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John J E Chua

Hebert Alberto Vargas, Gem M Kramer, Andrew M Scott, Andrew Weickhardt, Andreas A Meier, Nicole Parada, Bradley J Beattie, John L Humm, Kevin D Staton, Pat B Zanzonico, Serge K Lyashchenko, Jason S Lewis, Maqsood Yaqub, Ramon E Sosa, Alfons J van den Eertwegh, Ian D Davis, Uwe Ackermann, Kunthi Pathmaraj, Robert C Schuit, Albert D Windhorst, Sue Chua, Wolfgang A Weber, Steven M Larson, Howard I Scher, Adriaan A Lammertsma, Otto Hoekstra, Michael J Morris
18 F-fluorodihydrotestosterone (18 F-FDHT) is a radiolabeled analogue of the androgen receptor's primary ligand that is currently being credentialed as a biomarker for prognosis, response, and pharmacodynamic effects of new therapeutics. As part of the biomarker qualification process, we prospectively assessed its reproducibility and repeatability in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: We conducted a prospective multi-institutional study of mCRPC patients undergoing two (test/re-test) 18 F-FDHT PET/CT scans on two consecutive days...
April 6, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Michael Fraser, Veronica Y Sabelnykova, Takafumi N Yamaguchi, Lawrence E Heisler, Julie Livingstone, Vincent Huang, Yu-Jia Shiah, Fouad Yousif, Xihui Lin, Andre P Masella, Natalie S Fox, Michael Xie, Stephenie D Prokopec, Alejandro Berlin, Emilie Lalonde, Musaddeque Ahmed, Dominique Trudel, Xuemei Luo, Timothy A Beck, Alice Meng, Junyan Zhang, Alister D'Costa, Robert E Denroche, Haiying Kong, Shadrielle Melijah G Espiritu, Melvin L K Chua, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas B Buchner, Michèle Orain, Valérie Picard, Helène Hovington, Alexander Murison, Ken Kron, Nicholas J Harding, Christine P'ng, Kathleen E Houlahan, Kenneth C Chu, Bryan Lo, Francis Nguyen, Constance H Li, Ren X Sun, Richard de Borja, Christopher I Cooper, Julia F Hopkins, Shaylan K Govind, Clement Fung, Daryl Waggott, Jeffrey Green, Syed Haider, Michelle A Chan-Seng-Yue, Esther Jung, Zhiyuan Wang, Alain Bergeron, Alan Dal Pra, Louis Lacombe, Colin C Collins, Cenk Sahinalp, Mathieu Lupien, Neil E Fleshner, Housheng H He, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John D McPherson, Robert G Bristow, Paul C Boutros
Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries...
January 19, 2017: Nature
Beyenech Binotti, Nathan J Pavlos, Dietmar Riedel, Dirk Wenzel, Gerd Vorbrüggen, Amanda M Schalk, Karin Kühnel, Janina Boyken, Christian Erck, Henrik Martens, John J E Chua, Reinhard Jahn
Small GTPases of the Rab family not only regulate target recognition in membrane traffic but also control other cellular functions such as cytoskeletal transport and autophagy. Here we show that Rab26 is specifically associated with clusters of synaptic vesicles in neurites. Overexpression of active but not of GDP-preferring Rab26 enhances vesicle clustering, which is particularly conspicuous for the EGFP-tagged variant, resulting in a massive accumulation of synaptic vesicles in neuronal somata without altering the distribution of other organelles...
February 2, 2015: ELife
Tannistha Nandi, Matthew T G Holden, Mathew T G Holden, Xavier Didelot, Kurosh Mehershahi, Justin A Boddey, Ifor Beacham, Ian Peak, John Harting, Primo Baybayan, Yan Guo, Susana Wang, Lee Chee How, Bernice Sim, Angela Essex-Lopresti, Mitali Sarkar-Tyson, Michelle Nelson, Sophie Smither, Catherine Ong, Lay Tin Aw, Chua Hui Hoon, Stephen Michell, David J Studholme, Richard Titball, Swaine L Chen, Julian Parkhill, Patrick Tan
Burkholderia pseudomallei (Bp) is the causative agent of the infectious disease melioidosis. To investigate population diversity, recombination, and horizontal gene transfer in closely related Bp isolates, we performed whole-genome sequencing (WGS) on 106 clinical, animal, and environmental strains from a restricted Asian locale. Whole-genome phylogenies resolved multiple genomic clades of Bp, largely congruent with multilocus sequence typing (MLST). We discovered widespread recombination in the Bp core genome, involving hundreds of regions associated with multiple haplotypes...
January 2015: Genome Research
Linda J Chan, Craig M Smith, Berenice E Chua, Feng Lin, Ross A D Bathgate, Frances Separovic, Andrew L Gundlach, Mohammed Akhter Hossain, John D Wade
Relaxin, a heterodimeric polypeptide hormone, is a key regulator of collagen metabolism and multiple vascular control pathways in humans and rodents. Its actions are mediated via its cognate G-protein-coupled receptor, RXFP1 although it also "pharmacologically" activates RXFP2, the receptor for the related, insulin-like peptide 3 (INSL3), which has specific actions on reproduction and bone metabolism. Therefore, experimental tools to facilitate insights into the distinct biological actions of relaxin and INSL3 are required, particularly for studies of tissues containing both RXFP1 and RXFP2...
2013: Frontiers in Chemistry
Megan E Reller, Ufuoma Akoroda, Ajith Nagahawatte, Vasantha Devasiri, Wasantha Kodikaarachchi, John J Strouse, Robert Chua, Yan'an Hou, Angelia Chow, October M Sessions, Truls Østbye, Duane J Gubler, Christopher W Woods, Champica Bodinayake
BACKGROUND: Chikungunya virus (CHIKV) re-emerged in Sri Lanka in late 2006 after a 40-year hiatus. We sought to identify and characterize acute chikungunya infection (CHIK) in patients presenting with acute undifferentiated febrile illness in unstudied rural and semi-urban southern Sri Lanka in 2007. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled febrile patients ≥ 2 years of age, collected uniform epidemiologic and clinical data, and obtained serum samples for serology, virus isolation, and real-time reverse-transcriptase PCR (RT-PCR)...
2013: PloS One
John J E Chua, Reinhard Jahn, Dieter R Klopfenstein
Formation and normal function of neuronal synapses are intimately dependent on the delivery to and removal of biological materials from synapses by the intracellular transport machinery. Indeed, defects in intracellular transport contribute to the development and aggravation of neurodegenerative disorders. Despite its importance, regulatory mechanisms underlying this machinery remain poorly defined. We recently uncovered a phosphorylation-regulated mechanism that controls FEZ1-mediated Kinesin-1-based delivery of Stx1 into neuronal axons...
January 1, 2013: Worm
Frederick M Lartey, G-One Ahn, Bin Shen, Keith-Travis Cord, Tenille Smith, Joshua Y Chua, Sahar Rosenblum, Hongguang Liu, Michelle L James, Sophia Chernikova, Star W Lee, Laura J Pisani, Rabindra Tirouvanziam, John W Chen, Theo D Palmer, Frederick T Chin, Raphael Guzman, Edward E Graves, Billy W Loo
PURPOSE: The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [(18)F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([(18)F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model. PROCEDURES: Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later...
February 2014: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Caroline Lin Lin Chua, Graham V Brown, John A Hamilton, Malcolm E Molyneux, Stephen J Rogerson, Philippe Boeuf
In Plasmodium falciparum malaria, activation of monocytes and macrophages (monocytes/macrophages) can result in the production of various inflammatory mediators that contribute to immunopathology. Soluble CD163 (sCD163) is a specific marker of monocyte/macrophage activation typically found at increased levels during various inflammatory conditions and can be associated with poor clinical outcomes. To better understand the relationships between levels of sCD163 and clinical parameters in women with placental malaria, we measured plasma sCD163 levels in maternal peripheral and placental blood compartments at delivery and determined their correlations with birth weight and maternal haemoglobin concentrations...
2013: PloS One
John Jia En Chua, Eugenia Butkevich, Josephine M Worseck, Maike Kittelmann, Mads Grønborg, Elmar Behrmann, Ulrich Stelzl, Nathan J Pavlos, Maciej M Lalowski, Stefan Eimer, Erich E Wanker, Dieter Robert Klopfenstein, Reinhard Jahn
Presynaptic nerve terminals are formed from preassembled vesicles that are delivered to the prospective synapse by kinesin-mediated axonal transport. However, precisely how the various cargoes are linked to the motor proteins remains unclear. Here, we report a transport complex linking syntaxin 1a (Stx) and Munc18, two proteins functioning in synaptic vesicle exocytosis at the presynaptic plasma membrane, to the motor protein Kinesin-1 via the kinesin adaptor FEZ1. Mutation of the FEZ1 ortholog UNC-76 in Caenorhabditis elegans causes defects in the axonal transport of Stx...
April 10, 2012: Proceedings of the National Academy of Sciences of the United States of America
Murat Taşan, Harold J Drabkin, John E Beaver, Hon Nian Chua, Julie Dunham, Weidong Tian, Judith A Blake, Frederick P Roth
The body of human genomic and proteomic evidence continues to grow at ever-increasing rates, while annotation efforts struggle to keep pace. A surprisingly small fraction of human genes have clear, documented associations with specific functions, and new functions continue to be found for characterized genes. Here we assembled an integrated collection of diverse genomic and proteomic data for 21,341 human genes and make quantitative associations of each to 4333 Gene Ontology terms. We combined guilt-by-profiling and guilt-by-association approaches to exploit features unique to the data types...
February 2012: G3: Genes—Genomes—Genetics
Nathan J Pavlos, Mads Grønborg, Dietmar Riedel, John J E Chua, Janina Boyken, Tobias H Kloepper, Henning Urlaub, Silvio O Rizzoli, Reinhard Jahn
Rab GTPases are molecular switches that orchestrate protein complexes before membrane fusion reactions. In synapses, Rab3 and Rab5 proteins have been implicated in the exo-endocytic cycling of synaptic vesicles (SVs), but an involvement of additional Rabs cannot be excluded. Here, combining high-resolution mass spectrometry and chemical labeling (iTRAQ) together with quantitative immunoblotting and fluorescence microscopy, we have determined the exocytotic (Rab3a, Rab3b, Rab3c, and Rab27b) and endocytic (Rab4b, Rab5a/b, Rab10, Rab11b, and Rab14) Rab machinery of SVs...
October 6, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ross M Graham, Anita C G Chua, Kim W Carter, Roheeth D Delima, Daniel Johnstone, Carly E Herbison, Martin J Firth, Rebecca O'Leary, Elizabeth A Milward, John K Olynyk, Debbie Trinder
UNLABELLED: Iron and cholesterol are both essential metabolites in mammalian systems, and too much or too little of either can have serious clinical consequences. In addition, both have been associated with steatosis and its progression, contributing, inter alia, to an increase in hepatic oxidative stress. The interaction between iron and cholesterol is unclear, with no consistent evidence emerging with respect to changes in plasma cholesterol on the basis of iron status. We sought to clarify the role of iron in lipid metabolism by studying the effects of iron status on hepatic cholesterol synthesis in mice with differing iron status...
August 2010: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Wei Gao, Kyra Chua, John K Davies, Hayley J Newton, Torsten Seemann, Paul F Harrison, Natasha E Holmes, Hyun-Woo Rhee, Jong-In Hong, Elizabeth L Hartland, Timothy P Stinear, Benjamin P Howden
Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S...
2010: PLoS Pathogens
John J E Chua, Stefan Kindler, Janina Boyken, Reinhard Jahn
No abstract text is available yet for this article.
March 15, 2010: Journal of Cell Science
Mads Grønborg, Nathan J Pavlos, Irene Brunk, John J E Chua, Agnieszka Münster-Wandowski, Dietmar Riedel, Gudrun Ahnert-Hilger, Henning Urlaub, Reinhard Jahn
Synaptic vesicles (SVs) store neurotransmitters and release them by exocytosis. The vesicular neurotransmitter transporters discriminate which transmitter will be sequestered and stored by the vesicles. However, it is unclear whether the neurotransmitter phenotype of SVs is solely defined by the transporters or whether it is associated with additional proteins. Here we have compared the protein composition of SVs enriched in vesicular glutamate (VGLUT-1) and GABA transporters (VGAT), respectively, using quantitative proteomics...
January 6, 2010: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Scott M Sutherland, Michael Zappitelli, Steven R Alexander, Annabelle N Chua, Patrick D Brophy, Timothy E Bunchman, Richard Hackbarth, Michael J G Somers, Michelle Baum, Jordan M Symons, Francisco X Flores, Mark Benfield, David Askenazi, Deepa Chand, James D Fortenberry, John D Mahan, Kevin McBryde, Douglas Blowey, Stuart L Goldstein
BACKGROUND: Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry...
February 2010: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Francisco X Flores, Patrick D Brophy, Jordan M Symons, James D Fortenberry, Annabelle N Chua, Steven R Alexander, John D Mahan, Timothy E Bunchman, Douglas Blowey, Michael J G Somers, Michelle Baum, Richard Hackbarth, Deepa Chand, Kevin McBryde, Mark Benfield, Stuart L Goldstein
Pediatric stem cell transplant (SCT) recipients commonly develop acute renal failure (ARF). We report the demographic and survival data of pediatric SCT patients enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. Since 1 January 2001, 51/370 (13.8%) patients entered in the ppCRRT Registry had received a SCT. Median age was 13.63 (0.53-23.52) years. The primary reasons for the initiation of continuous renal replacement therapy (CRRT) were treatment of fluid overload (FO) and electrolyte imbalance (49%), FO only (39%), electrolyte imbalance only (8%) and other reasons (4%)...
April 2008: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Marcin Barszczewski, John J Chua, Alexander Stein, Ulrike Winter, Rainer Heintzmann, Felipe E Zilly, Dirk Fasshauer, Thorsten Lang, Reinhard Jahn
Regulated exocytosis in neurons and neuroendocrine cells requires the formation of a stable soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex consisting of synaptobrevin-2/vesicle-associated membrane protein 2, synaptosome-associated protein of 25 kDa (SNAP-25), and syntaxin 1. This complex is subsequently disassembled by the concerted action of alpha-SNAP and the ATPases associated with different cellular activities-ATPase N-ethylmaleimide-sensitive factor (NSF). We report that NSF inhibition causes accumulation of alpha-SNAP in clusters on plasma membranes...
March 2008: Molecular Biology of the Cell
Jordan M Symons, Annabelle N Chua, Michael J G Somers, Michelle A Baum, Timothy E Bunchman, Mark R Benfield, Patrick D Brophy, Douglas Blowey, James D Fortenberry, Deepa Chand, Francisco X Flores, Richard Hackbarth, Steven R Alexander, John Mahan, Kevin D McBryde, Stuart L Goldstein
BACKGROUND: This article reports demographic characteristics and intensive care unit survival for 344 patients from the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry, a voluntary multicenter observational network. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Ages were newborn to 25 yr, 58% were male, and weights were 1.3 to 160 kg. Patients spent a median of 2 d in the intensive care unit before CRRT (range 0 to 135). At CRRT initiation, 48% received diuretics and 66% received vasoactive drugs...
July 2007: Clinical Journal of the American Society of Nephrology: CJASN
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