; we build roads, dams, heavy goods vehicles, warehouses, factories, monocultures and rubbish tips. We take iron ore, sand, gravel, coal oil, water, air and wood from our environment in huge, ever-increasing qualities. Slag heaps, erosion and disrupted water flow are left behind. This man-made materialistic society is altering nature`s balance persistently and for the long term. This materialism is no longer ecologically sustainable. We must learn to prosper with less negative environmental impacts. The author has developed a means of measuring the intensity of environmental impact of products, processes and services, based on the material consumed to allow acurate comparisons. In this comprehensible informative book he reveals, for the first time publicly, the measure/formula by means of many practical examples and illustrations to show a way out of the crisis. (orig./UA) [Deutsch] Dieses Buch veranschaulicht, wieviel Umwelt wir fuer Produkte und Dienstleistungen des taeglichen Lebens verbrauchen, wie gross die `oekologischen Rucksaecke` unseres Konsums wirklich sind: Wir bauen Strassen, Daemme, Lastwagen, Lager, Fabriken, Supermaerkte, Legen Monokulturen und Abfalldeponien an. Aus der Umwelt holen wir Erze, Sand, Kies, Oel, Wasser, Luft und Holz in riesigen und immer wachsenden Mengen. Zurueck bleiben Abraumhalden, Erosionen und gestoerte Wasserlaeufe. Die menschengemachten Materialverschiebungen, die Stoffstroeme, veraendern die natuerlichen Balancen, nachhaltig und unaufhaltsam. Die Materialintensitaet unseres Wohlstandes ist oekologisch nicht mehr tragbar. Wir muessen lernen, Wohlstand mit weniger Umwelt zu erhalten und zu schaffen. Der Autor hat ein neues Mass (mips=Material-Intensitaet pro Serviceeinheit) entwickelt, dessen Basis der Stoffverbrauch ist und das es

  15. The Neglected Intrinsic Resistome of Bacterial Pathogens

    Science.gov (United States)

    Fajardo, Alicia; Martínez-Martín, Nadia; Mercadillo, María; Galán, Juan C.; Ghysels, Bart; Matthijs, Sandra; Cornelis, Pierre; Wiehlmann, Lutz; Tümmler, Burkhard; Baquero, Fernando; Martínez, José L.

    2008-01-01

    Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature. PMID:18286176

  16. The neglected intrinsic resistome of bacterial pathogens.

    Directory of Open Access Journals (Sweden)

    Alicia Fajardo

    Full Text Available Bacteria with intrinsic resistance to antibiotics are a worrisome health problem. It is widely believed that intrinsic antibiotic resistance of bacterial pathogens is mainly the consequence of cellular impermeability and activity of efflux pumps. However, the analysis of transposon-tagged Pseudomonas aeruginosa mutants presented in this article shows that this phenotype emerges from the action of numerous proteins from all functional categories. Mutations in some genes make P. aeruginosa more susceptible to antibiotics and thereby represent new targets. Mutations in other genes make P. aeruginosa more resistant and therefore define novel mechanisms for mutation-driven acquisition of antibiotic resistance, opening a new research field based in the prediction of resistance before it emerges in clinical environments. Antibiotics are not just weapons against bacterial competitors, but also natural signalling molecules. Our results demonstrate that antibiotic resistance genes are not merely protective shields and offer a more comprehensive view of the role of antibiotic resistance genes in the clinic and in nature.

  17. Digested disorder: Quarterly intrinsic disorder digest (January/February/March, 2013).

    Science.gov (United States)

    Uversky, Vladimir N

    2013-01-01

    The current literature on intrinsically disordered proteins is blooming. A simple PubMed search for "intrinsically disordered protein OR natively unfolded protein" returns about 1,800 hits (as of June 17, 2013), with many papers published quite recently. To keep interested readers up to speed with this literature, we are starting a "Digested Disorder" project, which will encompass a series of reader's digest type of publications aiming at the objective representation of the research papers and reviews on intrinsically disordered proteins. The only two criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest covers papers published during the period of January, February and March of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  18. Preparation of protein imprinted materials by hierarchical imprinting techniques and application in selective depletion of albumin from human serum.

    Science.gov (United States)

    Liu, Jinxiang; Deng, Qiliang; Tao, Dingyin; Yang, Kaiguang; Zhang, Lihua; Liang, Zhen; Zhang, Yukui

    2014-06-30

    Hierarchical imprinting was developed to prepare the protein imprinted materials, as the artificial antibody, for the selective depletion of HSA from the human serum proteome. Porcine serum albumin (PSA) was employed as the dummy template for the fabrication of the recognition sites. To demonstrate the advantages of the hierarchical imprinting, molecularly imprinted polymers prepared by hierarchical imprinting technique (h-MIPs) were compared with those obtained by bulk imprinting (b-MIPs), in terms of the binding capacity, adsorption kinetics, selectivity and synthesis reproducibility. The binding capacity of h-MIPs could reach 12 mg g(-1). And saturation binding could be reached in less than 20 min for the h-MIPs. In the protein mixture, h-MIPs exhibit excellent selectivity for PSA, with imprinting factors as about 3.6, much higher than those for non-template proteins. For the proteomic application, the identified protein group number in serum treated by h-MIPs was increased to 422, which is 21% higher than that obtained from the original serum, meanwhile the identified protein group number for the Albumin Removal kit was only 376. The results demonstrate that protein imprinted polymers prepared by hierarchical imprinting technique, might become the artificial antibodies for the selective depletion of high abundance proteins in proteome study.

  19. Highly Selective Fluorescent Sensing of Proteins Based on a Fluorescent Molecularly Imprinted Nanosensor

    Directory of Open Access Journals (Sweden)

    Shuo Wang

    2013-09-01

    Full Text Available A fluorescent molecularly imprinted nanosensor was obtained by grafting imprinted polymer onto the surface of multi-wall carbon nanotubes and post-imprinting treatment with fluorescein isothiocyanate (FITC. The fluorescence of lysozyme-imprinted polymer (Lys-MIP was quenched more strongly by Lys than that of nonimprinted polymer (NIP, which indicated that the Lys-MIP could recognize Lys. The resulted imprinted material has the ability to selectively sense a target protein, and an imprinting factor of 3.34 was achieved. The Lys-MIP also showed selective detection for Lys among other proteins such as cytochrome C (Cyt C, hemoglobin (HB and bovine serum albumin (BSA due to the imprinted sites in the Lys-MIP. This approach combines the high selectivity of surface molecular imprinting technology and fluorescence, and converts binding events into detectable signals by monitoring fluorescence spectra. Therefore, it will have further applications for Lys sensing.

  20. Detecting Nosocomial Intrinsic Infections through Relating Bacterial ...

    African Journals Online (AJOL)

    Sierra Leone Journal of Biomedical Research ... Surgical procedures often lead to both intrinsic and extrinsic infections. ... This study demonstrated surgical procedures as precursory to intrinsic infections and that bacterial pathogens found on wounds and endogenous indicators of surgery are links to intrinsic infection.

  1. Highly Selective Polypyrrole MIP-Based Gravimetric and Electrochemical Sensors for Picomolar Detection of Glyphosate.

    Science.gov (United States)

    Mazouz, Zouhour; Rahali, Seyfeddine; Fourati, Najla; Zerrouki, Chouki; Aloui, Nadia; Seydou, Mahamadou; Yaakoubi, Nourdin; Chehimi, Mohamed M; Othmane, Ali; Kalfat, Rafik

    2017-11-09

    There is a global debate and concern about the use of glyphosate (Gly) as an herbicide. New toxicological studies will determine its use in the future under new strict conditions or its replacement by alternative synthetic or natural herbicides. In this context, we designed biomimetic polymer sensing layers for the selective molecular recognition of Gly. Towards this end, complementary surface acoustic wave (SAW) and electrochemical sensors were functionalized with polypyrrole (PPy)-imprinted polymer for the selective detection of Gly. Their corresponding limits of detection were on the order of 1 pM, which are among the lowest values ever reported in literature. The relevant dissociation constants between PPy and Gly were estimated at [K d1 = (0.7 ± 0.3) pM and K d2 = (1.6 ± 1.4) µM] and [K d1 = (2.4 ± 0.9) pM and K d2 = (0.3 ± 0.1) µM] for electrochemical and gravimetric measurements, respectively. Quantum chemical calculations permitted to estimate the interaction energy between Gly and PPy film: ΔE = -145 kJ/mol. Selectivity and competitivity tests were investigated with the most common pesticides. This work conclusively shows that gravimetric and electrochemical results indicate that both MIP-based sensors are perfectly able to detect and distinguish glyphosate without any ambiguity.

  2. Highly Selective Polypyrrole MIP-Based Gravimetric and Electrochemical Sensors for Picomolar Detection of Glyphosate

    Directory of Open Access Journals (Sweden)

    Zouhour Mazouz

    2017-11-01

    Full Text Available There is a global debate and concern about the use of glyphosate (Gly as an herbicide. New toxicological studies will determine its use in the future under new strict conditions or its replacement by alternative synthetic or natural herbicides. In this context, we designed biomimetic polymer sensing layers for the selective molecular recognition of Gly. Towards this end, complementary surface acoustic wave (SAW and electrochemical sensors were functionalized with polypyrrole (PPy-imprinted polymer for the selective detection of Gly. Their corresponding limits of detection were on the order of 1 pM, which are among the lowest values ever reported in literature. The relevant dissociation constants between PPy and Gly were estimated at [Kd1 = (0.7 ± 0.3 pM and Kd2 = (1.6 ± 1.4 µM] and [Kd1 = (2.4 ± 0.9 pM and Kd2 = (0.3 ± 0.1 µM] for electrochemical and gravimetric measurements, respectively. Quantum chemical calculations permitted to estimate the interaction energy between Gly and PPy film: ΔE = −145 kJ/mol. Selectivity and competitivity tests were investigated with the most common pesticides. This work conclusively shows that gravimetric and electrochemical results indicate that both MIP-based sensors are perfectly able to detect and distinguish glyphosate without any ambiguity.

  3. Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX.

    Science.gov (United States)

    Linkuvienė, Vaida; Matulienė, Jurgita; Juozapaitienė, Vaida; Michailovienė, Vilma; Jachno, Jelena; Matulis, Daumantas

    2016-04-01

    Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the compound structure to thermodynamics relationship. It is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Subgroup-specific intrinsic disorder profiles of arabidopsis NAC transcription factors

    DEFF Research Database (Denmark)

    Stender, Emil G.; O'Shea, Charlotte; Skriver, Karen

    2015-01-01

    Protein intrinsic disorder (ID), referring to the lack of a fixed tertiary structure, is significant in signaling and transcription. We recently characterized ID in 6 phylogenetically representative Arabidopsis thaliana NAC transcription factors. Their transcription regulatory domains are mostly...

  5. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor

    DEFF Research Database (Denmark)

    Tran, E H; Kuziel, W A; Owens, T

    2000-01-01

    Macrophage inflammatory protein (MIP)-1alpha is a chemokine that is associated with Th1 cytokine responses. Expression and antibody blocking studies have implicated MIP-1alpha in multiple sclerosis (MS) and in experimental autoimmune encephalomyelitis (EAE). We examined the role of MIP-1alpha......-type mice in Th1 cytokine gene expression, the kinetics and severity of disease, and infiltration of the central nervous system by lymphocytes, macrophages and granulocytes. RNase protection assays showed comparable accumulation of mRNA for the chemokines interferon-inducible protein-10, RANTES, macrophage...

  6. Understanding the Reach of Agricultural Impacts from Climate Extremes in the Agricultural Model Intercomparison and Improvement Project (AgMIP)

    Science.gov (United States)

    Ruane, A. C.

    2016-12-01

    The Agricultural Model Intercomparison and Improvement Project (AgMIP) has been working since 2010 to build a modeling framework capable of representing the complexities of agriculture, its dependence on climate, and the many elements of society that depend on food systems. AgMIP's 30+ activities explore the interconnected nature of climate, crop, livestock, economics, food security, and nutrition, using common protocols to systematically evaluate the components of agricultural assessment and allow multi-model, multi-scale, and multi-method analysis of intertwining changes in socioeconomic development, environmental change, and technological adaptation. AgMIP is now launching Coordinated Global and Regional Assessments (CGRA) with a particular focus on unforeseen consequences of development strategies, interactions between global and local systems, and the resilience of agricultural systems to extreme climate events. Climate extremes shock the agricultural system through local, direct impacts (e.g., droughts, heat waves, floods, severe storms) and also through teleconnections propagated through international trade. As the climate changes, the nature of climate extremes affecting agriculture is also likely to change, leading to shifting intensity, duration, frequency, and geographic extents of extremes. AgMIP researchers are developing new scenario methodologies to represent near-term extreme droughts in a probabilistic manner, field experiments that impose heat wave conditions on crops, increased resolution to differentiate sub-national drought impacts, new behavioral functions that mimic the response of market actors faced with production shortfalls, analysis of impacts from simultaneous failures of multiple breadbasket regions, and more detailed mapping of food and socioeconomic indicators into food security and nutrition metrics that describe the human impact in diverse populations. Agricultural models illustrate the challenges facing agriculture, allowing

  7. Intrinsic cylindrical and spherical waves

    International Nuclear Information System (INIS)

    Ludlow, I K

    2008-01-01

    Intrinsic waveforms associated with cylindrical and spherical Bessel functions are obtained by eliminating the factors responsible for the inverse radius and inverse square radius laws of wave power per unit area of wavefront. The resulting expressions are Riccati-Bessel functions for both cases and these can be written in terms of amplitude and phase functions of order v and wave variable z. When z is real, it is shown that a spatial phase angle of the intrinsic wave can be defined and this, together with its amplitude function, is systematically investigated for a range of fixed orders and varying z. The derivatives of Riccati-Bessel functions are also examined. All the component functions exhibit different behaviour in the near field depending on the order being less than, equal to or greater than 1/2. Plots of the phase angle can be used to display the locations of the zeros of the general Riccati-Bessel functions and lead to new relations concerning the ordering of the real zeros of Bessel functions and the occurrence of multiple zeros when the argument of the Bessel function is fixed

  8. Towards a New Food System Assessment: AgMIP Coordinated Global and Regional Assessments of Climate Change

    Science.gov (United States)

    Rosenzweig, Cynthia E.; Thorburn, Peter

    2017-01-01

    Agricultural stakeholders need more credible information on which to base adaptation and mitigation policy decisions. In order to provide this, we must improve the rigor of agricultural modelling. Ensemble approaches can be used to address scale issues and integrated teams can overcome disciplinary silos. The AgMIP Coordinated Global and Regional Assessments of Climate Change and Food Security (CGRA) has the goal to link agricultural systems models using common protocols and scenarios to significantly improve understanding of climate effects on crops, livestock and livelihoods across multiple scales. The AgMIP CGRA assessment brings together experts in climate, crop, livestock, economics, and food security to develop Protocols to guide the process throughout the assessment. Scenarios are designed to consistently combine elements of intertwined storylines of future society including, socioeconomic development, greenhouse gas concentrations, and specific pathways of agricultural sector development. Through these approaches, AgMIP partners around the world are providing an evidence base for their stakeholders as they make decisions and investments.

  9. The microwave induced plasma with optical emission spectrometry (MIP-OES) in 23 elements determination in geological samples.

    Science.gov (United States)

    Niedzielski, P; Kozak, L; Wachelka, M; Jakubowski, K; Wybieralska, J

    2015-01-01

    The article presents the optimisation, validation and application of the microwave induced plasma optical emission spectrometry (MIP-OES) dedicated for a routine determination of Ag, Al, B, Ba, Bi, Ca, Cd, Cr, Cu, Fe, Ga, In, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Sr, Tl, Zn, in the geological samples. The three procedures of sample preparation has been proposed: sample digestion with the use of hydrofluoric acid for determination of total concentration of elements, extraction by aqua regia for determination of the quasi-total element concentration and extraction by hydrochloric acid solution to determine contents of the elements in acid leachable fraction. The detection limits were on the level 0.001-0.121 mg L(-1) (from 0.010-0.10 to 1.2-12 mg kg(-1) depend on the samples preparation procedure); the precision: 0.20-1.37%; accuracy 85-115% (for recovery for certified standards materials analysis and parallel analysis by independent analytical techniques: X-ray fluorescence (XRF) and flame absorption spectrometry (FAAS)). The conformity of the results obtained by MIP-OES analytical procedures with the results obtained by XRF and FAAS analysis allows to propose the procedures for studies of elemental composition of the fraction of the geological samples. Additionally, the MIP-OES technique is much less expensive than ICP techniques and much less time-consuming than AAS techniques. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Integrated Assessment by the People: Insights from AgMIP Regional Teams in Sub-Saharan Africa and South Asia

    Science.gov (United States)

    Antle, J. M.

    2017-12-01

    AgMIP has developed innovative protocol-based methods for regional integrated assessment (RIA) that can be implemented by national researchers working with local and national stakeholders (http://www.agmip.org/regional-integrated-assessments-handbook/). The approach has been implemented by regional teams in Sub-Saharan Africa and South Asia. This presentation first summarizes novel elements of the AgMIP RIA methods, and their strengths and limitations, based on their application by AgMIP researchers. Key insights from the application of these methods for climate impact and adaptation in Sub-Saharan Africa and South Asia are presented. A major finding is that detailed, site-specific, systems-based analysis show much more local and regional variation in impacts than studies based on analysis of individual crops, and provide the basis for analysis of multi-faceted technology and policy options to facilitate the transition to sustainable and resilient development pathways. The presentation concludes with observations about advancing integrated assessments carried out by and for national and local researchers and stakeholders.

  11. Inhibition of Intrinsic Thrombin Generation

    Directory of Open Access Journals (Sweden)

    Thomas W. Stief MD

    2006-01-01

    Full Text Available Background The contact phase of coagulation is of physiologic/pathophysiologic importance, whenever unphysiologic polynegative substances such as cell fragments (microparticles get in contact with blood. There are several clinically used inhibitors of intrinsic thrombin generation. Here the inhibitory concentrations 50% (IC50 of these anticoagulants are measured by the highly specific thrombin generation assay INCA. Methods Unfrozen pooled normal citrated plasma in polystyrole tubes was supplemented at 23°C in duplicate with 0–2 IU/ml low molecular weight heparin (dalteparin, 0–2 IU/ml unfractionated heparin, 0–500 KIU/ml aprotinin, or 0–40 mM arginine. 50 μl plasma or 1 IU/ml thrombin standard were pipetted into a polystyrole microtiter plate with flat bottom. 5 μl SiO 2 /CaCl 2 - reagent (INCA activator were added and after 0–30 min incubation at 37°C 100 μl 2.5 M arginine, pH 8.6, were added; arginine inhibits hemostasis activation and depolymerizes generated fibrin within 20 min at 23°C. The in the physiologic 37°C incubation phase generated thrombin was then chromogenically detected. The intra-assay CV values were < 5%. Results and Discussion The approximate IC50 were 0.01 IU/ml dalteparin, 0.02 IU/ml heparin, 25 KIU/ml aprotinin, and 12 mM arginine. The efficiency of any anticoagulant on intrinsic thrombin generation should be measured for each individual patient. Abbreviations IIa, thrombin; δA, increase in absorbance; APTT, activated partial thromboplastin time; CRT, coagulation reaction time (at 37°C in water-bath; F-wells, polystyrole microtiter plates with flat bottom; IC50, inhibitory concentration 50%; INCA, intrinsic coagulation activity assay; IU, international units; KIU, kallikrein inhibiting unis; LMWH, low molecular weight heparin; mA, milli-absorbance units; PSL, pathromtin SL®; RT, room temperature (23°C; U-wells, polystyrole microtiter plates with round bottom.

  12. Energy transport, polar amplification, and ITCZ shifts in the GeoMIP G1 ensemble

    Directory of Open Access Journals (Sweden)

    R. D. Russotto

    2018-02-01

    Full Text Available The polar amplification of warming and the ability of the Intertropical Convergence Zone (ITCZ to shift to the north or south are two very important problems in climate science. Examining these behaviors in global climate models (GCMs running solar geoengineering experiments is helpful not only for predicting the effects of solar geoengineering but also for understanding how these processes work under increased carbon dioxide (CO2. Both polar amplification and ITCZ shifts are closely related to the meridional transport of moist static energy (MSE by the atmosphere. This study examines changes in MSE transport in 10 fully coupled GCMs in experiment G1 of the Geoengineering Model Intercomparison Project (GeoMIP, in which the solar constant is reduced to compensate for the radiative forcing from abruptly quadrupled CO2 concentrations. In G1, poleward MSE transport decreases relative to preindustrial conditions in all models, in contrast to the Coupled Model Intercomparison Project phase 5 (CMIP5 abrupt4xCO2 experiment, in which poleward MSE transport increases. We show that since poleward energy transport decreases rather than increases, and local feedbacks cannot change the sign of an initial temperature change, the residual polar amplification in the G1 experiment must be due to the net positive forcing in the polar regions and net negative forcing in the tropics, which arise from the different spatial patterns of the simultaneously imposed solar and CO2 forcings. However, the reduction in poleward energy transport likely plays a role in limiting the polar warming in G1. An attribution study with a moist energy balance model shows that cloud feedbacks are the largest source of uncertainty regarding changes in poleward energy transport in midlatitudes in G1, as well as for changes in cross-equatorial energy transport, which are anticorrelated with ITCZ shifts.

  13. An AgMIP framework for improved agricultural representation in integrated assessment models

    Science.gov (United States)

    Ruane, Alex C.; Rosenzweig, Cynthia; Asseng, Senthold; Boote, Kenneth J.; Elliott, Joshua; Ewert, Frank; Jones, James W.; Martre, Pierre; McDermid, Sonali P.; Müller, Christoph; Snyder, Abigail; Thorburn, Peter J.

    2017-12-01

    Integrated assessment models (IAMs) hold great potential to assess how future agricultural systems will be shaped by socioeconomic development, technological innovation, and changing climate conditions. By coupling with climate and crop model emulators, IAMs have the potential to resolve important agricultural feedback loops and identify unintended consequences of socioeconomic development for agricultural systems. Here we propose a framework to develop robust representation of agricultural system responses within IAMs, linking downstream applications with model development and the coordinated evaluation of key climate responses from local to global scales. We survey the strengths and weaknesses of protocol-based assessments linked to the Agricultural Model Intercomparison and Improvement Project (AgMIP), each utilizing multiple sites and models to evaluate crop response to core climate changes including shifts in carbon dioxide concentration, temperature, and water availability, with some studies further exploring how climate responses are affected by nitrogen levels and adaptation in farm systems. Site-based studies with carefully calibrated models encompass the largest number of activities; however they are limited in their ability to capture the full range of global agricultural system diversity. Representative site networks provide more targeted response information than broadly-sampled networks, with limitations stemming from difficulties in covering the diversity of farming systems. Global gridded crop models provide comprehensive coverage, although with large challenges for calibration and quality control of inputs. Diversity in climate responses underscores that crop model emulators must distinguish between regions and farming system while recognizing model uncertainty. Finally, to bridge the gap between bottom-up and top-down approaches we recommend the deployment of a hybrid climate response system employing a representative network of sites to bias

  14. Energy transport, polar amplification, and ITCZ shifts in the GeoMIP G1 ensemble

    Science.gov (United States)

    Russotto, Rick D.; Ackerman, Thomas P.

    2018-02-01

    The polar amplification of warming and the ability of the Intertropical Convergence Zone (ITCZ) to shift to the north or south are two very important problems in climate science. Examining these behaviors in global climate models (GCMs) running solar geoengineering experiments is helpful not only for predicting the effects of solar geoengineering but also for understanding how these processes work under increased carbon dioxide (CO2). Both polar amplification and ITCZ shifts are closely related to the meridional transport of moist static energy (MSE) by the atmosphere. This study examines changes in MSE transport in 10 fully coupled GCMs in experiment G1 of the Geoengineering Model Intercomparison Project (GeoMIP), in which the solar constant is reduced to compensate for the radiative forcing from abruptly quadrupled CO2 concentrations. In G1, poleward MSE transport decreases relative to preindustrial conditions in all models, in contrast to the Coupled Model Intercomparison Project phase 5 (CMIP5) abrupt4xCO2 experiment, in which poleward MSE transport increases. We show that since poleward energy transport decreases rather than increases, and local feedbacks cannot change the sign of an initial temperature change, the residual polar amplification in the G1 experiment must be due to the net positive forcing in the polar regions and net negative forcing in the tropics, which arise from the different spatial patterns of the simultaneously imposed solar and CO2 forcings. However, the reduction in poleward energy transport likely plays a role in limiting the polar warming in G1. An attribution study with a moist energy balance model shows that cloud feedbacks are the largest source of uncertainty regarding changes in poleward energy transport in midlatitudes in G1, as well as for changes in cross-equatorial energy transport, which are anticorrelated with ITCZ shifts.

  15. New AgMIP Scenarios: Impacts of Volcanic Eruptions, Geoengineering, or Nuclear War on Agriculture

    Science.gov (United States)

    Robock, A.; Xia, L.

    2016-12-01

    Climate is one of the most important factors determining crop yields and world food supplies. To be well prepared for possible futures, it is necessary to study yield changes of major crops in response to different climate forcings. Previous studies mainly focus on the impact from global warming. Here we propose that the AgMIP community also study the impacts of stratospheric aerosols on agriculture. While nature can load the stratosphere with sulfate aerosols for several years from large volcanic eruptions, humans could also put sulfate aerosols into the stratosphere on purpose through geoengineering or soot as a result of the fires from a nuclear war. Stratospheric aerosols would change the temperature, precipitation, total insolation, and fraction of diffuse radiation due to their radiative impacts, and could produce more ultraviolet radiation by ozone destruction. Surface ozone concentration could also change by changed transport from the stratosphere as well as changed tropospheric chemistry. As a demonstration of these effects, using the crop model in the NCAR Community Land Model (CLM-crop), we have studied sulfate injection geoengineering and nuclear war impacts on global agriculture in response to temperature, precipitation and radiation changes, and found significant changes in patterns of global food production. With the new ozone module in CLM-crop, we simulated how surface ozone concentration change under sulfate injection geoengineering would change the agriculture response. Agriculture would benefit from less surface ozone concentration associated with the specific geoengineering scenario comparing with the global warming scenario. Here, we would like to encourage more crop modelers to improve crop models in terms of crop responses to ozone, ultraviolet radiation, and diffuse radiation. We also invite more global crop modeling groups to use the climate forcing we would be happy to provide to gain a better understanding of global agriculture responses

  16. Quarterly intrinsic disorder digest (January-February-March, 2014).

    Science.gov (United States)

    DeForte, Shelly; Reddy, Krishna D; Uversky, Vladimir N

    2016-01-01

    This is the 5 th issue of the Digested Disorder series that represents a reader's digest of the scientific literature on intrinsically disordered proteins. We continue to use only 2 criteria for inclusion of a paper to this digest: The publication date (a paper should be published within the covered time frame) and the topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the first quarter of 2014; i.e., during the period of January, February, and March of 2014. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included papers a short description is given on its major findings.

  17. A protocol for the intercomparison of marine fishery and ecosystem models: Fish-MIP v1.0

    Science.gov (United States)

    Tittensor, Derek P.; Eddy, Tyler D.; Lotze, Heike K.; Galbraith, Eric D.; Cheung, William; Barange, Manuel; Blanchard, Julia L.; Bopp, Laurent; Bryndum-Buchholz, Andrea; Büchner, Matthias; Bulman, Catherine; Carozza, David A.; Christensen, Villy; Coll, Marta; Dunne, John P.; Fernandes, Jose A.; Fulton, Elizabeth A.; Hobday, Alistair J.; Huber, Veronika; Jennings, Simon; Jones, Miranda; Lehodey, Patrick; Link, Jason S.; Mackinson, Steve; Maury, Olivier; Niiranen, Susa; Oliveros-Ramos, Ricardo; Roy, Tilla; Schewe, Jacob; Shin, Yunne-Jai; Silva, Tiago; Stock, Charles A.; Steenbeek, Jeroen; Underwood, Philip J.; Volkholz, Jan; Watson, James R.; Walker, Nicola D.

    2018-04-01

    Model intercomparison studies in the climate and Earth sciences communities have been crucial to building credibility and coherence for future projections. They have quantified variability among models, spurred model development, contrasted within- and among-model uncertainty, assessed model fits to historical data, and provided ensemble projections of future change under specified scenarios. Given the speed and magnitude of anthropogenic change in the marine environment and the consequent effects on food security, biodiversity, marine industries, and society, the time is ripe for similar comparisons among models of fisheries and marine ecosystems. Here, we describe the Fisheries and Marine Ecosystem Model Intercomparison Project protocol version 1.0 (Fish-MIP v1.0), part of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP), which is a cross-sectoral network of climate impact modellers. Given the complexity of the marine ecosystem, this class of models has substantial heterogeneity of purpose, scope, theoretical underpinning, processes considered, parameterizations, resolution (grain size), and spatial extent. This heterogeneity reflects the lack of a unified understanding of the marine ecosystem and implies that the assemblage of all models is more likely to include a greater number of relevant processes than any single model. The current Fish-MIP protocol is designed to allow these heterogeneous models to be forced with common Earth System Model (ESM) Coupled Model Intercomparison Project Phase 5 (CMIP5) outputs under prescribed scenarios for historic (from the 1950s) and future (to 2100) time periods; it will be adapted to CMIP phase 6 (CMIP6) in future iterations. It also describes a standardized set of outputs for each participating Fish-MIP model to produce. This enables the broad characterization of differences between and uncertainties within models and projections when assessing climate and fisheries impacts on marine ecosystems and the

  18. A protocol for the intercomparison of marine fishery and ecosystem models: Fish-MIP v1.0

    Directory of Open Access Journals (Sweden)

    D. P. Tittensor

    2018-04-01

    Full Text Available Model intercomparison studies in the climate and Earth sciences communities have been crucial to building credibility and coherence for future projections. They have quantified variability among models, spurred model development, contrasted within- and among-model uncertainty, assessed model fits to historical data, and provided ensemble projections of future change under specified scenarios. Given the speed and magnitude of anthropogenic change in the marine environment and the consequent effects on food security, biodiversity, marine industries, and society, the time is ripe for similar comparisons among models of fisheries and marine ecosystems. Here, we describe the Fisheries and Marine Ecosystem Model Intercomparison Project protocol version 1.0 (Fish-MIP v1.0, part of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP, which is a cross-sectoral network of climate impact modellers. Given the complexity of the marine ecosystem, this class of models has substantial heterogeneity of purpose, scope, theoretical underpinning, processes considered, parameterizations, resolution (grain size, and spatial extent. This heterogeneity reflects the lack of a unified understanding of the marine ecosystem and implies that the assemblage of all models is more likely to include a greater number of relevant processes than any single model. The current Fish-MIP protocol is designed to allow these heterogeneous models to be forced with common Earth System Model (ESM Coupled Model Intercomparison Project Phase 5 (CMIP5 outputs under prescribed scenarios for historic (from the 1950s and future (to 2100 time periods; it will be adapted to CMIP phase 6 (CMIP6 in future iterations. It also describes a standardized set of outputs for each participating Fish-MIP model to produce. This enables the broad characterization of differences between and uncertainties within models and projections when assessing climate and fisheries impacts on marine ecosystems

  19. Intrinsic rotation with gyrokinetic models

    International Nuclear Information System (INIS)

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.; Calvo, Iván

    2012-01-01

    The generation of intrinsic rotation by turbulence and neoclassical effects in tokamaks is considered. To obtain the complex dependences observed in experiments, it is necessary to have a model of the radial flux of momentum that redistributes the momentum within the tokamak in the absence of a preexisting velocity. When the lowest order gyrokinetic formulation is used, a symmetry of the model precludes this possibility, making small effects in the gyroradius over scale length expansion necessary. These effects that are usually small become important for momentum transport because the symmetry of the lowest order gyrokinetic formulation leads to the cancellation of the lowest order momentum flux. The accuracy to which the gyrokinetic equation needs to be obtained to retain all the physically relevant effects is discussed.

  20. Cathepsin D Specifically Cleaves the Chemokines Macrophage Inflammatory Protein-1α, Macrophage Inflammatory Protein-1β, and SLC That Are Expressed in Human Breast Cancer

    Science.gov (United States)

    Wolf, Marlene; Clark-Lewis, Ian; Buri, Caroline; Langen, Hanno; Lis, Maddalena; Mazzucchelli, Luca

    2003-01-01

    Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1α (CCL3), MIP-1β (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1α and MIP-1β degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu58 to Trp59 bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1β hybrids indicated that processing of MIP-1β might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1α, MIP-1β, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes. PMID:12651610

  1. Differential expression of elastic fibre components in intrinsically aged skin.

    Science.gov (United States)

    Langton, Abigail K; Sherratt, Michael J; Griffiths, Christopher E M; Watson, Rachel E B

    2012-02-01

    Intrinsic ageing of the skin is a subtle process resulting in some degree of skin laxity. The dermal elastic fibre network imbues skin with the capacity to recoil and loss of this property contributes to an aged, wrinkled appearance. Whilst elastic fibres have a complex, composite structure which allows them to fulfil multiple roles, the effects of intrinsic ageing on their discrete molecular components has not previously been explored. In this study, we have used a microarray-based approach to perform a novel survey of the changes in gene expression that occur in components of cutaneous elastic fibres as a result of intrinsic ageing. Age-related changes in gene expression were validated at the mRNA and protein levels using quantitative real-time polymerase chain reaction (qPCR) and immunostaining, respectively. The microarray revealed that the majority of elastic fibre network components were unchanged with age. However, three differentially expressed genes were identified: latent TGFβ-binding protein (LTBP)-2 which was up-regulated with age (fold change +1.58, P = 0.041); LTBP3 (fold change -1.67, P = 0.025) and the lysyl oxidase-like enzyme (LOXL1, fold change -1.47, P = 0.008) which were both down-regulated with age. Although the changes in gene expression for LTBP3 were not confirmed by either qPCR or immunostaining, the expression and tissue deposition of both LTBP2 and LOXL1 were significantly enhanced in intrinsically aged skin. Whilst the functional implications of these altered expression profiles remains to be elucidated, LTBP2 and LOXL1 are thought to play important roles in controlling and maintaining elastic fibre deposition, assembly and structure via binding to fibulin-5. Consequently, any age-related perturbations in the expression of these components may have important consequences on remodelling of the extracellular matrix and hence on the mechanical properties of intrinsically aged skin.

  2. Imprinted polymers with cyclodextrin pseudo-polyrotaxanes as pseudo-supports for protein recognition.

    Science.gov (United States)

    Guo, Minjie; Hu, Xin; Fan, Zhi; Liu, Jing; Wang, Xiaocong; Wang, Ying; Mi, Huaifeng

    2013-02-15

    We report a novel approach for preparing protein molecularly imprinted polymers (MIPs) with cyclodextrin pseudo-polyrotaxanes (CD-PPRs) as pseudo-supports, which are formed by self-assembling assistant recognition polymer chains with γ-cyclodextrins. The conformation of the CD-PPRs was characterised by 2D-NOESY, TGA and WAXD. To prepare MIPs, template bovine serum albumin (BSA) was first selectively assembled with modified CD-PPRs to form complexes in the presence of Cu ions. These assemblies were then immobilised by the polymerisation of acrylamide as the monomer and N,N'-methylenebisacrylamide as the cross-linker to prepare protein MIPs. The amount of BSA template adsorbed initially increased with the increase in the amount of CD-PPR and then decreased with the further increase in the CD-PPR content. To obtain the specific adsorption protein, MIPs were washed with KCl solutions of different concentrations. The results of sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed that the specific adsorption proteins could be collected with a 0.500 mol L(-1) KCl solution. The recognition specificity to the template relies on the spatial configuration constructed by CD-PPR and metal ions. Finally, this imprinted polymer was used to purify the template from the protein mixtures containing either two (BSA and ovalbumin) or four (BSA, ovalbumin, soybean trypsine inhibitor and lysozyme) different proteins. Both experiments have demonstrated MIPs high selectivity. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Identification of intrinsically disordered regions in PTEN and delineation of its function via a network approach.

    Science.gov (United States)

    Malaney, Prerna; Uversky, Vladimir N; Davé, Vrushank

    2015-05-01

    Intrinsically disordered proteins (IDPs) are proteins that lack stable higher order structures for the entire protein molecule or a significant portion of it. The discovery of IDPs evolved as an antithesis to the conventional structure-function paradigm wherein a higher order structure dictates protein function. Over the last decade, a number of proteins with functionally relevant unstructured regions have been discovered, which includes tumor suppressor PTEN. The protein domains that lack structure provide "hot-spots" for post-translational modifications (PTMs) and protein-protein interactions (PPIs), which facilitate their regulation and participation in multiple cellular processes. Consequently, dysregulation in IDPs contribute to aberrant cellular pathophysiology. Herein, we present PTEN and its translational isoform PTEN-L as a hybrid protein possessing ordered domain and intrinsically disordered C-terminal and an N-terminal tails. We review the role of intrinsic disorder in PTEN function and propose a methodology for the use of intrinsic disorder to study PTEN-regulated higher order protein-networks by associating basic principles of network biology to functional pathway analysis at the systems level. Published by Elsevier Inc.

  4. Incentives and intrinsic motivation in healthcare

    Directory of Open Access Journals (Sweden)

    Mikel Berdud

    2016-11-01

    Conclusions: The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated.

  5. Algebraic description of intrinsic modes in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A. (Los Alamos National Lab., NM (USA))

    1990-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intrinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. (author).

  6. Algebraic description of intrinsic modes in nuclei

    International Nuclear Information System (INIS)

    Leviatan, A.

    1990-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intrinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. (author)

  7. Asia-MIP: Multi Model-data Synthesis of Terrestrial Carbon Cycles in Asia

    Science.gov (United States)

    Ichii, K.; Kondo, M.; Ito, A.; Kang, M.; Sasai, T.; SATO, H.; Ueyama, M.; Kobayashi, H.; Saigusa, N.; Kim, J.

    2013-12-01

    Asia, which is characterized by monsoon climate and intense human activities, is one of the prominent understudied regions in terms of terrestrial carbon budgets and mechanisms of carbon exchange. To better understand terrestrial carbon cycle in Asia, we initiated multi-model and data intercomparison project in Asia (Asia-MIP). We analyzed outputs from multiple approaches: satellite-based observations (AVHRR and MODIS) and related products, empirically upscaled estimations (Support Vector Regression) using eddy-covariance observation network in Asia (AsiaFlux, CarboEastAsia, FLUXNET), ~10 terrestrial biosphere models (e.g. BEAMS, Biome-BGC, LPJ, SEIB-DGVM, TRIFFID, VISIT models), and atmospheric inversion analysis (e.g. TransCom models). We focused on the two difference temporal coverage: long-term (30 years; 1982-2011) and decadal (10 years; 2001-2010; data intensive period) scales. The regions of covering Siberia, Far East Asia, East Asia, Southeast Asia and South Asia (60-80E, 10S-80N), was analyzed in this study for assessing the magnitudes, interannual variability, and key driving factors of carbon cycles. We will report the progress of synthesis effort to quantify terrestrial carbon budget in Asia. First, we analyzed the recent trends in Gross Primary Productivities (GPP) using satellite-based observation (AVHRR) and multiple terrestrial biosphere models. We found both model outputs and satellite-based observation consistently show an increasing trend in GPP in most of the regions in Asia. Mechanisms of the GPP increase were analyzed using models, and changes in temperature and precipitation play dominant roles in GPP increase in boreal and temperate regions, whereas changes in atmospheric CO2 and precipitation are important in tropical regions. However, their relative contributions were different. Second, in the decadal analysis (2001-2010), we found that the negative GPP and carbon uptake anomalies in 2003 summer in Far East Asia is one of the largest

  8. The Hydrological Impact of Geoengineering in the Geoengineering Model Intercomparison Project (GeoMIP)

    Energy Technology Data Exchange (ETDEWEB)

    Tilmes, S.; Fasullo, John; Lamarque, J.-F.; Marsh, D.; Mills, Mike; Alterskjaer, Kari; Muri, Helene O.; Kristjansson, Jon E.; Boucher, Olivier; Schulz, M.; Cole, Jason N.; Curry, Charles L.; Jones, A.; Haywood, J.; Irvine, Peter; Ji, Duoying; Moore, John; Bou Karam, Diana; Kravitz, Benjamin S.; Rasch, Philip J.; Singh, Balwinder; Yoon, Jin-Ho; Niemeier, Ulrike; Schmidt, Hauke; Robock, Alan; Yang, Shuting; Watanabe, Shingo

    2013-10-14

    Abstract: The hydrologic impact of enhancing Earth’s albedo due to solar radiation management (SRM) is investigated using simulations from 12 models contributing to the Geoengineering Model Intercomparison Project (GeoMIP). An artificial experiment is investigated, where global mean temperature is preserved at pre-industrial conditions, while atmospheric carbon dioxide concentrations are quadrupled. The associated reduction of downwelling surface solar radiation in a high CO2 environment leads to a reduction of global evaporation of 10% and 4% and precipitation of 6.1% and 6.3% over land and ocean, respectively. An initial reduction of latent heat flux at the surface is largely driven by reduced evapotranspiration over land with instantly increasing CO2 concentrations in both experiments. A warming surface associated with the transient adjustment in the 4xCO2 experiment further generates an increase of global precipitation, with considerable regional changes, such as a significant precipitation reduction of 7% for the North American summer monsoon. Reduced global precipitation persists in the geoengineered experiment where temperatures are stabilized, with considerable regional rainfall deficits. Precipitation reductions that are consistent in sign across models are identified in the geoengineered experiment over monsoonal land regions of East Asia (6%), North America (7%), South America (6%) and South Africa (5%). In contrast to the 4xCO2 experiment, where the frequency of months with heavy precipitation intensity is increased by over 50%, it is reduced by up to 20% in the geoengineering scenario . The reduction in heavy precipitation is more pronounced over land than over the ocean, and accompanies a stronger reduction in evaporation over land. For northern mid-latitudes, maximum precipitation reduction over land ranges from 1 to 16% for individual models. For 45-65°N, the frequency of median to high intensity precipitation in summer is strongly reduced. These

  9. Geochemical indicators of intrinsic bioremediation

    International Nuclear Information System (INIS)

    Borden, R.C.; Gomez, C.A.; Becker, M.T.

    1995-01-01

    A detailed field investigation has been completed at a gasoline-contaminated aquifer near Rocky Point, NC, to examine possible indicators of intrinsic bioremediation and identify factors that may significantly influence the rae and extent of bioremediation. The dissolved plume of benzene, toluene, ethylbenzene, and xylene (BTEX) in ground water is naturally degrading. Toluene and o-xylene are most rapidly degraded followed by m-, p-xylene, and benzene. Ethylbenzene appears to degrade very slowly under anaerobic conditions present in the center of the plume. The rate and extent of biodegradation appears to be strongly influenced by the type and quantity of electron acceptors present in the aquifer. At the upgradient edge of the plume, nitrate, ferric iron, and oxygen are used as terminal electron acceptors during hydrocarbon biodegradation. The equivalent of 40 to 50 mg/l of hydrocarbon is degraded based on the increase in dissolved CO 2 relative to background ground water. Immediately downgradient of the source area, sulfate and iron are the dominant electron acceptors. Toluene and o-xylene are rapidly removed in this region. Once the available oxygen, nitrate, and sulfate are consumed, biodegradation is limited and appears to be controlled by mixing and aerobic biodegradation at the plume fringes

  10. Perspectives on Climate Effects on Agriculture: The International Efforts of AgMIP in Sub-Saharan Africa

    Science.gov (United States)

    Kihara, Job; MacCarthy, Dilys S.; Bationo, Andre; Koala, Saidou; Hickman, Jonathon; Koo, Jawoo; Vanya, Charles; Adiku, Samuel; Beletse, Yacob; Masikate, Patricia; hide

    2012-01-01

    Agriculture in Sub-Saharan Africa (SSA) is experiencing climate change-related effects that call for integrated regional assessments, yet capacity for these assessments has been low. The Agricultural Model Intercomparison and Improvement Project (AgMIP) is advancing research on integrated regional assessments of climate change that include climate, crop, and economic modeling and analysis. Through AgMIP, regional integrated assessments are increasingly gaining momentum in SSA, and multi-institutional regional research teams (RRTs) centered in East, West, and Southern· Africa are generating new information on climate change impacts and adaptation in selected agricultural systems. The research in Africa is organized into four RRTs and a coordination team. Each of the RRTs in SSA is composed of scientists from the Consultative Group of International Agricultural Research (CGIAR) institutions, National Agriculture Research institutes (NARs), and universities consisting of experts in crop and economic modeling, climate, and information technology. Stakeholder involvement to inform specific agricultural systems to be evaluated, key outputs, and the representative agricultural pathways (RAPs), is undertaken at two levels: regional and national, in order to contribute to decision making at these levels. Capacity building for integrated assessment (lA) is a key component that is undertaken continuously through interaction with experts in regional and SSA-wide workshops, and through joint creation of tools. Many students and research affiliates have been identified and entrained as part of capacity building in IA. Bi-monthly updates on scholarly publications in climate change in Africa also serve as a vehicle for knowledge-sharing. With 60 scientists already trained and actively engaged in IA and over 80 getting monthly briefs on the latest information on climate change, a climate-informed community of experts is gradually taking shape in SSA. (See Part 2, Appendices 3-5 in

  11. MiR-125b Inhibits LPS-Induced Inflammatory Injury via Targeting MIP-1α in Chondrogenic Cell ATDC5

    Directory of Open Access Journals (Sweden)

    Jinling Jia

    2018-03-01

    Full Text Available Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA. MicroRNAs (miRNAs play an important role in chondrogenesis and cartilage remodeling. This study explored the effect of miR-125b on inflammatory injury in chondrogenic cells. Methods: LPS was used to simulate inflammatory injury in murine chondrogenic ATDC5 cell lines. Targeting effect of miR-125b on MIP-1α 3’UTR was assessed by dual luciferase activity assay. Regulatory effect of miR-125b on MIP-1α expression and the potential regulatory mechanism on inflammatory injury were assessed by Western blot. Results: miR-125b expression was decreased in LPS-induced ATDC5 cells and overexpression of miR-125b inhibited LPS-induced cell viability decline, the rise of apoptosis and inflammatory factors’ productions. MIP-1α expression was negatively related to miR-125b, and miR-125b directly targeted with 3’UTR of MIP-1α. Knockdown of miR-125b promoted LPS-induced inflammatory response via upregulation of MIP-1α. miR-125b expression in LPS-induced ATDC5 cells was negatively related with activations of NF-κB and JNK signaling pathways. Overexpression of miR-125b inhibited LPS-induced inflammation injury via suppressing MIP-1α expression and inhibiting activations of NF-κB and JNK signaling pathways. Conclusion: miR-125b could play an important role in inflammatory injury of chondrogenic cells and miR-125b affected inflammatory injury of ATDC5 cells via regulating expression of MIP-1α and regulating NF-κB and JNK signaling pathways.

  12. Improving the snow physics of WEB-DHM and its point evaluation at the SnowMIP sites

    Directory of Open Access Journals (Sweden)

    M. Shrestha

    2010-12-01

    Full Text Available In this study, the snow physics of a distributed biosphere hydrological model, referred to as the Water and Energy Budget based Distributed Hydrological Model (WEB-DHM is significantly improved by incorporating the three-layer physically based energy balance snowmelt model of Simplified Simple Biosphere 3 (SSiB3 and the Biosphere-Atmosphere Transfer Scheme (BATS albedo scheme. WEB-DHM with improved snow physics is hereafter termed WEB-DHM-S. Since the in-situ observations of spatially-distributed snow variables with high resolution are currently not available over large regions, the new distributed system (WEB-DHM-S is at first rigorously tested with comprehensive point measurements. The stations used for evaluation comprise the four open sites of the Snow Model Intercomparison Project (SnowMIP phase 1 with different climate characteristics (Col de Porte in France, Weissfluhjoch in Switzerland, Goose Bay in Canada and Sleepers River in USA and one open/forest site of the SnowMIP phase 2 (Hitsujigaoka in Japan. The comparisons of the snow depth, snow water equivalent, surface temperature, snow albedo and snowmelt runoff at the SnowMIP1 sites reveal that WEB-DHM-S, in general, is capable of simulating the internal snow process better than the original WEB-DHM. Sensitivity tests (through incremental addition of model processes are performed to illustrate the necessity of improvements over WEB-DHM and indicate that both the 3-layer snow module and the new albedo scheme are essential. The canopy effects on snow processes are studied at the Hitsujigaoka site of the SnowMIP2 showing that the snow holding capacity of the canopy plays a vital role in simulating the snow depth on ground. Through these point evaluations and sensitivity studies, WEB-DHM-S has demonstrated the potential to address basin-scale snow processes (e.g., the snowmelt runoff, since it inherits the distributed hydrological framework from the WEB-DHM (e.g., the slope-driven runoff

  13. LEADERSHIP STYLE AND EMPLOYEES' INTRINSIC JOB ...

    African Journals Online (AJOL)

    Abstract. This study investigates the impact of leadership style on employees' intrinsic job satisfaction in the Cross River State Newspaper Corporation, Calabar,. Nigeria. The study examined the problem of dissatisfaction in the work place as far as intrinsic factors of job satisfaction are concerned. Structured questionnaire ...

  14. Intrinsic bioremediation of landfills interim report

    International Nuclear Information System (INIS)

    Brigmon, R.L.; Fliermans, C.B.

    1997-01-01

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP)

  15. Intrinsic bioremediation of landfills interim report

    Energy Technology Data Exchange (ETDEWEB)

    Brigmon, R.L. [Westinghouse Savannah River Company, Aiken, SC (United States); Fliermans, C.B.

    1997-07-14

    Intrinsic bioremediation is a risk management option that relies on natural biological and physical processes to contain the spread of contamination from a source. Evidence is presented in this report that intrinsic bioremediation is occurring at the Sanitary Landfill is fundamental to support incorportion into a Corrective Action Plan (CAP).

  16. An Intrinsic Coordinate System for Fingerprint Matching

    NARCIS (Netherlands)

    Bazen, A.M.; Gerez, Sabih H.; Bigun, J.; Smeraldi, F.

    2001-01-01

    In this paper, an intrinsic coordinate system is proposed for fingerprints. First the fingerprint is partitioned in regular regions, which are regions that contain no singular points. In each regular region, the intrinsic coordinate system is defined by the directional field. When using the

  17. The intrinsically disordered RNR inhibitor Sml1 is a dynamic dimer

    DEFF Research Database (Denmark)

    Danielsson, Jens; Liljedahl, Leena; Ba´ra´ny-Wallje, Elsa

    2008-01-01

    . Sml1 belongs to the class of intrinsically disordered proteins with a high degree of dynamics and very little stable structure. Earlier suggestions for a dimeric structure of Sml1 were confirmed, and from translation diffusion NMR measurements, a dimerization dissociation constant of 0.1 mM at 4...... natively disordered proteins....

  18. [Effect of macrophage inflammatory protein-1β on proliferation and apoptosis of human tongue squamous cell carcinoma CAL-27 cells in vitro].

    Science.gov (United States)

    Jia, Bo; Qiu, Xiao-Ling; Chu, Hong-Xing; Sun, Xiang; Pan, Jie; Wang, Zhi-Ping; Zhao, Jian-Jiang

    2017-08-20

    To detect CCR5 protein expression in different human tongue squamous cell carcinoma cells and observe the effect of macrophage inflammatory protein-1β (MIP-1β) on the proliferation and apoptosis of CAL-27 cells. Western blotting and immunofluorescence staining were used to detect the expression of the CCR5, the receptor of MIP-1β, in 3 human tongue squamous cell carcinoma cells UM-1, CAL-27, and Tca-8113. CCK-8 assay was used to assess the proliferation of CAL-27 cells stimulated with 10, 20, and 40 ng/mL MIP-1β for 12, 24, or 48 h. The apoptosis of the cells stimulated with MIP-1β (10, 20, and 40 ng/mL) for 24 h was analyzed using flow cytometry with Annexin V/PI double staining. CCR5 expression was detected both on the membrane and in the cytoplasm in all the 3 tongue squamous cell carcinoma cell lines. At the concentrations of 10, 20, and 40 ng/mL, MIP-1β stimulation for 12 and 24 h significantly promoted the proliferation of CAL-27 cells (Pproliferation of CAL-27 cells (Pcells (Pcells (P>0.05). CCR5 is expressed in all the 3 human tongue squamous cell carcinoma cells. MIP-1β can promote the proliferation of CAL-27 cells but high concentrations of MIP-1β also induced cell apoptosis. Prolonged stimulation of the cells with a high concentration of MIP-1β shows attenuated effect in promoting cell proliferation probably as a result of cell apoptosis induced by MIP-1β.

  19. Increased expression of the chemokines CXCL1 and MIP-1α by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats

    Directory of Open Access Journals (Sweden)

    Koemeter-Cox Andrew I

    2011-05-01

    Full Text Available Abstract Background Exposure to the nerve agent soman (GD causes neuronal cell death and impaired behavioral function dependent on the induction of status epilepticus (SE. Little is known about the maturation of this pathological process, though neuroinflammation and infiltration of neutrophils are prominent features. The purpose of this study is to quantify the regional and temporal progression of early chemotactic signals, describe the cellular expression of these factors and the relationship between expression and neutrophil infiltration in damaged brain using a rat GD seizure model. Methods Protein levels of 4 chemokines responsible for neutrophil infiltration and activation were quantified up to 72 hours in multiple brain regions (i.e. piriform cortex, hippocampus and thalamus following SE onset using multiplex bead immunoassays. Chemokines with significantly increased protein levels were localized to resident brain cells (i.e. neurons, astrocytes, microglia and endothelial cells. Lastly, neutrophil infiltration into these brain regions was quantified and correlated to the expression of these chemokines. Results We observed significant concentration increases for CXCL1 and MIP-1α after seizure onset. CXCL1 expression originated from neurons and endothelial cells while MIP-1α was expressed by neurons and microglia. Lastly, the expression of these chemokines directly preceded and positively correlated with significant neutrophil infiltration in the brain. These data suggest that following GD-induced SE, a strong chemotactic response originating from various brain cells, recruits circulating neutrophils to the injured brain. Conclusions A strong induction of neutrophil attractant chemokines occurs following GD-induced SE resulting in neutrophil influx into injured brain tissues. This process may play a key role in the progressive secondary brain pathology observed in this model though further study is warranted.

  20. Molecularly Imprinted Polymers (MIP for Selective Solid Phase Extraction of Celecoxib in Urine Samples Followed by High Performance Liquid Chromatography

    Directory of Open Access Journals (Sweden)

    Saeedeh Ansari

    2017-09-01

    Full Text Available In this study, for the analysis of human urine samples, a novel method explained for the determination of celecoxib, a nonsteroidal anti-inflammatory drug (NSAID, using molecularly imprinted solid-phase extraction (MISPE coupled with high-performance liquid chromatography (HPLC. The synthesis of the MIP was performed by precipitation polymerization in methacrylic acid (MAA, ethylene glycol dimethacrylate (EGDMA, chloroform, 2,2′-azobisisobutyronitrile (AIBN and celecoxib as the functional monomer, cross-linker monomer, solvent, initiator and target drug, respectively. The celecoxib imprinted polymer was utilized as a specific sorbent for the solid phase extraction (SPE of celecoxib from samples. The molecularly imprinted polymer (MIP performance was compared with the synthesized non-molecularly imprinted polymer (NIP. Scanning electron microscopy (SEM, FT-IR spectroscopy, UV-VIS spectrophotometry and thermogravimetric analysis (TGA/DTG were used for characterizing the synthesized polymers. Moreover, the MISPE procedure parameters such as pH, eluent solvent flow rate, eluent volume and sorbent mass that probably influence the extraction process have been optimized to achieve the highest celecoxib extraction efficiency. The relative standard deviation (RSD %, recovery percent, limit of detection (LOD and limit of quantification (LOQ of this proposed method were 1.12%, 96%, 8 µg L-1 and 26.7 µg L-1, respectively. The proposed MISPE-HPLC-UV method can be used for the separation and enrichment of trace amounts of celecoxib in human urine and biological samples.

  1. Impacts, Effectiveness and Regional Inequalities of the GeoMIP G1 to G4 Solar Radiation Management Scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Xiaoyong; Moore, John; Cui, Xuefeng; Rinke, Annette; Ji, Duoying; Kravitz, Benjamin S.; Yoon, Jin-Ho

    2015-06-01

    We evaluate the regional effectiveness of solar radiation management (SRM) to compensate for simultaneous changes in temperature and precipitation induced by increased greenhouse gas concentrations. We analyze results from multiple earth system models under four Geoengineering Model Intercomparison Project(GeoMIP) experiments with a modified form of the Residual Climate Response approach. Under the solar dimming geoengineering experiments G1(4xCO2) and G2(increasing CO2 by 1% per year), global average temperature is successfully restored to pre-industrial level over 50 years simulations. However, these two SRM experiments also produce a robust global precipitation decrease. The stratospheric aerosol GeoMIP geoengineering experiment, G4 has significantly greater regional inequality and lower effectiveness for compensating temperature change than G1 and G2. G4 also has significantly larger regional inequality for compensating precipitation change than G1and G2. However, there is no significant difference between precipitation change compensation effectiveness of G4 and G2, though there is much larger across model variability in G4 results. G3 has significant greater regional inequality for compensating temperature change than G1 and G2, and has significant lower effectiveness than G1. The effectiveness of four SRMs to compensate for temperature change is much higher than for precipitation. The large cross-model variation in adjustment percentage of compensated SAT and precipitation change by SRM to achieve optimal compensation effectiveness shed a light on the uncertainty accumulation effect in optimizing compensation effectiveness of SRM.

  2. Optimizing the Thermal Read-Out Technique for MIP-Based Biomimetic Sensors: Towards Nanomolar Detection Limits

    Directory of Open Access Journals (Sweden)

    Patrick Wagner

    2013-07-01

    Full Text Available In previous work, the novel heat-transfer method (HTM for the detection of small molecules with Molecularly Imprinted Polymers (MIP-type receptors was presented. In this study we focus on optimization of this sensor performance, with as final aim to lower the detection limit by reducing the noise level. It was determined that the noise originates foremost from the power supply, which can be controlled by varying the PID parameters. Therefore, the effect of the individual parameters was evaluated by tuning P, I and D separately at a temperature of 37 °C, giving a first indication of the optimal configuration. Next, a temperature profile was programmed and the standard deviation of the heat-transfer resistance over the entire regime was studied for a set of parameters. The optimal configuration, P1-I6-D0, reduced the noise level with nearly a factor of three compared to the original parameters of P10-I5-D0. With the optimized settings, the detection of L-nicotine in buffer solutions was studied and the detection limit improved significantly from 100 nM to 35 nM. Summarizing, optimization of the PID parameters and thereby improving the detection limit is a key parameter for first applications of the HTM-method for MIP receptors in analytical research.

  3. Optimizing the thermal read-out technique for MIP-based biomimetic sensors: towards nanomolar detection limits.

    Science.gov (United States)

    Geerets, Bram; Peeters, Marloes; van Grinsven, Bart; Bers, Karolien; de Ceuninck, Ward; Wagner, Patrick

    2013-07-16

    In previous work, the novel heat-transfer method (HTM) for the detection of small molecules with Molecularly Imprinted Polymers (MIP)-type receptors was presented. In this study we focus on optimization of this sensor performance, with as final aim to lower the detection limit by reducing the noise level. It was determined that the noise originates foremost from the power supply, which can be controlled by varying the PID parameters. Therefore, the effect of the individual parameters was evaluated by tuning P, I and D separately at a temperature of 37 °C, giving a first indication of the optimal configuration. Next, a temperature profile was programmed and the standard deviation of the heat-transfer resistance over the entire regime was studied for a set of parameters. The optimal configuration, P1-I6-D0, reduced the noise level with nearly a factor of three compared to the original parameters of P10-I5-D0. With the optimized settings, the detection of L-nicotine in buffer solutions was studied and the detection limit improved significantly from 100 nM to 35 nM. Summarizing, optimization of the PID parameters and thereby improving the detection limit is a key parameter for first applications of the HTM-method for MIP receptors in analytical research.

  4. Development of a highly sensitive MIP based-QCM nanosensor for selective determination of cholic acid level in body fluids

    International Nuclear Information System (INIS)

    Gültekin, Aytaç; Karanfil, Gamze; Sönmezoğlu, Savaş; Say, Rıdvan

    2014-01-01

    Determination of cholic acid is very important and necessary in body fluids due to its both pharmaceutical and clinical significance. In this study, a quartz crystal microbalance (QCM) nanosensor, which is imprinted cholic acid, has been developed for the assignation of cholic acid. The cholic acid selective memories have been generated on QCM electrode surface by using molecularly imprinted polymer (MIP) based on methacryloylamidohistidine-copper (II) (MAH-Cu(II)) pre-organized monomer. The cholic acid imprinted nanosensor was characterized by atomic force microscopy (AFM) and then analytical performance of the cholic acid imprinted QCM nanosensor was studied. The detection limit was found to be 0.0065 μM with linear range of 0.01–1000 μM. Moreover, the high value of Langmuir constant (b) (7.3 * 10 5 ) obtained by Langmuir graph showed that the cholic acid imprinted nanosensor had quite strong binding sites affinity. At the last step of this procedure, cholic acid levels in body fluids were determined by the prepared imprinted QCM nanosensor. - Graphical abstract: QCM responses of the cholic acid imprinted and non-imprinted nanosensors (C CA = 0.1 μM). - Highlights: • The purpose is to synthesize a new cholic acid imprinted QCM nanosensor by MIP. • Analytical applications of QCM nanosensor were investigated. • The cholic acid levels in body fluids were determined by prepared QCM nanosensor

  5. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription

    Directory of Open Access Journals (Sweden)

    Santoro Thomas J

    2005-02-01

    Full Text Available Abstract Background In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2 is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS. The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine. Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. Methods Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. Results The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti

  6. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription.

    Science.gov (United States)

    Tomita, Michiyo; Holman, Brita J; Santoro, Christopher P; Santoro, Thomas J

    2005-02-25

    BACKGROUND: In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chemokine.Curcumin is a spice principle in, and constitutes approximately 4 percent of, turmeric. Curcumin's immunomodulating and antioxidant activities suggest that it might be a useful adjunct in the treatment of neurodegenerative illnesses characterized by inflammation. Relatively unexplored, but relevant to its potential therapeutic efficacy in neuroinflammatory syndromes is the effect of curcumin on chemokine production. To examine the possibility that curcumin may influence CNS inflammation by mechanisms distinct from its known anti-oxidant activities, we studied the effect of this spice principle on the synthesis of MIP-2 by astrocytes. METHODS: Primary astrocytes were prepared from neonatal brains of CBA/CaJ mice. The cells were stimulated with lipopolysaccharide in the presence or absence of various amount of curcumin or epigallocatechin gallate. MIP-2 mRNA was analyzed using semi-quantitative PCR and MIP-2 protein production in the culture supernatants was quantified by ELISA. Astrocytes were transfected with a MIP-2 promoter construct, pGL3-MIP-2, and stimulated with lipopolysaccharide in the presence or absence of curcumin. RESULTS: The induction of MIP-2 gene expression and the production of MIP-2 protein were inhibited by curcumin. Curcumin also inhibited lipopolysaccharide-induced transcription of the MIP-2 promoter reporter gene construct in primary astrocytes. However MIP-2 gene induction by lipopolysaccharide was not inhibited by another anti-oxidant, epigallocatechin

  7. Algebraic description of intrinsic modes in nuclei

    International Nuclear Information System (INIS)

    Leviatan, A.

    1989-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. 28 refs., 1 fig

  8. Algebraic description of intrinsic modes in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Leviatan, A.

    1989-01-01

    We present a procedure for extracting normal modes in algebraic number-conserving systems of interacting bosons relevant for collective states in even-even nuclei. The Hamiltonian is resolved into intrinsic (bandhead related) and collective (in-band related) parts. Shape parameters are introduced through non-spherical boson bases. Intrinsic modes decoupled from the spurious modes are obtained from the intinsic part of the Hamiltonian in the limit of large number of bosons. Intrinsic states are constructed and serve to evaluate electromagnetic transition rates. The method is illustrated for systems with one type of boson as well as with proton-neutron bosons. 28 refs., 1 fig.

  9. Selective recruitment of Th2-type cells and evasion from a cytotoxic immune response mediated by viral macrophage inhibitory protein-II.

    Science.gov (United States)

    Weber, K S; Gröne, H J; Röcken, M; Klier, C; Gu, S; Wank, R; Proudfoot, A E; Nelson, P J; Weber, C

    2001-08-01

    The viral CC chemokine macrophage inhibitory protein-II (vMIP-II) encoded by human herpes virus 8 (HHV-8) binds to multiple chemokine receptors, however, its ability to control the initial recruitment of specific leukocyte subtypes from the peripheral circulation has not been fully clarified. Here we show that vMIP-II blocks the firm arrest and transmigration of monocytes or Th1-like T lymphocytes triggered by RANTES immobilized on activated human microvascular endothelium (HMVEC) under flow conditions. The internalization of the receptors CCR1 and CCR5 that mediate arrest and transmigration of these cells in response to RANTES was prevented by vMIP-II, supporting its role as an antagonist of CCR1 and CCR5. In contrast, vMIP-II triggered the firm arrest of eosinophils and Th2-like T cells by engaging CCR3, as confirmed by its down-regulation. Immunohistochemical analysis of HHV-8-associated Kaposi's sarcoma lesions marked by vMIP-II expression and mononuclear cell infiltration revealed a predominance of Th2-type CCR3(+) lymphocytes over Th1-type CXCR3(+)/CCR5(+) leukocytes, indicating that as a CCR3 agonist vMIP-II can drive a Th2-type immune response in vivo. Thus, our data provide evidence for a immunomodulatory role of vMIP-II in directing inflammatory cell recruitment away from a Th1-type towards a Th2-type response and thereby facilitating evasion from cytotoxic reactions.

  10. Astrocyte production of the chemokine macrophage inflammatory protein-2 is inhibited by the spice principle curcumin at the level of gene transcription

    OpenAIRE

    Tomita, Michiyo; Holman, Brita J; Santoro, Christopher P; Santoro, Thomas J

    2005-01-01

    Abstract Background In neuropathological processes associated with neutrophilic infiltrates, such as experimental allergic encephalitis and traumatic injury of the brain, the CXC chemokine, macrophage inflammatory protein-2 (MIP-2) is thought to play a pivotal role in the induction and perpetuation of inflammation in the central nervous system (CNS). The origin of MIP-2 in inflammatory disorders of the brain has not been fully defined but astrocytes appear to be a dominant source of this chem...

  11. Regional and global climate for the mid-Pliocene using the University of Toronto version of CCSM4 and PlioMIP2 boundary conditions

    Science.gov (United States)

    Chandan, Deepak; Peltier, W. Richard

    2017-07-01

    The Pliocene Model Intercomparison Project Phase 2 (PlioMIP2) is an international collaboration to simulate the climate of the mid-Pliocene interglacial, corresponding to marine isotope stage KM5c (3.205 Mya), using a wide selection of climate models with the objective of understanding the nature of the warming that is known to have occurred during the broader mid-Pliocene warm period. PlioMIP2 builds on the successes of PlioMIP by shifting the focus to a specific interglacial and using a revised set of geographic and orbital boundary conditions. In this paper, we present the details of the mid-Pliocene simulations that we have performed with a slightly modified version of the Community Climate System Model version 4 (CCSM4) and the enhanced variant of the PlioMIP2 boundary conditions. We discuss the simulated climatology through comparisons to our control simulations and to proxy reconstructions of the mid-Pliocene climate. With the new boundary conditions, the University of Toronto version of the CCSM4 model simulates a mid-Pliocene that is more than twice as warm as that with the boundary conditions used for PlioMIP Phase 1. The warming is more enhanced near the high latitudes, which is where most of the changes to the PlioMIP2 boundary conditions have been made. The elevated warming in the high latitudes leads to a better match between the simulated climatology and proxy-based reconstructions than possible with the previous version of the boundary conditions.

  12. Regional and global climate for the mid-Pliocene using the University of Toronto version of CCSM4 and PlioMIP2 boundary conditions

    Directory of Open Access Journals (Sweden)

    D. Chandan

    2017-07-01

    Full Text Available The Pliocene Model Intercomparison Project Phase 2 (PlioMIP2 is an international collaboration to simulate the climate of the mid-Pliocene interglacial, corresponding to marine isotope stage KM5c (3.205 Mya, using a wide selection of climate models with the objective of understanding the nature of the warming that is known to have occurred during the broader mid-Pliocene warm period. PlioMIP2 builds on the successes of PlioMIP by shifting the focus to a specific interglacial and using a revised set of geographic and orbital boundary conditions. In this paper, we present the details of the mid-Pliocene simulations that we have performed with a slightly modified version of the Community Climate System Model version 4 (CCSM4 and the enhanced variant of the PlioMIP2 boundary conditions. We discuss the simulated climatology through comparisons to our control simulations and to proxy reconstructions of the mid-Pliocene climate. With the new boundary conditions, the University of Toronto version of the CCSM4 model simulates a mid-Pliocene that is more than twice as warm as that with the boundary conditions used for PlioMIP Phase 1. The warming is more enhanced near the high latitudes, which is where most of the changes to the PlioMIP2 boundary conditions have been made. The elevated warming in the high latitudes leads to a better match between the simulated climatology and proxy-based reconstructions than possible with the previous version of the boundary conditions.

  13. Intrinsic endometriosis of ureter: a case report

    International Nuclear Information System (INIS)

    Hong, Myung Sun; Kim, Ho Chul; Yun, Ku Sup; Choi, Chul Soon; Bae, Sang Hoon; Kim, Sung Yong; Shin, Hyung Sik

    1995-01-01

    Endometriosis is a rare cause of an ureteral obstruction. We report a case of intrinsic ureteral endometriosis resulting in severe hydroureteronephrosis. The diagnosis of ureteral endometriosis may be considered in women with flank pain and ureteric obstruction within true pelvis

  14. The Intrinsic Dynamics of Psychological Process

    NARCIS (Netherlands)

    Vallacher, Robin R.; van Geert, Paul; Nowak, Andrzej

    2015-01-01

    Psychological processes unfold on various timescales in accord with internally generated patterns. The intrinsic dynamism of psychological process is difficult to investigate using traditional methods emphasizing cause–effect relations, however, and therefore is rarely incorporated into social

  15. Deuterium NMR, induced and intrinsic cholesteric lyomesophases

    International Nuclear Information System (INIS)

    Alcantara, M.R.

    1982-01-01

    Induced and intrinsic cholesteric lyotropic mesophases were studied. Induced cholesteric lyomesophases based on potassium laurate (KL) system, with small amounts of cholesterol added, were studied by deuterium NMR and by polarizing microscopy. Order profiles obtained from deuterium NMR of KL perdenderated chains in both induced cholesteric and normal mesophases were compared. The intrinsic cholesteric lyotropic mesophases were based on the amphiphile potassium N-lauroyl serinate (KLNS) in the resolved levo form. The study of the type I intrinsic cholesteric mesophase was made by optical microscopy under polarized light and the type II intrinsic cholesteric lyomesophase was characterized by deuterium NMR. The new texture was explained by the use of the theory of disclinations developed for thermotropic liquid crystals, specially for cholesteric type. (M.J.C.) [pt

  16. Intrinsic and acquired resistance mechanisms in enterococcus

    Science.gov (United States)

    Hollenbeck, Brian L.; Rice, Louis B.

    2012-01-01

    Enterococci have the potential for resistance to virtually all clinically useful antibiotics. Their emergence as important nosocomial pathogens has coincided with increased expression of antimicrobial resistance by members of the genus. The mechanisms underlying antibiotic resistance in enterococci may be intrinsic to the species or acquired through mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. This paper reviews the antibiotic resistance mechanisms in Enterococcus faecium and Enterococcus faecalis and discusses treatment options. PMID:23076243

  17. The intrinsic resistome of bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Jorge Andrés Olivares Pacheco

    2013-04-01

    Full Text Available Intrinsically resistant bacteria have emerged as a relevant health problem in the last years. Those bacterial species, several of them with an environmental origin, present naturally a low-level susceptibility to several drugs. It has been proposed that intrinsic resistance is mainly the consequence of the impermeability of cellular envelopes, the activity of multidrug efflux pumps or the lack of appropriate targets for a given family of drugs. However, recently published articles indicate that the characteristic phenotype of susceptibility to antibiotics of a given bacterial species depends on the concerted activity of several elements, what has been named as intrinsic resistome. These determinants comprise not just classical resistance genes. Other elements, several of them involved in basic bacterial metabolic processes, are of relevance for the intrinsic resistance of bacterial pathogens. In the present review we analyse recent publications on the intrinsic resistomes of Escherichia coli and Pseudomonas aeruginosa. We present as well information on the role that global regulators of bacterial metabolism, as Crc from P. aeruginosa, may have on modulating bacterial susceptibility to antibiotics. Finally, we discuss the possibility of searching inhibitors of the intrinsic resistome in the aim of improving the activity of drugs currently in use for clinical practice.

  18. Incentives and intrinsic motivation in healthcare.

    Science.gov (United States)

    Berdud, Mikel; Cabasés, Juan M; Nieto, Jorge

    It has been established in the literature that workers within public organisations are intrinsically motivated. This paper is an empirical study of the healthcare sector using methods of qualitative analysis research, which aims to answer the following hypotheses: 1) doctors are intrinsically motivated; 2) economic incentives and control policies may undermine doctors' intrinsic motivation; and 3) well-designed incentives may encourage doctors' intrinsic motivation. We conducted semi-structured interviews à-la-Bewley with 16 doctors from Navarre's Healthcare Service (Servicio Navarro de Salud-Osasunbidea), Spain. The questions were based on current theories of intrinsic motivation and incentives to test the hypotheses. Interviewees were allowed to respond openly without time constraints. Relevant information was selected, quantified and analysed by using the qualitative concepts of saturation and codification. The results seem to confirm the hypotheses. Evidence supporting hypotheses 1 and 2 was gathered from all interviewees, as well as indications of the validity of hypothesis 3 based on interviewees' proposals of incentives. The conclusions could act as a guide to support the optimal design of incentive policies and schemes within health organisations when healthcare professionals are intrinsically motivated. Copyright © 2016 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Digested disorder: Quarterly intrinsic disorder digest (April-May-June, 2013).

    Science.gov (United States)

    DeForte, Shelly; Reddy, Krishna D; Uversky, Vladimir N

    2013-01-01

    The current literature on intrinsically disordered proteins is overwhelming. To keep interested readers up to speed with this literature, we continue a "Digested Disorder" project and represent a series of reader's digest type articles objectively representing the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the period of April, May, and June of 2013. The papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  20. Digested disorder: Quarterly intrinsic disorder digest (July-August-September, 2013).

    Science.gov (United States)

    Reddy, Krishna D; DeForte, Shelly; Uversky, Vladimir N

    2014-01-01

    The current literature on intrinsically disordered proteins grows fast. To keep interested readers up to speed with this literature, we continue a "Digested Disorder" project and represent a new issue of reader's digest of the research papers and reviews on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the third quarter of 2013; i.e., during the period of June, July, and September of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  1. An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance.

    Science.gov (United States)

    Xu, Yongchang; Wei, Wenhui; Lei, Sheng; Lin, Jingxia; Srinivas, Swaminath; Feng, Youjun

    2018-04-10

    Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin) conferred by Neisseria eptA , the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE). The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli , Salmonella enterica , Klebsiella pneumoniae , etc.), rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and p hospho e thanol a mine [PEA] transferase) are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens. IMPORTANCE EptA and MCR-1 and -2 remodel the outer membrane, rendering bacteria resistant to colistin, a final resort against carbapenem-resistant pathogens. Structural and functional analyses of EptA and MCR-1 and -2 reveal parallel PE lipid substrate-recognizing cavities, which explains intrinsic and

  2. Lung region extraction based on the model information and the inversed MIP method by using chest CT images

    International Nuclear Information System (INIS)

    Tomita, Toshihiro; Miguchi, Ryosuke; Okumura, Toshiaki; Yamamoto, Shinji; Matsumoto, Mitsuomi; Tateno, Yukio; Iinuma, Takeshi; Matsumoto, Toru.

    1997-01-01

    We developed a lung region extraction method based on the model information and the inversed MIP method in the Lung Cancer Screening CT (LSCT). Original model is composed of typical 3-D lung contour lines, a body axis, an apical point, and a convex hull. First, the body axis. the apical point, and the convex hull are automatically extracted from the input image Next, the model is properly transformed to fit to those of input image by the affine transformation. Using the same affine transformation coefficients, typical lung contour lines are also transferred, which correspond to rough contour lines of input image. Experimental results applied for 68 samples showed this method quite promising. (author)

  3. Repeated PSMA-targeting radioligand therapy of metastatic prostate cancer with {sup 131}I-MIP-1095

    Energy Technology Data Exchange (ETDEWEB)

    Afshar-Oromieh, Ali; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Zechmann, Christian; Mier, Walter; Spohn, Fabian; Debus, Nils; Kratochwil, Clemens [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Armor, Thomas [Progenics Pharmaceuticals, Inc., New York, NY (United States); Holland-Letz, Tim [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Babich, John [Weill Cornell Medicine, Division of Radiopharmaceutical Sciences, Department of Radiology, New York, NY (United States); Weill Cornell Medicine, Citigroup Biomedical Imaging Center, New York, NY (United States); Weill Cornell Medicine, Meyer Cancer Center, New York, NY (United States)

    2017-06-15

    Prostate-specific membrane antigen (PSMA)-targeting radioligand therapy (RLT) was introduced in 2011. The first report described the antitumor and side effects of a single dose. The aim of this analysis was to evaluate toxicity and antitumor activity after single and repetitive therapies. Thirty-four men with metastatic castration-resistant prostate cancer received PSMA-RLT with {sup 131}I-MIP-1095. Twenty-three patients received a second, and three patients a third dose, timed at PSA progression after an initial response to the preceding therapy. The applied doses were separated in three groups: <3.5, 3.5-5.0 and >5.0 GBq. Antitumor and side-effects were analyzed by blood samples and other clinical data. Follow-up was conducted for up to 5 years. The best therapeutic effect was achieved by the first therapy. A PSA decline of ≥50% was achieved in 70.6% of the patients. The second and third therapies were significantly less effective. There was neither an association between the applied activity and PSA response or the time-to-progression. Hematologic toxicities were less prevalent but presented in a higher percentage of patients with increasing number of therapies. After hematologic toxicities, xerostomia was the second most frequent side effect and presented more often and with higher intensity after the second or third therapy. The first dose of RLT with {sup 131}I-MIP-1095 presented with low side effects and could significantly reduce the tumor burden in a majority of patients. The second and third therapies were less effective and presented with more frequent and more intense side effects, especially hematologic toxicities and xerostomia. (orig.)

  4. A SPITZER MIPS STUDY OF 2.5-2.0 M{sub Sun} STARS IN SCORPIUS-CENTAURUS

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Christine H.; Bitner, Martin [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Pecaut, Mark; Mamajek, Eric E. [Department of Physics and Astronomy, University of Rochester, Rochester, NY 14627 (United States); Su, Kate Y. L., E-mail: cchen@stsci.edu [Steward Observatory, University of Arizona, 933 North Cherry Avenue, Tucson, AZ 85721 (United States)

    2012-09-10

    We have obtained Spitzer Space Telescope Multiband Imaging Photometer for Spitzer (MIPS) 24 {mu}m and 70 {mu}m observations of 215 nearby, Hipparcos B- and A-type common proper-motion single and binary systems in the nearest OB association, Scorpius-Centaurus. Combining our MIPS observations with those of other ScoCen stars in the literature, we estimate 24 {mu}m B+A-type disk fractions of 17/67 (25{sup +6}{sub -5}%), 36/131 (27{sup +4}{sub -4}%), and 23/95 (24{sup +5}{sub -4}%) for Upper Scorpius ({approx}11 Myr), Upper Centaurus Lupus ({approx}15 Myr), and Lower Centaurus Crux ({approx}17 Myr), respectively, somewhat smaller disk fractions than previously obtained for F- and G-type members. We confirm previous IRAS excess detections and present new discoveries of 51 protoplanetary and debris disk systems, with fractional infrared luminosities ranging from L{sub IR}/L{sub *} = 10{sup -6} to 10{sup -2} and grain temperatures ranging from T{sub gr} = 40 to 300 K. In addition, we confirm that the 24 {mu}m and 70 {mu}m excesses (or fractional infrared luminosities) around B+A-type stars are smaller than those measured toward F+G-type stars and hypothesize that the observed disk property dependence on stellar mass may be the result of a higher stellar companion fraction around B- and A-type stars at 10-200 AU. Finally, we note that the majority of the ScoCen 24 {mu}m excess sources also possess 12 {mu}m excess, indicating that Earth-like planets may be forming via collisions in the terrestrial planet zone at {approx}10-100 Myr.

  5. Function and regulation of plant major intrinsic proteins

    DEFF Research Database (Denmark)

    Popovic, Milan

    Arsenic is a metalloid that is toxic to living organisms. The use of arsenic-contaminated ground water for drinking and for irrigation in agriculture presents serious health problems for millions of people in many parts of the world. Arsenate (As(V)) and arsenite (As(III)), the two most widespread...... in Arabidopsis. The function of N-terminus in regulation of AtNIP5;1 in planta remains elusive. ICPMS analysis of the elemental composition and expression analysis did not clarify the role of Nterminus of AtNIP5;1 in arsenic accumulation in Arabidopsis. Further research is needed to elucidate the role of N...

  6. Surprising Intrinsic Photostability of the Disulfide Bridge Common in Proteins

    DEFF Research Database (Denmark)

    Stephansen, Anne Boutrup; Brogaard, Rasmus Yding; Kuhlman, Thomas Scheby

    2012-01-01

    on the femtosecond time scale and found the reason for the existence of the S–S bridge as a natural building block in folded structures. The sulfur atoms will indeed move apart on the excited state but only to oscillate around the S–S center of mass. At long S–S distances, there is a strong coupling to the ground...... state, and the oscillatory motion enables the molecules to continuously revisit that particular region of the potential energy surface. When a structural feature such as a ring prevents the sulfur radicals from flying apart and thus assures a sufficient residence time in the active region...

  7. Enhancement of surface plasmon resonance signals using a MIP/GNPs/rGO nano-hybrid film for the rapid detection of ractopamine.

    Science.gov (United States)

    Yao, Ting; Gu, Xu; Li, Tengfei; Li, Junguo; Li, Jun; Zhao, Zhen; Wang, Jing; Qin, Yuchang; She, Yongxin

    2016-01-15

    A novel surface plasmon resonance (SPR) sensor that uses molecular imprinted polymers (MIPs) coated with gold nanoparticles (GNPs) and reduced graphene oxide (rGO) as a sensing nano-hybrid film was developed for detection of ractopamine. The MIPs were synthesized by precipitation polymerization and characterized by scanning electron microscopy and Scatchard analysis. The GNPs/rGO composite was synthesized by a single-step reduction of graphene oxide and HAuCl4 solution. The MIP/GNPs/rGO nano-hybrid film was immobilized onto a bare sensor chip and exhibited remarkable sensitivity and stability by the “grafting to” method with the assistance of ionic liquid (IL) as a binder. The prepared sensor showed class-specific selectivity for ractopamine (RAC) and its analogs under optimized conditions. The novel SPR sensor had a wide linear range over an RAC concentration from 20 to 1000 ng/mL with a detection limit of 5 ng/mL (S/N=3). The results demonstrated that the MIP/GNPs/rGO nano-hybrid film was suitable as the recognition element of the SPR sensorfor rapid screening and detection of beta-agonists such as RAC.

  8. The Model Intercomparison Project on the Climatic Response to Volcanic Forcing (VolMIP): Experimental Design and Forcing Input Data for CMIP6

    Science.gov (United States)

    Zanchettin, Davide; Khodri, Myriam; Timmreck, Claudia; Toohey, Matthew; Schmidt, Anja; Gerber, Edwin P.; Hegerl, Gabriele; Robock, Alan; Pausata, Francesco; Ball, William T.; hide

    2016-01-01

    The enhancement of the stratospheric aerosol layer by volcanic eruptions induces a complex set of responses causing global and regional climate effects on a broad range of timescales. Uncertainties exist regarding the climatic response to strong volcanic forcing identified in coupled climate simulations that contributed to the fifth phase of the Coupled Model Intercomparison Project (CMIP5). In order to better understand the sources of these model diversities, the Model Intercomparison Project on the climatic response to Volcanic forcing (VolMIP) has defined a coordinated set of idealized volcanic perturbation experiments to be carried out in alignment with the CMIP6 protocol. VolMIP provides a common stratospheric aerosol data set for each experiment to minimize differences in the applied volcanic forcing. It defines a set of initial conditions to assess how internal climate variability contributes to determining the response. VolMIP will assess to what extent volcanically forced responses of the coupled ocean-atmosphere system are robustly simulated by state-of-the-art coupled climate models and identify the causes that limit robust simulated behavior, especially differences in the treatment of physical processes. This paper illustrates the design of the idealized volcanic perturbation experiments in the VolMIP protocol and describes the common aerosol forcing input data sets to be used.

  9. One small step for MIP towards automated metaphor identification? Formulating general rules to determine basic meanings in large-scale approaches to metaphor

    NARCIS (Netherlands)

    Dorst, A.G.; Reijnierse, W.G.; Venhuizen, G.

    2013-01-01

    The manual annotation of large corpora is time-consuming and brings about issues of consistency. This paper aims to demonstrate how general rules for determining basic meanings can be formulated in large-scale projects involving multiple analysts applying MIP(VU) to authentic data. Three sets of

  10. The Hot Serial Cereal Experiment for modeling wheat response to temperature: field experiments and AgMIP-Wheat multi-model simulations

    NARCIS (Netherlands)

    Martre, P.; Kimball, B.A.; Ottman, M.J.; Wall, G.W.; White, J.; Asseng, S.; Ewert, F.; Cammarano, D.; Maiorano, Andrea; Supit, I.

    2017-01-01

    The data set reported here includes the part of a Hot Serial Cereal Experiment (HSC) experiment recently used in the AgMIP-Wheat project to analyze the uncertainty of 30 wheat models and quantify their response to temperature. The HSC experiment was conducted in an open-field in a semiarid

  11. The International Heat Stress Genotype Experiment for modeling wheat response to heat: field experiments and AgMIP-Wheat multi-model simulations

    NARCIS (Netherlands)

    Martre, P.; Reynolds, M.P.; Asseng, S.; Ewert, F.; Alderman, P.D.; Cammarano, D.; Maiorano, Andrea; Ruane, A.C.; Aggarwal, P.K.; Anothai, J.; Supit, I.

    2017-01-01

    The data set contains a portion of the International Heat Stress Genotype Experiment (IHSGE) data used in the AgMIP-Wheat project to analyze the uncertainty of 30 wheat crop models and quantify the impact of heat on global wheat yield productivity. It includes two spring wheat cultivars grown during

  12. The International Heat Stress Genotype Experiment for modeling wheat response to heat: field experiments and AgMIP-Wheat multi-model simulations

    DEFF Research Database (Denmark)

    Martre, Pierre; Reynolds, Matthew; Asseng, Senthold

    2017-01-01

    The data set contains a portion of the International Heat Stress Genotype Experiment (IHSGE) data used in the AgMIP-Wheat project to analyze the uncertainty of 30 wheat crop models and quantify the impact of heat on global wheat yield productivity. It includes two spring wheat cultivars grown dur...

  13. Intrinsic plasticity complements LTP in parallel fiber input gain control in cerebellar Purkinje cells

    Science.gov (United States)

    Belmeguenai, Amor; Hosy, Eric; Bengtsson, Fredrik; Pedroarena, Christine; Piochon, Claire; Teuling, Eva; He, Qionger; Ohtsuki, Gen; De Jeu, Marcel T.G.; Elgersma, Ype; De Zeeuw, Chris I.; Jörntell, Henrik; Hansel, Christian

    2010-01-01

    Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF) to Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinase A (PKA) and casein kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei (DCN), but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, non-potentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output. PMID:20943904

  14. Functionality of intrinsic disorder in tumor necrosis factor-α and its receptors.

    Science.gov (United States)

    Uversky, Vladimir N; El-Baky, Nawal Abd; El-Fakharany, Esmail M; Sabry, Amira; Mattar, Ehab H; Uversky, Alexey V; Redwan, Elrashdy M

    2017-11-01

    Tumor necrosis factor-α (TNF-α) is a pleiotropic inflammatory cytokine that exerts potent cytotoxic effects on solid tumor cells, while not affecting their normal counterparts. It is also known that TNF-α exerts many of its biological functions via interaction with specific receptors. To understand the potential roles of intrinsic disorder in the functioning of this important cytokine, we explored the peculiarities of intrinsic disorder distribution in human TNF-α and its homologs from various species, ranging from zebrafish to chimpanzee. We also studied the peculiarities of intrinsic disorder distribution in human TNF-α receptors, TNFR1 and TNFR2. Analysis revealed that cytoplasmic domains of TNF-α and its receptors are expected to be highly disordered. Furthermore, although the sequence identities of analyzed TNF-α homologs range from 99.57% (between human and chimpanzee proteins) to 22.33% (between frog and fish proteins), their intrinsic disorder profiles are characterized by a remarkable similarity. These observations indicate that the peculiarities of distribution of the intrinsic disorder propensity within the amino acid sequences are evolutionary conserved, and therefore could be of functional importance for this family of proteins. We also show that disordered and flexible regions of human TNF-α and its TNFR1 and TNFR2 receptors are crucial for some of their biological activities. © 2017 Federation of European Biochemical Societies.

  15. Management Control, Intrinsic Motivation and Creativity

    DEFF Research Database (Denmark)

    Godt Gregersen, Mikkel

    of the conclusion is that intrinsic motivation and management control can coexist under the conditions that all three basic needs, i.e. autonomy, competence and relatedness, are supported. This can happen when control takes point of departure in the individual employee. The second part of the conclusion......This thesis consists of a cape and three papers. The overall research question is: How can intrinsic motivation and management control coexist in a creative environment and how can coordination be possible in such a context? The cape ties together the research done in the three papers....... It is divided into six sections. The first section introduces the concepts of intrinsic motivation, creativity and management control. This is followed by a section on management control in a creative context. These two sections frame the thesis and introduce the setting in which the research has been done...

  16. Information assessment on predicting protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Gerstein Mark

    2004-10-01

    Full Text Available Abstract Background Identifying protein-protein interactions is fundamental for understanding the molecular machinery of the cell. Proteome-wide studies of protein-protein interactions are of significant value, but the high-throughput experimental technologies suffer from high rates of both false positive and false negative predictions. In addition to high-throughput experimental data, many diverse types of genomic data can help predict protein-protein interactions, such as mRNA expression, localization, essentiality, and functional annotation. Evaluations of the information contributions from different evidences help to establish more parsimonious models with comparable or better prediction accuracy, and to obtain biological insights of the relationships between protein-protein interactions and other genomic information. Results Our assessment is based on the genomic features used in a Bayesian network approach to predict protein-protein interactions genome-wide in yeast. In the special case, when one does not have any missing information about any of the features, our analysis shows that there is a larger information contribution from the functional-classification than from expression correlations or essentiality. We also show that in this case alternative models, such as logistic regression and random forest, may be more effective than Bayesian networks for predicting interactions. Conclusions In the restricted problem posed by the complete-information subset, we identified that the MIPS and Gene Ontology (GO functional similarity datasets as the dominating information contributors for predicting the protein-protein interactions under the framework proposed by Jansen et al. Random forests based on the MIPS and GO information alone can give highly accurate classifications. In this particular subset of complete information, adding other genomic data does little for improving predictions. We also found that the data discretizations used in the

  17. Insulin aggregation tracked by its intrinsic TRES

    Science.gov (United States)

    Chung, Li Hung C.; Birch, David J. S.; Vyshemirsky, Vladislav; Ryadnov, Maxim G.; Rolinski, Olaf J.

    2017-12-01

    Time-resolved emission spectra (TRES) have been used to detect conformational changes of intrinsic tyrosines within bovine insulin at a physiological pH. The approach offers the ability to detect the initial stages of insulin aggregation at the molecular level. The data analysis has revealed the existence of at least three fluorescent species undergoing dielectric relaxation and significant spectral changes due to insulin aggregation. The results indicate the suitability of the intrinsic TRES approach for insulin studies and for monitoring its stability during storage and aggregation in insulin delivery devices.

  18. Intrinsic viscosity of a suspension of cubes

    KAUST Repository

    Mallavajula, Rajesh K.

    2013-11-06

    We report on the viscosity of a dilute suspension of cube-shaped particles. Irrespective of the particle size, size distribution, and surface chemistry, we find empirically that cubes manifest an intrinsic viscosity [η]=3.1±0.2, which is substantially higher than the well-known value for spheres, [η]=2.5. The orientation-dependent intrinsic viscosity of cubic particles is determined theoretically using a finite-element solution of the Stokes equations. For isotropically oriented cubes, these calculations show [η]=3.1, in excellent agreement with our experimental observations. © 2013 American Physical Society.

  19. Intrinsic entropy perturbations from the dark sector

    Science.gov (United States)

    Celoria, Marco; Comelli, Denis; Pilo, Luigi

    2018-03-01

    Perfect fluids are modeled by using an effective field theory approach which naturally gives a self-consistent and unambiguous description of the intrinsic non-adiabatic contribution to pressure variations. We study the impact of intrinsic entropy perturbation on the superhorizon dynamics of the curvature perturbation Script R in the dark sector. The dark sector, made of dark matter and dark energy is described as a single perfect fluid. The non-perturbative vorticity's dynamics and the Weinberg theorem violation for perfect fluids are also studied.

  20. A model of intrinsic symmetry breaking

    International Nuclear Information System (INIS)

    Ge, Li; Li, Sheng; George, Thomas F.; Sun, Xin

    2013-01-01

    Different from the symmetry breaking associated with a phase transition, which occurs when the controlling parameter is manipulated across a critical point, the symmetry breaking presented in this Letter does not need parameter manipulation. Instead, the system itself suddenly undergoes symmetry breaking at a certain time during its evolution, which is intrinsic symmetry breaking. Through a polymer model, it is revealed that the origin of the intrinsic symmetry breaking is nonlinearity, which produces instability at the instance when the evolution crosses an inflexion point, where this instability breaks the original symmetry

  1. The synthesis of magnetic lysozyme-imprinted polymers by means of distillation-precipitation polymerization for selective protein enrichment.

    Science.gov (United States)

    Cao, Jiali; Zhang, Xihao; He, Xiwen; Chen, Langxing; Zhang, Yukui

    2014-02-01

    A protein imprinting approach for the synthesis of core-shell structure nanoparticles with a magnetic core and molecularly imprinted polymer (MIP) shell was developed using a simple distillation-precipitation polymerization method. In this work, Fe3O4 magnetic nanoparticles were first synthesized through a solvothermal method and then were conveniently surface-modified with 3-(methacryloyloxy)propyltrimethoxylsilane as anchor molecules to donate vinyl groups. Next a high-density MIP shell was coated onto the surface of the magnetic nanoparticles by the copolymerization of functional monomer acrylamide (AAm), cross-linking agent N,N'-methylenebisacrylamide (MBA), the initiator azodiisobutyronitrile (AIBN), and protein in acetonitrile heated at reflux. The morphology, adsorption, and recognition properties of the magnetic molecularly imprinted nanoparticles were investigated by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and rebinding experiments. The resulting MIP showed a high adsorption capacity (104.8 mg g(-1)) and specific recognition (imprinting factor=7.6) to lysozyme (Lyz). The as-prepared Fe3O4@Lyz-MIP nanoparticles with a mean diameter of 320 nm were coated with an MIP shell that was 20 nm thick, which enabled Fe3O4@Lyz-MIP to easily reach adsorption equilibrium. The high magnetization saturation (40.35 emu g(-1)) endows the materials with the convenience of magnetic separation under an external magnetic field and allows them to be subsequently reused. Furthermore, Fe3O4@Lyz-MIP could selectively extract a target protein from real egg-white samples under an external magnetic field. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Simple measurements for prediction of drug release from polymer matrices - Solubility parameters and intrinsic viscosity

    DEFF Research Database (Denmark)

    Madsen, Claus G; Skov, Anders; Baldursdottir, Stefania

    2015-01-01

    PURPOSE: This study describes how protein release from polymer matrices correlate with simple measurements on the intrinsic viscosity of the polymer solutions used for casting the matrices and calculations of the solubility parameters of polymers and solvents used. METHOD: Matrices of poly......(dl-lactide-co-glycolide) (PLGA) were cast with bovine serum albumin (BSA) as a model drug using different solvents (acetone, dichloromethane, ethanol and water). The amount of released protein from the different matrices was correlated with the Hildebrand and Hansen solubility parameters of the solvents, and the intrinsic...... from PLGA matrices varied depending on the solvent used for casting. The maximum amount of released BSA decreased with higher intrinsic viscosity, and increased with solubility parameter difference between the solvent and polymer used. The solvent used also had an effect on the matrix microstructure...

  3. Simple intrinsic defects in InAs :

    Energy Technology Data Exchange (ETDEWEB)

    Schultz, Peter Andrew

    2013-03-01

    This Report presents numerical tables summarizing properties of intrinsic defects in indium arsenide, InAs, as computed by density functional theory using semi-local density functionals, intended for use as reference tables for a defect physics package in device models.

  4. INTRINSIC AND EXTRINSIC MOTIVATION IN THE SELECTION ...

    African Journals Online (AJOL)

    A psychological perspective is considered that applies intrinsic and extrinsic motivational concepts to communication phenomena. The paper also tries to develop an analytical understanding of human communication-related behavior with respect to the two types of motives. Proposals are also put forward to communication ...

  5. Intrinsic and Extrinsic Motivation among Collegiate Instrumentalists

    Science.gov (United States)

    Diaz, Frank M.

    2010-01-01

    The purpose of this study was to gather and compare information on measures of intrinsic and extrinsic motivation among instrumentalists enrolled in collegiate ensembles. A survey instrument was developed to gather information concerning demographic data and responses to questions on motivational preference. Participants were undergraduate and…

  6. A rotational integral formula for intrinsic volumes

    DEFF Research Database (Denmark)

    Jensen, Eva Bjørn Vedel; Rataj, J.

    2008-01-01

    A rotational version of the famous Crofton formula is derived. The motivation for deriving the formula comes from local stereology, a new branch of stereology based on sections through fixed reference points. The formula shows how rotational averages of intrinsic volumes measured on sections...

  7. Original Paper Detecting Nosocomial Intrinsic Infections through ...

    African Journals Online (AJOL)

    2011-04-20

    Apr 20, 2011 ... Key Words: Bacterial pathogens, Endogenous indicators, NosocomiaI infection, Surgery. Received 30 October 2010/ Accepted 30 March 2011. INTRODUCTION. Micro-organisms from intrinsic and extrinsic sources have been known to cause nosocomial infections (CDC, 1991). The human body enables.

  8. Organisational Learning and Employees' Intrinsic Motivation

    Science.gov (United States)

    Remedios, Richard; Boreham, Nick

    2004-01-01

    This study examined the effects of organisational learning initiatives on employee motivation. Four initiatives consistent with theories of organisational learning were a priori ranked in terms of concepts that underpin intrinsic-motivation theory. Eighteen employees in a UK petrochemical company were interviewed to ascertain their experiences of…

  9. Intrinsic Motivation, Organizational Justice, and Creativity

    Science.gov (United States)

    Hannam, Kalli; Narayan, Anupama

    2015-01-01

    For employees to generate creative ideas that are not only original, but also useful to their company, they must interact with their workplace environment to determine organizational needs. Therefore, it is important to consider aspects of the individual as well as their environment when studying creativity. Intrinsic motivation, a predictor of…

  10. Discovery of Intrinsic Primitives on Triangle Meshes

    KAUST Repository

    Solomon, Justin

    2011-04-01

    The discovery of meaningful parts of a shape is required for many geometry processing applications, such as parameterization, shape correspondence, and animation. It is natural to consider primitives such as spheres, cylinders and cones as the building blocks of shapes, and thus to discover parts by fitting such primitives to a given surface. This approach, however, will break down if primitive parts have undergone almost-isometric deformations, as is the case, for example, for articulated human models. We suggest that parts can be discovered instead by finding intrinsic primitives, which we define as parts that posses an approximate intrinsic symmetry. We employ the recently-developed method of computing discrete approximate Killing vector fields (AKVFs) to discover intrinsic primitives by investigating the relationship between the AKVFs of a composite object and the AKVFs of its parts. We show how to leverage this relationship with a standard clustering method to extract k intrinsic primitives and remaining asymmetric parts of a shape for a given k. We demonstrate the value of this approach for identifying the prominent symmetry generators of the parts of a given shape. Additionally, we show how our method can be modified slightly to segment an entire surface without marking asymmetric connecting regions and compare this approach to state-of-the-art methods using the Princeton Segmentation Benchmark. © 2011 The Author(s).

  11. Radiation dosimetry and first therapy results with a {sup 124}I/{sup 131}I-labeled small molecule (MIP-1095) targeting PSMA for prostate cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zechmann, Christian M.; Afshar-Oromieh, Ali; Mier, Walter [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Armor, Tom; Joyal, John [Molecular Insight Pharmaceuticals, Boston, MA (United States); Stubbs, James B. [Radiation Dosimetry Systems RDS, Inc., Apharetta, GA (United States); Hadaschik, Boris [University Hospital Heidelberg, Department of Urology, Heidelberg (Germany); Kopka, Klaus [Division Radiopharmaceutical Chemistry, DKFZ, Heidelberg (Germany); Debus, Juergen [University Hospital Heidelberg, Department of Radiation Oncology, Heidelberg (Germany); Babich, John W. [Molecular Insight Pharmaceuticals, Boston, MA (United States); Cornell University, Division of Radiopharmacy, Department of Radiology, New York, NY (United States); Haberkorn, Uwe [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Clinical Cooperation Unit Nuclear Medicine, DKFZ, Heidelberg (Germany)

    2014-07-15

    Since the prostate-specific membrane antigen (PSMA) is frequently over-expressed in prostate cancer (PCa) several PSMA-targeting molecules are under development to detect and treat metastatic castration resistant prostate cancer (mCRPC). We investigated the tissue kinetics of a small molecule inhibitor of PSMA ((S)-2-(3-((S)-1-carboxy-5-(3-(4-[{sup 124}I]iodophenyl)ureido)pentyl)ureido) pentan edioicacid; MIP-1095) using PET/CT to estimate radiation dosimetry for the potential therapeutic use of {sup 131}I-MIP-1095 in men with mCRPC. We also report preliminary safety and efficacy of the first 28 consecutive patients treated under a compassionate-use protocol with a single cycle of {sup 131}I-MIP-1095. Sixteen patients with known prostate cancer underwent PET/CT imaging after i.v. administration of {sup 124}I-MIP-1095 (mean activity: 67.4 MBq). Each patient was scanned using PET/CT up to five times at 1, 4, 24, 48 and 72 h post injection. Volumes of interest were defined for tumor lesions and normal organs at each time point followed by dose calculations using the OLINDA/EXM software. Twenty-eight men with mCRPC were treated with a single cycle of {sup 131}I-MIP-1095 (mean activity: 4.8 GBq, range 2 to 7.2 GBq) and followed for safety and efficacy. Baseline and follow up examinations included a complete blood count, liver and kidney function tests, and measurement of serum PSA. I-124-MIP-1095 PET/CT images showed excellent tumor uptake and moderate uptake in liver, proximal intestine and within a few hours post-injection also in the kidneys. High uptake values were observed only in salivary and lacrimal glands. Dosimetry estimates for I-131-MIP-1095 revealed that the highest absorbed doses were delivered to the salivary glands (3.8 mSv/MBq), liver (1.7 mSv/MBq) and kidneys (1.4 mSv/MBq). The absorbed dose calculated for the red marrow was 0.37 mSv/MBq. PSA values decreased by >50 % in 60.7 % of the men treated. Of men with bone pain, 84.6 % showed complete or

  12. The Intracellular Distal Tail of the Na+/H+ Exchanger NHE1 Is Intrinsically Disordered

    DEFF Research Database (Denmark)

    Nørholm, Ann-Beth; Hendus-Altenburger, Ruth; Bjerre, Gabriel

    2011-01-01

    dysfunction is implicated in several clinically important diseases. This study shows, for the first time for any carrier protein, that the distal part of the C-terminal intracellular tail (the cdt, residues V686-Q815) from human (h) NHE1 is intrinsically disordered. Further, we experimentally demonstrated...

  13. Techniques for intrinsically labeling wheat with /sup 65/Zn

    Energy Technology Data Exchange (ETDEWEB)

    Starks, T.L.; Johnson, P.E.

    Several techniques of intrinsically labeling wheat with /sup 65/Zn were compared: stem injection of /sup 65/Zn, stem injection of /sup 65/Zn + ZnSO/sub 4/, foliar application of /sup 65/Zn, and the addition of /sup 65/Zn to a hydroponic solution. Incorporation levels of /sup 65/Zn into the grain were 62.6% stem injection, 45.2% stem-injected /sup 65/Zn + ZnSO/sub 4/, 57.5% foliar application, and 2.3% hydroponic solution. Four protein fractions were extracted from fat-free whole wheat flour. Distribution of /sup 65/Zn into the protein fractions for all treatments, was 8.5-20.3% in albumins and globulins, 47.4-60.3% in glutenins, 1-2.6% in gliadins, and 9.8-28.3% in the remaining proteins. Separation of the fractions by gel chromatography showed that protein and Zn distributions were similar among the treatments and when compared to the controls. Zinc-65 distribution was similar to the natural Zn distribution. These data illustrate that stem-injected /sup 65/Zn is incorporated in the same manner and ratios as Zn naturally utilized by wheat.

  14. Techniques for intrinsically labeling wheat with 65Zn

    International Nuclear Information System (INIS)

    Starks, T.L.; Johnson, P.E.

    1985-01-01

    Several techniques of intrinsically labeling wheat with 65 Zn were compared: stem injection of 65 Zn, stem injection of 65 Zn + ZnSO 4 , foliar application of 65 Zn, and the addition of 65 Zn to a hydroponic solution. Incorporation levels of 65 Zn into the grain were 62.6% stem injection, 45.2% stem-injected 65 Zn + ZnSO 4 , 57.5% foliar application, and 2.3% hydroponic solution. Four protein fractions were extracted from fat-free whole wheat flour. Distribution of 65 Zn into the protein fractions for all treatments, was 8.5-20.3% in albumins and globulins, 47.4-60.3% in glutenins, 1-2.6% in gliadins, and 9.8-28.3% in the remaining proteins. Separation of the fractions by gel chromatography showed that protein and Zn distributions were similar among the treatments and when compared to the controls. Zinc-65 distribution was similar to the natural Zn distribution. These data illustrate that stem-injected 65 Zn is incorporated in the same manner and ratios as Zn naturally utilized by wheat

  15. Assessment of molecularly imprinted polymers (MIPs) in the preconcentration of disperse red 73 dye prior to photoelectrocatalytic treatment.

    Science.gov (United States)

    Franco, Jefferson Honorio; Aissa, Alejandra Ben; Bessegato, Guilherme Garcia; Fajardo, Laura Martinez; Zanoni, Maria Valnice Boldrin; Pividori, María Isabel; Del Pilar Taboada Sotomayor, Maria

    2017-02-01

    Magnetic molecularly imprinted polymers (MMIPs) have become a research hotspot due to their two important characteristics: target recognition and magnetic separation. This paper presents the preparation, characterization, and optimization of an MMIP for the preconcentration of disperse red 73 dye (DR73) and its subsequent efficient degradation by photoelectrocatalytic treatment. The MMIPs were characterized by scanning electron microscopy (SEM), which revealed homogeneous distribution of the particles. Excellent encapsulation of magnetite was confirmed by transmission electron microscopy (TEM). A study of dye binding showed that the dye was retained more selectively in the MIP, compared to the NIP. The release of DR73 from the imprinted polymers into methanol and acetic acid was analyzed by UV-Vis spectrophotometry. The extracts showed higher absorbance values for MMIP, compared to MNIP, confirming greater adsorption of dye in the MMIP material. The extracts were then subjected to photoelectrocatalytic treatment. LC-MS/MS analysis following this treatment showed that the dye was almost completely degraded. Hence, the combination of MMIP extraction and photoelectrocatalysis offers an alternative way of selectively removing an organic contaminant, prior to proceeding with its complete degradation.

  16. Development of a highly sensitive MIP based-QCM nanosensor for selective determination of cholic acid level in body fluids.

    Science.gov (United States)

    Gültekin, Aytaç; Karanfil, Gamze; Sönmezoğlu, Savaş; Say, Rıdvan

    2014-09-01

    Determination of cholic acid is very important and necessary in body fluids due to its both pharmaceutical and clinical significance. In this study, a quartz crystal microbalance (QCM) nanosensor, which is imprinted cholic acid, has been developed for the assignation of cholic acid. The cholic acid selective memories have been generated on QCM electrode surface by using molecularly imprinted polymer (MIP) based on methacryloylamidohistidine-copper (II) (MAH-Cu(II)) pre-organized monomer. The cholic acid imprinted nanosensor was characterized by atomic force microscopy (AFM) and then analytical performance of the cholic acid imprinted QCM nanosensor was studied. The detection limit was found to be 0.0065μM with linear range of 0.01-1,000 μM. Moreover, the high value of Langmuir constant (b) (7.3*10(5)) obtained by Langmuir graph showed that the cholic acid imprinted nanosensor had quite strong binding sites affinity. At the last step of this procedure, cholic acid levels in body fluids were determined by the prepared imprinted QCM nanosensor. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Identifying the neural substrates of intrinsic motivation during task performance.

    Science.gov (United States)

    Lee, Woogul; Reeve, Johnmarshall

    2017-10-01

    Intrinsic motivation is the inherent tendency to seek out novelty and challenge, to explore and investigate, and to stretch and extend one's capacities. When people imagine performing intrinsically motivating tasks, they show heightened anterior insular cortex (AIC) activity. To fully explain the neural system of intrinsic motivation, however, requires assessing neural activity while people actually perform intrinsically motivating tasks (i.e., while answering curiosity-inducing questions or solving competence-enabling anagrams). Using event-related functional magnetic resonance imaging, we found that the neural system of intrinsic motivation involves not only AIC activity, but also striatum activity and, further, AIC-striatum functional interactions. These findings suggest that subjective feelings of intrinsic satisfaction (associated with AIC activations), reward processing (associated with striatum activations), and their interactions underlie the actual experience of intrinsic motivation. These neural findings are consistent with the conceptualization of intrinsic motivation as the pursuit and satisfaction of subjective feelings (interest and enjoyment) as intrinsic rewards.

  18. Iron bioavailability studies as assessed by intrinsic and extrinsic labeling techniques

    International Nuclear Information System (INIS)

    Johnson, C.D.

    1985-01-01

    Although soybeans are a rich source of iron and incorporation of soy protein into diets is increasing, the presence of phytate or fiber endogenous to the seeds may inhibit total iron absorption from diets including soy protein. Four studies on iron bioavailability as assessed by intrinsic and extrinsic labeling techniques in rats were completed. The effect of previous dietary protein on the absorption of intrinsically 59 Fe labeled defatted soy flour was determined in rats. The results indicated that the type of dietary protein (animal vs. plant) in pre-test diets would have little influence on iron absorption from a single soy protein test meal. Therefore, adaptation of soy protein does not improve bioavailability of iron. Soybean hulls were investigated as a source of iron fortification in bread. The results indicated that retention of 59 Fe from white bread baked with soy hulls did not differ from white bread fortified with bakery grade ferrous sulfate. The effect of endogenous soybean phytate on iron absorption in rats was measured using seeds of varying phytate content and intrinsically labeled with 59 Fe. Increasing concentration of phytate in whole soybean flour had no significant effect on iron absorption

  19. Iron bioavailability studies as assessed by intrinsic and extrinsic labeling techniques

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, C.D.

    1985-01-01

    Although soybeans are a rich source of iron and incorporation of soy protein into diets is increasing, the presence of phytate or fiber endogenous to the seeds may inhibit total iron absorption from diets including soy protein. Four studies on iron bioavailability as assessed by intrinsic and extrinsic labeling techniques in rats were completed. The effect of previous dietary protein on the absorption of intrinsically /sup 59/Fe labeled defatted soy flour was determined in rats. The results indicated that the type of dietary protein (animal vs. plant) in pre-test diets would have little influence on iron absorption from a single soy protein test meal. Therefore, adaptation of soy protein does not improve bioavailability of iron. Soybean hulls were investigated as a source of iron fortification in bread. The results indicated that retention of /sup 59/Fe from white bread baked with soy hulls did not differ from white bread fortified with bakery grade ferrous sulfate. The effect of endogenous soybean phytate on iron absorption in rats was measured using seeds of varying phytate content and intrinsically labeled with /sup 59/Fe. Increasing concentration of phytate in whole soybean flour had no significant effect on iron absorption.

  20. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy

    Science.gov (United States)

    Putinski, Charis; Abdul-Ghani, Mohammad; Stiles, Rebecca; Brunette, Steve; Dick, Sarah A.; Fernando, Pasan; Megeney, Lynn A.

    2013-01-01

    Cardiomyocyte hypertrophy is the cellular response that mediates pathologic enlargement of the heart. This maladaptation is also characterized by cell behaviors that are typically associated with apoptosis, including cytoskeletal reorganization and disassembly, altered nuclear morphology, and enhanced protein synthesis/translation. Here, we investigated the requirement of apoptotic caspase pathways in mediating cardiomyocyte hypertrophy. Cardiomyocytes treated with hypertrophy agonists displayed rapid and transient activation of the intrinsic-mediated cell death pathway, characterized by elevated levels of caspase 9, followed by caspase 3 protease activity. Disruption of the intrinsic cell death pathway at multiple junctures led to a significant inhibition of cardiomyocyte hypertrophy during agonist stimulation, with a corresponding reduction in the expression of known hypertrophic markers (atrial natriuretic peptide) and transcription factor activity [myocyte enhancer factor-2, nuclear factor kappa B (NF-κB)]. Similarly, in vivo attenuation of caspase activity via adenoviral expression of the biologic effector caspase inhibitor p35 blunted cardiomyocyte hypertrophy in response to agonist stimulation. Treatment of cardiomyocytes with procaspase 3 activating compound 1, a small-molecule activator of caspase 3, resulted in a robust induction of the hypertrophy response in the absence of any agonist stimulation. These results suggest that caspase-dependent signaling is necessary and sufficient to promote cardiomyocyte hypertrophy. These results also confirm that cell death signal pathways behave as active remodeling agents in cardiomyocytes, independent of inducing an apoptosis response. PMID:24101493

  1. Intrinsic Motivation in Open Source Software Development

    DEFF Research Database (Denmark)

    Bitzer, J.; W., Schrettl,; Schröder, Philipp

    2004-01-01

    This papers sheds light on the puzzling evidence that even though open source software (OSS) is a public good, it is developed for free by highly qualified, young and motivated individuals, and evolves at a rapid pace. We show that once OSS development is understood as the private provision...... of a public good, these features emerge quite naturally. We adapt a dynamic private-provision-of-public-goods model to reflects key aspects of the OSS phenomenon. In particular, instead of relying on extrinsic motives for programmers (e.g. signaling) the present model is driven by intrinsic motives of OSS...... programmers, such as user-programmers, play value or \\emph{homo ludens} payoff, and gift culture benefits. Such intrinsic motives feature extensively in the wider OSS literature and turn out to add new insights to the economic analysis....

  2. Does Aerobic Exercise Influence Intrinsic Brain Activity?

    DEFF Research Database (Denmark)

    Flodin, Pär; Jonasson, Lars S; Riklund, Katrin

    2017-01-01

    Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic...... exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling...... group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings...

  3. Documentation Requirements, Intrinsic Motivation, and Worker Absence

    DEFF Research Database (Denmark)

    Andersen, Lotte Bøgh; Kristensen, Nicolai; Pedersen, Lene Holm

    2015-01-01

    Command systems are widely used to monitor public service provision, but little is known about unintended effects on individual workers’ motivation and work effort. Using insights from motivation crowding theory, we estimate a SEM model that captures how Danish childcare assistants and social...... and higher sickness absence. The association is statistically significant, but very small in substantive terms. The result is nevertheless consistent with the expectation in motivation crowding theory and contributes to the literature by including a new, reliable behavioral variable—sickness absence....../healthcare assistants perceive documentation requirements. We analyze how this perception relates to intrinsic motivation measured in a survey and sickness absence as reported in administrative registers, and find that individuals who perceive documentation requirements as controlling have lower intrinsic motivation...

  4. Extrinsic and intrinsic determinants of nerve regeneration

    Directory of Open Access Journals (Sweden)

    Toby A. Ferguson

    2011-01-01

    Full Text Available After central nervous system (CNS injury axons fail to regenerate often leading to persistent neurologic deficit although injured peripheral nervous system (PNS axons mount a robust regenerative response that may lead to functional recovery. Some of the failures of CNS regeneration arise from the many glial-based inhibitory molecules found in the injured CNS, whereas the intrinsic regenerative potential of some CNS neurons is actively curtailed during CNS maturation and limited after injury. In this review, the molecular basis for extrinsic and intrinsic modulation of axon regeneration within the nervous system is evaluated. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which is used to develop improved treatments for nervous system injury.

  5. Intrinsic point defects in aluminum antimonide

    OpenAIRE

    Åberg, Daniel; Erhart, Paul; Williamson, Andrew J.; Lordi, Vincenzo

    2010-01-01

    Calculations within density functional theory on the basis of the local density approximation are carried out to study the properties of intrinsic point defects in aluminum antimonide. Special care is taken to address finite-size effects, band gap error, and symmetry reduction in the defect structures. The correction of the band gap is based on a set of GW calculations. The most important defects are identified to be the aluminum interstitial $Al_{i,Al}^{1+}$, the antimony antisites $Sb_{Al}^...

  6. Intrinsic luminescence of alkali silicate glasses

    Energy Technology Data Exchange (ETDEWEB)

    Arbuzov, V.I.; Grabovskis, V.Y.; Tolstoi, M.N.; Vitol, I.K.

    1986-09-01

    This study obtains additional information on L centers and their role in electron excitation and intrinsic luminescence of a whole series. (Li, Na, K, Rb, and Cs) of alkali silicate glasses. The authors compare the features of the interaction with radiation of specimens of glass and crystal of a similar chemical composition, since silicates of alkali metals can be obtained in both the glassy and crystalline states.

  7. Intrinsic work motivation and pension reform acceptance

    OpenAIRE

    Heinemann, Friedrich; Hennighausen, Tanja; Moessinger, Marc-Daniel

    2011-01-01

    Although demographic change leaves pay-as-you-go pension systems unsustainable, reforms, such as a higher pension age, are highly unpopular. This contribution looks into the role of intrinsic motivation as a driver for pension reform acceptance. Theoretical reasoning suggests that this driver should be relevant: The choice among different pension reform options (increasing pension age, increasing contributions, cutting pensions) can be analyzed within the framework of an optimal job separatio...

  8. A structural model of intrinsic motivation

    OpenAIRE

    Aguilar, Javier; González, Daniel; Aguilar, Amira

    2017-01-01

    The main purpose of this research was to develop and test a structural model of intrinsic motivation among students of the University of Sonora to the curriculum of their careers. A secondary objective was to overcome the limitations of the model developed among students of the UNAM. Eight psychometric scales developed by the authors in previous studies were used, which showed satisfactory reliability and validity values. The model tested was similar to the sample of the UNAM, except for the ...

  9. NMR of unfolded proteins

    Indian Academy of Sciences (India)

    In the post-genomic era, as more and more genome sequences are becoming known and hectic efforts are underway to decode the information content in them, it is becoming increasingly evident that flexibility in proteins plays a crucial role in many of the biological functions. Many proteins have intrinsic disorder either ...

  10. Moral Distress, Workplace Health, and Intrinsic Harm.

    Science.gov (United States)

    Weber, Elijah

    2016-05-01

    Moral distress is now being recognized as a frequent experience for many health care providers, and there's good evidence that it has a negative impact on the health care work environment. However, contemporary discussions of moral distress have several problems. First, they tend to rely on inadequate characterizations of moral distress. As a result, subsequent investigations regarding the frequency and consequences of moral distress often proceed without a clear understanding of the phenomenon being discussed, and thereby risk substantially misrepresenting the nature, frequency, and possible consequences of moral distress. These discussions also minimize the intrinsically harmful aspects of moral distress. This is a serious omission. Moral distress doesn't just have a negative impact on the health care work environment; it also directly harms the one who experiences it. In this paper, I claim that these problems can be addressed by first clarifying our understanding of moral distress, and then identifying what makes moral distress intrinsically harmful. I begin by identifying three common mistakes that characterizations of moral distress tend to make, and explaining why these mistakes are problematic. Next, I offer an account of moral distress that avoids these mistakes. Then, I defend the claim that moral distress is intrinsically harmful to the subject who experiences it. I conclude by explaining how acknowledging this aspect of moral distress should reshape our discussions about how best to deal with this phenomenon. © 2015 John Wiley & Sons Ltd.

  11. Intrinsic electron trapping in amorphous oxide

    Science.gov (United States)

    Strand, Jack; Kaviani, Moloud; Afanas’ev, Valeri V.; Lisoni, Judit G.; Shluger, Alexander L.

    2018-03-01

    We demonstrate that electron trapping at intrinsic precursor sites is endemic in non-glass-forming amorphous oxide films. The energy distributions of trapped electron states in ultra-pure prototype amorphous (a)-HfO2 insulator obtained from exhaustive photo-depopulation experiments demonstrate electron states in the energy range of 2–3 eV below the oxide conduction band. These energy distributions are compared to the results of density functional calculations of a-HfO2 models of realistic density. The experimental results can be explained by the presence of intrinsic charge trapping sites formed by under-coordinated Hf cations and elongated Hf–O bonds in a-HfO2. These charge trapping states can capture up to two electrons, forming polarons and bi-polarons. The corresponding trapping sites are different from the dangling-bond type defects responsible for trapping in glass-forming oxides, such as SiO2, in that the traps are formed without bonds being broken. Furthermore, introduction of hydrogen causes formation of somewhat energetically deeper electron traps when a proton is immobilized next to the trapped electron bi-polaron. The proposed novel mechanism of intrinsic charge trapping in a-HfO2 represents a new paradigm for charge trapping in a broad class of non-glass-forming amorphous insulators.

  12. Learning intrinsic excitability in medium spiny neurons.

    Science.gov (United States)

    Scheler, Gabriele

    2013-01-01

    We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parameterization of individual ion channels on the neuronal membrane potential-curent relationship (activation function). We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal modulation on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how modulation and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic modulation determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction.

  13. The optical spectra of 24 mu m galaxies in the cosmos field. I. Spitzer MIPS bright sources in the zCOSMOS-bright 10k catalog

    NARCIS (Netherlands)

    Caputi, K. I.; Lilly, S. J.; Aussel, H.; Sanders, D.; Frayer, D.; Le Fevre, O.; Renzini, A.; Zamorani, G.; Scodeggio, M.; Contini, T.; Scoville, N.; Carollo, C. M.; Hasinger, G.; Iovino, A.; Le Brun, V.; Le Floc'h, E.; Maier, C.; Mainieri, V.; Mignoli, M.; Salvato, M.; Schiminovich, D.; Silverman, J.; Surace, J.; Tasca, L.; Abbas, U.; Bardelli, S.; Bolzonella, M.; Bongiorno, A.; Bottini, D.; Capak, P.; Cappi, A.; Cassata, P.; Cimatti, A.; Cucciati, O.; de la Torre, S.; de Ravel, L.; Franzetti, P.; Fumana, M.; Garilli, B.; Halliday, C.; Ilbert, O.; Kampczyk, P.; Kartaltepe, J.; Kneib, J. -P.; Knobel, C.; Kovac, K.; Lamareille, F.; Leauthaud, A.; Le Borgne, J. F.; Maccagni, D.; Marinoni, C.; McCracken, H.; Meneux, B.; Oesch, P.; Pello, R.; Perez-Montero, E.; Porciani, C.; Ricciardelli, E.; Scaramella, R.; Scarlata, C.; Tresse, L.; Vergani, D.; Walcher, J.; Zamojski, M.; Zucca, E.

    2008-01-01

    We study zCOSMOS-bright optical spectra for 609 Spitzer MIPS 24 mu m-selected galaxies with S-24 (mu m) > 0: 30 mJy and I <22.5 (AB mag) over 1.5 deg(2) of the COSMOS field. From emission-line diagnostics we find the following: (1) SFRs derived from the observed H alpha lambda 6563 and H beta lambda

  14. Introducing Thermal Wave Transport Analysis (TWTA): A Thermal Technique for Dopamine Detection by Screen-Printed Electrodes Functionalized with Molecularly Imprinted Polymer (MIP) Particles.

    Science.gov (United States)

    Peeters, Marloes M; van Grinsven, Bart; Foster, Christopher W; Cleij, Thomas J; Banks, Craig E

    2016-04-26

    A novel procedure is developed for producing bulk modified Molecularly Imprinted Polymer (MIP) screen-printed electrodes (SPEs), which involves the direct mixing of the polymer particles within the screen-printed ink. This allowed reduction of the sample preparation time from 45 min to 1 min, and resulted in higher reproducibility of the electrodes. The samples are measured with a novel detection method, namely, thermal wave transport analysis (TWTA), relying on the analysis of thermal waves through a functional interface. As a first proof-of-principle, MIPs for dopamine are developed and successfully incorporated within a bulk modified MIP SPE. The detection limits of dopamine within buffer solutions for the MIP SPEs are determined via three independent techniques. With cyclic voltammetry this was determined to be 4.7 × 10(-6) M, whereas by using the heat-transfer method (HTM) 0.35 × 10(-6) M was obtained, and with the novel TWTA concept 0.26 × 10(-6) M is possible. This TWTA technique is measured simultaneously with HTM and has the benefits of reducing measurement time to less than 5 min and increasing effect size by nearly a factor of two. The two thermal methods are able to enhance dopamine detection by one order of magnitude compared to the electrochemical method. In previous research, it was not possible to measure neurotransmitters in complex samples with HTM, but with the improved signal-to-noise of TWTA for the first time, spiked dopamine concentrations were determined in a relevant food sample. In summary, novel concepts are presented for both the sensor functionalization side by employing screen-printing technology, and on the sensing side, the novel TWTA thermal technique is reported. The developed bio-sensing platform is cost-effective and suitable for mass-production due to the nature of screen-printing technology, which makes it very interesting for neurotransmitter detection in clinical diagnostic applications.

  15. Human intrinsic factor expressed in the plant Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Laursen, Niels B; Nexø, Ebba

    2003-01-01

    Intrinsic factor (IF) is the gastric protein that promotes the intestinal uptake of vitamin B12. Gastric IF from animal sources is used in diagnostic tests and in vitamin pills. However, administration of animal IF to humans becomes disadvantageous because of possible pathogenic transmission...... and contamination by other B12 binders. We tested the use of recombinant plants for large-scale production of pathogen-free human recombinant IF. Human IF was successfully expressed in the recombinant plant Arabidopsis thaliana. Extract from fresh plants possessed high B12-binding capacity corresponding to 70 mg...... to recombinant IF and gastric IF were alike, as was the interaction of recombinant and native IF with the specific receptor cubilin. The data presented show that recombinant plants have a great potential as a large-scale source of human IF for analytical and therapeutic purposes....

  16. Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    Full Text Available It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4(+ and CD8(+ T cells in relation to age, HIV and active Tuberculosis (TB co-infection in a cohort of Tanzanian volunteers (≤ 16 years of age, n = 108 and ≥ 18 years, n = 79. Independent of HIV co-infection, IFNγ(+ CMVpp65-specific CD4(+ T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27(low phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.

  17. The herpesvirus 8-encoded chemokine vMIP-II, but not the poxvirus-encoded chemokine MC148, inhibits the CCR10 receptor

    DEFF Research Database (Denmark)

    Lüttichau, H R; Lewis, I C; Gerstoft, J

    2001-01-01

    The viral chemokine antagonist vMIP-II encoded by human herpesvirus 8 (HHV8) and MC148 encoded by the poxvirus - Molluscum contagiosum - were tested against the newly identified chemokine receptor CCR10. As the CCR10 ligand ESkine / CCL27 had the highest identity to MC148 and because both...... chemokines are expressed in the skin we suspected MC148 to block CCR10. However, in calcium mobilization assays we found MC148 unable to block CCR10 in micromolar concentrations in contrast to vMIP-II. (125)I-MC148 was only able to bind to CCR8, but not to CCR10, CCR11, CXCR6 / BONZO, APJ, DARC or the orphan...... receptors BOB, EBI-II, GPR4, GPR17, HCR or RDC1. We conclude that MC148 is a highly selective CCR8 antagonist conceivably optimized to interfere with NK cell and monocyte invasion, whereas the broad-spectrum antagonist vMIP-II protects HHV8 by blocking multiple receptors....

  18. Monitoring of Low Levels of Furfural in Power Transformer Oil with a Sensor System Based on a POF-MIP Platform

    Directory of Open Access Journals (Sweden)

    Nunzio Cennamo

    2015-04-01

    Full Text Available In this work an innovative, miniaturized and low cost optical chemical sensor (POF-MIP platform, based on a molecular imprinted polymer (MIP and surface plasmon resonance in a plastic optical fiber (POF, is presented and preliminarily tested for monitoring of furfural (furan-2-carbaldehyde in transformer oil. To this end, the optical platform was coupled to an MIP layer, highly selective for furfural. The ability of the developed sensor to directly detect furfural in the insulating oil was investigated. The detection limit of the sensor has been found to be 9 ppb, with a linear response up to about 30 ppb. However there is a sensible response up to 0.15 ppm. Because of the small linearity range, the Hill equation is suggested for the quantification. The sensor has been effectively tested in real oil samples collected from aged electrical equipment removed from service. The assessed concentration of furfural is in good agreement with that evaluated by a high pressure liquid chromatography (HLPC method, confirming the good selectivity of the proposed sensor.

  19. Involvement of fractalkine and macrophage inflammatory protein-1 alpha in moderate-severe depression

    Directory of Open Access Journals (Sweden)

    Rosaria Alba Merendino

    2004-01-01

    Full Text Available MODERATE-severe depression (MSD is linked to overexpression of proinflammatory cytokines and chemokines. Fractalkine (FKN and macrophage inflammatory protein-1 alpha (MIP-1α are, respectively, members of CX3C and C-C chemokines, and both are involved in recruiting and activating mononuclear phagocytes in the central nervous system. We analysed the presence of FKN and MIP-1α in sera of untreated MSD patients and healthy donors. High FKN levels were observed in all MSD patients as compared with values only detectable in 26% of healthy donors. MIP-1α was measurable in 20% of patients, while no healthy donors showed detectable chemokine levels. In conclusion, we describe a previously unknown involvement of FKN in the pathogenesis of MSD, suggesting that FKN may represent a target for a specific immune therapy of this disease.

  20. The Soil Model Development and Intercomparison Panel (SoilMIP) of the International Soil Modeling Consortium (ISMC)

    Science.gov (United States)

    Vanderborght, Jan; Priesack, Eckart

    2017-04-01

    The Soil Model Development and Intercomparison Panel (SoilMIP) is an initiative of the International Soil Modeling Consortium. Its mission is to foster the further development of soil models that can predict soil functions and their changes (i) due to soil use and land management and (ii) due to external impacts of climate change and pollution. Since soil functions and soil threats are diverse but linked with each other, the overall aim is to develop holistic models that represent the key functions of the soil system and the links between them. These models should be scaled up and integrated in terrestrial system models that describe the feedbacks between processes in the soil and the other terrestrial compartments. We propose and illustrate a few steps that could be taken to achieve these goals. A first step is the development of scenarios that compare simulations by models that predict the same or different soil services. Scenarios can be considered at three different levels of comparisons: scenarios that compare the numerics (accuracy but also speed) of models, scenarios that compare the effect of differences in process descriptions, and scenarios that compare simulations with experimental data. A second step involves the derivation of metrics or summary statistics that effectively compare model simulations and disentangle parameterization from model concept differences. These metrics can be used to evaluate how more complex model simulations can be represented by simpler models using an appropriate parameterization. A third step relates to the parameterization of models. Application of simulation models implies that appropriate model parameters have to be defined for a range of environmental conditions and locations. Spatial modelling approaches are used to derive parameter distributions. Considering that soils and their properties emerge from the interaction between physical, chemical and biological processes, the combination of spatial models with process

  1. THE SPITZER SURVEY OF INTERSTELLAR CLOUDS IN THE GOULD BELT. IV. LUPUS V AND VI OBSERVED WITH IRAC AND MIPS

    International Nuclear Information System (INIS)

    Spezzi, Loredana; Vernazza, Pierre; Merin, Bruno; Allen, Lori E.; Evans, Neal J. II; Harvey, Paul M.; Joergensen, Jes K.; Bourke, Tyler L.; Peterson, Dawn; Cieza, Lucas A.; Dunham, Michael M.; Huard, Tracy L.; Tothill, Nick F. H.

    2011-01-01

    We present Gould's Belt (GB) Spitzer IRAC and MIPS observations of the Lupus V and VI clouds and discuss them in combination with near-infrared (2MASS) data. Our observations complement those obtained for other Lupus clouds within the frame of the Spitzer C ore to Disk(c2d) Legacy Survey. We found 43 young stellar object (YSO) candidates in Lupus V and 45 in Lupus VI, including two transition disks, using the standard c2d/GB selection method. None of these sources was classified as a pre-main-sequence star from previous optical, near-IR, and X-ray surveys. A large majority of these YSO candidates appear to be surrounded by thin disks (Class III; ∼79% in Lupus V and ∼87% in Lupus VI). These Class III abundances differ significantly from those observed for the other Lupus clouds and c2d/GB surveyed star-forming regions, where objects with optically thick disks (Class II) dominate the young population. We investigate various scenarios that can explain this discrepancy. In particular, we show that disk photoevaporation due to nearby OB stars is not responsible for the high fraction of Class III objects. The gas surface densities measured for Lupus V and VI lie below the star formation threshold (A V ∼ 8.6 mag), while this is not the case for other Lupus clouds. Thus, few Myr older age for the YSOs in Lupus V and VI with respect to other Lupus clouds is the most likely explanation of the high fraction of Class III objects in these clouds, while a higher characteristic stellar mass might be a contributing factor. Better constraints on the age and binary fraction of the Lupus clouds might solve the puzzle but require further observations.

  2. Importance and challenges of measuring intrinsic foot muscle strength

    Science.gov (United States)

    2012-01-01

    Background Intrinsic foot muscle weakness has been implicated in a range of foot deformities and disorders. However, to establish a relationship between intrinsic muscle weakness and foot pathology, an objective measure of intrinsic muscle strength is needed. The aim of this review was to provide an overview of the anatomy and role of intrinsic foot muscles, implications of intrinsic weakness and evaluate the different methods used to measure intrinsic foot muscle strength. Method Literature was sourced from database searches of MEDLINE, PubMed, SCOPUS, Cochrane Library, PEDro and CINAHL up to June 2012. Results There is no widely accepted method of measuring intrinsic foot muscle strength. Methods to estimate toe flexor muscle strength include the paper grip test, plantar pressure, toe dynamometry, and the intrinsic positive test. Hand-held dynamometry has excellent interrater and intrarater reliability and limits toe curling, which is an action hypothesised to activate extrinsic toe flexor muscles. However, it is unclear whether any method can actually isolate intrinsic muscle strength. Also most methods measure only toe flexor strength and other actions such as toe extension and abduction have not been adequately assessed. Indirect methods to investigate intrinsic muscle structure and performance include CT, ultrasonography, MRI, EMG, and muscle biopsy. Indirect methods often discriminate between intrinsic and extrinsic muscles, but lack the ability to measure muscle force. Conclusions There are many challenges to accurately measure intrinsic muscle strength in isolation. Most studies have measured toe flexor strength as a surrogate measure of intrinsic muscle strength. Hand-held dynamometry appears to be a promising method of estimating intrinsic muscle strength. However, the contribution of extrinsic muscles cannot be excluded from toe flexor strength measurement. Future research should clarify the relative contribution of intrinsic and extrinsic muscles

  3. Positive consequences of intrinsically rewarding work: A model to ...

    African Journals Online (AJOL)

    This study sought to empirically test a theoretical model outlining the relationships between intrinsic rewards, intrinsic motivation, work engagement and intention to quit, in an attempt to empirically assess whether intrinsic rewards result in improved levels of motivation, engagement and retention. Using a sample of 587 ...

  4. The value of nature: Economic, intrinsic, or both?

    Science.gov (United States)

    There has been a long standing argument that ecosystems have intrinsic value and therefore there is no need to put a price tag on Mother Nature. The concept of intrinsic value reflects the perspective that nature has value in its own right, independent of human uses. Intrinsic va...

  5. Personalizing Sample Databases with Facebook Information to Increase Intrinsic Motivation

    Science.gov (United States)

    Marzo, Asier; Ardaiz, Oscar; Sanz de Acedo, María Teresa; Sanz de Acedo, María Luisa

    2017-01-01

    Motivation is fundamental for students to achieve successful and complete learning. Motivation can be extrinsic, i.e., driven by external rewards, or intrinsic, i.e., driven by internal factors. Intrinsic motivation is the most effective and must be inspired by the task at hand. Here, a novel strategy is presented to increase intrinsic motivation…

  6. Intrinsic Motivation: An Overlooked Component for Student Success

    Science.gov (United States)

    Augustyniak, Robert A.; Ables, Adrienne Z.; Guilford, Philip; Lujan, Heidi L.; Cortright, Ronald N.; DiCarlo, Stephen E.

    2016-01-01

    Intrinsic motivation to learn involves engaging in learning opportunities because they are seen as enjoyable, interesting, or relevant to meeting one's core psychological needs. As a result, intrinsic motivation is associated with high levels of effort and task performance. Students with greater levels of intrinsic motivation demonstrate strong…

  7. The Development of Intrinsic Motivation for Physical Activity

    Science.gov (United States)

    2005-07-01

    The Development of Intrinsic Motivation for Physical Activity by James Dunigan Beaty Bachelor of Science Central Washington...2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE The Development of Intrinsic Motivation for Physical Activity 5a. CONTRACT...Government." 3 ABSTRACT The Development of Intrinsic Motivation for Physical Activity by James Dunigan Beaty Cynthia Carruthers, Ph.D

  8. Elements of the Competitive Situation That Affect Intrinsic Motivation.

    Science.gov (United States)

    Reeve, Johnmarshall; Deci, Edward L.

    1996-01-01

    Explores the effects of three elements of the competitive situation (competitive set, competitive outcome, and interpersonal context) on intrinsic motivation in a sample of college students (n=100). Competitive outcome and interpersonal context affected intrinsic motivation: winning increased intrinsic motivation, while pressured interpersonal…

  9. Metacognitive mastery and intrinsic motivation in schizophrenia.

    Science.gov (United States)

    Vohs, Jenifer L; Lysaker, Paul H

    2014-01-01

    Deficits in intrinsic motivation (IM) have been linked to poorer outcome in schizophrenia, but its proximal mechanisms remain poorly understood. This study examined whether metacognitive mastery, or the capacity to use knowledge of self, others, and context to identify and cope with psychological difficulties, predicted levels of IM for 6 months among 75 participants with prolonged schizophrenia. Repeated-measures analysis of variance revealed that high metacognitive mastery predicted consistently higher levels of IM; however, intermediate and low mastery did not produce unique IM profiles. The findings suggest that metacognitive mastery may have an important role in IM over time and could be a meaningful treatment target.

  10. Symplectic Structure of Intrinsic Time Gravity

    Directory of Open Access Journals (Sweden)

    Eyo Eyo Ita

    2016-08-01

    Full Text Available The Poisson structure of intrinsic time gravity is analysed. With the starting point comprising a unimodular three-metric with traceless momentum, a trace-induced anomaly results upon quantization. This leads to a revision of the choice of momentum variable to the (mixed index traceless momentric. This latter choice unitarily implements the fundamental commutation relations, which now take on the form of an affine algebra with SU(3 Lie algebra amongst the momentric variables. The resulting relations unitarily implement tracelessness upon quantization. The associated Poisson brackets and Hamiltonian dynamics are studied.

  11. Intrinsically conductive polymer thin film piezoresistors

    DEFF Research Database (Denmark)

    Lillemose, Michael; Spieser, Martin; Christiansen, N.O.

    2008-01-01

    We report on the piezoresistive effect in the intrinsically conductive polymer, polyaniline. A process recipe for indirect patterning of thin film polyaniline has been developed. Using a specially designed chip, the polyaniline thin films have been characterised with respect to resistivity...... and strain sensitivity using two- and four-point measurement method. We have found that polyaniline has a negative gauge factor of K = -4.9, which makes it a candidate for piezoresistive read-out in polymer based MEMS-devices. (C) 2007 Elsevier B.V. All rights reserved....

  12. Intrinsic chirp of single-cycle pulses

    International Nuclear Information System (INIS)

    Lin Qiang; Zheng Jian; Dai Jianming; Ho, I-Chen; Zhang, X.-C.

    2010-01-01

    The Fourier transform-limited electromagnetic pulse has been regarded to be free of chirps for a long time. This is no longer true if the pulse duration goes down to or less than one optical cycle. We report the experimental observation of intrinsic chirps in such pulses with the sub-single-cycle terahertz (THz) waveforms obtained with a standard THz time-domain spectroscopy system. The results confirm the break down of the carrier-envelope (CE) expression for single-cycle optical pulses, and may influence the experimental measurements and theoretical modeling with single-cycle pulses.

  13. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1α, suppress amyloid β-induced neurotoxicity

    International Nuclear Information System (INIS)

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja; Milatovic, Dejan; Splittgerber, Ryan; Fan, Guo-Huang; Richmond, Ann

    2011-01-01

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-β (Aβ). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1α (SDF-1α), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress Aβ-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1α significantly protected neurons from Aβ-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1α. Intra-cerebroventricular (ICV) injection of Aβ led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The Aβ-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F 2 -isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1α. Additionally, MIP-2 or SDF-1α was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against Aβ neurotoxicity in CXCR2−/− mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: ► Neuroprotective ability of the chemokines MIP2 and CXCL12 against Aβ toxicity. ► MIP-2 or CXCL12 prevented dendritic regression and apoptosis in vitro. ► Neuroprotection through activation of Akt, ERK

  14. Chemokines, macrophage inflammatory protein-2 and stromal cell-derived factor-1{alpha}, suppress amyloid {beta}-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Raman, Dayanidhi; Milatovic, Snjezana-Zaja [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Milatovic, Dejan [Department of Pediatrics/Pediatric Toxicology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Splittgerber, Ryan [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States); Fan, Guo-Huang [Department of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37221 (United States); Richmond, Ann, E-mail: ann.richmond@vanderbilt.edu [VA Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232 (United States)

    2011-11-15

    Alzheimer's disease (AD) is characterized by a progressive cognitive decline and accumulation of neurotoxic oligomeric peptides amyloid-{beta} (A{beta}). Although the molecular events are not entirely known, it has become evident that inflammation, environmental and other risk factors may play a causal, disruptive and/or protective role in the development of AD. The present study investigated the ability of the chemokines, macrophage inflammatory protein-2 (MIP-2) and stromal cell-derived factor-1{alpha} (SDF-1{alpha}), the respective ligands for chemokine receptors CXCR2 and CXCR4, to suppress A{beta}-induced neurotoxicity in vitro and in vivo. Pretreatment with MIP-2 or SDF-1{alpha} significantly protected neurons from A{beta}-induced dendritic regression and apoptosis in vitro through activation of Akt, ERK1/2 and maintenance of metalloproteinase ADAM17 especially with SDF-1{alpha}. Intra-cerebroventricular (ICV) injection of A{beta} led to reduction in dendritic length and spine density of pyramidal neurons in the CA1 area of the hippocampus and increased oxidative damage 24 h following the exposure. The A{beta}-induced morphometric changes of neurons and increase in biomarkers of oxidative damage, F{sub 2}-isoprostanes, were significantly inhibited by pretreatment with the chemokines MIP-2 or SDF-1{alpha}. Additionally, MIP-2 or SDF-1{alpha} was able to suppress the aberrant mislocalization of p21-activated kinase (PAK), one of the proteins involved in the maintenance of dendritic spines. Furthermore, MIP-2 also protected neurons against A{beta} neurotoxicity in CXCR2-/- mice, potentially through observed up regulation of CXCR1 mRNA. Understanding the neuroprotective potential of chemokines is crucial in defining the role for their employment during the early stages of neurodegeneration. -- Research highlights: Black-Right-Pointing-Pointer Neuroprotective ability of the chemokines MIP2 and CXCL12 against A{beta} toxicity. Black-Right-Pointing-Pointer MIP

  15. Intrinsic regulation of enteroendocrine fate by Numb.

    Science.gov (United States)

    Sallé, Jérémy; Gervais, Louis; Boumard, Benjamin; Stefanutti, Marine; Siudeja, Katarzyna; Bardin, Allison J

    2017-07-03

    How terminal cell fates are specified in dynamically renewing adult tissues is not well understood. Here we explore terminal cell fate establishment during homeostasis using the enteroendocrine cells (EEs) of the adult Drosophila midgut as a paradigm. Our data argue against the existence of local feedback signals, and we identify Numb as an intrinsic regulator of EE fate. Our data further indicate that Numb, with alpha-adaptin, acts upstream or in parallel of known regulators of EE fate to limit Notch signaling, thereby facilitating EE fate acquisition. We find that Numb is regulated in part through its asymmetric and symmetric distribution during stem cell divisions; however, its de novo synthesis is also required during the differentiation of the EE cell. Thus, this work identifies Numb as a crucial factor for cell fate choice in the adult Drosophila intestine. Furthermore, our findings demonstrate that cell-intrinsic control mechanisms of terminal cell fate acquisition can result in a balanced tissue-wide production of terminally differentiated cell types. © 2017 The Authors.

  16. Intrinsic position uncertainty impairs overt search performance.

    Science.gov (United States)

    Semizer, Yelda; Michel, Melchi M

    2017-08-01

    Uncertainty regarding the position of the search target is a fundamental component of visual search. However, due to perceptual limitations of the human visual system, this uncertainty can arise from intrinsic, as well as extrinsic, sources. The current study sought to characterize the role of intrinsic position uncertainty (IPU) in overt visual search and to determine whether it significantly limits human search performance. After completing a preliminary detection experiment to characterize sensitivity as a function of visual field position, observers completed a search task that required localizing a Gabor target within a field of synthetic luminance noise. The search experiment included two clutter conditions designed to modulate the effect of IPU across search displays of varying set size. In the Cluttered condition, the display was tiled uniformly with feature clutter to maximize the effects of IPU. In the Uncluttered condition, the clutter at irrelevant locations was removed to attenuate the effects of IPU. Finally, we derived an IPU-constrained ideal searcher model, limited by the IPU measured in human observers. Ideal searchers were simulated based on the detection sensitivity and fixation sequences measured for individual human observers. The IPU-constrained ideal searcher predicted performance trends similar to those exhibited by the human observers. In the Uncluttered condition, performance decreased steeply as a function of increasing set size. However, in the Cluttered condition, the effect of IPU dominated and performance was approximately constant as a function of set size. Our findings suggest that IPU substantially limits overt search performance, especially in crowded displays.

  17. Intrinsic terminators in Mycoplasma hyopneumoniae transcription.

    Science.gov (United States)

    Fritsch, Tiago Ebert; Siqueira, Franciele Maboni; Schrank, Irene Silveira

    2015-04-08

    Mycoplasma hyopneumoniae, an important pathogen of swine, exhibits a low guanine and cytosine (GC) content genome. M. hyopneumoniae genome is organised in long transcriptional units and promoter sequences have been mapped upstream of all transcription units. These analysis provided insights into the gene organisation and transcription initiation at the genome scale. However, the presence of transcriptional terminator sequences in the M. hyopneumoniae genome is poorly understood. In silico analyses demonstrated the presence of putative terminators in 82% of the 33 monocistronic units (mCs) and in 74% of the 116 polycistronic units (pCs) considering different classes of terminators. The functional activity of 23 intrinsic terminators was confirmed by RT-PCR and qPCR. Analysis of all terminators found by three software algorithms, combined with experimental results, allowed us to propose a pattern of RNA hairpin formation during the termination process and to predict the location of terminators in the M. hyopneumoniae genome sequence. The stem-loop structures of intrinsic terminators of mycoplasma diverge from the pattern of terminators found in other bacteria due the low content of guanine and cytosine. In M. hyopneumoniae, transcription can end after a transcriptional unit and before its terminator sequence and can also continue past the terminator sequence with RNA polymerases gradually releasing the RNA.

  18. Intrinsically secure fast reactors with dense cores

    International Nuclear Information System (INIS)

    Slessarev, Igor

    2007-01-01

    Secure safety, resistance to weapons material proliferation and problems of long-lived wastes remain the most important 'painful points' of nuclear power. Many innovative reactor concepts have been developed aimed at a radical enhancement of safety. The promising potential of innovative nuclear reactors allows for shifting accents in current reactor safety 'strategy' to reveal this worth. Such strategy is elaborated focusing on the priority for intrinsically secure safety features as well as on sure protection being provided by the first barrier of defence. Concerning the potential of fast reactors (i.e. sodium cooled, lead-cooled, etc.), there are no doubts that they are able to possess many favourable intrinsically secure safety features and to lay the proper foundation for a new reactor generation. However, some of their neutronic characteristics have to be radically improved. Among intrinsically secure safety properties, the following core parameters are significantly important: reactivity margin values, reactivity feed-back and coolant void effects. Ways of designing intrinsically secure safety features in fast reactors (titled hereafter as Intrinsically Secure Fast Reactors - ISFR) can be found in the frame of current reactor technologies by radical enhancement of core neutron economy and by optimization of core compositions. Simultaneously, respecting resistance to proliferation, by using non-enriched fuel feed as well as a core breeding gain close to zero, are considered as the important features (long-lived waste problems will be considered in a separate paper). This implies using the following reactor design options as well as closed fuel cycles with natural U as the reactor feed: ·Ultra-plate 'dense cores' of the ordinary (monolithic) type with negative total coolant void effects. ·Modular type cores. Multiple dense modules can be embedded in the common reflector for achieving the desired NPP total power. The modules can be used also independently (as

  19. The Neuroscience of Growth Mindset and Intrinsic Motivation.

    Science.gov (United States)

    Ng, Betsy

    2018-01-26

    Our actions can be triggered by intentions, incentives or intrinsic values. Recent neuroscientific research has yielded some results about the growth mindset and intrinsic motivation. With the advances in neuroscience and motivational studies, there is a global need to utilize this information to inform educational practice and research. Yet, little is known about the neuroscientific interplay between growth mindset and intrinsic motivation. This paper attempts to draw on the theories of growth mindset and intrinsic motivation, together with contemporary ideas in neuroscience, outline the potential for neuroscientific research in education. It aims to shed light on the relationship between growth mindset and intrinsic motivation in terms of supporting a growth mindset to facilitate intrinsic motivation through neural responses. Recent empirical research from the educational neuroscience perspective that provides insights into the interplay between growth mindset and intrinsic motivation will also be discussed.

  20. Enzyme activation through the utilization of intrinsic dianion binding energy.

    Science.gov (United States)

    Amyes, T L; Malabanan, M M; Zhai, X; Reyes, A C; Richard, J P

    2017-03-01

    We consider 'the proposition that the intrinsic binding energy that results from the noncovalent interaction of a specific substrate with the active site of the enzyme is considerably larger than is generally believed. An important part of this binding energy may be utilized to provide the driving force for catalysis, so that the observed binding energy represents only what is left over after this utilization' [Jencks,W.P. (1975) Adv. Enzymol. Relat. Areas. Mol. Biol. , , 219-410]. The large ~12 kcal/mol intrinsic substrate phosphodianion binding energy for reactions catalyzed by triosephosphate isomerase (TIM), orotidine 5'-monophosphate decarboxylase and glycerol-3-phosphate dehydrogenase is divided into 4-6 kcal/mol binding energy that is expressed on the formation of the Michaelis complex in anchoring substrates to the respective enzyme, and 6-8 kcal/mol binding energy that is specifically expressed at the transition state in activating the respective enzymes for catalysis. A structure-based mechanism is described where the dianion binding energy drives a conformational change that activates these enzymes for catalysis. Phosphite dianion plays the active role of holding TIM in a high-energy closed active form, but acts as passive spectator in showing no effect on transition-state structure. The result of studies on mutant enzymes is presented, which support the proposal that the dianion-driven enzyme conformational change plays a role in enhancing the basicity of side chain of E167, the catalytic base, by clamping the base between a pair of hydrophobic side chains. The insight these results provide into the architecture of enzyme active sites and the development of strategies for the de novo design of protein catalysts is discussed.

  1. Stratospheric Ozone Response in Experiments G3 and G4 of the Geoengineering Model Intercomparison Project (GeoMIP)

    Science.gov (United States)

    Pitari, Giovanni; Aquila, Valentina; Kravitz, Ben; Watanabe, Shingo; Tilmes, Simone; Mancini, Eva; DeLuca, Natalia; DiGenova, Glauco

    2013-01-01

    Geoengineering with stratospheric sulfate aerosols has been proposed as a means of temporarily cooling the planet, alleviating some of the side effects of anthropogenic CO2 emissions. However, one of the known side effects of stratospheric injections of sulfate aerosols is a decrease in stratospheric ozone. Here we show results from two general circulation models and two coupled chemistry climate models that have simulated stratospheric sulfate aerosol geoengineering as part of the Geoengineering Model Intercomparison Project (GeoMIP). Changes in photolysis rates and upwelling of ozone-poor air in the tropics reduce stratospheric ozone, suppression of the NOx cycle increases stratospheric ozone, and an increase in available surfaces for heterogeneous chemistry modulates reductions in ozone. On average, the models show a factor 20-40 increase of the sulfate aerosol surface area density (SAD) at 50 hPa in the tropics with respect to unperturbed background conditions and a factor 3-10 increase at mid-high latitudes. The net effect for a tropical injection rate of 5 Tg SO2 per year is a decrease in globally averaged ozone by 1.1-2.1 DU in the years 2040-2050 for three models which include heterogeneous chemistry on the sulfate aerosol surfaces. GISS-E2-R, a fully coupled general circulation model, performed simulations with no heterogeneous chemistry and a smaller aerosol size; it showed a decrease in ozone by 9.7 DU. After the year 2050, suppression of the NOx cycle becomes more important than destruction of ozone by ClOx, causing an increase in total stratospheric ozone. Contribution of ozone changes in this experiment to radiative forcing is 0.23 W m-2 in GISS-E2-R and less than 0.1 W m-2 in the other three models. Polar ozone depletion, due to enhanced formation of both sulfate aerosol SAD and polar stratospheric clouds, results in an average 5 percent increase in calculated surface UV-B.

  2. Solar radiation management impacts on agriculture in China: A case study in the Geoengineering Model Intercomparison Project (GeoMIP)

    Science.gov (United States)

    Xia, Lili; Robock, Alan; Cole, Jason; Curry, Charles L.; Ji, Duoying; Jones, Andy; Kravitz, Ben; Moore, John C.; Muri, Helene; Niemeier, Ulrike; Singh, Balwinder; Tilmes, Simone; Watanabe, Shingo; Yoon, Jin-Ho

    2014-07-01

    Geoengineering via solar radiation management could affect agricultural productivity due to changes in temperature, precipitation, and solar radiation. To study rice and maize production changes in China, we used results from 10 climate models participating in the Geoengineering Model Intercomparison Project (GeoMIP) G2 scenario to force the Decision Support System for Agrotechnology Transfer (DSSAT) crop model. G2 prescribes an insolation reduction to balance a 1% a-1 increase in CO2 concentration (1pctCO2) for 50 years. We first evaluated the DSSAT model using 30 years (1978-2007) of daily observed weather records and agriculture practices for 25 major agriculture provinces in China and compared the results to observations of yield. We then created three sets of climate forcing for 42 locations in China for DSSAT from each climate model experiment: (1) 1pctCO2, (2) G2, and (3) G2 with constant CO2 concentration (409 ppm) and compared the resulting agricultural responses. In the DSSAT simulations: (1) Without changing management practices, the combined effect of simulated climate changes due to geoengineering and CO2 fertilization during the last 15 years of solar reduction would change rice production in China by -3.0 ± 4.0 megaton (Mt) (2.4 ± 4.0%) as compared with 1pctCO2 and increase Chinese maize production by 18.1 ± 6.0 Mt (13.9 ± 5.9%). (2) The termination of geoengineering shows negligible impacts on rice production but a 19.6 Mt (11.9%) reduction of maize production as compared to the last 15 years of geoengineering. (3) The CO2 fertilization effect compensates for the deleterious impacts of changes in temperature, precipitation, and solar radiation due to geoengineering on rice production, increasing rice production by 8.6 Mt. The elevated CO2 concentration enhances maize production in G2, contributing 7.7 Mt (42.4%) to the total increase. Using the DSSAT crop model, virtually all of the climate models agree on the sign of the responses, even though

  3. Digested disorder, Quarterly intrinsic disorder digest (October-November-December, 2013).

    Science.gov (United States)

    DeForte, Shelly; Reddy, Krishna D; Uversky, Vladimir N

    2015-01-01

    This is the 4th issue of the Digested Disorder series that represents reader's digest of the scientific literature on intrinsically disordered proteins. The only 2 criteria for inclusion in this digest are the publication date (a paper should be published within the covered time frame) and topic (a paper should be dedicated to any aspect of protein intrinsic disorder). The current digest issue covers papers published during the fourth quarter of 2013; i.e. during the period of October, November, and December of 2013. Similar to previous issues, the papers are grouped hierarchically by topics they cover, and for each of the included paper a short description is given on its major findings.

  4. Quantum synchronization effects in intrinsic Josephson junctions

    International Nuclear Information System (INIS)

    Machida, M.; Kano, T.; Yamada, S.; Okumura, M.; Imamura, T.; Koyama, T.

    2008-01-01

    We investigate quantum dynamics of the superconducting phase in intrinsic Josephson junctions of layered high-T c superconductors motivated by a recent experimental observation for the switching rate enhancement in the low temperature quantum regime. We pay attention to only the capacitive coupling between neighboring junctions and perform large-scale simulations for the Schroedinger equation derived from the Hamiltonian considering the capacitive coupling alone. The simulation focuses on an issue whether the switching of a junction induces those of the other junctions or not. The results reveal that the superconducting phase dynamics show synchronous behavior with increasing the quantum character, e.g., decreasing the junction plane area and effectively the temperature. This is qualitatively consistent with the experimental result

  5. Intrinsic thermal expansion of crystal defects

    International Nuclear Information System (INIS)

    Ganne, J.-P.

    1981-02-01

    Although the phenomenon of thermal expansion has long been known, the intrinsic thermal expansion coefficient (ITEC) βsub(d) of a point defect, derived from its formation volume vsub(d), has never been measured directly. The differential dilatometer by interferometry built by ASTY and GILDER is described. It has allowed βsub(d) to be measured for several defects. Vacancies and small interstitial loops were produced in aluminium by low temperature (20 K) fast neutron irradiation followed by an anneal up to the beginning of stage III (160 K). The very high value of the measured ratio βsub(d)/β 0 (12+-4) is comparable with a lattice statics calculated (42) value (11.5 0 [fr

  6. Intrinsic topological superfluidity - fluctuations and response

    Science.gov (United States)

    Levin, K.; Wu, Chien-Te; Anderson, Brandon; Boyack, Rufus

    Recent interest in topological superconductivity is based primarily on exploiting proximity effects to obtain this important phase. However, in cold gases it is possible to contemplate ``intrinsic'' topological superfluidity produced with a synthetic spin-orbit coupling and Zeeman field. It is important for such future experiments to establish how low in temperature one needs to go to reach the ordered phase. Similarly, it will be helpful to have a probe of the normal (pseudogap) phase to determine if the ultimate superfluid order will be topological or trivial. In this talk, we address these issues by considering fluctuation effects in such a superfluid, and calculate the critical transition temperature and response functions. We see qualitative signatures of topological superfluidity in spin and charge response functions. We also explore the suppression of superfluidity due to fluctuations, and importantly find that the temperature scales necessary to reach topological superfluidity are reasonably accessible

  7. Intrinsic densitometry: In-plant evaluation

    International Nuclear Information System (INIS)

    Nishida, K.; Kurosawa, A.; Masui, J.; Hsue, S.T.

    1994-11-01

    A measurement of the plutonium concentration in a sample is always necessary for nuclear material control and accounting. This report describes the testing of the intrinsic densitometry (ID) technique for implant applications. The authors found that the ID method can determine the plutonium concentrations to between 2 and 3% at concentrations of 100 g/l to 200 g/l with quartz cells and a measurement time of 3600 s. The precision can be improved to 1 to 2% with a higher counting rate. The authors also found that nitric acid concentration and the impurity level of uranium in the product plutonium solution do not affect the concentration measurement. When this technique is applied to plutonium solutions in stainless steel pipes, they found that similar precision in plutonium concentration can be achieved using a high-count-rate detector. The precision, however, is reduced with aged plutonium solutions

  8. On the intrinsic colours of cepheids

    International Nuclear Information System (INIS)

    Efremov, Yu.N.

    1979-01-01

    Some consequences from new data on the photometrically obtained intrinsic colours are considered. It is shown that the small amplitude and almost sinusoidal light-curve cepheids (Cs-subtype) increase their pulsation amplitude towards the red instability strip edge, differing from the other galactic cepheids. This feature is discussed in connection with Efremov's (1968) hypothesis that the Cs-cepheids first cross the instability strip from left to right. The galactic cepheid period-colour relation obtained by Dean, Warren and Cousins (1978) satisfies rather well the LMC cepheid observations and, consequently, considerations for the period-luminosity relations are made. The residuals from the PL relation proposed by us correlate with the colour residuals from the DWC period-colour relation ΔV/delta(B-V) being equal to 2.7. The luminosity effect as a possible cause of the discrepancy between the spectroscopic cepheid colours and the photometric colours is briefly discussed. (Auth.)

  9. Intrinsic Dynamics of Quantum-Dash Lasers

    KAUST Repository

    Chen, Cheng

    2011-10-01

    Temperature-dependent intrinsic modulation response of InAs/InAlGaAs quantum-dash lasers was investigated by using pulse optical injection modulation to minimize the effects of parasitics and self-heating. Compared to typical quantum-well lasers, the quantum-dash lasers were found to have comparable differential gain but approximately twice the gain compression factor, probably due to carrier heating by free-carrier absorption, as opposed to stimulated transition. Therefore, the narrower modulation bandwidth of the quantum-dash lasers than that of quantum-well lasers was attributed to their higher gain compression factor. In addition, as expected, quantum-dash lasers with relatively long and uniform dashes exhibit higher temperature stability than quantum-well lasers. However, the lasers with relatively short and nonuniform dashes exhibit stronger temperature dependence, probably due to their higher surface-to-volume ratio and nonuniform dash sizes. © 2011 IEEE.

  10. Intrinsic thermoelectric power of group VB metals

    Directory of Open Access Journals (Sweden)

    Gunadhor Singh Okram

    2012-03-01

    Full Text Available We have reinvestigated the thermopower of group VB metals in polycrystalline forms in the temperature range of 6-300K, taking into account the critical nature of the sample surface and heat treatment especially for niobium. Strikingly small magnitude, negative sign, phonon drag dip and superconductivity not reported previously were observed in surface-cleaned single crystalline Nb. However, while thermopower magnitudes are small, mixed signs were found in the polycrystalline V, Nb and Ta samples. These properties were therefore interpreted as their intrinsic properties and were briefly discussed taking into account of the existing theory by fitting also the data that give the Fermi energies of 10.94 eV, 5.08 eV and 1.86eV, respectively.

  11. Intrinsic Ambipolarity and Rotation in Stellarators

    International Nuclear Information System (INIS)

    Helander, P.; Simakov, A. N.

    2008-01-01

    It is shown that collisional plasma transport is intrinsically ambipolar only in quasiaxisymmetric or quasihelically symmetric magnetic configurations. Only in such fields can the plasma rotate freely, and then only in the direction of quasisymmetry. In a non-quasi-symmetric magnetic field, the average radial electric field is determined by parallel viscosity, which in turn is usually governed by collisional processes. Locally, the radial electric field may be affected by turbulent Reynolds stress producing zonal flows, but on a radial average taken over several ion gyroradii, it is determined by parallel viscosity, at least if the turbulence is electrostatic and obeys the conventional gyrokinetic orderings. This differs from the situation in a tokamak, where there is no flow damping by parallel viscosity in the symmetry direction and the turbulent Reynolds stress may affect the global radial electric field

  12. IMPACT OF BARYONIC PHYSICS ON INTRINSIC ALIGNMENTS

    Energy Technology Data Exchange (ETDEWEB)

    Tenneti, Ananth; Gnedin, Nickolay Y. [Particle Astrophysics Center, Fermi National Accelerator Laboratory, Batavia, IL 60510 (United States); Feng, Yu, E-mail: vat@andrew.cmu.edu [Berkeley Center for Cosmological Physics, Department of Physics, University of California Berkeley, Berkeley, CA 94720 (United States)

    2017-01-10

    We explore the effects of specific assumptions in the subgrid models of star formation and stellar and active galactic nucleus feedback on intrinsic alignments of galaxies in cosmological simulations of the “MassiveBlack-II” family. Using smaller-volume simulations, we explore the parameter space of the subgrid star formation and feedback model and find remarkable robustness of the observable statistical measures to the details of subgrid physics. The one observational probe most sensitive to modeling details is the distribution of misalignment angles. We hypothesize that the amount of angular momentum carried away by the galactic wind is the primary physical quantity that controls the orientation of the stellar distribution. Our results are also consistent with a similar study by the EAGLE simulation team.

  13. Simultaneous modulation of the intrinsic and extrinsic pathways by simvastatin in mediating prostate cancer cell apoptosis

    International Nuclear Information System (INIS)

    Goc, Anna; Kochuparambil, Samith T; Al-Husein, Belal; Al-Azayzih, Ahmad; Mohammad, Shuaib; Somanath, Payaningal R

    2012-01-01

    Recent studies suggest the potential benefits of statins as anti-cancer agents. Mechanisms by which statins induce apoptosis in cancer cells are not clear. We previously showed that simvastatin inhibit prostate cancer cell functions and tumor growth. Molecular mechanisms by which simvastatin induce apoptosis in prostate cancer cells is not completely understood. Effect of simvastatin on PC3 cell apoptosis was compared with docetaxel using apoptosis, TUNEL and trypan blue viability assays. Protein expression of major candidates of the intrinsic pathway downstream of simvastatin-mediated Akt inactivation was analyzed. Gene arrays and western analysis of PC3 cells and tumor lysates were performed to identify the candidate genes mediating extrinsic apoptosis pathway by simvastatin. Data indicated that simvastatin inhibited intrinsic cell survival pathway in PC3 cells by enhancing phosphorylation of Bad, reducing the protein expression of Bcl-2, Bcl-xL and cleaved caspases 9/3. Over-expression of PC3 cells with Bcl-2 or DN-caspase 9 did not rescue the simvastatin-induced apoptosis. Simvastatin treatment resulted in increased mRNA and protein expression of molecules such as TNF, Fas-L, Traf1 and cleaved caspase 8, major mediators of intrinsic apoptosis pathway and reduced protein levels of pro-survival genes Lhx4 and Nme5. Our study provides the first report that simvastatin simultaneously modulates intrinsic and extrinsic pathways in the regulation of prostate cancer cell apoptosis in vitro and in vivo, and render reasonable optimism that statins could become an attractive anti-cancer agent

  14. Synthesis of size-tuneable CO2-philic imprinted polymeric particles (MIPs) for low-pressure CO2 capture using oil-in-oil suspension polymerisation

    OpenAIRE

    Nabavi, Seyed Ali; Vladisavljevic, Goran T.; Zhu, Yidi; Manovic, Vasilije

    2017-01-01

    Highly selective molecularly imprinted poly[ acrylamide-co-(ethylene glycol dimethacrylate)] polymer particles (MIPs) for CO2 capture were synthesized by suspension polymerization via oil-in-oil emulsion. Creation of CO2-philic, amide-decorated cavities in the polymer matrix led to a high affinity to CO2. At 0.15 bar CO2 partial pressure, the CO2/N2 selectivity was 49 (corresponding to 91% purity of the gas stream after regeneration), and reached 97 at ultralow CO2 parti...

  15. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

    Directory of Open Access Journals (Sweden)

    Mirna Perusina Lanfranca

    2014-05-01

    Full Text Available The herpes simplex virus type 1 (HSV-1 encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0, is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10, SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate regulatory mediators that include IFI16 (IFN γ-inducible protein 16, MyD88 (myeloid differentiation factor 88, and Mal (MyD88 adaptor-like protein. We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7 and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.

  16. Preparation and rebinding properties of protein-imprinted polysiloxane using mesoporous calcium silicate grafted non-woven polypropylene as matrix.

    Science.gov (United States)

    Kan, Bohong; Feng, Lingzhi; Zhao, Kongyin; Wei, Junfu; Zhu, Dunwan; Zhang, Linhua; Ren, Qian

    2016-03-01

    Calcium silicate particle containing mesoporous SiO2 (CaSiO3@SiO2) was grafted on the surface of non-woven polypropylene. The PP non-woven grafted calcium silicate containing mesoporous SiO2 (PP-g-CaSiO3@SiO2) was used as the matrix to prepare bovine serum albumin (BSA) molecularly imprinted polysiloxane (MIP) by using silanes as the functional monomers and BSA as the template. PP non-woven grafted BSA-imprinted polysiloxane (PP-g-CaSiO3@SiO2 MIP) was characterized by scanning electron microscope (SEM), Fourier transform infrared spectometry (FTIR) and drilling string compensator (DSC). Influence factors on the rebinding capacity of the MIP were investigated, such as grafting degree, the pH in treating CaSiO3 and the type and proportion of silanes. The rebinding properties of BSA on PP-g-CaSiO3@SiO2 and MIP were investigated under different conditions. The results indicated that the rebinding capacity of MIP for BSA reached 56.32 mg/g, which was 2.65 times of NIP. The non-woven polypropylene grafted BSA-imprinted polysiloxane could recognize the template protein and the selectivity factor (β) was above 2.4 when using ovalbumin, hemoglobin and γ-globulin as control proteins. The PP-g-CaSiO3@SiO2 MIP has favorable reusability. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Personality traits associated with intrinsic academic motivation in medical students.

    Science.gov (United States)

    Tanaka, Masaaki; Mizuno, Kei; Fukuda, Sanae; Tajima, Seiki; Watanabe, Yasuyoshi

    2009-04-01

    Motivation is one of the most important psychological concepts in education and is related to academic outcomes in medical students. In this study, the relationships between personality traits and intrinsic academic motivation were examined in medical students. The study group consisted of 119 Year 2 medical students at Osaka City University Graduate School of Medicine. They completed questionnaires dealing with intrinsic academic motivation (the Intrinsic Motivation Scale toward Learning) and personality (the Temperament and Character Inventory [TCI]). On simple regression analyses, the TCI dimensions of persistence, self-directedness, co-operativeness and self-transcendence were positively associated with intrinsic academic motivation. On multiple regression analysis adjusted for age and gender, the TCI dimensions of persistence, self-directedness and self-transcendence were positively associated with intrinsic academic motivation. The temperament dimension of persistence and the character dimensions of self-directedness and self-transcendence are associated with intrinsic academic motivation in medical students.

  18. Sources of intrinsic rotation in the low-flow ordering

    International Nuclear Information System (INIS)

    Parra, Felix I.; Barnes, Michael; Catto, Peter J.

    2011-01-01

    A low flow, δf gyrokinetic formulation to obtain the intrinsic rotation profiles is presented. The momentum conservation equation in the low-flow ordering contains new terms, neglected in previous first-principles formulations, that may explain the intrinsic rotation observed in tokamaks in the absence of external sources of momentum. The intrinsic rotation profile depends on the density and temperature profiles and on the up-down asymmetry.

  19. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

    2014-01-01

    and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  20. The effects of extrinsic rewards on children's intrinsic motivation

    OpenAIRE

    大槻, 千秋

    1981-01-01

    An experiment was conducted with preschool children to test whether a person's intrinsic motivation in an activity may be decreased by extrinsic salient rewards in Japan like in America. Children solved some jigsaw puzzles and received assorted candies, then they were observed how long they did other jigsaw puzzles. The results showed that the effects of extrinsic rewards on intrinsic motivation in an activity varied with the subject's social background. In uptown children's intrinsic motivat...