@phdthesis{Thierbach2004,
  author    = {Thierbach, Ren{\´e}},
  title     = {Identifikation des mitochondrialen Proteins Frataxin als stoffwechselmodulierenden Tumorsuppressor},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-0001943},
  school      = {Universit{\"a}t Potsdam},
  year      = {2004},
  abstract  = {Die Krebsentstehung wurde vor rund 80 Jahren auf ver{\"a}nderten zellul{\"a}ren Energiestoffwechsel zur{\"u}ckgef{\"u}hrt. Diese Hypothese konnte bisher weder experimentell bewiesen noch widerlegt werden. Durch den Einsatz zweier Modellsysteme mit unterschiedlicher Expression des mitochondrialen Proteins Frataxin konnte in der vorliegenden Arbeit gezeigt werden, dass der mitochondriale Energiestoffwechsel einen Einfluss auf die Tumorentstehung zu besitzen scheint. Eine Reduktion des mitochondrialen Energiestoffwechsels wurde durch die hepatozytenspezifische Ausschaltung des mitochondrialen Proteins Frataxin in M{\"a}usen erreicht. Der durch das Cre-/loxP-Rekombinasesystem erreichte organspezifische Knock-out wurde auf Transkriptions- und Translationsebene nachgewiesen. Anhand verminderter Aconitaseaktivit{\"a}t, geringeren Sauerstoffverbrauches und reduzierten ATP-Gehaltes im Lebergewebe wurde ein signifikant verminderter Energiestoffwechsel dargestellt. Zwar entsprach die Genotypenverteilung in den Versuchsgruppen der erwarteten Mendelschen Verteilung, dennoch war die mittlere Lebenserwartung der Knock-out-Tiere mit ca. 30 Wochen stark reduziert. Bereits in jungem Alter war bei diesen Tieren die Ausbildung von pr{\"a}neoplastischen Herden zu beobachten. Mit proteinbiochemischen Nachweistechniken konnte in Lebergewebe 4-8 Wochen alter Tiere eine verst{\"a}rkte Aktivierung des Apoptosesignalweges (Cytochrom C im Zytosol, verst{\"a}rkte Expression von Bax) sowie eine Modulation stressassoziierter Proteine (geringere Phosphorylierungsrate p38-MAPK, vermehrte Expression HSP-25, verminderte Expression HSP-70) aufgezeigt werden. Im inversen Ansatz wurde eine Steigerung des mitochondrialen Energiestoffwechsels durch stabile transgene Frataxin{\"u}berexpression in zwei Kolonkarzinomzelllinien erreicht. Diese Steigerung zeigte sich durch erh{\"o}hte Aconitaseaktivit{\"a}t, erh{\"o}hten Sauerstoffverbrauch, gesteigertes mitochondriales Membranpotenzial und erh{\"o}hten ATP-Gehalt in den Zellen. Die frataxin{\"u}berexprimierenden Zellen wuchsen signifikant langsamer als Kontrollzellen und zeigten im Soft-Agar-Assay und im Nacktmausmodell ein deutlich geringeres Potenzial zur Ausbildung von Kolonien bzw. Tumoren. Mittels Immunoblot war hier eine vermehrte Phosphorylierung der p38-MAPK festzustellen. Die zusammenfassende Betrachtung beider Modelle zeigt, dass ein reduzierter mitochondrialer Energiestoffwechsel durch Regulation der p38-MAPK und apoptotischer Signalwege ein erh{\"o}htes Krebsrisiko zu verursachen vermag.},
  language  = {de}
}
@phdthesis{Geissler2008,
  author    = {Geißler, Katja},
  title     = {Lebensstrategien seltener Stromtalpflanzen : aut{\"o}kologische Untersuchung von Cnidium dubium, Gratiola officinalis und Juncus atratus unter besonderer Ber{\"u}cksichtigung ihrer Stressresistenz},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-17468},
  school      = {Universit{\"a}t Potsdam},
  year      = {2008},
  abstract  = {Die vorliegende Dissertation behandelt die {\"O}kologie von Cnidium dubium (Schkuhr) Thell. (Sumpf-Brenndolde), Gratiola officinalis L. (Gottes-Gnadenkraut) und Juncus atratus Krocker (Schwarze Binse), drei gef{\"a}hrdeten Arten, die als sogenannte Stromtalpflanzen in Mitteleuropa in ihrem Vorkommen eng an die Flussauen gebunden sind. Die Arbeit basiert auf verschiedenen Simulationsexperimenten und Feldstudien in der Unteren Havelniederung, einem „Feuchtgebiet von internationaler Bedeutung". Sie behandelt Themenkomplexe wie das Samenbankverhalten, die Samenkeimung, die Stickstofflimitierung, die Konkurrenzkraft, das Verhalten der Pflanzen nach einer Sommertrockenheit und nach einer Winter/Fr{\"u}hjahrs{\"u}berflutung. Ferner widmet sie sich der Populationsbiologie der Arten und dem Verhalten der Pflanzen nach besonderen St{\"o}rungsereignissen wie Mahd, Herbivorie und der Sommerflut 2002. Der Leser erf{\"a}hrt, wie die Pflanzen in verschiedenen Lebensphasen auf die auentypische Umwelt reagieren und erh{\"a}lt umfassende Einblicke in physiologische Mechanismen, die der Anpassung an die typischen Bedingungen einer mitteleurop{\"a}ischen Flussaue dienen. Eine Interpretation der Ergebnisse zeigt auf, welche der spezifischen Eigenschaften zur Gef{\"a}hrdung der drei Stromtalarten beitragen. Die Arbeit ist f{\"u}r den Arten-, Biotop- und Landschaftsschutz interessant. Dar{\"u}ber hinaus bietet sie zahlreiche Ankn{\"u}pfungspunkte zur {\"o}kophysiologischen Grundlagenforschung. Die verst{\"a}rkte Nutzung physiologischer Methoden bei der Kl{\"a}rung {\"o}kologischer Fragestellungen wird angeregt.},
  language  = {de}
}
@phdthesis{Ivakov2011,
  author    = {Ivakov, Alexander},
  title     = {Metabolic interactions in leaf development in Arabidopsis thaliana},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-59730},
  school      = {Universit{\"a}t Potsdam},
  year      = {2011},
  abstract  = {Das Wachstum und {\"U}berleben von Pflanzen basiert auf der Photosynthese in den Bl{\"a}ttern. Diese beinhaltet die Aufnahme von Kohlenstoffdioxid aus der Atmosph{\"a}re und das simultane Einfangen von Lichtenergie zur Bildung organischer Molek{\"u}le. Diese werden nach dem Eintritt in den Metabolismus in viele andere Komponenten umgewandelt, welche die Grundlage f{\"u}r die Zunahme der Biomasse bilden. Bl{\"a}tter sind Organe, die auf die Fixierung von Kohlenstoffdioxid spezialisiert sind. Die Funktionen der Bl{\"a}tter beinhalten vor allem die Optimierung und Feinregulierung vieler Prozesse, um eine effektive Nutzung von Ressourcen und eine maximale Photosynthese zu gew{\"a}hrleisten. Es ist bekannt, dass sich die Morphologie der Bl{\"a}tter den Wachstumsbedingungen der Pflanze anpasst und eine wichtige Rolle bei der Optimierung der Photosynthese spielt. Trotzdem ist die Regulation dieser Art der Anpassung bisher nicht verstanden. Die allgemeine Zielsetzung dieser vorliegenden Arbeit ist das Verst{\"a}ndnis wie das Wachstum und die Morphologie der Bl{\"a}tter im Modellorganismus Arabidopsis thaliana reguliert werden. Besondere Aufmerksamkeit wurde hierbei der M{\"o}glichkeit geschenkt, dass es interne metabolische Signale in der Pflanze geben k{\"o}nnte, die das Wachstum und die Entwicklung von Bl{\"a}ttern beeinflussen. Um diese Fragestellung zu untersuchen, muss das Wachstum und die Entwicklung von Bl{\"a}ttern oberhalb des Levels des einzelnen Organs und im Kontext der gesamten Pflanze betrachtet werden, weil Bl{\"a}tter nicht eigenst{\"a}ndig wachsen, sondern von Ressourcen und regulatorischen Einfl{\"u}ssen der ganzen Pflanze abh{\"a}ngig sind. Aufgrund der Komplexit{\"a}t dieser Fragestellung wurden drei komplement{\"a}re Ans{\"a}tze durchgef{\"u}hrt. Im ersten und spezifischsten Ansatz wurde untersucht ob eine flussabw{\"a}rts liegende Komponente des Zucker-Signalwegs, Trehalose-6-Phosphat (Tre-6-P), das Blattwachstum und die Blattentwicklung beinflussen kann. Um diese Frage zu beantworten wurden transgene Arabidopsis-Linien mit einem gest{\"o}rten Gehalt von Tre-6-P durch die Expression von bakteriellen Proteinen die in dem metabolismus von trehalose beteiligt sind. Die Pflanzen-Linien wurden unter Standard-Bendingungen in Erde angebaut und ihr Metabolismus und ihre Blattmorphologie untersucht. Diese Experimente f{\"u}hrten auch zu einem unerwarteten Projekt hinsichtlich einer m{\"o}glichen Rolle von Tre-6-P in der Regulation der Stomata. In einem zweiten, allgemeineren Ansatz wurde untersucht, ob {\"A}nderungen im Zucker-Gehalt der Pflanzen die Morphogenese der Bl{\"a}tter als Antwort auf Licht beeinflussen. Dazu wurden eine Reihe von Mutanten, die im Zentralmetabolismus beeintr{\"a}chtigt sind, in derselben Lichtbedingung angezogen und bez{\"u}glich ihrer Blattmorphologie analysiert. In einem dritten noch allgemeineren Ansatz wurde die nat{\"u}rliche Variation von morphologischen Auspr{\"a}gungen der Bl{\"a}tter und Rosette anhand von wilden Arabidopsis {\"O}kotypen untersucht, um zu verstehen wie sich die Blattmorphologie auf die Blattfunktion und das gesamte Pflanzenwachstum auswirkt und wie unterschiedliche Eigenschaften miteinander verkn{\"u}pft sind. Das Verh{\"a}ltnis der Blattanzahl zum Gesamtwachstum der Pflanze und Blattgr{\"o}ße wurde gesondert weiter untersucht durch eine Normalisierung der Blattanzahl auf das Frischgewicht der Rosette, um den Parameter „leafing Intensity" abzusch{\"a}tzen. Leafing Intensity integrierte Blattanzahl, Blattgr{\"o}ße und gesamtes Rosettenwachstum in einer Reihe von Kompromiss-Interaktionen, die in einem Wachstumsvorteil resultieren, wenn Pflanzen weniger, aber gr{\"o}ßere Bl{\"a}tter pro Einheit Biomasse ausbilden. Dies f{\"u}hrte zu einem theoretischen Ansatz in dem ein einfaches allometrisch mathematisches Modell konstruiert wurde, um Blattanzahl, Blattgr{\"o}ße und Pflanzenwachstum im Kontext der gesamten Pflanze Arabidopsis zu verkn{\"u}pfen.},
  language  = {en}
}
@article{CatchpolePlatzerWeikertetal.2011,
  author    = {Catchpole, Gareth and Platzer, Alexander and Weikert, Cornelia and Kempkensteffen, Carsten and Johannsen, Manfred and Krause, Hans and Jung, Klaus and Miller, Kurt and Willmitzer, Lothar and Selbig, Joachim and Weikert, Steffen},
  title     = {Metabolic profiling reveals key metabolic features of renal cell carcinoma},
  series = {Journal of cellular and molecular medicine : a journal of translational medicine},
  volume    = {15},
  journal   = {Journal of cellular and molecular medicine : a journal of translational medicine},
  number    = {1},
  publisher = {Wiley-Blackwell},
  address   = {Malden},
  issn      = {1582-1838},
  doi       = {10.1111/j.1582-4934.2009.00939.x},
  pages     = {109 -- 118},
  year      = {2011},
  abstract  = {Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. alpha-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5\% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.},
  language  = {en}
}
@article{IslamSchaeublinWenketal.2012,
  author    = {Islam, Khan M. Shaiful and Schaeublin, H. and Wenk, C. and Wanner, Michael and Liesegang, Annette},
  title     = {Effect of dietary citric acid on the performance and mineral metabolism of broiler},
  series = {Journal of animal physiology and animal nutrition},
  volume    = {96},
  journal   = {Journal of animal physiology and animal nutrition},
  number    = {5},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0931-2439},
  doi       = {10.1111/j.1439-0396.2011.01225.x},
  pages     = {808 -- 817},
  year      = {2012},
  abstract  = {The objective of this study was to investigate the effect of dietary citric acid (CA) on the performance and mineral metabolism of broiler chicks. A total of 1720 Ross PM3 broiler chicks (days old) were randomly assigned to four groups (430 in each) and reared for a period of 35 days. The diets of groups 1, 2, 3 and 4 were supplemented with 0\%, 0.25\%, 0.75\% or 1.25\% CA by weight respectively. Feed and faeces samples were collected weekly and analysed for acid insoluble ash, calcium (Ca), phosphorus (P) and magnesium (Mg). The pH was measured in feed and faeces. At the age of 28 days, 10 birds from each group were slaughtered; tibiae were collected from each bird for the determination of bone mineral density, total ash, Ca, P, Mg and bone-breaking strength, and blood was collected for the measurement of osteocalcin, serum CrossLaps (R), Ca, P, Mg and 1,25(OH)(2)Vit-D in serum. After finishing the trial on day 37, all chicks were slaughtered by using the approved procedure. Birds that were fed CA diets were heavier (average body weights of 2030, 2079 and 2086 g in the 0.25\%, 0.75\% and 1.25\% CA groups, respectively, relative to the control birds (1986 g). Feed conversion efficiency (weight gain in g per kg of feed intake) was also higher in birds of the CA-fed groups (582, 595 and 587 g/kg feed intake for 0.25\%, 0.75\% and 1.25\% CA respectively), relative to the control birds (565 g/kg feed intake). The digestibility of Ca, P and Mg increased in the CA-fed groups, especially for the diets supplemented with 0.25\% and 0.75\% CA. Support for finding was also indicated in the results of the analysis of the tibia. At slaughter, the birds had higher carcass weights and higher graded carcasses in the groups that were fed the CA diets. The estimated profit margin was highest for birds fed the diet containing 0.25\% CA. Birds of the 0.75\% CA group were found to have the second highest estimated profit margin. Addition of CA up to a level of 1.25\% of the diet increased performance, feed conversion efficiency, carcass weight and carcass quality, but only in numerical terms. The addition of CA up to 0.75\% significantly increased the digestibility of macro minerals, bone ash content, bone mineral density and bone strength of the broiler chicks. It may, therefore, be concluded that the addition of 0.75\% CA in a standard diet is suitable for growth, carcass traits, macromineral digestibility and bone mineral density of broiler chicks.},
  language  = {en}
}
@misc{WagnerHillebrandWackeretal.2013,
  author    = {Wagner, Nicole D. and Hillebrand, Helmut and Wacker, Alexander and Frost, Paul C.},
  title     = {Nutritional indicators and their uses in ecology},
  series = {Ecology letters},
  volume    = {16},
  journal   = {Ecology letters},
  number    = {4},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {1461-023X},
  doi       = {10.1111/ele.12067},
  pages     = {535 -- 544},
  year      = {2013},
  abstract  = {The nutrition of animal consumers is an important regulator of ecological processes due to its effects on their physiology, life-history and behaviour. Understanding the ecological effects of poor nutrition depends on correctly diagnosing the nature and strength of nutritional limitation. Despite the need to assess nutritional limitation, current approaches to delineating nutritional constraints can be non-specific and imprecise. Here, we consider the need and potential to develop new complementary approaches to the study of nutritional constraints on animal consumers by studying and using a suite of established and emerging biochemical and molecular responses. These nutritional indicators include gene expression, transcript regulators, protein profiling and activity, and gross biochemical and elemental composition. The potential applications of nutritional indicators to ecological studies are highlighted to demonstrate the value that this approach would have to future studies in community and ecosystem ecology.},
  language  = {en}
}
@article{BrothersHiltAttermeyeretal.2013,
  author    = {Brothers, Soren M. and Hilt, Sabine and Attermeyer, Katrin and Grossart, Hans-Peter and Kosten, Sarian and Lischke, Betty and Mehner, Thomas and Meyer, Nils and Scharnweber, Inga Kristin and K{\"o}hler, Jan},
  title     = {A regime shift from macrophyte to phytoplankton dominance enhances carbon burial in a shallow, eutrophic lake},
  series = {Ecosphere : the magazine of the International Ecology University},
  volume    = {4},
  journal   = {Ecosphere : the magazine of the International Ecology University},
  number    = {11},
  publisher = {Wiley},
  address   = {Washington},
  issn      = {2150-8925},
  doi       = {10.1890/ES13-00247.1},
  pages     = {17},
  year      = {2013},
  abstract  = {Ecological regime shifts and carbon cycling in aquatic systems have both been subject to increasing attention in recent years, yet the direct connection between these topics has remained poorly understood. A four-fold increase in sedimentation rates was observed within the past 50 years in a shallow eutrophic lake with no surface in-or outflows. This change coincided with an ecological regime shift involving the complete loss of submerged macrophytes, leading to a more turbid, phytoplankton-dominated state. To determine whether the increase in carbon (C) burial resulted from a comprehensive transformation of C cycling pathways in parallel to this regime shift, we compared the annual C balances (mass balance and ecosystem budget) of this turbid lake to a similar nearby lake with submerged macrophytes, a higher transparency, and similar nutrient concentrations. C balances indicated that roughly 80\% of the C input was permanently buried in the turbid lake sediments, compared to 40\% in the clearer macrophyte-dominated lake. This was due to a higher measured C burial efficiency in the turbid lake, which could be explained by lower benthic C mineralization rates. These lower mineralization rates were associated with a decrease in benthic oxygen availability coinciding with the loss of submerged macrophytes. In contrast to previous assumptions that a regime shift to phytoplankton dominance decreases lake heterotrophy by boosting whole-lake primary production, our results suggest that an equivalent net metabolic shift may also result from lower C mineralization rates in a shallow, turbid lake. The widespread occurrence of such shifts may thus fundamentally alter the role of shallow lakes in the global C cycle, away from channeling terrestrial C to the atmosphere and towards burying an increasing amount of C.},
  language  = {en}
}
@misc{HortobagyiLesinskiFernandez‐del‐Olmoetal.2015,
  author    = {Hortob{\´a}gyi, Tibor and Lesinski, Melanie and Fernandez-del-Olmo, Miguel and Granacher, Urs},
  title     = {Small and inconsistent effects of whole body vibration on athletic performance},
  series = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe},
  number    = {627},
  issn      = {1866-8364},
  doi       = {10.25932/publishup-43199},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-431993},
  pages     = {23},
  year      = {2015},
  abstract  = {Purpose We quantified the acute and chronic effects of whole body vibration on athletic performance or its proxy measures in competitive and/or elite athletes. Methods Systematic literature review and meta-analysis. Results Whole body vibration combined with exercise had an overall 0.3 \% acute effect on maximal voluntary leg force (-6.4 \%, effect size = -0.43, 1 study), leg power (4.7 \%, weighted mean effect size = 0.30, 6 studies), flexibility (4.6 \%, effect size = -0.12 to 0.22, 2 studies), and athletic performance (-1.9 \%, weighted mean effect size = 0.26, 6 studies) in 191 (103 male, 88 female) athletes representing eight sports (overall effect size = 0.28). Whole body vibration combined with exercise had an overall 10.2 \% chronic effect on maximal voluntary leg force (14.6 \%, weighted mean effect size = 0.44, 5 studies), leg power (10.7 \%, weighted mean effect size = 0.42, 9 studies), flexibility (16.5 \%, effect size = 0.57 to 0.61, 2 studies), and athletic performance (-1.2 \%, weighted mean effect size = 0.45, 5 studies) in 437 (169 male, 268 female) athletes (overall effect size = 0.44). Conclusions Whole body vibration has small and inconsistent acute and chronic effects on athletic performance in competitive and/or elite athletes. These findings lead to the hypothesis that neuromuscular adaptive processes following whole body vibration are not specific enough to enhance athletic performance. Thus, other types of exercise programs (e.g., resistance training) are recommended if the goal is to improve athletic performance.},
  language  = {en}
}
@article{HocherHaumannRahnenfuehreretal.2016,
  author    = {Hocher, Berthold and Haumann, Hannah and Rahnenf{\"u}hrer, Jan and Reichetzeder, Christoph and Kalk, Philipp and Pfab, Thiemo and Tsuprykov, Oleg and Winter, Stefan and Hofmann, Ute and Li, Jian and P{\"u}schel, Gerhard Paul and Lang, Florian and Schuppan, Detlef and Schwab, Matthias and Schaeffeler, Elke},
  title     = {Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner},
  series = {Epigenetics : the official journal of the DNA Methylation Society},
  volume    = {11},
  journal   = {Epigenetics : the official journal of the DNA Methylation Society},
  publisher = {Routledge, Taylor \& Francis Group},
  address   = {Philadelphia},
  issn      = {1559-2294},
  doi       = {10.1080/15592294.2016.1184800},
  pages     = {539 -- 552},
  year      = {2016},
  abstract  = {Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.},
  language  = {en}
}
@article{SchwahnBeleggiaOmranianetal.2017,
  author    = {Schwahn, Kevin and Beleggia, Romina and Omranian, Nooshin and Nikoloski, Zoran},
  title     = {Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from Metabolomics Data},
  series = {Frontiers in plant science},
  volume    = {8},
  journal   = {Frontiers in plant science},
  publisher = {Frontiers Research Foundation},
  address   = {Lausanne},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2017.02152},
  pages     = {12},
  year      = {2017},
  abstract  = {Recent advances in metabolomics technologies have resulted in high-quality (time-resolved) metabolic profiles with an increasing coverage of metabolic pathways. These data profiles represent read-outs from often non-linear dynamics of metabolic networks. Yet, metabolic profiles have largely been explored with regression-based approaches that only capture linear relationships, rendering it difficult to determine the extent to which the data reflect the underlying reaction rates and their couplings. Here we propose an approach termed Stoichiometric Correlation Analysis (SCA) based on correlation between positive linear combinations of log-transformed metabolic profiles. The log-transformation is due to the evidence that metabolic networks can be modeled by mass action law and kinetics derived from it. Unlike the existing approaches which establish a relation between pairs of metabolites, SCA facilitates the discovery of higherorder dependence between more than two metabolites. By using a paradigmatic model of the tricarboxylic acid cycle we show that the higher-order dependence reflects the coupling of concentration of reactant complexes, capturing the subtle difference between the employed enzyme kinetics. Using time-resolved metabolic profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be used to quantify the difference in coupling of reactant complexes, and hence, reaction rates, underlying the stringent response in these model organisms. By using SCA with data from natural variation of wild and domesticated wheat and tomato accession, we demonstrate that the domestication is accompanied by loss of such couplings, in these species. Therefore, application of SCA to metabolomics data from natural variation in wild and domesticated populations provides a mechanistic way to understanding domestication and its relation to metabolic networks.},
  language  = {en}
}