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Sample records for tolerating misfolded membrane

  1. Physico-Pathologic Mechanisms Involved in Neurodegeneration: Misfolded Protein-Plasma Membrane Interactions.

    Science.gov (United States)

    Shrivastava, Amulya Nidhi; Aperia, Anita; Melki, Ronald; Triller, Antoine

    2017-07-05

    Several neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by prominent loss of synapses and neurons associated with the presence of abnormally structured or misfolded protein assemblies. Cell-to-cell transfer of misfolded proteins has been proposed for the intra-cerebral propagation of these diseases. When released, misfolded proteins diffuse in the 3D extracellular space before binding to the plasma membrane of neighboring cells, where they diffuse on a 2D plane. This reduction in diffusion dimension and the cell surface molecular crowding promote deleterious interactions with native membrane proteins, favoring clustering and further aggregation of misfolded protein assemblies. These processes open up new avenues for therapeutics development targeting the initial interactions of deleterious proteins with the plasma membrane or the subsequent pathological signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Chaperonins fight aminoglycoside-induced protein misfolding and promote short-term tolerance in Escherichia coli

    DEFF Research Database (Denmark)

    Goltermann, Lise; Good, Liam; Bentin, Thomas

    2013-01-01

    For almost half of a century, we have known that aminoglycoside antibiotics corrupt ribosomes, causing translational misreading, yet it remains unclear whether or not misreading triggers protein misfolding, and possible effects of chaperone action on drug susceptibilities are poorly understood...

  3. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.

    Directory of Open Access Journals (Sweden)

    Louise Madsen

    Full Text Available The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded secretory proteins via the ER-associated degradation pathway. This functional diversity of p97 depends on its association with various cofactors, and to further our understanding of p97 function it is important that these cofactors are identified and analyzed. Here, we isolate and characterize the human protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8 is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation.

  4. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins

    DEFF Research Database (Denmark)

    Madsen, Louise; Kriegenburg, Franziska; Lages Lino Vala, Andrea

    2011-01-01

    is a transmembrane protein that localizes to the ER membrane with its UBX domain facing the cytoplasm. Knock-down of Rep8 expression in human cells leads to a decreased association of p97 with the ER membrane and concomitantly a retarded degradation of misfolded ER-derived proteasome substrates. Thus, Rep8 tethers p......The protein known as p97 or VCP in mammals and Cdc48 in yeast is a versatile ATPase complex involved in several biological functions including membrane fusion, protein folding, and activation of membrane-bound transcription factors. In addition, p97 plays a central role in degradation of misfolded...... protein named Rep8 or Ubxd6 as a new cofactor of p97. Mouse Rep8 is highly tissue-specific and abundant in gonads. In testes, Rep8 is expressed in post-meiotic round spermatids, whereas in ovaries Rep8 is expressed in granulosa cells. Rep8 associates directly with p97 via its UBX domain. We show that Rep8...

  5. Plant plasma membrane proteomics for improving cold tolerance

    Directory of Open Access Journals (Sweden)

    Daisuke eTakahashi

    2013-04-01

    Full Text Available Plants are always exposed to various stresses. We have focused on freezing stress, which causes serious problems for agricultural management. When plants suffer freeze-induced damage, the plasma membrane is thought to be the primary site of injury because of its central role in regulation of various cellular processes. Cold tolerant species, however, adapt to such freezing conditions by modifying cellular components and functions (cold acclimation. One of the most important adaptation mechanisms to freezing is alteration of plasma membrane compositions and functions. Advanced proteomic technologies have succeeded in identification of many candidates that may play roles in adaptation of the plasma membrane to freezing stress. Proteomics results suggest that adaptations of plasma membrane functions to low temperature are associated with alterations of protein compositions during cold acclimation. Some of proteins identified by proteomic approaches have been verified their functional roles in freezing tolerance mechanisms further. Thus, accumulation of proteomic results in the plasma membrane is of importance for application to molecular breeding efforts to increase cold tolerance in crops.

  6. Facile preparation of salt-tolerant anion-exchange membrane adsorber using hydrophobic membrane as substrate.

    Science.gov (United States)

    Fan, Jinxin; Luo, Jianquan; Chen, Xiangrong; Wan, Yinhua

    2017-03-24

    In this study, a polyvinylidene fluoride (PVDF) hydrophobic membrane with high mechanical property was used as substrate to prepare salt-tolerant anion-exchange (STAE) membrane adsorber. Effective hydrophilization and functionalization of PVDF membrane was realized via polydopamine (PDA) deposition, thus overcoming the drawbacks of hydrophobic substrates including poor water permeability, inert property as well as severe non-specific adsorption. The following polyallylamine (PAH) coupling was carried out at pH 10.0, where unprotonated amine groups on PAH chains were more prone to couple with PDA. This membrane adsorber could remain 75% of protein binding capacity when NaCl concentration increased from 0 to 150mM, while its protein binding capacity was independent of flow rate from 10 to 100 membrane volume (MV)/min due to its high mechanical strength (tensile strength: 43.58±2.30MPa). With 200mM NaCl addition at pH 7.5, high purity (above 99%) and high recovery (almost 100%) of Immunoglobulin G (IgG) were obtained when using the STAE membrane adsorber to separate IgG/human serum albumin (HSA) mixture, being similar to that without NaCl at pH 6.0 (both under the flow rate of 10-100MV/min). Finally, the reliable reusability was confirmed by five reuse cycles of protein binding and elution operations. In comparison with commercial membrane adsorber, the new membrane adsorber exhibited a better mechanical property, higher IgG polishing efficiency and reusability, while the protein binding capacity was lower due to less NH 2 density on the membrane. The outcome of this work not only offers a facile and effective approach to prepare membrane adsorbers based on hydrophobic membranes, but also demonstrates great potential of this new designed STAE membrane adsorbers for efficient monoclonal antibody (mAb) polishing. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Protein Misfolding and Human Disease

    DEFF Research Database (Denmark)

    Gregersen, Niels; Bross, Peter Gerd; Vang, Søren

    2006-01-01

    phenylketonuria, Parkinson's disease, α-1-antitrypsin deficiency, familial neurohypophyseal diabetes insipidus, and short-chain acyl-CoA dehydrogenase deficiency. Despite the differences, an emerging paradigm suggests that the cellular effects of protein misfolding provide a common framework that may contribute...

  8. Semiotic Selection of Mutated or Misfolded Receptor Proteins

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio; Maggio, Roberto

    2013-01-01

    contention that the plasma membrane acts as the locus where several contextual cues may be integrated. As such it allows the semiotic selection of those receptor configurations that provide cells with the minimum essential requirements for agency. The occurrence of protein misfolding makes it impossible...... focused on the significance and semiotic nature of the interplay between membrane receptors and the epigenetic control of gene expression, as mediated by the control of mismatched repairing and protein folding mechanisms....

  9. Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance.

    Science.gov (United States)

    Guia, Sophie; Jaeger, Baptiste N; Piatek, Stefan; Mailfert, Sébastien; Trombik, Tomasz; Fenis, Aurore; Chevrier, Nicolas; Walzer, Thierry; Kerdiles, Yann M; Marguet, Didier; Vivier, Eric; Ugolini, Sophie

    2011-04-05

    Natural killer (NK) cell tolerance to self is partly ensured by major histocompatibility complex (MHC) class I-specific inhibitory receptors on NK cells, which dampen their reactivity when engaged. However, NK cells that do not detect self MHC class I are not autoreactive. We used dynamic fluorescence correlation spectroscopy to show that MHC class I-independent NK cell tolerance in mice was associated with the presence of hyporesponsive NK cells in which both activating and inhibitory receptors were confined in an actin meshwork at the plasma membrane. In contrast, the recognition of self MHC class I by inhibitory receptors "educated" NK cells to become fully reactive, and activating NK cell receptors became dynamically compartmentalized in membrane nanodomains. We propose that the confinement of activating receptors at the plasma membrane is pivotal to ensuring the self-tolerance of NK cells.

  10. Plasma membrane and salinity tolerance of barley plants

    International Nuclear Information System (INIS)

    Al-Rahmani, F. H.; Al-Mashhadani, M. S.; Al-Delemee, N. H.

    1997-01-01

    Barley cultivar, California Mario ut, was grown in a nutrient solution containing increasing Nacl concentrations up to 250 mm. The effect of Nacl on growth, mineral compost ion ant integrity of the plasma membrane was studied. Growth of the shoot'and root was stimulated or little affected by 10 and 20 ml Nacl. Further increase in Nacl concentrations depressed the growth. The depression was conspicuous between 100 and 250 mm Nacl. Increasing Nacl concentration decreased potassium content in the shoots and roots and led to steep increase in sodium accumulation. The integrity of the plasma membrane was measured in term of potassium leakage from the root tips. Rapid leakage of potassium was obtained at Nacl concentrations ranging from 100 to 250 mm. At the same concentrations of Nacl, adenosine triphosphatase activity in the root tips was increased. Results indicate that the plasma membrane of root cells was damaged by the increased levels of salinity. It was concluded that the plasma membrane of root cells is the primary site of salinity toxicity. (authors). 40 refs., 5 tabs. 3 figs

  11. Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

    Science.gov (United States)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah; Abdelhameed, Ali Saber; Khan, Rizwan Hasan

    2016-11-01

    In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially misfolded intermediates aggregate via the interaction with the complementary intermediates and consequently enhance oligomers formation that grows into fibrils and proto-fibrils. The amyloid fibrils for example, accumulate in the brain and central nervous system (CNS) as amyloid deposits in the Parkinson's disease (PD), Alzheimer's disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other neurodegenerative diseases. Treatment of such misfolding maladies is considered as one of the most important challenges of the 21st century. Currently, several treatments strategies have been and are being discovered. These therapeutic interventions partly reversed or prevented the pathological state. More recently, a new approach was discovered, which employs nanobodies that targets multisteps in fibril formation pathway that may possibly completely cure these misfolding diseases. Keeping the above views in mind in the current review, we have comprehensively discussed the different mechanisms underlying protein misfolding thereby leading to diseases conditions and their therapeutic interventions.

  12. Reformate tolerant electrocatalysts in solid polymer fuel cell membrane electrode assemblies

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, S J; Gunner, A G; Thompsett, D; Hards, G A

    1998-12-31

    The aim of the project was to evaluate a series of platinum group metal catalysts which had previously been identified from a wide range of areas related to carbon monoxide (CO) activation, and to demonstrate superior intrinsic reformate tolerance to current platinum/ruthenium technology as anode catalysts for Proton Exchange Membrane Fuel Cells (PEMFC). (author)

  13. Mechanisms of protein misfolding: Novel therapeutic approaches to protein-misfolding diseases

    DEFF Research Database (Denmark)

    Salahuddin, Parveen; Siddiqi, Mohammad Khursheed; Khan, Sanaullah

    2016-01-01

    ’s disease (PD), Alzheimer’s disease (AD), Prion disease and Amylo lateral Sclerosis (ALS). Furthermore, tau protein shows intrinsically disorder conformation; therefore its interaction with microtubule is impaired and this protein undergoes aggregation. This is also underlying cause of Alzheimers and other......In protein misfolding, protein molecule acquires wrong tertiary structure, thereby induces protein misfolding diseases. Protein misfolding can occur through various mechanisms. For instance, changes in environmental conditions, oxidative stress, dominant negative mutations, error in post......-translational modifications, increase in degradation rate and trafficking error. All of these factors cause protein misfolding thereby leading to diseases conditions. Both in vitro and in vivo observations suggest that partially unfolded or misfolded intermediates are particularly prone to aggregation. These partially...

  14. Markov state models of protein misfolding

    Science.gov (United States)

    Sirur, Anshul; De Sancho, David; Best, Robert B.

    2016-02-01

    Markov state models (MSMs) are an extremely useful tool for understanding the conformational dynamics of macromolecules and for analyzing MD simulations in a quantitative fashion. They have been extensively used for peptide and protein folding, for small molecule binding, and for the study of native ensemble dynamics. Here, we adapt the MSM methodology to gain insight into the dynamics of misfolded states. To overcome possible flaws in root-mean-square deviation (RMSD)-based metrics, we introduce a novel discretization approach, based on coarse-grained contact maps. In addition, we extend the MSM methodology to include "sink" states in order to account for the irreversibility (on simulation time scales) of processes like protein misfolding. We apply this method to analyze the mechanism of misfolding of tandem repeats of titin domains, and how it is influenced by confinement in a chaperonin-like cavity.

  15. Import and Export of Misfolded α-Synuclein

    Directory of Open Access Journals (Sweden)

    Lilia Rodriguez

    2018-05-01

    Full Text Available In Parkinson's disease, intracellular α-synuclein (α-syn inclusions form in neurons and are referred to as Lewy bodies. These aggregates spread through the brain following a specific pattern leading to the hypothesis that neuron-to-neuron transfer is critical for the propagation of Lewy body pathology. Here we review recent studies employing pre-formed fibrils generated from recombinant α-syn to evaluate the uptake, trafficking, and release of α-syn fibrils. We outline methods of internalization as well as cell surface receptors that have been described in the literature as regulating α-syn fibril uptake. Pharmacological and genetic studies indicate endocytosis is the primary method of α-syn internalization. Once α-syn fibrils have crossed the plasma membrane they are typically trafficked through the endo-lysosomal system with autophagy acting as the dominant method of α-syn clearance. Interestingly, both chaperone-mediated autophagy and macroautophagy have been implicated in the degradation of α-syn, although it remains unclear which system is chiefly responsible for the removal of α-syn fibrils. The major hallmark of α-syn spreading is the templating of misfolded properties onto healthy protein resulting in a conformational change; we summarize the evidence indicating misfolded α-syn can seed endogenous α-syn to form new aggregates. Finally, recent studies demonstrate that cells release misfolded and aggregated α-syn and that these processes may involve different chaperones. Nonetheless, the exact mechanism for the release of fibrillar α-syn remains unclear. This review highlights what is known, and what requires further clarification, regarding each step of α-syn transmission.

  16. Protein misfolding disorders: pathogenesis and intervention

    DEFF Research Database (Denmark)

    Gregersen, Niels

    2006-01-01

    of the functional structure of cellular proteins. Aberrant proteins, the result of production errors, inherited or acquired amino acid substitutions or damage, especially oxidative modifications, can in many cases not fold correctly and will be trapped in misfolded conformations. To rid the cell of misfolded...... be accompanied by a gain-of-function pathogenesis, which in many cases determines the pathological and clinical features. Examples are Parkinson and Huntington diseases. Although a number of strategies have been tried to decrease the amounts of accumulated and aggregated proteins, a likely future strategy seems......Newly synthesized proteins in the living cell must go through a folding process to attain their functional structure. To achieve this in an efficient fashion, all organisms, including humans, have evolved a large set of molecular chaperones that assist the folding as well as the maintenance...

  17. Protein Misfolding Cyclic Amplification of Infectious Prions.

    Science.gov (United States)

    Moda, Fabio

    2017-01-01

    Transmissible spongiform encephalopathies, or prion diseases, are a group of incurable disorders caused by the accumulation of an abnormally folded prion protein (PrP Sc ) in the brain. According to the "protein-only" hypothesis, PrP Sc is the infectious agent able to propagate the disease by acting as a template for the conversion of the correctly folded prion protein (PrP C ) into the pathological isoform. Recently, the mechanism of PrP C conversion has been mimicked in vitro using an innovative technique named protein misfolding cyclic amplification (PMCA). This technology represents a great tool for studying diverse aspects of prion biology in the field of basic research and diagnosis. Moreover, PMCA can be expanded for the study of the misfolding process associated to other neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and frontotemporal lobar degeneration. © 2017 Elsevier Inc. All rights reserved.

  18. Protein misfolding and obstructive lung disease.

    LENUS (Irish Health Repository)

    Greene, Catherine M

    2010-11-01

    The endoplasmic reticulum has evolved a number of mechanisms to manage the accumulation of incorrectly folded proteins. This results in loss of function of these proteins, but occasionally, in conditions such as α-1 antitrpysin (A1AT) deficiency, the misfolded protein can acquire a toxic gain of function promoting exaggerated ER stress responses and inflammation. Mutations leading to deficiency in a second serine proteinase inhibitor, α-1 antichymotrpysin (ACT), can induce potentially similar consequences. A1AT and ACT deficiencies are associated with chronic obstructive lung disease. Until recently, it was thought that the lung diseases associated with these conditions were entirely due to loss of antiprotease protection in the lung (i.e., loss of function), whereas gain of function was the major cause of the liver disease associated with A1AT deficiency. This paradigm is being increasingly challenged because ER stress is being recognized in bronchial epithelial cells and inflammatory cells normally resident in the lung, giving rise to an inflammatory phenotype that adds to the proteolytic burden associated with these conditions. In this article, we describe the cellular mechanisms that are activated to cope with an increasing burden of misfolded proteins within the ER in A1AT and ACT deficiency, show how these events are linked to inflammation, and outline the therapeutic strategies that can potentially interfere with production of misfolded proteins.

  19. Tolerance to chitosan by Trichoderma species is associated with low membrane fluidity.

    Science.gov (United States)

    Zavala-González, Ernesto A; Lopez-Moya, Federico; Aranda-Martinez, Almudena; Cruz-Valerio, Mayra; Lopez-Llorca, Luis Vicente; Ramírez-Lepe, Mario

    2016-07-01

    The effect of chitosan on growth of Trichoderma spp., a cosmopolitan genus widely exploited for their biocontrol properties was evaluated. Based on genotypic (ITS of 18S rDNA) characters, four isolates of Trichoderma were identified as T. pseudokoningii FLM16, T. citrinoviride FLM17, T. harzianum EZG47, and T. koningiopsis VSL185. Chitosan reduces radial growth of Trichoderma isolates in concentration-wise manner. T. koningiopsis VSL185 was the most chitosan tolerant isolate in all culture media amended with chitosan (0.5-2.0 mg ml(-1) ). Minimal Inhibitory Concentration (MIC) and Minimal Fungicidal Concentration (MFC) were determined showing that T. koningiopsis VSL185 displays higher chitosan tolerance with MIC value >2000 μg ml(-1) while for other Trichoderma isolates MIC values were around 10 μg ml(-1) . Finally, free fatty acid composition reveals that T. koningiopsis VSL185, chitosan tolerant isolate, displays lower linolenic acid (C18:3) content than chitosan sensitive Trichoderma isolates. Our findings suggest that low membrane fluidity is associated with chitosan tolerance in Trichoderma spp. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Experimental investigation of protein folding and misfolding.

    Science.gov (United States)

    Dobson, Christopher M

    2004-09-01

    Newly synthesised proteins need to fold, often to intricate and close-packed structures, in order to function. The underlying mechanism by which this complex process takes place both in vitro and in vivo is now becoming understood, at least in general terms, as a result of the application of a wide range of biophysical and computational methods used in combination with the techniques of biochemistry and protein engineering. It is increasingly apparent, however, that folding is not only crucial for generating biological activity, but that it is also coupled to a wide range of processes within the cell, ranging from the trafficking of proteins to specific organelles to the regulation of cell growth and differentiation. Not surprisingly, therefore, the failure of proteins to fold appropriately, or to remain correctly folded, is associated with a large number of cellular malfunctions that give rise to disease. Misfolding, and its consequences such as aggregation, can be investigated by extending the types of techniques used to study the normal folding process. Application of these techniques is enabling the development of a unified description of the interconversion and regulation of the different conformational states available to proteins in living systems. Such a description proves a generic basis for understanding the fundamental links between protein misfolding and its associated clinical disorders, such as Alzheimer's disease and Type II diabetes, and for exploring novel therapeutic strategies directed at their prevention and treatment on a rational basis.

  1. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    is linked to a different set of circumstances than the ones suggested by existing models in contemporary democratic theory. Reorienting the discussion of tolerance, the book raises the question of how to disclose new possibilities within our given context of affect and perception. Once we move away from......Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated...... by the desire to experiment and to become otherwise. The objective is to discuss what gets lost, conceptually as well as politically, when we neglect the subsistence of active tolerance within other practices of tolerance, and to develop a theory of active tolerance in which tolerance's mobilizing character...

  2. Effects of acclimation temperature on thermal tolerance and membrane phospholipid composition in the fruit fly Drosophila melanogaster

    DEFF Research Database (Denmark)

    Overgaard, Johannes; Tomcala, Ales; Sørensen, Jesper G

    2008-01-01

    and the composition of membrane GPLs in adult Drosophila melanogaster. Long-term cold survival was significantly improved by low acclimation temperature. After 60h at 0 degrees C, more than 80% of the 15 degrees C-acclimated flies survived while none of the 25 degrees C-acclimated flies survived. Cold shock tolerance...... acclimation temperature and correlated with the changes in GPL composition in membranes of adult D. melanogaster. Udgivelsesdato: 2008-Mar...

  3. Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants

    Science.gov (United States)

    Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

    2016-01-01

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na+/H+) antiporter that transports Na+ into the vacuole and exports H+ into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na+/H+ antiporter that exports Na+ to the extracellular space and imports H+ into the plant cell. Plants rely on these enzymes either to keep Na+ out of the cell or to sequester Na+ into vacuoles to avoid the toxic level of Na+ in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. PMID:26985021

  4. Co-overexpressing a Plasma Membrane and a Vacuolar Membrane Sodium/Proton Antiporter Significantly Improves Salt Tolerance in Transgenic Arabidopsis Plants.

    Science.gov (United States)

    Pehlivan, Necla; Sun, Li; Jarrett, Philip; Yang, Xiaojie; Mishra, Neelam; Chen, Lin; Kadioglu, Asim; Shen, Guoxin; Zhang, Hong

    2016-05-01

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane-bound sodium/proton (Na(+)/H(+)) antiporter that transports Na(+) into the vacuole and exports H(+) into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane-bound Na(+)/H(+) antiporter that exports Na(+) to the extracellular space and imports H(+) into the plant cell. Plants rely on these enzymes either to keep Na(+) out of the cell or to sequester Na(+) into vacuoles to avoid the toxic level of Na(+) in the cytoplasm. Overexpression of AtNHX1 or SOS1 could improve salt tolerance in transgenic plants, but the improved salt tolerance is limited. NaCl at concentration >200 mM would kill AtNHX1-overexpressing or SOS1-overexpressing plants. Here it is shown that co-overexpressing AtNHX1 and SOS1 could further improve salt tolerance in transgenic Arabidopsis plants, making transgenic Arabidopsis able to tolerate up to 250 mM NaCl treatment. Furthermore, co-overexpression of AtNHX1 and SOS1 could significantly reduce yield loss caused by the combined stresses of heat and salt, confirming the hypothesis that stacked overexpression of two genes could substantially improve tolerance against multiple stresses. This research serves as a proof of concept for improving salt tolerance in other plants including crops. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

  5. Tolerance

    DEFF Research Database (Denmark)

    Tønder, Lars

    Tolerance: A Sensorial Orientation to Politics is an experiment in re-orientation. The book is based on the wager that tolerance exceeds the more prevalent images of self-restraint and repressive benevolence because neither precludes the possibility of a more “active tolerance” motivated by the d...... these alternatives by returning to the notion of tolerance as the endurance of pain, linking this notion to exemplars and theories relevant to the politics of multiculturalism, religious freedom, and free speech....

  6. Carbon monoxide tolerant anodes for proton exchange membrane (PEM) fuel cells. 1. Catalyst development approach

    Energy Technology Data Exchange (ETDEWEB)

    Holleck, G L; Pasquariello, D M; Clauson, S L

    1998-07-01

    PEM fuel cells are highly attractive for distributed power and cogeneration systems. They are efficient and function virtually without noise or pollution. To be competitive PEM fuel cells must operate on fuel mixtures obtained by reforming of widely available natural gas or liquid hydrocarbons. Reformed fuel gas mixtures invariably contain CO, a strong poison for Pt. Therefore CO tolerant anode catalysts are essential for wide spread PEMFC introduction. It is the objective to develop effective CO tolerant fuel cell catalysts based on multi-component platinum-transition metal alloys. Towards this goal the authors have developed a novel approach for the synthesis and performance evaluation of multifunctional ternary alloy fuel cell catalysts. The alloys are prepared as well-defined thin films on standard TFE-bonded carbon substrates via a dc magnetron sputtering technique. The anodes are laminated to Nafion membranes and the electrochemical performance is measured in a representative fuel cell configuration with H{sub 2} and H{sub 2}/CO gas mixtures. The multi-target sputtering technique permits one to reproducibly synthesize true alloy films of controlled composition. The deposit morphology and electrode structure are determined by the standardized TFE bonded carbon substrate. The thin catalyst layer is concentrated at the electrode ionomer interface where it can be fully utilized in a representative fuel cell configuration. Thus, a true comparative fuel cell catalyst evaluation is possible. The effectiveness of this approach will be demonstrated with Pt, Pt-Ru and Pt-Ru-X catalyzed anodes.

  7. Protein aggregation and misfolding: good or evil?

    Science.gov (United States)

    Pastore, Annalisa; Temussi, Pierandrea

    2012-06-01

    Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open.

  8. Protein aggregation and misfolding: good or evil?

    International Nuclear Information System (INIS)

    Pastore, Annalisa; Temussi, Pierandrea

    2012-01-01

    Protein aggregation and misfolding have important implications in an increasing number of fields ranging from medicine to biology to nanotechnology and material science. The interest in understanding this field has accordingly increased steadily over the last two decades. During this time the number of publications that have been dedicated to protein aggregation has increased exponentially, tackling the problem from several different and sometime contradictory perspectives. This review is meant to summarize some of the highlights that come from these studies and introduce this topical issue on the subject. The factors that make a protein aggregate and the cellular strategies that defend from aggregation are discussed together with the perspectives that the accumulated knowledge may open. (topical review)

  9. Improving carbon tolerance of Ni-YSZ catalytic porous membrane by palladium addition for low temperature steam methane reforming

    Science.gov (United States)

    Lee, Sang Moon; Won, Jong Min; Kim, Geo Jong; Lee, Seung Hyun; Kim, Sung Su; Hong, Sung Chang

    2017-10-01

    Palladium was added on the Ni-YSZ catalytic porous membrane by wet impregnation and electroless plating methods. Its surface morphology characteristics and carbon deposition properties for the low temperature steam methane reforming were investigated. The addition of palladium could obviously be enhanced the catalytic activity as well as carbon tolerance of the Ni-YSZ porous membrane. The porous membranes were evaluated by scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), H2 temperature-programmed reduction (H2-TPR), CH4 temperature-programmed reduction (CH4-TPR), and O2 temperature-programmed oxidation (O2-TPO). It was found that the Pd-Ni-YSZ catalytic porous membrane showed the superior stability as well as the deposition of carbon on the surface during carbon dissociation adsorption at 650 °C was also suppressed.

  10. A review of fault tolerant control strategies applied to proton exchange membrane fuel cell systems

    Science.gov (United States)

    Dijoux, Etienne; Steiner, Nadia Yousfi; Benne, Michel; Péra, Marie-Cécile; Pérez, Brigitte Grondin

    2017-08-01

    Fuel cells are powerful systems for power generation. They have a good efficiency and do not generate greenhouse gases. This technology involves a lot of scientific fields, which leads to the appearance of strongly inter-dependent parameters. This makes the system particularly hard to control and increases fault's occurrence frequency. These two issues call for the necessity to maintain the system performance at the expected level, even in faulty operating conditions. It is called "fault tolerant control" (FTC). The present paper aims to give the state of the art of FTC applied to the proton exchange membrane fuel cell (PEMFC). The FTC approach is composed of two parts. First, a diagnosis part allows the identification and the isolation of a fault; it requires a good a priori knowledge of all the possible faults. Then, a control part allows an optimal control strategy to find the best operating point to recover/mitigate the fault; it requires the knowledge of the degradation phenomena and their mitigation strategies.

  11. Cell-Based Phenotyping Reveals QTL for Membrane Potential Maintenance Associated with Hypoxia and Salinity Stress Tolerance in Barley

    Directory of Open Access Journals (Sweden)

    Muhammad B. Gill

    2017-11-01

    Full Text Available Waterlogging and salinity are two major abiotic stresses that hamper crop production world-wide resulting in multibillion losses. Plant abiotic stress tolerance is conferred by many interrelated mechanisms. Amongst these, the cell’s ability to maintain membrane potential (MP is considered to be amongst the most crucial traits, a positive relationship between the ability of plants to maintain highly negative MP and its tolerance to both salinity and waterlogging stress. However, no attempts have been made to identify quantitative trait loci (QTL conferring this trait. In this study, the microelectrode MIFE technique was used to measure the plasma membrane potential of epidermal root cells of 150 double haploid (DH lines of barley (Hordeum vulgare L. from a cross between a Chinese landrace TX9425 and Japanese malting cultivar Naso Nijo under hypoxic conditions. A major QTL for the MP in the epidermal root cells in hypoxia-exposed plants was identified. This QTL was located on 2H, at a similar position to the QTL for waterlogging and salinity tolerance reported in previous studies. Further analysis confirmed that MP showed a significant contribution to both waterlogging and salinity tolerance. The fact that the QTL for MP was controlled by a single major QTL illustrates the power of the single-cell phenotyping approach and opens prospects for fine mapping this QTL and thus being more effective in marker assisted selection.

  12. Distinct role of hydration water in protein misfolding and aggregation revealed by fluctuating thermodynamics analysis.

    Science.gov (United States)

    Chong, Song-Ho; Ham, Sihyun

    2015-04-21

    Protein aggregation in aqueous cellular environments is linked to diverse human diseases. Protein aggregation proceeds through a multistep process initiated by conformational transitions, called protein misfolding, of monomer species toward aggregation-prone structures. Various forms of aggregate species are generated through the association of misfolded monomers including soluble oligomers and amyloid fibrils. Elucidating the molecular mechanisms and driving forces involved in the misfolding and subsequent association has been a central issue for understanding and preventing protein aggregation diseases such as Alzheimer's, Parkinson's, and type II diabetes. In this Account, we provide a thermodynamic perspective of the misfolding and aggregation of the amyloid-beta (Aβ) protein implicated in Alzheimer's disease through the application of fluctuating thermodynamics. This approach "dissects" the conventional thermodynamic characterization of the end states into the one of the fluctuating processes connecting them, and enables one to analyze variations in the thermodynamic functions that occur during the course of protein conformational changes. The central quantity in this approach is the solvent-averaged effective energy, f = Eu + Gsolv, comprising the protein potential energy (Eu) and the solvation free energy (Gsolv), whose time variation reflects the protein dynamics on the free energy landscape. Protein configurational entropy is quantified by the magnitude of fluctuations in f. We find that misfolding of the Aβ monomer when released from a membrane environment to an aqueous phase is driven by favorable changes in protein potential energy and configurational entropy, but it is also accompanied by an unfavorable increase in solvation free energy. The subsequent dimerization of the misfolded Aβ monomers occurs in two steps. The first step, where two widely separated monomers come into contact distance, is driven by water-mediated attraction, that is, by a

  13. Lipophilic Contaminants Influence Cold Tolerance of Invertebrates through Changes in Cell Membrane Fluidity

    DEFF Research Database (Denmark)

    Holmstrup, Martin; Bouvrais, Hélène; Westh, Peter

    2014-01-01

    Contaminants taken up by living organisms in the environment as a result of anthropogenic contamination can reduce the tolerance of natural stressors, e.g., low temperatures, but the physiological mechanisms behind these interactions of effects are poorly understood. The tolerance to low temperat...

  14. Cellular proteostasis: degradation of misfolded proteins by lysosomes

    Science.gov (United States)

    Jackson, Matthew P.

    2016-01-01

    Proteostasis refers to the regulation of the cellular concentration, folding, interactions and localization of each of the proteins that comprise the proteome. One essential element of proteostasis is the disposal of misfolded proteins by the cellular pathways of protein degradation. Lysosomes are an important site for the degradation of misfolded proteins, which are trafficked to this organelle by the pathways of macroautophagy, chaperone-mediated autophagy and endocytosis. Conversely, amyloid diseases represent a failure in proteostasis, in which proteins misfold, forming amyloid deposits that are not degraded effectively by cells. Amyloid may then exacerbate this failure by disrupting autophagy and lysosomal proteolysis. However, targeting the pathways that regulate autophagy and the biogenesis of lysosomes may present approaches that can rescue cells from the deleterious effects of amyloidogenic proteins. PMID:27744333

  15. Identification of Salt-Tolerant Sinorhizobium sp Strain BL3 Membrane Proteins Based on Proteomics

    DEFF Research Database (Denmark)

    Tanthanuch, Waraporn; Mohammed, Shabaz; Matthiesen, Rune

    2010-01-01

    functional categories, the two biggest of which were energy production and conversion, and proteins not in clusters of orthologous groups (COGs). In addition, a comparative analysis of membrane proteins between salt-stressed and non-stressed BL3 cells was conducted using a membrane enrichment method and off-line...... SCX fractionation coupled to nanoLC-MS/MS. These techniques would be useful for further comparative analysis of membrane proteins that function in the response to environmental stress....

  16. Protein degradation and protection against misfolded or damaged proteins

    Science.gov (United States)

    Goldberg, Alfred L.

    2003-12-01

    The ultimate mechanism that cells use to ensure the quality of intracellular proteins is the selective destruction of misfolded or damaged polypeptides. In eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S proteasome, prevents the accumulation of non-functional, potentially toxic proteins. This process is of particular importance in protecting cells against harsh conditions (for example, heat shock or oxidative stress) and in a variety of diseases (for example, cystic fibrosis and the major neurodegenerative diseases). A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.

  17. Towards Acid-Tolerated Ethanol Dehydration: Chitosan-Based Mixed Matrix Membranes Containing Cyano-Bridged Coordination Polymer Nanoparticles.

    Science.gov (United States)

    Wu, C-W; Kang, Chao-Hsiang; Lin, Yi-Feng; Tung, Kuo-Lun; Deng, Yu-Heng; Ahamad, Tansir; Alshehri, Saad M; Suzuki, Norihiro; Yamauchi, Yusuke

    2016-04-01

    Prussian blue (PB) nanoparticles, one of many cyano-bridged coordination polymers, are successfully incorporated into chitosan (CS) polymer to prepare PB/CS mixed matrix membranes (MMMs). The PB nanoparticles are uniformly distributed in the MMMs without the collapse of the original PB structure. As-prepared PB/CS MMMs are used for ethanol dehydration at 25 °C in the pervaporation process. The effect of loading PB in CS matrix on pervaporation performance is carefully investigated. The PB/CS membrane with 30 wt% PB loading shows the best performance with a permeate flux of 614 g. m-2 . h-1 and a separation factor of 1472. The pervaporation using our PB/CS membranes exhibits outstanding performance in comparison with the previously reported CS-based membranes and MMMs. Furthermore, the addition of PB allows PB/CS MMMs to be tolerant of acidic environment. The present work demonstrates good pervaporation performance of PB/CS MMMs for the separation of an ethanol/water (90:10 in wt%) solution. Our new system provides an opportunity for dehydration of bioethanol in the future.

  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. CO-Tolerant Pt–BeO as a Novel Anode Electrocatalyst in Proton Exchange Membrane Fuel Cells

    Directory of Open Access Journals (Sweden)

    Kyungjung Kwon

    2016-05-01

    Full Text Available Commercialization of proton exchange membrane fuel cells (PEMFCs requires less expensive catalysts and higher operating voltage. Substantial anodic overvoltage with the usage of reformed hydrogen fuel can be minimized by using CO-tolerant anode catalysts. Carbon-supported Pt–BeO is manufactured so that Pt particles with an average diameter of 4 nm are distributed on a carbon support. XPS analysis shows that a peak value of the binding energy of Be matches that of BeO, and oxygen is bound with Be or carbon. The hydrogen oxidation current of the Pt–BeO catalyst is slightly higher than that of a Pt catalyst. CO stripping voltammetry shows that CO oxidation current peaks at ~0.85 V at Pt, whereas CO is oxidized around 0.75 V at Pt–BeO, which confirms that the desorption of CO is easier in the presence of BeO. Although the state-of-the-art PtRu anode catalyst is dominant as a CO-tolerant hydrogen oxidation catalyst, this study of Be-based CO-tolerant material can widen the choice of PEMFC anode catalyst.

  20. Futile Na+ cycling at the root plasma membrane in rice (Oryza sativa L.): kinetics, energetics, and relationship to salinity tolerance.

    Science.gov (United States)

    Malagoli, Philippe; Britto, Dev T; Schulze, Lasse M; Kronzucker, Herbert J

    2008-01-01

    Globally, over one-third of irrigated land is affected by salinity, including much of the land under lowland rice cultivation in the tropics, seriously compromising yields of this most important of crop species. However, there remains an insufficient understanding of the cellular basis of salt tolerance in rice. Here, three methods of 24Na+ tracer analysis were used to investigate primary Na+ transport at the root plasma membrane in a salt-tolerant rice cultivar (Pokkali) and a salt-sensitive cultivar (IR29). Futile cycling of Na+ at the plasma membrane of intact roots occurred at both low and elevated levels of steady-state Na+ supply ([Na+]ext=1 mM and 25 mM) in both cultivars. At 25 mM [Na+]ext, a toxic condition for IR29, unidirectional influx and efflux of Na+ in this cultivar, but not in Pokkali, became very high [>100 micromol g (root FW)(-1) h(-1)], demonstrating an inability to restrict sodium fluxes. Current models of sodium transport energetics across the plasma membrane in root cells predict that, if the sodium efflux were mediated by Na+/H+ antiport, this toxic scenario would impose a substantial respiratory cost in IR29. This cost is calculated here, and compared with root respiration, which, however, comprised only approximately 50% of what would be required to sustain efflux by the antiporter. This suggests that either the conventional 'leak-pump' model of Na+ transport or the energetic model of proton-linked Na+ transport may require some revision. In addition, the lack of suppression of Na+ influx by both K+ and Ca2+, and by the application of the channel inhibitors Cs+, TEA+, and Ba2+, questions the participation of potassium channels and non-selective cation channels in the observed Na+ fluxes.

  1. Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach

    KAUST Repository

    Zhang, Huoming; Zhao, Changqing; Li, Xin; Zhu, Yi; Gan, Chee Sian; Wang, Yong; Ravasi, Timothy; Qian, Pei-Yuan; Wong, Siew Cheng; Sze, Siu Kwan

    2010-01-01

    Human monocytes' exposure to low-level lipopolysaccharide (LPS) induces temporary monocytic insensitivity to subsequent LPS challenge. The underlying mechanism of this phenomenon could have important clinical utilities in preventing and/or treating severe infections. In this study, we used an iTRAQ-based quantitative proteomic approach to comprehensively characterize the membrane proteomes of monocytes before and after LPS exposure. We identified a total of 1651 proteins, of which 53.6% were membrane proteins. Ninety-four percent of the proteins were quantified and 255 proteins were shown to be tightly regulated by LPS. Subcellular location analysis revealed organelle-specific response to LPS exposure: more than 90% of identified mitochondrial membrane proteins were significant downregulated, whereas the majority of proteins from other organelles such as ER, Golgi and ribosome were upregulated. Moreover, we found that the expression of most receptors potentially involved in LPS signal pathway (CD14, toll-like receptor 4, CD11/CD18 complex) were substantially decreased, while the expression of molecules involved in LPS neutralization were enhanced after LPS challenge. Together, these findings could be of significance in understanding the mechanism of LPS tolerance and provide values for designing new approaches for regulating monocytic responses in sepsis patients.

  2. Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach

    KAUST Repository

    Zhang, Huoming

    2010-07-02

    Human monocytes\\' exposure to low-level lipopolysaccharide (LPS) induces temporary monocytic insensitivity to subsequent LPS challenge. The underlying mechanism of this phenomenon could have important clinical utilities in preventing and/or treating severe infections. In this study, we used an iTRAQ-based quantitative proteomic approach to comprehensively characterize the membrane proteomes of monocytes before and after LPS exposure. We identified a total of 1651 proteins, of which 53.6% were membrane proteins. Ninety-four percent of the proteins were quantified and 255 proteins were shown to be tightly regulated by LPS. Subcellular location analysis revealed organelle-specific response to LPS exposure: more than 90% of identified mitochondrial membrane proteins were significant downregulated, whereas the majority of proteins from other organelles such as ER, Golgi and ribosome were upregulated. Moreover, we found that the expression of most receptors potentially involved in LPS signal pathway (CD14, toll-like receptor 4, CD11/CD18 complex) were substantially decreased, while the expression of molecules involved in LPS neutralization were enhanced after LPS challenge. Together, these findings could be of significance in understanding the mechanism of LPS tolerance and provide values for designing new approaches for regulating monocytic responses in sepsis patients.

  3. A novel CO>2- and SO>2-tolerant dual phase composite membrane for oxygen separation

    DEFF Research Database (Denmark)

    Cheng, Shiyang; Søgaard, Martin; Han, Li

    2015-01-01

    A novel dual phase composite oxygen membrane (Al0.02Ga0.02Zn0.96O1.02 – Gd0.1Ce0.9O1.95-δ) was successfully prepared and tested. The membrane shows chemical stability against CO2 and SO2, and a stable oxygen permeation over 300 hours in CO2 was demonstrated. ZnO is cheap and non-toxic...... and is therefore highly advantageous compared to other common materials used for the purpose....

  4. Arabidopsis dynamin-related protein 1E in sphingolipid-enriched plasma membrane domains is associated with the development of freezing tolerance.

    Science.gov (United States)

    Minami, Anzu; Tominaga, Yoko; Furuto, Akari; Kondo, Mariko; Kawamura, Yukio; Uemura, Matsuo

    2015-08-01

    The freezing tolerance of Arabidopsis thaliana is enhanced by cold acclimation, resulting in changes in the compositions and function of the plasma membrane. Here, we show that a dynamin-related protein 1E (DRP1E), which is thought to function in the vesicle trafficking pathway in cells, is related to an increase in freezing tolerance during cold acclimation. DRP1E accumulated in sphingolipid and sterol-enriched plasma membrane domains after cold acclimation. Analysis of drp1e mutants clearly showed that DRP1E is required for full development of freezing tolerance after cold acclimation. DRP1E fused with green fluorescent protein was visible as small foci that overlapped with fluorescent dye-labelled plasma membrane, providing evidence that DRP1E localizes non-uniformly in specific areas of the plasma membrane. These results suggest that DRP1E accumulates in sphingolipid and sterol-enriched plasma membrane domains and plays a role in freezing tolerance development during cold acclimation. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  5. A hydrophobic gold surface triggers misfolding and aggregation of the amyloidogenic Josephin domain in monomeric form, while leaving the oligomers unaffected.

    Directory of Open Access Journals (Sweden)

    Alessandra Apicella

    Full Text Available Protein misfolding and aggregation in intracellular and extracellular spaces is regarded as a main marker of the presence of degenerative disorders such as amyloidoses. To elucidate the mechanisms of protein misfolding, the interaction of proteins with inorganic surfaces is of particular relevance, since surfaces displaying different wettability properties may represent model systems of the cell membrane. Here, we unveil the role of surface hydrophobicity/hydrophilicity in the misfolding of the Josephin domain (JD, a globular-shaped domain of ataxin-3, the protein responsible for the spinocerebellar ataxia type 3. By means of a combined experimental and theoretical approach based on atomic force microscopy, Fourier transform infrared spectroscopy and molecular dynamics simulations, we reveal changes in JD morphology and secondary structure elicited by the interaction with the hydrophobic gold substrate, but not by the hydrophilic mica. Our results demonstrate that the interaction with the gold surface triggers misfolding of the JD when it is in native-like configuration, while no structural modification is observed after the protein has undergone oligomerization. This raises the possibility that biological membranes would be unable to affect amyloid oligomeric structures and toxicity.

  6. Crossed wires: 3D genome misfolding in human disease.

    Science.gov (United States)

    Norton, Heidi K; Phillips-Cremins, Jennifer E

    2017-11-06

    Mammalian genomes are folded into unique topological structures that undergo precise spatiotemporal restructuring during healthy development. Here, we highlight recent advances in our understanding of how the genome folds inside the 3D nucleus and how these folding patterns are miswired during the onset and progression of mammalian disease states. We discuss potential mechanisms underlying the link among genome misfolding, genome dysregulation, and aberrant cellular phenotypes. We also discuss cases in which the endogenous 3D genome configurations in healthy cells might be particularly susceptible to mutation or translocation. Together, these data support an emerging model in which genome folding and misfolding is critically linked to the onset and progression of a broad range of human diseases. © 2017 Norton and Phillips-Cremins.

  7. Protein folding and misfolding shining light by infrared spectroscopy

    CERN Document Server

    Fabian, Heinz

    2012-01-01

    Infrared spectroscopy is a new and innovative technology to study protein folding/misfolding events in the broad arsenal of techniques conventionally used in this field. The progress in understanding protein folding and misfolding is primarily due to the development of biophysical methods which permit to probe conformational changes with high kinetic and structural resolution. The most commonly used approaches rely on rapid mixing methods to initiate the folding event via a sudden change in solvent conditions. Traditionally, techniques such as fluorescence, circular dichroism or visible absorption are applied to probe the process. In contrast to these techniques, infrared spectroscopy came into play only very recently, and the progress made in this field up to date which now permits to probe folding events over the time scale from picoseconds to minutes has not yet been discussed in a book. The aim of this book is to provide an overview of the developments as seen by some of the main contributors to the field...

  8. Hemin as a generic and potent protein misfolding inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yanqin [School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005 (Australia); Carver, John A. [Discipline of Pharmacology, The University of Adelaide, Adelaide, SA 5005 (Australia); Ho, Lam H.; Elias, Abigail K. [School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005 (Australia); Musgrave, Ian F. [Research School of Chemistry, The Australian National University, Canberra, ACT 0200 (Australia); Pukala, Tara L., E-mail: tara.pukala@adelaide.edu.au [School of Chemistry and Physics, The University of Adelaide, Adelaide, SA 5005 (Australia)

    2014-11-14

    Highlights: • Hemin prevents Aβ42, α-synuclein and RCM-κ-casein forming amyloid fibrils. • Hemin inhibits the β-sheet structure formation of Aβ42. • Hemin reduces the cell toxicity caused by fibrillar Aβ42. • Hemin dissociates partially formed Aβ42 fibrils. • Hemin prevents amorphous aggregation by ADH, catalase and γs-crystallin. - Abstract: Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer’s disease, Parkinson’s disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics for the treatment of these diseases. In the present study, thioflavin T fluorescence and transmission electron microscopy experiments demonstrated that hemin prevents amyloid fibril formation of kappa-casein, amyloid beta peptide and α-synuclein by blocking β-sheet structure assembly which is essential in fibril aggregation. Further, inhibition of fibril formation by hemin significantly reduces the cytotoxicity caused by fibrillar amyloid beta peptide in vitro. Interestingly, hemin degrades partially formed amyloid fibrils and prevents further aggregation to mature fibrils. Light scattering assay results revealed that hemin also prevents protein amorphous aggregation of alcohol dehydrogenase, catalase and γs-crystallin. In summary, hemin is a potent agent which generically stabilises proteins against aggregation, and has potential as a key molecule for the development of therapeutics for protein misfolding diseases.

  9. Frustration in the energy landscapes of multidomain protein misfolding.

    Science.gov (United States)

    Zheng, Weihua; Schafer, Nicholas P; Wolynes, Peter G

    2013-01-29

    Frustration from strong interdomain interactions can make misfolding a more severe problem in multidomain proteins than in single-domain proteins. On the basis of bioinformatic surveys, it has been suggested that lowering the sequence identity between neighboring domains is one of nature's solutions to the multidomain misfolding problem. We investigate folding of multidomain proteins using the associative-memory, water-mediated, structure and energy model (AWSEM), a predictive coarse-grained protein force field. We find that reducing sequence identity not only decreases the formation of domain-swapped contacts but also decreases the formation of strong self-recognition contacts between β-strands with high hydrophobic content. The ensembles of misfolded structures that result from forming these amyloid-like interactions are energetically disfavored compared with the native state, but entropically favored. Therefore, these ensembles are more stable than the native ensemble under denaturing conditions, such as high temperature. Domain-swapped contacts compete with self-recognition contacts in forming various trapped states, and point mutations can shift the balance between the two types of interaction. We predict that multidomain proteins that lack these specific strong interdomain interactions should fold reliably.

  10. Mechanisms of protein misfolding in conformational lung diseases.

    LENUS (Irish Health Repository)

    McElvaney, N G

    2012-08-01

    Genetic or environmentally-induced alterations in protein structure interfere with the correct folding, assembly and trafficking of proteins. In the lung the expression of misfolded proteins can induce a variety of pathogenetic effects. Cystic fibrosis (CF) and alpha-1 antitrypsin (AAT) deficiency are two major clinically relevant pulmonary disorders associated with protein misfolding. Both are genetic diseases the primary causes of which are expression of mutant alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) and SERPINA1, respectively. The most common and best studied mutant forms of CFTR and AAT are ΔF508 CFTR and the Glu342Lys mutant of AAT called ZAAT, respectively. Non-genetic mechanisms can also damage protein structure and induce protein misfolding in the lung. Cigarette-smoke contains oxidants and other factors that can modify a protein\\'s structure, and is one of the most significant environmental causes of protein damage within the lung. Herein we describe the mechanisms controlling the folding of wild type and mutant versions of CFTR and AAT proteins, and explore the consequences of cigarette-smoke-induced effects on the protein folding machinery in the lung.

  11. Relationship of Triamine-Biocide Tolerance of Salmonella enterica Serovar Senftenberg to Antimicrobial Susceptibility, Serum Resistance and Outer Membrane Proteins.

    Science.gov (United States)

    Futoma-Kołoch, Bożena; Dudek, Bartłomiej; Kapczyńska, Katarzyna; Krzyżewska, Eva; Wańczyk, Martyna; Korzekwa, Kamila; Rybka, Jacek; Klausa, Elżbieta; Bugla-Płoskońska, Gabriela

    2017-07-11

    A new emerging phenomenon is the association between the incorrect use of biocides in the process of disinfection in farms and the emergence of cross-resistance in Salmonella populations. Adaptation of the microorganisms to the sub-inhibitory concentrations of the disinfectants is not clear, but may result in an increase of sensitivity or resistance to antibiotics, depending on the biocide used and the challenged Salmonella serovar. Exposure of five Salmonella enterica subsp. enterica serovar Senftenberg ( S. Senftenberg) strains to triamine-containing disinfectant did not result in variants with resistance to antibiotics, but has changed their susceptibility to normal human serum (NHS). Three biocide variants developed reduced sensitivity to NHS in comparison to the sensitive parental strains, while two isolates lost their resistance to serum. For S. Senftenberg, which exhibited the highest triamine tolerance (6 × MIC) and intrinsic sensitivity to 22.5% and 45% NHS, a downregulation of flagellin and enolase has been demonstrated, which might suggest a lower adhesion and virulence of the bacteria. This is the first report demonstrating the influence of biocide tolerance on NHS resistance. In conclusion, there was a potential in S. Senftenberg to adjust to the conditions, where the biocide containing triamine was present. However, the adaptation did not result in the increase of antibiotic resistance, but manifested in changes within outer membrane proteins' patterns. The strategy of bacterial membrane proteins' analysis provides an opportunity to adjust the ways of infection treatments, especially when it is connected to the life-threating bacteremia caused by Salmonella species.

  12. Anion-Exchange Membrane Fuel Cells with Improved CO2 Tolerance: Impact of Chemically Induced Bicarbonate Ion Consumption.

    Science.gov (United States)

    Katayama, Yu; Yamauchi, Kosuke; Hayashi, Kohei; Okanishi, Takeou; Muroyama, Hiroki; Matsui, Toshiaki; Kikkawa, Yuuki; Negishi, Takayuki; Watanabe, Shin; Isomura, Takenori; Eguchi, Koichi

    2017-08-30

    Over the last few decades, because of the significant development of anion exchange membranes, increasing efforts have been devoted the realization of anion exchange membrane fuel cells (AEMFCs) that operate with the supply of hydrogen generated on-site. In this paper, ammonia was selected as a hydrogen source, following which the effect of conceivable impurities, unreacted NH 3 and atmospheric CO 2 , on the performance of AEMFCs was established. As expected, we show that these impurities worsen the performance of AEMFCs significantly. Furthermore, with the help of in situ attenuated total reflection infrared (ATR-IR) spectroscopy, it was revealed that the degradation of the cell performance was primarily due to the inhibition of the hydrogen oxidation reaction (HOR). This is attributed to the active site occupation by CO-related adspecies derived from (bi)carbonate adspecies. Interestingly, this degradation in the HOR activity is suppressed in the presence of both NH 3 and HCO 3 - because of the bicarbonate ion consumption reaction induced by the existence of NH 3 . Further analysis using in situ ATR-IR and electrochemical methods revealed that the poisonous CO-related adspecies were completely removed under NH 3 -HCO 3 - conditions, accompanied by the improvement in HOR activity. Finally, a fuel cell test was conducted by using the practical AEMFC with the supply of NH 3 -contained H 2 gas to the anode and ambient air to the cathode. The result confirmed the validity of this positive effect of NH 3 -HCO 3 - coexistence on CO 2 -tolerence of AEMFCs. The cell performance achieved nearly 95% of that without any impurity in the fuels. These results clearly show the impact of the chemically induced bicarbonate ion consumption reaction on the realization of highly CO 2 -tolerent AEMFCs.

  13. Relative abundance of Delta(5)-sterols in plasma membrane lipids of root-tip cells correlates with aluminum tolerance of rice.

    Science.gov (United States)

    Khan, M Shahadat Hossain; Tawaraya, Keitarou; Sekimoto, Hiroshi; Koyama, Hiroyuki; Kobayashi, Yuriko; Murayama, Tetsuya; Chuba, Masaru; Kambayashi, Mihoko; Shiono, Yoshihito; Uemura, Matsuo; Ishikawa, Satoru; Wagatsuma, Tadao

    2009-01-01

    We investigated variations in aluminum (Al) tolerance among rice plants, using ancestor cultivars from the family line of the Al-tolerant and widely cultivated Japonica cultivar, Sasanishiki. The cultivar Rikuu-20 was Al sensitive, whereas a closely related cultivar that is a descendant of Rikuu-20, Rikuu-132, was Al tolerant. These two cultivars were compared to determine mechanisms underlying variations in Al tolerance. The sensitive cultivar Rikuu-20 showed increased permeability of the plasma membrane (PM) and greater Al uptake within 1 h of Al treatment. This could not be explained by organic acid release. Lipid composition of the PM differed between these cultivars, and may account for the difference in Al tolerance. The tolerant cultivar Rikuu-132 had a lower ratio of phospholipids to Delta(5)-sterols than the sensitive cultivar Rikuu-20, suggesting that the PM of Rikuu-132 is less negatively charged and less permeabilized than that of Rikuu-20. We used inhibitors of Delta(5)-sterol synthesis to alter the ratio of phospholipids to Delta(5)-sterols in both cultivars. These inhibitors reduced Al tolerance in Rikuu-132 and its Al-tolerant ancestor cultivars Kamenoo and Kyoku. In addition, Rikuu-132 showed a similar level of Al sensitivity when the ratio of phospholipids to Delta(5)-sterols was increased to match that of Rikuu-20 after treatment with uniconazole-P, an inhibitor of obtusifoliol-14alpha-demethylase. These results indicate that PM lipid composition is a factor underlying variations in Al tolerance among rice cultivars.

  14. 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.

  15. Heterologous expression of the yeast Tpo1p or Pdr5p membrane transporters in Arabidopsis confers plant xenobiotic tolerance.

    Science.gov (United States)

    Remy, Estelle; Niño-González, María; Godinho, Cláudia P; Cabrito, Tânia R; Teixeira, Miguel C; Sá-Correia, Isabel; Duque, Paula

    2017-07-03

    Soil contamination is a major hindrance for plant growth and development. The lack of effective strategies to remove chemicals released into the environment has raised the need to increase plant resilience to soil pollutants. Here, we investigated the ability of two Saccharomyces cerevisiae plasma-membrane transporters, the Major Facilitator Superfamily (MFS) member Tpo1p and the ATP-Binding Cassette (ABC) protein Pdr5p, to confer Multiple Drug Resistance (MDR) in Arabidopsis thaliana. Transgenic plants expressing either of the yeast transporters were undistinguishable from the wild type under control conditions, but displayed tolerance when challenged with the herbicides 2,4-D and barban. Plants expressing ScTPO1 were also more resistant to the herbicides alachlor and metolachlor as well as to the fungicide mancozeb and the Co 2+ , Cu 2+ , Ni 2+ , Al 3+ and Cd 2+ cations, while ScPDR5-expressing plants exhibited tolerance to cycloheximide. Yeast mutants lacking Tpo1p or Pdr5p showed increased sensitivity to most of the agents tested in plants. Our results demonstrate that the S. cerevisiae Tpo1p and Pdr5p transporters are able to mediate resistance to a broad range of compounds of agricultural interest in yeast as well as in Arabidopsis, underscoring their potential in future biotechnological applications.

  16. Differential activity of Plasma and Vacuolar Membrane Transporters contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa

    DEFF Research Database (Denmark)

    Bonales-Alatorre, Edgar; Pottosin, Igor; Shabala, Lana

    2013-01-01

    quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa....... These include: (i) a higher rate of Na+ exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na+ levels; (iii) better K+ retention in the leaf mesophyll; (iv) a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce......Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow...

  17. Hyperactive mutant of a wheat plasma membrane Na+/H+ antiporter improves the growth and salt tolerance of transgenic tobacco.

    Science.gov (United States)

    Zhou, Yang; Lai, Zesen; Yin, Xiaochang; Yu, Shan; Xu, Yuanyuan; Wang, Xiaoxiao; Cong, Xinli; Luo, Yuehua; Xu, Haixia; Jiang, Xingyu

    2016-12-01

    Wheat SOS1 (TaSOS1) activity could be relieved upon deletion of the C-terminal 168 residues (the auto-inhibitory domain). This truncated form of wheat SOS1 (TaSOS1-974) was shown to increase compensation (compared to wild-type TaSOS1) for the salt sensitivity of a yeast mutant strain, AXT3K, via increased Na + transportation out of cells during salinity stress. Expression of the plasma membrane proteins TaSOS1-974 or TaSOS1 improved the growth of transgenic tobacco plants compared with wild-type plants under normal conditions. However, plants expressing TaSOS1-974 grew better than TaSOS1-transformed plants. Upon salinity stress, Na + efflux and K + influx rates in the roots of transgenic plants expressing TaSOS1-974 or TaSOS1 were greater than those of wild-type plants. Furthermore, compared to TaSOS1-transgenic plants, TaSOS1-974-expressing roots showed faster Na + efflux and K + influx, resulting in less Na + and more K + accumulation in TaSOS1-974-transgenic plants compared to TaSOS1-transgenic and wild-type plants. TaSOS1-974-expressing plants had the lowest MDA content and electrolyte leakage among all tested plants, indicating that TaSOS1-974 might protect the plasma membrane against oxidative damage generated by salt stress. Overall, TaSOS1-974 conferred higher salt tolerance in transgenic plants compared to TaSOS1. Consistent with this result, transgenic plants expressing TaSOS1-974 showed a better growth performance than TaSOS1-expressing and wild-type plants under saline conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.

    Science.gov (United States)

    Verstraeten, Natalie; Knapen, Wouter Joris; Kint, Cyrielle Ines; Liebens, Veerle; Van den Bergh, Bram; Dewachter, Liselot; Michiels, Joran Elie; Fu, Qiang; David, Charlotte Claudia; Fierro, Ana Carolina; Marchal, Kathleen; Beirlant, Jan; Versées, Wim; Hofkens, Johan; Jansen, Maarten; Fauvart, Maarten; Michiels, Jan

    2015-07-02

    Within bacterial populations, a small fraction of persister cells is transiently capable of surviving exposure to lethal doses of antibiotics. As a bet-hedging strategy, persistence levels are determined both by stochastic induction and by environmental stimuli called responsive diversification. Little is known about the mechanisms that link the low frequency of persisters to environmental signals. Our results support a central role for the conserved GTPase Obg in determining persistence in Escherichia coli in response to nutrient starvation. Obg-mediated persistence requires the stringent response alarmone (p)ppGpp and proceeds through transcriptional control of the hokB-sokB type I toxin-antitoxin module. In individual cells, increased Obg levels induce HokB expression, which in turn results in a collapse of the membrane potential, leading to dormancy. Obg also controls persistence in Pseudomonas aeruginosa and thus constitutes a conserved regulator of antibiotic tolerance. Combined, our findings signify an important step toward unraveling shared genetic mechanisms underlying persistence. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Transcriptional responses of Leptospira interrogans to host innate immunity: significant changes in metabolism, oxygen tolerance, and outer membrane.

    Directory of Open Access Journals (Sweden)

    Feng Xue

    Full Text Available BACKGROUND: Leptospira interrogans is the major causative agent of leptospirosis. Phagocytosis plays important roles in the innate immune responses to L. interrogans infection, and L. interrogans can evade the killing of phagocytes. However, little is known about the adaptation of L. interrogans during this process. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the interaction of pathogenic Leptospira and innate immunity, we employed microarray and comparative genomics analyzing the responses of L. interrogans to macrophage-derived cells. During this process, L. interrogans altered expressions of many genes involved in carbohydrate and lipid metabolism, energy production, signal transduction, transcription and translation, oxygen tolerance, and outer membrane proteins. Among them, the catalase gene expression was significantly up-regulated, suggesting it may contribute to resisting the oxidative pressure of the macrophages. The expressions of several major outer membrane protein (OMP genes (e.g., ompL1, lipL32, lipL41, lipL48 and ompL47 were dramatically down-regulated (10-50 folds, consistent with previous observations that the major OMPs are differentially regulated in vivo. The persistent down-regulations of these major OMPs were validated by immunoblotting. Furthermore, to gain initial insight into the gene regulation mechanisms in L. interrogans, we re-defined the transcription factors (TFs in the genome and identified the major OmpR TF gene (LB333 that is concurrently regulated with the major OMP genes, suggesting a potential role of LB333 in OMPs regulation. CONCLUSIONS/SIGNIFICANCE: This is the first report on global responses of pathogenic Leptospira to innate immunity, which revealed that the down-regulation of the major OMPs may be an immune evasion strategy of L. interrogans, and a putative TF may be involved in governing these down-regulations. Alterations of the leptospiral OMPs up interaction with host antigen

  20. Differential Activity of Plasma and Vacuolar Membrane Transporters Contributes to Genotypic Differences in Salinity Tolerance in a Halophyte Species, Chenopodium quinoa

    Directory of Open Access Journals (Sweden)

    Edgar Bonales-Alatorre

    2013-04-01

    Full Text Available Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd., a facultative C3 halophyte species, can efficiently control the activity of slow (SV and fast (FV tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na+ is safely locked in the vacuole (Bonales-Alatorre et al. (2013 Plant Physiology. This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa. These include: (i a higher rate of Na+ exclusion from leaf mesophyll; (ii maintenance of low cytosolic Na+ levels; (iii better K+ retention in the leaf mesophyll; (iv a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v the ability to reduce the activity of SV and FV channels under saline conditions. These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species.

  1. Differential activity of plasma and vacuolar membrane transporters contributes to genotypic differences in salinity tolerance in a Halophyte Species, Chenopodium quinoa.

    Science.gov (United States)

    Bonales-Alatorre, Edgar; Pottosin, Igor; Shabala, Lana; Chen, Zhong-Hua; Zeng, Fanrong; Jacobsen, Sven-Erik; Shabala, Sergey

    2013-04-29

    Halophytes species can be used as a highly convenient model system to reveal key ionic and molecular mechanisms that confer salinity tolerance in plants. Earlier, we reported that quinoa (Chenopodium quinoa Willd.), a facultative C3 halophyte species, can efficiently control the activity of slow (SV) and fast (FV) tonoplast channels to match specific growth conditions by ensuring that most of accumulated Na+ is safely locked in the vacuole (Bonales-Alatorre et al. (2013) Plant Physiology). This work extends these finding by comparing the properties of tonoplast FV and SV channels in two quinoa genotypes contrasting in their salinity tolerance. The work is complemented by studies of the kinetics of net ion fluxes across the plasma membrane of quinoa leaf mesophyll tissue. Our results suggest that multiple mechanisms contribute towards genotypic differences in salinity tolerance in quinoa. These include: (i) a higher rate of Na+ exclusion from leaf mesophyll; (ii) maintenance of low cytosolic Na+ levels; (iii) better K+ retention in the leaf mesophyll; (iv) a high rate of H+ pumping, which increases the ability of mesophyll cells to restore their membrane potential; and (v) the ability to reduce the activity of SV and FV channels under saline conditions. These mechanisms appear to be highly orchestrated, thus enabling the remarkable overall salinity tolerance of quinoa species.

  2. Molecular chaperones in targeting misfolded proteins for ubiquitin-dependent degradation

    DEFF Research Database (Denmark)

    Kriegenburg, Franziska; Ellgaard, Lars; Hartmann-Petersen, Rasmus

    2012-01-01

    The accumulation of misfolded proteins presents a considerable threat to the health of individual cells and has been linked to severe diseases, including neurodegenerative disorders. Considering that, in nature, cells often are exposed to stress conditions that may lead to aberrant protein...... conformational changes, it becomes clear that they must have an efficient quality control apparatus to refold or destroy misfolded proteins. In general, cells rely on molecular chaperones to seize and refold misfolded proteins. If the native state is unattainable, misfolded proteins are targeted for degradation...... via the ubiquitin-proteasome system. The specificity of this proteolysis is generally provided by E3 ubiquitin-protein ligases, hundreds of which are encoded in the human genome. However, rather than binding the misfolded proteins directly, most E3s depend on molecular chaperones to recognize...

  3. Overexpression of a Plasma Membrane-Localized SbSRP-Like Protein Enhances Salinity and Osmotic Stress Tolerance in Transgenic Tobacco

    Directory of Open Access Journals (Sweden)

    Avinash Mishra

    2017-04-01

    Full Text Available An obligate halophyte, Salicornia brachiata grows in salt marshes and is considered to be a potential resource of salt- and drought-responsive genes. It is important to develop an understanding of the mechanisms behind enhanced salt tolerance. To increase this understanding, a novel SbSRP gene was cloned, characterized, over-expressed, and functionally validated in the model plant Nicotiana tabacum. The genome of the halophyte S. brachiata contains two homologs of an intronless SbSRP gene of 1,262 bp in length that encodes for a stress-related protein. An in vivo localization study confirmed that SbSRP is localized on the plasma membrane. Transgenic tobacco plants (T1 that constitutively over-express the SbSRP gene showed improved salinity and osmotic stress tolerance. In comparison to Wild Type (WT and Vector Control (VC plants, transgenic lines showed elevated relative water and chlorophyll content, lower malondialdehyde content, lower electrolyte leakage and higher accumulation of proline, free amino acids, sugars, polyphenols, and starch under abiotic stress treatments. Furthermore, a lower build-up of H2O2 content and superoxide-radicals was found in transgenic lines compared to WT and VC plants under stress conditions. Transcript expression of Nt-APX (ascorbate peroxidase, Nt-CAT (catalase, Nt-SOD (superoxide dismutase, Nt-DREB (dehydration responsive element binding factor, and Nt-AP2 (apetala2 genes was higher in transgenic lines under stress compared to WT and VC plants. The results suggested that overexpression of membrane-localized SbSRP mitigates salt and osmotic stress in the transgenic tobacco plant. It was hypothesized that SbSRP can be a transporter protein to transmit the environmental stimuli downward through the plasma membrane. However, a detailed study is required to ascertain its exact role in the abiotic stress tolerance mechanism. Overall, SbSRP is a potential candidate to be used for engineering salt and osmotic

  4. Co-overexpressing a plasma membrane and a vacuolar membrane sodium/proton antiporter significantly improves salt tolerance in transgenic Arabidopsis plants.

    Science.gov (United States)

    The Arabidopsis gene AtNHX1 encodes a vacuolar membrane bound sodium/proton (Sodium/Hydrogen) antiporter that transports sodium into the vacuole and exports hydrogen into the cytoplasm. The Arabidopsis gene SOS1 encodes a plasma membrane bound sodium/hydrogen antiporter that exports sodium to the ex...

  5. Overexpression of a maize plasma membrane intrinsic protein ZmPIP1;1 confers drought and salt tolerance in Arabidopsis.

    Science.gov (United States)

    Zhou, Lian; Zhou, Jing; Xiong, Yuhan; Liu, Chaoxian; Wang, Jiuguang; Wang, Guoqiang; Cai, Yilin

    2018-01-01

    Drought and salt stress are major abiotic stress that inhibit plants growth and development, here we report a plasma membrane intrinsic protein ZmPIP1;1 from maize and identified its function in drought and salt tolerance in Arabidopsis. ZmPIP1;1 was localized to the plasma membrane and endoplasmic reticulum in maize protoplasts. Treatment with PEG or NaCl resulted in induced expression of ZmPIP1;1 in root and leaves. Constitutive overexpression of ZmPIP1;1 in transgenic Arabidopsis plants resulted in enhanced drought and salt stress tolerance compared to wild type. A number of stress responsive genes involved in cellular osmoprotection in ZmPIP1;1 overexpression plants were up-regulated under drought or salt condition. ZmPIP1;1 overexpression plants showed higher activities of reactive oxygen species (ROS) scavenging enzymes such as catalase and superoxide dismutase, lower contents of stress-induced ROS such as superoxide, hydrogen peroxide and malondialdehyde, and higher levels of proline under drought and salt stress than did wild type. ZmPIP1;1 may play a role in drought and salt stress tolerance by inducing of stress responsive genes and increasing of ROS scavenging enzymes activities, and could provide a valuable gene for further plant breeding.

  6. Quality control of Photosystem II: the mechanisms for avoidance and tolerance of light and heat stresses are closely linked to membrane fluidity of the thylakoids

    Directory of Open Access Journals (Sweden)

    Yasusi Yamamoto

    2016-08-01

    Full Text Available When oxygenic photosynthetic organisms are exposed to excessive light and/or heat, Photosystem II is damaged and electron transport is blocked. In these events, reactive oxygen species, endogenous radicals and lipid peroxidation products generated by photochemical reaction and/or heat cause the damage. Regarding light stress, plants first dissipate excessive light energy captured by light-harvesting chlorophyll protein complexes as heat to avoid the hazards, but once light stress is unavoidable, they tolerate the stress by concentrating damage in a particular protein in photosystem II, i.e. the reaction-center binding D1 protein of Photosystem II. The damaged D1 is removed by specific proteases and replaced with a new copy produced through de novo synthesis (reversible photoinhibition. When light intensity becomes extremely high, irreversible aggregation of D1 occurs and thereby D1 turnover is prevented. Once the aggregated products accumulate in Photosystem II complexes, removal of them by proteases is difficult, and irreversible inhibition of Photosystem II takes place (irreversible photoinhibition. Important is that various aspects of both the reversible and irreversible photoinhibition are highly dependent on the membrane fluidity of the thylakoids. Heat stress-induced inactivation of photosystem II is an irreversible process, which may be also affected by the fluidity of the thylakoid membranes. Here I describe why the membrane fluidity is a key to regulate the avoidance and tolerance of Photosystem II on environmental stresses.

  7. Protein misfolding specifies recruitment to cytoplasmic inclusion bodies.

    Science.gov (United States)

    Bersuker, Kirill; Brandeis, Michael; Kopito, Ron R

    2016-04-25

    Inclusion bodies (IBs) containing aggregated disease-associated proteins and polyubiquitin (poly-Ub) conjugates are universal histopathological features of neurodegenerative diseases. Ub has been proposed to target proteins to IBs for degradation via autophagy, but the mechanisms that govern recruitment of ubiquitylated proteins to IBs are not well understood. In this paper, we use conditionally destabilized reporters that undergo misfolding and ubiquitylation upon removal of a stabilizing ligand to examine the role of Ub conjugation in targeting proteins to IBs that are composed of an N-terminal fragment of mutant huntingtin, the causative protein of Huntington's disease. We show that reporters are excluded from IBs in the presence of the stabilizing ligand but are recruited to IBs after ligand washout. However, we find that Ub conjugation is not necessary to target reporters to IBs. We also report that forced Ub conjugation by the Ub fusion degradation pathway is not sufficient for recruitment to IBs. Finally, we find that reporters and Ub conjugates are stable at IBs. These data indicate that compromised folding states, rather than conjugation to Ub, can specify recruitment to IBs. © 2016 Bersuker et al.

  8. Strain-dependent profile of misfolded prion protein aggregates.

    Science.gov (United States)

    Morales, Rodrigo; Hu, Ping Ping; Duran-Aniotz, Claudia; Moda, Fabio; Diaz-Espinoza, Rodrigo; Chen, Baian; Bravo-Alegria, Javiera; Makarava, Natallia; Baskakov, Ilia V; Soto, Claudio

    2016-02-15

    Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal manipulations. We show that PrP(Sc) aggregates distribute in a wide range of arrangements and the relative proportion of each species depends on the prion strain. We observed a direct correlation between the density of the predominant PrP(Sc) aggregates and the incubation periods for the strains studied. The relative presence of PrP(Sc) in fractions of different sucrose densities was indicative of the protein deposits present in the brain as analyzed by histology. Interestingly, no association was found between sensitivity to proteolytic degradation and aggregation profiles. Therefore, the organization of PrP molecules in terms of the density of aggregates generated may determine some of the particular strain properties, whereas others are independent from it. Our findings may contribute to understand the mechanisms of strain variation and the role of PrP(Sc) aggregates in prion-induced neurodegeneration.

  9. Development of an air bleeding technique and specific duration to improve the CO tolerance of proton-exchange membrane fuel cells

    International Nuclear Information System (INIS)

    Chung, Chen-Chung; Chen, Chiun-Hsun; Weng, De-Zheng

    2009-01-01

    This study investigated transient CO poisoning of a proton-exchange membrane fuel cell under either a fixed cell voltage or fixed current density. During CO poisoning tests, the cell performance decreases over time. Experiments were performed to identify which method yields better performance in CO poisoning tests. The results revealed that a change in cell voltage did not affect the stable polarization behavior after CO poisoning of the cell. On the other hand, a higher fixed current density yielded better tolerance of 52.7 ppm CO. The air bleeding technique was then applied using different timings for air introduction during CO poisoning tests. Air bleeding significantly improved the CO tolerance of the cell and recovered the performance after poisoning, regardless of the timing of air introduction. The effects of different anode catalyst materials on cell performance were also investigated during poisoning tests. Without air bleeding, a Pt-Ru alloy catalyst exhibited better CO tolerance than a pure Pt catalyst. However, the air bleeding technique can effectively increase the CO tolerance of cells regardless of the type of catalyst used.

  10. Krypton Derivatization of an O2 -Tolerant Membrane-Bound [NiFe] Hydrogenase Reveals a Hydrophobic Tunnel Network for Gas Transport.

    Science.gov (United States)

    Kalms, Jacqueline; Schmidt, Andrea; Frielingsdorf, Stefan; van der Linden, Peter; von Stetten, David; Lenz, Oliver; Carpentier, Philippe; Scheerer, Patrick

    2016-04-25

    [NiFe] hydrogenases are metalloenzymes catalyzing the reversible heterolytic cleavage of hydrogen into protons and electrons. Gas tunnels make the deeply buried active site accessible to substrates and inhibitors. Understanding the architecture and function of the tunnels is pivotal to modulating the feature of O2 tolerance in a subgroup of these [NiFe] hydrogenases, as they are interesting for developments in renewable energy technologies. Here we describe the crystal structure of the O2 -tolerant membrane-bound [NiFe] hydrogenase of Ralstonia eutropha (ReMBH), using krypton-pressurized crystals. The positions of the krypton atoms allow a comprehensive description of the tunnel network within the enzyme. A detailed overview of tunnel sizes, lengths, and routes is presented from tunnel calculations. A comparison of the ReMBH tunnel characteristics with crystal structures of other O2 -tolerant and O2 -sensitive [NiFe] hydrogenases revealed considerable differences in tunnel size and quantity between the two groups, which might be related to the striking feature of O2 tolerance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

    Science.gov (United States)

    Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

    2008-02-01

    Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

  12. Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

    Directory of Open Access Journals (Sweden)

    Humaira Adnan

    Full Text Available Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD, to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon, to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin containing genetically inactivated (± an N-terminal polyleucine tail A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF mutant (5-10x, F508delCFTR Golgi maturation (<10x, cell surface expression (20x and chloride transport (2x in F508del CFTR transfected cells and patient-derived F508delCFTR bronchiolar epithelia, without apparent cytopathology. These toxoids also increase glucocerobrosidase (GCC in N370SGCC Gaucher Disease fibroblasts (3x, another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

  13. Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

    Science.gov (United States)

    Adnan, Humaira; Zhang, Zhenbo; Park, Hyun-Joo; Tailor, Chetankumar; Che, Clare; Kamani, Mustafa; Spitalny, George; Binnington, Beth; Lingwood, Clifford

    2016-01-01

    Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin) containing genetically inactivated (± an N-terminal polyleucine tail) A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF) mutant (5-10x), F508delCFTR Golgi maturation (glucocerobrosidase (GCC) in N370SGCC Gaucher Disease fibroblasts (3x), another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

  14. IL-6 Inhibits Upregulation of Membrane-Bound TGF-β 1 on CD4+ T Cells and Blocking IL-6 Enhances Oral Tolerance.

    Science.gov (United States)

    Kuhn, Chantal; Rezende, Rafael Machado; M'Hamdi, Hanane; da Cunha, Andre Pires; Weiner, Howard L

    2017-02-01

    Oral administration of Ag induces regulatory T cells that express latent membrane-bound TGF-β (latency-associated peptide [LAP]) and have been shown to play an important role in the induction of oral tolerance. We developed an in vitro model to study modulation of LAP + on CD4 + T cells. The combination of anti-CD3 mAb, anti-CD28 mAb, and recombinant IL-2 induced expression of LAP on naive CD4 + T cells, independent of Foxp3 or exogenous TGF-β. In vitro generated CD4 + LAP + Foxp3 - T cells were suppressive in vitro, inhibiting proliferation of naive CD4 + T cells and IL-17A secretion by Th17 cells. Assessing the impact of different cytokines and neutralizing Abs against cytokines, we found that LAP induction was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNF-α. IL-6 abrogated the in vitro induction of CD4 + LAP + T cells by STAT3-dependent inhibition of Lrrc32 (glycoprotein A repetitions predominant [GARP]), the adapter protein that tethers TGF-β to the membrane. Oral tolerance induction was enhanced in mice lacking expression of IL-6R by CD4 + T cells and by treatment of wild-type mice with neutralizing anti-IL-6 mAb. These results suggest that proinflammatory cytokines interfere with oral tolerance induction and that blocking the IL-6 pathway is a potential strategy for enhancing oral tolerance in the setting of autoimmune and inflammatory diseases. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. IL-6 inhibits upregulation of membrane-bound TGF-beta 1 on CD4+ T cells and blocking IL-6 enhances oral tolerance

    Science.gov (United States)

    Kuhn, Chantal; Rezende, Rafael Machado; M'Hamdi, Hanane; da Cunha, Andre Pires; Weiner, Howard L.

    2016-01-01

    Oral administration of antigen induces regulatory T cells that express latent membrane-bound TGF-beta (LAP) and that have been shown to play an important role in the induction of oral tolerance. We developed an in vitro model to study modulation of LAP+ on CD4+ T cells. The combination of anti-CD3 mAb, anti-CD28 mAb and recombinant IL-2 induced expression of LAP on naïve CD4+ T cells, independent of FoxP3 or exogenous TGF-β. In vitro generated CD4+LAP+FoxP3− T cells were suppressive in vitro, inhibiting proliferation of naïve CD4+ T cells and IL-17A secretion by Th17 cells. Assessing the impact of different cytokines and neutralizing antibodies against cytokines we found that LAP induction was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNFα. IL-6 abrogated the in vitro induction of CD4+LAP+ T cells by STAT3 dependent inhibition of Lrrc32 (GARP), the adapter protein that tethers TGF-beta to the membrane. Oral tolerance induction was enhanced in mice lacking expression of IL-6R by CD4+ T cells and by treatment of wild-type mice with neutralizing anti-IL-6 mAb. These results suggest that pro-inflammatory cytokines interfere with oral tolerance induction and that blocking the IL-6 pathway is a potential strategy for enhancing oral tolerance in the setting of autoimmune and inflammatory diseases. PMID:28039301

  16. Rapid regulation of the plasma membrane H⁺-ATPase activity is essential to salinity tolerance in two halophyte species, Atriplex lentiformis and Chenopodium quinoa.

    Science.gov (United States)

    Bose, Jayakumar; Rodrigo-Moreno, Ana; Lai, Diwen; Xie, Yanjie; Shen, Wenbiao; Shabala, Sergey

    2015-02-01

    The activity of H(+)-ATPase is essential for energizing the plasma membrane. It provides the driving force for potassium retention and uptake through voltage-gated channels and for Na(+) exclusion via Na(+)/H(+) exchangers. Both of these traits are central to plant salinity tolerance; however, whether the increased activity of H(+)-ATPase is a constitutive trait in halophyte species and whether this activity is upregulated at either the transcriptional or post-translation level remain disputed. The kinetics of salt-induced net H(+), Na(+) and K(+) fluxes, membrane potential and AHA1/2/3 expression changes in the roots of two halophyte species, Atriplex lentiformis (saltbush) and Chenopodium quinoa (quinoa), were compared with data obtained from Arabidopsis thaliana roots. Intrinsic (steady-state) membrane potential values were more negative in A. lentiformis and C. quinoa compared with arabidopsis (-144 ± 3·3, -138 ± 5·4 and -128 ± 3·3 mV, respectively). Treatment with 100 mm NaCl depolarized the root plasma membrane, an effect that was much stronger in arabidopsis. The extent of plasma membrane depolarization positively correlated with NaCl-induced stimulation of vanadate-sensitive H(+) efflux, Na(+) efflux and K(+) retention in roots (quinoa > saltbush > arabidopsis). NaCl-induced stimulation of H(+) efflux was most pronounced in the root elongation zone. In contrast, H(+)-ATPase AHA transcript levels were much higher in arabidopsis compared with quinoa plants, and 100 mm NaCl treatment led to a further 3-fold increase in AHA1 and AHA2 transcripts in arabidopsis but not in quinoa. Enhanced salinity tolerance in the halophyte species studied here is not related to the constitutively higher AHA transcript levels in the root epidermis, but to the plant's ability to rapidly upregulate plasma membrane H(+)-ATPase upon salinity treatment. This is necessary for assisting plants to maintain highly negative membrane potential values and to

  17. Rapid regulation of the plasma membrane H+-ATPase activity is essential to salinity tolerance in two halophyte species, Atriplex lentiformis and Chenopodium quinoa

    Science.gov (United States)

    Bose, Jayakumar; Rodrigo-Moreno, Ana; Lai, Diwen; Xie, Yanjie; Shen, Wenbiao; Shabala, Sergey

    2015-01-01

    Background and Aims The activity of H+-ATPase is essential for energizing the plasma membrane. It provides the driving force for potassium retention and uptake through voltage-gated channels and for Na+ exclusion via Na+/H+ exchangers. Both of these traits are central to plant salinity tolerance; however, whether the increased activity of H+-ATPase is a constitutive trait in halophyte species and whether this activity is upregulated at either the transcriptional or post-translation level remain disputed. Methods The kinetics of salt-induced net H+, Na+ and K+ fluxes, membrane potential and AHA1/2/3 expression changes in the roots of two halophyte species, Atriplex lentiformis (saltbush) and Chenopodium quinoa (quinoa), were compared with data obtained from Arabidopsis thaliana roots. Key Results Intrinsic (steady-state) membrane potential values were more negative in A. lentiformis and C. quinoa compared with arabidopsis (−144 ± 3·3, −138 ± 5·4 and −128 ± 3·3 mV, respectively). Treatment with 100 mm NaCl depolarized the root plasma membrane, an effect that was much stronger in arabidopsis. The extent of plasma membrane depolarization positively correlated with NaCl-induced stimulation of vanadate-sensitive H+ efflux, Na+ efflux and K+ retention in roots (quinoa > saltbush > arabidopsis). NaCl-induced stimulation of H+ efflux was most pronounced in the root elongation zone. In contrast, H+-ATPase AHA transcript levels were much higher in arabidopsis compared with quinoa plants, and 100 mm NaCl treatment led to a further 3-fold increase in AHA1 and AHA2 transcripts in arabidopsis but not in quinoa. Conclusions Enhanced salinity tolerance in the halophyte species studied here is not related to the constitutively higher AHA transcript levels in the root epidermis, but to the plant’s ability to rapidly upregulate plasma membrane H+-ATPase upon salinity treatment. This is necessary for assisting plants to maintain highly negative

  18. Implications of permeation through intrinsic defects in graphene on the design of defect-tolerant membranes for gas separation.

    Science.gov (United States)

    Boutilier, Michael S H; Sun, Chengzhen; O'Hern, Sean C; Au, Harold; Hadjiconstantinou, Nicolas G; Karnik, Rohit

    2014-01-28

    Gas transport through intrinsic defects and tears is a critical yet poorly understood phenomenon in graphene membranes for gas separation. We report that independent stacking of graphene layers on a porous support exponentially decreases flow through defects. On the basis of experimental results, we develop a gas transport model that elucidates the separate contributions of tears and intrinsic defects on gas leakage through these membranes. The model shows that the pore size of the porous support and its permeance critically affect the separation behavior, and reveals the parameter space where gas separation can be achieved regardless of the presence of nonselective defects, even for single-layer membranes. The results provide a framework for understanding gas transport in graphene membranes and guide the design of practical, selectively permeable graphene membranes for gas separation.

  19. Establishment and application of a modified membrane-blot assay for Rhizomucor miehei lipases aimed at improving their methanol tolerance and thermostability.

    Science.gov (United States)

    He, Dong; Luo, Wen; Wang, Zhiyuan; Lv, Pengmei; Yuan, Zhenhong; Huang, Shaowei; Xv, Jingliang

    2017-07-01

    Directed evolution has been proved an effective way to improve the stability of proteins, but high throughput screening assays for directed evolution with simultaneous improvement of two or more properties are still rare. In this study, we aimed to establish a membrane-blot assay for use in the high-throughput screening of Rhizomucor miehei lipases (RMLs). With the assistance of the membrane-blot screening assay, a mutant E47K named G10 that showed improved thermal stability was detected in the first round of error-prone PCR. Using G10 as the parent, two variants G10-11 and G10-20 that showed improved thermal stability and methanol tolerance without loss of activity compared to the wild type RML were obtained. The T 50 60 -value of G10-11 and G10-20 increased by 12°C and 6.5°C, respectively. After incubation for 1h, the remaining residual activity of G10-11 and G10-20 was 63.45% and 74.33%, respectively, in 50% methanol, and 15.98% and 30.22%, respectively, in 80% methanol. Thus, we successfully developed a membrane-blot assay that could be used for the high-throughput screening of RMLs with improved thermostability and methanol tolerance. Based on our findings, we believe that our newly developed membrane-blot assay will have potential applications in directed evolution in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis?

    Science.gov (United States)

    Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Rouleau, Guy A

    2007-12-01

    The identification in 1993 of superoxide dismutase-1 (SOD1) mutations as the cause of 10 to 20% of familial amyotrophic lateral sclerosis cases, which represents 1 to 2% of all amyotrophic lateral sclerosis (ALS) cases, prompted a substantial amount of research into the mechanisms of SOD1-mediated toxicity. Recent experiments have demonstrated that oxidation of wild-type SOD1 leads to its misfolding, causing it to gain many of the same toxic properties as mutant SOD1. In vitro studies of oxidized/misfolded SOD1 and in vivo studies of misfolded SOD1 have indicated that these protein species are selectively toxic to motor neurons, suggesting that oxidized/misfolded SOD1 could lead to ALS even in individuals who do not carry an SOD1 mutation. It has also been reported that glial cells secrete oxidized/misfolded mutant SOD1 to the extracellular environment, where it can trigger the selective death of motor neurons, offering a possible explanation for the noncell autonomous nature of mutant SOD1 toxicity and the rapid progression of disease once the first symptoms develop. Therefore, considering that sporadic (SALS) and familial ALS (FALS) cases are clinically indistinguishable, the toxic properties of mutated SOD1 are similar to that of oxidized/misfolded wild-type SOD1 (wtSOD1), and secreted/extracellular misfolded SOD1 is selectively toxic to motor neurons, we propose that oxidized/misfolded SOD1 is the cause of most forms of classic ALS and should be a prime target for the design of ALS treatments.

  1. Dual Functional Small Molecule Probes as Fluorophore and Ligand for Misfolding Proteins

    OpenAIRE

    Zhang, Xueli; Ran, Chongzhao

    2013-01-01

    Misfolding of a protein is a destructive process for variety of diseases that include neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, Huntington disease, mad cow disease, amyotrophic lateral sclerosis (ALS), and frontal temporal dementia (FTD), and other non-CNS diseases such as diabetes, cystic fibrosis, and lysosomal storage diseases. Formation of various misfunctional large assembles of the misfolded protein is the primary consequence. To detect the formation of ...

  2. Protein misfolding and cellular stress in disease and ageing - Concepts and protocols

    Directory of Open Access Journals (Sweden)

    Carlo Alberto Redi

    2011-09-01

    Full Text Available To those readers that already got the Protein misfolding and disease volume, this new title can sound as an update or a second edition of the previous volume: well, this is not the case. To those colleagues that would like to enter the fascinating field of protein’s misfolding this new volume constitutes an excellent opportunity to be driven on the causes and mechanisms that are actually know to produce the misfolding. For both types of scientists this volume is a must: the subtitle already sounds as a warning since it reads concepts and protocols rather than methods and protocols. In other words, there is an entire section (part I, chapters 1-8 devoted to explain the concepts and the approaches we have gathered in these last years on the misfolding. These chapters are presented in the review style so that the relevant bibliographies are all there; in addition, this section is presenting the conceptual paradigma linking protein misfolding to ageing by conceiving the disease itself as premature ageing processes. Thus, the reader can take profit from this first part and become acquiented on the molecular effects brought about by protein misfolding at a cellular level and, generally speaking, on the pathogenetic mechanisms thereafter triggered by soluble prefibrillar aggregates...

  3. The membrane tethered transcription factor EcbZIP17 from finger millet promotes plant growth and enhances tolerance to abiotic stresses.

    Science.gov (United States)

    Ramakrishna, Chopperla; Singh, Sonam; Raghavendrarao, Sangala; Padaria, Jasdeep C; Mohanty, Sasmita; Sharma, Tilak Raj; Solanke, Amolkumar U

    2018-02-01

    The occurrence of various stresses, as the outcome of global climate change, results in the yield losses of crop plants. Prospecting of genes in stress tolerant plant species may help to protect and improve their agronomic performance. Finger millet (Eleusine coracana L.) is a valuable source of superior genes and alleles for stress tolerance. In this study, we isolated a novel endoplasmic reticulum (ER) membrane tethered bZIP transcription factor from finger millet, EcbZIP17. Transgenic tobacco plants overexpressing this gene showed better vegetative growth and seed yield compared with wild type (WT) plants under optimal growth conditions and confirmed upregulation of brassinosteroid signalling genes. Under various abiotic stresses, such as 250 mM NaCl, 10% PEG6000, 400 mM mannitol, water withdrawal, and heat stress, the transgenic plants showed higher germination rate, biomass, primary and secondary root formation, and recovery rate, compared with WT plants. The transgenic plants exposed to an ER stress inducer resulted in greater leaf diameter and plant height as well as higher expression of the ER stress-responsive genes BiP, PDIL, and CRT1. Overall, our results indicated that EcbZIP17 improves plant growth at optimal conditions through brassinosteroid signalling and provide tolerance to various environmental stresses via ER signalling pathways.

  4. Changes in the Sterol Composition of the Plasma Membrane Affect Membrane Potential, Salt Tolerance and the Activity of Multidrug Resistance Pumps in Saccharomyces cerevisiae

    Czech Academy of Sciences Publication Activity Database

    Kodedová, Marie; Sychrová, Hana

    2015-01-01

    Roč. 10, č. 9 (2015), e0139306 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) EE2.3.30.0025; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : Saccharomyces cerevisiae * ergosterol synthesis * multidrug resistance * membrane potential * diS-C3(3) assay Subject RIV: EE - Microbiology, Virology Impact factor: 3.057, year: 2015

  5. Effects of Cellular Pathway Disturbances on Misfolded Superoxide Dismutase-1 in Fibroblasts Derived from ALS Patients.

    Directory of Open Access Journals (Sweden)

    Isil Keskin

    Full Text Available Mutations in superoxide dismutase-1 (SOD1 are a common known cause of amyotrophic lateral sclerosis (ALS. The neurotoxicity of mutant SOD1s is most likely caused by misfolded molecular species, but disease pathogenesis is still not understood. Proposed mechanisms include impaired mitochondrial function, induction of endoplasmic reticulum stress, reduction in the activities of the proteasome and autophagy, and the formation of neurotoxic aggregates. Here we examined whether perturbations in these cellular pathways in turn influence levels of misfolded SOD1 species, potentially amplifying neurotoxicity. For the study we used fibroblasts, which express SOD1 at physiological levels under regulation of the native promoter. The cells were derived from ALS patients expressing 9 different SOD1 mutants of widely variable molecular characteristics, as well as from patients carrying the GGGGCC-repeat-expansion in C9orf72 and from non-disease controls. A specific ELISA was used to quantify soluble, misfolded SOD1, and aggregated SOD1 was analysed by western blotting. Misfolded SOD1 was detected in all lines. Levels were found to be much lower in non-disease control and the non-SOD1 C9orf72 ALS lines. This enabled us to validate patient fibroblasts for use in subsequent perturbation studies. Mitochondrial inhibition, endoplasmic reticulum stress or autophagy inhibition did not affect soluble misfolded SOD1 and in most cases, detergent-resistant SOD1 aggregates were not detected. However, proteasome inhibition led to uniformly large increases in misfolded SOD1 levels in all cell lines and an increase in SOD1 aggregation in some. Thus the ubiquitin-proteasome pathway is a principal determinant of misfolded SOD1 levels in cells derived both from patients and controls and a decline in activity with aging could be one of the factors behind the mid-to late-life onset of inherited ALS.

  6. Diminished self-chaperoning activity of the DeltaF508 mutant of CFTR results in protein misfolding.

    Directory of Open Access Journals (Sweden)

    Adrian W R Serohijos

    2008-02-01

    Full Text Available The absence of a functional ATP Binding Cassette (ABC protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR from apical membranes of epithelial cells is responsible for cystic fibrosis (CF. Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1. Biochemical and cell biological studies show that the DeltaF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the DeltaF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-DeltaF508 variants exhibited significantly higher folding probabilities than the original NBD1-DeltaF508, thereby partially rescuing folding ability of the NBD1-DeltaF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of

  7. Does acute led (Pb) contamination influence membrane fatty acid composition and freeze tolerance in intertidal blue mussels in arctic Greenland?

    DEFF Research Database (Denmark)

    Thyrring, Jakob; Juhl, Bodil Klein; Holmstrup, Martin

    2015-01-01

    In their natural habitats, organisms are exposed to multiple stressors. Heavy metal contamination stresses the cell membrane due to increased peroxidation of lipids. Likewise, sub-zero air temperatures potentially reduce membrane functionality in ectothermal animals. We tested if acute lead (Pb......) exposure for 7 days would influence survival in intertidal blue mussels (Mytilus edulis) after exposure to realistic sub-zero air temperatures. A full factorial experiment with five tissue Pb concentrations between 0 and 3500 lg Pb/g and six sub-zero temperatures from 0 to -17 °C were used to test...

  8. Effects of acclimation temperature on thermal tolerance and membrane phospholipid composition in the fruit fly Drosophila melanogaster

    Czech Academy of Sciences Publication Activity Database

    Overgaard, J.; Tomčala, Aleš; Sorensen, J. G.; Holmstrup, M.; Krogh, P. H.; Šimek, Petr; Košťál, Vladimír

    2008-01-01

    Roč. 54, č. 3 (2008), s. 619-629 ISSN 0022-1910 R&D Projects: GA ČR GA206/07/0269 Institutional research plan: CEZ:AV0Z50070508 Keywords : homeoviscous adaptation * membrane phospholipid * PE Subject RIV: ED - Physiology Impact factor: 2.155, year: 2008

  9. Metagenomic identification of a novel salt tolerance gene from the human gut microbiome which encodes a membrane protein with homology to a brp/blh-family β-carotene 15,15'-monooxygenase.

    Directory of Open Access Journals (Sweden)

    Eamonn P Culligan

    Full Text Available The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane.

  10. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.

    Science.gov (United States)

    Ciechanover, Aaron; Kwon, Yong Tae

    2015-03-13

    Mammalian cells remove misfolded proteins using various proteolytic systems, including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated autophagy (CMA) and macroautophagy. The majority of misfolded proteins are degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated, unfolded and cleaved into small peptides when passing through the narrow chamber of the proteasome. The substrates that expose a specific degradation signal, the KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA. Aggregation-prone substrates resistant to both the UPS and the CMA can be degraded by macroautophagy, in which cargoes are segregated into autophagosomes before degradation by lysosomal hydrolases. Although most misfolded and aggregated proteins in the human proteome can be degraded by cellular protein quality control, some native and mutant proteins prone to aggregation into β-sheet-enriched oligomers are resistant to all known proteolytic pathways and can thus grow into inclusion bodies or extracellular plaques. The accumulation of protease-resistant misfolded and aggregated proteins is a common mechanism underlying protein misfolding disorders, including neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), prion diseases and Amyotrophic Lateral Sclerosis (ALS). In this review, we provide an overview of the proteolytic pathways in neurons, with an emphasis on the UPS, CMA and macroautophagy, and discuss the role of protein quality control in the degradation of pathogenic proteins in neurodegenerative diseases. Additionally, we examine existing putative therapeutic strategies to efficiently remove cytotoxic proteins from degenerating neurons.

  11. Protein misfolding and disease: from the test tube to the organism.

    Science.gov (United States)

    Luheshi, Leila M; Crowther, Damian C; Dobson, Christopher M

    2008-02-01

    Protein misfolding is the underlying cause of many highly debilitating disorders ranging from Alzheimer's Disease to Cystic Fibrosis. Great strides have been made recently in understanding what causes proteins to misfold, primarily through the use of biophysical and computational techniques that enable systematic and quantitative analysis of the effects of a range of different perturbations in proteins. Correlation of the results of such analyses with observations made in animal models of disease has however been limited by their seemingly irreconcilable differences in methodology and scope. Several recent studies have however begun to overcome this limitation by combining the two approaches. This strategy has made it possible to investigate many of the consequences of protein misfolding in vivo, ranging from disease pathogenesis to epigenetic regulation, in the context of the fundamental physico-chemical principles derived from extensive and highly detailed studies undertaken in vitro.

  12. Protein misfolding, amyotrophic lateral sclerosis and guanabenz: protocol for a phase II RCT with futility design (ProMISe trial).

    Science.gov (United States)

    Bella, Eleonora Dalla; Tramacere, Irene; Antonini, Giovanni; Borghero, Giuseppe; Capasso, Margherita; Caponnetto, Claudia; Chiò, Adriano; Corbo, Massimo; Eleopra, Roberto; Filosto, Massimiliano; Giannini, Fabio; Granieri, Enrico; Bella, Vincenzo La; Lunetta, Christian; Mandrioli, Jessica; Mazzini, Letizia; Messina, Sonia; Monsurrò, Maria Rosaria; Mora, Gabriele; Riva, Nilo; Rizzi, Romana; Siciliano, Gabriele; Silani, Vincenzo; Simone, Isabella; Sorarù, Gianni; Volanti, Paolo; Lauria, Giuseppe

    2017-08-11

    Recent studies suggest that endoplasmic reticulum stress may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS) through an altered regulation of the proteostasis, the cellular pathway-balancing protein synthesis and degradation. A key mechanism is thought to be the dephosphorylation of eIF2α, a factor involved in the initiation of protein translation. Guanabenz is an alpha-2-adrenergic receptor agonist safely used in past to treat mild hypertension and is now an orphan drug. A pharmacological action recently discovered is its ability to modulate the synthesis of proteins by the activation of translational factors preventing misfolded protein accumulation and endoplasmic reticulum overload. Guanabenz proved to rescue motoneurons from misfolding protein stress both in in vitro and in vivo ALS models, making it a potential disease-modifying drug in patients. It is conceivable investigating whether its neuroprotective effects based on the inhibition of eIF2α dephosphorylation can change the progression of ALS. Protocolised Management In Sepsis is a multicentre, randomised, double-blind, placebo-controlled phase II clinical trial with futility design. We will investigate clinical outcomes, safety, tolerability and biomarkers of neurodegeneration in patients with ALS treated with guanabenz or riluzole alone for 6 months. The primary aim is to test if guanabenz can reduce the proportion of patients progressed to a higher stage of disease at 6 months compared with their baseline stage as measured by the ALS Milano-Torino Staging (ALS-MITOS) system and to the placebo group. Secondary aims are safety, tolerability and change in at least one biomarker of neurodegeneration in the guanabenz arm compared with the placebo group. Findings will provide reliable data on the likelihood that guanabenz can slow the course of ALS in a phase III trial. The study protocol was approved by the Ethics Committee of IRCCS 'Carlo Besta Foundation' of Milan

  13. Transgenic banana plants overexpressing a native plasma membrane aquaporin MusaPIP1;2 display high tolerance levels to different abiotic stresses.

    Science.gov (United States)

    Sreedharan, Shareena; Shekhawat, Upendra K S; Ganapathi, Thumballi R

    2013-10-01

    Water transport across cellular membranes is regulated by a family of water channel proteins known as aquaporins (AQPs). As most abiotic stresses like suboptimal temperatures, drought or salinity result in cellular dehydration, it is imperative to study the cause-effect relationship between AQPs and the cellular consequences of abiotic stress stimuli. Although plant cells have a high isoform diversity of AQPs, the individual and integrated roles of individual AQPs in optimal and suboptimal physiological conditions remain unclear. Herein, we have identified a plasma membrane intrinsic protein gene (MusaPIP1;2) from banana and characterized it by overexpression in transgenic banana plants. Cellular localization assay performed using MusaPIP1;2::GFP fusion protein indicated that MusaPIP1;2 translocated to plasma membrane in transformed banana cells. Transgenic banana plants overexpressing MusaPIP1;2 constitutively displayed better abiotic stress survival characteristics. The transgenic lines had lower malondialdehyde levels, elevated proline and relative water content and higher photosynthetic efficiency as compared to equivalent controls under different abiotic stress conditions. Greenhouse-maintained hardened transgenic plants showed faster recovery towards normal growth and development after cessation of abiotic stress stimuli, thereby underlining the importance of these plants in actual environmental conditions wherein the stress stimuli is often transient but severe. Further, transgenic plants where the overexpression of MusaPIP1;2 was made conditional by tagging it with a stress-inducible native dehydrin promoter also showed similar stress tolerance characteristics in in vitro and in vivo assays. Plants developed in this study could potentially enable banana cultivation in areas where adverse environmental conditions hitherto preclude commercial banana cultivation. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons

  14. Osmotic tolerance of avian spermatozoa: Influence of time, temperature, cryoprotectant and membrane ion pump function on sperm viability

    Science.gov (United States)

    Blanco, J.M.; Long, J.A.; Gee, G.; Donoghue, A.M.; Wildt, D.E.

    2008-01-01

    Potential factors influencing sperm survival under hypertonic conditions were evaluated in the Sandhill crane (Grus canadensis) and turkey (Meleagridis gallopavo). Sperm osmotolerance (300-3000 mOsm/kg) was evaluated after: (1) equilibration times of 2, 10, 45 and 60 min at 4 ?C versus 21 ?C; (2) pre-equilibrating with dimethylacetamide (DMA) or dimethylsulfoxide (Me2SO) at either 4 ?C or 21 ?C; and (3) inhibition of the Na+/K+ and the Na+/H+ antiporter membrane ionic pumps. Sperm viability was assessed using the eosin-nigrosin live/dead stain. Species-specific differences occurred in response to hypertonic conditions with crane sperm remaining viable under extreme hypertonicity (3000 mOsm/kg), whereas turkey sperm viability was compromised with only slightly hypertonic (500 mOsm/kg) conditions. The timing of spermolysis under hypertonic conditions was also species-specific, with a shorter interval for turkey (2 min) than crane (10 min) sperm. Turkey sperm osmotolerance was slightly improved by lowering the incubation temperature from 21 to 4 ?C. Pre-equilibrating sperm with DMA reduced the incidence of hypertonic spermolysis only in the crane, at both room and refrigeration temperature. Inhibiting the Na+/K+ and the Na+/H+ antiporter membrane ion pumps did not impair resistance of crane and turkey spermatozoa to hypertonic stress; pump inhibition actually increased turkey sperm survival compared to control sperm. Results demonstrate marked species specificity in osmotolerance between crane and turkey sperm, as well as in the way temperature and time of exposure affect sperm survival under hypertonic conditions. Differences are independent of the role of osmotic pumps in these species.

  15. Why do alpha-beta parallel proteins, like flavodoxins, form misfolded off-pathway intermediates?

    NARCIS (Netherlands)

    Nabuurs, S.M.

    2009-01-01

    The question: “Why do α-β parallel proteins, like flavodoxins, form misfolded off-pathway
    intermediates?" is the main subject of this thesis. A. vinelandii apoflavodoxin is chosen as protein
    of interest as it is a representative of α-β parallel proteins, which are widely prevalent in

  16. Activity and Stability of Dispersed Multi Metallic Pt-based Catalysts for CO Tolerance in Proton Exchange Membrane Fuel Cell Anodes.

    Science.gov (United States)

    Hassan, Ayaz; Ticianelli, Edson A

    2018-01-01

    Studies aiming at improving the activity and stability of dispersed W and Mo containing Pt catalysts for the CO tolerance in proton exchange membrane fuel cell (PEMFC) anodes are revised for the following catalyst systems: (1) a carbon supported PtMo electrocatalyst submitted to heat treatments; (2) Pt and PtMo nanoparticles deposited on carbon-supported molybdenum carbides (Mo2C/C); (3) ternary and quaternary materials formed by PtMoFe/C, PtMoRu/C and PtMoRuFe/C and; (4) Pt nanoparticles supported on tungsten carbide/carbon catalysts and its parallel evaluation with carbon supported PtW catalyst. The heat-treated (600 oC) Pt-Mo/C catalyst showed higher hydrogen oxidation activity in the absence and in the presence of CO and better stability, compared to all other Mo-containing catalysts. PtMoRuFe, PtMoFe, PtMoRu supported on carbon and Pt supported on Mo2C/C exhibited similar CO tolerances but better stability, as compared to as-prepared PtMo supported on carbon. Among the tungsten-based catalysts, tungsten carbide supported Pt catalyst showed reasonable performance and reliable stability in comparison to simple carbon supported PtW catalyst, though an uneven level of catalytic activity towards H2 oxidation in presence of CO is observed for the former as compared to Mo containing catalyst. However, a small dissolution of Mo, Ru, Fe and W from the anodes and their migration toward cathodes during the cell operation is observed. These results indicate that the fuel cell performance and stability has been improved but not yet totally resolved.

  17. Activity and Stability of Dispersed Multi Metallic Pt-based Catalysts for CO Tolerance in Proton Exchange Membrane Fuel Cell Anodes

    Directory of Open Access Journals (Sweden)

    AYAZ HASSAN

    2018-04-01

    Full Text Available ABSTRACT Studies aiming at improving the activity and stability of dispersed W and Mo containing Pt catalysts for the CO tolerance in proton exchange membrane fuel cell (PEMFC anodes are revised for the following catalyst systems: (1 a carbon supported PtMo electrocatalyst submitted to heat treatments; (2 Pt and PtMo nanoparticles deposited on carbon-supported molybdenum carbides (Mo2C/C; (3 ternary and quaternary materials formed by PtMoFe/C, PtMoRu/C and PtMoRuFe/C and; (4 Pt nanoparticles supported on tungsten carbide/carbon catalysts and its parallel evaluation with carbon supported PtW catalyst. The heat-treated (600 oC Pt-Mo/C catalyst showed higher hydrogen oxidation activity in the absence and in the presence of CO and better stability, compared to all other Mo-containing catalysts. PtMoRuFe, PtMoFe, PtMoRu supported on carbon and Pt supported on Mo2C/C exhibited similar CO tolerances but better stability, as compared to as-prepared PtMo supported on carbon. Among the tungsten-based catalysts, tungsten carbide supported Pt catalyst showed reasonable performance and reliable stability in comparison to simple carbon supported PtW catalyst, though an uneven level of catalytic activity towards H2 oxidation in presence of CO is observed for the former as compared to Mo containing catalyst. However, a small dissolution of Mo, Ru, Fe and W from the anodes and their migration toward cathodes during the cell operation is observed. These results indicate that the fuel cell performance and stability has been improved but not yet totally resolved.

  18. High alkaline tolerant electrolyte membrane with improved conductivity and mechanical strength via lithium chloride/dimethylacetamide dissolved microcrystalline cellulose for Zn-Air batteries

    International Nuclear Information System (INIS)

    Zhang, Yuansong; Li, Cong; Cai, Xiaoxia; Yao, Jinshui; Li, Mei; Zhang, Xian; Liu, Qinze

    2016-01-01

    LiCl/DMAc (dimethylacetamide) solution dissolved microcrystalline cellulose (LD-MCC) showed potential benefits to the alkaline solid polymer electrolyte (ASPE). High alkali tolerance (up to 70 wt% KOH loading), remarkable improvements in ionic conductivity (from 0.018 S cm −1 to 0.153 S cm −1 ) and mechanical properties (3-fold increase in tensile strength from 0.28 MPa to 0.76 MPa) were achieved just via an incorporation of 5 wt% of LD-MCC into the ASPE matrix. Wide-angle X-ray diffraction indicated that LD-MCC entrapped KOH and hindered its aggregation. X-ray Energy Dispersive Spectrometer revealed that K + was preferentially located on the LD-MCC surfaces rather than the polymeric matrix. Scanning Electron Microscopy of freeze-dry sample demonstrated a submicro-porous morphology with reduced average pore size (175 nm) after the incorporation of LD-MCC in ASPE matrix. The incorporated LD-MCC acted as KOH stabilizer, hydrophilicity agent and OH − transport media. Distinct micro-structures before and after the incorporation of LD-MCC were investigated to reveal the special role of LD-MCC in the performance improvement of ASPE membrane.

  19. Infectious Tolerance

    OpenAIRE

    Jonuleit, Helmut; Schmitt, Edgar; Kakirman, Hacer; Stassen, Michael; Knop, Jürgen; Enk, Alexander H.

    2002-01-01

    Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, ...

  20. Kosmotropic anions promote conversion of recombinant prion protein into a PrPSc-like misfolded form.

    Directory of Open Access Journals (Sweden)

    Rodrigo Diaz-Espinoza

    Full Text Available Prions are self-propagating proteins involved in transmissible spongiform encephalopaties in mammals. An aberrant conformation with amyloid-like features of a cell surface protein, termed prion protein (PrP, is thought to be the essential component of the infectious particle, though accessory co-factor molecules such as lipids and nucleotides may be involved. The cellular co-factors and environmental conditions implicated in PrP misfolding are not completely understood. To address this issue, several studies have been done inducing misfolding of recombinant PrP (recPrP into classical amyloid structures using partially denaturing conditions. In this work, we report that misfolding of recPrP into PrP(Sc-like aggregates can be induced by simply incubating the protein in the presence of kosmotropic salts at concentrations that are known to retain or increase the stability of the protein. We used a simple experimental reaction (protein, buffer and salts submitted to agitation/incubation cycles at physiological temperature and pH. The formation of protease resistant-recPrP was time and salt-concentration dependent and required the presence of kosmotropic anions such as F(- or SO(4(-2. The molecular weights of the protease resistant recPrP fragments are reminiscent of those found in degradation assays of bona fide PrP(Sc. The aggregates also exhibited PrP(Sc-like ultrastructural features including rod-shape morphology under electron microscope, high beta-sheet content and thioflavin-T positive signal. The formation of recPrP aggregates with PrP(Sc biochemical features under conditions closer to physiological in the absence of organic co-factor molecules provides a simple setup that may prove helpful to understand the molecular mechanism of PrP misfolding.

  1. An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis

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    Melissa S Rotunno

    2013-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder that targets motor neurons, leading to paralysis and death within a few years of disease onset. While several genes have been linked to the inheritable, or familial, form of ALS, much less is known about the cause(s of sporadic ALS, which accounts for approximately 90% of ALS cases. Due to the clinical similarities between familial and sporadic ALS, it is plausible that both forms of the disease converge on a common pathway and, therefore, involve common factors. Recent evidence suggests the Cu,Zn-superoxide dismutase (SOD1 protein to be one such factor that is common to both sporadic and familial ALS. In 1993, mutations were uncovered in SOD1 that represent the first known genetic cause of familial ALS. While the exact mechanism of mutant-SOD1 toxicity is still not known today, most evidence points to a gain of toxic function that stems, at least in part, from the propensity of this protein to misfold. In the wild-type SOD1 protein, non-genetic perturbations such as metal depletion, disruption of the quaternary structure, and oxidation, can also induce SOD1 to misfold. In fact, these aforementioned post-translational modifications cause wild-type SOD1 to adopt a toxic conformation that is similar to familial ALS-linked SOD1 variants. These observations, together with the detection of misfolded wild-type SOD1 within human post-mortem sporadic ALS samples, have been used to support the controversial hypothesis that misfolded forms of wild-type SOD1 contribute to sporadic ALS pathogenesis. In this review, we present data from the literature that both support and contradict this hypothesis. We also discuss SOD1 as a potential therapeutic target for both familial and sporadic ALS.

  2. Histochemical approaches to assess cell-to-cell transmission of misfolded proteins in neurodegenerative diseases

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    G. Natale

    2013-03-01

    Full Text Available Formation, aggregation and transmission of abnormal proteins are common features in neurodegenerative disorders including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. The mechanisms underlying protein alterations in neurodegenerative diseases remain controversial. Novel findings highlighted altered protein clearing systems as common biochemical pathways which generate protein misfolding, which in turn causes protein aggregation and protein spreading. In fact, proteinaceous aggregates are prone to cell-to-cell propagation. This is reminiscent of what happens in prion disorders, where the prion protein misfolds thus forming aggregates which spread to neighbouring cells. For this reason, the term prionoids is currently used to emphasize how several misfolded proteins are transmitted in neurodegenerative diseases following this prion-like pattern. Histochemical techniques including the use of specific antibodies covering both light and electron microscopy offer a powerful tool to describe these phenomena and investigate specific molecular steps. These include: prion like protein alterations; glycation of prion-like altered proteins to form advanced glycation end-products (AGEs; mechanisms of extracellular secretion; interaction of AGEs with specific receptors placed on neighbouring cells (RAGEs. The present manuscript comments on these phenomena aimed to provide a consistent scenario of the available histochemical approaches to dissect each specific step.

  3. Early Delivery of Misfolded PrP from ER to Lysosomes by Autophagy

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    Cortes, Constanza J.; Qin, Kefeng; Norstrom, Eric M.; Green, William N.; Bindokas, Vytautas P.; Mastrianni, James A.

    2013-01-01

    Prion diseases are linked to the accumulation of a misfolded isoform (PrPSc) of prion protein (PrP). Evidence suggests that lysosomes are degradation endpoints and sites of the accumulation of PrPSc. We questioned whether lysosomes participate in the early quality control of newly generated misfolded PrP. We found PrP carrying the disease-associated T182A mutation (Mut-PrP) was delivered to lysosomes in a Golgi-independent manner. Time-lapse live cell imaging revealed early formation and uptake of GFP-tagged Mut-PrP aggregates into LysoTracker labeled vesicles. Compared with Wt-PrP, Mut-PrP expression was associated with an elevation in several markers of the autophagy-lysosomal pathway, and it extensively colocalized with the autophagosome-specific marker, LC3B. In autophagy deficient (ATG5−/−) mouse embryonic fibroblasts, or in normal cells treated with the autophagy-inhibitor 3-MA, Mut-PrP colocalization with lysosomes was reduced to a similar extent. Additionally, 3-MA selectively impaired the degradation of insoluble Mut-PrP, resulting in an increase in protease-resistant PrP, whereas the induction of autophagy by rapamycin reduced it. These findings suggest that autophagy might function as a quality control mechanism to limit the accumulation of misfolded PrP that normally leads to the generation of PrPSc. PMID:24454378

  4. Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

    International Nuclear Information System (INIS)

    Haigh, Cathryn L.; Drew, Simon C.

    2015-01-01

    The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation

  5. Cavitation during the protein misfolding cyclic amplification (PMCA) method – The trigger for de novo prion generation?

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    Haigh, Cathryn L., E-mail: chaigh@unimelb.edu.au [Department of Pathology, The University of Melbourne, Victoria 3010 (Australia); Drew, Simon C., E-mail: sdrew@unimelb.edu.au [Florey Department of Neuroscience and Mental Health, The University of Melbourne, Victoria 3010 (Australia)

    2015-06-05

    The protein misfolding cyclic amplification (PMCA) technique has become a widely-adopted method for amplifying minute amounts of the infectious conformer of the prion protein (PrP). PMCA involves repeated cycles of 20 kHz sonication and incubation, during which the infectious conformer seeds the conversion of normally folded protein by a templating interaction. Recently, it has proved possible to create an infectious PrP conformer without the need for an infectious seed, by including RNA and the phospholipid POPG as essential cofactors during PMCA. The mechanism underpinning this de novo prion formation remains unknown. In this study, we first establish by spin trapping methods that cavitation bubbles formed during PMCA provide a radical-rich environment. Using a substrate preparation comparable to that employed in studies of de novo prion formation, we demonstrate by immuno-spin trapping that PrP- and RNA-centered radicals are generated during sonication, in addition to PrP-RNA cross-links. We further show that serial PMCA produces protease-resistant PrP that is oxidatively modified. We suggest a unique confluence of structural (membrane-mimetic hydrophobic/hydrophilic bubble interface) and chemical (ROS) effects underlie the phenomenon of de novo prion formation by PMCA, and that these effects have meaningful biological counterparts of possible relevance to spontaneous prion formation in vivo. - Highlights: • Sonication during PMCA generates free radicals at the surface of cavitation bubbles. • PrP-centered and RNA-centered radicals are formed in addition to PrP-RNA adducts. • De novo prions may result from ROS and structural constraints during cavitation.

  6. Characterization of Uranium Tolerance and Biomineralization Potential of Caulobacter crescentus

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    Park, D.

    2015-12-01

    Due to its high toxicity and mobility, U(VI) poses a major environmental threat to ecosystems. The ubiquitous aerobic bacterium Caulobacter cresecentus is an attractive candidate for U(VI) bioremediation because of its ability to survive in low-nutrient environments (5, 6), tolerate high U concentrations and mineralize U(VI) aerobically through the formation of uranyl phosphate (U-Pi) precipitates. Despite these attractive environmental properties, both a systems level understanding of the adaptive response pathways involved in U tolerance and the environmental conditions affecting the biomineralization process and stability of biogenic U-Pi minerals remain limited. By measuring changes in both mRNA and protein expression during exposure to high U levels, we have identified the core stress response pathways involved in U tolerance. Pathways associated with heat shock, lipospolysaccharide biosynthesis and transport, outer membrane lipoprotein transport and outermembrane assembly were highly induced at both the RNA and protein levels. Correspondingly, removal of integral components of proteolysis pathways including clpA, clpS and degP significantly reduced U tolerance under biomineralization conditions. Surprisingly, in contrast to many other heavy metals, U did not cause oxidative stress or DNA damage. Together, these analyses indicate that U predominately targets the outermembrane and causes mis-folding of both cytoplasmic and extracytoplasmic proteins. Efforts are currently underway to characterize the morphological and structural properties of biogenic U-Pi minerals and the environmental factors that influence their production and stability. Preliminary AFM studies suggest that U-Pi minerals formed under biomineralization conditions appear morphologically distinct from those formed abiotically between U(VI) and inorganic phosphate. Additionally, we observed that biomineralization tolerates a wide pH range (pH 6-9). Our long-range goal is the development of a

  7. Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

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    Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

    2017-10-06

    Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. A Bystander Mechanism Explains the Specific Phenotype of a Broadly Expressed Misfolded Protein.

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    Lauren Klabonski

    2016-12-01

    Full Text Available Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C.elegans protein DAF-28. DAF-28(R37C is broadly expressed, but only causes dysfunction in one specific neuron, ASI, leading to a distinct developmental phenotype. We find that this phenotype is caused by selective disruption of normal biogenesis of an unrelated endogenous protein, DAF-7/TGF-β. The combined deficiency of DAF-28 and DAF-7 biogenesis, but not of DAF-28 alone, explains the gain-of-function phenotype-deficient pro-growth signaling by the ASI neuron. Using functional, fluorescently-tagged protein, we find that, in animals with mutant DAF-28/IGF, the wild-type DAF-7/TGF-β is mislocalized to and accumulates in the proximal axon of the ASI neuron. Activation of two different branches of the unfolded protein response can modulate both the developmental phenotype and DAF-7 mislocalization in DAF-28(R37C animals, but appear to act through divergent mechanisms. Our finding that bystander targeting of TGF-β explains the phenotype caused by a folding mutation in an IGF-like protein suggests that, in conformational diseases, bystander misfolding may specify the distinct phenotypes caused by different folding mutations.

  9. The ER stress sensor PERK luminal domain functions as a molecular chaperone to interact with misfolded proteins

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    Wang, Peng; Li, Jingzhi; Sha, Bingdong

    2016-11-29

    PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins. The data strongly support the hypothesis that the PERK luminal domain can interact directly with misfolded proteins to induce ER stress signaling. To illustrate the mechanism by which the PERK luminal domain interacts with misfolded proteins, the crystal structure of the human PERK luminal domain was determined to 3.2 Å resolution. Two dimers of the PERK luminal domain constitute a tetramer in the asymmetric unit. Superimposition of the PERK luminal domain molecules indicated that the β-sandwich domain could adopt multiple conformations. It is hypothesized that the PERK luminal domain may utilize its flexible β-sandwich domain to recognize and interact with a broad range of misfolded proteins.

  10. TDP-43 or FUS-induced misfolded human wild-type SOD1 can propagate intercellularly in a prion-like fashion.

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    Pokrishevsky, Edward; Grad, Leslie I; Cashman, Neil R

    2016-03-01

    Amyotrophic lateral sclerosis (ALS), which appears to spread through the neuroaxis in a spatiotemporally restricted manner, is linked to heritable mutations in genes encoding SOD1, TDP-43, FUS, C9ORF72, or can occur sporadically without recognized genetic mutations. Misfolded human wild-type (HuWt) SOD1 has been detected in both familial and sporadic ALS patients, despite mutations in SOD1 accounting for only 2% of total cases. We previously showed that accumulation of pathological TDP-43 or FUS coexist with misfolded HuWtSOD1 in patient motor neurons, and can trigger its misfolding in cultured cells. Here, we used immunocytochemistry and immunoprecipitation to demonstrate that TDP-43 or FUS-induced misfolded HuWtSOD1 can propagate from cell-to-cell via conditioned media, and seed cytotoxic misfolding of endogenous HuWtSOD1 in the recipient cells in a prion-like fashion. Knockdown of SOD1 using siRNA in recipient cells, or incubation of conditioned media with misfolded SOD1-specific antibodies, inhibits intercellular transmission, indicating that HuWtSOD1 is an obligate seed and substrate of propagated misfolding. In this system, intercellular spread of SOD1 misfolding is not accompanied by transmission of TDP-43 or FUS pathology. Our findings argue that pathological TDP-43 and FUS may exert motor neuron pathology in ALS through the initiation of propagated misfolding of SOD1.

  11. Mathematical Modeling of Protein Misfolding Mechanisms in Neurological Diseases: A Historical Overview.

    Science.gov (United States)

    Carbonell, Felix; Iturria-Medina, Yasser; Evans, Alan C

    2018-01-01

    Protein misfolding refers to a process where proteins become structurally abnormal and lose their specific 3-dimensional spatial configuration. The histopathological presence of misfolded protein (MP) aggregates has been associated as the primary evidence of multiple neurological diseases, including Prion diseases, Alzheimer's disease, Parkinson's disease, and Creutzfeldt-Jacob disease. However, the exact mechanisms of MP aggregation and propagation, as well as their impact in the long-term patient's clinical condition are still not well understood. With this aim, a variety of mathematical models has been proposed for a better insight into the kinetic rate laws that govern the microscopic processes of protein aggregation. Complementary, another class of large-scale models rely on modern molecular imaging techniques for describing the phenomenological effects of MP propagation over the whole brain. Unfortunately, those neuroimaging-based studies do not take full advantage of the tremendous capabilities offered by the chemical kinetics modeling approach. Actually, it has been barely acknowledged that the vast majority of large-scale models have foundations on previous mathematical approaches that describe the chemical kinetics of protein replication and propagation. The purpose of the current manuscript is to present a historical review about the development of mathematical models for describing both microscopic processes that occur during the MP aggregation and large-scale events that characterize the progression of neurodegenerative MP-mediated diseases.

  12. α-Synuclein Immunotherapy Blocks Uptake and Templated Propagation of Misfolded α-Synuclein and Neurodegeneration

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    Hien T. Tran

    2014-06-01

    Full Text Available Accumulation of misfolded alpha-synuclein (α-syn into Lewy bodies (LBs and Lewy neurites (LNs is a major hallmark of Parkinson’s disease (PD and dementia with LBs (DLB. Recent studies showed that synthetic preformed fibrils (pffs recruit endogenous α-syn and induce LB/LN pathology in vitro and in vivo, thereby implicating propagation and cell-to-cell transmission of pathological α-syn as mechanisms for the progressive spread of LBs/LNs. Here, we demonstrate that α-syn monoclonal antibodies (mAbs reduce α-syn pff-induced LB/LN formation and rescue synapse/neuron loss in primary neuronal cultures by preventing both pff uptake and subsequent cell-to-cell transmission of pathology. Moreover, intraperitoneal (i.p. administration of mAb specific for misfolded α-syn into nontransgenic mice injected intrastriatally with α-syn pffs reduces LB/LN pathology, ameliorates substantia nigra dopaminergic neuron loss, and improves motor impairments. We conclude that α-syn antibodies could exert therapeutic effects in PD/DLB by blocking entry of pathological α-syn and/or its propagation in neurons.

  13. Misfolded Gβ is recruited to cytoplasmic dynein by Nudel for efficient clearance

    Institute of Scientific and Technical Information of China (English)

    Yihan Wan; Zhenye Yang; Jing Guo; Qiangge Zhang; Liyong Zeng; Wei Song; Yue Xiao; Xueliang Zhu

    2012-01-01

    The Gβγ heterodimer is an important signal transducer.Gβ,however,is prone to misfolding due to its requirement for Gγ and chaperones for proper folding.How cells dispose of misfolded Gβ (mfGβ) is not clear.Here,we showed that mfGβ was able to be polyubiquitinated and subsequently degraded by the proteasome.It was sequestered in aggresomes after the inhibition of the proteasome activity with MG132.Sustained activation of Gβγ signaling further elevated cellular levels of the ubiquitinated Gβ.Moreover,Nudel,a regulator of cytoplasmic dynein,the microtubule minus end-directed motor,directly interacted with both the unubiquitinated and ubiquitinated mfGβ.Increasing the levels of both mfGβ and Nudel promoted the association of Gβ with both Nudel and dynein,resulting in robust aggresome formation in a dynein-dependent manner.Depletion of Nudel by RNAi reduced the dynein-associated mfGβ,impaired the MG132-induced aggresome formation,and markedly prolonged the half-life of nascent Gβ.Therefore,cytosolic mfGβ is recruited to dynein by Nudel and transported to the centrosome for rapid sequestration and degradation.Such a process not only eliminates mfGβ efficiently for the control of protein quality,but may also help to terminate the Gβγ signaling.

  14. Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.

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    Moudjou, Mohammed; Chapuis, Jérôme; Mekrouti, Mériem; Reine, Fabienne; Herzog, Laetitia; Sibille, Pierre; Laude, Hubert; Vilette, Didier; Andréoletti, Olivier; Rezaei, Human; Dron, Michel; Béringue, Vincent

    2016-07-07

    Prions are formed of misfolded assemblies (PrP(Sc)) of the variably N-glycosylated cellular prion protein (PrP(C)). In infected species, prions replicate by seeding the conversion and polymerization of host PrP(C). Distinct prion strains can be recognized, exhibiting defined PrP(Sc) biochemical properties such as the glycotype and specific biological traits. While strain information is encoded within the conformation of PrP(Sc) assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. Here, we investigated the specific role of PrP(C) glycosylation status. First, we developed an efficient protein misfolding cyclic amplification method using cells expressing the PrP(C) species of interest as substrate. Applying the technique to PrP(C) glycosylation mutants expressing cells revealed that neither PrP(C) nor PrP(Sc) glycoform stoichiometry was instrumental to PrP(Sc) formation and strainness perpetuation. Our study supports the view that strain properties, including PrP(Sc) glycotype are enciphered within PrP(Sc) structural backbone, not in the attached glycans.

  15. Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

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    Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

    2014-11-01

    Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

  16. Applying chaperones to protein-misfolding disorders: molecular chaperones against α-synuclein in Parkinson's disease.

    Science.gov (United States)

    Chaari, Ali; Hoarau-Véchot, Jessica; Ladjimi, Moncef

    2013-09-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the accumulation of a protein called α-synuclein (α-syn) into inclusions known as lewy bodies (LB) within neurons. This accumulation is also due to insufficient formation and activity of dopamine produced in certain neurons within the substantia nigra. Lewy bodies are the pathological hallmark of the idiopathic disorder and the cascade that allows α-synuclein to misfold, aggregate and form these inclusions has been the subject of intensive research. Targeting these early steps of oligomerization is one of the main therapeutic approaches in order to develop neurodegenerative-modifying agents. Because the folding and refolding of alpha synuclein is the key point of this cascade, we are interested in this review to summarize the role of some molecular chaperones proteins such as Hsp70, Hsp90 and small heat shock proteins (sHsp) and Hsp 104. Hsp70 and its co-chaperone, Hsp70 and small heat shock proteins can prevent neurodegeneration by preventing α-syn misfolding, oligomerization and aggregation in vitro and in Parkinson disease animal models. Hsp104 is able to resolve disordered protein aggregates and cross beta amyloid conformers. Together, these chaperones have a complementary effect and can be a target for therapeutic intervention in PD. Published by Elsevier B.V.

  17. Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Yasser Iturria-Medina

    2014-11-01

    Full Text Available Misfolded proteins (MP are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database. Furthermore, this model strongly supports a the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

  18. A SNARE-Like Superfamily Protein SbSLSP from the Halophyte Salicornia brachiata Confers Salt and Drought Tolerance by Maintaining Membrane Stability, K(+)/Na(+) Ratio, and Antioxidant Machinery.

    Science.gov (United States)

    Singh, Dinkar; Yadav, Narendra Singh; Tiwari, Vivekanand; Agarwal, Pradeep K; Jha, Bhavanath

    2016-01-01

    About 1000 salt-responsive ESTs were identified from an extreme halophyte Salicornia brachiata. Among these, a novel salt-inducible gene SbSLSP (Salicornia brachiata SNARE-like superfamily protein), showed up-regulation upon salinity and dehydration stress. The presence of cis-regulatory motifs related to abiotic stress in the putative promoter region supports our finding that SbSLSP gene is inducible by abiotic stress. The SbSLSP protein showed a high sequence identity to hypothetical/uncharacterized proteins from Beta vulgaris, Spinacia oleracea, Eucalyptus grandis, and Prunus persica and with SNARE-like superfamily proteins from Zostera marina and Arabidopsis thaliana. Bioinformatics analysis predicted a clathrin adaptor complex small-chain domain and N-myristoylation site in the SbSLSP protein. Subcellular localization studies indicated that the SbSLSP protein is mainly localized in the plasma membrane. Using transgenic tobacco lines, we establish that overexpression of SbSLSP resulted in elevated tolerance to salt and drought stress. The improved tolerance was confirmed by alterations in a range of physiological parameters, including high germination and survival rate, higher leaf chlorophyll contents, and reduced accumulation of Na(+) ion and reactive oxygen species (ROS). Furthermore, overexpressing lines also showed lower water loss, higher cell membrane stability, and increased accumulation of proline and ROS-scavenging enzymes. Overexpression of SbSLSP also enhanced the transcript levels of ROS-scavenging and signaling enzyme genes. This study is the first investigation of the function of the SbSLSP gene as a novel determinant of salinity/drought tolerance. The results suggest that SbSLSP could be a potential candidate to increase salinity and drought tolerance in crop plants for sustainable agriculture in semi-arid saline soil.

  19. A SNARE-like superfamily protein SbSLSP from the halophyte Salicornia brachiata confers salt and drought tolerance by maintaining membrane stability, K+/Na+ ratio, and antioxidant machinery

    Directory of Open Access Journals (Sweden)

    Dinkar eSingh

    2016-06-01

    Full Text Available About 1000 salt-responsive ESTs were identified from an extreme halophyte Salicornia brachiata. Among these, a novel salt-inducible gene SbSLSP, (Salicornia brachiata SNARE-like superfamily protein showed up-regulation upon salinity and dehydration stress. The presence of cis-regulatory motifs related to abiotic stress in the putative promoter region supports our finding that SbSLSP gene is inducible by abiotic stress. The SbSLSP protein showed a high sequence identity to hypothetical/uncharacterised proteins from Beta vulgaris, Spinacia oleracea, Eucalyptus grandis and Prunus persica and with SNARE-like superfamily proteins from Zostera marina and Arabidopsis thaliana. Bioinformatics analysis predicted a clathrin adaptor complex small-chain domain and N-myristoylation site in the SbSLSP protein. Subcellular localisation studies indicated that the SbSLSP protein is mainly localised in the plasma membrane. Using transgenic tobacco lines, we establish that overexpression of SbSLSP resulted in elevated tolerance to salt and drought stress. The improved tolerance was confirmed by alterations in a range of physiological parameters, including high germination and survival rate, higher leaf chlorophyll contents, and reduced accumulation of Na+ ion and reactive oxygen species (ROS. Furthermore, overexpressing lines also showed lower water loss, higher cell membrane stability and increased accumulation of proline and ROS-scavenging enzymes. Overexpression of SbSLSP also enhanced the transcript levels of ROS-scavenging and signalling enzyme genes. This study is the first investigation of the function of the SbSLSP gene as a novel determinant of salinity/drought tolerance. The results suggest that SbSLSP could be a potential candidate to increase salinity and drought tolerance in crop plants for sustainable agriculture in semi-arid saline soil.

  20. Infectious Tolerance

    Science.gov (United States)

    Jonuleit, Helmut; Schmitt, Edgar; Kakirman, Hacer; Stassen, Michael; Knop, Jürgen; Enk, Alexander H.

    2002-01-01

    Regulatory CD4+CD25+ T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4+ T cells by human CD25+ Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25+ Treg cells. Coactivation of CD25+ Treg cells with Treg cell–depleted CD4+ T cells results in anergized CD4+ T cells that in turn inhibit the activation of conventional, freshly isolated CD4+ T helper (Th) cells. This infectious suppressive activity, transferred from CD25+ Treg cells via cell contact, is cell contact–independent and partially mediated by soluble transforming growth factor (TGF)-β. The induction of suppressive properties in conventional CD4+ Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF-β in CD25+ Treg cell–induced immunosuppression. PMID:12119350

  1. GCK-MODY diabetes as a protein misfolding disease: the mutation R275C promotes protein misfolding, self-association and cellular degradation.

    Science.gov (United States)

    Negahdar, Maria; Aukrust, Ingvild; Molnes, Janne; Solheim, Marie H; Johansson, Bente B; Sagen, Jørn V; Dahl-Jørgensen, Knut; Kulkarni, Rohit N; Søvik, Oddmund; Flatmark, Torgeir; Njølstad, Pål R; Bjørkhaug, Lise

    2014-01-25

    GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C>T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (kcat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. Total fatty acid content of the plasma membrane of Saccharomyces cerevisiae is more responsible for ethanol tolerance than the degree of unsaturation.

    Science.gov (United States)

    Kim, Hyun-Soo; Kim, Na-Rae; Choi, Wonja

    2011-03-01

    The effect of change in unsaturated fatty acid composition on ethanol tolerance in Saccharomyces cerevisiae overexpressing ScOLE1 (∆9 fatty acid desaturase gene of S. cerevisiae), CaFAD2 (∆12 fatty acid desaturase gene of Candida albicans), or CaFAD3 (ω3 fatty acid desaturase gene of C. albicans) was examined. ScOLE1 over-expression increased the total unsaturated fatty acid content and enhanced ethanol tolerance, compared with a control strain. In contrast, overexpression of CaFAD2 and CaFAD3, which led to production of linoleic acid (18:2) and α-linolenic acid (18:3), respectively, neither changed total unsaturated fatty acids nor enhanced ethanol tolerance. The total unsaturated fatty acid content rather than the degree of unsaturation is thus an important factor for ethanol tolerance.

  3. AAV exploits subcellular stress associated with inflammation, endoplasmic reticulum expansion, and misfolded proteins in models of cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Jarrod S Johnson

    2011-05-01

    Full Text Available Barriers to infection act at multiple levels to prevent viruses, bacteria, and parasites from commandeering host cells for their own purposes. An intriguing hypothesis is that if a cell experiences stress, such as that elicited by inflammation, endoplasmic reticulum (ER expansion, or misfolded proteins, then subcellular barriers will be less effective at preventing viral infection. Here we have used models of cystic fibrosis (CF to test whether subcellular stress increases susceptibility to adeno-associated virus (AAV infection. In human airway epithelium cultured at an air/liquid interface, physiological conditions of subcellular stress and ER expansion were mimicked using supernatant from mucopurulent material derived from CF lungs. Using this inflammatory stimulus to recapitulate stress found in diseased airways, we demonstrated that AAV infection was significantly enhanced. Since over 90% of CF cases are associated with a misfolded variant of Cystic Fibrosis Transmembrane Conductance Regulator (ΔF508-CFTR, we then explored whether the presence of misfolded proteins could independently increase susceptibility to AAV infection. In these models, AAV was an order of magnitude more efficient at transducing cells expressing ΔF508-CFTR than in cells expressing wild-type CFTR. Rescue of misfolded ΔF508-CFTR under low temperature conditions restored viral transduction efficiency to that demonstrated in controls, suggesting effects related to protein misfolding were responsible for increasing susceptibility to infection. By testing other CFTR mutants, G551D, D572N, and 1410X, we have shown this phenomenon is common to other misfolded proteins and not related to loss of CFTR activity. The presence of misfolded proteins did not affect cell surface attachment of virus or influence expression levels from promoter transgene cassettes in plasmid transfection studies, indicating exploitation occurs at the level of virion trafficking or processing. Thus

  4. GCK-MODY diabetes associated with protein misfolding, cellular self-association and degradation.

    Science.gov (United States)

    Negahdar, Maria; Aukrust, Ingvild; Johansson, Bente B; Molnes, Janne; Molven, Anders; Matschinsky, Franz M; Søvik, Oddmund; Kulkarni, Rohit N; Flatmark, Torgeir; Njølstad, Pål Rasmus; Bjørkhaug, Lise

    2012-11-01

    GCK-MODY, dominantly inherited mild fasting hyperglycemia, has been associated with >600 different mutations in the glucokinase (GK)-encoding gene (GCK). When expressed as recombinant pancreatic proteins, some mutations result in enzymes with normal/near-normal catalytic properties. The molecular mechanism(s) of GCK-MODY due to these mutations has remained elusive. Here, we aimed to explore the molecular mechanisms for two such catalytically 'normal' GCK mutations (S263P and G264S) in the F260-L270 loop of GK. When stably overexpressed in HEK293 cells and MIN6 β-cells, the S263P- and G264S-encoded mutations generated misfolded proteins with an increased rate of degradation (S263P>G264S) by the protein quality control machinery, and a propensity to self-associate (G264S>S263P) and form dimers (SDS resistant) and aggregates (partly Triton X-100 insoluble), as determined by pulse-chase experiments and subcellular fractionation. Thus, the GCK-MODY mutations S263P and G264S lead to protein misfolding causing destabilization, cellular dimerization/aggregation and enhanced rate of degradation. In silico predicted conformational changes of the F260-L270 loop structure are considered to mediate the dimerization of both mutant proteins by a domain swapping mechanism. Thus, similar properties may represent the molecular mechanisms for additional unexplained GCK-MODY mutations, and may also contribute to the disease mechanism in other previously characterized GCK-MODY inactivating mutations. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Inactivation of Template-Directed Misfolding of Infectious Prion Protein by Ozone

    Science.gov (United States)

    Ding, Ning; Price, Luke M.; Braithwaite, Shannon L.; Balachandran, Aru; Belosevic, Miodrag

    2012-01-01

    Misfolded prions (PrPSc) are well known for their resistance to conventional decontamination processes. The potential risk of contamination of the water environment, as a result of disposal of specified risk materials (SRM), has raised public concerns. Ozone is commonly utilized in the water industry for inactivation of microbial contaminants and was tested in this study for its ability to inactivate prions (263K hamster scrapie = PrPSc). Treatment variables included initial ozone dose (7.6 to 25.7 mg/liter), contact time (5 s and 5 min), temperature (4°C and 20°C), and pH (pH 4.4, 6.0, and 8.0). Exposure of dilute suspensions of the infected 263K hamster brain homogenates (IBH) (0.01%) to ozone resulted in the in vitro destruction of the templating properties of PrPSc, as measured by the protein misfolding cyclic amplification (PMCA) assay. The highest levels of prion inactivation (≥4 log10) were observed with ozone doses of 13.0 mg/liter, at pH 4.4 and 20°C, resulting in a CT (the product of residual ozone concentration and contact time) value as low as 0.59 mg · liter−1 min. A comparison of ozone CT requirements among various pathogens suggests that prions are more susceptible to ozone degradation than some model bacteria and protozoa and that ozone treatment may be an effective solution for inactivating prions in water and wastewater. PMID:22138993

  6. ApoE4-specific Misfolded Intermediate Identified by Molecular Dynamics Simulations.

    Directory of Open Access Journals (Sweden)

    Benfeard Williams

    2015-10-01

    Full Text Available The increased risk of developing Alzheimer's disease (AD is associated with the APOE gene, which encodes for three variants of Apolipoprotein E, namely E2, E3, E4, differing only by two amino acids at positions 112 and 158. ApoE4 is known to be the strongest risk factor for AD onset, while ApoE3 and ApoE2 are considered to be the AD-neutral and AD-protective isoforms, respectively. It has been hypothesized that the ApoE isoforms may contribute to the development of AD by modifying the homeostasis of ApoE physiological partners and AD-related proteins in an isoform-specific fashion. Here we find that, despite the high sequence similarity among the three ApoE variants, only ApoE4 exhibits a misfolded intermediate state characterized by isoform-specific domain-domain interactions in molecular dynamics simulations. The existence of an ApoE4-specific intermediate state can contribute to the onset of AD by altering multiple cellular pathways involved in ApoE-dependent lipid transport efficiency or in AD-related protein aggregation and clearance. We present what we believe to be the first structural model of an ApoE4 misfolded intermediate state, which may serve to elucidate the molecular mechanism underlying the role of ApoE4 in AD pathogenesis. The knowledge of the structure for the ApoE4 folding intermediate provides a new platform for the rational design of alternative therapeutic strategies to fight AD.

  7. Accumulation of Misfolded SOD1 in Dorsal Root Ganglion Degenerating Proprioceptive Sensory Neurons of Transgenic Mice with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Javier Sábado

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is an adult-onset progressive neurodegenerative disease affecting upper and lower motoneurons (MNs. Although the motor phenotype is a hallmark for ALS, there is increasing evidence that systems other than the efferent MN system can be involved. Mutations of superoxide dismutase 1 (SOD1 gene cause a proportion of familial forms of this disease. Misfolding and aggregation of mutant SOD1 exert neurotoxicity in a noncell autonomous manner, as evidenced in studies using transgenic mouse models. Here, we used the SOD1G93A mouse model for ALS to detect, by means of conformational-specific anti-SOD1 antibodies, whether misfolded SOD1-mediated neurotoxicity extended to neuronal types other than MNs. We report that large dorsal root ganglion (DRG proprioceptive neurons accumulate misfolded SOD1 and suffer a degenerative process involving the inflammatory recruitment of macrophagic cells. Degenerating sensory axons were also detected in association with activated microglial cells in the spinal cord dorsal horn of diseased animals. As large proprioceptive DRG neurons project monosynaptically to ventral horn MNs, we hypothesise that a prion-like mechanism may be responsible for the transsynaptic propagation of SOD1 misfolding from ventral horn MNs to DRG sensory neurons.

  8. Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways.

    Science.gov (United States)

    Zilka, Norbert; Kazmerova, Zuzana; Jadhav, Santosh; Neradil, Peter; Madari, Aladar; Obetkova, Dominika; Bugos, Ondrej; Novak, Michal

    2012-03-07

    Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease.

  9. Interplay between Molecular Chaperones and the Ubiquitin-Proteasome System in Targeting of Misfolded Proteins for Degradation

    DEFF Research Database (Denmark)

    Poulsen, Esben Guldahl

    interacting with purified 26S proteasomes, and the subsequent characterization of two novel proteasome interacting proteins. The third study was aimed at analyzing the chaperone-assisted pathway leading to degradation of misfolded kinetochore proteins in S. pombe. In this study chaperones, E2s, E3s and DUBs...

  10. Erv14 cargo receptor participates in yeast salt tolerance via its interaction with the plasma-membrane Nha1 cation/proton antiporter

    Czech Academy of Sciences Publication Activity Database

    Rosas-Santiago, P.; Zimmermannová, Olga; Vera-Estrella, R.; Sychrová, Hana; Pantoja, O.

    2016-01-01

    Roč. 1858, č. 1 (2016), s. 67-74 ISSN 0005-2736 Institutional support: RVO:67985823 Keywords : Erv14p * Nha1p * protein–protein interaction * mislocalization * salt-tolerance * yeast Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.498, year: 2016

  11. Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.

    Science.gov (United States)

    Hantouche, Christine; Williamson, Brittany; Valinsky, William C; Solomon, Joshua; Shrier, Alvin; Young, Jason C

    2017-02-10

    Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Effect of fullerenol surface chemistry on nanoparticle binding-induced protein misfolding

    Science.gov (United States)

    Radic, Slaven; Nedumpully-Govindan, Praveen; Chen, Ran; Salonen, Emppu; Brown, Jared M.; Ke, Pu Chun; Ding, Feng

    2014-06-01

    Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation -- a common strategy for solubilizing and functionalizing fullerene -- on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and dynamics of ubiquitin. We found that all derivatives bound to the model protein. Specifically, the more hydrophilic nanoparticles with a higher number of hydroxyl groups bound to the surface of the protein via hydrogen bonds, which stabilized the protein without inducing large conformational changes in the protein structure. In contrast, fullerene derivatives with a smaller number of hydroxyl groups buried their hydrophobic surface inside the protein, thereby causing protein denaturation. Overall, our results revealed a distinct role of surface chemistry on nanoparticle-protein binding and binding-induced protein misfolding.Fullerene and its derivatives with different surface chemistry have great potential in biomedical applications. Accordingly, it is important to delineate the impact of these carbon-based nanoparticles on protein structure, dynamics, and subsequently function. Here, we focused on the effect of hydroxylation -- a common strategy for solubilizing and functionalizing fullerene -- on protein-nanoparticle interactions using a model protein, ubiquitin. We applied a set of complementary computational modeling methods, including docking and molecular dynamics simulations with both explicit and implicit solvent, to illustrate the impact of hydroxylated fullerenes on the structure and

  13. Genetic complexity in a Drosophila model of diabetes-associated misfolded human proinsulin.

    Science.gov (United States)

    Park, Soo-Young; Ludwig, Michael Z; Tamarina, Natalia A; He, Bin Z; Carl, Sarah H; Dickerson, Desiree A; Barse, Levi; Arun, Bharath; Williams, Calvin L; Miles, Cecelia M; Philipson, Louis H; Steiner, Donald F; Bell, Graeme I; Kreitman, Martin

    2014-02-01

    Drosophila melanogaster has been widely used as a model of human Mendelian disease, but its value in modeling complex disease has received little attention. Fly models of complex disease would enable high-resolution mapping of disease-modifying loci and the identification of novel targets for therapeutic intervention. Here, we describe a fly model of permanent neonatal diabetes mellitus and explore the complexity of this model. The approach involves the transgenic expression of a misfolded mutant of human preproinsulin, hINS(C96Y), which is a cause of permanent neonatal diabetes. When expressed in fly imaginal discs, hINS(C96Y) causes a reduction of adult structures, including the eye, wing, and notum. Eye imaginal discs exhibit defects in both the structure and the arrangement of ommatidia. In the wing, expression of hINS(C96Y) leads to ectopic expression of veins and mechano-sensory organs, indicating disruption of wild-type signaling processes regulating cell fates. These readily measurable "disease" phenotypes are sensitive to temperature, gene dose, and sex. Mutant (but not wild-type) proinsulin expression in the eye imaginal disc induces IRE1-mediated XBP1 alternative splicing, a signal for endoplasmic reticulum stress response activation, and produces global change in gene expression. Mutant hINS transgene tester strains, when crossed to stocks from the Drosophila Genetic Reference Panel, produce F1 adults with a continuous range of disease phenotypes and large broad-sense heritability. Surprisingly, the severity of mutant hINS-induced disease in the eye is not correlated with that in the notum in these crosses, nor with eye reduction phenotypes caused by the expression of two dominant eye mutants acting in two different eye development pathways, Drop (Dr) or Lobe (L), when crossed into the same genetic backgrounds. The tissue specificity of genetic variability for mutant hINS-induced disease has, therefore, its own distinct signature. The genetic dominance

  14. Larger aggregates of mutant seipin in Celia's Encephalopathy, a new protein misfolding neurodegenerative disease.

    Science.gov (United States)

    Ruiz-Riquelme, Alejandro; Sánchez-Iglesias, Sofía; Rábano, Alberto; Guillén-Navarro, Encarna; Domingo-Jiménez, Rosario; Ramos, Adriana; Rosa, Isaac; Senra, Ana; Nilsson, Peter; García, Ángel; Araújo-Vilar, David; Requena, Jesús R

    2015-11-01

    Celia's Encephalopathy (MIM #615924) is a recently discovered fatal neurodegenerative syndrome associated with a new BSCL2 mutation (c.985C>T) that results in an aberrant isoform of seipin (Celia seipin). This mutation is lethal in both homozygosity and compounded heterozygosity with a lipodystrophic BSCL2 mutation, resulting in a progressive encephalopathy with fatal outcomes at ages 6-8. Strikingly, heterozygous carriers are asymptomatic, conflicting with the gain of toxic function attributed to this mutation. Here we report new key insights about the molecular pathogenic mechanism of this new syndrome. Intranuclear inclusions containing mutant seipin were found in brain tissue from a homozygous patient suggesting a pathogenic mechanism similar to other neurodegenerative diseases featuring brain accumulation of aggregated, misfolded proteins. Sucrose gradient distribution showed that mutant seipin forms much larger aggregates as compared with wild type (wt) seipin, indicating an impaired oligomerization. On the other hand, the interaction between wt and Celia seipin confirmed by coimmunoprecipitation (CoIP) assays, together with the identification of mixed oligomers in sucrose gradient fractionation experiments can explain the lack of symptoms in heterozygous carriers. We propose that the increased aggregation and subsequent impaired oligomerization of Celia seipin leads to cell death. In heterozygous carriers, wt seipin might prevent the damage caused by mutant seipin through its sequestration into harmless mixed oligomers. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclical amplification with beads (PMCAb)

    Science.gov (United States)

    Johnson, Chad J.; Aiken, Judd M.; McKenzie, Debbie; Samuel, Michael D.; Pedersen, Joel A.

    2012-01-01

    Protein misfolding cyclic amplification (PMCA) has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb) has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD) agent without compromising the specificity of the assay (i.e., no false positive results). Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7×10−13 dilution of 10% brain homogenate (1.3 fg of source brain). Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP)1536+/−mice) allowed detection of CWD agent from the 10−6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 105. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility.

  16. Highly efficient amplification of chronic wasting disease agent by protein misfolding cyclic amplification with beads (PMCAb.

    Directory of Open Access Journals (Sweden)

    Chad J Johnson

    Full Text Available Protein misfolding cyclic amplification (PMCA has emerged as an important technique for detecting low levels of pathogenic prion protein in biological samples. The method exploits the ability of the pathogenic prion protein to convert the normal prion protein to a proteinase K-resistant conformation. Inclusion of Teflon® beads in the PMCA reaction (PMCAb has been previously shown to increase the sensitivity and robustness of detection for the 263 K and SSLOW strains of hamster-adapted prions. Here, we demonstrate that PMCAb with saponin dramatically increases the sensitivity of detection for chronic wasting disease (CWD agent without compromising the specificity of the assay (i.e., no false positive results. Addition of Teflon® beads increased the robustness of the PMCA reaction, resulting in a decrease in the variability of PMCA results. Three rounds of serial PMCAb allowed detection of CWD agent from a 6.7 × 10(-13 dilution of 10% brain homogenate (1.3 fg of source brain. Titration of the same brain homogenate in transgenic mice expressing cervid prion protein (Tg(CerPrP1536(+/- mice allowed detection of CWD agent from the 10(-6 dilution of 10% brain homogenate. PMCAb is, thus, more sensitive than bioassay in transgenic mice by a factor exceeding 10(5. Additionally, we are able to amplify CWD agent from brain tissue and lymph nodes of CWD-positive white-tailed deer having Prnp alleles associated with reduced disease susceptibility.

  17. Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Gregor Ilc

    2013-08-01

    Full Text Available The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process whereby most α-helical motifs are replaced by β-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal domain region of PrPC and cause spontaneous conversion to PrPSc. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify “hot spots” in PrPC involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrPC epitopes thought to be involved in modulating prion susceptibility. Here we present a detailed overview of our solution-state NMR studies on human prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research.

  18. Hsp70-GlcNAc-binding activity is released by stress, proteasome inhibition, and protein misfolding

    International Nuclear Information System (INIS)

    Guinez, Celine; Mir, Anne-Marie; Leroy, Yves; Cacan, Rene; Michalski, Jean-Claude; Lefebvre, Tony

    2007-01-01

    Numerous recent works strengthen the idea that the nuclear and cytosolic-specific O-GlcNAc glycosylation protects cells against injuries. We have first investigated O-GlcNAc level and Hsp70-GlcNAc-binding activity (HGBA) behaviour after exposure of HeLa and HepG 2 cells to a wide variety of stresses. O-GlcNAc and HGBA responses were different according to the stress and according to the cell. HGBA was released for almost all stresses, while O-GlcNAc level was modified either upwards or downwards, depending to the stress. Against all expectations, we demonstrated that energy charge did not significantly vary with stress whereas UDP-GlcNAc pools were more dramatically affected even if differences in UDP-GlcNAc contents were not correlated with O-GlcNAc variations suggesting that O-GlcNAc transferase is itself finely regulated during cell injury. Finally, HGBA could be triggered by proteasome inhibition and by L-azetidine-2-carboxylic acid (a proline analogue) incorporation demonstrating that protein misfolding is one of the key-activator of this Hsp70 property

  19. H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

    KAUST Repository

    Zolea, Fabiana

    2015-10-09

    The redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.

  20. Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Shannon E.; Nguyen, Elaine; Donegan, Rebecca K.; Patterson-Orazem, Athéna C.; Hazel, Anthony; Gumbart, James C.; Lieberman, Raquel L.

    2017-11-01

    Glaucoma-associated myocilin is a member of the olfactomedins, a protein family involved in neuronal development and human diseases. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a Y-shaped parallel dimer-of-dimers with distinct tetramer and dimer regions. The structure of the dimeric C-terminal 7-heptad repeats elucidates an unexpected repeat pattern involving inter-strand stabilization by oppositely charged residues. Molecular dynamics simulations reveal an alternate accessible conformation in which the terminal inter-strand disulfide limits the extent of unfolding and results in a kinked configuration. By inference, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of naturally occurring extracellular coiled coils and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma.

  1. Structure and Misfolding of the Flexible Tripartite Coiled-Coil Domain of Glaucoma-Associated Myocilin.

    Science.gov (United States)

    Hill, Shannon E; Nguyen, Elaine; Donegan, Rebecca K; Patterson-Orazem, Athéna C; Hazel, Anthony; Gumbart, James C; Lieberman, Raquel L

    2017-11-07

    Glaucoma-associated myocilin is a member of the olfactomedins, a protein family involved in neuronal development and human diseases. Molecular studies of the myocilin N-terminal coiled coil demonstrate a unique tripartite architecture: a Y-shaped parallel dimer-of-dimers with distinct tetramer and dimer regions. The structure of the dimeric C-terminal 7-heptad repeats elucidates an unexpected repeat pattern involving inter-strand stabilization by oppositely charged residues. Molecular dynamics simulations reveal an alternate accessible conformation in which the terminal inter-strand disulfide limits the extent of unfolding and results in a kinked configuration. By inference, full-length myocilin is also branched, with two pairs of C-terminal olfactomedin domains. Selected variants within the N-terminal region alter the apparent quaternary structure of myocilin but do so without compromising stability or causing aggregation. In addition to increasing our structural knowledge of naturally occurring extracellular coiled coils and biomedically important olfactomedins, this work broadens the scope of protein misfolding in the pathogenesis of myocilin-associated glaucoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Conformational Analysis of Misfolded Protein Aggregation by FRET and Live-Cell Imaging Techniques

    Directory of Open Access Journals (Sweden)

    Akira Kitamura

    2015-03-01

    Full Text Available Cellular homeostasis is maintained by several types of protein machinery, including molecular chaperones and proteolysis systems. Dysregulation of the proteome disrupts homeostasis in cells, tissues, and the organism as a whole, and has been hypothesized to cause neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS and Huntington’s disease (HD. A hallmark of neurodegenerative disorders is formation of ubiquitin-positive inclusion bodies in neurons, suggesting that the aggregation process of misfolded proteins changes during disease progression. Hence, high-throughput determination of soluble oligomers during the aggregation process, as well as the conformation of sequestered proteins in inclusion bodies, is essential for elucidation of physiological regulation mechanism and drug discovery in this field. To elucidate the interaction, accumulation, and conformation of aggregation-prone proteins, in situ spectroscopic imaging techniques, such as Förster/fluorescence resonance energy transfer (FRET, fluorescence correlation spectroscopy (FCS, and bimolecular fluorescence complementation (BiFC have been employed. Here, we summarize recent reports in which these techniques were applied to the analysis of aggregation-prone proteins (in particular their dimerization, interactions, and conformational changes, and describe several fluorescent indicators used for real-time observation of physiological states related to proteostasis.

  3. H ferritin silencing induces protein misfolding in K562 cells: A Raman analysis

    KAUST Repository

    Zolea, Fabiana; Biamonte, Flavia; Candeloro, Patrizio; Di Sanzo, Maddalena; Cozzi, Anna; Di Vito, Anna; Quaresima, Barbara; Lobello, Nadia; Trecroci, Francesca; Di Fabrizio, Enzo M.; Levi, Sonia; Cuda, Giovanni; Costanzo, Francesco

    2015-01-01

    The redox state of the cell is involved in the regulation of many physiological functions as well as in the pathogenesis of several diseases, and is strictly dependent on the amount of iron in its catalytically active state. Alterations of iron homeostasis determine increased steady-state concentrations of Reactive Oxygen Species (ROS) that cause lipid peroxidation, DNA damage and altered protein folding. Ferritin keeps the intracellular iron in a non-toxic and readily available form and consequently plays a central role in iron and redox homeostasis. The protein is composed by 24 subunits of the H- and L-type, coded by two different genes, with structural and functional differences. The aim of this study was to shed light on the role of the single H ferritin subunit (FHC) in keeping the native correct protein three-dimensional structure. To this, we performed Raman spectroscopy on protein extracts from K562 cells subjected to FHC silencing. The results show a significant increase in the percentage of disordered structures content at a level comparable to that induced by H2O2 treatment in control cells. ROS inhibitor and iron chelator were able to revert protein misfolding. This integrated approach, involving Raman spectroscopy and targeted-gene silencing, indicates that an imbalance of the heavy-to-light chain ratio in the ferritin composition is able to induce severe but still reversible modifications in protein folding and uncovers new potential pathogenetic mechanisms associated to intracellular iron perturbation.

  4. Heavy metals and metalloids as a cause for protein misfolding and aggregation.

    Science.gov (United States)

    Tamás, Markus J; Sharma, Sandeep K; Ibstedt, Sebastian; Jacobson, Therese; Christen, Philipp

    2014-02-25

    While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.

  5. A novel vacuolar membrane H+-ATPase c subunit gene (ThVHAc1) from Tamarix hispida confers tolerance to several abiotic stresses in Saccharomyces cerevisiae.

    Science.gov (United States)

    Gao, Caiqiu; Wang, Yucheng; Jiang, Bo; Liu, Guifeng; Yu, Lili; Wei, Zhigang; Yang, Chuanping

    2011-02-01

    Plant vacuolar H(+)-ATPase (V-ATPase) plays an important role in response to different adverse environmental conditions. In the present study, we cloned and characterized a V-ATPase c subunit gene (ThVHAc1) from Tamarix hispida. The deduced ThVHAc1 amino acid sequence lacks a signal peptide and ThVHAc1 is a highly hydrophobic protein with four transmembrane regions. A transient expression assay showed that the ThVHAc1-GFP fusion protein is expressed on onion epidermal endomembrane cells. Real-time RT-PCR demonstrated that ThVHAc1 gene expression was induced by NaCl, NaHCO(3), PEG and CdCl(2) stress in T. hispida roots, stems and leaves. Exogenous application of abscisic acid (ABA) also stimulated ThVHAc1 transcript levels in the absence of stress, suggesting that ThVHAc1 is involved in ABA-dependent stress signaling pathway. Furthermore, the transgenic yeast expressing ThVHAc1 increased salt, drought, ultraviolet (UV), oxidative, heavy metal, cold and high temperature tolerance. Our results suggested that the ThVHAc1 gene from T. hispida serves a stress tolerance role in the species.

  6. Cucumber metal tolerance protein CsMTP9 is a plasma membrane H⁺-coupled antiporter involved in the Mn²⁺ and Cd²⁺ efflux from root cells.

    Science.gov (United States)

    Migocka, Magdalena; Papierniak, Anna; Kosieradzka, Anna; Posyniak, Ewelina; Maciaszczyk-Dziubinska, Ewa; Biskup, Robert; Garbiec, Arnold; Marchewka, Tadeusz

    2015-12-01

    Members of the plant metal tolerance protein (MTP) family have been classified into three major groups - Zn-CDF, Mn-CDF and Zn/Fe-CDF - however, the selectivity of most of the MTPs has not been confirmed yet. Cucumber gene CsMTP9 encoding a putative CDF transporter homologous to members of the Mn-CDF cluster is expressed exclusively in roots. The relative abundance of CsMTP9 transcript and protein in roots is significantly increased under Mn excess and Cd. Immunolocalization with specific antibodies revealed that CsMTP9 is a plasma membrane transporter that localizes to the inner PM domain of root endodermal cells. The plasma membrane localization of CsMTP9 was confirmed by the expression of the fusion proteins of GFP (green fluorescent protein) and CsMTP9 in yeast and protoplasts prepared from Arabidopsis cells. In yeast, CsMTP9 transports Mn(2+) and Cd(2+) via a proton-antiport mechanism with an apparent Km values of approximately 10 μm and 2.5 μm for Mn(2+) and Cd(2+) , respectively. In addition, CsMTP9 expression in yeast rescues the Mn- and Cd-hypersensitive phenotypes through the enhanced efflux of Mn(2+) and Cd(2+) from yeast cells. Similarly, the overexpression of CsMTP9 in A. thaliana confers increased resistance of plants to Mn excess and Cd but not to other heavy metals and leads to the enhanced translocation of manganese and cadmium from roots to shoots. These findings indicate that CsMTP9 is a plasma membrane H(+) -coupled Mn(2+) and Cd(2+) antiporter involved in the efflux of manganese and cadmium from cucumber root cells by the transport of both metals from endodermis into vascular cylinder. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  7. The Role of S-Nitrosylation and S-Glutathionylation of Protein Disulphide Isomerase in Protein Misfolding and Neurodegeneration

    Directory of Open Access Journals (Sweden)

    M. Halloran

    2013-01-01

    Full Text Available Neurodegenerative diseases involve the progressive loss of neurons, and a pathological hallmark is the presence of abnormal inclusions containing misfolded proteins. Although the precise molecular mechanisms triggering neurodegeneration remain unclear, endoplasmic reticulum (ER stress, elevated oxidative and nitrosative stress, and protein misfolding are important features in pathogenesis. Protein disulphide isomerase (PDI is the prototype of a family of molecular chaperones and foldases upregulated during ER stress that are increasingly implicated in neurodegenerative diseases. PDI catalyzes the rearrangement and formation of disulphide bonds, thus facilitating protein folding, and in neurodegeneration may act to ameliorate the burden of protein misfolding. However, an aberrant posttranslational modification of PDI, S-nitrosylation, inhibits its protective function in these conditions. S-nitrosylation is a redox-mediated modification that regulates protein function by covalent addition of nitric oxide- (NO- containing groups to cysteine residues. Here, we discuss the evidence for abnormal S-nitrosylation of PDI (SNO-PDI in neurodegeneration and how this may be linked to another aberrant modification of PDI, S-glutathionylation. Understanding the role of aberrant S-nitrosylation/S-glutathionylation of PDI in the pathogenesis of neurodegenerative diseases may provide insights into novel therapeutic interventions in the future.

  8. S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in neurodegenerative disorders of protein misfolding.

    Science.gov (United States)

    Nakamura, T; Lipton, S A

    2007-07-01

    Although activation of glutamate receptors is essential for normal brain function, excessive activity leads to a form of neurotoxicity known as excitotoxicity. Key mediators of excitotoxic damage include overactivation of N-methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with production of free radicals and other injurious pathways. Overproduction of free radical nitric oxide (NO) contributes to acute and chronic neurodegenerative disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and thus change protein function. S-nitrosylation can result in neuroprotective or neurodestructive consequences depending on the protein involved. Many neurodegenerative diseases manifest conformational changes in proteins that result in misfolding and aggregation. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. Molecular chaperones - such as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock proteins - can provide neuroprotection by facilitating proper protein folding. Here, we review the effect of S-nitrosylation on protein function under excitotoxic conditions, and present evidence that NO contributes to degenerative conditions by S-nitrosylating-specific chaperones that would otherwise prevent accumulation of misfolded proteins and neuronal cell death. In contrast, we also review therapeutics that can abrogate excitotoxic damage by preventing excessive NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail excessive activity.

  9. The transporter SynPAM71 is located in the plasma membrane and thylakoids, and mediates manganese tolerance in Synechocystis PCC6803

    DEFF Research Database (Denmark)

    Gandini, Chiara; Schmidt, Sidsel Birkelund; Husted, Søren

    2017-01-01

    symptoms were observed in WT cells exposed to excess Mn. Moreover, CyanoP, which is involved in the early steps of PSII assembly, is massively upregulated in ΔSynPAM71. SynPAM71 was detected in both the plasma membrane and, to a lesser extent, the thylakoid membranes. Our results suggest that SynPAM71......Manganese (Mn) is an essential constituent of photosystem II (PSII) and therefore indispensable for oxygenic photosynthesis. Very little is known about how Mn is transported, delivered and retained in photosynthetic cells. Recently, the thylakoid-localized transporter PAM71 has been linked...... to chloroplast Mn homeostasis in Arabidopsis thaliana. Here, we characterize the function of its homolog in Synechocystis (SynPAM71). We used a loss-of-function line (ΔSynPAM71), wild-type (WT) cells exposed to Mn stress and strains expressing a tagged variant of SynPAM71 to characterize the role of SynPAM71...

  10. Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein

    Science.gov (United States)

    Agarwal, Sonya; Döring, Kristina; Gierusz, Leszek A.; Iyer, Pooja; Lane, Fiona M.; Graham, James F.; Goldmann, Wilfred; Pinheiro, Teresa J. T.; Gill, Andrew C.

    2015-10-01

    The β2-α2 loop of PrPC is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrPC appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2-α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that ‘rigidity’ in the β2-α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region.

  11. Prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.

    Directory of Open Access Journals (Sweden)

    Mauricio Torres

    2010-12-01

    Full Text Available Prion-related disorders (PrDs are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed PrP(RES. Altered endoplasmic reticulum (ER homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of PrDs. The ER operates as a major intracellular calcium store, playing a crucial role in pathological events related to neuronal dysfunction and death. Here we investigated the possible impact of PrP misfolding on ER calcium homeostasis in infectious and familial models of PrDs. Neuro2A cells chronically infected with scrapie prions showed decreased ER-calcium content that correlated with a stronger upregulation of UPR-inducible chaperones, and a higher sensitivity to ER stress-induced cell death. Overexpression of the calcium pump SERCA stimulated calcium release and increased the neurotoxicity observed after exposure of cells to brain-derived infectious PrP(RES. Furthermore, expression of PrP mutants that cause hereditary Creutzfeldt-Jakob disease or fatal familial insomnia led to accumulation of PrP(RES and their partial retention at the ER, associated with a drastic decrease of ER calcium content and higher susceptibility to ER stress. Finally, similar results were observed when a transmembrane form of PrP was expressed, which is proposed as a neurotoxic intermediate. Our results suggest that alterations in calcium homeostasis and increased susceptibility to ER stress are common pathological features of both infectious and familial PrD models.

  12. Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin.

    Science.gov (United States)

    He, Bin Z; Ludwig, Michael Z; Dickerson, Desiree A; Barse, Levi; Arun, Bharath; Vilhjálmsson, Bjarni J; Jiang, Pengyao; Park, Soo-Young; Tamarina, Natalia A; Selleck, Scott B; Wittkopp, Patricia J; Bell, Graeme I; Kreitman, Martin

    2014-02-01

    The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of the mutant preproinsulin (hINS(C96Y)) in the eye imaginal disc mimics the human disease: it activates conserved stress-response pathways and leads to cell death (reduction in eye area). Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable distribution of eye-degeneration phenotypes in a hINS(C96Y) background. A genome-wide association study (GWAS) in 154 sequenced lines identified a sharp peak on chromosome 3L, which mapped to a 400-bp linkage block within an intron of the gene sulfateless (sfl). RNAi knockdown of sfl enhanced the eye-degeneration phenotype in a mutant-hINS-dependent manner. RNAi against two additional genes in the heparan sulfate (HS) biosynthetic pathway (ttv and botv), in which sfl acts, also modified the eye phenotype in a hINS(C96Y)-dependent manner, strongly suggesting a novel link between HS-modified proteins and cellular responses to misfolded proteins. Finally, we evaluated allele-specific expression difference between the two major sfl-intronic haplotypes in heterozygtes. The results showed significant heterogeneity in marker-associated gene expression, thereby leaving the causal mutation(s) and its mechanism unidentified. In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.

  13. Production of membrane proteins without cells or detergents.

    Science.gov (United States)

    Rajesh, Sundaresan; Knowles, Timothy; Overduin, Michael

    2011-04-30

    The production of membrane proteins in cellular systems is besieged by several problems due to their hydrophobic nature which often causes misfolding, protein aggregation and cytotoxicity, resulting in poor yields of stable proteins. Cell-free expression has emerged as one of the most versatile alternatives for circumventing these obstacles by producing membrane proteins directly into designed hydrophobic environments. Efficient optimisation of expression and solubilisation conditions using a variety of detergents, membrane mimetics and lipids has yielded structurally and functionally intact membrane proteins, with yields several fold above the levels possible from cell-based systems. Here we review recently developed techniques available to produce functional membrane proteins, and discuss amphipols, nanodisc and styrene maleic acid lipid particle (SMALP) technologies that can be exploited alongside cell-free expression of membrane proteins. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Crafting tolerance

    DEFF Research Database (Denmark)

    Kirchner, Antje; Freitag, Markus; Rapp, Carolin

    2011-01-01

    Ongoing changes in social structures, orientation, and value systems confront us with the growing necessity to address and understand transforming patterns of tolerance as well as specific aspects, such as social tolerance. Based on hierarchical analyses of the latest World Values Survey (2005......–08) and national statistics for 28 countries, we assess both individual and contextual aspects that influence an individual's perception of different social groupings. Using a social tolerance index that captures personal attitudes toward these groupings, we present an institutional theory of social tolerance. Our...

  15. Differences between amyloid-β aggregation in solution and on the membrane: insights into elucidation of the mechanistic details of Alzheimer's disease.

    Science.gov (United States)

    Kotler, Samuel A; Walsh, Patrick; Brender, Jeffrey R; Ramamoorthy, Ayyalusamy

    2014-10-07

    The association of the amyloid-β (Aβ) peptide with cellular membranes is hypothesized to be the underlying phenomenon of neurotoxicity in Alzheimer's disease. Misfolding of proteins and peptides, as is the case with Aβ, follows a progression from a monomeric state, through intermediates, ending at long, unbranched amyloid fibers. This tutorial review offers a perspective on the association of toxic Aβ structures with membranes as well as details of membrane-associated mechanisms of toxicity.

  16. Differences between amyloid-β aggregation in solution and on the membrane: Insights towards elucidation of the mechanistic details of Alzheimer’s disease

    Science.gov (United States)

    Kotler, Samuel A.; Walsh, Patrick; Brender, Jeffrey R.; Ramamoorthy, Ayyalusamy

    2014-01-01

    The association of the amyloid-β (Aβ) peptide with cellular membranes is hypothesized to be the underlying phenomenon of neurotoxicity in Alzheimer’s disease. Misfolding of proteins and peptides, as is the case with Aβ, follows a progression from a monomeric state, through intermediates, ending at long, unbranched amyloid fibers. This tutorial review offers a perspective into the association of toxic Aβ structures with membrane as well as details into membrane-associated mechanisms of toxicity. PMID:24464312

  17. Membrane-associated proteomics of chickpea identifies Sad1/UNC-84 protein (CaSUN1), a novel component of dehydration signaling

    Science.gov (United States)

    Jaiswal, Dinesh Kumar; Mishra, Poonam; Subba, Pratigya; Rathi, Divya; Chakraborty, Subhra; Chakraborty, Niranjan

    2014-02-01

    Dehydration affects almost all the physiological processes including those that result in the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which in turn elicits a highly conserved signaling, the unfolded protein response (UPR). We investigated the dehydration-responsive membrane-associated proteome of a legume, chickpea, by 2-DE coupled with mass spectrometry. A total of 184 protein spots were significantly altered over a dehydration treatment of 120 h. Among the differentially expressed proteins, a non-canonical SUN domain protein, designated CaSUN1 (Cicer arietinum Sad1/UNC-84), was identified. CaSUN1 localized to the nuclear membrane and ER, besides small vacuolar vesicles. The transcripts were downregulated by both abiotic and biotic stresses, but not by abscisic acid treatment. Overexpression of CaSUN1 conferred stress tolerance in transgenic Arabidopsis. Furthermore, functional complementation of the yeast mutant, slp1, could rescue its growth defects. We propose that the function of CaSUN1 in stress response might be regulated via UPR signaling.

  18. Protein misfolding cyclic amplification induces the conversion of recombinant prion protein to PrP oligomers causing neuronal apoptosis.

    Science.gov (United States)

    Yuan, Zhen; Yang, Lifeng; Chen, Baian; Zhu, Ting; Hassan, Mohammad Farooque; Yin, Xiaomin; Zhou, Xiangmei; Zhao, Deming

    2015-06-01

    The formation of neurotoxic prion protein (PrP) oligomers is thought to be a key step in the development of prion diseases. Recently, it was determined that the sonication and shaking of recombinant PrP can convert PrP monomers into β-state oligomers. Herein, we demonstrate that β-state oligomeric PrP can be generated through protein misfolding cyclic amplification from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP, and that these oligomers can be used for subsequent research into the mechanisms of PrP-induced neurotoxicity. We have characterized protein misfolding cyclic amplification-induced monomer-to-oligomer conversion of PrP from three species using western blotting, circular dichroism, size-exclusion chromatography, and resistance to proteinase K (PK) digestion. We have further shown that all of the resulting β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, whereas the corresponding monomeric PrP were not toxic. In addition, we found that this toxicity is the result of oligomer-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3 in both wild-type and PrP(-/-) cortical neurons. It is our hope that these results may contribute to our understanding of prion transformation within the brain. We found that β-state oligomeric PrPs can be generated through protein misfolding cyclic amplification (PMCA) from recombinant full-length hamster, human, rabbit, and mutated rabbit PrP. β-oligomers are toxic to primary mouse cortical neurons independent of the presence of PrP(C) in the neurons, while the corresponding monomeric PrPs were not toxic. This toxicity is the result of oligomers-induced apoptosis via regulation of Bcl-2, Bax, and caspase-3. These results may contribute to our understanding of prion transformation within the brain. © 2015 International Society for Neurochemistry.

  19. Expansion of the octarepeat domain alters the misfolding pathway but not the folding pathway of the prion protein.

    Science.gov (United States)

    Leliveld, S Rutger; Stitz, Lothar; Korth, Carsten

    2008-06-10

    A misfolded conformation of the prion protein (PrP), PrP (Sc), is the essential component of prions, the infectious agents that cause transmissible neurodegenerative diseases. Insertional mutations that lead to an increase in the number of octarepeats (ORs) in PrP are linked to familial human prion disease. In this study, we investigated how expansion of the OR domain causes PrP to favor a prion-like conformation. Therefore, we compared the conformational and aggregation modulating properties of wild-type versus expanded OR domains, either as a fusion construct with the protein G B1 domain (GB1-OR) or as an integral part of full-length mouse PrP (MoPrP). Using circular dichroism spectroscopy, we first demonstrated that ORs are not unfolded but exist as an ensemble of three distinct conformers: polyproline helix-like, beta-turn, and "Trp-related". Domain expansion had little effect on the conformation of GB1-OR fusion proteins. When part of MoPrP however, OR domain expansion changed PrP's folding landscape, not by hampering the production of native alpha-helical monomers but by greatly reducing the propensity to form amyloid and by altering the assembly of misfolded, beta-rich aggregates. These features may relate to subtle pH-dependent conformational differences between wild-type and mutant monomers. In conclusion, we propose that PrP insertional mutations are pathogenic because they enhance specific misfolding pathways of PrP rather than by undermining native folding. This idea was supported by a trial bioassay in transgenic mice overexpressing wild-type MoPrP, where intracerebral injection of recombinant MoPrP with an expanded OR domain but not wild-type MoPrP caused prion disease.

  20. A two-step protein quality control pathway for a misfolded DJ-1 variant in fission yeast

    DEFF Research Database (Denmark)

    Mathiassen, Søs Grønbæk; Larsen, Ida B.; Poulsen, Esben Guldahl

    2015-01-01

    A mutation, L166P, in the cytosolic protein, PARK7/DJ-1, causes protein misfolding and is linked to Parkinson disease. Here, we identify the fission yeast protein Sdj1 as the orthologue of DJ-1 and calculate by in silico saturation mutagenesis the effects of point mutants on its structural...... stability. We also map the degradation pathways for Sdj1-L169P, the fission yeast orthologue of the disease-causing DJ-1 L166P protein. Sdj1-L169P forms inclusions, which are enriched for the Hsp104 disaggregase. Hsp104 and Hsp70-type chaperones are required for efficient degradation of Sdj1-L169P...

  1. Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment

    Science.gov (United States)

    Zhou, Minghai; Ottenberg, Gregory; Sferrazza, Gian Franco; Hubbs, Christopher; Fallahi, Mohammad; Rumbaugh, Gavin; Brantley, Alicia F.

    2015-01-01

    The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD+) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD+ followed by decreased ATP production, and are completely rescued by treatment with NAD+ or its precursor nicotinamide because of restoration of physiological NAD+ levels. Toxic prion protein-induced NAD+ depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD+. Intranasal NAD+ treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD+ starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD+ replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases. PMID:25678560

  2. Common features in the unfolding and misfolding of PDZ domains and beyond: the modulatory effect of domain swapping and extra-elements.

    Science.gov (United States)

    Murciano-Calles, Javier; Güell-Bosch, Jofre; Villegas, Sandra; Martinez, Jose C

    2016-01-12

    PDZ domains are protein-protein interaction modules sharing the same structural arrangement. To discern whether they display common features in their unfolding/misfolding behaviour we have analyzed in this work the unfolding thermodynamics, together with the misfolding kinetics, of the PDZ fold using three archetypical examples: the second and third PDZ domains of the PSD95 protein and the Erbin PDZ domain. Results showed that all domains passed through a common intermediate, which populated upon unfolding, and that this in turn drove the misfolding towards worm-like fibrillar structures. Thus, the unfolding/misfolding behaviour appears to be shared within these domains. We have also analyzed how this landscape can be modified upon the inclusion of extra-elements, as it is in the nNOS PDZ domain, or the organization of swapped species, as happens in the second PDZ domain of the ZO2 protein. Although the intermediates still formed upon thermal unfolding, the misfolding was prevented to varying degrees.

  3. Membrane fluidity adjustments in ethanol-stressed Oenococcus oeni cells

    NARCIS (Netherlands)

    Silveira, da M.G.; Golovina, E.A.; Hoekstra, F.A.; Rombouts, F.M.; Abee, T.

    2003-01-01

    The effect of ethanol on the cytoplasmic membrane of Oenococcus oeni cells and the role of membrane changes in the acquired tolerance to ethanol were investigated. Membrane tolerance to ethanol was defined as the resistance to ethanol-induced leakage of preloaded carboxyfluorescein (cF) from cells.

  4. Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma.

    Science.gov (United States)

    Daus, Martin L

    2016-01-04

    In 1982, the term "prions" (proteinaceous infectious particles) was coined to specify a new principle of infection. A misfolded isoform of a cellular protein has been described as the causative agent of a fatal neurodegenerative disease. At the beginning of prion research scientists assumed that the infectious agent causing transmissible spongiform encephalopathy (TSE) was a virus, but some unconventional properties of these pathogens were difficult to bring in line with the prevailing viral model. The discovery that prions (obviously devoid of any coding nucleic acid) can store and transmit information similarly to DNA was initially even denoted as being "heretical" but is nowadays mainly accepted by the scientific community. This review describes, from a historical point of view, how the "protein-only hypothesis" expands the Central Dogma. Definition of both, the prion principle and the Central Dogma, have been essential steps to understand information storage and transfer within and among cells and organisms. Furthermore, the current understanding of the infectivity of prion-proteins after misfolding is summarized succinctly. Finally, prion-like amyloids and functional amyloids, as found in yeast and bacteria, will be discussed.

  5. Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma

    Directory of Open Access Journals (Sweden)

    Martin L. Daus

    2016-01-01

    Full Text Available In 1982, the term “prions” (proteinaceous infectious particles was coined to specify a new principle of infection. A misfolded isoform of a cellular protein has been described as the causative agent of a fatal neurodegenerative disease. At the beginning of prion research scientists assumed that the infectious agent causing transmissible spongiform encephalopathy (TSE was a virus, but some unconventional properties of these pathogens were difficult to bring in line with the prevailing viral model. The discovery that prions (obviously devoid of any coding nucleic acid can store and transmit information similarly to DNA was initially even denoted as being “heretical” but is nowadays mainly accepted by the scientific community. This review describes, from a historical point of view, how the “protein-only hypothesis” expands the Central Dogma. Definition of both, the prion principle and the Central Dogma, have been essential steps to understand information storage and transfer within and among cells and organisms. Furthermore, the current understanding of the infectivity of prion-proteins after misfolding is summarized succinctly. Finally, prion-like amyloids and functional amyloids, as found in yeast and bacteria, will be discussed.

  6. Caenorhabditis elegans as a model system for studying non-cell-autonomous mechanisms in protein-misfolding diseases

    Directory of Open Access Journals (Sweden)

    Carmen I. Nussbaum-Krammer

    2014-01-01

    Full Text Available Caenorhabditis elegans has a number of distinct advantages that are useful for understanding the basis for cellular and organismal dysfunction underlying age-associated diseases of protein misfolding. Although protein aggregation, a key feature of human neurodegenerative diseases, has been typically explored in vivo at the single-cell level using cells in culture, there is now increasing evidence that proteotoxicity has a non-cell-autonomous component and is communicated between cells and tissues in a multicellular organism. These discoveries have opened up new avenues for the use of C. elegans as an ideal animal model system to study non-cell-autonomous proteotoxicity, prion-like propagation of aggregation-prone proteins, and the organismal regulation of stress responses and proteostasis. This Review focuses on recent evidence that C. elegans has mechanisms to transmit certain classes of toxic proteins between tissues and a complex stress response that integrates and coordinates signals from single cells and tissues across the organism. These findings emphasize the potential of C. elegans to provide insights into non-cell-autonomous proteotoxic mechanisms underlying age-related protein-misfolding diseases.

  7. Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset.

    Directory of Open Access Journals (Sweden)

    Christine Vande Velde

    Full Text Available Mutations in superoxide dismutase (SOD1 are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS.

  8. Om tolerance

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2007-01-01

    Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik.......Begrebet tolerance og dets betydninger diskuteres med henblik på en tydeliggørelse af begrebets forbindelse med stat, religion, ytringsfrihed, skeptisk erkendelsesteori, antropologi og pædagogik....

  9. Emulsification using microporous membranes

    Directory of Open Access Journals (Sweden)

    Goran T. Vladisavljević

    2011-10-01

    Full Text Available Membrane emulsification is a process of injecting a pure dispersed phase or pre-emulsion through a microporous membrane into the continuous phase. As a result of the immiscibility of the two phases, droplets of the dispersed phase are formed at the outlets of membrane pores. The droplets formed in the process are removed from the membrane surface by applying cross-flow or stirring of the continuous phase or using a dynamic (rotating or vibrating membrane. The most commonly used membrane for emulsification is the Shirasu Porous Glass (SPG membrane, fabricated through spinodal decomposition in a melt consisting of Japanese volcanic ash (Shirasu, boric acid and calcium carbonate. Microsieve membranes are increasingly popular as an alternative to highly tortuous glass and ceramic membranes. Microsieves are usually fabricated from nickel by photolithography and electroplating or they can be manufactured from silicon nitride via Reactive Ion Etching (RIE. An advantage of microsieves compared to the SPG membrane is in much higher transmembrane fluxes and higher tolerance to fouling by the emulsion ingredients due to the existence of short, straight through pores. Unlike conventional emulsification devices such as high-pressure valve homogenisers and rotor-stator devices, membrane emulsification devices permit a precise control over the mean pore size over a wide range and during the process insignificant amount of energy is dissipated as heat. The drop size is primarily determined by the pore size, but it depends also on other parameters, such as membrane wettability, emulsion formulation, shear stress on the membrane surface, transmembrane pressure, etc.

  10. Membrane dynamics

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

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

  11. Amyloid and membrane complexity: The toxic interplay revealed by AFM.

    Science.gov (United States)

    Canale, Claudio; Oropesa-Nuñez, Reinier; Diaspro, Alberto; Dante, Silvia

    2018-01-01

    Lipid membranes play a fundamental role in the pathological development of protein misfolding diseases. Several pieces of evidence suggest that the lipid membrane could act as a catalytic surface for protein aggregation. Furthermore, a leading theory indicates the interaction between the cell membrane and misfolded oligomer species as the responsible for cytotoxicity, hence, for neurodegeneration in disorders such as Alzheimer's and Parkinson's disease. The definition of the mechanisms that drive the interaction between pathological protein aggregates and plasma membrane is fundamental for the development of effective therapies for a large class of diseases. Atomic force microscopy (AFM) has been employed to study how amyloid aggregates affect the cell physiological properties. Considerable efforts were spent to characterize the interaction with model systems, i.e., planar supported lipid bilayers, but some works also addressed the problem directly on living cells. Here, an overview of the main works involving the use of the AFM on both model system and living cells will be provided. Different kind of approaches will be presented, as well as the main results derived from the AFM analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Towards Tolerance

    NARCIS (Netherlands)

    Lisette Kuyper; Jurjen Iedema; Saskia Keuzenkamp

    2013-01-01

    Across Europe, public attitudes towards lesbian, gay and bisexual (LGB) individuals range from broad tolerance to widespread rejection. Attitudes towards homosexuality are more than mere individual opinions, but form part of the social and political structures which foster or hinder the equality

  13. Intolerant tolerance.

    Science.gov (United States)

    Khushf, G

    1994-04-01

    The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights.

  14. The domain-specific and temperature-dependent protein misfolding phenotype of variant medium-chain acyl-CoA dehydrogenase

    NARCIS (Netherlands)

    Jank, Johanna M.; Maier, Esther M.; Reiβ, Dunja D.; Haslbeck, Martin; Kemter, Kristina F.; Truger, Marietta S.; Sommerhoff, Christian P.; Ferdinandusse, Sacha; Wanders, Ronald J.; Gersting, Søren W.; Muntau, Ania C.

    2014-01-01

    The implementation of expanded newborn screening programs reduced mortality and morbidity in medium-chain acyl-CoA dehydrogenase deficiency (MCADD) caused by mutations in the ACADM gene. However, the disease is still potentially fatal. Missense induced MCADD is a protein misfolding disease with a

  15. Temporal resolution of misfolded prion protein transport, accumulation, glial activation, and neuronal death in the retinas of mice inoculated with scrapie

    Science.gov (United States)

    Currently, there is a lack of pathologic landmarks to describe the progression of prion disease in vivo. The goal of this work was to determine the temporal relationship between the transport of misfolded prion protein from the brain to the retina, the accumulation of PrPSc in the retina, the respon...

  16. Salt Tolerance

    OpenAIRE

    Xiong, Liming; Zhu, Jian-Kang

    2002-01-01

    Studying salt stress is an important means to the understanding of plant ion homeostasis and osmo-balance. Salt stress research also benefits agriculture because soil salinity significantly limits plant productivity on agricultural lands. Decades of physiological and molecular studies have generated a large body of literature regarding potential salt tolerance determinants. Recent advances in applying molecular genetic analysis and genomics tools in the model plant Arabidopsis thaliana are sh...

  17. Membrane fusion

    DEFF Research Database (Denmark)

    Bendix, Pól Martin

    2015-01-01

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

  18. Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Buck, Teresa M; Jordan, Rick; Lyons-Weiler, James; Adelman, Joshua L; Needham, Patrick G; Kleyman, Thomas R; Brodsky, Jeffrey L

    2015-06-01

    Misfolded membrane proteins are retained in the endoplasmic reticulum (ER) and are subject to ER-associated degradation, which clears the secretory pathway of potentially toxic species. While the transcriptional response to environmental stressors has been extensively studied, limited data exist describing the cellular response to misfolded membrane proteins. To this end, we expressed and then compared the transcriptional profiles elicited by the synthesis of three ER retained, misfolded ion channels: The α-subunit of the epithelial sodium channel, ENaC, the cystic fibrosis transmembrane conductance regulator, CFTR, and an inwardly rectifying potassium channel, Kir2.1, which vary in their mass, membrane topologies, and quaternary structures. To examine transcriptional profiles in a null background, the proteins were expressed in yeast, which was previously used to examine the degradation requirements for each substrate. Surprisingly, the proteins failed to induce a canonical unfolded protein response or heat shock response, although messages encoding several cytosolic and ER lumenal protein folding factors rose when αENaC or CFTR was expressed. In contrast, the levels of these genes were unaltered by Kir2.1 expression; instead, the yeast iron regulon was activated. Nevertheless, a significant number of genes that respond to various environmental stressors were upregulated by all three substrates, and compared with previous microarray data we deduced the existence of a group of genes that reflect a novel misfolded membrane protein response. These data indicate that aberrant proteins in the ER elicit profound yet unique cellular responses. Copyright © 2015 the American Physiological Society.

  19. The Type II Hsp40 Sis1 cooperates with Hsp70 and the E3 ligase Ubr1 to promote degradation of terminally misfolded cytosolic protein.

    Directory of Open Access Journals (Sweden)

    Daniel W Summers

    Full Text Available Mechanisms for cooperation between the cytosolic Hsp70 system and the ubiquitin proteasome system during protein triage are not clear. Herein, we identify new mechanisms for selection of misfolded cytosolic proteins for degradation via defining functional interactions between specific cytosolic Hsp70/Hsp40 pairs and quality control ubiquitin ligases. These studies revolved around the use of S. cerevisiae to elucidate the degradation pathway of a terminally misfolded reporter protein, short-lived GFP (slGFP. The Type I Hsp40 Ydj1 acts with Hsp70 to suppress slGFP aggregation. In contrast, the Type II Hsp40 Sis1 is required for proteasomal degradation of slGFP. Sis1 and Hsp70 operate sequentially with the quality control E3 ubiquitin ligase Ubr1 to target slGFP for degradation. Compromise of Sis1 or Ubr1 function leads slGFP to accumulate in a Triton X-100-soluble state with slGFP degradation intermediates being concentrated into perinuclear and peripheral puncta. Interestingly, when Sis1 activity is low the slGFP that is concentrated into puncta can be liberated from puncta and subsequently degraded. Conversely, in the absence of Ubr1, slGFP and the puncta that contain slGFP are relatively stable. Ubr1 mediates proteasomal degradation of slGFP that is released from cytosolic protein handling centers. Pathways for proteasomal degradation of misfolded cytosolic proteins involve functional interplay between Type II Hsp40/Hsp70 chaperone pairs, PQC E3 ligases, and storage depots for misfolded proteins.

  20. Chaperoning Proteins for Destruction: Diverse Roles of Hsp70 Chaperones and their Co-Chaperones in Targeting Misfolded Proteins to the Proteasome

    Directory of Open Access Journals (Sweden)

    Ayala Shiber

    2014-07-01

    Full Text Available Molecular chaperones were originally discovered as heat shock-induced proteins that facilitate proper folding of proteins with non-native conformations. While the function of chaperones in protein folding has been well documented over the last four decades, more recent studies have shown that chaperones are also necessary for the clearance of terminally misfolded proteins by the Ub-proteasome system. In this capacity, chaperones protect misfolded degradation substrates from spontaneous aggregation, facilitate their recognition by the Ub ligation machinery and finally shuttle the ubiquitylated substrates to the proteasome. The physiological importance of these functions is manifested by inefficient proteasomal degradation and the accumulation of protein aggregates during ageing or in certain neurodegenerative diseases, when chaperone levels decline. In this review, we focus on the diverse roles of stress-induced chaperones in targeting misfolded proteins to the proteasome and the consequences of their compromised activity. We further discuss the implications of these findings to the identification of new therapeutic targets for the treatment of amyloid diseases.

  1. Identification of RAPD markers linked to salinity tolerance in wheat

    African Journals Online (AJOL)

    armghan_shehzad

    The individual plants from F2 population segregation for salinity tolerance and the parents ..... plasma membrane Na+/H+ antiporters that are energized by proton gradients ... tonoplast by vascular Na+/ H+ antiporters into the cell vacuoles ...

  2. Na+/K+-ATPase is present in scrapie-associated fibrils, modulates PrP misfolding in vitro and links PrP function and dysfunction.

    Directory of Open Access Journals (Sweden)

    James F Graham

    Full Text Available Transmissible spongiform encephalopathies are characterised by widespread deposition of fibrillar and/or plaque-like forms of the prion protein. These aggregated forms are produced by misfolding of the normal prion protein, PrP(C, to the disease-associated form, PrP(Sc, through mechanisms that remain elusive but which require either direct or indirect interaction between PrP(C and PrP(Sc isoforms. A wealth of evidence implicates other non-PrP molecules as active participants in the misfolding process, to catalyse and direct the conformational conversion of PrP(C or to provide a scaffold ensuring correct alignment of PrP(C and PrP(Sc during conversion. Such molecules may be specific to different scrapie strains to facilitate differential prion protein misfolding. Since molecular cofactors may become integrated into the growing protein fibril during prion conversion, we have investigated the proteins contained in prion disease-specific deposits by shotgun proteomics of scrapie-associated fibrils (SAF from mice infected with 3 different strains of mouse-passaged scrapie. Concomitant use of negative control preparations allowed us to identify and discount proteins that are enriched non-specifically by the SAF isolation protocol. We found several proteins that co-purified specifically with SAF from infected brains but none of these were reproducibly and demonstrably specific for particular scrapie strains. The α-chain of Na(+/K(+-ATPase was common to SAF from all 3 strains and we tested the ability of this protein to modulate in vitro misfolding of recombinant PrP. Na(+/K(+-ATPase enhanced the efficiency of disease-specific conversion of recombinant PrP suggesting that it may act as a molecular cofactor. Consistent with previous results, the same protein inhibited fibrillisation kinetics of recombinant PrP. Since functional interactions between PrP(C and Na(+/K(+-ATPase have previously been reported in astrocytes, our data highlight this molecule as

  3. Repressive Tolerance

    DEFF Research Database (Denmark)

    Pedersen, Morten Jarlbæk

    2017-01-01

    Consultation of organised interests and others when drafting laws is often seen as an important source of both input and output legitimacy. But whereas the input side of the equation stems from the very process of listening to societal actors, output legitimacy can only be strengthened if consult......Consultation of organised interests and others when drafting laws is often seen as an important source of both input and output legitimacy. But whereas the input side of the equation stems from the very process of listening to societal actors, output legitimacy can only be strengthened...... a substantial effect on the substance of laws – shows that there is a great difference in the amenability of different branches of government but that, in general, authorities do not listen much despite a very strong consultation institution and tradition. A suggestion for an explanation could be pointing...... to an administrative culture of repressive tolerance of organised interests: authorities listen but only reacts in a very limited sense. This bears in it the risk of jeopardising the knowledge transfer from societal actors to administrative ditto thus harming the consultation institutions’ potential for strengthening...

  4. Functional Rescue of a Misfolded Drosophila melanogaster Dopamine Transporter Mutant Associated with a Sleepless Phenotype by Pharmacological Chaperones.

    Science.gov (United States)

    Kasture, Ameya; El-Kasaby, Ali; Szöllősi, Daniel; Asjad, H M Mazhar; Grimm, Alexandra; Stockner, Thomas; Hummel, Thomas; Freissmuth, Michael; Sucic, Sonja

    2016-09-30

    Folding-defective mutants of the human dopamine transporter (DAT) cause a syndrome of infantile dystonia/parkinsonism. Here, we provide a proof-of-principle that the folding deficit is amenable to correction in vivo by two means, the cognate DAT ligand noribogaine and the HSP70 inhibitor, pifithrin-μ. We examined the Drosophila melanogaster (d) mutant dDAT-G108Q, which leads to a sleepless phenotype in flies harboring this mutation. Molecular dynamics simulations suggested an unstable structure of dDAT-G108Q consistent with a folding defect. This conjecture was verified; heterologously expressed dDAT-G108Q and the human (h) equivalent hDAT-G140Q were retained in the endoplasmic reticulum in a complex with endogenous folding sensors (calnexin and HSP70-1A). Incubation of the cells with noribogaine (a DAT ligand selective for the inward-facing state) and/or pifithrin-μ (an HSP70 inhibitor) restored folding of, and hence dopamine transport by, dDAT-G108Q and hDAT-G140Q. The mutated versions of DAT were confined to the cell bodies of the dopaminergic neurons in the fly brain and failed to reach the axonal compartments. Axonal delivery was restored, and sleep time was increased to normal length (from 300 to 1000 min/day) if the dDAT-G108Q-expressing flies were treated with noribogaine and/or pifithrin-μ. Rescuing misfolded versions of DAT by pharmacochaperoning is of therapeutic interest; it may provide opportunities to remedy disorders arising from folding-defective mutants of human DAT and of other related SLC6 transporters. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Membrane Biophysics

    CERN Document Server

    Ashrafuzzaman, Mohammad

    2013-01-01

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

  6. Pd Alloy Membranes for Hydrogen Separation from Coal-Derived Syngas

    National Research Council Canada - National Science Library

    Alptekin, Gokhan O; DeVoss, Sarah; Amalfitano, Bob; Way, Douglas; Thoen, Paul; Lusk, Mark

    2006-01-01

    TDA Research Inc., in collaboration with Colorado School of Mines (CSM) is developing a sulfur and CO-tolerant membrane to produce the clean hydrogen from syngas using Pd membrane films prepared on a variety of supports (e.g...

  7. Two rice plasma membrane intrinsic proteins, OsPIP2;4 and OsPIP2;7, are involved in transport and providing tolerance to boron toxicity.

    Science.gov (United States)

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

    2014-01-01

    Boron (B) toxicity is responsible for low cereal crop production in a number of regions worldwide. In this report, we characterized two rice genes, OsPIP2;4 and OsPIP2;7, for their involvement in B permeability and tolerance. Transcript analysis demonstrated that the expression of OsPIP2;4 and OsPIP2;7 were downregulated in shoots and strongly upregulated in rice roots by high B treatment. Expression of both OsPIP2;4 and OsPIP2;7 in yeast HD9 strain lacking Fps1, ACR3, and Ycf1 resulted in an increased B sensitivity. Furthermore, yeast HD9 strain expressing OsPIP2;4 and OsPIP2;7 accumulated significantly higher B as compared to empty vector control, which suggests their involvement in B transport. Overexpression of OsPIP2;4 and OsPIP2;7 in Arabidopsis imparted higher tolerance under B toxicity. Arabidopsis lines overexpressing OsPIP2;4 and OsPIP2;7 showed significantly higher biomass production and greater root length, however there was no difference in B accumulation in long term uptake assay. Short-term uptake assay using tracer B (¹⁰B) in shoots and roots demonstrated increased ¹⁰B accumulation in Arabidopsis lines expressing OsPIP2;4 and OsPIP2;7, compare to wild type control plants. Efflux assay of B in the roots showed that ¹⁰B was effluxed from the Arabidopsis transgenic plants overexpressing OsPIP2;4 or OsPIP2;7 during the initial 1-h of assay. These data indicate that OsPIP2;4 and OsPIP2;7 are involved in mediating B transport in rice and provide tolerance via efflux of excess B from roots and shoot tissues. These genes will be highly useful in developing B tolerant crops for enhanced yield in the areas affected by high B toxicity.

  8. Membrane paradigm

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  9. Membrane processes

    Science.gov (United States)

    Staszak, Katarzyna

    2017-11-01

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

  10. Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism.

    Science.gov (United States)

    Muntau, Ania C; Gersting, Søren W

    2010-12-01

    The lecture dedicated to Professor Horst Bickel describes the advances, successes, and opportunities concerning the understanding of the biochemical and molecular basis of phenylketonuria and the innovative treatment strategies introduced for these patients during the last 60 years. These concepts were transferred to other inborn errors of metabolism and led to significant reduction in morbidity and to an improvement in quality of life. Important milestones were the successful development of a low-phenylalanine diet for phenylketonuria patients, the recognition of tetrahydrobiopterin as an option to treat these individuals pharmacologically, and finally market approval of this drug. The work related to the discovery of a pharmacological treatment led metabolic researchers and pediatricians to new insights into the molecular processes linked to mutations in the phenylalanine hydroxylase gene at the cellular and structural level. Again, phenylketonuria became a prototype disorder for a previously underestimated but now rapidly expanding group of diseases: protein misfolding disorders with loss of function. Due to potential general biological mechanisms underlying these disorders, the door may soon open to a systematic development of a new class of pharmaceutical products. These pharmacological chaperones are likely to correct misfolding of proteins involved in numerous genetic and nongenetic diseases.

  11. Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis.

    Science.gov (United States)

    Parone, Philippe A; Da Cruz, Sandrine; Han, Joo Seok; McAlonis-Downes, Melissa; Vetto, Anne P; Lee, Sandra K; Tseng, Eva; Cleveland, Don W

    2013-03-13

    Mitochondria have been proposed as targets for toxicity in amyotrophic lateral sclerosis (ALS), a progressive, fatal adult-onset neurodegenerative disorder characterized by the selective loss of motor neurons. A decrease in the capacity of spinal cord mitochondria to buffer calcium (Ca(2+)) has been observed in mice expressing ALS-linked mutants of SOD1 that develop motor neuron disease with many of the key pathological hallmarks seen in ALS patients. In mice expressing three different ALS-causing SOD1 mutants, we now test the contribution of the loss of mitochondrial Ca(2+)-buffering capacity to disease mechanism(s) by eliminating ubiquitous expression of cyclophilin D, a critical regulator of Ca(2+)-mediated opening of the mitochondrial permeability transition pore that determines mitochondrial Ca(2+) content. A chronic increase in mitochondrial buffering of Ca(2+) in the absence of cyclophilin D was maintained throughout disease course and was associated with improved mitochondrial ATP synthesis, reduced mitochondrial swelling, and retention of normal morphology. This was accompanied by an attenuation of glial activation, reduction in levels of misfolded SOD1 aggregates in the spinal cord, and a significant suppression of motor neuron death throughout disease. Despite this, muscle denervation, motor axon degeneration, and disease progression and survival were unaffected, thereby eliminating mutant SOD1-mediated loss of mitochondrial Ca(2+) buffering capacity, altered mitochondrial morphology, motor neuron death, and misfolded SOD1 aggregates, as primary contributors to disease mechanism for fatal paralysis in these models of familial ALS.

  12. Teaching Tolerance? Associational Diversity and Tolerance Formation

    DEFF Research Database (Denmark)

    Rapp, Carolin; Freitag, Markus

    2015-01-01

    , a closer look is taken at how associational diversity relates to the formation of tolerance and the importance of associations as schools of tolerance are evaluated. The main theoretical argument follows contact theory, wherein regular and enduring contact in diverse settings reduces prejudice and thereby...

  13. Primordial membranes

    DEFF Research Database (Denmark)

    Hanczyc, Martin M; Monnard, Pierre-Alain

    2017-01-01

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

  14. Isolation of butanol- and isobutanol-tolerant bacteria and physiological characterization of their butanol tolerance.

    Science.gov (United States)

    Kanno, Manabu; Katayama, Taiki; Tamaki, Hideyuki; Mitani, Yasuo; Meng, Xian-Ying; Hori, Tomoyuki; Narihiro, Takashi; Morita, Naoki; Hoshino, Tamotsu; Yumoto, Isao; Kimura, Nobutada; Hanada, Satoshi; Kamagata, Yoichi

    2013-11-01

    Despite their importance as a biofuel production platform, only a very limited number of butanol-tolerant bacteria have been identified thus far. Here, we extensively explored butanol- and isobutanol-tolerant bacteria from various environmental samples. A total of 16 aerobic and anaerobic bacteria that could tolerate greater than 2.0% (vol/vol) butanol and isobutanol were isolated. A 16S rRNA gene sequencing analysis revealed that the isolates were phylogenetically distributed over at least nine genera: Bacillus, Lysinibacillus, Rummeliibacillus, Brevibacillus, Coprothermobacter, Caloribacterium, Enterococcus, Hydrogenoanaerobacterium, and Cellulosimicrobium, within the phyla Firmicutes and Actinobacteria. Ten of the isolates were phylogenetically distinct from previously identified butanol-tolerant bacteria. Two relatively highly butanol-tolerant strains CM4A (aerobe) and GK12 (obligate anaerobe) were characterized further. Both strains changed their membrane fatty acid composition in response to butanol exposure, i.e., CM4A and GK12 exhibited increased saturated and cyclopropane fatty acids (CFAs) and long-chain fatty acids, respectively, which may serve to maintain membrane fluidity. The gene (cfa) encoding CFA synthase was cloned from strain CM4A and expressed in Escherichia coli. The recombinant E. coli showed relatively higher butanol and isobutanol tolerance than E. coli without the cfa gene, suggesting that cfa can confer solvent tolerance. The exposure of strain GK12 to butanol by consecutive passages even enhanced the growth rate, indicating that yet-unknown mechanisms may also contribute to solvent tolerance. Taken together, the results demonstrate that a wide variety of butanol- and isobutanol-tolerant bacteria that can grow in 2.0% butanol exist in the environment and have various strategies to maintain structural integrity against detrimental solvents.

  15. Lactose tolerance tests

    Science.gov (United States)

    Hydrogen breath test for lactose tolerance ... Two common methods include: Lactose tolerance blood test Hydrogen breath test The hydrogen breath test is the preferred method. It measures the amount of hydrogen ...

  16. Membranous nephropathy

    Science.gov (United States)

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

  17. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms...... or interpretations of recognition and toleration are considered, confusing and problematic uses of the terms are noted, and the compatibility of toleration and recognition is discussed. The article argues that there is a range of legitimate and importantly different conceptions of both toleration and recognition...

  18. Fault Tolerant Feedback Control

    DEFF Research Database (Denmark)

    Stoustrup, Jakob; Niemann, H.

    2001-01-01

    An architecture for fault tolerant feedback controllers based on the Youla parameterization is suggested. It is shown that the Youla parameterization will give a residual vector directly in connection with the fault diagnosis part of the fault tolerant feedback controller. It turns out...... that there is a separation be-tween the feedback controller and the fault tolerant part. The closed loop feedback properties are handled by the nominal feedback controller and the fault tolerant part is handled by the design of the Youla parameter. The design of the fault tolerant part will not affect the design...... of the nominal feedback con-troller....

  19. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2004-01-01

    BackgroundDimensioning and TolerancingTolerance Format and Decimal PlacesConverting Plus/Minus Dimensions and Tolerances into Equal Bilaterally Toleranced DimensionsVariation and Sources of VariationTolerance AnalysisWorst-case Tolerance StackupsStatistical Tolerance StackupsGeometric Dimensioning and Tolerancing (GD&T)Converting Plus/Minus Tolerancing to Positional Tolerancing and Projected Tolerance ZonesDiametral and Radial Tolerance StackupsSpecifying Material Condition Modifiers and Their Effect on Tolerance Stackups The Tolerance Stackup SketchThe Tolerance Stackup Report FormTolerance S

  20. Axionic membranes

    International Nuclear Information System (INIS)

    Aurilia, A.; Spallucci, E.

    1992-01-01

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

  1. Engineering microbes for tolerance to next-generation biofuels

    Directory of Open Access Journals (Sweden)

    Dunlop Mary J

    2011-09-01

    Full Text Available Abstract A major challenge when using microorganisms to produce bulk chemicals such as biofuels is that the production targets are often toxic to cells. Many biofuels are known to reduce cell viability through damage to the cell membrane and interference with essential physiological processes. Therefore, cells must trade off biofuel production and survival, reducing potential yields. Recently, there have been several efforts towards engineering strains for biofuel tolerance. Promising methods include engineering biofuel export systems, heat shock proteins, membrane modifications, more general stress responses, and approaches that integrate multiple tolerance strategies. In addition, in situ recovery methods and media supplements can help to ease the burden of end-product toxicity and may be used in combination with genetic approaches. Recent advances in systems and synthetic biology provide a framework for tolerance engineering. This review highlights recent targeted approaches towards improving microbial tolerance to next-generation biofuels with a particular emphasis on strategies that will improve production.

  2. Metamaterial membranes

    International Nuclear Information System (INIS)

    Restrepo-Flórez, Juan Manuel; Maldovan, Martin

    2017-01-01

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

  3. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2013-01-01

    Under conditions of pluralism different cultures, interests or values can come into conflict, which raises the problem of how to secure peaceful co-existence. The idea of toleration historically emerged as an answer to this problem. Recently Rainer Forst has argued that toleration should not just...... be based on a modus vivendi designed to secure peaceful co-existence, but should be based on moral reasons. Forst therefore advances what he calls the ‘respect conception’ of toleration as an in itself morally desirable type of relationship, which is furthermore the only conception of toleration...... that avoids various so-called ‘paradoxes of toleration’. The paper first examines whether Forst’s respect conception can be applied descriptively to distinguish between actual patterns of behaviour and classify different acts of toleration. Then the focus is shifted to toleration out of respect as a normative...

  4. Chelating polymeric membranes

    KAUST Repository

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

    2015-01-01

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

  5. Tolerance in Drosophila

    OpenAIRE

    Atkinson, Nigel S.

    2009-01-01

    The set of genes that underlie ethanol tolerance (inducible resistance) are likely to overlap with the set of genes responsible for ethanol addiction. Whereas addiction is difficult to recognize in simple model systems, behavioral tolerance is readily identifiable and can be induced in large populations of animals. Thus, tolerance lends itself to analysis in model systems with powerful genetics. Drosophila melanogaster has been used by a variety of laboratories for the identification of genes...

  6. Generating high temperature tolerant transgenic plants: Achievements and challenges.

    Science.gov (United States)

    Grover, Anil; Mittal, Dheeraj; Negi, Manisha; Lavania, Dhruv

    2013-05-01

    Production of plants tolerant to high temperature stress is of immense significance in the light of global warming and climate change. Plant cells respond to high temperature stress by re-programming their genetic machinery for survival and reproduction. High temperature tolerance in transgenic plants has largely been achieved either by over-expressing heat shock protein genes or by altering levels of heat shock factors that regulate expression of heat shock and non-heat shock genes. Apart from heat shock factors, over-expression of other trans-acting factors like DREB2A, bZIP28 and WRKY proteins has proven useful in imparting high temperature tolerance. Besides these, elevating the genetic levels of proteins involved in osmotic adjustment, reactive oxygen species removal, saturation of membrane-associated lipids, photosynthetic reactions, production of polyamines and protein biosynthesis process have yielded positive results in equipping transgenic plants with high temperature tolerance. Cyclic nucleotide gated calcium channel proteins that regulate calcium influxes across the cell membrane have recently been shown to be the key players in induction of high temperature tolerance. The involvement of calmodulins and kinases in activation of heat shock factors has been implicated as an important event in governing high temperature tolerance. Unfilled gaps limiting the production of high temperature tolerant transgenic plants for field level cultivation are discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Compromise and Toleration

    DEFF Research Database (Denmark)

    Rostbøll, Christian F.

    Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature, justifi...... in compromise are more stringent than those for being tolerated. Still, the limits of compromise cannot be drawn to narrowly if it is to remain its value as a form of agreement that respects and embodies the differences of opinion in society.......Political compromise is akin to toleration, since both consist of an "agreement to disagree." Compromise and toleration also share a predicament of being regarded as ambiguous virtues that require of us to accept something we actually regard as wrong. However, we misunderstand the nature......, justification, and limits of compromise if we see it merely as a matter of toleration. While toleration is mainly a matter of accepting citizens' equal right to co-existence as subjects to law, political compromise includes the parties in making law – it makes them co-authors of law. Toleration entails...

  8. Tolerances in micro manufacturing

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Zhang, Yang; Islam, Aminul

    This paper describes a method for analysis of tolerances in micro manufacturing. It proposes a mapping oftolerances to dimensions and compares this with current available international standards. The analysisdocuments that tolerances are not scaled down as the absolute dimension. In practice...

  9. Fault tolerant computing systems

    International Nuclear Information System (INIS)

    Randell, B.

    1981-01-01

    Fault tolerance involves the provision of strategies for error detection damage assessment, fault treatment and error recovery. A survey is given of the different sorts of strategies used in highly reliable computing systems, together with an outline of recent research on the problems of providing fault tolerance in parallel and distributed computing systems. (orig.)

  10. Toleration out of respect?

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    be based on a modus vivendi designed to secure peaceful co-existence, but should be based on moral reasons. Forst therefore advances what he calls the ‘respect conception’ of toleration as an in itself morally desirable type of relationship, which is furthermore the only conception of toleration...

  11. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms or inter...

  12. Remember Tolerance Differently

    DEFF Research Database (Denmark)

    Tønder, Lars

    2012-01-01

    This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history, not by inv......This essay questions the linear conception of history which often accompanies the way contemporary democratic theory tends to disavow tolerance's discontinuities and remainders. In the spirit of Foucault's genealogy of descent, the idea is to develop a new sense of tolerance's history......, not by invoking a critique external to contemporary democratic theory, but by witnessing the history of tolerance paraliptically, with an eye to what it obscures and yet presupposes....

  13. Two Outer Membrane Proteins Contribute to Caulobacter crescentus Cellular Fitness by Preventing Intracellular S-Layer Protein Accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Overton, K. Wesley; Park, Dan M.; Yung, Mimi C.; Dohnalkova, Alice; Smit, John; Jiao, Yongqin

    2016-09-23

    ABSTRACT

    Surface layers, or S-layers, are two-dimensional protein arrays that form the outermost layer of many bacteria and archaea. They serve several functions, including physical protection of the cell from environmental threats. The high abundance of S-layer proteins necessitates a highly efficient export mechanism to transport the S-layer protein from the cytoplasm to the cell exterior.Caulobacter crescentusis unique in that it has two homologous, seemingly redundant outer membrane proteins, RsaFaand RsaFb, which together with other components form a type I protein translocation pathway for S-layer export. These proteins have homology toEscherichia coliTolC, the outer membrane channel of multidrug efflux pumps. Here we provide evidence that, unlike TolC, RsaFaand RsaFbare not involved in either the maintenance of membrane stability or the active export of antimicrobial compounds. Rather, RsaFaand RsaFbare required to prevent intracellular accumulation and aggregation of the S-layer protein RsaA; deletion of RsaFaand RsaFbled to a general growth defect and lowered cellular fitness. Using Western blotting, transmission electron microscopy, and transcriptome sequencing (RNA-seq), we show that loss of both RsaFaand RsaFbled to accumulation of insoluble RsaA in the cytoplasm, which in turn caused upregulation of a number of genes involved in protein misfolding and degradation pathways. These findings provide new insight into the requirement for RsaFaand RsaFbin cellular fitness and tolerance to antimicrobial agents and further our understanding of the S-layer export mechanism on both the transcriptional and translational levels in

  14. A Multirelational Account of Toleration

    DEFF Research Database (Denmark)

    Ferretti, Maria Paola; Lægaard, Sune

    2013-01-01

    Toleration classically denotes a relation between two agents that is characterised by three components: objection, power, and acceptance overriding the objection. Against recent claims that classical toleration is not applicable in liberal democracies and that toleration must therefore either be ...

  15. Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

    Science.gov (United States)

    Rapoport, Basil

    2014-01-01

    Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties (“immunogenicity”) that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) “reveal,” but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen

  16. Genetic Approaches to Develop Salt Tolerant Germplasm

    KAUST Repository

    Tester, Mark A.

    2015-08-19

    Forty percent of the world\\'s food is produced under irrigation, and this is directly threatened by over-exploitation and changes in the global environment. One way to address this threat is to develop systems for increasing our ability to use lower quality water, in particular saline water. Low cost partial desalination of brackish water, use of saline water for cooling and increases in the salinity tolerance of crops can all contribute to the development of this new agricultural system. In this talk, the focus will be on the use of forward genetic approaches for discovery of genes related to salinity tolerance in barley and tomatoes. Rather than studying salinity tolerance as a trait in itself, we dissect salinity tolerance into a series of components that are hypothesised to contribute to overall salinity tolerance (following the paradigm of Munns & Tester, 2008). For example, one significant component of tolerance of most crop plants to moderate soil salinity is due to the ability to maintain low concentrations of Na+ in the leaves, and much analysis of this aspect has been done (e.g. Roy et al., 2013, 2014). A major site for the control of shoot Na+ accumulation is at the plasma membrane of the mature stele of the root. Alleles of HKT, a major gene underlying this transport process have been characterized and, in work led by Dr Rana Munns (CSIRO), have now been introgressed into commercial durum wheat and led to significantly increased yields in saline field conditions (Munns et al., 2012). The genotyping of mapping populations is now highly efficient. However, the ability to quantitatively phenotype these populations is now commonly limiting forward progress in plant science. The increasing power of digital imaging and computational technologies offers the opportunity to relieve this phenotyping bottleneck. The Plant Accelerator is a 4500m2 growth facility that provides non-destructive phenotyping of large populations of plants (http

  17. State, religion and toleration

    DEFF Research Database (Denmark)

    Huggler, Jørgen

    2009-01-01

    Contribution to Religion and State - From separation to cooperation? Legal-philosophical reflections for a de-secularized world. (IVR Cracow Special Workshop). Eds. Bart. C. Labuschagne & Ari M. Solon. Abstract: Toleration is indeed a complex phenomenon. A discussion of the concept will have...... to underline not only the broadmindedness and liberty of individuals or of groups, but also the relevant distinctions and arguments in political philosophy, epistemology, philosophy of religion and philosophical anthropology and their connection with educational issues. Through a discussion of these relations......, the essay argues three theses: (1) Toleration is not reducible to an ethics of spiritual freedom. (2) Toleration is not neutral to fanatism. (3) Toleration involves esteem for the person....

  18. Advanced Hydrogen Transport Membranes for Vision 21 Fossil Fuel Plants

    Energy Technology Data Exchange (ETDEWEB)

    Carl R. Evenson; Shane E. Roark

    2006-03-31

    The objective of this project was to develop an environmentally benign, inexpensive, and efficient method for separating hydrogen from gas mixtures produced during industrial processes, such as coal gasification. A family of hydrogen separation membranes was developed including single phase mixed conducting ceramics, ceramic/ceramic composites, cermet membranes, cermet membranes containing a hydrogen permeable metal, and intermediate temperature composite layered membranes. Each membrane type had different operating parameters, advantages, and disadvantages that were documented over the course of the project. Research on these membranes progressed from ceramics to cermets to intermediate temperature composite layered membranes. During this progression performance was increased from 0.01 mL x min{sup -1} x cm{sup -2} up to 423 mL x min{sup -1} x cm{sup -2}. Eltron and team membranes not only developed each membrane type, but also membrane surface catalysis and impurity tolerance, creation of thin film membranes, alternative applications such as membrane promoted alkane dehydrogenation, demonstration of scale-up testing, and complete engineering documentation including process and mechanical considerations necessary for inclusion of Eltron membranes in a full scale integrated gasification combined cycle power plant. The results of this project directly led to a new $15 million program funded by the Department of Energy. This new project will focus exclusively on scale-up of this technology as part of the FutureGen initiative.

  19. A Theory of Tolerance

    OpenAIRE

    Corneo, Giacomo; Jeanne, Olivier

    2006-01-01

    We develop an economic theory of tolerance where styles of behaviour are invested with symbolic value. Value systems are endogenous and taught by parents to their children. In conjunction with actual behaviour, value systems determine the esteem enjoyed by individuals. Intolerant individuals have all symbolic value invested in a single style of behaviour, whereas tolerant people have diversified values. The proposed model identifies a link between the unpredictability of children's lifestyles...

  20. Proton Conductivity and Operational Features Of PBI-Based Membranes

    DEFF Research Database (Denmark)

    Qingfeng, Li; Jensen, Jens Oluf; Precht Noyé, Pernille

    2005-01-01

    As an approach to high temperature operation of PEMFCs, acid-doped PBI membranes are under active development. The membrane exhibits high proton conductivity under low water contents at temperatures up to 200°C. Mechanisms of proton conduction for the membranes have been proposed. Based on the me...... on the membranes fuel cell tests have been demonstrated. Operating features of the PBI cell include no humidification, high CO tolerance, better heat utilization and possible integration with fuel processing units. Issues for further development are also discussed....

  1. Development of isothermal-isobaric replica-permutation method for molecular dynamics and Monte Carlo simulations and its application to reveal temperature and pressure dependence of folded, misfolded, and unfolded states of chignolin

    Science.gov (United States)

    Yamauchi, Masataka; Okumura, Hisashi

    2017-11-01

    We developed a two-dimensional replica-permutation molecular dynamics method in the isothermal-isobaric ensemble. The replica-permutation method is a better alternative to the replica-exchange method. It was originally developed in the canonical ensemble. This method employs the Suwa-Todo algorithm, instead of the Metropolis algorithm, to perform permutations of temperatures and pressures among more than two replicas so that the rejection ratio can be minimized. We showed that the isothermal-isobaric replica-permutation method performs better sampling efficiency than the isothermal-isobaric replica-exchange method and infinite swapping method. We applied this method to a β-hairpin mini protein, chignolin. In this simulation, we observed not only the folded state but also the misfolded state. We calculated the temperature and pressure dependence of the fractions on the folded, misfolded, and unfolded states. Differences in partial molar enthalpy, internal energy, entropy, partial molar volume, and heat capacity were also determined and agreed well with experimental data. We observed a new phenomenon that misfolded chignolin becomes more stable under high-pressure conditions. We also revealed this mechanism of the stability as follows: TYR2 and TRP9 side chains cover the hydrogen bonds that form a β-hairpin structure. The hydrogen bonds are protected from the water molecules that approach the protein as the pressure increases.

  2. Robotic membranes

    DEFF Research Database (Denmark)

    Ramsgaard Thomsen, Mette

    2008-01-01

    The relationship between digital and analogue is often constructed as one of opposition. The perception that the world is permeated with underlying patterns of data, describing events and matter alike, suggests that information can be understood apart from the substance to which it is associated......, and that its encoded logic can be constructed and reconfigured as an isolated entity. This disembodiment of information from materiality implies that an event like a thunderstorm, or a material like a body, can be described equally by data, in other words it can be read or written. The following prototypes......, Vivisection and Strange Metabolisms, were developed at the Centre for Information Technology and Architecture (CITA) at the Royal Danish Academy of Fine Arts in Copenhagen as a means of engaging intangible digital data with tactile physical material. As robotic membranes, they are a dual examination...

  3. Surface expression, single-channel analysis and membrane topology of recombinant Chlamydia trachomatis Major Outer Membrane Protein

    Directory of Open Access Journals (Sweden)

    McClafferty Heather

    2005-01-01

    Full Text Available Abstract Background Chlamydial bacteria are obligate intracellular pathogens containing a cysteine-rich porin (Major Outer Membrane Protein, MOMP with important structural and, in many species, immunity-related roles. MOMP forms extensive disulphide bonds with other chlamydial proteins, and is difficult to purify. Leaderless, recombinant MOMPs expressed in E. coli have yet to be refolded from inclusion bodies, and although leadered MOMP can be expressed in E. coli cells, it often misfolds and aggregates. We aimed to improve the surface expression of correctly folded MOMP to investigate the membrane topology of the protein, and provide a system to display native and modified MOMP epitopes. Results C. trachomatis MOMP was expressed on the surface of E. coli cells (including "porin knockout" cells after optimizing leader sequence, temperature and medium composition, and the protein was functionally reconstituted at the single-channel level to confirm it was folded correctly. Recombinant MOMP formed oligomers even in the absence of its 9 cysteine residues, and the unmodified protein also formed inter- and intra-subunit disulphide bonds. Its topology was modeled as a (16-stranded β-barrel, and specific structural predictions were tested by removing each of the four putative surface-exposed loops corresponding to highly immunogenic variable sequence (VS domains, and one or two of the putative transmembrane strands. The deletion of predicted external loops did not prevent folding and incorporation of MOMP into the E. coli outer membrane, in contrast to the removal of predicted transmembrane strands. Conclusions C. trachomatis MOMP was functionally expressed on the surface of E. coli cells under newly optimized conditions. Tests of its predicted membrane topology were consistent with β-barrel oligomers in which major immunogenic regions are displayed on surface-exposed loops. Functional surface expression, coupled with improved understanding of MOMP

  4. Escaping the tolerance trap

    International Nuclear Information System (INIS)

    Hammoudeh, S.; Madan, V.

    1994-01-01

    In order to examine the implications of the weakening of OPEC's responsiveness in adjusting its production levels, this paper explicitly incorporates rigidity in the quantity adjustment mechanism, thereby extending previous research which assumed smooth quantity adjustments. The rigidity is manifested in a tolerance range for the discrepancy between the declared target price and that of the market. This environment gives rise to a 'tolerance trap' which impedes the convergence process and inevitably brings the market to a standstill before its reaches the targeted price and revenue objectives. OPEC's reaction to the standstill has important implications for the achievement of the target-based equilibrium and for the potential collapse of the market price. This paper examines OPEC's policy options in the tolerance trap and reveals that the optional policy in order to break this impasse and move closer to the equilibrium point is gradually to reduce output and not to flood the market. (Author)

  5. Rapid and Highly Sensitive Detection of Variant Creutzfeldt-Jakob Disease Abnormal Prion Protein on Steel Surfaces by Protein Misfolding Cyclic Amplification: Application to Prion Decontamination Studies.

    Directory of Open Access Journals (Sweden)

    Maxime Belondrade

    Full Text Available The prevalence of variant Creutzfeldt-Jakob disease (vCJD in the population remains uncertain, although it has been estimated that 1 in 2000 people in the United Kingdom are positive for abnormal prion protein (PrPTSE by a recent survey of archived appendix tissues. The prominent lymphotropism of vCJD prions raises the possibility that some surgical procedures may be at risk of iatrogenic vCJD transmission in healthcare facilities. It is therefore vital that decontamination procedures applied to medical devices before their reprocessing are thoroughly validated. A current limitation is the lack of a rapid model permissive to human prions. Here, we developed a prion detection assay based on protein misfolding cyclic amplification (PMCA technology combined with stainless-steel wire surfaces as carriers of prions (Surf-PMCA. This assay allowed the specific detection of minute quantities (10-8 brain dilution of either human vCJD or ovine scrapie PrPTSE adsorbed onto a single steel wire, within a two week timeframe. Using Surf-PMCA we evaluated the performance of several reference and commercially available prion-specific decontamination procedures. Surprisingly, we found the efficiency of several marketed reagents to remove human vCJD PrPTSE was lower than expected. Overall, our results demonstrate that Surf-PMCA can be used as a rapid and ultrasensitive assay for the detection of human vCJD PrPTSE adsorbed onto a metallic surface, therefore facilitating the development and validation of decontamination procedures against human prions.

  6. Interaction of the 106-126 prion peptide with lipid membranes and potential implication for neurotoxicity

    International Nuclear Information System (INIS)

    Dupiereux, Ingrid; Zorzi, Willy; Lins, Laurence; Brasseur, Robert; Colson, Pierre; Heinen, Ernst; Elmoualij, Benaissa

    2005-01-01

    Prion diseases are fatal neurodegenerative disorders characterized by the accumulation in the brain of an abnormally misfolded, protease-resistant, and β-sheet rich pathogenic isoform (PrP sc ) of the cellular prion protein (PrP c ). In the present work, we were interested to study the mode of prion protein interaction with the membrane using the 106-126 peptide and small unilamellar lipid vesicles as model. As previously demonstrated, we showed by MTS assay that PrP 106-126 induces alterations in the human neuroblastoma SH-SY5Y cell line. We demonstrated for the first time by lipid-mixing assay and by the liposome vesicle leakage test that PrP 106-126, a non-tilted peptide, induces liposome fusion thus a potential cell membrane destabilization, as supported by membrane integrity assay (LDH). By circular dichroism (CD) analysis we showed that the fusogenic property of PrP 106-126 in the presence of liposome is associated with a predominantly β-sheet structure. These data suggest that the fusogenic property associated with a predominant β-sheet structure exhibited by the prion peptides contributes to the neurotoxicity of these peptides by destabilizing cellular membranes. The latter might be attached at the membrane surface in a parallel orientation as shown by molecular modeling

  7. From the endoplasmic reticulum to the plasma membrane: mechanisms of CFTR folding and trafficking.

    Science.gov (United States)

    Farinha, Carlos M; Canato, Sara

    2017-01-01

    CFTR biogenesis starts with its co-translational insertion into the membrane of endoplasmic reticulum and folding of the cytosolic domains, towards the acquisition of a fully folded compact native structure. Efficiency of this process is assessed by the ER quality control system that allows the exit of folded proteins but targets unfolded/misfolded CFTR to degradation. If allowed to leave the ER, CFTR is modified at the Golgi and reaches the post-Golgi compartments to be delivered to the plasma membrane where it functions as a cAMP- and phosphorylation-regulated chloride/bicarbonate channel. CFTR residence at the membrane is a balance of membrane delivery, endocytosis, and recycling. Several adaptors, motor, and scaffold proteins contribute to the regulation of CFTR stability and are involved in continuously assessing its structure through peripheral quality control systems. Regulation of CFTR biogenesis and traffic (and its dysregulation by mutations, such as the most common F508del) determine its overall activity and thus contribute to the fine modulation of chloride secretion and hydration of epithelial surfaces. This review covers old and recent knowledge on CFTR folding and trafficking from its synthesis to the regulation of its stability at the plasma membrane and highlights how several of these steps can be modulated to promote the rescue of mutant CFTR.

  8. Fault tolerant linear actuator

    Science.gov (United States)

    Tesar, Delbert

    2004-09-14

    In varying embodiments, the fault tolerant linear actuator of the present invention is a new and improved linear actuator with fault tolerance and positional control that may incorporate velocity summing, force summing, or a combination of the two. In one embodiment, the invention offers a velocity summing arrangement with a differential gear between two prime movers driving a cage, which then drives a linear spindle screw transmission. Other embodiments feature two prime movers driving separate linear spindle screw transmissions, one internal and one external, in a totally concentric and compact integrated module.

  9. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  10. Inequality, Tolerance, and Growth

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    This paper argues for the importance of individuals' tolerance of inequality for economic growth. By using the political ideology of governments as a measure of revealed tolerance of inequality, the paper shows that controlling for ideology improves the accuracy with which the effects of inequality...... are measured. Results show that inequality reduces growth but more so in societies where people perceive it as being relatively unfair. Further results indicate that legal quality and social trust are likely transmission channels for the effects of inequality....

  11. Does lipophilicity of toxic compounds determine effects on drought tolerance of the soil collembolan Folsomia candida?

    International Nuclear Information System (INIS)

    Skovlund, Gitte; Damgaard, Christian; Bayley, Mark; Holmstrup, Martin

    2006-01-01

    The ability of Collembola to survive drought stress is crucial for their distribution in the terrestrial environment. Previous studies have suggested that several toxic compounds affect the drought tolerance of Folsomia candida in a synergistic manner and that these compounds have the feature in common that they elicit their toxicity by causing membrane damage. We hypothesised that the detrimental effect of toxic chemicals on drought tolerance in F. candida depends on the lipophilicity (log K ow ) of the compound because a higher log K ow would mean a closer interaction with membranes. In this study the three chemicals 4-nonylphenol, pyrene and p,p'-DDE were tested. Surprisingly, 4-nonylphenol, with the lowest log K ow , was the most potent with respect to reducing drought tolerance followed by pyrene, suggesting that interactions between drought tolerance and chemical stress do not depend on lipophilicity alone. - Toxic stress may reduce drought tolerance of Collembola

  12. Recent advances on polymeric membranes for membrane reactors

    KAUST Repository

    Buonomenna, M. G.; Choi, Seung Hak

    2012-01-01

    . The successful use of membranes in membrane reactors is primary the result of two developments concerning: (i) membrane materials and (ii) membrane structures. The selection of a suited material and preparation technique depends on the application the membrane

  13. Newly Identified Wild Rice Accessions Conferring High Salt Tolerance Might Use a Tissue Tolerance Mechanism in Leaf

    Science.gov (United States)

    Prusty, Manas R.; Kim, Sung-Ryul; Vinarao, Ricky; Entila, Frederickson; Egdane, James; Diaz, Maria G. Q.; Jena, Kshirod K.

    2018-01-01

    Cultivated rice (Oryza sativa L.) is very sensitive to salt stress. So far a few rice landraces have been identified as a source of salt tolerance and utilized in rice improvement. These tolerant lines primarily use Na+ exclusion mechanism in root which removes Na+ from the xylem stream by membrane Na+ and K+ transporters, and resulted in low Na+ accumulation in shoot. Identification of a new donor source conferring high salt tolerance is imperative. Wild relatives of rice having wide genetic diversity are regarded as a potential source for crop improvement. However, they have been less exploited against salt stress. Here, we simultaneously evaluated all 22 wild Oryza species along with the cultivated tolerant lines including Pokkali, Nona Bokra, and FL478, and sensitive check varieties under high salinity (240 mM NaCl). Based on the visual salt injury score, three species (O. alta, O. latifolia, and O. coarctata) and four species (O. rhizomatis, O. eichingeri, O. minuta, and O. grandiglumis) showed higher and similar level of tolerance compared to the tolerant checks, respectively. All three CCDD genome species exhibited salt tolerance, suggesting that the CCDD genome might possess the common genetic factors for salt tolerance. Physiological and biochemical experiments were conducted using the newly isolated tolerant species together with checks under 180 mM NaCl. Interestingly, all wild species showed high Na+ concentration in shoot and low concentration in root unlike the tolerant checks. In addition, the wild-tolerant accessions showed a tendency of a high tissue tolerance in leaf, low malondialdehyde level in shoot, and high retention of chlorophyll in the young leaves. These results suggest that the wild species employ tissue tolerance mechanism to manage salt stress. Gene expression analyses of the key salt tolerance-related genes suggested that high Na+ in leaf of wild species might be affected by OsHKT1;4-mediated Na+ exclusion in leaf and the following Na

  14. Toleration, Groups, and Multiculturalism

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2014-01-01

    have the ability to interfere with the group’s activities, an object of dislike or disapproval, an agent enjoying non-interference or a moral patient. This means that 'toleration of groups' can mean quite different things depending on the exact meaning of 'group' in relation to each component...

  15. Fault Tolerant Control Systems

    DEFF Research Database (Denmark)

    Bøgh, S. A.

    This thesis considered the development of fault tolerant control systems. The focus was on the category of automated processes that do not necessarily comprise a high number of identical sensors and actuators to maintain safe operation, but still have a potential for improving immunity to component...

  16. Toleration and its enemies

    DEFF Research Database (Denmark)

    Jarvad, Ib Martin

    2010-01-01

    After a presentation of the development of freedom of expression in Danish constitutional law, to freedom of the press in European human rights law - the Jersild case- to a right to mock and ridicule other faiths in recent Danish practice, the essay of Locke on toleration is examined, its...

  17. A little toleration, please

    Science.gov (United States)

    McKnight, C.

    2000-01-01

    Value pluralism does not imply relativism or subjectivism about values. What it does is allow respect for an at least limited toleration of values with which one may profoundly disagree. Thus a doctor can respect the autonomy of a patient whose values he does not share. Key Words: Pluralism • multiculturalism • relativism • subjectivism • patient autonomy PMID:11129842

  18. Does Chlorination of Seawater Reverse Osmosis Membranes Control Biofouling?

    KAUST Repository

    Khan, Muhammad Tariq; Hong, Pei-Ying; Nada, Nabil; Croue, Jean Philippe

    2015-01-01

    Biofouling is the major problem of reverse osmosis (RO) membranes used for desalting seawater (SW). The use of chlorine is a conventional and common practice to control/prevent biofouling. Unlike polyamide RO membranes, cellulose triacetate (CTA) RO membranes display a high chlorine tolerance. Due to this characteristic, CTA membranes are used in most of the RO plants located in the Middle East region where the elevated seawater temperature and water quality promote the risk of membrane biofouling. However, there is no detailed study on the investigation/characterization of CTA-RO membrane fouling. In this investigation, the fouling profile of a full–scale SWRO desalination plant operating with not only continuous chlorination of raw seawater but also intermittent chlorination of CTA-RO membranes was studied. Detailed water quality and membrane fouling analyses were conducted. Profiles of microbiological, inorganic, and organic constituents of analysed fouling layers were extensively discussed. Our results clearly identified biofilm development on these membranes. The incapability of chlorination on preventing biofilm formation on SWRO membranes could be assigned to its failure in effectively reaching throughout the different regions of the permeators. This failure could have occurred due to three main factors: plugging of membrane fibers, chlorine consumption by organics accumulated on the front side fibers, or chlorine adaptation of certain bacterial populations.

  19. Does Chlorination of Seawater Reverse Osmosis Membranes Control Biofouling?

    KAUST Repository

    Khan, Muhammad Tariq

    2015-04-01

    Biofouling is the major problem of reverse osmosis (RO) membranes used for desalting seawater (SW). The use of chlorine is a conventional and common practice to control/prevent biofouling. Unlike polyamide RO membranes, cellulose triacetate (CTA) RO membranes display a high chlorine tolerance. Due to this characteristic, CTA membranes are used in most of the RO plants located in the Middle East region where the elevated seawater temperature and water quality promote the risk of membrane biofouling. However, there is no detailed study on the investigation/characterization of CTA-RO membrane fouling. In this investigation, the fouling profile of a full–scale SWRO desalination plant operating with not only continuous chlorination of raw seawater but also intermittent chlorination of CTA-RO membranes was studied. Detailed water quality and membrane fouling analyses were conducted. Profiles of microbiological, inorganic, and organic constituents of analysed fouling layers were extensively discussed. Our results clearly identified biofilm development on these membranes. The incapability of chlorination on preventing biofilm formation on SWRO membranes could be assigned to its failure in effectively reaching throughout the different regions of the permeators. This failure could have occurred due to three main factors: plugging of membrane fibers, chlorine consumption by organics accumulated on the front side fibers, or chlorine adaptation of certain bacterial populations.

  20. Magnetically controlled permeability membranes

    KAUST Repository

    Kosel, Jurgen

    2013-10-31

    A bioactive material delivery system can include a thermoresponsive polymer membrane and nanowires distributed within the thermoresponsive polymer membrane. Magnetic activation of a thermoresponsive polymer membrane can take place via altering the magnetization or dimensions of nanowires dispersed or ordered within the membrane matrix.

  1. Magnetically controlled permeability membranes

    KAUST Repository

    Kosel, Jü rgen; Khashab, Niveen M.; Zaher, Amir

    2013-01-01

    A bioactive material delivery system can include a thermoresponsive polymer membrane and nanowires distributed within the thermoresponsive polymer membrane. Magnetic activation of a thermoresponsive polymer membrane can take place via altering the magnetization or dimensions of nanowires dispersed or ordered within the membrane matrix.

  2. Deconstructing tolerance with clobazam

    Science.gov (United States)

    Wechsler, Robert T.; Sankar, Raman; Montouris, Georgia D.; White, H. Steve; Cloyd, James C.; Kane, Mary Clare; Peng, Guangbin; Tworek, David M.; Shen, Vivienne; Isojarvi, Jouko

    2016-01-01

    Objective: To evaluate potential development of tolerance to adjunctive clobazam in patients with Lennox-Gastaut syndrome. Methods: Eligible patients enrolled in open-label extension study OV-1004, which continued until clobazam was commercially available in the United States or for a maximum of 2 years outside the United States. Enrolled patients started at 0.5 mg·kg−1·d−1 clobazam, not to exceed 40 mg/d. After 48 hours, dosages could be adjusted up to 2.0 mg·kg−1·d−1 (maximum 80 mg/d) on the basis of efficacy and tolerability. Post hoc analyses evaluated mean dosages and drop-seizure rates for the first 2 years of the open-label extension based on responder categories and baseline seizure quartiles in OV-1012. Individual patient listings were reviewed for dosage increases ≥40% and increasing seizure rates. Results: Data from 200 patients were included. For patients free of drop seizures, there was no notable change in dosage over 24 months. For responder groups still exhibiting drop seizures, dosages were increased. Weekly drop-seizure rates for 100% and ≥75% responders demonstrated a consistent response over time. Few patients had a dosage increase ≥40% associated with an increase in seizure rates. Conclusions: Two-year findings suggest that the majority of patients do not develop tolerance to the antiseizure actions of clobazam. Observed dosage increases may reflect best efforts to achieve seizure freedom. It is possible that the clinical development of tolerance to clobazam has been overstated. ClinicalTrials.gov identifier: NCT00518713 and NCT01160770. Classification of evidence: This study provides Class III evidence that the majority of patients do not develop tolerance to clobazam over 2 years of treatment. PMID:27683846

  3. Dust-Tolerant Intelligent Electrical Connection System

    Science.gov (United States)

    Lewis, Mark; Dokos, Adam; Perotti, Jose; Calle, Carlos; Mueller, Robert; Bastin, Gary; Carlson, Jeffrey; Townsend, Ivan, III; Immer, Chirstopher; Medelius, Pedro

    2012-01-01

    Faults in wiring systems are a serious concern for the aerospace and aeronautic (commercial, military, and civilian) industries. Circuit failures and vehicle accidents have occurred and have been attributed to faulty wiring created by open and/or short circuits. Often, such circuit failures occur due to vibration during vehicle launch or operation. Therefore, developing non-intrusive fault-tolerant techniques is necessary to detect circuit faults and automatically route signals through alternate recovery paths while the vehicle or lunar surface systems equipment is in operation. Electrical connector concepts combining dust mitigation strategies and cable diagnostic technologies have significant application for lunar and Martian surface systems, as well as for dusty terrestrial applications. The dust-tolerant intelligent electrical connection system has several novel concepts and unique features. It combines intelligent cable diagnostics (health monitoring) and automatic circuit routing capabilities into a dust-tolerant electrical umbilical. It retrofits a clamshell protective dust cover to an existing connector for reduced gravity operation, and features a universal connector housing with three styles of dust protection: inverted cap, rotating cap, and clamshell. It uses a self-healing membrane as a dust barrier for electrical connectors where required, while also combining lotus leaf technology for applications where a dust-resistant coating providing low surface tension is needed to mitigate Van der Waals forces, thereby disallowing dust particle adhesion to connector surfaces. It also permits using a ruggedized iris mechanism with an embedded electrodynamic dust shield as a dust barrier for electrical connectors where required.

  4. Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

    International Nuclear Information System (INIS)

    Chou, D.T.; Khan, S.; Forde, J.; Hirsh, K.R.

    1985-01-01

    The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of [ 3 H]-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify the neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for [ 3 H]-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures

  5. Induction of bacterial lipoprotein tolerance is associated with suppression of toll-like receptor 2 expression.

    LENUS (Irish Health Repository)

    Wang, Jiang Huai

    2012-02-03

    Tolerance to bacterial cell wall components including lipopolysaccharide (LPS) may represent an essential regulatory mechanism during bacterial infection. Two members of the Toll-like receptor (TLR) family, TLR2 and TLR4, recognize the specific pattern of bacterial cell wall components. TLR4 has been found to be responsible for LPS tolerance. However, the role of TLR2 in bacterial lipoprotein (BLP) tolerance and LPS tolerance is unclear. Pretreatment of human THP-1 monocytic cells with a synthetic bacterial lipopeptide induced tolerance to a second BLP challenge with diminished tumor necrosis factor-alpha and interleukin-6 production, termed BLP tolerance. Furthermore, BLP-tolerized THP-1 cells no longer responded to LPS stimulation, indicating a cross-tolerance to LPS. Induction of BLP tolerance was CD14-independent, as THP-1 cells that lack membrane-bound CD14 developed tolerance both in serum-free conditions and in the presence of a specific CD14 blocking monoclonal antibody (MEM-18). Pre-exposure of THP-1 cells to BLP suppressed mitogen-activated protein kinase phosphorylation and nuclear factor-kappaB activation in response to subsequent BLP and LPS stimulation, which is comparable with that found in LPS-tolerized cells, indicating that BLP tolerance and LPS tolerance may share similar intracellular pathways. However, BLP strongly enhanced TLR2 expression in non-tolerized THP-1 cells, whereas LPS stimulation had no effect. Furthermore, a specific TLR2 blocking monoclonal antibody (2392) attenuated BLP-induced, but not LPS-induced, tumor necrosis factor-alpha and interleukin-6 production, indicating BLP rather than LPS as a ligand for TLR2 engagement and activation. More importantly, pretreatment of THP-1 cells with BLP strongly inhibited TLR2 activation in response to subsequent BLP stimulation. In contrast, LPS tolerance did not prevent BLP-induced TLR2 overexpression. These results demonstrate that BLP tolerance develops through down-regulation of TLR2

  6. Insights into plant plasma membrane aquaporin trafficking.

    Science.gov (United States)

    Hachez, Charles; Besserer, Arnaud; Chevalier, Adrien S; Chaumont, François

    2013-06-01

    Plasma membrane intrinsic proteins (PIPs) are plant aquaporins that facilitate the diffusion of water and small uncharged solutes through the cell membrane. Deciphering the network of interacting proteins that modulate PIP trafficking to and activity in the plasma membrane is essential to improve our knowledge about PIP regulation and function. This review highlights the most recent advances related to PIP subcellular routing and dynamic redistribution, identifies some key molecular interacting proteins, and indicates exciting directions for future research in this field. A better understanding of the mechanisms by which plants optimize water movement might help in identifying new molecular players of agronomical relevance involved in the control of cellular water uptake and drought tolerance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Insight into PreImplantation Factor (PIF* mechanism for embryo protection and development: target oxidative stress and protein misfolding (PDI and HSP through essential RIKP [corrected] binding site.

    Directory of Open Access Journals (Sweden)

    Eytan R Barnea

    Full Text Available Endogenous PIF, upon which embryo development is dependent, is secreted only by viable mammalian embryos, and absent in non-viable ones. Synthetic PIF (sPIF administration promotes singly cultured embryos development and protects against their demise caused by embryo-toxic serum. To identify and characterize critical sPIF-embryo protein interactions novel biochemical and bio-analytical methods were specifically devised.FITC-PIF uptake/binding by cultured murine and equine embryos was examined and compared with scrambled FITC-PIF (control. Murine embryo (d10 lysates were fractionated by reversed-phase HPLC, fractions printed onto microarray slides and probed with Biotin-PIF, IDE and Kv1.3 antibodies, using fluorescence detection. sPIF-based affinity column was developed to extract and identify PIF-protein interactions from lysates using peptide mass spectrometry (LC/MS/MS. In silico evaluation examined binding of PIF to critical targets, using mutation analysis.PIF directly targets viable cultured embryos as compared with control peptide, which failed to bind. Multistep Biotin-PIF targets were confirmed by single-step PIF-affinity column based isolation. PIF binds protein disulfide isomerases a prolyl-4-hydroxylase β-subunit, (PDI, PDIA4, PDIA6-like containing the antioxidant thioredoxin domain. PIF also binds protective heat shock proteins (70&90, co-chaperone, BAG-3. Remarkably, PIF targets a common RIKP [corrected] site in PDI and HSP proteins. Further, single PIF amino acid mutation significantly reduced peptide-protein target bonding. PIF binds promiscuous tubulins, neuron backbones and ACTA-1,2 visceral proteins. Significant anti-IDE, while limited anti-Kv1.3b antibody-binding to Biotin-PIF positive lysates HPLC fractions were documented.Collectively, data identifies PIF shared targets on PDI and HSP in the embryo. Such are known to play a critical role in protecting against oxidative stress and protein misfolding. PIF-affinity-column is a

  8. Heat tolerance in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari

    As a consequence of global climate change, heat stress together with other abiotic stresses will remain an important determinant of future food security. Wheat (Triticum aestivum L.) is the third most important crop of the world feeding one third of the world population. Being a crop of temperate...... climate, wheat is sensitive to heat stress. We need to understand how our crops will perform in these changing climatic conditions and how we can develop varieties, which are more tolerant. The PhD study focussed on understanding heat tolerance in wheat with a combined approach of plant physiology...... and quantitative genetics in particular, plant phenotyping based quantitative trait loci (QTL) discovery for a physiological trait under heat stress. Chlorophyll a fluorescence trait, Fv/Fm was used as a phenotyping tool, as it reflects the effect of heat stress on maximum photochemical efficiency of photosystem...

  9. Socially-Tolerable Discrimination

    OpenAIRE

    Amegashie, J. Atsu

    2008-01-01

    History is replete with overt discrimination on the basis of race, gender, age, citizenship, ethnicity, marital status, academic performance, health status, volume of market transactions, religion, sexual orientation, etc. However, these forms of discrimination are not equally tolerable. For example, discrimination based on immutable or prohibitively unalterable characteristics such as race, gender, or ethnicity is much less acceptable. Why? I develop a simple rent-seeking model of conflict w...

  10. Membrane engineering via trans unsaturated fatty acids production improves Escherichia coli robustness and production of biorenewables.

    Science.gov (United States)

    Tan, Zaigao; Yoon, Jong Moon; Nielsen, David R; Shanks, Jacqueline V; Jarboe, Laura R

    2016-05-01

    Constructing microbial biocatalysts that produce biorenewables at economically viable yields and titers is often hampered by product toxicity. For production of short chain fatty acids, membrane damage is considered the primary mechanism of toxicity, particularly in regards to membrane integrity. Previous engineering efforts in Escherichia coli to increase membrane integrity, with the goal of increasing fatty acid tolerance and production, have had mixed results. Herein, a novel approach was used to reconstruct the E. coli membrane by enabling production of a novel membrane component. Specifically, trans unsaturated fatty acids (TUFA) were produced and incorporated into the membrane of E. coli MG1655 by expression of cis-trans isomerase (Cti) from Pseudomonas aeruginosa. While the engineered strain was found to have no increase in membrane integrity, a significant decrease in membrane fluidity was observed, meaning that membrane polarization and rigidity were increased by TUFA incorporation. As a result, tolerance to exogenously added octanoic acid and production of octanoic acid were both increased relative to the wild-type strain. This membrane engineering strategy to improve octanoic acid tolerance was found to require fine-tuning of TUFA abundance. Besides improving tolerance and production of carboxylic acids, TUFA production also enabled increased tolerance in E. coli to other bio-products, e.g. alcohols, organic acids, aromatic compounds, a variety of adverse industrial conditions, e.g. low pH, high temperature, and also elevated styrene production, another versatile bio-chemical product. TUFA permitted enhanced growth due to alleviation of bio-product toxicity, demonstrating the general effectiveness of this membrane engineering strategy towards improving strain robustness. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  11. Water Uptake and Acid Doping of Polybenzimidazoles as Electrolyte Membranes for Fuel Cells

    DEFF Research Database (Denmark)

    Qingfeng, Li; He, R.; Berg, Rolf W.

    2004-01-01

    Acid-doped polybenzimidazole (PBI) membranes have been demonstrated for fuel cell applications with advanced features such as high operating temperatures, little humidification, excellent CO tolerance, and promising durability. The water uptake and acid doping of PBI membranes have been studied...

  12. Hybrid adsorptive membrane reactor

    Science.gov (United States)

    Tsotsis, Theodore T [Huntington Beach, CA; Sahimi, Muhammad [Altadena, CA; Fayyaz-Najafi, Babak [Richmond, CA; Harale, Aadesh [Los Angeles, CA; Park, Byoung-Gi [Yeosu, KR; Liu, Paul K. T. [Lafayette Hill, PA

    2011-03-01

    A hybrid adsorbent-membrane reactor in which the chemical reaction, membrane separation, and product adsorption are coupled. Also disclosed are a dual-reactor apparatus and a process using the reactor or the apparatus.

  13. Premature rupture of membranes

    Science.gov (United States)

    ... gov/ency/patientinstructions/000512.htm Premature rupture of membranes To use the sharing features on this page, ... water that surrounds your baby in the womb. Membranes or layers of tissue hold in this fluid. ...

  14. Oxygen transport membrane

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates to a novel composite oxygen transport membrane as well as its preparation and uses thereof.......The present invention relates to a novel composite oxygen transport membrane as well as its preparation and uses thereof....

  15. Membrane with integrated spacer

    NARCIS (Netherlands)

    Balster, J.H.; Stamatialis, Dimitrios; Wessling, Matthias

    2010-01-01

    Many membrane processes are severely influenced by concentration polarisation. Turbulence promoting spacers placed in between the membranes can reduce the diffusional resistance of concentration polarisation by inducing additional mixing. Electrodialysis (ED) used for desalination suffers from

  16. Gel layer formation on membranes in Membrane Bioreactors

    NARCIS (Netherlands)

    Van den Brink, P.F.H.

    2014-01-01

    The widespread application of membrane bioreactors (MBRs) for municipal wastewater treatment is hampered by membrane fouling. Fouling increases energy demand, reduces process performance and creates the need for more frequent (chemical) membrane cleaning or replacement. Membrane fouling in MBRs is

  17. Smart membranes for monitoring membrane based desalination processes

    KAUST Repository

    Laleg-Kirati, Taous-Meriem; Karam, Ayman M.

    2017-01-01

    Various examples are related to smart membranes for monitoring membrane based process such as, e.g., membrane distillation processes. In one example, a membrane, includes a porous surface and a plurality of sensors (e.g., temperature, flow and

  18. Fault Tolerant Computer Architecture

    CERN Document Server

    Sorin, Daniel

    2009-01-01

    For many years, most computer architects have pursued one primary goal: performance. Architects have translated the ever-increasing abundance of ever-faster transistors provided by Moore's law into remarkable increases in performance. Recently, however, the bounty provided by Moore's law has been accompanied by several challenges that have arisen as devices have become smaller, including a decrease in dependability due to physical faults. In this book, we focus on the dependability challenge and the fault tolerance solutions that architects are developing to overcome it. The two main purposes

  19. Toleration, Synthesis or Replacement?

    DEFF Research Database (Denmark)

    Holtermann, Jakob v. H.; Madsen, Mikael Rask

    2016-01-01

    , in order to answer is not yet another partisan suggestion, but rather an attempt at making intelligible both the oppositions and the possibilities of synthesis between normative and empirical approaches to law. Based on our assessment and rational reconstruction of current arguments and positions, we...... therefore outline a taxonomy consisting of the following three basic, ideal-types in terms of the epistemological understanding of the interface of law and empirical studies: toleration, synthesis and replacement. This tripartite model proves useful with a view to teasing out and better articulating...

  20. Model cell membranes

    DEFF Research Database (Denmark)

    Günther-Pomorski, Thomas; Nylander, Tommy; Cardenas Gomez, Marite

    2014-01-01

    The high complexity of biological membranes has motivated the development and application of a wide range of model membrane systems to study biochemical and biophysical aspects of membranes in situ under well defined conditions. The aim is to provide fundamental understanding of processes control...

  1. Idiopathic epiretinal membrane

    NARCIS (Netherlands)

    Bu, Shao-Chong; Kuijer, Roelof; Li, Xiao-Rong; Hooymans, Johanna M M; Los, Leonoor I

    2014-01-01

    Background: Idiopathic epiretinal membrane (iERM) is a fibrocellular membrane that proliferates on the inner surface of the retina at the macular area. Membrane contraction is an important sight-threatening event and is due to fibrotic remodeling. Methods: Analysis of the current literature

  2. Meniscus Membranes For Separation

    Science.gov (United States)

    Dye, Robert C.; Jorgensen, Betty; Pesiri, David R.

    2005-09-20

    Gas separation membranes, especially meniscus-shaped membranes for gas separations are disclosed together with the use of such meniscus-shaped membranes for applications such as thermal gas valves, pre-concentration of a gas stream, and selective pre-screening of a gas stream. In addition, a rapid screening system for simultaneously screening polymer materials for effectiveness in gas separation is provided.

  3. Meniscus membranes for separations

    Science.gov (United States)

    Dye, Robert C [Irvine, CA; Jorgensen, Betty [Jemez Springs, NM; Pesiri, David R [Aliso Viejo, CA

    2004-01-27

    Gas separation membranes, especially meniscus-shaped membranes for gas separations are disclosed together with the use of such meniscus-shaped membranes for applications such as thermal gas valves, pre-concentration of a gas stream, and selective pre-screening of a gas stream. In addition, a rapid screening system for simultaneously screening polymer materials for effectiveness in gas separation is provided.

  4. Ethnopoly promotes tolerance

    CERN Document Server

    CERN Bulletin

    2010-01-01

    On Friday 23 April, 225 primary school children from the eight schools in Meyrin-Cointrin and their accompanying adults took part in a big game of Ethnopoly. Private individuals, associations, administrations, shopkeepers and CERN all opened their doors to them to talk about their countries, their customs and what they are doing to promote tolerance and integration.   The CERN stand set up at ForumMeyrin for the Ethnopoly game. Scurrying from one place to another, the 10 and 11 year olds were made aware of the rich cultural diversity of their commune, which is home to 130 different nationalities. Physicists and engineers from CERN took up residence in the Forum Meyrin for the day in order to talk to the children about the advantages of international collaboration, a subject dear to the Organization's heart. They welcomed around fifty children in the course of the day, conveying to them a message of tolerance: despite their differences, the 10,000 scientists and other members of the CERN...

  5. Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR.

    Science.gov (United States)

    Varkey, Jobin; Langen, Ralf

    2017-07-01

    The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single

  6. Membrane remodeling by amyloidogenic and non-amyloidogenic proteins studied by EPR

    Science.gov (United States)

    Varkey, Jobin; Langen, Ralf

    2017-07-01

    The advancement in site-directed spin labeling of proteins has enabled EPR studies to expand into newer research areas within the umbrella of protein-membrane interactions. Recently, membrane remodeling by amyloidogenic and non-amyloidogenic proteins has gained a substantial interest in relation to driving and controlling vital cellular processes such as endocytosis, exocytosis, shaping of organelles like endoplasmic reticulum, Golgi and mitochondria, intracellular vesicular trafficking, formation of filopedia and multivesicular bodies, mitochondrial fusion and fission, and synaptic vesicle fusion and recycling in neurotransmission. Misregulation in any of these processes due to an aberrant protein (mutation or misfolding) or alteration of lipid metabolism can be detrimental to the cell and cause disease. Dissection of the structural basis of membrane remodeling by proteins is thus quite necessary for an understanding of the underlying mechanisms, but it remains a formidable task due to the difficulties of various common biophysical tools in monitoring the dynamic process of membrane binding and bending by proteins. This is largely since membranes generally complicate protein structure analysis and this problem is amplified for structural analysis in the presence of different types of membrane curvatures. Recent EPR studies on membrane remodeling by proteins show that a significant structural information can be generated to delineate the role of different protein modules, domains and individual amino acids in the generation of membrane curvature. These studies also show how EPR can complement the data obtained by high resolution techniques such as X-ray and NMR. This perspective covers the application of EPR in recent studies for understanding membrane remodeling by amyloidogenic and non-amyloidogenic proteins that is useful for researchers interested in using or complimenting EPR to gain better understanding of membrane remodeling. We also discuss how a single

  7. Separation membrane development

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.W. [Savannah River Technology Center, Aiken, SC (United States)

    1998-08-01

    A ceramic membrane has been developed to separate hydrogen from other gases. The method used is a sol-gel process. A thin layer of dense ceramic material is coated on a coarse ceramic filter substrate. The pore size distribution in the thin layer is controlled by a densification of the coating materials by heat treatment. The membrane has been tested by permeation measurement of the hydrogen and other gases. Selectivity of the membrane has been achieved to separate hydrogen from carbon monoxide. The permeation rate of hydrogen through the ceramic membrane was about 20 times larger than Pd-Ag membrane.

  8. Microporous silica membranes

    DEFF Research Database (Denmark)

    Boffa, Vittorio; Yue, Yuanzheng

    2012-01-01

    Hydrothermal stability is a crucial factor for the application of microporous silica-based membranes in industrial processes. Indeed, it is well established that steam exposure may cause densification and defect formation in microporous silica membranes, which are detrimental to both membrane...... permeability and selectivity. Numerous previous studies show that microporous transition metal doped-silica membranes are hydrothermally more stable than pure silica membranes, but less permeable. Here we present a quantitative study on the impact of type and concentration of transition metal ions...... on the microporous structure, stability and permeability of amorphous silica-based membranes, providing information on how to design chemical compositions and synthetic paths for the fabrication of silica-based membranes with a well accessible and highly stabile microporous structure....

  9. Clustering on Membranes

    DEFF Research Database (Denmark)

    Johannes, Ludger; Pezeshkian, Weria; Ipsen, John H

    2018-01-01

    Clustering of extracellular ligands and proteins on the plasma membrane is required to perform specific cellular functions, such as signaling and endocytosis. Attractive forces that originate in perturbations of the membrane's physical properties contribute to this clustering, in addition to direct...... protein-protein interactions. However, these membrane-mediated forces have not all been equally considered, despite their importance. In this review, we describe how line tension, lipid depletion, and membrane curvature contribute to membrane-mediated clustering. Additional attractive forces that arise...... from protein-induced perturbation of a membrane's fluctuations are also described. This review aims to provide a survey of the current understanding of membrane-mediated clustering and how this supports precise biological functions....

  10. Fault-tolerant computing systems

    International Nuclear Information System (INIS)

    Dal Cin, M.; Hohl, W.

    1991-01-01

    Tests, Diagnosis and Fault Treatment were chosen as the guiding themes of the conference. However, the scope of the conference included reliability, availability, safety and security issues in software and hardware systems as well. The sessions were organized for the conference which was completed by an industrial presentation: Keynote Address, Reconfiguration and Recover, System Level Diagnosis, Voting and Agreement, Testing, Fault-Tolerant Circuits, Array Testing, Modelling, Applied Fault Tolerance, Fault-Tolerant Arrays and Systems, Interconnection Networks, Fault-Tolerant Software. One paper has been indexed separately in the database. (orig./HP)

  11. Commercialization of radiation tolerant camera

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yong Bum; Choi, Young Soo; Kim, Sun Ku; Lee, Jong Min; Cha, Bung Hun; Lee, Nam Ho; Byun, Eiy Gyo; Yoo, Seun Wook; Choi, Bum Ki; Yoon, Sung Up; Kim, Hyun Gun; Sin, Jeong Hun; So, Suk Il

    1999-12-01

    In this project, radiation tolerant camera which tolerates 10{sup 6} - 10{sup 8} rad total dose is developed. In order to develop radiation tolerant camera, radiation effect of camera components was examined and evaluated, and camera configuration was studied. By the result of evaluation, the components were decided and design was performed. Vidicon tube was selected to use by image sensor and non-browning optics and camera driving circuit were applied. The controller needed for CCTV camera system, lens, light, pan/tilt controller, was designed by the concept of remote control. And two type of radiation tolerant camera were fabricated consider to use in underwater environment or normal environment. (author)

  12. Commercialization of radiation tolerant camera

    International Nuclear Information System (INIS)

    Lee, Yong Bum; Choi, Young Soo; Kim, Sun Ku; Lee, Jong Min; Cha, Bung Hun; Lee, Nam Ho; Byun, Eiy Gyo; Yoo, Seun Wook; Choi, Bum Ki; Yoon, Sung Up; Kim, Hyun Gun; Sin, Jeong Hun; So, Suk Il

    1999-12-01

    In this project, radiation tolerant camera which tolerates 10 6 - 10 8 rad total dose is developed. In order to develop radiation tolerant camera, radiation effect of camera components was examined and evaluated, and camera configuration was studied. By the result of evaluation, the components were decided and design was performed. Vidicon tube was selected to use by image sensor and non-browning optics and camera driving circuit were applied. The controller needed for CCTV camera system, lens, light, pan/tilt controller, was designed by the concept of remote control. And two type of radiation tolerant camera were fabricated consider to use in underwater environment or normal environment. (author)

  13. Application of dynamic membranes in anaerobic membranes in anaerobic membrane bioreactor systems

    NARCIS (Netherlands)

    Erşahin, M.E.

    2015-01-01

    Anaerobic membrane bioreactors (AnMBRs) physically ensure biomass retention by the application of a membrane filtration process. With growing application experiences from aerobic membrane bioreactors (MBRs), the combination of membrane and anaerobic processes has received much attention and become

  14. B Cell Tolerance in Health and Disease

    Directory of Open Access Journals (Sweden)

    Murali Gururajan

    2014-02-01

    Full Text Available B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids and have been shown to play crucial roles in the development of autoimmunity in several animal models. In the periphery availability of BAFF, a B cell survival factor plays a critical role in the survival of self-reactive B cells. Antibodies against BAFF have been found to be effective therapeutic agents in lupus like autoimmune diseases. Recent developments are targeting anergy to control the growth of chronic lymphocytic leukemia cells.

  15. Salt Tolerance in Soybean

    Institute of Scientific and Technical Information of China (English)

    Tsui-Hung Phang; Guihua Shao; Hon-Ming Lam

    2008-01-01

    Soybean is an Important cash crop and its productivity is significantly hampered by salt stress. High salt Imposes negative impacts on growth, nodulation, agronomy traits, seed quality and quantity, and thus reduces the yield of soybean. To cope with salt stress, soybean has developed several tolerance mechanisms, including: (I) maintenance of ion homeostasis; (ii) adjustment in response to osmotic stress; (iii) restoration of osmotic balance; and (iv) other metabolic and structural adaptations. The regulatory network for abiotic stress responses in higher plants has been studied extensively in model plants such as Arabidopsis thaliana. Some homologous components involved in salt stress responses have been identified in soybean. In this review, we tried to integrate the relevant works on soybean and proposes a working model to descdbe Its salt stress responses at the molecular level.

  16. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  17. Chemical genomic guided engineering of gamma-valerolactone tolerant yeast.

    Science.gov (United States)

    Bottoms, Scott; Dickinson, Quinn; McGee, Mick; Hinchman, Li; Higbee, Alan; Hebert, Alex; Serate, Jose; Xie, Dan; Zhang, Yaoping; Coon, Joshua J; Myers, Chad L; Landick, Robert; Piotrowski, Jeff S

    2018-01-12

    Gamma valerolactone (GVL) treatment of lignocellulosic bomass is a promising technology for degradation of biomass for biofuel production; however, GVL is toxic to fermentative microbes. Using a combination of chemical genomics with the yeast (Saccharomyces cerevisiae) deletion collection to identify sensitive and resistant mutants, and chemical proteomics to monitor protein abundance in the presence of GVL, we sought to understand the mechanism toxicity and resistance to GVL with the goal of engineering a GVL-tolerant, xylose-fermenting yeast. Chemical genomic profiling of GVL predicted that this chemical affects membranes and membrane-bound processes. We show that GVL causes rapid, dose-dependent cell permeability, and is synergistic with ethanol. Chemical genomic profiling of GVL revealed that deletion of the functionally related enzymes Pad1p and Fdc1p, which act together to decarboxylate cinnamic acid and its derivatives to vinyl forms, increases yeast tolerance to GVL. Further, overexpression of Pad1p sensitizes cells to GVL toxicity. To improve GVL tolerance, we deleted PAD1 and FDC1 in a xylose-fermenting yeast strain. The modified strain exhibited increased anaerobic growth, sugar utilization, and ethanol production in synthetic hydrolysate with 1.5% GVL, and under other conditions. Chemical proteomic profiling of the engineered strain revealed that enzymes involved in ergosterol biosynthesis were more abundant in the presence of GVL compared to the background strain. The engineered GVL strain contained greater amounts of ergosterol than the background strain. We found that GVL exerts toxicity to yeast by compromising cellular membranes, and that this toxicity is synergistic with ethanol. Deletion of PAD1 and FDC1 conferred GVL resistance to a xylose-fermenting yeast strain by increasing ergosterol accumulation in aerobically grown cells. The GVL-tolerant strain fermented sugars in the presence of GVL levels that were inhibitory to the unmodified strain

  18. Probing lipid membrane electrostatics

    Science.gov (United States)

    Yang, Yi

    The electrostatic properties of lipid bilayer membranes play a significant role in many biological processes. Atomic force microscopy (AFM) is highly sensitive to membrane surface potential in electrolyte solutions. With fully characterized probe tips, AFM can perform quantitative electrostatic analysis of lipid membranes. Electrostatic interactions between Silicon nitride probes and supported zwitterionic dioleoylphosphatidylcholine (DOPC) bilayer with a variable fraction of anionic dioleoylphosphatidylserine (DOPS) were measured by AFM. Classical Gouy-Chapman theory was used to model the membrane electrostatics. The nonlinear Poisson-Boltzmann equation was numerically solved with finite element method to provide the potential distribution around the AFM tips. Theoretical tip-sample electrostatic interactions were calculated with the surface integral of both Maxwell and osmotic stress tensors on tip surface. The measured forces were interpreted with theoretical forces and the resulting surface charge densities of the membrane surfaces were in quantitative agreement with the Gouy-Chapman-Stern model of membrane charge regulation. It was demonstrated that the AFM can quantitatively detect membrane surface potential at a separation of several screening lengths, and that the AFM probe only perturbs the membrane surface potential by external field created by the internai membrane dipole moment. The analysis yields a dipole moment of 1.5 Debye per lipid with a dipole potential of +275 mV for supported DOPC membranes. This new ability to quantitatively measure the membrane dipole density in a noninvasive manner will be useful in identifying the biological effects of the dipole potential. Finally, heterogeneous model membranes were studied with fluid electric force microscopy (FEFM). Electrostatic mapping was demonstrated with 50 nm resolution. The capabilities of quantitative electrostatic measurement and lateral charge density mapping make AFM a unique and powerful

  19. Shaping tolerant attitudes towards immigrants

    DEFF Research Database (Denmark)

    Rapp, Carolin

    2017-01-01

    This article contributes to the ongoing discussion on how tolerance may be fostered in Western European countries and to the question of how contextual factors such as welfare state expenditures may contribute to this formation. Tolerance is understood as a basic democratic principle that helps c...

  20. Legal Quality, Inequality, and Tolerance

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    Previous findings suggest that income inequality leads to lower legal quality. This paper argues that voters' tolerance of inequality exerts an additional influence. Empirical findings suggest that inequality leads to lower legal quality due to its effect on trust while the tolerance of inequality...

  1. Legal Quality, Inequality, and Tolerance

    DEFF Research Database (Denmark)

    Bjørnskov, Christian

    2004-01-01

    Previous findings suggest that income inequality leads to lower legal quality. This paper argues that voters' tolerance of inequality exerts an additional influence. Empirical findings suggest that inequality leads to lower legal quality due to its effect on trust while the tolerance of inequality...

  2. Tolerance Issue in Kazakh Culture

    Science.gov (United States)

    Aubakirova, Saltanat S.; Ismagambetova, Zukhra N.; Karabayeva, Aliya G.; Rysbekova, Shamshiya S.; Mirzabekova, Alma Sh.

    2016-01-01

    In this article the authors reveal the basic cultural mechanisms that influence the formation of the tolerance strategy in Kazakh and Kazakhstan society, show its basic directions, as well as its importance for the modern Kazakhstan society and the formation of intercultural communication with foreign countries. Tolerance is a necessary element of…

  3. Tolerance-Based Feature Transforms

    NARCIS (Netherlands)

    Reniers, Dennie; Telea, Alexandru

    2007-01-01

    Tolerance-based feature transforms (TFTs) assign to each pixel in an image not only the nearest feature pixels on the boundary (origins), but all origins from the minimum distance up to a user-defined tolerance. In this paper, we compare four simple-to-implement methods for computing TFTs on binary

  4. Salt tolerance at single cell level in giant-celled Characeae

    Directory of Open Access Journals (Sweden)

    Mary Jane eBeilby

    2015-04-01

    Full Text Available Characean plants provide an excellent experimental system for electrophysiology and physiology due to: (i very large cell size, (ii position on phylogenetic tree near the origin of land plants and (iii continuous spectrum from very salt sensitive to very salt tolerant species. A range of experimental techniques is described, some unique to characean plants. Application of these methods provided electrical characteristics of membrane transporters, which dominate the membrane conductance under different outside conditions. With this considerable background knowledge the electrophysiology of salt sensitive and salt tolerant genera can be compared under salt and/or osmotic stress. Both salt tolerant and salt sensitive Characeae show a rise in membrane conductance and simultaneous increase in Na+ influx upon exposure to saline medium. Salt tolerant Chara longifolia and Lamprothamnium sp. exhibit proton pump stimulation upon both turgor decrease and salinity increase, allowing the membrane PD to remain negative. The turgor is regulated through the inward K+ rectifier and 2H+/Cl- symporter. Lamprothamnium plants can survive in hypersaline media up to twice seawater strength and withstand large sudden changes in salinity. Salt-sensitive Chara australis succumbs to 50 - 100 mM NaCl in few days. Cells exhibit no pump stimulation upon turgor decrease and at best transient pump stimulation upon salinity increase. Turgor is not regulated. The membrane PD exhibits characteristic noise upon exposure to salinity. Depolarization of membrane PD to excitation threshold sets off trains of action potentials, leading to further loses of K+ and Cl-. In final stages of salt damage the H+/OH- channels are thought to become the dominant transporter, dissipating the proton gradient and bringing the cell PD close to 0. The differences in transporter electrophysiology and their synergy under osmotic and/or saline stress in salt sensitive and salt tolerant characean cells

  5. Evaluating relative contribution of osmotolerance and tissue tolerance mechanisms toward salinity stress tolerance in three Brassica species.

    Science.gov (United States)

    Chakraborty, Koushik; Bose, Jayakumar; Shabala, Lana; Eyles, Alieta; Shabala, Sergey

    2016-10-01

    Three different species of Brassica, with differential salt sensitivity were used to understand physiological mechanisms of salt tolerance operating in these species and to evaluate the relative contribution of different strategies to cope with salt load. Brassica napus was the most tolerant species in terms of the overall performance, with Brassica juncea and Brassica oleracea being much more sensitive to salt stress with no obvious difference between them. While prominent reduction in net CO2 assimilation was observed in both sensitive species, physiological mechanisms beyond this reduction differed strongly. Brassica juncea plants possessed high osmotolerance and were able to maintain high transpiration rate but showed a significant reduction in leaf chlorophyll content and efficiency of leaf photochemistry. On the contrary, B. oleracea plants possessed the highest (among the three species) tissue tolerance but showed a very significant stomatal limitation of photosynthesis. Electrophysiological experiments revealed that the high tissue tolerance in B. oleracea was related to the ability of leaf mesophyll cells to maintain highly negative membrane potential in the presence of high apoplastic Na(+) . In addition to high osmotolerance, the most tolerant B. napus showed also lesser accumulation of toxic Na(+) and Cl(-) in the leaf, possessed moderate tissue tolerance and had a superior K(+) retention ability. Taken together, the results from this study indicate that the three Brassica species employ very different mechanisms to cope with salinity and, despite its overall sensitivity to salinity, B. oleracea could be recommended as a valuable 'donor' of tissue tolerance genes to confer this trait for marker-assisted breeding programs. © 2016 Scandinavian Plant Physiology Society.

  6. Ion-conducting membranes

    Science.gov (United States)

    Masel, Richard I.; Sajjad, Syed Dawar; Gao, Yan; Liu, Zengcai; Chen, Qingmei

    2017-12-26

    An anion-conducting polymeric membrane comprises a terpolymer of styrene, vinylbenzyl-R.sub.s and vinylbenzyl-R.sub.x. R.sub.s is a positively charged cyclic amine group. R.sub.x is at least one constituent selected from the group consisting Cl, OH and a reaction product between an OH or Cl and a species other than a simple amine or a cyclic amine. The total weight of the vinylbenzyl-R.sub.x groups is greater than 0.3% of the total weight of the membrane. In a preferred embodiment, the membrane is a Helper Membrane that increases the faradaic efficiency of an electrochemical cell into which the membrane is incorporated, and also allows product formation at lower voltages than in cells without the Helper Membrane.

  7. Gas separation with membranes

    International Nuclear Information System (INIS)

    Schulz, G.; Michele, H.; Werner, U.

    1982-01-01

    Gas separation with membranes has already been tested in numerous fields of application, e.g. uranium enrichment of H 2 separation. In many of these processes the mass transfer units, so-called permeators, have to be connected in tandem in order to achieve high concentrations. A most economical operating method provides for each case an optimization of the cascades with regard to the membrane materials, construction and design of module. By utilization of the concentration gradient along the membrane a new process development has been accomplished - the continuously operating membrane rectification unit. Investment and operating costs can be reduced considerably for a number of separating processes by combining a membrane rectification unit with a conventional recycling cascade. However, the new procedure requires that the specifications for the module construction, flow design, and membrane properties be reconsidered. (orig.) [de

  8. Chelating polymeric membranes

    KAUST Repository

    Peinemann, Klaus-Viktor

    2015-01-22

    The present application offers a solution to the current problems associated with recovery and recycling of precious metals from scrap material, discard articles, and other items comprising one or more precious metals. The solution is premised on a microporous chelating polymeric membrane. Embodiments include, but are not limited to, microporous chelating polymeric membranes, device comprising the membranes, and methods of using and making the same.

  9. Gas separation membranes

    Science.gov (United States)

    Schell, William J.

    1979-01-01

    A dry, fabric supported, polymeric gas separation membrane, such as cellulose acetate, is prepared by casting a solution of the polymer onto a shrinkable fabric preferably formed of synthetic polymers such as polyester or polyamide filaments before washing, stretching or calendering (so called griege goods). The supported membrane is then subjected to gelling, annealing, and drying by solvent exchange. During the processing steps, both the fabric support and the membrane shrink a preselected, controlled amount which prevents curling, wrinkling or cracking of the membrane in flat form or when spirally wound into a gas separation element.

  10. Anion exchange membrane

    Science.gov (United States)

    Verkade, John G; Wadhwa, Kuldeep; Kong, Xueqian; Schmidt-Rohr, Klaus

    2013-05-07

    An anion exchange membrane and fuel cell incorporating the anion exchange membrane are detailed in which proazaphosphatrane and azaphosphatrane cations are covalently bonded to a sulfonated fluoropolymer support along with anionic counterions. A positive charge is dispersed in the aforementioned cations which are buried in the support to reduce the cation-anion interactions and increase the mobility of hydroxide ions, for example, across the membrane. The anion exchange membrane has the ability to operate at high temperatures and in highly alkaline environments with high conductivity and low resistance.

  11. Photoresponsive nanostructured membranes

    KAUST Repository

    Madhavan, Poornima

    2016-07-26

    The perspective of adding stimuli-response to isoporous membranes stimulates the development of separation devices with pores, which would open or close under control of environment chemical composition, temperature or exposure to light. Changes in pH and temperature have been previously investigated. In this work, we demonstrate for the first time the preparation of photoresponsive isoporous membranes, applying self-assembly non-solvent induced phase separation to a new light responsive block copolymer. First, we optimized the membrane formation by using poly(styrene-b-anthracene methyl methacrylate-b-methylmethacrylate) (PS-b-PAnMMA-b-PMMA) copolymer, identifying the most suitable solvent, copolymer block length, and other parameters. The obtained final triblock copolymer membrane morphologies were characterized using atomic force and electron microscopy. The microscopic analysis reveals that the PS-b-PAnMMA-b-PMMA copolymer can form both lamellar and ordered hexagonal nanoporous structures on the membrane top layer in appropriate solvent compositions. The nanostructured membrane emits fluorescence due to the presence of the anthracene mid-block. On irradiation of light the PS-b-PAnMMA-b-PMMA copolymer membranes has an additional stimuli response. The anthracene group undergoes conformational changes by forming [4 + 4] cycloadducts and this alters the membrane\\'s water flux and solute retention. © 2016 The Royal Society of Chemistry.

  12. Tolerance and chimerism.

    Science.gov (United States)

    Kolb, Hans-Jochem; Guenther, Wolfgang; Gyurkocza, Boglarka; Hoetzl, Florian; Simoes, Belinda; Falk, Christine; Schleuning, Michael; Ledderose, Georg

    2003-05-15

    Stem-cell transplantation from human leukocyte antigen (HLA)-haploidentical family members carries a high risk of rejection and graft-versus-host disease (GVHD) if donor and recipient differ by more than one HLA antigen. The authors have developed treatment protocols from studies in dog leukocyte antigen-haploidentical dogs that prevent rejection and modify GVHD to the extent that patients with aggressive hematologic neoplasia can be treated with success. Principal improvements have been achieved in the use of cyclophosphamide and total-body irradiation for conditioning and T-cell depletion for prevention of GVHD. More recently, the combination of marrow and CD6-depleted mobilized donor blood cells (MDBC) has been introduced for HLA-haploidentical transplantation on the basis that CD6-depleted MDBC contain immunoregulatory cells besides stem cells and natural killer cells. Clinical results are reported on 36 patients with high-risk hematologic neoplasia. The results encourage the use of HLA-haploidentical stem-cell transplantation at an earlier stage of the disease. This method could also be of use for tolerance induction in organ transplantation.

  13. One Step Biomass Gas Reforming-Shift Separation Membrane Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Michael J. [Gas Technology Institute; Souleimanova, Razima [Gas Technology Institute

    2012-12-28

    NETL showed Pd80Cu20 with the highest flux, therefore it was chosen as the initial and eventually, final candidate membrane. The criteria for choice were high hydrogen flux, long-term stability, and H2S tolerance. Results from SCHOTT using glass membranes showed a maximum of 0.25 SCFH/ft2, that is an order of magnitude better than the ceramic membrane but still two orders of magnitude lower than the metallic membrane. A membrane module was designed to be tested with an actual biomass gasifier. Some parts of the module were ordered but the work was stopped when a no go decision was made by the DOE.

  14. Membrane fusion and exocytosis.

    Science.gov (United States)

    Jahn, R; Südhof, T C

    1999-01-01

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

  15. Mechanical tolerance stackup and analysis

    CERN Document Server

    Fischer, Bryan R

    2011-01-01

    Use Tolerance Analysis Techniques to Avoid Design, Quality, and Manufacturing Problems Before They Happen Often overlooked and misunderstood, tolerance analysis is a critical part of improving products and their design processes. Because all manufactured products are subject to variation, it is crucial that designers predict and understand how these changes can affect form, fit, and function of parts and assemblies--and then communicate their findings effectively. Written by one of the developers of ASME Y14.5 and other geometric dimension and tolerancing (GD&T) standards, Mechanical Tolerance

  16. Advanced cloud fault tolerance system

    Science.gov (United States)

    Sumangali, K.; Benny, Niketa

    2017-11-01

    Cloud computing has become a prevalent on-demand service on the internet to store, manage and process data. A pitfall that accompanies cloud computing is the failures that can be encountered in the cloud. To overcome these failures, we require a fault tolerance mechanism to abstract faults from users. We have proposed a fault tolerant architecture, which is a combination of proactive and reactive fault tolerance. This architecture essentially increases the reliability and the availability of the cloud. In the future, we would like to compare evaluations of our proposed architecture with existing architectures and further improve it.

  17. NEW POLYMER ELECTROLYTE MEMBRANES FOR FUEL CELLS OPERATING ABOVE 100°C

    DEFF Research Database (Denmark)

    Li, Qingfeng; Jensen, Jens Oluf; He, Ronghuan

    2003-01-01

    The state-of-the-art of PEMFC technology is based on perfluorosulfonic acid (PFSA) polymer membranes operating at a typical temperature of 80°C. The newest development in the field is alternative polymer electrolytes for operation above 100°C. This paper is devoted to a review on the development......, which is classified into three groups: modified PFSA membranes, alternative sulfonated polymer and their inorganic composite membranes and acid-base complex membranes. High temperature PEMFC has been demonstrated with advanced features such as fast electrode kinetics, high CO tolerance, simple thermal...

  18. Tolerance to and cross tolerance between ethanol and nicotine.

    Science.gov (United States)

    Collins, A C; Burch, J B; de Fiebre, C M; Marks, M J

    1988-02-01

    Female DBA mice were subjected to one of four treatments: ethanol-containing or control diets, nicotine (0.2, 1.0, 5.0 mg/kg/hr) infusion or saline infusion. After removal from the liquid diets or cessation of infusion, the animals were challenged with an acute dose of ethanol or nicotine. Chronic ethanol-fed mice were tolerant to the effects of ethanol on body temperature and open field activity and were cross tolerant to the effects of nicotine on body temperature and heart rate. Nicotine infused animals were tolerant to the effects of nicotine on body temperature and rotarod performance and were cross tolerant to the effects of ethanol on body temperature. Ethanol-induced sleep time was decreased in chronic ethanol- but not chronic nicotine-treated mice. Chronic drug treatment did not alter the elimination rate of either drug. Chronic ethanol treatment did not alter the number or affinity of brain nicotinic receptors whereas chronic nicotine treatment elicited an increase in the number of [3H]-nicotine binding sites. Tolerance and cross tolerance between ethanol and nicotine is discussed in terms of potential effects on desensitization of brain nicotinic receptors.

  19. Plasma membrane ATPases

    DEFF Research Database (Denmark)

    Palmgren, Michael Broberg; Bækgaard, Lone; Lopez Marques, Rosa Laura

    2011-01-01

    The plasma membrane separates the cellular contents from the surrounding environment. Nutrients must enter through the plasma membrane in order to reach the cell interior, and toxic metabolites and several ions leave the cell by traveling across the same barrier. Biological pumps in the plasma me...

  20. Polymide gas separation membranes

    Science.gov (United States)

    Ding, Yong; Bikson, Benjamin; Nelson, Joyce Katz

    2004-09-14

    Soluble polyamic acid salt (PAAS) precursors comprised of tertiary and quaternary amines, ammonium cations, sulfonium cations, or phosphonium cations, are prepared and fabricated into membranes that are subsequently imidized and converted into rigid-rod polyimide articles, such as membranes with desirable gas separation properties. A method of enhancing solubility of PAAS polymers in alcohols is also disclosed.

  1. Enantioseparation with liquid membranes

    NARCIS (Netherlands)

    Gössi, Angelo; Riedl, Wolfgang; Schuur, Boelo

    Chiral resolution of racemic products is a challenging and important task in the pharmaceutical, agrochemical, flavor, polymer and fragrances industries. One of the options for these challenging separations is to use liquid membranes. Although liquid membranes have been known for almost four decades

  2. Silicon nitride nanosieve membrane

    NARCIS (Netherlands)

    Tong, D.H.; Jansen, Henricus V.; Gadgil, V.J.; Bostan, C.G.; Berenschot, Johan W.; van Rijn, C.J.M.; Elwenspoek, Michael Curt

    2004-01-01

    An array of very uniform cylindrical nanopores with a pore diameter as small as 25 nm has been fabricated in an ultrathin micromachined silicon nitride membrane using focused ion beam (FIB) etching. The pore size of this nanosieve membrane was further reduced to below 10 nm by coating it with

  3. Membrane capacitive deionization

    NARCIS (Netherlands)

    Biesheuvel, P.M.; Wal, van der A.

    2010-01-01

    Membrane capacitive deionization (MCDI) is an ion-removal process based on applying an electrical potential difference across an aqueous solution which flows in between oppositely placed porous electrodes, in front of which ion-exchange membranes are positioned. Due to the applied potential, ions

  4. Photoresponsive nanostructured membranes

    KAUST Repository

    Madhavan, Poornima; Sutisna, Burhannudin; Sougrat, Rachid; Nunes, Suzana Pereira

    2016-01-01

    The perspective of adding stimuli-response to isoporous membranes stimulates the development of separation devices with pores, which would open or close under control of environment chemical composition, temperature or exposure to light. Changes in pH and temperature have been previously investigated. In this work, we demonstrate for the first time the preparation of photoresponsive isoporous membranes, applying self-assembly non-solvent induced phase separation to a new light responsive block copolymer. First, we optimized the membrane formation by using poly(styrene-b-anthracene methyl methacrylate-b-methylmethacrylate) (PS-b-PAnMMA-b-PMMA) copolymer, identifying the most suitable solvent, copolymer block length, and other parameters. The obtained final triblock copolymer membrane morphologies were characterized using atomic force and electron microscopy. The microscopic analysis reveals that the PS-b-PAnMMA-b-PMMA copolymer can form both lamellar and ordered hexagonal nanoporous structures on the membrane top layer in appropriate solvent compositions. The nanostructured membrane emits fluorescence due to the presence of the anthracene mid-block. On irradiation of light the PS-b-PAnMMA-b-PMMA copolymer membranes has an additional stimuli response. The anthracene group undergoes conformational changes by forming [4 + 4] cycloadducts and this alters the membrane's water flux and solute retention. © 2016 The Royal Society of Chemistry.

  5. Accident tolerant fuel analysis

    International Nuclear Information System (INIS)

    2014-01-01

    Safety is central to the design, licensing, operation, and economics of Nuclear Power Plants (NPPs). Consequently, the ability to better characterize and quantify safety margin holds the key to improved decision making about light water reactor design, operation, and plant life extension. A systematic approach to characterization of safety margins and the subsequent margins management options represents a vital input to the licensee and regulatory analysis and decision making that will be involved. The purpose of the Risk Informed Safety Margin Characterization (RISMC) Pathway research and development (R&D) is to support plant decisions for risk-informed margins management by improving economics and reliability, and sustaining safety, of current NPPs. Goals of the RISMC Pathway are twofold: (1) Develop and demonstrate a risk-assessment method coupled to safety margin quantification that can be used by NPP decision makers as part of their margin recovery strategies. (2) Create an advanced ''RISMC toolkit'' that enables more accurate representation of NPP safety margin. In order to carry out the R&D needed for the Pathway, the Idaho National Laboratory is performing a series of case studies that will explore methods- and tools-development issues, in addition to being of current interest in their own right. One such study is a comparative analysis of safety margins of plants using different fuel cladding types: specifically, a comparison between current-technology Zircaloy cladding and a notional ''accident-tolerant'' (e.g., SiC-based) cladding. The present report begins the process of applying capabilities that are still under development to the problem of assessing new fuel designs. The approach and lessons learned from this case study will be included in future Technical Basis Guides produced by the RISMC Pathway. These guides will be the mechanism for developing the specifications for RISMC tools and for defining how plant

  6. Molecular Interactions at Membranes

    DEFF Research Database (Denmark)

    Jagalski, Vivien

    . Today, we know more than ever before about the properties of biological membranes. Advanced biophysical techniques and sophisticated membrane models allow us to answer specific questions about the structure of the components within membranes and their interactions. However, many detailed structural...... the surface-immobilization of LeuT by exchanging the detergent with natural phosphatidylcholine (PC) lipids. Various surface sensitive techniques, including neutron reflectometry (NR), are employed and finally enabled us to confirm the gross structure of LeuT in a lipid environment as predicted by molecular...... dynamic simulations. In a second study, the co-localization of three toxic plant-derived diterpene resin acids (RAs) within DPPC membranes was investigated. These compounds are reported to disrupt the membrane and increase its fluidity. The RAs used in this study vary in their toxicity while...

  7. Membrane technology and applications

    International Nuclear Information System (INIS)

    Khalil, F.H.

    1997-01-01

    The main purpose of this dissertation is to prepare and characterize some synthetic membranes obtained by radiation-induced graft copolymerization of and A Am unitary and binary system onto nylon-6 films. The optimum conditions at which the grafting process proceeded homogeneously were determined. Some selected properties of the prepared membranes were studied. Differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), x-ray diffraction (XRD), mechanical properties and U.V./vis, instruments and techniques were used to characterize the prepared membranes. The use of such membranes for the decontamination of radioactive waste and some heavy metal ions as water pollutants were investigated. These grafted membranes showed good cation exchange properties and may be of practical interest in waste water treatment whether this water was radioactive or not. 4 tabs., 68 figs., 146 refs

  8. TEMPERATURE TOLERANCES AND OSMOREGULATION IN ...

    African Journals Online (AJOL)

    The salinity and temperature tolerances of some burrowiq bivalves which oc:eur ... Along most of the estuary the salinity normally remains close to that of seawater (35'/.) ...... grapsoid crabs, Hemigrapsus nudus and Hemigrapsus oregonensis.

  9. TOLERANCE OF Abelmoschus esculentus (L

    African Journals Online (AJOL)

    Cletus

    Key word: - Tolerance, diesel oil, polluted soil, Abelmoschus esculentus. INTRODUCTION ... errors -of the mean values were calculated for the replicate readings and data .... African Schools and Colleges, 2nd Ed. University Press Limited ...

  10. Antibiotic tolerance and microbial biofilms

    DEFF Research Database (Denmark)

    Folkesson, Anders

    Increased tolerance to antimicrobial agents is thought to be an important feature of microbes growing in biofilms. We study the dynamics of antibiotic action within hydrodynamic flow chamber biofilms of Escherichia coli and Pseudomonas aeruginosa using isogenic mutants and fluorescent gene...... expression reporters and we address the question of how biofilm organization affects antibiotic susceptibility. The dynamics of microbial killing is monitored by viable count determination, and confocal laser microscopy. Our work shows that the apparent increased antibiotic tolerance is due to the formation...... of antibiotic tolerant subpopulations within the biofilm. The formation of these subpopulations is highly variable and dependent on the antibiotic used, the biofilm structural organization and the induction of specific tolerance mechanisms....

  11. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  12. Women’s G Tolerance

    Science.gov (United States)

    1986-08-01

    for the groups matched by age (70 pairs), weight sickness, uncomfortable feelings of distension in arms (26 pairs), and act~vity status (84 pairs...mass-spring-damper) s ,stem Straining G tolerance, being dpendent on skeletal having a resonant frequency above about I Hz. As muscular strength and...of the women’s G tolerance stud\\ scclic variations in muscular strength and endurance. was below 0.1 Hz (11), the production of any significant

  13. Fault-tolerant rotary actuator

    Science.gov (United States)

    Tesar, Delbert

    2006-10-17

    A fault-tolerant actuator module, in a single containment shell, containing two actuator subsystems that are either asymmetrically or symmetrically laid out is provided. Fault tolerance in the actuators of the present invention is achieved by the employment of dual sets of equal resources. Dual resources are integrated into single modules, with each having the external appearance and functionality of a single set of resources.

  14. Behavioral Tolerance to Anticholinergic Agents

    Science.gov (United States)

    1986-11-20

    Medicine , 47, 137-141. 7. Kurtz, P.J. (1977) Behavioral and biochemical effects of the carbamate insecticide, mobam. Pharmacology Biochemistry & Behavior...tolerance to marihuana in rats. Pharmacology Biochemistry and Behavior, 1, 73-76. 43 40. Olson, J. and Carder, B. (1974) Behavioral tolerance to... marihuana as a function of amount of prior training. Pharmacology Biochemistry and Behavior, 2, 243-247. 41. Sidman, M. (1960) Tactics of Scientific

  15. Analysis of Natural Variation in Bermudagrass (Cynodon dactylon) Reveals Physiological Responses Underlying Drought Tolerance

    Science.gov (United States)

    Cheng, Zhangmin; Ye, Tiantian; Chan, Zhulong

    2012-01-01

    Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H2O2 content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system. PMID:23285294

  16. Analysis of natural variation in bermudagrass (Cynodon dactylon) reveals physiological responses underlying drought tolerance.

    Science.gov (United States)

    Shi, Haitao; Wang, Yanping; Cheng, Zhangmin; Ye, Tiantian; Chan, Zhulong

    2012-01-01

    Bermudagrass (Cynodon dactylon) is a widely used warm-season turfgrass and one of the most drought tolerant species. Dissecting the natural variation in drought tolerance and physiological responses will bring us powerful basis and novel insight for plant breeding. In the present study, we evaluated the natural variation of drought tolerance among nine bermudagrass varieties by measuring physiological responses after drought stress treatment through withholding water. Three groups differing in drought tolerance were identified, including two tolerant, five moderately tolerant and two susceptible varieties. Under drought stress condition, drought sensitive variety (Yukon) showed relative higher water loss, more severe cell membrane damage (EL), and more accumulation of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA), while drought tolerant variety (Tifgreen) exhibited significantly higher antioxidant enzymes activities. Further results indicated that drought induced cell injury in different varieties (Yukon, SR9554 and Tifgreen) exhibited liner correlation with leaf water content (LWC), H₂O₂ content, MDA content and antioxidant enzyme activities. Additionally, Tifgreen plants had significantly higher levels of osmolytes (proline level and soluble sugars) when compared with Yukon and SR9554 under drought stress condition. Taken together, our results indicated that natural variation of drought stress tolerance in bermudagrass varieties might be largely related to the induced changes of water status, osmolyte accumulation and antioxidant defense system.

  17. Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test

    Directory of Open Access Journals (Sweden)

    Rohit Babbar

    2018-03-01

    Full Text Available IntroductionImpaired glucose tolerance (IGT is diagnosed by a standardized oral glucose tolerance test (OGTT. However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.MethodsGiven a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA, proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1 year.ResultsThe most accurate prediction of IGT was reached with the recursive partitioning method (accuracy = 0.78. For all classifiers, mean accuracy was 0.73 ± 0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.ConclusionMachine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a

  18. Microfabricated hydrogen sensitive membranes

    Energy Technology Data Exchange (ETDEWEB)

    Naddaf, A.; Kraetz, L. [Lehrstuhl fuer Thermische Verfahrenstechnik, Technische Universitaet Kaiserslautern (Germany); Detemple, P.; Schmitt, S.; Hessel, V. [Institut fuer Mikrotechnik Mainz GmbH, Mainz (Germany); Faqir, N. [University of Jordan, Amman (Jordan); Bart, H.J.

    2009-01-15

    Thin, defect-free palladium, palladium/copper and palladium/silver hydrogen absorbing membranes were microfabricated. A dual sputtering technique was used to deposit the palladium alloy membranes of only 1 {mu}m thickness on a nonporous silicon substrate. Advanced silicon etching (ASE) was applied on the backside to create a mechanically stable support structure for the thin films. Performance evaluation was carried out for different gases in a temperature range of 20 C to 298 C at a constant differential pressure of 110 kPa at the two sides of the membrane. The composite membranes show an excellent permeation rate of hydrogen, which appears to be 0.05 Pa m{sup 3} s{sup -1} and 0.01.10{sup -3} Pa m{sup 3} s{sup -1} at 20 C for the microfabricated 23 % silver and the 53 % copper composite membranes, respectively. The selectivity to hydrogen over a gas mixture containing, in addition to hydrogen, carbon monoxide, carbon dioxide and nitrogen was measured. The mass spectrometer did not detect any CO{sub 2} or CO, showing that the membrane is completely hydrogen selective. The microfabricated membranes exhibit both high mechanical strength (they easily withstand pressures up to 4 bar) and high thermal stability (up to 650 C). (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  19. Catalytic nanoporous membranes

    Science.gov (United States)

    Pellin, Michael J; Hryn, John N; Elam, Jeffrey W

    2013-08-27

    A nanoporous catalytic membrane which displays several unique features Including pores which can go through the entire thickness of the membrane. The membrane has a higher catalytic and product selectivity than conventional catalysts. Anodic aluminum oxide (AAO) membranes serve as the catalyst substrate. This substrate is then subjected to Atomic Layer Deposition (ALD), which allows the controlled narrowing of the pores from 40 nm to 10 nm in the substrate by deposition of a preparatory material. Subsequent deposition of a catalytic layer on the inner surfaces of the pores reduces pore sizes to less than 10 nm and allows for a higher degree of reaction selectivity. The small pore sizes allow control over which molecules enter the pores, and the flow-through feature can allow for partial oxidation of reactant species as opposed to complete oxidation. A nanoporous separation membrane, produced by ALD is also provided for use in gaseous and liquid separations. The membrane has a high flow rate of material with 100% selectivity. Also provided is a method for producing a catalytic membrane having flow-through pores and discreet catalytic clusters adhering to the inside surfaces of the pores.

  20. Composite polymer membranes for proton exchange membrane fuel cells operating at elevated temperatures and reduced humidities

    Science.gov (United States)

    Zhang, Tao

    Proton Exchange Membrane Fuel Cells (PEMFCs) are the leading candidate in the fuel cell technology due to the high power density, solid electrolyte, and low operational temperature. However, PEMFCs operating in the normal temperature range (60-80°C) face problems including poor carbon monoxide tolerance and heat rejection. The poisoning effect can be significantly relieved by operating the fuel cell at elevated temperature, which also improves the heat rejection and electrochemical kinetics. Low relative humidity (RH) operation is also desirable to simplify the reactant humidification system. However, at elevated temperatures, reduced RH PEMFC performance is seriously impaired due to irreversible water loss from presently employed state-of-the-art polymer membrane, Nafion. This thesis focuses on developing polymer electrolyte membranes with high water retention ability for operation in elevated temperature (110-150°C), reduced humidity (˜50%RH) PEMFCs. One approach is to alter Nafion by adding inorganic particles such as TiO2, SiO2, Zr(HPO 4)2, etc. While the presence of these materials in Nafion has proven beneficial, a reduction or no improvement in the PEMFC performance of Nafion/TiO2 and Nafion/Zr(HPO4)2 membranes is observed with reduced particle sizes or increased particle loadings in Nafion. It is concluded that the PEMFC performance enhancement associated with addition of these inorganic particles was not due to the particle hydrophilicity. Rather, the particle, partially located in the hydrophobic region of the membrane, benefits the cell performance by altering the membrane structure. Water transport properties of some Nafion composite membranes were investigated by NMR methods including pulsed field gradient spin echo diffusion, spin-lattice relaxation, and spectral measurements. Compared to unmodified Nafion, composite membranes materials exhibit longer longitudinal relaxation time constant T1. In addition to the Nafion material, sulfonated styrene

  1. Rotating bubble membrane radiator

    Science.gov (United States)

    Webb, Brent J.; Coomes, Edmund P.

    1988-12-06

    A heat radiator useful for expelling waste heat from a power generating system aboard a space vehicle is disclosed. Liquid to be cooled is passed to the interior of a rotating bubble membrane radiator, where it is sprayed into the interior of the bubble. Liquid impacting upon the interior surface of the bubble is cooled and the heat radiated from the outer surface of the membrane. Cooled liquid is collected by the action of centrifical force about the equator of the rotating membrane and returned to the power system. Details regarding a complete space power system employing the radiator are given.

  2. Adsorption and Orientation of Human Islet Amyloid Polypeptide (hIAPP Monomer at Anionic Lipid Bilayers: Implications for Membrane-Mediated Aggregation

    Directory of Open Access Journals (Sweden)

    Guanghong Wei

    2013-03-01

    Full Text Available Protein misfolding and aggregation cause serious degenerative diseases, such as Alzheimer’s and type II diabetes. Human islet amyloid polypeptide (hIAPP is the major component of amyloid deposits found in the pancreas of type II diabetic patients. Increasing evidence suggests that β-cell death is related to the interaction of hIAPP with the cellular membrane, which accelerates peptide aggregation. In this study, as a first step towards understanding the membrane-mediated hIAPP aggregation, we investigate the atomic details of the initial step of hIAPP-membrane interaction, including the adsorption orientation and conformation of hIAPP monomer at an anionic POPG lipid bilayer by performing all-atom molecular dynamics simulations. We found that hIAPP monomer is quickly adsorbed to bilayer surface, and the adsorption is initiated from the N-terminal residues driven by strong electrostatic interactions of the positively-charged residues K1 and R11 with negatively-charged lipid headgroups. hIAPP binds parallel to the lipid bilayer surface as a stable helix through residues 7–22, consistent with previous experimental study. Remarkably, different simulations lead to the same binding orientation stabilized by electrostatic and H-bonding interactions, with residues R11, F15 and S19 oriented towards membrane and hydrophobic residues L12, A13, L16 and V17 exposed to solvent. Implications for membrane-mediated hIAPP aggregation are discussed.

  3. 75 FR 29908 - Prothioconazole; Pesticide Tolerances

    Science.gov (United States)

    2010-05-28

    .... The straw numerical value (5 ppm) is matched between the U.S. and Codex. The tolerance definition for... lower (0.07 ppm) than the recommended U.S. group tolerance. The 0.07 ppm value is the current U.S. tolerance value for wheat, but will be replaced by the cereal grain group tolerance. Canada does not...

  4. 78 FR 40027 - Novaluron; Pesticide Tolerances

    Science.gov (United States)

    2013-07-03

    ...). This regulation additionally deletes the time- limited tolerance for strawberry, as that tolerance..., pears, potatoes, strawberries, and tomatoes and utilized estimates for PCT for recently registered uses... deletes the time-limited tolerance for strawberry, as that tolerance expired on December 31, 2011. VI...

  5. Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

    Science.gov (United States)

    Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

    2012-01-01

    Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Hollow-Fiber Spacesuit Water Membrane Evaporator

    Science.gov (United States)

    Bue, Grant; Trevino, Luis; Tsioulos, Gus; Mitchell, Keith; Settles, Joseph

    2013-01-01

    The hollow-fiber spacesuit water membrane evaporator (HoFi SWME) is being developed to perform the thermal control function for advanced spacesuits and spacecraft to take advantage of recent advances in micropore membrane technology in providing a robust, heat-rejection device that is less sensitive to contamination than is the sublimator. After recent contamination tests, a commercial-off-the-shelf (COTS) micro porous hollow-fiber membrane was selected for prototype development as the most suitable candidate among commercial hollow-fiber evaporator alternatives. An innovative design that grouped the fiber layers into stacks, which were separated by small spaces and packaged into a cylindrical shape, was developed into a full-scale prototype for the spacesuit application. Vacuum chamber testing has been performed to characterize heat rejection as a function of inlet water temperature and water vapor back-pressure, and to show contamination resistance to the constituents expected to be found in potable water produced by the wastewater reclamation distillation processes. Other tests showed tolerance to freezing and suitability to reject heat in a Mars pressure environment. In summary, HoFi SWME is a lightweight, compact evaporator for heat rejection in the spacesuit that is robust, contamination- insensitive, freeze-tolerant, and able to reject the required heat of spacewalks in microgravity, lunar, and Martian environments. The HoFi is packaged to reject 810 W of heat through 800 hours of use in a vacuum environment, and 370 W in a Mars environment. The device also eliminates free gas and dissolved gas from the coolant loop.

  7. Membrane Assisted Enzyme Fractionation

    DEFF Research Database (Denmark)

    Yuan, Linfeng

    to the variation in size of the proteins and a reasonable separation factor can be observed only when the size difference is in the order of 10 or more. This is partly caused by concentration polarization and membrane fouling which hinders an effective separation of the proteins. Application of an electric field...... across the porous membrane has been demonstrated to be an effective way to reduce concentration polarization and membrane fouling. In addition, this technique can also be used to separate the proteins based on difference in charge, which to some extent overcome the limitations of size difference...... of proteins on the basis of their charge, degree of hydrophobicity, affinity or size. Adequate purity is often not achieved unless several purification steps are combined thereby increasing cost and reducing product yield. Conventional fractionation of proteins using ultrafiltration membranes is limited...

  8. Fuel cell membrane humidification

    Science.gov (United States)

    Wilson, Mahlon S.

    1999-01-01

    A polymer electrolyte membrane fuel cell assembly has an anode side and a cathode side separated by the membrane and generating electrical current by electrochemical reactions between a fuel gas and an oxidant. The anode side comprises a hydrophobic gas diffusion backing contacting one side of the membrane and having hydrophilic areas therein for providing liquid water directly to the one side of the membrane through the hydrophilic areas of the gas diffusion backing. In a preferred embodiment, the hydrophilic areas of the gas diffusion backing are formed by sewing a hydrophilic thread through the backing. Liquid water is distributed over the gas diffusion backing in distribution channels that are separate from the fuel distribution channels.

  9. Wrinkles in reinforced membranes

    Science.gov (United States)

    Takei, Atsushi; Brau, Fabian; Roman, Benoît; Bico, José.

    2012-02-01

    We study, through model experiments, the buckling under tension of an elastic membrane reinforced with a more rigid strip or a fiber. In these systems, the compression of the rigid layer is induced through Poisson contraction as the membrane is stretched perpendicularly to the strip. Although strips always lead to out-of-plane wrinkles, we observe a transition from out-of-plane to in plane wrinkles beyond a critical strain in the case of fibers embedded into the elastic membranes. The same transition is also found when the membrane is reinforced with a wall of the same material depending on the aspect ratio of the wall. We describe through scaling laws the evolution of the morphology of the wrinkles and the different transitions as a function of material properties and stretching strain.

  10. Novel Catalytic Membrane Reactors

    Energy Technology Data Exchange (ETDEWEB)

    None

    2009-02-01

    This factsheet describes a research project that will focus on the development and application of nonporous high gas flux perfluoro membranes with high temperature rating and excellent chemical resistance.

  11. Identification of Proteins Involved in Salinity Tolerance in Salicornia bigelovii

    KAUST Repository

    Salazar Moya, Octavio Ruben

    2017-11-01

    With a global growing demand in food production, agricultural output must increase accordingly. An increased use of saline soils and brackish water would contribute to the required increase in world food production. Abiotic stresses, such as salinity and drought, are also major limiters of crop growth globally - most crops are relatively salt sensitive and are significantly affected when exposed to salt in the range of 50 to 200 mM NaCl. Genomic resources from plants that naturally thrive in highly saline environments have the potential to be valuable in the generation of salt tolerant crops; however, these resources have been largely unexplored. Salicornia bigelovii is a plant native to Mexico and the United States that grows in salt marshes and coastal regions. It can thrive in environments with salt concentrations higher than seawater. In contrast to most crops, S. bigelovii is able to accumulate very high concentrations (in the order of 1.5 M) of Na+ and Cl- in its photosynthetically active succulent shoots. Part of this tolerance is likely to include the storage of Na+ in the vacuoles of the shoots, making S. bigelovii a good model for understanding mechanisms of Na+ compartmentalization in the vacuoles and a good resource for gene discovery. In this research project, phenotypic, genomic, transcriptomic, and proteomic approaches have been used for the identification of candidate genes involved in salinity tolerance in S. bigelovii. The genomes and transcriptomes of three Salicornia species have been sequenced. This information has been used to support the characterization of the salt-induced transcriptome of S. bigelovii shoots and the salt-induced proteome of various organellar membrane enriched fractions from S. bigelovii shoots, which led to the creation of organellar membrane proteomes. Yeast spot assays at different salt concentrations revealed several proteins increasing or decreasing yeast salt tolerance. This work aims to create the basis for

  12. Temperature responsive track membranes

    International Nuclear Information System (INIS)

    Omichi, H.; Yoshido, M.; Asano, M.; Tamada, H.

    1994-01-01

    A new track membrane was synthesized by introducing polymeric hydrogel to films. Such a monomer as amino acid group containing acryloyl or methacryloyl was either co-polymerized with diethylene glycol-bis-ally carbonate followed by on beam irradiation and chemical etching, or graft co-polymerized onto a particle track membrane of CR-39. The pore size was controlled in water by changing the water temperature. Some films other than CR-39 were also examined. (author). 11 refs, 7 figs

  13. Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography.

    Science.gov (United States)

    Vu, Anh T; Wang, Xinying; Wickramasinghe, S Ranil; Yu, Bing; Yuan, Hua; Cong, Hailin; Luo, Yongli; Tang, Jianguo

    2015-08-01

    Hydrophobic interaction membrane chromatography has gained interest due to its excellent performance in the purification of humanized monoclonal antibodies. The membrane material used in hydrophobic interaction membrane chromatography has typically been commercially available polyvinylidene fluoride. In this contribution, newly developed inverse colloidal crystal membranes that have uniform pores, high porosity and, therefore, high surface area for protein binding are used as hydrophobic interaction membrane chromatography membranes for humanized monoclonal antibody immunoglobulin G purification. The capacity of the inverse colloidal crystal membranes developed here is up to ten times greater than commercially available polyvinylidene fluoride membranes with a similar pore size. This work highlights the importance of developing uniform pore size high porosity membranes in order to maximize the capacity of hydrophobic interaction membrane chromatography. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Fabrication of electrospun nanofibrous membranes for membrane distillation application

    KAUST Repository

    Francis, Lijo

    2013-02-01

    Nanofibrous membranes of Matrimid have been successfully fabricated using an electrospinning technique under optimized conditions. Nanofibrous membranes are found to be highly hydrophobic with a high water contact angle of 130°. Field emission scanning electron microscopy and pore size distribution analysis revealed the big pore size structure of electrospun membranes to be greater than 2 μm and the pore size distribution is found to be narrow. Flat sheet Matrimid membranes were fabricated via casting followed by phase inversion. The morphology, pore size distribution, and water contact angle were measured and compared with the electrospun membranes. Both membranes fabricated by electrospinning and phase inversion techniques were tested in a direct contact membrane distillation process. Electrospun membranes showed high water vapor flux of 56 kg/m2-h, which is very high compared to the casted membrane as well as most of the fabricated and commercially available highly hydrophobic membranes. ©2013 Desalination Publications.

  15. Far Western: probing membranes.

    Science.gov (United States)

    Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

    2007-08-01

    INTRODUCTIONThe far-Western technique described in this protocol is fundamentally similar to Western blotting. In Western blots, an antibody is used to detect a query protein on a membrane. In contrast, in a far-Western blot (also known as an overlay assay) the antibody is replaced by a recombinant GST fusion protein (produced and purified from bacteria), and the assay detects the interaction of this protein with target proteins on a membrane. The membranes are washed and blocked, incubated with probe protein, washed again, and subjected to autoradiography. The GST fusion (probe) proteins are often labeled with (32)P; alternatively, the membrane can be probed with unlabeled GST fusion protein, followed by detection using commercially available GST antibodies. The nonradioactive approach is substantially more expensive (due to the purchase of antibody and detection reagents) than using radioactively labeled proteins. In addition, care must be taken to control for nonspecific interactions with GST alone and a signal resulting from antibody cross-reactivity. In some instances, proteins on the membrane are not able to interact after transfer. This may be due to improper folding, particularly in the case of proteins expressed from a phage expression library. This protocol describes a way to overcome this by washing the membrane in denaturation buffer, which is then serially diluted to permit slow renaturation of the proteins.

  16. OXYGEN TRANSPORT CERAMIC MEMBRANES

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Sukumar Bandopadhyay; Dr. Nagendra Nagabhushana

    2000-10-01

    This is the third quarterly report on oxygen Transport Ceramic Membranes. In the following, the report describes the progress made by our university partners in Tasks 1 through 6, experimental apparatus that was designed and built for various tasks of this project, thermodynamic calculations, where applicable and work planned for the future. (Task 1) Design, fabricate and evaluate ceramic to metal seals based on graded ceramic powder/metal braze joints. (Task 2) Evaluate the effect of defect configuration on ceramic membrane conductivity and long term chemical and structural stability. (Task 3) Determine materials mechanical properties under conditions of high temperatures and reactive atmospheres. (Task 4) Evaluate phase stability and thermal expansion of candidate perovskite membranes and develop techniques to support these materials on porous metal structures. (Task 5) Assess the microstructure of membrane materials to evaluate the effects of vacancy-impurity association, defect clusters, and vacancy-dopant association on the membrane performance and stability. (Task 6) Measure kinetics of oxygen uptake and transport in ceramic membrane materials under commercially relevant conditions using isotope labeling techniques.

  17. Bacterial membrane proteomics.

    Science.gov (United States)

    Poetsch, Ansgar; Wolters, Dirk

    2008-10-01

    About one quarter to one third of all bacterial genes encode proteins of the inner or outer bacterial membrane. These proteins perform essential physiological functions, such as the import or export of metabolites, the homeostasis of metal ions, the extrusion of toxic substances or antibiotics, and the generation or conversion of energy. The last years have witnessed completion of a plethora of whole-genome sequences of bacteria important for biotechnology or medicine, which is the foundation for proteome and other functional genome analyses. In this review, we discuss the challenges in membrane proteome analysis, starting from sample preparation and leading to MS-data analysis and quantification. The current state of available proteomics technologies as well as their advantages and disadvantages will be described with a focus on shotgun proteomics. Then, we will briefly introduce the most abundant proteins and protein families present in bacterial membranes before bacterial membrane proteomics studies of the last years will be presented. It will be shown how these works enlarged our knowledge about the physiological adaptations that take place in bacteria during fine chemical production, bioremediation, protein overexpression, and during infections. Furthermore, several examples from literature demonstrate the suitability of membrane proteomics for the identification of antigens and different pathogenic strains, as well as the elucidation of membrane protein structure and function.

  18. Rheological properties of poly(vinyl alcohol) (PVA) derived composite membranes for fuel cells

    International Nuclear Information System (INIS)

    Remiš, T

    2017-01-01

    Rheological properties of new anhydrous proton conducting membrane based on PVA, tetraethyl orthosilicate (TEOS),sulfosuccinic acid (SSA), titanium dioxide (TiO 2 )was examined at various stoichiometric ratios. SSA was used as sulfonating agents to form a crosslinked structure and as proton source, whereas TEO Sand TiO 2 were utilized to improve the thermal and mechanical properties of the membrane. In order to verify that all the substances were immobilized into the matrix, the membranes were analysed by means of FT-IR. The rheological, mechanical and thermal properties of the membranes were investigated using rheometer ARES G2 and thermogravimetic analyser (TGA).The analysis of mixed PVA solutions exhibited a unique behaviour of viscosity with increased crosslink density. The dynamic storage modulus G´ of dried composite membranes shows better mechanical resistance and increased tolerance to pressure applied during membrane electrode assembly (MEA). (paper)

  19. Rheological properties of poly(vinyl alcohol) (PVA) derived composite membranes for fuel cells

    Science.gov (United States)

    Remiš, T.

    2017-01-01

    Rheological properties of new anhydrous proton conducting membrane based on PVA, tetraethyl orthosilicate (TEOS),sulfosuccinic acid (SSA), titanium dioxide (TiO2)was examined at various stoichiometric ratios. SSA was used as sulfonating agents to form a crosslinked structure and as proton source, whereas TEO Sand TiO2were utilized to improve the thermal and mechanical properties of the membrane. In order to verify that all the substances were immobilized into the matrix, the membranes were analysed by means of FT-IR. The rheological, mechanical and thermal properties of the membranes were investigated using rheometer ARES G2 and thermogravimetic analyser (TGA).The analysis of mixed PVA solutions exhibited a unique behaviour of viscosity with increased crosslink density. The dynamic storage modulus G´ of dried composite membranes shows better mechanical resistance and increased tolerance to pressure applied during membrane electrode assembly (MEA).

  20. Biomimetic membranes and methods of making biomimetic membranes

    Science.gov (United States)

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

    2016-11-08

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

  1. Polyurethane Nanofiber Membranes for Waste Water Treatment by Membrane Distillation

    OpenAIRE

    Jiříček, T.; Komárek, M.; Lederer, T.

    2017-01-01

    Self-sustained electrospun polyurethane nanofiber membranes were manufactured and tested on a direct-contact membrane distillation unit in an effort to find the optimum membrane thickness to maximize flux rate and minimize heat losses across the membrane. Also salt retention and flux at high salinities up to 100 g kg−1 were evaluated. Even though the complex structure of nanofiber layers has extreme specific surface and porosity, membrane performance was surprisingly predictable; the highest ...

  2. B cells in operational tolerance.

    Science.gov (United States)

    Chesneau, M; Danger, R; Soulillou, J-P; Brouard, S

    2018-02-16

    Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunosuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal. This review summarizes studies that suggest a role for B cells as biomarkers of operational tolerance and discusses the use of B cells as a predictive tool for immunologic risk. Copyright © 2018. Published by Elsevier Inc.

  3. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Awaya, Kazuhiko; Kuniki, Hiromichi; Neki, Miyuki

    1978-01-01

    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F 1 -type cells. F 1 -type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F 1 -skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F 1 -type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  4. Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Möbius, Wiebke; Wehr, Michael C; Krämer-Albers, Eva-Maria; Brügger, Britta; Nave, Klaus-Armin

    2009-05-13

    Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension of the glial cell membrane with a characteristic composition of proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention and disease, presumably attributable to failure of misfolded proteins to pass the ER quality control. Because many myelin proteins partition into cholesterol-rich membrane rafts, their interaction with cholesterol could potentially be part of the ER quality control system. Here, we provide in vitro and in vivo evidence that the major peripheral myelin protein P0 requires cholesterol for exiting the ER and reaching the myelin compartment. Cholesterol dependency of P0 trafficking in heterologous cells is mediated by a cholesterol recognition/interaction amino acid consensus (CRAC) motif. Mutant mice lacking cholesterol biosynthesis in Schwann cells suffer from severe hypomyelination with numerous uncompacted myelin stretches. This demonstrates that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction.

  5. Spinal cord thyrotropin releasing hormone receptors of morphine tolerant-dependent and abstinent rats

    Energy Technology Data Exchange (ETDEWEB)

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

    1990-07-01

    The effect of chronic administration of morphine and its withdrawal on the binding of 3H-(3-MeHis2)thyrotropin releasing hormone (3H-MeTRH) to membranes of the spinal cord of the rat was determined. Male Sprague-Dawley rats were implanted with either 6 placebo or 6 morphine pellets (each containing 75-mg morphine base) during a 7-day period. Two sets of animals were used. In one, the pellets were left intact at the time of sacrificing (tolerant-dependent) and in the other, the pellets were removed 16 hours prior to sacrificing (abstinent rats). In placebo-pellet-implanted rats, 3H-MeTRH bound to the spinal cord membranes at a single high affinity binding site with a Bmax of 21.3 +/- 1.6 fmol/mg protein, and an apparent dissociation constant Kd of 4.7 +/- 0.8 nM. In morphine tolerant-dependent or abstinent rats, the binding constants of 3H-MeTRH to spinal cord membranes were unaffected. Previous studies from this laboratory indicate that TRH can inhibit morphine tolerance-dependence and abstinence processes without modifying brain TRH receptors. Together with the present results, it appears that the inhibitory effect of TRH on morphine tolerance-dependence and abstinence is probably not mediated via central TRH receptors but may be due to its interaction with other neurotransmitter systems.

  6. Methods to establish flaw tolerances

    International Nuclear Information System (INIS)

    Varga, T.

    1978-01-01

    Three conventional methods used to establish flaw tolerances are compared with new approaches using fracture mechanics. The conventional methods are those based on (a) non-destructive testing methods; (b) fabrication and quality assurance experience; and (c) service and damage experience. Pre-requisites of fracture mechanics methods are outlined, and summaries given of linear elastic mechanics (LEFM) and elastoplastic fracture mechanics (EPFM). The latter includes discussion of C.O.D.(crack opening displacement), the J-integral and equivalent energy. Proposals are made for establishing flaw tolerances. (U.K.)

  7. Tolerating extremism : to what extent should intolerance be tolerated?

    NARCIS (Netherlands)

    Guiora, Amos Neuser

    2013-01-01

    In discussing extremism, the key questions are: to whom is a duty owed and what are the limits of intolerance that are to be tolerated? Answering these questions requires examining limits and rights; analyzing them in the context of extremism is the ‘core’ of this book. While freedom of speech and

  8. Outer membrane targeting of Pseudomonas aeruginosa proteins shows variable dependence on the components of Bam and Lol machineries.

    Science.gov (United States)

    Hoang, Hanh H; Nickerson, Nicholas N; Lee, Vincent T; Kazimirova, Anastasia; Chami, Mohamed; Pugsley, Anthony P; Lory, Stephen

    2011-01-01

    In Gram-negative bacteria, the Lol and Bam machineries direct the targeting of lipidated and nonlipidated proteins, respectively, to the outer membrane (OM). Using Pseudomonas aeruginosa strains with depleted levels of specific Bam and Lol proteins, we demonstrated a variable dependence of different OM proteins on these targeting pathways. Reduction in the level of BamA significantly affected the ability of the β-barrel membrane protein OprF to localize to the OM, while the targeting of three secretins that are functionally related OM proteins was less affected (PilQ and PscC) or not at all affected (XcpQ). Depletion of LolB affected all lipoproteins examined and had a variable effect on the nonlipidated proteins. While the levels of OprF, PilQ, and PscC were significantly reduced by LolB depletion, XcpQ was unaffected and was correctly localized to the OM. These results suggest that certain β-barrel proteins such as OprF primarily utilize the complete Bam machinery. The Lol machinery participates in the OM targeting of secretins to variable degrees, likely through its involvement in the assembly of lipidated Bam components. XcpQ, but not PilQ or PscC, was shown to assemble spontaneously into liposomes as multimers. This work raises the possibility that there is a gradient of utilization of Bam and Lol insertion and targeting machineries. Structural features of individual proteins, including their β-barrel content, may determine the propensity of these proteins for folding (or misfolding) during periplasmic transit and OM insertion, thereby influencing the extent of utilization of the Bam targeting machinery, respectively. Targeting of lipidated and nonlipidated proteins to the outer membrane (OM) compartment in Gram-negative bacteria involves the transfer across the periplasm utilizing the Lol and Bam machineries, respectively. We show that depletion of Bam and Lol components in Pseudomonas aeruginosa does not lead to a general OM protein translocation defect

  9. Renewable energy powered membrane technology. 2. The effect of energy fluctuations on performance of a photovoltaic hybrid membrane system.

    Science.gov (United States)

    Richards, B S; Capão, D P S; Schäfer, A I

    2008-06-15

    This paper reports on the performance fluctuations during the operation of a batteryless hybrid ultrafiltration--nanofiltration/reverse osmosis (UF-NF/RO) membrane desalination system powered by photovoltaics treating brackish groundwater in outback Australia. The renewable energy powered membrane (RE-membrane) system is designed to supply clean drinking water to a remote community of about 50 inhabitants. The performance of the RE-membrane system over four different solar days is summarized using four different NF membranes (BW30, NF90, ESPA4, TFC-S), and examined in more detail for the BW30 membrane. On an Australian spring day, the system produced 1.1 m3 of permeate with an average conductivity of 0.28 mS x cm(-1), recovering 28% of the brackish (8.29 mS x cm(-1) conductivity) feedwater with an average specific energy consumption of 2.3 kWh x m(-3). The RE-membrane system tolerated large fluctuations in solar irradiance (500--1200 W x m(-2)), resulting in only small increases in the permeate conductivity. When equipped with the NF90 (cloudy day) and ESPA4 (rainy day) membranes, the system was still able to produce 1.36 m(-3) and 0.85 m(-3) of good quality permeate, respectively. The TFC-S membrane was not able to produce adequate water quality from the bore water tested. It is concluded that batteryless operation is a simple and robust way to operate such systems under conditions ranging from clear skies to medium cloud cover.

  10. Recent advances on polymeric membranes for membrane reactors

    KAUST Repository

    Buonomenna, M. G.

    2012-06-24

    Membrane reactors are generally applied in high temperature reactions (>400 °C). In the field of fine chemical synthesis, however, much milder conditions are generally applicable and polymeric membranes were applied without their damage. The successful use of membranes in membrane reactors is primary the result of two developments concerning: (i) membrane materials and (ii) membrane structures. The selection of a suited material and preparation technique depends on the application the membrane is to be used in. In this chapter a review of up to date literature about polymers and configuration catalyst/ membranes used in some recent polymeric membrane reactors is given. The new emerging concept of polymeric microcapsules as catalytic microreactors has been proposed. © 2012 Bentham Science Publishers. All rights reserved.

  11. Flow and fouling in membrane filters: Effects of membrane morphology

    Science.gov (United States)

    Sanaei, Pejman; Cummings, Linda J.

    2015-11-01

    Membrane filters are widely-used in microfiltration applications. Many types of filter membranes are produced commercially, for different filtration applications, but broadly speaking the requirements are to achieve fine control of separation, with low power consumption. The answer to this problem might seem obvious: select the membrane with the largest pore size and void fraction consistent with the separation requirements. However, membrane fouling (an inevitable consequence of successful filtration) is a complicated process, which depends on many parameters other than membrane pore size and void fraction; and which itself greatly affects the filtration process and membrane functionality. In this work we formulate mathematical models that can (i) account for the membrane internal morphology (internal structure, pore size & shape, etc.); (ii) fouling of membranes with specific morphology; and (iii) make some predictions as to what type of membrane morphology might offer optimum filtration performance.

  12. Polyurethane Nanofiber Membranes for Waste Water Treatment by Membrane Distillation

    Directory of Open Access Journals (Sweden)

    T. Jiříček

    2017-01-01

    Full Text Available Self-sustained electrospun polyurethane nanofiber membranes were manufactured and tested on a direct-contact membrane distillation unit in an effort to find the optimum membrane thickness to maximize flux rate and minimize heat losses across the membrane. Also salt retention and flux at high salinities up to 100 g kg−1 were evaluated. Even though the complex structure of nanofiber layers has extreme specific surface and porosity, membrane performance was surprisingly predictable; the highest flux was achieved with the thinnest membranes and the best energy efficiency was achieved with the thickest membranes. All membranes had salt retention above 99%. Nanotechnology offers the potential to find modern solutions for desalination of waste waters, by introducing new materials with revolutionary properties, but new membranes must be developed according to the target application.

  13. Smart membranes for monitoring membrane based desalination processes

    KAUST Repository

    Laleg-Kirati, Taous-Meriem

    2017-10-12

    Various examples are related to smart membranes for monitoring membrane based process such as, e.g., membrane distillation processes. In one example, a membrane, includes a porous surface and a plurality of sensors (e.g., temperature, flow and/or impedance sensors) mounted on the porous surface. In another example, a membrane distillation (MD) process includes the membrane. Processing circuitry can be configured to monitor outputs of the plurality of sensors. The monitored outputs can be used to determine membrane degradation, membrane fouling, or to provide an indication of membrane replacement or cleaning. The sensors can also provide temperatures or temperature differentials across the porous surface, which can be used to improve modeling or control the MD process.

  14. Physics of biological membranes

    Science.gov (United States)

    Mouritsen, Ole G.

    The biological membrane is a complex system consisting of an aqueous biomolecular planar aggregate of predominantly lipid and protein molecules. At physiological temperatures, the membrane may be considered a thin (˜50Å) slab of anisotropic fluid characterized by a high lateral mobility of the various molecular components. A substantial fraction of biological activity takes place in association with membranes. As a very lively piece of condensed matter, the biological membrane is a challenging research topic for both the experimental and theoretical physicists who are facing a number of fundamental physical problems including molecular self-organization, macromolecular structure and dynamics, inter-macromolecular interactions, structure-function relationships, transport of energy and matter, and interfacial forces. This paper will present a brief review of recent theoretical and experimental progress on such problems, with special emphasis on lipid bilayer structure and dynamics, lipid phase transitions, lipid-protein and lipid-cholesterol interactions, intermembrane forces, and the physical constraints imposed on biomembrane function and evolution. The paper advocates the dual point of view that there are a number of interesting physics problems in membranology and, at the same time, that the physical properties of biomembranes are important regulators of membrane function.

  15. Relationship between sodium influx and salt tolerance of nitrogen-fixing cyanobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Apte, S.K.; Reddy, B.R.; Thomas, J.

    1987-08-01

    The relationship between sodium uptake and cyanobacterial salt (NaCl) tolerance has been examined in two filamentous, heterocystous, nitrogen-fixing species of Anabaena. During diazotrophic growth at neutral pH of the growth medium, Anabaena sp. strain L-31, a freshwater strain, showed threefold higher uptake of Na+ than Anabaena torulosa, a brackish-water strain, and was considerably less salt tolerant (50% lethal dose of NaCl, 55 mM) than the latter (50% lethal dose of NaCl, 170 mM). Alkaline pH or excess K+ (more than 25 mM) in the medium causes membrane depolarization and inhibits Na+ influx in both cyanobacteria (S.K. Apte and J. Thomas, Eur. J. Biochem. 154:395-401, 1986). The presence of nitrate or ammonium in the medium caused inhibition of Na+ influx accompanied by membrane depolarization. These experimental manipulations affecting Na+ uptake demonstrated a good negative correlation between Na+ influx and salt tolerance. All treatments which inhibited Na+ influx (such as alkaline pH, K+ above 25 mM, NO3-, and NH4+), enhanced salt tolerance of not only the brackish-water but also the freshwater cyanobacterium. The results indicate that curtailment of Na+ influx, whether inherent or effected by certain environmental factors (e.g., combined nitrogen, alkaline pH), is a major mechanism of salt tolerance in cyanobacteria. (Refs. 27)

  16. Tolerance of snakes to hypergravity

    Science.gov (United States)

    Lillywhite, H. B.; Ballard, R. E.; Hargens, A. R.

    1996-01-01

    Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.

  17. Assessing Your Board's Risk Tolerance

    Science.gov (United States)

    Griswold, John S.; Jarvis, William F.

    2014-01-01

    In the wake of the financial crisis, trustees of many endowed nonprofit institutions realized that their portfolio was riskier than they thought and their own ability to tolerate loss wasn't as strong as they imagined. What can board and investment committee members do to improve their ability to assess their--and their institution's--capacity for…

  18. Toleration, Multiculturalism and Mistaken Belief

    Science.gov (United States)

    Standish, Paul

    2006-01-01

    Doubts have been expressed about the virtue of toleration, especially in view of what some have seen as its complicity with a morality of anything goes. More rigorous arguments have been provided by Peter Gardner and Harvey Siegel against the relativism evident in certain versions of multiculturalism and in the new religious studies. This article…

  19. Liver plasma membranes: an effective method to analyze membrane proteome.

    Science.gov (United States)

    Cao, Rui; Liang, Songping

    2012-01-01

    Plasma membrane proteins are critical for the maintenance of biological systems and represent important targets for the treatment of disease. The hydrophobicity and low abundance of plasma membrane proteins make them difficult to analyze. The protocols given here are the efficient isolation/digestion procedures for liver plasma membrane proteomic analysis. Both protocol for the isolation of plasma membranes and protocol for the in-gel digestion of gel-embedded plasma membrane proteins are presented. The later method allows the use of a high detergent concentration to achieve efficient solubilization of hydrophobic plasma membrane proteins while avoiding interference with the subsequent LC-MS/MS analysis.

  20. Aquaporin-2 membrane targeting

    DEFF Research Database (Denmark)

    Olesen, Emma T B; Fenton, Robert A

    2017-01-01

    The targeting of the water channel aquaporin-2 (AQP2) to the apical plasma membrane of kidney collecting duct principal cells is regulated mainly by the antidiuretic peptide hormone arginine vasopressin (AVP). This process is of crucial importance for the maintenance of body water homeostasis...... of aquaporin-2 (AQP2) to the apical plasma membrane of collecting duct (CD) principal cells (10, 20). This process is mainly regulated by the actions of AVP on the type 2 AVP receptor (V2R), although the V1a receptor may also play a minor role (26). The V2R is classified within the group of 7-transmembrane....... For example, 1) stimulation with the nonspecific AC activator forskolin increases AQP2 membrane accumulation in a mouse cortical collecting duct cell line [e.g., Norregaard et al. (16)]; 2) cAMP increases CD water permeability (15); 3) the cAMP-activated protein kinase A (PKA) can phosphorylate AQP2 on its...

  1. Tracking the evolution of a cold stress associated gene family in cold tolerant grasses

    DEFF Research Database (Denmark)

    Sandve, Simen R; Rudi, Heidi; Asp, Torben

    2008-01-01

    to the repeat motifs of the IRI-domain in cold tolerant grasses. Finally we show that the LRR-domain of carrot and grass IRI proteins both share homology to an Arabidopsis thaliana LRR-trans membrane protein kinase (LRR-TPK). Conclusion The diverse IRI-like genes identified in this study tell a tale...... of a complex evolutionary history including birth of an ice binding domain, a burst of gene duplication events after cold tolerant grasses radiated from rice, protein domain structure differentiation between paralogs, and sub- and/or neofunctionalisation of IRI-like proteins. From our sequence analysis we...

  2. Membrane adsorber for endotoxin removal

    Directory of Open Access Journals (Sweden)

    Karina Moita de Almeida

    Full Text Available ABSTRACT The surface of flat-sheet nylon membranes was modified using bisoxirane as the spacer and polyvinyl alcohol as the coating polymer. The amino acid histidine was explored as a ligand for endotoxins, aiming at its application for endotoxin removal from aqueous solutions. Characterization of the membrane adsorber, analysis of the depyrogenation procedures and the evaluation of endotoxin removal efficiency in static mode are discussed. Ligand density of the membranes was around 7 mg/g dry membrane, allowing removal of up to 65% of the endotoxins. The performance of the membrane adsorber prepared using nylon coated with polyvinyl alcohol and containing histidine as the ligand proved superior to other membrane adsorbers reported in the literature. The lack of endotoxin adsorption on nylon membranes without histidine confirmed that endotoxin removal was due to the presence of the ligand at the membrane surface. Modified membranes were highly stable, exhibiting a lifespan of approximately thirty months.

  3. Hybrid Filter Membrane

    Science.gov (United States)

    Laicer, Castro; Rasimick, Brian; Green, Zachary

    2012-01-01

    Cabin environmental control is an important issue for a successful Moon mission. Due to the unique environment of the Moon, lunar dust control is one of the main problems that significantly diminishes the air quality inside spacecraft cabins. Therefore, this innovation was motivated by NASA s need to minimize the negative health impact that air-suspended lunar dust particles have on astronauts in spacecraft cabins. It is based on fabrication of a hybrid filter comprising nanofiber nonwoven layers coated on porous polymer membranes with uniform cylindrical pores. This design results in a high-efficiency gas particulate filter with low pressure drop and the ability to be easily regenerated to restore filtration performance. A hybrid filter was developed consisting of a porous membrane with uniform, micron-sized, cylindrical pore channels coated with a thin nanofiber layer. Compared to conventional filter media such as a high-efficiency particulate air (HEPA) filter, this filter is designed to provide high particle efficiency, low pressure drop, and the ability to be regenerated. These membranes have well-defined micron-sized pores and can be used independently as air filters with discreet particle size cut-off, or coated with nanofiber layers for filtration of ultrafine nanoscale particles. The filter consists of a thin design intended to facilitate filter regeneration by localized air pulsing. The two main features of this invention are the concept of combining a micro-engineered straight-pore membrane with nanofibers. The micro-engineered straight pore membrane can be prepared with extremely high precision. Because the resulting membrane pores are straight and not tortuous like those found in conventional filters, the pressure drop across the filter is significantly reduced. The nanofiber layer is applied as a very thin coating to enhance filtration efficiency for fine nanoscale particles. Additionally, the thin nanofiber coating is designed to promote capture of

  4. Mitigating leaks in membranes

    Energy Technology Data Exchange (ETDEWEB)

    Karnik, Rohit N.; Bose, Suman; Boutilier, Michael S.H.; Hadjiconstantinou, Nicolas G.; Jain, Tarun Kumar; O' Hern, Sean C.; Laoui, Tahar; Atieh, Muataz A.; Jang, Doojoon

    2018-02-27

    Two-dimensional material based filters, their method of manufacture, and their use are disclosed. In one embodiment, a membrane may include an active layer including a plurality of defects and a deposited material associated with the plurality of defects may reduce flow therethrough. Additionally, a majority of the active layer may be free from the material. In another embodiment, a membrane may include a porous substrate and an atomic layer deposited material disposed on a surface of the porous substrate. The atomic layer deposited material may be less hydrophilic than the porous substrate and an atomically thin active layer may be disposed on the atomic layer deposited material.

  5. Membrane accessibility of glutathione

    DEFF Research Database (Denmark)

    Garcia, Almudena; Eljack, N., D.; Sani, ND

    2015-01-01

    Regulation of the ion pumping activity of the Na(+),K(+)-ATPase is crucial to the survival of animal cells. Recent evidence has suggested that the activity of the enzyme could be controlled by glutathionylation of cysteine residue 45 of the β-subunit. Crystal structures so far available indicate...... that this cysteine is in a transmembrane domain of the protein. Here we have analysed via fluorescence and NMR spectroscopy as well as molecular dynamics simulations whether glutathione is able to penetrate into the interior of a lipid membrane. No evidence for any penetration of glutathione into the membrane...

  6. Fouling resistant membrane spacers

    KAUST Repository

    Ghaffour, Noreddine

    2017-10-12

    Disclosed herein are spacers having baffle designs and perforations for efficiently and effectively separating one or more membrane layers a membrane filtration system. The spacer (504) includes a body (524) formed at least in part by baffles (520) that are interconnected, and the baffles define boundaries of openings or apertures (525) through a thickness direction of the body of the spacer. Alternatively or additionally, passages or perforations (526A, 526B) may be present in the spacer layer or baffles for fluid flow there through, with the passages and baffles having a numerous different shapes and sizes.

  7. Organic separations with membranes

    International Nuclear Information System (INIS)

    Funk, E.W.

    1993-01-01

    This paper presents an overview of present and emerging applications of membrane technology for the separation and purification of organic materials. This technology is highly relevant for programs aimed at minimizing waste in processing and in the treatment of gaseous and liquid effluents. Application of membranes for organic separation is growing rapidly in the petrochemical industry to simplify processing and in the treatment of effluents, and it is expected that this technology will be useful in numerous other industries including the processing of nuclear waste materials

  8. Recent Insights in Islet Amyloid Polypeptide-Induced Membrane Disruption and Its Role in β-Cell Death in Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Lucie Khemtémourian

    2008-01-01

    Full Text Available The presence of fibrillar protein deposits (amyloid of human islet amyloid polypeptide (hIAPP in the pancreatic islets of Langerhans is thought to be related to death of the insulin-producing islet β-cells in type 2 diabetes mellitus (DM2. The mechanism of hIAPP-induced β-cell death is not understood. However, there is growing evidence that hIAPP-induced disruption of β-cell membranes is the cause of hIAPP cytotoxicity. Amyloid cytotoxicity by membrane damage has not only been suggested for hIAPP, but also for peptides and proteins related to other misfolding diseases, like Alzheimer’s disease, Parkinson’s disease, and prion diseases. Here we review the interaction of hIAPP with membranes, and discuss recent progress in the field, with a focus on hIAPP structure and on the proposed mechanisms of hIAPP-induced membrane damage in relation to β-cell death in DM2.

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

    International Nuclear Information System (INIS)

    Tibor Hianik

    2006-01-01

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

  10. Fouling in Membrane Distillation, Osmotic Distillation and Osmotic Membrane Distillation

    Directory of Open Access Journals (Sweden)

    Mourad Laqbaqbi

    2017-03-01

    Full Text Available Various membrane separation processes are being used for seawater desalination and treatment of wastewaters in order to deal with the worldwide water shortage problem. Different types of membranes of distinct morphologies, structures and physico-chemical characteristics are employed. Among the considered membrane technologies, membrane distillation (MD, osmotic distillation (OD and osmotic membrane distillation (OMD use porous and hydrophobic membranes for production of distilled water and/or concentration of wastewaters for recovery and recycling of valuable compounds. However, the efficiency of these technologies is hampered by fouling phenomena. This refers to the accumulation of organic/inorganic deposits including biological matter on the membrane surface and/or in the membrane pores. Fouling in MD, OD and OMD differs from that observed in electric and pressure-driven membrane processes such electrodialysis (ED, membrane capacitive deionization (MCD, reverse osmosis (RO, nanofiltration (NF, ultrafiltration (UF, microfiltration (MF, etc. Other than pore blockage, fouling in MD, OD and OMD increases the risk of membrane pores wetting and reduces therefore the quantity and quality of the produced water or the concentration efficiency of the process. This review deals with the observed fouling phenomena in MD, OD and OMD. It highlights different detected fouling types (organic fouling, inorganic fouling and biofouling, fouling characterization techniques as well as various methods of fouling reduction including pretreatment, membrane modification, membrane cleaning and antiscalants application.

  11. Membrane order in the plasma membrane and endocytic recycling compartment.

    Science.gov (United States)

    Iaea, David B; Maxfield, Frederick R

    2017-01-01

    The cholesterol content of membranes plays an important role in organizing membranes for signal transduction and protein trafficking as well as in modulating the biophysical properties of membranes. While the properties of model or isolated membranes have been extensively studied, there has been little evaluation of internal membranes in living cells. Here, we use a Nile Red based probe, NR12S, and ratiometric live cell imaging, to analyze the membrane order of the plasma membrane and endocytic recycling compartment. We find that after a brief incubation to allow endocytosis, NR12S is distributed between the plasma membrane and the endocytic recycling compartment. The NR12S reports that the endocytic recycling compartment is more highly ordered than the plasma membrane. We also find that the plasma membrane and the endocytic recycling compartment are differentially affected by altering cellular cholesterol levels. The membrane order of the plasma membrane, but not the endocytic recycling compartment, is altered significantly when cellular cholesterol content is increased or decreased by 20%. These results demonstrate that changes in cellular cholesterol differentially alter membrane order within different organelles.

  12. Histological evaluation of different biodegradable and non-biodegradable membranes implanted subcutaneously in rats

    DEFF Research Database (Denmark)

    Zhao, S; Pinholt, E M; Madsen, J E

    2000-01-01

    Different types of biodegradable membranes have become available for guided tissue regeneration. The purpose of this study was to evaluate histologically three different biodegradable membranes (Bio-Gide, Resolut and Vicryl) and one non-biodegradable membrane (expanded polytetrafluoroethylene/e-PTFE...... that e-PTFE was well tolerated and encapsulated by a fibrous connective tissue capsule. There was capsule formation around Resolut and Vicryl and around Bio-Gide in the early phase there was a wide inflammatory zone already. e-PTFE and Vicryl were stable materials while Resolut and Bio-Gide fragmented...

  13. Physiological determinants of human acute hypoxia tolerance.

    Science.gov (United States)

    2013-11-01

    AbstractIntroduction. We investigated possible physiological determinants of variability in hypoxia tolerance in subjects given a 5-minute normobaric exposure to 25,000 ft equivalent. Physiological tolerance to hypoxia was defined as the magnitude of...

  14. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2017-01-01

    In this review, we briefly summarize the current understanding of how fungal pathogens can persist antifungal treatment without heritable resistance mutations by forming tolerant persister cells. Fungal infections tolerant to antifungal treatment have become a major medical problem. One mechanism...

  15. Drought and submergence tolerance in plants

    Energy Technology Data Exchange (ETDEWEB)

    Du, Hewei; Zhou, Yufan; Oksenberg, Nir; Ronald, Pamela

    2017-11-14

    The invention provides methods of genetically modified plants to increase tolerance to drought and/or submergence. The invention additionally provides plants having increased drought and/or submergence tolerance engineered using such methods.

  16. Urbanism, Migration, and Tolerance: A Reassessment.

    Science.gov (United States)

    Wilson, Thomas C.

    1991-01-01

    Urbanism's impact on the personality may be stronger than previously thought. Finds that urban residence has a strong positive effect on tolerance. Migration also promotes tolerance, regardless of the size of the destination community. (DM)

  17. Fabrication of electrospun nanofibrous membranes for membrane distillation application

    KAUST Repository

    Francis, Lijo; Maab, Husnul; Alsaadi, Ahmad Salem; Nunes, Suzana Pereira; Ghaffour, NorEddine; Amy, Gary L.

    2013-01-01

    Nanofibrous membranes of Matrimid have been successfully fabricated using an electrospinning technique under optimized conditions. Nanofibrous membranes are found to be highly hydrophobic with a high water contact angle of 130°. Field emission

  18. Giant plasma membrane vesicles: models for understanding membrane organization.

    Science.gov (United States)

    Levental, Kandice R; Levental, Ilya

    2015-01-01

    The organization of eukaryotic membranes into functional domains continues to fascinate and puzzle cell biologists and biophysicists. The lipid raft hypothesis proposes that collective lipid interactions compartmentalize the membrane into coexisting liquid domains that are central to membrane physiology. This hypothesis has proven controversial because such structures cannot be directly visualized in live cells by light microscopy. The recent observations of liquid-liquid phase separation in biological membranes are an important validation of the raft hypothesis and enable application of the experimental toolbox of membrane physics to a biologically complex phase-separated membrane. This review addresses the role of giant plasma membrane vesicles (GPMVs) in refining the raft hypothesis and expands on the application of GPMVs as an experimental model to answer some of key outstanding problems in membrane biology. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Adaptive silicone-membrane lenses: planar vs. shaped membrane

    CSIR Research Space (South Africa)

    Schneider, F

    2009-08-01

    Full Text Available Engineering, Georges-Koehler-Allee 102, Freiburg 79110, Germany florian.schneider@imtek.uni-freiburg.de ABSTRACT We compare the performance and optical quality of two types of adaptive fluidic silicone-membrane lenses. The membranes feature either a...-membrane lenses: planar vs. shaped membrane Florian Schneider1,2, Philipp Waibel2 and Ulrike Wallrabe2 1 CSIR, Materials Science and Manufacturing, PO Box 395, Pretoria 0001, South Africa 2 University of Freiburg – IMTEK, Department of Microsystems...

  20. Nanodisc-solubilized membrane protein library reflects the membrane proteome

    OpenAIRE

    Marty, Michael T.; Wilcox, Kyle C.; Klein, William L.; Sligar, Stephen G.

    2013-01-01

    The isolation and identification of unknown membrane proteins offers the prospect of discovering new pharmaceutical targets and identifying key biochemical receptors. However, interactions between membrane protein targets and soluble ligands are difficult to study in vitro due to the insolubility of membrane proteins in non-detergent systems. Nanodiscs, nanoscale discoidal lipid bilayers encircled by a membrane scaffold protein belt, have proven to be an effective platform to solubilize membr...

  1. Trienoic fatty acids and plant tolerance of temperature

    Directory of Open Access Journals (Sweden)

    Routaboul Jean-Marc

    2002-01-01

    Full Text Available The biophysical reactions of light harvesting and electron transport during photosynthesis take place in a uniquely constructed bilayer, the thylakoid. In all photosynthetic eukaryotes, the complement of atypical glycerolipid molecules that form the foundation of this membrane are characterised by sugar head-groups and a very high level of unsaturation in the fatty acids that occupy the central portion of the thylakoid bilayer. alpha-linolenic (18:3 or a combination of 18:3 and hexadecatrienoic (16:3 acids typically account for approximately two-thirds of all thylakoid membrane fatty acids and over 90% of the fatty acids of monogalactosyl diacylglycerol, the major thylakoid lipid [1, 2]. The occurrence of trienoic fatty acids as a major component of the thylakoid membrane is especially remarkable since these fatty acids form highly reactive targets for active oxygen species and free radicals, which are often the by-products of oxygenic photosynthesis. Photosynthesis is one of the most temperature-sensitive functions of plant [3, 4]. There remains a widespread belief that these trienoic fatty acids might have some crucial role in plants to be of such universal occurrence, especially in photosynthesis tolerance of temperature [5].

  2. Imaging of membranous dysmenorrhea

    Energy Technology Data Exchange (ETDEWEB)

    Rouanet, J.P.; Daclin, P.Y.; Turpin, F.; Karam, R.; Prayssac-Salanon, A. [Dept. of Radiology, C. M. C. Beausoleil, Montpellier (France); Courtieu, C.R. [Dept. of Gynecology, C. M. C. Beausoleil, Montpellier (France); Maubon, A.J. [Dept. of Radiology, C. M. C. Beausoleil, Montpellier (France); Dept. of Radiology, C. H. U. Dupuytren, Limoges (France)

    2001-06-01

    Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed. (orig.)

  3. Imaging of membranous dysmenorrhea

    International Nuclear Information System (INIS)

    Rouanet, J.P.; Daclin, P.Y.; Turpin, F.; Karam, R.; Prayssac-Salanon, A.; Courtieu, C.R.; Maubon, A.J.

    2001-01-01

    Membranous dysmenorrhea is an unusual clinical entity. It is characterized by the expulsion of huge fragments of endometrium during the menses, favored by hormonal abnormality or drug intake. This report describes a case with clinical, US, and MRI findings before the expulsion. Differential diagnoses are discussed. (orig.)

  4. HOLLOW FIBRE MEMBRANE

    NARCIS (Netherlands)

    Wessling, Matthias; Stamatialis, Dimitrios; Kopec, K.K.; Dutczak, S.M.

    2011-01-01

    The present invention relates to a process for manufacturing a hollow fibre membrane having a supporting layer and a separating layer, said process comprising: (a)extruding a spinning composition comprising a first polymer and a solvent for the first polymer through an inner annular orifice of a

  5. HOLLOW FIBRE MEMBRANE

    NARCIS (Netherlands)

    Wessling, Matthias; Stamatialis, Dimitrios; Kopec, K.K.; Dutczak, S.M.

    2013-01-01

    The present invention relates to a process for manufacturing a hollow fibre membrane having a supporting layer and a separating layer, said process comprising: (a) extruding a spinning composition comprising a first polymer and a solvent for the first polymer through an inner annular orifice of a

  6. Fusion of biological membranes

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics; Volume 64; Issue 6. Fusion of biological membranes. K Katsov M Müller M Schick. Invited Talks:- Topic 11. Biologically motivated problems (protein-folding models, dynamics at the scale of the cell; biological networks, evolution models, etc.) Volume 64 Issue 6 June 2005 pp ...

  7. Membranes and Fluorescence microscopy

    DEFF Research Database (Denmark)

    Bagatolli, Luis

    2009-01-01

    Fluorescence spectroscopy-based techniques using conventional fluorimeters have been extensively applied since the late 1960s to study different aspects of membrane-related phenomena, i.e., mainly relating to lipid-lipid and lipid-protein (peptide) interactions. Even though fluorescence...

  8. Bioelectrochemistry II membrane phenomena

    CERN Document Server

    Blank, M

    1987-01-01

    This book contains the lectures of the second course devoted to bioelectro­ chemistry, held within the framework of the International School of Biophysics. In this course another very large field of bioelectrochemistry, i. e. the field of Membrane Phenomena, was considered, which itself consists of several different, but yet related subfields. Here again, it can be easily stated that it is impossible to give a complete and detailed picture of all membrane phenomena of biological interest in a short course of about one and half week. Therefore the same philosophy, as the one of the first course, was followed, to select a series of lectures at postgraduate level, giving a synthesis of several membrane phenomena chosen among the most'important ones. These lectures should show the large variety of membrane-regulated events occurring in living bodies, and serve as sound interdisciplinary basis to start a special­ ized study of biological phenomena, for which the investigation using the dual approach, physico-che...

  9. Membrane Transfer Phenomena (MTP)

    Science.gov (United States)

    Mason, Larry

    1996-01-01

    Progress has been made in several areas of the definition, design, and development of the Membrane Transport Apparatus (MTA) instrument and associated sensors and systems. Progress is also reported in the development of software modules for instrument control, experimental image and data acquisition, and data analysis.

  10. Extracorporeal membrane oxygenation (ECMO)

    African Journals Online (AJOL)

    Extracorporeal membrane oxygenation (ECMO) is not a novel therapy in the true sense of the ... Intention-to-treat analysis showed benefit for ECMO, with a relative risk ... no doubt that VV-ECMO is an advance in medical technology, and that.

  11. Inhibiting TNF-α signaling does not attenuate induction of endotoxin tolerance

    Directory of Open Access Journals (Sweden)

    Loosbroock C

    2014-12-01

    Full Text Available Christopher Loosbroock, Kenneth W Hunter Department of Microbiology and Immunology, University of Nevada School of Medicine, Reno, NV, USA Abstract: Tumor necrosis factor-alpha (TNF-α is a central mediator of inflammatory responses elicited by Toll-like receptor agonists, such as the Gram-negative bacterial outer membrane antigen lipopolysaccharide (LPS. TNF-α is responsible for altering vascular permeability and activating infiltrating inflammatory cells, such as monocytes and neutrophils. Interestingly, TNF-α has also demonstrated the ability to induce tolerance to subsequent challenges with TNF-α or LPS in monocyte and macrophage cell populations. Tolerance is characterized by the inability to mount a typical inflammatory response during subsequent challenges following the initial exposure to an inflammatory mediator such as LPS. The ability of TNF-α to induce a tolerant-like state with regard to LPS is most likely a regulatory mechanism to prevent excessive inflammation. We hypothesized that the induction of tolerance or the degree of tolerance is dependent upon the production of TNF-α during the primary response to LPS. To investigate TNF-α-dependent tolerance, human monocytic THP-1 cells were treated with TNF-α-neutralizing antibodies or antagonistic TNF-α receptor antibodies before primary LPS stimulation and then monitored for the production of TNF-α during the primary and challenge stimulation. During the primary stimulation, anti-TNF-α treatment effectively attenuated the production of TNF-α and interleukin-1β; however, this reduced production did not impact the induction of endotoxin tolerance. These results demonstrate that interfering with TNF-α signaling attenuates production of inflammatory cytokines without affecting the induction of tolerance. Keywords: endotoxin tolerance, lipopolysaccharide, tumor necrosis factor-alpha, anti-tumor necrosis factor-alpha, THP-1 cells

  12. Alternative energy efficient membrane bioreactor using reciprocating submerged membrane.

    Science.gov (United States)

    Ho, J; Smith, S; Roh, H K

    2014-01-01

    A novel membrane bioreactor (MBR) pilot system, using membrane reciprocation instead of air scouring, was operated at constant high flux and daily fluctuating flux to demonstrate its application under peak and diurnal flow conditions. Low and stable transmembrane pressure was achieved at 40 l/m(2)/h (LMH) by use of repetitive membrane reciprocation. The results reveal that the inertial forces acting on the membrane fibers effectively propel foulants from the membrane surface. Reciprocation of the hollow fiber membrane is beneficial for the constant removal of solids that may build up on the membrane surface and inside the membrane bundle. The membrane reciprocation in the reciprocating MBR pilot consumed less energy than coarse air scouring used in conventional MBR systems. Specific energy consumption for the membrane reciprocation was 0.072 kWh/m(3) permeate produced at 40 LMH flux, which is 75% less than for a conventional air scouring system as reported in literature without consideration of energy consumption for biological aeration (0.29 kWh/m(3)). The daily fluctuating flux test confirmed that the membrane reciprocation is effective to handle fluctuating flux up to 50 LMH. The pilot-scale reciprocating MBR system successfully demonstrated that fouling can be controlled via 0.43 Hz membrane reciprocation with 44 mm or higher amplitude.

  13. Recent advances on membranes and membrane reactors for hydrogen production

    NARCIS (Netherlands)

    Gallucci, F.; Fernandez Gesalaga, E.; Corengia, P.; Sint Annaland, van M.

    2013-01-01

    Membranes and membrane reactors for pure hydrogen production are widely investigated not only because of the important application areas of hydrogen, but especially because mechanically and chemically stable membranes with high perm-selectivity towards hydrogen are available and are continuously

  14. Influence of membrane properties on fouling in submerged membrane bioreactors

    NARCIS (Netherlands)

    van der Marel, P.; Zwijnenburg, A.; Kemperman, Antonius J.B.; Wessling, Matthias; Temmink, Hardy; van der Meer, Walterus Gijsbertus Joseph

    2010-01-01

    Polymeric flat-sheet membranes with different properties were used in filtration experiments with activated sludge from a pilot-scale MBR to investigate the influence of membrane pore size, surface porosity, pore morphology, and hydrophobicity on membrane fouling. An improved flux-step method was

  15. Nanodisc-solubilized membrane protein library reflects the membrane proteome.

    Science.gov (United States)

    Marty, Michael T; Wilcox, Kyle C; Klein, William L; Sligar, Stephen G

    2013-05-01

    The isolation and identification of unknown membrane proteins offers the prospect of discovering new pharmaceutical targets and identifying key biochemical receptors. However, interactions between membrane protein targets and soluble ligands are difficult to study in vitro due to the insolubility of membrane proteins in non-detergent systems. Nanodiscs, nanoscale discoidal lipid bilayers encircled by a membrane scaffold protein belt, have proven to be an effective platform to solubilize membrane proteins and have been used to study a wide variety of purified membrane proteins. This report details the incorporation of an unbiased population of membrane proteins from Escherichia coli membranes into Nanodiscs. This solubilized membrane protein library (SMPL) forms a soluble in vitro model of the membrane proteome. Since Nanodiscs contain isolated proteins or small complexes, the SMPL is an ideal platform for interactomics studies and pull-down assays of membrane proteins. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the protein population before and after formation of the Nanodisc library indicates that a large percentage of the proteins are incorporated into the library. Proteomic identification of several prominent bands demonstrates the successful incorporation of outer and inner membrane proteins into the Nanodisc library.

  16. Autophagosomal membranes assemble at ER-plasma membrane contact sites.

    Science.gov (United States)

    Nascimbeni, Anna Chiara; Codogno, Patrice; Morel, Etienne

    2017-01-01

    The biogenesis of autophagosome, the double membrane bound organelle related to macro-autophagy, is a complex event requiring numerous key-proteins and membrane remodeling events. Our recent findings identify the extended synaptotagmins, crucial tethers of Endoplasmic Reticulum-plasma membrane contact sites, as key-regulators of this molecular sequence.

  17. 75 FR 17566 - Flutolanil; Pesticide Tolerances

    Science.gov (United States)

    2010-04-07

    ... ppm, and the greater tolerance value is needed to accommodate indirect residues from soybean..., and soybean hay at 2.5 ppm are being revoked since the same tolerance values are being established...; Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This...

  18. 77 FR 49732 - Cyprodinil; Pesticide Tolerances

    Science.gov (United States)

    2012-08-17

    .../puree (1x) and lemon/lime juice (1x) were used to modify the tolerance values. iii. Cancer. Based on the... the tolerance necessitate a higher value. Additionally, Codex has an established MRL on grape at 3 ppm...; Pesticide Tolerances AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: This...

  19. 15 CFR 750.11 - Shipping tolerances.

    Science.gov (United States)

    2010-01-01

    ... in the ECCN applicable to your item reads “ $ value” or “in $ value”, there is no shipping tolerance... is no shipping tolerance with respect to the number of units. However, the value of all of your... shipping tolerance on this license because the items are controlled by an ECCN where “$ value” is the...

  20. 78 FR 18511 - Thiamethoxam; Pesticide Tolerances

    Science.gov (United States)

    2013-03-27

    ... Health Risk Assessment of New Uses on Strawberry, Pistachio, and Citrus; New Tolerance for Tea; and... Uses on Strawberry, Pistachio, and Citrus; New Tolerance for Tea; and Revised PHI and Tolerance for... ``Clothianidin--Aggregate Human Health Risk Assessment of New Uses on Strawberry, Pistachio, and Citrus; New...

  1. 77 FR 28493 - Propylene Oxide; Tolerance Actions

    Science.gov (United States)

    2012-05-15

    .... SUMMARY: EPA is establishing the tree nut crop group tolerance and separate tolerances on pistachio and...; nut, tree, group 14; and pistachio; and in 40 CFR 180.491(a)(2) tolerances for propylene chlorohydrin at 10.0 ppm on nut, pine; nut, tree, group 14; and pistachio. Also, in accordance with current Agency...

  2. 75 FR 26673 - Clethodim; Pesticide Tolerances

    Science.gov (United States)

    2010-05-12

    ... regulation establishes tolerances for residues of clethodim in or on the raw agricultural commodity artichoke... clethodim, in or on the raw agricultural commodity artichoke, globe at 1.3 parts per million (ppm... bushberry subgroup 13-07B tolerance from 3.0 ppm to 0.20 ppm and the globe artichoke tolerance from 1.3 ppm...

  3. Selection and characterisation of high ethanol tolerant ...

    African Journals Online (AJOL)

    15% ethanol tolerance. High level ethanol tolerant Saccharomyces yeast, Orc 6, was investigated for its potential application in ethanologenic fermentations. Data presented in this study revealed that Orc 6 yeast isolate tolerated osmotic stress above 12% (w/v) sorbitol and 15% (w/v) sucrose equivalent of osmotic pressure ...

  4. Zero Tolerance: Advantages and Disadvantages. Research Brief

    Science.gov (United States)

    Walker, Karen

    2009-01-01

    What are the positives and negatives of zero tolerance? What should be considered when examining a school's program? Although there are no definitive definitions of zero tolerance, two commonly used ones are as follows: "Zero tolerance means that a school will automatically and severely punish a student for a variety of infractions" (American Bar…

  5. Four Saccharomyces species differ in their tolerance to various stresses though they have similar basic physiological parameters

    Czech Academy of Sciences Publication Activity Database

    Zemančíková, Jana; Kodedová, Marie; Papoušková, Klára; Sychrová, Hana

    2018-01-01

    Roč. 63, č. 2 (2018), s. 217-227 ISSN 0015-5632 R&D Projects: GA ČR(CZ) GA15-03708S Institutional support: RVO:67985823 Keywords : saccharomyces * stress tolerance * intracellular pH * membrane potential Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 1.521, year: 2016

  6. What is Fault Tolerant Control

    DEFF Research Database (Denmark)

    Blanke, Mogens; Frei, C. W.; Kraus, K.

    2000-01-01

    Faults in automated processes will often cause undesired reactions and shut-down of a controlled plant, and the consequences could be damage to the plant, to personnel or the environment. Fault-tolerant control is the synonym for a set of recent techniques that were developed to increase plant...... availability and reduce the risk of safety hazards. Its aim is to prevent that simple faults develop into serious failure. Fault-tolerant control merges several disciplines to achieve this goal, including on-line fault diagnosis, automatic condition assessment and calculation of remedial actions when a fault...... is detected. The envelope of the possible remedial actions is wide. This paper introduces tools to analyze and explore structure and other fundamental properties of an automated system such that any redundancy in the process can be fully utilized to enhance safety and a availability....

  7. Human tolerance to space flight

    Science.gov (United States)

    Huntoon, C. L.

    1989-01-01

    Medical studies of astronauts and cosmonauts before, during, and after space missions have identified several effects of weightlessness and other factors that influence the ability of humans to tolerate space flight. Weightlessness effects include space motion sickness, cardiovascular abnormalities, reduction in immune system function, loss of red blood cells, loss of bone mass, and muscle atrophy. Extravehicular activity (EVA) increases the likelihood that decompression sickness may occur. Radiation also gives reason for concern about health of crewmembers, and psychological factors are important on long-term flights. Countermeasures that have been used include sensory preadaptation, prebreathing and use of various air mixtures for EVA, loading with water and electrolytes, exercise, use of pharmacological agents and special diets, and psychological support. It appears that humans can tolerate and recover satisfactorily from at least one year of space flight, but a number of conditions must be further ameliorated before long-duration missions can be considered routine.

  8. Fault Tolerant External Memory Algorithms

    DEFF Research Database (Denmark)

    Jørgensen, Allan Grønlund; Brodal, Gerth Stølting; Mølhave, Thomas

    2009-01-01

    Algorithms dealing with massive data sets are usually designed for I/O-efficiency, often captured by the I/O model by Aggarwal and Vitter. Another aspect of dealing with massive data is how to deal with memory faults, e.g. captured by the adversary based faulty memory RAM by Finocchi and Italiano....... However, current fault tolerant algorithms do not scale beyond the internal memory. In this paper we investigate for the first time the connection between I/O-efficiency in the I/O model and fault tolerance in the faulty memory RAM, and we assume that both memory and disk are unreliable. We show a lower...... bound on the number of I/Os required for any deterministic dictionary that is resilient to memory faults. We design a static and a dynamic deterministic dictionary with optimal query performance as well as an optimal sorting algorithm and an optimal priority queue. Finally, we consider scenarios where...

  9. Copper tolerance of Trichoderma species

    Directory of Open Access Journals (Sweden)

    Jovičić-Petrović Jelena

    2014-01-01

    Full Text Available Some Trichoderma strains can persist in ecosystems with high concentrations of heavy metals. The aim of this research was to examine the variability of Trichoderma strains isolated from different ecosystems, based on their morphological properties and restriction analysis of ITS fragments. The fungal growth was tested on potato dextrose agar, amended with Cu(II concentrations ranging from 0.25 to 10 mmol/l, in order to identify copper-resistant strains. The results indicate that some isolated strains of Trichoderma sp. show tolerance to higher copper concentrations. Further research to examine the ability of copper bioaccumulation by tolerant Trichoderma strains is needed. [Projekat Ministarstva nauke Republike Srbije, br. TR 31080 i br. III 43010

  10. A damage-tolerant glass.

    Science.gov (United States)

    Demetriou, Marios D; Launey, Maximilien E; Garrett, Glenn; Schramm, Joseph P; Hofmann, Douglas C; Johnson, William L; Ritchie, Robert O

    2011-02-01

    Owing to a lack of microstructure, glassy materials are inherently strong but brittle, and often demonstrate extreme sensitivity to flaws. Accordingly, their macroscopic failure is often not initiated by plastic yielding, and almost always terminated by brittle fracture. Unlike conventional brittle glasses, metallic glasses are generally capable of limited plastic yielding by shear-band sliding in the presence of a flaw, and thus exhibit toughness-strength relationships that lie between those of brittle ceramics and marginally tough metals. Here, a bulk glassy palladium alloy is introduced, demonstrating an unusual capacity for shielding an opening crack accommodated by an extensive shear-band sliding process, which promotes a fracture toughness comparable to those of the toughest materials known. This result demonstrates that the combination of toughness and strength (that is, damage tolerance) accessible to amorphous materials extends beyond the benchmark ranges established by the toughest and strongest materials known, thereby pushing the envelope of damage tolerance accessible to a structural metal.

  11. OXYGEN TRANSPORT CERAMIC MEMBRANES

    International Nuclear Information System (INIS)

    Dr. Sukumar Bandopadhyay; Dr. Nagendra Nagabhushana

    2001-01-01

    Conversion of natural gas to liquid fuels and chemicals is a major goal for the Nation as it enters the 21st Century. Technically robust and economically viable processes are needed to capture the value of the vast reserves of natural gas on Alaska's North Slope, and wean the Nation from dependence on foreign petroleum sources. Technologies that are emerging to fulfill this need are all based syngas as an intermediate. Syngas (a mixture of hydrogen and carbon monoxide) is a fundamental building block from which chemicals and fuels can be derived. Lower cost syngas translates directly into more cost-competitive fuels and chemicals. The currently practiced commercial technology for making syngas is either steam methane reforming (SMR) or a two-step process involving cryogenic oxygen separation followed by natural gas partial oxidation (POX). These high-energy, capital-intensive processes do not always produce syngas at a cost that makes its derivatives competitive with current petroleum-based fuels and chemicals. This project has the following 6 main tasks: Task 1--Design, fabricate and evaluate ceramic to metal seals based on graded ceramic powder/metal braze joints. Task 2--Evaluate the effect of defect configuration on ceramic membrane conductivity and long term chemical and structural stability. Task 3--Determine materials mechanical properties under conditions of high temperatures and reactive atmospheres. Task 4--Evaluate phase stability and thermal expansion of candidate perovskite membranes and develop techniques to support these materials on porous metal structures. Task 5--Assess the microstructure of membrane materials to evaluate the effects of vacancy-impurity association, defect clusters, and vacancy-dopant association on the membrane performance and stability. Task 6--Measure kinetics of oxygen uptake and transport in ceramic membrane materials under commercially relevant conditions using isotope labeling techniques

  12. Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity.

    Science.gov (United States)

    Min, Y; Lowy, C; Islam, S; Khan, F S; Swaminathan, R

    2011-06-01

    Plasma leptin and adiponectin, and membrane phospholipid fatty acid composition are implicated into the mechanism of insulin resistance but no clear pattern has emerged. Hence, this study examined these variables in subjects presenting to the diabetic clinic for a diagnostic glucose tolerance test. Body composition, glucose, glycated hemoglobin, insulin, leptin, adiponectin, and red cell and plasma phospholipid fatty acids were assessed from 42 normal and 28 impaired glucose tolerant subjects. Insulin sensitivity was determined by homeostatic model assessment. The plasma phosphatidylcholine fatty acid composition of the impaired glucose tolerant subjects was similar to that of normal subjects. However, the impaired glucose tolerant subjects had significantly lower linoleic (Pphosphatidylcholine and phosphatidylethanolamine compared with the normal subjects. Moreover, red cell phosphatidylcholine docosahexaenoic acid correlated positively with adiponectin (r=0.290, Pinsulin (r=-0.335, Pinsulin resistance (r=-0.322, Pinsulin level whereas insulin was the only component that predicted the membrane fatty acids. We postulate that membrane phospholipids fatty acids have an indirect role in determining insulin concentration but insulin has a major role in determining membrane fatty acid composition.

  13. Salt stress in Plantago - The role of membranes, channels and pumps

    NARCIS (Netherlands)

    Prins, HBA

    1995-01-01

    In the present article the cellular mechanism of Na+ transport across the plasma membrane and tonoplast of root cells of Plantago media (salt sensitive) and Plantago maritima (salt tolerant) is discussed based on findings obtained mainly by patch clamp technique. It is conluded that the combination

  14. Metabolic dysfunction and unabated respiration precede the loss of membrane integrity during dehydration of germinating radicles

    NARCIS (Netherlands)

    Leprince, O.; Harren, F.J.M.; Alberda, M.; Hoekstra, F.A.

    2000-01-01

    This study shows that dehydration induces imbalanced metabolism before loss of membrane integrity in desiccation-sensitive germinated radicles. Using a photoacoustic detection system, responses of CO2 emission and fermentation to drying were analyzed non-invasively in desiccation-tolerant and

  15. Modelling Accident Tolerant Fuel Concepts

    Energy Technology Data Exchange (ETDEWEB)

    Hales, Jason Dean [Idaho National Laboratory; Gamble, Kyle Allan Lawrence [Idaho National Laboratory

    2016-05-01

    The catastrophic events that occurred at the Fukushima-Daiichi nuclear power plant in 2011 have led to widespread interest in research of alternative fuels and claddings that are proposed to be accident tolerant. The United States Department of Energy (DOE) through its Nuclear Energy Advanced Modeling and Simulation (NEAMS) program has funded an Accident Tolerant Fuel (ATF) High Impact Problem (HIP). The ATF HIP is a three-year project to perform research on two accident tolerant concepts. The final outcome of the ATF HIP will be an in-depth report to the DOE Advanced Fuels Campaign (AFC) giving a recommendation on whether either of the two concepts should be included in their lead test assembly scheduled for placement into a commercial reactor in 2022. The two ATF concepts under investigation in the HIP are uranium silicide fuel and iron-chromium-aluminum (FeCrAl) alloy cladding. Utilizing the expertise of three national laboratory participants (Idaho National Laboratory, Los Alamos National Laboratory, and Argonne National Laboratory), a comprehensive multiscale approach to modeling is being used that includes atomistic modeling, molecular dynamics, rate theory, phase-field, and fuel performance simulations. Model development and fuel performance analysis are critical since a full suite of experimental studies will not be complete before AFC must prioritize concepts for focused development. In this paper, we present simulations of the two proposed accident tolerance fuel systems: U3Si2 fuel with Zircaloy-4 cladding, and UO2 fuel with FeCrAl cladding. Sensitivity analyses are completed using Sandia National Laboratories’ Dakota software to determine which input parameters (e.g., fuel specific heat) have the greatest influence on the output metrics of interest (e.g., fuel centerline temperature). We also outline the multiscale modelling approach being employed. Considerable additional work is required prior to preparing the recommendation report for the Advanced

  16. Historical overview of immunological tolerance.

    Science.gov (United States)

    Schwartz, Ronald H

    2012-04-01

    A fundamental property of the immune system is its ability to mediate self-defense with a minimal amount of collateral damage to the host. The system uses several different mechanisms to achieve this goal, which is collectively referred to as the "process of immunological tolerance." This article provides an introductory historical overview to these various mechanisms, which are discussed in greater detail throughout this collection, and then briefly describes what happens when this process fails, a state referred to as "autoimmunity."

  17. SALT TOLERANCE OF CROP PLANTS

    OpenAIRE

    Hamdia, M. A; Shaddad, M. A. K.

    2010-01-01

    Several environmental factors adversely affect plant growth and development and final yield performance of a crop. Drought, salinity, nutrient imbalances (including mineral toxicities and deficiencies) and extremes of temperature are among the major environmental constraints to crop productivity worldwide. Development of crop plants with stress tolerance, however, requires, among others, knowledge of the physiological mechanisms and genetic controls of the contributing traits at different pla...

  18. Fault Tolerant Wind Farm Control

    DEFF Research Database (Denmark)

    Odgaard, Peter Fogh; Stoustrup, Jakob

    2013-01-01

    In the recent years the wind turbine industry has focused on optimizing the cost of energy. One of the important factors in this is to increase reliability of the wind turbines. Advanced fault detection, isolation and accommodation are important tools in this process. Clearly most faults are deal...... scenarios. This benchmark model is used in an international competition dealing with Wind Farm fault detection and isolation and fault tolerant control....

  19. Membrane distillation for milk concentration

    NARCIS (Netherlands)

    Moejes, S.N.; Romero Guzman, Maria; Hanemaaijer, J.H.; Barrera, K.H.; Feenstra, L.; Boxtel, van A.J.B.

    2015-01-01

    Membrane distillation is an emerging technology to concentrate liquid products while producing high quality water as permeate. Application for desalination has been studied extensively the past years, but membrane distillation has also potential to produce concentrated food products like

  20. Filtration characteristics in membrane bioreactors

    NARCIS (Netherlands)

    Evenblij, H.

    2006-01-01

    Causes of and remedies for membrane fouling in Membrane Bioreactors for wastewater treatment are only poorly understood and described in scientific literature. A Filtration Characterisation Installation and a measurement protocol were developed with the aim of a) unequivocally determination and

  1. From shell to membrane theory

    International Nuclear Information System (INIS)

    Destuynder, P.

    1981-02-01

    A new formulation of the membrane theory is presented in this paper. The assumptions which allow the Budiansky-Sanders' model or the membrane theory to be deduced from the three-dimensional case are pointed out [fr

  2. SALT TOLERANCE OF CROP PLANTS

    Directory of Open Access Journals (Sweden)

    Hamdia, M. A

    2010-09-01

    Full Text Available Several environmental factors adversely affect plant growth and development and final yield performance of a crop. Drought, salinity, nutrient imbalances (including mineral toxicities and deficiencies and extremes of temperature are among the major environmental constraints to crop productivity worldwide. Development of crop plants with stress tolerance, however, requires, among others, knowledge of the physiological mechanisms and genetic controls of the contributing traits at different plant developmental stages. In the past 2 decades, biotechnology research has provided considerable insights into the mechanism of biotic stress tolerance in plants at the molecular level. Furthermore, different abiotic stress factors may provoke osmotic stress, oxidative stress and protein denaturation in plants, which lead to similar cellular adaptive responses such as accumulation of compatible solutes, induction of stress proteins, and acceleration of reactive oxygen species scavenging systems. Recently, the authores try to improve plant tolerance to salinity injury through either chemical treatments (plant hormones, minerals, amino acids, quaternary ammonium compounds, polyamines and vitamins or biofertilizers treatments (Asymbiotic nitrogen-fixing bacteria, symbiotic nitrogen-fixing bacteria and mycorrhiza or enhanced a process used naturally by plants to minimise the movement of Na+ to the shoot, using genetic modification to amplify the process, helping plants to do what they already do - but to do it much better."

  3. Tolerance of Snakes to Hypergravity

    Science.gov (United States)

    Lillywhite, H. B.; Ballard, R. E.; Hargens, A. R.

    1994-01-01

    Sensitivity of carotid blood flow to +Gz (head-to-tail) acceleration was studied in six species of snakes hypothesized to show varied adaptive cardiovascular responses to gravity. Blood flow in the proximal carotid artery was measured in 15 snakes before, during and following stepwise increments of +0.25Gz force produced on a 2.4 m diameter centrifuge. During centrifugation each snake was confined to a straight position within an individually- fitted acrylic tube with the head facing the center of rotation. We measured the centrifugal force at the tail of the snake in order to quantify the maximum intensity of force gradient promoting antero-posterior pooling of blood. Tolerance to increased gravity was quantified as the acceleration force at which carotid blood flow ceased. This parameter varied according to the gravitational adaptation of species defined by their ecology and behavior. At the extremes, carotid blood flow decreased in response to increasing gravity and approached zero near +1Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2Gz. Surprisingly, tolerant (arboreal) species withstood hypergravic forces of +2 to +3 G. for periods up to 1 h without cessation of carotid blood flow or apparent loss of consciousness. Data suggest that relatively tight skin of the tolerant species provides a natural antigravity suit which is of prime importance in counteracting Gz stress on blood circulation.

  4. Fundamentals of membrane bioreactors materials, systems and membrane fouling

    CERN Document Server

    Ladewig, Bradley

    2017-01-01

    This book provides a critical, carefully researched, up-to-date summary of membranes for membrane bioreactors. It presents a comprehensive and self-contained outline of the fundamentals of membrane bioreactors, especially their relevance as an advanced water treatment technology. This outline helps to bring the technology to the readers’ attention, and positions the critical topic of membrane fouling as one of the key impediments to its more widescale adoption. The target readership includes researchers and industrial practitioners with an interest in membrane bioreactors.

  5. Cheap Thin Film Oxygen Membranes

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention provides a membrane, comprising a porous support layer a gas tight electronically and ionically conducting membrane layer and a catalyst layer, characterized in that the electronically and ionically conducting membrane layer is formed from a material having a crystallite...... structure with a crystal size of about 1 to 100 nm, and a method for producing same....

  6. Mesoporous and microporous titania membranes

    NARCIS (Netherlands)

    Sekulic, J.

    2004-01-01

    The research described in this thesis deals with the synthesis and properties of ceramic oxide membrane materials. Since most of the currently available inorganic membranes with required separation properties have limited reliability and long-term stability, membranes made of new oxide materials

  7. Membranes suited for immobilizing biomolecules

    NARCIS (Netherlands)

    2009-01-01

    The present invention relates to flow-through membranes suitable for the immobilization of biomols., methods for the prepn. of such membranes and the use of such membranes for the immobilization of biomols. and subsequent detection of immobilized biomols. The invention concerns a flow-through

  8. Fault-tolerant architecture: Evaluation methodology

    International Nuclear Information System (INIS)

    Battle, R.E.; Kisner, R.A.

    1992-08-01

    The design and reliability of four fault-tolerant architectures that may be used in nuclear power plant control systems were evaluated. Two architectures are variations of triple-modular-redundant (TMR) systems, and two are variations of dual redundant systems. The evaluation includes a review of methods of implementing fault-tolerant control, the importance of automatic recovery from failures, methods of self-testing diagnostics, block diagrams of typical fault-tolerant controllers, review of fault-tolerant controllers operating in nuclear power plants, and fault tree reliability analyses of fault-tolerant systems

  9. Thermal Adaptation of the Archaeal and Bacterial Lipid Membranes

    Science.gov (United States)

    Koga, Yosuke

    2012-01-01

    The physiological characteristics that distinguish archaeal and bacterial lipids, as well as those that define thermophilic lipids, are discussed from three points of view that (1) the role of the chemical stability of lipids in the heat tolerance of thermophilic organisms: (2) the relevance of the increase in the proportion of certain lipids as the growth temperature increases: (3) the lipid bilayer membrane properties that enable membranes to function at high temperatures. It is concluded that no single, chemically stable lipid by itself was responsible for the adaptation of surviving at high temperatures. Lipid membranes that function effectively require the two properties of a high permeability barrier and a liquid crystalline state. Archaeal membranes realize these two properties throughout the whole biological temperature range by means of their isoprenoid chains. Bacterial membranes meet these requirements only at or just above the phase-transition temperature, and therefore their fatty acid composition must be elaborately regulated. A recent hypothesis sketched a scenario of the evolution of lipids in which the “lipid divide” emerged concomitantly with the differentiation of archaea and bacteria. The two modes of thermal adaptation were established concurrently with the “lipid divide.” PMID:22927779

  10. Thermal Adaptation of the Archaeal and Bacterial Lipid Membranes

    Directory of Open Access Journals (Sweden)

    Yosuke Koga

    2012-01-01

    Full Text Available The physiological characteristics that distinguish archaeal and bacterial lipids, as well as those that define thermophilic lipids, are discussed from three points of view that (1 the role of the chemical stability of lipids in the heat tolerance of thermophilic organisms: (2 the relevance of the increase in the proportion of certain lipids as the growth temperature increases: (3 the lipid bilayer membrane properties that enable membranes to function at high temperatures. It is concluded that no single, chemically stable lipid by itself was responsible for the adaptation of surviving at high temperatures. Lipid membranes that function effectively require the two properties of a high permeability barrier and a liquid crystalline state. Archaeal membranes realize these two properties throughout the whole biological temperature range by means of their isoprenoid chains. Bacterial membranes meet these requirements only at or just above the phase-transition temperature, and therefore their fatty acid composition must be elaborately regulated. A recent hypothesis sketched a scenario of the evolution of lipids in which the “lipid divide” emerged concomitantly with the differentiation of archaea and bacteria. The two modes of thermal adaptation were established concurrently with the “lipid divide.”

  11. Overexpression of a Panax ginseng tonoplast aquaporin alters salt tolerance, drought tolerance and cold acclimation ability in transgenic Arabidopsis plants.

    Science.gov (United States)

    Peng, Yanhui; Lin, Wuling; Cai, Weiming; Arora, Rajeev

    2007-08-01

    Water movement across cellular membranes is regulated largely by a family of water channel proteins called aquaporins (AQPs). Since several abiotic stresses such as, drought, salinity and freezing, manifest themselves via altering water status of plant cells and are linked by the fact that they all result in cellular dehydration, we overexpressed an AQP (tonoplast intrinsic protein) from Panax ginseng, PgTIP1, in transgenic Arabidopsis thaliana plants to test its role in plant's response to drought, salinity and cold acclimation (induced freezing tolerance). Under favorable conditions, PgTIP1 overexpression significantly increased plant growth as determined by the biomass production, and leaf and root morphology. PgTIP1 overexpression had beneficial effect on salt-stress tolerance as indicated by superior growth status and seed germination of transgenic plants under salt stress; shoots of salt-stressed transgenic plants also accumulated greater amounts of Na(+) compared to wild-type plants. Whereas PgTIP1 overexpression diminished the water-deficit tolerance of plants grown in shallow (10 cm deep) pots, the transgenic plants were significantly more tolerant to water stress when grown in 45 cm deep pots. The rationale for this contrasting response, apparently, comes from the differences in the root morphology and leaf water channel activity (speed of dehydration/rehydration) between the transgenic and wild-type plants. Plants overexpressed with PgTIP1 exhibited lower (relative to wild-type control) cold acclimation ability; however, this response was independent of cold-regulated gene expression. Our results demonstrate a significant function of PgTIP1 in growth and development of plant cells, and suggest that the water movement across tonoplast (via AQP) represents a rate-limiting factor for plant vigor under favorable growth conditions and also significantly affect responses of plant to drought, salt and cold stresses.

  12. Impact of sludge flocs on membrane fouling in membrane bioreactors

    DEFF Research Database (Denmark)

    Christensen, Morten Lykkegaard; Niessen, Wolfgang; Jørgensen, Mads Koustrup

    Membrane bioreactors (MBR) are widely used for wastewater treatment, but membrane fouling reduces membrane performance and thereby increases the cost for membranes and fouling control. Large variation in filtration properties measured as flux decline was observed for the different types of sludges....... Further, the flux could partly be reestablished after the relaxation period depending on the sludge composition. The results underline that sludge properties are important for membrane fouling and that control of floc properties, as determined by the composition of the microbial communities...... and the physico-chemical properties, is an efficient method to reduce membrane fouling in the MBR. High concentration of suspended extracellular substances (EPS) and small particles (up to 10 µm) resulted in pronounced fouling propensity. The membrane fouling resistance was reduced at high concentration...

  13. IRON-TOLERANT CYANOBACTERIA: IMPLICATIONS FOR ASTROBIOLOGY

    Science.gov (United States)

    Brown, Igor I.; Allen, Carlton C.; Mummey, Daniel L.; Sarkisova, Svetlana A.; McKay, David S.

    2006-01-01

    The review is dedicated to the new group of extremophiles - iron tolerant cyanobacteria. The authors have analyzed earlier published articles about the ecology of iron tolerant cyanobacteria and their diversity. It was concluded that contemporary iron depositing hot springs might be considered as relative analogs of Precambrian environment. The authors have concluded that the diversity of iron-tolerant cyanobacteria is understudied. The authors also analyzed published data about the physiological peculiarities of iron tolerant cyanobacteria. They made the conclusion that iron tolerant cyanobacteria may oxidize reduced iron through the photosystem of cyanobacteria. The involvement of both Reaction Centers 1 and 2 is also discussed. The conclusion that iron tolerant protocyanobacteria could be involved in banded iron formations generation is also proposed. The possible mechanism of the transition from an oxygenic photosynthesis to an oxygenic one is also discussed. In the final part of the review the authors consider the possible implications of iron tolerant cyanobacteria for astrobiology.

  14. Pulse radiolysis studies of model membranes

    International Nuclear Information System (INIS)

    Heijman, M.G.J.

    1984-01-01

    In this thesis the influence of the structure of membranes on the processes in cell membranes were examined. Different models of the membranes were evaluated. Pulse radiolysis was used as the technique to examine the membranes. (R.B.)

  15. Regulation of galactolipid biosynthesis by overexpression of the rice MGD gene contributes to enhanced aluminum tolerance in tobacco

    Directory of Open Access Journals (Sweden)

    Meijuan eZhang

    2016-03-01

    Full Text Available Membrane lipid alterations affect Al tolerance in plants, but little is known about the regulation of membrane lipid metabolism in response to Al stress. Transgenic tobacco (Nicotiana tabacum overexpressing rice monogalactosyldiacylglycerol (MGDG synthase (OsMGD gene and wild-type tobacco plants were exposed to AlCl3, and the impact of Al toxicity on root growth, Al accumulation, plasma membrane integrity, lipid peroxidation and membrane lipid composition were investigated. Compared with the wild type, the transgenic plants exhibited rapid regrowth of roots after removal of Al and less damage to membrane integrity and lipid peroxidation under Al stress, meanwhile, the Al accumulation showed no difference between wild-type and transgenic plants. Lipid analysis showed that Al treatment dramatically decreased the content of MGDG and the ratio of MGDG to digalactosyldiacylglycerol (DGDG in wild-type plants, while it was unchanged in transgenic plants. The stable of MGDG level and the ratio of MGDG/DGDG contribute to maintain the membrane stability and permeability. Moreover, Al caused a significant increase in phospholipids in wild-type plants, resulting in a high proportion of phospholipids and low proportion of galactolipids, but these proportions were unaffected in transgenic plants. The high proportion of phospholipids could contribute to a higher rate of Al3+ binding in the membrane and thereby leads to more membrane perturbation and damage. These results show that the regulation of galactolipid biosynthesis could play an important role in maintaining membrane structure and function under Al stress.

  16. Root plasma membrane transporters controlling K+/Na+ homeostasis in salt-stressed bBarley1[C][W

    DEFF Research Database (Denmark)

    Chen, Zhonghua; Pottosin, Igor I.; Cuin, Tracey A.

    2007-01-01

    are well combined to withstand saline conditions. These mechanisms include: (1) better control of membrane voltage so retaining a more negative membrane potential; (2) intrinsically higher H1 pump activity; (3) better ability of root cells to pump Na1 from the cytosol to the external medium; and (4) higher......Plant salinity tolerance is a polygenic trait with contributions from genetic, developmental, and physiological interactions, in addition to interactions between the plant and its environment. In this study, we show that in salt-tolerant genotypes of barley (Hordeum vulgare), multiple mechanisms...... of the cytosolic K1-to-Na1 ratio being a key determinant of plant salinity tolerance, and suggest multiple pathways of controlling that important feature in salt-tolerant plants....

  17. Acid-doped Polybenzimidazole Membranes as Electrolyte for Fuel Cells Operating Above 100°C

    DEFF Research Database (Denmark)

    Qingfeng, Li; Jensen, Jens Oluf; He, Ronhuan

    2003-01-01

    The technical achievement and challenges for the PEMFC technology based on perfluorosulfonic acid (PFSA) polymer membranes (e.g. Nafion®) are briefly discussed. The newest development in the field is alternative polymer electrolytes for operation above 100°C. As one of the successful approaches...... to high operational temperatures, the development and evaluation of acid doped PBI membranes are reviewed, covering polymer synthesis, membrane casting, acid doping, physiochemical characterization and fuel cell tests. A high temperature PEMFC system operational at up to 200°C is demonstrated with no gas...... humidification and high CO-tolerance up to 10 vol%. This high CO tolerance allows for a direct use of reformed hydrogen without further CO removal, which opens the possibility for an integrated reformer-fuel cell system. The content of this review is to a large extent based on research performed by the authors...

  18. The genetic characteristics in cytology and plant physiology of two wheat (Triticum aestivum) near isogenic lines with different freezing tolerances.

    Science.gov (United States)

    Wang, Wenqiang; Hao, Qunqun; Wang, Wenlong; Li, Qinxue; Wang, Wei

    2017-11-01

    Freezing tolerance in taft plants relied more upon an ABA-independent- than an ABA-dependent antifreeze signaling pathway. Two wheat (Triticum aestivum) near isogenic lines (NIL) named tafs (freezing sensitivity) and taft (freezing tolerance) were isolated in the laboratory and their various cytological and physiological characteristics under freezing conditions were studied. Proplastid, cell membrane, and mitochondrial ultrastructure were less damaged by freezing treatment in taft than tafs plants. Chlorophyll, ATP, and thylakoid membrane protein contents were significantly higher, but malondialdehyde content was significantly lower in taft than tafs plants under freezing condition. Antioxidant capacity, as indicated by reactive oxygen species accumulation and antioxidant enzyme activity, and the relative gene expression were significantly greater in taft than tafs plants. Soluble sugars and abscisic acid (ABA) contents were significantly higher in taft plants than in tafs plants under both normal and freezing conditions. The upregulated expression levels of certain freezing tolerance-related genes were greater in taft than tafs plants under freezing treatment. The addition of sodium tungstate, an ABA synthesis inhibitor, led to only partial freezing tolerance inhibition in taft plants and the down-regulated expression of some ABA-dependent genes. Thus, both ABA-dependent and ABA-independent signaling pathways are involved in the freezing tolerance of taft plants. At the same time, freezing tolerance in taft plants relied more upon an ABA-independent- than an ABA-dependent antifreeze signaling pathway.

  19. Membrane microparticles and diseases.

    Science.gov (United States)

    Wu, Z-H; Ji, C-L; Li, H; Qiu, G-X; Gao, C-J; Weng, X-S

    2013-09-01

    Membrane microparticles (MPs) are plasma membrane-derived vesicles shed by various types of activated or apoptotic cells including platelets, monocytes, endothelial cells, red blood cells, and granulocytes. MPs are being increasingly recognized as important regulators of cell-to-cell interactions. Recent evidences suggest they may play important functions not only in homeostasis but also in the pathogenesis of a number of diseases such as vascular diseases, cancer, infectious diseases and diabetes mellitus. Accordingly, inhibiting the production of MPs may serve as a novel therapeutic strategy for these diseases. Here we review recent advances on the mechanism underlying the generation of MPs and the role of MPs in vascular diseases, cancer, diabetes, inflammation, and pathogen infection.

  20. Physics of smectic membranes

    Science.gov (United States)

    Pieranski, P.; Beliard, L.; Tournellec, J.-Ph.; Leoncini, X.; Furtlehner, C.; Dumoulin, H.; Riou, E.; Jouvin, B.; Fénerol, J.-P.; Palaric, Ph.; Heuving, J.; Cartier, B.; Kraus, I.

    1993-03-01

    Due to their layered structure, smectic liquid crystals can form membranes, similar to soap bubbles, that can be spanned on frames. Such smectic membranes have been used extensively as samples in many structural X-ray studies of smectic liquid crystals. In this context they have been considered as very convenient and highly perfect samples but little attention has been paid to the reasons for their existence and to the process of their formation. Our aim here is to address a first list of questions, which are the most urgent to answer. We will also describe experiments and models that have been conceived especially in order to understand the physics of these fascinating systems.

  1. Inefficacy of osmotic backwash induced by sodium chloride salt solution in controlling SWRO membrane fouling

    Science.gov (United States)

    Farooque, A. Mohammed; Al-Jeshi, Subhi; Saeed, Mohamed O.; Alreweli, Ali

    2014-12-01

    isolated from membranes tolerated exposure to high salt concentrations at pH range of 7-8. In addition, the overall findings of the study indicate that SWRO membranes can be operated in Gulf seawater at a recovery of 30 % without using any chemicals, such as coagulant, disinfectant and antiscalant, for an acceptable period of time without performing membrane cleaning. This is highly likely, if media filters are used in the pretreatment and SWRO membranes are operated at normal flux and recovery ratio.

  2. Radiation effects on cell membranes

    International Nuclear Information System (INIS)

    Koeteles, G.J.

    1982-01-01

    The recent developments in the field of membrane biology of eukaryotic cells result in revival of relevant radiobiological studies. The spatial relations and chemical nature of membrane components provide rather sensitive targets. Experimental data are presented concerning the effects of relatively low doses of X-irradiation and low concentration of tritiated water (HTO) on various receptor functions - concanavalin A, cationized ferritin, poliovirus - of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the multifold roles of radiationinduced membrane phenomena on the development and regeneration of radiation injuries. (orig.)

  3. Radiation effects on cell membranes

    Energy Technology Data Exchange (ETDEWEB)

    Koeteles, G.J.

    1982-11-01

    The recent developments in the field of membrane biology of eukaryotic cells result in revival of relevant radiobiological studies. The spatial relations and chemical nature of membrane components provide rather sensitive targets. Experimental data are presented concerning the effects of relatively low doses of X-irradiation and low concentration of tritiated water (HTO) on various receptor functions - concanavalin A, cationized ferritin, poliovirus - of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the multifold roles of radiationinduced membrane phenomena on the development and regeneration of radiation injuries.

  4. The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.

    Science.gov (United States)

    Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L

    2013-06-01

    The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.

  5. Choroidal neovascular membrane

    OpenAIRE

    Bhatt Nitul; Diamond James; Jalali Subhadra; Das Taraprasad

    1998-01-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose o...

  6. Generalized chiral membrane dynamics

    International Nuclear Information System (INIS)

    Cordero, R.; Rojas, E.

    2003-01-01

    We develop the dynamics of the chiral superconducting membranes (with null current) in an alternative geometrical approach. Besides of this, we show the equivalence of the resulting description with the one known Dirac-Nambu-Goto (DNG) case. Integrability for chiral string model is obtained using a proposed light-cone gauge. In a similar way, domain walls are integrated by means of a simple Ansatz. (Author)

  7. Membrane Stability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, D.T. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1997-09-30

    The Electrosynthesis Co. Inc. (ESC) was contracted by the Westinghouse Savannah River Company to investigate the long term performance and durability of cell components (anode, membrane, cathode) in an electrochemical caustic recovery process using a simulated SRC liquid waste as anolyte solution. This report details the results of two long-term studies conducted using an ICI FM01 flow cell. This cell is designed and has previously been demonstrated to scale up directly into the commercial scale ICI FM21 cell.

  8. Membrane technology applications

    Energy Technology Data Exchange (ETDEWEB)

    Golomb, A

    1990-10-01

    Due to a continuing emphasis on increasing the efficiency of utilizing the Province's electrical energy system, a Membrane Testing and Development Facility (MTDF) has been established at Ontario Hydro Research Division. The MTDF comprises bench-scale and pilot-scale reverse osmosis (RO) and ultrafiltration (UF) systems. RO and UF are membrane separation technologies which with microfiltration (MF) have found numerous industrial applications in wastewater treatment and/or byproduct recovery. Since no phase change is involved in RO and UF, they are more energy efficient separation processes than, say, evaporation or distillation. Initial tests have been carried out to demonstrate the capability of the newly-established MTDF. Bench- and pilot-scale RO treatment, at 4.1 MPa applied pressure, of a simulated nickel plating waste rinse stream was demonstrated. RO membrane rejection efficiencies for nickel were 99+% (in the bench scale test) and 99.9+% (on the pilot scale). Volume reduction factors of about 25 were attained, at purified water flux rates in the range 1 to 1.5 m{sup 3}/m{sup 2} per day. Good correlation was noted between bench-scale and pilot-scale RO test results. Pilot-scale UF of a simulated industrial cutting oil/water waste emulsion at 0.40 MPa gave 99+% oil rejection (pilot scale) at a flux rate of 0.7 m{sup 3}/m{sup 2} per day. A volume reduction of about 5.2 was attained. Overviews of opportunities for membrane separation technology applied to the metal cutting and surface finishing industries, and the food and beverage industry are given. Capabilities (and some present needs) of the MTDF are outlined, with recommendations. 17 refs., 10 figs., 7 tabs.

  9. Electrochemical polymer electrolyte membranes

    CERN Document Server

    Fang, Jianhua; Wilkinson, David P

    2015-01-01

    Electrochemical Polymer Electrolyte Membranes covers PEMs from fundamentals to applications, describing their structure, properties, characterization, synthesis, and use in electrochemical energy storage and solar energy conversion technologies. Featuring chapters authored by leading experts from academia and industry, this authoritative text: Discusses cutting-edge methodologies in PEM material selection and fabricationPoints out important challenges in developing PEMs and recommends mitigation strategies to improve PEM performanceAnalyzes the cur

  10. Neutrons and model membranes

    Science.gov (United States)

    Fragneto, G.

    2012-11-01

    Current research in membrane protein biophysics highlights the emerging role of lipids in shaping membrane protein function. Cells and organisms have developed sophisticated mechanisms for controlling the lipid composition and many diseases are related to the failure of these mechanisms. One of the recent advances in the field is the discovery of the existence of coexisting micro-domains within a single membrane, important for regulating some signaling pathways. Many important properties of these domains remain poorly characterized. The characterization and analysis of bio-interfaces represent a challenge. Performing measurements on these few nanometer thick, soft, visco-elastic and dynamic systems is close to the limits of the available tools and methods. Neutron scattering techniques including small angle scattering, diffraction, reflectometry as well as inelastic methods are rapidly developing for these studies and are attracting an increasing number of biologists and biophysicists at large facilities. This manuscript will review some recent progress in the field and provide perspectives for future developments. It aims at highlighting neutron reflectometry as a versatile method to tackle questions dealing with the understanding and function of biomembranes and their components. The other important scattering methods are only briefly introduced.

  11. Viral membrane fusion

    International Nuclear Information System (INIS)

    Harrison, Stephen C.

    2015-01-01

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  12. Novel Catalytic Membrane Reactors

    Energy Technology Data Exchange (ETDEWEB)

    Stuart Nemser, PhD

    2010-10-01

    There are many industrial catalytic organic reversible reactions with amines or alcohols that have water as one of the products. Many of these reactions are homogeneously catalyzed. In all cases removal of water facilitates the reaction and produces more of the desired chemical product. By shifting the reaction to right we produce more chemical product with little or no additional capital investment. Many of these reactions can also relate to bioprocesses. Given the large number of water-organic compound separations achievable and the ability of the Compact Membrane Systems, Inc. (CMS) perfluoro membranes to withstand these harsh operating conditions, this is an ideal demonstration system for the water-of-reaction removal using a membrane reactor. Enhanced reaction synthesis is consistent with the DOE objective to lower the energy intensity of U.S. industry 25% by 2017 in accord with the Energy Policy Act of 2005 and to improve the United States manufacturing competitiveness. The objective of this program is to develop the platform technology for enhancing homogeneous catalytic chemical syntheses.

  13. Quantum charged rigid membrane

    Energy Technology Data Exchange (ETDEWEB)

    Cordero, Ruben [Departamento de Fisica, Escuela Superior de Fisica y Matematicas del I.P.N., Unidad Adolfo Lopez Mateos, Edificio 9, 07738 Mexico, D.F. (Mexico); Molgado, Alberto [Unidad Academica de Fisica, Universidad Autonoma de Zacatecas, Zacatecas Zac. (Mexico); Rojas, Efrain, E-mail: cordero@esfm.ipn.mx, E-mail: amolgado@fisica.uaz.edu.mx, E-mail: efrojas@uv.mx [Departamento de Fisica, Facultad de Fisica e Inteligencia Artificial, Universidad Veracruzana, 91000 Xalapa, Veracruz (Mexico)

    2011-03-21

    The early Dirac proposal to model the electron as a charged membrane is reviewed. A rigidity term, instead of the natural membrane tension, involving linearly the extrinsic curvature of the worldvolume swept out by the membrane is considered in the action modeling the bubble in the presence of an electromagnetic field. We set up this model as a genuine second-order derivative theory by considering a non-trivial boundary term which plays a relevant part in our formulation. The Lagrangian in question is linear in the bubble acceleration and by means of the Ostrogradski-Hamiltonian approach, we observed that the theory comprises the management of both first- and second-class constraints. We thus show that our second-order approach is robust allowing for a proper quantization. We found an effective quantum potential which permits us to compute bounded states for the system. We comment on the possibility of describing brane world universes by invoking this kind of second-order correction terms.

  14. Quantum charged rigid membrane

    International Nuclear Information System (INIS)

    Cordero, Ruben; Molgado, Alberto; Rojas, Efrain

    2011-01-01

    The early Dirac proposal to model the electron as a charged membrane is reviewed. A rigidity term, instead of the natural membrane tension, involving linearly the extrinsic curvature of the worldvolume swept out by the membrane is considered in the action modeling the bubble in the presence of an electromagnetic field. We set up this model as a genuine second-order derivative theory by considering a non-trivial boundary term which plays a relevant part in our formulation. The Lagrangian in question is linear in the bubble acceleration and by means of the Ostrogradski-Hamiltonian approach, we observed that the theory comprises the management of both first- and second-class constraints. We thus show that our second-order approach is robust allowing for a proper quantization. We found an effective quantum potential which permits us to compute bounded states for the system. We comment on the possibility of describing brane world universes by invoking this kind of second-order correction terms.

  15. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  16. Screening of Pearl Millet F1 Hybrids for Heat Tolerance at Early Seedling Stage

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Yadav

    2014-01-01

    Full Text Available Ten pearl millet genotypes selected on the basis of response to supra-optimal temperature tolerance were crossed in a half-diallel mating system. The 45 F1 hybrids produced were tested along with parents for heat tolerance and related traits at seedling stage. Field screening and laboratory screening techniques were simultaneously used for the evaluation of F1 hybrids and their parents. Heat tolerance was measured as seedling thermotolerance index (STI and seed to seedling thermotolerance index (SSTI under field conditions, but membrane thermostability (MTS in the laboratory. The hybrid H77/29-2 × CVJ-2-5-3-1-3 showed highest STI value followed by H77/833-2 × 96AC-93. The genotype H77/833-2 × 96AC-93 had the highest worth for SSTI. These three indices were highly correlated among themselves. STI values were invariably high, whereas SSTI has lower values, as it also covers the effect of under soil mortality (USM. It was seen that the heat tolerance indices STI and SSTI were not showing any perceptible pooled correlation with developmental traits except germination and emergence rate. Based on our results, it could be suggested that membrane thermostability (MTS may be used for screening large number of genotypes. Field based indices STI and SSTI may be used for evaluation of hybrids and varieties before they are released.

  17. Parallel artificial liquid membrane extraction

    DEFF Research Database (Denmark)

    Gjelstad, Astrid; Rasmussen, Knut Einar; Parmer, Marthe Petrine

    2013-01-01

    This paper reports development of a new approach towards analytical liquid-liquid-liquid membrane extraction termed parallel artificial liquid membrane extraction. A donor plate and acceptor plate create a sandwich, in which each sample (human plasma) and acceptor solution is separated by an arti......This paper reports development of a new approach towards analytical liquid-liquid-liquid membrane extraction termed parallel artificial liquid membrane extraction. A donor plate and acceptor plate create a sandwich, in which each sample (human plasma) and acceptor solution is separated...... by an artificial liquid membrane. Parallel artificial liquid membrane extraction is a modification of hollow-fiber liquid-phase microextraction, where the hollow fibers are replaced by flat membranes in a 96-well plate format....

  18. Solid-state membrane module

    Science.gov (United States)

    Gordon, John Howard [Salt Lake City, UT; Taylor, Dale M [Murray, UT

    2011-06-07

    Solid-state membrane modules comprising at least one membrane unit, where the membrane unit has a dense mixed conducting oxide layer, and at least one conduit or manifold wherein the conduit or manifold comprises a dense layer and at least one of a porous layer and a slotted layer contiguous with the dense layer. The solid-state membrane modules may be used to carry out a variety of processes including the separating of any ionizable component from a feedstream wherein such ionizable component is capable of being transported through a dense mixed conducting oxide layer of the membrane units making up the membrane modules. For ease of construction, the membrane units may be planar.

  19. The failure-tolerant leader.

    Science.gov (United States)

    Farson, Richard; Keyes, Ralph

    2002-08-01

    "The fastest way to succeed," IBM's Thomas Watson, Sr., once said, "is to double your failure rate." In recent years, more and more executives have embraced Watson's point of view, coming to understand what innovators have always known: Failure is a prerequisite to invention. But while companies may grasp the value of making mistakes at the level of corporate practices, they have a harder time accepting the idea at the personal level. People are afraid to fail, and corporate culture reinforces that fear. In this article, psychologist and former Harvard Business School professor Richard Farson and coauthor Ralph Keyes discuss how companies can reduce the fear of miscues. What's crucial is the presence of failure-tolerant leaders--executives who, through their words and actions, help employees overcome their anxieties about making mistakes and, in the process, create a culture of intelligent risk-taking that leads to sustained innovation. Such leaders don't just accept productive failure, they promote it. Drawing from their research in business, politics, sports, and science, the authors identify common practices among failure-tolerant leaders. These leaders break down the social and bureaucratic barriers that separate them from their followers. They engage at a personal level with the people they lead. They avoid giving either praise or criticism, preferring to take a nonjudgmental, analytical posture as they interact with staff. They openly admit their own mistakes rather than trying to cover them up or shifting the blame. And they try to root out the destructive competitiveness built into most organizations. Above all else, failure-tolerant leaders push people to see beyond traditional definitions of success and failure. They know that as long as a person views failure as the opposite of success, rather than its complement, he or she will never be able to take the risks necessary for innovation.

  20. Flux Enhancement in Membrane Distillation Using Nanofiber Membranes

    Directory of Open Access Journals (Sweden)

    T. Jiříček

    2016-01-01

    Full Text Available Membrane distillation (MD is an emerging separation technology, whose largest application potential lies in the desalination of highly concentrated solutions, which are out of the scope of reverse osmosis. Despite many attractive features, this technology is still awaiting large industrial application. The main reason is the lack of commercially available membranes with fluxes comparable to reverse osmosis. MD is a thermal separation process driven by a partial vapour pressure difference. Flux, distillate purity, and thermal efficiency are always in conflict, all three being strictly connected with pore size, membrane hydrophobicity, and thickness. The world has not seen the ideal membrane yet, but nanofibers may offer a solution to these contradictory requirements. Membranes of electrospun PVDF were tested under various conditions on a direct contact (DCMD unit, in order to determine the optimum conditions for maximum flux. In addition, their performance was compared to commonly available PTFE, PE, and PES membranes. It was confirmed that thinner membranes have higher fluxes and a lower distillate purity and also higher energy losses via conduction across the membrane. As both mass and heat transfer are connected, it is best to develop new membranes with a target application in mind, for the specific membrane module and operational conditions.

  1. In vitro selection of mutants: Inducible gene regulation for salt tolerance

    International Nuclear Information System (INIS)

    Winicov, I.; Bastola, D.R.; Deutch, C.E.; Pethe, V.V.; Petrusa, L.

    2001-01-01

    Regulation of differentially expressed genes in plants may be involved in inducing tolerance to stress. Isogenic salt-sensitive and salt-tolerant alfalfa lines were investigated for molecular differences in their response to salt. The genes, which are differentially induced by salt in the salt-tolerant alfalfa cells and are also regulated by salt at the whole plant level, were cloned. Both transcriptional and post- transcriptional mechanisms influenced salt-induced product accumulation in the salt-tolerant alfalfa. The salt-tolerant plants doubled proline concentration rapidly in roots, while salt-sensitive plants showed a delayed response. To understand the regulatory system in the salt-tolerant alfalfa, two genes that are expressed in roots were studied. Alfin1 encodes a zinc-finger type putative DNA transcription factor conserved in alfalfa, rice and Arabidopsis, and MsPRP2 encodes a protein that serves as a cell wall- membrane linker in roots. Recombinant Alfin1 protein was selected, amplified, cloned and its consensus sequence was identified. The recombinant Alfin1 also bound specifically to fragments of the MsPRP2 promoter in vitro, containing the Alfin1 binding consensus sequence. The results show unambiguously binding specificity of Alfin1 DNA, supporting its role in gene regulation. Alfin1 function was tested in transformed alfalfa in vivo by over-expressing Alfin1 from 35S CaMV promoter. The transgenic plants appeared normal. However, plants harboring the anti-sense construct did not grow well in soil, indicating that Alfin1 expression was essential. Alfin1 over-expression in transgenic alfalfa led to enhanced levels of MsPRP2 transcript accumulation, demonstrating that Alfin1 functioned in vivo in gene regulation. Since MsPRP2 gene is also induced by salt, it is likely that Alfin1 is an important transcription factor for gene regulation in salt-tolerant alfalfa, and an excellent target for manipulation to improve salt tolerance. (author)

  2. Noise tolerant spatiotemporal chaos computing.

    Science.gov (United States)

    Kia, Behnam; Kia, Sarvenaz; Lindner, John F; Sinha, Sudeshna; Ditto, William L

    2014-12-01

    We introduce and design a noise tolerant chaos computing system based on a coupled map lattice (CML) and the noise reduction capabilities inherent in coupled dynamical systems. The resulting spatiotemporal chaos computing system is more robust to noise than a single map chaos computing system. In this CML based approach to computing, under the coupled dynamics, the local noise from different nodes of the lattice diffuses across the lattice, and it attenuates each other's effects, resulting in a system with less noise content and a more robust chaos computing architecture.

  3. Anhydrobiosis and Freezing-Tolerance

    DEFF Research Database (Denmark)

    McGill, Lorraine; Shannon, Adam; Pisani, Davide

    2015-01-01

    Anhydrobiotic animals can survive the loss of both free and bound water from their cells. While in this state they are also resistant to freezing. This physiology adapts anhydrobiotes to harsh environments and it aids their dispersal. Panagrolaimus davidi, a bacterial feeding anhydrobiotic nematode...... Panagrolaimus strains from tropical, temperate, continental and polar habitats and we analysed their phylogenetic relationships. We found that several other Panagrolaimus isolates can also survive freezing when fully hydrated and that tissue extracts from these freezing-tolerant nematodes can inhibit the growth...

  4. The peer effect on pain tolerance.

    Science.gov (United States)

    Engebretsen, Solveig; Frigessi, Arnoldo; Engø-Monsen, Kenth; Furberg, Anne-Sofie; Stubhaug, Audun; de Blasio, Birgitte Freiesleben; Nielsen, Christopher Sivert

    2018-05-19

    Twin studies have found that approximately half of the variance in pain tolerance can be explained by genetic factors, while shared family environment has a negligible effect. Hence, a large proportion of the variance in pain tolerance is explained by the (non-shared) unique environment. The social environment beyond the family is a potential candidate for explaining some of the variance in pain tolerance. Numerous individual traits have previously shown to be associated with friendship ties. In this study, we investigate whether pain tolerance is associated with friendship ties. We study the friendship effect on pain tolerance by considering data from the Tromsø Study: Fit Futures I, which contains pain tolerance measurements and social network information for adolescents attending first year of upper secondary school in the Tromsø area in Northern Norway. Pain tolerance was measured with the cold-pressor test (primary outcome), contact heat and pressure algometry. We analyse the data by using statistical methods from social network analysis. Specifically, we compute pairwise correlations in pain tolerance among friends. We also fit network autocorrelation models to the data, where the pain tolerance of an individual is explained by (among other factors) the average pain tolerance of the individual's friends. We find a significant and positive relationship between the pain tolerance of an individual and the pain tolerance of their friends. The estimated effect is that for every 1 s increase in friends' average cold-pressor tolerance time, the expected cold-pressor pain tolerance of the individual increases by 0.21 s (p-value: 0.0049, sample size n=997). This estimated effect is controlled for sex. The friendship effect remains significant when controlling for potential confounders such as lifestyle factors and test sequence among the students. Further investigating the role of sex on this friendship effect, we only find a significant peer effect of male friends

  5. Membranes, methods of making membranes, and methods of separating gases using membranes

    Science.gov (United States)

    Ho, W. S. Winston

    2012-10-02

    Membranes, methods of making membranes, and methods of separating gases using membranes are provided. The membranes can include at least one hydrophilic polymer, at least one cross-linking agent, at least one base, and at least one amino compound. The methods of separating gases using membranes can include contacting a gas stream containing at least one of CO.sub.2, H.sub.2S, and HCl with one side of a nonporous and at least one of CO.sub.2, H.sub.2S, and HCl selectively permeable membrane such that at least one of CO.sub.2, H.sub.2S, and HCl is selectively transported through the membrane.

  6. Overturning dogma: tolerance of insects to mixed-sterol diets is not universal.

    Science.gov (United States)

    Behmer, Spencer T

    2017-10-01

    Insects cannot synthesize sterols de novo, but like all eukaryotes they use them as cell membrane inserts where they influence membrane fluidity and rigidity. They also use a small amount for metabolic purposes, most notably as essential precursors for steroid hormones. It has been a long-held view that most insects require a small amount of specific sterol (often cholesterol) for metabolic purposes, but for membrane purposes (where the bulk of sterols are used) specificity in sterol structure was less important. Under this model, it was assumed that insects could tolerate mixed-sterol diets as long as a small amount of cholesterol was available. In the current paper this dogma is overturned, using data from plant-feeding insects that were fed mixed-sterol diets with different amounts and ratios of dietary sterols. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Polyazole hollow fiber membranes for direct contact membrane distillation

    KAUST Repository

    Maab, Husnul; Alsaadi, Ahmad Salem; Francis, Lijo; Livazovic, Sara; Ghaffour, NorEddine; Amy, Gary L.; Nunes, Suzana Pereira

    2013-01-01

    Porous hollow fiber membranes were fabricated from fluorinated polyoxadiazole and polytriazole by a dry-wet spinning method for application in desalination of Red Sea water by direct contact membrane distillation (DCMD). The data were compared with commercially available hollow fiber MD membranes prepared from poly(vinylidene fluoride). The membranes were characterized by electron microscopy, liquid entry pressure (LEP), and pore diameter measurements. Finally, the hollow fiber membranes were tested for DCMD. Salt selectivity as high as 99.95% and water fluxes as high as 35 and 41 L m -2 h-1 were demonstrated, respectively, for polyoxadiazole and polytriazole hollow fiber membranes, operating at 80 C feed temperature and 20 C permeate. © 2013 American Chemical Society.

  8. Polyazole hollow fiber membranes for direct contact membrane distillation

    KAUST Repository

    Maab, Husnul

    2013-08-07

    Porous hollow fiber membranes were fabricated from fluorinated polyoxadiazole and polytriazole by a dry-wet spinning method for application in desalination of Red Sea water by direct contact membrane distillation (DCMD). The data were compared with commercially available hollow fiber MD membranes prepared from poly(vinylidene fluoride). The membranes were characterized by electron microscopy, liquid entry pressure (LEP), and pore diameter measurements. Finally, the hollow fiber membranes were tested for DCMD. Salt selectivity as high as 99.95% and water fluxes as high as 35 and 41 L m -2 h-1 were demonstrated, respectively, for polyoxadiazole and polytriazole hollow fiber membranes, operating at 80 C feed temperature and 20 C permeate. © 2013 American Chemical Society.

  9. Chemical degradation mechanisms of membranes for alkaline membrane fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Yoong-Kee [National Institute of Advanced Industrial Science and Technology, Umezono 1-1-1, Tsukuba (Japan); Henson, Neil J.; Kim, Yu Seung [Los Alamos National Laboratory, Los Alamos, NM (United States)

    2015-12-31

    Chemical degradation mechanisms of membranes for alkaline membrane fuel cells have been investigated using density functional theory (DFT). We have elucidated that the aryl-ether moiety of membranes is one of the weakest site against attack of hydroxide ions. The results of DFT calculations for hydroxide initiated aryl-ether cleavage indicated that the aryl-ether cleavage occurred prior to degradation of cationic functional group. Such a weak nature of the aryl-ether group arises from the electron deficiency of the aryl group as well as the low bond dissociation energy. The DFT results suggests that removal of the aryl-ether group in the membrane should enhance the stability of membranes under alkaline conditions. In fact, an ether fee poly(phenylene) membrane exhibits excellent stability against the attack from hydroxide ions.

  10. Tolerance doses for treatment planning

    International Nuclear Information System (INIS)

    Lyman, J.T.

    1985-10-01

    Data for the tolerance of normal tissues or organs to (low-LET) radiation has been compiled from a number of sources which are referenced at the end of this document. This tolerance dose data are ostensibly for uniform irradiation of all or part of an organ, and are for either 5% (TD 5 ) or 50% (TD 50 ) complication probability. The ''size'' of the irradiated organ is variously stated in terms of the absolute volume or the fraction of the organ volume irradiated, or the area or the length of the treatment field. The accuracy of these data is questionable. Much of the data represents doses that one or several experienced therapists have estimated could be safely given rather than quantitative analyses of clinical observations. Because these data have been obtained from multiple sources with possible different criteria for the definition of a complication, there are sometimes different values for what is apparently the same endpoint. The data from some sources shows a tendancy to be quantized in 5 Gy increments. This reflects the size of possible round off errors. It is believed that all these data have been accumulated without the benefit of 3-D dose distributions and therefore the estimates of the size of the volume and/or the uniformity of the irradiation may be less accurate than is now possible. 19 refs., 4 figs

  11. Radiation tolerance of amorphous semiconductors

    International Nuclear Information System (INIS)

    Nicolaides, R.V.; DeFeo, S.; Doremus, L.W.

    1976-01-01

    In an attempt to determine the threshold radiation damage in amorphous semiconductors, radiation tests were performed on amorphous semiconductor thin film materials and on threshold and memory devices. The influence of flash x-rays and neutron radiation upon the switching voltages, on- and off-state characteristics, dielectric response, optical transmission, absorption band edge and photoconductivity were measured prior to, during and following irradiation. These extensive tests showed the high radiation tolerance of amorphous semiconductor materials. Electrical and optical properties, other than photoconductivity, have a neutron radiation tolerance threshold above 10 17 nvt in the steady state and 10 14 nvt in short (50 μsec to 16 msec) pulses. Photoconductivity increases by 1 1 / 2 orders of magnitude at the level of 10 14 nvt (short pulses of 50 μsec). Super flash x-rays up to 5000 rads (Si), 20 nsec, do not initiate switching in off-state samples which are voltage biased up to 90 percent of the threshold voltage. Both memory and threshold amorphous devices are capable of switching on and off during nuclear radiation transients at least as high as 2 x 10 14 nvt in 50 μsec pulses

  12. Microbial stress tolerance for biofuels. Systems biology

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zonglin Lewis (ed.) [National Center for Agricultural Utilization Research, USDA-ARS, Peoria, IL (United States)

    2012-07-01

    The development of sustainable and renewable biofuels is attracting growing interest. It is vital to develop robust microbial strains for biocatalysts that are able to function under multiple stress conditions. This Microbiology Monograph provides an overview of methods for studying microbial stress tolerance for biofuels applications using a systems biology approach. Topics covered range from mechanisms to methodology for yeast and bacteria, including the genomics of yeast tolerance and detoxification; genetics and regulation of glycogen and trehalose metabolism; programmed cell death; high gravity fermentations; ethanol tolerance; improving biomass sugar utilization by engineered Saccharomyces; the genomics on tolerance of Zymomonas mobilis; microbial solvent tolerance; control of stress tolerance in bacterial host organisms; metabolomics for ethanologenic yeast; automated proteomics work cell systems for strain improvement; and unification of gene expression data for comparable analyses under stress conditions. (orig.)

  13. Role of phytosterols in drought stress tolerance in rice.

    Science.gov (United States)

    Kumar, M S Sujith; Ali, Kishwar; Dahuja, Anil; Tyagi, Aruna

    2015-11-01

    Phytosterols are integral components of the membrane lipid bilayer in plants. They regulate membrane fluidity to influence its properties, functions and structure. An increase in accumulation of phytosterols namely campesterol, stigmasterol and β-sitosterol was observed in rice as seedlings matured. The levels of the major phytosterol, β-sitosterol in N22 (drought tolerant) rice seedlings was found to increase proportionately with severity of drought stress. Its levels were 145, 216, 345 and 364 μg/g FW after subjecting to water stress for 3, 6, 9 and 12 days respectively, while for IR64 (drought susceptible), levels were 137, 198, 227 and 287 μg/g FW at the same stages. Phytosterols were also found to increase with maturity as observed at 30, 50 and 75 days after planting. The activity of HMG-CoA reductase (EC 1.1.1.34) which is considered to be a key limiting enzyme in the biosynthesis of phytosterols was 0.55, 0.56, 0.78 and 0.85 μmol/min/L at 3, 6, 9 and 12 days of water stress in N22 and 0.31, 0.50, 0.54 and 0.65 μmol/min/L in case of IR64 respectively. The elevation in the levels of phytosterols as well as the activity of HMG-CoA reductase during drought stress indicates the role of phytosterols in providing tolerance to stress. Copyright © 2015. Published by Elsevier Masson SAS.

  14. Reorganization of Azospirillum brasilense cell membrane is mediated by lipid composition adjustment to maintain optimal fluidity during water deficit.

    Science.gov (United States)

    Cesari, A B; Paulucci, N S; Biasutti, M A; Reguera, Y B; Gallarato, L A; Kilmurray, C; Dardanelli, M S

    2016-01-01

    We study the Azospirillum brasilense tolerance to water deficit and the dynamics of adaptive process at the level of the membrane. Azospirillum brasilense was exposed to polyethylene glycol (PEG) growth and PEG shock. Tolerance, phospholipids and fatty acid (FA) composition and membrane fluidity were determined. Azospirillum brasilense was able to grow in the presence of PEG; however, its viability was reduced. Cells grown with PEG showed membrane fluidity similar to those grown without, the lipid composition was modified, increasing phosphatidylcholine and decreasing phosphatidylethanolamine amounts. The unsaturation FAs degree was reduced. The dynamics of the adaptive response revealed a decrease in fluidity 20 min after the addition of PEG, indicating that the PEG has a fluidizing effect on the hydrophobic region of the cell membrane. Fluidity returned to initial values after 60 min of PEG exposure. Azospirillum brasilense is able to perceive osmotic changes by changing the membrane fluidity. This effect is offset by changes in the composition of membrane phospholipid and FA, contributing to the homeostasis of membrane fluidity under water deficit. This knowledge can be used to develop new Azospirillum brasilense formulations showing an adapted membrane to water deficit. © 2015 The Society for Applied Microbiology.

  15. Amodiaquine polymeric membrane electrode.

    Science.gov (United States)

    Malongo, T Kimbeni; Blankert, B; Kambu, O; Amighi, K; Nsangu, J; Kauffmann, J-M

    2006-04-11

    The construction and electrochemical response characteristics of two types of poly(vinyl chloride) (PVC) membrane sensors for the determination of amodiaquine hydrochloride (ADQ.2HCl) are described. The sensing membrane comprised an ion-pair formed between the cationic drug and sodium tetraphenyl borate (NaTPB) or potassium tetrakis(4-chlorophenyl) borate (KTCPB) in a plasticized PVC matrix. Eight PVC membrane ion-selective electrodes were fabricated and studied. Several plasticizers were studied namely, dioctyl phthalate (DOP), 2-nitrophenyl octyl ether (NPOE), dioctyl phenylphosphonate (DOPP) and bis(2-ethylhexyl)adipate (EHA). The sensors display a fast, stable and near-Nernstian response over a relative wide ADQ concentration range (3.2 x 10(-6) to 2.0 x 10(-2) M), with slopes comprised between 28.5 and 31.4 mV dec(-1) in a pH range comprised between pH 3.7 and 5.5. The assay of amodiaquine hydrochloride in pharmaceutical dosage forms using one of the proposed sensors gave average recoveries of 104.3 and 99.9 with R.S.D. of 0.3 and 0.6% for tablets (Malaritab) and a reconstituted powder containing ADQ.2HCl, respectively. The sensor was also used for dissolution profile studies of two drug formulations. The sensor proved to have a good selectivity for ADQ.2HCl over some inorganic and organic compounds, however, berberine chloride interfered significantly. The results were validated by comparison with a spectrophotometric assay according to the USP pharmacopoeia.

  16. Boron nutrition and chilling tolerance of warm climate crop species.

    Science.gov (United States)

    Huang, Longbin; Ye, Zhengqian; Bell, Richard W; Dell, Bernard

    2005-10-01

    Field observations and glasshouse studies have suggested links between boron (B)-deficiency and leaf damage induced by low temperature in crop plants, but causal relationships between these two stresses at physiological, biochemical and molecular levels have yet to be explored. Limited evidence at the whole-plant level suggests that chilling temperature in the root zone restricts B uptake capacity and/or B distribution/utilization efficiency in the shoot, but the nature of this interaction depends on chilling tolerance of species concerned, the mode of low temperature treatment (abrupt versus gradual temperature decline) and growth conditions (e.g. photon flux density and relative humidity) that may exacerbate chilling stress. This review explores roles of B nutrition in chilling tolerance of continual root or transient shoot chills in crop species adapted to warm season conditions. It reviews current research on combined effects of chilling temperature (ranging from >0 to 20 degrees C) and B deficiency on growth and B nutrition responses in crop species differing in chilling tolerance. For subtropical/tropical species (e.g. cucumber, cassava, sunflower), root chilling at 10-17 degrees C decreases B uptake efficiency and B utilization in the shoot and increases the shoot : root ratio, but chilling-tolerant temperate species (e.g. oilseed rape, wheat) require much lower root chill temperatures (2-5 degrees C) to achieve the same responses. Boron deficiency exacerbates chilling injuries in leaf tissues, particularly under high photon flux density. Suggested mechanisms for B x chilling interactions in plants are: (a) chilling-induced reduction in plasmalemma hydraulic conductivity, membrane fluidity, water channel activity and root pressure, which contribute to the decrease in root hydraulic conductance, water uptake and associated B uptake; (b) chilling-induced stomatal dysfunction affecting B transport from root to shoot and B partitioning in the shoot; and (c) B

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

    Directory of Open Access Journals (Sweden)

    Yuanqing Ma

    2017-11-01

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

  18. Oxygen Transport Membranes

    Energy Technology Data Exchange (ETDEWEB)

    S. Bandopadhyay

    2008-08-30

    The focus of this research was to develop new membrane materials by synthesizing different compounds and determining their defect structures, crystallographic structures and electrical properties. In addition to measuring electrical conductivity, oxygen vacancy concentration was also evaluated using thermogravimetry, Neutron diffraction and Moessbauer Spectroscopy. The reducing conditions (CO{sub 2}/CO/H{sub 2} gas mixtures with steam) as encountered in a reactor environment can be expected to have significant influence on the mechanical properties of the oxides membranes. Various La based materials with and without Ti were selected as candidate membrane materials for OTM. The maximum electrical conductivity of LSF in air as a function of temperature was achieved at < 600 C and depends on the concentration of Sr (acceptor dopant). Oxygen occupancy in LSF was estimated using Neutron diffractometry and Moessbauer Spectroscopy by measuring magnetic moment changes depending on the Fe{sup 3+} and Fe{sup 4+} ratio. After extensive studies of candidate materials, lanthanum ferrites (LSF and LSFT) were selected as the favored materials for the oxygen transport membrane (OTM). LSF is a very good material for an OTM because of its high electronic and oxygen ionic conductivity if long term stability and mechanical strength are improved. LSFT not only exhibits p-type behavior in the high oxygen activity regime, but also has n-type conduction in reducing atmospheres. Higher concentrations of oxygen vacancies in the low oxygen activity regime may improve the performance of LSFT as an OTM. The hole concentration is related to the difference in the acceptor and donor concentration by the relation p = [Sr'{sub La}]-[Ti{sm_bullet}{sub Fe}]. The chemical formulation predicts that the hole concentration is, p = 0.8-0.45 or 0.35. Experimental measurements indicated that p is about {approx} 0.35. The activation energy of conduction is 0.2 eV which implies that LSCF conducts via the

  19. Molecularly Imprinted Membranes

    Science.gov (United States)

    Trotta, Francesco; Biasizzo, Miriam; Caldera, Fabrizio

    2012-01-01

    Although the roots of molecularly imprinted polymers lie in the beginning of 1930s in the past century, they have had an exponential growth only 40–50 years later by the works of Wulff and especially by Mosbach. More recently, it was also proved that molecular imprinted membranes (i.e., polymer thin films) that show recognition properties at molecular level of the template molecule are used in their formation. Different procedures and potential application in separation processes and catalysis are reported. The influences of different parameters on the discrimination abilities are also discussed. PMID:24958291

  20. Choroidal neovascular membrane

    Directory of Open Access Journals (Sweden)

    Bhatt Nitul

    1998-01-01

    Full Text Available Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician′s viewpoint.

  1. Choroidal neovascular membrane.

    Science.gov (United States)

    Bhatt, N S; Diamond, J G; Jalali, S; Das, T

    1998-06-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician's viewpoint.

  2. SCHEME ANALYSIS TREE DIMENSIONS AND TOLERANCES PROCESSING

    OpenAIRE

    Constanta RADULESCU; Liviu Marius CÎRŢÎNĂ; Constantin MILITARU

    2011-01-01

    This paper presents one of the steps that help us to determine the optimal tolerances depending on thetechnological capability of processing equipment. To determine the tolerances in this way is necessary to takethe study and to represent schematically the operations are used in technological process of making a piece.Also in this phase will make the tree diagram of the dimensions and machining tolerances, dimensions andtolerances shown that the design execution. Determination processes, and ...

  3. Generalized tolerance sensitivity and DEA metric sensitivity

    OpenAIRE

    Neralić, Luka; E. Wendell, Richard

    2015-01-01

    This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  4. Generalized tolerance sensitivity and DEA metric sensitivity

    Directory of Open Access Journals (Sweden)

    Luka Neralić

    2015-03-01

    Full Text Available This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA. Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

  5. High-performance membrane-electrode assembly with an optimal polytetrafluoroethylene content for high-temperature polymer electrolyte membrane fuel cells

    DEFF Research Database (Denmark)

    Jeong, Gisu; Kim, MinJoong; Han, Junyoung

    2016-01-01

    Although high-temperature polymer electrolyte membrane fuel cells (HT-PEMFCs) have a high carbon monoxide tolerance and allow for efficient water management, their practical applications are limited due to their lower performance than conventional low-temperature PEMFCs. Herein, we present a high......-performance membrane-electrode assembly (MEA) with an optimal polytetrafluoroethylene (PTFE) content for HT-PEMFCs. Low or excess PTFE content in the electrode leads to an inefficient electrolyte distribution or severe catalyst agglomeration, respectively, which hinder the formation of triple phase boundaries...

  6. 76 FR 22045 - Fluopicolide; Pesticide Tolerances

    Science.gov (United States)

    2011-04-20

    ... regulation establishes tolerances for residues of fluopicolide and its metabolites in or on multiple... occurred at dose levels where significant maternal toxicity (severe body weight gain decrements and...

  7. Enhancing drought tolerance in C(4) crops.

    Science.gov (United States)

    Lopes, Marta S; Araus, Jose Luis; van Heerden, Philippus D R; Foyer, Christine H

    2011-05-01

    Adaptation to abiotic stresses is a quantitative trait controlled by many different genes. Enhancing the tolerance of crop plants to abiotic stresses such as drought has therefore proved to be somewhat elusive in terms of plant breeding. While many C(4) species have significant agronomic importance, most of the research effort on improving drought tolerance has focused on maize. Ideally, drought tolerance has to be achieved without penalties in yield potential. Possibilities for success in this regard are highlighted by studies on maize hybrids performed over the last 70 years that have demonstrated that yield potential and enhanced stress tolerance are associated traits. However, while our understanding of the molecular mechanisms that enable plants to tolerate drought has increased considerably in recent years, there have been relatively few applications of DNA marker technologies in practical C(4) breeding programmes for improved stress tolerance. Moreover, until recently, targeted approaches to drought tolerance have concentrated largely on shoot parameters, particularly those associated with photosynthesis and stay green phenotypes, rather than on root traits such as soil moisture capture for transpiration, root architecture, and improvement of effective use of water. These root traits are now increasingly considered as important targets for yield improvement in C(4) plants under drought stress. Similarly, the molecular mechanisms underpinning heterosis have considerable potential for exploitation in enhancing drought stress tolerance. While current evidence points to the crucial importance of root traits in drought tolerance in C(4) plants, shoot traits may also be important in maintaining high yields during drought.

  8. Synthesis of Fault-Tolerant Embedded Systems

    DEFF Research Database (Denmark)

    Eles, Petru; Izosimov, Viacheslav; Pop, Paul

    2008-01-01

    This work addresses the issue of design optimization for fault- tolerant hard real-time systems. In particular, our focus is on the handling of transient faults using both checkpointing with rollback recovery and active replication. Fault tolerant schedules are generated based on a conditional...... process graph representation. The formulated system synthesis approaches decide the assignment of fault-tolerance policies to processes, the optimal placement of checkpoints and the mapping of processes to processors, such that multiple transient faults are tolerated, transparency requirements...

  9. Establishing soil loss tolerance: an overview

    Directory of Open Access Journals (Sweden)

    Costanza Di Stefano

    2016-09-01

    Full Text Available Soil loss tolerance is a criterion for establishing if a soil is potentially subjected to erosion risk, productivity loss and if a river presents downstream over-sedimentation or other off-site effects are present at basin scale. At first this paper reviews the concept of tolerable soil loss and summarises the available definitions and the knowledge on the recommended values and evaluating criteria. Then a threshold soil loss value, at the annual temporal scale, established for limiting riling was used for defining the classical soil loss tolerance. Finally, some research needs on tolerable soil loss are listed.

  10. Novicidin interactions with phospholipid membranes

    DEFF Research Database (Denmark)

    Balakrishnan, Vijay Shankar

    Antimicrobial peptides target bacterial cell membranes and are considered as potential antibiotics. Their interactions with cell membranes are studied using different approaches. This thesis comprises of the biophysical investigations on the antimicrobial peptide Novicidin, interacting with lipos......Antimicrobial peptides target bacterial cell membranes and are considered as potential antibiotics. Their interactions with cell membranes are studied using different approaches. This thesis comprises of the biophysical investigations on the antimicrobial peptide Novicidin, interacting...... with liposomes. The lipid-induced changes in the peptide due to membrane binding, and the peptide-induced changes in the membrane properties were investigated using various spectroscopic and calorimetric methods, and the structural and thermodynamic aspects of peptide-lipid interactions are discussed. This helps...

  11. Mathematical modelling of membrane separation

    DEFF Research Database (Denmark)

    Vinther, Frank

    This thesis concerns mathematical modelling of membrane separation. The thesis consists of introductory theory on membrane separation, equations of motion, and properties of dextran, which will be the solute species throughout the thesis. Furthermore, the thesis consist of three separate mathemat......This thesis concerns mathematical modelling of membrane separation. The thesis consists of introductory theory on membrane separation, equations of motion, and properties of dextran, which will be the solute species throughout the thesis. Furthermore, the thesis consist of three separate...... mathematical models, each with a different approach to membrane separation. The first model is a statistical model investigating the interplay between solute shape and the probability of entering the membrane. More specific the transition of solute particles from being spherical to becoming more elongated...

  12. Pectin methylesterase31 positively regulates salt stress tolerance in Arabidopsis.

    Science.gov (United States)

    Yan, Jingwei; He, Huan; Fang, Lin; Zhang, Aying

    2018-02-05

    The alteration of cell wall component and structure is an important adaption to saline environment. Pectins, a major cell wall component, are often present in a highly methylesterified form. The level of methyl esterification determined by pectin methylesterases (PMEs) influences many important wall properties that are believed to relate to the adaption to saline stress. However, little is known about the function of PMEs in response to salt stress. Here, we established a link between pectin methylesterase31 (PME31) and salt stress tolerance. Salt stress significantly increases PME31 expression. PME31 is located in the plasma membrane and the expression level of PME31 was high in dry seeds. Knock-down mutants in PME31 conferred hypersensitive phenotypes to salt stress in seed germination and post-germination growth. Real-time PCR analysis revealed that the transcript levels of several stress genes (DREB2A, RD29A and RD29B) are lower in pme31-2 mutant than that in the wild type in response to salt stress. These results suggested that PME31 could positively modulate salt stress tolerance. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. big bang gene modulates gut immune tolerance in Drosophila.

    Science.gov (United States)

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

    2013-02-19

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

  14. Usnic acid controls the acidity tolerance of lichens

    International Nuclear Information System (INIS)

    Hauck, Markus; Juergens, Sascha-Rene

    2008-01-01

    The hypotheses were tested that, firstly, lichens producing the dibenzofuran usnic acid colonize substrates characterized by specific pH ranges, secondly, this preferred pH is in a range where soluble usnic acid and its corresponding anion occur in similar concentrations, and thirdly, usnic acid makes lichens vulnerable to acidity. Lichens with usnic acid prefer an ambient pH range between 3.5 and 5.5 with an optimum between 4.0 and 4.5. This optimum is close to the pK a1 value of usnic acid of 4.4. Below this optimum pH, dissolved SO 2 reduces the chlorophyll fluorescence yield more in lichens with than without their natural content of usnic acid. This suggests that usnic acid influences the acidity tolerance of lichens. The putative mechanism of the limited acidity tolerance of usnic acid-containing lichens is the acidification of the cytosol by molecules of protonated usnic acid shuttling protons through the plasma membrane at an apoplastic pH a1 . - Combined field and experimental data suggest that usnic acid makes lichens sensitive to acidity at pH <3.5

  15. Calcium dependence of eugenol tolerance and toxicity in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Stephen K Roberts

    Full Text Available Eugenol is a plant-derived phenolic compound which has recognised therapeutical potential as an antifungal agent. However little is known of either its fungicidal activity or the mechanisms employed by fungi to tolerate eugenol toxicity. A better exploitation of eugenol as a therapeutic agent will therefore depend on addressing this knowledge gap. Eugenol initiates increases in cytosolic Ca2+ in Saccharomyces cerevisiae which is partly dependent on the plasma membrane calcium channel, Cch1p. However, it is unclear whether a toxic cytosolic Ca2+elevation mediates the fungicidal activity of eugenol. In the present study, no significant difference in yeast survival was observed following transient eugenol treatment in the presence or absence of extracellular Ca2+. Furthermore, using yeast expressing apoaequorin to report cytosolic Ca2+ and a range of eugenol derivatives, antifungal activity did not appear to be coupled to Ca2+ influx or cytosolic Ca2+ elevation. Taken together, these results suggest that eugenol toxicity is not dependent on a toxic influx of Ca2+. In contrast, careful control of extracellular Ca2+ (using EGTA or BAPTA revealed that tolerance of yeast to eugenol depended on Ca2+ influx via Cch1p. These findings expose significant differences between the antifungal activity of eugenol and that of azoles, amiodarone and carvacrol. This study highlights the potential to use eugenol in combination with other antifungal agents that exhibit differing modes of action as antifungal agents to combat drug resistant infections.

  16. Alterations in membrane trafficking and pathophysiological implications in lysosomal storage disorders.

    Science.gov (United States)

    Kuech, Eva-Maria; Brogden, Graham; Naim, Hassan Y

    2016-11-01

    Lysosomal storage disorders are a heterogeneous group of more than 50 distinct inborn metabolic diseases affecting about 1 in 5000 to 7000 live births. The diseases often result from mutations followed by functional deficiencies of enzymes or transporters within the acidic environment of the lysosome, which mediate the degradation of a wide subset of substrates, including glycosphingolipids, glycosaminoglycans, cholesterol, glycogen, oligosaccharides, peptides and glycoproteins, or the export of the respective degradation products from the lysosomes. The progressive accumulation of uncleaved substrates occurs in multiple organs and finally causes a broad spectrum of different pathologies including visceral, neurological, skeletal and hematologic manifestations. Besides deficient lysosomal enzymes and transporters other defects may lead to lysosomal storage disorders, including activator defects, membrane defects or defects in modifier proteins. In this review we concentrate on four different lysosomal storage disorders: Niemann-Pick type C, Fabry disease, Gaucher disease and Pompe disease. While the last three are caused by defective lysosomal hydrolases, Niemann-Pick type C is caused by the inability to export LDL-derived cholesterol out of the lysosome. We want to emphasise potential implications of membrane trafficking defects on the pathology of these diseases, as many mutations interfere with correct lysosomal protein trafficking and alter cellular lipid homeostasis. Current therapeutic strategies are summarised, including substrate reduction therapy as well as pharmacological chaperone therapy which directly aim to improve folding and lysosomal transport of misfolded mutant proteins. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  17. Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.

    Science.gov (United States)

    Müller, Mario M; Lehmann, Roland; Klassert, Tilman E; Reifenstein, Stella; Conrad, Theresia; Moore, Christoph; Kuhn, Anna; Behnert, Andrea; Guthke, Reinhard; Driesch, Dominik; Slevogt, Hortense

    2017-04-12

    Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.

  18. Radiation effects on cell membranes

    International Nuclear Information System (INIS)

    Koeteles, G.J.

    1982-01-01

    Experimental data are presented concerning the effects of relatively low doses of x radiation and low concentration of tritiated water (HTO) on various receptor functions - concanavalin A, cationized ferritin, poliovirus of plasma membranes of animal and human cells which point to early and temporary disturbances of the composite structures and functions of membranes. References are given to the manifold influence of radiation-induced membrane phenomenon on the development and regeneration of radiation injuries. (author)

  19. Decrumpling membranes by quantum effects

    Science.gov (United States)

    Borelli, M. E. S.; Kleinert, H.

    2001-02-01

    The phase diagram of an incompressible fluid membrane subject to quantum and thermal fluctuations is calculated exactly in a large number of dimensions of configuration space. At zero temperature, a crumpling transition is found at a critical bending rigidity 1/αc. For membranes of fixed lateral size, a crumpling transition occurs at nonzero temperatures in an auxiliary mean field approximation. As the lateral size L of the membrane becomes large, the flat regime shrinks with 1/ln L.

  20. Epiretinal membrane surgery

    DEFF Research Database (Denmark)

    Hamoudi, Hassan; Correll Christensen, Ulrik; La Cour, Morten

    2017-01-01

    Purpose: To assess the impact of combined phacoemulsification-vitrectomy and sequential surgery for idiopathic epiretinal membrane (ERM) on refractive error (RE) and macular morphology. Methods: In this prospective clinical trial, we allocated phakic eyes with ERM to (1) cataract surgery and subs......Purpose: To assess the impact of combined phacoemulsification-vitrectomy and sequential surgery for idiopathic epiretinal membrane (ERM) on refractive error (RE) and macular morphology. Methods: In this prospective clinical trial, we allocated phakic eyes with ERM to (1) cataract surgery...... and achieved spherical equivalent); secondary outcomes were best-corrected visual acuity (BCVA), and incidence of cystoid macular oedema (CME) defined as >10% increment of central subfield macular thickness (CSMT). Results: Sixty-two eyes were enrolled. The mean RE showed a small myopic shift of -0.36D in all...... between the groups. Four cases (17%) in the CAT group had resolved visual complaints and improved BCVA after cataract surgery resulting in no need for PPV within the follow-up period. Conclusion: Surgery for idiopathic ERM in phakic eyes with either phaco-vitrectomy or sequential surgery are equal...