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https://www.readbyqxmd.com/read/29790577/esophageal-igg4-levels-correlate-with-histopathologic-and-transcriptomic-features-in-eosinophilic-esophagitis
#1
Chen E Rosenberg, Melissa K Mingler, Julie M Caldwell, Margaret H Collins, Patricia C Fulkerson, David W Morris, Vincent A Mukkada, Philip E Putnam, Tetsuo Shoda, Ting Wen, Marc E Rothenberg
BACKGROUND: Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. METHODS: This case-control study included pediatric subjects with EoE (≥ 15 eosinophils/HPF) and non-EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1-IgG4 using the Luminex 100 system; IgE was quantified by ELISA...
May 23, 2018: Allergy
https://www.readbyqxmd.com/read/29784554/renal-stress-and-kidney-injury-biomarkers-in-response-to-endurance-cycling-in-the-heat-with-and-without-ibuprofen
#2
Brendon P McDermott, Cody R Smith, Cory L Butts, Aaron R Caldwell, Elaine C Lee, Jakob L Vingren, Colleen X Munoz, Laura J Kunces, Keith Williamson, Matthew S Ganio, Lawrence E Armstrong
Exercise, especially in the heat, can contribute to acute kidney injury, which can expedite chronic kidney disease onset. The additional stress of ibuprofen use is hypothesized to increase renal stress. OBJECTIVES: To observe the effects of endurance cycling in the heat on renal function. Secondarily, we investigated the effect of ibuprofen ingestion on kidney stress. DESIGN: Randomized, placebo controlled and observational methods were utilized. METHODS: Forty cyclists (52±9y, 21...
May 16, 2018: Journal of Science and Medicine in Sport
https://www.readbyqxmd.com/read/29780547/protecting-group-free-radical-c-h-trifluoromethylation-of-peptides
#3
Naoko Ichiishi, John P Caldwell, Melissa Lin, Wendy Zhong, Xiaohong Zhu, Eric Streckfuss, Hai-Young Kim, Craig A Parish, Shane W Krska
Two radical-based approaches have been developed to effect the trifluoromethylation of aryl C-H bonds in native peptides either using stoichiometric oxidant or visible light photoredox catalysis. The reported methods are able to derivatize tyrosine and tryptophan sidechains under biocompatible conditions, and a number of examples are reported involving fully unprotected peptides with up to 51 amino acids. The development of this chemistry adds to the growing array of chemical methods for selectively modifying amino acid residues in the context of complex peptides...
May 7, 2018: Chemical Science
https://www.readbyqxmd.com/read/29762666/discovery-and-validation-of-methylation-biomarkers-for-ulcerative-colitis-associated-neoplasia
#4
Andrew D Beggs, Jonathan James, Germaine Caldwell, Toby Prout, Mark P Dilworth, Phillipe Taniere, Tariq Iqbal, Dion G Morton, Glenn Matthews
Background and aims: Ulcerative colitis (UC) is associated with a higher background risk of dysplasia and/or neoplasia due to chronic inflammation. There exist few biomarkers for identification of patients with dysplasia, and targeted biopsies in this group of patients are inaccurate in reliably identifying dysplasia. We aimed to examine the epigenome of UC dysplasia and to identify and validate potential biomarkers. Methods: Colonic samples from patients with UC-associated dysplasia or neoplasia underwent epigenome-wide analysis on the Illumina 450K methylation array...
May 14, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29748634/gene-by-environment-interactions-that-disrupt-mitochondrial-homeostasis-cause-neurodegeneration-in-c-elegans-parkinson-s-models
#5
Hanna Kim, Rylee J Perentis, Guy A Caldwell, Kim A Caldwell
Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29746468/seasonal-temperature-variation-influences-climate-suitability-for-dengue-chikungunya-and-zika-transmission
#6
John H Huber, Marissa L Childs, Jamie M Caldwell, Erin A Mordecai
Dengue, chikungunya, and Zika virus epidemics transmitted by Aedes aegypti mosquitoes have recently (re)emerged and spread throughout the Americas, Southeast Asia, the Pacific Islands, and elsewhere. Understanding how environmental conditions affect epidemic dynamics is critical for predicting and responding to the geographic and seasonal spread of disease. Specifically, we lack a mechanistic understanding of how seasonal variation in temperature affects epidemic magnitude and duration. Here, we develop a dynamic disease transmission model for dengue virus and Aedes aegypti mosquitoes that integrates mechanistic, empirically parameterized, and independently validated mosquito and virus trait thermal responses under seasonally varying temperatures...
May 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29729938/slc9a3-nhe3-dysregulation-and-dilated-intercellular-spaces-in-eosinophilic-esophagitis
#7
Chang Zeng, Simone Vanoni, David Wu, Julie M Caldwell, Justin C Wheeler, Kavisha Arora, Taeko K Noah, Lisa Waggoner, John A Besse, Amnah N Yamani, Jazib Uddin, Mark Rochman, Ting Wen, Mirna Chehade, Margaret Collins, Vincent Mukkada, Philip Putnam, Anjaparavanda P Naren, Marc E Rothenberg, Simon P Hogan
BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by histopathologic modifications of esophageal tissue including eosinophil-rich inflammation, basal zone hyperplasia (BZH) and dilated intercellular spaces (DIS). The underlying molecular processes that drive the histopathologic features of EoE remain largely unexplored. OBJECTIVE: To investigate the involvement of SLC9A3 in esophageal epithelial [pH]i and DIS formation and the histopathological features of EoE...
May 3, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29698625/sphingolipids-as-targets-for-inhalation-treatment-of-cystic-fibrosis
#8
Katrin Anne Becker, Joachim Riethmüller, Aaron P Seitz, Aaron Gardner, Ryan Boudreau, Markus Kamler, Burkhard Kleuser, Edward Schuchman, Charles C Caldwell, Michael J Edwards, Heike Grassmé, Malcolm Brodlie, Erich Gulbins
Studies over the past several years have demonstrated the important role of sphingolipids in cystic fibrosis (CF), chronic obstructive pulmonary disease and acute lung injury. Ceramide is increased in airway epithelial cells and alveolar macrophages of CF mice and humans, while sphingosine is dramatically decreased. This increase in ceramide results in chronic inflammation, increased death of epithelial cells, release of DNA into the bronchial lumen and thereby an impairment of mucociliary clearance; while the lack of sphingosine in airway epithelial cells causes high infection susceptibility in CF mice and possibly patients...
April 24, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29694188/search-for-neutrinoless-double-%C3%AE-decay-in-76-ge-with-the-majorana-demonstrator
#9
C E Aalseth, N Abgrall, E Aguayo, S I Alvis, M Amman, I J Arnquist, F T Avignone, H O Back, A S Barabash, P S Barbeau, C J Barton, P J Barton, F E Bertrand, T Bode, B Bos, M Boswell, A W Bradley, R L Brodzinski, V Brudanin, M Busch, M Buuck, A S Caldwell, T S Caldwell, Y-D Chan, C D Christofferson, P-H Chu, J I Collar, D C Combs, R J Cooper, C Cuesta, J A Detwiler, P J Doe, J A Dunmore, Yu Efremenko, H Ejiri, S R Elliott, J E Fast, P Finnerty, F M Fraenkle, Z Fu, B K Fujikawa, E Fuller, A Galindo-Uribarri, V M Gehman, T Gilliss, G K Giovanetti, J Goett, M P Green, J Gruszko, I S Guinn, V E Guiseppe, A L Hallin, C R Haufe, L Hehn, R Henning, E W Hoppe, T W Hossbach, M A Howe, B R Jasinski, R A Johnson, K J Keeter, J D Kephart, M F Kidd, A Knecht, S I Konovalov, R T Kouzes, B D LaFerriere, J Leon, K T Lesko, L E Leviner, J C Loach, A M Lopez, P N Luke, J MacMullin, S MacMullin, M G Marino, R D Martin, R Massarczyk, A B McDonald, D-M Mei, S J Meijer, J H Merriman, S Mertens, H S Miley, M L Miller, J Myslik, J L Orrell, C O'Shaughnessy, G Othman, N R Overman, G Perumpilly, W Pettus, D G Phillips, A W P Poon, K Pushkin, D C Radford, J Rager, J H Reeves, A L Reine, K Rielage, R G H Robertson, M C Ronquest, N W Ruof, A G Schubert, B Shanks, M Shirchenko, K J Snavely, N Snyder, D Steele, A M Suriano, D Tedeschi, W Tornow, J E Trimble, R L Varner, S Vasilyev, K Vetter, K Vorren, B R White, J F Wilkerson, C Wiseman, W Xu, E Yakushev, H Yaver, A R Young, C-H Yu, V Yumatov, I Zhitnikov, B X Zhu, S Zimmermann
The Majorana Collaboration is operating an array of high purity Ge detectors to search for neutrinoless double-β decay in ^{76}Ge. The Majorana Demonstrator comprises 44.1 kg of Ge detectors (29.7 kg enriched in ^{76}Ge) split between two modules contained in a low background shield at the Sanford Underground Research Facility in Lead, South Dakota. Here we present results from data taken during construction, commissioning, and the start of full operations. We achieve unprecedented energy resolution of 2...
March 30, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29694176/improved-limit-on-neutrinoless-double-%C3%AE-decay-of-76-ge-from-gerda-phase-ii
#10
M Agostini, A M Bakalyarov, M Balata, I Barabanov, L Baudis, C Bauer, E Bellotti, S Belogurov, A Bettini, L Bezrukov, J Biernat, T Bode, D Borowicz, V Brudanin, R Brugnera, A Caldwell, C Cattadori, A Chernogorov, T Comellato, V D'Andrea, E V Demidova, N Di Marco, A Domula, E Doroshkevich, V Egorov, R Falkenstein, A Gangapshev, A Garfagnini, P Grabmayr, V Gurentsov, K Gusev, J Hakenmüller, A Hegai, M Heisel, S Hemmer, R Hiller, W Hofmann, M Hult, L V Inzhechik, J Janicskó Csáthy, J Jochum, M Junker, V Kazalov, Y Kermaidic, T Kihm, I V Kirpichnikov, A Kirsch, A Kish, A Klimenko, R Kneißl, K T Knöpfle, O Kochetov, V N Kornoukhov, V V Kuzminov, M Laubenstein, A Lazzaro, M Lindner, I Lippi, A Lubashevskiy, B Lubsandorzhiev, G Lutter, C Macolino, B Majorovits, W Maneschg, M Miloradovic, R Mingazheva, M Misiaszek, P Moseev, I Nemchenok, K Panas, L Pandola, K Pelczar, L Pertoldi, A Pullia, C Ransom, S Riboldi, N Rumyantseva, C Sada, F Salamida, C Schmitt, B Schneider, S Schönert, A-K Schütz, O Schulz, B Schwingenheuer, O Selivanenko, E Shevchik, M Shirchenko, H Simgen, A Smolnikov, L Stanco, L Vanhoefer, A A Vasenko, A Veresnikova, K von Sturm, V Wagner, A Wegmann, T Wester, C Wiesinger, M Wojcik, E Yanovich, I Zhitnikov, S V Zhukov, D Zinatulina, A Zschocke, A J Zsigmond, K Zuber, G Zuzel
The GERDA experiment searches for the lepton-number-violating neutrinoless double-β decay of ^{76}Ge (^{76}Ge→^{76}Se+2e^{-}) operating bare Ge diodes with an enriched ^{76}Ge fraction in liquid argon. The exposure for broad-energy germanium type (BEGe) detectors is increased threefold with respect to our previous data release. The BEGe detectors feature an excellent background suppression from the analysis of the time profile of the detector signals. In the analysis window a background level of 1.0_{-0...
March 30, 2018: Physical Review Letters
https://www.readbyqxmd.com/read/29671583/optochemical-control-of-protein-localization-and-activity-within-cell-like-compartments
#11
Reese M Caldwell, Jessica G Bermudez, David Thai, Chanat Aonbangkhen, Benjamin S Schuster, Taylor Courtney, Alexander Deiters, Daniel A Hammer, David M Chenoweth, Matthew C Good
We report inducible dimerization strategies for controlling protein positioning, enzymatic activity, and organelle assembly inside synthetic cell-like compartments upon photostimulation. Using a photocaged TMP-Haloligand compound, we demonstrate small molecule and light-induced dimerization of DHFR and Haloenzyme to localize proteins to a compartment boundary and reconstitute tripartite sfGFP assembly. Using photocaged rapamycin and fragments of split TEV protease fused to FRB and FKBP, we establish optical triggering of protease activity inside cell-size compartments...
April 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29661878/plasticity-of-aminoglycoside-binding-to-antibiotic-kinase-aph-2-ia
#12
Shane J Caldwell, Albert M Berghuis
APH(2")-Ia aminoglycoside resistance enzyme forms the C-terminal domain of the bifunctional AAC(6')-Ie/APH(2")-Ia enzyme and confers high-level resistance to natural 4,6-disubstituted aminoglycosides. In addition, reports have suggested that the enzyme can phosphorylate 4,5-disubstituted compounds and aminoglycosides with substitutions at the N1-position. Previously determined structures of the enzyme with aminoglycosides bound have not indicated how these non-canonical substrates could bind and be modified by the enzyme...
April 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29655756/effects-of-ocean-warming-and-acidification-combined-with-nutrient-enrichment-on-chemical-composition-and-functional-properties-of-ulva-rigida
#13
Guang Gao, Anthony S Clare, Eleni Chatzidimitriou, Craig Rose, Gary Caldwell
Ulva is increasingly viewed as a food source in the world. Here, Ulva rigida was cultured at two levels of temperature (14, 18 °C), pH (7.95, 7.55, corresponding to low and high pCO2 ), and nitrate conditions (6 μmol L-1 , 150 μmol L-1 ), to investigate the effects of ocean warming, acidification, and eutrophication on food quality of Ulva species. High temperature increased the content of each amino acid. High nitrate increased the content of all amino acids except aspartic acid and cysteine. High temperature, pCO2 , and nitrate also increased the content of most fatty acids...
August 30, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29643102/research-priority-setting-in-childhood-chronic-disease-a-systematic-review
#14
Harrison Lindsay Odgers, Allison Tong, Pamela Lopez-Vargas, Andrew Davidson, Adam Jaffe, Anne McKenzie, Ross Pinkerton, Melissa Wake, Peter Richmond, Sally Crowe, Patrina Ha Yuen Caldwell, Sophie Hill, Jennifer Couper, Suzy Haddad, Behrouz Kassai, Jonathan C Craig
OBJECTIVE: To evaluate research priority setting approaches in childhood chronic diseases and to describe the priorities of stakeholders including patients, caregivers/families and health professionals. DESIGN: We conducted a systematic review of MEDLINE, Embase, PsycINFO and CINAHL from inception to 16 October 2016. Studies that elicited stakeholder priorities for paediatric chronic disease research were eligible for inclusion. Data on the prioritisation process were extracted using an appraisal checklist...
April 11, 2018: Archives of Disease in Childhood
https://www.readbyqxmd.com/read/29613852/pulmonary-infection-of-cystic-fibrosis-mice-with-staphylococcus-aureus-requires-expression-of-%C3%AE-toxin
#15
Simone Keitsch, Joachim Riethmüller, Matthias Soddemann, Carolin Sehl, Barbara Wilker, Michael J Edwards, Charles C Caldwell, Martin Fraunholz, Erich Gulbins, Nd Katrin Anne Becker
Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of α-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of α-toxin in JE2-Δhla reduced pathogenicity of S...
April 1, 2018: Biological Chemistry
https://www.readbyqxmd.com/read/29610530/nanoparticle-induced-neuronal-toxicity-across-placental-barriers-is-mediated-by-autophagy-and-dependent-on-astrocytes
#16
Simon J Hawkins, Lucy A Crompton, Aman Sood, Margaret Saunders, Noreen T Boyle, Amy Buckley, Aedín M Minogue, Sarah F McComish, Natalia Jiménez-Moreno, Oscar Cordero-Llana, Petros Stathakos, Catherine E Gilmore, Stephen Kelly, Jon D Lane, C Patrick Case, Maeve A Caldwell
The potential for maternal nanoparticle (NP) exposures to cause developmental toxicity in the fetus without the direct passage of NPs has previously been shown, but the mechanism remained elusive. We now demonstrate that exposure of cobalt and chromium NPs to BeWo cell barriers, an in vitro model of the human placenta, triggers impairment of the autophagic flux and release of interleukin-6. This contributes to the altered differentiation of human neural progenitor cells and DNA damage in the derived neurons and astrocytes...
April 2, 2018: Nature Nanotechnology
https://www.readbyqxmd.com/read/29608550/amitriptyline-treatment-mitigates-sepsis-induced-tumor-necrosis-factor-expression-and-coagulopathy
#17
Brent T Xia, Nadine Beckmann, Leah K Winer, Young Kim, Holly S Goetzman, Rosalie E Veile, Erich Gulbins, Michael D Goodman, Vanessa Nomellini, Charles C Caldwell
During sepsis, the early innate response and inflammatory cytokine cascade are associated with activation of the coagulation cascade. Acute hypercoagulability can contribute to lethal sequela of vascular thrombosis, tissue ischemia, and organ failure. We investigated if amitriptyline (AMIT), an antidepressant drug with a number of anti-inflammatory effects, could ameliorate sepsis in a murine model of sepsis - cecal ligation and puncture (CLP). We hypothesized that AMIT treatment would reduce inflammation and mitigate sepsis-induced coagulopathy...
March 30, 2018: Shock
https://www.readbyqxmd.com/read/29599292/mitochondrial-oxidative-stress-causes-insulin-resistance-without-disrupting-oxidative-phosphorylation
#18
Daniel J Fazakerley, Annabel Y Minard, James R Krycer, Kristen C Thomas, Jacqueline Stöckli, Dylan J Harney, James G Burchfield, Ghassan J Maghzal, Stuart T Caldwell, Richard C Hartley, Roland Stocker, Michael P Murphy, David E James
Mitochondrial oxidative stress, mitochondrial dysfunction, or both have been implicated in insulin resistance. However, disentangling the individual roles of these processes in insulin resistance has been difficult because they often occur in tandem, and tools that selectively increase oxidant production without impairing mitochondrial respiration have been lacking. Using the dimer/monomer status of peroxiredoxin isoforms as an indicator of compartmental hydrogen peroxide burden, we provide evidence that oxidative stress is localized to mitochondria in insulin-resistant 3T3-L1 adipocytes and adipose tissue from mice...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29590092/itaconate-is-an-anti-inflammatory-metabolite-that-activates-nrf2-via-alkylation-of-keap1
#19
Evanna L Mills, Dylan G Ryan, Hiran A Prag, Dina Dikovskaya, Deepthi Menon, Zbigniew Zaslona, Mark P Jedrychowski, Ana S H Costa, Maureen Higgins, Emily Hams, John Szpyt, Marah C Runtsch, Martin S King, Joanna F McGouran, Roman Fischer, Benedikt M Kessler, Anne F McGettrick, Mark M Hughes, Richard G Carroll, Lee M Booty, Elena V Knatko, Paul J Meakin, Michael L J Ashford, Louise K Modis, Gino Brunori, Daniel C Sévin, Padraic G Fallon, Stuart T Caldwell, Edmund R S Kunji, Edward T Chouchani, Christian Frezza, Albena T Dinkova-Kostova, Richard C Hartley, Michael P Murphy, Luke A O'Neill
The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities...
March 28, 2018: Nature
https://www.readbyqxmd.com/read/29575987/network-meta-analysis-in-health-psychology-and-behavioural-medicine-a-primer
#20
G J Molloy, C Noone, D Caldwell, N J Welton, J Newell
Progress in the science and practice of health psychology depends on the systematic synthesis of quantitative psychological evidence. Meta-analyses of experimental studies have led to important advances in understanding health-related behaviour change interventions. Fundamental questions regarding such interventions have been systematically investigated through synthesising relevant experimental evidence using standard pairwise meta-analytic procedures that provide reliable estimates of the magnitude, homogeneity and potential biases in effects observed...
March 25, 2018: Health Psychology Review
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