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https://www.readbyqxmd.com/read/27921450/oral-pharmacokinetic-interaction-of-ester-rich-fruit-juices-and-pharmaceutical-excipients-with-tenofovir-disoproxil-fumarate-in-male-wistar-rats
#1
Joseph Shailender, Punna Rao Ravi, Paramita Saha, Srividya Myneni
The aim of this study was to evaluate the role of intestinal esterases on the absorption process of tenofovir disoproxil fumarate (TDF). The esterase inhibition capacity of fruit juices (FJs) rich in ester linkages and pharmaceutical excipients (having ester) was performed in vitro by incubating TDF with each FJ and excipient in the intestinal washings. The ex vivo everted gut sac model was also used to evaluate the absorption enhancement capacity of these FJs and excipients. Single dose oral pharmacokinetic studies were performed by concomitant administration of TDF with each of the selected FJs and excipients...
December 6, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27920770/the-use-of-transposon-insertion-sequencing-to-interrogate-the-core-functional-genome-of-the-legume-symbiont-rhizobium-leguminosarum
#2
Benjamin J Perry, Mir S Akter, Christopher K Yost
The free-living legume symbiont Rhizobium leguminosarum is of significant economic value because of its ability to provide fixed nitrogen to globally important leguminous food crops, such as peas and lentils. Discovery based research into the genetics and physiology of R. leguminosarum provides the foundational knowledge necessary for understanding the bacterium's complex lifestyle, necessary for augmenting its use in an agricultural setting. Transposon insertion sequencing (INSeq) facilitates high-throughput forward genetic screening at a genomic scale to identify individual genes required for growth in a specific environment...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27920298/malate-synthase-and-%C3%AE-methylmalyl-coa-lyase-reactions-in-the-methylaspartate-cycle-in-haloarcula-hispanica
#3
Farshad Borjian, Jing Han, Jing Hou, Hua Xiang, Jan Zarzycki, Ivan A Berg
: Haloarchaea are extremely halophilic heterotrophic microorganisms belonging to the class Halobacteria (Euryarchaeota). Almost half of the haloarchaea possesses the genes coding for enzymes of the methylaspartate cycle, a recently discovered anaplerotic acetate assimilation pathway. In this cycle, the enzymes of the tricarboxylic acid cycle together with the dedicated enzymes of the methylaspartate cycle convert two acetyl-CoA molecules to malate. The methylaspartate cycle involves two reactions catalyzed by homologous enzymes belonging to the CitE-like enzyme superfamily, the malyl-CoA lyase/thioesterase (haloarchaeal malate synthase, hMS, Hah_2476 in Haloarcula hispanica) and the β-methylmalyl-CoA lyase (hMCL, Hah_1341)...
December 5, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27919791/biosensor-assisted-transcriptional-regulator-engineering-for-methylobacterium-extorquens-am1-to-improve-mevalonate-synthesis-by-increasing-the-acetyl-coa-supply
#4
Wei-Fan Liang, Lan-Yu Cui, Jin-Yu Cui, Kai-Wen Yu, Song Yang, Chong Zhang, Xin-Hui Xing
Acetyl-CoA is not only an important intermediate metabolite for cells but also a significant precursor for production of industrially interesting metabolites. Methylobacterium extorquens AM1, a model strain of methylotrophic cell factories using methanol as carbon source, is of interest because it produces abundant coenzyme A compounds capable of directing to synthesis of different useful compounds from methanol. However, acetyl-CoA always does not efficiently accumulate in M. extorquens AM1, as it is located in the center of three cyclic central metabolic pathways...
December 3, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27914869/glycolysis-without-pyruvate-kinase-in-clostridium-thermocellum
#5
Daniel G Olson, Manuel Hörl, Tobias Fuhrer, Jingxuan Cui, Jilai Zhou, Marybeth I Maloney, Daniel Amador-Noguez, Liang Tian, Uwe Sauer, Lee R Lynd
The metabolism of Clostridium thermocellum is notable in that it assimilates sugar via the EMP pathway but does not possess a pyruvate kinase enzyme. In the wild type organism, there are three proposed pathways for conversion of phosphoenolpyruvate (PEP) to pyruvate, which differ in their cofactor usage. One path uses pyruvate phosphate dikinase (PPDK), another pathway uses the combined activities of PEP carboxykinase (PEPCK) and oxaloacetate decarboxylase (ODC). Yet another pathway, the malate shunt, uses the combined activities of PEPCK, malate dehydrogenase and malic enzyme...
November 30, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27912165/biomarker-analysis-of-american-toad-anaxyrus-americanus-and-grey-tree-frog-hyla-versicolor-tadpoles-following-exposure-to-atrazine
#6
Marcía N Snyder, W Matthew Henderson, Donna A Glinski, S Thomas Purucker
The objective of the current study was to use a biomarker-based approach to investigate the influence of atrazine exposure on American toad (Anaxyrus americanus) and grey tree frog (Hyla versicolor) tadpoles. Atrazine is one of the most frequently detected herbicides in environmental matrices throughout the United States. In surface waters, it has been found at concentrations from 0.04-2859μg/L and thus presents a likely exposure scenario for non-target species such as amphibians. Studies have examined the effect of atrazine on the metamorphic parameters of amphibians, however, the data are often contradictory...
November 21, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27911809/unique-attributes-of-cyanobacterial-metabolism-revealed-by-improved-genome-scale-metabolic-modeling-and-essential-gene-analysis
#7
Jared T Broddrick, Benjamin E Rubin, David G Welkie, Niu Du, Nathan Mih, Spencer Diamond, Jenny J Lee, Susan S Golden, Bernhard O Palsson
The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911807/enhanced-limonene-production-in-cyanobacteria-reveals-photosynthesis-limitations
#8
Xin Wang, Wei Liu, Changpeng Xin, Yi Zheng, Yanbing Cheng, Su Sun, Runze Li, Xin-Guang Zhu, Susie Y Dai, Peter M Rentzepis, Joshua S Yuan
Terpenes are the major secondary metabolites produced by plants, and have diverse industrial applications as pharmaceuticals, fragrance, solvents, and biofuels. Cyanobacteria are equipped with efficient carbon fixation mechanism, and are ideal cell factories to produce various fuel and chemical products. Past efforts to produce terpenes in photosynthetic organisms have gained only limited success. Here we engineered the cyanobacterium Synechococcus elongatus PCC 7942 to efficiently produce limonene through modeling guided study...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911769/reductive-carboxylation-is-a-major-metabolic-pathway-in-the-retinal-pigment-epithelium
#9
Jianhai Du, Aya Yanagida, Kaitlen Knight, Abbi L Engel, Anh Huan Vo, Connor Jankowski, Martin Sadilek, Van Thi Bao Tran, Megan A Manson, Aravind Ramakrishnan, James B Hurley, Jennifer R Chao
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells that requires an active metabolism to maintain outer retinal homeostasis and compensate for oxidative stress. Using (13)C metabolic flux analysis in human RPE cells, we found that RPE has an exceptionally high capacity for reductive carboxylation, a metabolic pathway that has recently garnered significant interest because of its role in cancer cell survival. The capacity for reductive carboxylation in RPE exceeds that of all other cells tested, including retina, neural tissue, glial cells, and a cancer cell line...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911401/an-optimized-protocol-to-analyze-glycolysis-and-mitochondrial-respiration-in-lymphocytes
#10
Javier Traba, Pietro Miozzo, Billur Akkaya, Susan K Pierce, Munir Akkaya
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types...
November 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27909940/enhancement-of-rapamycin-production-by-metabolic-engineering-in-streptomyces-hygroscopicus-based-on-genome-scale-metabolic-model
#11
Lanqing Dang, Jiao Liu, Cheng Wang, Huanhuan Liu, Jianping Wen
Rapamycin, as a macrocyclic polyketide with immunosuppressive, antifungal, and anti-tumor activity produced by Streptomyces hygroscopicus, is receiving considerable attention for its significant contribution in medical field. However, the production capacity of the wild strain is very low. Hereby, a computational guided engineering approach was proposed to improve the capability of rapamycin production. First, a genome-scale metabolic model of Streptomyces hygroscopicus ATCC 29253 was constructed based on its annotated genome and biochemical information...
December 1, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#12
Xingxing Jian, Ningchuan Li, Cheng Zhang, Qiang Hua
BACKGROUND: Succinic acid is a valuable product due to its wide-ranging utilities. To improve succinate production and reduce by-products formation, Escherichia coli NZN111 was constructed by insertional inactivation of lactate dehydrogenase (LDH) and pyruvate formate lyase (PFL) encoded by the genes ldhA and pflB, respectively. However, this double-deletion mutant is incapable of anaerobically growing on glucose in rich or minimal medium even with acetate supplementation. A widespread hold view is that the inactivation of NADH-dependent LDH limits the regeneration of NAD(+) and consequently disables proper growth under anaerobic conditions...
2016: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/27907077/transcriptome-and-multivariable-data-analysis-of-corynebacterium-glutamicum-under-different-dissolved-oxygen-conditions-in-bioreactors
#13
Yang Sun, Wenwen Guo, Fen Wang, Feng Peng, Yankun Yang, Xiaofeng Dai, Xiuxia Liu, Zhonghu Bai
Dissolved oxygen (DO) is an important factor in the fermentation process of Corynebacterium glutamicum, which is a widely used aerobic microbe in bio-industry. Herein, we described RNA-seq for C. glutamicum under different DO levels (50%, 30% and 0%) in 5 L bioreactors. Multivariate data analysis (MVDA) models were used to analyze the RNA-seq and metabolism data to investigate the global effect of DO on the transcriptional distinction of the substance and energy metabolism of C. glutamicum. The results showed that there were 39 and 236 differentially expressed genes (DEGs) under the 50% and 0% DO conditions, respectively, compared to the 30% DO condition...
2016: PloS One
https://www.readbyqxmd.com/read/27906079/muscle-specific-loss-of-bmal1-leads-to-disrupted-tissue-glucose-metabolism-and-systemic-glucose-homeostasis
#14
Brianna D Harfmann, Elizabeth A Schroder, Maureen T Kachman, Brian A Hodge, Xiping Zhang, Karyn A Esser
BACKGROUND: Diabetes is the seventh leading cause of death in the USA, and disruption of circadian rhythms is gaining recognition as a contributing factor to disease prevalence. This disease is characterized by hyperglycemia and glucose intolerance and symptoms caused by failure to produce and/or respond to insulin. The skeletal muscle is a key insulin-sensitive metabolic tissue, taking up ~80 % of postprandial glucose. To address the role of the skeletal muscle molecular clock to insulin sensitivity and glucose tolerance, we generated an inducible skeletal muscle-specific Bmal1 (-/-) mouse (iMSBmal1 (-/-))...
March 30, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27906055/mesenchymal-stem-cells-multipotent-stromal-cells-mscs-are-glycolytic-and-thus-glucose-is-a-limiting-factor-of-in-vitro-models-of-msc-starvation
#15
Austin Nuschke, Melanie Rodrigues, Albin W Wells, Kyle Sylakowski, Alan Wells
BACKGROUND: Mesenchymal stem/multipotent stromal cells (MSCs) contribute to tissue repair but are challenged during wound healing when the blood supply is disrupted, thereby limiting nutrient delivery. Survival mechanisms against 'starvation' include autophagy, which we previously found to enhance differentiation efficiency. MSC response to models of in vitro nutrient deprivation are of great interest for improving MSC survival and therapeutic efficacy; however, the rate-limiting nutrients are unknown...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27903998/survival-benefit-of-hemodiafiltration-compared-with-prolonged-high-flux-hemodialysis
#16
Petar S Djuric, Aleksandar Jankovic, Jovan Popovic, Jelena Tosic Dragovic, Ana Bulatovic, Zivka Djuric, Milos Mitrovic, Nada Dimkovic
INTRODUCTION:  Patients on dialysis have a high rate of death, mainly of cardiovascular cause. Nephrologists are actively looking for ways to improve patients' outcomes, and alternative dialysis strategies, such as long conventional hemodialysis and hemodiafiltration, are currently being investigated. The aim of this study was to compare anemia, nutrition, inflammation, mineral metabolism, and 3-year survival rates between patients treated with hemodiafiltration and prolonged high-flux hemodialysis (HFH)...
November 2016: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/27903818/properties-of-alternative-microbial-hosts-used-in-synthetic-biology-towards-the-design-of-a-modular-chassis
#17
REVIEW
Juhyun Kim, Manuel Salvador, Elizabeth Saunders, Jaime González, Claudio Avignone-Rossa, Jose Ignacio Jiménez
The chassis is the cellular host used as a recipient of engineered biological systems in synthetic biology. They are required to propagate the genetic information and to express the genes encoded in it. Despite being an essential element for the appropriate function of genetic circuits, the chassis is rarely considered in their design phase. Consequently, the circuits are transferred to model organisms commonly used in the laboratory, such as Escherichia coli, that may be suboptimal for a required function...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27903654/carbon-and-acyl-chain-flux-during-stress-induced-triglyceride-accumulation-by-stable-isotopic-labeling-of-the-polar-microalga-coccomyxa-subellipsoidea-c169
#18
James W Allen, Concetta C DiRusso, Paul N Black
Deriving biofuels and other lipoid products from algae is a promising future technology directly addressing global issues of atmospheric CO2 balance. To better understand the metabolism of triglyceride synthesis in algae, we examined their metabolic origins in the model species, Coccomyxa subellipsoidea C169, using stable isotopic labeling. Labeling patterns arising from (13)C-U-glucose, (13)CO2, or D2O supplementation were analyzed by GC-MS and/or LC-MS over time courses during nitrogen (N) starvation to address the roles of catabolic carbon (C) recycling, acyl chain redistribution, and de novo fatty acid (FA) synthesis during the expansion of the lipid bodies...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27901115/p53-coordinates-dna-repair-with-nucleotide-synthesis-by-suppressing-pfkfb3-expression-and-promoting-the-pentose-phosphate-pathway
#19
Derek A Franklin, Yizhou He, Patrick L Leslie, Andrey P Tikunov, Nick Fenger, Jeffrey M Macdonald, Yanping Zhang
Activation of p53 in response to DNA damage is essential for tumor suppression. Although previous studies have emphasized the importance of p53-dependent cell cycle arrest and apoptosis for tumor suppression, recent studies have suggested that other areas of p53 regulation, such as metabolism and DNA damage repair (DDR), are also essential for p53-dependent tumor suppression. However, the intrinsic connections between p53-mediated DDR and metabolic regulation remain incompletely understood. Here, we present data suggesting that p53 promotes nucleotide biosynthesis in response to DNA damage by repressing the expression of the phosphofructokinase-2 (PFK2) isoform 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a rate-limiting enzyme that promotes glycolysis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27899364/identification-of-shared-and-unique-serum-lipid-profiles-in-diabetes-mellitus-and-myocardial-infarction
#20
Sanela Kjellqvist, Christian Klose, Michal A Surma, George Hindy, Inês G Mollet, Anna Johansson, Patrick Chavaux, Johan Gottfries, Kai Simons, Olle Melander, Céline Fernandez
BACKGROUND: Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. METHODS AND RESULTS: We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmö Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI...
November 29, 2016: Journal of the American Heart Association
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