5 results
Characterisation of age and polarity at onset in bipolar disorder
- Janos L. Kalman, Loes M. Olde Loohuis, Annabel Vreeker, Andrew McQuillin, Eli A. Stahl, Douglas Ruderfer, Maria Grigoroiu-Serbanescu, Georgia Panagiotaropoulou, Stephan Ripke, Tim B. Bigdeli, Frederike Stein, Tina Meller, Susanne Meinert, Helena Pelin, Fabian Streit, Sergi Papiol, Mark J. Adams, Rolf Adolfsson, Kristina Adorjan, Ingrid Agartz, Sofie R. Aminoff, Heike Anderson-Schmidt, Ole A. Andreassen, Raffaella Ardau, Jean-Michel Aubry, Ceylan Balaban, Nicholas Bass, Bernhard T. Baune, Frank Bellivier, Antoni Benabarre, Susanne Bengesser, Wade H Berrettini, Marco P. Boks, Evelyn J. Bromet, Katharina Brosch, Monika Budde, William Byerley, Pablo Cervantes, Catina Chillotti, Sven Cichon, Scott R. Clark, Ashley L. Comes, Aiden Corvin, William Coryell, Nick Craddock, David W. Craig, Paul E. Croarkin, Cristiana Cruceanu, Piotr M. Czerski, Nina Dalkner, Udo Dannlowski, Franziska Degenhardt, Maria Del Zompo, J. Raymond DePaulo, Srdjan Djurovic, Howard J. Edenberg, Mariam Al Eissa, Torbjørn Elvsåshagen, Bruno Etain, Ayman H. Fanous, Frederike Fellendorf, Alessia Fiorentino, Andreas J. Forstner, Mark A. Frye, Janice M. Fullerton, Katrin Gade, Julie Garnham, Elliot Gershon, Michael Gill, Fernando S. Goes, Katherine Gordon-Smith, Paul Grof, Jose Guzman-Parra, Tim Hahn, Roland Hasler, Maria Heilbronner, Urs Heilbronner, Stephane Jamain, Esther Jimenez, Ian Jones, Lisa Jones, Lina Jonsson, Rene S. Kahn, John R. Kelsoe, James L. Kennedy, Tilo Kircher, George Kirov, Sarah Kittel-Schneider, Farah Klöhn-Saghatolislam, James A. Knowles, Thorsten M. Kranz, Trine Vik Lagerberg, Mikael Landen, William B. Lawson, Marion Leboyer, Qingqin S. Li, Mario Maj, Dolores Malaspina, Mirko Manchia, Fermin Mayoral, Susan L. McElroy, Melvin G. McInnis, Andrew M. McIntosh, Helena Medeiros, Ingrid Melle, Vihra Milanova, Philip B. Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Markus M. Nöthen, Tomas Novak, John I. Nurnberger, Niamh O'Brien, Kevin S. O'Connell, Claire O'Donovan, Michael C. O'Donovan, Nils Opel, Abigail Ortiz, Michael J. Owen, Erik Pålsson, Carlos Pato, Michele T. Pato, Joanna Pawlak, Julia-Katharina Pfarr, Claudia Pisanu, James B. Potash, Mark H Rapaport, Daniela Reich-Erkelenz, Andreas Reif, Eva Reininghaus, Jonathan Repple, Hélène Richard-Lepouriel, Marcella Rietschel, Kai Ringwald, Gloria Roberts, Guy Rouleau, Sabrina Schaupp, William A Scheftner, Simon Schmitt, Peter R. Schofield, K. Oliver Schubert, Eva C. Schulte, Barbara Schweizer, Fanny Senner, Giovanni Severino, Sally Sharp, Claire Slaney, Olav B. Smeland, Janet L. Sobell, Alessio Squassina, Pavla Stopkova, John Strauss, Alfonso Tortorella, Gustavo Turecki, Joanna Twarowska-Hauser, Marin Veldic, Eduard Vieta, John B. Vincent, Wei Xu, Clement C. Zai, Peter P. Zandi, Psychiatric Genomics Consortium (PGC) Bipolar Disorder Working Group, International Consortium on Lithium Genetics (ConLiGen), Colombia-US Cross Disorder Collaboration in Psychiatric Genetics, Arianna Di Florio, Jordan W. Smoller, Joanna M. Biernacka, Francis J. McMahon, Martin Alda, Bertram Müller-Myhsok, Nikolaos Koutsouleris, Peter Falkai, Nelson B. Freimer, Till F.M. Andlauer, Thomas G. Schulze, Roel A. Ophoff
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- Journal:
- The British Journal of Psychiatry / Volume 219 / Issue 6 / December 2021
- Published online by Cambridge University Press:
- 25 August 2021, pp. 659-669
- Print publication:
- December 2021
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Background
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
‘They deserve a treat’: the nature and antecedents of parental licensing surrounding children’s physical activity
- Kwok Hong Law, James A Dimmock, Ashleigh L Thornton, Joanna C Nicholas, Gordon Ho, Daniel F Gucciardi, Kym J Guelfi, Ben Jackson
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- Journal:
- Public Health Nutrition / Volume 24 / Issue 8 / June 2021
- Published online by Cambridge University Press:
- 28 August 2020, pp. 2098-2108
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Objective:
Little is known about parents’ compensatory health beliefs (CHB) surrounding their children’s engagement in physical activity (PA). Our aim was to provide evidence regarding the nature of, and factors underpinning, parents’ PA-related compensatory beliefs for their children.
Design:A qualitative descriptive approach and thematic content analysis were employed.
Setting:Parents were recruited from community sport and PA programmes.
Participants:Eighteen parents aged 32–52 years (mean age = 40·8 (sd 5·4) years; six males; twelve females).
Results:Analyses indicated that parents compensate through ‘passive’ or ‘active’ means. Among parents who compensated, most described their provision of ‘treat’ foods/drinks and a minority described allowing extended sedentary time to their children. Parents’ reasons underpinning these beliefs related to their child’s general physical/health status and psychological characteristics, and their own motivation and mood state.
Conclusions:These findings provide the first evidence of unhealthy dietary and sedentary behaviour CHB that parents may hold regarding their children’s involvement in PA.
Investigation of the Internal Structure of a Modern Seafloor Hydrothermal Chimney With a Combination of EBSD, EPMA, and XRD
- Matthew Glenn, Siyu Hu, Stephen Barnes, Aaron Torpy, Anthony E. Hughes, Colin M. MacRae, Nathan A.S. Webster, Nicholas C. Wilson, Joanna Parr, Ray Binns
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- Journal:
- Microscopy and Microanalysis / Volume 26 / Issue 4 / August 2020
- Published online by Cambridge University Press:
- 20 May 2020, pp. 793-807
- Print publication:
- August 2020
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Samples from the sphalerite-dominated zone of a seafloor massive sulfide chimney, the Satanic Mills Chimney of the PACMANUS hydrothermal field, have been investigated to determine the internal macrostructure and microstructure of this zone, the phases present, and the distribution of metals. A combination of electron probe microanalysis, electron backscattered diffraction, and x-ray diffraction has been used. At the macroscale, this zone of the chimney wall is heavily porous and is comprised primarily of sphalerite, enclosing minor chalcopyrite, pyrite, and wurtzite. A Pb–As sulfosalt layer of possible microbial origins is present at the outer edge of the sphalerite matrix, next to a pore. The sphalerite has grown in globules on the order of 300 μm in diameter. At the microscale, the sphalerite features a colloform texture and a duplex-type grain structure consisting of either fine-grain regions in the center surrounded by coarse-grained regions or radiating coarse grains only. Pb- and As-rich bands have been detected in the colloform sphalerite, and growth twins have been observed in both the sphalerite and chalcopyrite crystals. A qualitative description of the growth of a typical globule is given, including nucleation, crystal growth, and solute redistribution.
Contributors
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- By Federica Agosta, Alberto Albanese, Timothy J. Amrhein, A. M. Barrett, Walter S. Bartynski, Felix Benninger, Thomas Brandt, Andrew G. Burke, Michelle Cameron, Elisa Canu, Louis R. Caplan, Christine M. Carr, Daniel J. A. Connolly, Firouz Daneshgari, John DeLuca, Marianne de Visser, Marianne Dieterich, Antonio E. Elia, Joseph H. Feinberg, Massimo Filippi, Lauren C. Frey, Gaëtan Garraux, Andrea Ginestroni, Peter J. Goadsby, Bronwyn E. Hamilton, Simon J. Hickman, Holly E. Hinson, Jon P. Jennings, Jan Kassubek, Horacio Kaufmann, David M. Kaylie, Joanna Kitley, Vladimir S. Kostic, C. T. Paul Krediet, Megan C. Leary, Farooq H. Maniyar, Ken R. Maravilla, Mario Mascalchi, Rajarshi Mazumder, Priyesh Mehta, Jacqueline A. Palace, Raj M. Paspulati, Christopher A. Potter, Angelo Quattrini, Louis P. Riccelli, Nilo Riva, Maria A. Rocca, Mirabelle B. Sajisevi, Richard Salazar-Montero, Nicholas D. Schiff, Jack H. Simon, Israel Steiner, Carl D. Stevens, Bart P. van de Warrenburg, Judith van Gaalen, William J. Weiner, Jane L. Weissman, Jay Yao, G. Bryan Young
- Edited by Massimo Filippi, Jack H. Simon
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- Book:
- Imaging Acute Neurologic Disease
- Published online:
- 05 October 2014
- Print publication:
- 11 September 2014, pp vi-viii
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Thermodynamic linkage between the binding of protons and inhibitors to HIV-1 protease
- JOANNA TRYLSKA, JAN ANTOSIEWICZ, MACIEJ GELLER, C. NICHOLAS HODGE, RONALD M. KLABE, MARTHA S. HEAD, MICHAEL K. GILSON
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- Journal:
- Protein Science / Volume 8 / Issue 1 / January 1999
- Published online by Cambridge University Press:
- 01 January 1999, pp. 180-195
- Print publication:
- January 1999
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The aspartyl dyad of free HIV-1 protease has apparent pKas of ∼3 and ∼6, but recent NMR studies indicate that the aspartyl dyad is fixed in the doubly protonated form over a wide pH range when cyclic urea inhibitors are bound, and in the monoprotonated form when the inhibitor KNI-272 is bound. We present computations and measurements related to these changes in protonation and to the thermodynamic linkage between protonation and inhibition. The Poisson–Boltzmann model of electrostatics is used to compute the apparent pKas of the aspartyl dyad in the free enzyme and in complexes with four different inhibitors. The calculations are done with two parameter sets. One assigns ε = 4 to the solute interior and uses a detailed model of ionization; the other uses ε = 20 for the solute interior and a simplified representation of ionization. For the free enzyme, both parameter sets agree well with previously measured apparent pKas of ∼3 and ∼6. However, the calculations with an internal dielectric constant of 4 reproduce the large pKa shifts upon binding of inhibitors, but the calculations with an internal dielectric constant of 20 do not. This observation has implications for the accurate calculation of pKas in complex protein environments.
Because binding of a cyclic urea inhibitor shifts the pKas of the aspartyl dyad, changing the pH is expected to change its apparent binding affinity. However, we find experimentally that the affinity is independent of pH from 5.5 to 7.0. Possible explanations for this discrepancy are discussed.