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Metabolomic disorders: confirmed presence of potentially treatable abnormalities in patients with treatment refractory depression and suicidal behavior
- Lisa A. Pan, Anna Maria Segreti, Joseph Wrobleski, Annie Shaw, Keith Hyland, Marion Hughes, David N. Finegold, Robert K. Naviaux, David A. Brent, Jerry Vockley, David G. Peters
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- Journal:
- Psychological Medicine / Volume 53 / Issue 13 / October 2023
- Published online by Cambridge University Press:
- 04 November 2022, pp. 6046-6054
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Background
Refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. Approximately 15% of patients with major depressive disorder are refractory to currently available treatments. We hypothesized metabolic abnormalities contributing to treatment refractory depression are associated with distinct findings identifiable in the cerebrospinal fluid (CSF). Our hypothesis was confirmed by a previous small case-controlled study. Here we present a second, larger replication study.
MethodsWe conducted a case-controlled, targeted, metabolomic evaluation of 141 adolescent and adult patients with well-characterized history of depression refractory to three maximum-dose, adequate-duration medication treatments, and 36 healthy controls. Plasma, urine, and CSF metabolic profiling were performed by coupled gas chromatography/mass spectrometry, and high-performance liquid chromatography, electrospray ionization, tandem mass spectrometry.
ResultsAbnormalities were identified in 67 of 141 treatment refractory depression participants. The CSF abnormalities included: low cerebral folate (n = 20), low tetrahydrobiopterin intermediates (n = 11), and borderline low-tetrahydrobiopterin intermediates (n = 20). Serum abnormalities included abnormal acylcarnitine profile (n = 12) and abnormal serum amino acids (n = 20). Eighteen patients presented with two or more abnormal metabolic findings. Sixteen patients with cerebral folate deficiency and seven with low tetrahydrobiopterin intermediates in CSF showed improvement in depression symptom inventories after treatment with folinic acid and sapropterin, respectively. No healthy controls had a metabolite abnormality.
ConclusionsExamination of metabolic disorders in treatment refractory depression identified an unexpectedly large proportion of patients with potentially treatable abnormalities. The etiology of these abnormalities and their potential roles in pathogenesis remain to be determined.
Contributors
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. Douglas Meeks, Monica Jyotsna Melanchthon, Ilie Melniciuc-Puica, Everett Mendoza, Raymond A. Mentzer, William W. Menzies, Ina Merdjanova, Franziska Metzger, Constant J. Mews, Marvin Meyer, Carol Meyers, Vasile Mihoc, Gunner Bjerg Mikkelsen, Maria Inêz de Castro Millen, Clyde Lee Miller, Bonnie J. Miller-McLemore, Alexander Mirkovic, Paul Misner, Nozomu Miyahira, R. W. L. Moberly, Gerald Moede, Aloo Osotsi Mojola, Sunanda Mongia, Rebeca Montemayor, James Moore, Roger E. Moore, Craig E. Morrison O.Carm, Jeffry H. Morrison, Keith Morrison, Wilson J. Moses, Tefetso Henry Mothibe, Mokgethi Motlhabi, Fulata Moyo, Henry Mugabe, Jesse Ndwiga Kanyua Mugambi, Peggy Mulambya-Kabonde, Robert Bruce Mullin, Pamela Mullins Reaves, Saskia Murk Jansen, Heleen L. Murre-Van den Berg, Augustine Musopole, Isaac M. T. Mwase, Philomena Mwaura, Cecilia Nahnfeldt, Anne Nasimiyu Wasike, Carmiña Navia Velasco, Thulani Ndlazi, Alexander Negrov, James B. Nelson, David G. Newcombe, Carol Newsom, Helen J. Nicholson, George W. E. Nickelsburg, Tatyana Nikolskaya, Damayanthi M. A. Niles, Bertil Nilsson, Nyambura Njoroge, Fidelis Nkomazana, Mary Beth Norton, Christian Nottmeier, Sonene Nyawo, Anthère Nzabatsinda, Edward T. Oakes, Gerald O'Collins, Daniel O'Connell, David W. Odell-Scott, Mercy Amba Oduyoye, Kathleen O'Grady, Oyeronke Olajubu, Thomas O'Loughlin, Dennis T. Olson, J. Steven O'Malley, Cephas N. Omenyo, Muriel Orevillo-Montenegro, César Augusto Ornellas Ramos, Agbonkhianmeghe E. Orobator, Kenan B. Osborne, Carolyn Osiek, Javier Otaola Montagne, Douglas F. Ottati, Anna May Say Pa, Irina Paert, Jerry G. Pankhurst, Aristotle Papanikolaou, Samuele F. Pardini, Stefano Parenti, Peter Paris, Sung Bae Park, Cristián G. Parker, Raquel Pastor, Joseph Pathrapankal, Daniel Patte, W. Brown Patterson, Clive Pearson, Keith F. Pecklers, Nancy Cardoso Pereira, David Horace Perkins, Pheme Perkins, Edward N. Peters, Rebecca Todd Peters, Bishop Yeznik Petrossian, Raymond Pfister, Peter C. Phan, Isabel Apawo Phiri, William S. F. Pickering, Derrick G. Pitard, William Elvis Plata, Zlatko Plese, John Plummer, James Newton Poling, Ronald Popivchak, Andrew Porter, Ute Possekel, James M. Powell, Enos Das Pradhan, Devadasan Premnath, Jaime Adrían Prieto Valladares, Anne Primavesi, Randall Prior, María Alicia Puente Lutteroth, Eduardo Guzmão Quadros, Albert Rabil, Laurent William Ramambason, Apolonio M. Ranche, Vololona Randriamanantena Andriamitandrina, Lawrence R. Rast, Paul L. Redditt, Adele Reinhartz, Rolf Rendtorff, Pål Repstad, James N. Rhodes, John K. Riches, Joerg Rieger, Sharon H. Ringe, Sandra Rios, Tyler Roberts, David M. Robinson, James M. Robinson, Joanne Maguire Robinson, Richard A. H. Robinson, Roy R. Robson, Jack B. Rogers, Maria Roginska, Sidney Rooy, Rev. Garnett Roper, Maria José Fontelas Rosado-Nunes, Andrew C. Ross, Stefan Rossbach, François Rossier, John D. Roth, John K. Roth, Phillip Rothwell, Richard E. Rubenstein, Rosemary Radford Ruether, Markku Ruotsila, John E. Rybolt, Risto Saarinen, John Saillant, Juan Sanchez, Wagner Lopes Sanchez, Hugo N. Santos, Gerhard Sauter, Gloria L. Schaab, Sandra M. Schneiders, Quentin J. Schultze, Fernando F. Segovia, Turid Karlsen Seim, Carsten Selch Jensen, Alan P. F. Sell, Frank C. Senn, Kent Davis Sensenig, Damían Setton, Bal Krishna Sharma, Carolyn J. Sharp, Thomas Sheehan, N. Gerald Shenk, Christian Sheppard, Charles Sherlock, Tabona Shoko, Walter B. Shurden, Marguerite Shuster, B. Mark Sietsema, Batara Sihombing, Neil Silberman, Clodomiro Siller, Samuel Silva-Gotay, Heikki Silvet, John K. Simmons, Hagith Sivan, James C. Skedros, Abraham Smith, Ashley A. Smith, Ted A. Smith, Daud Soesilo, Pia Søltoft, Choan-Seng (C. S.) Song, Kathryn Spink, Bryan Spinks, Eric O. Springsted, Nicolas Standaert, Brian Stanley, Glen H. Stassen, Karel Steenbrink, Stephen J. Stein, Andrea Sterk, Gregory E. Sterling, Columba Stewart, Jacques Stewart, Robert B. Stewart, Cynthia Stokes Brown, Ken Stone, Anne Stott, Elizabeth Stuart, Monya Stubbs, Marjorie Hewitt Suchocki, David Kwang-sun Suh, Scott W. Sunquist, Keith Suter, Douglas Sweeney, Charles H. Talbert, Shawqi N. Talia, Elsa Tamez, Joseph B. Tamney, Jonathan Y. Tan, Yak-Hwee Tan, Kathryn Tanner, Feiya Tao, Elizabeth S. Tapia, Aquiline Tarimo, Claire Taylor, Mark Lewis Taylor, Bishop Abba Samuel Wolde Tekestebirhan, Eugene TeSelle, M. Thomas Thangaraj, David R. Thomas, Andrew Thornley, Scott Thumma, Marcelo Timotheo da Costa, George E. “Tink” Tinker, Ola Tjørhom, Karen Jo Torjesen, Iain R. Torrance, Fernando Torres-Londoño, Archbishop Demetrios [Trakatellis], Marit Trelstad, Christine Trevett, Phyllis Trible, Johannes Tromp, Paul Turner, Robert G. Tuttle, Archbishop Desmond Tutu, Peter Tyler, Anders Tyrberg, Justin Ukpong, Javier Ulloa, Camillus Umoh, Kristi Upson-Saia, Martina Urban, Monica Uribe, Elochukwu Eugene Uzukwu, Richard Vaggione, Gabriel Vahanian, Paul Valliere, T. J. Van Bavel, Steven Vanderputten, Peter Van der Veer, Huub Van de Sandt, Louis Van Tongeren, Luke A. Veronis, Noel Villalba, Ramón Vinke, Tim Vivian, David Voas, Elena Volkova, Katharina von Kellenbach, Elina Vuola, Timothy Wadkins, Elaine M. Wainwright, Randi Jones Walker, Dewey D. Wallace, Jerry Walls, Michael J. Walsh, Philip Walters, Janet Walton, Jonathan L. Walton, Wang Xiaochao, Patricia A. Ward, David Harrington Watt, Herold D. Weiss, Laurence L. Welborn, Sharon D. Welch, Timothy Wengert, Traci C. West, Merold Westphal, David Wetherell, Barbara Wheeler, Carolinne White, Jean-Paul Wiest, Frans Wijsen, Terry L. Wilder, Felix Wilfred, Rebecca Wilkin, Daniel H. Williams, D. Newell Williams, Michael A. Williams, Vincent L. Wimbush, Gabriele Winkler, Anders Winroth, Lauri Emílio Wirth, James A. Wiseman, Ebba Witt-Brattström, Teofil Wojciechowski, John Wolffe, Kenman L. Wong, Wong Wai Ching, Linda Woodhead, Wendy M. Wright, Rose Wu, Keith E. Yandell, Gale A. Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
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- 05 August 2012
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- 20 September 2010, pp xi-xliv
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Neutron Scattering to Characterize Cu/Mg(Li) Destabilized Hydrogen Storage Materials
- Maria Helena Braga, Michael Joseph Wolverton, Anna Lobet-Megias, Luc L. Daemen
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- Journal:
- MRS Online Proceedings Library Archive / Volume 1262 / 2010
- Published online by Cambridge University Press:
- 01 February 2011, 1262-W03-05
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- 2010
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Cu-Li-Mg-(H,D) was studied as an example of destabilizer of the Ti-(H,D) system. A Cu-Li-Mg alloy was prepared resulting in the formation of a system with 60.5 at% of CuLi0.08Mg1.92, 23.9 at% of CuMg2 and 15.6 at% of Cu2Mg. Titanium was added to a fraction of this mixture so that 68.2 at% (47.3 wt%) of the final mixture was Ti. The mixture was ground and kept at 200 °C/473 K for 7h under H2 or 9h under D2 at P = 34 bar. Under those conditions, neutron powder diffraction shows the formation of TiD2, as well as of the deuteride of CuLi0.08Mg1.92. Similarly inelastic neutron scattering shows that at 10 K TiH2 is present in the sample, together with the hydride of CuLi0.08Mg1.92. Interestingly, at 10 K TiH2 is very clearly detected and at 300 K TiH2 is still clearly present as indicated by the neutron vibrational spectrum, but CuLi0.08Mg1.92-H is not detected anymore. These results indicate that Ti(H,D)2 is possibly formed by diffusion of hydrogen from the Cu-Li-Mg-(H,D) alloys. This is an intriguing result since TiH2 is normally synthesized from the metal at T > 400°C/673 K (and most commonly at T ˜ 700 °C/973 K). In the presence of CuLi0.08Mg1.92, TiH2 forms at a temperature that is 300 – 400 K lower than that needed to synthesize it just from the elements.
Mitochondrial assembly: protein import
- David A. Hood, Anna-Maria Joseph
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- Journal:
- Proceedings of the Nutrition Society / Volume 63 / Issue 2 / May 2004
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- 05 March 2007, pp. 293-300
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The protein import process of mitochondria is vital for the assembly of the hundreds of nuclear-derived proteins into an expanding organelle reticulum. Most of our knowledge of this complex multisubunit network comes from studies of yeast and fungal systems, with little information known about the protein import process in mammalian cells, particularly skeletal muscle. However, growing evidence indicates that the protein import machinery can respond to changes in the energy status of the cell. In particular, contractile activity, a powerful inducer of mitochondrial biogenesis, has been shown to alter the stoichiometry of the protein import apparatus via changes in several protein import machinery components. These adaptations include the induction of cytosolic molecular chaperones that transport precursors to the matrix, the up-regulation of outer membrane import receptors, and the increase in matrix chaperonins that facilitate the import and proper folding of the protein for subsequent compartmentation in the matrix or inner membrane. The physiological importance of these changes is an increased capacity for import into the organelle at any given precursor concentration. Defects in the protein import machinery components have been associated with mitochondrial disorders. Thus, contractile activity may serve as a possible mechanism for up-regulation of mitochondrial protein import and compensation for mitochondrial phenotype alterations observed in diseased muscle.
Eating at fast-food restaurants is associated with dietary intake, demographic, psychosocial and behavioural factors among African Americans in North Carolina
- Jessie A Satia, Joseph A Galanko, Anna Maria Siega-Riz
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- Journal:
- Public Health Nutrition / Volume 7 / Issue 8 / December 2004
- Published online by Cambridge University Press:
- 02 January 2007, pp. 1089-1096
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Objective:
To examine associations of the frequency of eating at fast-food restaurants with demographic, behavioural and psychosocial factors and dietary intake in African American adults.
Methods:Self-reported data from a population-based cross-sectional survey of 658 African Americans, aged 20–70 years, in North Carolina. An 11-page questionnaire assessed eating at fast-food restaurants, demographic, behavioural and diet-related psychosocial factors, and dietary intake (fruit, vegetable, total fat and saturated fat intakes, and fat-related dietary behaviours).
Results:The participants were aged 43.9±11.6 years (mean±standard deviation), 41% were male, 37% were college graduates and 75% were overweight or obese. Seventy-six per cent reported eating at fast-food restaurants during the previous 3 months: 4% usually, 22% often and 50% sometimes. Frequency of eating at fast-food restaurants was positively associated with total fat and saturated fat intakes and fat-related dietary behaviours (P < 0.0001) and inversely associated with vegetable intake (P < 0.05). For example, mean daily fat intake was 39.0 g for usually/often respondents and 28.3 g for those reporting rare/never eating at fast-food restaurants. Participants who reported usual/often eating at fast-food restaurants were younger, never married, obese, physically inactive and multivitamin non-users (all P < 0.01). Frequency of eating at fast-food restaurants was positively associated with fair/poor self-rated health, weak belief in a diet–cancer relationship, low self-efficacy for healthy eating, weight dissatisfaction, and perceived difficulties of preparing healthy meals and ordering healthy foods in restaurants (all P < 0.05). Frequency of eating at fast-food restaurants did not differ significantly by sex, education, smoking, ability to purchase healthy foods or knowledge of the Food Guide Pyramid.
Conclusions:Eating at fast-food restaurants is associated with higher fat and lower vegetable intakes in African Americans. Interventions to reduce fast-food consumption and obesity in African Americans should consider demographic and behavioural characteristics and address attitudes about diet–disease relationships and convenience barriers to healthy eating.
Plasticity of skeletal muscle mitochondria in response to contractile activity
- Peter J. Adhihetty, Isabella Irrcher, Anna-Maria Joseph, Vladimir Ljubicic, David A. Hood
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- Journal:
- Experimental Physiology / Volume 88 / Issue 1 / January 2003
- Published online by Cambridge University Press:
- 09 January 2003, pp. 99-107
- Print publication:
- January 2003
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Regularly performed exercise in the form of endurance training produces a well-established adaptation in skeletal muscle termed mitochondrial biogenesis. The physiological benefit of this is an enhanced performance of muscle when subject to endurance exercise. This is not only of great advantage for athletic endeavours, but it also clearly improves the quality of life of previously sedentary individuals and those involved in injury rehabilitation. Here we review the molecular basis for mitochondrial biogenesis in muscle, from the initial signals arising in contracting muscle, to the transcription factors involved in mitochondrial and nuclear DNA transcription, as well as the post-translational import mechanisms required for the synthesis of the organelle. We discuss specific protein components associated with reactive oxygen species production, and suggest some questions which remain unanswered with respect to the role of exercise-induced mitochondrial biogenesis in ageing, apoptosis and disease. Experimental Physiology (2003) 88.1, 99-107.
American Literature
- James Woodress, S. V. Baum, J. Albert Robbins, Joseph Schiffman, Bibliographical Committee of the American Literature Group, Lars Åhnebrink, A. Lynn Altenbernd, Roger M. Asselineau, Ashbel Brice, Herbert Brown, Louis J. Budd, Anna Maria Crinò, Sherwood Cummings, John E. Englekirk, Bernhard Fabian, John C. Guilds, Jr., Edward Hagemann, Walter Harding, Richard M. Ludwig, Robert J. Kane, Wisner P. Kinne, Ernest Marchand, Arthur L. Scott, Herman E. Spivey
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- Journal:
- PMLA / Publications of the Modern Language Association of America / Volume 73 / Issue 2 / April 1958
- Published online by Cambridge University Press:
- 02 December 2020, pp. 192-216
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- April 1958
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