@article{renzi_epigenetic_2025,
	title = {Epigenetic suppression of creatine kinase {B} in adipocytes links endoplasmic reticulum stress to obesity-associated inflammation},
	volume = {92},
	issn = {2212-8778},
	url = {https://www.sciencedirect.com/science/article/pii/S2212877824002138},
	doi = {10.1016/j.molmet.2024.102082},
	abstract = {In white adipose tissue, disturbed creatine metabolism through reduced creatine kinase B (CKB) transcription contributes to obesity-related inflammation. However, the mechanisms regulating CKB expression in human white adipocytes remain unclear. By screening conditions perturbed in obesity, we identified endoplasmic reticulum (ER) stress as a key suppressor of CKB transcription across multiple cell types. Through follow-up studies, we found that ER stress through the IRE1–XBP1s pathway, promotes CKB promoter methylation via the methyltransferase DNMT3A. This epigenetic change represses CKB transcription, shifting metabolism towards glycolysis and increasing the production of the pro-inflammatory chemokine CCL2. We validated our findings in vivo, demonstrating that individuals living with obesity show an inverse relationship between CKB expression and promoter methylation in white adipocytes, along with elevated CCL2 secretion. Overall, our study uncovers a regulatory axis where ER stress drives inflammation in obesity by reducing CKB abundance, and consequently altering the bioenergetic state of the cell.},
	urldate = {2025-01-10},
	journal = {Molecular Metabolism},
	author = {Renzi, Gianluca and Vlassakev, Ivan and Hansen, Mattias and Higos, Romane and Lecoutre, Simon and Elmastas, Merve and Hodek, Ondrej and Moritz, Thomas and Alaeddine, Lynn M. and Frendo–Cumbo, Scott and Dahlman, Ingrid and Kerr, Alastair and Maqdasy, Salwan and Mejhert, Niklas and Rydén, Mikael},
	month = feb,
	year = {2025},
	keywords = {Chromatin remodeling, Creatine pathway, Glycolysis, Immunometabolism, Tunicamycin},
	pages = {102082},
}

In white adipose tissue, disturbed creatine metabolism through reduced creatine kinase B (CKB) transcription contributes to obesity-related inflammation. However, the mechanisms regulating CKB expression in human white adipocytes remain unclear. By screening conditions perturbed in obesity, we identified endoplasmic reticulum (ER) stress as a key suppressor of CKB transcription across multiple cell types. Through follow-up studies, we found that ER stress through the IRE1–XBP1s pathway, promotes CKB promoter methylation via the methyltransferase DNMT3A. This epigenetic change represses CKB transcription, shifting metabolism towards glycolysis and increasing the production of the pro-inflammatory chemokine CCL2. We validated our findings in vivo, demonstrating that individuals living with obesity show an inverse relationship between CKB expression and promoter methylation in white adipocytes, along with elevated CCL2 secretion. Overall, our study uncovers a regulatory axis where ER stress drives inflammation in obesity by reducing CKB abundance, and consequently altering the bioenergetic state of the cell.

@article{marien_natures_2025,
	title = {Nature’s {Master} of {Ceremony}: {The} {Populus} {Circadian} {Clock} as {Orchestrator} of {Tree} {Growth} and {Phenology}},
	volume = {2},
	copyright = {2025 The Author(s)},
	issn = {2948-281X},
	shorttitle = {Nature’s {Master} of {Ceremony}},
	url = {https://www.nature.com/articles/s44323-025-00034-4},
	doi = {10.1038/s44323-025-00034-4},
	abstract = {Understanding the timely regulation of plant growth and phenology is crucial for assessing a terrestrial ecosystem’s productivity and carbon budget. The circadian clock, a system of genetic oscillators, acts as ‘Master of Ceremony’ during plant physiological processes. The mechanism is particularly elusive in trees despite its relevance. The primary and secondary tree growth, leaf senescence, bud set, and bud burst timing were investigated in 68 constructs transformed into Populus hybrids and compared with untransformed or transformed controls grown in natural or controlled conditions. The results were analyzed using generalized additive models with ordered-factor-smooth interaction smoothers. This meta-analysis shows that several genetic components are associated with the clock. Especially core clock-regulated genes affected tree growth and phenology in both controlled and field conditions. Our results highlight the importance of field trials and the potential of using the clock to generate trees with improved characteristics for sustainable silviculture (e.g., reprogrammed to new photoperiodic regimes and increased growth).},
	language = {en},
	number = {1},
	urldate = {2025-04-11},
	journal = {npj Biological Timing and Sleep},
	author = {Mariën, Bertold and Robinson, Kathryn M. and Jurca, Manuela and Michelson, Ingrid H. and Takata, Naoki and Kozarewa, Iwanka and Pin, Pierre A. and Ingvarsson, Pär K. and Moritz, Thomas and Ibáñez, Cristian and Nilsson, Ove and Jansson, Stefan and Penfield, Steve and Yu, Jun and Eriksson, Maria E.},
	month = apr,
	year = {2025},
	note = {Publisher: Nature Publishing Group},
	keywords = {Biological techniques, Plant sciences},
	pages = {1--19},
}

Understanding the timely regulation of plant growth and phenology is crucial for assessing a terrestrial ecosystem’s productivity and carbon budget. The circadian clock, a system of genetic oscillators, acts as ‘Master of Ceremony’ during plant physiological processes. The mechanism is particularly elusive in trees despite its relevance. The primary and secondary tree growth, leaf senescence, bud set, and bud burst timing were investigated in 68 constructs transformed into Populus hybrids and compared with untransformed or transformed controls grown in natural or controlled conditions. The results were analyzed using generalized additive models with ordered-factor-smooth interaction smoothers. This meta-analysis shows that several genetic components are associated with the clock. Especially core clock-regulated genes affected tree growth and phenology in both controlled and field conditions. Our results highlight the importance of field trials and the potential of using the clock to generate trees with improved characteristics for sustainable silviculture (e.g., reprogrammed to new photoperiodic regimes and increased growth).

@article{miranda-cervantes_pantothenate_2025,
	title = {Pantothenate kinase 4 controls skeletal muscle substrate metabolism},
	volume = {16},
	copyright = {2025 The Author(s)},
	issn = {2041-1723},
	url = {https://www.nature.com/articles/s41467-024-55036-w},
	doi = {10.1038/s41467-024-55036-w},
	abstract = {Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.},
	language = {en},
	number = {1},
	urldate = {2025-01-10},
	journal = {Nature Communications},
	author = {Miranda-Cervantes, Adriana and Fritzen, Andreas M. and Raun, Steffen H. and Hodek, Ondřej and Møller, Lisbeth L. V. and Johann, Kornelia and Deisen, Luisa and Gregorevic, Paul and Gudiksen, Anders and Artati, Anna and Adamski, Jerzy and Andersen, Nicoline R. and Sigvardsen, Casper M. and Carl, Christian S. and Voldstedlund, Christian T. and Kjøbsted, Rasmus and Hauck, Stefanie M. and Schjerling, Peter and Jensen, Thomas E. and Cebrian-Serrano, Alberto and Jähnert, Markus and Gottmann, Pascal and Burtscher, Ingo and Lickert, Heiko and Pilegaard, Henriette and Schürmann, Annette and Tschöp, Matthias H. and Moritz, Thomas and Müller, Timo D. and Sylow, Lykke and Kiens, Bente and Richter, Erik A. and Kleinert, Maximilian},
	month = jan,
	year = {2025},
	note = {Publisher: Nature Publishing Group},
	keywords = {Diabetes, Fat metabolism, Homeostasis, Metabolomics},
	pages = {345},
}

Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.

@article{lecoutre_reduced_2024,
	title = {Reduced adipocyte glutaminase activity promotes energy expenditure and metabolic health},
	volume = {6},
	copyright = {2024 The Author(s)},
	issn = {2522-5812},
	url = {https://www.nature.com/articles/s42255-024-01083-y},
	doi = {10.1038/s42255-024-01083-y},
	abstract = {Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.},
	language = {en},
	number = {7},
	urldate = {2024-07-29},
	journal = {Nature Metabolism},
	author = {Lecoutre, Simon and Maqdasy, Salwan and Rizo-Roca, David and Renzi, Gianluca and Vlassakev, Ivan and Alaeddine, Lynn M. and Higos, Romane and Jalkanen, Jutta and Zhong, Jiawei and Zareifi, Danae S. and Frendo-Cumbo, Scott and Massier, Lucas and Hodek, Ondrej and Juvany, Marta and Moritz, Thomas and de Castro Barbosa, Thais and Omar-Hmeadi, Muhmmad and López-Yus, Marta and Merabtene, Fatiha and Abatan, Jimon Boniface and Marcelin, Geneviève and El Hachem, Elie-Julien and Rouault, Christine and Bergo, Martin O. and Petrus, Paul and Zierath, Juleen R. and Clément, Karine and Krook, Anna and Mejhert, Niklas and Rydén, Mikael},
	month = jul,
	year = {2024},
	note = {Publisher: Nature Publishing Group},
	keywords = {Fat metabolism, Obesity},
	pages = {1329--1346},
}

Glutamine and glutamate are interconverted by several enzymes and alterations in this metabolic cycle are linked to cardiometabolic traits. Herein, we show that obesity-associated insulin resistance is characterized by decreased plasma and white adipose tissue glutamine-to-glutamate ratios. We couple these stoichiometric changes to perturbed fat cell glutaminase and glutamine synthase messenger RNA and protein abundance, which together promote glutaminolysis. In human white adipocytes, reductions in glutaminase activity promote aerobic glycolysis and mitochondrial oxidative capacity via increases in hypoxia-inducible factor 1α abundance, lactate levels and p38 mitogen-activated protein kinase signalling. Systemic glutaminase inhibition in male and female mice, or genetically in adipocytes of male mice, triggers the activation of thermogenic gene programs in inguinal adipocytes. Consequently, the knockout mice display higher energy expenditure and improved glucose tolerance compared to control littermates, even under high-fat diet conditions. Altogether, our findings highlight white adipocyte glutamine turnover as an important determinant of energy expenditure and metabolic health.

@article{carneiro_schinus_2024,
	title = {Schinus terebinthifolia {Raddi}—{Untargeted} {Metabolomics} {Approach} to {Investigate} the {Chemical} {Variation} in {Volatile} and {Non}-{Volatile} {Compounds}},
	volume = {14},
	copyright = {http://creativecommons.org/licenses/by/3.0/},
	issn = {2218-1989},
	url = {https://www.mdpi.com/2218-1989/14/11/612},
	doi = {10.3390/metabo14110612},
	abstract = {Context: Schinus terebinthifolia Raddi is used in Brazilian folk medicine due to the wound healing and antiseptic properties of its bark, and its fruit are used as a condiment. However, the aerial parts of this plant have been studied and present some bioactive compounds as well. Objectives: The aim of this study was to investigate the variation in volatile and non-volatile composition of S. terebinthifolia leaves using untargeted metabolomics. Material and Methods: The leaves of four trees were collected over one year; ethanolic extracts were analyzed by UHPLC-MS and fresh leaves were analyzed by GC-MS using HS-SPME. The data were processed using online software. Results: The results suggest seasonality interfered little with the chemical composition of leaves. On the other hand, the sex of the plant clearly determined the chemical composition of both volatile and non-volatile compounds. Discussion and conclusions: Chemical variability between plants with male and female flowers is fundamental information for the standardized use of its leaves. Compounds with important biological activities were putatively identified, confirming the potential use of S. terebinthifolia leaves as a source of bioactive compounds, reducing waste and increasing economic gains for local farmers throughout the year.},
	language = {en},
	number = {11},
	urldate = {2024-11-29},
	journal = {Metabolites},
	author = {Carneiro, Mara Junqueira and Pinheiro, Guilherme Perez and Antunes, Elisa Ribeiro Miranda and Hantao, Leandro Wang and Moritz, Thomas and Sawaya, Alexandra Christine Helena Frankland},
	month = nov,
	year = {2024},
	note = {Number: 11
Publisher: Multidisciplinary Digital Publishing Institute},
	keywords = {\textit{Aroeira}, GC-MS, UHPLC-MS, pink pepper, plant sex, seasonality},
	pages = {612},
}

Context: Schinus terebinthifolia Raddi is used in Brazilian folk medicine due to the wound healing and antiseptic properties of its bark, and its fruit are used as a condiment. However, the aerial parts of this plant have been studied and present some bioactive compounds as well. Objectives: The aim of this study was to investigate the variation in volatile and non-volatile composition of S. terebinthifolia leaves using untargeted metabolomics. Material and Methods: The leaves of four trees were collected over one year; ethanolic extracts were analyzed by UHPLC-MS and fresh leaves were analyzed by GC-MS using HS-SPME. The data were processed using online software. Results: The results suggest seasonality interfered little with the chemical composition of leaves. On the other hand, the sex of the plant clearly determined the chemical composition of both volatile and non-volatile compounds. Discussion and conclusions: Chemical variability between plants with male and female flowers is fundamental information for the standardized use of its leaves. Compounds with important biological activities were putatively identified, confirming the potential use of S. terebinthifolia leaves as a source of bioactive compounds, reducing waste and increasing economic gains for local farmers throughout the year.

@article{le_provost_oak_2023,
	title = {Oak stands along an elevation gradient have different molecular strategies for regulating bud phenology},
	volume = {23},
	issn = {1471-2229},
	url = {https://doi.org/10.1186/s12870-023-04069-2},
	doi = {10.1186/s12870-023-04069-2},
	abstract = {Global warming raises serious concerns about the persistence of species and populations locally adapted to their environment, simply because of the shift it produces in their adaptive landscape. For instance, the phenological cycle of tree species may be strongly affected by higher winter temperatures and late frost in spring. Given the variety of ecosystem services they provide, the question of forest tree adaptation has received increasing attention in the scientific community and catalyzed research efforts in ecology, evolutionary biology and functional genomics to study their adaptive capacity to respond to such perturbations.},
	number = {1},
	urldate = {2023-03-03},
	journal = {BMC Plant Biology},
	author = {Le Provost, Gregoire and Lalanne, Céline and Lesur, Isabelle and Louvet, Jean-Marc and Delzon, Sylvain and Kremer, Antoine and Labadie, Karine and Aury, Jean-Marc and Da Silva, Corinne and Moritz, Thomas and Plomion, Christophe},
	month = feb,
	year = {2023},
	keywords = {Bud phenology, Elevation cline, Gene expression, Hormone quantification, Response to temperature, Sessile oak},
	pages = {108},
}

Global warming raises serious concerns about the persistence of species and populations locally adapted to their environment, simply because of the shift it produces in their adaptive landscape. For instance, the phenological cycle of tree species may be strongly affected by higher winter temperatures and late frost in spring. Given the variety of ecosystem services they provide, the question of forest tree adaptation has received increasing attention in the scientific community and catalyzed research efforts in ecology, evolutionary biology and functional genomics to study their adaptive capacity to respond to such perturbations.

@article{hodek_structural_2023,
	title = {Structural elucidation of 3-nitrophenylhydrazine derivatives of tricarboxylic acid cycle acids and optimization of their fragmentation to boost sensitivity in liquid chromatography-mass spectrometry},
	volume = {1222},
	issn = {1570-0232},
	url = {https://www.sciencedirect.com/science/article/pii/S1570023223001290},
	doi = {10.1016/j.jchromb.2023.123719},
	abstract = {Carboxylic acids participate in many metabolic pathways including tricarboxylic acid (TCA) cycle. Therefore, there have been ongoing attempts to develop sensitive liquid chromatography-mass spectrometry methods over the last decades. Derivatization of the carboxylic acids with 3-nitrophenylhydrazine presents a well-established methodology, and yet the derivatized species of polycarboxylic acids and their fragmentation in collision-induced dissociation have not been fully studied before. In our study, we elucidated how annotation of most abundant 3-nitrophenylhydrazine derivatives and optimization of their fragmentation in multiple reaction monitoring can boost the sensitivity, especially for polycarboxylic acids. Finally, the optimized liquid chromatography-tandem mass spectrometry method allowed for low detection limits ranging from 10 pM for 2-oxoglutaric acid to 800 pM for pyruvic acid. All TCA carboxylates were quantified in 20 µL of human plasma and the targeted method was validated in the same matrix. The same methodology with a modified gradient elution was also applied to untargeted screening of fatty acids by using high-resolution mass spectrometry enabling identification of 29 medium- to long-chain fatty acids in human plasma. The TCA carboxylates were also quantified in 105 of C2C12 mouse myuotube cells grown under different treatments to proof applicability of the methodology to biological studies in a wider sense. However, unfortunately all the TCA carboxylates were also found in the derivatized blanks in substantial amounts, which prevents from using the methodology for quantification of the carboxylates in less than 105 cells.},
	language = {en},
	urldate = {2023-04-21},
	journal = {Journal of Chromatography B},
	author = {Hodek, Ondřej and Henderson, John and Argemi-Muntadas, Lidia and Khan, Adnan and Moritz, Thomas},
	month = apr,
	year = {2023},
	keywords = {3-nitrophenylhydrazine, Carboxylic acid, Derivatization, Liquid chromatography-mass spectrometry},
	pages = {123719},
}

Carboxylic acids participate in many metabolic pathways including tricarboxylic acid (TCA) cycle. Therefore, there have been ongoing attempts to develop sensitive liquid chromatography-mass spectrometry methods over the last decades. Derivatization of the carboxylic acids with 3-nitrophenylhydrazine presents a well-established methodology, and yet the derivatized species of polycarboxylic acids and their fragmentation in collision-induced dissociation have not been fully studied before. In our study, we elucidated how annotation of most abundant 3-nitrophenylhydrazine derivatives and optimization of their fragmentation in multiple reaction monitoring can boost the sensitivity, especially for polycarboxylic acids. Finally, the optimized liquid chromatography-tandem mass spectrometry method allowed for low detection limits ranging from 10 pM for 2-oxoglutaric acid to 800 pM for pyruvic acid. All TCA carboxylates were quantified in 20 µL of human plasma and the targeted method was validated in the same matrix. The same methodology with a modified gradient elution was also applied to untargeted screening of fatty acids by using high-resolution mass spectrometry enabling identification of 29 medium- to long-chain fatty acids in human plasma. The TCA carboxylates were also quantified in 105 of C2C12 mouse myuotube cells grown under different treatments to proof applicability of the methodology to biological studies in a wider sense. However, unfortunately all the TCA carboxylates were also found in the derivatized blanks in substantial amounts, which prevents from using the methodology for quantification of the carboxylates in less than 105 cells.

@article{derba-maceluch_xylan_2023,
	title = {Xylan glucuronic acid side chains fix suberin-like aliphatic compounds to wood cell walls},
	volume = {238},
	issn = {1469-8137},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/nph.18712},
	doi = {10.1111/nph.18712},
	abstract = {Wood is the most important repository of assimilated carbon in the biosphere, in the form of large polymers (cellulose, hemicelluloses including glucuronoxylan, and lignin) that interactively form a composite, together with soluble extractives including phenolic and aliphatic compounds. Molecular interactions among these compounds are not fully understood. We have targeted the expression of a fungal α-glucuronidase to the wood cell wall of aspen (Populus tremula L. × tremuloides Michx.) and Arabidopsis (Arabidopsis thaliana (L.) Heynh), to decrease contents of the 4-O-methyl glucuronopyranose acid (mGlcA) substituent of xylan, to elucidate mGlcA's functions. The enzyme affected the content of aliphatic insoluble cell wall components having composition similar to suberin, which required mGlcA for binding to cell walls. Such suberin-like compounds have been previously identified in decayed wood, but here, we show their presence in healthy wood of both hardwood and softwood species. By contrast, γ-ester bonds between mGlcA and lignin were insensitive to cell wall-localized α-glucuronidase, supporting the intracellular formation of these bonds. These findings challenge the current view of the wood cell wall composition and reveal a novel function of mGlcA substituent of xylan in fastening of suberin-like compounds to cell wall. They also suggest an intracellular initiation of lignin–carbohydrate complex assembly.},
	language = {en},
	number = {1},
	urldate = {2023-03-10},
	journal = {New Phytologist},
	author = {Derba-Maceluch, Marta and Mitra, Madhusree and Hedenström, Mattias and Liu, Xiaokun and Gandla, Madhavi L. and Barbut, Félix R. and Abreu, Ilka N. and Donev, Evgeniy N. and Urbancsok, János and Moritz, Thomas and Jönsson, Leif J. and Tsang, Adrian and Powlowski, Justin and Master, Emma R. and Mellerowicz, Ewa J.},
	month = jan,
	year = {2023},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/nph.18712},
	keywords = {Populus, lignin-carbohydrate complexes (LCCs), lignin–carbohydrate complexes, saccharification, suberin, wood cell wall, xylan},
	pages = {297--312},
}

Wood is the most important repository of assimilated carbon in the biosphere, in the form of large polymers (cellulose, hemicelluloses including glucuronoxylan, and lignin) that interactively form a composite, together with soluble extractives including phenolic and aliphatic compounds. Molecular interactions among these compounds are not fully understood. We have targeted the expression of a fungal α-glucuronidase to the wood cell wall of aspen (Populus tremula L. × tremuloides Michx.) and Arabidopsis (Arabidopsis thaliana (L.) Heynh), to decrease contents of the 4-O-methyl glucuronopyranose acid (mGlcA) substituent of xylan, to elucidate mGlcA's functions. The enzyme affected the content of aliphatic insoluble cell wall components having composition similar to suberin, which required mGlcA for binding to cell walls. Such suberin-like compounds have been previously identified in decayed wood, but here, we show their presence in healthy wood of both hardwood and softwood species. By contrast, γ-ester bonds between mGlcA and lignin were insensitive to cell wall-localized α-glucuronidase, supporting the intracellular formation of these bonds. These findings challenge the current view of the wood cell wall composition and reveal a novel function of mGlcA substituent of xylan in fastening of suberin-like compounds to cell wall. They also suggest an intracellular initiation of lignin–carbohydrate complex assembly.

@article{linden_circum-arctic_2022,
	title = {Circum-{Arctic} distribution of chemical anti-herbivore compounds suggests biome-wide trade-off in defence strategies in {Arctic} shrubs},
	issn = {1600-0587},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/ecog.06166},
	doi = {10.1111/ecog.06166},
	abstract = {Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence. We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.},
	language = {en},
	urldate = {2022-09-08},
	journal = {Ecography},
	author = {Lindén, Elin and te Beest, Mariska and Aubreu, Ilka and Moritz, Thomas and Sundqvist, Maja K. and Barrio, Isabel C. and Boike, Julia and Bryant, John P. and Bråthen, Kari Anne and Buchwal, Agata and Bueno, C. Guillermo and Currier, Alain and Egelkraut, Dagmar D. and Forbes, Bruce C. and Hallinger, Martin and Heijmans, Monique and Hermanutz, Luise and Hik, David S. and Hofgaard, Annika and Holmgren, Milena and Huebner, Diane C. and Høye, Toke T. and Jónsdóttir, Ingibjörg S. and Kaarlejärvi, Elina and Kissler, Emilie and Kumpula, Timo and Limpens, Juul and Myers-Smith, Isla H. and Normand, Signe and Post, Eric and Rocha, Adrian V. and Schmidt, Niels Martin and Skarin, Anna and Soininen, Eeva M. and Sokolov, Aleksandr and Sokolova, Natalia and Speed, James D. M. and Street, Lorna and Tananaev, Nikita and Tremblay, Jean-Pierre and Urbanowicz, Christine and Watts, David A. and Zimmermann, Heike and Olofsson, Johan},
	month = aug,
	year = {2022},
	keywords = {Arctic, Betula, birch, herbivory, metabolomics, plant chemical defence, shrubs, tundra},
	pages = {e06166},
}

Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations. We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence. We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.

@article{maqdasy_impaired_2022,
	title = {Impaired phosphocreatine metabolism in white adipocytes promotes inflammation},
	volume = {4},
	copyright = {2022 The Author(s)},
	issn = {2522-5812},
	url = {https://www.nature.com/articles/s42255-022-00525-9},
	doi = {10.1038/s42255-022-00525-9},
	abstract = {The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.},
	language = {en},
	number = {2},
	urldate = {2022-02-17},
	journal = {Nature Metabolism},
	author = {Maqdasy, Salwan and Lecoutre, Simon and Renzi, Gianluca and Frendo-Cumbo, Scott and Rizo-Roca, David and Moritz, Thomas and Juvany, Marta and Hodek, Ondrej and Gao, Hui and Couchet, Morgane and Witting, Michael and Kerr, Alastair and Bergo, Martin O. and Choudhury, Robin P. and Aouadi, Myriam and Zierath, Juleen R. and Krook, Anna and Mejhert, Niklas and Rydén, Mikael},
	month = feb,
	year = {2022},
	keywords = {Fat metabolism, Mechanisms of disease, Obesity},
	pages = {1--13},
}

The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.

@article{liebsch_metabolic_2022,
	title = {Metabolic control of arginine and ornithine levels paces the progression of leaf senescence},
	volume = {189},
	issn = {0032-0889},
	url = {https://doi.org/10.1093/plphys/kiac244},
	doi = {10.1093/plphys/kiac244},
	abstract = {Leaf senescence can be induced by stress or aging, sometimes in a synergistic manner. It is generally acknowledged that the ability to withstand senescence-inducing conditions can provide plants with stress resilience. Although the signaling and transcriptional networks responsible for a delayed senescence phenotype, often referred to as a functional stay-green trait, have been actively investigated, very little is known about the subsequent metabolic adjustments conferring this aptitude to survival. First, using the individually darkened leaf (IDL) experimental setup, we compared IDLs of wild-type (WT) Arabidopsis (Arabidopsis thaliana) to several stay-green contexts, that is IDLs of two functional stay-green mutant lines, oresara1-2 (ore1-2) and an allele of phytochrome-interacting factor 5 (pif5), as well as to leaves from a WT plant entirely darkened (DP). We provide compelling evidence that arginine and ornithine, which accumulate in all stay-green contexts—likely due to the lack of induction of amino acids (AAs) transport—can delay the progression of senescence by fueling the Krebs cycle or the production of polyamines (PAs). Secondly, we show that the conversion of putrescine to spermidine (SPD) is controlled in an age-dependent manner. Thirdly, we demonstrate that SPD represses senescence via interference with ethylene signaling by stabilizing the ETHYLENE BINDING FACTOR1 and 2 (EBF1/2) complex. Taken together, our results identify arginine and ornithine as central metabolites influencing the stress- and age-dependent progression of leaf senescence. We propose that the regulatory loop between the pace of the AA export and the progression of leaf senescence provides the plant with a mechanism to fine-tune the induction of cell death in leaves, which, if triggered unnecessarily, can impede nutrient remobilization and thus plant growth and survival.},
	number = {4},
	urldate = {2022-08-08},
	journal = {Plant Physiology},
	author = {Liebsch, Daniela and Juvany, Marta and Li, Zhonghai and Wang, Hou-Ling and Ziolkowska, Agnieszka and Chrobok, Daria and Boussardon, Clément and Wen, Xing and Law, Simon R and Janečková, Helena and Brouwer, Bastiaan and Lindén, Pernilla and Delhomme, Nicolas and Stenlund, Hans and Moritz, Thomas and Gardeström, Per and Guo, Hongwei and Keech, Olivier},
	month = aug,
	year = {2022},
	pages = {1943--1960},
}

Leaf senescence can be induced by stress or aging, sometimes in a synergistic manner. It is generally acknowledged that the ability to withstand senescence-inducing conditions can provide plants with stress resilience. Although the signaling and transcriptional networks responsible for a delayed senescence phenotype, often referred to as a functional stay-green trait, have been actively investigated, very little is known about the subsequent metabolic adjustments conferring this aptitude to survival. First, using the individually darkened leaf (IDL) experimental setup, we compared IDLs of wild-type (WT) Arabidopsis (Arabidopsis thaliana) to several stay-green contexts, that is IDLs of two functional stay-green mutant lines, oresara1-2 (ore1-2) and an allele of phytochrome-interacting factor 5 (pif5), as well as to leaves from a WT plant entirely darkened (DP). We provide compelling evidence that arginine and ornithine, which accumulate in all stay-green contexts—likely due to the lack of induction of amino acids (AAs) transport—can delay the progression of senescence by fueling the Krebs cycle or the production of polyamines (PAs). Secondly, we show that the conversion of putrescine to spermidine (SPD) is controlled in an age-dependent manner. Thirdly, we demonstrate that SPD represses senescence via interference with ethylene signaling by stabilizing the ETHYLENE BINDING FACTOR1 and 2 (EBF1/2) complex. Taken together, our results identify arginine and ornithine as central metabolites influencing the stress- and age-dependent progression of leaf senescence. We propose that the regulatory loop between the pace of the AA export and the progression of leaf senescence provides the plant with a mechanism to fine-tune the induction of cell death in leaves, which, if triggered unnecessarily, can impede nutrient remobilization and thus plant growth and survival.

@article{hodek_mixed-mode_2022,
	title = {Mixed-mode chromatography-mass spectrometry enables targeted and untargeted screening of carboxylic acids in biological samples},
	volume = {14},
	issn = {1759-9679},
	url = {https://pubs.rsc.org/en/content/articlelanding/2022/ay/d1ay02143e},
	doi = {10/gpkx25},
	abstract = {Carboxylic acids are crucial metabolites in the tricarboxylic acid (TCA) cycle and thus participate in central carbon metabolism (CCM). Research dependent on the analysis of metabolites involved in central carbon metabolism requires fast separation and sensitive detection of carboxylic acids using liquid chromatography-mass spectrometry (LC-MS). However, successful separation of all carboxylic acids from the TCA cycle by liquid chromatography remains a challenging task because of their high polarity and thus low retention on the conventional reversed-phase columns. In this study, we tested a reversed-phase/anion exchange mixed-mode stationary phase (Waters BEH C18 AX) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed and optimized a method that enables a 10 minute separation of all carboxylic acids from the TCA cycle and lactic acid without prior derivatization or addition of ion-pair reagents in the mobile phase. The developed method was validated for quantification of 8 acids in murine brown preadipocytes, 5 acids in human plasma and 6 acids in Arabidopsis thaliana leaves with limits of quantification ranging from 0.1 μM for malic acid to 10 μM for isocitric acid. Moreover, the mixed-mode chromatography enabled untargeted screening of medium- to long-chain fatty acids in murine brown preadipocytes, Arabidopsis thaliana, and human plasma, where 23 fatty acids were identified by using liquid chromatography with high-resolution mass spectrometry (HRMS).},
	language = {en},
	number = {10},
	urldate = {2022-02-25},
	journal = {Analytical Methods},
	author = {Hodek, Ondřej and Argemi-Muntadas, Lidia and Khan, Adnan and Moritz, Thomas},
	month = jan,
	year = {2022},
	pages = {1015--1022},
}

Carboxylic acids are crucial metabolites in the tricarboxylic acid (TCA) cycle and thus participate in central carbon metabolism (CCM). Research dependent on the analysis of metabolites involved in central carbon metabolism requires fast separation and sensitive detection of carboxylic acids using liquid chromatography-mass spectrometry (LC-MS). However, successful separation of all carboxylic acids from the TCA cycle by liquid chromatography remains a challenging task because of their high polarity and thus low retention on the conventional reversed-phase columns. In this study, we tested a reversed-phase/anion exchange mixed-mode stationary phase (Waters BEH C18 AX) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). We developed and optimized a method that enables a 10 minute separation of all carboxylic acids from the TCA cycle and lactic acid without prior derivatization or addition of ion-pair reagents in the mobile phase. The developed method was validated for quantification of 8 acids in murine brown preadipocytes, 5 acids in human plasma and 6 acids in Arabidopsis thaliana leaves with limits of quantification ranging from 0.1 μM for malic acid to 10 μM for isocitric acid. Moreover, the mixed-mode chromatography enabled untargeted screening of medium- to long-chain fatty acids in murine brown preadipocytes, Arabidopsis thaliana, and human plasma, where 23 fatty acids were identified by using liquid chromatography with high-resolution mass spectrometry (HRMS).

@article{marabita_multiomics_2022,
	title = {Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health},
	volume = {13},
	issn = {2405-4712},
	url = {https://www.cell.com/cell-systems/abstract/S2405-4712(21)00451-8},
	doi = {10.1016/j.cels.2021.11.001},
	language = {English},
	number = {3},
	urldate = {2022-04-08},
	journal = {Cell Systems},
	author = {Marabita, Francesco and James, Tojo and Karhu, Anu and Virtanen, Heidi and Kettunen, Kaisa and Stenlund, Hans and Boulund, Fredrik and Hellström, Cecilia and Neiman, Maja and Mills, Robert and Perheentupa, Teemu and Laivuori, Hannele and Helkkula, Pyry and Byrne, Myles and Jokinen, Ilkka and Honko, Harri and Kallonen, Antti and Ermes, Miikka and Similä, Heidi and Lindholm, Mikko and Widén, Elisabeth and Ripatti, Samuli and Perälä-Heape, Maritta and Engstrand, Lars and Nilsson, Peter and Moritz, Thomas and Miettinen, Timo and Sallinen, Riitta and Kallioniemi, Olli},
	month = mar,
	year = {2022},
	keywords = {P4 medicine, lifestyle changes, multiomics data integration, personalized medicine, precision health, precision medicine, systems medicine},
	pages = {241--255.e7},
}

@article{wang_sucrose_2022,
	title = {Sucrose synthase activity is not required for cellulose biosynthesis in {Arabidopsis}},
	volume = {110},
	issn = {1365-313X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/tpj.15752},
	doi = {10.1111/tpj.15752},
	abstract = {Biosynthesis of plant cell walls requires UDP-glucose as the substrate for cellulose biosynthesis, and as an intermediate for the synthesis of other matrix polysaccharides. The sucrose cleaving enzyme sucrose synthase (SUS) is thought to have a central role in UDP-glucose biosynthesis, and a long-held and much debated hypothesis postulates that SUS is required to supply UDP-glucose to cellulose biosynthesis. To investigate the role of SUS in cellulose biosynthesis of Arabidopsis thaliana we characterized mutants in which four or all six Arabidopsis SUS genes were disrupted. These sus mutants showed no growth phenotypes, vascular tissue cell wall defects, or changes in cellulose content. Moreover, the UDP-glucose content of rosette leaves of the sextuple sus mutants was increased by approximately 20\% compared with wild type. It can thus be concluded that cellulose biosynthesis is able to employ alternative UDP-glucose biosynthesis pathway(s), and thereby the model of SUS requirements for cellulose biosynthesis in Arabidopsis can be refuted.},
	language = {en},
	number = {5},
	urldate = {2022-06-09},
	journal = {The Plant Journal},
	author = {Wang, Wei and Viljamaa, Sonja and Hodek, Ondrej and Moritz, Thomas and Niittylä, Totte},
	year = {2022},
	keywords = {Arabidopsis thaliana, UDP-glucose, cellulose, sucrose synthase},
	pages = {1493--1497},
}

Biosynthesis of plant cell walls requires UDP-glucose as the substrate for cellulose biosynthesis, and as an intermediate for the synthesis of other matrix polysaccharides. The sucrose cleaving enzyme sucrose synthase (SUS) is thought to have a central role in UDP-glucose biosynthesis, and a long-held and much debated hypothesis postulates that SUS is required to supply UDP-glucose to cellulose biosynthesis. To investigate the role of SUS in cellulose biosynthesis of Arabidopsis thaliana we characterized mutants in which four or all six Arabidopsis SUS genes were disrupted. These sus mutants showed no growth phenotypes, vascular tissue cell wall defects, or changes in cellulose content. Moreover, the UDP-glucose content of rosette leaves of the sextuple sus mutants was increased by approximately 20% compared with wild type. It can thus be concluded that cellulose biosynthesis is able to employ alternative UDP-glucose biosynthesis pathway(s), and thereby the model of SUS requirements for cellulose biosynthesis in Arabidopsis can be refuted.

@article{cataldo_human_2022,
	title = {The human batokine {EPDR1} regulates β-cell metabolism and function},
	volume = {66},
	issn = {2212-8778},
	url = {https://www.sciencedirect.com/science/article/pii/S2212877822001983},
	doi = {10.1016/j.molmet.2022.101629},
	abstract = {Objective
Ependymin-Related Protein 1 (EPDR1) was recently identified as a secreted human batokine regulating mitochondrial respiration linked to thermogenesis in brown fat. Despite that EPDR1 is expressed in human pancreatic β-cells and that glucose-stimulated mitochondrial metabolism is critical for stimulus-secretion coupling in β-cells, the role of EPDR1 in β-cell metabolism and function has not been investigated.
Methods
EPDR1 mRNA levels in human pancreatic islets from non-diabetic (ND) and type 2 diabetes (T2D) subjects were assessed. Human islets, EndoC-βH1 and INS1 832/13 cells were transfected with scramble (control) and EPDR1 siRNAs (EPDR1-KD) or treated with human EPDR1 protein, and glucose-stimulated insulin secretion (GSIS) assessed by ELISA. Mitochondrial metabolism was investigated by extracellular flux analyzer, confocal microscopy and mass spectrometry-based metabolomics analysis.
Results
EPDR1 mRNA expression was upregulated in human islets from T2D and obese donors and positively correlated to BMI of donors. In T2D donors, EPDR1 mRNA levels negatively correlated with HbA1c and positively correlated with GSIS. EPDR1 silencing in human islets and β-cell lines reduced GSIS whereas treatment with human EPDR1 protein increased GSIS. Epdr1 silencing in INS1 832/13 cells reduced glucose- and pyruvate- but not K+-stimulated insulin secretion. Metabolomics analysis in Epdr1-KD INS1 832/13 cells suggests diversion of glucose-derived pyruvate to lactate production and decreased malate-aspartate shuttle and the tricarboxylic acid (TCA) cycle activity. The glucose-stimulated rise in mitochondrial respiration and ATP/ADP-ratio was impaired in Epdr1-deficient cells.
Conclusion
These results suggests that to maintain glucose homeostasis in obese people, upregulation of EPDR1 may improve β-cell function via channelling glycolysis-derived pyruvate to the mitochondrial TCA cycle.},
	language = {en},
	urldate = {2022-12-22},
	journal = {Molecular Metabolism},
	author = {Cataldo, Luis Rodrigo and Gao, Qian and Argemi-Muntadas, Lidia and Hodek, Ondrej and Cowan, Elaine and Hladkou, Sergey and Gheibi, Sevda and Spégel, Peter and Prasad, Rashmi B. and Eliasson, Lena and Scheele, Camilla and Fex, Malin and Mulder, Hindrik and Moritz, Thomas},
	month = dec,
	year = {2022},
	keywords = {Beta cells, Insulin secretion, Lactate, Mitochondrial metabolism, TCA cycle, Type 2 diabetes},
	pages = {101629},
}

Objective Ependymin-Related Protein 1 (EPDR1) was recently identified as a secreted human batokine regulating mitochondrial respiration linked to thermogenesis in brown fat. Despite that EPDR1 is expressed in human pancreatic β-cells and that glucose-stimulated mitochondrial metabolism is critical for stimulus-secretion coupling in β-cells, the role of EPDR1 in β-cell metabolism and function has not been investigated. Methods EPDR1 mRNA levels in human pancreatic islets from non-diabetic (ND) and type 2 diabetes (T2D) subjects were assessed. Human islets, EndoC-βH1 and INS1 832/13 cells were transfected with scramble (control) and EPDR1 siRNAs (EPDR1-KD) or treated with human EPDR1 protein, and glucose-stimulated insulin secretion (GSIS) assessed by ELISA. Mitochondrial metabolism was investigated by extracellular flux analyzer, confocal microscopy and mass spectrometry-based metabolomics analysis. Results EPDR1 mRNA expression was upregulated in human islets from T2D and obese donors and positively correlated to BMI of donors. In T2D donors, EPDR1 mRNA levels negatively correlated with HbA1c and positively correlated with GSIS. EPDR1 silencing in human islets and β-cell lines reduced GSIS whereas treatment with human EPDR1 protein increased GSIS. Epdr1 silencing in INS1 832/13 cells reduced glucose- and pyruvate- but not K+-stimulated insulin secretion. Metabolomics analysis in Epdr1-KD INS1 832/13 cells suggests diversion of glucose-derived pyruvate to lactate production and decreased malate-aspartate shuttle and the tricarboxylic acid (TCA) cycle activity. The glucose-stimulated rise in mitochondrial respiration and ATP/ADP-ratio was impaired in Epdr1-deficient cells. Conclusion These results suggests that to maintain glucose homeostasis in obese people, upregulation of EPDR1 may improve β-cell function via channelling glycolysis-derived pyruvate to the mitochondrial TCA cycle.

@article{melo_metabolomic_2021,
	title = {A metabolomic study of {Gomphrena} agrestis in {Brazilian} {Cerrado} suggests drought-adaptive strategies on metabolism},
	volume = {11},
	copyright = {2021 The Author(s)},
	issn = {2045-2322},
	url = {https://www.nature.com/articles/s41598-021-92449-9},
	doi = {10.1038/s41598-021-92449-9},
	abstract = {Drought is the main factor that limits the distribution and productivity of plant species. In the Brazilian Cerrado, the vegetation is adapted to a seasonal climate with long- and short-term periods of drought. To analyze the metabolic strategies under such conditions, a metabolomic approach was used to characterize Gomphrena agrestis Mart. (Amaranthaceae) a native species that grows under natural conditions, in a rock-field area. Roots and leaves material from native specimens were sampled along different seasons of the year and LC–MS and GC–MS analyzed for multiple chemical constituents. The datasets derived from the different measurements were combined and evaluated using multivariate analysis. Principal component analysis was used to obtain an overview of the samples and identify outliers. Later, the data was analyzed with orthogonal projection to latent structures discriminant analysis to obtain valid models that could explain the metabolite variations in the different seasons. Two hundred and eighty metabolites were annotated, generating a unique database to characterize metabolic strategies used to cope with the effects of drought. The accumulation of fructans in the thickened roots is consistent with the storage of carbons during the rainy season to support the energy demand during a long period of drought. The accumulation of Abscisic acid, sugars and sugar alcohols, phenolics, and pigment in the leaves suggests physiological adaptations. To cope with long-term drought, the data suggests that tissue water status and storage of reserves are important to support plant survival and regrowth. However, during short-term drought, osmoregulation and oxidative protection seems to be essential, probably to support the maintenance of active photosynthesis.},
	language = {en},
	number = {1},
	urldate = {2021-11-04},
	journal = {Scientific Reports},
	author = {Melo, Geraldo Aclécio and Abreu, Ilka Nacif and de Oliveira, Maíra Baista and Budzinski, Ilara Gabriela Frasson and Silva, Lucinélia Vieira and Pimenta, Marcio Antônio Silva and Moritz, Thomas},
	month = jun,
	year = {2021},
	keywords = {Plant physiology, Plant sciences, Plant stress responses},
	pages = {12933},
}

Drought is the main factor that limits the distribution and productivity of plant species. In the Brazilian Cerrado, the vegetation is adapted to a seasonal climate with long- and short-term periods of drought. To analyze the metabolic strategies under such conditions, a metabolomic approach was used to characterize Gomphrena agrestis Mart. (Amaranthaceae) a native species that grows under natural conditions, in a rock-field area. Roots and leaves material from native specimens were sampled along different seasons of the year and LC–MS and GC–MS analyzed for multiple chemical constituents. The datasets derived from the different measurements were combined and evaluated using multivariate analysis. Principal component analysis was used to obtain an overview of the samples and identify outliers. Later, the data was analyzed with orthogonal projection to latent structures discriminant analysis to obtain valid models that could explain the metabolite variations in the different seasons. Two hundred and eighty metabolites were annotated, generating a unique database to characterize metabolic strategies used to cope with the effects of drought. The accumulation of fructans in the thickened roots is consistent with the storage of carbons during the rainy season to support the energy demand during a long period of drought. The accumulation of Abscisic acid, sugars and sugar alcohols, phenolics, and pigment in the leaves suggests physiological adaptations. To cope with long-term drought, the data suggests that tissue water status and storage of reserves are important to support plant survival and regrowth. However, during short-term drought, osmoregulation and oxidative protection seems to be essential, probably to support the maintenance of active photosynthesis.

@article{sjogren_branched-chain_2021,
	title = {Branched-chain amino acid metabolism is regulated by {ERRα} in primary human myotubes and is further impaired by glucose loading in type 2 diabetes},
	volume = {64},
	issn = {1432-0428},
	url = {https://doi.org/10.1007/s00125-021-05481-9},
	doi = {10.1007/s00125-021-05481-9},
	abstract = {Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified.},
	language = {en},
	number = {9},
	urldate = {2022-04-08},
	journal = {Diabetologia},
	author = {Sjögren, Rasmus J. O. and Rizo-Roca, David and Chibalin, Alexander V. and Chorell, Elin and Furrer, Regula and Katayama, Shintaro and Harada, Jun and Karlsson, Håkan K. R. and Handschin, Christoph and Moritz, Thomas and Krook, Anna and Näslund, Erik and Zierath, Juleen R.},
	month = sep,
	year = {2021},
	pages = {2077--2091},
}

Increased levels of branched-chain amino acids (BCAAs) are associated with type 2 diabetes pathogenesis. However, most metabolomic studies are limited to an analysis of plasma metabolites under fasting conditions, rather than the dynamic shift in response to a metabolic challenge. Moreover, metabolomic profiles of peripheral tissues involved in glucose homeostasis are scarce and the transcriptomic regulation of genes involved in BCAA catabolism is partially unknown. This study aimed to identify differences in circulating and skeletal muscle BCAA levels in response to an OGTT in individuals with normal glucose tolerance (NGT) or type 2 diabetes. Additionally, transcription factors involved in the regulation of the BCAA gene set were identified.

@article{gandla_overexpression_2021,
	title = {Overexpression of vesicle-associated membrane protein {PttVAP27}-17 as a tool to improve biomass production and the overall saccharification yields in {Populus} trees},
	volume = {14},
	issn = {1754-6834},
	url = {https://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/s13068-021-01895-0},
	doi = {10/gjd7kj},
	abstract = {Abstract
            
              Background
              Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth.
            
            
              Results
              
                In this study, we report on transgenic hybrid aspen (
                Populus tremula
                ×
                tremuloides
                ) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct for
                Populus tremula
                ×
                tremuloides
                vesicle-associated membrane protein (VAMP)-associated protein
                PttVAP27-17
                that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20–44\% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26–50\% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24\% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control.
              
            
            
              Conclusions
              The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.},
	language = {en},
	number = {1},
	urldate = {2021-06-03},
	journal = {Biotechnology for Biofuels},
	author = {Gandla, Madhavi Latha and Mähler, Niklas and Escamez, Sacha and Skotare, Tomas and Obudulu, Ogonna and Möller, Linus and Abreu, Ilka N. and Bygdell, Joakim and Hertzberg, Magnus and Hvidsten, Torgeir R. and Moritz, Thomas and Wingsle, Gunnar and Trygg, Johan and Tuominen, Hannele and Jönsson, Leif J.},
	month = dec,
	year = {2021},
	pages = {43},
}

Abstract Background Bioconversion of wood into bioproducts and biofuels is hindered by the recalcitrance of woody raw material to bioprocesses such as enzymatic saccharification. Targeted modification of the chemical composition of the feedstock can improve saccharification but this gain is often abrogated by concomitant reduction in tree growth. Results In this study, we report on transgenic hybrid aspen ( Populus tremula × tremuloides ) lines that showed potential to increase biomass production both in the greenhouse and after 5 years of growth in the field. The transgenic lines carried an overexpression construct for Populus tremula × tremuloides vesicle-associated membrane protein (VAMP)-associated protein PttVAP27-17 that was selected from a gene-mining program for novel regulators of wood formation. Analytical-scale enzymatic saccharification without any pretreatment revealed for all greenhouse-grown transgenic lines, compared to the wild type, a 20–44% increase in the glucose yield per dry weight after enzymatic saccharification, even though it was statistically significant only for one line. The glucose yield after enzymatic saccharification with a prior hydrothermal pretreatment step with sulfuric acid was not increased in the greenhouse-grown transgenic trees on a dry-weight basis, but increased by 26–50% when calculated on a whole biomass basis in comparison to the wild-type control. Tendencies to increased glucose yields by up to 24% were present on a whole tree biomass basis after acidic pretreatment and enzymatic saccharification also in the transgenic trees grown for 5 years on the field when compared to the wild-type control. Conclusions The results demonstrate the usefulness of gene-mining programs to identify novel genes with the potential to improve biofuel production in tree biotechnology programs. Furthermore, multi-omic analyses, including transcriptomic, proteomic and metabolomic analyses, performed here provide a toolbox for future studies on the function of VAP27 proteins in plants.

@article{abreu_metabolite_2020,
	title = {A metabolite roadmap of the wood‐forming tissue in {Populus} tremula},
	volume = {228},
	issn = {0028-646X, 1469-8137},
	url = {https://onlinelibrary.wiley.com/doi/10.1111/nph.16799},
	doi = {10.1111/nph.16799},
	language = {en},
	number = {5},
	urldate = {2021-06-07},
	journal = {New Phytologist},
	author = {Abreu, Ilka N. and Johansson, Annika I. and Sokołowska, Katarzyna and Niittylä, Totte and Sundberg, Björn and Hvidsten, Torgeir R. and Street, Nathaniel R. and Moritz, Thomas},
	month = dec,
	year = {2020},
	pages = {1559--1572},
}

@article{abreu_changes_2020,
	title = {Changes in lipid and carotenoid metabolism in {Chlamydomonas} reinhardtii during induction of {CO2}-concentrating mechanism: {Cellular} response to low {CO2} stress},
	volume = {52},
	issn = {22119264},
	shorttitle = {Changes in lipid and carotenoid metabolism in {Chlamydomonas} reinhardtii during induction of {CO2}-concentrating mechanism},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S221192642030967X},
	doi = {10/gjcxj6},
	language = {en},
	urldate = {2021-06-07},
	journal = {Algal Research},
	author = {Abreu, Ilka N. and Aksmann, Anna and Bajhaiya, Amit K. and Benlloch, Reyes and Giordano, Mario and Pokora, Wojciech and Selstam, Eva and Moritz, Thomas},
	month = dec,
	year = {2020},
	pages = {102099},
}

@article{antunes_differentiation_2020,
	title = {Differentiation of two {Maytenus} species and their hybrid via untargeted metabolomics},
	volume = {158},
	issn = {09266690},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0926669020309316},
	doi = {10/gjcxhq},
	language = {en},
	urldate = {2021-06-07},
	journal = {Industrial Crops and Products},
	author = {Antunes, Elisa Ribeiro Miranda and Duarte, Rodolfo Santos and Moritz, Thomas and Sawaya, Alexandra Christine Helena Frankland},
	month = dec,
	year = {2020},
	pages = {113014},
}

@article{tebani_integration_2020,
	title = {Integration of molecular profiles in a longitudinal wellness profiling cohort},
	volume = {11},
	issn = {2041-1723},
	url = {http://www.nature.com/articles/s41467-020-18148-7},
	doi = {10.1038/s41467-020-18148-7},
	abstract = {Abstract
            An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Nature Communications},
	author = {Tebani, Abdellah and Gummesson, Anders and Zhong, Wen and Koistinen, Ina Schuppe and Lakshmikanth, Tadepally and Olsson, Lisa M. and Boulund, Fredrik and Neiman, Maja and Stenlund, Hans and Hellström, Cecilia and Karlsson, Max J. and Arif, Muhammad and Dodig-Crnković, Tea and Mardinoglu, Adil and Lee, Sunjae and Zhang, Cheng and Chen, Yang and Olin, Axel and Mikes, Jaromir and Danielsson, Hanna and von Feilitzen, Kalle and Jansson, Per-Anders and Angerås, Oskar and Huss, Mikael and Kjellqvist, Sanela and Odeberg, Jacob and Edfors, Fredrik and Tremaroli, Valentina and Forsström, Björn and Schwenk, Jochen M. and Nilsson, Peter and Moritz, Thomas and Bäckhed, Fredrik and Engstrand, Lars and Brodin, Petter and Bergström, Göran and Uhlen, Mathias and Fagerberg, Linn},
	month = dec,
	year = {2020},
	pages = {4487},
}

Abstract An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.

@article{khoomrung_metabolic_2020,
	title = {Metabolic {Profiling} and {Compound}-{Class} {Identification} {Reveal} {Alterations} in {Serum} {Triglyceride} {Levels} in {Mice} {Immunized} with {Human} {Vaccine} {Adjuvant} {Alum}},
	volume = {19},
	issn = {1535-3893, 1535-3907},
	url = {https://pubs.acs.org/doi/10.1021/acs.jproteome.9b00517},
	doi = {10.1021/acs.jproteome.9b00517},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Journal of Proteome Research},
	author = {Khoomrung, Sakda and Nookaew, Intawat and Sen, Partho and Olafsdottir, Thorunn A. and Persson, Josefine and Moritz, Thomas and Andersen, Peter and Harandi, Ali M. and Nielsen, Jens},
	month = jan,
	year = {2020},
	pages = {269--278},
}

@article{bergman_heterologous_2019,
	title = {Heterologous phosphoketolase expression redirects flux towards acetate, perturbs sugar phosphate pools and increases respiratory demand in {Saccharomyces} cerevisiae},
	volume = {18},
	issn = {1475-2859},
	url = {https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-019-1072-6},
	doi = {10/gh8zrg},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Microbial Cell Factories},
	author = {Bergman, Alexandra and Hellgren, John and Moritz, Thomas and Siewers, Verena and Nielsen, Jens and Chen, Yun},
	month = dec,
	year = {2019},
	pages = {25},
}

@article{papazian_leaf_2019,
	title = {Leaf metabolic signatures induced by real and simulated herbivory in black mustard ({Brassica} nigra)},
	volume = {15},
	issn = {1573-3882, 1573-3890},
	url = {http://link.springer.com/10.1007/s11306-019-1592-4},
	doi = {10.1007/s11306-019-1592-4},
	abstract = {Abstract
            
              Introduction
              The oxylipin methyl jasmonate (MeJA) is a plant hormone active in response signalling and defence against herbivores. Although MeJA is applied experimentally to mimic herbivory and induce plant defences, its downstream effects on the plant metabolome are largely uncharacterized, especially in the context of primary growth and tissue-specificity of the response.
            
            
              Objectives
              
                We investigated the effects of MeJA-simulated and real caterpillar herbivory on the foliar metabolome of the wild plant
                Brassica nigra
                and monitored the herbivore-induced responses in relation to leaf ontogeny.
              
            
            
              Methods
              As single or multiple herbivory treatments, MeJA- and mock-sprayed plants were consecutively exposed to caterpillars or left untreated. Gas chromatography (GC) and liquid chromatography (LC) time-of-flight mass-spectrometry (TOF-MS) were combined to analyse foliar compounds, including central primary and specialized defensive plant metabolites.
            
            
              Results
              Plant responses were stronger in young leaves, which simultaneously induced higher chlorophyll levels. Both MeJA and caterpillar herbivory induced similar, but not identical, accumulation of tricarboxylic acids (TCAs), glucosinolates (GSLs) and phenylpropanoids (PPs), but only caterpillar feeding led to depletion of amino acids. MeJA followed by caterpillars caused higher induction of defence compounds, including a three-fold increase in the major defence compound allyl-GSL (sinigrin). When feeding on MeJA-treated plants, caterpillars gained less weight indicative of the reduced host-plant quality and enhanced resistance.
            
            
              Conclusions
              The metabolomics approach showed that plant responses induced by herbivory extend beyond the regulation of defence metabolism and are tightly modulated throughout leaf development. This leads to a new understanding of the plant metabolic potential that can be exploited for future plant protection strategies.},
	language = {en},
	number = {10},
	urldate = {2021-06-07},
	journal = {Metabolomics},
	author = {Papazian, Stefano and Girdwood, Tristan and Wessels, Bernard A. and Poelman, Erik H. and Dicke, Marcel and Moritz, Thomas and Albrectsen, Benedicte R.},
	month = oct,
	year = {2019},
	pages = {130},
}

Abstract Introduction The oxylipin methyl jasmonate (MeJA) is a plant hormone active in response signalling and defence against herbivores. Although MeJA is applied experimentally to mimic herbivory and induce plant defences, its downstream effects on the plant metabolome are largely uncharacterized, especially in the context of primary growth and tissue-specificity of the response. Objectives We investigated the effects of MeJA-simulated and real caterpillar herbivory on the foliar metabolome of the wild plant Brassica nigra and monitored the herbivore-induced responses in relation to leaf ontogeny. Methods As single or multiple herbivory treatments, MeJA- and mock-sprayed plants were consecutively exposed to caterpillars or left untreated. Gas chromatography (GC) and liquid chromatography (LC) time-of-flight mass-spectrometry (TOF-MS) were combined to analyse foliar compounds, including central primary and specialized defensive plant metabolites. Results Plant responses were stronger in young leaves, which simultaneously induced higher chlorophyll levels. Both MeJA and caterpillar herbivory induced similar, but not identical, accumulation of tricarboxylic acids (TCAs), glucosinolates (GSLs) and phenylpropanoids (PPs), but only caterpillar feeding led to depletion of amino acids. MeJA followed by caterpillars caused higher induction of defence compounds, including a three-fold increase in the major defence compound allyl-GSL (sinigrin). When feeding on MeJA-treated plants, caterpillars gained less weight indicative of the reduced host-plant quality and enhanced resistance. Conclusions The metabolomics approach showed that plant responses induced by herbivory extend beyond the regulation of defence metabolism and are tightly modulated throughout leaf development. This leads to a new understanding of the plant metabolic potential that can be exploited for future plant protection strategies.

@article{kloth_pectin_2019,
	title = {{PECTIN} {ACETYLESTERASE9} {Affects} the {Transcriptome} and {Metabolome} and {Delays} {Aphid} {Feeding}},
	volume = {181},
	issn = {0032-0889, 1532-2548},
	url = {https://academic.oup.com/plphys/article/181/4/1704-1720/6000543},
	doi = {10.1104/pp.19.00635},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {Plant Physiology},
	author = {Kloth, Karen J. and Abreu, Ilka N. and Delhomme, Nicolas and Petřík, Ivan and Villard, Cloé and Ström, Cecilia and Amini, Fariba and Novák, Ondřej and Moritz, Thomas and Albrectsen, Benedicte R.},
	month = dec,
	year = {2019},
	pages = {1704--1720},
}

@article{zhu_targeted_2019,
	title = {Targeted {Multiple} {Reaction} {Monitoring} {Analysis} of {CSF} {Identifies} {UCHL1} and {GPNMB} as {Candidate} {Biomarkers} for {ALS}},
	volume = {69},
	issn = {0895-8696, 1559-1166},
	url = {http://link.springer.com/10.1007/s12031-019-01411-y},
	doi = {10.1007/s12031-019-01411-y},
	abstract = {Abstract
            The neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) share some common molecular deficits including disruption of protein homeostasis leading to disease-specific protein aggregation. While insoluble protein aggregates are the defining pathological confirmation of diagnosis, patient stratification based on early molecular etiologies may identify distinct subgroups within a clinical diagnosis that would respond differently in therapeutic development programs. We are developing targeted multiple reaction monitoring (MRM) mass spectrometry methods to rigorously quantify CSF proteins from known disease genes involved in lysosomal, ubiquitin-proteasomal, and autophagy pathways. Analysis of CSF from 21 PD, 21 ALS, and 25 control patients, rigorously matched for gender, age, and age of sample, revealed significant changes in peptide levels between PD, ALS, and control. In patients with PD, levels of two peptides for chromogranin B (CHGB, secretogranin 1) were significantly reduced. In CSF of patients with ALS, levels of two peptides from ubiquitin carboxy-terminal hydrolase like protein 1 (UCHL1) and one peptide each for glycoprotein non-metastatic melanoma protein B (GPNMB) and cathepsin D (CTSD) were all increased. Analysis of patients with ALS separated into two groups based on length of survival after CSF sampling revealed that the increases in GPNMB and UCHL1 were specific for short-lived ALS patients. While analysis of additional cohorts is required to validate these candidate biomarkers, this study suggests methods for stratification of ALS patients for clinical trials and identifies targets for drug efficacy measurements during therapeutic development.},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {Journal of Molecular Neuroscience},
	author = {Zhu, Shaochun and Wuolikainen, Anna and Wu, Junfang and Öhman, Anders and Wingsle, Gunnar and Moritz, Thomas and Andersen, Peter M. and Forsgren, Lars and Trupp, Miles},
	month = dec,
	year = {2019},
	pages = {643--657},
}

Abstract The neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) share some common molecular deficits including disruption of protein homeostasis leading to disease-specific protein aggregation. While insoluble protein aggregates are the defining pathological confirmation of diagnosis, patient stratification based on early molecular etiologies may identify distinct subgroups within a clinical diagnosis that would respond differently in therapeutic development programs. We are developing targeted multiple reaction monitoring (MRM) mass spectrometry methods to rigorously quantify CSF proteins from known disease genes involved in lysosomal, ubiquitin-proteasomal, and autophagy pathways. Analysis of CSF from 21 PD, 21 ALS, and 25 control patients, rigorously matched for gender, age, and age of sample, revealed significant changes in peptide levels between PD, ALS, and control. In patients with PD, levels of two peptides for chromogranin B (CHGB, secretogranin 1) were significantly reduced. In CSF of patients with ALS, levels of two peptides from ubiquitin carboxy-terminal hydrolase like protein 1 (UCHL1) and one peptide each for glycoprotein non-metastatic melanoma protein B (GPNMB) and cathepsin D (CTSD) were all increased. Analysis of patients with ALS separated into two groups based on length of survival after CSF sampling revealed that the increases in GPNMB and UCHL1 were specific for short-lived ALS patients. While analysis of additional cohorts is required to validate these candidate biomarkers, this study suggests methods for stratification of ALS patients for clinical trials and identifies targets for drug efficacy measurements during therapeutic development.

@article{rende_two-step_2019,
	title = {Two-step derivatization for determination of sugar phosphates in plants by combined reversed phase chromatography/tandem mass spectrometry},
	volume = {15},
	issn = {1746-4811},
	url = {https://plantmethods.biomedcentral.com/articles/10.1186/s13007-019-0514-9},
	doi = {10.1186/s13007-019-0514-9},
	abstract = {Abstract
            
              Background
              Sugar phosphates are important intermediates of central carbon metabolism in biological systems, with roles in glycolysis, the pentose–phosphate pathway, tricarboxylic acid (TCA) cycle, and many other biosynthesis pathways. Understanding central carbon metabolism requires a simple, robust and comprehensive analytical method. However, sugar phosphates are notoriously difficult to analyze by traditional reversed phase liquid chromatography.
            
            
              Results
              
                Here, we show a two-step derivatization of sugar phosphates by methoxylamine and propionic acid anhydride after chloroform/methanol (3:7) extraction from
                Populus
                leaf and developing wood that improves separation, identification and quantification of sugar phosphates by ultra high performance liquid chromatography–electrospray ionization–mass spectrometry (UHPLC–ESI–MS). Standard curves of authentic sugar phosphates were generated for concentrations from pg to ng/μl with a correlation coefficient
                R
                2
                 {\textgreater} 0.99. The method showed high sensitivity and repeatability with relative standard deviation (RSD) {\textless} 20\% based on repeated extraction, derivatization and detection. The analytical accuracy for
                Populus
                leaf extracts, determined by a two-level spiking approach of selected metabolites, was 79–107\%.
              
            
            
              Conclusion
              
                The results show the reliability of combined reversed phase liquid chromatography–tandem mass spectrometry for sugar phosphate analysis and demonstrate the presence of two unknown sugar phosphates in
                Populus
                extracts.},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Plant Methods},
	author = {Rende, Umut and Niittylä, Totte and Moritz, Thomas},
	month = dec,
	year = {2019},
	pages = {127},
}

Abstract Background Sugar phosphates are important intermediates of central carbon metabolism in biological systems, with roles in glycolysis, the pentose–phosphate pathway, tricarboxylic acid (TCA) cycle, and many other biosynthesis pathways. Understanding central carbon metabolism requires a simple, robust and comprehensive analytical method. However, sugar phosphates are notoriously difficult to analyze by traditional reversed phase liquid chromatography. Results Here, we show a two-step derivatization of sugar phosphates by methoxylamine and propionic acid anhydride after chloroform/methanol (3:7) extraction from Populus leaf and developing wood that improves separation, identification and quantification of sugar phosphates by ultra high performance liquid chromatography–electrospray ionization–mass spectrometry (UHPLC–ESI–MS). Standard curves of authentic sugar phosphates were generated for concentrations from pg to ng/μl with a correlation coefficient R 2  \textgreater 0.99. The method showed high sensitivity and repeatability with relative standard deviation (RSD) \textless 20% based on repeated extraction, derivatization and detection. The analytical accuracy for Populus leaf extracts, determined by a two-level spiking approach of selected metabolites, was 79–107%. Conclusion The results show the reliability of combined reversed phase liquid chromatography–tandem mass spectrometry for sugar phosphate analysis and demonstrate the presence of two unknown sugar phosphates in Populus extracts.

@article{obudulu_multi-omics_2018,
	title = {A multi-omics approach reveals function of {Secretory} {Carrier}-{Associated} {Membrane} {Proteins} in wood formation of​ ​​{Populus}​​ ​trees},
	volume = {19},
	issn = {1471-2164},
	url = {https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-4411-1},
	doi = {10.1186/s12864-017-4411-1},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {BMC Genomics},
	author = {Obudulu, Ogonna and Mähler, Niklas and Skotare, Tomas and Bygdell, Joakim and Abreu, Ilka N. and Ahnlund, Maria and Latha Gandla, Madhavi and Petterle, Anna and Moritz, Thomas and Hvidsten, Torgeir R. and Jönsson, Leif J. and Wingsle, Gunnar and Trygg, Johan and Tuominen, Hannele},
	month = dec,
	year = {2018},
	pages = {11},
}

@article{law_darkened_2018,
	title = {Darkened {Leaves} {Use} {Different} {Metabolic} {Strategies} for {Senescence} and {Survival}},
	volume = {177},
	issn = {0032-0889, 1532-2548},
	url = {https://academic.oup.com/plphys/article/177/1/132-150/6116945},
	doi = {10.1104/pp.18.00062},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Plant Physiology},
	author = {Law, Simon R. and Chrobok, Daria and Juvany, Marta and Delhomme, Nicolas and Lindén, Pernilla and Brouwer, Bastiaan and Ahad, Abdul and Moritz, Thomas and Jansson, Stefan and Gardeström, Per and Keech, Olivier},
	month = may,
	year = {2018},
	pages = {132--150},
}

@article{torell_metabolic_2018,
	title = {Metabolic {Profiling} of {Multiorgan} {Samples}: {Evaluation} of {MODY5}/{RCAD} {Mutant} {Mice}},
	volume = {17},
	issn = {1535-3893, 1535-3907},
	shorttitle = {Metabolic {Profiling} of {Multiorgan} {Samples}},
	url = {https://pubs.acs.org/doi/10.1021/acs.jproteome.7b00821},
	doi = {10/gdxhnh},
	language = {en},
	number = {7},
	urldate = {2021-06-07},
	journal = {Journal of Proteome Research},
	author = {Torell, Frida and Bennett, Kate and Cereghini, Silvia and Fabre, Mélanie and Rännar, Stefan and Lundstedt-Enkel, Katrin and Moritz, Thomas and Haumaitre, Cécile and Trygg, Johan and Lundstedt, Torbjörn},
	month = jul,
	year = {2018},
	pages = {2293--2306},
}

@article{jamtgard_optimising_2018,
	title = {Optimising methods for the recovery and quantification of di- and tripeptides in soil},
	volume = {56},
	issn = {1838-675X},
	url = {http://www.publish.csiro.au/?paper=SR17279},
	doi = {10.1071/SR17279},
	abstract = {Di- and tripeptides are intermediaries in the nitrogen cycle and are likely to have roles in the soil–microbe–plant continuum, but they have hitherto been difficult to measure in soils. To lay the base for future studies of oligopeptides in soil, we added 10 known di- and tripeptides with diverse chemical properties to forest and agricultural soils and then recovered the peptides by means of induced diffusive fluxes using microdialysis, a minimally-intrusive soil sampling technique. The concentration of the peptides recovered with the probes was 25–39\% (relative recovery) of the concentration in the external solution, and followed the same trend as previously observed for amino acids, with smaller peptides (e.g. Gly-Gly) recovered at a higher rate than larger ones (e.g. Tyr-Phe). After derivatisation with AccQ-Tag™, a standard method for amino acids, peptides were analysed by ultra-high-pressure liquid chromatography-triple quadrupole mass spectrometry. Multiple reaction monitoring mass spectrometry was used to quantify specific peptides with a short run time of 15 min and a detection limit of 0.01–0.02 pmol injected (0.005–0.01 pmol µL–1) for the different peptides. This methodology allowed successful analysis of all standard di- and tripeptides tested here. We conclude that microdialysis in combination with UHPLC-MS will allow measurement of plant-relevant fluxes of di- and tripeptides in undisturbed soil.},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {Soil Research},
	author = {Jämtgård, Sandra and Robinson, Nicole and Moritz, Thomas and Colgrave, Michelle L. and Schmidt, Susanne},
	year = {2018},
	pages = {404},
}

Di- and tripeptides are intermediaries in the nitrogen cycle and are likely to have roles in the soil–microbe–plant continuum, but they have hitherto been difficult to measure in soils. To lay the base for future studies of oligopeptides in soil, we added 10 known di- and tripeptides with diverse chemical properties to forest and agricultural soils and then recovered the peptides by means of induced diffusive fluxes using microdialysis, a minimally-intrusive soil sampling technique. The concentration of the peptides recovered with the probes was 25–39% (relative recovery) of the concentration in the external solution, and followed the same trend as previously observed for amino acids, with smaller peptides (e.g. Gly-Gly) recovered at a higher rate than larger ones (e.g. Tyr-Phe). After derivatisation with AccQ-Tag™, a standard method for amino acids, peptides were analysed by ultra-high-pressure liquid chromatography-triple quadrupole mass spectrometry. Multiple reaction monitoring mass spectrometry was used to quantify specific peptides with a short run time of 15 min and a detection limit of 0.01–0.02 pmol injected (0.005–0.01 pmol µL–1) for the different peptides. This methodology allowed successful analysis of all standard di- and tripeptides tested here. We conclude that microdialysis in combination with UHPLC-MS will allow measurement of plant-relevant fluxes of di- and tripeptides in undisturbed soil.

@article{kong_simultaneous_2018,
	title = {Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in biological samples by hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry},
	volume = {46},
	issn = {0305-1048, 1362-4962},
	url = {https://academic.oup.com/nar/article/46/11/e66/4937551},
	doi = {10.1093/nar/gky203},
	language = {en},
	number = {11},
	urldate = {2021-06-07},
	journal = {Nucleic Acids Research},
	author = {Kong, Ziqing and Jia, Shaodong and Chabes, Anna Lena and Appelblad, Patrik and Lundmark, Richard and Moritz, Thomas and Chabes, Andrei},
	month = jun,
	year = {2018},
	pages = {e66--e66},
}

@article{le_hir_at_2017,
	title = {At \textit{{bHLH68}} transcription factor contributes to the regulation of {ABA} homeostasis and drought stress tolerance in \textit{{Arabidopsis} thaliana}},
	volume = {160},
	issn = {00319317},
	url = {http://doi.wiley.com/10.1111/ppl.12549},
	doi = {10.1111/ppl.12549},
	language = {en},
	number = {3},
	urldate = {2021-06-07},
	journal = {Physiologia Plantarum},
	author = {Le Hir, Rozenn and Castelain, Mathieu and Chakraborti, Dipankar and Moritz, Thomas and Dinant, Sylvie and Bellini, Catherine},
	month = jul,
	year = {2017},
	pages = {312--327},
}

@article{lesniewska_defense_2017,
	title = {Defense {Responses} in {Aspen} with {Altered} {Pectin} {Methylesterase} {Activity} {Reveal} the {Hormonal} {Inducers} of {Tyloses}},
	volume = {173},
	issn = {0032-0889, 1532-2548},
	url = {https://academic.oup.com/plphys/article/173/2/1409-1419/6116100},
	doi = {10.1104/pp.16.01443},
	language = {en},
	number = {2},
	urldate = {2021-06-07},
	journal = {Plant Physiology},
	author = {Leśniewska, Joanna and Öhman, David and Krzesłowska, Magdalena and Kushwah, Sunita and Barciszewska-Pacak, Maria and Kleczkowski, Leszek A. and Sundberg, Björn and Moritz, Thomas and Mellerowicz, Ewa J.},
	month = feb,
	year = {2017},
	pages = {1409--1419},
}

@article{adolfsson_enhanced_2017,
	title = {Enhanced {Secondary}- and {Hormone} {Metabolism} in {Leaves} of {Arbuscular} {Mycorrhizal} \textit{{Medicago} truncatula}},
	volume = {175},
	issn = {0032-0889, 1532-2548},
	url = {https://academic.oup.com/plphys/article/175/1/392-411/6117013},
	doi = {10/gbvxq8},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Plant Physiology},
	author = {Adolfsson, Lisa and Nziengui, Hugues and Abreu, Ilka N and Šimura, Jan and Beebo, Azeez and Herdean, Andrei and Aboalizadeh, Jila and Široká, Jitka and Moritz, Thomas and Novák, Ondřej and Ljung, Karin and Schoefs, Benoît and Spetea, Cornelia},
	month = sep,
	year = {2017},
	pages = {392--411},
}

@article{davoine_functional_2017,
	title = {Functional metabolomics as a tool to analyze {Mediator} function and structure in plants},
	volume = {12},
	issn = {1932-6203},
	url = {https://dx.plos.org/10.1371/journal.pone.0179640},
	doi = {10/gcjk93},
	language = {en},
	number = {6},
	urldate = {2021-06-07},
	journal = {PLOS ONE},
	author = {Davoine, Celine and Abreu, Ilka N. and Khajeh, Khalil and Blomberg, Jeanette and Kidd, Brendan N. and Kazan, Kemal and Schenk, Peer M. and Gerber, Lorenz and Nilsson, Ove and Moritz, Thomas and Björklund, Stefan},
	editor = {Mantovani, Roberto},
	month = jun,
	year = {2017},
	pages = {e0179640},
}

@article{dobrowolska_metabolome_2017,
	title = {Metabolome and transcriptome profiling reveal new insights into somatic embryo germination in {Norway} spruce ({Picea} abies)},
	volume = {37},
	issn = {0829-318X, 1758-4469},
	url = {https://academic.oup.com/treephys/article/37/12/1752/3896382},
	doi = {10/gcwvts},
	language = {en},
	number = {12},
	urldate = {2021-06-07},
	journal = {Tree Physiology},
	author = {Dobrowolska, Izabela and Businge, Edward and Abreu, Ilka N and Moritz, Thomas and Egertsdotter, Ulrika},
	month = dec,
	year = {2017},
	pages = {1752--1766},
}

@article{carlsson_nitrogen_2017,
	title = {Nitrogen uptake and assimilation in proliferating embryogenic cultures of {Norway} spruce—{Investigating} the specific role of glutamine},
	volume = {12},
	issn = {1932-6203},
	url = {https://dx.plos.org/10.1371/journal.pone.0181785},
	doi = {10/gcjnr5},
	language = {en},
	number = {8},
	urldate = {2021-06-07},
	journal = {PLOS ONE},
	author = {Carlsson, Johanna and Svennerstam, Henrik and Moritz, Thomas and Egertsdotter, Ulrika and Ganeteg, Ulrika},
	editor = {Min, Xiang Jia},
	month = aug,
	year = {2017},
	pages = {e0181785},
}

@article{papazian_central_2016,
	title = {Central {Metabolic} {Responses} to {Ozone} and {Herbivory} {Affect} {Photosynthesis} and {Stomatal} {Closure}},
	volume = {172},
	issn = {0032-0889, 1532-2548},
	url = {https://academic.oup.com/plphys/article/172/3/2057-2078/6115987},
	doi = {10/f3vft5},
	language = {en},
	number = {3},
	urldate = {2021-06-07},
	journal = {Plant Physiology},
	author = {Papazian, Stefano and Khaling, Eliezer and Bonnet, Christelle and Lassueur, Steve and Reymond, Philippe and Moritz, Thomas and Blande, James D. and Albrectsen, Benedicte R.},
	month = nov,
	year = {2016},
	pages = {2057--2078},
}

@article{chrobok_dissecting_2016,
	title = {Dissecting the {Metabolic} {Role} of {Mitochondria} during {Developmental} {Leaf} {Senescence}},
	volume = {172},
	issn = {0032-0889, 1532-2548},
	url = {https://academic.oup.com/plphys/article/172/4/2132-2153/6115841},
	doi = {10/f3vc6g},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {Plant Physiology},
	author = {Chrobok, Daria and Law, Simon R. and Brouwer, Bastiaan and Lindén, Pernilla and Ziolkowska, Agnieszka and Liebsch, Daniela and Narsai, Reena and Szal, Bozena and Moritz, Thomas and Rouhier, Nicolas and Whelan, James and Gardeström, Per and Keech, Olivier},
	month = dec,
	year = {2016},
	pages = {2132--2153},
}

@article{budzinski_integrated_2016,
	title = {Integrated analysis of gene expression from carbon metabolism, proteome and metabolome, reveals altered primary metabolism in {Eucalyptus} grandis bark, in response to seasonal variation},
	volume = {16},
	issn = {1471-2229},
	url = {http://bmcplantbiol.biomedcentral.com/articles/10.1186/s12870-016-0839-8},
	doi = {10/f3vbf9},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {BMC Plant Biology},
	author = {Budzinski, Ilara Gabriela Frasson and Moon, David H. and Morosini, Júlia Silva and Lindén, Pernilla and Bragatto, Juliano and Moritz, Thomaz and Labate, Carlos Alberto},
	month = dec,
	year = {2016},
	pages = {149},
}

@article{malm_metabolomic_2016,
	title = {Metabolomic {Quality} {Assessment} of {EDTA} {Plasma} and {Serum} {Samples}},
	volume = {14},
	issn = {1947-5535, 1947-5543},
	url = {http://www.liebertpub.com/doi/10.1089/bio.2015.0092},
	doi = {10/f3tq4s},
	language = {en},
	number = {5},
	urldate = {2021-06-07},
	journal = {Biopreservation and Biobanking},
	author = {Malm, Linus and Tybring, Gunnel and Moritz, Thomas and Landin, Britta and Galli, Joakim},
	month = oct,
	year = {2016},
	pages = {416--423},
}

@article{wuolikainen_multi-platform_2016,
	title = {Multi-platform mass spectrometry analysis of the {CSF} and plasma metabolomes of rigorously matched amyotrophic lateral sclerosis, {Parkinson}'s disease and control subjects},
	volume = {12},
	issn = {1742-206X, 1742-2051},
	url = {http://xlink.rsc.org/?DOI=C5MB00711A},
	doi = {10.1039/C5MB00711A},
	abstract = {Schematic view of the study design and the mass spectrometry platforms used for metabolomics analysis.
          , 
            Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are protein-aggregation diseases that lack clear molecular etiologies. Biomarkers could aid in diagnosis, prognosis, planning of care, drug target identification and stratification of patients into clinical trials. We sought to characterize shared and unique metabolite perturbations between ALS and PD and matched controls selected from patients with other diagnoses, including differential diagnoses to ALS or PD that visited our clinic for a lumbar puncture. Cerebrospinal fluid (CSF) and plasma from rigorously age-, sex- and sampling-date matched patients were analyzed on multiple platforms using gas chromatography (GC) and liquid chromatography (LC)–mass spectrometry (MS). We applied constrained randomization of run orders and orthogonal partial least squares projection to latent structure-effect projections (OPLS-EP) to capitalize upon the study design. The combined platforms identified 144 CSF and 196 plasma metabolites with diverse molecular properties. Creatine was found to be increased and creatinine decreased in CSF of ALS patients compared to matched controls. Glucose was increased in CSF of ALS patients and α-hydroxybutyrate was increased in CSF and plasma of ALS patients compared to matched controls. Leucine, isoleucine and ketoleucine were increased in CSF of both ALS and PD. Together, these studies, in conjunction with earlier studies, suggest alterations in energy utilization pathways and have identified and further validated perturbed metabolites to be used in panels of biomarkers for the diagnosis of ALS and PD.},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {Molecular BioSystems},
	author = {Wuolikainen, Anna and Jonsson, Pär and Ahnlund, Maria and Antti, Henrik and Marklund, Stefan L. and Moritz, Thomas and Forsgren, Lars and Andersen, Peter M. and Trupp, Miles},
	year = {2016},
	pages = {1287--1298},
}

Schematic view of the study design and the mass spectrometry platforms used for metabolomics analysis. , Amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) are protein-aggregation diseases that lack clear molecular etiologies. Biomarkers could aid in diagnosis, prognosis, planning of care, drug target identification and stratification of patients into clinical trials. We sought to characterize shared and unique metabolite perturbations between ALS and PD and matched controls selected from patients with other diagnoses, including differential diagnoses to ALS or PD that visited our clinic for a lumbar puncture. Cerebrospinal fluid (CSF) and plasma from rigorously age-, sex- and sampling-date matched patients were analyzed on multiple platforms using gas chromatography (GC) and liquid chromatography (LC)–mass spectrometry (MS). We applied constrained randomization of run orders and orthogonal partial least squares projection to latent structure-effect projections (OPLS-EP) to capitalize upon the study design. The combined platforms identified 144 CSF and 196 plasma metabolites with diverse molecular properties. Creatine was found to be increased and creatinine decreased in CSF of ALS patients compared to matched controls. Glucose was increased in CSF of ALS patients and α-hydroxybutyrate was increased in CSF and plasma of ALS patients compared to matched controls. Leucine, isoleucine and ketoleucine were increased in CSF of both ALS and PD. Together, these studies, in conjunction with earlier studies, suggest alterations in energy utilization pathways and have identified and further validated perturbed metabolites to be used in panels of biomarkers for the diagnosis of ALS and PD.

@article{obudulu_quantitative_2016,
	title = {Quantitative proteomics reveals protein profiles underlying major transitions in aspen wood development},
	volume = {17},
	issn = {1471-2164},
	url = {http://www.biomedcentral.com/1471-2164/17/119},
	doi = {10.1186/s12864-016-2458-z},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {BMC Genomics},
	author = {Obudulu, Ogonna and Bygdell, Joakim and Sundberg, Björn and Moritz, Thomas and Hvidsten, Torgeir R. and Trygg, Johan and Wingsle, Gunnar},
	month = dec,
	year = {2016},
	pages = {119},
}

@article{linden_reduced_2016,
	title = {Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by $^{\textrm{13}}$ {C} labelling},
	volume = {67},
	issn = {0022-0957, 1460-2431},
	url = {https://academic.oup.com/jxb/article-lookup/doi/10.1093/jxb/erw030},
	doi = {10.1093/jxb/erw030},
	language = {en},
	number = {10},
	urldate = {2021-06-07},
	journal = {Journal of Experimental Botany},
	author = {Lindén, Pernilla and Keech, Olivier and Stenlund, Hans and Gardeström, Per and Moritz, Thomas},
	month = may,
	year = {2016},
	pages = {3123--3135},
}

@article{budzinski_seasonal_2016,
	title = {Seasonal {Variation} of {Carbon} {Metabolism} in the {Cambial} {Zone} of {Eucalyptus} grandis},
	volume = {7},
	issn = {1664-462X},
	url = {http://journal.frontiersin.org/Article/10.3389/fpls.2016.00932/abstract},
	doi = {10/f3vjsv},
	urldate = {2021-06-07},
	journal = {Frontiers in Plant Science},
	author = {Budzinski, Ilara G. F. and Moon, David H. and Lindén, Pernilla and Moritz, Thomas and Labate, Carlos A.},
	month = jun,
	year = {2016},
}

@article{mahboubi_13c_2015,
	title = {{13C} {Tracking} after {13CO2} {Supply} {Revealed} {Diurnal} {Patterns} of {Wood} {Formation} in {Aspen}},
	volume = {168},
	issn = {1532-2548 (Electronic) 0032-0889 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/25931520},
	doi = {10.1104/pp.15.00292},
	abstract = {Wood of trees is formed from carbon assimilated in the photosynthetic tissues. Determining the temporal dynamics of carbon assimilation, subsequent transport into developing wood, and incorporation to cell walls would further our understanding of wood formation in particular and tree growth in general. To investigate these questions, we designed a (13)CO2 labeling system to study carbon transport and incorporation to developing wood of hybrid aspen (Populus tremula x tremuloides). Tracking of (13)C incorporation to wood over a time course using nuclear magnetic resonance spectroscopy revealed diurnal patterns in wood cell wall biosynthesis. The dark period had a differential effect on (13)C incorporation to lignin and cell wall carbohydrates. No (13)C was incorporated into aromatic amino acids of cell wall proteins in the dark, suggesting that cell wall protein biosynthesis ceased during the night. The results show previously unrecognized temporal patterns in wood cell wall biosynthesis, suggest diurnal cycle as a possible cue in the regulation of carbon incorporation to wood, and establish a unique (13)C labeling method for the analysis of wood formation and secondary growth in trees.},
	language = {en},
	number = {2},
	urldate = {2021-06-07},
	journal = {Plant Physiol},
	author = {Mahboubi, A. and Linden, P. and Hedenstrom, M. and Moritz, T. and Niittylä, T.},
	month = jun,
	year = {2015},
	keywords = {*Circadian Rhythm, Analysis of Variance, Carbon Dioxide/*metabolism, Carbon Isotopes, Cell Wall/metabolism, Cellulose/metabolism, Magnetic Resonance Spectroscopy, Metabolic Networks and Pathways, Metabolome, Models, Biological, Phloem/metabolism, Plant Leaves/metabolism, Populus/*physiology, Principal Component Analysis, Sucrose/metabolism, Wood/*growth \& development},
	pages = {478--89},
}

Wood of trees is formed from carbon assimilated in the photosynthetic tissues. Determining the temporal dynamics of carbon assimilation, subsequent transport into developing wood, and incorporation to cell walls would further our understanding of wood formation in particular and tree growth in general. To investigate these questions, we designed a (13)CO2 labeling system to study carbon transport and incorporation to developing wood of hybrid aspen (Populus tremula x tremuloides). Tracking of (13)C incorporation to wood over a time course using nuclear magnetic resonance spectroscopy revealed diurnal patterns in wood cell wall biosynthesis. The dark period had a differential effect on (13)C incorporation to lignin and cell wall carbohydrates. No (13)C was incorporated into aromatic amino acids of cell wall proteins in the dark, suggesting that cell wall protein biosynthesis ceased during the night. The results show previously unrecognized temporal patterns in wood cell wall biosynthesis, suggest diurnal cycle as a possible cue in the regulation of carbon incorporation to wood, and establish a unique (13)C labeling method for the analysis of wood formation and secondary growth in trees.

@article{petersson_cell-type_2015,
	title = {Cell-type specific metabolic profiling of {Arabidopsis} thaliana protoplasts as a tool for plant systems biology},
	volume = {11},
	issn = {1573-3882 (Print) 1573-3882 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/26491421},
	doi = {10.1007/s11306-015-0814-7},
	abstract = {Flow cytometry combined with cell sorting of protoplasts has previously been used successfully for transcript profiling of the Arabidopsis thaliana root. We have developed the technique further, and in this paper we present a robust and reliable method for metabolite profiling in specific cell types isolated from Arabidopsis roots. The method uses a combination of fluorescence-activated cell sorting and gas chromatography-time of flight-mass spectrometry analysis. Cortical and endodermal cells from the green fluorescent protein (GFP)-expressing enhancer trap line J0571 were analysed and compared with non-GFP-expressing cells and intact root tissue. Of the metabolites identified, several showed significant differences in concentration between cell types. Multivariate statistical analysis was used to compare metabolite patterns between cell and tissue types, showing that the patterns differed substantially. Isolation of specific cell populations combined with highly sensitive MS-analysis will be a powerful tool for future studies of plant metabolism, and can also be combined with transcript and protein profiling for in-depth analyses of cellular processes.},
	language = {en},
	number = {6},
	urldate = {2021-06-07},
	journal = {Metabolomics},
	author = {Petersson, S. V. and Linden, P. and Moritz, T. and Ljung, K.},
	month = dec,
	year = {2015},
	note = {Edition: 2015/10/23},
	keywords = {Arabidopsis thaliana, Flow cytometry, Gas chromatography-mass spectrometry, Metabolite profiling, Multivariate statistical analysis, Untargeted metabolomics},
	pages = {1679--1689},
}

Flow cytometry combined with cell sorting of protoplasts has previously been used successfully for transcript profiling of the Arabidopsis thaliana root. We have developed the technique further, and in this paper we present a robust and reliable method for metabolite profiling in specific cell types isolated from Arabidopsis roots. The method uses a combination of fluorescence-activated cell sorting and gas chromatography-time of flight-mass spectrometry analysis. Cortical and endodermal cells from the green fluorescent protein (GFP)-expressing enhancer trap line J0571 were analysed and compared with non-GFP-expressing cells and intact root tissue. Of the metabolites identified, several showed significant differences in concentration between cell types. Multivariate statistical analysis was used to compare metabolite patterns between cell and tissue types, showing that the patterns differed substantially. Isolation of specific cell populations combined with highly sensitive MS-analysis will be a powerful tool for future studies of plant metabolism, and can also be combined with transcript and protein profiling for in-depth analyses of cellular processes.

@article{martinez-bello_silencing_2015,
	title = {Silencing {C19}-{GA} 2-oxidases induces parthenocarpic development and inhibits lateral branching in tomato plants},
	volume = {66},
	issn = {1460-2431 (Electronic) 0022-0957 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/26093022},
	doi = {10/f3p6nj},
	abstract = {Gibberellins (GAs) are phytohormones that regulate a wide range of developmental processes in plants. Levels of active GAs are regulated by biosynthetic and catabolic enzymes like the GA 2-oxidases (GA2oxs). In tomato (Solanum lycopersicum L.) C19 GA2oxs are encoded by a small multigenic family of five members with some degree of redundancy. In order to investigate their roles in tomato, the silencing of all five genes in transgenic plants was induced. A significant increase in active GA4 content was found in the ovaries of transgenic plants. In addition, the transgenic unfertilized ovaries were much bigger than wild-type ovaries (about 30 times) and a certain proportion (5-37\%) were able to develop parthenocarpically. Among the GA2ox family, genes GA2ox1 and -2 seem to be the most relevant for this phenotype since their expression was induced in unfertilized ovaries and repressed in developing fruits, inversely correlating with ovary growth. Interestingly, transgenic lines exhibited a significant inhibition of branching and a higher content of active GA4 in axillary buds. This phenotype was reverted, in transgenic plants, by the application of paclobutrazol, a GA biosynthesis inhibitor, suggesting a role for GAs as repressors of branching. In summary, this work demonstrates that GA 2-oxidases regulate gibberellin levels in ovaries and axillary buds of tomato plants and their silencing is responsible for parthenocarpic fruit growth and branching inhibition.},
	language = {en},
	number = {19},
	urldate = {2021-06-07},
	journal = {J Exp Bot},
	author = {Martinez-Bello, L. and Moritz, T. and Lopez-Diaz, I.},
	month = sep,
	year = {2015},
	note = {Edition: 2015/06/21},
	keywords = {*Gene Expression Regulation, Plant, Branching, Fruit/genetics/growth \& development/metabolism, GA 2-oxidases, Gene Expression Regulation, Developmental, Gene Silencing, Gibberellins/metabolism, Lycopersicon esculentum/*genetics/*growth \& development/metabolism, Mixed Function Oxygenases/*genetics/metabolism, Plant Proteins/*genetics/metabolism, Plant Stems/genetics/growth \& development/metabolism, Plants, Genetically Modified/genetics/growth \& development/metabolism, Sequence Analysis, DNA, gibberellins, parthenocarpy, silencing, tomato.},
	pages = {5897--910},
}

Gibberellins (GAs) are phytohormones that regulate a wide range of developmental processes in plants. Levels of active GAs are regulated by biosynthetic and catabolic enzymes like the GA 2-oxidases (GA2oxs). In tomato (Solanum lycopersicum L.) C19 GA2oxs are encoded by a small multigenic family of five members with some degree of redundancy. In order to investigate their roles in tomato, the silencing of all five genes in transgenic plants was induced. A significant increase in active GA4 content was found in the ovaries of transgenic plants. In addition, the transgenic unfertilized ovaries were much bigger than wild-type ovaries (about 30 times) and a certain proportion (5-37%) were able to develop parthenocarpically. Among the GA2ox family, genes GA2ox1 and -2 seem to be the most relevant for this phenotype since their expression was induced in unfertilized ovaries and repressed in developing fruits, inversely correlating with ovary growth. Interestingly, transgenic lines exhibited a significant inhibition of branching and a higher content of active GA4 in axillary buds. This phenotype was reverted, in transgenic plants, by the application of paclobutrazol, a GA biosynthesis inhibitor, suggesting a role for GAs as repressors of branching. In summary, this work demonstrates that GA 2-oxidases regulate gibberellin levels in ovaries and axillary buds of tomato plants and their silencing is responsible for parthenocarpic fruit growth and branching inhibition.

@article{eriksson_transgenic_2015,
	title = {Transgenic hybrid aspen trees with increased gibberellin ({GA}) concentrations suggest that {GA} acts in parallel with {FLOWERING} {LOCUS} {T2} to control shoot elongation},
	volume = {205},
	issn = {1469-8137},
	url = {https://nph.onlinelibrary.wiley.com/doi/abs/10.1111/nph.13144},
	doi = {10/f3nxc2},
	abstract = {Bioactive gibberellins (GAs) have been implicated in short day (SD)-induced growth cessation in Populus, because exogenous applications of bioactive GAs to hybrid aspens (Populus tremula × tremuloides) under SD conditions delay growth cessation. However, this effect diminishes with time, suggesting that plants may cease growth following exposure to SDs due to a reduction in sensitivity to GAs. In order to validate and further explore the role of GAs in growth cessation, we perturbed GA biosynthesis or signalling in hybrid aspen plants by overexpressing AtGA20ox1, AtGA2ox2 and PttGID1.3 (encoding GA biosynthesis enzymes and a GA receptor). We found trees with elevated concentrations of bioactive GA, due to overexpression of AtGA20ox1, continued to grow in SD conditions and were insensitive to the level of FLOWERING LOCUS T2 (FT2) expression. As transgenic plants overexpressing the PttGID1.3 GA receptor responded in a wild-type (WT) manner to SD conditions, this insensitivity did not result from limited receptor availability. As high concentrations of bioactive GA during SD conditions were sufficient to sustain shoot elongation growth in hybrid aspen trees, independent of FT2 expression levels, we conclude elongation growth in trees is regulated by both GA- and long day-responsive pathways, similar to the regulation of flowering in Arabidopsis thaliana.},
	language = {en},
	number = {3},
	urldate = {2021-08-31},
	journal = {New Phytologist},
	author = {Eriksson, Maria E. and Hoffman, Daniel and Kaduk, Mateusz and Mauriat, Mélanie and Moritz, Thomas},
	year = {2015},
	note = {\_eprint: https://nph.onlinelibrary.wiley.com/doi/pdf/10.1111/nph.13144},
	keywords = {Flowering Locus T2 (FT2), Populus, gibberellins (GA), growth cessation, photoperiod},
	pages = {1288--1295},
}

Bioactive gibberellins (GAs) have been implicated in short day (SD)-induced growth cessation in Populus, because exogenous applications of bioactive GAs to hybrid aspens (Populus tremula × tremuloides) under SD conditions delay growth cessation. However, this effect diminishes with time, suggesting that plants may cease growth following exposure to SDs due to a reduction in sensitivity to GAs. In order to validate and further explore the role of GAs in growth cessation, we perturbed GA biosynthesis or signalling in hybrid aspen plants by overexpressing AtGA20ox1, AtGA2ox2 and PttGID1.3 (encoding GA biosynthesis enzymes and a GA receptor). We found trees with elevated concentrations of bioactive GA, due to overexpression of AtGA20ox1, continued to grow in SD conditions and were insensitive to the level of FLOWERING LOCUS T2 (FT2) expression. As transgenic plants overexpressing the PttGID1.3 GA receptor responded in a wild-type (WT) manner to SD conditions, this insensitivity did not result from limited receptor availability. As high concentrations of bioactive GA during SD conditions were sufficient to sustain shoot elongation growth in hybrid aspen trees, independent of FT2 expression levels, we conclude elongation growth in trees is regulated by both GA- and long day-responsive pathways, similar to the regulation of flowering in Arabidopsis thaliana.

@article{kolmert_quantitative_2014,
	title = {A quantitative {LC}/{MS} method targeting urinary 1-methyl-4-imidazoleacetic acid for safety monitoring of the global histamine turnover in clinical studies},
	volume = {406},
	issn = {1618-2642, 1618-2650},
	url = {http://link.springer.com/10.1007/s00216-013-7594-6},
	doi = {10/f225w6},
	language = {en},
	number = {6},
	urldate = {2021-06-08},
	journal = {Analytical and Bioanalytical Chemistry},
	author = {Kolmert, J. and Forngren, B. and Lindberg, J. and Öhd, J. and Åberg, K. M. and Nilsson, G. and Moritz, T. and Nordström, A.},
	month = feb,
	year = {2014},
	pages = {1751--1762},
}

@article{biswal_aspen_2014,
	title = {Aspen pectate lyase {PtxtPL1}-27 mobilizes matrix polysaccharides from woody tissues and improves saccharification yield},
	volume = {7},
	issn = {1754-6834},
	url = {http://biotechnologyforbiofuels.biomedcentral.com/articles/10.1186/1754-6834-7-11},
	doi = {10/f22tkm},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Biotechnology for Biofuels},
	author = {Biswal, Ajaya K and Soeno, Kazuo and Gandla, Madhavi and Immerzeel, Peter and Pattathil, Sivakumar and Lucenius, Jessica and Serimaa, Ritva and Hahn, Michael G and Moritz, Thomas and Jönsson, Leif J and Israelsson-Nordström, Maria and Mellerowicz, Ewa J},
	year = {2014},
	pages = {11},
}

@article{dettmer_choline_2014,
	title = {{CHOLINE} {TRANSPORTER}-{LIKE1} is required for sieve plate development to mediate long-distance cell-to-cell communication},
	volume = {5},
	issn = {2041-1723},
	url = {http://www.nature.com/articles/ncomms5276},
	doi = {10/f3p42k},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Nature Communications},
	author = {Dettmer, Jan and Ursache, Robertas and Campilho, Ana and Miyashima, Shunsuke and Belevich, Ilya and O’Regan, Seana and Mullendore, Daniel Leroy and Yadav, Shri Ram and Lanz, Christa and Beverina, Luca and Papagni, Antonio and Schneeberger, Korbinian and Weigel, Detlef and Stierhof, York-Dieter and Moritz, Thomas and Knoblauch, Michael and Jokitalo, Eija and Helariutta, Ykä},
	month = sep,
	year = {2014},
	pages = {4276},
}

@article{mauriat_gibberellins_2014,
	title = {Gibberellins inhibit adventitious rooting in hybrid aspen and {Arabidopsis} by affecting auxin transport},
	volume = {78},
	issn = {09607412},
	url = {http://doi.wiley.com/10.1111/tpj.12478},
	doi = {10/f22tk3},
	language = {en},
	number = {3},
	urldate = {2021-06-08},
	journal = {The Plant Journal},
	author = {Mauriat, Mélanie and Petterle, Anna and Bellini, Catherine and Moritz, Thomas},
	month = may,
	year = {2014},
	pages = {372--384},
}

@article{frescatadarosa_high_2014,
	title = {High lipid order of {Arabidopsis} cell‐plate membranes mediated by sterol and {DYNAMIN}‐{RELATED} {PROTEIN1A} function},
	volume = {80},
	issn = {0960-7412, 1365-313X},
	url = {https://onlinelibrary.wiley.com/doi/10.1111/tpj.12674},
	doi = {10/f3nxhn},
	language = {en},
	number = {5},
	urldate = {2021-06-08},
	journal = {The Plant Journal},
	author = {Frescatada‐Rosa, Márcia and Stanislas, Thomas and Backues, Steven K. and Reichardt, Ilka and Men, Shuzhen and Boutté, Yohann and Jürgens, Gerd and Moritz, Thomas and Bednarek, Sebastian Y. and Grebe, Markus},
	month = dec,
	year = {2014},
	pages = {745--757},
}

@article{normark_maladjusted_2014,
	title = {Maladjusted {Host} {Immune} {Responses} {Induce} {Experimental} {Cerebral} {Malaria}-{Like} {Pathology} in a {Murine} {Borrelia} and {Plasmodium} {Co}-{Infection} {Model}},
	volume = {9},
	issn = {1932-6203},
	url = {https://dx.plos.org/10.1371/journal.pone.0103295},
	doi = {10/f22k7v},
	language = {en},
	number = {7},
	urldate = {2021-06-08},
	journal = {PLoS ONE},
	author = {Normark, Johan and Nelson, Maria and Engström, Patrik and Andersson, Marie and Björk, Rafael and Moritz, Thomas and Fahlgren, Anna and Bergström, Sven},
	editor = {Wooten, R. Mark},
	month = jul,
	year = {2014},
	pages = {e103295},
}

@article{trupp_metabolite_2014,
	title = {Metabolite and {Peptide} {Levels} in {Plasma} and {CSF} {Differentiating} {Healthy} {Controls} from {Patients} with {Newly} {Diagnosed} {Parkinson}'s {Disease}},
	volume = {4},
	issn = {1877718X, 18777171},
	url = {https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JPD-140389},
	doi = {10/f23vd3},
	number = {3},
	urldate = {2021-06-08},
	journal = {Journal of Parkinson's Disease},
	author = {Trupp, Miles and Jonsson, Pär and Öhrfelt, Annika and Zetterberg, Henrik and Obudulu, Ogonna and Malm, Linus and Wuolikainen, Anna and Linder, Jan and Moritz, Thomas and Blennow, Kaj and Antti, Henrik and Forsgren, Lars},
	year = {2014},
	pages = {549--560},
}

@article{keefover-ring_no_2014,
	title = {No {Evidence} of {Geographical} {Structure} of {Salicinoid} {Chemotypes} within {Populus} {Tremula}},
	volume = {9},
	issn = {1932-6203},
	url = {https://dx.plos.org/10.1371/journal.pone.0107189},
	doi = {10/f25fhm},
	language = {en},
	number = {10},
	urldate = {2021-06-08},
	journal = {PLoS ONE},
	author = {Keefover-Ring, Ken and Ahnlund, Maria and Abreu, Ilka Nacif and Jansson, Stefan and Moritz, Thomas and Albrectsen, Benedicte Riber},
	editor = {Yin, Tongming},
	month = oct,
	year = {2014},
	pages = {e107189},
}

@article{mousavi_serum_2014,
	title = {Serum {Metabolomic} {Biomarkers} of {Dementia}},
	volume = {4},
	issn = {1664-5464},
	url = {https://www.karger.com/Article/FullText/364816},
	doi = {10/f242b6},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {Dementia and Geriatric Cognitive Disorders Extra},
	author = {Mousavi, Malahat and Jonsson, P�r and Antti, Henrik and Adolfsson, Rolf and Nordin, Annelie and Bergdahl, Jan and Eriksson, K�re and Moritz, Thomas and Nilsson, Lars-G�ran and Nyberg, Lars},
	month = jul,
	year = {2014},
	pages = {252--262},
}

@article{le_hir_abcg9_2013,
	title = {{ABCG9}, {ABCG11} and {ABCG14} {ABC} transporters are required for vascular development in {Arabidopsis}},
	volume = {76},
	issn = {09607412},
	url = {http://doi.wiley.com/10.1111/tpj.12334},
	doi = {10/f22xd4},
	language = {en},
	number = {5},
	urldate = {2021-06-08},
	journal = {The Plant Journal},
	author = {Le Hir, Rozenn and Sorin, Clément and Chakraborti, Dipankar and Moritz, Thomas and Schaller, Hubert and Tellier, Frédérique and Robert, Stéphanie and Morin, Halima and Bakó, Laszlo and Bellini, Catherine},
	month = dec,
	year = {2013},
	pages = {811--824},
}

@article{miranda_co-expression_2013,
	title = {Co-expression analysis, proteomic and metabolomic study on the impact of a {Deg}/{HtrA} protease triple mutant in {Synechocystis} sp. {PCC} 6803 exposed to temperature and high light stress},
	volume = {78},
	issn = {18743919},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1874391912006926},
	doi = {10/f2z4z6},
	language = {en},
	urldate = {2021-06-08},
	journal = {Journal of Proteomics},
	author = {Miranda, Hélder and Cheregi, Otilia and Netotea, Sergiu and Hvidsten, Torgeir R. and Moritz, Thomas and Funk, Christiane},
	month = jan,
	year = {2013},
	pages = {294--311},
}

@article{srivastava_onpls_2013,
	title = {{OnPLS} integration of transcriptomic, proteomic and metabolomic data shows multi-level oxidative stress responses in the cambium of transgenic {hipI}- superoxide dismutase {Populus} plants},
	volume = {14},
	issn = {1471-2164},
	url = {https://doi.org/10.1186/1471-2164-14-893},
	doi = {10/f2zk6q},
	abstract = {Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.},
	number = {1},
	urldate = {2021-06-07},
	journal = {BMC Genomics},
	author = {Srivastava, Vaibhav and Obudulu, Ogonna and Bygdell, Joakim and Löfstedt, Tommy and Rydén, Patrik and Nilsson, Robert and Ahnlund, Maria and Johansson, Annika and Jonsson, Pär and Freyhult, Eva and Qvarnström, Johanna and Karlsson, Jan and Melzer, Michael and Moritz, Thomas and Trygg, Johan and Hvidsten, Torgeir R. and Wingsle, Gunnar},
	month = dec,
	year = {2013},
	keywords = {OnPLS, Oxidative stress, Poplar, Statistical integration, Systems biology},
	pages = {893},
}

Reactive oxygen species (ROS) are involved in the regulation of diverse physiological processes in plants, including various biotic and abiotic stress responses. Thus, oxidative stress tolerance mechanisms in plants are complex, and diverse responses at multiple levels need to be characterized in order to understand them. Here we present system responses to oxidative stress in Populus by integrating data from analyses of the cambial region of wild-type controls and plants expressing high-isoelectric-point superoxide dismutase (hipI-SOD) transcripts in antisense orientation showing a higher production of superoxide. The cambium, a thin cell layer, generates cells that differentiate to form either phloem or xylem and is hypothesized to be a major reason for phenotypic perturbations in the transgenic plants. Data from multiple platforms including transcriptomics (microarray analysis), proteomics (UPLC/QTOF-MS), and metabolomics (GC-TOF/MS, UPLC/MS, and UHPLC-LTQ/MS) were integrated using the most recent development of orthogonal projections to latent structures called OnPLS. OnPLS is a symmetrical multi-block method that does not depend on the order of analysis when more than two blocks are analysed. Significantly affected genes, proteins and metabolites were then visualized in painted pathway diagrams.

@article{businge_effect_2013,
	title = {The effect of carbohydrates and osmoticum on storage reserve accumulation and germination of {Norway} spruce somatic embryos},
	volume = {149},
	issn = {00319317},
	url = {http://doi.wiley.com/10.1111/ppl.12039},
	doi = {10/f2zr7w},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {Physiologia Plantarum},
	author = {Businge, Edward and Bygdell, Joakim and Wingsle, Gunnar and Moritz, Thomas and Egertsdotter, Ulrika},
	month = oct,
	year = {2013},
	pages = {273--285},
}

@article{wuolikainen_als_2012,
	title = {{ALS} patients with mutations in the {SOD1} gene have an unique metabolomic profile in the cerebrospinal fluid compared with {ALS} patients without mutations},
	volume = {105},
	issn = {10967192},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1096719211006184},
	doi = {10/ffcrdm},
	language = {en},
	number = {3},
	urldate = {2021-06-08},
	journal = {Molecular Genetics and Metabolism},
	author = {Wuolikainen, Anna and Andersen, Peter M. and Moritz, Thomas and Marklund, Stefan L. and Antti, Henrik},
	month = mar,
	year = {2012},
	pages = {472--478},
}

@article{madsen_altered_2012,
	title = {Altered {Metabolic} {Signature} in {Pre}-{Diabetic} {NOD} {Mice}},
	volume = {7},
	issn = {1932-6203},
	url = {https://dx.plos.org/10.1371/journal.pone.0035445},
	doi = {10/f23mgb},
	language = {en},
	number = {4},
	urldate = {2021-06-08},
	journal = {PLoS ONE},
	author = {Madsen, Rasmus and Banday, Viqar Showkat and Moritz, Thomas and Trygg, Johan and Lejon, Kristina},
	editor = {Maedler, Kathrin},
	month = apr,
	year = {2012},
	pages = {e35445},
}

@article{danielsson_development_2012,
	title = {Development of a gas chromatography/mass spectrometry based metabolomics protocol by means of statistical experimental design},
	volume = {8},
	issn = {1573-3882, 1573-3890},
	url = {http://link.springer.com/10.1007/s11306-011-0283-6},
	doi = {10/cbcwmc},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Metabolomics},
	author = {Danielsson, Anders P. H. and Moritz, Thomas and Mulder, Hindrik and Spégel, Peter},
	month = feb,
	year = {2012},
	pages = {50--63},
}

@article{zang_effects_2012,
	title = {Effects of oestrogen and testosterone therapy on serum metabolites in postmenopausal women},
	volume = {77},
	issn = {03000664},
	url = {http://doi.wiley.com/10.1111/j.1365-2265.2012.04374.x},
	doi = {10/f2znjv},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {Clinical Endocrinology},
	author = {Zang, Hong and Moritz, Thomas and Norstedt, Gunnar and Hirschberg, Angelica L. and Tollet-Egnell, Petra},
	month = aug,
	year = {2012},
	pages = {288--295},
}

@article{surowiec_mass_2012,
	title = {Mass spectrometric identification of new minor indigoids in shellfish purple dye from {Hexaplex} trunculus},
	volume = {94},
	issn = {01437208},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0143720812000320},
	doi = {10/f2zz55},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {Dyes and Pigments},
	author = {Surowiec, Izabella and Nowik, Witold and Moritz, Thomas},
	month = aug,
	year = {2012},
	pages = {363--369},
}

@article{madsen_metabolic_2012,
	title = {Metabolic {Responses} to {Change} in {Disease} {Activity} during {Tumor} {Necrosis} {Factor} {Inhibition} in {Patients} with {Rheumatoid} {Arthritis}},
	volume = {11},
	issn = {1535-3893, 1535-3907},
	url = {https://pubs.acs.org/doi/10.1021/pr300296v},
	doi = {10/f24g7h},
	language = {en},
	number = {7},
	urldate = {2021-06-08},
	journal = {Journal of Proteome Research},
	author = {Madsen, Rasmus and Rantapää-Dahlqvist, Solbritt and Lundstedt, Torbjörn and Moritz, Thomas and Trygg, Johan},
	month = jul,
	year = {2012},
	pages = {3796--3804},
}

@article{businge_metabolite_2012,
	title = {Metabolite profiling reveals clear metabolic changes during somatic embryo development of {Norway} spruce ({Picea} abies)},
	volume = {32},
	issn = {0829-318X, 1758-4469},
	url = {https://academic.oup.com/treephys/article-lookup/doi/10.1093/treephys/tpr142},
	doi = {10/f24n88},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {Tree Physiology},
	author = {Businge, E. and Brackmann, K. and Moritz, T. and Egertsdotter, U.},
	month = feb,
	year = {2012},
	pages = {232--244},
}

@article{gerber_multivariate_2012,
	title = {Multivariate curve resolution provides a high-throughput data processing pipeline for pyrolysis-gas chromatography/mass spectrometry},
	volume = {95},
	issn = {01652370},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0165237012000137},
	doi = {10/fxs9zf},
	language = {en},
	urldate = {2021-06-08},
	journal = {Journal of Analytical and Applied Pyrolysis},
	author = {Gerber, Lorenz and Eliasson, Mattias and Trygg, Johan and Moritz, Thomas and Sundberg, Björn},
	month = may,
	year = {2012},
	pages = {95--100},
}

@article{chorell_physical_2012,
	title = {Physical fitness level is reflected by alterations in the human plasma metabolome},
	volume = {8},
	issn = {1742-206X, 1742-2051},
	url = {http://xlink.rsc.org/?DOI=c2mb05428k},
	doi = {10/fxnw3m},
	language = {en},
	number = {4},
	urldate = {2021-06-08},
	journal = {Molecular BioSystems},
	author = {Chorell, Elin and Svensson, Michael B. and Moritz, Thomas and Antti, Henrik},
	year = {2012},
	pages = {1187},
}

@article{dubois_comparison_2011,
	title = {Comparison of the role of gibberellins and ethylene in response to submergence of two lowland rice cultivars, {Senia} and {Bomba}},
	volume = {168},
	issn = {01761617},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0176161710004050},
	doi = {10/b3z5h8},
	language = {en},
	number = {3},
	urldate = {2021-06-08},
	journal = {Journal of Plant Physiology},
	author = {Dubois, Vincent and Moritz, Thomas and García-Martínez, José L.},
	month = feb,
	year = {2011},
	pages = {233--241},
}

@article{madsen_diagnostic_2011,
	title = {Diagnostic properties of metabolic perturbations in rheumatoid arthritis},
	volume = {13},
	issn = {1478-6362},
	url = {https://arthritis-research.biomedcentral.com/articles/10.1186/ar3243},
	doi = {10/fdbqs3},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Arthritis Research \& Therapy},
	author = {Madsen, Rasmus K and Lundstedt, Torbjörn and Gabrielsson, Jon and Sennbro, Carl-Johan and Alenius, Gerd-Marie and Moritz, Thomas and Rantapää-Dahlqvist, Solbritt and Trygg, Johan},
	month = feb,
	year = {2011},
	pages = {R19},
}

@article{wuolikainen_disease-related_2011,
	title = {Disease-{Related} {Changes} in the {Cerebrospinal} {Fluid} {Metabolome} in {Amyotrophic} {Lateral} {Sclerosis} {Detected} by {GC}/{TOFMS}},
	volume = {6},
	issn = {1932-6203},
	url = {https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0017947},
	doi = {10/fkwd4d},
	abstract = {Background/Aim The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF. Methodology Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls. Principal Findings The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar. Conclusions/Significance Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease.},
	language = {en},
	number = {4},
	urldate = {2021-06-08},
	journal = {PLOS ONE},
	author = {Wuolikainen, Anna and Moritz, Thomas and Marklund, Stefan L. and Antti, Henrik and Andersen, Peter Munch},
	month = apr,
	year = {2011},
	note = {Publisher: Public Library of Science},
	keywords = {Amyotrophic lateral sclerosis, Cerebrospinal fluid, Drug metabolism, Glutamic acid, Metabolic analysis, Metabolites, Metabolomics, Mutation},
	pages = {e17947},
}

Background/Aim The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF. Methodology Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls. Principal Findings The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar. Conclusions/Significance Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease.

@article{mauriat_proper_2011,
	title = {Proper gibberellin localization in vascular tissue is required to control auxin-dependent leaf development and bud outgrowth in hybrid aspen: {GA}-dependent auxin transport in vascular tissue},
	volume = {67},
	issn = {09607412},
	shorttitle = {Proper gibberellin localization in vascular tissue is required to control auxin-dependent leaf development and bud outgrowth in hybrid aspen},
	url = {http://doi.wiley.com/10.1111/j.1365-313X.2011.04635.x},
	doi = {10/bnx4nt},
	language = {en},
	number = {5},
	urldate = {2021-06-08},
	journal = {The Plant Journal},
	author = {Mauriat, Mélanie and Sandberg, Linda G. and Moritz, Thomas},
	month = sep,
	year = {2011},
	pages = {805--816},
}

@article{ma_sucroseregulated_2011,
	title = {The sucrose‐regulated {Arabidopsis} transcription factor {bZIP11} reprograms metabolism and regulates trehalose metabolism},
	volume = {191},
	issn = {0028-646X, 1469-8137},
	url = {https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8137.2011.03735.x},
	doi = {10/b9vhbj},
	language = {en},
	number = {3},
	urldate = {2021-06-08},
	journal = {New Phytologist},
	author = {Ma, Jingkun and Hanssen, Micha and Lundgren, Krister and Hernández, Lázaro and Delatte, Thierry and Ehlert, Andrea and Liu, Chun‐Ming and Schluepmann, Henriette and Dröge‐Laser, Wolfgang and Moritz, Thomas and Smeekens, Sjef and Hanson, Johannes},
	month = aug,
	year = {2011},
	pages = {733--745},
}

@article{abreu_uhplc-esitofms_2011,
	title = {{UHPLC}-{ESI}/{TOFMS} {Determination} of salicylate-like phenolic gycosides in {Populus} tremula leaves},
	volume = {37},
	doi = {10/c8755j},
	abstract = {Associations of salicylate-like phenolic glycosides (PGs) with biological activity have been reported in Salix and Populus trees, but only for a few compounds, and in relation to a limited number of herbivores. By considering the full diversity of PGs, we may improve our ability to recognize genotypes or chemotype groups and enhance our understanding of their ecological function. Here, we present a fast and efficient general method for salicylate determination in leaves of Eurasian aspen that uses ultra-high performance liquid chromatography-electrospray ionization/time-of-flight mass spectrometry (UHPLC-ESI/TOFMS). The time required for the liquid chromatography separations was 13.5 min per sample, compared to around 60 min per sample for most HPLC protocols. In leaf samples from identical P. tremula genotypes with diverse propagation and treatment histories, we identified nine PGs. We found the compound-specific mass chromatograms to be more informative than the UV-visible chromatograms for compound identification and when quantitating samples with large variability in PG content. Signature compounds previously reported for P. tremoloides (tremulacin, tremuloidin, salicin, and salicortin) always were present, and five PGs (2'-O-cinnamoyl-salicortin, 2'-O-acetyl-salicortin, 2'-O-acetyl-salicin, acetyl-tremulacin, and salicyloyl-salicin) were detected for the first time in P. tremula. By using information about the formic acid adduct that appeared for PGs in the LTQ-Orbitrap MS environment, novel compounds like acetyl-tremulacin could be tentatively identified without the use of standards. The novel PGs were consistently either present in genotypes regardless of propagation and damage treatment or were not detectable. In some genotypes, concentrations of 2'-O-acetyl-salicortin and 2'-O-cinnamoyl-salicortin were similar to levels of biologically active PGs in other Salicaceous trees. Our study suggests that we may expect a wide variation in PG content in aspen populations which is of interest both for studies of interactions with herbivores and for mapping population structure.

Electronic supplementary material
The online version of this article (doi:10.1007/s10886-011-9991-7) contains supplementary material, which is available to authorized users.},
	journal = {Journal of chemical ecology},
	author = {Abreu, Ilka and Ahnlund, Maria and Moritz, Thomas and Albrectsen, Benedicte},
	month = aug,
	year = {2011},
	pages = {857--70},
}

Associations of salicylate-like phenolic glycosides (PGs) with biological activity have been reported in Salix and Populus trees, but only for a few compounds, and in relation to a limited number of herbivores. By considering the full diversity of PGs, we may improve our ability to recognize genotypes or chemotype groups and enhance our understanding of their ecological function. Here, we present a fast and efficient general method for salicylate determination in leaves of Eurasian aspen that uses ultra-high performance liquid chromatography-electrospray ionization/time-of-flight mass spectrometry (UHPLC-ESI/TOFMS). The time required for the liquid chromatography separations was 13.5 min per sample, compared to around 60 min per sample for most HPLC protocols. In leaf samples from identical P. tremula genotypes with diverse propagation and treatment histories, we identified nine PGs. We found the compound-specific mass chromatograms to be more informative than the UV-visible chromatograms for compound identification and when quantitating samples with large variability in PG content. Signature compounds previously reported for P. tremoloides (tremulacin, tremuloidin, salicin, and salicortin) always were present, and five PGs (2'-O-cinnamoyl-salicortin, 2'-O-acetyl-salicortin, 2'-O-acetyl-salicin, acetyl-tremulacin, and salicyloyl-salicin) were detected for the first time in P. tremula. By using information about the formic acid adduct that appeared for PGs in the LTQ-Orbitrap MS environment, novel compounds like acetyl-tremulacin could be tentatively identified without the use of standards. The novel PGs were consistently either present in genotypes regardless of propagation and damage treatment or were not detectable. In some genotypes, concentrations of 2'-O-acetyl-salicortin and 2'-O-cinnamoyl-salicortin were similar to levels of biologically active PGs in other Salicaceous trees. Our study suggests that we may expect a wide variation in PG content in aspen populations which is of interest both for studies of interactions with herbivores and for mapping population structure. Electronic supplementary material The online version of this article (doi:10.1007/s10886-011-9991-7) contains supplementary material, which is available to authorized users.

@article{renberg_metabolomic_2010,
	title = {A {Metabolomic} {Approach} to {Study} {Major} {Metabolite} {Changes} during {Acclimation} to {Limiting} {CO2} in \textit{{Chlamydomonas} reinhardtii}},
	volume = {154},
	issn = {1532-2548},
	url = {https://academic.oup.com/plphys/article/154/1/187/6111228},
	doi = {10/b3xzqv},
	abstract = {Abstract
            Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high- and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Plant Physiology},
	author = {Renberg, Linda and Johansson, Annika I. and Shutova, Tatiana and Stenlund, Hans and Aksmann, Anna and Raven, John A. and Gardeström, Per and Moritz, Thomas and Samuelsson, Göran},
	month = sep,
	year = {2010},
	pages = {187--196},
}

Abstract Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high- and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.

@article{kozarewa_alteration_2010,
	title = {Alteration of {PHYA} expression change circadian rhythms and timing of bud set in {Populus}},
	volume = {73},
	issn = {0167-4412, 1573-5028},
	url = {http://link.springer.com/10.1007/s11103-010-9619-2},
	doi = {10/dp553q},
	language = {en},
	number = {1-2},
	urldate = {2021-06-08},
	journal = {Plant Molecular Biology},
	author = {Kozarewa, Iwanka and Ibáñez, Cristian and Johansson, Mikael and Ögren, Erling and Mozley, David and Nylander, Eva and Chono, Makiko and Moritz, Thomas and Eriksson, Maria E.},
	month = may,
	year = {2010},
	pages = {143--156},
}

@article{hoffman_changes_2010,
	title = {Changes in diurnal patterns within the {Populus} transcriptome and metabolome in response to photoperiod variation},
	volume = {33},
	issn = {1365-3040},
	doi = {10/d2xk8m},
	abstract = {Changes in seasonal photoperiod provides an important environmental signal that affects the timing of winter dormancy in perennial, deciduous, temperate tree species, such as hybrid aspen (Populus tremula x Populus tremuloides). In this species, growth cessation, cold acclimation and dormancy are induced in the autumn by the detection of day-length shortening that occurs at a given critical day length. Important components in the detection of such day-length changes are photoreceptors and the circadian clock, and many plant responses at both the gene regulation and metabolite levels are expected to be diurnal. To directly examine this expectation and study components in these events, here we report transcriptomic and metabolomic responses to a change in photoperiod from long to short days in hybrid aspen. We found about 16\% of genes represented on the arrays to be diurnally regulated, as assessed by our pre-defined criteria. Furthermore, several of these genes were involved in circadian-associated processes, including photosynthesis and primary and secondary metabolism. Metabolites affected by the change in photoperiod were mostly involved in carbon metabolism. Taken together, we have thus established a molecular catalog of events that precede a response to winter.},
	language = {eng},
	number = {8},
	journal = {Plant, Cell \& Environment},
	author = {Hoffman, Daniel E. and Jonsson, Pär and Bylesjö, Max and Trygg, Johan and Antti, Henrik and Eriksson, Maria E. and Moritz, Thomas},
	month = aug,
	year = {2010},
	pmid = {20302601},
	keywords = {Carbohydrate Metabolism, Circadian Rhythm, DNA, Complementary, Gene Expression Profiling, Gene Expression Regulation, Plant, Genes, Plant, Metabolome, Oligonucleotide Array Sequence Analysis, Photoperiod, Populus, Seasons},
	pages = {1298--1313},
}

Changes in seasonal photoperiod provides an important environmental signal that affects the timing of winter dormancy in perennial, deciduous, temperate tree species, such as hybrid aspen (Populus tremula x Populus tremuloides). In this species, growth cessation, cold acclimation and dormancy are induced in the autumn by the detection of day-length shortening that occurs at a given critical day length. Important components in the detection of such day-length changes are photoreceptors and the circadian clock, and many plant responses at both the gene regulation and metabolite levels are expected to be diurnal. To directly examine this expectation and study components in these events, here we report transcriptomic and metabolomic responses to a change in photoperiod from long to short days in hybrid aspen. We found about 16% of genes represented on the arrays to be diurnally regulated, as assessed by our pre-defined criteria. Furthermore, several of these genes were involved in circadian-associated processes, including photosynthesis and primary and secondary metabolism. Metabolites affected by the change in photoperiod were mostly involved in carbon metabolism. Taken together, we have thus established a molecular catalog of events that precede a response to winter.

@article{danielsson_development_2010,
	title = {Development and optimization of a metabolomic method for analysis of adherent cell cultures},
	volume = {404},
	issn = {00032697},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0003269710002502},
	doi = {10/fhmpbx},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Analytical Biochemistry},
	author = {Danielsson, Anders P.H. and Moritz, Thomas and Mulder, Hindrik and Spégel, Peter},
	month = sep,
	year = {2010},
	pages = {30--39},
}

@article{waldenstrom_ischaemic_2010,
	title = {Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium: an experimental study in the pig},
	volume = {199},
	issn = {17481708, 17481716},
	shorttitle = {Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium},
	url = {http://doi.wiley.com/10.1111/j.1748-1716.2009.02071.x},
	doi = {10/dsp97q},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Acta Physiologica},
	author = {Waldenström, A. and Haney, M. and Biber, B. and Kavianipour, M. and Moritz, T. and Strandén, P. and Wikström, G. and Ronquist, G.},
	month = may,
	year = {2010},
	pages = {1--9},
}

@article{thysell_metabolomic_2010,
	title = {Metabolomic {Characterization} of {Human} {Prostate} {Cancer} {Bone} {Metastases} {Reveals} {Increased} {Levels} of {Cholesterol}},
	volume = {5},
	issn = {1932-6203},
	url = {https://dx.plos.org/10.1371/journal.pone.0014175},
	doi = {10/d69xb9},
	language = {en},
	number = {12},
	urldate = {2021-06-08},
	journal = {PLoS ONE},
	author = {Thysell, Elin and Surowiec, Izabella and Hörnberg, Emma and Crnalic, Sead and Widmark, Anders and Johansson, Annika I. and Stattin, Pär and Bergh, Anders and Moritz, Thomas and Antti, Henrik and Wikström, Pernilla},
	editor = {Creighton, Chad},
	month = dec,
	year = {2010},
	pages = {e14175},
}

@article{spegel_metabolomic_2010,
	title = {Metabolomic analysis of a human oral glucose tolerance test reveals fatty acids as reliable indicators of regulated metabolism},
	volume = {6},
	issn = {1573-3882, 1573-3890},
	url = {http://link.springer.com/10.1007/s11306-009-0177-z},
	doi = {10/frw67z},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Metabolomics},
	author = {Spégel, Peter and Danielsson, Anders P. H. and Bacos, Karl and Nagorny, Cecilia L. F. and Moritz, Thomas and Mulder, Hindrik and Filipsson, Karin},
	month = mar,
	year = {2010},
	pages = {56--66},
}

@article{krus_pyruvate_2010,
	title = {Pyruvate dehydrogenase kinase 1 controls mitochondrial metabolism and insulin secretion in {INS}-1 832/13 clonal β-cells},
	volume = {429},
	issn = {0264-6021, 1470-8728},
	url = {https://portlandpress.com/biochemj/article/429/1/205/45438/Pyruvate-dehydrogenase-kinase-1-controls},
	doi = {10/d2d23m},
	abstract = {Tight coupling between cytosolic and mitochondrial metabolism is key for GSIS (glucose-stimulated insulin secretion). In the present study we examined the regulatory contribution of PDH (pyruvate dehydrogenase) kinase 1, a negative regulator of PDH, to metabolic coupling in 832/13 clonal β-cells. Knockdown of PDH kinase 1 with siRNA (small interfering RNA) reduced its mRNA ({\textgreater}80\%) and protein level ({\textgreater}40\%) after 72 h. PDH activity, glucose-stimulated cellular oxygen consumption and pyruvate-stimulated mitochondrial oxygen consumption increased 1.7- (P{\textless}0.05), 1.6- (P{\textless}0.05) and 1.6-fold (P{\textless}0.05) respectively. Gas chromatography/MS revealed an altered metabolite profile upon silencing of PDH kinase 1, determined by increased levels of the tricarboxylic acid cycle intermediates malate, fumarate and α-ketoglutarate. These metabolic alterations were associated with exaggerated GSIS (5-fold compared with 3.1-fold in control cells; P{\textless}0.01). Insulin secretion, provoked by leucine and dimethylsuccinate, which feed into the tricarboxylic acid cycle bypassing PDH, was unaffected. The oxygen consumption and metabolic data strongly suggest that knockdown of PDH kinase 1 in β-cells permits increased metabolic flux of glucose-derived carbons into the tricarboxylic acid cycle via PDH. Enhanced insulin secretion is probably caused by increased generation of tricarboxylic acid cycle-derived reducing equivalents for mitochondrial electron transport to generate ATP and/or stimulatory metabolic intermediates. On the basis of these findings, we suggest that PDH kinase 1 is an important regulator of PDH in clonal β-cells and that PDH kinase 1 and PDH are important for efficient metabolic coupling. Maintaining low PDH kinase 1 expression/activity, keeping PDH in a dephosphorylated and active state, may be important for β-cells to achieve the metabolic flux rates necessary for maximal GSIS.},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Biochemical Journal},
	author = {Krus, Ulrika and Kotova, Olga and Spégel, Peter and Hallgard, Elna and Sharoyko, Vladimir V. and Vedin, Anna and Moritz, Thomas and Sugden, Mary C. and Koeck, Thomas and Mulder, Hindrik},
	month = jul,
	year = {2010},
	pages = {205--213},
}

Tight coupling between cytosolic and mitochondrial metabolism is key for GSIS (glucose-stimulated insulin secretion). In the present study we examined the regulatory contribution of PDH (pyruvate dehydrogenase) kinase 1, a negative regulator of PDH, to metabolic coupling in 832/13 clonal β-cells. Knockdown of PDH kinase 1 with siRNA (small interfering RNA) reduced its mRNA (\textgreater80%) and protein level (\textgreater40%) after 72 h. PDH activity, glucose-stimulated cellular oxygen consumption and pyruvate-stimulated mitochondrial oxygen consumption increased 1.7- (P\textless0.05), 1.6- (P\textless0.05) and 1.6-fold (P\textless0.05) respectively. Gas chromatography/MS revealed an altered metabolite profile upon silencing of PDH kinase 1, determined by increased levels of the tricarboxylic acid cycle intermediates malate, fumarate and α-ketoglutarate. These metabolic alterations were associated with exaggerated GSIS (5-fold compared with 3.1-fold in control cells; P\textless0.01). Insulin secretion, provoked by leucine and dimethylsuccinate, which feed into the tricarboxylic acid cycle bypassing PDH, was unaffected. The oxygen consumption and metabolic data strongly suggest that knockdown of PDH kinase 1 in β-cells permits increased metabolic flux of glucose-derived carbons into the tricarboxylic acid cycle via PDH. Enhanced insulin secretion is probably caused by increased generation of tricarboxylic acid cycle-derived reducing equivalents for mitochondrial electron transport to generate ATP and/or stimulatory metabolic intermediates. On the basis of these findings, we suggest that PDH kinase 1 is an important regulator of PDH in clonal β-cells and that PDH kinase 1 and PDH are important for efficient metabolic coupling. Maintaining low PDH kinase 1 expression/activity, keeping PDH in a dephosphorylated and active state, may be important for β-cells to achieve the metabolic flux rates necessary for maximal GSIS.

@article{petersson_auxin_2009,
	title = {An {Auxin} {Gradient} and {Maximum} in the \textit{{Arabidopsis}} {Root} {Apex} {Shown} by {High}-{Resolution} {Cell}-{Specific} {Analysis} of {IAA} {Distribution} and {Synthesis}},
	volume = {21},
	issn = {1532-298X, 1040-4651},
	url = {https://academic.oup.com/plcell/article/21/6/1659/6095411},
	doi = {10/ddgn83},
	abstract = {Abstract
            Local concentration gradients of the plant growth regulator auxin (indole-3-acetic acid [IAA]) are thought to instruct the positioning of organ primordia and stem cell niches and to direct cell division, expansion, and differentiation. High-resolution measurements of endogenous IAA concentrations in support of the gradient hypothesis are required to substantiate this hypothesis. Here, we introduce fluorescence-activated cell sorting of green fluorescent protein–marked cell types combined with highly sensitive mass spectrometry methods as a novel means for analyses of IAA distribution and metabolism at cellular resolution. Our results reveal the presence of IAA concentration gradients within the Arabidopsis thaliana root tip with a distinct maximum in the organizing quiescent center of the root apex. We also demonstrate that the root apex provides an important source of IAA and that cells of all types display a high synthesis capacity, suggesting a substantial contribution of local biosynthesis to auxin homeostasis in the root tip. Our results indicate that local biosynthesis and polar transport combine to produce auxin gradients and maxima in the root tip.},
	language = {en},
	number = {6},
	urldate = {2021-06-08},
	journal = {The Plant Cell},
	author = {Petersson, Sara V. and Johansson, Annika I. and Kowalczyk, Mariusz and Makoveychuk, Alexander and Wang, Jean Y. and Moritz, Thomas and Grebe, Markus and Benfey, Philip N. and Sandberg, Göran and Ljung, Karin},
	month = aug,
	year = {2009},
	pages = {1659--1668},
}

Abstract Local concentration gradients of the plant growth regulator auxin (indole-3-acetic acid [IAA]) are thought to instruct the positioning of organ primordia and stem cell niches and to direct cell division, expansion, and differentiation. High-resolution measurements of endogenous IAA concentrations in support of the gradient hypothesis are required to substantiate this hypothesis. Here, we introduce fluorescence-activated cell sorting of green fluorescent protein–marked cell types combined with highly sensitive mass spectrometry methods as a novel means for analyses of IAA distribution and metabolism at cellular resolution. Our results reveal the presence of IAA concentration gradients within the Arabidopsis thaliana root tip with a distinct maximum in the organizing quiescent center of the root apex. We also demonstrate that the root apex provides an important source of IAA and that cells of all types display a high synthesis capacity, suggesting a substantial contribution of local biosynthesis to auxin homeostasis in the root tip. Our results indicate that local biosynthesis and polar transport combine to produce auxin gradients and maxima in the root tip.

@article{mauriat_analyses_2009,
	title = {Analyses of {GA20ox}- and {GID1}-over-expressing aspen suggest that gibberellins play two distinct roles in wood formation},
	volume = {58},
	issn = {1365-313X},
	doi = {10/cqnj6n},
	abstract = {Gibberellins (GAs) are involved in many aspects of plant development, including shoot growth, flowering and wood formation. Increased levels of bioactive GAs are known to induce xylogenesis and xylem fiber elongation in aspen. However, there is currently little information on the response pathway(s) that mediate GA effects on wood formation. Here we characterize an important element of the GA pathway in hybrid aspen: the GA receptor, GID1. Four orthologs of GID1 were identified in Populus tremula x P. tremuloides (PttGID1.1-1.4). These were functional when expressed in Arabidopsis thaliana, and appear to present a degree of sub-functionalization in hybrid aspen. PttGID1.1 and PttGID1.3 were over-expressed in independent lines of hybrid aspen using either the 35S promoter or a xylem-specific promoter (LMX5). The 35S:PttGID1 over-expressors shared several phenotypic traits previously described in 35S:AtGA20ox1 over-expressors, including rapid growth, increased elongation, and increased xylogenesis. However, their xylem fibers were not elongated, unlike those of 35S:AtGA20ox1 plants. Similar differences in the xylem fiber phenotype were observed when PttGID1.1, PttGID1.3 or AtGA20ox1 were expressed under the control of the LMX5 promoter, suggesting either that PttGID1.1 and PttGID1.3 play no role in fiber elongation or that GA homeostasis is strongly controlled when GA signaling is altered. Our data suggest that GAs are required in two distinct wood-formation processes that have tissue-specific signaling pathways: xylogenesis, as mediated by GA signaling in the cambium, and fiber elongation in the developing xylem.},
	language = {eng},
	number = {6},
	journal = {The Plant Journal: For Cell and Molecular Biology},
	author = {Mauriat, Mélanie and Moritz, Thomas},
	month = jun,
	year = {2009},
	pmid = {19228336},
	keywords = {Amino Acid Sequence, Arabidopsis, Cloning, Molecular, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Plant, Gibberellins, Mixed Function Oxygenases, Molecular Sequence Data, Plant Proteins, Plants, Genetically Modified, Populus, Promoter Regions, Genetic, RNA, Plant, Receptors, Cell Surface, Sequence Alignment, Wood},
	pages = {989--1003},
}

Gibberellins (GAs) are involved in many aspects of plant development, including shoot growth, flowering and wood formation. Increased levels of bioactive GAs are known to induce xylogenesis and xylem fiber elongation in aspen. However, there is currently little information on the response pathway(s) that mediate GA effects on wood formation. Here we characterize an important element of the GA pathway in hybrid aspen: the GA receptor, GID1. Four orthologs of GID1 were identified in Populus tremula x P. tremuloides (PttGID1.1-1.4). These were functional when expressed in Arabidopsis thaliana, and appear to present a degree of sub-functionalization in hybrid aspen. PttGID1.1 and PttGID1.3 were over-expressed in independent lines of hybrid aspen using either the 35S promoter or a xylem-specific promoter (LMX5). The 35S:PttGID1 over-expressors shared several phenotypic traits previously described in 35S:AtGA20ox1 over-expressors, including rapid growth, increased elongation, and increased xylogenesis. However, their xylem fibers were not elongated, unlike those of 35S:AtGA20ox1 plants. Similar differences in the xylem fiber phenotype were observed when PttGID1.1, PttGID1.3 or AtGA20ox1 were expressed under the control of the LMX5 promoter, suggesting either that PttGID1.1 and PttGID1.3 play no role in fiber elongation or that GA homeostasis is strongly controlled when GA signaling is altered. Our data suggest that GAs are required in two distinct wood-formation processes that have tissue-specific signaling pathways: xylogenesis, as mediated by GA signaling in the cambium, and fiber elongation in the developing xylem.

@article{redestig_compensation_2009,
	title = {Compensation for {Systematic} {Cross}-{Contribution} {Improves} {Normalization} of {Mass} {Spectrometry} {Based} {Metabolomics} {Data}},
	volume = {81},
	issn = {0003-2700, 1520-6882},
	url = {https://pubs.acs.org/doi/10.1021/ac901143w},
	doi = {10/fr25p2},
	language = {en},
	number = {19},
	urldate = {2021-06-08},
	journal = {Analytical Chemistry},
	author = {Redestig, Henning and Fukushima, Atsushi and Stenlund, Hans and Moritz, Thomas and Arita, Masanori and Saito, Kazuki and Kusano, Miyako},
	month = oct,
	year = {2009},
	pages = {7974--7980},
}

@article{van_der_merwe_decreased_2009,
	title = {Decreased {Mitochondrial} {Activities} of {Malate} {Dehydrogenase} and {Fumarase} in {Tomato} {Lead} to {Altered} {Root} {Growth} and {Architecture} via {Diverse} {Mechanisms}},
	volume = {149},
	issn = {1532-2548},
	url = {https://academic.oup.com/plphys/article/149/2/653/6107909},
	doi = {10/dnz8fc},
	abstract = {Abstract
            Transgenic tomato (Solanum lycopersicum) plants in which either mitochondrial malate dehydrogenase or fumarase was antisense inhibited have previously been characterized to exhibit altered photosynthetic metabolism. Here, we demonstrate that these manipulations also resulted in differences in root growth, with both transgenics being characterized by a dramatic reduction of root dry matter deposition and respiratory activity but opposite changes with respect to root area. A range of physiological, molecular, and biochemical experiments were carried out in order to determine whether changes in root morphology were due to altered metabolism within the root itself, alterations in the nature of the transformants' root exudation, consequences of alteration in the efficiency of photoassimilate delivery to the root, or a combination of these factors. Grafting experiments in which the transformants were reciprocally grafted to wild-type controls suggested that root length and area were determined by the aerial part of the plant but that biomass was not. Despite the transgenic roots displaying alteration in the expression of phytohormone-associated genes, evaluation of the levels of the hormones themselves revealed that, with the exception of gibberellins, they were largely unaltered. When taken together, these combined experiments suggest that root biomass and growth are retarded by root-specific alterations in metabolism and gibberellin contents. These data are discussed in the context of current models of root growth and biomass partitioning.},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {Plant Physiology},
	author = {van der Merwe, Margaretha J. and Osorio, Sonia and Moritz, Thomas and Nunes-Nesi, Adriano and Fernie, Alisdair R.},
	month = feb,
	year = {2009},
	pages = {653--669},
}

Abstract Transgenic tomato (Solanum lycopersicum) plants in which either mitochondrial malate dehydrogenase or fumarase was antisense inhibited have previously been characterized to exhibit altered photosynthetic metabolism. Here, we demonstrate that these manipulations also resulted in differences in root growth, with both transgenics being characterized by a dramatic reduction of root dry matter deposition and respiratory activity but opposite changes with respect to root area. A range of physiological, molecular, and biochemical experiments were carried out in order to determine whether changes in root morphology were due to altered metabolism within the root itself, alterations in the nature of the transformants' root exudation, consequences of alteration in the efficiency of photoassimilate delivery to the root, or a combination of these factors. Grafting experiments in which the transformants were reciprocally grafted to wild-type controls suggested that root length and area were determined by the aerial part of the plant but that biomass was not. Despite the transgenic roots displaying alteration in the expression of phytohormone-associated genes, evaluation of the levels of the hormones themselves revealed that, with the exception of gibberellins, they were largely unaltered. When taken together, these combined experiments suggest that root biomass and growth are retarded by root-specific alterations in metabolism and gibberellin contents. These data are discussed in the context of current models of root growth and biomass partitioning.

@article{hytonen_gibberellin_2009,
	title = {Gibberellin mediates daylength-controlled differentiation of vegetative meristems in strawberry ({Fragaria} × ananassa {Duch})},
	volume = {9},
	issn = {1471-2229},
	url = {http://bmcplantbiol.biomedcentral.com/articles/10.1186/1471-2229-9-18},
	doi = {10/fk39gx},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {BMC Plant Biology},
	author = {Hytönen, Timo and Elomaa, Paula and Moritz, Thomas and Junttila, Olavi},
	year = {2009},
	pages = {18},
}

@article{frenkel_improper_2009,
	title = {Improper excess light energy dissipation in {Arabidopsis} results in a metabolic reprogramming},
	volume = {9},
	issn = {1471-2229},
	url = {https://doi.org/10.1186/1471-2229-9-12},
	doi = {10/ffdbr8},
	abstract = {Plant performance is affected by the level of expression of PsbS, a key photoprotective protein involved in the process of feedback de-excitation (FDE), or the qE component of non-photochemical quenching, NPQ.},
	number = {1},
	urldate = {2021-06-08},
	journal = {BMC Plant Biology},
	author = {Frenkel, Martin and Külheim, Carsten and Jänkänpää, Hanna Johansson and Skogström, Oskar and Dall'Osto, Luca and Ågren, Jon and Bassi, Roberto and Moritz, Thomas and Moen, Jon and Jansson, Stefan},
	month = jan,
	year = {2009},
	keywords = {Herbivore Preference, Partial Little Square Discriminant Analysis, Partial Little Square Discriminant Analysis Model, Photooxidative Stress, Photosynthetic Light Reaction},
	pages = {12},
}

Plant performance is affected by the level of expression of PsbS, a key photoprotective protein involved in the process of feedback de-excitation (FDE), or the qE component of non-photochemical quenching, NPQ.

@article{bylesjo_integrated_2009,
	title = {Integrated {Analysis} of {Transcript}, {Protein} and {Metabolite} {Data} {To} {Study} {Lignin} {Biosynthesis} in {Hybrid} {Aspen}},
	volume = {8},
	issn = {1535-3893, 1535-3907},
	url = {https://pubs.acs.org/doi/10.1021/pr800298s},
	doi = {10/ddqkpn},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Journal of Proteome Research},
	author = {Bylesjö, Max and Nilsson, Robert and Srivastava, Vaibhav and Grönlund, Andreas and Johansson, Annika I. and Jansson, Stefan and Karlsson, Jan and Moritz, Thomas and Wingsle, Gunnar and Trygg, Johan},
	month = jan,
	year = {2009},
	pages = {199--210},
}

@article{galindo_metabolomic_2009,
	title = {Metabolomic evaluation of pulsed electric field-induced stress on potato tissue},
	volume = {230},
	issn = {0032-0935, 1432-2048},
	url = {http://link.springer.com/10.1007/s00425-009-0950-2},
	doi = {10/bg94jg},
	language = {en},
	number = {3},
	urldate = {2021-06-08},
	journal = {Planta},
	author = {Galindo, Federico Gómez and Dejmek, Petr and Lundgren, Krister and Rasmusson, Allan G. and Vicente, António and Moritz, Thomas},
	month = aug,
	year = {2009},
	pages = {469--479},
}

@article{wuolikainen_optimization_2009,
	title = {Optimization of procedures for collecting and storing of {CSF} for studying the metabolome in {ALS}},
	volume = {10},
	issn = {1748-2968, 1471-180X},
	url = {http://www.tandfonline.com/doi/full/10.1080/17482960902871009},
	doi = {10/cjcnvg},
	language = {en},
	number = {4},
	urldate = {2021-06-08},
	journal = {Amyotrophic Lateral Sclerosis},
	author = {Wuolikainen, Anna and Hedenström, Mattias and Moritz, Thomas and Marklund, Stefan L. and Antti, Henrik and Andersen, Peter M.},
	month = jan,
	year = {2009},
	pages = {229--236},
}

@article{chorell_predictive_2009,
	title = {Predictive {Metabolomics} {Evaluation} of {Nutrition}-{Modulated} {Metabolic} {Stress} {Responses} in {Human} {Blood} {Serum} {During} the {Early} {Recovery} {Phase} of {Strenuous} {Physical} {Exercise}},
	volume = {8},
	issn = {1535-3893, 1535-3907},
	url = {https://pubs.acs.org/doi/10.1021/pr900081q},
	doi = {10/fn674z},
	language = {en},
	number = {6},
	urldate = {2021-06-08},
	journal = {Journal of Proteome Research},
	author = {Chorell, Elin and Moritz, Thomas and Branth, Stefan and Antti, Henrik and Svensson, Michael B.},
	month = jun,
	year = {2009},
	pages = {2966--2977},
}

@article{van_der_merwe_role_2009,
	title = {The role and regulation of the tricarboxylic acid cycle in {Solanum} lycopersicum roots},
	volume = {75},
	issn = {02546299},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0254629909001203},
	doi = {10/d84qt3},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {South African Journal of Botany},
	author = {Van der Merwe, M.J. and Osorio, S. and Moritz, T. and Nunes-Nesi, A. and Fernie, A.R.},
	month = apr,
	year = {2009},
	pages = {424},
}

@article{andersen_second_2008,
	title = {A {Second} {Pathway} to {Degrade} {Pyrimidine} {Nucleic} {Acid} {Precursors} in {Eukaryotes}},
	volume = {380},
	issn = {00222836},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0022283608005846},
	doi = {10/dbbqnk},
	language = {en},
	number = {4},
	urldate = {2021-06-10},
	journal = {Journal of Molecular Biology},
	author = {Andersen, Gorm and Björnberg, Olof and Polakova, Silvia and Pynyaha, Yuriy and Rasmussen, Anna and Møller, Kasper and Hofer, Anders and Moritz, Thomas and Sandrini, Michael Paolo Bastner and Merico, Anna-Maria and Compagno, Concetta and Åkerlund, Hans-Erik and Gojković, Zoran and Piškur, Jure},
	month = jul,
	year = {2008},
	pages = {656--666},
}

@article{zheng_arabidopsis_2008,
	title = {Arabidopsis sterol carrier protein-2 is required for normal development of seeds and seedlings},
	volume = {59},
	issn = {1460-2431, 0022-0957},
	url = {https://academic.oup.com/jxb/article-lookup/doi/10.1093/jxb/ern201},
	doi = {10/c2pqd9},
	language = {en},
	number = {12},
	urldate = {2021-06-10},
	journal = {Journal of Experimental Botany},
	author = {Zheng, Bing Song and Rönnberg, Elin and Viitanen, Lenita and Salminen, Tiina A. and Lundgren, Krister and Moritz, Thomas and Edqvist, Johan},
	month = sep,
	year = {2008},
	pages = {3485--3499},
}

@article{bruce_evaluation_2008,
	title = {Evaluation of a protocol for metabolic profiling studies on human blood plasma by combined ultra-performance liquid chromatography/mass spectrometry: {From} extraction to data analysis},
	volume = {372},
	issn = {00032697},
	shorttitle = {Evaluation of a protocol for metabolic profiling studies on human blood plasma by combined ultra-performance liquid chromatography/mass spectrometry},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S0003269707006161},
	doi = {10/fm7np6},
	language = {en},
	number = {2},
	urldate = {2021-06-10},
	journal = {Analytical Biochemistry},
	author = {Bruce, Stephen J. and Jonsson, Pär and Antti, Henrik and Cloarec, Olivier and Trygg, Johan and Marklund, Stefan L. and Moritz, Thomas},
	month = jan,
	year = {2008},
	pages = {237--249},
}

@article{gallego-giraldo_gibberellin_2008,
	title = {Gibberellin {Homeostasis} in {Tobacco} is {Regulated} by {Gibberellin} {Metabolism} {Genes} with {Different} {Gibberellin} {Sensitivity}},
	volume = {49},
	issn = {1471-9053, 0032-0781},
	url = {https://academic.oup.com/pcp/article-lookup/doi/10.1093/pcp/pcn042},
	doi = {10/ckqdfn},
	language = {en},
	number = {5},
	urldate = {2021-06-10},
	journal = {Plant and Cell Physiology},
	author = {Gallego-Giraldo, Lina and Ubeda-Tomás, Susana and Gisbert, Carmina and García-Martínez, José L. and Moritz, Thomas and López-Díaz, Isabel},
	month = may,
	year = {2008},
	pages = {679--690},
}

@article{depuydt_modulation_2008,
	title = {Modulation of the {Hormone} {Setting} by \textit{{Rhodococcus} fascians} {Results} in {Ectopic} \textit{{KNOX}} {Activation} in {Arabidopsis}},
	volume = {146},
	issn = {1532-2548},
	url = {https://academic.oup.com/plphys/article/146/3/1267/6107230},
	doi = {10/dkp574},
	abstract = {Abstract
            The biotrophic actinomycete Rhodococcus fascians has a profound impact on plant development and a common aspect of the symptomatology is the deformation of infected leaves. In Arabidopsis (Arabidopsis thaliana), the serrated leaf margins formed upon infection resemble the leaf phenotype of transgenic plants with ectopic expression of KNOTTED-like homeobox (KNOX) genes. Through transcript profiling, we demonstrate that class-I KNOX genes are transcribed in symptomatic leaves. Functional analysis revealed that BREVIPEDICELLUS/KNOTTED-LIKE1 and mainly SHOOT MERISTEMLESS were essential for the observed leaf dissection. However, these results also positioned the KNOX genes downstream in the signaling cascade triggered by R. fascians infection. The much faster activation of ARABIDOPSIS RESPONSE REGULATOR5 and the establishment of homeostatic and feedback mechanisms to control cytokinin (CK) levels support the overrepresentation of this hormone in infected plants due to the secretion by the pathogen, thereby placing the CK response high up in the cascade. Hormone measurements show a net decrease of tested CKs, indicating either that secretion by the bacterium and degradation by the plant are in balance, or, as suggested by the strong reaction of 35S:CKX plants, that other CKs are at play. At early time points of the interaction, activation of gibberellin 2-oxidase presumably installs a local hormonal setting favorable for meristematic activity that provokes leaf serrations. The results are discussed in the context of symptom development, evasion of plant defense, and the establishment of a specific niche by R. fascians.},
	language = {en},
	number = {3},
	urldate = {2021-06-10},
	journal = {Plant Physiology},
	author = {Depuydt, Stephen and Doležal, Karel and Van Lijsebettens, Mieke and Moritz, Thomas and Holsters, Marcelle and Vereecke, Danny},
	month = mar,
	year = {2008},
	pages = {1267--1281},
}

Abstract The biotrophic actinomycete Rhodococcus fascians has a profound impact on plant development and a common aspect of the symptomatology is the deformation of infected leaves. In Arabidopsis (Arabidopsis thaliana), the serrated leaf margins formed upon infection resemble the leaf phenotype of transgenic plants with ectopic expression of KNOTTED-like homeobox (KNOX) genes. Through transcript profiling, we demonstrate that class-I KNOX genes are transcribed in symptomatic leaves. Functional analysis revealed that BREVIPEDICELLUS/KNOTTED-LIKE1 and mainly SHOOT MERISTEMLESS were essential for the observed leaf dissection. However, these results also positioned the KNOX genes downstream in the signaling cascade triggered by R. fascians infection. The much faster activation of ARABIDOPSIS RESPONSE REGULATOR5 and the establishment of homeostatic and feedback mechanisms to control cytokinin (CK) levels support the overrepresentation of this hormone in infected plants due to the secretion by the pathogen, thereby placing the CK response high up in the cascade. Hormone measurements show a net decrease of tested CKs, indicating either that secretion by the bacterium and degradation by the plant are in balance, or, as suggested by the strong reaction of 35S:CKX plants, that other CKs are at play. At early time points of the interaction, activation of gibberellin 2-oxidase presumably installs a local hormonal setting favorable for meristematic activity that provokes leaf serrations. The results are discussed in the context of symptom development, evasion of plant defense, and the establishment of a specific niche by R. fascians.

@article{de_grauwe_reduced_2008,
	title = {Reduced gibberellin response affects ethylene biosynthesis and responsiveness in the {Arabidopsis} \textit{gai eto2‐1} double mutant},
	volume = {177},
	issn = {0028-646X, 1469-8137},
	url = {https://onlinelibrary.wiley.com/doi/10.1111/j.1469-8137.2007.02263.x},
	doi = {10/bjkq86},
	language = {en},
	number = {1},
	urldate = {2021-06-10},
	journal = {New Phytologist},
	author = {De Grauwe, Liesbeth and Chaerle, Laury and Dugardeyn, Jasper and Decat, Jan and Rieu, Ivo and Vriezen, Wim H. and Moritz, Thomas and Beemster, Gerrit T. S. and Phillips, Andy L. and Harberd, Nicholas P. and Hedden, Peter and Van Der Straeten, Dominique},
	month = jan,
	year = {2008},
	pages = {128--141},
}

@article{men_sterol-dependent_2008,
	title = {Sterol-dependent endocytosis mediates post-cytokinetic acquisition of {PIN2} auxin efflux carrier polarity},
	volume = {10},
	issn = {1465-7392, 1476-4679},
	url = {http://www.nature.com/articles/ncb1686},
	doi = {10/chxrxg},
	language = {en},
	number = {2},
	urldate = {2021-06-10},
	journal = {Nature Cell Biology},
	author = {Men, Shuzhen and Boutté, Yohann and Ikeda, Yoshihisa and Li, Xugang and Palme, Klaus and Stierhof, York-Dieter and Hartmann, Marie-Andrée and Moritz, Thomas and Grebe, Markus},
	month = feb,
	year = {2008},
	pages = {237--244},
}

@article{gutierrez_lack_2008,
	title = {The lack of a systematic validation of reference genes: a serious pitfall undervalued in reverse transcription-polymerase chain reaction ({RT}-{PCR}) analysis in plants},
	volume = {6},
	issn = {14677644, 14677652},
	shorttitle = {The lack of a systematic validation of reference genes},
	url = {http://doi.wiley.com/10.1111/j.1467-7652.2008.00346.x},
	doi = {10/d6bcb9},
	language = {en},
	number = {6},
	urldate = {2021-06-10},
	journal = {Plant Biotechnology Journal},
	author = {Gutierrez, Laurent and Mauriat, Mlanie and Gunin, Stphanie and Pelloux, Jrme and Lefebvre, Jean-Franois and Louvet, Romain and Rusterucci, Christine and Moritz, Thomas and Guerineau, Franois and Bellini, Catherine and Van Wuytswinkel, Olivier},
	month = aug,
	year = {2008},
	pages = {609--618},
}

@article{wiklund_visualization_2008,
	title = {Visualization of {GC}/{TOF}-{MS}-{Based} {Metabolomics} {Data} for {Identification} of {Biochemically} {Interesting} {Compounds} {Using} {OPLS} {Class} {Models}},
	volume = {80},
	issn = {0003-2700, 1520-6882},
	url = {https://pubs.acs.org/doi/10.1021/ac0713510},
	doi = {10/bjbc4d},
	language = {en},
	number = {1},
	urldate = {2021-06-10},
	journal = {Analytical Chemistry},
	author = {Wiklund, Susanne and Johansson, Erik and Sjöström, Lina and Mellerowicz, Ewa J. and Edlund, Ulf and Shockcor, John P. and Gottfries, Johan and Moritz, Thomas and Trygg, Johan},
	month = jan,
	year = {2008},
	pages = {115--122},
}

@article{kusano_application_2007,
	title = {Application of a metabolomic method combining one-dimensional and two-dimensional gas chromatography-time-of-flight/mass spectrometry to metabolic phenotyping of natural variants in rice},
	volume = {855},
	issn = {15700232},
	url = {https://linkinghub.elsevier.com/retrieve/pii/S1570023207003479},
	doi = {10/ds6j34},
	language = {en},
	number = {1},
	urldate = {2021-06-10},
	journal = {Journal of Chromatography B},
	author = {Kusano, Miyako and Fukushima, Atsushi and Kobayashi, Makoto and Hayashi, Naomi and Jonsson, Pär and Moritz, Thomas and Ebana, Kaworu and Saito, Kazuki},
	month = aug,
	year = {2007},
	pages = {71--79},
}

@article{bjorklund_cross-talk_2007,
	title = {Cross-talk between gibberellin and auxin in development of {Populus} wood: gibberellin stimulates polar auxin transport and has a common transcriptome with auxin: {Cross}-talk between {GA} and auxin in wood development},
	volume = {52},
	issn = {09607412},
	shorttitle = {Cross-talk between gibberellin and auxin in development of {Populus} wood},
	url = {http://doi.wiley.com/10.1111/j.1365-313X.2007.03250.x},
	doi = {10/chbxht},
	language = {en},
	number = {3},
	urldate = {2021-06-10},
	journal = {The Plant Journal},
	author = {Björklund, Simon and Antti, Henrik and Uddestrand, Ida and Moritz, Thomas and Sundberg, Björn},
	month = sep,
	year = {2007},
	pages = {499--511},
}

@article{bylesjo_data_2007,
	title = {Data integration in plant biology: the {O2PLS} method for combined modeling of transcript and metabolite data},
	volume = {52},
	issn = {09607412, 1365313X},
	shorttitle = {Data integration in plant biology},
	url = {http://doi.wiley.com/10.1111/j.1365-313X.2007.03293.x},
	doi = {10/dq2z2k},
	language = {en},
	number = {6},
	urldate = {2021-06-10},
	journal = {The Plant Journal},
	author = {Bylesjö, Max and Eriksson, Daniel and Kusano, Miyako and Moritz, Thomas and Trygg, Johan},
	month = dec,
	year = {2007},
	pages = {1181--1191},
}

@article{druart_environmental_2007,
	title = {Environmental and hormonal regulation of the activity-dormancy cycle in the cambial meristem involves stage-specific modulation of transcriptional and metabolic networks: {Molecular} analysis of cambial activity-dormancy cycle},
	volume = {50},
	issn = {09607412, 1365313X},
	shorttitle = {Environmental and hormonal regulation of the activity-dormancy cycle in the cambial meristem involves stage-specific modulation of transcriptional and metabolic networks},
	url = {http://doi.wiley.com/10.1111/j.1365-313X.2007.03077.x},
	doi = {10/cgt589},
	language = {en},
	number = {4},
	urldate = {2021-06-10},
	journal = {The Plant Journal},
	author = {Druart, Nathalie and Johansson, Annika and Baba, Kyoko and Schrader, Jarmo and Sjödin, Andreas and Bhalerao, Rupali R. and Resman, Lars and Trygg, Johan and Moritz, Thomas and Bhalerao, Rishikesh P.},
	month = apr,
	year = {2007},
	pages = {557--573},
}

@article{vandenbussche_ethylene-induced_2007,
	title = {Ethylene-induced {Arabidopsis} hypocotyl elongation is dependent on but not mediated by gibberellins},
	volume = {58},
	issn = {0022-0957, 1460-2431},
	url = {https://academic.oup.com/jxb/article-lookup/doi/10.1093/jxb/erm288},
	doi = {10/c9kqxg},
	language = {en},
	number = {15-16},
	urldate = {2021-06-10},
	journal = {Journal of Experimental Botany},
	author = {Vandenbussche, F. and Vancompernolle, B. and Rieu, I. and Ahmad, M. and Phillips, A. and Moritz, T. and Hedden, P. and Van Der Straeten, D.},
	month = nov,
	year = {2007},
	pages = {4269--4281},
}

@article{bylesjo_orthogonal_2007,
	title = {Orthogonal projections to latent structures as a strategy for microarray data normalization},
	volume = {8},
	issn = {1471-2105},
	url = {https://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-8-207},
	doi = {10/dfs78z},
	language = {en},
	number = {1},
	urldate = {2021-06-10},
	journal = {BMC Bioinformatics},
	author = {Bylesjö, Max and Eriksson, Daniel and Sjödin, Andreas and Jansson, Stefan and Moritz, Thomas and Trygg, Johan},
	month = dec,
	year = {2007},
	pages = {207},
}

@article{guy_plant_2007,
	title = {Plant metabolomics coming of age},
	volume = {132},
	issn = {00319317},
	url = {http://doi.wiley.com/10.1111/j.1399-3054.2007.01020.x},
	doi = {10/dt585v},
	language = {en},
	number = {2},
	urldate = {2021-06-10},
	journal = {Physiologia Plantarum},
	author = {Guy, Charles and Kopka, Joachim and Moritz, Thomas},
	month = dec,
	year = {2007},
	pages = {113--116},
}

@article{thysell_reliable_2007,
	title = {Reliable {Profile} {Detection} in {Comparative} {Metabolomics}},
	volume = {11},
	issn = {1536-2310, 1557-8100},
	url = {http://www.liebertpub.com/doi/10.1089/omi.2007.0006},
	doi = {10/cvvjjh},
	language = {en},
	number = {2},
	urldate = {2021-06-10},
	journal = {OMICS: A Journal of Integrative Biology},
	author = {Thysell, Elin and Pohjanen, Elin and Lindberg, Johan and Schuppe-Koistinen, Ina and Moritz, Thomas and Jonsson, Pär and Antti, Henrik},
	month = jun,
	year = {2007},
	pages = {209--224},
}

@article{achard_plant_2007,
	title = {The plant stress hormone ethylene controls floral transition via {DELLA}-dependent regulation of floral meristem-identity genes},
	volume = {104},
	issn = {0027-8424, 1091-6490},
	url = {http://www.pnas.org/cgi/doi/10.1073/pnas.0610717104},
	doi = {10/d92wbd},
	language = {en},
	number = {15},
	urldate = {2021-06-10},
	journal = {Proceedings of the National Academy of Sciences},
	author = {Achard, P. and Baghour, M. and Chapple, A. and Hedden, P. and Van Der Straeten, D. and Genschik, P. and Moritz, T. and Harberd, N. P.},
	month = apr,
	year = {2007},
	pages = {6484--6489},
}

@article{kusano_unbiased_2007,
	title = {Unbiased characterization of genotype-dependent metabolic regulations by metabolomic approach in {Arabidopsis} thaliana},
	volume = {1},
	issn = {1752-0509},
	url = {http://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-1-53},
	doi = {10/djdc4c},
	language = {en},
	number = {1},
	urldate = {2021-06-10},
	journal = {BMC Systems Biology},
	author = {Kusano, Miyako and Fukushima, Atsushi and Arita, Masanori and Jonsson, Pär and Moritz, Thomas and Kobayashi, Makoto and Hayashi, Naomi and Tohge, Takayuki and Saito, Kazuki},
	year = {2007},
	pages = {53},
}

@article{keller_arabidopsis_2006,
	title = {Arabidopsis {REGULATOR} {OF} {AXILLARY} {MERISTEMS1} controls a leaf axil stem cell niche and modulates vegetative development},
	volume = {18},
	issn = {1040-4651},
	doi = {10.1105/tpc.105.038588},
	abstract = {Shoot branching is a major determinant of variation in plant stature. Branches, which form secondary growth axes, originate from stem cells activated in leaf axils. The initial steps by which axillary meristems (AMs) are specified and their stem cells organized are still poorly understood. We identified gain- and loss-of-function alleles at the Arabidopsis thaliana REGULATOR OF AXILLARY MERISTEMS1 (RAX1) locus. RAX1 is encoded by the Myb-like transcription factor MYB37 and is an Arabidopsis homolog of the tomato ( Solanum lycopersicum) Blind gene. RAX1 is transiently expressed in a small central domain within the boundary zone separating shoot apical meristem and leaf primordia early in leaf primordium development. RAX1 genetically interacts with CUP-SHAPED COTYLEDON (CUC) genes and is required for the expression of CUC2 in the RAX1 expression domain, suggesting that RAX1 acts through CUC2. We propose that RAX1 functions to positionally specify a stem cell niche for AM formation. RAX1 also affects the timing of developmental phase transitions by negatively regulating gibberellic acid levels in the shoot apex. RAX1 thus defines a novel activity that links the specification of AM formation with the modulation of the rate of progression through developmental phases.},
	language = {English},
	number = {3},
	journal = {Plant Cell},
	author = {Keller, T. and Abbott, J. and Moritz, T. and Doerner, P.},
	month = mar,
	year = {2006},
	note = {Place: Rockville
Publisher: Amer Soc Plant Biologists
WOS:000236004900009},
	keywords = {arabidopsis-thaliana, cup-shaped-cotyledon, expression, gene   family, gibberellin, growth, initiation, organogenesis, shoot apical meristem, t-dna},
	pages = {598--611},
}

Shoot branching is a major determinant of variation in plant stature. Branches, which form secondary growth axes, originate from stem cells activated in leaf axils. The initial steps by which axillary meristems (AMs) are specified and their stem cells organized are still poorly understood. We identified gain- and loss-of-function alleles at the Arabidopsis thaliana REGULATOR OF AXILLARY MERISTEMS1 (RAX1) locus. RAX1 is encoded by the Myb-like transcription factor MYB37 and is an Arabidopsis homolog of the tomato ( Solanum lycopersicum) Blind gene. RAX1 is transiently expressed in a small central domain within the boundary zone separating shoot apical meristem and leaf primordia early in leaf primordium development. RAX1 genetically interacts with CUP-SHAPED COTYLEDON (CUC) genes and is required for the expression of CUC2 in the RAX1 expression domain, suggesting that RAX1 acts through CUC2. We propose that RAX1 functions to positionally specify a stem cell niche for AM formation. RAX1 also affects the timing of developmental phase transitions by negatively regulating gibberellic acid levels in the shoot apex. RAX1 thus defines a novel activity that links the specification of AM formation with the modulation of the rate of progression through developmental phases.

@article{andersson-gunneras_biosynthesis_2006,
	title = {Biosynthesis of cellulose-enriched tension wood in {Populus}: global analysis of transcripts and metabolites identifies biochemical and developmental regulators in secondary wall biosynthesis},
	volume = {45},
	issn = {1365-313X},
	shorttitle = {Biosynthesis of cellulose-enriched tension wood in {Populus}},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-313X.2005.02584.x},
	doi = {10/fkwhm3},
	abstract = {Stems and branches of angiosperm trees form tension wood (TW) when exposed to a gravitational stimulus. One of the main characteristics of TW, which distinguishes it from normal wood, is the formation of fibers with a thick inner gelatinous cell wall layer mainly composed of crystalline cellulose. Hence TW is enriched in cellulose, and deficient in lignin and hemicelluloses. An expressed sequence tag library made from TW-forming tissues in Populus tremula (L.) × tremuloides (Michx.) and data from transcript profiling using microarray and metabolite analysis were obtained during TW formation in Populus tremula (L.) in two growing seasons. The data were examined with the aim of identifying the genes responsible for the change in carbon (C) flow into various cell wall components, and the mechanisms important for the formation of the gelatinous cell wall layer (G-layer). A specific effort was made to identify carbohydrate-active enzymes with a putative function in cell wall biosynthesis. An increased C flux to cellulose was suggested by a higher abundance of sucrose synthase transcripts. However, genes related to the cellulose biosynthetic machinery were not generally affected, although the expression of secondary wall-specific CesA genes was modified in both directions. Other pathways for which the data suggested increased activity included lipid and glucosamine biosynthesis and the pectin degradation machinery. In addition, transcripts encoding fasciclin-like arabinogalactan proteins were particularly increased and found to lack true Arabidopsis orthologs. Major pathways for which the transcriptome and metabolome analysis suggested decreased activity were the pathway for C flux through guanosine 5′-diphosphate (GDP) sugars to mannans, the pentose phosphate pathway, lignin biosynthesis, and biosynthesis of cell wall matrix carbohydrates. Several differentially expressed auxin- and ethylene-related genes and transcription factors were also identified.},
	language = {en},
	number = {2},
	urldate = {2021-06-11},
	journal = {The Plant Journal},
	author = {Andersson-Gunnerås, Sara and Mellerowicz, Ewa J. and Love, Jonathan and Segerman, Bo and Ohmiya, Yasunori and Coutinho, Pedro M. and Nilsson, Peter and Henrissat, Bernard and Moritz, Thomas and Sundberg, Björn},
	year = {2006},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-313X.2005.02584.x},
	keywords = {cell walls, cellulose, development, hemicellulose, lignin, poplar},
	pages = {144--165},
}

Stems and branches of angiosperm trees form tension wood (TW) when exposed to a gravitational stimulus. One of the main characteristics of TW, which distinguishes it from normal wood, is the formation of fibers with a thick inner gelatinous cell wall layer mainly composed of crystalline cellulose. Hence TW is enriched in cellulose, and deficient in lignin and hemicelluloses. An expressed sequence tag library made from TW-forming tissues in Populus tremula (L.) × tremuloides (Michx.) and data from transcript profiling using microarray and metabolite analysis were obtained during TW formation in Populus tremula (L.) in two growing seasons. The data were examined with the aim of identifying the genes responsible for the change in carbon (C) flow into various cell wall components, and the mechanisms important for the formation of the gelatinous cell wall layer (G-layer). A specific effort was made to identify carbohydrate-active enzymes with a putative function in cell wall biosynthesis. An increased C flux to cellulose was suggested by a higher abundance of sucrose synthase transcripts. However, genes related to the cellulose biosynthetic machinery were not generally affected, although the expression of secondary wall-specific CesA genes was modified in both directions. Other pathways for which the data suggested increased activity included lipid and glucosamine biosynthesis and the pectin degradation machinery. In addition, transcripts encoding fasciclin-like arabinogalactan proteins were particularly increased and found to lack true Arabidopsis orthologs. Major pathways for which the transcriptome and metabolome analysis suggested decreased activity were the pathway for C flux through guanosine 5′-diphosphate (GDP) sugars to mannans, the pentose phosphate pathway, lignin biosynthesis, and biosynthesis of cell wall matrix carbohydrates. Several differentially expressed auxin- and ethylene-related genes and transcription factors were also identified.

@article{eriksson_ga4_2006,
	title = {{GA4} {Is} the {Active} {Gibberellin} in the {Regulation} of {LEAFY} {Transcription} and {Arabidopsis} {Floral} {Initiation}},
	volume = {18},
	issn = {1040-4651},
	url = {https://doi.org/10.1105/tpc.106.042317},
	doi = {10.1105/tpc.106.042317},
	abstract = {Flower initiation in Arabidopsis thaliana under noninductive short-day conditions is dependent on the biosynthesis of the plant hormone gibberellin (GA). This dependency can be explained, at least partly, by GA regulation of the flower meristem identity gene LEAFY (LFY) and the flowering time gene SUPPRESSOR OF CONSTANS1. Although it is well established that GA4 is the active GA in the regulation of Arabidopsis shoot elongation, the identity of the GA responsible for the regulation of Arabidopsis flowering has not been established. Through a combination of GA quantifications and sensitivity assays, we show that GA4 is the active GA in the regulation of LFY transcription and Arabidopsis flowering time under short-day conditions. The levels of GA4 and sucrose increase dramatically in the shoot apex shortly before floral initiation, and the regulation of genes involved in GA metabolism suggests that this increase is possibly due to transport of GAs and sucrose from outside sources to the shoot apex. Our results demonstrate that in the dicot Arabidopsis, in contrast with the monocot Lolium temulentum, GA4 is the active GA in the regulation of both shoot elongation and flower initiation.},
	number = {9},
	urldate = {2024-10-07},
	journal = {The Plant Cell},
	author = {Eriksson, Sven and Böhlenius, Henrik and Moritz, Thomas and Nilsson, Ove},
	month = sep,
	year = {2006},
	pages = {2172--2181},
}

Flower initiation in Arabidopsis thaliana under noninductive short-day conditions is dependent on the biosynthesis of the plant hormone gibberellin (GA). This dependency can be explained, at least partly, by GA regulation of the flower meristem identity gene LEAFY (LFY) and the flowering time gene SUPPRESSOR OF CONSTANS1. Although it is well established that GA4 is the active GA in the regulation of Arabidopsis shoot elongation, the identity of the GA responsible for the regulation of Arabidopsis flowering has not been established. Through a combination of GA quantifications and sensitivity assays, we show that GA4 is the active GA in the regulation of LFY transcription and Arabidopsis flowering time under short-day conditions. The levels of GA4 and sucrose increase dramatically in the shoot apex shortly before floral initiation, and the regulation of genes involved in GA metabolism suggests that this increase is possibly due to transport of GAs and sucrose from outside sources to the shoot apex. Our results demonstrate that in the dicot Arabidopsis, in contrast with the monocot Lolium temulentum, GA4 is the active GA in the regulation of both shoot elongation and flower initiation.

@article{achard_integration_2006,
	title = {Integration of plant responses to environmentally activated phytohormonal signals},
	volume = {311},
	issn = {0036-8075},
	doi = {10/fd7637},
	abstract = {Plants live in fixed locations and survive adversity by integrating growth responses to diverse environmental signals. Here, we show that the nuclear-localized growth-repressing DELLA proteins of Arabidopsis integrate responses to independent hormonal and environmental signals of adverse conditions. The growth restraint conferred by DELLA proteins is beneficial and promotes survival. We propose that DELLAs permit flexible and appropriate modulation of plant growth in response to changes in natural environments.},
	language = {English},
	number = {5757},
	journal = {Science},
	author = {Achard, P. and Cheng, H. and De Grauwe, L. and Decat, J. and Schoutteten, H. and Moritz, T. and Van Der Straeten, D. and Peng, J. R. and Harberd, N. P.},
	month = jan,
	year = {2006},
	note = {Place: Washington
Publisher: Amer Assoc Advancement Science
WOS:000234546300040},
	keywords = {arabidopsis-thaliana, floral   development, gene-expression, gibberellin response, growth, modulation, overexpression, protein, transcription factor, transduction},
	pages = {91--94},
}

Plants live in fixed locations and survive adversity by integrating growth responses to diverse environmental signals. Here, we show that the nuclear-localized growth-repressing DELLA proteins of Arabidopsis integrate responses to independent hormonal and environmental signals of adverse conditions. The growth restraint conferred by DELLA proteins is beneficial and promotes survival. We propose that DELLAs permit flexible and appropriate modulation of plant growth in response to changes in natural environments.

@article{benschop_long-term_2006,
	title = {Long-term submergence-induced elongation in {Rumex} palustris requires abscisic acid-dependent biosynthesis of gibberellin},
	volume = {141},
	issn = {0032-0889},
	doi = {10/fpnvsb},
	abstract = {Rumex palustris (polygonceae) responds to complete submergence with enhanced elongation of its youngest petioles. This process requires the presence of gibberellin (GA) and is associated with an increase in the concentration of GA 1 in elongating petioles. We have examined how GA biosynthesis was regulated in submerged plants. Therefore, cDNAs encoding GA-biosynthetic enzymes GA20-oxidase and GA3-oxidase, and the GA-deactivating enzyme GA2-oxidase were cloned from R. palustris and the kinetics of transcription of the corresponding genes was determined during a 24 h submergence period. The submergence-induced elongation response could be separated into several phases: (1) during the first phase of 4 h, petiole elongation was insensitive to GA; (2) from 4 to 6 h onward growth was limited by GA; and (3) from 15 h onward underwater elongation was dependent, but not limited by GA. Submergence induced an increase of GA 1 concentration, as well as enhanced transcript levels of RpGA3ox1. Exogenous abscisic acid repressed the transcript levels of RpGA20ox1 and RpGA3ox1 and thus inhibited the submergence-induced increase in GA(1). Abscisic acid had no effect on the tissue responsiveness to GA.},
	language = {English},
	number = {4},
	journal = {Plant Physiology},
	author = {Benschop, Joris J. and Bou, Jordi and Peeters, Anton J. M. and Wagemaker, Niels and Guhl, Kerstin and Ward, Dennis and Hedden, Peter and Moritz, Thomas and Voesenek, Laurentius A. C. J.},
	month = aug,
	year = {2006},
	note = {Place: Rockville
Publisher: Amer Soc Plant Biologists
WOS:000239636800044},
	keywords = {20-oxidase genes, arabidopsis, ethylene, expression, pea, petiole elongation, plant, rice, shoot elongation, stem elongation},
	pages = {1644--1652},
}

Rumex palustris (polygonceae) responds to complete submergence with enhanced elongation of its youngest petioles. This process requires the presence of gibberellin (GA) and is associated with an increase in the concentration of GA 1 in elongating petioles. We have examined how GA biosynthesis was regulated in submerged plants. Therefore, cDNAs encoding GA-biosynthetic enzymes GA20-oxidase and GA3-oxidase, and the GA-deactivating enzyme GA2-oxidase were cloned from R. palustris and the kinetics of transcription of the corresponding genes was determined during a 24 h submergence period. The submergence-induced elongation response could be separated into several phases: (1) during the first phase of 4 h, petiole elongation was insensitive to GA; (2) from 4 to 6 h onward growth was limited by GA; and (3) from 15 h onward underwater elongation was dependent, but not limited by GA. Submergence induced an increase of GA 1 concentration, as well as enhanced transcript levels of RpGA3ox1. Exogenous abscisic acid repressed the transcript levels of RpGA20ox1 and RpGA3ox1 and thus inhibited the submergence-induced increase in GA(1). Abscisic acid had no effect on the tissue responsiveness to GA.

@article{bylesjo_masqot-gui_2006,
	title = {{MASQOT}-{GUI}: spot quality assessment for the two-channel microarray platform},
	volume = {22},
	issn = {1367-4803},
	shorttitle = {{MASQOT}-{GUI}},
	url = {https://doi.org/10.1093/bioinformatics/btl434},
	doi = {10.1093/bioinformatics/btl434},
	abstract = {Summary: MASQOT-GUI provides an open-source, platform-independent software pipeline for two-channel microarray spot quality control. This includes gridding, segmentation, quantification, quality assessment and data visualization. It hosts a set of independent applications, with interactions between the tools as well as import and export support for external software. The implementation of automated multivariate quality control assessment, which is a unique feature of MASQOT-GUI, is based on the previously documented and evaluated MASQOT methodology. Further abilities of the application are outlined and illustrated.Availability: MASQOT-GUI is Java-based and licensed under the GNU LGPL. Source code and installation files are available for download at Contact: This email address is being protected from spambots. You need JavaScript enabled to view it. information: Supplementary data are available at Bioinformatics online},
	number = {20},
	urldate = {2021-06-11},
	journal = {Bioinformatics},
	author = {Bylesjö, Max and Sjödin, Andreas and Eriksson, Daniel and Antti, Henrik and Moritz, Thomas and Jansson, Stefan and Trygg, Johan},
	month = oct,
	year = {2006},
	pages = {2554--2555},
}

Summary: MASQOT-GUI provides an open-source, platform-independent software pipeline for two-channel microarray spot quality control. This includes gridding, segmentation, quantification, quality assessment and data visualization. It hosts a set of independent applications, with interactions between the tools as well as import and export support for external software. The implementation of automated multivariate quality control assessment, which is a unique feature of MASQOT-GUI, is based on the previously documented and evaluated MASQOT methodology. Further abilities of the application are outlined and illustrated.Availability: MASQOT-GUI is Java-based and licensed under the GNU LGPL. Source code and installation files are available for download at Contact: This email address is being protected from spambots. You need JavaScript enabled to view it. information: Supplementary data are available at Bioinformatics online

@article{jonsson_predictive_2006,
	title = {Predictive metabolite profiling applying hierarchical multivariate curve resolution to {GC}-{MS} datas - {A} potential tool for multi-parametric diagnosis},
	volume = {5},
	issn = {1535-3893},
	doi = {10.1021/pr0600071},
	abstract = {A method for predictive metabolite profiling based on resolution of GC-MS data followed by multivariate data analysis is presented and applied to three different biofluid data sets (rat urine, aspen leaf extracts, and human blood plasma). Hierarchical multivariate curve resolution (H-MCR) was used to simultaneously resolve the GC-MS data into pure profiles, describing the relative metabolite concentrations between samples, for multivariate analysis. Here, we present an extension of the H-MCR method allowing treatment of independent samples according to processing parameters estimated from a set of training samples. Predictions or inclusion of the new samples, based on their metabolite profiles, into an existing model could then be carried out, which is a requirement for a working application within, e. g., clinical diagnosis. Apart from allowing treatment and prediction of independent samples the proposed method also reduces the time for the curve resolution process since only a subset of representative samples have to be processed while the remaining samples can be treated according to the obtained processing parameters. The time required for resolving the 30 training samples in the rat urine example was approximately 13 h, while the treatment of the 30 test samples according to the training parameters required only approximately 30 s per sample ( similar to 15 min in total). In addition, the presented results show that the suggested approach works for describing metabolic changes in different biofluids, indicating that this is a general approach for high-throughput predictive metabolite profiling, which could have important applications in areas such as plant functional genomics, drug toxicity, treatment efficacy and early disease diagnosis.},
	language = {English},
	number = {6},
	journal = {Journal of Proteome Research},
	author = {Jonsson, Par and Johansson, Elin Sjovik and Wuolikainen, Anna and Lindberg, Johan and Schuppe-Koistinen, Ina and Kusano, Miyako and Sjostrom, Michael and Trygg, Johan and Moritz, Thomas and Antti, Henrik},
	month = jun,
	year = {2006},
	note = {Place: Washington
Publisher: Amer Chemical Soc
WOS:000237973400012},
	keywords = {chemometrics, chromatography, clinical diagnosis, components, curve resolution, design, gc-ms, genomics, h-mcr, high-throughput, identifying differences, metabolic profiling, metabolomics, metabonomics, o-pls, projections, samples, strategy},
	pages = {1407--1414},
}

A method for predictive metabolite profiling based on resolution of GC-MS data followed by multivariate data analysis is presented and applied to three different biofluid data sets (rat urine, aspen leaf extracts, and human blood plasma). Hierarchical multivariate curve resolution (H-MCR) was used to simultaneously resolve the GC-MS data into pure profiles, describing the relative metabolite concentrations between samples, for multivariate analysis. Here, we present an extension of the H-MCR method allowing treatment of independent samples according to processing parameters estimated from a set of training samples. Predictions or inclusion of the new samples, based on their metabolite profiles, into an existing model could then be carried out, which is a requirement for a working application within, e. g., clinical diagnosis. Apart from allowing treatment and prediction of independent samples the proposed method also reduces the time for the curve resolution process since only a subset of representative samples have to be processed while the remaining samples can be treated according to the obtained processing parameters. The time required for resolving the 30 training samples in the rat urine example was approximately 13 h, while the treatment of the 30 test samples according to the training parameters required only approximately 30 s per sample ( similar to 15 min in total). In addition, the presented results show that the suggested approach works for describing metabolic changes in different biofluids, indicating that this is a general approach for high-throughput predictive metabolite profiling, which could have important applications in areas such as plant functional genomics, drug toxicity, treatment efficacy and early disease diagnosis.

@article{king_regulation_2006,
	title = {Regulation of flowering in the long-day grass {Lolium} temulentum by {Gibberellins} and the {FLOWERING} {LOCUS} {T} gene},
	volume = {141},
	issn = {0032-0889},
	doi = {10/bc3fw3},
	abstract = {Seasonal control of flowering often involves leaf sensing of daylength coupled to time measurement and generation and transport of florigenic signals to the shoot apex. We show that transmitted signals in the grass Lolium temulentum may include gibberellins ( GAs) and the FLOWERING LOCUS T ( FT) gene. Within 2 h of starting a florally inductive long day ( LD), expression of a 20-oxidase GA biosynthetic gene increases in the leaf; its product, GA 20, then increases 5.7-fold versus short day; its substrate, GA 19, decreases equivalently; and a bioactive product, GA 5, increases 4-fold. A link between flowering, LD, GAs, and GA biosynthesis is shown in three ways: ( 1) applied GA 19 became florigenic on exposure to LD; ( 2) expression of LtGA20ox1, an important GA biosynthetic gene, increased in a florally effective LD involving incandescent lamps, but not with noninductive fluorescent lamps; and ( 3) paclobutrazol, an inhibitor of an early step of GA biosynthesis, blocked flowering, but only if applied before the LD. Expression studies of a 2-oxidase catabolic gene showed no changes favoring a GA increase. Thus, the early LD increase in leaf GA 5 biosynthesis, coupled with subsequent doubling in GA 5 content at the shoot apex, provides a substantial trail of evidence for GA 5 as a LD florigen. LD signaling may also involve transport of FT mRNA or protein because expression of LtFT and LtCONSTANS increased rapidly, substantially ({\textgreater} 80-fold for FT), and independently of GA. However, because a LD from fluorescent lamps induced LtFT expression but not flowering, the nature of the light response of FT requires clarification.},
	language = {English},
	number = {2},
	journal = {Plant Physiology},
	author = {King, Rod W. and Moritz, Thomas and Evans, Lloyd T. and Martin, Jerome and Andersen, Claus H. and Blundell, Cheryl and Kardailsky, Igor and Chandler, Peter M.},
	month = jun,
	year = {2006},
	note = {Place: Rockville
Publisher: Amer Soc Plant Biologists
WOS:000238168800025},
	keywords = {20-oxidase, biosynthesis, expression, in-vitro, inflorescence initiation, metabolism, molecular-cloning, photoperiod, shoot apices, stem   elongation},
	pages = {498--507},
}

Seasonal control of flowering often involves leaf sensing of daylength coupled to time measurement and generation and transport of florigenic signals to the shoot apex. We show that transmitted signals in the grass Lolium temulentum may include gibberellins ( GAs) and the FLOWERING LOCUS T ( FT) gene. Within 2 h of starting a florally inductive long day ( LD), expression of a 20-oxidase GA biosynthetic gene increases in the leaf; its product, GA 20, then increases 5.7-fold versus short day; its substrate, GA 19, decreases equivalently; and a bioactive product, GA 5, increases 4-fold. A link between flowering, LD, GAs, and GA biosynthesis is shown in three ways: ( 1) applied GA 19 became florigenic on exposure to LD; ( 2) expression of LtGA20ox1, an important GA biosynthetic gene, increased in a florally effective LD involving incandescent lamps, but not with noninductive fluorescent lamps; and ( 3) paclobutrazol, an inhibitor of an early step of GA biosynthesis, blocked flowering, but only if applied before the LD. Expression studies of a 2-oxidase catabolic gene showed no changes favoring a GA increase. Thus, the early LD increase in leaf GA 5 biosynthesis, coupled with subsequent doubling in GA 5 content at the shoot apex, provides a substantial trail of evidence for GA 5 as a LD florigen. LD signaling may also involve transport of FT mRNA or protein because expression of LtFT and LtCONSTANS increased rapidly, substantially (\textgreater 80-fold for FT), and independently of GA. However, because a LD from fluorescent lamps induced LtFT expression but not flowering, the nature of the light response of FT requires clarification.

@article{pohjanen_statistical_2006,
	title = {Statistical multivariate metabolite profiling for aiding biomarker pattern detection and mechanistic interpretations in {GC}/{MS} based metabolomics},
	volume = {2},
	issn = {1573-3890},
	url = {https://doi.org/10.1007/s11306-006-0032-4},
	doi = {10.1007/s11306-006-0032-4},
	abstract = {A strategy for robust and reliable mechanistic statistical modelling of metabolic responses in relation to drug induced toxicity is presented. The suggested approach addresses two cases commonly occurring within metabonomic toxicology studies, namely; 1) A pre-defined hypothesis about the biological mechanism exists and 2) No such hypothesis exists. GC/MS data from a liver toxicity study consisting of rat urine from control rats and rats exposed to a proprietary AstraZeneca compound were resolved by means of hierarchical multivariate curve resolution (H-MCR) generating 287 resolved chromatographic profiles with corresponding mass spectra. Filtering according to significance in relation to drug exposure rendered in 210 compound profiles, which were subjected to further statistical analysis following correction to account for the control variation over time. These dose related metabolite traces were then used as new observations in the subsequent analyses. For case 1, a multivariate approach, named Target Batch Analysis, based on OPLS regression was applied to correlate all metabolite traces to one or more key metabolites involved in the pre-defined hypothesis. For case 2, principal component analysis (PCA) was combined with hierarchical cluster analysis (HCA) to create a robust and interpretable framework for unbiased mechanistic screening. Both the Target Batch Analysis and the unbiased approach were cross-verified using the other method to ensure that the results did match in terms of detected metabolite traces. This was also the case, implying that this is a working concept for clustering of metabolites in relation to their toxicity induced dynamic profiles regardless if there is a pre-existing hypothesis or not. For each of the methods the detected metabolites were subjected to identification by means of data base comparison as well as verification in the raw data. The proposed strategy should be seen as a general approach for facilitating mechanistic modelling and interpretations in metabolomic studies.},
	language = {en},
	number = {4},
	urldate = {2021-06-11},
	journal = {Metabolomics},
	author = {Pohjanen, Elin and Thysell, Elin and Lindberg, Johan and Schuppe-Koistinen, Ina and Moritz, Thomas and Jonsson, Pär and Antti, Henrik},
	month = dec,
	year = {2006},
	pages = {257--268},
}

A strategy for robust and reliable mechanistic statistical modelling of metabolic responses in relation to drug induced toxicity is presented. The suggested approach addresses two cases commonly occurring within metabonomic toxicology studies, namely; 1) A pre-defined hypothesis about the biological mechanism exists and 2) No such hypothesis exists. GC/MS data from a liver toxicity study consisting of rat urine from control rats and rats exposed to a proprietary AstraZeneca compound were resolved by means of hierarchical multivariate curve resolution (H-MCR) generating 287 resolved chromatographic profiles with corresponding mass spectra. Filtering according to significance in relation to drug exposure rendered in 210 compound profiles, which were subjected to further statistical analysis following correction to account for the control variation over time. These dose related metabolite traces were then used as new observations in the subsequent analyses. For case 1, a multivariate approach, named Target Batch Analysis, based on OPLS regression was applied to correlate all metabolite traces to one or more key metabolites involved in the pre-defined hypothesis. For case 2, principal component analysis (PCA) was combined with hierarchical cluster analysis (HCA) to create a robust and interpretable framework for unbiased mechanistic screening. Both the Target Batch Analysis and the unbiased approach were cross-verified using the other method to ensure that the results did match in terms of detected metabolite traces. This was also the case, implying that this is a working concept for clustering of metabolites in relation to their toxicity induced dynamic profiles regardless if there is a pre-existing hypothesis or not. For each of the methods the detected metabolites were subjected to identification by means of data base comparison as well as verification in the raw data. The proposed strategy should be seen as a general approach for facilitating mechanistic modelling and interpretations in metabolomic studies.

@article{ruonala_transitions_2006,
	title = {Transitions in the functioning of the shoot apical meristem in birch ({Betula} pendula) involve ethylene},
	volume = {46},
	issn = {0960-7412},
	doi = {10/dmkh9w},
	abstract = {In many trees, a short photoperiod (SD) triggers substantial physiological adjustments necessary for over-wintering. We have used transgenic ethylene-insensitive birches (Betula pendula), which express the Arabidopsis ethylene receptor gene ETR1 carrying the dominant mutation etr1-1, to investigate the role of ethylene in SD-induced responses in the shoot apical meristem (SAM). Under SD, the ethylene-insensitive trees ceased elongation growth comparably to the wild-type. In contrast, the formation of terminal buds, which in trees is typically induced by SD, was abolished. However, although delayed, endo-dormancy did eventually develop in the ethylene-insensitive trees. This, together with the rapid resumption of growth in the ethylene-insensitive trees after transfer from non-permissive to permissive conditions suggests that ethylene facilitates the SD-induced terminal bud formation, as well as growth arrest. In addition, apical buds of the ethylene-insensitive birch did not accumulate abscisic acid (ABA) under SD, suggesting interaction between ethylene and ABA signalling in the bud. Alterations in SAM functioning were further exemplified by reduced apical dominance and early flowering in ethylene-insensitive birches. Gene expression analysis of shoot apices revealed that the ethylene-insensitive birch lacked the marked increase in expression of a beta-xylosidase gene typical to the SD-exposed wild-type. The ethylene-dependent beta-xylosidase gene expression is hypothesized to relate to modification of cell walls in terminal buds during SD-induced growth cessation. Our results suggest that ethylene is involved in terminal bud formation and in the timely suppression of SAM activity, not only in the shoot apex, but also in axillary and reproductive meristems.},
	language = {English},
	number = {4},
	journal = {Plant Journal},
	author = {Ruonala, R. and Rinne, P. L. H. and Baghour, M. and Moritz, T. and Tuominen, H. and Kangasjarvi, J.},
	month = may,
	year = {2006},
	note = {Place: Hoboken
Publisher: Wiley
WOS:000237098000008},
	keywords = {abscisic-acid, apical dominance, arabidopsis-thaliana, beta-xylosidase gene, birch, bud dormancy, cell-wall metabolism, dormancy, ethylene, expression, flowering, freezing   tolerance, induction, lateral bud growth, response pathway, xylosidase},
	pages = {628--640},
}

In many trees, a short photoperiod (SD) triggers substantial physiological adjustments necessary for over-wintering. We have used transgenic ethylene-insensitive birches (Betula pendula), which express the Arabidopsis ethylene receptor gene ETR1 carrying the dominant mutation etr1-1, to investigate the role of ethylene in SD-induced responses in the shoot apical meristem (SAM). Under SD, the ethylene-insensitive trees ceased elongation growth comparably to the wild-type. In contrast, the formation of terminal buds, which in trees is typically induced by SD, was abolished. However, although delayed, endo-dormancy did eventually develop in the ethylene-insensitive trees. This, together with the rapid resumption of growth in the ethylene-insensitive trees after transfer from non-permissive to permissive conditions suggests that ethylene facilitates the SD-induced terminal bud formation, as well as growth arrest. In addition, apical buds of the ethylene-insensitive birch did not accumulate abscisic acid (ABA) under SD, suggesting interaction between ethylene and ABA signalling in the bud. Alterations in SAM functioning were further exemplified by reduced apical dominance and early flowering in ethylene-insensitive birches. Gene expression analysis of shoot apices revealed that the ethylene-insensitive birch lacked the marked increase in expression of a beta-xylosidase gene typical to the SD-exposed wild-type. The ethylene-dependent beta-xylosidase gene expression is hypothesized to relate to modification of cell walls in terminal buds during SD-induced growth cessation. Our results suggest that ethylene is involved in terminal bud formation and in the timely suppression of SAM activity, not only in the shoot apex, but also in axillary and reproductive meristems.

@article{a_extraction_2005,
	title = {Extraction and {GC}/{MS} {Analysis} of the {Human} {Blood} {Plasma} {Metabolome}},
	volume = {77},
	issn = {0003-2700},
	url = {https://doi.org/10.1021/ac051211v},
	doi = {10.1021/ac051211v},
	abstract = {Analysis of the entire set of low molecular weight compounds (LMC), the metabolome, could provide deeper insights into mechanisms of disease and novel markers for diagnosis. In the investigation, we developed an extraction and derivatization protocol, using experimental design theory (design of experiment), for analyzing the human blood plasma metabolome by GC/MS. The protocol was optimized by evaluating the data for more than 500 resolved peaks using multivariate statistical tools including principal component analysis and partial least-squares projections to latent structures (PLS). The performance of five organic solvents (methanol, ethanol, acetonitrile, acetone, chloroform), singly and in combination, was investigated to optimize the LMC extraction. PLS analysis demonstrated that methanol extraction was particularly efficient and highly reproducible. The extraction and derivatization conditions were also optimized. Quantitative data for 32 endogenous compounds showed good precision and linearity. In addition, the determined amounts of eight selected compounds agreed well with analyses by independent methods in accredited laboratories, and most of the compounds could be detected at absolute levels of ∼0.1 pmol injected, corresponding to plasma concentrations between 0.1 and 1 μM. The results suggest that the method could be usefully integrated into metabolomic studies for various purposes, e.g., for identifying biological markers related to diseases.},
	number = {24},
	urldate = {2021-06-11},
	journal = {Analytical Chemistry},
	author = {A, Jiye and Trygg, Johan and Gullberg, Jonas and Johansson, Annika I. and Jonsson, Pär and Antti, Henrik and Marklund, Stefan L. and Moritz, Thomas},
	month = dec,
	year = {2005},
	note = {Publisher: American Chemical Society},
	pages = {8086--8094},
}

Analysis of the entire set of low molecular weight compounds (LMC), the metabolome, could provide deeper insights into mechanisms of disease and novel markers for diagnosis. In the investigation, we developed an extraction and derivatization protocol, using experimental design theory (design of experiment), for analyzing the human blood plasma metabolome by GC/MS. The protocol was optimized by evaluating the data for more than 500 resolved peaks using multivariate statistical tools including principal component analysis and partial least-squares projections to latent structures (PLS). The performance of five organic solvents (methanol, ethanol, acetonitrile, acetone, chloroform), singly and in combination, was investigated to optimize the LMC extraction. PLS analysis demonstrated that methanol extraction was particularly efficient and highly reproducible. The extraction and derivatization conditions were also optimized. Quantitative data for 32 endogenous compounds showed good precision and linearity. In addition, the determined amounts of eight selected compounds agreed well with analyses by independent methods in accredited laboratories, and most of the compounds could be detected at absolute levels of ∼0.1 pmol injected, corresponding to plasma concentrations between 0.1 and 1 μM. The results suggest that the method could be usefully integrated into metabolomic studies for various purposes, e.g., for identifying biological markers related to diseases.

@article{jonsson_extraction_2005,
	title = {Extraction, interpretation and validation of information for comparing samples in metabolic {LC}/{MS} data sets},
	volume = {130},
	issn = {1364-5528},
	url = {https://pubs.rsc.org/en/content/articlelanding/2005/an/b501890k},
	doi = {10.1039/B501890K},
	abstract = {LC/MS is an analytical technique that, due to its high sensitivity, has become increasingly popular for the generation of metabolic signatures in biological samples and for the building of metabolic data bases. However, to be able to create robust and interpretable (transparent) multivariate models for the comparison of many samples, the data must fulfil certain specific criteria: (i) that each sample is characterized by the same number of variables, (ii) that each of these variables is represented across all observations, and (iii) that a variable in one sample has the same biological meaning or represents the same metabolite in all other samples. In addition, the obtained models must have the ability to make predictions of, e.g. related and independent samples characterized accordingly to the model samples. This method involves the construction of a representative data set, including automatic peak detection, alignment, setting of retention time windows, summing in the chromatographic dimension and data compression by means of alternating regression, where the relevant metabolic variation is retained for further modelling using multivariate analysis. This approach has the advantage of allowing the comparison of large numbers of samples based on their LC/MS metabolic profiles, but also of creating a means for the interpretation of the investigated biological system. This includes finding relevant systematic patterns among samples, identifying influential variables, verifying the findings in the raw data, and finally using the models for predictions. The presented strategy was here applied to a population study using urine samples from two cohorts, Shanxi (People’s Republic of China) and Honolulu (USA). The results showed that the evaluation of the extracted information data using partial least square discriminant analysis (PLS-DA) provided a robust, predictive and transparent model for the metabolic differences between the two populations. The presented findings suggest that this is a general approach for data handling, analysis, and evaluation of large metabolic LC/MS data sets.},
	language = {en},
	number = {5},
	urldate = {2021-06-11},
	journal = {Analyst},
	author = {Jonsson, Pär and Bruce, Stephen J. and Moritz, Thomas and Trygg, Johan and Sjöström, Michael and Plumb, Robert and Granger, Jennifer and Maibaum, Elaine and Nicholson, Jeremy K. and Holmes, Elaine and Antti, Henrik},
	month = apr,
	year = {2005},
	note = {Publisher: The Royal Society of Chemistry},
	pages = {701--707},
}

LC/MS is an analytical technique that, due to its high sensitivity, has become increasingly popular for the generation of metabolic signatures in biological samples and for the building of metabolic data bases. However, to be able to create robust and interpretable (transparent) multivariate models for the comparison of many samples, the data must fulfil certain specific criteria: (i) that each sample is characterized by the same number of variables, (ii) that each of these variables is represented across all observations, and (iii) that a variable in one sample has the same biological meaning or represents the same metabolite in all other samples. In addition, the obtained models must have the ability to make predictions of, e.g. related and independent samples characterized accordingly to the model samples. This method involves the construction of a representative data set, including automatic peak detection, alignment, setting of retention time windows, summing in the chromatographic dimension and data compression by means of alternating regression, where the relevant metabolic variation is retained for further modelling using multivariate analysis. This approach has the advantage of allowing the comparison of large numbers of samples based on their LC/MS metabolic profiles, but also of creating a means for the interpretation of the investigated biological system. This includes finding relevant systematic patterns among samples, identifying influential variables, verifying the findings in the raw data, and finally using the models for predictions. The presented strategy was here applied to a population study using urine samples from two cohorts, Shanxi (People’s Republic of China) and Honolulu (USA). The results showed that the evaluation of the extracted information data using partial least square discriminant analysis (PLS-DA) provided a robust, predictive and transparent model for the metabolic differences between the two populations. The presented findings suggest that this is a general approach for data handling, analysis, and evaluation of large metabolic LC/MS data sets.

@article{schauer_gcms_2005,
	title = {{GC}–{MS} libraries for the rapid identification of metabolites in complex biological samples},
	volume = {579},
	issn = {1873-3468},
	url = {https://febs.onlinelibrary.wiley.com/doi/abs/10.1016/j.febslet.2005.01.029},
	doi = {10/fg7786},
	abstract = {Gas chromatography–mass spectrometry based metabolite profiling of biological samples is rapidly becoming one of the cornerstones of functional genomics and systems biology. Thus, the technology needs to be available to many laboratories and open exchange of information is required such as those achieved for transcript and protein data. The key-step in metabolite profiling is the unambiguous identification of metabolites in highly complex metabolite preparations with composite structure. Collections of mass spectra, which comprise frequently observed identified and non-identified metabolites, represent the most effective means to pool the identification efforts currently performed in many laboratories around the world. Here, we describe a platform for mass spectral and retention time index libraries that will enable this process (MSRI; www.csbdb.mpimp-golm.mpg.de/gmd.html). This resource should ameliorate many of the problems that each laboratory will face both for the initial establishment of metabolome analysis and for its maintenance at a constant sample throughput.},
	language = {en},
	number = {6},
	urldate = {2021-08-31},
	journal = {FEBS Letters},
	author = {Schauer, Nicolas and Steinhauser, Dirk and Strelkov, Sergej and Schomburg, Dietmar and Allison, Gordon and Moritz, Thomas and Lundgren, Krister and Roessner-Tunali, Ute and Forbes, Megan G. and Willmitzer, Lothar and Fernie, Alisdair R. and Kopka, Joachim},
	year = {2005},
	keywords = {GC, GC–MS, Gas chromatography–mass spectrometry, MS, MST, Mass spectral library, Metabolite profiling, Metabolomics, RI, Retention time index, TOF, gas chromatography, mass spectral metabolite tag, mass spectrometry, retention time index, time of flight},
	pages = {1332--1337},
}

Gas chromatography–mass spectrometry based metabolite profiling of biological samples is rapidly becoming one of the cornerstones of functional genomics and systems biology. Thus, the technology needs to be available to many laboratories and open exchange of information is required such as those achieved for transcript and protein data. The key-step in metabolite profiling is the unambiguous identification of metabolites in highly complex metabolite preparations with composite structure. Collections of mass spectra, which comprise frequently observed identified and non-identified metabolites, represent the most effective means to pool the identification efforts currently performed in many laboratories around the world. Here, we describe a platform for mass spectral and retention time index libraries that will enable this process (MSRI; www.csbdb.mpimp-golm.mpg.de/gmd.html). This resource should ameliorate many of the problems that each laboratory will face both for the initial establishment of metabolome analysis and for its maintenance at a constant sample throughput.

@article{jonsson_high-throughput_2005,
	title = {High-{Throughput} {Data} {Analysis} for {Detecting} and {Identifying} {Differences} between {Samples} in {GC}/{MS}-{Based} {Metabolomic} {Analyses}},
	volume = {77},
	issn = {0003-2700},
	url = {https://doi.org/10.1021/ac050601e},
	doi = {10.1021/ac050601e},
	abstract = {In metabolomics, the objective is to identify differences in metabolite profiles between samples. A widely used tool in metabolomics investigations is gas chromatography−mass spectrometry (GC/MS). More than 400 compounds can be detected in a single analysis, if overlapping GC/MS peaks are deconvoluted. However, the deconvolution process is time-consuming and difficult to automate, and additional processing is needed in order to compare samples. Therefore, there is a need to improve and automate the data processing strategy for data generated in GC/MS-based metabolomics; if not, the processing step will be a major bottleneck for high-throughput analyses. Here we describe a new semiautomated strategy using a hierarchical multivariate curve resolution approach that processes all samples simultaneously. The presented strategy generates (after appropriate treatment, e.g., multivariate analysis) tables of all the detected metabolites that differ in relative concentrations between samples. The processing of 70 samples took similar time to that of the GC/TOFMS analyses of the samples. The strategy has been validated using two different sets of samples:  a complex mixture of standard compounds and Arabidopsis samples.},
	number = {17},
	urldate = {2021-06-11},
	journal = {Analytical Chemistry},
	author = {Jonsson, Pär and Johansson, Annika I. and Gullberg, Jonas and Trygg, Johan and A, Jiye and Grung, Bjørn and Marklund, Stefan and Sjöström, Michael and Antti, Henrik and Moritz, Thomas},
	month = sep,
	year = {2005},
	note = {Publisher: American Chemical Society},
	pages = {5635--5642},
}

In metabolomics, the objective is to identify differences in metabolite profiles between samples. A widely used tool in metabolomics investigations is gas chromatography−mass spectrometry (GC/MS). More than 400 compounds can be detected in a single analysis, if overlapping GC/MS peaks are deconvoluted. However, the deconvolution process is time-consuming and difficult to automate, and additional processing is needed in order to compare samples. Therefore, there is a need to improve and automate the data processing strategy for data generated in GC/MS-based metabolomics; if not, the processing step will be a major bottleneck for high-throughput analyses. Here we describe a new semiautomated strategy using a hierarchical multivariate curve resolution approach that processes all samples simultaneously. The presented strategy generates (after appropriate treatment, e.g., multivariate analysis) tables of all the detected metabolites that differ in relative concentrations between samples. The processing of 70 samples took similar time to that of the GC/TOFMS analyses of the samples. The strategy has been validated using two different sets of samples:  a complex mixture of standard compounds and Arabidopsis samples.

@article{israelsson_tissue-specific_2005,
	title = {Tissue-specific localization of gibberellins and expression of gibberellin-biosynthetic and signaling genes in wood-forming tissues in aspen},
	volume = {44},
	issn = {1365-313X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-313X.2005.02547.x},
	doi = {10/b9g6dq},
	abstract = {Bioactive gibberellins (GAs) are known regulators of shoot growth and development in plants. In an attempt to identify where GAs are formed, we have analyzed the expression patterns of six GA biosynthesis genes and two genes with predicted roles in GA signaling and responses in relation to measured levels of GAs. The analysis was based on tangential sections, giving tissue-specific resolution across the cambial region of aspen trees (Populus tremula). Gibberellin quantification by GC/MS-SRM showed that the bioactive GA1 and GA4 were predominantly located in the zone of expansion of xylem cells. Based on co-localization of the expression of the late GA biosynthesis gene GA 20-oxidase 1 and bioactive GAs, we suggest that de novo GA biosynthesis occurs in the expanding xylem. However, expression levels of the first committed GA biosynthesis enzyme, ent-copalyl diphosphate synthase, were high in the phloem, suggesting that a GA precursor(s) may be transported to the xylem. The expression of the GA signaling and response genes DELLA-like1 and GIP-like1 coincided well with sites of high bioactive GA levels. We therefore suggest that the main role of GA during wood formation is to regulate early stages of xylem differentiation, including cell elongation.},
	language = {en},
	number = {3},
	urldate = {2021-06-11},
	journal = {The Plant Journal},
	author = {Israelsson, Maria and Sundberg, Björn and Moritz, Thomas},
	year = {2005},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-313X.2005.02547.x},
	keywords = {DELLA, Populus, fiber, gibberellin-biosynthetic genes, gibberellins, wood formation},
	pages = {494--504},
}

Bioactive gibberellins (GAs) are known regulators of shoot growth and development in plants. In an attempt to identify where GAs are formed, we have analyzed the expression patterns of six GA biosynthesis genes and two genes with predicted roles in GA signaling and responses in relation to measured levels of GAs. The analysis was based on tangential sections, giving tissue-specific resolution across the cambial region of aspen trees (Populus tremula). Gibberellin quantification by GC/MS-SRM showed that the bioactive GA1 and GA4 were predominantly located in the zone of expansion of xylem cells. Based on co-localization of the expression of the late GA biosynthesis gene GA 20-oxidase 1 and bioactive GAs, we suggest that de novo GA biosynthesis occurs in the expanding xylem. However, expression levels of the first committed GA biosynthesis enzyme, ent-copalyl diphosphate synthase, were high in the phloem, suggesting that a GA precursor(s) may be transported to the xylem. The expression of the GA signaling and response genes DELLA-like1 and GIP-like1 coincided well with sites of high bioactive GA levels. We therefore suggest that the main role of GA during wood formation is to regulate early stages of xylem differentiation, including cell elongation.

@article{jonsson_strategy_2004,
	title = {A {Strategy} for {Identifying} {Differences} in {Large} {Series} of {Metabolomic} {Samples} {Analyzed} by {GC}/{MS}},
	volume = {76},
	issn = {0003-2700},
	url = {https://doi.org/10.1021/ac0352427},
	doi = {10/dm24rr},
	abstract = {In metabolomics, the purpose is to identify and quantify all the metabolites in a biological system. Combined gas chromatography and mass spectrometry (GC/MS) is one of the most commonly used techniques in metabolomics together with 1H NMR, and it has been shown that more than 300 compounds can be distinguished with GC/MS after deconvolution of overlapping peaks. To avoid having to deconvolute all analyzed samples prior to multivariate analysis of the data, we have developed a strategy for rapid comparison of nonprocessed MS data files. The method includes baseline correction, alignment, time window determinations, alternating regression, PLS-DA, and identification of retention time windows in the chromatograms that explain the differences between the samples. Use of alternating regression also gives interpretable loadings, which retain the information provided by m/z values that vary between the samples in each retention time window. The method has been applied to plant extracts derived from leaves of different developmental stages and plants subjected to small changes in day length. The data show that the new method can detect differences between the samples and that it gives results comparable to those obtained when deconvolution is applied prior to the multivariate analysis. We suggest that this method can be used for rapid comparison of large sets of GC/MS data, thereby applying time-consuming deconvolution only to parts of the chromatograms that contribute to explain the differences between the samples.},
	number = {6},
	urldate = {2021-06-30},
	journal = {Analytical Chemistry},
	author = {Jonsson, Pär and Gullberg, Jonas and Nordström, Anders and Kusano, Miyako and Kowalczyk, Mariusz and Sjöström, Michael and Moritz, Thomas},
	month = mar,
	year = {2004},
	note = {Publisher: American Chemical Society},
	pages = {1738--1745},
}

In metabolomics, the purpose is to identify and quantify all the metabolites in a biological system. Combined gas chromatography and mass spectrometry (GC/MS) is one of the most commonly used techniques in metabolomics together with 1H NMR, and it has been shown that more than 300 compounds can be distinguished with GC/MS after deconvolution of overlapping peaks. To avoid having to deconvolute all analyzed samples prior to multivariate analysis of the data, we have developed a strategy for rapid comparison of nonprocessed MS data files. The method includes baseline correction, alignment, time window determinations, alternating regression, PLS-DA, and identification of retention time windows in the chromatograms that explain the differences between the samples. Use of alternating regression also gives interpretable loadings, which retain the information provided by m/z values that vary between the samples in each retention time window. The method has been applied to plant extracts derived from leaves of different developmental stages and plants subjected to small changes in day length. The data show that the new method can detect differences between the samples and that it gives results comparable to those obtained when deconvolution is applied prior to the multivariate analysis. We suggest that this method can be used for rapid comparison of large sets of GC/MS data, thereby applying time-consuming deconvolution only to parts of the chromatograms that contribute to explain the differences between the samples.

@article{curaba_atga3ox2_2004,
	title = {{AtGA3ox2}, a {Key} {Gene} {Responsible} for {Bioactive} {Gibberellin} {Biosynthesis}, {Is} {Regulated} during {Embryogenesis} by {LEAFY} {COTYLEDON2} and {FUSCA3} in {Arabidopsis}},
	volume = {136},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.104.047266},
	doi = {10/d4dh37},
	abstract = {Embryonic regulators LEC2 (LEAFY COTYLEDON2) and FUS3 (FUSCA3) are involved in multiple aspects of Arabidopsis (Arabidopsis thaliana) seed development, including repression of leaf traits and premature germination and activation of seed storage protein genes. In this study, we show that gibberellin (GA) hormone biosynthesis is regulated by LEC2 and FUS3 pathways. The level of bioactive GAs is increased in immature seeds of lec2 and fus3 mutants relative to wild-type level. In addition, we show that the formation of ectopic trichome cells on lec2 and fus3 embryos is a GA-dependent process as in true leaves, suggesting that the GA pathway is misactivated in embryonic mutants. We next demonstrate that the GA-biosynthesis gene AtGA3ox2, which encodes the key enzyme AtGA3ox2 that catalyzes the conversion of inactive to bioactive GAs, is ectopically activated in embryos of the two mutants. Interestingly, both β-glucuronidase reporter gene expression and in situ hybridization indicate that FUS3 represses AtGA3ox2 expression mainly in epidermal cells of embryo axis, which is distinct from AtGA3ox2 pattern at germination. Finally, we show that the FUS3 protein physically interacts with two RY elements (CATGCATG) present in the AtGA3ox2 promoter. This work suggests that GA biosynthesis is directly controlled by embryonic regulators during Arabidopsis embryonic development.},
	number = {3},
	urldate = {2021-06-15},
	journal = {Plant Physiology},
	author = {Curaba, Julien and Moritz, Thomas and Blervaque, Renaud and Parcy, François and Raz, Vered and Herzog, Michel and Vachon, Gilles},
	month = nov,
	year = {2004},
	pages = {3660--3669},
}

Embryonic regulators LEC2 (LEAFY COTYLEDON2) and FUS3 (FUSCA3) are involved in multiple aspects of Arabidopsis (Arabidopsis thaliana) seed development, including repression of leaf traits and premature germination and activation of seed storage protein genes. In this study, we show that gibberellin (GA) hormone biosynthesis is regulated by LEC2 and FUS3 pathways. The level of bioactive GAs is increased in immature seeds of lec2 and fus3 mutants relative to wild-type level. In addition, we show that the formation of ectopic trichome cells on lec2 and fus3 embryos is a GA-dependent process as in true leaves, suggesting that the GA pathway is misactivated in embryonic mutants. We next demonstrate that the GA-biosynthesis gene AtGA3ox2, which encodes the key enzyme AtGA3ox2 that catalyzes the conversion of inactive to bioactive GAs, is ectopically activated in embryos of the two mutants. Interestingly, both β-glucuronidase reporter gene expression and in situ hybridization indicate that FUS3 represses AtGA3ox2 expression mainly in epidermal cells of embryo axis, which is distinct from AtGA3ox2 pattern at germination. Finally, we show that the FUS3 protein physically interacts with two RY elements (CATGCATG) present in the AtGA3ox2 promoter. This work suggests that GA biosynthesis is directly controlled by embryonic regulators during Arabidopsis embryonic development.

@article{israelsson_cloning_2004,
	title = {Cloning and {Overproduction} of {Gibberellin} 3-{Oxidase} in {Hybrid} {Aspen} {Trees}. {Effects} on {Gibberellin} {Homeostasis} and {Development}},
	volume = {135},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.104.038935},
	doi = {10/bpzz6v},
	abstract = {To broaden our understanding of gibberellin (GA) biosynthesis and the mechanism whereby GA homeostasis is maintained in plants, we have investigated the degree to which the enzyme GA 3-oxidase (GA3ox) limits the formation of bioactive GAs in elongating shoots of hybrid aspen (Populus tremula × Populus tremuloides). We describe the cloning of a hybrid aspen GA3ox and its functional characterization, which confirmed that it has 3β-hydroxylation activity and more efficiently converts GA9 to GA4 than GA20 to GA1. To complement previous studies, in which transgenic GA 20-oxidase (GA20ox) overexpressers were found to produce 20-fold higher bioactive GA levels and subsequently grew faster than wild-type plants, we overexpressed an Arabidopsis GA3ox in hybrid aspen. The generated GA3ox overexpresser lines had increased 3β-hydroxylation activity but exhibited no major changes in morphology. The nearly unaltered growth pattern was associated with relatively small changes in GA1 and GA4 levels, although tissue-dependent differences were observed. The absence of increases in bioactive GA levels did not appear to be due to feedback or feed-forward regulation of dioxygenase transcripts, according to semiquantitative reverse transcription polymerase chain reaction analysis of PttGA20ox1, PttGA3ox1, and two putative PttGA2ox genes. We conclude that 20-oxidation is the limiting step, rather than 3β-hydroxylation, in the formation of GA1 and GA4 in elongating shoots of hybrid aspen, and that ectopic GA3ox expression alone cannot increase the flux toward bioactive GAs. Finally, several lines of evidence now suggest that GA4 has a more pivotal role in the tree hybrid aspen than previously believed.},
	number = {1},
	urldate = {2021-06-15},
	journal = {Plant Physiology},
	author = {Israelsson, Maria and Mellerowicz, Ewa and Chono, Makiko and Gullberg, Jonas and Moritz, Thomas},
	month = may,
	year = {2004},
	pages = {221--230},
}

To broaden our understanding of gibberellin (GA) biosynthesis and the mechanism whereby GA homeostasis is maintained in plants, we have investigated the degree to which the enzyme GA 3-oxidase (GA3ox) limits the formation of bioactive GAs in elongating shoots of hybrid aspen (Populus tremula × Populus tremuloides). We describe the cloning of a hybrid aspen GA3ox and its functional characterization, which confirmed that it has 3β-hydroxylation activity and more efficiently converts GA9 to GA4 than GA20 to GA1. To complement previous studies, in which transgenic GA 20-oxidase (GA20ox) overexpressers were found to produce 20-fold higher bioactive GA levels and subsequently grew faster than wild-type plants, we overexpressed an Arabidopsis GA3ox in hybrid aspen. The generated GA3ox overexpresser lines had increased 3β-hydroxylation activity but exhibited no major changes in morphology. The nearly unaltered growth pattern was associated with relatively small changes in GA1 and GA4 levels, although tissue-dependent differences were observed. The absence of increases in bioactive GA levels did not appear to be due to feedback or feed-forward regulation of dioxygenase transcripts, according to semiquantitative reverse transcription polymerase chain reaction analysis of PttGA20ox1, PttGA3ox1, and two putative PttGA2ox genes. We conclude that 20-oxidation is the limiting step, rather than 3β-hydroxylation, in the formation of GA1 and GA4 in elongating shoots of hybrid aspen, and that ectopic GA3ox expression alone cannot increase the flux toward bioactive GAs. Finally, several lines of evidence now suggest that GA4 has a more pivotal role in the tree hybrid aspen than previously believed.

@article{nordstrom_derivatization_2004,
	title = {Derivatization for {LC}-{Electrospray} {Ionization}-{MS}:  {A} {Tool} for {Improving} {Reversed}-{Phase} {Separation} and {ESI} {Responses} of {Bases}, {Ribosides}, and {Intact} {Nucleotides}},
	volume = {76},
	issn = {0003-2700},
	shorttitle = {Derivatization for {LC}-{Electrospray} {Ionization}-{MS}},
	url = {https://doi.org/10.1021/ac0499017},
	doi = {10/b9ckbc},
	abstract = {We have developed a method for analyzing polar compounds by reversed-phase LC-ESI-MS following esterification of the analytes' free hydroxyl groups with propionyl or benzoyl acid anhydride. The method was applied to members of the plant hormone group cytokinins, which includes adenine bases, ribosides/glycosides, and nucleotides substituted at N-6 with an isoprenoid side chain, spanning a wide range of polarity. It was also used to analyze other compounds of biological importance, e.g., the nucleotides AMP, ADP, and ATP. The formation of more hydrophobic derivatives had a significant impact on two aspects of the analysis. The retention on a reversed-phase material was greatly increased without the use of any acetate/formate buffer or ion pairing reagent, and the ESI response was enhanced, due to the higher surface activities of the derivatives. Detection limits of propionylated cytokinins were in the high-attomole to low-femtomole range, an improvement by factors of 10−100 compared to previously reported figures. Using an automated SPE-based purification method, 12 endogenous cytokinins were quantified in extracts from 20- to 100-mg samples of leaves (from the plant Arabidopsis thaliana) with high accuracy and precision. Furthermore, the chromatographic properties of the benzoylated AMP, ADP, and ATP in the reversed-phase LC−MS system were much better in terms of retention, separation, and sensitivity than those of their underivatized counterparts, even without the use of any ion pairing reagent. Our data show that derivatization followed by LC-ESI-MS is an effective strategy for analyzing low molecular weight compounds, enabling compounds with a wide range of polarity to be determined in a single-injection LC−MS analysis.},
	number = {10},
	urldate = {2021-06-30},
	journal = {Analytical Chemistry},
	author = {Nordström, Anders and Tarkowski, Petr and Tarkowska, Danuse and Dolezal, Karel and Åstot, Crister and Sandberg, Göran and Moritz, Thomas},
	month = may,
	year = {2004},
	note = {Publisher: American Chemical Society},
	pages = {2869--2877},
}

We have developed a method for analyzing polar compounds by reversed-phase LC-ESI-MS following esterification of the analytes' free hydroxyl groups with propionyl or benzoyl acid anhydride. The method was applied to members of the plant hormone group cytokinins, which includes adenine bases, ribosides/glycosides, and nucleotides substituted at N-6 with an isoprenoid side chain, spanning a wide range of polarity. It was also used to analyze other compounds of biological importance, e.g., the nucleotides AMP, ADP, and ATP. The formation of more hydrophobic derivatives had a significant impact on two aspects of the analysis. The retention on a reversed-phase material was greatly increased without the use of any acetate/formate buffer or ion pairing reagent, and the ESI response was enhanced, due to the higher surface activities of the derivatives. Detection limits of propionylated cytokinins were in the high-attomole to low-femtomole range, an improvement by factors of 10−100 compared to previously reported figures. Using an automated SPE-based purification method, 12 endogenous cytokinins were quantified in extracts from 20- to 100-mg samples of leaves (from the plant Arabidopsis thaliana) with high accuracy and precision. Furthermore, the chromatographic properties of the benzoylated AMP, ADP, and ATP in the reversed-phase LC−MS system were much better in terms of retention, separation, and sensitivity than those of their underivatized counterparts, even without the use of any ion pairing reagent. Our data show that derivatization followed by LC-ESI-MS is an effective strategy for analyzing low molecular weight compounds, enabling compounds with a wide range of polarity to be determined in a single-injection LC−MS analysis.

@article{gullberg_design_2004,
	title = {Design of experiments: an efficient strategy to identify factors influencing extraction and derivatization of {Arabidopsis} thaliana samples in metabolomic studies with gas chromatography/mass spectrometry},
	volume = {331},
	issn = {0003-2697},
	shorttitle = {Design of experiments},
	url = {https://www.sciencedirect.com/science/article/pii/S0003269704003811},
	doi = {10/ftg6fz},
	abstract = {The usual aim in metabolomic studies is to quantify the entire metabolome of each of a series of biological samples. To do this for complex biological matrices, e.g., plant tissues, efficient and reproducible extraction protocols must be developed. However, derivatization protocols must also be developed if GC/MS (one of the mostly widely used analytical methods for metabolomics) is involved. The aim of this study was to investigate how different chemical and physical factors (extraction solvent, derivatization reagents, and temperature) affect the extraction and derivatization of the metabolome from leaves of the plant Arabidopsis thaliana. Using design of experiment procedures, variation was systematically introduced, and the effects of this variation were analyzed using regression models. The results show that this approach allows a reliable protocol for metabolomic analysis of Arabidopsis to be determined with a relatively limited number of experiments. Following two different investigations an extraction and derivatization protocol was chosen. Further, the reproducibility of the analysis of 66 endogenous compounds was investigated, and it was shown that both hydrophilic and lipophilic compounds were detected with high reproducibility.},
	language = {en},
	number = {2},
	urldate = {2021-06-30},
	journal = {Analytical Biochemistry},
	author = {Gullberg, Jonas and Jonsson, Pär and Nordström, Anders and Sjöström, Michael and Moritz, Thomas},
	month = aug,
	year = {2004},
	keywords = {Derivatization, Design of experiments, Extraction, Mass spectrometry, Metabolomics},
	pages = {283--295},
}

The usual aim in metabolomic studies is to quantify the entire metabolome of each of a series of biological samples. To do this for complex biological matrices, e.g., plant tissues, efficient and reproducible extraction protocols must be developed. However, derivatization protocols must also be developed if GC/MS (one of the mostly widely used analytical methods for metabolomics) is involved. The aim of this study was to investigate how different chemical and physical factors (extraction solvent, derivatization reagents, and temperature) affect the extraction and derivatization of the metabolome from leaves of the plant Arabidopsis thaliana. Using design of experiment procedures, variation was systematically introduced, and the effects of this variation were analyzed using regression models. The results show that this approach allows a reliable protocol for metabolomic analysis of Arabidopsis to be determined with a relatively limited number of experiments. Following two different investigations an extraction and derivatization protocol was chosen. Further, the reproducibility of the analysis of 66 endogenous compounds was investigated, and it was shown that both hydrophilic and lipophilic compounds were detected with high reproducibility.

@article{corbesier_gibberellins_2004,
	title = {Gibberellins and the floral transition in {Sinapis} alba},
	volume = {122},
	issn = {0031-9317},
	doi = {10/fqn2j7},
	abstract = {The putative role of gibberellins in the transition to flowering was investigated in Sinapis alba, a caulescent long-day (LD) plant. It was observed that: (1) physiological doses of exogenous gibberellins (GA(1), GA(3), GA(9)) do not cause the floral shift of the meristem when applied to plants grown in short days but have some positive effect on the flowering response to a suboptimal LD; no inhibition was observed in any case; (2) GA-biosynthesis inhibitors (prohexadione-Ca and paclobutrazol) considerably inhibit stem growth but have some negative effect on flowering only when a suboptimal LD is given; and (3) the floral transition induced by one 22-h LD does not correlate with any detectable change in GA content of the apical bud, of the leaves, and of the phloem exudate reaching the apex. Taken together, these results suggest that GAs do not act as a major signal for photoperiodic flower induction in Sinapis.},
	language = {English},
	number = {1},
	journal = {Physiologia Plantarum},
	author = {Corbesier, L. and Kustermans, G. and Perilleux, C. and Melzer, S. and Moritz, T. and Havelange, A. and Bernier, G.},
	month = sep,
	year = {2004},
	note = {Place: Hoboken
Publisher: Wiley
WOS:000223589000018},
	keywords = {arabidopsis-thaliana, biosynthesis, cytokinins, endogenous gibberellins, induction, localization, phloem, photoperiod, shoot, stem growth},
	pages = {152--158},
}

The putative role of gibberellins in the transition to flowering was investigated in Sinapis alba, a caulescent long-day (LD) plant. It was observed that: (1) physiological doses of exogenous gibberellins (GA(1), GA(3), GA(9)) do not cause the floral shift of the meristem when applied to plants grown in short days but have some positive effect on the flowering response to a suboptimal LD; no inhibition was observed in any case; (2) GA-biosynthesis inhibitors (prohexadione-Ca and paclobutrazol) considerably inhibit stem growth but have some negative effect on flowering only when a suboptimal LD is given; and (3) the floral transition induced by one 22-h LD does not correlate with any detectable change in GA content of the apical bud, of the leaves, and of the phloem exudate reaching the apex. Taken together, these results suggest that GAs do not act as a major signal for photoperiodic flower induction in Sinapis.

@article{jiye_global_2004,
	title = {Global analysis of low-molecular-weight compounds in human plasma using {GC}/{TOF}-{MS}},
	volume = {36},
	issn = {0360-2532},
	language = {English},
	journal = {Drug Metabolism Reviews},
	author = {Jiye, A. and Trygg, J. and Gullberg, J. and Moritz, T. and Marklund, S.},
	month = aug,
	year = {2004},
	note = {Place: Philadelphia
Publisher: Taylor \& Francis Inc
WOS:000224023200489},
	pages = {246--246},
}

@article{cox_roles_2004,
	title = {The {Roles} of {Ethylene}, {Auxin}, {Abscisic} {Acid}, and {Gibberellin} in the {Hyponastic} {Growth} of {Submerged} {Rumex} palustris {Petioles}},
	volume = {136},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.104.049197},
	doi = {10/bkt5tx},
	abstract = {Rumex palustris responds to complete submergence with upward movement of the younger petioles. This so-called hyponastic response, in combination with stimulated petiole elongation, brings the leaf blade above the water surface and restores contact with the atmosphere. We made a detailed study of this differential growth process, encompassing the complete range of the known signal transduction pathway: from the cellular localization of differential growth, to the hormonal regulation, and the possible involvement of a cell wall loosening protein (expansin) as a downstream target. We show that hyponastic growth is caused by differential cell elongation across the petiole base, with cells on the abaxial (lower) surface elongating faster than cells on the adaxial (upper) surface. Pharmacological studies and endogenous hormone measurements revealed that ethylene, auxin, abscisic acid (ABA), and gibberellin regulate different and sometimes overlapping stages of hyponastic growth. Initiation of hyponastic growth and (maintenance of) the maximum petiole angle are regulated by ethylene, ABA, and auxin, whereas the speed of the response is influenced by ethylene, ABA, and gibberellin. We found that a submergence-induced differential redistribution of endogenous indole-3-acetic acid in the petiole base could play a role in maintenance of the response, but not in the onset of hyponastic growth. Since submergence does not induce a differential expression of expansins across the petiole base, it is unlikely that this cell wall loosening protein is the downstream target for the hormones that regulate the differential cell elongation leading to submergence-induced hyponastic growth in R. palustris.},
	number = {2},
	urldate = {2021-06-15},
	journal = {Plant Physiology},
	author = {Cox, Marjolein C.H. and Benschop, Joris J. and Vreeburg, Robert A.M. and Wagemaker, Cornelis A.M. and Moritz, Thomas and Peeters, Anton J.M. and Voesenek, Laurentius A.C.J.},
	month = oct,
	year = {2004},
	pages = {2948--2960},
}

Rumex palustris responds to complete submergence with upward movement of the younger petioles. This so-called hyponastic response, in combination with stimulated petiole elongation, brings the leaf blade above the water surface and restores contact with the atmosphere. We made a detailed study of this differential growth process, encompassing the complete range of the known signal transduction pathway: from the cellular localization of differential growth, to the hormonal regulation, and the possible involvement of a cell wall loosening protein (expansin) as a downstream target. We show that hyponastic growth is caused by differential cell elongation across the petiole base, with cells on the abaxial (lower) surface elongating faster than cells on the adaxial (upper) surface. Pharmacological studies and endogenous hormone measurements revealed that ethylene, auxin, abscisic acid (ABA), and gibberellin regulate different and sometimes overlapping stages of hyponastic growth. Initiation of hyponastic growth and (maintenance of) the maximum petiole angle are regulated by ethylene, ABA, and auxin, whereas the speed of the response is influenced by ethylene, ABA, and gibberellin. We found that a submergence-induced differential redistribution of endogenous indole-3-acetic acid in the petiole base could play a role in maintenance of the response, but not in the onset of hyponastic growth. Since submergence does not induce a differential expression of expansins across the petiole base, it is unlikely that this cell wall loosening protein is the downstream target for the hormones that regulate the differential cell elongation leading to submergence-induced hyponastic growth in R. palustris.

@article{israelsson_changes_2003,
	title = {Changes in gene expression in the wood-forming tissue of transgenic hybrid aspen with increased secondary growth},
	volume = {52},
	issn = {1573-5028},
	url = {https://doi.org/10.1023/A:1025097410445},
	doi = {10/b7zwj2},
	abstract = {Transgenic lines of hybrid aspen with elevated levels of gibberellin (GA) show greatly increased numbers of xylem fibres and increases in xylem fibre length. These plants therefore provide excellent models for studying secondary growth. We have used cDNA microarry analysis to investigate how gene transcription in the developing xylem is affected by GA-induced growth. A recent investigation has shown that genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under developmental-stage-specific transcriptional control. The present study shows that the highest transcript changes in our transgenic trees occurs in genes generally restricted to the early stages of xylogenesis, including cell division, early expansion and late expansion. The results reveal genes among those arrayed that are up-regulated with an increased xylem production, thus indicating key components in the production of wood.},
	language = {en},
	number = {4},
	urldate = {2022-03-11},
	journal = {Plant Molecular Biology},
	author = {Israelsson, Maria and Eriksson, Maria E. and Hertzberg, Magnus and Aspeborg, Henrik and Nilsson, Peter and Moritz, Thomas},
	month = jul,
	year = {2003},
	pages = {893--903},
}

Transgenic lines of hybrid aspen with elevated levels of gibberellin (GA) show greatly increased numbers of xylem fibres and increases in xylem fibre length. These plants therefore provide excellent models for studying secondary growth. We have used cDNA microarry analysis to investigate how gene transcription in the developing xylem is affected by GA-induced growth. A recent investigation has shown that genes encoding lignin and cellulose biosynthetic enzymes, as well as a number of transcription factors and other potential regulators of xylogenesis, are under developmental-stage-specific transcriptional control. The present study shows that the highest transcript changes in our transgenic trees occurs in genes generally restricted to the early stages of xylogenesis, including cell division, early expansion and late expansion. The results reveal genes among those arrayed that are up-regulated with an increased xylem production, thus indicating key components in the production of wood.

@article{eriksson_daylength_2002,
	title = {Daylength and spatial expression of a gibberellin 20-oxidase isolated from hybrid aspen ({Populus} tremula {L}. × {P}. tremuloides {Michx}.)},
	volume = {214},
	issn = {1432-2048},
	url = {https://doi.org/10.1007/s00425-001-0703-3},
	doi = {10/bn4z3p},
	abstract = {Physiologically active gibberellins (GAs) are key regulators of shoot growth in trees. To investigate this mechanism of GA-controlled growth in hybrid aspen, we cloned cDNAs encoding gibberellin 20-oxidase (GA 20-oxidase), a key, highly regulated enzyme in the biosynthesis of GAs. Clones were isolated from leaf and cambium cDNA libraries using probes generated by polymerase chain reaction, based on conserved domains of GA 20-oxidases. Upon expression in Escherichia coli, the GST-fusion protein was shown to oxidise GA12 as well as oxidising the 13-hydroxylated substrate GA53, successively to GA9 and GA20, respectively. The gene PttGA20ox1 was expressed in meristematic cells and growing tissues such as expanding internodes, leaves and roots. The expression was negatively regulated by both GA4 and overexpression of phytochrome A. RNA analysis also showed that the expression was down-regulated in late-expanding leaf tissue in response to short days (SDs). Actively growing tissues such as early elongating internodes, petioles and leaf blades had the highest levels of C19-GAs. Upon transfer to SDs an accumulation of GA19 was observed in early elongating internodes and leaf blades. The levels of C19-GAs were also to some extent changed upon transfer to SDs. The levels of GA20 were down-regulated in internodes, and those of GA1 were significantly reduced in early expanding leaf blades. In roots the metabolites GA19 and GA8 decreased upon shifts to SDs, while GA20 accumulated slightly. The down-regulation of GA 20-oxidase activity in response to SDs was further indicated by studies of [14C]GA12 metabolism in shoots, demonstrating that the substrate for GA 20-oxidase, [14C]GA53, accumulates in SDs.},
	language = {en},
	number = {6},
	urldate = {2021-10-19},
	journal = {Planta},
	author = {Eriksson, Maria E. and Moritz, Thomas},
	month = apr,
	year = {2002},
	pages = {920--930},
}

Physiologically active gibberellins (GAs) are key regulators of shoot growth in trees. To investigate this mechanism of GA-controlled growth in hybrid aspen, we cloned cDNAs encoding gibberellin 20-oxidase (GA 20-oxidase), a key, highly regulated enzyme in the biosynthesis of GAs. Clones were isolated from leaf and cambium cDNA libraries using probes generated by polymerase chain reaction, based on conserved domains of GA 20-oxidases. Upon expression in Escherichia coli, the GST-fusion protein was shown to oxidise GA12 as well as oxidising the 13-hydroxylated substrate GA53, successively to GA9 and GA20, respectively. The gene PttGA20ox1 was expressed in meristematic cells and growing tissues such as expanding internodes, leaves and roots. The expression was negatively regulated by both GA4 and overexpression of phytochrome A. RNA analysis also showed that the expression was down-regulated in late-expanding leaf tissue in response to short days (SDs). Actively growing tissues such as early elongating internodes, petioles and leaf blades had the highest levels of C19-GAs. Upon transfer to SDs an accumulation of GA19 was observed in early elongating internodes and leaf blades. The levels of C19-GAs were also to some extent changed upon transfer to SDs. The levels of GA20 were down-regulated in internodes, and those of GA1 were significantly reduced in early expanding leaf blades. In roots the metabolites GA19 and GA8 decreased upon shifts to SDs, while GA20 accumulated slightly. The down-regulation of GA 20-oxidase activity in response to SDs was further indicated by studies of [14C]GA12 metabolism in shoots, demonstrating that the substrate for GA 20-oxidase, [14C]GA53, accumulates in SDs.

@article{welling_independent_2002,
	title = {Independent {Activation} of {Cold} {Acclimation} by {Low} {Temperature} and {Short} {Photoperiod} in {Hybrid} {Aspen}},
	volume = {129},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.003814},
	doi = {10/bwp2sf},
	abstract = {Temperate zone woody plants cold acclimate in response to both short daylength (SD) and low temperature (LT). We were able to show that these two environmental cues induce cold acclimation independently by comparing the wild type (WT) and the transgenic hybrid aspen (Populus tremula × Populus tremuloides Michx.) line 22 overexpressing the oat (Avena sativa) PHYTOCHROME A gene. Line 22 was not able to detect the SD and, consequently, did not stop growing in SD conditions. This resulted in an impaired freezing tolerance development under SD. In contrast, exposure to LT resulted in cold acclimation of line 22 to a degree comparable with the WT. In contrast to the WT, line 22 could not dehydrate the overwintering tissues or induce the production of dehydrins (DHN) under SD conditions. Furthermore, abscisic acid (ABA) content of the buds of line 22 were the same under SD and long daylength, whereas prolonged SD exposure decreased the ABA level in the WT. LT exposure resulted in a rapid accumulation of DHN in both the WT and line 22. Similarly, ABA content increased transiently in both the WT and line 22. Our results indicate that phytochrome A is involved in photoperiodic regulation of ABA and DHN levels, but at LT they are regulated by a different mechanism. Although SD and LT induce cold acclimation independently, ABA and DHN may play important roles in both modes of acclimation.},
	number = {4},
	urldate = {2021-10-19},
	journal = {Plant Physiology},
	author = {Welling, Annikki and Moritz, Thomas and Palva, E. Tapio and Junttila, Olavi},
	month = aug,
	year = {2002},
	pages = {1633--1641},
}

Temperate zone woody plants cold acclimate in response to both short daylength (SD) and low temperature (LT). We were able to show that these two environmental cues induce cold acclimation independently by comparing the wild type (WT) and the transgenic hybrid aspen (Populus tremula × Populus tremuloides Michx.) line 22 overexpressing the oat (Avena sativa) PHYTOCHROME A gene. Line 22 was not able to detect the SD and, consequently, did not stop growing in SD conditions. This resulted in an impaired freezing tolerance development under SD. In contrast, exposure to LT resulted in cold acclimation of line 22 to a degree comparable with the WT. In contrast to the WT, line 22 could not dehydrate the overwintering tissues or induce the production of dehydrins (DHN) under SD conditions. Furthermore, abscisic acid (ABA) content of the buds of line 22 were the same under SD and long daylength, whereas prolonged SD exposure decreased the ABA level in the WT. LT exposure resulted in a rapid accumulation of DHN in both the WT and line 22. Similarly, ABA content increased transiently in both the WT and line 22. Our results indicate that phytochrome A is involved in photoperiodic regulation of ABA and DHN levels, but at LT they are regulated by a different mechanism. Although SD and LT induce cold acclimation independently, ABA and DHN may play important roles in both modes of acclimation.

@article{peng_molecular_2002,
	title = {Molecular and physiological characterization of {Arabidopsis} {GAI} alleles obtained in targeted {Ds}-tagging experiments},
	volume = {214},
	issn = {1432-2048},
	url = {https://doi.org/10.1007/s004250100643},
	doi = {10.1007/s004250100643},
	abstract = {Bioactive gibberellin (GA) is an essential regulator of vascular plant development. The GAI gene of Arabidopsis thaliana (L.) Heynh. encodes a product (GAI) that is involved in GA signalling. The dominant mutant gai allele encodes an altered product (gai) that confers reduced GA responses, dwarfism, and elevated endogenous GA levels. Recessive, presumed loss-of-function alleles of GAI confer normal height and resistance to the GA biosynthesis inhibitor paclobutrazol. One explanation for these observations is that GAI is a growth repressor whose activity is opposed by GA, whilst gai retains a constitutive repressor activity that is less affected by GA. Previously, we described gai-t6, a mutant allele which contains an insertion of a maize Ds transposable element into gai. Here we describe the molecular and physiological characterization of two further alleles (gai-t5, gai-t7) identified during the Ds mutagenesis experiment. These alleles confer paclobutrazol resistance and normal endogenous GA levels. Thus the phenotype conferred by gai-t5, gai-t6 and gai-t7 is not due to elevated GA levels, but is due to loss of gai, a constitutively active plant growth repressor.},
	language = {en},
	number = {4},
	urldate = {2021-10-19},
	journal = {Planta},
	author = {Peng, Jinrong and Richards, Donald E. and Moritz, Thomas and Ezura, Hiroshi and Carol, Pierre and Harberd, Nicholas P.},
	month = feb,
	year = {2002},
	pages = {591--596},
}

Bioactive gibberellin (GA) is an essential regulator of vascular plant development. The GAI gene of Arabidopsis thaliana (L.) Heynh. encodes a product (GAI) that is involved in GA signalling. The dominant mutant gai allele encodes an altered product (gai) that confers reduced GA responses, dwarfism, and elevated endogenous GA levels. Recessive, presumed loss-of-function alleles of GAI confer normal height and resistance to the GA biosynthesis inhibitor paclobutrazol. One explanation for these observations is that GAI is a growth repressor whose activity is opposed by GA, whilst gai retains a constitutive repressor activity that is less affected by GA. Previously, we described gai-t6, a mutant allele which contains an insertion of a maize Ds transposable element into gai. Here we describe the molecular and physiological characterization of two further alleles (gai-t5, gai-t7) identified during the Ds mutagenesis experiment. These alleles confer paclobutrazol resistance and normal endogenous GA levels. Thus the phenotype conferred by gai-t5, gai-t6 and gai-t7 is not due to elevated GA levels, but is due to loss of gai, a constitutively active plant growth repressor.

@article{uggla_function_2001,
	title = {Function and {Dynamics} of {Auxin} and {Carbohydrates} during {Earlywood}/{Latewood} {Transition} in {Scots} {Pine1}},
	volume = {125},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.125.4.2029},
	doi = {10/csvzgg},
	abstract = {In temperate regions the annual pattern of wood development is characterized by the formation of radially narrow and thick walled latewood cells. This takes place at the later part of the growing season when cambial cell division declines. To gain new insight into the regulation of this process, micro-analytical techniques were used to visualize the distribution of indole-3-acetic acid (IAA), soluble carbohydrates, and activities of sucrose (Suc)-metabolizing enzymes across the cambial region tissues in Scots pine (Pinus sylvestris). The total amount of IAA in the cambial region did not change with latewood initiation. But its radial distribution pattern was altered, resulting in an increased concentration in the cambial meristem and its recent derivatives. Thus, initiation of latewood formation and cessation of cambial cell division is not a consequence of decreased IAA concentrations in dividing and expanding cells. Rather, IAA most likely has a role in defining the altered developmental pattern associated with latewood formation. Carbohydrates and enzyme activities showed distinctive radial distribution patterns. Suc peaked in the phloem and decreased sharply to low levels across the cambial zone, whereas fructose and glucose reached their highest levels in the maturing tracheids. Suc synthase was the dominating Suc cleaving enzyme with a peak in the secondary wall-forming tracheids and in the phloem. Soluble acid invertase peaked in dividing and expanding cells. Suc-phosphate synthase had its highest activities in the phloem. Activities of cell wall bound invertase were low. The absence of major seasonal variations indicates that carbohydrate availability is not a trigger for latewood initiation. However, steep concentration gradients of the sugars suggest a role for sugar signaling in vascular development.},
	number = {4},
	urldate = {2021-11-02},
	journal = {Plant Physiology},
	author = {Uggla, Claes and Magel, Elisabeth and Moritz, Thomas and Sundberg, Björn},
	month = apr,
	year = {2001},
	pages = {2029--2039},
}

In temperate regions the annual pattern of wood development is characterized by the formation of radially narrow and thick walled latewood cells. This takes place at the later part of the growing season when cambial cell division declines. To gain new insight into the regulation of this process, micro-analytical techniques were used to visualize the distribution of indole-3-acetic acid (IAA), soluble carbohydrates, and activities of sucrose (Suc)-metabolizing enzymes across the cambial region tissues in Scots pine (Pinus sylvestris). The total amount of IAA in the cambial region did not change with latewood initiation. But its radial distribution pattern was altered, resulting in an increased concentration in the cambial meristem and its recent derivatives. Thus, initiation of latewood formation and cessation of cambial cell division is not a consequence of decreased IAA concentrations in dividing and expanding cells. Rather, IAA most likely has a role in defining the altered developmental pattern associated with latewood formation. Carbohydrates and enzyme activities showed distinctive radial distribution patterns. Suc peaked in the phloem and decreased sharply to low levels across the cambial zone, whereas fructose and glucose reached their highest levels in the maturing tracheids. Suc synthase was the dominating Suc cleaving enzyme with a peak in the secondary wall-forming tracheids and in the phloem. Soluble acid invertase peaked in dividing and expanding cells. Suc-phosphate synthase had its highest activities in the phloem. Activities of cell wall bound invertase were low. The absence of major seasonal variations indicates that carbohydrate availability is not a trigger for latewood initiation. However, steep concentration gradients of the sugars suggest a role for sugar signaling in vascular development.

@article{gocal_gamyb-like_2001,
	title = {{GAMYB}-like {Genes}, {Flowering}, and {Gibberellin}  {Signaling} in {Arabidopsis}},
	volume = {127},
	issn = {0032-0889},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133573/},
	abstract = {We have identified three Arabidopsis genes with GAMYB-like activity, AtMYB33, AtMYB65, and AtMYB101, which can substitute for barley (Hordeum vulgare) GAMYB in transactivating the barley α-amylase promoter. We have investigated the relationships between gibberellins (GAs), these GAMYB-like genes, and petiole elongation and flowering of Arabidopsis. Within 1 to 2 d of transferring plants from short- to long-day photoperiods, growth rate and erectness of petioles increased, and there were morphological changes at the shoot apex associated with the transition to flowering. These responses were accompanied by accumulation of GAs in the petioles (GA1 by 11-fold and GA4 by 3-fold), and an increase in expression of AtMYB33 at the shoot apex. Inhibition of GA biosynthesis using paclobutrazol blocked the petiole elongation induced by long days. Causality was suggested by the finding that, with GA treatment, plants flowered in short days, AtMYB33 expression increased at the shoot apex, and the petioles elongated and grew erect. That AtMYB33 may mediate a GA signaling role in flowering was supported by its ability to bind to a specific 8-bp sequence in the promoter of the floral meristem-identity gene, LEAFY, this same sequence being important in the GA response of the LEAFY promoter. One or more of these AtMYB genes may also play a role in the root tip during germination and, later, in stem tissue. These findings extend our earlier studies of GA signaling in the Gramineae to include a dicot species, Arabidopsis, and indicate that GAMYB-like genes may mediate GA signaling in growth and flowering responses.},
	number = {4},
	urldate = {2021-11-02},
	journal = {Plant Physiology},
	author = {Gocal, Gregory F.W. and Sheldon, Candice C. and Gubler, Frank and Moritz, Thomas and Bagnall, David J. and MacMillan, Colleen P. and Li, Song F. and Parish, Roger W. and Dennis, Elizabeth S. and Weigel, Detlef and King, Rod W.},
	month = dec,
	year = {2001},
	pmid = {11743113},
	pmcid = {PMC133573},
	pages = {1682--1693},
}

We have identified three Arabidopsis genes with GAMYB-like activity, AtMYB33, AtMYB65, and AtMYB101, which can substitute for barley (Hordeum vulgare) GAMYB in transactivating the barley α-amylase promoter. We have investigated the relationships between gibberellins (GAs), these GAMYB-like genes, and petiole elongation and flowering of Arabidopsis. Within 1 to 2 d of transferring plants from short- to long-day photoperiods, growth rate and erectness of petioles increased, and there were morphological changes at the shoot apex associated with the transition to flowering. These responses were accompanied by accumulation of GAs in the petioles (GA1 by 11-fold and GA4 by 3-fold), and an increase in expression of AtMYB33 at the shoot apex. Inhibition of GA biosynthesis using paclobutrazol blocked the petiole elongation induced by long days. Causality was suggested by the finding that, with GA treatment, plants flowered in short days, AtMYB33 expression increased at the shoot apex, and the petioles elongated and grew erect. That AtMYB33 may mediate a GA signaling role in flowering was supported by its ability to bind to a specific 8-bp sequence in the promoter of the floral meristem-identity gene, LEAFY, this same sequence being important in the GA response of the LEAFY promoter. One or more of these AtMYB genes may also play a role in the root tip during germination and, later, in stem tissue. These findings extend our earlier studies of GA signaling in the Gramineae to include a dicot species, Arabidopsis, and indicate that GAMYB-like genes may mediate GA signaling in growth and flowering responses.

@article{king_gibberellins_2001,
	title = {Gibberellins {Are} {Not} {Required} for {Normal} {Stem} {Growth} in {Arabidopsis} thaliana in the {Absence} of {GAI} and {RGA}},
	volume = {159},
	issn = {1943-2631},
	url = {https://doi.org/10.1093/genetics/159.2.767},
	doi = {10/gn2mhv},
	abstract = {The growth of Arabidopsis thaliana is quantitatively regulated by the phytohormone gibberellin (GA) via two closely related nuclear GA-signaling components, GAI and RGA. Here we test the hypothesis that GAI and RGA function as “GA-derepressible repressors” of plant growth. One prediction of this hypothesis is that plants lacking GAI and RGA do not require GA for normal stem growth. Analysis of GA-deficient mutants lacking GAI and RGA confirms this prediction and suggests that in the absence of GAI and RGA, “growth” rather than “no growth” is the default state of plant stems. The function of the GA-signaling system is thus to act as a control system regulating the amount of this growth. We also demonstrate that the GA dose dependency of hypocotyl elongation is altered in mutants lacking GAI and RGA and propose that increments in GAI/RGA repressor function can explain the quantitative nature of GA responses.},
	number = {2},
	urldate = {2021-11-02},
	journal = {Genetics},
	author = {King, Kathryn E and Moritz, Thomas and Harberd, Nicholas P},
	month = oct,
	year = {2001},
	pages = {767--776},
}

The growth of Arabidopsis thaliana is quantitatively regulated by the phytohormone gibberellin (GA) via two closely related nuclear GA-signaling components, GAI and RGA. Here we test the hypothesis that GAI and RGA function as “GA-derepressible repressors” of plant growth. One prediction of this hypothesis is that plants lacking GAI and RGA do not require GA for normal stem growth. Analysis of GA-deficient mutants lacking GAI and RGA confirms this prediction and suggests that in the absence of GAI and RGA, “growth” rather than “no growth” is the default state of plant stems. The function of the GA-signaling system is thus to act as a control system regulating the amount of this growth. We also demonstrate that the GA dose dependency of hypocotyl elongation is altered in mutants lacking GAI and RGA and propose that increments in GAI/RGA repressor function can explain the quantitative nature of GA responses.

@article{king_long-day_2001,
	title = {Long-{Day} {Induction} of {Flowering} in {Lolium} temulentum {Involves} {Sequential} {Increases} in {Specific}  {Gibberellins} at the {Shoot} {Apex}},
	volume = {127},
	issn = {0032-0889},
	url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC125097/},
	abstract = {One challenge for plant biology has been to identify floral stimuli at the shoot apex. Using sensitive and specific gas chromatography-mass spectrometry techniques, we have followed changes in gibberellins (GAs) at the shoot apex during long day (LD)-regulated induction of flowering in the grass Lolium temulentum. Two separate roles of GAs in flowering are indicated. First, within 8 h of an inductive LD, i.e. at the time of floral evocation, the GA5 content of the shoot apex doubled to about 120 ng g−1 dry weight. The concentration of applied GA5 required for floral induction of excised apices (R.W. King, C. Blundell, L.T. Evans [1993] Aust J Plant Physiol 20: 337–348) was similar to that in the shoot apex. Leaf-applied [2H4] GA5 was transported intact from the leaf to the shoot apex, flowering being proportional to the amount of GA5 imported. Thus, GA5 could be part of the LD stimulus for floral evocation of L. temulentum or, alternatively, its increase at the shoot apex could follow import of a primary floral stimulus. Later, during inflorescence differentiation and especially after exposure to additional LD, a second GA action was apparent. The content of GA1 and GA4 in the apex increased greatly, whereas GA5 decreased by up to 75\%. GA4 applied during inflorescence differentiation strongly promoted flowering and stem elongation, whereas it was ineffective for earlier floral evocation although it caused stem growth at all times of application. Thus, we conclude that GA1 and GA4 are secondary, late-acting LD stimuli for inflorescence differentiation in L. temulentum.},
	number = {2},
	urldate = {2021-11-02},
	journal = {Plant Physiology},
	author = {King, Rod W. and Moritz, Thomas and Evans, Lloyd T. and Junttila, Olavi and Herlt, Anthony J.},
	month = oct,
	year = {2001},
	pmid = {11598236},
	pmcid = {PMC125097},
	pages = {624--632},
}

One challenge for plant biology has been to identify floral stimuli at the shoot apex. Using sensitive and specific gas chromatography-mass spectrometry techniques, we have followed changes in gibberellins (GAs) at the shoot apex during long day (LD)-regulated induction of flowering in the grass Lolium temulentum. Two separate roles of GAs in flowering are indicated. First, within 8 h of an inductive LD, i.e. at the time of floral evocation, the GA5 content of the shoot apex doubled to about 120 ng g−1 dry weight. The concentration of applied GA5 required for floral induction of excised apices (R.W. King, C. Blundell, L.T. Evans [1993] Aust J Plant Physiol 20: 337–348) was similar to that in the shoot apex. Leaf-applied [2H4] GA5 was transported intact from the leaf to the shoot apex, flowering being proportional to the amount of GA5 imported. Thus, GA5 could be part of the LD stimulus for floral evocation of L. temulentum or, alternatively, its increase at the shoot apex could follow import of a primary floral stimulus. Later, during inflorescence differentiation and especially after exposure to additional LD, a second GA action was apparent. The content of GA1 and GA4 in the apex increased greatly, whereas GA5 decreased by up to 75%. GA4 applied during inflorescence differentiation strongly promoted flowering and stem elongation, whereas it was ineffective for earlier floral evocation although it caused stem growth at all times of application. Thus, we conclude that GA1 and GA4 are secondary, late-acting LD stimuli for inflorescence differentiation in L. temulentum.

@article{astot_alternative_2000,
	title = {An alternative cytokinin biosynthesis pathway},
	volume = {97},
	copyright = {Copyright © 2000, The National Academy of Sciences},
	issn = {0027-8424, 1091-6490},
	url = {https://www.pnas.org/content/97/26/14778},
	doi = {10/dt77jp},
	abstract = {Studies of de novo cytokinin biosynthesis in isopentenyltransferase (ipt)-transformed Arabidopsis thaliana, involving in vivo deuterium labeling and mass spectrometry, showed that the biosynthetic rate of zeatinriboside-5′-monophosphate was around 66-fold higher than that of isopentenyladenosine-5′-monophosphate (iPMP), the proposed primary product of the Agrobacterium ipt. Double tracer analysis, using [2H6] isopentenyladenosine and deuterium oxide, provided evidence for an alternative, iPMP-independent, biosynthetic pathway for zeatin-type cytokinins, present in both ipt-expressing and wild-type Arabidopsis thaliana. Reduction of the biosynthetic flux in the alternative pathway by use of mevastatin, an inhibitor for 3-hydroxy-3-methylglutaryl CoA reductase, indicated a terpenoid origin for the side-chain precursor of the iPMP independent pathway.},
	language = {en},
	number = {26},
	urldate = {2021-11-08},
	journal = {Proceedings of the National Academy of Sciences},
	author = {Åstot, Crister and Dolezal, Karel and Nordström, Anders and Wang, Qun and Kunkel, Tim and Moritz, Thomas and Chua, Nam-Hai and Sandberg, Göran},
	month = dec,
	year = {2000},
	pmid = {11114204},
	note = {Publisher: National Academy of Sciences
Section: Biological Sciences},
	pages = {14778--14783},
}

Studies of de novo cytokinin biosynthesis in isopentenyltransferase (ipt)-transformed Arabidopsis thaliana, involving in vivo deuterium labeling and mass spectrometry, showed that the biosynthetic rate of zeatinriboside-5′-monophosphate was around 66-fold higher than that of isopentenyladenosine-5′-monophosphate (iPMP), the proposed primary product of the Agrobacterium ipt. Double tracer analysis, using [2H6] isopentenyladenosine and deuterium oxide, provided evidence for an alternative, iPMP-independent, biosynthetic pathway for zeatin-type cytokinins, present in both ipt-expressing and wild-type Arabidopsis thaliana. Reduction of the biosynthetic flux in the alternative pathway by use of mevastatin, an inhibitor for 3-hydroxy-3-methylglutaryl CoA reductase, indicated a terpenoid origin for the side-chain precursor of the iPMP independent pathway.

@article{astot_deuterium_2000,
	title = {Deuterium in vivo labelling of cytokinins in {Arabidopsis} thaliana analysed by capillary liquid chromatography/frit-fast atom bombardment mass spectrometry},
	volume = {35},
	issn = {1096-9888},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291096-9888%28200001%2935%3A1%3C13%3A%3AAID-JMS901%3E3.0.CO%3B2-I},
	doi = {10.1002/(SICI)1096-9888(200001)35:1<13::AID-JMS901>3.0.CO;2-I},
	abstract = {A method was developed for analysing the biosynthetic rate of the cytokinin class of plant hormones. Transgenic, cytokinin-overproducing Arabidopsis thaliana plants were incubated in liquid culture media enriched with 30\% deuterium oxide, and incorporation into the different parts of the cytokinin molecule was analysed by capillary liquid chromatography/frit-fast atom bombardment mass spectrometry after precolumn propionylation. The sugar moieties of the cytokinins generally showed a high and independent incorporation, so the analysis in this study focused on the cytokinin base moieties. It was observed that during a 24 h incubation period almost all labelling was incorporated into the side-chain, rather than the adenine moiety. The incorporation dynamics of isopentenyladenosine-5′-monophosphate, zeatinriboside-5′-monophosphate (ZRMP) and zeatin-9-glucoside were investigated through analysis of the cytokinin base fragments in high-resolution selective ion monitoring mode. Using a fractional synthetic rate approach, the biosynthetic rate of ZRMP was determined to be 18 ng h−1 g−1 fresh weight, giving a turnover time of 25 h. A method for the mass isotopomer abundance analysis of the cytokinins in the zeatin family, based on selective reaction monitoring, was also developed to gain further sensitivity. Use of this technique showed that there was a higher level of enrichment in zeatin nucleotide than in the corresponding nucleoside, in agreement with the hypothesis that cytokinin nucleotides are primary products in this pathway. Copyright © 2000 John Wiley \& Sons, Ltd.},
	language = {en},
	number = {1},
	urldate = {2021-11-08},
	journal = {Journal of Mass Spectrometry},
	author = {Åstot, Crister and Dolezal, Karel and Moritz, Thomas and Sandberg, Göran},
	year = {2000},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/\%28SICI\%291096-9888\%28200001\%2935\%3A1\%3C13\%3A\%3AAID-JMS901\%3E3.0.CO\%3B2-I},
	keywords = {Arabidopsis thaliana, cytokinin biosynthesis, fast atom bombardment, in vivo labelling, isotopomer},
	pages = {13--22},
}

A method was developed for analysing the biosynthetic rate of the cytokinin class of plant hormones. Transgenic, cytokinin-overproducing Arabidopsis thaliana plants were incubated in liquid culture media enriched with 30% deuterium oxide, and incorporation into the different parts of the cytokinin molecule was analysed by capillary liquid chromatography/frit-fast atom bombardment mass spectrometry after precolumn propionylation. The sugar moieties of the cytokinins generally showed a high and independent incorporation, so the analysis in this study focused on the cytokinin base moieties. It was observed that during a 24 h incubation period almost all labelling was incorporated into the side-chain, rather than the adenine moiety. The incorporation dynamics of isopentenyladenosine-5′-monophosphate, zeatinriboside-5′-monophosphate (ZRMP) and zeatin-9-glucoside were investigated through analysis of the cytokinin base fragments in high-resolution selective ion monitoring mode. Using a fractional synthetic rate approach, the biosynthetic rate of ZRMP was determined to be 18 ng h−1 g−1 fresh weight, giving a turnover time of 25 h. A method for the mass isotopomer abundance analysis of the cytokinins in the zeatin family, based on selective reaction monitoring, was also developed to gain further sensitivity. Use of this technique showed that there was a higher level of enrichment in zeatin nucleotide than in the corresponding nucleoside, in agreement with the hypothesis that cytokinin nucleotides are primary products in this pathway. Copyright © 2000 John Wiley & Sons, Ltd.

@article{eriksson_increased_2000,
	title = {Increased gibberellin biosynthesis in transgenic trees promotes growth, biomass production and xylem fiber length},
	volume = {18},
	copyright = {2000 Nature America Inc.},
	issn = {1546-1696},
	url = {https://www.nature.com/articles/nbt0700_784},
	doi = {10.1038/77355},
	abstract = {In most tree-breeding programs worldwide, increasing the trees' growth rates and stem volumes and shortening their rotation times are important aims. Such trees would yield more biomass per unit area. Here we show that overexpressing a key regulatory gene in the biosynthesis of the plant hormone gibberellin (GA) in hybrid aspen (Populus tremula × P. tremuloides) improves growth rate and biomass. In addition, these transgenic trees have more numerous and longer xylem fibers than unmodified wild-type (wt) plants. Long fibers are desirable in the production of strong paper, but it has not as yet proved possible to influence this trait by traditional breeding techniques. We also show that GA has an antagonistic effect on root initiation, as the transgenic lines showed poorer rooting than the control plants when potted in soil. However, the negative effect on rooting efficiencies in the initial establishment of young plantlets in the growth chamber did not significantly affect root growth at later stages.},
	language = {en},
	number = {7},
	urldate = {2021-11-08},
	journal = {Nature Biotechnology},
	author = {Eriksson, Maria E. and Israelsson, Maria and Olsson, Olof and Moritz, Thomas},
	month = jul,
	year = {2000},
	note = {Bandiera\_abtest: a
Cg\_type: Nature Research Journals
Number: 7
Primary\_atype: Research
Publisher: Nature Publishing Group},
	keywords = {Agriculture, Bioinformatics, Biomedical Engineering/Biotechnology, Biomedicine, Biotechnology, Life Sciences, general},
	pages = {784--788},
}

In most tree-breeding programs worldwide, increasing the trees' growth rates and stem volumes and shortening their rotation times are important aims. Such trees would yield more biomass per unit area. Here we show that overexpressing a key regulatory gene in the biosynthesis of the plant hormone gibberellin (GA) in hybrid aspen (Populus tremula × P. tremuloides) improves growth rate and biomass. In addition, these transgenic trees have more numerous and longer xylem fibers than unmodified wild-type (wt) plants. Long fibers are desirable in the production of strong paper, but it has not as yet proved possible to influence this trait by traditional breeding techniques. We also show that GA has an antagonistic effect on root initiation, as the transgenic lines showed poorer rooting than the control plants when potted in soil. However, the negative effect on rooting efficiencies in the initial establishment of young plantlets in the growth chamber did not significantly affect root growth at later stages.

@article{eklof_transgenic_2000,
	title = {Transgenic tobacco plants co-expressing {Agrobacterium} iaa and ipt genes have wild-type hormone levels but display both auxin- and cytokinin-overproducing phenotypes},
	volume = {23},
	issn = {1365-313X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-313x.2000.00762.x},
	doi = {10/dkzdj3},
	abstract = {Transgenic tobacco lines simultaneously expressing the Agrobacterium iaaM, iaaH and ipt genes, obtained by crossing lines expressing ipt with lines expressing iaaM and iaaH, were used to study in planta interactions between auxin and cytokinins. All phenotypic traits of the respective parental lines characteristic of cytokinin and auxin overproduction were present in the cross. Indole-3-acetic acid (IAA) and combined zeatin riboside (ZR) and zeatin riboside-5′-monophosphate (ZRMP) contents were analysed by mass spectrometry in young, developing leaves from the cross, the parental lines and the wild type. Unexpectedly, hormone levels in the cross were very similar to wild-type levels. Thus IAA levels in the cross were much lower throughout vegetative development than in the parental IAA overproducing line, although expression of the bacterial IAA biosynthesis genes was not reduced. The results suggest that effects on apical dominance, adventitious root formation, leaf morphology and other traits commonly ± associated with IAA and cytokinin overproduction, and observed in the iaaËipt cross, cannot be explained solely by analysis of auxin and cytokinin contents in individual organs. As traits associated with both hormones are expressed in close spatial and temporal proximity, it is likely that cellular resolution of hormone contents is essential to explain physiological responses to auxins and cytokinins.},
	language = {en},
	number = {2},
	urldate = {2021-11-08},
	journal = {The Plant Journal},
	author = {Eklöf, Staffan and Åstot, Crister and Sitbon, Folke and Moritz, Thomas and Olsson, Olof and Sandberg, Göran},
	year = {2000},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-313x.2000.00762.x},
	keywords = {IAA, Nicotiana tabacum, cytokinin, morphology, ratio hypothesis, transgenic plants},
	pages = {279--284},
}

Transgenic tobacco lines simultaneously expressing the Agrobacterium iaaM, iaaH and ipt genes, obtained by crossing lines expressing ipt with lines expressing iaaM and iaaH, were used to study in planta interactions between auxin and cytokinins. All phenotypic traits of the respective parental lines characteristic of cytokinin and auxin overproduction were present in the cross. Indole-3-acetic acid (IAA) and combined zeatin riboside (ZR) and zeatin riboside-5′-monophosphate (ZRMP) contents were analysed by mass spectrometry in young, developing leaves from the cross, the parental lines and the wild type. Unexpectedly, hormone levels in the cross were very similar to wild-type levels. Thus IAA levels in the cross were much lower throughout vegetative development than in the parental IAA overproducing line, although expression of the bacterial IAA biosynthesis genes was not reduced. The results suggest that effects on apical dominance, adventitious root formation, leaf morphology and other traits commonly ± associated with IAA and cytokinin overproduction, and observed in the iaaËipt cross, cannot be explained solely by analysis of auxin and cytokinin contents in individual organs. As traits associated with both hormones are expressed in close spatial and temporal proximity, it is likely that cellular resolution of hormone contents is essential to explain physiological responses to auxins and cytokinins.

@article{valkonen_dwarf_1999,
	title = {Dwarf (di)haploid pito mutants obtained from a tetraploid potato cultivar ({Solanum} tuberosum subsp. tuberosum) via anther culture are defective in gibberellin biosynthesis},
	volume = {149},
	issn = {0168-9452},
	url = {https://www.sciencedirect.com/science/article/pii/S0168945299001417},
	doi = {10/b29hzp},
	abstract = {Nine dwarf (di)haploid lines (2n=2×=24) were obtained from the tetraploid (2n=4×=48), long day-adapted potato cultivar ‘Pito’ (Solanum tuberosum subsp. tuberosum) through anther culture. They grew slowly, had very short internodes, compact and ball-shaped appearance, and dark green leaves. Dwarfism was due to a recessive gene, designated pito. Endogenous gibberellin contents were measured in the leaves of dwarf and wild-type lines by gas chromatography linked to mass spectrometry (GC-MS). High amounts of GA19, GA20, GA29, GA1, and GA8 were detected in the wild-type plants, which indicated that the early 13-hydroxylation pathway was predominantly used for GA biosynthesis in S. t. subsp. tuberosum. Also GA53, GA15 and GA9 were detected but not quantified. Very low endogenous amounts of all analysed GAs were detected in the pito mutants, indicating a block at an early part of the GA biosynthesis pathway. The dwarf lines strongly and quickly responded to the exogenous application of low amounts (79 nM) of bioactive GA (GA3), which restored normal growth and confirmed that the pito dwarfs were synthesis mutants and not GA response mutants.},
	language = {en},
	number = {1},
	urldate = {2021-11-08},
	journal = {Plant Science},
	author = {Valkonen, Jari P. T. and Moritz, Thomas and Watanabe, Kazuo N. and Rokka, Veli-Matti},
	month = nov,
	year = {1999},
	keywords = {Dwarf, Gas chromatography mass spectrometry GC-MS, Gibberellin, Potato},
	pages = {51--57},
}

Nine dwarf (di)haploid lines (2n=2×=24) were obtained from the tetraploid (2n=4×=48), long day-adapted potato cultivar ‘Pito’ (Solanum tuberosum subsp. tuberosum) through anther culture. They grew slowly, had very short internodes, compact and ball-shaped appearance, and dark green leaves. Dwarfism was due to a recessive gene, designated pito. Endogenous gibberellin contents were measured in the leaves of dwarf and wild-type lines by gas chromatography linked to mass spectrometry (GC-MS). High amounts of GA19, GA20, GA29, GA1, and GA8 were detected in the wild-type plants, which indicated that the early 13-hydroxylation pathway was predominantly used for GA biosynthesis in S. t. subsp. tuberosum. Also GA53, GA15 and GA9 were detected but not quantified. Very low endogenous amounts of all analysed GAs were detected in the pito mutants, indicating a block at an early part of the GA biosynthesis pathway. The dwarf lines strongly and quickly responded to the exogenous application of low amounts (79 nM) of bioactive GA (GA3), which restored normal growth and confirmed that the pito dwarfs were synthesis mutants and not GA response mutants.

@article{peng_extragenic_1999,
	title = {Extragenic {Suppressors} of the {Arabidopsis} {gaiMutation} {Alter} the {Dose}-{Response} {Relationship} of {Diverse} {Gibberellin} {Responses1}},
	volume = {119},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.119.4.1199},
	doi = {10/bd2xj4},
	abstract = {Active gibberellins (GAs) are endogenous factors that regulate plant growth and development in a dose-dependent fashion. Mutant plants that are GA deficient, or exhibit reduced GA responses, display a characteristic dwarf phenotype. Extragenic suppressor analysis has resulted in the isolation of Arabidopsis mutations, which partially suppress the dwarf phenotype conferred by GA deficiency and reduced GA-response mutations. Here we describe detailed studies of the effects of two of these suppressors,spy-7 and gar2–1, on several different GA-responsive growth processes (seed germination, vegetative growth, stem elongation, chlorophyll accumulation, and flowering) and on the in planta amounts of active and inactive GA species. The results of these experiments show that spy-7 and gar2–1affect the GA dose-response relationship for a wide range of GA responses and suggest that all GA-regulated processes are controlled through a negatively acting GA-signaling pathway.},
	number = {4},
	urldate = {2021-11-08},
	journal = {Plant Physiology},
	author = {Peng, Jinrong and Richards, Donald E. and Moritz, Thomas and Caño-Delgado, Ana and Harberd, Nicholas P.},
	month = apr,
	year = {1999},
	pages = {1199--1208},
}

Active gibberellins (GAs) are endogenous factors that regulate plant growth and development in a dose-dependent fashion. Mutant plants that are GA deficient, or exhibit reduced GA responses, display a characteristic dwarf phenotype. Extragenic suppressor analysis has resulted in the isolation of Arabidopsis mutations, which partially suppress the dwarf phenotype conferred by GA deficiency and reduced GA-response mutations. Here we describe detailed studies of the effects of two of these suppressors,spy-7 and gar2–1, on several different GA-responsive growth processes (seed germination, vegetative growth, stem elongation, chlorophyll accumulation, and flowering) and on the in planta amounts of active and inactive GA species. The results of these experiments show that spy-7 and gar2–1affect the GA dose-response relationship for a wide range of GA responses and suggest that all GA-regulated processes are controlled through a negatively acting GA-signaling pathway.

@article{fridborg_arabidopsis_1999,
	title = {The {Arabidopsis} {Dwarf} {Mutant} shi {Exhibits} {Reduced} {Gibberellin} {Responses} {Conferred} by {Overexpression} of a {New} {Putative} {Zinc} {Finger} {Protein}},
	volume = {11},
	issn = {1040-4651},
	url = {https://doi.org/10.1105/tpc.11.6.1019},
	doi = {10/cx9c78},
	abstract = {shi (for short internodes), a semidominant dwarfing mutation of Arabidopsis caused by a transposon insertion, confers a phenotype typical of mutants defective in the biosynthesis of gibberellin (GA). However, the application of GA does not correct the dwarf phenotype of shi plants, suggesting that shi is defective in the perception of or in the response to GA. In agreement with this observation, the level of active GAs was elevated in shi plants, which is the result expected when feedback control of GA biosynthesis is reduced. Cloning of the SHI gene revealed that in shi, the transposon is inserted into the untranslated leader so that a cauliflower mosaic virus 35S promoter in the transposon reads out toward the SHI open reading frame. This result, together with mRNA analysis, suggests that the phenotype of the shi mutant is a result of overexpression of the SHI open reading frame. The predicted amino acid sequence of SHI has acidic and glutamine-rich stretches and shows sequence similarity over a putative zinc finger region to three presumptive Arabidopsis proteins. This suggests that SHI may act as a negative regulator of GA responses through transcriptional control.},
	number = {6},
	urldate = {2021-11-08},
	journal = {The Plant Cell},
	author = {Fridborg, Ingela and Kuusk, Sandra and Moritz, Thomas and Sundberg, Eva},
	month = jun,
	year = {1999},
	pages = {1019--1031},
}

shi (for short internodes), a semidominant dwarfing mutation of Arabidopsis caused by a transposon insertion, confers a phenotype typical of mutants defective in the biosynthesis of gibberellin (GA). However, the application of GA does not correct the dwarf phenotype of shi plants, suggesting that shi is defective in the perception of or in the response to GA. In agreement with this observation, the level of active GAs was elevated in shi plants, which is the result expected when feedback control of GA biosynthesis is reduced. Cloning of the SHI gene revealed that in shi, the transposon is inserted into the untranslated leader so that a cauliflower mosaic virus 35S promoter in the transposon reads out toward the SHI open reading frame. This result, together with mRNA analysis, suggests that the phenotype of the shi mutant is a result of overexpression of the SHI open reading frame. The predicted amino acid sequence of SHI has acidic and glutamine-rich stretches and shows sequence similarity over a putative zinc finger region to three presumptive Arabidopsis proteins. This suggests that SHI may act as a negative regulator of GA responses through transcriptional control.

@article{olsen_ectopic_1997,
	title = {Ectopic expression of oat phytochrome {A} in hybrid aspen changes critical daylength for growth and prevents cold acclimatization},
	volume = {12},
	issn = {1365-313X},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-313x.1997.12061339.x},
	doi = {10/c5z6sf},
	abstract = {Survival of temperate-zone tree species under the normal summer-winter cycle is dependent on proper timing of apical growth cessation and cold acclimatization. This timing is primarily based on the perception of daylength, and through evolution many tree species have developed photoperiodic ecotypes which are closely adapted to the local light conditions. The longest photoperiod inducing growth cessation, the critical photoperiod, is inherited as a quantitative character. The phytochrome pigment family is the probable receptor of daylength, but the exact role of phytochrome and the physiological basis for the different responses between photoperiodic ecotypes are not known. This report shows for the first time that over-expression of the oat phytochrome A gene (PHYA) in a tree significantly changes the critical daylength and effectively prevents cold acclimatization. While the critical daylength for elongation growth in the wild-type of hybrid aspen (Populus tremula × tremuloides) was approximately 15 h, transgenic lines with a strong expression of the oat PHYA gene did not stop growing even under a photoperiod of 6 h. Quantitative analysis of gibberellins (GA) as well as indole-3-acetic acid (IAA) revealed that levels of these were not down-regulated under short days in the transgenic plants expressing high levels of oat PHYA, as in the wild-type. These results indicate that photoperiodic responses in trees might be regulated by the amount of PHYA gene expressed in the plants, and that the amount of phytochrome A (phyA) affects the metabolism of GAs and IAA.},
	language = {en},
	number = {6},
	urldate = {2022-03-11},
	journal = {The Plant Journal},
	author = {Olsen, Jorunn E. and Junttila, Olavi and Nilsen, Jarle and Eriksson, Maria E. and Martinussen, Inger and Olsson, Olof and Sandberg, Göran and Moritz, Thomas},
	year = {1997},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-313x.1997.12061339.x},
	pages = {1339--1350},
}

Survival of temperate-zone tree species under the normal summer-winter cycle is dependent on proper timing of apical growth cessation and cold acclimatization. This timing is primarily based on the perception of daylength, and through evolution many tree species have developed photoperiodic ecotypes which are closely adapted to the local light conditions. The longest photoperiod inducing growth cessation, the critical photoperiod, is inherited as a quantitative character. The phytochrome pigment family is the probable receptor of daylength, but the exact role of phytochrome and the physiological basis for the different responses between photoperiodic ecotypes are not known. This report shows for the first time that over-expression of the oat phytochrome A gene (PHYA) in a tree significantly changes the critical daylength and effectively prevents cold acclimatization. While the critical daylength for elongation growth in the wild-type of hybrid aspen (Populus tremula × tremuloides) was approximately 15 h, transgenic lines with a strong expression of the oat PHYA gene did not stop growing even under a photoperiod of 6 h. Quantitative analysis of gibberellins (GA) as well as indole-3-acetic acid (IAA) revealed that levels of these were not down-regulated under short days in the transgenic plants expressing high levels of oat PHYA, as in the wild-type. These results indicate that photoperiodic responses in trees might be regulated by the amount of PHYA gene expressed in the plants, and that the amount of phytochrome A (phyA) affects the metabolism of GAs and IAA.

@incollection{junttila_phytochrome_1997,
	address = {Boston, MA},
	title = {Phytochrome {Overexpression} and {Cold} {Hardiness} in {Transgenic} {Populus}},
	isbn = {978-1-4899-0277-1},
	url = {https://doi.org/10.1007/978-1-4899-0277-1_22},
	abstract = {Photoperiodic effects on woody plants were reported already by Gardner and Allard in 1923 and comprehensive studies during the ’50s confirmed the role of photoperiod as an important environmental regulator of growth and growth cessation in many northern tree species (Nitsch, 1957; Wareing, 1956). In woody plants cessation of apical growth is a prerequisite for cold acclimation (Weiser, 1970) and photoperiod, as a factor controlling growth cessation, is therefore an important environmental signal for initiation of cold acclimation. In many cases a proper timing of acclimation and deacclimation, in respect to annual variation of temperature conditions, is more critical for winter survival than the maximum level of frost hardiness. Also in such coniferous species where cessation of apical growth is not controlled by photoperiod, short photoperiod is necessary for good cold acclimation, low temperature causes no or only a limited level of hardiness if combined with long day conditions (Schwarz, 1970; Aronsson, 1975; Christersson, 1978; Jonsson et al., 1981). Thus, photoperiod may have both an indirect, through induction of growth cessation, and a more direct influence on cold acclimation in woody plants.},
	language = {en},
	urldate = {2022-03-11},
	booktitle = {Plant {Cold} {Hardiness}: {Molecular} {Biology}, {Biochemistry}, and {Physiology}},
	publisher = {Springer US},
	author = {Junttila, O. and Olsen, J. E. and Nilsen, J. and Martinussen, I. and Moritz, T. and Eriksson, M. and Olsson, O. and Sandberg, G.},
	editor = {Li, Paul H. and Chen, Tony H. H.},
	year = {1997},
	doi = {10.1007/978-1-4899-0277-1_22},
	keywords = {Cold Acclimation, Cold Hardiness, Growth Cessation, Photoperiodic Response, Short Photoperiod},
	pages = {245--255},
}

Photoperiodic effects on woody plants were reported already by Gardner and Allard in 1923 and comprehensive studies during the ’50s confirmed the role of photoperiod as an important environmental regulator of growth and growth cessation in many northern tree species (Nitsch, 1957; Wareing, 1956). In woody plants cessation of apical growth is a prerequisite for cold acclimation (Weiser, 1970) and photoperiod, as a factor controlling growth cessation, is therefore an important environmental signal for initiation of cold acclimation. In many cases a proper timing of acclimation and deacclimation, in respect to annual variation of temperature conditions, is more critical for winter survival than the maximum level of frost hardiness. Also in such coniferous species where cessation of apical growth is not controlled by photoperiod, short photoperiod is necessary for good cold acclimation, low temperature causes no or only a limited level of hardiness if combined with long day conditions (Schwarz, 1970; Aronsson, 1975; Christersson, 1978; Jonsson et al., 1981). Thus, photoperiod may have both an indirect, through induction of growth cessation, and a more direct influence on cold acclimation in woody plants.

@article{nilsson_expression_1996,
	title = {Expression of the {Agrobacterium} rhizogenes {rolC} {Gene} in a {Deciduous} {Forest} {Tree} {Alters} {Growth} and {Development} and {Leads} to {Stem} {Fasciation}},
	volume = {112},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.112.2.493},
	doi = {10.1104/pp.112.2.493},
	abstract = {We have altered the growth and development of a deciduous forest tree by transforming hybrid aspen (Populus tremula x Populus tremuloides) with the Agrobacterium rhizogenes rolC gene expressed under the strong cauliflower mosaic virus 35S promoter. We demonstrate that the genetically manipulated perennial plants, after a period of dormancy, maintain the induced phenotypical changes during the second growing period. Furthermore, mass-spectrometrical quantifications of the free and conjugated forms of indole-3-acetic acid and cytokinins and several gibberellins on one transgenic line correlate the induced developmental alterations such as stem fasciation to changes in plant hormone metabolism. We also show that the presence of the RolC protein increases the levels of the free cytokinins, but not by a process involving hydrolysis of the inactive cytokinin conjugates.},
	number = {2},
	urldate = {2024-10-07},
	journal = {Plant Physiology},
	author = {Nilsson, O. and Moritz, T. and Sundberg, B. and Sandberg, G. and Olsson, O.},
	month = oct,
	year = {1996},
	pages = {493--502},
}

We have altered the growth and development of a deciduous forest tree by transforming hybrid aspen (Populus tremula x Populus tremuloides) with the Agrobacterium rhizogenes rolC gene expressed under the strong cauliflower mosaic virus 35S promoter. We demonstrate that the genetically manipulated perennial plants, after a period of dormancy, maintain the induced phenotypical changes during the second growing period. Furthermore, mass-spectrometrical quantifications of the free and conjugated forms of indole-3-acetic acid and cytokinins and several gibberellins on one transgenic line correlate the induced developmental alterations such as stem fasciation to changes in plant hormone metabolism. We also show that the presence of the RolC protein increases the levels of the free cytokinins, but not by a process involving hydrolysis of the inactive cytokinin conjugates.

@article{nilsson_hormonal_1993,
	title = {Hormonal {Characterization} of {Transgenic} {Tobacco} {Plants} {Expressing} the {rolC} {Gene} of {Agrobacterium} rhizogenes {TL}-{DNA}},
	volume = {102},
	issn = {0032-0889},
	url = {https://doi.org/10.1104/pp.102.2.363},
	doi = {10.1104/pp.102.2.363},
	abstract = {Transgenic tobacco (Nicotiana tabacum L. cv Wisconsin 38) plants expressing the Agrobacterium rhizogenes rolC gene under the control of the cauliflower mosaic virus 35S RNA promoter were constructed. These plants displayed several morphological alterations reminiscent of changes in indole-3-acetic acid (IAA), cytokinin, and gibberellin (GA) content. However, investigations showed that neither the IAA pool size nor its rate of turnover were altered significantly in the rolC plants. The biggest difference between rolC and wild-type plants was in the concentrations of the cytokinin, isopentenyladenosine (iPA) and the gibberellin GA19. Radio-immunoassay and liquid chromatography-mass spectrometry measurements revealed a drastic reduction in rolC plants of iPA as well as in several other cytokinins tested, suggesting a possible reduction in the synthesis rate of cytokinins. Furthermore, gas chromatography-mass spectrometry quantifications of GA19 showed a 5- to 6-fold increase in rolC plants compared with wild-type plants, indicating a reduced activity of the GA19 oxidase, a proposed regulatory step in the gibberellin biosynthesis. Thus, we conclude that RolC activity in transgenic plants leads to major alterations in the metabolism of cytokinins and gibberellins.},
	number = {2},
	urldate = {2024-10-07},
	journal = {Plant Physiology},
	author = {Nilsson, O. and Moritz, T. and Imbault, N. and Sandberg, G. and Olsson, O.},
	month = jun,
	year = {1993},
	pages = {363--371},
}

Transgenic tobacco (Nicotiana tabacum L. cv Wisconsin 38) plants expressing the Agrobacterium rhizogenes rolC gene under the control of the cauliflower mosaic virus 35S RNA promoter were constructed. These plants displayed several morphological alterations reminiscent of changes in indole-3-acetic acid (IAA), cytokinin, and gibberellin (GA) content. However, investigations showed that neither the IAA pool size nor its rate of turnover were altered significantly in the rolC plants. The biggest difference between rolC and wild-type plants was in the concentrations of the cytokinin, isopentenyladenosine (iPA) and the gibberellin GA19. Radio-immunoassay and liquid chromatography-mass spectrometry measurements revealed a drastic reduction in rolC plants of iPA as well as in several other cytokinins tested, suggesting a possible reduction in the synthesis rate of cytokinins. Furthermore, gas chromatography-mass spectrometry quantifications of GA19 showed a 5- to 6-fold increase in rolC plants compared with wild-type plants, indicating a reduced activity of the GA19 oxidase, a proposed regulatory step in the gibberellin biosynthesis. Thus, we conclude that RolC activity in transgenic plants leads to major alterations in the metabolism of cytokinins and gibberellins.

@article{imbault_separation_1993,
	title = {Separation and identification of cytokinins using combined capillary liquid chromatography/mass spectrometry},
	volume = {22},
	copyright = {Copyright © 1993 John Wiley \& Sons, Ltd.},
	issn = {1096-9888},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/bms.1200220310},
	doi = {10.1002/bms.1200220310},
	abstract = {Non-derivatized cytokinins were analysed by liquid chromatography/mass spectrometry (LC/MS). The effluent from a capillary reversed-phase high-performance liquid chromatography column was introduced into the ion source of a double-focusing mass spectrometer via a frit interface, and ions were generated by fast atom bombardment (FAB) with 1\% glycerol in the mobile phase acting as a matrix. Positive FAB spectra were obtained for base, riboside, ribotide and glucoside forms of cytokinins. The spectra were found to provide useful information for identification and structural elucidation of cytokinins. The LC/MS system was used to identify iso-pentenyladenosine in a purified extract from Norway spruce (Picea abies) needles. Quantitative analysis of iso-pentenyladenosine using (2H6)isopentenyladenosine as internal standard indicated levels of 1.2 ng g−1 fresh weight.},
	language = {en},
	number = {3},
	urldate = {2024-10-07},
	journal = {Biological Mass Spectrometry},
	author = {Imbault, Nadine and Moritz, Thomas and Nilsson, Ove and Chen, Hao-Jie and Bollmark, Marie and Sandberg, Göran},
	year = {1993},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1002/bms.1200220310},
	pages = {201--210},
}

Non-derivatized cytokinins were analysed by liquid chromatography/mass spectrometry (LC/MS). The effluent from a capillary reversed-phase high-performance liquid chromatography column was introduced into the ion source of a double-focusing mass spectrometer via a frit interface, and ions were generated by fast atom bombardment (FAB) with 1% glycerol in the mobile phase acting as a matrix. Positive FAB spectra were obtained for base, riboside, ribotide and glucoside forms of cytokinins. The spectra were found to provide useful information for identification and structural elucidation of cytokinins. The LC/MS system was used to identify iso-pentenyladenosine in a purified extract from Norway spruce (Picea abies) needles. Quantitative analysis of iso-pentenyladenosine using (2H6)isopentenyladenosine as internal standard indicated levels of 1.2 ng g−1 fresh weight.

@article{chowdhury_fluorogenic_2023,
	title = {Fluorogenic properties of 4-dimethylaminocinnamaldehyde ({DMACA}) enable high resolution imaging of cell-wall-bound proanthocyanidins in plant root tissues},
	volume = {13},
	issn = {1664-462X},
	url = {https://www.frontiersin.org/articles/10.3389/fpls.2022.1060804},
	doi = {10.3389/fpls.2022.1060804},
	abstract = {Proanthocyanidins (PAs) are polymeric phenolic compounds found in plants and used in many industrial applications. Despite strong evidence of herbivore and pathogen resistance-related properties of PAs, their in planta function is not fully understood. Determining the location and dynamics of PAs in plant tissues and cellular compartments is crucial to understand their mode of action. Such an approach requires microscopic localization with fluorescent dyes that specifically bind to PAs. Such dyes have hitherto been lacking. Here, we show that 4-dimethylaminocinnamaldehyde (DMACA) can be used as a PA-specific fluorescent dye that allows localization of PAs at high resolution in cell walls and inside cells using confocal microscopy, revealing features of previously unreported wall-bound PAs. We demonstrate several novel usages of DMACA as a fluorophore by taking advantage of its double staining compatibility with other fluorescent dyes. We illustrate the use of the dye alone and its co-localization with cell wall polymers in different Populus root tissues. The easy-to-use fluorescent staining method, together with its high photostability and compatibility with other fluorogenic dyes, makes DMACA a valuable tool for uncovering the biological function of PAs at a cellular level in plant tissues. DMACA can also be used in other plant tissues than roots, however care needs to be taken when tissues contain compounds that autofluoresce in the red spectral region which can be confounded with the PA-specific DMACA signal.},
	urldate = {2023-02-10},
	journal = {Frontiers in Plant Science},
	author = {Chowdhury, Jamil and Ferdous, Jannatul and Lihavainen, Jenna and Albrectsen, Benedicte Riber and Lundberg-Felten, Judith},
	month = feb,
	year = {2023},
	keywords = {⛔ No DOI found},
}

Proanthocyanidins (PAs) are polymeric phenolic compounds found in plants and used in many industrial applications. Despite strong evidence of herbivore and pathogen resistance-related properties of PAs, their in planta function is not fully understood. Determining the location and dynamics of PAs in plant tissues and cellular compartments is crucial to understand their mode of action. Such an approach requires microscopic localization with fluorescent dyes that specifically bind to PAs. Such dyes have hitherto been lacking. Here, we show that 4-dimethylaminocinnamaldehyde (DMACA) can be used as a PA-specific fluorescent dye that allows localization of PAs at high resolution in cell walls and inside cells using confocal microscopy, revealing features of previously unreported wall-bound PAs. We demonstrate several novel usages of DMACA as a fluorophore by taking advantage of its double staining compatibility with other fluorescent dyes. We illustrate the use of the dye alone and its co-localization with cell wall polymers in different Populus root tissues. The easy-to-use fluorescent staining method, together with its high photostability and compatibility with other fluorogenic dyes, makes DMACA a valuable tool for uncovering the biological function of PAs at a cellular level in plant tissues. DMACA can also be used in other plant tissues than roots, however care needs to be taken when tissues contain compounds that autofluoresce in the red spectral region which can be confounded with the PA-specific DMACA signal.

@article{chowdhury_laccaria_2022,
	title = {Laccaria bicolor pectin methylesterases are involved in ectomycorrhiza development with {Populus} tremula × {Populus} tremuloides},
	volume = {236},
	issn = {1469-8137},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/nph.18358},
	doi = {10.1111/nph.18358},
	abstract = {The development of ectomycorrhizal (ECM) symbioses between soil fungi and tree roots requires modification of root cell walls. The pectin-mediated adhesion between adjacent root cells loosens to accommodate fungal hyphae in the Hartig net, facilitating nutrient exchange between partners. We investigated the role of fungal pectin modifying enzymes in Laccaria bicolor for ECM formation with Populus tremula × Populus tremuloides. We combine transcriptomics of cell-wall-related enzymes in both partners during ECM formation, immunolocalisation of pectin (Homogalacturonan, HG) epitopes in different methylesterification states, pectin methylesterase (PME) activity assays and functional analyses of transgenic L. bicolor to uncover pectin modification mechanisms and the requirement of fungal pectin methylesterases (LbPMEs) for ECM formation. Immunolocalisation identified remodelling of pectin towards de-esterified HG during ECM formation, which was accompanied by increased LbPME1 expression and PME activity. Overexpression or RNAi of the ECM-induced LbPME1 in transgenic L. bicolor lines led to reduced ECM formation. Hartig Nets formed with LbPME1 RNAi lines were shallower, whereas those formed with LbPME1 overexpressors were deeper. This suggests that LbPME1 plays a role in ECM formation potentially through HG de-esterification, which initiates loosening of adjacent root cells to facilitate Hartig net formation.},
	language = {en},
	number = {2},
	urldate = {2022-10-03},
	journal = {New Phytologist},
	author = {Chowdhury, Jamil and Kemppainen, Minna and Delhomme, Nicolas and Shutava, Iryna and Zhou, Jingjing and Takahashi, Junko and Pardo, Alejandro G. and Lundberg-Felten, Judith},
	month = oct,
	year = {2022},
	keywords = {Laccaria bicolor, Populus, cell wall, cell-wall, cell-wall remodelling, cell-wall-modifying enzymes, ectomycorrhiza, pectin, pectin methylesterase},
	pages = {639--655},
}

The development of ectomycorrhizal (ECM) symbioses between soil fungi and tree roots requires modification of root cell walls. The pectin-mediated adhesion between adjacent root cells loosens to accommodate fungal hyphae in the Hartig net, facilitating nutrient exchange between partners. We investigated the role of fungal pectin modifying enzymes in Laccaria bicolor for ECM formation with Populus tremula × Populus tremuloides. We combine transcriptomics of cell-wall-related enzymes in both partners during ECM formation, immunolocalisation of pectin (Homogalacturonan, HG) epitopes in different methylesterification states, pectin methylesterase (PME) activity assays and functional analyses of transgenic L. bicolor to uncover pectin modification mechanisms and the requirement of fungal pectin methylesterases (LbPMEs) for ECM formation. Immunolocalisation identified remodelling of pectin towards de-esterified HG during ECM formation, which was accompanied by increased LbPME1 expression and PME activity. Overexpression or RNAi of the ECM-induced LbPME1 in transgenic L. bicolor lines led to reduced ECM formation. Hartig Nets formed with LbPME1 RNAi lines were shallower, whereas those formed with LbPME1 overexpressors were deeper. This suggests that LbPME1 plays a role in ECM formation potentially through HG de-esterification, which initiates loosening of adjacent root cells to facilitate Hartig net formation.

@article{escamez_fluorescence_2021,
	title = {Fluorescence {Lifetime} {Imaging} as an {In} {Situ} and {Label}-{Free} {Readout} for the {Chemical} {Composition} of {Lignin}},
	volume = {9},
	url = {https://doi.org/10.1021/acssuschemeng.1c06780},
	doi = {10/gnr3sb},
	abstract = {Naturally fluorescent polymeric molecules such as collagen, resilin, cutin, suberin, or lignin can serve as renewable sources of bioproducts. Theoretical physics predicts that the fluorescence lifetime of these polymers is related to their chemical composition. We verified this prediction for lignin, a major structural element in plant cell walls that form woody biomass. Lignin is composed of different phenylpropanoid units, and its composition affects its properties, biological functions, and the utilization of wood biomass. We carried out fluorescence lifetime imaging microscopy (FLIM) measurements of wood cell wall lignin in a population of 90 hybrid aspen trees genetically engineered to display differences in cell wall chemistry and structure. We also measured the wood cell wall composition by classical analytical methods in these trees. Using statistical modeling and machine learning algorithms, we identified parameters of fluorescence lifetime that predict the content of S-type and G-type lignin units, the two main types of units in the lignin of angiosperm (flowering) plants. In a first step toward tailoring lignin biosynthesis toward improvement of woody biomass feedstocks, we show how FLIM can reveal the dynamics of lignin biosynthesis in two different biological contexts, including in vivo while lignin is being synthesized in the walls of living cells.},
	number = {51},
	urldate = {2021-12-14},
	journal = {ACS Sustainable Chemistry \& Engineering},
	author = {Escamez, Sacha and Terryn, Christine and Gandla, Madhavi Latha and Yassin, Zakiya and Scheepers, Gerhard and Näsholm, Torgny and Sundman, Ola and Jönsson, Leif J. and Lundberg-Felten, Judith and Tuominen, Hannele and Niittylä, Totte and Paës, Gabriel},
	month = dec,
	year = {2021},
	pages = {17381--17392},
}

Naturally fluorescent polymeric molecules such as collagen, resilin, cutin, suberin, or lignin can serve as renewable sources of bioproducts. Theoretical physics predicts that the fluorescence lifetime of these polymers is related to their chemical composition. We verified this prediction for lignin, a major structural element in plant cell walls that form woody biomass. Lignin is composed of different phenylpropanoid units, and its composition affects its properties, biological functions, and the utilization of wood biomass. We carried out fluorescence lifetime imaging microscopy (FLIM) measurements of wood cell wall lignin in a population of 90 hybrid aspen trees genetically engineered to display differences in cell wall chemistry and structure. We also measured the wood cell wall composition by classical analytical methods in these trees. Using statistical modeling and machine learning algorithms, we identified parameters of fluorescence lifetime that predict the content of S-type and G-type lignin units, the two main types of units in the lignin of angiosperm (flowering) plants. In a first step toward tailoring lignin biosynthesis toward improvement of woody biomass feedstocks, we show how FLIM can reveal the dynamics of lignin biosynthesis in two different biological contexts, including in vivo while lignin is being synthesized in the walls of living cells.

@article{plett_novel_2021,
	title = {Novel {Microdialysis} {Technique} {Reveals} a {Dramatic} {Shift} in {Metabolite} {Secretion} during the {Early} {Stages} of the {Interaction} between the {Ectomycorrhizal} {Fungus} {Pisolithus} microcarpus and {Its} {Host} {Eucalyptus} grandis},
	volume = {9},
	copyright = {http://creativecommons.org/licenses/by/3.0/},
	url = {https://www.mdpi.com/2076-2607/9/9/1817},
	doi = {10.3390/microorganisms9091817},
	abstract = {The colonisation of tree roots by ectomycorrhizal (ECM) fungi is the result of numerous signalling exchanges between organisms, many of which occur before physical contact. However, information is lacking about these exchanges and the compounds that are secreted by each organism before contact. This is in part due to a lack of low disturbance sampling methods with sufficient temporal and spatial resolution to capture these exchanges. Using a novel in situ microdialysis approach, we sampled metabolites released from Eucalyptus grandis and Pisolithus microcarpus independently and during indirect contact over a 48-h time-course using UPLC-MS. A total of 560 and 1530 molecular features (MFs; ESI- and ESI+ respectively) were identified with significant differential abundance from control treatments. We observed that indirect contact between organisms altered the secretion of MFs to produce a distinct metabolomic profile compared to either organism independently. Many of these MFs were produced within the first hour of contact and included several phenylpropanoids, fatty acids and organic acids. These findings show that the secreted metabolome, particularly of the ECM fungus, can rapidly shift during the early stages of pre-symbiotic contact and highlight the importance of observing these early interactions in greater detail. We present microdialysis as a useful tool for examining plant–fungal signalling with high temporal resolution and with minimal experimental disturbance.},
	language = {en},
	number = {9},
	urldate = {2021-10-14},
	journal = {Microorganisms},
	author = {Plett, Krista L. and Buckley, Scott and Plett, Jonathan M. and Anderson, Ian C. and Lundberg-Felten, Judith and Jämtgård, Sandra},
	month = sep,
	year = {2021},
	pages = {1817},
}

The colonisation of tree roots by ectomycorrhizal (ECM) fungi is the result of numerous signalling exchanges between organisms, many of which occur before physical contact. However, information is lacking about these exchanges and the compounds that are secreted by each organism before contact. This is in part due to a lack of low disturbance sampling methods with sufficient temporal and spatial resolution to capture these exchanges. Using a novel in situ microdialysis approach, we sampled metabolites released from Eucalyptus grandis and Pisolithus microcarpus independently and during indirect contact over a 48-h time-course using UPLC-MS. A total of 560 and 1530 molecular features (MFs; ESI- and ESI+ respectively) were identified with significant differential abundance from control treatments. We observed that indirect contact between organisms altered the secretion of MFs to produce a distinct metabolomic profile compared to either organism independently. Many of these MFs were produced within the first hour of contact and included several phenylpropanoids, fatty acids and organic acids. These findings show that the secreted metabolome, particularly of the ECM fungus, can rapidly shift during the early stages of pre-symbiotic contact and highlight the importance of observing these early interactions in greater detail. We present microdialysis as a useful tool for examining plant–fungal signalling with high temporal resolution and with minimal experimental disturbance.

@article{seyfferth_populuspterf85_2021,
	title = {{PopulusPtERF85} {Balances} {Xylem} {Cell} {Expansion} and {Secondary} {Cell} {Wall} {Formation} in {Hybrid} {Aspen}},
	volume = {10},
	copyright = {http://creativecommons.org/licenses/by/3.0/},
	url = {https://www.mdpi.com/2073-4409/10/8/1971},
	doi = {10.3390/cells10081971},
	abstract = {Secondary growth relies on precise and specialized transcriptional networks that determine cell division, differentiation, and maturation of xylem cells. We identified a novel role for the ethylene-induced Populus Ethylene Response Factor PtERF85 (Potri.015G023200) in balancing xylem cell expansion and secondary cell wall (SCW) formation in hybrid aspen (Populus tremula x tremuloides). Expression of PtERF85 is high in phloem and cambium cells and during the expansion of xylem cells, while it is low in maturing xylem tissue. Extending PtERF85 expression into SCW forming zones of woody tissues through ectopic expression reduced wood density and SCW thickness of xylem fibers but increased fiber diameter. Xylem transcriptomes from the transgenic trees revealed transcriptional induction of genes involved in cell expansion, translation, and growth. The expression of genes associated with plant vascular development and the biosynthesis of SCW chemical components such as xylan and lignin, was down-regulated in the transgenic trees. Our results suggest that PtERF85 activates genes related to xylem cell expansion, while preventing transcriptional activation of genes related to SCW formation. The importance of precise spatial expression of PtERF85 during wood development together with the observed phenotypes in response to ectopic PtERF85 expression suggests that PtERF85 contributes to the transition of fiber cells from elongation to secondary cell wall deposition.},
	language = {en},
	number = {8},
	urldate = {2021-09-02},
	journal = {Cells},
	author = {Seyfferth, Carolin and Wessels, Bernard A. and Vahala, Jorma and Kangasjärvi, Jaakko and Delhomme, Nicolas and Hvidsten, Torgeir R. and Tuominen, Hannele and Lundberg-Felten, Judith},
	month = aug,
	year = {2021},
	keywords = {ERF85 (CRF4), cell wall thickness, lignin, ribosome biogenesis, wood development, xylem expansion},
	pages = {1971},
}

Secondary growth relies on precise and specialized transcriptional networks that determine cell division, differentiation, and maturation of xylem cells. We identified a novel role for the ethylene-induced Populus Ethylene Response Factor PtERF85 (Potri.015G023200) in balancing xylem cell expansion and secondary cell wall (SCW) formation in hybrid aspen (Populus tremula x tremuloides). Expression of PtERF85 is high in phloem and cambium cells and during the expansion of xylem cells, while it is low in maturing xylem tissue. Extending PtERF85 expression into SCW forming zones of woody tissues through ectopic expression reduced wood density and SCW thickness of xylem fibers but increased fiber diameter. Xylem transcriptomes from the transgenic trees revealed transcriptional induction of genes involved in cell expansion, translation, and growth. The expression of genes associated with plant vascular development and the biosynthesis of SCW chemical components such as xylan and lignin, was down-regulated in the transgenic trees. Our results suggest that PtERF85 activates genes related to xylem cell expansion, while preventing transcriptional activation of genes related to SCW formation. The importance of precise spatial expression of PtERF85 during wood development together with the observed phenotypes in response to ectopic PtERF85 expression suggests that PtERF85 contributes to the transition of fiber cells from elongation to secondary cell wall deposition.

@article{henriksson_mycorrhizal_2021,
	title = {The mycorrhizal tragedy of the commons},
	volume = {24},
	issn = {1461-023X, 1461-0248},
	url = {https://onlinelibrary.wiley.com/doi/10.1111/ele.13737},
	doi = {10/gkcr8h},
	language = {en},
	number = {6},
	urldate = {2021-06-03},
	journal = {Ecology Letters},
	author = {Henriksson, Nils and Franklin, Oskar and Tarvainen, Lasse and Marshall, John and Lundberg‐Felten, Judith and Eilertsen, Lill and Näsholm, Torgny},
	editor = {Selosse, Marc‐André},
	month = jun,
	year = {2021},
	pages = {1215--1224},
}

@article{kemppainen_fluorescent_2020,
	title = {Fluorescent protein expression in the ectomycorrhizal fungus {Laccaria} bicolor: a plasmid toolkit for easy use of fluorescent markers in basidiomycetes},
	volume = {66},
	issn = {0172-8083, 1432-0983},
	shorttitle = {Fluorescent protein expression in the ectomycorrhizal fungus {Laccaria} bicolor},
	url = {http://link.springer.com/10.1007/s00294-020-01060-4},
	doi = {10.1007/s00294-020-01060-4},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {Current Genetics},
	author = {Kemppainen, Minna and Chowdhury, Jamil and Lundberg-Felten, Judith and Pardo, Alejandro},
	month = aug,
	year = {2020},
	pages = {791--811},
}

@article{wessels_ap2erf_2019,
	title = {An {AP2}/{ERF} transcription factor {ERF139} coordinates xylem cell expansion and secondary cell wall deposition},
	volume = {224},
	issn = {0028-646X, 1469-8137},
	shorttitle = {An {\textless}span style="font-variant},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/nph.15960},
	doi = {10/gjcsfs},
	language = {en},
	number = {4},
	urldate = {2021-06-07},
	journal = {New Phytologist},
	author = {Wessels, Bernard and Seyfferth, Carolin and Escamez, Sacha and Vain, Thomas and Antos, Kamil and Vahala, Jorma and Delhomme, Nicolas and Kangasjärvi, Jaakko and Eder, Michaela and Felten, Judith and Tuominen, Hannele},
	month = dec,
	year = {2019},
	pages = {1585--1599},
}

@article{seyfferth_ethylene_2019,
	title = {Ethylene {Signaling} {Is} {Required} for {Fully} {Functional} {Tension} {Wood} in {Hybrid} {Aspen}},
	volume = {10},
	issn = {1664-462X},
	url = {https://www.frontiersin.org/article/10.3389/fpls.2019.01101/full},
	doi = {10.3389/fpls.2019.01101},
	urldate = {2021-06-07},
	journal = {Frontiers in Plant Science},
	author = {Seyfferth, Carolin and Wessels, Bernard A. and Gorzsás, András and Love, Jonathan W. and Rüggeberg, Markus and Delhomme, Nicolas and Vain, Thomas and Antos, Kamil and Tuominen, Hannele and Sundberg, Björn and Felten, Judith},
	month = sep,
	year = {2019},
	pages = {1101},
}

@article{felten_ethylene_2018,
	title = {Ethylene signaling induces gelatinous layers with typical features of tension wood in hybrid aspen},
	volume = {218},
	issn = {0028646X},
	url = {http://doi.wiley.com/10.1111/nph.15078},
	doi = {10.1111/nph.15078},
	language = {en},
	number = {3},
	urldate = {2021-06-07},
	journal = {New Phytologist},
	author = {Felten, Judith and Vahala, Jorma and Love, Jonathan and Gorzsás, András and Rüggeberg, Markus and Delhomme, Nicolas and Leśniewska, Joanna and Kangasjärvi, Jaakko and Hvidsten, Torgeir R. and Mellerowicz, Ewa J. and Sundberg, Björn},
	month = may,
	year = {2018},
	pages = {999--1014},
}

@article{seyfferth_ethylene-related_2018,
	title = {Ethylene-{Related} {Gene} {Expression} {Networks} in {Wood} {Formation}},
	volume = {9},
	issn = {1664-462X},
	url = {http://journal.frontiersin.org/article/10.3389/fpls.2018.00272/full},
	doi = {10/gc7vds},
	urldate = {2021-06-07},
	journal = {Frontiers in Plant Science},
	author = {Seyfferth, Carolin and Wessels, Bernard and Jokipii-Lukkari, Soile and Sundberg, Björn and Delhomme, Nicolas and Felten, Judith and Tuominen, Hannele},
	month = mar,
	year = {2018},
	pages = {272},
}

@article{waller_sharing_2018,
	title = {Sharing resources for mutual benefit: crosstalk between disciplines deepens the understanding of mycorrhizal symbioses across scales},
	volume = {217},
	issn = {0028646X},
	shorttitle = {Sharing resources for mutual benefit},
	url = {http://doi.wiley.com/10.1111/nph.14912},
	doi = {10/ghbzdd},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {New Phytologist},
	author = {Waller, Lauren P. and Felten, Judith and Hiiesalu, Inga and Vogt-Schilb, Hélène},
	month = jan,
	year = {2018},
	pages = {29--32},
}

@article{vayssieres_development_2015,
	title = {Development of the {Poplar}-{Laccaria} bicolor {Ectomycorrhiza} {Modifies} {Root} {Auxin} {Metabolism}, {Signaling}, and {Response}},
	volume = {169},
	issn = {1532-2548 (Electronic) 0032-0889 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/26084921},
	doi = {10.1104/pp.114.255620},
	abstract = {Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation.},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Plant Physiol},
	author = {Vayssieres, A. and Pencik, A. and Felten, J. and Kohler, A. and Ljung, K. and Martin, F. and Legue, V.},
	month = sep,
	year = {2015},
	note = {Edition: 2015/06/19},
	keywords = {*Signal Transduction/drug effects, Gene Expression Regulation, Plant/drug effects, Indoleacetic Acids/*metabolism/pharmacology, Laccaria/drug effects/*physiology, Metabolome/drug effects, Models, Biological, Multivariate Analysis, Mycorrhizae/drug effects/*physiology, Plant Proteins/metabolism, Plant Roots/drug effects/growth \& development/*metabolism/*microbiology, Populus/drug effects/*microbiology},
	pages = {890--902},
}

Root systems of host trees are known to establish ectomycorrhizae (ECM) interactions with rhizospheric fungi. This mutualistic association leads to dramatic developmental modifications in root architecture, with the formation of numerous short and swollen lateral roots ensheathed by a fungal mantle. Knowing that auxin plays a crucial role in root development, we investigated how auxin metabolism, signaling, and response are affected in poplar (Populus spp.)-Laccaria bicolor ECM roots. The plant-fungus interaction leads to the arrest of lateral root growth with simultaneous attenuation of the synthetic auxin response element DR5. Measurement of auxin-related metabolites in the free-living partners revealed that the mycelium of L. bicolor produces high concentrations of the auxin indole-3-acetic acid (IAA). Metabolic profiling showed an accumulation of IAA and changes in the indol-3-pyruvic acid-dependent IAA biosynthesis and IAA conjugation and degradation pathways during ECM formation. The global analysis of auxin response gene expression and the regulation of AUXIN SIGNALING F-BOX PROTEIN5, AUXIN/IAA, and AUXIN RESPONSE FACTOR expression in ECM roots suggested that symbiosis-dependent auxin signaling is activated during the colonization by L. bicolor. Taking all this evidence into account, we propose a model in which auxin signaling plays a crucial role in the modification of root growth during ECM formation.

@article{felten_vibrational_2015,
	title = {Vibrational spectroscopic image analysis of biological material using multivariate curve resolution-alternating least squares ({MCR}-{ALS})},
	volume = {10},
	issn = {1750-2799 (Electronic) 1750-2799 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/25569330},
	doi = {10.1038/nprot.2015.008},
	abstract = {Raman and Fourier transform IR (FTIR) microspectroscopic images of biological material (tissue sections) contain detailed information about their chemical composition. The challenge lies in identifying changes in chemical composition, as well as locating and assigning these changes to different conditions (pathology, anatomy, environmental or genetic factors). Multivariate data analysis techniques are ideal for decrypting such information from the data. This protocol provides a user-friendly pipeline and graphical user interface (GUI) for data pre-processing and unmixing of pixel spectra into their contributing pure components by multivariate curve resolution-alternating least squares (MCR-ALS) analysis. The analysis considers the full spectral profile in order to identify the chemical compounds and to visualize their distribution across the sample to categorize chemically distinct areas. Results are rapidly achieved (usually {\textless}30-60 min per image), and they are easy to interpret and evaluate both in terms of chemistry and biology, making the method generally more powerful than principal component analysis (PCA) or heat maps of single-band intensities. In addition, chemical and biological evaluation of the results by means of reference matching and segmentation maps (based on k-means clustering) is possible.},
	language = {en},
	number = {2},
	urldate = {2021-06-07},
	journal = {Nat Protoc},
	author = {Felten, J. and Hall, H. and Jaumot, J. and Tauler, R. and de Juan, A. and Gorzsas, A.},
	month = feb,
	year = {2015},
	note = {Edition: 2015/01/09},
	keywords = {*Multivariate Analysis, *Spectroscopy, Fourier Transform Infrared, *Spectrum Analysis, Raman, Animals, Image Processing, Computer-Assisted/*methods, Islets of Langerhans/chemistry, Least-Squares Analysis, Mice, Inbred C57BL, Populus/chemistry, User-Computer Interface, Xylem/chemistry},
	pages = {217--40},
}

Raman and Fourier transform IR (FTIR) microspectroscopic images of biological material (tissue sections) contain detailed information about their chemical composition. The challenge lies in identifying changes in chemical composition, as well as locating and assigning these changes to different conditions (pathology, anatomy, environmental or genetic factors). Multivariate data analysis techniques are ideal for decrypting such information from the data. This protocol provides a user-friendly pipeline and graphical user interface (GUI) for data pre-processing and unmixing of pixel spectra into their contributing pure components by multivariate curve resolution-alternating least squares (MCR-ALS) analysis. The analysis considers the full spectral profile in order to identify the chemical compounds and to visualize their distribution across the sample to categorize chemically distinct areas. Results are rapidly achieved (usually \textless30-60 min per image), and they are easy to interpret and evaluate both in terms of chemistry and biology, making the method generally more powerful than principal component analysis (PCA) or heat maps of single-band intensities. In addition, chemical and biological evaluation of the results by means of reference matching and segmentation maps (based on k-means clustering) is possible.

@article{ditengou_volatile_2015,
	title = {Volatile signalling by sesquiterpenes from ectomycorrhizal fungi reprogrammes root architecture},
	volume = {6},
	issn = {2041-1723 (Electronic) 2041-1723 (Linking)},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/25703994},
	doi = {10.1038/ncomms7279},
	abstract = {The mutualistic association of roots with ectomycorrhizal fungi promotes plant health and is a hallmark of boreal and temperate forests worldwide. In the pre-colonization phase, before direct contact, lateral root (LR) production is massively stimulated, yet little is known about the signals exchanged during this step. Here, we identify sesquiterpenes (SQTs) as biologically active agents emitted by Laccaria bicolor while interacting with Populus or Arabidopsis. We show that inhibition of fungal SQT production by lovastatin strongly reduces LR proliferation and that (-)-thujopsene, a low-abundance SQT, is sufficient to stimulate LR formation in the absence of the fungus. Further, we show that the ectomycorrhizal ascomycote, Cenococcum geophilum, which cannot synthesize SQTs, does not promote LRs. We propose that the LR-promoting SQT signal creates a win-win situation by enhancing the root surface area for plant nutrient uptake and by improving fungal access to plant-derived carbon via root exudates.},
	language = {en},
	number = {1},
	urldate = {2021-06-07},
	journal = {Nat Commun},
	author = {Ditengou, F. A. and Muller, A. and Rosenkranz, M. and Felten, J. and Lasok, H. and van Doorn, M. M. and Legue, V. and Palme, K. and Schnitzler, J. P. and Polle, A.},
	month = feb,
	year = {2015},
	note = {Edition: 2015/02/24},
	keywords = {*Sesquiterpenes, Arabidopsis, Ascomycota, Indoleacetic Acids/metabolism, Laccaria/*physiology, Mycorrhizae/*physiology, Plant Roots/*growth \& development/metabolism, Populus/*growth \& development, Superoxides/metabolism, Symbiosis, Volatile Organic Compounds},
	pages = {6279},
}

The mutualistic association of roots with ectomycorrhizal fungi promotes plant health and is a hallmark of boreal and temperate forests worldwide. In the pre-colonization phase, before direct contact, lateral root (LR) production is massively stimulated, yet little is known about the signals exchanged during this step. Here, we identify sesquiterpenes (SQTs) as biologically active agents emitted by Laccaria bicolor while interacting with Populus or Arabidopsis. We show that inhibition of fungal SQT production by lovastatin strongly reduces LR proliferation and that (-)-thujopsene, a low-abundance SQT, is sufficient to stimulate LR formation in the absence of the fungus. Further, we show that the ectomycorrhizal ascomycote, Cenococcum geophilum, which cannot synthesize SQTs, does not promote LRs. We propose that the LR-promoting SQT signal creates a win-win situation by enhancing the root surface area for plant nutrient uptake and by improving fungal access to plant-derived carbon via root exudates.

@article{vahala_genomewide_2013,
	title = {A genome‐wide screen for ethylene‐induced {Ethylene} {Response} {Factors} ( {\textless}span style="font-variant:small-caps;"{\textgreater}{ERF}{\textless}/span{\textgreater} s) in hybrid aspen stem identifies \textit{ {\textless}span style="font-variant:small-caps;"{\textgreater}{ERF}{\textless}/span{\textgreater} } genes that modify stem growth and wood properties},
	volume = {200},
	issn = {0028-646X, 1469-8137},
	shorttitle = {A genome‐wide screen for ethylene‐induced {Ethylene} {Response} {Factors} ( {\textless}span style="font-variant},
	url = {https://onlinelibrary.wiley.com/doi/10.1111/nph.12386},
	doi = {10/f2zvjg},
	language = {en},
	number = {2},
	urldate = {2021-06-08},
	journal = {New Phytologist},
	author = {Vahala, Jorma and Felten, Judith and Love, Jonathan and Gorzsás, András and Gerber, Lorenz and Lamminmäki, Airi and Kangasjärvi, Jaakko and Sundberg, Björn},
	month = oct,
	year = {2013},
	pages = {511--522},
}

@article{ranocha_arabidopsis_2013,
	title = {Arabidopsis {WAT1} is a vacuolar auxin transport facilitator required for auxin homoeostasis},
	volume = {4},
	issn = {2041-1723},
	url = {http://www.nature.com/articles/ncomms3625},
	doi = {10/f23w2p},
	language = {en},
	number = {1},
	urldate = {2021-06-08},
	journal = {Nature Communications},
	author = {Ranocha, Philippe and Dima, Oana and Nagy, Réka and Felten, Judith and Corratgé-Faillie, Claire and Novák, Ondřej and Morreel, Kris and Lacombe, Benoît and Martinez, Yves and Pfrunder, Stephanie and Jin, Xu and Renou, Jean-Pierre and Thibaud, Jean-Baptiste and Ljung, Karin and Fischer, Urs and Martinoia, Enrico and Boerjan, Wout and Goffner, Deborah},
	month = dec,
	year = {2013},
	pages = {2625},
}

@article{felten_ectomycorrhizal_2009,
	title = {The {Ectomycorrhizal} {Fungus} \textit{{Laccaria} bicolor} {Stimulates} {Lateral} {Root} {Formation} in {Poplar} and {Arabidopsis} through {Auxin} {Transport} and {Signaling}},
	volume = {151},
	issn = {1532-2548},
	url = {https://academic.oup.com/plphys/article/151/4/1991/6109870},
	doi = {10/dsjkhv},
	abstract = {Abstract
            The early phase of the interaction between tree roots and ectomycorrhizal fungi, prior to symbiosis establishment, is accompanied by a stimulation of lateral root (LR) development. We aimed to identify gene networks that regulate LR development during the early signal exchanges between poplar (Populus tremula × Populus alba) and the ectomycorrhizal fungus Laccaria bicolor with a focus on auxin transport and signaling pathways. Our data demonstrated that increased LR development in poplar and Arabidopsis (Arabidopsis thaliana) interacting with L. bicolor is not dependent on the ability of the plant to form ectomycorrhizae. LR stimulation paralleled an increase in auxin accumulation at root apices. Blocking plant polar auxin transport with 1-naphthylphthalamic acid inhibited LR development and auxin accumulation. An oligoarray-based transcript profile of poplar roots exposed to molecules released by L. bicolor revealed the differential expression of 2,945 genes, including several components of polar auxin transport (PtaPIN and PtaAUX genes), auxin conjugation (PtaGH3 genes), and auxin signaling (PtaIAA genes). Transcripts of PtaPIN9, the homolog of Arabidopsis AtPIN2, and several PtaIAAs accumulated specifically during the early interaction phase. Expression of these rapidly induced genes was repressed by 1-naphthylphthalamic acid. Accordingly, LR stimulation upon contact with L. bicolor in Arabidopsis transgenic plants defective in homologs of these genes was decreased or absent. Furthermore, in Arabidopsis pin2, the root apical auxin increase during contact with the fungus was modified. We propose a model in which fungus-induced auxin accumulation at the root apex stimulates LR formation through a mechanism involving PtaPIN9-dependent auxin redistribution together with PtaIAA-based auxin signaling.},
	language = {en},
	number = {4},
	urldate = {2021-06-08},
	journal = {Plant Physiology},
	author = {Felten, Judith and Kohler, Annegret and Morin, Emmanuelle and Bhalerao, Rishikesh P. and Palme, Klaus and Martin, Francis and Ditengou, Franck A. and Legué, Valérie},
	month = dec,
	year = {2009},
	pages = {1991--2005},
}

Abstract The early phase of the interaction between tree roots and ectomycorrhizal fungi, prior to symbiosis establishment, is accompanied by a stimulation of lateral root (LR) development. We aimed to identify gene networks that regulate LR development during the early signal exchanges between poplar (Populus tremula × Populus alba) and the ectomycorrhizal fungus Laccaria bicolor with a focus on auxin transport and signaling pathways. Our data demonstrated that increased LR development in poplar and Arabidopsis (Arabidopsis thaliana) interacting with L. bicolor is not dependent on the ability of the plant to form ectomycorrhizae. LR stimulation paralleled an increase in auxin accumulation at root apices. Blocking plant polar auxin transport with 1-naphthylphthalamic acid inhibited LR development and auxin accumulation. An oligoarray-based transcript profile of poplar roots exposed to molecules released by L. bicolor revealed the differential expression of 2,945 genes, including several components of polar auxin transport (PtaPIN and PtaAUX genes), auxin conjugation (PtaGH3 genes), and auxin signaling (PtaIAA genes). Transcripts of PtaPIN9, the homolog of Arabidopsis AtPIN2, and several PtaIAAs accumulated specifically during the early interaction phase. Expression of these rapidly induced genes was repressed by 1-naphthylphthalamic acid. Accordingly, LR stimulation upon contact with L. bicolor in Arabidopsis transgenic plants defective in homologs of these genes was decreased or absent. Furthermore, in Arabidopsis pin2, the root apical auxin increase during contact with the fungus was modified. We propose a model in which fungus-induced auxin accumulation at the root apex stimulates LR formation through a mechanism involving PtaPIN9-dependent auxin redistribution together with PtaIAA-based auxin signaling.