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https://www.readbyqxmd.com/read/28088694/metabolic-network-modeling-with-model-organisms
#1
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/28087695/novel-interconnections-in-lipid-metabolism-revealed-by-overexpression-of-sphingomyelin-synthase-1
#2
Gergana M Deevska, Patrick P Dotson, Alexander A Karakashian, Giorgis Isaac, Mark Wrona, Samuel B Kelly, Alfred H Merrill, Mariana N Nikolova-Karakashian
This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1), exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin), but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have less triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function...
January 13, 2017: Journal of Biological Chemistry
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
#3
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
#4
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
#5
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
#6
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/28077078/transcriptomic-evidence-for-the-control-of-soybean-root-isoflavonoid-content-by-regulation-of-overlapping-phenylpropanoid-pathways
#7
Mehran Dastmalchi, Patrick Chapman, Jaeju Yu, Ryan S Austin, Sangeeta Dhaubhadel
BACKGROUND: Isoflavonoids are a class of specialized metabolites found predominantly in legumes. They play a role in signaling for symbiosis with nitrogen-fixing bacteria and inhibiting pathogen infection. RESULTS: A transcriptomic approach using soybean cultivars with high (Conrad and AC Colombe) and low (AC Glengarry and Pagoda) root isoflavonoid content was used to find elements that underlie this variation. Two genes, encoding the flavonoid-metabolizing enzymes, flavonoid 3'-hydroxylase (GmF3'H) and dihydroflavonol 4-reductase (GmDFR), had lower expression levels in high isoflavonoid cultivars...
January 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28070286/influence-of-hydrological-pathways-on-dissolved-organic-carbon-fluxes-in-tropical-streams
#8
Eline Nayara Dantas da Costa, Jéssica Carneiro de Souza, Marilane Andrade Pereira, Marcelo Friederichs Landim de Souza, Weber Friederichs Landim de Souza, Daniela Mariano Lopes da Silva
Water flow pathways and water balance are fundamental components for understanding the dynamics of C in the soil/water interface of small basins. The objective of this study was to describe the seasonal variations and estimate the annual balance of dissolved organic carbon (DOC) by comparing two tropical microbasins (preserved forest-PF and cacao plantation-CP). Twenty-one weekly collections were conducted from September to December 2012 and from April to June 2013. The calculation of the partial balance considered precipitation (P) as inflow and the stream as outflow...
January 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28069660/antioxidant-treatment-attenuates-lactate-production-in-diabetic-nephropathy
#9
Christoffer Laustsen, Per Mose Nielsen, Thomas Stokholm Nørlinger, Haiyun Qi, Uffe Kjærgaard Pedersen, Lotte Bonde Bertelsen, Jakob Appel Østergaard, Allan Flyvbjerg, Jan Henrik Ardenkjær-Larsen, Fredrik Palm, Hans Stødkilde-Jørgensen
The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-(13)C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28067669/targeting-deregulated-ampk-mtorc1-pathways-improves-muscle-function-in-myotonic-dystrophy-type-i
#10
Marielle Brockhoff, Nathalie Rion, Kathrin Chojnowska, Tatiana Wiktorowicz, Christopher Eickhorst, Beat Erne, Stephan Frank, Corrado Angelini, Denis Furling, Markus A Rüegg, Michael Sinnreich, Perrine Castets
Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28065897/trfba-an-algorithm-to-integrate-genome-scale-metabolic-and-transcriptional-regulatory-networks-with-incorporation-of-expression-data
#11
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/28065856/hypoxia-promotes-mitochondrial-glutamine-metabolism-through-hif1%C3%AE-gdh-pathway-in-human-lung-cancer-cells
#12
Zi-Feng Jiang, Min Wang, Jian-Lin Xu, Ya-Jing Ning
Drug-resistance is common in human lung cancer therapy. Hypoxia remarkably contributes to drug-resistance in lung cancer but the underlying mechanism remains elusive. Here we demonstrate that hypoxia-induced glutamine metabolism is involved in drug resistance in lung cancer cells. Hypoxia increases glutamine up-take, glutamate to α-ketoglutarate flux and the generation of ATP in lung cancer cells by up-regulating the expression of glutamate dehydrogenase (GDH). Hypoxia-induced expression of GDH relies on the up-regulation of HIF1α but not HIF2α...
January 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28064439/eugenol-specialty-chemical-production-in-transgenic-poplar-populus-tremula-%C3%A3-p-alba-field-trials
#13
Da Lu, Xianghe Yuan, Sung-Jin Kim, Joaquim V Marques, P Pawan Chakravarthy, Syed G A Moinuddin, Randi Luchterhand, Barri Herman, Laurence B Davin, Norman G Lewis
A foundational study assessed effects of biochemical pathway introduction into poplar to produce eugenol, chavicol, p-anol, isoeugenol, and their sequestered storage products, from potentially available substrates, coniferyl and p-coumaryl alcohols. At the onset, it was unknown whether significant carbon flux to monolignols vs other phenylpropanoid (acetate) pathway metabolites would be kinetically favored. Various transgenic poplar lines generated eugenol and chavicol glucosides in ca. 0.45% (~0.35 and ~0...
January 8, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28061878/blockage-of-glycolysis-by-targeting-pfkfb3-suppresses-tumor-growth-and-metastasis-in-head-and-neck-squamous-cell-carcinoma
#14
Hui-Min Li, Jie-Gang Yang, Zhuo-Jue Liu, Wei-Ming Wang, Zi-Li Yu, Jian-Gang Ren, Gang Chen, Wei Zhang, Jun Jia
BACKGROUND: Many cancers including head and neck squamous cell carcinoma (HNSCC) are characterized by a metabolic rewiring with increased glucose uptake and lactate production, termed as aerobic glycolysis. Targeting aerobic glycolysis presents a promising strategy for cancer therapy. This study investigates the therapeutic potential of glycolysis blockage by targeting phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) in HNSCC. METHODS: 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one (PFK15) was used as a selective antagonist of PFKFB3...
January 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28059601/metabolic-interactions-between-cysteamine-and-epigallocatechin-gallate
#15
Valentina Izzo, Federico Pietrocola, Valentina Sica, Sylvère Durand, Sylvie Lachkar, David Enot, José Manuel Bravo-San Pedro, Alexis Chery, Speranza Esposito, Valeria Raia, Luigi Maiuri, Maria Chiara Maiuri, Guido Kroemer
Phase II clinical trials indicate that the combination of cysteamine plus epigallocatechin gallate (EGCG) is effective against cystic fibrosis in patients bearing the most frequent etiological mutation (CFTRΔF508). Here, we investigated the interaction between both agents on cultured respiratory epithelia cells from normal and CFTRΔF508-mutated donors. We observed that the combination of both agents affected metabolic circuits (and in particular the tricarboxylic acid cycle) in a unique way and that cysteamine plus EGCG reduced cytoplasmic protein acetylation more than each of the two components alone...
January 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28059587/metabolic-effects-of-fasting-on-human-and-mouse-blood-in-vivo
#16
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
#17
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
#18
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
#19
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/28053663/utilization-of-xylose-by-engineered-strains-of-ashbya-gossypii-for-the-production-of-microbial-oils
#20
David Díaz-Fernández, Patricia Lozano-Martínez, Rubén M Buey, José Luis Revuelta, Alberto Jiménez
BACKGROUND: Ashbya gossypii is a filamentous fungus that is currently exploited for the industrial production of riboflavin. The utilization of A. gossypii as a microbial biocatalyst is further supported by its ability to grow in low-cost feedstocks, inexpensive downstream processing and the availability of an ease to use molecular toolbox for genetic and genomic modifications. Consequently, A. gossypii has been also introduced as an ideal biotechnological chassis for the production of inosine, folic acid, and microbial oils...
2017: Biotechnology for Biofuels
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