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Статті в журналах з теми "Regulated metabolic network"
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Ohno, Satoshi, Saori Uematsu, and Shinya Kuroda. "Quantitative metabolic fluxes regulated by trans-omic networks." Biochemical Journal 479, no. 6 (March 31, 2022): 787–804. http://dx.doi.org/10.1042/bcj20210596.
Повний текст джерелаАнотація:
Cells change their metabolism in response to internal and external conditions by regulating the trans-omic network, which is a global biochemical network with multiple omic layers. Metabolic flux is a direct measure of the activity of a metabolic reaction that provides valuable information for understanding complex trans-omic networks. Over the past decades, techniques to determine metabolic fluxes, including 13C-metabolic flux analysis (13C-MFA), flux balance analysis (FBA), and kinetic modeling, have been developed. Recent studies that acquire quantitative metabolic flux and multi-omic data have greatly advanced the quantitative understanding and prediction of metabolism-centric trans-omic networks. In this review, we present an overview of 13C-MFA, FBA, and kinetic modeling as the main techniques to determine quantitative metabolic fluxes, and discuss their advantages and disadvantages. We also introduce case studies with the aim of understanding complex metabolism-centric trans-omic networks based on the determination of metabolic fluxes.
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Schramm, Thorben, and Hannes Link. "Von der Stöchiometrie zur Kontrolle metabolischer Netzwerke." BIOspektrum 27, no. 1 (February 2021): 34–36. http://dx.doi.org/10.1007/s12268-021-1538-0.
Повний текст джерелаАнотація:
AbstractCellular metabolism is very complex and extensively regulated. For many organisms we know almost the complete set of biochemical reactions in their metabolic network. However, it is not well understood how these reactions are regulated and how they interact in order to enable cellular functions. In this review, we describe recent methodological advances to study metabolic networks with a focus on bacterial metabolism.
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Davis, Jacob D., and Eberhard O. Voit. "Metrics for regulated biochemical pathway systems." Bioinformatics 35, no. 12 (November 14, 2018): 2118–24. http://dx.doi.org/10.1093/bioinformatics/bty942.
Повний текст джерелаАнотація:
Abstract Motivation The assessment of graphs through crisp numerical metrics has long been a hallmark of biological network analysis. However, typical graph metrics ignore regulatory signals that are crucially important for optimal pathway operation, for instance, in biochemical or metabolic studies. Here we introduce adjusted metrics that are applicable to both static networks and dynamic systems. Results The metrics permit quantitative characterizations of the importance of regulation in biochemical pathway systems, including systems designed for applications in synthetic biology or metabolic engineering. They may also become criteria for effective model reduction. Availability and implementation The source code is available at https://gitlab.com/tienbien44/metrics-bsa
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Mosca, Ettore, Matteo Barcella, Roberta Alfieri, Annamaria Bevilacqua, Gianfranco Canti, and Luciano Milanesi. "Systems biology of the metabolic network regulated by the Akt pathway." Biotechnology Advances 30, no. 1 (January 2012): 131–41. http://dx.doi.org/10.1016/j.biotechadv.2011.08.004.
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Peplow, Andrew W., Andrew G. Tag, Gulnara F. Garifullina, and Marian N. Beremand. "Identification of New Genes Positively Regulated by Tri10 and a Regulatory Network for Trichothecene Mycotoxin Production." Applied and Environmental Microbiology 69, no. 5 (May 2003): 2731–36. http://dx.doi.org/10.1128/aem.69.5.2731-2736.2003.
Повний текст джерелаАнотація:
ABSTRACT Tri10, a regulatory gene in trichothecene mycotoxin-producing Fusarium species, is required for trichothecene biosynthesis and the coordinated expression of four trichothecene pathway-specific genes (Tri4, Tri5, Tri6, and Tri101) and the isoprenoid biosynthetic gene for farnesyl pyrophosphate synthetase (FPPS). We showed that six more trichothecene genes (Tri3, Tri7, Tri8, Tri9, Tri11, and Tri12) are regulated by Tri10. We also constructed a cDNA library from a strain of Fusarium sporotrichioides that overexpresses Tri10 (↑Tri10) and used cDNA derived from the ↑Tri10 strain and a non-Tri10-expressing strain (ΔTri10) to differentially screen macroarrays prepared from the cDNA library. This screen identified 15 additional Tri10-regulated transcripts. Four of these transcripts represent Tri1, Tri13, and Tri14 and a gene designated Tri15. Three other sequences are putative orthologs of genes for isoprenoid biosynthesis, the primary metabolic pathway preceding trichothecene biosynthesis. The remaining eight sequences have been designated Ibt (influenced by Tri10) genes. Of the 26 transcripts now known to be positively regulated by Tri10, 22 are positively coregulated by Tri6, a gene that encodes a previously characterized trichothecene pathway-specific transcription factor. These 22 Tri10- and Tri6-coregulated sequences include all of the known Tri genes (except for Tri10), the FPPS gene, and the other three putative isoprenoid biosynthetic genes. Tri6 also regulates a transcript that is not regulated by Tri10. Thus, Tri10 and Tri6 regulate overlapping sets of genes that include a common group of multiple genes for both primary and secondary metabolism.
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Heo, Ji-Won, and Sung-Eun Kim. "Comparative Transcriptomic Profiling of Organs Associated With Metabolic Dysfunction in Cancer-Induced Cachexia." Current Developments in Nutrition 5, Supplement_2 (June 2021): 501. http://dx.doi.org/10.1093/cdn/nzab041_016.
Повний текст джерелаАнотація:
Abstract Objectives Approximately 50–80% of cancer patients suffer from cachexia represented by weight loss mainly due to loss of skeletal muscle. Cancer-induced cachexia is a complex metabolic syndrome associated with not only systemic inflammation but also perturbations to energy metabolism. In this study, we profiled gene expression patterns of different organs in CT-26 tumor bearing mice in order to understand metabolic dysfunction in cancer cachexia. Methods The transcriptomic profiles of skeletal muscle, adipose tissue, and liver of CT26-tumor bearing mice were generated using SurePrint G3 Mouse Gene Expression 8 × 60 K v2 (Agilent, Inc.). Functional and network analyses were performed using Gene Set Enrichment Analysis and Ingenuity Pathway Analysis (QIAGEN). Results We identified 299, 508, and 1,311 genes differentially regulated in skeletal muscle, adipose tissue, and liver, respectively. In the skeletal muscle, lipid biosynthetic process and mitochondrial electron transport were negatively regulated and network involved in glutamine metabolism was up-regulated. In adipose tissue, tricarboxylic acid cycle was down-regulated and lipid metabolism was associated with several genes including Thrsp, Plvap, and Sphk1. In the liver, regulation of gluconeogenesis was down-regulated, while production of lactic acid and uptake of D-glucose were related with H6pd and Pkm whose expression was up-regulated during cancer cachexia. Furthermore, the top network matched by genes commonly up-regulated in all organs included Bcl3, Csf2rb, Fcgr2a, and Lilrb3, which are known to be associated with inflammation and muscle wasting. Conclusions Our data suggest that skeletal muscle, adipose tissue, and liver present distinct gene expression profiles associated with inflammation and energy metabolism and several genes up-regulated in all organs might be candidate biomarkers for the prevention and early detection of cancer cachexia. Funding Sources This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education.
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Yang, Xiguang, Xiaopeng Duan, Zhenglin Xia, Rui Huang, Ke He, and Guoan Xiang. "The Regulation Network of Glycerolipid Metabolism as Coregulators of Immunotherapy-Related Myocarditis." Cardiovascular Therapeutics 2023 (June 21, 2023): 1–23. http://dx.doi.org/10.1155/2023/8774971.
Повний текст джерелаАнотація:
Background. To date, immunotherapy for patients with malignant tumors has shown a significant association with myocarditis. However, the mechanism of metabolic reprogramming changes for immunotherapy-related cardiotoxicity is still not well understood. Methods. The CD45+ single-cell RNA sequencing (scRNA-seq) of the Pdcd1-/-Ctla4+/- and wild-type mouse heart in GSE213486 was downloaded to demonstrate the heterogeneity of immunocyte atlas in immunotherapy-related myocarditis. The liquid chromatography–tandem mass spectrometry (LC-MS/MS) spectrum metabolomics analysis detects the metabolic network differences. The drug prediction, organelle level interaction, mitochondrial level regulatory network, and phosphorylation site prediction for key regulators have also been screened via multibioinformatics analysis methods. Results. The scRNA analysis shows that the T cell is the main regulatory cell subpopulation in the pathological progress of immunotherapy-related myocarditis. Mitochondrial regulation pathway significantly participated in pseudotime trajectory- (PTT-) related differential expressed genes (DEGs) in the T cell subpopulation. Additionally, both the gene set enrichment analysis (GSEA) of PTT-related DEGs and LC-MS/MS metabolomics analysis showed that mitochondrial-regulated glycerolipid metabolism plays a central role in metabolic reprogramming changes for immunotherapy-related cardiotoxicity. Finally, the hub-regulated protease of diacylglycerol kinase zeta (Dgkz) was significantly identified and widely played various roles in glycerolipid metabolism, oxidative phosphorylation, and lipid kinase activation. Conclusion. Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.
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Ramana, Chilakamarti V. "Regulation of a Metabolic Gene Signature in Response to Respiratory Viruses and Type I Interferon Signaling." Journal of Molecular Pathology 5, no. 1 (March 7, 2024): 133–52. http://dx.doi.org/10.3390/jmp5010009.
Повний текст джерелаАнотація:
Respiratory viruses are the causative agents responsible for seasonal epidemics and occasional pandemic outbreaks and are a leading cause of death worldwide. Type I interferon (IFNα/β) signaling in the lung epithelial cells plays a major role in the innate immunity to respiratory viruses. Gene signatures are a set of differentially expressed genes in a particular disease or condition and are used to diagnose, monitor, and predict disease progression. These signatures can be used to identify regulatory modules and gene regulatory networks (GRNs) in mammalian signal transduction pathways. Considerable progress has been made in the identification of type I interferon-regulated gene signatures in the host response to respiratory viruses, including antiviral, immunomodulatory, apoptosis, and transcription factor signatures. Respiratory virus infections and host defenses require a dramatic change in the metabolic flux of macromolecules involved in nucleotide, lipid, and protein metabolism. The profiling of IFN-stimulated metabolic genes induced in the host response to several respiratory viruses led to the identification of a common gene signature in human lung epithelial cells and in the lungs of mouse models of respiratory virus infection. The regulation of the metabolic gene signature was correlated with the induction of IFN-beta (IFN-β) and IFN-inducible transcription factors at the RNA level in lung epithelial cells. Furthermore, the gene signature was also detected in response to bacterial lipopolysaccharide-induced acute lung injury. A protein interaction network analysis revealed that metabolic enzymes interact with IFN-regulated transcription factors and members of the unfolded protein response (UPR) to form a module and potentially regulate type I interferon signaling, constituting a feedback loop. In addition, components of the metabolic gene expression signature were differentially regulated in the lung tissues of COVID-19 patients compared with healthy controls. These results suggest that the metabolic gene signature is a potential therapeutic target for the treatment of respiratory virus infections and inflammatory diseases.
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Lai, Liang-Chuan, Alexander L. Kosorukoff, Patricia V. Burke, and Kurt E. Kwast. "Metabolic-State-Dependent Remodeling of the Transcriptome in Response to Anoxia and Subsequent Reoxygenation in Saccharomyces cerevisiae." Eukaryotic Cell 5, no. 9 (September 2006): 1468–89. http://dx.doi.org/10.1128/ec.00107-06.
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ABSTRACT We conducted a comprehensive genomic analysis of the temporal response of yeast to anaerobiosis (six generations) and subsequent aerobic recovery (≈2 generations) to reveal metabolic-state (galactose versus glucose)-dependent differences in gene network activity and function. Analysis of variance showed that far fewer genes responded (raw P value of ≤10−8) to the O2 shifts in glucose (1,603 genes) than in galactose (2,388 genes). Gene network analysis reveals that this difference is due largely to the failure of “stress”-activated networks controlled by Msn2/4, Fhl1, MCB, SCB, PAC, and RRPE to transiently respond to the shift to anaerobiosis in glucose as they did in galactose. After ≈1 generation of anaerobiosis, the response was similar in both media, beginning with the deactivation of Hap1 and Hap2/3/4/5 networks involved in mitochondrial functions and the concomitant derepression of Rox1-regulated networks for carbohydrate catabolism and redox regulation and ending (≥2 generations) with the activation of Upc2- and Mot3-regulated networks involved in sterol and cell wall homeostasis. The response to reoxygenation was rapid (<5 min) and similar in both media, dominated by Yap1 networks involved in oxidative stress/redox regulation and the concomitant activation of heme-regulated ones. Our analyses revealed extensive networks of genes subject to combinatorial regulation by both heme-dependent (e.g., Hap1, Hap2/3/4/5, Rox1, Mot3, and Upc2) and heme-independent (e.g., Yap1, Skn7, and Puf3) factors under these conditions. We also uncover novel functions for several cis-regulatory sites and trans-acting factors and define functional regulons involved in the physiological acclimatization to changes in oxygen availability.
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Gholizadeh, Maryam, Jamal Fayazi, Yazdan Asgari, Hakimeh Zali, and Lars Kaderali. "Reconstruction and Analysis of Cattle Metabolic Networks in Normal and Acidosis Rumen Tissue." Animals 10, no. 3 (March 11, 2020): 469. http://dx.doi.org/10.3390/ani10030469.
Повний текст джерелаАнотація:
The objective of this study was to develop a system-level understanding of acidosis biology. Therefore, the genes expression differences between the normal and acidosis rumen epithelial tissues were first examined using the RNA-seq data in order to understand the molecular mechanisms involved in the disease and then their corresponding metabolic networks constructed. A number of 1074 genes, 978 isoforms, 1049 transcription start sites (TSS), 998 coding DNA sequence (CDS) and 2 promoters were identified being differentially expressed in the rumen tissue between the normal and acidosis samples (p < 0.05). The functional analysis of 627 up-regulated genes revealed their involvement in ion transmembrane transport, filament organization, regulation of cell adhesion, regulation of the actin cytoskeleton, ATP binding, glucose transmembrane transporter activity, carbohydrate binding, growth factor binding and cAMP metabolic process. Additionally, 111 differentially expressed enzymes were identified between the rumen epithelial tissue of the normal and acidosis steers with 46 up-regulated and 65 down-regulated ones in the acidosis group. The pathways and reactions analyses associated with the up-regulated enzymes indicate that most of these enzymes are involved in the fatty acid metabolism, biosynthesis of amino acids, pyruvate and carbon metabolism while most of the down-regulated ones are involved in purine and pyrimidine, vitamin B6 and antibiotics metabolisms. The degree distribution of both metabolic networks follows a power-law one, hence displaying a scale-free property. The top 15 hub metabolites were determined in the acidosis metabolic network with most of them involved in the fatty acid oxidation, VFA biosynthesis, amino acid biogenesis and glutathione metabolism which plays an important role in the stress condition. The limitations of this study were low number of animals and using only epithelial tissue (ventral sac) for RNA-seq.
Дисертації з теми "Regulated metabolic network"
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Berges, Mareike Berges Verfasser], and Dieter [Akademischer Betreuer] [Jahn. "Transcriptional, proteomic and metabolic networks of the Fur regulated iron metabolism of Clostridium difficile / Mareike Berges Berges ; Betreuer: Dieter Jahn." Braunschweig : Technische Universität Braunschweig, 2017. http://d-nb.info/1175890375/34.
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Giese, Gabrielle E. "A Low Vitamin B12 Induced Transcriptional Mechanism That Regulates Metabolic Activity of the Methionine/S-Adenosylmethionine Cycle in Caenorhabditis elegans." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1147.
Повний текст джерелаАнотація:
Cells must regulate their metabolism in order to grow, adapt to changes in nutrient availability and maintain homeostasis. Flux, or the turnover of metabolites, through the metabolic network can be regulated at the allosteric and transcriptional levels. While study of allosteric regulation is limited to biochemical examination of individual proteins, transcriptional control of metabolism can be explored at a systems level. We endeavored to elucidate transcriptional mechanisms of metabolic flux regulation in the model organism Caenorhabditis elegans (C. elegans). We also worked to create a visual tool to explore metabolic pathways that will support future efforts in the research of metabolic gene regulation. C. elegans is a small, free-living nematode that feeds on bacteria and experiences a high level of diversity in nutrient level and composition. Previously, we identified a mechanism by which the essential cofactor, vitamin B12, regulates the expression of genes involved in the degradation of propionate, referred to as B12‑mechanism‑I. This mechanism functions to prevent the toxic accumulation of propionate and requires the TFs NHR-10 and NHR-68. Using genetic screens as well as transcriptomic and metabolomic approaches, we discover a second mechanism by which vitamin B12 regulates metabolic gene expression: B12-mechanism-II. Unlike B12-mechanism-I, B12-mechanism-II is independent of propionate, requires the transcription factor NHR-114 and functions to maintain the metabolic activity of the Methionine/S-adenosylmethionine cycle in a tightly regulated regime. We also present WormPaths, an online resource that allows visualization of C. elegans metabolic pathways and enables metabolic pathway enrichment of user-uploaded transcriptomic data.
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Thuillier, Kerian. "Méthodes de satisfiabilité hybrides pour l'inférence de régulations booléennes contrôlant des réseaux métaboliques." Electronic Thesis or Diss., Université de Rennes (2023-....), 2024. http://www.theses.fr/2024URENS032.
Повний текст джерелаАнотація:
Les systèmes biologiques sont des systèmes multi-échelles complexes composés de nombreux mécanismes biologiques interconnectés. Parmi ces échelles, il y a le métabolisme, qui transforme les nutriments en énergie et en biomasse, et le système de régulation, qui agit comme un contrôleur de l’activité métabolique. Modéliser le couplage du métabolisme et de la régulation est difficile et nécessite d'intégrer les formalismes algébriques différentiels modélisant le métabolisme avec les formalismes discrets modélisant la régulation. Bien qu'il existe des formalismes de simulation de la dynamique hybride de ce couplage, il n'existe aucune méthode pour synthétiser les contrôleurs régulant l'activité métabolique, i.e. les règles de régulation. Cette thèse présente trois formulations du problème de synthèse comme des problèmes d'optimisation combinatoire sous contraintes, logiques et hybrides (logiques et linéaires), quantifiées. Chaque formulation fait l'objet d'une approche de résolution dédiée. La première repose sur des méthodes de satisfiabilité, tandis que les deux autres utilisent des méthodes de résolution hybrides couplant des contraintes logiques et linéaires. En particulier, la thèse présente une méthode générique pour résoudre les problèmes d'optimisation combinatoire sous contraintes linéaires quantifiées. Ces travaux ont conduit au développement de deux logiciels, MERRIN et MerrinASP, qui étendent le paradigme de programmation par ensembles réponses (ASP) avec des contraintes linéaires quantifiées. Cette thèse met également à disposition des jeux de données synthétiques simulant différents types de données omiques, ainsi que le protocole utilisé pour les générerBiological systems are complex multi-scale systems composed of many interconnected biological mechanisms. These scales include the metabolism, which transforms nutrients into energy and biomass, and the regulatory system, which acts as a controller of metabolic activity. Modeling the coupling of metabolism and regulation is difficult and requires integrating the differential-algebraic formalisms of metabolism with the discrete formalisms of regulation. Although formalisms for simulating the hybrid dynamics of this coupling exist, no method allows for the synthesis of the controllers that regulate metabolic activity, that is, the regulatory rules. This thesis presents three formulations of the synthesis problem as combinatorial optimization problems under logical and hybrid (logical and linear) quantified constraints. A dedicated solving method is given for each formulation. The first formulation is solved using satisfiability methods, while the other two rely on hybrid solving methods that integrate logical constraints and linear arithmetic. In particular, the thesis presents a generic framework for solving combinatorial optimization problems under quantified linear constraints. These formalizations have led to the development of two tools, MERRIN and MerrinASP, which extend Answer Set Programming (ASP) with quantified linear constraints. This thesis also provides synthetic datasets that simulate different types of omics data, as well as the protocol used to generate them
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Geryk, Jan. "Architektura regulační sítě metabolismu." Doctoral thesis, 2013. http://www.nusl.cz/ntk/nusl-328678.
Повний текст джерелаАнотація:
The thesis focus on the modularity of metabolic network and foremost on the architecture of regulatory network representing direct regulatory interactions between metabolites and enzymes. I focus on the "modularity measure" in my first work. Modularity measure is quantitative measure of network modularity commonly used for module identification. It was showed that algorithms using this measure can produce modules that are composed of two clearly pronounced sub-modules. Maximum size of module for which there is a risk that is is composed of two sub-modules is called resolution limit of modularity measure. In my first work I generalize resolution limit of modularity measure. The generalized version provide insight to the origin of resolution limit in the null-model used by modularity measure. Moreover it is showed that the risk of omitting of sub-modular structures applies for bigger modules than mentioned in the original publication. The second work is focused on the question how does the modular structure of E. coli metabolic network change if we add regulatory interactions. I find that the modularity of modular core of network slightly increase after regulatory edges addition. The modularity increase is significant with respect to randomized ensemble of regulatory networks. Identified modules...
Частини книг з теми "Regulated metabolic network"
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Radulescu, Ovidiu, Anne Siegel, Elisabeth Pécou, Clément Chatelain, and Sandrine Lagarrigue. "Genetically Regulated Metabolic Networks: Gale-Nikaido Modules and Differential Inequalities." In Lecture Notes in Computer Science, 110–30. Berlin, Heidelberg: Springer Berlin Heidelberg, 2011. http://dx.doi.org/10.1007/978-3-642-19748-2_6.
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Thuillier, Kerian, Caroline Baroukh, Alexander Bockmayr, Ludovic Cottret, Loïc Paulevé, and Anne Siegel. "Learning Boolean Controls in Regulated Metabolic Networks: A Case-Study." In Computational Methods in Systems Biology, 159–80. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-85633-5_10.
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Hua, Brittney, Ielyzaveta Slarve, Aditi A. Datta, Chenxi Xu, Chien-yu Chen, and Bangyan L. Stiles. "Transcriptional Regulation by ERR and Its Role in NAFLD Pathogenesis." In Non-alcoholic Fatty Liver Disease - New Insight and Glance Into Disease Pathogenesis. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.109089.
Повний текст джерелаАнотація:
Members of estrogen-related receptors (ERRs) are orphan nuclear receptors (NRs) that play primary roles in mitochondrial biogenesis and bioenergetics. The ERRs regulate a range of cellular functions, including oxidative phosphorylation (OXPHOS) as well as glucose and lipid metabolism. ERRs are considered important targets for the treatment of metabolic diseases, particularly type II diabetes (T2D), insulin resistance (IR) and obesity. In this review, we will overview the transcriptional network regulated by the members of ERR transcriptional factors and elaborate on the regulation of ERR via its binding to PGC-1α, the primary co-activator of ERR as well as post-translational regulation of ERRs by upstream kinase signals. Recent development in ERR’s cellular function has identified lipid metabolism/lipogenesis as a process that ERR regulates, and this function significantly impacts metabolic syndrome. Here, we will focus on their roles in lipid metabolic regulation and discuss the in vivo functions of ERRs in the development of non-alcoholic fatty liver disease (NAFLD), a comorbid metabolic syndrome concurrent with T2D, IR as well as obesity. Finally, we will explore ERRs as potential therapeutic targets by discussing the ligands that serve as antagonist/agonists for ERRs as well as efforts that target DNA binding of ERR as a transcriptional factor.
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Lesk, Arthur M. "Proteins as catalysts: enzyme structure, kinetics, and mechanism." In Introduction to Protein Science. Oxford University Press, 2016. http://dx.doi.org/10.1093/hesc/9780198716846.003.0005.
Повний текст джерелаАнотація:
This chapter evaluates the role of proteins as catalysts, focusing on enzymes. Cells produce thousands of enzymes. Most act intracellularly, to catalyze a network of metabolic reactions, and the replication, transcription, translation, and repair of DNA. A smoothly integrated operation of the metabolic network requires control mechanisms. The chapter begins by looking at the crucial features of enzymes: catalysis, specificity with respect to substrate and reaction, and ability to be regulated. It then considers the general ideas of enzyme kinetics, including the Michaelis–Menten model, and the measurement and interpretation of the Michaelis constant KM and the maximum velocity (under conditions of saturation of enzyme by substrate) Vmax. The chapter also studies the idea of an enzyme mechanism, the different types of enzyme inhibitors, the mechanism of blood coagulation, motor proteins, and the principles of membrane transport and allosteric change.
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Carraway, Coralie A. Carothers. "The cytoskeleton in the transduction of signal and regulation of cellular function." In Cytoskeleton: signalling and cell regulation, 1–8. Oxford University PressOxford, 1999. http://dx.doi.org/10.1093/oso/9780199637829.003.0001.
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Abstract Cells are constantly bombarded with signals from their environments, and their responses to these cues determine all aspects of their function. Each type of cell responds to these environmental stimuli in a sensitive selective, and temporally ordered manner. Each signal is perceived and integrated into a carefully regulated cellular response which reflects a hierarchy imposed by each cell. Responses to stimuli can range from relatively simple ones, such as activation of a housekeeping metabolic pathway, to global reorganizations which encompass multiple metabolic pathways and elicit massive morpho logical alterations. In many cases there is at least minimal involvement of portions of the intracellular cytoskeletal network. In some instances, such as mitogenesis, complete disassembly and reassembly of all the cytoskeletal net works is required. In these cases morphology becomes destiny, and the pathways which link cell activation to cytoskeletal changes are key to the transmission of signals for the pleiotypic effects necessary for appropriate cellular response.
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Deamer, David W. "Bioenergetics and Primitive Metabolic Pathways." In Assembling Life. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780190646387.003.0012.
Повний текст джерелаАнотація:
It seems inescapable that at some point primitive cells incorporated chemical reactions related to what we now call metabolism. In all life today, metabolic reactions are driven by sources of chemical or photochemical energy, and each step is catalyzed by enzymes and regulated by feedback systems. There have been multiple proposals for the kinds of reactions that could have been incorporated into early life, but so far there is little consensus about a plausible way for metabolism to begin. This chapter will briefly review the main ideas that are familiar to chemists as solution chemistry but then ask a new question from the epigraph: how can reactions in bulk aqueous solutions be captured in membranous compartments? This question is still virtually unexplored, but I can offer some ideas in the hope of guiding potentially fruitful approaches. Because metabolism is such a complex process, it is helpful to use bullet points to help clarify the discussion. The first is a list of questions that guide the discussion, the second is list of facts to keep in mind, and the third is a list of assumptions that introduce the argument. Questions to be addressed: What are the primary metabolic reactions used by life today? What reactions can occur in prebiotic conditions that are related to metabolism? How can potential nutrient solutes cross membranes in order to support metabolism? How could metabolic systems become incorporated into primitive cellular life? Metabolism can be defined as the activity of catalyzed networks of intracellular chemical reactions that alter nutrient compounds available in the environment into a variety of compounds that are used by living systems. Most of the reactions are energetically downhill, so there is an intimate association between the energy sources available to life and the kinds of reactions that can occur. Here is a summary of energy sources used by life today: Light is by far the most abundant energy source, totaling 1360 watts per square meter as infrared and visible wavelengths. Chemical energy in the form of reduced carbon compounds is made available by photosynthesis.
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Zhan, Xianquan, and Na Li. "The Anti-Cancer Effects of Anti-Parasite Drug Ivermectin in Ovarian Cancer." In Ovarian Cancer - Updates in Tumour Biology and Therapeutics [Working Title]. IntechOpen, 2021. http://dx.doi.org/10.5772/intechopen.95556.
Повний текст джерелаАнотація:
Ivermectin is an old, common, and classic anti-parasite drug, which has been found to have a broad-spectrum anti-cancer effect on multiple human cancers. This chapter will focus on the anti-cancer effects of ivermectin on ovarian cancer. First, ivermectin was found to suppress cell proliferation and growth, block cell cycle progression, and promote cell apoptosis in ovarian cancer. Second, drug pathway network, qRT-PCR, and immunoaffinity blot analyses found that ivermectin acts through molecular networks to target the key molecules in energy metabolism pathways, including PFKP in glycolysis, IDH2 and IDH3B in Kreb’s cycle, ND2, ND5, CYTB, and UQCRH in oxidative phosphorylation, and MCT1 and MCT4 in lactate shuttle, to inhibit ovarian cancer growth. Third, the integrative analysis of TCGA transcriptomics and mitochondrial proteomics in ovarian cancer revealed that 16 survival-related lncRNAs were mediated by ivermectin, SILAC quantitative proteomics analysis revealed that ivermectin extensively inhibited the expressions of RNA-binding protein EIF4A3 and 116 EIF4A3-interacted genes including those key molecules in energy metabolism pathways, and also those lncRNAs regulated EIF4A3-mRNA axes. Thus, ivermectin mediated lncRNA-EIF4A3-mRNA axes in ovarian cancer to exert its anticancer capability. Further, lasso regression identified the prognostic model of ivermectin-related three-lncRNA signature (ZNRF3-AS1, SOS1-IT1, and LINC00565), which is significantly associated with overall survival and clinicopathologic characteristics in ovarian cancer patients. These ivermectin-related molecular pattern alterations benefit for prognostic assessment and personalized drug therapy toward 3P medicine practice in ovarian cancer.
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Sisk, Cheryl L., and Russell D. Romeo. "Puberty." In Coming of Age, 9–21. Oxford University Press, 2019. http://dx.doi.org/10.1093/oso/9780195314373.003.0002.
Повний текст джерелаАнотація:
Chapter 2 provides an overview of the neural and endocrine mechanisms that govern the timing and onset of puberty (reproductive maturation). The cells and hormones that comprise the hypothalamic–pituitary–gonadal (HPG) axis are introduced, followed by an explanation of how both negative and positive neuroendocrine feedback loops regulate circulating levels of gonadal steroid hormones in males and females. The rest of the chapter is devoted to mechanisms that govern the timing of puberty and activation of the HPG axis at the onset of puberty. The role of the metabolic hormone leptin as a permissive signal for the timing of puberty, the role of neural excitation and disinhibition in the awakening of the gonadotropin-releasing hormone (GnRH) neurons at the onset of puberty, and the role of the neuropeptide kisspeptin as a proximal driver of HPG axis activation are highlighted. Finally, recent research on hierarchical gene networks that are ultimately responsible for the developmental unfolding of activation of GnRH neurons at puberty onset is reviewed.
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Rosenfeld, John M., Hung-Ying Kao, and Ronald M. Evans. "The Nuclear Receptor Superfamily." In Hormones, Genes, And Cancer, 38–98. Oxford University PressNew York, NY, 2003. http://dx.doi.org/10.1093/oso/9780195135763.003.0003.
Повний текст джерелаАнотація:
Abstract Lipophilic hormones, including steroids, thyroids, and retinoids, regulate complex processes in cellular differentiation, metabolic homeostasis, and animal development. Their ability to diffuse into target cells and bind with high affinity and specificity to their cognate intracellular receptors allows these molecules to coordinate physiological responses by regulating the expression of gene networks. The proteins directly involved in transducing these hormonal signals are known broadly as nuclear receptors (NRs). Upon binding to their specific ligand, NRs modulate the transcription of target genes through interactions with discrete DNA-binding sites known as hormone response elements, cofactor molecules, and general transcriptional machinery. As ligand-activated transcription factors, hormone NRs are indispensable for proper growth and development and often perform essential roles in specifying cell lineages, inducing differentiation, and controlling cellular growth and function. The multitude of mechanisms by which this class of transcription factors orchestrates complex transcriptional control currently makes this protein family one of the most intensely studied areas of molecular biology.
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Mohan, Vandana, Dhirender Kaushik, and Komal Arora. "Role of Acetylcholine in Chronic Diseases." In Acetylcholine - Recent Advances and New Perspectives [Working Title]. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.110663.
Повний текст джерелаАнотація:
The complex and extensive network of brain signals plays a vital role in maintaining physiological mechanisms and homeostasis. Acetylcholine, a chief neurotransmitter of the parasympathetic nervous system, is an important component of the cholinergic system along with cholinergic receptors, acetylcholinesterase, and choline acetyltransferase. It is responsible for mediating cell-to-cell communication and regulates various peripheral and non-neuronal cholinergic signals. Any alteration in the levels of acetylcholine leads to chronic diseases. Chronic diseases, the leading causes of disability, require continuing health care, medical attention, and potential therapeutics. This chapter will cover a brief overview of acetylcholine including its synthesis and degradation, the cholinergic system, and the influence of acetylcholine on different chronic diseases including neurological complications, metabolic disorders, cardiac diseases, and immune disorders. Moreover, the mechanistic approach of acetylcholine in different diseases and the therapies for recovering the levels of acetylcholine will be reviewed in this chapter. Further, this will illustrate the acetylcholine interaction with various cells implicated in the diseases. The insights on agonists and antagonists of acetylcholine and different targets of cholinergic receptors that could help to design better strategies to control these chronic diseases will also be provided.
Тези доповідей конференцій з теми "Regulated metabolic network"
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Jensen, P. A., and J. A. Papin. "A scalable systems analysis approach for regulated metabolic networks." In 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE, 2009. http://dx.doi.org/10.1109/iembs.2009.5334060.
Повний текст джерела
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Shah, Supriya, Joyce V. Lee, Alessandro Carrer, Nathaniel W. Snyder, and Kathryn E. Wellen. "Abstract A31: Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation." In Abstracts: AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; September 14-17, 2014; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-8514.pi3k14-a31.
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Tseng, Wei-Ju, Hainan Zhu, Beom Kang Huh, Chantal de Bakker, Shiming Luo, Juyu Tang, Ling Qin, and X. Sherry Liu. "Assessment of the Vascular and Trabecular Microstructures Using Micro Computed Tomography, Vascular Network Perfusion, and Image Registration Techniques." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14699.
Повний текст джерелаАнотація:
Bone is a dynamic organ that constantly undergoes remodeling throughout one’s life. The remodeling process is required to repair damaged bone tissue and more importantly, to regulate calcium and phosphate homeostasis through the osteocytic network in conjunction with the microvascular network within bone marrow. Recently, techniques combining micro computed tomography (μCT) imaging with vascular network perfusion were developed to allow for 3-D visualization of the bone vascular network structure [1]. However, simultaneous visualization of the trabecular and vascular microstructures using standard μCT remains challenging, and thus the precise relationships between blood vessel formation and trabecular remodeling, as well as the impact of these relationships on metabolic bone diseases such as osteoporosis, remain unclear.
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Cai, Xiaoyu, Marcio de Queiroz, Glen Meades, and Grover Waldrop. "Modeling the Negative Feedback Mechanism in the Enzyme Carboxyltransferase." In ASME 2011 Dynamic Systems and Control Conference and Bath/ASME Symposium on Fluid Power and Motion Control. ASMEDC, 2011. http://dx.doi.org/10.1115/dscc2011-6171.
Повний текст джерелаАнотація:
The enzyme acetyl-CoA carboxylase catalyzes the first committed step in fatty acid synthesis in all organisms. The E. coli form of the carboxyltransferase subunit was recently found to regulate its own activity and expression by binding its own mRNA. By binding acetyl-CoA or the mRNA encoding its own subunits, Carboxyltransferase is able to sense the metabolic state of the cell and attenuate its own translation and enzymatic activity using a negative feedback mechanism. In this paper, this network of interactions is modeled mathematically using mass action kinetics. Numerical simulations of the model show agreement with experimental results.
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Rao, Aparna D., Lorey K. Smith, Tiffany J. Parmenter та Grant A. McArthur. "Abstract B23: Mutant NRAS regulates glycolysis in melanoma through ERK, mTOR and the MYC/HIF1α/MondoA network of transcriptional regulators". У Abstracts: AACR Special Conference: Metabolism and Cancer; June 7-10, 2015; Bellevue, WA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1557-3125.metca15-b23.
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Dai, Chen, Jennifer Arceo, James Arnold, Junmin Wu, Norman J. Dovichi, Arun Sreekumar, Jun Li, and Laurie E. Littlepage. "Abstract 3475: Novel correlation-based network analysis of breast tumor metabolism identifies the glycerol channel protein Aquaporin-7 as a regulator of breast cancer metastasis." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-3475.
Повний текст джерелаЗвіти організацій з теми "Regulated metabolic network"
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Fromm, Hillel, Paul Michael Hasegawa, and Aaron Fait. Calcium-regulated Transcription Factors Mediating Carbon Metabolism in Response to Drought. United States Department of Agriculture, June 2013. http://dx.doi.org/10.32747/2013.7699847.bard.
Повний текст джерелаАнотація:
Original objectives: The long-term goal of the proposed research is to elucidate the transcription factors, genes and metabolic networks involved in carbon metabolism and partitioning in response to water deficit. The proposed research focuses on the GTLcalcium/calmodulinbindingTFs and the gene and metabolic networks modulated by these TFs in Arabidopsis thaliana. The specific objectives are as follows. Objective-1 (USA): Physiological analyses of GTL1 loss- and gain-of-function plants under water sufficient and drought stress conditions Objective 2 (USA / Israel-TAU): Characterizion of GTL target genes and bioinformatic analysis of data to eulcidate gene-network topology. Objective-3 (Israel-TAU): Regulation of GTLmediated transcription by Ca²⁺/calmodulin: mechanism and biological significance. Objective-4 (Israel-BGU): Metabolic networks and carbon partitioning in response to drought. Additional direction: In the course of the project we added another direction, which was reported in the 2nd annual report, to elucidate genes controlling drought avoidance. The TAU team has isolated a few unhydrotropic (hyd) mutants and are in the process of mapping these mutations (of hyd13 and hyd15; see last year's report for a description of these mutants under salt stress) in the Arabidopsis genome by map-based cloning and deep sequencing. For this purpose, each hyd mutant was crossed with a wild type plant of the Landsberg ecotype, and at the F2 stage, 500-700 seedlings showing the unhydrotropic phenotype were collected separately and pooled DNA samples were subkected to the Illumina deep sequencing technology. Bioinformatics were used to identify the exact genomic positions of the mutations (based on a comparison of the genomic sequences of the two Arabidopsis thaliana ecotypes (Columbia and Landsberg). Background: To feed the 9 billion people or more, expected to live on Earth by the mid 21st century, the production of high-quality food must increase substantially. Based on a 2009 Declaration of the World Summit on Food Security, a target of 70% more global food production by the year 2050 was marked, an unprecedented food-production growth rate. Importantly, due to the larger areas of low-yielding land globally, low-yielding environments offer the greatest opportunity for substantial increases in global food production. Nowadays, 70% of the global available water is used by agriculture, and 40% of the world food is produced from irrigated soils. Therefore, much needs to be done towards improving the efficiency of water use by plants, accompanied by increased crop yield production under water-limiting conditions. Major conclusions, solutions and achievements: We established that AtGTL1 (Arabidopsis thaliana GT-2 LIKE1) is a focal determinant in water deficit (drought) signaling and tolerance, and water use efficiency (WUE). The GTL1 transcription factor is an upstream regulator of stomatal development as a transrepressor of AtSDD1, which encodes a subtilisin protease that activates a MAP kinase pathway that negatively regulates stomatal lineage and density. GTL1 binds to the core GT3 cis-element in the SDD1 promoter and transrepresses its expression under water-sufficient conditions. GTL1 loss-of-function mutants have reduced stomatal number and transpiration, and enhanced drought tolerance and WUE. In this case, higher WUE under water sufficient conditions occurs without reduction in absolute biomass accumulation or carbon assimilation, indicating that gtl1-mediated effects on stomatal conductance and transpiration do not substantially affect CO₂ uptake. These results are proof-of-concept that fine-tuned regulation of stomatal density can result in drought tolerance and higher WUE with maintenance of yield stability. Implications: Accomplishments during the IS-4243-09R project provide unique tools for continued discovery research to enhance plant drought tolerance and WUE.
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Fait, Aaron, Grant Cramer, and Avichai Perl. Towards improved grape nutrition and defense: The regulation of stilbene metabolism under drought. United States Department of Agriculture, May 2014. http://dx.doi.org/10.32747/2014.7594398.bard.
Повний текст джерелаАнотація:
The goals of the present research proposal were to elucidate the physiological and molecular basis of the regulation of stilbene metabolism in grape, against the background of (i) grape metabolic network behavior in response to drought and of (ii) varietal diversity. The specific objectives included the study of the physiology of the response of different grape cultivars to continuous WD; the characterization of the differences and commonalities of gene network topology associated with WD in berry skin across varieties; the study of the metabolic response of developing berries to continuous WD with specific attention to the stilbene compounds; the integration analysis of the omics data generated; the study of isolated drought-associated stress factors on the regulation of stilbene biosynthesis in plantaand in vitro. Background to the topic Grape quality has a complex relationship with water input. Regulated water deficit (WD) is known to improve wine grapes by reducing the vine growth (without affecting fruit yield) and boosting sugar content (Keller et al. 2008). On the other hand, irregular rainfall during the summer can lead to drought-associated damage of fruit developmental process and alter fruit metabolism (Downey et al., 2006; Tarara et al., 2008; Chalmers et al., 792). In areas undergoing desertification, WD is associated with high temperatures. This WD/high temperature synergism can limit the areas of grape cultivation and can damage yields and fruit quality. Grapes and wine are the major source of stilbenes in human nutrition, and multiple stilbene-derived compounds, including isomers, polymers and glycosylated forms, have also been characterized in grapes (Jeandet et al., 2002; Halls and Yu, 2008). Heterologous expression of stilbenesynthase (STS) in a variety of plants has led to an enhanced resistance to pathogens, but in others the association has not been proven (Kobayashi et al., 2000; Soleas et al., 1995). Tomato transgenic plants harboring a grape STS had increased levels of resveratrol, ascorbate, and glutathione at the expense of the anthocyanin pathways (Giovinazzo et al. 2005), further emphasizing the intermingled relation among secondary metabolic pathways. Stilbenes are are induced in green and fleshy parts of the berries by biotic and abiotic elicitors (Chong et al., 2009). As is the case for other classes of secondary metabolites, the biosynthesis of stilbenes is not very well understood, but it is known to be under tight spatial and temporal control, which limits the availability of these compounds from plant sources. Only very few studies have attempted to analyze the effects of different environmental components on stilbene accumulation (Jeandet et al., 1995; Martinez-Ortega et al., 2000). Targeted analyses have generally shown higher levels of resveratrol in the grape skin (induced), in seeded varieties, in varieties of wine grapes, and in dark-skinned varieties (Gatto et al., 2008; summarized by Bavaresco et al., 2009). Yet, the effect of the grape variety and the rootstock on stilbene metabolism has not yet been thoroughly investigated (Bavaresco et al., 2009). The study identified a link between vine hydraulic behavior and physiology of stress with the leaf metabolism, which the PIs believe can eventually lead to the modifications identified in the developing berries that interested the polyphenol metabolism and its regulation during development and under stress. Implications are discussed below.
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Jander, Georg, Gad Galili, and Yair Shachar-Hill. Genetic, Genomic and Biochemical Analysis of Arabidopsis Threonine Aldolase and Associated Molecular and Metabolic Networks. United States Department of Agriculture, January 2010. http://dx.doi.org/10.32747/2010.7696546.bard.
Повний текст джерелаАнотація:
Since the amino acids threonine and isoleucine can be limiting in mammalian diet and there is interest in increasing their abundance in certain crop plants. To meet this need, a BARD proposal was written with two main research objectives: (i) investigate new avenues for manipulating threonine and isoleucine content in plants and (ii) study the role of threonine aldolase in plant metabolism. Research conducted to meet these goals included analysis of the sub-cellular localization of threonine aldolase in the plant, analysis of metabolic flux in developing embryos, over- and under-expression of Arabidopsis threonine aldolases, and transcriptional and metabolic analysis of perturbations resulting from altered threonine aldolase expression. Additionally, the broader metabolic effects of increasing lysine biosynthesis were investigated. An interesting observation that came up in the course of the project is that threonine aldolase activity affects methionine gamma-lyase in Arabidopsis. Further research showed that threonine deaminase and methionine gamma-lyase both contribute to isoleucine biosynthesis in plants. Therefore, isoleucine content can be altered by manipulating the expression of either or both of these enzymes. Additionally, both enzymes contribute to the up to 100-fold increase in isoleucine that is observed in drought-stressed Arabidopsis. Toward the end of the project it was discovered that through different projects, both groups had been able to independently up-regulate phenylalanine accumulation by different mechanisms. The Galili lab transformed Arabidopsis with a feedbackinsensitive bacterial enzyme and the Jander lab found a feedback insensitive mutation in Arabidopsis arogenate dehydratase. Exchange of the respective plant lines has allowed a comparative analysis of the different methods for increasing phenylalanine content and the creation of double mutants. The research that was conducted as part of this BARD project has led to new insights into plant amino acid metabolism. Additionally, new approaches that were found to increase the accumulation of threonine, isoleucine, and phenylalanine in plants have potential practical applications. Increased threonine and isoleucine levels can increase the nutritional value of crop plants. Elevated isoleucine accumulation may increase the osmotic stress tolerance of plants. Up-regulation of phenylalanine biosynthesis can be used to increase the production of downstream higher-value plant metabolites of biofuel feed stocks.
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Aharoni, Asaph, Zhangjun Fei, Efraim Lewinsohn, Arthur Schaffer, and Yaakov Tadmor. System Approach to Understanding the Metabolic Diversity in Melon. United States Department of Agriculture, July 2013. http://dx.doi.org/10.32747/2013.7593400.bard.
Повний текст джерелаАнотація:
Fruit quality is determined by numerous genetic factors that affect taste, aroma, color, texture, nutritional value and shelf life. To unravel the genetic components involved in the metabolic pathways behind these traits, the major goal of the project was to identify novel genes that are involved in, or that regulate, these pathways using correlation analysis between genotype, metabolite and gene expression data. The original and specific research objectives were: (1) Collection of replicated fruit from a population of 96 RI lines derived from parents distinguished by great diversity in fruit development and quality phenotypes, (2) Phenotypic and metabolic profiling of mature fruit from all 96 RI lines and their parents, (3) 454 pyrosequencing of cDNA representing mRNA of mature fruit from each line to facilitate gene expression analysis based on relative EST abundance, (4) Development of a database modeled after an existing database developed for tomato introgression lines (ILs) to facilitate online data analysis by members of this project and by researchers around the world. The main functions of the database will be to store and present metabolite and gene expression data so that correlations can be drawn between variation in target traits or metabolites across the RI population members and variation in gene expression to identify candidate genes which may impact phenotypic and chemical traits of interest, (5) Selection of RI lines for segregation and/or hybridization (crosses) analysis to ascertain whether or not genes associated with traits through gene expression/metabolite correlation analysis are indeed contributors to said traits. The overall research strategy was to utilize an available recombinant inbred population of melon (Cucumis melo L.) derived from phenotypically diverse parents and for which over 800 molecular markers have been mapped for the association of metabolic trait and gene expression QTLs. Transcriptomic data were obtained by high throughput sequencing using the Illumina platform instead of the originally planned 454 platform. The change was due to the fast advancement and proven advantages of the Illumina platform, as explained in the first annual scientific report. Metabolic data were collected using both targeted (sugars, organic acids, carotenoids) and non-targeted metabolomics analysis methodologies. Genes whose expression patterns were associated with variation of particular metabolites or fruit quality traits represent candidates for the molecular mechanisms that underlie them. Candidate genes that may encode enzymes catalyzingbiosynthetic steps in the production of volatile compounds of interest, downstream catabolic processes of aromatic amino acids and regulatory genes were selected and are in the process of functional analyses. Several of these are genes represent unanticipated effectors of compound accumulation that could not be identified using traditional approaches. According to the original plan, the Cucurbit Genomics Network (http://www.icugi.org/), developed through an earlier BARD project (IS-3333-02), was expanded to serve as a public portal for the extensive metabolomics and transcriptomic data resulting from the current project. Importantly, this database was also expanded to include genomic and metabolomic resources of all the cucurbit crops, including genomes of cucumber and watermelon, EST collections, genetic maps, metabolite data and additional information. In addition, the database provides tools enabling researchers to identify genes, the expression patterns of which correlate with traits of interest. The project has significantly expanded the existing EST resource for melon and provides new molecular tools for marker-assisted selection. This information will be opened to the public by the end of 2013, upon the first publication describing the transcriptomic and metabolomics resources developed through the project. In addition, well-characterized RI lines are available to enable targeted breeding for genes of interest. Segregation of the RI lines for specific metabolites of interest has been shown, demonstrating the utility in these lines and our new molecular and metabolic data as a basis for selection targeting specific flavor, quality, nutritional and/or defensive compounds. To summarize, all the specific goals of the project have been achieved and in many cases exceeded. Large scale trascriptomic and metabolomic resources have been developed for melon and will soon become available to the community. The usefulness of these has been validated. A number of novel genes involved in fruit ripening have been selected and are currently being functionally analyzed. We thus fully addressed our obligations to the project. In our view, however, the potential value of the project outcomes as ultimately manifested may be far greater than originally anticipated. The resources developed and expanded under this project, and the tools created for using them will enable us, and others, to continue to employ resulting data and discoveries in future studies with benefits both in basic and applied agricultural - scientific research.