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metabolic flux analysis

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https://www.readbyqxmd.com/read/28098205/reliable-and-efficient-solution-of-genome-scale-models-of-metabolism-and-macromolecular-expression
#1
Ding Ma, Laurence Yang, Ronan M T Fleming, Ines Thiele, Bernhard O Palsson, Michael A Saunders
Constraint-Based Reconstruction and Analysis (COBRA) is currently the only methodology that permits integrated modeling of Metabolism and macromolecular Expression (ME) at genome-scale. Linear optimization computes steady-state flux solutions to ME models, but flux values are spread over many orders of magnitude. Data values also have greatly varying magnitudes. Standard double-precision solvers may return inaccurate solutions or report that no solution exists. Exact simplex solvers based on rational arithmetic require a near-optimal warm start to be practical on large problems (current ME models have 70,000 constraints and variables and will grow larger)...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092823/ph-lactate-and-hypoxia-reciprocity-in-regulating-high-affinity-monocarboxylate-transporter-expression-in-glioblastoma
#2
James P Caruso, Brandon J Koch, Philip D Benson, Elsa Varughese, Michael D Monterey, Amy E Lee, Ajal M Dave, Sam Kiousis, Andrew E Sloan, Saroj P Mathupala
Highly malignant brain tumors harbor the aberrant propensity for aerobic glycolysis, the excessive conversion of glucose to lactic acid even in the presence of ample tissue oxygen. Lactic acid is rapidly effluxed to the tumor microenvironment via a group of plasma-membrane transporters denoted monocarboxylate transporters (MCTs) to prevent "self-poisoning." One isoform, MCT2, has the highest affinity for lactate and thus should have the ability to respond to microenvironment conditions such as hypoxia, lactate, and pH to help maintain high glycolytic flux in the tumor...
January 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28088694/metabolic-network-modeling-with-model-organisms
#3
REVIEW
L Safak Yilmaz, Albertha Jm Walhout
Flux balance analysis (FBA) with genome-scale metabolic network models (GSMNM) allows systems level predictions of metabolism in a variety of organisms. Different types of predictions with different accuracy levels can be made depending on the applied experimental constraints ranging from measurement of exchange fluxes to the integration of gene expression data. Metabolic network modeling with model organisms has pioneered method development in this field. In addition, model organism GSMNMs are useful for basic understanding of metabolism, and in the case of animal models, for the study of metabolic human diseases...
January 12, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28087530/pgas-a-low-ph-induced-promoter-as-a-dynamic-gene-expression-control-tool-for-the-metabolic-engineering-of-aspergillus-niger
#4
Xian Yin, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Long Liu, Jian Chen
: The dynamic control of gene expression is important for adjusting fluxes in order to obtain desired products and achieve appropriate cell growth, particularly when the synthesis of a desired product drains metabolites required for cell growth. For dynamic gene expression, a promoter responsive to a particular environmental stressor is vital. Here, we report a low pH-inducible promoter, Pgas, which promotes minimal gene expression at pH values of greater than 5.0, but functioned efficiently at low pH values, such as pH 2...
January 13, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28087332/exo-mfa-a-13c-metabolic-flux-analysis-to-dissect-tumor-microenvironment-secreted-exosome-contributions-towards-cancer-cell-metabolism
#5
Abhinav Achreja, Hongyun Zhao, Lifeng Yang, Tae Hyun Yun, Juan Marini, Deepak Nagrath
Dissecting the pleiotropic roles of tumor micro-environment (TME) on cancer progression has been brought to the foreground of research on cancer pathology. Extracellular vesicles such as exosomes, transport proteins, lipids, and nucleic acids, to mediate intercellular communication between TME components and have emerged as candidates for anti-cancer therapy. We previously reported that cancer-associated fibroblast (CAF) derived exosomes (CDEs) contain metabolites in their cargo that are utilized by cancer cells for central carbon metabolism and promote cancer growth...
January 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28081159/osmoregulation-in-the-halophilic-bacterium-halomonas-elongata-a-case-study-for-integrative-systems-biology
#6
Viktoria Kindzierski, Silvia Raschke, Nicole Knabe, Frank Siedler, Beatrix Scheffer, Katharina Pflüger-Grau, Friedhelm Pfeiffer, Dieter Oesterhelt, Alberto Marin-Sanguino, Hans-Jörg Kunte
Halophilic bacteria use a variety of osmoregulatory methods, such as the accumulation of one or more compatible solutes. The wide diversity of compounds that can act as compatible solute complicates the task of understanding the different strategies that halophilic bacteria use to cope with salt. This is specially challenging when attempting to go beyond the pathway that produces a certain compatible solute towards an understanding of how the metabolic network as a whole addresses the problem. Metabolic reconstruction based on genomic data together with Flux Balance Analysis (FBA) is a promising tool to gain insight into this problem...
2017: PloS One
https://www.readbyqxmd.com/read/28077967/integrated-omics-analyses-reveal-the-details-of-metabolic-adaptation-of-clostridium-thermocellum-to-lignocellulose-derived-growth-inhibitors-released-during-the-deconstruction-of-switchgrass
#7
Suresh Poudel, Richard J Giannone, Miguel Rodriguez, Babu Raman, Madhavi Z Martin, Nancy L Engle, Jonathan R Mielenz, Intawat Nookaew, Steven D Brown, Timothy J Tschaplinski, David Ussery, Robert L Hettich
BACKGROUND: Clostridium thermocellum is capable of solubilizing and converting lignocellulosic biomass into ethanol. Although much of the work-to-date has centered on characterizing this microbe's growth on model cellulosic substrates, such as cellobiose, Avicel, or filter paper, it is vitally important to understand its metabolism on more complex, lignocellulosic substrates to identify relevant industrial bottlenecks that could undermine efficient biofuel production. To this end, we have examined a time course progression of C...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28065897/trfba-an-algorithm-to-integrate-genome-scale-metabolic-and-transcriptional-regulatory-networks-with-incorporation-of-expression-data
#8
Ehsan Motamedian, Maryam Mohammadi, Seyed Abbas Shojaosadati, Mona Heydari
MOTIVATION: Integration of different biological networks and data-types has been a major challenge in systems biology. The present study introduces the transcriptional regulated flux balance analysis (TRFBA) algorithm that integrates transcriptional regulatory and metabolic models using a set of expression data for various perturbations. RESULTS: TRFBA considers the expression levels of genes as a new continuous variable and introduces two new linear constraints...
January 8, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28059587/metabolic-effects-of-fasting-on-human-and-mouse-blood-in-vivo
#9
Federico Pietrocola, Yohann Demont, Francesca Castoldi, David Enot, Sylvère Durand, Michaela Semeraro, Elisa Elena Baracco, Jonathan Pol, Jose Manuel Bravo-San Pedro, Chloé Bordenave, Sarah Levesque, Juliette Humeau, Alexis Chery, Didier Métivier, Frank Madeo, M Chiara Maiuri, Guido Kroemer
Starvation is a strong physiological stimulus of macroautophagy/autophagy. In this study, we addressed the question as to whether it would be possible to measure autophagy in blood cells after nutrient deprivation. Fasting of mice for 48 h (which causes ∼20% weight loss) or starvation of human volunteers for up to 4 days (which causes <2% weight loss) provokes major changes in the plasma metabolome, yet induces only relatively minor alterations in the intracellular metabolome of circulating leukocytes...
January 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28056797/comparative-proteomic-analysis-reveals-a-dynamic-pollen-plasma-membrane-protein-map-and-the-membrane-landscape-of-receptor-like-kinases-and-transporters-important-for-pollen-tube-growth-and-interaction-with-pistils-in-rice
#10
Ning Yang, Tai Wang
BACKGROUND: The coordination of pollen tube (PT) growth, guidance and timely growth arrest and rupture mediated by PT-pistil interaction is crucial for the PT to transport sperm cells into ovules for double fertilization. The plasma membrane (PM) represents an important interface for cell-cell interaction, and PM proteins of PTs are pioneers for mediating PT integrity and interaction with pistils. Thus, understanding the mechanisms underlying these events is important for proteomics. RESULTS: Using the efficient aqueous polymer two-phase system and alkali buffer treatment, we prepared high-purity PM from mature and germinated pollen of rice...
January 5, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/28056047/combining-targeted-metabolomic-data-with-a-model-of-glucose-metabolism-toward-progress-in-chondrocyte-mechanotransduction
#11
Daniel Salinas, Cody A Minor, Ross P Carlson, Carley N McCutchen, Brendan M Mumey, Ronald K June
Osteoarthritis is a debilitating disease likely involving altered metabolism of the chondrocytes in articular cartilage. Chondrocytes can respond metabolically to mechanical loads via cellular mechanotransduction, and metabolic changes are significant because they produce the precursors to the tissue matrix necessary for cartilage health. However, a comprehensive understanding of how energy metabolism changes with loading remains elusive. To improve our understanding of chondrocyte mechanotransduction, we developed a computational model to calculate the rate of reactions (i...
2017: PloS One
https://www.readbyqxmd.com/read/28053665/improved-growth-rate-in-clostridium-thermocellum-hydrogenase-mutant-via-perturbed-sulfur-metabolism
#12
Ranjita Biswas, Charlotte M Wilson, Richard J Giannone, Dawn M Klingeman, Thomas Rydzak, Manesh B Shah, Robert L Hettich, Steven D Brown, Adam M Guss
BACKGROUND: Metabolic engineering is a commonly used approach to develop organisms for an industrial function, but engineering aimed at improving one phenotype can negatively impact other phenotypes. This lack of robustness can prove problematic. Cellulolytic bacterium Clostridium thermocellum is able to rapidly ferment cellulose to ethanol and other products. Recently, genes involved in H2 production, including the hydrogenase maturase hydG and NiFe hydrogenase ech, were deleted from the chromosome of C...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28045126/ecolicore2-a-reference-network-model-of-the-central-metabolism-of-escherichia-coli-and-relationships-to-its-genome-scale-parent-model
#13
Oliver Hädicke, Steffen Klamt
Genome-scale metabolic modeling has become an invaluable tool to analyze properties and capabilities of metabolic networks and has been particularly successful for the model organism Escherichia coli. However, for several applications, smaller metabolic (core) models are needed. Using a recently introduced reduction algorithm and the latest E. coli genome-scale reconstruction iJO1366, we derived EColiCore2, a model of the central metabolism of E. coli. EColiCore2 is a subnetwork of iJO1366 and preserves predefined phenotypes including optimal growth on different substrates...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043922/reconstruction-of-a-genome-scale-metabolic-model-and-in-silico-analysis-of-the-polymalic-acid-producer-aureobasidium-pullulans-cctcc-m2012223
#14
Jun Feng, Jing Yang, Xiaorong Li, Meijin Guo, Bochu Wang, Shang-Tian Yang, Xiang Zou
Aureobasidium pullulans is a yeast-like fungus used for producing biopolymers e.g. polymalic acid (PMA) and pullulan. A high PMA producing strain, A. pullulans CCTCC M2012223, was isolated and sequenced in our previous study. To understand its metabolic performance, a genome-scale metabolic model, iZX637, consisting of 637 genes, 1347 reactions and 1133 metabolites, was reconstructed based on genome annotation and literature mining studies. The iZX637 model was validated by simulating cell growth, utilization of carbon and nitrogen sources, and gene essentiality analysis in A...
December 30, 2016: Gene
https://www.readbyqxmd.com/read/28042698/geochemically-distinct-carbon-isotope-distributions-in-allochromatium-vinosum-dsm-180-t-grown-photoautotrophically-and-photoheterotrophically
#15
T Tang, W Mohr, S R Sattin, D R Rogers, P R Girguis, A Pearson
Anoxygenic, photosynthetic bacteria are common at redox boundaries. They are of interest in microbial ecology and geosciences through their role in linking the carbon, sulfur, and iron cycles, yet much remains unknown about how their flexible carbon metabolism-permitting either autotrophic or heterotrophic growth-is recorded in the bulk sedimentary and lipid biomarker records. Here, we investigated patterns of carbon isotope fractionation in a model photosynthetic sulfur-oxidizing bacterium, Allochromatium vinosum DSM180(T) ...
January 1, 2017: Geobiology
https://www.readbyqxmd.com/read/28039859/cholesterol-crystallisation-in-human-atherosclerosis-is-triggered-in-smooth-muscle-cells-during-the-transition-from-fatty-streak-to-fibroatheroma
#16
Benoît Ho-Tin-Noé, Sophie Vo, Richard Bayles, Stephen Ferrière, Hayette Ladjal, Sondes Toumi, Catherine Deschildre, Véronique Ollivier, Jean-Baptiste Michel
Recent studies have shown that in addition to being major constituents of the atheromatous core, solid cholesterol crystals (CCs) promote atherosclerotic lesion development and rupture by causing mechanical damage and exerting cytotoxic and pro-inflammatory effects. These findings suggest that targeting CCs might represent a therapeutic strategy for plaque stabilisation. However, little is known about how cholesterol crystallisation is initiated in human atherothrombotic disease. Here, we investigated these mechanisms...
December 31, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/28038952/metabotypes-of-breast-cancer-cell-lines-revealed-by-non-targeted-metabolomics
#17
Sébastien Dubuis, Franziska Baenke, Nina Scherbichler, Leila T Alexander, Almut Schulze, Nicola Zamboni
We present an analysis of intracellular metabolism by non-targeted, high-throughput metabolomics profiling of 18 breast cell lines. We profiled >900 putatively annotated metabolite ions for >100 samples collected under both normoxic and hypoxic conditions and revealed extensive heterogeneity across all metabolic pathways and cell lines. Cell line-specific metabolome profiles dominated over patterns associated with malignancy or with the clinical nomenclature of breast cancer cells. Such characteristic metabolome profiles were reproducible across different laboratories and experiments and exhibited mild to robust changes with change in experimental conditions...
December 27, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28034771/lkb1-promotes-metabolic-flexibility-in-response-to-energy-stress
#18
Seth J Parker, Robert U Svensson, Ajit S Divakaruni, Austin E Lefebvre, Anne N Murphy, Reuben J Shaw, Christian M Metallo
The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using (13)C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1...
December 26, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28031032/metabolic-model-of-central-carbon-and-energy-metabolisms-of-growing-arabidopsis-thaliana-in-relation-to-sucrose-translocation
#19
Maksim Zakhartsev, Irina Medvedeva, Yury Orlov, Ilya Akberdin, Olga Krebs, Waltraud X Schulze
BACKGROUND: Sucrose translocation between plant tissues is crucial for growth, development and reproduction of plants. Systemic analysis of these metabolic and underlying regulatory processes allow a detailed understanding of carbon distribution within the plant and the formation of associated phenotypic traits. Sucrose translocation from 'source' tissues (e.g. mesophyll) to 'sink' tissues (e.g. root) is tightly bound to the proton gradient across the membranes. The plant sucrose transporters are grouped into efflux exporters (SWEET family) and proton-symport importers (SUC, STP families)...
December 28, 2016: BMC Plant Biology
https://www.readbyqxmd.com/read/28029042/carbon-isotopomer-analysis-with-non-unifom-sampling-hsqc-nmr-for-cell-extract-and-live-cell-metabolomics-studies
#20
Sujin Lee, He Wen, Yong Jin An, Jin Wook Cha, Yoon-Joo Ko, Sven G Hyberts, Sunghyouk Park
Isotopomer analysis using either (13)C NMR or LC/GC-MS has been an invaluable tool for studying metabolic activities in a variety of systems. Traditional challenges are, however, that (13)C-detected NMR is insensitive despite its high resolution, and that MS-based techniques cannot easily differentiate positional isotopomers. In addition, current (13)C NMR or LC/GC-MS has limitations in detecting metabolites in living cells. Here, we describe a non-uniform sampling-based 2D heteronuclear single quantum coherence (NUS HSQC) approach to measure metabolic isotopomers in both cell lysates and living cells...
December 27, 2016: Analytical Chemistry
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