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https://www.readbyqxmd.com/read/28301576/restored-mutant-receptor-corticoid-binding-in-chaperone-complexes-by-trimethylamine-n-oxide
#1
Aaron L Miller, W Austin Elam, Betty H Johnson, Shagufta H Khan, Raj Kumar, E Brad Thompson
Without a glucocorticoid (GC) ligand, the transcription factor glucocorticoid receptor (GR) is largely cytoplasmic, with its GC-binding domain held in high affinity conformation by a cluster of chaperones. Binding a GC causes serial dis- and re-associations with chaperones, translocation of the GR to the nucleus, where it binds to DNA sites and associates with coregulatory proteins and basic transcription complexes. Herein, we describe the effects of a potent protective osmolyte, trimethylamine N-oxide (TMAO), on a conditions-dependent "activation-labile" mutant GR (GRact/l), which under GR-activating conditions cannot bind GCs in cells or in cell cytosols...
2017: PloS One
https://www.readbyqxmd.com/read/28293920/the-intriguing-link-between-the-intestinal-microbiota-and-cardiovascular-disease
#2
Giuseppe Lippi, Elisa Danese, Camilla Mattiuzzi, Emmanuel J Favaloro
Human microbiota is a term conventionally used to define the normal flora of microbes living in all of us, most of which are resident in the gastrointestinal tract. Despite it having been known for some time that the vast majority of intestinal bacteria exert a strong influence on human life, recent technologic breakthroughs have made it possible to more accurately characterize the host microbial communities and explore their relationship with many human diseases. Notably, the evidence accumulated over the past 10 years suggests that a reasonable relationship can now be established between gut microbiota composition and the risk of cardiovascular disease...
March 14, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28265960/impact-of-bariatric-surgery-on-metabolic-and-gut-microbiota-profile-a-systematic-review-and-meta-analysis
#3
REVIEW
Dimitrios E Magouliotis, Vasiliki S Tasiopoulou, Eleni Sioka, Christina Chatedaki, Dimitrios Zacharoulis
We aim to review the available literature on obese patients treated with bariatric procedures, in order to assess their effect on the metabolic and gut microbiota profiles. A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Twenty-two studies (562 patients) met the inclusion criteria. This study points to significant amelioration of postoperative levels of glucose, insulin, triglycerides, total cholesterol, LDL, HDL, HOMA-IR, food intake, and diabetes remission...
March 6, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28228526/trimethylamine-n-oxide-stabilizes-proteins-via-a-distinct-mechanism-compared-with-betaine-and-glycine
#4
Yi-Ting Liao, Anthony C Manson, Michael R DeLyser, William G Noid, Paul S Cremer
We report experimental and computational studies investigating the effects of three osmolytes, trimethylamine N-oxide (TMAO), betaine, and glycine, on the hydrophobic collapse of an elastin-like polypeptide (ELP). All three osmolytes stabilize collapsed conformations of the ELP and reduce the lower critical solution temperature (LSCT) linearly with osmolyte concentration. As expected from conventional preferential solvation arguments, betaine and glycine both increase the surface tension at the air-water interface...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28218056/regulation-of-the-escherichia-coli-ydhy-t-operon-in-the-presence-of-alternative-electron-acceptors
#5
Naji Al Ibrahim, Jeffrey Green
The Escherichia coli K-12 ydhY-T operon, coding for a predicted oxidoreductase complex, is activated under anaerobic conditions and repressed in the presence of nitrate or nitrite. Anaerobic activation is mediated by the transcription factor FNR and nitrate/nitrite repression is mediated by NarXL and NarQP. In vitro transcription reactions revealed that the DNA upstream of ydhY-T contains sufficient information for RNA polymerase alone to initiate transcription from five locations. FNR severely inhibited synthesis of two of these transcripts (located upstream of, and within, the FNR binding site) and activated the FNR-dependent promoter previously identified in vivo...
February 3, 2017: Microbiology
https://www.readbyqxmd.com/read/28196478/genetic-analysis-of-impaired-trimethylamine-metabolism-using-whole-exome-sequencing
#6
Yiran Guo, Liang-Dar Hwang, Jiankang Li, Jason Eades, Chung Wen Yu, Corrine Mansfield, Alexis Burdick-Will, Xiao Chang, Yulan Chen, Fujiko F Duke, Jianguo Zhang, Steven Fakharzadeh, Paul Fennessey, Brendan J Keating, Hui Jiang, Hakon Hakonarson, Danielle R Reed, George Preti
BACKGROUND: Trimethylaminuria (TMAU) is a genetic disorder whereby people cannot convert trimethylamine (TMA) to its oxidized form (TMAO), a process that requires the liver enzyme FMO3. Loss-of-function variants in the FMO3 gene are a known cause of TMAU. In addition to the inability to metabolize TMA precursors like choline, patients often emit a characteristic odor because while TMAO is odorless, TMA has a fishy smell. The Monell Chemical Senses Center is a research institute with a program to evaluate people with odor complaints for TMAU...
February 15, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28191513/dietary-cholesterol-and-egg-yolk-should-be-avoided-by-patients-at-risk-of-vascular-disease
#7
REVIEW
J David Spence
Recent recommendations that limits to dietary cholesterol be dropped were probably heavily influenced by propaganda from the egg industry. After conviction for false advertising, the industry has spent hundreds of millions of dollars to convince the public, physicians, and policy makers that dietary cholesterol and egg yolk are harmless. However, there are good reasons for longstanding recommendations that dietary cholesterol be limited to <200 mg/ day in persons at risk of vascular disease. It is seldom understood that this essentially means all people in developed countries who expect to attain an advanced age...
April 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28176881/functional-coupling-of-human-microphysiology-systems-intestine-liver-kidney-proximal-tubule-blood-brain-barrier-and-skeletal-muscle
#8
Lawrence Vernetti, Albert Gough, Nicholas Baetz, Sarah Blutt, James R Broughman, Jacquelyn A Brown, Jennifer Foulke-Abel, Nesrin Hasan, Julie In, Edward Kelly, Olga Kovbasnjuk, Jonathan Repper, Nina Senutovitch, Janet Stabb, Catherine Yeung, Nick C Zachos, Mark Donowitz, Mary Estes, Jonathan Himmelfarb, George Truskey, John P Wikswo, D Lansing Taylor
Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28169544/correction-to-comparison-of-different-tmao-force-fields-and-their-impact-on-the-folding-equilibrium-of-a-hydrophobic-polymer
#9
Francisco Rodríguez-Ropero, Philipp Rötzscher, Nico F A van der Vegt
No abstract text is available yet for this article.
February 7, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28153917/trimethylamine-n-oxide-in-atherogenesis-impairing-endothelial-self-repair-capacity-and-enhancing-monocyte-adhesion
#10
GuoHua Ma, Bing Pan, Yue Chen, CaiXia Guo, MingMing Zhao, LeMin Zheng, BuXing Chen
Several studies have reported a strong association between high plasma level of Trimethylamine N-oxide (TMAO) and atherosclerosis development. However, the exact mechanism underlying this correlation is unknown. In this study, we try to explore the impact of TMAO on endothelial dysfunction. After TMAO treatment, Human umbilical vein endothelial cells (HUVECs) showed significant impairment in cellular proliferation and HUVECs-ECM adhesion compared to control. Likewise, TMAO markedly suppressed HUVECs migration in transwell migration assay and wound healing assay...
February 2, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28153322/fast-and-reliable-method-for-as-speciation-in-urine-samples-containing-low-levels-of-as-by-lc-icp-ms-focus-on-epidemiological-studies
#11
V M O Carioni, J A McElroy, J M Guthrie, R A Ngwenyama, J D Brockman
The speciation analysis of As in urine samples can provide important information for epidemiological studies. Considering that these studies involve hundreds or thousands of samples, a fast and reliable method using a simple LC system with short-length mixed bed ion exchange chromatographic column coupled to ICP-MS for As speciation in human urine samples was developed in this work. Separation of AB+TMAO, DMA, AC, MMA and As(III)+As(V) was accomplished within 5min with good resolution when ammonium carbonate solutions were used as mobile phases and H2O2 was added to samples to quantitatively convert As(III)-As(V)...
April 1, 2017: Talanta
https://www.readbyqxmd.com/read/28149990/trimethylamine-n-oxide-its-hydration-structure-surface-activity-and-biological-function-viewed-by-vibrational-spectroscopy-and-molecular-dynamics-simulations
#12
Tatsuhiko Ohto, Johannes Hunger, Ellen H G Backus, Wataru Mizukami, Mischa Bonn, Yuki Nagata
The osmolyte molecule trimethylamine-N-oxide (TMAO) stabilizes the structure of proteins. As functional proteins are generally found in aqueous solutions, an important aspect of this stabilization is the interaction of TMAO with water. Here, we review, using vibrational spectroscopy and molecular dynamics simulations, recent studies on the structure and dynamics of TMAO with its surrounding water molecules. This article ends with an outlook on the open questions on TMAO-protein and TMAO-urea interactions in aqueous environments...
February 2, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28129384/blood-trimethylamine-n-oxide-originates-from-microbiota-mediated-breakdown-of-phosphatidylcholine-and-absorption-from-small-intestine
#13
Wolfgang Stremmel, Kathrin V Schmidt, Vera Schuhmann, Frank Kratzer, Sven F Garbade, Claus-Dieter Langhans, Gert Fricker, Jürgen G Okun
Elevated serum trimethylamine-N-oxide (TMAO) was previously reported to be associated with an elevated risk for cardiovascular events. TMAO originates from the microbiota-dependent breakdown of food-derived phosphatidylcholine (PC) to trimethylamine (TMA), which is oxidized by hepatic flavin-containing monooxygenases to TMAO. Our aim was to investigate the predominant site of absorption of the bacterial PC-breakdown product TMA. A healthy human proband was exposed to 6.9 g native phosphatidylcholine, either without concomitant treatment or during application with the topical antibiotic rifaximin, or exposed only to 6...
2017: PloS One
https://www.readbyqxmd.com/read/28127030/acute-coronary-syndromes-microbial-dependent-tmao-as-a-prognostic-marker-in-acs
#14
Irene Fernández-Ruiz
No abstract text is available yet for this article.
January 27, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28116386/tmao-and-urea-in-the-hydration-shell-of-the-protein-snase
#15
Nikolai Smolin, Vladimir P Voloshin, Alexey V Anikeenko, Alfons Geiger, Roland Winter, Nikolai N Medvedev
We performed all-atom MD simulations of the protein SNase in aqueous solution and in the presence of two major osmolytes, trimethylamine-N-oxide (TMAO) and urea, as cosolvents at various concentrations and compositions and at different pressures and temperatures. The distributions of the cosolvent molecules and their orientation in the surroundings of the protein were analyzed in great detail. The distribution of urea is largely conserved near the protein. It varies little with pressure and temperature, and does practically not depend on the addition of TMAO...
January 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28102930/modulation-of-the-thermodynamic-signatures-of-an-rna-thermometer-by-osmolytes-and-salts
#16
Mimi Gao, Loana Arns, Roland Winter
Folding of ribonucleic acids (RNAs) is driven by several factors, such as base pairing and stacking, chain entropy, and ion-mediated electrostatics, which have been studied in great detail. However, the power of background molecules in the cellular milieu is often neglected. Herein, we study the effect of common osmolytes on the folding equilibrium of a hairpin-structured RNA and, using pressure perturbation, provide novel thermodynamic and volumetric insights into the modulation mechanism. The presence of TMAO causes an increased thermal stability and a more positive volume change for the helix-to-coil transition, whereas urea destabilizes the hairpin and leads to an increased expansibility of the unfolded state...
January 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28091798/intake-of-up-to-3-eggs-day-increases-hdl-cholesterol-and-plasma-choline-while-plasma-trimethylamine-n-oxide-is-unchanged-in-a-healthy-population
#17
Diana M DiMarco, Amanda Missimer, Ana Gabriela Murillo, Bruno S Lemos, Olga V Malysheva, Marie A Caudill, Christopher N Blesso, Maria Luz Fernandez
Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m(2)] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each...
March 2017: Lipids
https://www.readbyqxmd.com/read/28077467/gut-microbiota-dependent-trimethylamine-n-oxide-in-acute-coronary-syndromes-a-prognostic-marker-for-incident-cardiovascular-events-beyond-traditional-risk-factors
#18
Xinmin S Li, Slayman Obeid, Roland Klingenberg, Baris Gencer, François Mach, Lorenz Räber, Stephan Windecker, Nicolas Rodondi, David Nanchen, Olivier Muller, Melroy X Miranda, Christian M Matter, Yuping Wu, Lin Li, Zeneng Wang, Hassan S Alamri, Valentin Gogonea, Yoon-Mi Chung, W H Wilson Tang, Stanley L Hazen, Thomas F Lüscher
AIMS: Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown. METHODS AND RESULTS: We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts...
January 11, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28077427/serum-trimethylamine-n-oxide-carnitine-choline-and-betaine-in-relation-to-colorectal-cancer-risk-in-the-alpha-tocopherol-and-beta-carotene-study
#19
Kristin A Guertin, Xinmin S Li, Barry I Graubard, Demetrius Albanes, Stephanie J Weinstein, James J Goedert, Zeneng Wang, Stanley L Hazen, Rashmi Sinha
BACKGROUND: TMAO, a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. METHODS: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study...
January 11, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28062632/trimethylamine-n-oxide-and-risk-stratification-after-acute-myocardial-infarction
#20
Toru Suzuki, Liam M Heaney, Donald J L Jones, Leong L Ng
BACKGROUND: Risk stratification in acute myocardial infarction (MI) remains a clinical challenge. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, was investigated for its ability to assist in risk stratification for acute MI hospitalizations. METHODS: TMAO was analyzed in 1079 acute MI patients. Associations with adverse outcome of all-cause mortality or reinfarction (death/MI) for shorter (6-month) and longer (2-year) terms were assessed and compared to other cohort-specific biomarkers...
January 2017: Clinical Chemistry
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