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The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research
- Roman Kotov, David C. Cicero, Christopher C. Conway, Colin G. DeYoung, Alexandre Dombrovski, Nicholas R. Eaton, Michael B. First, Miriam K. Forbes, Steven E. Hyman, Katherine G. Jonas, Robert F. Krueger, Robert D. Latzman, James J. Li, Brady D. Nelson, Darrel A. Regier, Craig Rodriguez-Seijas, Camilo J. Ruggero, Leonard J. Simms, Andrew E. Skodol, Irwin D. Waldman, Monika A. Waszczuk, David Watson, Thomas A. Widiger, Sylia Wilson, Aidan G. C. Wright
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- Journal:
- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 02 June 2022, pp. 1666-1678
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The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.
Safety of Using a Combinatorial Pharmacogenomic Test for Patients with Major Depressive Disorder in the GUIDED trial
- Sagar V. Parikh, Gabriela K. Khazanov, Michael E. Thase, Anthony J. Rothschild, Boadie W. Dunlop, Charles DeBattista, Charles R. Conway, Brent P. Forester, Richard C. Shelton, Matthew Macaluso, James Li, Kunbo Yu, Michael R. Jablonski, Stephanie Meek, John F. Greden
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- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, pp. 169-170
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Background
Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED).
Materials and MethodsPatients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI.
ResultsMost patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41–2.83) and RR 2.25 (95% CI 1.39–3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15–0.99, p=0.048). No other significant differences in risk were observed at week 8.
ConclusionThese data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients.
FundingMyriad Neuroscience/Assurex Health
Electrical Components Involved in Avian-Caused Outages in Iran
- MAHMOOD KOLNEGARI, GREG J. CONWAY, ALI AKBAR BASIRI, CONNOR T. PANTER, MANDANA HAZRATI, MARYAM SHAMS RAFIEE, MIGUEL FERRER, JAMES F. DWYER
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- Journal:
- Bird Conservation International / Volume 31 / Issue 3 / September 2021
- Published online by Cambridge University Press:
- 03 November 2020, pp. 364-378
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Avian electrocutions are a global conservation problem. Power outages associated with electrocutions are problematic for electric utilities focused on delivering reliable electric power. We used contextual data, photographs, line voltage, outage type and assessments of power line components to quantify outage-causing avian electrocutions throughout each of Iran’s 31 provinces. We evaluated records of 222 avian-caused outages involving 235 electrocuted birds in 2018. Of these, 14.5% involved species of conservation concern, and a few (at least eight) sparked fires when the plumage of electrocuted birds ignited and fell into dry vegetation. Most avian-caused outages (96%) involved distribution voltages, and 91% involved phase-to-ground contacts attributable to grounded concrete pylons with grounded steel crossarms. These are the most common type of power line structure in Iran. Insulators were involved in 37% of outage-causing avian electrocutions, fused cutouts 29%, transformers 33%, and midspan collisions 1%. Given the numbers of these components in the electrical system, fused cutouts and transformers were involved in more outage-causing avian electrocutions than expected due to chance. The average body size of electrocuted birds was largest for incidents involving suspension insulators, smaller for birds electrocuted on other insulators, and smallest for electrocutions on fused cutouts and transformers. Given that most avian electrocutions do not cause outages and given the similarity across electric systems in the region, our findings likely indicate a much larger avian electrocution concern throughout the middle east. Retrofitting power line components to reduce avian contacts would reduce impacts to wildlife and improve the electrical system’s reliability, reduce costs associated with unplanned outages, and reduce risks associated power line ignitions of fires.
150 HAM-D6 Outcomes in a Randomized, Controlled Trial Evaluating the Utility of Combinatorial Pharmacogenomics in Depression
- Boadie W. Dunlop, Sagar V. Parikh, Maitrey Patel, Anthony J. Rothschild, Michael E. Thase, Charles DeBattista, Charles R. Conway, Brent P. Forester, Richard C. Shelton, Matthew Macaluso, James Li, Krystal Brown, Lisa Brown, Michael R. Jablonski, John F. Greden
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 295-296
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Background:
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Methods:Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
Results:At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Conclusions:Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Funding Acknowledgements:Assurex Health, Inc.
49 Combinatorial Pharmacogenomics to Guide Treatment Selection for Major Depressive Disorder: A Large, Blinded, Randomized Controlled Trial
- John F. Greden, Anthony J. Rosthschild, Michael Thase, Boadie W. Dunlop, DMH Charles DeBattista, Charles R. Conway, Brent P. Forester, Francis M. Mondimore, Richard C. Shelton, James Li, Alexa Gilbert, Lindsey Burns, Michael Jablonski, Bryan Dechairo, Sagar Parikh
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- Journal:
- CNS Spectrums / Volume 24 / Issue 1 / February 2019
- Published online by Cambridge University Press:
- 12 March 2019, pp. 202-203
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Background
Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.
Methods1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.
ResultsAt week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.
ConclusionsCombinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.
Funding Acknowledgements: This study was supported by Assurex Health, Inc.
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- By Douglas L. Arnold, Laura J. Balcer, Amit Bar-Or, Sergio E. Baranzini, Frederik Barkhof, Robert A. Bermel, Francois A. Bethoux, Dennis N. Bourdette, Richard K. Burt, Peter A. Calabresi, Zografos Caramanos, Tanuja Chitnis, Stacey S. Cofield, Jeffrey A. Cohen, Nadine Cohen, Alasdair J. Coles, Devon Conway, Stuart D. Cook, Gary R. Cutter, Peter J. Darlington, Ann Dodds-Frerichs, Ranjan Dutta, Gilles Edan, Michelle Fabian, Franz Fazekas, Massimo Filippi, Elizabeth Fisher, Paulo Fontoura, Corey C. Ford, Robert J. Fox, Natasha Frost, Alex Z. Fu, Siegrid Fuchs, Kazuo Fujihara, Kristin M. Galetta, Jeroen J.G. Geurts, Gavin Giovannoni, Nada Gligorov, Ralf Gold, Andrew D. Goodman, Myla D. Goldman, Jenny Guerre, Stephen L. Hauser, Peter B. Imrey, Douglas R. Jeffery, Stephen E. Jones, Adam I. Kaplin, Michael W. Kattan, B. Mark Keegan, Kyle C. Kern, Zhaleh Khaleeli, Samia J. Khoury, Joep Killestein, Soo Hyun Kim, R. Philip Kinkel, Stephen C. Krieger, Lauren B. Krupp, Emmanuelle Le Page, David Leppert, Scott Litwiller, Fred D. Lublin, Henry F. McFarland, Joseph C. McGowan, Don Mahad, Jahangir Maleki, Ruth Ann Marrie, Paul M. Matthews, Francesca Milanetti, Aaron E. Miller, Deborah M. Miller, Xavier Montalban, Charity J. Morgan, Ichiro Nakashima, Sridar Narayanan, Avindra Nath, Paul W. O’Connor, Jorge R. Oksenberg, A. John Petkau, Michael D. Phillips, J. Theodore Phillips, Tammy Phinney, Sean J. Pittock, Sarah M. Planchon, Chris H. Polman, Alexander Rae-Grant, Stephen M. Rao, Stephen C. Reingold, Maria A. Rocca, Richard A. Rudick, Amber R. Salter, Paula Sandler, Jaume Sastre-Garriga, John R. Scagnelli, Dana J. Serafin, Lynne Shinto, Nancy L. Sicotte, Jack H. Simon, Per Soelberg Sørensen, Ryan E. Stagg, James M. Stankiewicz, Lael A. Stone, Amy Sullivan, Matthew Sutliff, Jessica Szpak, Alan J. Thompson, Bruce D. Trapp, Helen Tremlett, Maria Trojano, Orla Tuohy, Rhonda R. Voskuhl, Marc K. Walton, Mike P. Wattjes, Emmanuelle Waubant, Martin S. Weber, Howard L Weiner, Brian G. Weinshenker, Bianca Weinstock-Guttman, Jeffrey L. Winters, Jerry S. Wolinsky, Vijayshree Yadav, E. Ann Yeh, Scott S. Zamvil
- Edited by Jeffrey A. Cohen, Richard A. Rudick
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- Multiple Sclerosis Therapeutics
- Published online:
- 05 December 2011
- Print publication:
- 20 October 2011, pp viii-xii
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- By Phillip L. Ackerman, Soon Ang, Susan M. Barnett, G. David Batty, Anna S. Beninger, Jillian Brass, Meghan M. Burke, Nancy Cantor, Priyanka B. Carr, David R. Caruso, Stephen J. Ceci, Lillia Cherkasskiy, Joanna Christodoulou, Andrew R. A. Conway, Christine E. Daley, Janet E. Davidson, Jim Davies, Katie Davis, Ian J. Deary, Colin G. DeYoung, Ron Dumont, Carol S. Dweck, Linn Van Dyne, Pascale M. J. Engel de Abreu, Joseph F. Fagan, David Henry Feldman, Kurt W. Fischer, Marisa H. Fisher, James R. Flynn, Liane Gabora, Howard Gardner, Glenn Geher, Sarah J. Getz, Judith Glück, Ashok K. Goel, Megan M. Griffin, Elena L. Grigorenko, Richard J. Haier, Diane F. Halpern, Christopher Hertzog, Robert M. Hodapp, Earl Hunt, Alan S. Kaufman, James C. Kaufman, Scott Barry Kaufman, Iris A. Kemp, John F. Kihlstrom, Joni M. Lakin, Christina S. Lee, David F. Lohman, N. J. Mackintosh, Brooke Macnamara, Samuel D. Mandelman, John D. Mayer, Richard E. Mayer, Martha J. Morelock, Ted Nettelbeck, Raymond S. Nickerson, Weihua Niu, Anthony J. Onwuegbuzie, Jonathan A. Plucker, Sally M. Reis, Joseph S. Renzulli, Heiner Rindermann, L. Todd Rose, Anne Russon, Peter Salovey, Scott Seider, Ellen L. Short, Keith E. Stanovich, Ursula M. Staudinger, Robert J. Sternberg, Carli A. Straight, Lisa A. Suzuki, Mei Ling Tan, Maggie E. Toplak, Susana Urbina, Richard K. Wagner, Richard F. West, Wendy M. Williams, John O. Willis, Thomas R. Zentall
- Edited by Robert J. Sternberg, Oklahoma State University, Scott Barry Kaufman, New York University
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- The Cambridge Handbook of Intelligence
- Published online:
- 05 June 2012
- Print publication:
- 30 May 2011, pp xi-xiv
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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
- Published online:
- 05 August 2012
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- 20 September 2010, pp xi-xliv
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Cryo-transmission electron microscopy of Ag nanoparticles grown on an ionic liquid substrate
- Dalaver H. Anjum, Rebecca M. Stiger, James J. Finley, James F. Conway
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- Journal:
- Journal of Materials Research / Volume 25 / Issue 7 / July 2010
- Published online by Cambridge University Press:
- 31 January 2011, pp. 1264-1271
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- July 2010
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We report a novel method of growing silver nanostructures by cathodic sputtering onto an ionic liquid (IL) and our visualization by transmission cryo-electron microscopy to avoid beam-induced motion of the nanoparticles. By freezing the IL suspension and controlling electron dose, we can assess properties of particle size, morphology, crystallinity, and aggregation in situ and at high detail. We observed round silver nanoparticles with a well-defined diameter of 7.0 ± 1.5 nm that are faceted with crystalline cubic structures and ˜80% of the particles have multiply twinned faults. We also applied cryo-electron tomography to investigate the structure of the nanoparticles and to directly visualize the IL wetting around them. In addition to particles, we observed nanorods that appear to have assembled from individual nanoparticles. Reexamination of the samples after 4–5 days from initial preparation showed significant changes in morphology, and potential mechanisms for this are discussed.
Contributors
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- By Joanne R. Adler, David A. Alexander, Laurence Alison, Catherine C. Ayoub, Peter Banister, Anthony R. Beech, Amanda Biggs, Julian Boon, Adrian Bowers, Neil Brewer, Eric Broekaert, Paula Brough, Jennifer M. Brown, Kevin Browne, Elizabeth A. Campbell, David Canter, Michael Carlin, Shihning Chou, Martin A. Conway, Claire Cooke, David Cooke, Ilse Derluyn, Robert J. Edelmann, Vincent Egan, Tom Ellis, Marie Eyre, David P. Farrington, Seena Fazel, Daniel B. Fishman, Victoria Follette, Katarina Fritzon, Elizabeth Gilchrist, Nathan D. Gillard, Renée Gobeil, Agnieszka Golec de Zavala, Jane Goodman-Delahunty, Lynsey Gozna, Don Grubin, Gisli H. Gudjonsson, Helinä Häkkänen-Nyholm, Guy Hall, Nathan Hall, Roisin Hall, Sean Hammond, Leigh Harkins, Grant T. Harris, Camilla Herbert, Robert D. Hoge, Todd E. Hogue, Clive R. Hollin, Lorraine Hope, Miranda A. H. Horvath, Kevin Howells, Carol A. Ireland, Jane L. Ireland, Mark Kebbell, Michael King, Bruce D. Kirkcaldy, Heidi La Bash, Cara Laney, William R. Lindsay, Elizabeth F. Loftus, L. E. Marshall, W. L. Marshall, James McGuire, Neil McKeganey, T. M. McMillan, Mary McMurran, Joav Merrick, Becky Milne, Joanne M. Nadkarni, Claire Nee, M. D. O’Brien, William O’Donohue, Darragh O’Neill, Jane Palmer, Adria Pearson, Derek Perkins, Devon L. L. Polaschek, Louise E. Porter, Charlotte C. Powell, Graham E. Powell, Martine Powell, Christine Puckering, Ethel Quayle, Vernon L. Quinsey, Marnie E. Rice, Randall Richardson-Vejlgaard, Richard Rogers, Louis B Schlesinger, Carolyn Semmler, G. A. Serran, Ralph C. Serin, John L. Taylor, Max Taylor, Brian Thomas-Peter, Paul A. Tiffin, Graham Towl, Rosie Travers, Arlene Vetere, Graham Wagstaff, Helen Wakeling, Fiona Warren, Brandon C. Welsh, David Wexler, Margaret Wilson, Dan Yarmey, Susan Young
- Edited by Jennifer M. Brown, London School of Economics and Political Science, Elizabeth A. Campbell, University of Glasgow
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- The Cambridge Handbook of Forensic Psychology
- Published online:
- 06 July 2010
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- 29 April 2010, pp xix-xxiii
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Macro Molecular Dynamics by Multiple Particle Analysis: Classifying Distinct Conformational States by Generalized Projection Matching
- J. Bernard Heymann, James F. Conway, Alasdair C. Steven
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- Journal:
- Microscopy and Microanalysis / Volume 10 / Issue S02 / August 2004
- Published online by Cambridge University Press:
- 01 August 2004, pp. 30-31
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- August 2004
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Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.
Vive La Différence! Mapping Macromolecular Complexes by Generalized Difference Imaging
- Alasdair C. Steven, James F. Conway, Naiqian Cheng, Norman R. Watts, Paul T. Wingfield
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- Journal:
- Microscopy and Microanalysis / Volume 6 / Issue S2 / August 2000
- Published online by Cambridge University Press:
- 02 July 2020, pp. 252-253
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- August 2000
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Overview. Three-dimensional cryo-electron microscopy holds great potential for the investigation of macromolecular complexes, including viruses, the cytoskeleton, and the nanomachines that carry out many vital cellular functions. Such complexes often contain protein subunits of different kinds, with cumulative molecular weights running well into the megadalton range. To rationalize their functional assignments in structural terms, the first order of business is to map the locations of the component subunits of a given complex. A more detailed objective then becomes to understand the organization of their domains and the overall layout of the polypeptide chains. With current methodology, resolutions below 20Å are often achievable in cryo-EM, extending below 10 Å in favorable cases. Although resolutions of this order yield valuable morphological information, they do not usually suffice to identify individual subunits within a complex. Generalized difference imaging offers a solution to this problem of molecular mapping.
Proteolytic Control of Bacteriophage HK97 Capsid Maturation.
- Robert L. Duda, James F. Conway, Naiqian Cheng, Alasdair C. Steven, Roger W. Hendrix
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- Journal:
- Microscopy and Microanalysis / Volume 4 / Issue S2 / July 1998
- Published online by Cambridge University Press:
- 02 July 2020, pp. 984-985
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- July 1998
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HK97 is a tailed temperate bacteriophage of E. coli that builds an icosahedral capsid using steps that include regulated assembly, proteolysis, radical conformational changes and the formation of novel covalent bonds (Fig. 1). This pathway is being exploited as a model system to explore how the formation of multiprotein complexes can be regulated by each of these mechanisms. We have identified and purified at least four intermediates (Prohead I, Prohead II, Head I and Head II) and examined them by cryo-electron microscopy and three dimensional reconstruction procedures (Fig. 2). Comparison of particle reconstructions at resolution of about 25 - 30 A have lead to major insights into the causes and purposes of the regulated changes that we have also characterized biochemically and genetically.
Prohead I consists of 420 copies of the 42 kDa gp5 capsid protein arranged as 72 blister-shaped morphological capsomers in a thick walled hollow T=7 icosahedral particle with a diameter of -470 Å.
Prohead Perestroika: Bacteriophage T7 Capsid Before and After Maturation
- Mario E. Cerritelli, James F. Conway, Naiqian Cheng, Alasdair C. Steven
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- Journal:
- Microscopy and Microanalysis / Volume 3 / Issue S2 / August 1997
- Published online by Cambridge University Press:
- 02 July 2020, pp. 93-94
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- August 1997
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Bacteriophage T7 provides a well defined system to study the assembly of a moderately complex virus. The mature virion consists of a 60 nm icosahedral capsid containing the linear 40 kb genome and an internal protein “core”, and a short tail. The capsid originates as a DNA-free prohead, whose assembly requires both the major capsid protein (gpl0, ∼ 420 copies) and the scaffolding protein (gp9, ∼180 copies). Native proheads incorporate an oligomeric ring of the connector/portal protein at one vertex and the inner core, but prohead-like particles assemble when gp10 and gp9 alone are expressed. In maturation -as with other dsDNA phages - the T7 prohead undergoes a major conformational change, in which the shell structure alters dramatically, and the scaffolding protein is expelled. We have used cryo-EM in combination with other techniques to study this transition and to investigate the interactions between scaffold and surface shell in the T7 prohead.
Highly purified preparations of proheads were generated from the co-expression of head and scaffolding proteins from the cloned gene in E. coli. Tail-less mature capsids as well as DNA-filled heads were prepared from infection of a T7 strain that completely lacks the tail genes.
John Paul II: Touching the Heart of Black Africa
- James F. Conway
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Pope John Paul II explored the African continent this May with all the stamina, exuberance, and gusto of the nineteenth-century missionary-explorers Stanley and Livingston. He had to call on his talents as linguist, diplomat, humanist, and intellectual to deal with the complex problems he faced —and continues to face. For examples: How should Rome react to the continuing Africanization of the evangelization of the Church? What is the position of Christianity vis-à-vis the proliferation of Marxist/socialist experiments in Africa? Can Christianity coexist peacefully with Islam in a continent where the latter is growing at a rate of 3 1/2 million adherents per year?
Cuba, After Chile's Bloody Fall
- James F. Conway
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Laurence Birns's fine article, “Chile: A Bloody Fall” (Worldview, November, 1973), came to my attention after I returned from a few weeks' visit to Cuba, a visit that coincided with the fall of Allende. The overthrow of Allende drew enormous response.
“Fidel, Allende, el pueblo les defiende”— Fidel, Allende, the people will defend you—shouted some 500,000 Cubans who jammed the Plaza of the Revolution on the afternoon of September 28 in Havana. A bold-colored outdoor mosaic locates Chile's martyr catty-corner to the Che Guevara monument and just in front of that of Cuba's liberator, José Marti. Allende's finger is pointing skyward in one of his favorite gestures. The inscription below reads: “The forces of fascism will not crush the Chilean people.”