40 results on '"Gasset, Maria"'
Search Results
2. Conversion of α-Helices β-Sheets Features in the Formation of the scrapie Prion Proteins
- Author
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Pan, Keh-Ming, Baldwin, Michael, Nguyen, Jack, Gasset, Maria, Serban, Ana, Groth, Darlene, Mehlhorn, Ingrid, Huang, Ziwei, Fletterick, Robert J., Cohen, Fred E., and Prusiner, Stanley B.
- Published
- 1993
3. Predicted α-Helical Regions of the Prion Protein when Synthesized as Peptides Form Amyloid
- Author
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Gasset, Maria, Baldwin, Michael A., Lloyd, David H., Gabriel, Jean-Marc, Holtzman, David M., Cohen, Fred, Fletterick, Robert, and Prusiner, Stanley B.
- Published
- 1992
4. Perturbation of the Secondary Structure of the Scrapie Prion Protein Under Conditions that Alter Infectivity
- Author
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Gasset, Maria, Baldwin, Michael A., Fletterick, Robert J., and Prusiner, Stanley B.
- Published
- 1993
5. Spectroscopic Characterization of Conformational Differences between PrP C and PrP Sc : An α -helix to β -sheet Transition
- Author
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Baldwin, Michael A., Pan, Keh-Ming, Nguyen, Jack, Huang, Ziwei, Groth, Darlene, Serban, Ana, Gasset, Maria, Mehlhorn, Ingrid, Fletterick, Robert J., Cohen, Fred E., and Prusiner, Stanley B.
- Published
- 1994
6. Inter- and Intra-octarepeat Cu(II) Site Geometries in the Prion Protein: IMPLICATIONS IN Cu(II) BINDING COOPERATIVITY AND Cu(II)-MEDIATED ASSEMBLIES
- Author
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Morante, Silvia, González-Iglesias, Reinerio, Potrich, Cristina, Meneghini, Carlo, Meyer-Klaucke, Wolfram, Menestrina, Gianfranco, and Gasset, María
- Published
- 2004
- Full Text
- View/download PDF
7. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins
- Author
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Keh-Ming Pan, Baldwin, Michael, Nguyen, Jack, Gasset, Maria, Serban, Ana, Groth, Darlene, Mehlhorn, Ingrid, Ziwei Huang, Fletterick, Robert J., Cohen, Fred E., and Prusiner, Stanley B.
- Subjects
Prions -- Research ,Proteins -- Conformation ,Genetic translation -- Research ,Fourier transform infrared spectroscopy -- Usage ,Science and technology - Abstract
An analysis of the structural modification during synthesis of prion protein PrP(Sc) involved the application of nondenaturing techniques to purify PrP(Sc) from the cellular prion protein PrPC, and the definition of their secondary structures. The transformation of alpha-helices into beta-sheets is involved in the formation of PrPSc, and an unknown chemical change in a small portion of PrPSc may trigger this mechanism.
- Published
- 1993
8. Predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid
- Author
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Gasset, Maria, Baldwin, Michael A., Lloyd, david H., Gabriel, Jean-Marc, Holtzman, David M., Cohen, Fred, Fletterick, Robert, and Prusiner, Stanley B.
- Subjects
Prions -- Research ,Peptides -- Synthesis ,Science and technology - Abstract
Structural analysis based on comparisons of the amino acid sequences of 11 mammalian and 1 avian prion proteins (PrP) predicted four alpha-helical structures. To test the prediction, peptides homologous to portions of the Syrian hamster prion proteins (PrP) sequence were synthesized. Contrary to predictions, three of the four structures formed amyloids. The findings indicate that the conversion of the cellular PrP isoform to the scrapie isoform could be due to the transition of alpha helices to beta-sheets.If such is the case, prion diseases could be considered as disorders of proteinconformations.
- Published
- 1992
9. Role of an Intrasubunit Disulfide in the Association State of the Cytosolic Homo-oligomer Methionine Adenosyltransferase
- Author
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Sánchez-Pérez, Gabino F., Gasset, Marı́a, Calvete, Juan J., and Pajares, Marı́a A.
- Published
- 2003
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- View/download PDF
10. Are Amyloid Fibrils RNA-Traps? A Molecular Dynamics Perspective
- Author
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Meli, Massimiliano, primary, Gasset, Maria, additional, and Colombo, Giorgio, additional
- Published
- 2018
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- View/download PDF
11. Structural characterization of prefibrillar intermediates and amyloid fibrils by small-angle X-ray scattering
- Author
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Sigurdsson, Einar M, Calero, Miguel, Gasset, Maria, Langkilde, Annette Eva, Vestergaard, Bente, Sigurdsson, Einar M, Calero, Miguel, Gasset, Maria, Langkilde, Annette Eva, and Vestergaard, Bente
- Published
- 2012
12. Biosynthesis of Prion Protein Nucleocytoplasmic Isoforms by Alternative Initiation of Translation
- Author
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Juanes, María E., Elvira, Gema, García-Grande, Aranzazu, Calero, Miguel, and Gasset, María
- Published
- 2009
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13. Dynamic Diagnosis of Familial Prion Diseases Supports the β2-α2 Loop as a Universal Interference Target
- Author
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Meli, Massimiliano, primary, Gasset, Maria, additional, and Colombo, Giorgio, additional
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- 2011
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14. PrPSc Incorporation to Cells Requires Endogenous Glycosaminoglycan Expression
- Author
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Hijazi, Nuha, primary, Kariv-Inbal, Zehavit, additional, Gasset, Maria, additional, and Gabizon, Ruth, additional
- Published
- 2005
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15. Conformational Features and Thermal Stability of Bovine Seminal Plasma Protein PDC-109 Oligomers and Phosphorylcholine-Bound Complexes
- Author
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Gasset, Maria, primary, Saiz, Jose L., additional, Laynez, Josel, additional, Sanz, Libia, additional, Gentzel, Marc, additional, Topfer-Petersen, Edda, additional, and Calvete, Juan J., additional
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- 1997
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16. Analysis of the Structural Organization and Thermal Stability of two Spermadhesins. Calorimetric, Circular Dichroic and Fourier-Transform Infrared Spectroscopic Studies
- Author
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Menendez, Margarita, primary, Gasset, Maria, additional, Laynez, Jose, additional, Lopez-Zumel, Consuelo, additional, Usobiaga, Pilar, additional, Topper-Petersen, Edda, additional, and Calvete, Juan J., additional
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- 1995
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17. The Non-Peptidic Part Determines the Internalization Mechanism and Intracellular Trafficking of Peptide Amphiphiles.
- Author
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Missirlis, Dimitris, Teesalu, Tambet, Black, Matthew, Tirrell, Matthew, and Gasset, Maria
- Subjects
AMPHIPHILES ,PEPTIDE amphiphiles ,NANOSTRUCTURED materials ,DRUG lipophilicity ,EXOCYTOSIS ,CELL physiology - Abstract
Background: Peptide amphiphiles (PAs) are a class of amphiphilic molecules able to self-assemble into nanomaterials that have shown efficient in vivo targeted delivery. Understanding the interactions of PAs with cells and the mechanisms of their internalization and intracellular trafficking is critical in their further development for therapeutic delivery applications. Methodology/Principal Findings: PAs of a novel, cell- and tissue-penetrating peptide were synthesized possessing two different lipophilic tail architectures and their interactions with prostate cancer cells were studied in vitro. Cell uptake of peptides was greatly enhanced post-modification. Internalization occurred via lipid-raft mediated endocytosis and was common for the two analogs studied. On the contrary, we identified the non-peptidic part as the determining factor of differences between intracellular trafficking and retention of PAs. PAs composed of di-stearyl lipid tails linked through poly(ethylene glycol) to the peptide exhibited higher exocytosis rates and employed different recycling pathways compared to ones consisting of di-palmitic-coupled peptides. As a result, cell association of the former PAs decreased with time. Conclusions/Significance: Control over peptide intracellular localization and retention is possible by appropriate modification with synthetic hydrophobic tails. We propose this as a strategy to design improved peptide-based delivery systems. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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18. Evidence on the Formation of Singlet Oxygen in the Donor Side Photoinhibition of Photosystem II: EPR Spin-Trapping Study.
- Author
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Yadav, Deepak Kumar, Pospíšil, Pavel, and Gasset, Maria
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REACTIVE oxygen species ,PHOTOSYSTEMS ,CHLOROPHYLL ,RADICALS (Chemistry) ,ELECTRON paramagnetic resonance spectroscopy ,LIPIDS - Abstract
When photosystem II (PSII) is exposed to excess light, singlet oxygen (¹O
2 ) formed by the interaction of molecular oxygen with triplet chlorophyll. Triplet chlorophyll is formed by the charge recombination of triplet radical pair ³[P680•+ Pheo]•- in the acceptor-side photoinhibition of PSII. Here, we provide evidence on the formation of ¹O2 in the donor side photoinhibition of PSII. Light-induced ¹O2 production in Tris-treated PSII membranes was studied by electron paramagnetic resonance (EPR) spin-trapping spectroscopy, as monitored by TEMPONE EPR signal. Light-induced formation of carbon-centered radicals (R• ) was observed by POBN-R adduct EPR signal. Increased oxidation of organic molecules at high pH enhanced the formation of TEMPONE and POBN-R adduct EPR signals in Tris-treated PSII membranes. Interestingly, the scavenging of R• by propyl gallate significantly suppressed ¹O2 . Based on our results, it is concluded that ¹O2 formation correlates with R• formation on the donor side of PSII due to oxidation of organic molecules (lipids and proteins) by long-lived P680•+ /TyrZ• . It is proposed here that the Russell mechanism for the recombination of two peroxyl radicals formed by the interaction of R• with molecular oxygen is a plausible mechanism for ¹O2 formation in the donor side photoinhibition of PSII. [ABSTRACT FROM AUTHOR]- Published
- 2012
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19. Peptide Nanovesicles Formed by the Self-Assembly of Branched Amphiphilic Peptides.
- Author
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Gudlur, Sushanth, Sukthankar, Pinakin, Jian Gao, Avila, L. Adriana, Hiromasa, Yasuaki, Chen, Jianhan, Iwamoto, Takeo, Tomich, John M., and Gasset, Maria
- Subjects
PEPTIDES ,DRUG delivery systems ,GLYCERIDES ,MOLECULAR structure ,HYDROGEN bonding ,EPITHELIAL cells - Abstract
Peptide-based packaging systems show great potential as safer drug delivery systems. They overcome problems associated with lipid-based or viral delivery systems, vis-a-vis stability, specificity, inflammation, antigenicity, and tune-ability. Here, we describe a set of 15 & 23-residue branched, amphiphilic peptides that mimic phosphoglycerides in molecular architecture. These peptides undergo supramolecular self-assembly and form solvent-filled, bilayer delimited spheres with 50-200 nm diameters as confirmed by TEM, STEM and DLS. Whereas weak hydrophobic forces drive and sustain lipid bilayer assemblies, these all-peptide structures are stabilized potentially by both hydrophobic interactions and hydrogen bonds and remain intact at low micromolar concentrations and higher temperatures. A linear peptide lacking the branch point showed no self-assembly properties. We have observed that these peptide vesicles can trap fluorescent dye molecules within their interior and are taken up by N/N 1003A rabbit lens epithelial cells grown in culture. These assemblies are thus potential drug delivery systems that can overcome some of the key limitations of the current packaging systems. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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20. Gliadin Peptides Induce Tissue Transglutaminase Activation and ER-Stress through Ca2+ Mobilization in Caco-2 Cells.
- Author
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Caputo, Ivana, Secondo, Agnese, Lepretti, Marilena, Paolella, Gaetana, Auricchio, Salvatore, Barone, Maria Vittoria, Esposito, Carla, and Gasset, Maria
- Subjects
CELIAC disease ,GLIADINS ,POST-translational modification ,LIVER diseases ,CROSSLINKING (Polymerization) ,POLYMERASE chain reaction - Abstract
Background: Celiac disease (CD) is an intestinal inflammatory condition that develops in genetically susceptible individuals after exposure to dietary wheat gliadin. The role of post-translational modifications of gliadin catalyzed by tissue transglutaminase (tTG) seems to play a crucial role in CD. However, it remains to be established how and where tTG is activated in vivo. We have investigated whether gliadin peptides modulate intracellular Ca
2+ homeostasis and tTG activity. Methods/Principal Findings: We studied Ca2+ homeostasis in Caco-2 cells by single cell microfluorimetry. Under our conditions, A-gliadin peptides 31-43 and 57-68 rapidly mobilized Ca2+ from intracellular stores. Specifically, peptide 31-43 mobilized Ca2+ from the endoplasmic reticulum (ER) and mitochondria, whereas peptide 57-68 mobilized Ca2+ only from mitochondria. We also found that gliadin peptide-induced Ca2+ mobilization activates the enzymatic function of intracellular tTG as revealed by in situ tTG activity using the tTG substrate pentylamine-biotin. Moreover, we demonstrate that peptide 31-43, but not peptide 57-68, induces an increase of tTG expression. Finally, we monitored the expression of glucose- regulated protein-78 and of CCAAT/enhancer binding protein-homologous protein, which are two biochemical markers of ER-stress, by real-time RT-PCR and western blot. We found that chronic administration of peptide 31-43, but not of peptide 57-68, induces the expression of both genes. Conclusions: By inducing Ca2+ mobilization from the ER, peptide 31-43 could promote an ER-stress pathway that may be relevant in CD pathogenesis. Furthermore, peptides 31-43 and 57-68, by activating intracellular tTG, could alter inflammatory key regulators, and induce deamidation of immunogenic peptides and gliadin-tTG crosslinking in enterocytes and specialized antigen-presenting cells. [ABSTRACT FROM AUTHOR]- Published
- 2012
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21. Intracellular Context Affects Levels of a Chemically Dependent Destabilizing Domain.
- Author
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Sellmyer, Mark A., Ling-chun Chen, Egeler, Emily L., Rakhit, Rishi, Wandless, Thomas J., and Gasset, Maria
- Subjects
PROTEIN research ,ENDOPLASMIC reticulum ,CYTOLOGICAL research ,MAMMALIAN cell cycle ,MAMMALOGICAL research ,CYTOPLASM - Abstract
The ability to regulate protein levels in live cells is crucial to understanding protein function. In the interest of advancing the tool set for protein perturbation, we developed a protein destabilizing domain (DD) that can confer its instability to a fused protein of interest. This destabilization and consequent degradation can be rescued in a reversible and dose-dependent manner with the addition of a small molecule that is specific for the DD, Shield-1. Proteins encounter different local protein quality control (QC) machinery when targeted to cellular compartments such as the mitochondrial matrix or endoplasmic reticulum (ER). These varied environments could have profound effects on the levels and regulation of the cytoplasmically derived DD. Here we show that DD fusions in the cytoplasm or nucleus can be efficiently degraded in mammalian cells; however, targeting fusions to the mitochondrial matrix or ER lumen leads to accumulation even in the absence of Shield-1. Additionally, we characterize the behaviour of the DD with perturbants that modulate protein production, degradation, and local protein QC machinery. Chemical induction of the unfolded protein response in the ER results in decreased levels of an ER-targeted DD indicating the sensitivity of the DD to the degradation environment. These data reinforce that DD is an effective tool for protein perturbation, show that the local QC machinery affects levels of the DD, and suggest that the DD may be a useful probe for monitoring protein quality control machinery. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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- View/download PDF
22. Development of the Fc-III Tagged Protein Expression System for Protein Purification and Detection.
- Author
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Shan Feng, Enbing Tian, Lei Zhang, Qingtao Wang, Haiteng Deng, and Gasset, Maria
- Subjects
PROTEINS ,PEPTIDES ,IMMUNOGLOBULINS ,ESCHERICHIA coli ,BIOCHEMISTRY ,PROTEOMICS - Abstract
In the present work, we developed the Fc-III tagged protein expression system for protein purification and detection. The Fc-III sequence encodes for a 13 residue peptide and this peptide is cyclized by disulfide bond formation when the fusion protein is expressed. The Fc-III-fusion proteins selectively bind to immunoglobulin Fc domains (IgG-Fc) expressed from E. coli. We showed the efficient purification of Fc-III tagged proteins by immobilized non-native IgG- Fc and the detection of the cellular locations of fusion proteins by fluorescent-conjugated IgG-Fc. Our results prove that Fc-III tagged protein expression system is a simple and efficient tool for protein purification and detection and is a useful addition to the biochemistry and proteomics toolbox. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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23. Expression and In Situ Localization of Two Major PR Proteins of Grapevine Berries during Development and after UV-C Exposition.
- Author
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Colas, Steven, Afoufa-Bastien, Damien, Jacquens, Lucile, Clément, Christophe, Baillieul, Fabienne, Mazeyrat-Gourbeyre, Florence, Monti-Dedieu, Laurence, and Gasset, Maria
- Subjects
VITIS vinifera ,PLANT development ,PLANT defenses ,GENE expression in plants ,IN situ hybridization ,GENETIC regulation in plants - Abstract
In grapevine Vitis vinifera L. cv Pinot noir, the Pathogenesis-Related (PR) proteins CHI4D and TL3 are among the most abundant extractable PR proteins of ripe berries and accumulate during berry ripening from véraison until full maturation. Evidence was supplied in favor of the involvement of these two protein families in plant defense mechanisms and plant development. In order to better understand CHI4D and TL3 function in grapevine, we analyzed their temporal and spatial pattern of expression during maturation and after an abiotic stress (UV-C) by in situ hybridization (ISH) and immunohistolocalization. In ripening berries, CHI4D and TL3 genes were mainly expressed in the exocarp and around vascular bundles of the mesocarp. In UV-C exposed berries, CHI4D and TL3 gene expression was strongly induced before ve´raison. Corresponding proteins localized in the exocarp and, to a lesser extent, around vascular bundles of the mesocarp. The spatial and temporal accumulation of the two PR proteins during berry maturation and after an abiotic stress is discussed in relation to their putative roles in plant defense. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
24. Organic and Inorganic Carbon in Paddy Soil as Evaluated by Mid-Infrared Photoacoustic Spectroscopy.
- Author
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Changwen, Du, Zhou Jianmin, Goyne, Keith W., and Gasset, Maria
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SOILS ,WETLANDS ,CLIMATE change ,FOOD production ,HUMUS ,ATMOSPHERE ,FOURIER transforms - Abstract
Paddy soils are classified as wetlands which play a vital role in climatic change and food production. Soil carbon (C), especially soil organic C (SOC), in paddy soils has been received considerable attention as of recent. However, considerably less attention has been given to soil inorganic carbon (SIC) in paddy soils and the relationship between SOC and SIC at interface between soil and the atmosphere. The objective of this research was to investigate the utility of applying Fourier transform mid-infrared photoacoustic spectroscopy (FTIR-PAS) to explore SOC and SIC present near the surface (0-10 µm) of paddy soils. The FTIR-PAS spectra revealed an unique absorption region in the wavenumber range of 1,350-1,500 cm
-1 that was dominated by C-O (carbonate) and C-H bending vibrations (organic materials), and these vibrations were used to represented SIC and SOC, respectively. A circular distribution between SIC and SOC on the surface of paddy soils was determined using principal component analysis (PCA), and the distribution showed no significant relationship with the age of paddy soil. However, SIC and SOC were negatively correlated, and higher SIC content was observed near the soil surface. This relationship suggests that SIC in soil surface plays important roles in the soil C dynamics. [ABSTRACT FROM AUTHOR]- Published
- 2012
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- View/download PDF
25. Atmospheric Pressure Plasma: A High-Performance Tool for the Efficient Removal of Biofilms.
- Author
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Fricke, Katja, Koban, Ina, Tresp, Helena, Jablonowski, Lukasz, Schröder, Karsten, Kramer, Axel, Weltmann, Klaus-Dieter, von Woedtke, Thomas, Kocher, Thomas, and Gasset, Maria
- Subjects
PLASMA gases ,BIOMEDICAL materials ,MICROORGANISMS ,MEDICAL care ,BIOFILMS ,SPECTRUM analysis - Abstract
The medical use of non-thermal physical plasmas is intensively investigated for sterilization and surface modification of biomedical materials. A further promising application is the removal or etching of organic substances, e.g., biofilms, from surfaces, because remnants of biofilms after conventional cleaning procedures are capable to entertain inflammatory processes in the adjacent tissues. In general, contamination of surfaces by micro-organisms is a major source of problems in health care. Especially biofilms are the most common type of microbial growth in the human body and therefore, the complete removal of pathogens is mandatory for the prevention of inflammatory infiltrate. Physical plasmas offer a huge potential to inactivate micro-organisms and to remove organic materials through plasma-generated highly reactive agents. Method: In this study a Candida albicans biofilm, formed on polystyrene (PS) wafers, as a prototypic biofilm was used to verify the etching capability of the atmospheric pressure plasma jet operating with two different process gases (argon and argon/oxygen mixture). The capability of plasma-assisted biofilm removal was assessed by microscopic imaging. Results: The Candida albicans biofilm, with a thickness of 10 to 20 mm, was removed within 300 s plasma treatment when oxygen was added to the argon gas discharge, whereas argon plasma alone was practically not sufficient in biofilm removal. The impact of plasma etching on biofilms is localized due to the limited presence of reactive plasma species validated by optical emission spectroscopy. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
26. Proteome Analysis of the UVB-Resistant Marine Bacterium Photobacterium angustum S14.
- Author
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Matallana-Surget, Sabine, Joux, Fabien, Wattiez, Ruddy, Lebaron, Philippe, and Gasset, Maria
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PHOTOBACTERIUM ,ULTRAVIOLET radiation ,CELL growth ,PROTEINS ,BIOMARKERS ,ANTIOXIDANTS ,CARRIER proteins ,MARINE organisms - Abstract
The proteome of the marine bacterium Photobacterium angustum S14 was exposed to UVB and analyzed by the implementation of both the post-digest ICPL labeling method and 2D-DIGE technique using exponentially growing cells. A total of 40 and 23 proteins were quantified in all replicates using either the ICPL or 2D-DIGE methods, respectively. By combining both datasets from 8 biological replicates (4 biological replicates for each proteomics technique), 55 proteins were found to respond significantly to UVB radiation in P. angustum. A total of 8 UVB biomarkers of P. angustum were quantified in all replicates using both methods. Among them, the protein found to present the highest increase in abundance (almost a 3-fold change) was RecA, which is known to play a crucial role in the so-called recombinational repair process. We also observed a high number of antioxidants, transport proteins, metabolism-related proteins, transcription/ translation regulators, chaperonins and proteases. We also discuss and compare the UVB response and global protein expression profiles obtained for two different marine bacteria with trophic lifestyles: the copiotroph P. angustum and oligotroph Sphingopyxis alaskensis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
27. Enhanced Cellulose Degradation Using Cellulase-Nanosphere Complexes.
- Author
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Blanchette, Craig, Lacayo, Catherine I., Fischer, Nicholas O., Hwang, Mona, Thelen, Michael P., and Gasset, Maria
- Subjects
ENZYMES ,PLANT biomass ,SUGARS ,BIOMASS energy ,POLYMERS ,PLANT cell walls ,CELLULOSE ,CELLULOSOMES - Abstract
Enzyme catalyzed conversion of plant biomass to sugars is an inherently inefficient process, and one of the major factors limiting economical biofuel production. This is due to the physical barrier presented by polymers in plant cell walls, including semi-crystalline cellulose, to soluble enzyme accessibility. In contrast to the enzymes currently used in industry, bacterial cellulosomes organize cellulases and other proteins in a scaffold structure, and are highly efficient in degrading cellulose. To mimic this clustered assembly of enzymes, we conjugated cellulase obtained from Trichoderma viride to polystyrene nanospheres (cellulase:NS) and tested the hydrolytic activity of this complex on cellulose substrates from purified and natural sources. Cellulase:NS and free cellulase were equally active on soluble carboxymethyl cellulose (CMC); however, the complexed enzyme displayed a higher affinity in its action on microcrystalline cellulose. Similarly, we found that the cellulase:NS complex was more efficient in degrading natural cellulose structures in the thickened walls of cultured wood cells. These results suggest that nanoparticle-bound enzymes can improve catalytic efficiency on physically intractable substrates. We discuss the potential for further enhancement of cellulose degradation by physically clustering combinations of different glycosyl hydrolase enzymes, and applications for using cellulase:NS complexes in biofuel production. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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28. Spectroscopic Characterization of Conformational Differences between PrP<latex>$^{\text{C}}$</latex> and PrP<latex>$^{\text{Sc}}$</latex>: An <latex>$\alpha $</latex>-helix to <latex>$\beta $</latex>-sheet Transition.
- Author
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Baldwin, Michael A., Pan, Keh-Ming, Nguyen, Jack, Huang, Ziwei, Groth, Darlene, Serban, Ana, Gasset, Maria, Mehlhorn, Ingrid, Fletterick, Robert J., Cohen, Fred E., and Prusiner, Stanley B.
- Published
- 1994
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29. Influence of cholesterol on gramicidin-induced HII phase formation in phosphatidylcholine model membranes
- Author
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Gasset, Maria, primary, Killian, J.Antoinette, additional, Tournois, Huibert, additional, and de Kruijff, Ben, additional
- Published
- 1988
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30. Biochemical and conformational characterisation of HSP-3, a stallion seminal plasma protein of the cysteine-rich secretory protein (CRISP) family
- Author
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Magdaleno, Leticia, Gasset, Marı́a, Varea, Julio, Schambony, Alexandra M, Urbanke, Claus, Raida, Manfred, Töpfer-Petersen, Edda, and Calvete, Juan J
- Published
- 1997
- Full Text
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31. Membrane insertion for the detection of lipopolysaccharides: Exploring the dynamics of amphiphile-in-lipid assays
- Author
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Gasset, Maria [Consejo Superior de Investigaciones Cientificas (Spain)]
- Published
- 2016
- Full Text
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32. PrPSc Incorporation to Cells Requires Endogenous Glycosaminoglycan Expression.
- Author
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Hijazi, Nuha, Kariv-Inbal, Zehavit, Gasset, Maria, and Gabizon, Ruth
- Subjects
- *
GLYCOSAMINOGLYCANS , *MUCOPOLYSACCHARIDES , *PROTEOMICS , *CELLS , *PROTEINS , *COMMUNICABLE diseases , *HEPARIN , *ANTICOAGULANTS , *PROTEOLYTIC enzymes - Abstract
Many lines of evidence suggest an interaction between glycosaminoglycans (GAGs) and the PrP proteins as well as a possible role for GAGs in prion disease pathogenesis. In this work, we sought to determine whether the PrP. GAG interaction affects the incorporation of PrPSc (the scrapie isoform of PrP) to normal cells. This may be the first step in prion disease pathogenesis. To this effect, we incubated proteinase K-digested hamster scrapie brain homogenates with several lines of Chinese hamster ovary (CHO) cells in the presence or absence of heparin. Our results show that over a large range of PrPSc concentrations the binding of PrPSc to wild type CHO cells, which do not express detectable PrP, was equivalent to the binding of PrPSc to CHO cells overexpressing PrP. A significant part of PrPSc binding to both lines could be inhibited by heparin. Additional evidence that PrPSc binding to cells was dependent on the presence of GAGs could be concluded from the fact that the binding of PrPSc to CHO cells missing GAGs on the cell surface was significantly reduced. Interestingly, preincubation of scrapie brain homogenate with heparin before intraperitoneal inoculation into normal hamsters resulted in a significant delay in prion disease manifestation. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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- View/download PDF
33. El impacto familiar del síndrome de Down: Desarrollo y validación de la escala de impacto familiar del síndrome de Down (Serrano, 2017) y elaboración de un manual de orientación y apoyo para familias y padres con hijos con síndrome Down
- Author
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Serrano Fernández, Laura, Izuzquiza Gasset, Maria Dolores (dir.), UAM. Departamento de Didáctica y Teoría de la Educación, Izuzquiza Gasset, Maria Dolores, Universidad Autónoma de Madrid. Facultad de Formación de Profesorado y Educación, Departamento de Didáctica y Teoría de la Educación, C/ Francisco Tomás y Valiente, 3, 28049 Madrid, Tel.+34914974493, and Izuzquiza Gasset, María Dolores
- Subjects
Down, Síndrome de - Manuales - Tesis doctorales ,orientación pedagógica ,ambiente familiar ,educación especial ,Educación ,Síndrome de Down ,Down, Síndrome de - Abstract
La presencia de la discapacidad en un miembro de la familia ocasiona transformaciones en los roles familiares, así como en su dinámica. El objetivo de esta tesis es crear y validar un instrumento de evaluación del impacto que un miembro con síndrome de Down (SD) provoca, tanto en las principales dimensiones de la rutina familiar, como en los miembros que la conforman y la elaboración de un manual de apoyo y orientación a las familias. Para ello, se ha optado por un diseño metodológico mixto, con una primera fase cualitativa en la que se busca desarrollar los ítems de la escala y concretar las principales áreas de impacto familiar, y una segunda etapa cuantitativa en la que se procede a la validación de la escala. Durante la fase cualitativa se han efectuado entrevistas semiestructuradas a cuatro profesionales del ámbito de la educación especial y a tres padres y tres madres con un hijo con SD, a partir de las cuáles se ha elaborado una escala piloto. En la etapa cuantitativa, la escala piloto se ha remitido a una muestra de 31 personas como paso previo a la elaboración de una versión definitiva validada por una muestra de 117 individuos. Como resultado se ha desarrollado una versión definitiva del instrumento que cuenta con 30 ítems que presenta un alfa de Cronbach de 0,783, y se ha certificado asimismo su validez de constructo. El análisis factorial de la escala ha determinado la existencia de cinco dimensiones de impacto diferenciadas. Los resultados de la escala y de la fase cualitativa coinciden en señalar un impacto heterogéneo que implica tanto puntos positivos como negativos, a partir de los que se ha elaborado un manual de apoyo y orientación a las familias. Madrid ESP
- Published
- 2018
34. Myelin Organization in the Nodal, Paranodal, and Juxtaparanodal Regions Revealed by Scanning X-Ray Microdiffraction
- Author
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Gasset, Maria
- Published
- 2014
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35. Aptamarker prediction of brain amyloid-β status in cognitively normal individuals at risk for Alzheimer’s disease
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Penner, G, Lecocq, S, Chopin, A, Vedoya, X, Lista, S, Vergallo, A, Cavedo, E, Lejeune, F, Dubois, B, Hampel, H, Bakardjian, H, Benali, H, Bertin, H, Bonheur, J, Boukadida, L, Boukerrou, N, Chiesa, Pa, Colliot, O, Dubois, M, Epelbaum, S, Gagliardi, G, Genthon, R, Habert, M, Houot, M, Kas, A, Lamari, F, Levy, M, Metzinger, C, Mochel, F, Nyasse, F, Poisson, C, Potier, M, Revillon, M, Santos, A, Andrade, Ks, Sole, M, Surtee, M, de Schotten, Mt, Younsi, N, Afshar, M, Aguilar, Lf, Akman-Anderson, L, Aremas, J, Avila, J, Babiloni, C, Baldacci, F, Batrla, R, Benda, N, Black, Kl, Bokde, Alw, Bonuccelli, U, Broich, K, Cacciola, F, Caraci, F, Caruso, G, Castrillo, J, Ceravolo, R, Corbo, M, Corvol, J, Cuello, Ac, Cummings, Jl, Depypere, H, Duggento, A, Emanuele, E, Escott-Price, V, Federoff, H, Ferretti, Mt, Fiandaca, M, Frank, Ra, Garaci, F, Geerts, H, Giacobini, E, Giorgi, Fs, Goetzl, Ej, Graziani, M, Haberkamp, M, Hanisch, B, Herholz, K, Hernandez, F, Imbimbo, Bp, Kapogiannis, D, Karran, E, Kiddle, Sj, Kim, Sh, Koronyo, Y, Koronyo-Hamaoui, M, Langevin, T, Lehericy, S, Lemercier, P, Llavero, F, Lorenceau, J, Lucia, A, Mango, D, Mapstone, M, Neri, C, Nistico, R, O'Bryant, Se, Palermo, G, Perry, G, Ritchie, C, Rossi, S, Saidi, A, Santarnecchi, E, Schneider, Ls, Sporns, O, Toschi, N, Valenzuela, Pl, Vellas, B, Verdooner, Sr, Villain, N, Giudici, Kv, Watling, M, Welikovitch, La, Woodcock, J, Younesi, E, Zugaza, Jl, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gasset, Maria
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Male ,Aging ,Amyloid β ,MESH: SELEX Aptamer Technique ,[SDV]Life Sciences [q-bio] ,Oligonucleotides ,Artificial Gene Amplification and Extension ,Disease ,Neurodegenerative ,Alzheimer's Disease ,Pathology and Laboratory Medicine ,Biochemistry ,Polymerase Chain Reaction ,Diagnostic Radiology ,Negative selection ,Medical Conditions ,Mathematical and Statistical Techniques ,0302 clinical medicine ,MESH: Aged, 80 and over ,MESH: Early Diagnosis ,80 and over ,Medicine and Health Sciences ,Biomarker discovery ,Tomography ,Aged, 80 and over ,MESH: Aged ,screening and diagnosis ,0303 health sciences ,Multidisciplinary ,Nucleotides ,Mathematical Models ,Radiology and Imaging ,SELEX Aptamer Technique ,Settore MED/37 - Neuroradiologia ,Neurodegenerative Diseases ,MESH: Case-Control Studies ,MESH: Amyloid beta-Peptides ,Detection ,Neurology ,Neurological ,Medicine ,Biomedical Imaging ,Female ,Biotechnology ,4.2 Evaluation of markers and technologies ,Research Article ,Amyloid ,General Science & Technology ,Imaging Techniques ,Science ,Aptamer ,Neuroimaging ,and over ,Computational biology ,Biology ,Research and Analysis Methods ,03 medical and health sciences ,Clinical Research ,Diagnostic Medicine ,Alzheimer Disease ,Mental Health and Psychiatry ,Acquired Cognitive Impairment ,Humans ,Risk factor ,Molecular Biology Techniques ,Molecular Biology ,Aged ,030304 developmental biology ,Amyloid beta-Peptides ,MESH: Humans ,Prevention ,Neurosciences ,Alzheimer Precision Medicine Initiative ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Biology and Life Sciences ,Omics ,MESH: Male ,Brain Disorders ,4.1 Discovery and preclinical testing of markers and technologies ,Early Diagnosis ,Case-Control Studies ,MESH: Biomarkers ,Dementia ,INSIGHT-preAD study group ,MESH: Female ,Biomarkers ,Positron Emission Tomography ,030217 neurology & neurosurgery ,MESH: Alzheimer Disease ,Neuroscience - Abstract
International audience; The traditional approach to biomarker discovery for any pathology has been through hypothesis-based research one candidate at a time. The objective of this study was to develop an agnostic approach for the simultaneous screening of plasma for consistent molecular differences between a group of individuals exhibiting a pathology and a group of healthy individuals. To achieve this, we focused on developing a predictive tool based on plasma for the amount of brain amyloid-β deposition as observed in PET scans. The accumulation of brain amyloid-β (Aβ) plaques is a key risk factor for the development of Alzheimer's disease. A contrast was established between cognitively normal individuals above the age of 70 that differed for the amount of brain amyloid-β observed in PET scans (INSIGHT study group). Positive selection was performed against a pool of plasma from individuals with high brain amyloid and negative selection against a pool of plasma from individuals with low brain amyloid This enriched, selected library was then applied to plasma samples from 11 individuals with high levels of brain amyloid and 11 individuals with low levels of brain Aβ accumulation. Each of these individually selected libraries was then characterized by next generation sequencing, and the relative frequency of 10,000 aptamer sequences that were observed in each selection was screened for ability to explain variation in brain amyloid using sparse partial least squares discriminant analysis. From this analysis a subset of 44 aptamers was defined, and the individual aptamers were synthesized. This subset was applied to plasma samples from 70 cognitively normal individuals all above the age of 70 that differed for brain amyloid deposition. 54 individuals were used as a training set, and 15 as a test set. Three of the 15 individuals in the test set were mis-classified resulting in an overall accuracy of 80% with 86% sensitivity and 75% specificity. The aptamers included in the subset serve directly as biomarkers, thus we have named them Aptamarkers. There are two potential applications of these results: extending the predictive capacity of these aptamers across a broader range of individuals, and/or using the individual aptamers to identify targets through covariance analysis and reverse omics approaches. We are currently expanding applications of the Aptamarker platform to other diseases and target matrices.
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- 2021
36. Boronate complex formation with Dopa containing mussel adhesive protein retards ph-induced oxidation and enables adhesion to mica
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J. Herbert Waite, Yunfei Chen, Jacob N. Israelachvili, Eric Danner, Yajing Kan, and Gasset, Maria
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General Science & Technology ,Materials Science ,Biophysics ,lcsh:Medicine ,02 engineering and technology ,010402 general chemistry ,Biochemistry ,Protein Chemistry ,01 natural sciences ,Redox ,Biomaterials ,Acetic acid ,chemistry.chemical_compound ,Adhesives ,Oxidation ,Oxidizing agent ,Polymer chemistry ,Animals ,Post-Translational Modification ,Protein Interactions ,lcsh:Science ,chemistry.chemical_classification ,Multidisciplinary ,Chemistry ,Physics ,lcsh:R ,Chemical Reactions ,Proteins ,Biology and Life Sciences ,Polymer ,Adhesion ,021001 nanoscience & nanotechnology ,Boronic Acids ,Dihydroxyphenylalanine ,0104 chemical sciences ,Amino acid ,Mollusca ,Covalent bond ,Physical Sciences ,Aluminum Silicates ,lcsh:Q ,Structural Proteins ,Adhesive ,0210 nano-technology ,Research Article ,Biotechnology - Abstract
© 2014 Kan et al. The biochemistry of mussel adhesion has inspired the design of surface primers, adhesives, coatings and gels for technological applications. These mussel-inspired systems often focus on incorporating the amino acid 3,4-dihydroxyphenyl-L-alanine (Dopa) or a catecholic analog into a polymer. Unfortunately, effective use of Dopa is compromised by its susceptibility to auto-oxidation at neutral pH. Oxidation can lead to loss of adhesive function and undesired covalent cross-linking. Mussel foot protein 5 (Mfp-5), which contains ∼30 mole % Dopa, is a superb adhesive under reducing conditions but becomes nonadhesive after pH-induced oxidation. Here we report that the bidentate complexation of borate by Dopa to form a catecholato-boronate can be exploited to retard oxidation. Although exposure of Mfp-5 to neutral pH typically oxidizes Dopa, resulting in a
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- 2014
37. Expression and characterization of Drosophila signal peptide peptidase-like (sppL), a gene that encodes an intramembrane protease
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Brian Biehs, Thomas B. Kornberg, David J. Casso, Songmei Liu, and Gasset, Maria
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Enzymologic ,lcsh:Medicine ,Sequence Homology ,Genes, Insect ,Biochemistry ,Animals, Genetically Modified ,0302 clinical medicine ,Complementary ,Catalytic Domain ,Molecular Cell Biology ,Drosophila Proteins ,Aspartic Acid Endopeptidases ,Developmental ,Cloning, Molecular ,lcsh:Science ,Peptide sequence ,Phylogeny ,Regulation of gene expression ,Genetics ,0303 health sciences ,Multidisciplinary ,biology ,Gene Expression Regulation, Developmental ,Amino Acid ,Drosophila melanogaster ,Essential gene ,Signal peptide peptidase ,Drosophila Protein ,Research Article ,Subcellular Fractions ,Biotechnology ,Proteases ,Protein Structure ,DNA, Complementary ,Intramembrane protease ,General Science & Technology ,1.1 Normal biological development and functioning ,Molecular Sequence Data ,Genetically Modified ,Gene Expression Regulation, Enzymologic ,Molecular Genetics ,03 medical and health sciences ,Underpinning research ,Animals ,Humans ,Amino Acid Sequence ,Biology ,030304 developmental biology ,Sequence Homology, Amino Acid ,Base Sequence ,lcsh:R ,Proteins ,Molecular ,DNA ,biology.organism_classification ,Protein Structure, Tertiary ,Gene Expression Regulation ,Genes ,Mutation ,biology.protein ,Unfolded Protein Response ,lcsh:Q ,Generic health relevance ,Insect ,030217 neurology & neurosurgery ,Tertiary ,Developmental Biology ,Cloning - Abstract
Intramembrane proteases of the Signal Peptide Peptidase (SPP) family play important roles in developmental, metabolic and signaling pathways. Although vertebrates have one SPP and four SPP-like (SPPL) genes, we found that insect genomes encode one Spp and one SppL. Characterization of the Drosophila sppL gene revealed that the predicted SppL protein is a highly conserved structural homolog of the vertebrate SPPL3 proteases, with a predicted nine-transmembrane topology, an active site containing aspartyl residues within a transmembrane region, and a carboxy-terminal PAL domain. SppL protein localized to both the Golgi and ER. Whereas spp is an essential gene that is required during early larval stages and whereas spp loss-of-function reduced the unfolded protein response (UPR), sppL loss of function had no apparent phenotype. This was unexpected given that genetic knockdown phenotypes in other organisms suggested significant roles for Spp-related proteases.
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- 2012
38. Oligomerization of ZFYVE27 (Protrudin) Is Necessary to Promote Neurite Extension
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Anna Sikorska, Ashraf U. Mannan, Marta M. Czyzewska, D. V. Krishna Pantakani, Chiranjeevi Bodda, Gasset, Maria, and Biology
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Cytoplasm ,Anatomy and Physiology ,Vesicular Transport Proteins ,lcsh:Medicine ,Spastin ,Biochemistry ,Polyethylene Glycols ,Motor Neuron Diseases ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Biopolymers ,Molecular Cell Biology ,Neurobiology of Disease and Regeneration ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Neuronal Morphology ,Peripheral membrane protein ,Neurochemistry ,Neurodegenerative Diseases ,Cellular Structures ,Cell biology ,Neurology ,Medicine ,Research Article ,Subcellular Fractions ,Neurite ,Immunoprecipitation ,Octoxynol ,ZFYVE27 (Protrudin) ,Neurogenesis ,Biology ,spastic paraplegia ,neurite extensions ,Neurological System ,Protein–protein interaction ,03 medical and health sciences ,Tetramer ,Two-Hybrid System Techniques ,Genetics ,Neurites ,Animals ,Phosphatidylinositol ,030304 developmental biology ,lcsh:R ,chemistry ,Cellular Neuroscience ,NIH 3T3 Cells ,lcsh:Q ,Carrier Proteins ,030217 neurology & neurosurgery ,Neuroscience - Abstract
ZFYVE27 (Protrudin) was originally identified as an interacting partner of spastin, which is most frequently mutated in hereditary spastic paraplegia. ZFYVE27 is a novel member of FYVE family, which is implicated in the formation of neurite extensions by promoting directional membrane trafficking in neurons. Now, through a yeast two-hybrid screen, we have identified that ZFYVE27 interacts with itself and the core interaction region resides within the third hydrophobic region (HR3) of the protein. We confirmed the ZFYVE27’s self-interaction in the mammalian cells by co-immunoprecipitation and co-localization studies. To decipher the oligomeric nature of ZFYVE27, we performed sucrose gradient centrifugation and showed that ZFYVE27 oligomerizes into dimer/tetramer forms. Sub-cellular fractionation and Triton X-114 membrane phase separation analysis indicated that ZFYVE27 is a peripheral membrane protein. Furthermore, ZFYVE27 also binds to phosphatidylinositol 3-phosphate lipid moiety. Interestingly, cells expressing ZFYVE27DHR3 failed to produce protrusions instead caused swelling of cell soma. When ZFYVE27DHR3 was co-expressed with wild-type ZFYVE27 (ZFYVE27WT), it exerted a dominant negative effect on ZFYVE27WT as the cells co-expressing both proteins were also unable to induce protrusions and showed cytoplasmic swelling. Altogether, it is evident that a functionally active form of oligomer is crucial for ZFYVE27 ability to promote neurite extensions. peerReviewed
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- 2011
39. A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence on Caenorhabditis elegans
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Hinrich Schulenburg, Wolfgang R. Streit, Hubert Mayerhofer, Patrick Bijtenhoorn, Jochen Müller-Dieckmann, Stephanie Grond, Rolf Daniel, Katja Dierking, Christina Schipper, Andrea Thürmer, Elzbieta Brzuszkiewicz, Matthias Szesny, Christian Utpatel, Claudia Hornung, and Gasset, Maria
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Bacterial Diseases ,Reductase ,medicine.disease_cause ,Biochemistry ,chemistry.chemical_compound ,Molecular Cell Biology ,0303 health sciences ,Multidisciplinary ,Virulence ,Enzyme Classes ,Quorum Sensing ,food and beverages ,Animal Models ,Enzymes ,Infectious Diseases ,Quorum Quenching ,biofilm ,bacteria ,Caenorhabditis elegans ,Pseudomonas aeruginosa ,Medicine ,Oxidoreductases ,Research Article ,Signal Transduction ,Science ,Biology ,Microbiology ,Molecular Genetics ,03 medical and health sciences ,Pyocyanin ,Model Organisms ,Bacterial Proteins ,medicine ,Genetics ,Animals ,Gene Regulation ,Pseudomonas Infections ,030304 developmental biology ,030306 microbiology ,Gene Expression Profiling ,Biofilm ,Bacteriology ,biochemical phenomena, metabolism, and nutrition ,Quorum sensing ,chemistry ,Biofilms ,Pyocyanine ,Heterologous expression ,Metagenomics ,Bacterial Biofilms ,NADP - Abstract
In Pseudomonas aeruginosa, the expression of a number of virulence factors, as well as biofilm formation, are controlled by quorum sensing (QS). N-Acylhomoserine lactones (AHLs) are an important class of signaling molecules involved in bacterial QS and in many pathogenic bacteria infection and host colonization are AHL-dependent. The AHL signaling molecules are subject to inactivation mainly by hydrolases (Enzyme Commission class number EC 3) (i.e. N-acyl-homoserine lactonases and N-acyl-homoserine-lactone acylases). Only little is known on quorum quenching mechanisms of oxidoreductases (EC 1). Here we report on the identification and structural characterization of the first NADP-dependent short-chain dehydrogenase/reductase (SDR) involved in inactivation of N-(3-oxo-dodecanoyl)-L-homoserine lactone (3-oxo-C(12)-HSL) and derived from a metagenome library. The corresponding gene was isolated from a soil metagenome and designated bpiB09. Heterologous expression and crystallographic studies established BpiB09 as an NADP-dependent reductase. Although AHLs are probably not the native substrate of this metagenome-derived enzyme, its expression in P. aeruginosa PAO1 resulted in significantly reduced pyocyanin production, decreased motility, poor biofilm formation and absent paralysis of Caenorhabditis elegans. Furthermore, a genome-wide transcriptome study suggested that the level of lasI and rhlI transcription together with 36 well known QS regulated genes was significantly (≥10-fold) affected in P. aeruginosa strains expressing the bpiB09 gene in pBBR1MCS-5. Thus AHL oxidoreductases could be considered as potent tools for the development of quorum quenching strategies.
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- 2011
40. Systematic Exploitation of Multiple Receptor Conformations for Virtual Ligand Screening
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Giovanni Bottegoni, Ruben Abagyan, Walter Rocchia, Andrea Cavalli, Manuel Rueda, Bottegoni G., Rocchia W., Rueda M., Abgyan R., Cavalli A, and Gasset, Maria
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Protein Conformation ,lcsh:Medicine ,Ligands ,Bioinformatics ,Biochemistry ,Computational Chemistry ,Protein structure ,Receptors ,Drug Discovery ,Macromolecular Structure Analysis ,Combinatorial Chemistry Techniques ,Biomacromolecule-Ligand Interactions ,lcsh:Science ,Protocol (object-oriented programming) ,Multidisciplinary ,Drug discovery ,Chemistry ,Physics ,Cell Surface ,Medicine ,Biophysic Al Simulations ,Algorithms ,Research Article ,Biotechnology ,Protein Binding ,Protein Structure ,Drugs and Devices ,Drug Research and Development ,General Science & Technology ,Biophysics ,Receptors, Cell Surface ,Computational biology ,Protein Chemistry ,Chemical Biology ,Humans ,Set (psychology) ,Biology ,Flexibility (engineering) ,Virtual screening ,Ligand ,lcsh:R ,Proteins ,Computational Biology ,Small Molecules ,Drug Design ,lcsh:Q ,Generic health relevance ,Medicinal Chemistry - Abstract
The role of virtual ligand screening in modern drug discovery is to mine large chemical collections and to prioritize for experimental testing a comparatively small and diverse set of compounds with expected activity against a target. Several studies have pointed out that the performance of virtual ligand screening can be improved by taking into account receptor flexibility. Here, we systematically assess how multiple crystallographic receptor conformations, a powerful way of discretely representing protein plasticity, can be exploited in screening protocols to separate binders from non-binders. Our analyses encompass 36 targets of pharmaceutical relevance and are based on actual molecules with reported activity against those targets. The results suggest that an ensemble receptor-based protocol displays a stronger discriminating power between active and inactive molecules as compared to its standard single rigid receptor counterpart. Moreover, such a protocol can be engineered not only to enrich a higher number of active compounds, but also to enhance their chemical diversity. Finally, some clear indications can be gathered on how to select a subset of receptor conformations that is most likely to provide the best performance in a real life scenario.
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- 2011
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