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3. Structural insights into the semiquinone form of human Cytochrome P450 reductase by DEER distance measurements between a native flavin and a spin labelled non‐canonical amino acid.

Author

Bizet, Maxime, Byrne, Deborah, Biaso, Frédéric, Gerbaud, Guillaume, Etienne, Emilien, Briola, Giuseppina, Guigliarelli, Bruno, Urban, Philippe, Dorlet, Pierre, Kalai, Tamas, Truan, Gilles, and Martinho, Marlène

Subjects
*NITROXIDES, *SPIN labels, *CYTOCHROME P-450, *SEMIQUINONE, *ELECTRON paramagnetic resonance spectroscopy, *FLAVIN adenine dinucleotide
Abstract

The flavoprotein Cytochrome P450 reductase (CPR) is the unique electron pathway from NADPH to Cytochrome P450 (CYPs). The conformational dynamics of human CPR in solution, which involves transitions from a "locked/closed" to an "unlocked/open" state, is crucial for electron transfer. To date, however, the factors guiding these changes remain unknown. By Site‐Directed Spin Labelling coupled to Electron Paramagnetic Resonance spectroscopy, we have incorporated a non‐canonical amino acid onto the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) domains of soluble human CPR, and labelled it with a specific nitroxide spin probe. Taking advantage of the endogenous FMN cofactor, we successfully measured for the first time, the distance distribution by DEER between the semiquinone state FMNH• and the nitroxide. The DEER data revealed a salt concentration‐dependent distance distribution, evidence of an "open" CPR conformation at high salt concentrations exceeding previous reports. We also conducted molecular dynamics simulations which unveiled a diverse ensemble of conformations for the "open" semiquinone state of the CPR at high salt concentration. This study unravels the conformational landscape of the one electron reduced state of CPR, which had never been studied before. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Bacterial adaptation to cold: Conservation of a short J‐domain co‐chaperone and its protein partners in environmental proteobacteria.

Author

Weber, Lana, Gilat, Atar, Maillot, Nathanael, Byrne, Deborah, Arnoux, Pascal, Giudici‐Orticoni, Marie‐Thérèse, Méjean, Vincent, Ilbert, Marianne, Genest, Olivier, Rosenzweig, Rina, and Dementin, Sébastien

Subjects
COLD adaptation, BACTERIAL adaptation, OPERONS, MOLECULAR chaperones, SHEWANELLA oneidensis, PROTEOBACTERIA, BACTERIAL genomes
Abstract

Bacterial genomes are a huge reservoir of genes encoding J‐domain protein co‐chaperones that recruit the molecular chaperone DnaK to assist protein substrates involved in survival, adaptation, or fitness. The atc operon of the aquatic mesophilic bacterium Shewanella oneidensis encodes the proteins AtcJ, AtcA, AtcB, and AtcC, and all of them, except AtcA, are required for growth at low temperatures. AtcJ is a short J‐domain protein that interacts with DnaK, but also with AtcC through its 21 amino acid C‐terminal domain. This interaction network is critical for cold growth. Here, we show that AtcJ represents a subfamily of short J‐domain proteins that (i) are found in several environmental, mostly aquatic, β‐ or ɣ‐proteobacteria and (ii) contain a conserved PX7W motif in their C‐terminal extension. Using a combination of NMR, biochemical and genetic approaches, we show that the hydrophobic nature of the tryptophan of the S. oneidensis AtcJ PX7W motif determines the strong AtcJ–AtcC interaction essential for cold growth. The AtcJ homologues are encoded by operons containing at least the S. oneidensis atcA, atcB, and atcC homologues. These findings suggest a conserved network of DnaK and Atc proteins necessary for low‐temperature growth and, given the variation in the atc operons, possibly for other biological functions. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Evidence for [2Fe-2S] 2+ and Linear [3Fe-4S] 1+ Clusters in a Unique Family of Glycine/Cysteine-Rich Fe-S Proteins from Megavirinae Giant Viruses

Author

Villalta, Alejandro, Srour, Batoul, Lartigue, Audrey, Clémancey, Martin, Byrne, Deborah, Chaspoul, Florence, Loquet, Antoine, Guigliarelli, Bruno, Blondin, Geneviève, Abergel, Chantal, Burlat, Bénédicte, Information génomique et structurale (IGS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Bioénergétique et Ingénierie des Protéines (BIP ), Physiochimie des Métaux (PMB), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Institut de Microbiologie de la Méditerranée (IMM), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), ANR-16-CE11-0033,VIRiON,Etude des protéines Fer-Soufre des virus géants à la recherche de réponses sur l'origine de la vie(2016), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and European Project: 832601,Cells and giant viruses: a win-win co-evolution

Subjects
Colloid and Surface Chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, General Chemistry, Supporting Information Placeholder, Biochemistry, Catalysis
Abstract

International audience; We have discovered a protein with an amino acid composition exceptionally rich in glycine and cysteine residues in the giant virus mimivirus. This small 6 kDa protein is among the most abundant proteins in the icosahedral 0.75 μm viral particles; it has no predicted function but is probably essential for infection. The aerobically purified red-brownish protein overproduced inEscherichia coli contained both iron and inorganic sulfide. UV/vis, EPR, and Mössbauer studies revealed that the viral protein, coined GciS, accommodated two distinct Fe-S clusters: a diamagnetic S = 0 [2Fe-2S]2+ cluster and a paramagnetic S = 5/2 linear [3Fe-4S]1+ cluster, a geometry rarely stabilized in native proteins. Orthologs of mimivirus GciS were identified within all clades of Megavirinae, a Mimiviridae subfamily infecting Acanthamoeba, including the distantly related tupanviruses, and displayed the same spectroscopic features. Thus, these glycine/cysteine-rich proteins form a new family of viral Fe-S proteins sharing unique Fe-S cluster binding properties.

Published
2023

13. A qualitative analysis of women's postnatal experiences of breastfeeding supports during the perinatal period in Ireland.

Author

Lawlor, Niamh, Prihodova, Lucia, Byrne, Deborah, Etherton, Megan, Rahill, Felicienne, Wilson, Catie, and O'Sullivan, Elizabeth J.

Subjects
BREASTFEEDING, PERINATAL period, CHILDBIRTH at home, PUERPERIUM, MEDICAL personnel, THEMATIC analysis, OPEN-ended questions
Abstract

Ireland has among the lowest rates of breastfeeding worldwide. Despite policies to support breastfeeding, breastfeeding initiation and exclusivity remain low in Ireland. Greater knowledge about support received in the maternity unit may—in part—shed light on why this is so. Our aim was to analyse women's experiences of the breastfeeding supports available in the early postnatal period in Ireland. We conducted an analysis of an open-ended question on a cross-sectional survey about breastfeeding support conducted in the Republic of Ireland in 2022. Participants were asked to provide comments about the breastfeeding support they received in the maternity unit or during your home birth. Data were analysed using Braun and Clarke's six-step Thematic Analysis Framework. There were 5,412 unique responses to the survey and 2,264 responses to the question of interest. Two themes were generated from the data: (i) 'Breastfeeding support in theory but not in practice.' Although breastfeeding was promoted by healthcare professionals antenatally, breastfeeding challenges were rarely mentioned. Participants then felt unsupported in overcoming challenges postnatally. (ii) 'Support was either inaccessible due to lack of staff/time, inadequate; i.e., unhelpful or non-specific, and/or physically inappropriate.' Most participants described receiving supports that were less than optimal in aiding them to establish breastfeeding. While many described difficulties in accessing supports, others found support to be 'non-specific,' 'rushed' and sometimes 'rough.' A lack of knowledge, time and support from healthcare professionals was frequently described, which was often recognised as a failing of the healthcare system. Women require practical, informative, and specific breastfeeding support. Barriers such as lack of time and trained staff in the maternity unit need to be addressed. [ABSTRACT FROM AUTHOR]

Published
2023
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14. Study of human Cytochrome P450 reductase by Electron Paramagnetic Resonance

Author

Bizet, Maxime, Byrne, Deborah, Gerbaud, Guillaume, Biaso, Frédéric, Dorlet, Pierre, Urban, Philippe, Truan, Gilles, Martinho, Marlène, Bioénergétique et Ingénierie des Protéines (BIP ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Protein Expression and Purification Core Facility, European Molecular Biology Laboratory, Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Biophysics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell Biology, Biochemistry
Abstract

International audience; Human cytochrome P450 reductase is a membrane protein located on the cytoplasmic side of the endoplasmic reticulum. It contains two binding domains for FAD and FMN, which are connected by a flexible region [1]. CPR transfers electrons from NADPH to cytochromes P450 through flavins. Two crystallographic structures were obtained for Rattus norvegicus showing "closed" and "open" conformations [2] These two structures show different distances between the flavin cofactors. Indeed, for inter-flavin Electronic Transfer (ET), the two FAD and FMN domains must be nearby (a "closed" conformation), but inter-protein ET (FMN to CYPs) requires a more "open" conformation. The understanding and characterization of domain movement associated with ET is essential and will be studied by measuring distances between two paramagnetic centers via two approaches: 1) using endogenous probes by isolating the flavin radical, and 2) by Site-Directed Spin Labeling and EPR, based on the insertion of paramagnetic nitroxide probes. Classically, these are specific to cysteines [3]. However, C566 is involved in the enzymatic activity and cannot be modified. The incorporation of non-natural amino acids and their labelling with specific nitroxides has been shown to be a powerful alternative [4] First experiments on human soluble CPR concerning the labelling of non-natural amino acids, as well as the trapping of flavin centers will be presented.

Published
2022

19. MARC Manual: Understanding and Using MARC Records. Second Edition.

Author

Byrne, Deborah J. and Byrne, Deborah J.

Abstract

The MARC (Machine-Readable Cataloging) format allows the capability of accessing library catalog records by any piece of information found in the catalog record. A library's MARC database is its most expensive investment in library automation, and the most crucial factor in the success of the library's automation. Intended for librarians or students new to MARC as well as more experienced MARC users, this book explains what MARC is and how it works, and offers a background on MARC database construction and management. This manual explains MARC records, interpreting many of the details that can be encountered in cataloging with or using MARC data. Import considerations and specifications for MARC database processing, MARC products, and online systems are discussed. This second edition provides updated information, and new information on MARC format integration and MARC format for community information. The book is divided into 13 chapters: (1) "MARC Theory and Development"; (2) "MARC Format Structure and Content Designation"; (3) "MARC Format Integration"; (4) "Patterns in the MARC Format"; (5) "Major MARC Bibliographic Codes"; (6) "MARC Records in Electronic Form"; (7) "MARC Database Processing"; (8) "MARC Database Products"; (9) "MARC-Based Online Systems"; (10) "MARC Authority Format"; (11) "MARC Format for Holdings Data"; (12) "MARC Format for Community Information"; and (13) "MARC Use in Different Types of Libraries." Includes a glossary and index. (SWC)

Published
1998

22. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19:The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial

Author

Angus, Derek C, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen C, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa M, Horvat, Christopher, Hullegie, Sebastiaan J, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick R, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, McAuley, Daniel, McGlothin, Anna, McGuinness, Shay, McVerry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger J, McArthur, Colin, Webb, Steven A, Gordon, Anthony C, Writing Committee for the REMAP-CAP Investigators, Angus, Derek, Cheng, Allen, De Jong, Menno, Gordon, Anthony, Lawler, Patrick, Webb, Steve, Campbell, Lewis, Forbes, Andrew, Gattas, David, Heritier, Stephane, Higgins, Lisa, Peake, Sandra, Presneill, Jeffrey, Seppelt, Ian, Trapani, Tony, Young, Paul, Bagshaw, Sean, Daneman, Nick, Ferguson, Niall, Misak, Cheryl, Hullegie, Sebastiaan, Pletz, Mathias, Rohde, Gernot, Rowan, Kathy, Alexander, Brian, Basile, Kim, Girard, Timothy, Huang, David, Vates, Jennifer, Beasley, Richard, Fowler, Robert, McGloughlin, Steve, Morpeth, Susan, Paterson, David, Venkatesh, Bala, Uyeki, Tim, Baillie, Kenneth, Duffy, Eamon, Fowler, Rob, Hills, Thomas, Orr, Katrina, Patanwala, Asad, Tong, Steve, Netea, Mihai, Bihari, Shilesh, Carrier, Marc, Fergusson, Dean, Goligher, Ewan, Haidar, Ghady, Hunt, Beverley, Kumar, Anand, Laffan, Mike, Lawless, Patrick, Lother, Sylvain, McCallum, Peter, Middeldopr, Saskia, McQuilten, Zoe, Neal, Matthew, Pasi, John, Schutgens, Roger, Stanworth, Simon, Turgeon, Alexis, Weissman, Alexandra, Adhikari, Neill, Anstey, Matthew, Brant, Emily, de Man, Angelique, Lamonagne, Francois, Masse, Marie-Helene, Udy, Andrew, Arnold, Donald, Begin, Phillipe, Charlewood, Richard, Chasse, Michael, Coyne, Mark, Cooper, Jamie, Daly, James, Gosbell, Iain, Harvala-Simmonds, Heli, Hills, Tom, MacLennan, Sheila, Menon, David, McDyer, John, Pridee, Nicole, Roberts, David, Shankar-Hari, Manu, Thomas, Helen, Tinmouth, Alan, Triulzi, Darrell, Walsh, Tim, Wood, Erica, Calfee, Carolyn, O’Kane, Cecilia, Shyamsundar, Murali, Sinha, Pratik, Thompson, Taylor, Young, Ian, Bihari, Shailesh, Hodgson, Carol, Laffey, John, McAuley, Danny, Orford, Neil, Neto, Ary, Lewis, Roger, McGlothlin, Anna, Miller, Eliza, Singh, Vanessa, Zammit, Claire, van Bentum Puijk, Wilma, Bouwman, Wietske, Mangindaan, Yara, Parker, Lorraine, Peters, Svenja, Rietveld, Ilse, Raymakers, Kik, Ganpat, Radhika, Brillinger, Nicole, Markgraf, Rene, Ainscough, Kate, Brickell, Kathy, Anjum, Aisha, Lane, Janis-Best, Richards-Belle, Alvin, Saull, Michelle, Wiley, Daisy, Bion, Julian, Connor, Jason, Gates, Simon, Manax, Victoria, van der Poll, Tom, Reynolds, John, van Beurden, Marloes, Effelaar, Evelien, Schotsman, Joost, Boyd, Craig, Harland, Cain, Shearer, Audrey, Wren, Jess, Clermont, Giles, Garrard, William, Kalchthaler, Kyle, King, Andrew, Ricketts, Daniel, Malakoutis, Salim, Marroquin, Oscar, Music, Edvin, Quinn, Kevin, Cate, Heidi, Pearson, Karen, Collins, Joanne, Hanson, Jane, Williams, Penny, Jackson, Shane, Asghar, Adeeba, Dyas, Sarah, Sutu, Mihaela, Murphy, Sheenagh, Williamson, Dawn, Mguni, Nhlanhla, Potter, Alison, Porter, David, Goodwin, Jayne, Rook, Clare, Harrison, Susie, Williams, Hannah, Campbell, Hilary, Lomme, Kaatje, Williamson, James, Sheffield, Jonathan, van’t Hoff, Willian, McCracken, Phobe, Young, Meredith, Board, Jasmin, Mart, Emma, Knott, Cameron, Smith, Julie, Boschert, Catherine, Affleck, Julia, Ramanan, Mahesh, D’Souza, Ramsy, Pateman, Kelsey, Shakih, Arif, Cheung, Winston, Kol, Mark, Wong, Helen, Shah, Asim, Wagh, Atul, Simpson, Joanne, Duke, Graeme, Chan, Peter, Cartner, Brittney, Hunter, Stephanie, Laver, Russell, Shrestha, Tapaswi, Regli, Adrian, Pellicano, Annamaria, McCullough, James, Tallott, Mandy, Kumar, Nikhil, Panwar, Rakshit, Brinkerhoff, Gail, Koppen, Cassandra, Cazzola, Federica, Brain, Matthew, Mineall, Sarah, Fischer, Roy, Biradar, Vishwanath, Soar, Natalie, White, Hayden, Estensen, Kristen, Morrison, Lynette, Smith, Joanne, Cooper, Melanie, Health, Monash, Shehabi, Yahya, Al-Bassam, Wisam, Hulley, Amanda, Whitehead, Christina, Lowrey, Julie, Gresha, Rebecca, Walsham, James, Meyer, Jason, Harward, Meg, Venz, Ellen, Williams, Patricia, Kurenda, Catherine, Smith, Kirsy, Smith, Margaret, Garcia, Rebecca, Barge, Deborah, Byrne, Deborah, Byrne, Kathleen, Driscoll, Alana, Fortune, Louise, Janin, Pierre, Yarad, Elizabeth, Hammond, Naomi, Bass, Frances, Ashelford, Angela, Waterson, Sharon, Wedd, Steve, McNamara, Robert, Buhr, Heidi, Coles, Jennifer, Schweikert, Sacha, Wibrow, Bradley, Rauniyar, Rashmi, Myers, Erina, Fysh, Ed, Dawda, Ashlish, Mevavala, Bhaumik, Litton, Ed, Ferrier, Janet, Nair, Priya, Buscher, Hergen, Reynolds, Claire, Santamaria, John, Barbazza, Leanne, Homes, Jennifer, Smith, Roger, Murray, Lauren, Brailsford, Jane, Forbes, Loretta, Maguire, Teena, Mariappa, Vasanth, Smith, Judith, Simpson, Scott, Maiden, Matthew, Bone, Allsion, Horton, Michelle, Salerno, Tania, Sterba, Martin, Geng, Wenli, Depuydt, Pieter, De Waele, Jan, De Bus, Liesbet, Fierens, Jan, Bracke, Stephanie, Reeve, Brenda, Dechert, William, Chassé, Michaël, Carrier, François Martin, Boumahni, Dounia, Benettaib, Fatna, Ghamraoui, Ali, Bellemare, David, Cloutier, Ève, Francoeur, Charles, Lamontagne, François, D’Aragon, Frédérick, Carbonneau, Elaine, Leblond, Julie, Vazquez-Grande, Gloria, Marten, Nicole, Wilson, Maggie, Albert, Martin, Serri, Karim, Cavayas, Alexandros, Duplaix, Mathilde, Williams, Virginie, Rochwerg, Bram, Karachi, Tim, Oczkowski, Simon, Centofanti, John, Millen, Tina, Duan, Erick, Tsang, Jennifer, Patterson, Lisa, English, Shane, Watpool, Irene, Porteous, Rebecca, Miezitis, Sydney, McIntyre, Lauralyn, Brochard, Laurent, Burns, Karen, Sandhu, Gyan, Khalid, Imrana, Binnie, Alexandra, Powell, Elizabeth, McMillan, Alexandra, Luk, Tracy, Aref, Noah, Andric, Zdravko, Cviljevic, Sabina, Đimoti, Renata, Zapalac, Marija, Mirković, Gordan, Baršić, Bruno, Kutleša, Marko, Kotarski, Viktor, Vujaklija Brajković, Ana, Babel, Jakša, Sever, Helena, Dragija, Lidija, Kušan, Ira, Vaara, Suvi, Pettilä, Leena, Heinonen, Jonna, Kuitunen, Anne, Karlsson, Sari, Vahtera, Annukka, Kiiski, Heikki, Ristimäki, Sanna, Azaiz, Amine, Charron, Cyril, Godement, Mathieu, Geri, Guillaume, Vieillard-Baron, Antoine, Pourcine, Franck, Monchi, Mehran, Luis, David, Mercier, Romain, Sagnier, Anne, Verrier, Nathalie, Caplin, Cecile, Siami, Shidasp, Aparicio, Christelle, Vautier, Sarah, Jeblaoui, Asma, Fartoukh, Muriel, Courtin, Laura, Labbe, Vincent, Leparco, Cécile, Muller, Grégoire, Nay, Mai-Anh, Kamel, Toufik, Benzekri, Dalila, Jacquier, Sophie, Mercier, Emmanuelle, Chartier, Delphine, Salmon, Charlotte, Dequin, PierreFrançois, Schneider, Francis, Morel, Guillaume, L’Hotellier, Sylvie, Badie, Julio, Berdaguer, Fernando Daniel, Malfroy, Sylvain, Mezher, Chaouki, Bourgoin, Charlotte, Megarbane, Bruno, Voicu, Sebastian, Deye, Nicolas, Malissin, Isabelle, Sutterlin, Laetitia, Guitton, Christophe, Darreau, Cédric, Landais, Mickaël, Chudeau, Nicolas, Robert, Alain, Moine, Pierre, Heming, Nicholas, Maxime, Virginie, Bossard, Isabelle, Nicholier, Tiphaine Barbarin, Colin, Gwenhael, Zinzoni, Vanessa, Maquigneau, Natacham, Finn, André, Kreß, Gabriele, Hoff, Uwe, Friedrich Hinrichs, Carl, Nee, Jens, Hagel, Stefan, Ankert, Juliane, Kolanos, Steffi, Bloos, Frank, Petros, Sirak, Pasieka, Bastian, Kunz, Kevin, Appelt, Peter, Schütze, Bianka, Kluge, Stefan, Nierhaus, Axel, Jarczak, Dominik, Roedl, Kevin, Weismann, Dirk, Frey, Anna, Klinikum Neukölln, Vivantes, Reill, Lorenz, Distler, Michael, Maselli, Astrid, Bélteczki, János, Magyar, István, Fazekas, Ágnes, Kovács, Sándor, Szőke, Viktória, Szigligeti, Gábor, Leszkoven, János, Collins, Daniel, Breen, Patrick, Frohlich, Stephen, Whelan, Ruth, McNicholas, Bairbre, Scully, Michael, Casey, Siobhan, Kernan, Maeve, Doran, Peter, O’Dywer, Michael, Smyth, Michelle, Hayes, Leanne, Hoiting, Oscar, Peters, Marco, Rengers, Els, Evers, Mirjam, Prinssen, Anton, Bosch Ziekenhuis, Jeroen, Simons, Koen, Rozendaal, Wim, Polderman, F, de Jager, P, Moviat, M, Paling, A, Salet, A, Rademaker, Emma, Peters, Anna Linda, de Jonge, E, Wigbers, J, Guilder, E, Butler, M, Cowdrey, Keri-Anne, Newby, Lynette, Chen, Yan, Simmonds, Catherine, McConnochie, Rachael, Ritzema Carter, Jay, Henderson, Seton, Van Der Heyden, Kym, Mehrtens, Jan, Williams, Tony, Kazemi, Alex, Song, Rima, Lai, Vivian, Girijadevi, Dinu, Everitt, Robert, Russell, Robert, Hacking, Danielle, Buehner, Ulrike, Williams, Erin, Browne, Troy, Grimwade, Kate, Goodson, Jennifer, Keet, Owen, Callender, Owen, Martynoga, Robert, Trask, Kara, Butler, Amelia, Schischka, Livia, Young, Chelsea, Lesona, Eden, Olatunji, Shaanti, Robertson, Yvonne, José, Nuno, Amaro dos Santos Catorze, Teodoro, de Lima Pereira, Tiago Nuno Alfaro, Neves Pessoa, Lucilia Maria, Castro Ferreira, Ricardo Manuel, Pereira Sousa Bastos, Joana Margarida, Aysel Florescu, Simin, Stanciu, Delia, Zaharia, Miahela Florentina, Kosa, Alma Gabriela, Codreanu, Daniel, Marabi, Yaseen, Al Qasim, Eman, Moneer Hagazy, Mohamned, Al Swaidan, Lolowa, Arishi, Hatim, Muñoz-Bermúdez, Rosana, Marin-Corral, Judith, Salazar Degracia, Anna, Parrilla Gómez, Francisco, Mateo López, Maria Isabel, Rodriguez Fernandez, Jorge, Cárcel Fernández, Sheila, Carmona Flores, Rosario, León López, Rafael, de la Fuente Martos, Carmen, Allan, Angela, Polgarova, Petra, Farahi, Neda, McWilliam, Stephen, Hawcutt, Daniel, Rad, Laura, O’Malley, Laura, Whitbread, Jennifer, Kelsall, Olivia, Wild, Laura, Thrush, Jessica, Wood, Hannah, Austin, Karen, Donnelly, Adrian, Kelly, Martin, O’Kane, Sinéad, McClintock, Declan, Warnock, Majella, Johnston, Paul, Gallagher, Linda Jude, Mc Goldrick, Clare, Mc Master, Moyra, Strzelecka, Anna, Jha, Rajeev, Kalogirou, Michael, Ellis, Christine, Krishnamurthy, Vinodh, Deelchand, Vashish, Silversides, Jon, McGuigan, Peter, Ward, Kathryn, O’Neill, Aisling, Finn, Stephanie, Phillips, Barbara, Mullan, Dee, Oritz-Ruiz de Gordoa, Laura, Thomas, Matthew, Sweet, Katie, Grimmer, Lisa, Johnson, Rebekah, Pinnell, Jez, Robinson, Matt, Gledhill, Lisa, Wood, Tracy, Morgan, Matt, Cole, Jade, Hill, Helen, Davies, Michelle, Antcliffe, David, Templeton, Maie, Rojo, Roceld, Coghlan, Phoebe, Smee, Joanna, Mackay, Euan, Cort, Jon, Whileman, Amanda, Spencer, Thomas, Spittle, Nick, Kasipandian, Vidya, Patel, Amit, Allibone, Suzanne, Genetu, Roman Mary, Ramali, Mohamed, Ghosh, Alison, Bamford, Peter, London, Emily, Cawley, Kathryn, Faulkner, Maria, Jeffrey, Helen, Smith, Tim, Brewer, Chris, Gregory, Jane, Limb, James, Cowton, Amanda, O’Brien, Julie, Nikitas, Nikitas, Wells, Colin, Lankester, Liana, Pulletz, Mark, Birch, Jenny, Wiseman, Sophie, Horton, Sarah, Alegria, Ana, Turki, Salah, Elsefi, Tarek, Crisp, Nikki, Allen, Louise, McCullagh, Iain, Robinson, Philip, Hays, Carole, Babio-Galan, Maite, Stevenson, Hannah, Khare, Divya, Pinder, Meredith, Selvamoni, Selvin, Gopinath, Amitha, Pugh, Richard, Menzies, Daniel, Mackay, Callum, Allan, Elizabeth, Davies, Gwyneth, Puxty, Kathryn, McCue, Claire, Cathcart, Susanne, Hickey, Naomi, Ireland, Jane, Yusuff, Hakeem, Isgro, Graziella, Brightling, Chris, Bourne, Michelle, Craner, Michelle, Watters, Malcolm, Prout, Rachel, Davies, Louisa, Pegler, Suzannah, Kyeremeh, Lynsey, Arbane, Gill, Wilson, Karen, Gomm, Linda, Francia, Federica, Brett, Stephen, Sousa Arias, Sonia, Elin Hall, Rebecca, Budd, Joanna, Small, Charlotte, Birch, Janine, Collins, Emma, Henning, Jeremy, Bonner, Stephen, Hugill, Keith, Cirstea, Emanuel, Wilkinson, Dean, Karlikowski, Michal, Sutherland, Helen, Wilhelmsen, Elva, Woods, Jane, North, Julie, Sundaran, Dhinesh, Hollos, Laszlo, Coburn, Susan, Walsh, Joanne, Turns, Margaret, Hopkins, Phil, Smith, John, Noble, Harriet, Depante, Maria Theresa, Clarey, Emma, Laha, Shondipon, Verlander, Mark, Williams, Alexandra, Huckle, Abby, Hall, Andrew, Cooke, Jill, Gardiner-Hill, Caroline, Maloney, Carolyn, Qureshi, Hafiz, Flint, Neil, Nicholson, Sarah, Southin, Sara, Nicholson, Andrew, Borgatta, Barbara, Turner-Bone, Ian, Reddy, Amie, Wilding, Laura, Chamara Warnapura, Loku, Agno Sathianathan, Ronan, Golden, David, Hart, Ciaran, Jones, Jo, Bannard-Smith, Jonathan, Henry, Joanne, Birchall, Katie, Pomeroy, Fiona, Quayle, Rachael, Makowski, Arystarch, Misztal, Beata, Ahmed, Iram, KyereDiabour, Thyra, Naiker, Kevin, Stewart, Richard, Mwaura, Esther, Mew, Louise, Wren, Lynn, Willams, Felicity, Innes, Richard, Doble, Patricia, Hutter, Joanne, Shovelton, Charmaine, Plumb, Benjamin, Szakmany, Tamas, Hamlyn, Vincent, Hawkins, Nancy, Lewis, Sarah, Dell, Amanda, Gopal, Shameer, Ganguly, Saibal, Smallwood, Andrew, Harris, Nichola, Metherell, Stella, Lazaro, Juan Martin, Newman, Tabitha, Fletcher, Simon, Nortje, Jurgens, Fottrell-Gould, Deirdre, Randell, Georgina, Zaman, Mohsin, Elmahi, Einas, Jones, Andrea, Hall, Kathryn, Mills, Gary, Ryalls, Kim, Bowler, Helen, Sall, Jas, Bourne, Richard, Borrill, Zoe, Duncan, Tracey, Lamb, Thomas, Shaw, Joanne, Fox, Claire, Moreno Cuesta, Jeronimo, Xavier, Kugan, Purohit, Dharam, Elhassan, Munzir, Bakthavatsalam, Dhanalakshmi, Rowland, Matthew, Hutton, Paula, Bashyal, Archana, Davidson, Neil, Hird, Clare, Chhablani, Manish, Phalod, Gunjan, Kirkby, Amy, Archer, Simon, Netherton, Kimberley, Reschreiter, Henrik, Camsooksai, Julie, Patch, Sarah, Jenkins, Sarah, Pogson, David, Rose, Steve, Daly, Zoe, Brimfield, Lutece, Claridge, Helen, Parekh, Dhruv, Bergin, Colin, Bates, Michelle, Dasgin, Joanne, McGhee, Christopher, Sim, Malcolm, Hay, Sophie Kennedy, Henderson, Steven, Phull, Mandeep-Kaur, Zaidi, Abbas, Pogreban, Tatiana, Rosaroso, Lace Paulyn, Harvey, Daniel, Lowe, Benjamin, Meredith, Megan, Ryan, Lucy, Hormis, Anil, Walker, Rachel, Collier, Dawn, Kimpton, Sarah, Oakley, Susan, Rooney, Kevin, Rodden, Natalie, Hughes, Emma, Thomson, Nicola, McGlynn, Deborah, Walden, Andrew, Jacques, Nicola, Coles, Holly, Tilney, Emma, Vowell, Emma, Schuster-Bruce, Martin, Pitts, Sally, Miln, Rebecca, Purandare, Laura, Vamplew, Luke, Spivey, Michael, Bean, Sarah, Burt, Karen, Moore, Lorraine, Day, Christopher, Gibson, Charly, Gordon, Elizabeth, Zitter, Letizia, Keenan, Samantha, Baker, Evelyn, Cherian, Shiney, Cutler, Sean, Roynon-Reed, Anna, Harrington, Kate, Raithatha, Ajay, Bauchmuller, Kris, Ahmad, Norfaizan, Grecu, Irina, Trodd, Dawn, Martin, Jane, Wrey Brown, Caroline, Arias, Ana-Marie, Craven, Thomas, Hope, David, Singleton, Jo, Clark, Sarah, Rae, Nicola, Welters, Ingeborg, Hamilton, David Oliver, Williams, Karen, Waugh, Victoria, Shaw, David, Puthucheary, Zudin, Martin, Timothy, Santos, Filipa, Uddin, Ruzena, Somerville, Alastair, Tatham, Kate Colette, Jhanji, Shaman, Black, Ethel, Dela Rosa, Arnold, Howle, Ryan, Tully, Redmond, Drummond, Andrew, Dearden, Joy, Philbin, Jennifer, Munt, Sheila, Vuylsteke, Alain, Chan, Charles, Victor, Saji, Matsa, Ramprasad, Gellamucho, Minerva, Creagh-Brown, Ben, Tooley, Joe, Montague, Laura, De Beaux, Fiona, Bullman, Laetitia, Kersiake, Ian, Demetriou, Carrie, Mitchard, Sarah, Ramos, Lidia, White, Katie, Donnison, Phil, Johns, Maggie, Casey, Ruth, Mattocks, Lehentha, Salisbury, Sarah, Dark, Paul, Claxton, Andrew, McLachlan, Danielle, Slevin, Kathryn, Lee, Stephanie, Hulme, Jonathan, Joseph, Sibet, Kinney, Fiona, Senya, Ho Jan, Oborska, Aneta, Kayani, Abdul, Hadebe, Bernard, Orath Prabakaran, Rajalakshmi, Nichols, Lesley, Thomas, Matt, Worner, Ruth, Faulkner, Beverley, Gendall, Emma, Hayes, Kati, Hamilton-Davies, Colin, Chan, Carmen, Mfuko, Celina, Abbass, Hakam, Mandadapu, Vineela, Leaver, Susannah, Forton, Daniel, Patel, Kamal, Paramasivam, Elankumaran, Powell, Matthew, Gould, Richard, Wilby, Elizabeth, Howcroft, Clare, Banach, Dorota, Fernández de Pinedo Artaraz, Ziortza, Cabreros, Leilani, White, Ian, Croft, Maria, Holland, Nicky, Pereira, Rita, Zaki, Ahmed, Johnson, David, Jackson, Matthew, Garrard, Hywel, Juhaz, Vera, Roy, Alistair, Rostron, Anthony, Woods, Lindsey, Cornell, Sarah, Pillai, Suresh, Harford, Rachel, Rees, Tabitha, Ivatt, Helen, Sundara Raman, Ajay, Davey, Miriam, Lee, Kelvin, Barber, Russell, Chablani, Manish, Brohi, Farooq, Jagannathan, Vijay, Clark, Michele, Purvis, Sarah, Wetherill, Bill, Dushianthan, Ahilanandan, Cusack, Rebecca, de Courcy-Golder, Kim, Smith, Simon, Jackson, Susan, Attwood, Ben, Parsons, Penny, Page, Valerie, Zhao, Xiao Bei, Oza, Deepali, Rhodes, Jonathan, Anderson, Tom, Morris, Sheila, Xia Le Tai, Charlotte, Thomas, Amy, Keen, Alexandra, Digby, Stephen, Cowley, Nicholas, Southern, David, Reddy, Harsha, Campbell, Andy, Watkins, Claire, Smuts, Sara, Touma, Omar, Barnes, Nicky, Alexander, Peter, Felton, Tim, Ferguson, Susan, Sellers, Katharine, Bradley-Potts, Joanne, Yates, David, Birkinshaw, Isobel, Kell, Kay, Marshall, Nicola, Carr-Knott, Lisa, Writing Committee for the REMAP-CAP Investigators, Menon, David [0000-0002-3228-9692], Apollo - University of Cambridge Repository, Medical Microbiology and Infection Prevention, and AII - Infectious diseases

Subjects
Male, Hydrocortisone, Anti-Inflammatory Agents, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], 01 natural sciences, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Adrenal Cortex Hormones, Clinical endpoint, Medicine, 030212 general & internal medicine, Hydrocortisone/administration & dosage, Original Investigation, 2. Zero hunger, Mortality rate, Shock, Covid19, General Medicine, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, Treatment Outcome, Early Termination of Clinical Trials, Corticosteroid, Female, Coronavirus Infections, medicine.drug, Adult, medicine.medical_specialty, Respiration, Artificial/statistics & numerical data, medicine.drug_class, Anti-Inflammatory Agents/administration & dosage, Pneumonia, Viral, UNCOVER, Adrenal Cortex Hormones/therapeutic use, 03 medical and health sciences, Betacoronavirus, All institutes and research themes of the Radboud University Medical Center, Internal medicine, Humans, 0101 mathematics, Adverse effect, Pandemics, business.industry, SARS-CoV-2, 010102 general mathematics, COVID-19, Odds ratio, Coronavirus Infections/drug therapy, Pneumonia, Viral/drug therapy, Respiration, Artificial, COVID-19 Drug Treatment, Shock/drug therapy, Human medicine, business
Abstract

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19.Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.

Published
2020

24. Zinc induces temperature-dependent reversible self-assembly of Tau

Author

Roman, Andrei, Devred, François, Byrne, Deborah, La Rocca, Romain, Ninkina, Natalia, Peyrot, Vincent, Tsvetkov, Philipp, Roman, Andrei Yu., Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut de Microbiologie de la Méditerranée (IMM), Institute of Physiologically Active Compounds, Russian Academy of Sciences - Chernogolovka, and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
Amyloid, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, chemistry.chemical_element, [SDV.CAN]Life Sciences [q-bio]/Cancer, tau Proteins, Zinc, Polymerization, 03 medical and health sciences, 0302 clinical medicine, Dynamic light scattering, Structural Biology, mental disorders, Humans, Chelation, Binding site, Molecular Biology, 030304 developmental biology, Neurons, 0303 health sciences, Binding Sites, Heparin, Chemistry, Temperature, Neurodegenerative Diseases, Isothermal titration calorimetry, In vitro, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Biophysics, Turbidimetry, Tau, Protein Processing, Post-Translational, Aggregation self - assembly, 030217 neurology & neurosurgery, Intracellular
Abstract

International audience; Tau is an intrinsically disordered microtubule associated protein that is implicated in several neurodegenerative disorders called Tau opathies. In these diseases, Tau is found in the form of intracellular inclusions that consist of aggregated paired helical filaments (PHFs) in neurons. Given the importance of this irreversible PHF formation in neurodegenerative disease, Tau aggregation has been extensively studied. Several different factors, such as mutations or post translational modifications, have been shown to influence the formation of late stage non-reversible Tau aggregates. It was recently shown that zinc ions accelerated heparin induced oligomerization of Tau constructs. Indeed, in vitro studies of PHFs have usually been performed in the presence of additional co-factors, such as heparin, in order to accelerate their formation. Using turbidimetry, we investigated the impact of zinc ions on Tau in the absence of heparin and found that zinc is able to induce a temperature dependent reversible oligomerization of Tau. The obtained oligomers were not amyloid like, and dissociated instantly following zinc chelation or a temperature decrease. Finally, a combination of isothermal titration calorimetry and dynamic light scattering experiments showed zinc binding to a high affinity binding site and three low affinity sites on Tau, accompanied by a change in Tau folding. Altogether, our findings stress the importance of zinc in Tau oligomerization. This newly identified Zn-induced oligomerization mechanism may be a part of a pathway different of and concurrent to Tau aggregation cascade leading to PHF formation.

Published
2019

25. NirD curtails the stringent response by inhibiting RelA activity in Escherichia coli.

Author

Léger, Loïc, Byrne, Deborah, Guiraud, Paul, Germain, Elsa, and Maisonneuve, Etienne

Subjects
*BACTERIAL metabolism, *CATALYTIC domains, *GUANOSINE, *IN vitro studies, *IN vivo studies
Abstract

Bacteria regulate their metabolism to adapt and survive adverse conditions, in particular to stressful downshifts in nutrient availability. These shifts trigger the so-called stringent response, coordinated by the signaling molecules guanosine tetra and pentaphosphate collectively referred to as (p)ppGpp. In Escherichia coli, accumulation of theses alarmones depends on the (p) ppGpp synthetase RelA and the bifunctional (p)ppGpp synthetase/hydrolase SpoT. A tight regulation of these intracellular activities is therefore crucial to rapidly adjust the (p)ppGpp levels in response to environmental stresses but also to avoid toxic consequences of (p)ppGpp overaccumulation. In this study, we show that the small protein NirD restrains RelA-dependent accumulation of (p)ppGpp and can inhibit the stringent response in E. coli. Mechanistically, our in vivo and in vitro studies reveal that NirD directly binds the catalytic domains of RelA to balance (p) ppGpp accumulation. Finally, we show that NirD can control RelA activity by directly inhibiting the rate of (p)ppGpp synthesis. [ABSTRACT FROM AUTHOR]

Published
2021
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26. Zinc binding to RNA recognition motif of TDP-43 induces the formation of amyloid-like aggregates

Author

Garnier, Cyrille, Devred, Francois, Byrne, Deborah, Puppo, Remy, Roman, Andrei Yu., Malesinski, Soazig, Golovin, Andrey V., Lebrun, Regine, Ninkina, Natalia N., Tsvetkov, Philipp O., Mécanismes moléculaires dans les démences neurodégénératives (MMDN), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Microbiologie de la Méditerranée (IMM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institute of Physiologically Active Compounds, Russian Academy of Sciences - Chernogolovka, Lomonosov Moscow State University (MSU), School of Biosciences [Cardiff], Cardiff University, Devred, François, École pratique des hautes études (EPHE), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)

Subjects
Amyloid, Binding Sites, Science, [SDV]Life Sciences [q-bio], nutritional and metabolic diseases, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, macromolecular substances, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, nervous system diseases, DNA-Binding Proteins, Molecular Docking Simulation, [SDV] Life Sciences [q-bio], [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Zinc, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Protein Binding
Abstract

Aggregation of TDP-43 (transactive response DNA binding protein 43 kDa) is a hallmark of certain forms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Moreover, intracellular TDP-43-positive inclusions are often found in other neurodegenerative diseases. Recently it was shown that zinc ions can provoke the aggregation of endogenous TDP-43 in cells, allowing to assume a direct interaction of TDP-43 with zinc ions. In this work, we investigated zinc binding to the 102–269 TDP-43 fragment, which comprise the two RNA recognition motifs. Using isothermal titration calorimetry, mass spectrometry, and differential scanning fluorimetry, we showed that zinc binds to this TDP-43 domain with a dissociation constant in the micromolar range and modifies its tertiary structure leading to a decrease of its thermostability. Moreover, the study by dynamic light scattering and negative stain electron microscopy demonstrated that zinc ions induce auto-association process of this TDP-43 fragment into rope-like structures. These structures are thioflavin-T-positive allowing to hypothesize the direct implication of zinc ions in pathological aggregation of TDP-43.

Published
2017

27. The Global Redox Responding RegB/RegA Signal Transduction System Regulates the Genes Involved in Ferrous Iron and Inorganic Sulfur Compound Oxidation of the Acidophilic Acidithiobacillus ferrooxidans

Author

Moinier, Danielle, Byrne, Deborah, Amouric, Agnes, Bonnefoy, Violaine, Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Institut de Microbiologie de la Méditerranée (IMM)

Subjects
Microbiology (medical), inorganic chemicals, two-component signal transducing system, [SDV.GEN]Life Sciences [q-bio]/Genetics, inorganic sulfur compound oxidation, lcsh:QR1-502, Acidithiobacillus ferrooxidans, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Microbiology, lcsh:Microbiology, redox potential, RegB/RegA, [SDE]Environmental Sciences, ferrous iron oxidation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Original Research
Abstract

International audience; The chemical attack of ore by ferric iron and/or sulfuric acid releases valuable metals. The products of these reactions are recycled by iron and sulfur oxidizing microorganisms. These acidophilic chemolithotrophic prokaryotes, among which Acidithiobacillus ferrooxidans, grow at the expense of the energy released from the oxidation of ferrous iron and/or inorganic sulfur compounds (ISCs). In At. ferrooxidans, it has been shown that the expression of the genes encoding the proteins involved in these respiratory pathways is dependent on the electron donor and that the genes involved in iron oxidation are expressed before those responsible for ISCs oxidation when both iron and sulfur are present. Since the redox potential increases during iron oxidation but remains stable during sulfur oxidation, we have put forward the hypothesis that the global redox responding two components system RegB/RegA is involved in this regulation. To understand the mechanism of this system and its role in the regulation of the aerobic respiratory pathways in At. ferrooxidans, the binding of different forms of RegA (DNA binding domain, wild-type, unphosphorylated and phosphorylated-like forms of RegA) on the regulatory region of different genes/operons involved in ferrous iron and ISC oxidation has been analyzed. We have shown that the four RegA forms are able to bind specifically the upstream region of these genes. Interestingly, the phosphorylation of RegA did not change its affinity for its cognate DNA. The transcriptional start site of these genes/operons has been determined. In most cases, the RegA binding site(s) was (were) located upstream from the -35 (or -24) box suggesting that RegA does not interfere with the RNA polymerase binding. Based on the results presented in this report, the role of the RegB/RegA systemin the regulation of the ferrous iron and ISC oxidation pathways in At. ferrooxidans is discussed.

Published
2017

29. mRNA deep sequencing reveals 75 new genes and a complex transcriptional landscape in Mimivirus

Author

Legendre, Matthieu, Audic, Stephane, Poirot, Olivier, Hingamp, Pascal, Seltzer, Virginie, Byrne, Deborah, Lartigue, Audrey, Lescot, Magali, Bernadac, Alain, Poulain, Julie, Abergel, Chantal, and Claverie, Jean-Michel

Subjects
Nucleotide sequencing -- Usage, Genetic transcription -- Research, Protozoa -- Genetic aspects, Messenger RNA -- Research, Health
Published
2010

30. The nucleoid as a scaffold for the assembly of bacterial signaling complexes.

Author

Moine, Audrey, Espinosa, Leon, Martineau, Eugenie, Yaikhomba, Mutum, Jazleena, P. J., Byrne, Deborah, Biondi, Emanuele G., Notomista, Eugenio, Brilli, Matteo, Molle, Virginie, Gayathri, Pananghat, Mignot, Tâm, and Mauriello, Emilia M. F.

Subjects
NUCLEOIDS, CHEMORECEPTORS, MYXOCOCCUS xanthus, NUCLEOTIDE sequencing, DNA-binding proteins
Abstract

The FrzCD chemoreceptor from the gliding bacterium Myxococcus xanthus forms cytoplasmic clusters that occupy a large central region of the cell body also occupied by the nucleoid. In this work, we show that FrzCD directly binds to the nucleoid with its N-terminal positively charged tail and recruits active signaling complexes at this location. The FrzCD binding to the nucleoid occur in a DNA-sequence independent manner and leads to the formation of multiple distributed clusters that explore constrained areas. This organization might be required for cooperative interactions between clustered receptors as observed in membrane-bound chemosensory arrays. [ABSTRACT FROM AUTHOR]

Published
2017
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31. RAISING THE BAR.

Author

Byrne, Deborah

Subjects
*INTELLIGENCE levels
Abstract

The article discusses the architectural design of the Ken Soble Tower in Hamilton, Ontario designed by architect ERA Architects Inc.

Published
2021

32. Engaging Nursing Students in Advance Care Planning.

Author

Overbaugh, Kristen, Byrne, Deborah, and DiGiacomo, Pat

Abstract

The article presents the discussion on nurses responsible for assisting patients in end-of-life decision-making and goals of care conversations including undergraduate nursing students to developing competency in advance care planning (ACP).

Published
2023
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33. Glycan Dependence of Galectin-3 Self-Association Properties.

Author

Halimi, Hubert, Rigato, Annafrancesca, Byrne, Deborah, Ferracci, Géraldine, Sebban-Kreuzer, Corinne, ElAntak, Latifa, and Guerlesquin, Francoise

Subjects
GLYCANS, GALECTINS, CELL membranes, NUCLEAR magnetic resonance, BIOMACROMOLECULES, CELL adhesion
Abstract

Human Galectin-3 is found in the nucleus, the cytoplasm and at the cell surface. This lectin is constituted of two domains: an unfolded N-terminal domain and a C-terminal Carbohydrate Recognition Domain (CRD). There are still uncertainties about the relationship between the quaternary structure of Galectin-3 and its carbohydrate binding properties. Two types of self-association have been described for this lectin: a C-type self-association and a N-type self-association. Herein, we have analyzed Galectin-3 oligomerization by Dynamic Light Scattering using both the recombinant CRD and the full length lectin. Our results proved that LNnT induces N-type self-association of full length Galectin-3. Moreover, from Nuclear Magnetic Resonance (NMR) and Surface Plasmon Resonance experiments, we observed no significant specificity or affinity variations for carbohydrates related to the presence of the N-terminal domain of Galectin-3. NMR mapping clearly established that the N-terminal domain interacts with the CRD. We propose that LNnT induces a release of the N-terminal domain resulting in the glycan-dependent self-association of Galectin-3 through N-terminal domain interactions. [ABSTRACT FROM AUTHOR]

Published
2014
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34. Identification of a Src kinase SH3 binding site in the C-terminal domain of the human ErbB2 receptor tyrosine kinase.

Author

Bornet, Olivier, Nouailler, Matthieu, Feracci, Michaël, Sebban-Kreuzer, Corinne, Byrne, Deborah, Halimi, Hubert, Morelli, Xavier, Badache, Ali, and Guerlesquin, Françoise

Subjects
BINDING sites, PROTEIN-tyrosine kinases, POLYPROLINE, PROTO-oncogenes, CANCER genes
Abstract

Highlights: [•] Polyproline motif included in ErbB2 C-terminal domain. [•] Fyn SH3 binds ErbB2 PPII motif. [•] ErbB2 C-terminal domain interacts with a Src kinase. [Copyright &y& Elsevier]

Published
2014
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35. Observation of the FeCN and FeCO Vibrations in the Active Site of [NiFe] Hydrogenase by Nuclear Resonance Vibrational Spectroscopy.

Author

Kamali, Saeed, Wang, Hongxin, Mitra, Devrani, Ogata, Hideaki, Lubitz, Wolfgang, Manor, Brian C., Rauchfuss, Thomas B., Byrne, Deborah, Bonnefoy, Violaine, Jenney, Francis E., Adams, Michael W. W., Yoda, Yoshitaka, Alp, Ercan, Zhao, Jiyong, and Cramer, Stephen P.

Abstract

Nuclear inelastic scattering of 57Fe labeled [NiFe] hydrogenase is shown to give information on different states of the enzyme. It was thus possible to detect and assign FeCO and FeCN bending and stretching vibrations of the active site outside the spectral range of the FeS cluster normal modes. [ABSTRACT FROM AUTHOR]

Published
2013
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36. Detektion von Fe-CN- und Fe-CO-Schwingungen im aktiven Zentrum der [NiFe]-Hydrogenase durch inelastische kernresonante Streuung.

Author

Kamali, Saeed, Wang, Hongxin, Mitra, Devrani, Ogata, Hideaki, Lubitz, Wolfgang, Manor, Brian C., Rauchfuss, Thomas B., Byrne, Deborah, Bonnefoy, Violaine, Jenney, Francis E., Adams, Michael W. W., Yoda, Yoshitaka, Alp, Ercan, Zhao, Jiyong, and Cramer, Stephen P.

Abstract

Blick ins Zentrum: Die Methode der inelastischen kernresonanten Streuung (NRVS) wurde genutzt, um 57Fe ‐ markierte [NiFe] ‐ Hydrogenase in unterschiedlichen Zuständen des Enzyms zu untersuchen. Damit gelang es, die Fe ‐ CO ‐ und Fe ‐ CN ‐ Beuge ‐ und ‐ Streckschwingung außerhalb des Spektralbereichs der Normalmoden der Fe ‐ S ‐ Cluster zu detektieren und zuzuordnen (siehe Spektrum). [ABSTRACT FROM AUTHOR]

Published
2013
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37. Mechanism of Zn 2+ and Ca 2+ Binding to Human S100A1.

Author

Baksheeva, Viktoriia E., Roman, Andrei Yu., Villard, Claude, Devred, François, Byrne, Deborah, Yatoui, Dahbia, Zalevsky, Arthur O., Vologzhannikova, Alisa A., Sokolov, Andrey S., Permyakov, Sergei E., Golovin, Andrey V., Shaw, Gary S., Tsvetkov, Philipp O., and Zernii, Evgeni Yu.

Subjects
ZINC ions, CELL differentiation, CELLULAR control mechanisms, CELLULAR signal transduction, MONOMERS, CALCIUM ions
Abstract

S100A1 is a member of the S100 family of small ubiquitous Ca2+-binding proteins, which participates in the regulation of cell differentiation, motility, and survival. It exists as homo- or heterodimers. S100A1 has also been shown to bind Zn2+, but the molecular mechanisms of this binding are not yet known. In this work, using ESI-MS and ITC, we demonstrate that S100A1 can coordinate 4 zinc ions per monomer, with two high affinity (KD~4 and 770 nm) and two low affinity sites. Using competitive binding experiments between Ca2+ and Zn2+ and QM/MM molecular modeling we conclude that Zn2+ high affinity sites are located in the EF-hand motifs of S100A1. In addition, two lower affinity sites can bind Zn2+ even when the EF-hands are saturated by Ca2+, resulting in a 2Ca2+:S100A1:2Zn2+ conformer. Finally, we show that, in contrast to calcium, an excess of Zn2+ produces a destabilizing effect on S100A1 structure and leads to its aggregation. We also determined a higher affinity to Ca2+ (KD~0.16 and 24 μm) than was previously reported for S100A1, which would allow this protein to function as a Ca2+/Zn2+-sensor both inside and outside cells, participating in diverse signaling pathways under normal and pathological conditions. [ABSTRACT FROM AUTHOR]

Published
2021
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38. Mimivirus TyrRS: preliminary structural and functional characterization of the first amino-acyl tRNA synthetase found in a virus.

Author

Abergel, Chantal, Chenivesse, Sabine, Byrne, Deborah, Suhre, Karsten, Arondel, Vincent, and Claverie, Jean-Michel

Subjects
DNA viruses, VIRUSES, MYCOPLASMA, GENOMES, TRANSFER RNA, GENES
Abstract

The amoeba-infecting Mimivirus is the largest known double-stranded DNA virus, with a 400 nm particle size, comparable to that of mycoplasma. The complete sequence of its 1.2 Mbp genome has recently been determined [Raoult et al. (2004), Science, 306, 1344-1350] and revealed numerous genes that were not expected to be found in a virus, such as genes encoding translation components, including 4-amino-acyl tRNA synthetases and homologues to various translation initiation, elongation and termination factors. A comprehensive structural and functional study of these Mimivirus gene products was initiated, as they may hold important clues about the origin of DNA viruses. Here, the first preliminary crystallographic and functional results obtained on one of these targets, Mimivirus TyrRS, are reported. Preliminary phasing was obtained using an original combination of homology modelling and normal mode analysis. Experimental evidence that Mimivirus tyrosyl tRNA synthetase recombinant gene product does indeed activate tyrosine is also presented. [ABSTRACT FROM AUTHOR]

Published
2005
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40. What internal motivators drive RNs to pursue a BSN?

Author

Byrne, Deborah, Mayo, Roxanne, and Rosner, Christine

Subjects
*ACADEMIC achievement, *ASSOCIATE degree nurses, *HOSPITALS, *MOTIVATION (Psychology), *NURSES, *NURSES' attitudes, *NURSING education, *SCALE analysis (Psychology), *SURVEYS, *VOCATIONAL guidance, *PILOT projects, *BACHELOR of science degree, *RE-entry students, *EDUCATIONAL mobility, *DIPLOMAS (Education), *PLANNED behavior theory, *HOSPITAL nursing staff, RESEARCH evaluation
Abstract

The article explains why registered nurses (RN) thrive to pursue a Bachelor of Science in Nursing (BSN) program. According to the American Nurses Association, due to the changing healthcare environment, competencies associated with baccalaureate-level education are needed. It discusses a pilot study which designed using Ajzen's theory to examine the planned behavior of a nurse.

Published
2014
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41. Antihypertensive Effect of Carteolol in Thiazide-Treated Hypertensive Subjects.

Author

Velasquez, Manuel T., Byrne, Deborah, and Hoffmann, Raymond G.

Abstract

The antihypertensive effect of carteolol, a new potent nonselective beta-adrenergic antagonist, was investigated in a double-blind, parallel study of 35 patients with mild-to-moderate, essential hypertension whose blood pressures were not adequately controlled with a diuretic. Patients were randomly assigned to receive placebo, carteolol 5 mg, or carteolol 20 mg once a day in addition to hydrochlorothiazide 50 mg for six weeks. Thirty-four patients completed the study: 11 patients received placebo (group 1), 12 patients received carteolol 5 mg (group 2), and 11 patients received carteolol 20 mg (group 3). After six weeks of treatment, the two groups that received carteolol had significant reductions in systolic (SBP) and diastolic (DBP) blood pressure from baseline in both the supine and standing positions. In group 2, mean SBP decreases for supine and standing positions were 11 ± 2.1 and 11 ± 1.9 mm Hg, respectively (P < .01) and 8 ± 1.2 and 9 ± 1.3 mm Hg, respectively, for DBP (P < .01); whereas in group 3, values were 8 ± 2.8 and 12 ± 3.0 mm Hg for SBP, in 5 ± 1.9 and 9 ± 3.1 mm Hg, respectively, for DBP (P < .01). The hypotensive effect was associated with slight but significant decreases in heart rate (P < .01 in group 2 and P < .05 in group 3). Reductions in SBP and DBP with the 20-mg dose were not significantly different from those with the 5-mg dose. With both carteolol regimens, the fall in mean blood pressure did not correlate with the initial level; but in the group taking the 5-mg dose, it did correlate significantly with the decrease in heart rate (r = .72, P < .01). Side effects attributable to carteolol were infrequent and did not persist during continued therapy. It is concluded that carteolol, when combined with hydrochlorothiazide, is effective in reducing blood pressure in patients with mild to moderate hypertension. [ABSTRACT FROM AUTHOR]

Published
1985
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42. A divergent CheW confers plasticity to nucleoid-associated chemosensory arrays.

Author

Guiseppi, Annick, Vicente, Juan Jesus, Herrou, Julien, Byrne, Deborah, Barneoud, Aurelie, Moine, Audrey, Espinosa, Leon, Basse, Marie-Jeanne, Molle, Virginie, Mignot, Tâm, Roche, Philippe, and Mauriello, Emilia M. F.

Subjects
MYXOCOCCUS xanthus, MASTICATION, CHEMOTAXIS, AMINO acids, PROTEINS
Abstract

Chemosensory systems are highly organized signaling pathways that allow bacteria to adapt to environmental changes. The Frz chemosensory system from M. xanthus possesses two CheW-like proteins, FrzA (the core CheW) and FrzB. We found that FrzB does not interact with FrzE (the cognate CheA) as it lacks the amino acid region responsible for this interaction. FrzB, instead, acts upstream of FrzCD in the regulation of M. xanthus chemotaxis behaviors and activates the Frz pathway by allowing the formation and distribution of multiple chemosensory clusters on the nucleoid. These results, together, show that the lack of the CheA-interacting region in FrzB confers new functions to this small protein. Author summary: Chemosensory systems are signaling complexes that are widespread in bacteria and allow the modulation of different cellular functions, such as taxis and development, in response to the environment. We show that the Myxococcus xanthus FrzB is a divergent CheW lacking the region involved in the interaction with the histidine kinase FrzE. Instead, it acts upstream of FrzCD to allow the formation of multiple distributed Frz chemosensory arrays at the nucleoid. The loss of the CheA-interacting region in FrzB might have been selected to confer plasticity to nucleoid-associated chemosensory systems. By unraveling a new accessory protein and its function, this work opens new insights into the knowledge of the regulatory potentials of bacterial chemosensory systems. [ABSTRACT FROM AUTHOR]

Published
2019
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43. Female Genital Mutilation.

Author

Byrne, Deborah

Abstract

The article relates the views of the author and midwife on female genital mutilation for childbirth. She works at a maternity health facility in Salford, England and assisted a woman who had undergone female genital mutilation, which has led her to discover more about female genital mutilation and how it affects women. Evidently, the procedure has a significant life-long negative health impact on women.

Published
2006

44. Becoming.

Author

Byrne, Deborah

Published
2015

45. A Water Birth Denied.

Author

Byrne, Deborah

Abstract

The article relates experiences and views of the author and midwife at a birth center during the labor and water birth by a patient named Lucy. Apparently, another midwife named Catherine did not allow Lucy to birth in the pool as she had not been trained in water births. The author expressed her concern over the fact that some birth center facilities would withheld some facilities to women during labor owing to lack of knowledge or experience on the midwife's part.

Published
2006

46. Cover Picture: Observation of the FeCN and FeCO Vibrations in the Active Site of [NiFe] Hydrogenase by Nuclear Resonance Vibrational Spectroscopy (Angew. Chem. Int. Ed. 2/2013).

Author

Kamali, Saeed, Wang, Hongxin, Mitra, Devrani, Ogata, Hideaki, Lubitz, Wolfgang, Manor, Brian C., Rauchfuss, Thomas B., Byrne, Deborah, Bonnefoy, Violaine, Jenney, Francis E., Adams, Michael W. W., Yoda, Yoshitaka, Alp, Ercan, Zhao, Jiyong, and Cramer, Stephen P.

Abstract

The active site of [NiFe] hydrogenase is an excellent catalyst for hydrogen conversion with an intriguing ability to recover from exposure to dioxygen. In their Communication on page 724 ff., W. Lubitz, S. P. Cramer, and co‐workers use the synchrotron technique of nuclear resonance vibrational spectroscopy to identify normal modes associated with active‐site FeCN and FeCO motion. [ABSTRACT FROM AUTHOR]

Published
2013
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47. Titelbild: Detektion von Fe-CN- und Fe-CO-Schwingungen im aktiven Zentrum der [NiFe]-Hydrogenase durch inelastische kernresonante Streuung (Angew. Chem. 2/2013).

Author

Kamali, Saeed, Wang, Hongxin, Mitra, Devrani, Ogata, Hideaki, Lubitz, Wolfgang, Manor, Brian C., Rauchfuss, Thomas B., Byrne, Deborah, Bonnefoy, Violaine, Jenney, Francis E., Adams, Michael W. W., Yoda, Yoshitaka, Alp, Ercan, Zhao, Jiyong, and Cramer, Stephen P.

Abstract

Das aktive Zentrum der [NiFe] ‐ Hydrogenase ist ein exzellenter Katalysator der Wasserstoffumsetzung mit der faszinierenden Fähigkeit, sich nach Sauerstoffexposition zurückzubilden. W. Lubitz, S. P. Cramer et al. nutzen in ihrer Zuschrift auf S. 752 ff. die Synchrotrontechnik der kernresonanten inelastischen Streuung, um Normalmoden der Fe ‐ CN ‐ und Fe ‐ CO ‐ Bewegung im aktiven Zentrum zu identifizieren. [ABSTRACT FROM AUTHOR]

Published
2013
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48. Binding of two zinc ions promotes liquid-liquid phase separation of Tau.

Author

Yatoui, Dahbia, Tsvetkov, Philipp O., La Rocca, Romain, Baksheeva, Viktoriia E., Allegro, Diane, Breuzard, Gilles, Ferracci, Géraldine, Byrne, Deborah, and Devred, François

Subjects
*ZINC ions, *PHASE separation, *TAU proteins, *ISOTHERMAL titration calorimetry, *TUBULINS, *METALLOTHIONEIN
Abstract

Tau is a naturally disordered microtubule associated protein which forms intraneuronal aggregates in several neurodegenerative diseases including Alzheimer's disease (AD). It was reported that zinc interaction with tau protein can trigger its aggregation. Recently we identified three zinc binding sites located in the N-terminal part, repeat region and the C-terminal part of tau. Here we characterized zinc binding to each of the three sites using isothermal titration calorimetry (ITC) and determined the impact of each site on aggregation using dynamic light scattering (DLS) assays. First, we confirmed the presence of three zinc binding sites on tau and determined the thermodynamic parameters of binding of zinc to these sites. We found a high-affinity zinc binding site located in the repeat region of tau and two N- and C-terminus binding sites with a lower binding constant for zinc. Second, we showed that tau aggregation necessitates zinc binding to the high affinity site in the R2R3 region, while LLPS necessitates zinc binding to any two binding sites. With regard to the role of zinc ions in the aggregation of proteins in neurodegenerative diseases, these findings bring new insights to the understanding of the aggregation mechanism of tau protein induced by zinc. • Zinc is known to trigger tau aggregation and droplet formation. • Three zinc-binding sites have been identified in a NMR study. • Zinc binding site located in the R2R3 domain is crucial for tau aggregation. • Zinc binding to only one site does not induce tau aggregation nor LLPS. • Any two of three existing zinc-binding sites are necessary to induce droplets. [ABSTRACT FROM AUTHOR]

Published
2022
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49. An ArsR/SmtB Family Member Is Involved in the Regulation by Arsenic of the Arsenite Oxidase Operon in Thiomonas arsenitoxydans.

Author

Moinier, Danielle, Slyemi, Djamila, Byrne, Deborah, Lignon, Sabrina, Lebrun, Régine, Talla, Emmanuel, and Bonnefoy, Violaine

Subjects
*ARSENITES, *MOLYBDATES, *OXIDASE genetics, *METALLOPROTEINS, *ACIDOPHILIC bacteria, *CHEMOAUTOTROPHIC bacteria
Abstract

The genetic organization of the aioBA operon, encoding the arsenite oxidase of the moderately acidophilic and facultative chemoautotrophic bacterium Thiomonas arsenitoxydans, is different from that of the aioBA operon in the other arsenite oxidizers, in that it encodes AioF, a metalloprotein belonging to the ArsR/SmtB family. AioF is stabilized by arsenite, arsenate, or antimonite but not molybdate. Arsenic is tightly attached to AioF, likely by cysteine residues. When loaded with arsenite or arsenate, AioF is able to bind specifically to the regulatory region of the aio operon at two distinct positions. In Thiomonas arsenitoxydans, the promoters of aioX and aioB are convergent, suggesting that transcriptional interference occurs. These results indicate that the regulation of the aioBA operon is more complex in Thiomonas arsenitoxydans than in the other aioBA containing arsenite oxidizers and that the arsenic binding protein AioF is involved in this regulation. On the basis of these data, a model to explain the tight control of aioBA expression by arsenic in Thiomonas arsenitoxydans is proposed. [ABSTRACT FROM AUTHOR]

Published
2014
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50. An enterprise directory solution with DB2.

Author

Shi, Shepherd S. B., Stokes, Ellen, Byrne, Deborah, Corn, Cindy F., Bachmann, David, and Jones, Tom

Subjects
*DIRECTORIES, *COMPUTER network protocols, *COMPUTER software, *COMPUTER network resources
Abstract

LDAP (Lightweight Directory Access Protocol) is a technology that can provide directory services to a range of applications. Directory service, a critical part of distributed computing, is the central point where network services, security services, and applications can form an integrated distributed computing environment. The simplicity of LDAP enables users to store and retrieve data easily from the directory. Nevertheless, as the use of directory services becomes more widespread, directories will need to scale to support millions of entries and millions of user requests with subsecond predictable performance. LDAP directories can be implemented using various storage mechanisms such as flat files, b-trees, or databases. This paper discusses an implementation of LDAP that uses the IBM DATABASE 2 Trademark relational database as the data store and query engine to meet the directory service requirements. Performance analysis is provided to show that a relational database can be used to successfully meet the performance and scale needs of an LDAP directory while remaining secure and competitive with other vendor implementations. [ABSTRACT FROM AUTHOR]

Published
2000
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