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Jin Geng, Chenchen Yang, Bingjian Wang, Xiwen Zhang, Tingting Hu, Yang Gu, Ju Li
BACKGROUND: Many studies have identified trimethylamine N-oxide (TMAO) as a new risk factor of cardiovascular diseases. It has been suggested that TMAO promotes atherosclerosis development. However, the underlying mechanism is still unclear. METHODS: Apoe-/- mice were fed a high-fat diet and given water with or without TMAO for 8-week. Histological and immunohistological analyses were used to evaluate the atherogenic effect of TMAO in vivo. We also employed peritoneal elicited macrophages and RAW264...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Krishna M Boini, Tahir Hussain, Pin-Lan Li, Sai Koka
BACKGROUND/AIM: Plasma trimethylamine-N-oxide (TMAO), a product of intestinal microbial metabolism of dietary phosphatidylcholine has been recently associated with atherosclerosis and increased risk of cardiovascular diseases (CVD) in rodents and humans. However, the molecular mechanisms of how TMAO induces atherosclerosis and CVD progression are still unclear. The present study tested whether TMAO induces NLRP3 inflammasome formation and activation and thereby contributes to endothelial injury initiating atherogenesis...
November 6, 2017: Cellular Physiology and Biochemistry
Leandro Martinez, Seishi Shimizu
Preferential solvation is a fundamental parameter for the interpretation of solubility and solute structural stability. The molecular basis for solute-solvent interactions can be obtained through distribution functions, and the thermodynamic connection to experimental data depends on the computation of distribution integrals, specifically Kirkwood-Buff integrals for the determination of preferential interactions. Standard radial distribution functions, however, are not convenient for the study of the solvation of complex, non-spherical solutes, as proteins...
November 9, 2017: Journal of Chemical Theory and Computation
Chongliang Gao, Gianluca Catucci, Silvia Castrignanò, Gianfranco Gilardi, Sheila J Sadeghi
Human flavin-containing monooxygenase 3 (hFMO3) catalyses the oxygenation of a wide variety of compounds including drugs as well as dietary compounds. It is the major hepatic enzyme involved in the production of the N-oxide of trimethylamine (TMAO) and clinical studies have uncovered a striking correlation between plasma TMAO concentration and cardiovascular disease. Certain mutations within the hFMO3 gene cause defective trimethylamine (TMA) N-oxygenation leading to trimethylaminuria (TMAU) also known as fish-odour syndrome...
November 7, 2017: Scientific Reports
Gints Kalnins, Eduards Sevostjanovs, Dace Hartmane, Solveiga Grinberga, Kaspars Tars
CntA oxygenase is a Rieske 2S-2Fe cluster-containing protein that has been previously described as able to produce trimethylamine (TMA) from carnitine, gamma-butyrobetaine, glycine betaine, and in one case, choline. TMA found in humans is exclusively of bacterial origin, and its metabolite, trimethylamine oxide (TMAO), has been associated with atherosclerosis and heart and renal failure. We isolated four different Rieske oxygenases and determined that there are no significant differences in their substrate panels...
November 7, 2017: Journal of Basic Microbiology
Shahar Sukenik, Shaked Dunsky, Avishai Barnoy, Ilan Shumilin, Daniel Harries
Under environmental duress, many organisms accumulate large amounts of osmolytes - molecularly small organic solutes. Osmolytes are known to counteract stress, driving proteins to their compact native states by their exclusion from protein surfaces. In contrast, the effect of osmolytes on lipid membranes is poorly understood and widely debated. Many fully membrane-permeable osmolytes exert an apparent attractive force between lipid membranes, yet all proposed models fail to fully account for the origin of this force...
November 7, 2017: Physical Chemistry Chemical Physics: PCCP
Lora L Iannotti, Chessa K Lutter, William F Waters, Carlos Andres Gallegos Riofrío, Carla Malo, Gregory Reinhart, Ana Palacios, Celia Karp, Melissa Chapnick, Katherine Cox, Santiago Aguirre, Luis Narvaez, Fernando López, Rohini Sidhu, Pamela Kell, Xuntian Jiang, Hideji Fujiwara, Daniel S Ory, Rebecca Young, Christine P Stewart
Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63.Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids.Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador...
November 1, 2017: American Journal of Clinical Nutrition
Daniel Markthaler, Johannes Zeman, Jörg Baz, Jens Smiatek, Niels Hansen
Five molecular models for trimethylamine N-oxide (TMAO) to be used in conjunction with compatible models for liquid water are evaluated by comparison of molecular dynamics (MD) simulation results to experimental data as functions of TMAO molality. The experimental data comprise thermodynamic properties (density, apparent molar volume, and partial molar volume at infinite dilution), transport properties (self-diffusion and shear viscosity), structural properties (radial distribution functions and degree of hydrogen bonding), and dielectric properties (dielectric spectra and static permittivity)...
November 17, 2017: Journal of Physical Chemistry. B
Sunil Veeravalli, Kersti Karu, Flora Scott, Diede Fennema, Ian R Phillips, Elizabeth A Shephard
The objectives of the study were to determine the contribution, in mice, of members of the flavin-containing monooxygenase (FMO) family to the production of trimethylamine N-oxide (TMAO), a potential proatherogenic molecule, and whether, under normal dietary conditions, differences in TMAO production were associated with changes in plasma cholesterol concentration or with an index of atherosclerosis (Als). Concentrations of urinary trimethylamine (TMA) and TMAO and of plasma cholesterol were measured in 10-week-old male and female C57BL/6J and CD-1 mice and in mouse lines deficient in various Fmo genes (Fmo1(-/-), 2(-/-), 4(-/-) and Fmo5(-/-) )...
October 25, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Sunil Veeravalli, Kersti Karu, Ian R Phillips, Elizabeth A Shephard
Our method describes the quantification in mouse urine of trimethylamine (TMA), trimethylamine N-oxide (TMAO) and creatinine. The method combines derivatization of TMA, with ethyl bromoacetate, and LC chromatographic separation on an ACE C18 column. The effluent was continuously electrosprayed into the linear ion trap mass spectrometer (LTQ), which operated in selective ion monitoring (SIM) modes set for targeted analytes and their internal standards (IS). All validation parameters were within acceptable ranges of analytical method validation guidelines...
2017: MethodsX
Eke G Gruppen, Erwin Garcia, Margery A Connelly, Elias J Jeyarajah, James D Otvos, Stephan J L Bakker, Robin P F Dullaart
Trimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that is cleared by the kidney and linked to renal function. We explored the relationship between TMAO and all-cause mortality, and determined whether this association was modified by renal function. A prospective study was performed among PREVEND participants to examine associations of plasma TMAO with all-cause mortality. After median follow-up of 8.3 years in 5,469 participants, 322 subjects died. TMAO was positively associated with age, body mass index, type 2 diabetes mellitus and inversely with estimated glomerular filtration rate (eGFRcreatcysC)(all P < 0...
October 23, 2017: Scientific Reports
Tatiana B Eronina, Valeriya V Mikhaylova, Natalia A Chebotareva, Vera A Borzova, Igor K Yudin, Boris I Kurganov
To characterize the initial stages of protein aggregation, the kinetics of aggregation of UV-irradiated glycogen phosphorylase b (UV-Phb) was studied under conditions when the aggregation proceeded at a low rate (10°C, 0.03M Hepes buffer, pH6.8, containing 0.1M NaCl). Aggregation of UV-Phb was induced by polyethylene glycol and Ficoll-70, acting as crowders, or a natural osmolyte trimethylamine N-oxide (TMAO). It has been shown that the initial rate of the stage of aggregate growth is proportional to the protein concentration squared, suggesting that the order of aggregation with respect to the protein is equal to two...
October 18, 2017: Biophysical Chemistry
Lidia Sanchez-Alcoholado, Daniel Castellano-Castillo, Laura Jordán-Martínez, Isabel Moreno-Indias, Pilar Cardila-Cruz, Daniel Elena, Antonio J Muñoz-Garcia, Maria I Queipo-Ortuño, Manuel Jimenez-Navarro
Gut microbiota composition has been reported as a factor linking host metabolism with the development of cardiovascular diseases (CVD) and intestinal immunity. Such gut microbiota has been shown to aggravate CVD by contributing to the production of trimethylamine N-oxide (TMAO), which is a pro-atherogenic compound. Treg cells expressing the transcription factor Forkhead box protein P3 (FoxP3) play an essential role in the regulation of immune responses to commensal microbiota and have an atheroprotective role...
2017: Frontiers in Microbiology
Elizabeth Leese, Malcolm Clench, Jackie Morton, Philip H E Gardiner, Vikki A Carolan
This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive's Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As(3+); arsenate, As(5+); monomethylarsonic acid, MMA(5+); and dimethylarsinic acid, DMA(5+)). Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (µLC-ICP-MS) and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS) were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE...
May 20, 2017: Toxics
Felix Lehmkühler, Yury Forov, Mirko Elbers, Ingo Steinke, Christoph J Sahle, Christopher Weis, Naruki Tsuji, Masayoshi Itou, Yoshiharu Sakurai, Agnieszka Poulain, Christian Sternemann
We present an X-ray Compton scattering study on aqueous trimethylamine N-oxide (TMAO) and guanidine hydrochloride solutions (GdnHCl) as a function of temperature. Independent from the concentration of the solvent, Compton profiles almost resemble results for liquid water as a function of temperature. However, the number of hydrogen bonds per water molecule extracted from the Compton profiles suggests a decrease of hydrogen bonds with rising temperature for all studied samples, and the differences between water and the solutions are weak...
October 25, 2017: Physical Chemistry Chemical Physics: PCCP
Marta Di Carlo, Donato Giovannelli, Daniele Fattorini, Nadine Le Bris, Costantino Vetriani, Francesco Regoli
Hydrothermal vent systems are inhabited by dense benthic communities adapted to extreme conditions such as high temperature, hydrogen sulphide (H2S) and elevated fluxes of metals. In the present work, a wide range of trace elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Sb, Se, V and Zn) were measured in tissues of three tube dwelling annelids, Alvinella pompejana, Alvinella caudata and Riftia pachyptila, which colonize distinct habitats of the East Pacific Rise (EPR) at 2500 m depth. Metals concentrations in alvinellids were often 2-4 orders of magnitude higher than those commonly found in marine organisms, while much lower values were observed in the vestimentiferan polychaete...
October 5, 2017: Marine Environmental Research
Gabriele Giacomo Schiattarella, Anna Sannino, Evelina Toscano, Giuseppe Giugliano, Giuseppe Gargiulo, Anna Franzone, Bruno Trimarco, Giovanni Esposito, Cinzia Perrino
Aims: Gut microbiota-derived metabolite trimethylamine-N-oxide (TMAO) is emerging as a new potentially important cause of increased cardiovascular risk. The purpose of this meta-analysis was to systematically estimate and quantify the association between TMAO plasma levels, mortality, and major adverse cardio and cerebrovascular events (MACCE). Methods and results: MEDLINE, ISI Web of Science, and SCOPUS databases were searched for ad hoc studies published up to April 2017...
October 14, 2017: European Heart Journal
Xiaoguang Sunny Li, Shu Li, Gottfried Kellermann
Determination of trimethylamine N-oxide (TMAO) and trimethylamine (TMA) in biological and environmental samples has drawn great attention recently due to their increasing association with human health and disease. It remains a challenge to simultaneously quantify TMAO and TMA in a simple, fast and cost-effective manner due to pre-analytical and analytical constraints. For the first time, we describe a dilute and shoot approach combined with LC-MS/MS detection for the simultaneous measurement of the analytes in spot urine samples with high throughput...
November 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
K Chase, F Doval, M Vershinin
Kinesin-1 is a mechanochemical enzyme which mediates long distance intracellular cargo transport along microtubules in a wide variety of eukaryotic cells. Kinesin is also relatively easy to purify and shows robust function in vitro, leading to numerous proposals for using the kinesin-1/microtubule system for nanoscale transport in engineered devices. However, kinesin in vitro shows signs of degradation at ∼30 °C which severely limits its usability in biomimetic engineering. Notably, kinesin-1 functions robustly in animal cells at body temperatures as high as 40 °C which suggests that kinesin functioning can be stabilized beyond what is observed in vitro...
November 25, 2017: Biochemical and Biophysical Research Communications
Weiwei Cheng, Jing Lu, Boxing Li, Weishi Lin, Zheng Zhang, Xiao Wei, Chengming Sun, Mingguo Chi, Wei Bi, Bingjun Yang, Aimin Jiang, Jing Yuan
Functional oligosaccharides, known as prebiotics, and ordinary dietary fiber have important roles in modulating the structure of intestinal microbiota. To investigate their effects on the intestinal microecosystem, three kinds of diets containing different prebiotics were used to feed mice for 3 weeks, as follows: GI (galacto-oligosaccharides and inulin), PF (polydextrose and insoluble dietary fiber from bran), and a GI/PF mixture (GI and PF, 1:1), 16S rRNA gene sequencing and metabolic analysis of mice feces were then conducted...
2017: Frontiers in Microbiology
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